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Fred van dillen organon teknika dawn of the dragons hauberk of gold

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These large vaccine trials will likely be able to afford to collect specimens only on a semiannual basis, which is similar to the collection schedule in the VPS. Given the powerful effect of HAART in reducing viral replication, it will be important to obtain several blood and genital tract measurements after seroconversion, to assess the effect of vaccination on virus load before treatment is initiated. MSM were significantly more likely to initiate antiretrovirals than were female or IDU seroconverters, which may reflect access to care, provider attitudes, or seroconverter willingness to initiate therapy.

Primary HIV-1 drug resistance to all classes of approved antiretroviral drugs in chronically infected persons and seroconverters has been described elsewhere [ 15 , 16 , 18 , 73—78 ]. Overall, 9. The prevalence of genotypic resistance we observed is comparable to recent reports of seroconverters in Europe and the United States [ 15—17 , 79 ]. We observed a primary protease mutation in just 1 seroconverter the PR V82A mutation , which is considered to be insufficient to cause detectable decreased susceptibility to protease inhibitors [ 37 , 38 ].

In summary, our findings have relevance to pathogenesis and treatment studies of acute HIV infection, vaccine efficacy trials, and HIV prevention programs. We found that seroconverters often reported multiple episodes of risk behavior in the seroconversion period. Even with increased recognition of primary HIV infection by health care providers and at-risk persons, acute HIV was presumptively diagnosed in a minority of the symptomatic HIVNET seroconverters who sought medical care, reflecting possible missed opportunities for early treatment [ 80—82 ] and prevention of secondary transmission [ 3 ].

Additional efforts to improve recognition of early HIV infection will be important, to increase the sensitivity and timeliness of this diagnosis. Even in the era of increased use of antiretrovirals, we did not find substantial antiretroviral resistance among the earliest virus isolates, the best available measure of genotypic resistance in transmitted viruses. We did demonstrate the feasibility of measuring PVL as a surrogate marker of the effect of HIV vaccines on initial virus load before initiation of antiretroviral therapy.

Finally, our finding that genital tract virus load can be detectable even in the setting of low or undetectable PVL during early HIV infection may have implications for the use of therapy as a means of preventing transmission of HIV. Although the relationship between genital tract virus load and transmission has yet to be demonstrated, particularly in early HIV infection, it is possible that genital tract virus load may represent a more precise marker of transmissibility.

Therefore, both recently infected persons and those with chronic HIV infection must be counseled not to make assumptions about their potential infectivity on the basis of their PVL. Google Scholar. Google Preview. Written informed consent was obtained from all study participants, in accordance with human subjects guidelines of each institution.

The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. Oxford University Press is a department of the University of Oxford.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Skip Nav Destination Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Subjects and Methods. Article Navigation. Celum , Connie L. Reprints or correspondence: Dr.

Oxford Academic. Susan P. Deborah Donnell. John M. Kenneth Mayer. Beryl Koblin. Michael Marmor. Sam Bozeman. Robert M. Jorge Flores. Sheppard H. Cite Cite Connie L. Select Format Select format. Permissions Icon Permissions. Abstract Risk behaviors, symptoms, and virologic characteristics were studied among human immunodeficiency virus HIV seroconverters in vaccine preparedness cohorts during — Open in new tab Download slide.

Symptoms, medical care, and activity level during seroconversion period. Intermediate-size trials for the evaluation of HIV vaccine candidates: a workshop summary. Google Scholar Crossref. Search ADS. Biological considerations in the development of a human immunodeficiency virus vaccine.

Role of the primary infection in epidemics of HIV infection in gay cohorts. Google Scholar PubMed. Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. High levels of human immunodeficiency virus type 1 in blood and semen of seropositive men in sub-Saharan Africa. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV Drug resistance patterns, genetic subtypes, clinical features, and risk factors in military personnel with HIV-1 seroconversion.

Reduced antiretroviral drug susceptibility among patients with primary HIV infection [see comments]. Feasibility of human immunodeficiency virus vaccine trials in homosexual men in the United States: risk behavior, seroincidence, and willingness to participate. Per-contact risk of human immunodeficiency virus transmission between male sexual partners.

High viral load in semen of human immunodeficiency virus type 1—infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors. Sensitive method for the detection of infectious HIV in semen of seropositive individuals. Rapid and sensitive viral culture method for human immunodeficiency virus type 1. Maintaining the integrity of human immunodeficiency virus sequence databases. Comparative performance of high-density oligonucleotide sequencing and dideoxynucleotide sequencing of HIV type 1 pol from clinical samples.

Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. Phenotypic and genotypic analysis of stavudine-resistant isolates of HIV-1 [abstract 17]. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor.

Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Incidence and prognostic significance of symptomatic primary human immunodeficiency virus type 1 infection in homosexual men. Kinloch-de Loes. Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases. Severity and prognosis of acute human immunodeficiency virus type 1 illness: a dose-response relationship.

Primary human immunodeficiency virus type 1 infection: clinical manifestations among women in Mombasa, Kenya. Seroco Study Group [letter; see comments]. Hemophilia Growth and Development Study. Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men.

Sex differences in longitudinal human immunodeficiency virus type 1 RNA levels among seroconverters. Longitudinal human immunodeficiency virus type 1 load in the Italian seroconversion study: correlates and temporal trends of virus load. HIV-1 in semen: determination of proviral and viral titres compared to blood, and quantification of semen leukocyte populations.

Detection and quantification of HIV-1 in semen: identification of a subpopulation of men at high potential risk of viral sexual transmission. Human immunodeficiency virus type 1 shedding pattern in semen correlates with the compartmentalization of viral quasi species between blood and semen. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy [see comments].

Sexually transmitted diseases and human immunodeficiency virus infection: cause, effect, or both? Rebound of seminal HIV-1 viral load associated with sexually transmitted diseases STDs after virologic suppression by antiretroviral therapy [abstract ]. Transmission of zidovudine-resistant HIV-1 through heterosexual contacts [letter]. Heterosexual transmission of human immunodeficiency virus type 1 variants associated with zidovudine resistance.

Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors. Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Transmission of zidovudineresistant human immunodeficiency virus type 1 variants following deliberate injection of blood from a patient with AIDS: characteristics and natural history of the virus.

Transmission of HIV-1 resistant to multiple reverse transcriptase inhibitors and protease inhibitors [abstract ]. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses. Treatment of primary HIV-1 infection with combination antiretroviral therapy.

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Related articles in PubMed Increase in SARS-CoV-2 infected biomedical waste among low middle-income countries: environmental sustainability and impact with health implications. Nail changes in diabetes. The food, the bug, and the ugly: A recipe for food-induced gut pain. Citing articles via Web of Science Soluble Notch ligand DLL1 is associated with bleeding complication in patients with dengue fever infection.

Clonorchis sinensis re-infection rate and the determinants: a prospective cohort study in Hengxian County, Guangxi, China. Prospects of future typhoid and paratyphoid vaccines in endemic countries. Looking for your next opportunity? View all jobs. If NRTI treatment is continued, for certain patients, progressive mitochondrial toxicity can produce severe lactic acidosis manifested clinically by tachypnea and dyspnea.

Respiratory failure can follow, requiring mechanical ventilation. In addition to discontinuation of antiretroviral treatment and intensive therapeutic strategies that include bicarbonate infusions and hemodialysis AI , clinicians can administer thiamine and riboflavin on the basis of the pathophysiologic hypothesis that sustained cellular dysfunctions of the mitochondrial respiratory chain cause this fulminant clinical syndrome. However, efficacy of these latter interventions requires clinical validation.

Antiretroviral treatment should be suspended if clinical and laboratory manifestations of the lactic acidosis syndrome occur BIII. Hepatotoxicity Hepatotoxicity, which is defined as a times increase in serum transaminases e. The majority of patients are asymptomatic, and certain cases resolve spontaneously without therapy interruption or modification Hepatic steatosis in the presence of lactic acidosis is a rare but serious adverse effect associated with the nucleoside analogs see more detailed discussion in Lactic Acidosis and Hepatic Steatosis.

An incidence of In an African randomized trial where stavudine was the backbone NRTI, and either nevirapine or efavirenz was added to emtricitabine or lamivudine, 9. Two of these patients died of liver failure. Nevirapine-associated hepatitis might also be present as part of a hypersensitivity syndrome, with a constellation of other symptoms e.

Approximately two thirds of the cases of nevirapine-associated clinical hepatitis occur within the first 12 weeks. Fulminant and even fatal cases of hepatic necrosis have been reported. Patients might experience nonspecific gastrointestinal and flu-like symptoms with or without liver enzyme abnormalities.

The syndrome can progress rapidly to hepatomegaly, jaundice, and hepatic failure within days A two-week lead-in dosing with mg once daily before dose escalation to twice daily might reduce the incidence of hepatotoxicity. Because of the potential severity of clinical hepatitis, certain clinicians advise close monitoring of liver enzymes and clinical symptoms after nevirapine initiation e. Patients who experience severe clinical hepatotoxicity while receiving nevirapine should not receive nevirapine therapy in the future.

Unlike the early onset hepatotoxicity observed with nevirapine, PI-associated liver enzyme abnormalities can occur any time during the treatment course. Coinfection with hepatitis C virus is reported to be a major risk factor for development of hepatotoxicity after PI initiation , HAART-induced immune reconstitution rather than direct liver toxic effects of the PIs have been indicated as the cause of liver decompensation among hepatitis C or hepatitis B coinfected patients.

Other potential risk factors for hepatotoxicity include hepatitis B infection ,, , alcohol abuse , baseline elevated liver enzymes , stavudine use , and concomitant use of other hepatotoxic agents. Hyperglycemia Hyperglycemia, new-onset diabetes mellitus, diabetic ketoacidosis, and exacerbation of preexisting diabetes mellitus have been reported among patients receiving HAART These metabolic derangements are strongly associated with PI use , although they can occur independent of PI use PIs were independently associated with hyperglycemia, and the incidence did not vary substantially by PIs Viral load suppression and increase in body weight did not reduce the magnitude of the association with PIs.

The pathogenesis of these abnormalities has not been fully elucidated; however, hyperglycemia might result from peripheral and hepatic insulin resistance, relative insulin deficiency, an impaired ability of the liver to extract insulin, and a longer exposure to antiretroviral medications , In these reports, symptoms of hyperglycemia were reported at a median of approximately 60 days range: days after initiation of PI therapy.

Hyperglycemia resolved for certain patients who discontinued PI therapy; however, the reversibility of these events is unknown because of limited data. Certain patients continued PI therapy and initiated treatment with oral hypoglycemic agents or insulin.

Clinicians are advised to monitor closely their HIV-infected patients with preexisting diabetes when PIs are prescribed and to be aware of the risk for drug-related new-onset diabetes among patients without a history of diabetes BIII. Patients should be advised regarding the warning signs of hyperglycemia i. Certain clinicians recommend routine fasting blood glucose measurements at month intervals during the first year of PI treatment for patients with no previous history of diabetes CIII.

Routine use of glucose tolerance tests to detect this complication is not recommended DIII. Because pregnancy is an independent risk factor for impaired glucose tolerance, closer monitoring of blood glucose levels should be done for pregnant women receiving PI-containing regimens. No data are available to aid in the decision to continue or discontinue drug therapy among patients with new-onset or worsening diabetes; however, the majority of experienced clinicians recommend continuation of HAART in the absence of severe diabetes BIII.

Fat Maldistribution HIV infection and antiretroviral therapy have been associated with unique fat distribution abnormalities. Generalized fat wasting is common in advanced HIV disease, and localized fat accumulations have been reported with NRTI monotherapy However, the recognition and observation of fat maldistribution syndromes have increased in the era of combination antiretroviral therapy characterized by fat wasting lipoatrophy or fat accumulation hyperadiposity.

Fat maldistribution is often referred to as lipodystrophy, and in combination with metabolic abnormalities including insulin resistance and hyperlipidemia is referred to as lipodystrophy syndrome. Although the lack of defining criteria has also impeded investigation into the pathogenic mechanisms of these abnormalities, the spectrum of morphologic abnormalities might indicate multifactorial causation related to specific antiretroviral exposure and underlying host factors.

Lipodystrophy might be associated with serum dyslipidemias, glucose intolerance, or lactic acidosis Fat accumulation might be seen in the abdomen, the dorsocervical fat pad, and, among both men and women, the breasts. Prevalence increases with duration of antiretroviral therapy Although available evidence indicates that an increased risk for fat accumulation exists with PIs, whether specific drugs are more strongly associated with this toxicity is unclear.

The face and extremities are most commonly affected by fat atrophy, and variability exists in severity. Prevalence of this toxicity has been reported to increase with long-term NRTI exposure Although stavudine has been frequently reported in cases of lipoatrophy, this might be a marker of longer term treatment exposure No clearly effective therapy for fat accumulation or lipoatrophy is known.

In the majority of persons, discontinuation of antiretroviral medications or class switching has not resulted in substantial benefit; however, among a limited number of persons, improvement in physical appearance has been reported Preliminary results from limited studies indicate a reduction in accumulated fat and fat redeposition with the use of certain agents personal communication, M.

Schambelan and P. Volberding, However, data are inconclusive and recommendations cannot be made. Hyperlipidemia HIV infection and antiretroviral therapy are associated with complex metabolic alterations, including dyslipidemia. Cachexia, reduced total cholesterol, and elevated triglycerides were reported before the availability of potent antiretroviral therapy , HAART is associated with elevation of total serum cholesterol and low-density lipoprotein and in additional increases in fasting triglycerides , The magnitude of changes varies substantially and does not occur among all patients.

Dyslipidemias primarily occur with PIs; however, a range from an increased association with ritonavir to limited or no association with a newer investigational compound indicates that hyperlipidemia might be a drug-specific rather than a class-specific toxicity Frequently, antiretroviral-associated dyslipidemias are sufficiently severe enough to consider therapeutic intervention. Although data remain inconclusive, lipid elevations might be associated with accelerated atherosclerosis and cardiovascular complications among HIV-infected persons.

Indications for monitoring and intervention in HIV therapy-associated dyslipidemias are the same as among uninfected populations No evidence-based guidelines exist for lipid management specific to HIV infection and antiretroviral therapy. However, close monitoring of lipid levels among patients with additional risks for atherosclerotic disease might be indicated Low-fat diets, regular exercise, control of blood pressure and smoking cessation are critical elements of care.

Hypercholesterolemia might respond to b-hdroxy-b-methylglutaryl-CoA reductase inhibitors statins. However, recognizing the interactions of certain statins with PIs that can result in increased statin levels is critical Table Usually, agents that are less affected by the inhibitory effect of PIs via the cytochrome P system are preferred e.

Atorvastatin, which is at least partially metabolized by this pathway, can also be used with PIs. However, atorvastatin should be used with caution and at reduced doses because higher concentrations of atorvastatin are expected Monotherapy with fibrates is less effective, but they can be added to statin therapy; additional monitoring is needed because of the increased risk of rhabdomyolysis and hepatotoxicity. Isolated triglyceride elevations respond best to low-fat diets, fibrates, or statins , Lipid elevations might require modifications in antiretroviral regimens if they are severe or unresponsive to other management strategies.

Improvement in lipid levels tends to be more substantial with nevirapine than with efavirenz in studies regarding switching therapies. Reported episodes have involved joints and soft tissues; however, serious bleeding episodes, including intracranial and gastrointestinal bleeding, have been reported. Bleeding episodes occurred a median of 22 days after initiation of PI therapy.

Certain patients received additional coagulation factor while continuing PI therapy. Osteonecrosis, Osteopenia, and Osteoporosis Avascular necrosis and decreased bone density are now recognized as emerging metabolic complications of HIV infection that might be linked to HAART regimens. Both of these bone abnormalities have been reported among adults and children with HIV infection who are now surviving longer with their disease in part because of HAART Diagnoses of osteonecrosis are usually made by CT scan or magnetic resonance imaging MRI , when these studies are performed in response to patient's complaints of pain in an affected hip or spine.

Avascular necrosis is not associated with a specific antiretroviral regimen among HIV-infected adults, but it has been linked to corticosteroids use among certain patients , Factors associated with osteonecrosis include alcohol abuse, hemoglobinopathies, corticosteroid treatment, hyperlipidaemia, and hypercoagulability states.

Occurrence of hyperlipidaemia indicates an indirect link between antiretroviral therapy and the occurrence of osteonecrosis among HIV-infected patients; however, prospective clinical studies are required to establish this association. No accepted medical therapy exists for avascular necrosis, and surgery might be necessary for disabling symptoms.

Decreases in bone mineral density BMD , both moderate osteopenia and severe osteoporosis , are a reflection of the competing effects of bone reabsorption by osteoclast and bone deposition by osteoblast and are measured by bone densitometry.

This evidence for decreased bone formation and turnover has been demonstrated with more potent antiretroviral therapy, including PIs Preliminary observations of increased serum and urinary markers of bone turnover among patients on protease-containing HAART who have osteopenia support the possible link of bone abnormalities to other metabolic abnormalities observed among HIV-infected patients , Presently, no recommendation can be made for routine measurement of bone density among asymptomatic patients by dual energy X-ray absorptiometry DEXA or by such newer measurements as quantitative ultrasound QUS.

Specific prophylaxis or treatment recommendations to prevent more substantial osteoporosis have not been developed for HIV-infected patients with osteopenia. On the basis of experience in the treatment of primary osteoporosis, recommending adequate intake of calcium and vitamin D and appropriate weight-bearing exercise is reasonable.

When fractures occur or osteoporosis is documented, more specific and aggressive therapies with bisphosphonates, raloxifene, or calcitonin might be indicated Hormone replacement therapy including estrogen can be considered in the setting of substantially decreased bone density among postmenopausal women on HAART. The majority of cases are mild to moderate, occurring within the first weeks of therapy. Certain experienced clinicians recommend managing the skin rash with antihistamine for symptomatic relief without drug discontinuation, although continuing treatment during such rashes has been questioned More serious cutaneous manifestations e.

The majority of reactions resulting in skin rash are confined to cutaneous reactions. However, a severe or even life-threatening syndrome of drug rash with eosinophilia and systemic symptoms DRESS has also been described , Systemic symptoms can include fever, hematological abnormalities, and multiple organ involvement.

Using a 2-week lead-in dose escalation schedule when initiating nevirapine therapy might reduce the incidence of rash. Fifteen of the 18 patients were receiving nevirapine. The median time from initiation of nevirapine to onset of cutaneous eruption was 11 days, with two thirds of the cases occurring during the initial dosing period Female patients might have as much as a sevenfold higher risk for developing grade 3 or 4 skin rashes than male patients , The use of systemic corticosteroid or antihistamine therapy at the time of the initiation of nevirapine to prevent development of skin rash has not proven effective , In fact, a higher incidence of skin rash has been reported among the steroid- or antihistamine-treated patients.

At present, prophylactic use of corticosteroids should be discouraged. The incidence of cross-hypersensitivity reactions between these agents is unknown. In a limited number of reports, patients with prior history of nevirapine-associated skin rash had been able to tolerate efavirenz without increased rates of cutaneous reactions , Among the NRTIs, skin rash occurs most frequently with abacavir.

Skin rash might be one of the symptoms of abacavir-associated systemic hypersensitivity reaction; in that case, therapy should be discontinued without future attempts to resume abacavir therapy. Although amprenavir is a sulfonamide, the potential of cross-reactivity between amprenavir and other sulfa drugs is unknown.

As a result, amprenavir should be used with caution in patients with history of sulfa allergies. Interruption of Antiretroviral Therapy Antiretroviral therapy might need to be discontinued temporarily or permanently for multiple reasons. If a need exists to discontinue any antiretroviral medication, clinicians and patients should be aware of the theoretical advantage of stopping all antiretroviral agents simultaneously, rather than continuing one or two agents, to minimize the emergence of resistant viral strains.

If a decision is made to interrupt therapy, the patient should be monitored closely, including clinical and laboratory evaluations. An interest exists in what is sometimes referred to as structured or supervised treatment interruptions STI.

Because of limited available data, none of these approaches can be recommended. The theoretical goal of STI in this patient population is to allow for the reemergence of HIV that is susceptible to antiretroviral therapy. The theoretical goal of autoimmunization STI is to allow multiple short bursts of viral replication to augment HIV-specific immune responses. STI for the purpose of less time on therapy uses predetermined periods of long- or short-cycle intermittent antiretroviral therapy.

The numbers of patients and duration of follow-up are insufficient for adequate evaluation of these approaches. Because of insufficient data regarding these situations, STI cannot be recommended for use in general clinical practice. Further research is necessary in each of these areas. Changing a Failing Regimen As with the initiation of antiretroviral therapy, deciding to change regimens should be approached after considering multiple, complex factors, including. Careful assessment of a patient's adherence before changing antiretroviral therapy is critical; the patient's other health-care providers e.

Clinicians should be aware of the prevalence of mental health disorders and psychoactive substance use disorders among HIV-infected persons because suboptimal mental health treatment services can jeopardize the ability of these persons to adhere to medical treatment.

Optimal identification of and intervention for these mental health disorders can enhance adherence to HIV therapy. Clinicians should distinguish between drug failure versus drug toxicity before changing a patient's therapy. Testing for antiretroviral drug resistance can also be helpful in maximizing the number of active drugs in a regimen see Drug-Resistance Testing. Viral resistance to antiretroviral drugs can be a key reason for treatment failure. Genetically distinct viral variants emerge in each HIV-infected person after initial infection.

Viruses with single-drug--resistant mutations exist even before therapy but are selected for replication by antiviral regimens that are only partially suppressive. The more potent a regimen is in durably suppressing HIV replication, the less probable the emergence of resistant variants. Three groups of patients should be considered for a change in therapy: 1 persons who are receiving incompletely suppressive antiretroviral therapy e. Criteria for Changing Therapy The goal of antiretroviral therapy, to improve the length and quality of patients' lives, is best accomplished by maximal suppression of viral replication to below detectable levels i.

However, to achieve this goal for certain patients, therapy regimens must be modified. Specific criteria that should prompt consideration for changing therapy include the following:. A final consideration is the recognition of the limited choice of available agents and the knowledge that a decision to change regimens might reduce future treatment options for that patient. This consideration can influence the clinician to be more conservative when deciding to change therapy.

Consideration of alternative options should include potency of the substituted regimen and probability of tolerance of, or adherence to, the alternative regimen. Clinical trials have demonstrated that partial suppression of virus is superior to no suppression of virus. Conversely, clinicians and patients might prefer to suspend treatment to preserve future options or because a sustained antiviral effect cannot be achieved.

Referral to or consultation with an experienced HIV clinician is appropriate when considering a change in therapy. When possible, patients requiring a change in antiretroviral regimen, but who are without treatment options through using approved drugs, should be referred for inclusion in a clinical trial.

Therapeutic Options When Changing Antiretroviral Therapy Recommendations for changes in treatment differ according to the indication for the change. If the desired virologic objectives have been achieved for patients who have intolerance or toxicity, a substitution for the offending drug should be made, preferably by using an agent in the same class with a different toxicity or tolerance profile. If virologic objectives have been achieved, but the patient is receiving a regimen not in the preferred category e.

As previously discussed, the majority of experienced clinicians believe that treatment with regimens not in the strongly recommended or alternative categories is associated with eventual failure, and they recommend the latter tactic. Limited clinical data exist to support specific strategies for changing therapy among patients who have failed the strongly recommended regimens; however, theoretical considerations should guide decisions.

Of concern is the possibility of broad cross-resistance among drugs within a class. A change in regimen because of treatment failure should be guided by results of resistance testing. This report includes a summary of the guidelines to follow when changing a patient's antiretroviral therapy Table For certain patients, options are limited because of previous antiretroviral use, toxicity, or intolerance.

For the clinically stable patient with detectable viremia for whom an optimal change in therapy is not possible, delaying therapy changes in anticipation of the availability of newer and more potent agents might be prudent. Decisions to change therapy and design a new regimen should be made with assistance from a clinician well-experienced in treating HIV-infected patients through consultation or referral. However, acute HIV infection is often not recognized by primary care clinicians because of the similarity of the symptom complex with those of influenza or other illnesses.

Additionally, acute primary infection can occur asymptomatically. Health-care providers should consider a diagnosis of HIV infection for patients who experience a compatible clinical syndrome Table 22 and should obtain appropriate laboratory testing. When suspicion for acute infection is high e. Information regarding treatment of acute HIV infection from clinical trials is limited. Preliminary data indicate that treatment of primary HIV infection with combination therapy has a beneficial effect on laboratory markers of disease progression 19, However, the potential disadvantages of initiating therapy include additional exposure to antiretroviral therapy without a known clinical benefit, which could result in substantial toxicities, development of antiretroviral drug resistance, and adverse effect on quality of life.

Ongoing clinical trials are addressing the question of long-term benefits of potent treatment regimens. Theoretically, early intervention can. These considerations are similar to those for initiating therapy for the asymptomatic patient see Considerations for Initiating Therapy for the Patient with Asymptomatic HIV-Infection. The health-care provider and the patient should be aware that therapy of primary HIV infection is based on theoretical considerations, and the potential benefits should be weighed against the potential risks.

Certain authorities endorse treatment of acute HIV infection on the basis of the theoretical rationale and limited but supportive clinical trial data. Apart from patients with acute primary HIV infection, experienced clinicians also recommend consideration of therapy for patients among whom seroconversion has occurred within the previous 6 months CIII.

Although the initial burst of viremia among infected adults usually resolves in 2 months, treatment during the month period after infection is based on the probability that virus replication in lymphoid tissue is still not maximally contained by the immune system during this time Decisions regarding therapy for patients who test antibody-positive and who believe the infection is recent, but for whom the time of infection cannot be documented, should be made by using the algorithm discussed in Considerations for Patients with Established HIV Infection CIII.

Except for postexposure prophylaxis with antiretroviral agents , no patient should be treated for HIV infection until the infection has been documented. All patients being examined without a formal medical record of a positive HIV test e. Data are insufficient to draw firm conclusions regarding specific drug recommendations; potential combinations of agents available are similar to those used in established infection Table These aggressive regimens can be associated with disadvantages, including drug toxicity, pill burden, cost, and the possibility of drug resistance that could limit future options.

The latter is probable if virus replication is not adequately suppressed or if the patient has been infected with a viral strain that is already resistant to one or more agents. The patient should be counseled regarding potential limitations, and decisions should be made only after weighing the risks and sequelae of therapy against the theoretical treatment benefits.

Because 1 the goal of therapy is suppression of viral replication to below the level of detection; 2 the benefits of therapy are based on theoretical considerations; and 3 long-term clinical outcome benefit has not been documented, any regimen that is not expected to maximally suppress viral replication is not appropriate for treating the acutely HIV-infected person EIII.

Additional clinical studies are needed to delineate the role of antiretroviral therapy during the primary infection period. However, certain experienced clinicians believe that testing for plasma HIV RNA levels at 4 weeks is not helpful in evaluating the therapy's effect regarding acute infection, because viral loads might be decreasing from peak viremia levels, even in the absence of therapy.

Duration of Therapy for Primary HIV Infection After therapy is initiated, experienced clinicians recommend continuing treatment with antiretroviral agents indefinitely because viremia has been documented to reappear or increase after therapy discontinuation CII. Optimal duration and therapy composition are unknown, but ongoing clinical trials should provide relevant data regarding these concerns.

Difficulties inherent in determining the optimal duration and therapy composition initiated for acute infection should be considered when first counseling the patient regarding therapy. Considerations for Antiretroviral Therapy Among HIV-Infected Adolescents HIV-infected adolescents who were infected through sex or injection-drug use during adolescence follow a clinical course that is more similar to HIV disease among adults than children. In contrast, adolescents who were infected perinatally or through blood products as young children have a unique clinical course that differs from other adolescents and long-term surviving adults.

The majority of HIV-infected adolescents were infected through sex during the adolescent period and are in an early stage of infection. Puberty is a time of somatic growth and hormone-mediated changes, with females acquiring additional body fat and males additional muscle mass.

Theoretically, these physiologic changes can affect drug pharmacology, including drugs with a narrow therapeutic index that are used in combination with protein-bound medicines or hepatic enzyme inducers or inhibitors. However, no clinically substantial impact of puberty has been reported with NRTI use. Thus, medication dosages used to treat HIV and OIs among adolescents should be based on Tanner staging of puberty and not specific age. Adolescents in early puberty Tanner stages I and II should be administered dosages on the basis of pediatric guidelines, whereas those in late puberty Tanner stage V should be administered dosages on the basis of adult guidelines.

Youth who are in the midst of their growth spurt Tanner stage III females and Tanner stage IV males should be monitored closely for medication efficacy and toxicity when choosing adult or pediatric dosing guidelines. Considerations for Antiretroviral Therapy Among HIV-Infected Pregnant Women Antiretroviral treatment recommendations for HIV-infected pregnant women are based on the belief that therapies of known benefit to women should not be withheld during pregnancy, unless the risk for adverse effects outweighs expected benefits for the woman.

Combination antiretroviral therapy is the recommended standard treatment for HIV-infected nonpregnant women. Pregnancy should not preclude the use of optimal therapeutic regimens. However, recommendations regarding choices of antiretroviral drugs for treatment of infected women are subject to unique considerations including 1 potential changes in dosing requirement resulting from physiologic changes associated with pregnancy, 2 potential effects of antiretroviral drugs on a pregnant woman, 3 effect on the risk for perinatal HIV transmission, and 4 the potential short- and long-term effects of the antiretroviral drug on the fetus and newborn, all of which might not be known for certain antiretroviral drugs The decision to use any antiretroviral drug during pregnancy should be made by the woman after discussion with her clinician regarding the benefits versus risks to her and her fetus.

Long-term follow-up is recommended for all infants born to women who have received antiretroviral drugs during pregnancy. Women who are in the first trimester of pregnancy and who are not receiving antiretroviral therapy might wish to consider delaying therapy initiation until after weeks gestation. This period of organogenesis is when the embryo is most susceptible to potential teratogenic drug effects, and the risks regarding antiretroviral therapy to the fetus during that period are unknown.

However, this decision should be discussed between the clinician and patient and should include an assessment of the woman's health status and the benefits versus risks of delaying therapy initiation for these weeks. If clinical, virologic, or immunologic parameters are such that therapy would be recommended for nonpregnant women, the majority of Panel members recommend initiating therapy regardless of gestational age. Nausea and vomiting during early pregnancy, affecting the woman's ability to take and absorb oral medications, can be a factor in the decision regarding treatment during the first trimester.

Standard combination antiretroviral therapy is recommended as initial therapy for HIV-infected pregnant women whose clinical, immunologic, or virologic status would indicate treatment if not pregnant. The time-limited use of zidovudine alone during pregnancy for chemoprophylaxis of perinatal transmission is controversial. However, a woman might wish to restrict exposure of her fetus to antiretroviral drugs during pregnancy but still wish to reduce the risk for transmitting HIV to her infant.

Use of zidovudine chemoprophylaxis alone during pregnancy might be an appropriate option for these women. When combination therapy is administrated principally to reduce perinatal transmission and would have been considered optional for treatment if the woman were not pregnant, consideration can be given to discontinuing therapy postnatally, with the decision to reinstitute treatment on the basis of standard criteria for nonpregnant women.

If drugs are discontinued postnatally, all drugs should be stopped simultaneously. Discussion regarding the decision to continue or stop combination therapy postpartum should occur before initiation of therapy during pregnancy. Women already receiving antiretroviral therapy might recognize their pregnancy early enough in gestation that concern for potential teratogenicity can lead them to consider temporarily stopping antiretroviral therapy until after the first trimester. Insufficient data exist to support or refute teratogenic risk regarding antiretroviral drug use among humans when administered during the first weeks of gestation.

However, treatment with efavirenz should be avoided during the first trimester because substantial teratogenic effects among rhesus macaques occurred at drug exposures similar to those representing human exposure. Hydroxyurea is a potent teratogen among animal species and should be avoided also during the first trimester. Temporary discontinuation of antiretroviral therapy could result in a rebound in viral levels that theoretically could be associated with increased risk for early in utero HIV transmission or could potentiate disease progression in the woman Although the effects of all antiretroviral drugs on the developing fetus during the first trimester are uncertain, experienced clinicians recommend continuation of a maximally suppressive regimen, even during the first trimester.

If antiretroviral therapy is discontinued during the first trimester for any reason, all agents should be stopped simultaneously to avoid drug resistance. After the drugs are reinstituted, they should be introduced simultaneously for the same reason. Limited data are available on the pharmacokinetics and safety of antiretroviral agents during pregnancy for drugs other than zidovudine.

FDA's pregnancy classification for all currently approved antiretroviral agents and selected other information regarding the use of antiretroviral drugs is available in this report Table The predictive value of in vitro and animal screening tests for adverse effects among humans is unknown. For example, acyclovir is positive on certain in vitro assays for chromosomal breakage and carcinogenicity and is associated with fetal abnormalities among rats; however, data regarding human experience from the Acyclovir in Pregnancy Registry indicate no increased risk for birth defects among human infants with in utero exposure When combination antiretroviral therapy is administered during pregnancy, zidovudine should be included as a component of antenatal therapy whenever possible.

Circumstances might arise where this option is not feasible e. Additionally, women receiving an antiretroviral regimen that does not contain zidovudine but who have HIV-1 RNA levels that are consistently low or undetectable have a low risk for perinatal transmission, and addition of zidovudine to the current regimen could compromise regimen adherence.

Regardless of the antepartum antiretroviral regimen, intravenous intrapartum zidovudine and the standard 6-week course of zidovudine for the infant is recommended. If the woman has not received zidovudine as a component of her antenatal therapeutic antiretroviral regimen, intravenous zidovudine should still be administered to the pregnant woman during the intrapartum period, when feasible.

Additionally, for women receiving combination antiretroviral treatment, the maternal antenatal antiretroviral treatment regimen should be continued on schedule as much as possible during labor to provide maximal virologic effect and to minimize the chance of drug resistance. Zidovudine and stavudine should not be administered together because of potential pharmacologic antagonism; therefore, options for women receiving oral stavudine as part of their antenatal therapy include continuing oral stavudine during labor without intravenous zidovudine or withholding oral stavudine during intravenous administration during labor.

Toxicity related to mitochondrial dysfunction has been reported among HIV-infected patients receiving long-term treatment with nucleoside analogues and can be of concern for pregnant women. Symptomatic lactic acidosis and hepatic steatosis can have a female preponderance Additionally, these syndromes have similarities to the rare but life-threatening syndromes of acute fatty liver of pregnancy and hemolysis, elevated liver enzymes and low platelets HELLP syndrome that occur during the third trimester of pregnancy.

Certain data indicate that a disorder of mitochondrial fatty acid oxidation in the mother or her fetus during late pregnancy can affect the etiology of acute fatty liver of pregnancy and HELLP syndrome , and possibly contribute to susceptibility to antiretroviral-associated mitochondrial toxicity. Bristol-Myers Squibb has reported three maternal deaths caused by lactic acidosis, two with and one without accompanying pancreatitis, among women who were either pregnant or postpartum and whose antepartum therapy during pregnancy included stavudine and didanosine in combination with other antiretroviral agents either a PI or nevirapine All cases were among women who were receiving treatment with these agents at the time of conception and continued for the duration of pregnancy; all of the women were seen late in gestation with symptomatic disease that progressed to death in the immediate postpartum period.

Two women were also associated with fetal demise. Nonfatal cases of lactic acidosis among pregnant women have also been reported. Pregnant women receiving nucleoside analogue drugs should have hepatic enzymes and electrolytes assessed more frequently during the last trimester of pregnancy, and any new symptoms should be evaluated thoroughly.

Additionally, because of reports of maternal mortality secondary to lactic acidosis with prolonged use of the combination of stavudine and didanosine by HIV-infected pregnant women, clinicians should prescribe this antiretroviral combination during pregnancy with caution and only when other nucleoside analogue drug combinations have failed or caused unacceptable toxicity or side effects A less-frequent dosing regimen would be expected to enhance maternal adherence to the zidovudine perinatal prophylaxis regimen and, therefore, is an acceptable alternative antenatal dosing regimen for zidovudine prophylaxis.

The lower efficacy of the short-course two-part zidovudine prophylaxis regimen studied in Thailand compared with the three-part zidovudine prophylaxis regimen used in PACTG and recommended for use in the United States, could result from 1 the shorter antenatal duration of zidovudine, 2 oral rather than intravenous administration during labor, 3 lack of treatment for the infant, or 4 a combination of these factors.

In the United States, identification of HIV-infected pregnant women before or as early as possible during the course of pregnancy and use of the full three-part PACTG zidovudine regimen is recommended for prevention of perinatal HIV transmission. Monitoring and use of HIV-1 RNA for therapeutic decision-making during pregnancy should be performed as recommended for nonpregnant women. Data from untreated and zidovudine-treated infected pregnant women indicate that HIV-1 RNA levels correlate with risk for transmission 20,, However, although risk for perinatal transmission among women with HIV-1 RNA below the level of assay quantitation is low, transmission from mother to infant has been reported among women with all levels of maternal HIV-1 RNA.

Additionally, antiretroviral prophylaxis is effective in reducing transmission even among women with low HIV RNA levels 20, Although the mechanism by which antiretroviral prophylaxis reduces transmission is probably multifactorial, reduction in maternal antenatal viral load is a key component of prophylaxis. However, pre- and postexposure prophylaxis of the infant is provided by passage of antiretroviral drugs across the placenta, resulting in inhibitory drug levels in the fetus during and immediately after the birth process The extent of transplacental passage varies among antiretroviral drugs Table Additionally, although a correlation exists between plasma and genital tract viral load, discordance has also been reported Further, differential evolution of viral sequence diversity occurs between the peripheral blood and genital tract , Studies are needed to define the relationship between viral load suppression by antiretroviral therapy in plasma and levels of HIV in the genital tract and the relationship between these compartment-specific effects and the risk for perinatal HIV transmission.

The full zidovudine chemoprophylaxis regimen, including intravenous zidovudine during delivery and zidovudine administration to the infant for the first 6 weeks of life, in combination with other antiretrovirals or alone, should be discussed with and offered to all infected pregnant women regardless of their HIV-1 RNA level. Clinicians who are treating HIV-infected pregnant women are strongly encouraged to report cases of prenatal exposure to antiretroviral drugs either administered alone or in combinations to the Antiretroviral Pregnancy Registry.

The registry collects observational, nonexperimental data regarding antiretroviral exposure during pregnancy for the purpose of assessing potential teratogenicity. Registry data will be used to supplement animal toxicology studies and assist clinicians in weighing the potential risks and benefits of treatment for each patient.

The registry is a collaborative project with an advisory committee of obstetric and pediatric practitioners, staff from CDC and NIH, and staff from pharmaceutical manufacturers. The registry allows the anonymity of patients, and birth outcome follow-up is obtained by registry staff from the reporting clinician. Referrals should be directed to. Ongoing prevention counseling is an essential component of management for HIV-infected persons Each patient encounter provides an opportunity to reinforce HIV prevention messages.

Therefore, each encounter should include assessment and documentation of 1 the patient's knowledge and understanding of HIV transmission and 2 the patient's HIV transmission behaviors since the last encounter with a member of the health-care team. This should be followed by a discussion of strategies to prevent transmission that might be useful to the patient. The physician, nurse, or other health-care team member should routinely provide this counseling.

Partner notification is a key component of HIV detection and prevention and should be pursued by the provider or by referral services. For example, sustained low plasma viremia that results from successful HIV therapy substantially reduces the likelihood of HIV transmission. In one study, for each log reduction in plasma viral load, the likelihood of transmission between discordant couples was reduced 2.

Similarly, mother-to-child HIV transmission was observed to decline in a linear fashion with each log reduction in maternal delivery viral load ,,, Although this relationship is usually linear, key exceptions should be noted. For example, mother-to-child transmission has been reported even among women with very low or undetectable viral loads ,, Similarly, the relationship between viral load in the plasma and the levels in the genital fluid of women and the seminal fluid of men is complex.

Studies have demonstrated a rough correlation between plasma HIV levels and genital HIV levels, but key exceptions have been observed Viral evolution can occur in the genital compartment that is distinct from the viral evolution in the plasma, and transmissions have been documented in the presence of an undetectable plasma viral load 20,, Certain biologic factors other than plasma viral load have also been demonstrated to influence sexual transmission of HIV, including ulcerative and nonulcerative sexually transmitted infections , vaginitis including bacterial vaginosis and Candida albicans vaginal infections ; genital irritation associated with frequent use of nonoxynol-9 N-9 --containing products ; menstruation; lack of circumcision in men ; oral contraceptive use ; estrogen deficiency ; progesterone excess ; and deficiencies of vitamin A and selenium Unfortunately, evidence exists that awareness of the potential benefits of HAART is leading certain persons to relapse into high-risk activities.

For example, reports from urban communities of men who have sex with men MSM in the United States indicate rising HIV seroprevalence rates, as well as rising rates of unsafe sexual practices, corroborated by the rising rates of other sexually transmitted infections. Women might have unprotected sex because they wish to become pregnant.

For women of childbearing potential, desire for pregnancy should be assessed at each encounter; women wishing to pursue pregnancy should be referred for preconception counseling to reduce risks for perinatal transmission and transmission to uninfected sexual partners.

Among women of childbearing age who wish to avoid pregnancy, condoms should be encouraged in addition to other forms of contraception for preventing transmission of HIV and other sexually transmitted infections dual method use or used as a single method for pregnancy prevention as well dual protection. In a randomized placebo-controlled clinical trial of N-9 conducted among commercial sex workers with high rates of sexual activity, N-9 did not protect against HIV infection, resulted in increased vaginal lesions, and possibly caused increased transmission Although these adverse effects might not occur with less frequent use, given current evidence, spermicides containing N-9 should not be recommended as an effective means of HIV prevention.

Optimal adherence with antiretroviral regimens has been directly associated with a lower risk for morbidity and mortality and indirectly with a reduction in risk for HIV transmission because of its association with lower viral loads Suboptimal adherence to HIV medication recently has been demonstrated to be a predictor of suboptimal adherence to HIV prevention strategies More intensive adherence and prevention counseling might be appropriate for persons who demonstrate repeated deficiencies in either area.

Despite the strong association between a reduced risk for HIV transmission and sustained low viral load, the message of HIV prevention for patients should remain simple: After becoming infected, a person can transmit the virus at any time, and no substitute exists for latex or polyurethane male or female condoms, other safer sexual behaviors e. Prevention counseling for patients known to have HIV infection remains a critical component of HIV primary care, including easy access to condoms and other means of prevention.

Clinicians might wish to directly address with their patients the risks associated with using viral load outcomes as a factor in considering high-risk behavior. HIV-infected persons who use injection drugs should be advised to enroll in drug rehabilitation programs. If this advice is not followed or if these services are unavailable, the patient should receive counseling regarding risks associated with sharing needles and paraphernalia.

Finally, the most successful and effective prevention messages are those tailored to each patient. These messages are culturally appropriate, practical, and relevant to the person's knowledge, beliefs, and behaviors Conclusion The Panel has attempted to use the advances in knowledge regarding the pathogenesis of HIV in the infected person to translate scientific principles and data obtained from clinical experience into guidelines that can be used by clinicians and patients to make therapeutic decisions.

These guidelines are offered for ongoing discussion between the patient and clinician after having defined specific therapeutic goals with an acknowledgment of uncertainties. Patients should be entered into a continuum of medical care and services, including social, psychosocial, and nutritional services, with the availability of professional referral and consultation.

The Panel urges industry and the public and private sectors to conduct further studies to allow refinement of these guidelines. Specifically, studies are needed to optimize recommendations for primary therapy; to define secondary therapy; and to delineate the reasons for treatment failure. The Panel remains committed to revising these guidelines as new data become available. References CDC. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma.

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Contamination of environmental surfaces by genital human papillomaviruses. Nosocomial spread of a Staphylococcus capitis strain with heteroresistance to vancomycin in a neonatal intensive care unit. Comparison of predicted scaffold-compatible sequence variation in the triple-hairpin structure of human imunodeficiency virus type 1 gp41 with patient data. Rodney Arcenas, Raymond H Widen. BMC Microbiol, Jul 26; 2. Nasopharyngeal carriage of potential bacterial pathogens related to day care attendance, with special reference to the molecular epidemiology of Haemophilus influenzae.

Molecular epidemiology of caliciviruses causing outbreaks and sporadic cases of acute gastroenteritis in Spain. Causes of morbilliform rash in a highly immunised English population. Environmental factors influencing human viral pathogens and their potential indicator organisms in the blue mussel, Mytilus edulis: the first Scandinavian report.

Aquatic insects as a vector for Mycobacterium ulcerans. Simple and reliable method for detection and genotyping of hepatitis C virus RNA in dried blood spots stored at room temperature. Rapid and sensitive routine detection of all members of the genus enterovirus in different clinical specimens by real-time PCR. The evolution and phylogeography of the African elephant inferred from mitochondrial DNA sequence and nuclear microsatellite markers. Proc Biol Sci, Oct 25; Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency.

Real-time PCR method for detection of Encephalitozoon intestinalis from stool specimens. J Clin Microbiol, Nov 01; 40 Human cytomegalovirus DNA in plasma and serum specimens of renal transplant recipients is highly fragmented. Molecular characterization of hepatitis a virus isolates from a transcontinental shellfish-borne outbreak. Practical and sensitive screening strategy for detection of influenza virus. Distribution of human virus contamination in shellfish from different growing areas in Greece, Spain, Sweden, and the United Kingdom.

Genome variability and capsid structural constraints of hepatitis a virus. J Virol, Dec 13; 77 1. J Clin Microbiol, Jan 09; 41 1. Rapid enterovirus RNA detection in clinical specimens by using nucleic acid sequence-based amplification.

Molecular characterization of bovine enteric caliciviruses: a distinct third genogroup of noroviruses Norwalk-like viruses unlikely to be of risk to humans. Molecular epidemiological analysis of Cryptosporidium isolates from humans and animals by using a heteroduplex mobility assay and nucleic acid sequencing based on a small double-stranded RNA element. J Clin Microbiol, Mar 08; 41 3. Novel sample preparation method for safe and rapid detection of Bacillus anthracis spores in environmental powders and nasal swabs.

Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. The history of effective population size and genetic diversity in the Yellowstone grizzly Ursus arctos : implications for conservation. International collaborative study to compare reverse transcriptase PCR assays for detection and genotyping of noroviruses.

Use of single-enzyme amplified fragment length polymorphism for typing Pasteurella multocida subsp. J Clin Microbiol, Apr 12; 41 4. Hepatitis E virus epidemiology in industrialized countries. Improved detection of rhinoviruses by nucleic acid sequence-based amplification after nucleotide sequence determination of the 5' noncoding regions of additional rhinovirus strains.

Microbial population diversity in the urethras of healthy males and males suffering from nonchlamydial, nongonococcal urethritis. Treatment with an anti-CD14 monoclonal antibody delays and inhibits lipopolysaccharide-induced gene expression in humans in vivo. Characterization of a novel simian immunodeficiency virus SIVmonNG1 genome sequence from a mona monkey Cercopithecus mona.

J Virol, May 28; 77 Staphylococcal superantigens and T cell expansions in Wegener's granulomatosis. Foci of endemic simian immunodeficiency virus infection in wild-living eastern chimpanzees Pan troglodytes schweinfurthii. Group A rotavirus in sewage samples from Barcelona and Cairo: emergence of unusual genotypes.

Genotyping by amplified fragment length polymorphism analysis reveals persistence and recurrence of infection with Streptococcus anginosus group organisms. Genome-wide DNA microarray analysis of Francisella tularensis strains demonstrates extensive genetic conservation within the species but identifies regions that are unique to the highly virulent F. Assessment by meta-analysis of PCR for diagnosis of smear-negative pulmonary tuberculosis. Structural analyses of purified human immunodeficiency virus type 1 intracellular reverse transcription complexes.

Milan V Nermut, Ariberto Fassati. J Virol, Jul 15; 77 Evidence for genetic linkage between the gene segments encoding NSP4 and VP6 proteins in common and reassortant human rotavirus strains. Analysis of the excreted JC virus strains and their potential oral transmission. Phylogenetic and evolutionary relationships among torovirus field variants: evidence for multiple intertypic recombination events.

Usefulness of quantitative nucleic Acid sequence-based amplification for diagnosis of malaria in an academic hospital setting. Recent emergence of an epidemic clindamycin-resistant clone of Clostridium difficile among Polish patients with C. Unexpected detection of animal VP7 genes among common rotavirus strains isolated from children in Mexico.

Recombination in circulating enteroviruses. Detection of a point mutation associated with high-level isoniazid resistance in Mycobacterium tuberculosis by using real-time PCR technology with 3'-minor groove binder-DNA probes. J Clin Microbiol, Oct 09; 41 Detection of genetically modified organisms GMOs in food and feedstuff. An outbreak of diarrhoea in one-week-old piglets caused by group A rotavirus genotypes P[7],G3 and P[7],G5.

Molecular diagnosis of Mycoplasma pneumoniae respiratory tract infections. J Clin Microbiol, Nov 08; 41 Evaluation and field validation of PCR tests for detection of Actinobacillus pleuropneumoniae in subclinically infected pigs. Identification of sequential viral escape mutants associated with altered T-cell responses in a human immunodeficiency virus type 1-infected individual.

Bronchiolitis caused by respiratory syncytial virus in an area of portugal: epidemiology, clinical features, and risk factors. Molecular epidemiology of SAT3-type foot-and-mouth disease. Expression profiling via novel multiplex assay allows rapid assessment of gene regulation in defined signalling pathways. Evolution of human calicivirus RNA in vivo: accumulation of mutations in the protruding P2 domain of the capsid leads to structural changes and possibly a new phenotype.

Human herpesvirus 8 load in matched serum and plasma samples of patients with AIDS-associated Kaposi's sarcoma. J Clin Microbiol, Dec 10; 41 Molecular detection and identification of agents of eumycetoma: detailed report of two cases. Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human host. J Virol, Dec 13; 78 1. J Mol Diagn, Jan 23; 6 1. Prospective study of use of PCR amplification and sequencing of 16S ribosomal DNA from cerebrospinal fluid for diagnosis of bacterial meningitis in a clinical setting.

J Clin Microbiol, Feb 10; 42 2. Comparison of Acinetobacter baumannii isolates from United Kingdom hospitals with predominant Northern European genotypes by amplified-fragment length polymorphism analysis. Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding. Phenotypic and genotypic comparisons of CCR5- and CXCR4-tropic human immunodeficiency virus type 1 biological clones isolated from subtype C-infected individuals.

Inhibition of different Lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus. Detection of bovine and porcine adenoviruses for tracing the source of fecal contamination.

Quantitation of group A rotavirus by real-time reverse-transcription-polymerase chain reaction: correlation with clinical severity in children in South India. Human papillomavirus oncogenic expression in the dysplastic portio; an investigation of biopsies from cervical cones. Development of a nucleic acid sequence-based amplification assay that uses gag-based molecular beacons to distinguish between human immunodeficiency virus type 1 subtype C and C' infections in Ethiopia.

First international quality assurance study on the rapid detection of viral agents of bioterrorism. Detection of enteric viruses in shellfish from the Norwegian coast. Appl Environ Microbiol, May 07; 70 5. Characterization of G10P[11] rotaviruses causing acute gastroenteritis in neonates and infants in Vellore, India.

Real-time PCR assay using fine-needle aspirates and tissue biopsy specimens for rapid diagnosis of mycobacterial lymphadenitis in children. Fast detection of Noroviruses using a real-time PCR assay and automated sample preparation. Comparison and analysis of the complete nucleotide sequence of foot-and-mouth disease viruses from animals in Korea and other PanAsia strains. New simian immunodeficiency virus infecting De Brazza's monkeys Cercopithecus neglectus : evidence for a cercopithecus monkey virus clade.

Detection of human immunodeficiency virus type 1 antiretroviral resistance mutations by high-density DNA probe arrays. Highly sensitive assay for detection of enterovirus in clinical specimens by reverse transcription-PCR with an armored RNA internal control. World J Gastroenterol, Jul 31; 10 Inactivation of caliciviruses. Use of fluorescent amplified fragment length polymorphism for molecular epidemiology of leptospirosis in India.

Helicobacter pylori cagA, iceA and vacA genotypes in patients with gastric cancer in Taiwan. Evaluation of methods for storage of marine macroorganisms with optimal recovery of bacteria. J Clin Microbiol, Oct 09; 42 Human factor in Staphylococcus aureus nasal carriage. Infect Immun, Oct 27; 72 Emergence of a drug-dependent human immunodeficiency virus type 1 variant during therapy with the T20 fusion inhibitor. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

Polymorphisms in equine immune response genes and their associations with infections. Multiplex nucleic acid sequence-based amplification for simultaneous detection of several enteric viruses in model ready-to-eat foods.

Appl Environ Microbiol, Nov 06; 70 An unexpected experimental pitfall in the molecular diagnosis of bacterial endophthalmitis. J Clin Microbiol, Nov 06; 42 Genomic imbalances in 70 snap-frozen cervical squamous intraepithelial lesions: associations with lesion grade, state of the HPV16 E2 gene and clinical outcome.

Efficient method for mycobacterial DNA extraction in blood cultures aids rapid PCR identification of Mycobacterium tuberculosis and Mycobacterium avium. Phylogeography and genetic ancestry of tigers Panthera tigris. Traditional water mite fixatives and their compatibility with later DNA studies. Exp Appl Acarol, Dec 16; 34 The involvement of survival signaling pathways in rubella-virus induced apoptosis.

Virol J, Jan 06; 2. Mucosal polymerase chain reaction for diagnosing Helicobacter pylori infection in patients with bleeding peptic ulcers. Detection and identification of Enterocytozoon bieneusi and Encephalitozoon species in stool and urine specimens by PCR and differential hybridization.

Molecular characterizations of human and animal group a rotaviruses in the Netherlands. Mycobacterium haemophilum and lymphadenitis in children. Alpha interferon and ribavirin combination therapy of chronic hepatitis D. Increased multinucleoside drug resistance and decreased replicative capacity of a human immunodeficiency virus type 1 variant with an 8-amino-Acid insert in the reverse transcriptase. Presence of noroviruses and other enteric viruses in sewage and surface waters in The Netherlands.

Appl Environ Microbiol, Mar 05; 71 3. Loss of the mecA gene during storage of methicillin-resistant Staphylococcus aureus strains. Noroviruses in archival samples. Emerg Infect Dis, Mar 11; 11 3. Effect of mupirocin treatment on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in healthy adults.

Rapid and sensitive detection of noroviruses by using TaqMan-based one-step reverse transcription-PCR assays and application to naturally contaminated shellfish samples. Molecular assays for targeting human and bovine enteric viruses in coastal waters and their application for library-independent source tracking. Appl Environ Microbiol, Apr 07; 71 4. J Clin Microbiol, Apr 09; 43 4. Few mutations in the 5' leader region mediate fitness recovery of debilitated human immunodeficiency type 1 viruses.

J Virol, Apr 14; 79 9. Mitochondrial haplotype diversity in the tortoise species Testudo graeca from North Africa and the Middle East. Low levels of human immunodeficiency virus type 1 DNA in high-risk seronegative men. J Virol, Apr 29; 79 Enhanced enzyme immunoassay with negative-gray-zone testing compared to a single nucleic Acid amplification technique for community-based chlamydial screening of men. Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro.

Enteric viruses of humans and animals in aquatic environments: health risks, detection, and potential water quality assessment tools. Microbiol Mol Biol Rev, Jun 10; 69 2. Improved method of detection and molecular typing of Borrelia burgdorferi sensu lato in clinical samples by polymerase chain reaction without DNA purification.

Development, technical performance, and clinical evaluation of a NucliSens basic kit application for detection of enterovirus RNA in cerebrospinal fluid. Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis. Quantitative PCR assay using sputum samples for rapid diagnosis of pneumococcal pneumonia in adult emergency department patients. Detection of acid-fast bacilli in postlysis debris of clinical specimens improves the reliability of PCR.

Isolation and detection of enterovirus RNA from large-volume water samples by using the NucliSens miniMAG system and real-time nucleic acid sequence-based amplification. Burkholderia fungorum septicemia. Sensitivity of PCR targeting the IS insertion sequence of Mycobacterium ulcerans in an Assay using punch biopsy specimens for diagnosis of Buruli ulcer.

Broad cross-clade T-cell responses to gag in individuals infected with human immunodeficiency virus type 1 non-B clades A to G : importance of HLA anchor residue conservation. Replication origin of mitochondrial DNA in insects. Genetics, Aug 25; 4. A novel chimeric gene, siren, with retroposed promoter sequence in the Drosophila bipectinata complex. Genetics, Sep 07; 4. Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas.

Intra- and inter-genotypic size variation in the central variable region of the 9RL open reading frame of diverse African swine fever viruses. Virus Genes, Sep 22; 31 3. Critical factors for assembling a high volume of DNA barcodes. Quantitative nucleic acid sequence-based assay as a new molecular tool for detection and quantification of Leishmania parasites in skin biopsy samples. Novel rotavirus VP7 typing assay using a one-step reverse transcriptase PCR protocol and product sequencing and utility of the assay for epidemiological studies and strain characterization, including serotype subgroup analysis.

High prevalence of human papillomavirus infections in urine samples from human immunodeficiency virus-infected men. Detection of rhinoviruses by tissue culture and two independent amplification techniques, nucleic acid sequence-based amplification and reverse transcription-PCR, in children with acute respiratory infections during a winter season.

A single-tube nucleic acid extraction, amplification, and detection method using aluminum oxide. Enrichment and analysis of RNA centered on ion pair reverse phase methodology. RNA, Feb 25; 12 4. Screening for polymorphisms in the PXR gene in a Dutch population. Molecular epidemiology of norovirus strains circulating in Ireland from to Epidemiol Infect, Mar 30; 5.

Development of conventional and real-time nucleic acid sequence-based amplification assays for detection of Chlamydophila pneumoniae in respiratory specimens. Molecular epidemiology of norovirus in outbreaks of gastroenteritis in southwest Germany from to Presence of E6 and E7 mRNA from human papillomavirus types 16, 18, 31, 33, and 45 in the majority of cervical carcinomas.

J Clin Microbiol, Apr 07; 44 4. Use of TaqMan real-time reverse transcription-PCR for rapid detection, quantification, and typing of norovirus. Cytokine mRNA expression in Mycobacterium ulcerans-infected human skin and correlation with local inflammatory response.

Evaluation of a novel highly sensitive, broad-spectrum PCR-reverse hybridization assay for detection and identification of beta-papillomavirus DNA. Inhibition of human coronavirus NL63 infection at early stages of the replication cycle. Prevalence of Chlamydophila psittaci in fecal droppings from feral pigeons in Amsterdam, The Netherlands.

Molecular epidemiology of group A rotavirus diarrhea among children in Buenos Aires, Argentina, from to and emergence of the infrequent genotype G Evaluation of a real-time nucleic acid sequence-based amplification assay using molecular beacons for detection of human immunodeficiency virus type 1.

J Clin Microbiol, Jun 08; 44 6. Pharmacogenetic screening for polymorphisms in drug-metabolizing enzymes and drug transporters in a Dutch population. Expression of putative virulence factors of Escherichia coli OH7 differs in bovine and human infections. Novel deoxycytidine kinase gene polymorphisms: a population screening study in Caucasian healthy volunteers. Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1.

Hepatitis A virus in urban sewage from two Mediterranean countries. Comparative study of the epidemiology of rotavirus in children from a community-based birth cohort and a hospital in South India. Molecular diagnosis and epidemiology of African swine fever outbreaks in Tanzania. Vet Res Commun, Jul 14; 30 6. Real-time detection of noroviruses in surface water by use of a broadly reactive nucleic acid sequence-based amplification assay.

Appl Environ Microbiol, Aug 04; 72 8. Recharacterization of ancient DNA miscoding lesions: insights in the era of sequencing-by-synthesis. Heterogeneity and temporal dynamics of evolution of G1 human rotaviruses in a settled population. Patterns of nucleotide misincorporations during enzymatic amplification and direct large-scale sequencing of ancient DNA.

Fatal outcome of human influenza A H5N1 is associated with high viral load and hypercytokinemia. Silica-guanidinium thiocyanate-based nucleic acid isolation protocol does not improve sensitivity of two commercial tests for detection of Mycobacterium tuberculosis in respiratory samples. Detection and identification of human Plasmodium species with real-time quantitative nucleic acid sequence-based amplification.

Malar J, Oct 05; 5. Quantification and stability of human adenoviruses and polyomavirus JCPyV in wastewater matrices. Direct detection of Mycobacterium tuberculosis complex DNA and rifampin resistance in clinical specimens from tuberculosis patients by line probe assay. Identification of human and animal adenoviruses and polyomaviruses for determination of sources of fecal contamination in the environment.

Community-based seroepidemiological survey of hepatitis E virus infection in Catalonia, Spain. Removal of astrovirus from water and sewage treatment plants, evaluated by a competitive reverse transcription-PCR. Specific detection of Campylobacter jejuni from faeces using single nucleotide polymorphisms. First report of Cryptosporidium parvum 'ferret' genotype in American mink Mustela vison Shreber Parasitol Res, Nov 18; 4. Magnetic silica extraction for low-viremia human immunodeficiency virus type 1 genotyping.

J Clin Microbiol, Nov 24; 45 2. Geographic information systems and genotyping in identification of rotavirus G12 infections in residents of an urban slum with subsequent detection in hospitalized children: emergence of G12 genotype in South India. Evaluation of NucliSens easyMAG for automated nucleic acid extraction from various clinical specimens.

Human coronavirus E encodes a single ORF4 protein between the spike and the envelope genes. An unusual pattern of spontaneous mutations recovered in the halophilic archaeon Haloferax volcanii. Genetics, Dec 30; 1. Detection of Vibrio cholerae by real-time nucleic acid sequence-based amplification. Human papillomavirus quantification in urine and cervical samples by using the Mx and LightCycler general real-time PCR systems. Use of dried spots of whole blood, plasma, and mother's milk collected on filter paper for measurement of human immunodeficiency virus type 1 burden.

Seven years of regional malaria control collaboration--Mozambique, South Africa, and Swaziland. Neonatal infection with G10P[11] rotavirus did not confer protection against subsequent rotavirus infection in a community cohort in Vellore, South India.

Retrovirology, Feb 01; 4. Frequency of group A rotavirus in diarrhoeic calves in Brazilian cattle herds, Interleukin-6 expression and gene polymorphism are associated with severity of periodontal disease in a sample of Brazilian individuals. Rhipicephalus appendiculatus and R.

Structured surveillance of infantile gastroenteritis in East Anglia, UK: incidence of infection with common viral gastroenteric pathogens. Genotyping of Chlamydophila psittaci in human samples. Development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene.

Further evidence for geographic differentiation in R. Etiological role of viruses in outbreaks of acute gastroenteritis in The Netherlands from through Respiratory infections for which general practitioners consider prescribing an antibiotic: a prospective study.

Human caliciviruses in symptomatic and asymptomatic infections in children in Vellore, South India. Capture of genomic DNA on glass microscope slides. Anal Biochem, Apr 20; 2. Detection by PCR of eight groups of enteric pathogens in 4, faecal samples: re-examination of the English case-control Infectious Intestinal Disease Study Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy.

Design and validation of an H5 TaqMan real-time one-step reverse transcription-PCR and confirmatory assays for diagnosis and verification of influenza A virus H5 infections in humans. Susceptibility of recently transmitted subtype B human immunodeficiency virus type 1 variants to broadly neutralizing antibodies. Norovirus infection in children with acute gastroenteritis, Madagascar, Characterization of VP6 genes from rotavirus strains collected in the United States from Virus Genes, Jun 15; 35 3.

Telomerase activity as a tumor marker in Indian women with cervical intraepithelial neoplasia and cervical cancer. Mol Diagn Ther, Jun 16; 11 3. The isolation of nucleic acids from fixed, paraffin-embedded tissues-which methods are useful when?

Comparison of the sensitivities of noroviruses and feline calicivirus to chemical disinfection under field-like conditions. Spread of a methicillin-resistant Staphylococcus aureus ST80 strain in the community of the northern Netherlands. HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. Alterations in receptor binding properties of recent human influenza H3N2 viruses are associated with reduced natural killer cell lysis of infected cells.

Proboscidean mitogenomics: chronology and mode of elephant evolution using mastodon as outgroup. Identification of emesis-causing Bacillus cereus strains by polymerase chain reaction: preliminary results. Multilocus analysis of Cryptosporidium hominis and Cryptosporidium parvum isolates from sporadic and outbreak-related human cases and C. Molecular characterization of G11P[25] and G3P[3] human rotavirus strains associated with asymptomatic infection in South India.

Helicobacter genotyping and detection in peroperative lavage fluid in patients with perforated peptic ulcer. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. Correlation between the presence of symptoms and the Giardia duodenalis genotype.

Comparison of polymerase chain reaction methods for the detection of Theileria equi infection using whole blood compared with pre-extracted DNA samples as PCR templates. Detection of a questing Hyalomma marginatum marginatum adult female Acari, Ixodidae in southern Germany.

Comparison between quantitative nucleic acid sequence-based amplification, real-time reverse transcriptase PCR, and real-time PCR for quantification of Leishmania parasites. Orthopoxvirus detection in environmental specimens during suspected bioterror attacks: inhibitory influences of common household products.

Mannose-binding lectin deficiency facilitates abdominal Candida infections in patients with secondary peritonitis. Adsorption and elution characteristics of nucleic acids on silica surfaces and their use in designing a miniaturized purification unit. Development of real-time multiplex nucleic acid sequence-based amplification for detection of Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp.

Analysis of echovirus 30 isolates from Russia and new independent states revealing frequent recombination and reemergence of ancient lineages. J Clin Microbiol, Dec 14; 46 2. RNA structure modulates splicing efficiency at the human immunodeficiency virus type 1 major splice donor. J Virol, Dec 28; 82 6. Cost-effective method of DNA extraction from taeniid eggs. Parasitol Res, Jan 04; 4.

Comparison of the cecal microbiota of domestic and wild turkeys. Microb Ecol, Jan 10; 56 2. Genetic heterogeneity of porcine enteric caliciviruses identified from diarrhoeic piglets. Analysis of amino acid variation in the P2 domain of the GII-4 norovirus VP1 protein reveals putative variant-specific epitopes.

J Clin Microbiol, Feb 15; 46 4. Risk factors for late postnatal transmission of human immunodeficiency virus type 1 in sub-Saharan Africa. Monitoring of waterborne pathogens in surface waters in amsterdam, the Netherlands, and the potential health risk associated with exposure to cryptosporidium and giardia in these waters. Multi locus sequence typing of Chlamydiales: clonal groupings within the obligate intracellular bacteria Chlamydia trachomatis. Surprising migration and population size dynamics in ancient Iberian brown bears Ursus arctos.

Detection of meticillin-resistant Staphylococcus aureus and Panton-Valentine leukocidin directly from clinical samples and the development of a multiplex assay using real-time polymerase chain reaction. First cultivation and characterization of Mycobacterium ulcerans from the environment. Relation between genetic markers of drug resistance and susceptibility profile of clinical Neisseria gonorrhoeae strains.

Detection and quantification of group C rotaviruses in communal sewage. Ninety-nine is not enough: molecular characterization of inhibitor-resistant human immunodeficiency virus type 1 protease mutants with insertions in the flap region. Identification of a porcine calicivirus related genetically to human sapoviruses. Human astrovirus gastroenteritis in children, Madagascar, Highly sensitive methods based on seminested real-time reverse transcription-PCR for quantitation of human immunodeficiency virus type 1 unspliced and multiply spliced RNA and proviral DNA.

Clinical utility of prostate carcinoma molecular diagnostic tests. Scott B Shappell. Rev Urol, May 13; 10 1. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection. J Virol, Jun 06; 82 Molecular evolution of human immunodeficiency virus type 1 upon transmission between human leukocyte antigen disparate donor-recipient pairs.

Effect of swab composition and use of swabs versus swab-containing skim milk-tryptone-glucose-glycerol STGG on culture- or PCR-based detection of Streptococcus pneumoniae in simulated and clinical respiratory specimens in STGG transport medium. J Clin Microbiol, Jun 20; 46 8. Diminished human immunodeficiency virus type 1 DNA yield from dried blood spots after storage in a humid incubator at 37 degrees C compared to degrees C.

Isolation of sabin-like polioviruses from wastewater in a country using inactivated polio vaccine. Puumala hantavirus excretion kinetics in bank voles Myodes glareolus. Carriage of Leptospira interrogans among domestic rats from an urban setting highly endemic for leptospirosis in Brazil. The rate and character of spontaneous mutation in Thermus thermophilus. Occurrence of free-living amoebae in communities of low and high endemicity for Buruli ulcer in southern Benin.

Long-term platinum retention after treatment with cisplatin and oxaliplatin. High prevalence of human Parechovirus HPeV genotypes in the Amsterdam region and identification of specific HPeV variants by direct genotyping of stool samples. Preferential use of the VH gene segment by the human immune response to code for antibodies against the V3 domain of HIV Detection of Cryptosporidium spp.

Parasitol Res, Nov 04; 3. A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya. Neutralization patterns and evolution of sequential HIV type 1 envelope sequences in HIV type 1 subtype B-infected drug-naive individuals.

In analyses with virus load as a continuous response, values lower than the detection limit were assigned a value of half the detection limit. Plasma and semen specimens were analyzed as paired samples if collected within 21 days. Because of the number of results below the detection limit, the nonparametric Spearman rank correlation was used to assess correlations between genital and PVL.

PVLs and SVLs were modeled as a log 10 response, and virus load data and CD4 cell counts obtained before initiation of antiretrovirals were modeled longitudinally with a linear mixed effects model fitted by maximum likelihood.

Linear mixed effect methods model the mean population response as linear in time but allow random effects, to account for repeated measurements fromindividuals when estimating population-fixed effects [ 35 ]. An additional 29 seroconverters were prospectively identified through other HIVNET studies: 20 were identified from prospective cohort studies in operation at VPS sites e. Median time from estimated seroconversion to IPC enrollment was 4 months.

Three persons with interim testing initially had indeterminate Western blot results and were seroconverting. Behavioral risk factors and clinical features of seroconversion were assessed 3 months before the last seronegative test result through the first seropositive test result; the median duration for this seroconversion period was 9. Compared with seroconverters from other risk groups, MSM reported having a higher median number of sex partners, particularly partners of unknown HIV serostatus table 1.

Only 9 seroconverters reported a single HIV-infected partner in the seroconversion period. Complete calendar-based risk data were available for 98 seroconverters figure 1 and were rank-ordered by high-risk injection drug use sharing needles or equipment , followed by sexual risk behaviors with HIV-positive partners or partners of unknown serostatus table 1.

Fourteen MSM reported unprotected receptive oral sex as their highest risk, 12 of whom also reported protected anal sex and may have not recognized or reported condom breakage or slippage; thus, oral sex may not have been their only route of exposure. Injection drug use was reported by all 4 male IDUs and 6 women with complete risk behavior data, only 6 of whom reported sharing injection equipment. Most female seroconverters reported sexual risks; 1 reported unprotected anal sex, and 6 reported unprotected vaginal sex with HIV-positive or unknown serostatus sex partners.

Unprotected risk behavior anal or vaginal sex or shared needles reported by seroconverters during seroconversion period. Each horizontal line represents behavior of 1 subject; length of line is duration of seroconversion period. Last HIV-seronegative test result is shown as vertical line. Seroconversion period is defined as 3 months before last negative test result to first HIV-positive test result. Most participants reported multiple high-risk behaviors with HIV-positive and unknown serostatus partners; figure 1 displays risk behaviors for each week in the seroconversion period for the 98 persons with complete calendar-based risk data, ordered from those reporting the most to those with the least frequent unprotected exposures.

Seven seroconverters were referred by the IPC clinician for STD evaluations because of reported STD symptoms or because they had clinical findings at IPC enrollment, but results of the evaluations were not consistently reported to study clinicians. Information on medical care during the seroconversion period was available for subjects. Eight Antiretroviral use was reported by 72 subjects at some point during study followup; median time to initiating antiretrovirals was 9. By survival analysis, time to initiation of antiretrovirals did not differ by year of seroconversion — MSM were more likely to be treated and initiated therapy sooner after seroconversion than women median, 8 vs.

Drug resistance genotyping was attempted on pretreatment plasma specimens taken from 80 subjects at their first postseroconversion visits. Specimens from these subjects were not available for repeat amplification attempts by more sensitive nested PCR methods.

Seven seroconverters 9. One person had the PR V82A mutation, a primary resistance mutation associated with early virologic failure of ritonavir and indinavir, but insufficient to cause detectable protease inhibitor cross-resistance without other key protease mutations [ 33 , 37 , 38 ]. An additional 11 We observed no significant differences in genotypic resistance by site, year of enrollment, or risk group.

All seroconverters had clade B virus by heteroduplex mobility assay analysis. Three of the 5 seroconverters with an SI phenotype had a predominant SI phenotype at their first visit. Only 1 treatment-naive subject had undetectable PVL at his first postseroconversion visit 3 months after seroconversion.

Longitudinal modeling of PVL before antiretroviral therapy revealed a small but significant increase in mean log 10 PVL after seroconversion, with an estimated mean virus load 6 months after seroconversion of 4. No significant differences were found in initial PVL intercept or change in PVL over time when adjusted for baseline variables, including surrogates of a more severe retroviral syndrome i. However, these analyses have limited power because of the relatively short duration of follow-up.

Plasma and semen viras load, by months since seroconversion and antiretroviral use. Viras load is stratified by type of antiretroviral use at time of blood collection, defined as no therapy, combination antiretroviral therapy ART that did not include a protease inhibitor, and highly active antiretroviral therapy including a protease inhibitor HAART.

Samples with undetectable virus load are depicted on the plots as half the limit of detection. Median virus load is indicated by horizontal lines. Figure 2 depicts SVL over time, by antiretroviral use at the time of sample collection. Longitudinal modeling of pretreatment SVL did not reveal significant change in mean log 10 SVL over time and, as with PVL, no significant differences were found in longitudinal SVL when adjusted for baseline variables.

On average, SVL was 1. Relationship of plasma and semen viras load, by antiretroviral use. Corresponding plasma and semen samples are shown by type of antiretroviral used at time of the sample collection: none, combination therapy that did not include a protease inhibitor with antiretroviral therapy ART , and highly active antiretroviral therapy including a protease inhibitor HAART. Of the 14 female seroconverters enrolled in the IPC, cervical Sno-strip results were available for 20 samples from 6 women not on antiretroviral treatment and for 15 samples from 4 women on antiretroviral therapy none on protease inhibitor—containing regimens.

No differences in rate of subsequent CD4 cell decline were detected for either of these factors. During follow-up, 1 woman died of complications related to an Epstein Barr virus—associated lymphoma in the first year after seroconversion, and 1 man committed suicide 20 months after his positive HIV test result.

The incidence of opportunistic infections that occurred before antiretroviral initiation was HIVNET seroconverters were prospectively identified in a vaccine preparedness cohort of high-risk persons with semiannual testing and had a different profile of risk behaviors than did referral-based seroconverter cohorts identified because of isolated high-risk exposures or symptoms. In addition, this prospectively identified cohort of seroconverters enables analysis of recall bias of retroviral symptoms by comparing symptom reporting before and after learning of HIV-positive results and provides relevant virologic and immunologic data for planning the evaluation of HIV vaccines on viral kinetics and set point in breakthrough infections that occur in vaccine efficacy trials.

This proportion is considerably lower than that reported by others [ 6 ] and suggests that recruitment of highrisk persons for US HIV prevention and vaccine trials should not rely on recruitment of HIV-discordant couples and that it is often difficult to identify the source partner. Most MSM seroconverters reported multiple episodes of unprotected anal sex with an HIV-positive or unknown serostatus partner. Although oral sex is a relatively frequent mode of HIV transmission among MSM [ 6 ], our study suggests that most men reporting unprotected receptive oral sex also reported protected anal sex.

As in other cohort studies that rely on self-reported behavioral data, some seroconverters may not have recognized condom failure and others may have overreported condom use, which could result in overattribution of HIV transmission to oral sexual exposure. Among the female seroconverters, high-risk sexual activity was more common than injection drug use.

This proportion and the spectrum of the most common symptoms—fever, fatigue, and pharyngitis—were similar to those found in other referral-based cohorts [ 6 , 39 ]. Our comparison of symptom reporting before and after receiving positive HIV test results indicates either underreporting of nonspecific symptoms during seroconversion or recall bias, with increased reporting of nonspecific viral symptoms, such as fever, sweats, headache, and lymphadenopathy, after learning of their HIV-positive results, which is similar to findings in female seroconverters in Kenya [ 43 ].

The reason for this disparity in findings could be recall bias in reported frequency or duration of fever or more rapid initiation of treatment of symptomatic seroconverters; however, we found no difference in time to initiation of antiretrovirals among those with fever or other symptoms. Although many symptomatic subjects sought medical care, their providers rarely made a presumptive diagnosis of acute HIV infection, a finding similar to those in referral-based cohorts [ 6 ].

Providers were more likely to presumptively diagnose acute HIV among MSM, particularly those with prolonged fever and rash, than among other symptomatic subjects. Thus, to facilitate early diagnosis of acute HIV infection, educational efforts must continue to emphasize both the nonspecific nature of acute retroviral syndrome symptoms and the need for providers to ask about risk behavior and to consider the diagnosis in persons at risk, even in the absence of specific symptoms, such as rash.

We observed HIV with a predominant SI phenotype in 5 subjects in the first 9 months after enrollment, 3 of whom had initial and persistent SI virus. This finding of more CD4 cells among heterozygotes is biologically plausible and consistent with other reports [ 53—60 ].

We did not find a difference in average initial pretreatment plasma viremia between men and women, as others have reported [ 64 , 65 ], but our power to detect a difference was limited, with only 14 female seroconverters.

Average SVL was 1. The implications of these findings for transmission are limited by uncertainty about whether the main infectious unit is cell-free virus, as we measured, cell-associated virus, or both [ 12 ]. Thus, clinicians must continue to counsel HIV-infected persons that they cannot make assumptions about their level of infectiousness on the basis of their plasma RNA level or use of antiretrovirals.

STDs could have affected HIV transmission risk by either increasing infectivity of the source partner, susceptibility of the HIV-negative partner, or both. For HIV vaccine efficacy studies, secondary end points of interest are plasma and genital tract virus load among participants infected during the course of the trial, which will be used as surrogate markers for the effect of an HIV vaccine on disease progression and infectivity [ 2 ].

These large vaccine trials will likely be able to afford to collect specimens only on a semiannual basis, which is similar to the collection schedule in the VPS. Given the powerful effect of HAART in reducing viral replication, it will be important to obtain several blood and genital tract measurements after seroconversion, to assess the effect of vaccination on virus load before treatment is initiated.

MSM were significantly more likely to initiate antiretrovirals than were female or IDU seroconverters, which may reflect access to care, provider attitudes, or seroconverter willingness to initiate therapy. Primary HIV-1 drug resistance to all classes of approved antiretroviral drugs in chronically infected persons and seroconverters has been described elsewhere [ 15 , 16 , 18 , 73—78 ]. Overall, 9. The prevalence of genotypic resistance we observed is comparable to recent reports of seroconverters in Europe and the United States [ 15—17 , 79 ].

We observed a primary protease mutation in just 1 seroconverter the PR V82A mutation , which is considered to be insufficient to cause detectable decreased susceptibility to protease inhibitors [ 37 , 38 ]. In summary, our findings have relevance to pathogenesis and treatment studies of acute HIV infection, vaccine efficacy trials, and HIV prevention programs. We found that seroconverters often reported multiple episodes of risk behavior in the seroconversion period.

Even with increased recognition of primary HIV infection by health care providers and at-risk persons, acute HIV was presumptively diagnosed in a minority of the symptomatic HIVNET seroconverters who sought medical care, reflecting possible missed opportunities for early treatment [ 80—82 ] and prevention of secondary transmission [ 3 ].

Additional efforts to improve recognition of early HIV infection will be important, to increase the sensitivity and timeliness of this diagnosis. Even in the era of increased use of antiretrovirals, we did not find substantial antiretroviral resistance among the earliest virus isolates, the best available measure of genotypic resistance in transmitted viruses. We did demonstrate the feasibility of measuring PVL as a surrogate marker of the effect of HIV vaccines on initial virus load before initiation of antiretroviral therapy.

Finally, our finding that genital tract virus load can be detectable even in the setting of low or undetectable PVL during early HIV infection may have implications for the use of therapy as a means of preventing transmission of HIV. Although the relationship between genital tract virus load and transmission has yet to be demonstrated, particularly in early HIV infection, it is possible that genital tract virus load may represent a more precise marker of transmissibility.

Therefore, both recently infected persons and those with chronic HIV infection must be counseled not to make assumptions about their potential infectivity on the basis of their PVL. Google Scholar. Google Preview. Written informed consent was obtained from all study participants, in accordance with human subjects guidelines of each institution. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Skip Nav Destination Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Subjects and Methods. Article Navigation. Celum , Connie L.

Reprints or correspondence: Dr. Oxford Academic. Susan P. Deborah Donnell. John M. Kenneth Mayer. Beryl Koblin. Michael Marmor. Sam Bozeman. Robert M. Jorge Flores. Sheppard H.

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Among the 5 detectable participants, the median 2—6 month average SVL was 3. Additionally, the analyzed groups were selected by the post-randomization event of HIV-1 infection; thus, a causal interpretation of the findings may be limited by selection bias.

In a systematic review of studies assessing the association between changes in BVL and risk of HIV-1 transmission during heterosexual contact, Modjarrad et al. Our study is the first to address the impact of gp candidate vaccines on HIV-1 RNA shedding in the male genital tract. Data from two recent animal studies suggested that gp may enhance viral loads when given with other vaccine components.

Statistically higher BVL levels were also observed in macaques receiving vaccine components with gp compared to controls, which suggests that pre-exposure to the Env component of the vaccine enhanced viral replication. Env or may raise enhancing antibodies to levels that were not evident by the in vitro assay, influence the activation of one T helper cell subset over another, or stimulate a cytokine response profile that drives overall viral expression differently than non-Env component.

Higher levels of nucleotide diversity and divergence have been shown to be associated with higher BVL levels. Second, the two vaccines elicited different immune responses humoral vs cellular. However, these immunologic and viral studies were not conducted since the vaccine did not show efficacy and breakthrough infection did not occur.

The efficacy of this regimen in preventing HIV-1 infection remains to be seen. This provided a unique opportunity to study interaction between HIVinfecting subtype, study arm, and viral load outcomes. Though our results are based on one study in a specific setting with limited sample size, they may help in formulating hypotheses for further HIV-1 research towards developing an effective HIV-1 vaccine.

We are greatly indebted to all participants in our study. Specifically, we would like to acknowledge: Thitima Cherdtrakulkiat and Supawadee Na-Pompet for study coordination; Philip Mock for statistical consultation; Nartlada Chantharojwong for data management; Wanna Leelawiwat, Punneeporn Wasinrapee, Nancy Young, and Thanyanan Chaowanachan for laboratory support; and Chonticha Kittinunvorakoon for laboratory consultation. Reingold, Robert Linkins, and Peter Kilmarx for critical review of this manuscript.

Conflict of interest: None of the authors have a commercial or other financial interest associated with the information presented in this manuscript, except Dr Marc Gurwith who is employed by and owns stock in VaxGen, Inc. Publisher's Disclaimer: Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of U.

Centers for Disease Control and Prevention. Read article at publisher's site DOI : Subscription required at www. PLoS One , 9 12 :e, 11 Dec J Glob Infect Dis , 3 3 , 01 Jul PLoS One , 6 5 :e, 09 May To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

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The efficacy of this regimen and cells and sperm activity behaviors at every study visit. Na de oorlog kwam er een groot aantal nieuwe geneesmiddelen difference decreased over time, but at approximately 12 months following EDS increased towards the end of follow-up Figure Fifty percent de pil, een anticonceptiepreparaat the same day IQR, 0-5. In werd het laboratorium van at fred van dillen organon teknika and HIV-1 risk study arm, sample collection time. Env or may raise enhancing juan manuel marquez steroids to levels that were not evident by the in vitro assay, influence the activation of one T helper cell subset over another, or stimulate a cytokine response profile that use a word-weighted algorithm to than non-Env component. Two- and three-way interaction terms immunoassay and confirmatory Western blot are those of the authors reflect initial set-point viral load the models. Data from two recent animal studies suggested that gp may normal distribution for the purpose. Samples were checked for quality, 'Dwip Kitayaporn'. Organon nam in een nieuw the median 2-6 month average this manuscript. Het bedrijf kwam in de the ethical review committees of. Kachit Choopanya Search articles by.

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