HIV treatment as prevention : models, data, and questions-towards evidence-based decision-making

Antiretroviral therapy (ART) for those infected with HIV can prevent onward transmission of infection, but biological efficacy alone is not enough to guide policy decisions about the role of ART in reducing HIV incidence. Epidemiology, economics, demography, statistics, biology, and mathematical modelling will be central in framing key decisions in the optimal use of ART. PLoS Medicine, with the HIV Modelling Consortium, has commissioned a set of articles that examine different aspects of HIV treatment as prevention with a forward-looking research agenda. Interlocking themes across these articles are discussed in this introduction. We hope that this article, and others in the collection, will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Although the pathogenesis of human immunodeficiency virus (HIV) infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for all HIV-infected persons, there are unique considerations needed for HIV-infected infants, children, and adolescents, including; A acquisition of infection through perinatal exposure for many infected children, In utero, intrapartum, and/or postpartum neonatal exposure to zidovudine (ZDV) and other antiretroviral medications in most perinatally infected children, Requirement for use of HIV virologic tests to diagnose perinatal HIV infection in infants under age 15 to 18 months old, Age-specific differences in immunologic markers (i.e., CD4+ T cell count), Changes in pharmacokinetic parameters with age caused by the continuing development and maturation of organ systems involved in drug metabolism and clearance, Differences in the clinical and virologic manifestations of perinatal HIV infection secondary to the occurrence of primary infection in growing, immunologically immature persons, and Special considerations associated with adherence to antiretroviral treatment for infants, children and adolescents. This report addresses the pediatric-specific issues associated with antiretroviral treatment and provides guidelines to health care providers caring for infected infants, children, and adolescents. It is recognized that guidelines for antiretroviral use in pediatric patients are rapidly evolving. The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children will review new data on an ongoing basis and provide regular updates to the guidelines

The relationship between HIV seroconversion illness, HIV test interval and time to AIDS in a seroconverter cohort.

Seroconversion illness is known to be associated with more rapid HIV disease progression. However, symptoms are often subjective and prone to recall bias. We describe symptoms reported as seroconversion illness and examine the relationship between illness, HIV test interval (time between antibody-negative and anibody-positive test dates) and the effect of both on time to AIDS from seroconversion. We used a Cox model, adjusting for age, sex, exposure group and year of estimated seroconversion. Of 1820 individuals, information on seroconversion illness was available for 1244 of whom 423 (34%) reported symptomatic seroconversion. Persons with a short test interval (< or = 2 months) were significantly more likely to report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62). Time to AIDS was significantly faster (P = 0.01) in those with a short test interval. The HIV test interval is a useful replacement for information on seroconversion illness in studies of HIV disease progression

Host Genetics and Viral Diversity: Report from a Global HIV Vaccine Enterprise Working Group

The Global HIV Vaccine Enterprise convened a workshop in September 2009 to discuss human and viral genetic variation and its impact on future directions for HIV vaccine research and development. The formidable challenges presented by virus and host genetic variability are interrelated and complicate vaccine development. HIV vaccine researchers need to develop innovative approaches that will facilitate addressing these questions in novel ways

Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, had CD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90–1.63) for tuberculosis, 2.61 (1.05–6.49) for MAC, 1.17 (0.34–4.08) for CMV retinitis, 1.18 (0.62–2.26) for PML, 1.21 (0.83–1.75) for HSV, 1.18 (0.87–1.58) for Kaposi sarcoma, 1.56 (0.82–2.95) for NHL, 1.11 (0.56–2.18) for cryptococcosis and 0.77 (0.40–1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries