PACTG P1045 (VERSION 10) PREVALENCE OF MORPHOLOGIC AND METABOLIC ABNORMALITI

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite unarguable advances in HIV care associated with highly active antiretroviral therapy (HAART), it is now apparent that many patients on these regimens are developing potentially deleterious metabolic effects, including insulin resistance, dyslipidemia, osteopenia and osteoporosis, and hyperlactatemia. Changes in body fat distribution often referred to as lipodystrophy have also been described. These changes involve both fat accumulation (abdominal visceral obesity, dorsocervical fat pad or buffalo hump, breast enlargement, lipomatosis) and fat loss (lipoatrophy in the face, limbs and gluteal regions). Although the long-term risks associated with this combination of complications in patients with HIV infection are unknown, there is mounting concern that these effects may impact the long-term prognosis in patients whose life expectancies have been significantly extended due to effective viral suppression by HAART. Moreover, adherence to otherwise life-saving antiretroviral therapy has been adversely influenced by the concern about the very obvious physical changes. Early anecdotal reports led to the assumption that protease inhibitors (PIs) were directly responsible for both the metabolic and morphologic alterations . Indeed, there is considerable evidence from studies in both HIV- positive and HIV-negative subjects that some PIs can induce insulin resistance and increase triglyceride and cholesterol levels. However, it is now clear that both metabolic changes and fat distribution abnormalities also occur in PI-naive patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs). In addition to class-specific effects, there is emerging evidence that there are differences with each class of drugs in the nature and magnitude of their metabolic effects. In addition to exposure to both PI- and NRTI-containing regimens, a number of non-drug risk factors such as age, gender, race, and baseline body composition have been identified in cohort studies. Potentially deleterious metabolic effects, including insulin resistance, dyslipidemia, osteopenia, osteoporosis, hyperlactatemia, and lipodystrophy are being associated with life-prolonging HAART in HIV-infected children. Studies conducted to date present a very wide range in findings, with regard to both prevalence and putative associations with the conditions, and composition and duration of ART therapy. Much larger prospective studies are needed with standardized definitions, anthropometric measurements, and laboratory evaluations. This study will compare the prevalence of abnormalities in glucose metabolism, serum lipid levels, body composition, fat deposition and distribution, and bone density in: 1. vertically HIV-infected children and youth on ART and HIV-uninfected children and youth. 2. vertically HIV-infected children and youth who are receiving PI-containing regimens and vertically HIV- infected children and youth who are not receiving PI-containing regimens. 3. vertically HIV-infected children and youth on ART and HIV-uninfected children and youth according to Tanner stage. Additionally, the study will: 1. To compare the prevalence of abnormalities in glucose metabolism, serum lipid levels, body composition, fat deposition and distribution, and bone density in vertically and horizontally HIV-infected females on ART through collaboration with ATN 021. 2. To explore the relationship of duration of exposure to highly active antiretroviral therapy (HAART) and the specific components of HAART therapy to prevalence of abnormalities in glucose metabolism, serum lipid levels, body composition, fat deposition and distribution, and bone density. 3. To explore the relationship between drug and non-drug factors and risk of specific aberrations in the morphologic and metabolic parameters that are being