PACTG 1039 (VERSION 10) A PHASE III RANDOMIZED TRIAL OF THE SAFETY AND ANTIR

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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. ABSTRACT I. HYPOTHESIS Important issues must be considered when providing treatment to pregnant women who intend to discontinue treatment postpartum. The aim of this trial is to examine the safety and efficacy of treatment with three NRTIs versus two NRTIs and one PI. The hypothesis is treating pregnant women who do not meet the current PHS guidelines for initiation of therapy (and would not start treatment if they were not pregnant) with an all NRTI regimen (abacavir/lamivudine/zidovudine) will 1) reduce the risk of maternal to child transmission of HIV to the lowest attainable level, 2) minimize the risk of fetal toxicity and maternal drug side effects, 3) preserve therapeutic options for the mother for the future and 4) minimize the likelihood of developing resistance to antiretrovirals used during pregnancy and in the future. II. SPECIFIC AIMS Primary To examine the safety and efficacy of treatment with three NRTIs versus two NRTIs and one PI, by comparing the proportion of women in group A and B with virologic suppression to < 400 copies per mL at 34 weeks gestation (or the last viral load prior to delivery if this occurs < 34 weeks), while continuing on assigned therapy. Secondary 1. To compare HIV-related health status of women at delivery by CD4+ lymphocyte counts and plasma HIV-1 viral load. 2. To describe adherence to therapy among women in Groups A and B. 3. To assess the HIV- related health status of women postpartum as determined by CD4+lymphocyte counts and plasma HIV-1 viral load at 3, 6, and 12 months postpartum, and prior to the initiation of any new antiretroviral therapy. 4. To compare the development of HIV-1 genotypic resistance among women in Group A and Group B at the time of delivery, and at 3, 6, and 12 months postpartum and in all cases of treatment failure and prior to the initiation of any new antiretroviral therapy. 5. To compare the incidence of abnormal glucose tolerance, gestational diabetes and abnormal lactate levels during pregnancy between Group A and B. 6. To compare the incidence of adverse outcomes among infants born to women in Group A and B, including: anemia, hypoglycemia and abnormal liver function studies, prematurity, and low birth weight, perinatal HIV transmission. 7. To evaluate retrospectively the predictive value, sensitivity and specificity of polymorphisms in HLA-B57, HLA-DR7 and HLA-DQ3 in identifying pregnant women at risk for development of abacavir hypersensitivity. 8. To determine the peak concentration and area under the curve (AUC) of lopinavir/ritonavir (533/133 mg taken PO Q12H) in the first 12 women enrolled in Group B at steady-state in the third trimester of pregnancy (see section 9.0). 9. To compare the concentration of T-cell receptor-rearrangement excision DNA circles (TREC) in Group A and B at entry, delivery, and at 6 weeks postpartum.