Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus: A Randomized Controlled Trial.

OBJECTIVE: To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. METHODS: The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. RESULTS: Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. CONCLUSION: Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01061151.

Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.

OBJECTIVE: We aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities. DESIGN: Secondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE). METHODS: Data from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo vaginal ring. We further assessed for the effect of the vaginal ring device on cervical cytology by comparing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population. RESULTS: Cervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo vaginal ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo vaginal ring arms (P = 0.24). CONCLUSION: These findings indicate that neither use of the dapivirine vaginal ring nor the vaginal ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.