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Background: Monthly use of the dapivirine vaginal ring has been shown to be safe and effective for HIV-1 prevention in nonpregnant reproductive-aged women. The impact of dapivirine on pregnancy outcomes and infant is not known. We compared pregnancy incidence and outcomes by study arm among HIV-1-uninfected women who became pregnant while participating in MTN-020/ASPIRE., Methods: ASPIRE was a randomized, double-blind, placebo-controlled phase III safety and effectiveness study of the dapivirine ring for HIV-1 prevention. Sexually active women aged 18-45 years from Malawi, South Africa, Uganda, and Zimbabwe were enrolled. Urine pregnancy tests were performed monthly, and, if positive, study product was withheld during pregnancy and breastfeeding. Pregnancy-related outcomes included the following: pregnancy incidence, pregnancy outcomes (live birth, preterm birth, pregnancy loss, and congenital anomalies), and infant growth., Results: Of 2629 women enrolled in ASPIRE, 169 became pregnant during follow-up, resulting in 179 incident pregnancies and 181 pregnancy outcomes. No difference in pregnancy incidence by study arm was observed (hazard ratio = 0.93; 95% confidence interval: 0.68 to 1.26). The distribution of pregnancy outcomes was similar by study arm, and no difference was noted in the frequency or pattern of congenital anomalies or infant growth parameters by study arm., Conclusions: Dapivirine use in the periconception period does not seem to be associated with adverse effects on pregnancy or infant outcomes. Our findings provide support for additional safety studies of the dapivirine ring throughout pregnancy.

Objective: To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use., Design: A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention., Methods: Use of a highly effective method of contraception was an eligibility criterion for study participation. Urine pregnancy tests were performed monthly. Pregnancy incidence by arm was calculated separately for each hormonal contraceptive method and compared using an Andersen-Gill proportional hazards model stratified by site and censored at HIV-1 infection., Results: Of 2629 women enrolled, 2310 women returned for follow-up and reported using a hormonal contraceptive method at any point during study participation (1139 in the dapivirine arm and 1171 in the placebo arm). Pregnancy incidence in the dapivirine arm versus placebo among women using injectable depot medroxyprogesterone acetate was 0.43% vs. 0.54%, among women using injectable norethisterone enanthate was 1.15% vs. 0%, among women using hormonal implants was 0.22% vs. 0.69%, and among women using oral contraceptive pills was 32.26% vs. 28.01%. Pregnancy incidence did not differ by study arm for any of the hormonal contraceptive methods., Conclusions: Use of the dapivirine ring does not reduce the effectiveness of hormonal contraceptives for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, potentially because of poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.

Objective: Maternal-to-child-transmission of HIV-1 infection remains a significant cause of HIV-1 infection despite successful prevention strategies. Testing protective HIV-1 vaccines remains a critical priority. The immunogenicity of ALVAC-HIV vCP1521 (ALVAC) in infants born to HIV-1-infected women in Uganda was evaluated in the first pediatric HIV-1 vaccine study in Africa., Design: HIV Prevention Trials Network 027 was a randomized, double-blind, placebo-controlled phase I trial to evaluate the safety and immunogenicity of ALVAC in 60 infants born to HIV-1-infected mothers with CD4 counts of >500 cells per microliter, which were randomized to the ALVAC vaccine or placebo. ALVAC-HIV vCP1521 is an attenuated recombinant canarypox virus expressing HIV-1 clade E env, clade B gag, and protease gene products., Methods: Infants were vaccinated at birth and 4, 8, and 12 weeks of age with ALVAC or placebo. Cellular and humoral immune responses were evaluated using interferon-γ enzyme-linked immunosorbent spot, carboxyfluorescein diacetate succinimidyl ester proliferation, intracellular cytokine staining, and binding and neutralizing antibody assays. Fisher exact test was used to compare positive responses between the study arms., Results: Low levels of antigen-specific CD4 and CD8 T-cell responses (intracellular cytokine assay) were detected at 24 months (CD4-6/36 vaccine vs. 1/9 placebo; CD8-5/36 vaccine vs. 0/9 placebo) of age. There was a nonsignificant trend toward higher cellular immune response rates in vaccine recipients compared with placebo. There were minimal binding antibody responses and no neutralizing antibodies detected., Conclusions: HIV-1-exposed infants are capable of generating low levels of cellular immune responses to ALVAC vaccine, similar to responses seen in adults.

Background: The development of a safe and effective vaccine against HIV type 1 for the prevention of mother-to-child transmission of HIV would significantly advance the goal of eliminating HIV infection in children. Safety and feasibility results from phase 1, randomized, double-blind, placebo-controlled trial of ALVAC-HIV vCP1521 in infants born to HIV type 1-infected women in Uganda are reported., Methods: HIV-exposed infants were enrolled at birth and randomized (4:1) to receive vaccine or saline placebo intramuscular injections at birth, 4, 8, and 12 weeks of age. Vaccine reactogenicity was assessed at vaccination and days 1 and 2 postvaccination. Infants were followed until 24 months of age. HIV infection status was determined by HIV DNA polymerase chain reaction., Results: From October 2006 to May 2007, 60 infants (48 vaccine and 12 placebo) were enrolled with 98% retention at 24 months. One infant was withdrawn, but there were no missed visits or vaccinations among the 59 infants retained. Immune responses elicited by diphtheria, polio, hepatitis B, haemophilus influenzae type B, and measles vaccination were similar in the 2 arms. The vaccine was well tolerated with no severe or life-threatening reactogenicity events. Adverse events were equally distributed across both study arms. Four infants were diagnosed as HIV infected [3 at birth (2 vaccine and 1 placebo) and 1 in vaccine arm at 2 weeks of age]., Conclusion: The ALVAC-HIV vCP1521 vaccination was feasible and safe in infants born to HIV-infected women in Uganda. The conduct of high-quality infant HIV vaccine trials is achievable in Africa.