Background: Women infected with HIV have a risk of preterm birth (PTB) that is twice that among uninfected women, and treatment with antiretroviral therapy (ART) may further increase this risk. Progesterone supplementation reduces the risk of preterm delivery in women who have a shortened cervix in the midtrimester. We propose to study the feasibility of a trial of vaginal progesterone (VP) to prevent PTB among HIV-infected women receiving ART in pregnancy. Given low adherence among women self-administering vaginal study product in recent microbicide trials, we plan to investigate whether adequate adherence to VP can be achieved prior to launching a full-scale efficacy trial.
Methods and design: One hundred forty HIV-infected pregnant women in Lusaka, Zambia, will be randomly allocated to daily self-administration of either VP or matched placebo, starting between 20 and 24 gestational weeks. The primary outcome will be adherence, defined as the proportion of participants who achieve at least 80% use of study product, assessed objectively with a validated dye stain assay that confirms vaginal insertion of returned single-use applicators. Secondary outcomes will be study uptake, retention, and preliminary efficacy. We will concurrently perform semi-structured interviews with participants enrolled in the study and with women who decline enrollment to assess the acceptability of VP to prevent PTB and of enrollment to a randomized controlled trial.
Discussion: We hypothesize that VP could prevent PTB among women receiving ART in pregnancy. In preparation for a trial to test this hypothesis, we plan to assess whether participants will be adherent to study product and protocol.
Trial registration: ClinicalTrial.gov, NCT02970552.
Keywords: Antiretroviral therapy; HIV; Preterm birth; Progesterone; Sub-Saharan Africa.