Women with pregnancies had lower adherence to 1% tenofovir vaginal gel as HIV preexposure prophylaxis in CAPRISA 004, a phase IIB randomized-controlled trial

Lynn T Matthews, Sengeziwe Sibeko, Leila E Mansoor, Nonhlanhla Yende-Zuma, David R Bangsberg, Quarraisha Abdool Karim, Lynn T Matthews, Sengeziwe Sibeko, Leila E Mansoor, Nonhlanhla Yende-Zuma, David R Bangsberg, Quarraisha Abdool Karim

Abstract

Background: Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of the links between pregnancy and adherence to this prevention strategy.

Methods: We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of >80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (>80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test.

Results: Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% [IQR: 45-83] vs. 60% [IQR: 50-100], p = 0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95%CI: 0.41-0.66, p<0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% [IQR: 46-83] vs. 55% [IQR: 20-100], p = 0.68).

Conclusions: Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, NCT00441298, http://www.clinicaltrials.gov/ct2/show/NCT00441298.

Conflict of interest statement

Competing Interests: Tenofovir was provided by Gilead Sciences and the gel was manufactured and supplied for the CAPRISA 004 trial by CONRAD. Tenofovir is marketed by Gilead Sciences under the trade name Viread. Professor Abdool Karim notes that the following application for a patent for the study product in this trial should be noted: Application number: PCT/US2011/039505; Effect of tenofovir gel on Herpes Simplex Type I and II infection; Inventors: Salim S. Abdool Karim, Quarraisha Abdool Karim, Ayesha Kharsany, Thomas Cichlar, and James Rooney; Countries: United States of America. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Screening, enrollment, and pregnancy events…
Figure 1. Screening, enrollment, and pregnancy events in the CAPRISA 004 vaginal tenofovir gel trial.

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