Pregnancy in HIV Clinical Trials in Sub Saharan Africa: Failure of Consent or Contraception?

Agnes Ssali,Stella Namukwaya,Leonard Bufumbo,Janet Seeley,Rosalind Parkes-Ratanshi,Anatoli Kamali,David G Lalloo

doi:10.1371/journal.pone.0073556

Abstract

ObjectiveHigher than expected pregnancy rates have been observed in HIV related clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore the factors contributing to high pregnancy rates among participants in two HIV clinical trials in Sub-Saharan Africa.MethodsFemale and male participants enrolled in one of two clinical HIV trials in south-west Uganda were approached. The trials were a phase III microbicide efficacy trial among HIV negative women using vaginal gel (MDP); and a trial of primary prevention prophylaxis for invasive cryptococcal disease using fluconazole among HIV infected men and women in Uganda (CRYPTOPRO). 14 focus group discussions and 8 in-depth interviews were conducted with HIV positive and negative women and their male partners over a six month period. Areas explored were their experiences about why and when one should get pregnant, factors affecting use of contraceptives, HIV status disclosure and trial product use.ResultsAll respondents acknowledged being advised of the importance of avoiding pregnancy during the trial. Factors reported to contribute to pregnancy included; trust that the investigational product (oral capsules/vaginal gel) would not harm the baby, need for children, side effects that led to inconsistent contraceptive use, low acceptance of condom use among male partners. Attitudes towards getting pregnant are fluid within couples over time and the trials often last for more than a year. Researchers need to account for high pregnancy rates in their sample size calculations, and consider lesser used female initiated contraceptive options e.g. diaphragm or female condoms. In long clinical trials where there is a high fetal or maternal risk due to investigational product, researchers and ethics committees should consider a review of participants contraceptive needs/pregnancy desire review after a fixed period, as need for children, partners and health status of participants may alter over time.

Highlights

Sub Saharan Africa has the highest fertility rate of any world region, at 5.77 children born per woman [1]
We identified non-pregnant female man’’ Female HIV-ve completed pregnancy (MDP) and CRYPTOPRO participants living within similar vicinity as the pregnant women, as additional potential enrolees to the study
Did the participants understand the consent process? All MDP and CRYPTOPRO participants who were interviewed in this study acknowledged the importance of avoiding pregnancy during the trial

Summary

Introduction

Sub Saharan Africa has the highest fertility rate of any world region, at 5.77 children born per woman [1]. In Uganda the fertility rate in 2009 was 6.7 children born per woman [2]. In couples affected by HIV desire for pregnancy and contraceptive needs are complex issues [4]. A Ugandan study of desire for children and pregnancy risk in HIV infected men and women showed that 27% of men reported wanting more children. Another study in Uganda showed that 59% HIV positive women in HIV sero-discordant couples desired to get pregnant [6]. Among women on antiretroviral therapy in rural Uganda followed for 2.4 years, only 7% of 711 women reported wanting more children at any time point, by the end of the follow up period 16.9% women had become pregnant [7]. In Rwanda and Zambia, contraceptive knowledge, use and concerns amongst HIV discordant couples were examined and despite high levels of knowledge of contraception 90%, use of contraceptive methods remains relatively low (at between 30–59%) [8]

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Discussion

Conclusion