Injectable and oral contraceptives and risk of HIV acquisition in women: an  analysis of data from the MDP301 trial

Angela M Crook; Deborah Ford; Mitzy Gafos; Richard Hayes; Anatoli Kamali; Saidi Kapiga; Andrew Nunn; Maureen Chisembele; Gita Ramjee; Helen Rees; Sheena McCormack

doi:10.1093/humrep/deu113

Contraception Adverse Effects

Injectable and oral contraceptives and risk of HIV acquisition in women: an analysis of data from the MDP301 trial

Crook AM, Ford D, Gafos M, Hayes R, Kamali A, Kapiga S, Nunn A, Chisembele M, Ramjee G, Rees H, McCormack S

Published August 2014 Human Reproduction (Oxford, England), 29(8), 1810-1817

DOI 10.1093/humrep/deu113 PMID 24838704 PMC PMC4093991

RRM Academy Synopsis

DMPA injectable contraceptive linked to higher HIV risk

DMPA, an injected form of birth control, was linked to a 49% higher risk of HIV over 52 weeks in a 2014 study of 8,663 HIV-negative women in Africa. The causal hazard ratio was 1.49 (95% CI 1.06-2.08) compared with no hormonal birth control. Birth control pills showed no added risk.

Key Findings

At the start of the study, 29% of women used DMPA, 14% used Net-En (another birth control shot), and 16% used birth control pills. The rest used no hormonal birth control.
After adjustment, the hazard ratio for HIV was 1.38 (95% CI 1.07-1.78) for DMPA and 1.18 (95% CI 0.86-1.62) for Net-En, compared with no hormonal birth control.
Birth control pills showed no higher HIV risk: adjusted hazard ratio 0.97 (95% CI 0.68-1.38) versus no hormonal birth control.
In a model estimating the effect of using hormonal birth control continuously for 52 weeks, DMPA's hazard ratio for HIV was 1.49 (95% CI 1.06-2.08).
HIV struck 6.2 per 100 person-years among DMPA users, 6.3 among Net-En users, 3.8 among birth control pill users, and 3.5 among women using no hormonal birth control.

Interpretation

The study is a secondary analysis of the MDP301 trial, a vaginal microbicide gel trial for HIV prevention in women at six African sites. The DMPA finding held steady across age groups, HSV-2 status, and study sites. Public health guidance weighs added HIV risk from DMPA against the unplanned pregnancies and deaths that limiting the method could cause. The authors say this modest rise does not justify dropping DMPA where it is the only method and HIV rates are low. They point to South Africa, where HIV rates stay high and other methods exist, and call for WHO to review its advice and widen access to other long-acting birth control.

RRM Context

RRM Academy names DMPA and similar drugs suppressive medications. They override the body's own hormone signals. Fertility charting tracks a woman's own cycle without adding outside hormones. Women who chart their cycle face no exposure to the shot this trial linked to higher HIV risk.

Our editorial summary of this paper, not the article's abstract.

Abstract

Study Question

Do injectable and oral contraceptives increase the risk of human immunodeficiency virus (HIV) acquisition in women?

Summary Answer

After adjusting for confounders, evidence of a significantly increased risk of HIV remained for women using injectable depo-medroxyprogesterone (DMPA) (hazard ratio = 1.49, 95% confidence interval (1.06-2.08)) but not for injectable norethisterone-enanthate (Net-En) or oral contraceptive pills (OC).

What Is Known Already

An association between the use of some types of hormonal contraception (HC) methods and an increased risk of HIV, possibly through changes in the genital tract environment and alterations in the immune response, has been previously observed, although not consistently. A recent systematic review of these studies has highlighted the need for more definitive evidence.

Study Design, Size, Duration

A secondary data analysis of the MDP301 phase 3 microbicide trial was conducted to estimate the effects of use of different methods of HC on the risk of HIV acquisition in women. HIV-negative women (n = 8663) with a median age of 28 years were included in the analysis; 382 HIV seroconverted by 52 weeks follow-up; 10% of women-years were lost to follow-up before 52 weeks.

Participants/Materials, Setting, Methods

Contraceptive use was reported at each 4-weekly visit. Cox proportional hazards (PH) models were used to estimate the effects of baseline and current use of injectable DMPA, injectable Net-En and OC compared with no HC, on the risk of HIV, adjusting for baseline and time-updated covariates. Causal effects for 52 weeks of HC use compared with no HC were estimated in a weighted Cox model, censoring women at deviation from baseline HC use (or non-use) or pregnancy.

Main Results and the Role of Chance

At baseline, 2499 (29%) women were on DMPA, 1180 (14%) on Net-En, and 1410 (16%) on OC; 3574 (40%) not on HC, started HC in follow-up. Adjusted hazard ratios (HR) for baseline HC use, compared with no HC, were 1.38 (95% confidence interval (CI) 1.07-1.78) for DMPA; 1.18 (0.86-1.62) for Net-En and 0.97 (0.68-1.38) for OC. The estimated causal effects of DMPA and Net-En over 52 weeks were: HR = 1.49 (95% CI 1.06-2.08) and HR = 1.31 (95% CI 0.62-1.61), respectively.

Limitations, Reasons for Caution

A main limitation of the study was that it was a secondary analysis of data from a study that was not designed to investigate this question. Despite our best efforts, we cannot exclude residual confounding to explain the effect of DMPA.

Wider Implications of the Findings

The results of this study should be reviewed by the World Health Organization to determine whether current recommendations on the use of DMPA in settings with high HIV prevalence require modification.

Study Funding/Competing Interests

MDP is a partnership of African and European academic/government institutions with commercial organizations, which is funded by the UK Government (DFID and MRC), with support from IPM and EDCTP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests

None.

Topics

Contraception

Adverse Effects Cardiovascular Effects

Contraception › Adverse Effects › Cardiovascular Effects

Angela M Crook, Deborah Ford, Mitzy Gafos, Richard Hayes, Anatoli Kamali, Saidi Kapiga, Andrew Nunn, Maureen Chisembele, Gita Ramjee, Helen Rees, Sheena McCormack

A Crook, Debbie Ford, Deb Ford, D Ford, M Gafos, Rick Hayes, Dick Hayes, Rich Hayes, R Hayes, A Kamali, S Kapiga, Andy Nunn, Drew Nunn, A Nunn, M Chisembele, G Ramjee, H Rees, S McCormack

PMID 24838704 24838704 DOI 10.1093/humrep/deu113 10.1093/humrep/deu113 Crook et al. 2014, Crook 2014

Keywords

Contraceptive Agents, Female