Previous analyses, including a cohort study in Kenya and secondary results from a randomised controlled trial in Zambia, have suggested that hormonal contraception may accelerate HIV disease progression in women not yet on antiretroviral treatment (ART). However, an analysis of a cohort of over 4500 women across multiple sites in Africa and elsewhere found no evidence that hormonal contraception affects mortality or disease progression. Elizabeth Stringer, of the University of Alabama at Birmingham, reported the findings to the Sixteenth Conference on Retroviruses and Opportunistic Infections last week on behalf of a research team from Zambia and the US.
Hormonal contraceptives are the class of birth-control treatments that act on the female hormone system. This study looked at a large cohort of antiretroviral-naive women to examine the effects of hormonal contraceptives on disease progression. Women were selected from participants in the MTCT Plus Initiative, a programme of family-based HIV care and treatment conducted in 14 sites (Thailand and 13 countries in sub-Saharan Africa). While MTCT Plus provided condoms and encouraged their use, many women also reported the use of other contraceptives.
All women included in this analysis were ART-naive at the time of enrollment, had available data on CD4 cell counts and contraception use, and were not pregnant (and were at least three months postpartum if they had previously given birth). The analysis looked at the risks of death, and of disease progression to the point of eligibility for ART (i.e. CD4 cell count decline to 200 cells/mm3, progressing to WHO Stage IV, or progressing to WHO Stage III with CD4 cell counts below 350 cells/mm3). Risks were compared between women using three types of contraception:
- no contraception, or non-hormonal methods only (e.g. condoms and IUDs)
- oral hormonal contraception (oestrogen/progestin – the 'Pill')
- progestin-only hormonal contraception (implants and injectables such as DMPA)
A total of 7846 women were enrolled between August 2002 and December 2006, of whom 4530 fit the inclusion criteria. At study entry, 3099 reported using non-hormonal or no contraception, 830 reported using injectable or implant hormonal contraception (HC), and 226 using oral HC. Another 375 women were excluded from the analysis as their contraceptive method was not known. Although there were some demographic differences between the groups, the groups were clinically similar, with median baseline CD4 cell counts of roughly 420 cells/mm3.
None of the analyses performed in the study found any effect of hormonal contraceptives (HC) on progression to ART eligibility or to death. The following are the hazard ratios for mortality or progression, compared to women who used no contraceptives or non-hormonal contraceptives, based on the contraceptive method used at baseline:
- unadjusted hazard ratio for injectable/implant HCs: 1.0; 95% CI, 0.8 to 1.2
- adjusted hazard ratio for injectable/implant HCs: 1.0; 95% CI, 0.9 to 1.2
- unadjusted hazard ratio for oral HCs: 1.0; 95% CI, 0.7 to 1.3
- adjusted hazard ratio for oral HCs: 0.9; 95% CI, 0.6 to 1.2
Nor were any significant differences found in the following additional analyses:
- mortality risk and risk of progression to ART eligibility, analysed separately
- time-varying analysis controlling for the actual time spent on each contraceptive method, rather than carrying forward the type used at baseline, or
- analysis by individual site.
There were 66 deaths overall, for a mortality rate of 1.1/100 person-years (95% CI, 0.9 to 1.4), and 881 women progressed to ART eligibility (a rate of 17.0/100 person-years, 95% CI, 15.9 to 18.2).
The investigators concluded that, in contrast to some other, smaller studies, this analysis found no evidence that hormonal contraception accelerates HIV disease progression. The study's strengths were its large size, geographical scope and diversity of participants; its weaknesses were the lack of randomisation and the reliance on self-report for type of contraceptive exposure. Also, no distinction was made between the different types of progestin-based, non-oral hormonal contraception.
While these results were encouraging, Stringer stated that further research is needed, particularly to examine the effects of different types of contraceptive agents on disease progression.
Stringer E et al. Effect of hormonal contraception on HIV disease progression: a multi-country cohort analysis. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 175, 2009.