Even if Depo-Provera and other contraceptive injections raise the risk of HIV infection, withdrawing them from use in African countries would greatly increase maternal mortality, a modelling study has shown. The loss of life due to pregnancy complications and unsafe abortions would far outweigh the number of HIV infections prevented, according to the study published in the December issue of Global Health: Science and Practice.
Observational studies have produced conflicting evidence about a possible link between hormonal contraception – especially depot medroxyprogesterone acetate (DMPA, often marketed as Depo-Provera), a long-acting progesterone-only injectable – and women's risk of HIV infection. It’s not clear whether an apparent increase in HIV infections reflects a real biological effect of the contraceptive or if the results are skewed by factors which the researchers haven’t been able to fully take into account, particularly differences in the sexual behaviour of contraceptive users and non-users.
Pooling the results of these studies, a recent meta-analysis found that HIV-negative women using DMPA may be at increased risk of acquiring HIV, with a pooled hazard ratio of 1.4 (95% confidence interval 1.2-1.6). More definitive data is likely to come from ECHO, an ongoing randomised clinical trial, which may report results in 2019.
In the meantime, the World Health Organization recommends that DMPA and other long-acting progestogen-only injectables should remain accessible to women at high risk of HIV, “because the advantages of these methods generally outweigh the possible increased risk of HIV acquisition”. However, women at high risk of HIV who choose to use these methods should be counselled about the possible increased risk of HIV and how to reduce this risk.
The recently published modelling study sheds light on the balance of benefits and risks with the use of injectable contraceptives. It focuses on nine countries in sub-Saharan Africa, the world region which has both the greatest burden of HIV and of maternal mortality. In Africa, for every 200 live births, one woman dies during pregnancy, during childbirth or following an abortion. Access to services providing modern contraceptives is poor; around a third of pregnancies in Africa are unintended; and over 98% of abortions are unsafe.
The researchers used a decision-analytic model to assess the potential impact of changing family planning provision (removing DMPA / Depo-Provera and other progesterone-only injectables) in Burkina Faso, Chad, Democratic Republic of the Congo, Kenya, Senegal, South Africa, Malawi, Tanzania, and Uganda. The countries chosen reflect variations in maternal mortality, contraceptive mix and uptake, and HIV incidence. They are the countries, say the researchers, "where the balance between benefit and harm is most nuanced".
For each country, the model incorporated data on HIV incidence, access to HIV treatment, usage of different contraceptive methods, maternal mortality and life expectancy. Country-by-country variation in these factors affected the results.
In line with the meta-analysis, the researchers assumed that injectables are associated with a 1.4 increased risk of acquiring HIV.
The population of focus was women of reproductive age, who did not have HIV and were not planning a pregnancy. The main analysis considered the number of life-years lost or gained. Clearly, a maternal death would be an immediate loss of life. An HIV infection with access to HIV treatment was assumed to result in a 25% reduction in life expectancy. An HIV infection without HIV treatment would result in a 75% reduction in life expectancy.
However, it should be noted that this focus on deaths could obscure attention from the wider impact of poor health. Both living with HIV and having complications in pregnancy could have a long-term impact on quality of life. Nonetheless, the researchers did not use a measure which would reflect this, such as quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs).
The main scenario considered was DMPA being withdrawn, without replacement by equally effective reversible contraceptive methods. In this scenario, considering the nine countries together, for every 100,000 women, there would be 9000 life-years lost. There was variation between countries, but in all countries the impact would be negative.
For example, in Kenya, for every 100,000 women, there would be 6600 life-years lost. This is largely due to there being an additional 341 maternal deaths per 100,000. While there would be 49 fewer HIV infections per 100,000 women, the decreased use of contraception by women living with HIV would result in 35 additional HIV infections in infants per 100,000 women, so overall there would only be 14 fewer HIV infections a year per 100,000.
Even in South Africa – a country with a very high HIV incidence and relatively low maternal mortality – for every 100,000 women, there would be 1000 life-years lost. There would be 146 additional maternal deaths per 100,000 women. The 117 fewer HIV infections per 100,000 women would be negated by 114 additional HIV infections in infants per 100,000 women.
An additional scenario considered the effect of replacing DMPA with usage of an equally effective contraceptive, such as an intra-uterine device (IUD) or implant. This analysis found that in all countries apart from South Africa, an unrealistically large proportion of women (over 93%) would need to switch to the new method for there not to be a negative impact on life-years. The researchers say that in any change of family planning provision, significant efforts need to be made to ensure that women find alternative contraceptive methods accessible and acceptable.
“Our model found that removal of POIs [progesterone-only injectables] from the market without effective and acceptable contraception replacement would have a net negative effect on maternal health, life expectancy, and mortality, and this persisted under a variety of modeled scenarios,” the authors conclude. “Policy and programmatic decisions about the role of POIs in family planning programs must therefore be made cautiously, with continued recognition of the interconnectedness of these health issues.”
Rodriguez MI et al. Re-evaluating the possible increased risk of HIV acquisition with progestin-only injectables versus maternal mortality and life expectancy in Africa: a decision analysis. Global Health: Science and Practice. 2017;5(4):581-591. (Full text freely available.)