Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk

Abstract

Background: Some, but not all, observational studies have suggested an increase in the risk of HIV acquisition for women using injectable hormonal contraception (IHC).

Methods: We used country-level data to explore the effects of reducing IHC use on the number of HIV infections, the number of live births and the resulting net consequences on AIDS deaths and maternal mortality for each country.

Results: High IHC use coincides with high HIV incidence primarily in southern and eastern Africa. If IHC increases the risk of HIV acquisition, this could generate 27 000-130 000 infections per year globally, 87-88% of which occur in this region. Reducing IHC use could result in fewer HIV infections but also a substantial increase in live births and maternal mortality in countries with high IHC use, high birth rates and high maternal mortality: mainly southern and eastern Africa, South-East Asia, and Central and South America. For most countries, the net impact of reducing IHC use on maternal and AIDS-related deaths is dependent on the magnitude of the assumed IHC-HIV interaction.

Conclusions: If IHC use increases HIV acquisition risk, reducing IHC could reduce new HIV infections; however, this must be balanced against other important consequences, including unintended pregnancy, which impacts maternal and infant mortality. Unless the true effect size approaches a relative risk of 2.19, it is unlikely that reductions in IHC could result in public health benefit, with the possible exception of those countries in southern Africa with the largest HIV epidemics.

Figure 1. Prevalence of injectable hormonal contraceptive (IHC) use and HIV prevalence by country.

Countries are coloured according to HIV prevalence[–20] and IHC use[2] among 15-49 year-old women: red = high IHC and high HIV; pink = high IHC and low HIV; orange = low IHC and high HIV; yellow = low IHC and low HIV. HIV prevalence above 1% and IHC prevalence in the top quartile globally are defined as high and all values below these thresholds are low. HIV prevalence data was unavailable for 15-49 year-old women in Brazil, China, the Democratic Republic of the Congo (DRC) and Thailand therefore we use reported HIV prevalence from antenatal clinics for Brazil,[17] DRC,[19] and Thailand[20] and adult HIV prevalence for China.[18]

Figure 2. A. Excess HIV infections per year attributable to a hypothesised IHC-HIV interaction.

Countries are ranked according to the total number of HIV infections per year that would be attributed to a putative IHC-HIV interaction with effect size (1) RR=1.2 and (2) RR=2.19.[5] The ten countries with the highest excess infections are shown together with selected examples from different regions. Country rankings out of 116 countries with available data are annotated next to the respective bars. Data for all other countries can be found in supplementary table 2 (online).

B. Excess live births per year resulting from cessation of all IHC use;

C. Excess maternal deaths per year resulting from cessation of all IHC use.

It is assumed that all women previously using IHC are transitioned to either no contraception or a hypothetical alternative, in proportion to the method mix reported by the non-IHC-using population for each country.[2] Countries are ranked according to the excess number of live births per year that can be attributed to cessation of all IHC use. The ten countries with the highest numbers of excess births are shown together with the examples from fig. 2A. Country rankings out of 134 countries with available data are annotated next to the relevant bars. Data for all other countries can be found in supplementary table 2 (online).

Figure 3. Change in the number of net maternal and HIV-related deaths resulting from cessation of IHC use.

A. Direction of change. Countries are coloured according to the direction of change in the net number of maternal and HIV-related deaths that result directly from stopping IHC use assuming (1) RR=1.2 and (2) RR=2.19: red = expected increase in net maternal and HIV-related deaths (>0.5% under both RR assumptions); pink = change in net deaths is dependent on the effect size (>0.5% increase only when RR=1.2); cream = reductions in IHC use unlikely to provide public health benefit in terms of deaths prevented (<0.5% change with both estimates); yellow = change in net deaths is dependent on the effect size (>0.5% decrease only when RR = 2.19); green = expected decrease in net deaths (>0.5% under both RR assumptions); grey = data not available.

B. Absolute change. The change in net maternal and HIV-related deaths on cessation of all IHC use, assuming (1) RR=1.0 (yellow), (2) RR=1.2 (light blue) and (3) RR=2.19 (dark blue), shown for the countries presented in fig. 2. Data for all other countries can be found in supplementary table 2 (online).