What impact could DMPA use have had in South Africa and how might its continued use affect the future of the HIV epidemic?

Abstract

Introduction Some studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa. Methods We simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The “With Effect” scenario assumes that DMPA increases susceptibility to HIV infection by 1.20‐fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The “No Effect” scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV‐related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic. Results A causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037. Conclusions If there is a causal association between DMPA use and HIV risk, it could have substantially increased the scale of the HIV epidemic in South Africa, affecting not only the users of DMPA, but also their partners and the wider population. The magnitude of this potential effect demands careful data collection and a careful consideration of policy choices for contraception in settings with large HIV epidemics.

Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models

“…In this modelling study, we used five well described existing HIV models to estimate the impact of different disruptions to HIV prevention and treatment services as a result of the COVID-19 pandemic on HIV-related mortality and incidence. These models were Goals, 10 Optima HIV, 11 HIV Synthesis, 12 an Imperial College London Model, 13 and Epidemiological MODeling software (EMOD). 14 This study arose from discussions within an ad hoc group composed of the authors and other individuals (listed in the Acknowledgments).…”

“…Each model is based on information provided by a wide array of previous studies, as has been described previously. 10 , 11 , 12 , 13 , 14 Importantly, the models make assumptions relating to effects of ART interruption that account for the fact that immune recovery during ART tends to be lost quite rapidly after interruption of treatment. These assumptions are based on, for example, empirical observations 15 , 17 that showed a median loss of 187 CD4 cells per μL after ART interruption and 25% of people have a loss of more than 317 cells per μL in 2 months.…”

Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out

“…A recent modeling paper concluded that if there is a 20% increased risk of HIV-1 acquisition associated with DMPA-IM use in girls and women, compared with no associated increased risk for DMPA-IM, this could have substantially increased the scale of the HIV epidemic in South Africa, affecting not only the users of DMPA-IM but also their male partners and the wider population. 33 This article highlights the importance of carefully considering the future consequences of contraceptive policy choices, even for increased HIV risks of 20%.…”

Responding to the ECHO trial results: modelling the potential impact of changing contraceptive method mix on HIV and reproductive health in South Africa

“…However, some have argued that a lack of statistical significance for a positive interaction in the ECHO trial does not preclude the possibility of some effect of DMPA on HIV acquisition, merely that it reduces the chance of a strong association [8][9][10][11], because the trial was not designed to detect a hazard ratio below 1.5 (and post-trial analyses revealed that an observed HR of 1.3 or above would have been statistically significant, due to higher than expected subject retention and HIV incidence) [12,13]. Furthermore, for ethical reasons, the trial provided a comparison of HIV risk among DMPA users versus users of other existing contraceptives, rather than no contraceptive.…”

“…University of Cape Town, Cape Town, South Africa;8 Aurum Institute, Smith JA et al Journal of the International AIDS Society 2020, 23:e25620 http://onlinelibrary.wiley.com/doi/10.1002/jia2.25620/full | https://doi.org/10.1002/jia2.25620…”