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

INTRODUCTION: Some observational data suggest that the progestogen injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase a woman's risk of HIV acquisition but a randomized clinical trial did not find a statistically significant increase in HIV risk for women using DMPA compared to two other methods. However, it could not rule out up to 30% increased HIV risk for DMPA users. We evaluate changes to contraceptive method mix in South Africa under different assumptions about the existence and strength of a possible undetected relationship between DMPA use and HIV risk. METHODS: A mathematical model was developed to simulate the ongoing HIV epidemic and contraceptive method mix in South Africa to estimate how changes in method mix could impact HIV- and reproductive health-related outcomes. We made different assumptions about the relationship between DMPA use and HIV risk, from no relationship to a 30% increase in HIV risk for women using DMPA. Scenario analyses were used to investigate the impact of switching away from DMPA predominance to new patterns of contraceptive use. RESULTS: In South Africa, the HIV-related benefits of reduced DMPA use could be as great as the harms of increased adverse reproductive health outcomes over 20 years, if DMPA did increase the risk of HIV acquisition by a relative hazard of infection of 1.1 or greater. A reduction in DMPA use among HIV-positive women would have no benefit in terms of HIV infections, but would incur additional negative reproductive health outcomes. The most important driver of adverse reproductive health outcomes is the proportion of women who switch away from DMPA to no contraceptive method. CONCLUSIONS: If there is any real increased HIV risk for DMPA users that has not been detected by the recent randomized trial, a reduction in DMPA use could reduce the ongoing number of new HIV infections. However, such a change would place more women at risk of adverse reproductive health effects. It is imperative that these effects are minimized by focusing on expanding access to safe, effective and acceptable alternative contraceptive methods for all women.

Correction to: The potential impact of a "curative intervention" for HIV: a modelling study.

[This corrects the article DOI: 10.1186/s41256-019-0107-1.].

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

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.

The potential impact of a "curative intervention" for HIV: a modelling study.

BACKGROUND: Efforts to develop an HIV "cure" (i.e., an intervention leading to durable ART-free remission or eradication of HIV infection) have become better resourced and coordinated in recent years. Given, however, the availability of other interventions for prevention and treatment of HIV disease, it is unclear whether, to what extent, and under which circumstances a curative intervention would have an impact in ending the AIDS epidemic and which characteristics of its implementation would be most important. We designed a range of analyses to investigate these unknowns. METHODS: We used a deterministic, compartmental model of HIV infection in South Africa to estimate the impact of a curative intervention. We first examined how its impact would be affected by the state of the epidemic at the time that it is introduced, by the timing and pace of scale-up, and by various targeting strategies. We then investigated the impact of a curative intervention relative to its ability to maintain viral suppression. FINDINGS: To the extent that other interventions have failed to control the epidemic, i.e., if incidence and AIDS deaths remain high, a curative intervention would result in a larger reduction in incidence. Earlier and faster scale-up allows for greater impact. We also found that a curative intervention would more efficiently reduce transmission if it is prioritised to those not able to obtain or remain on ART and to those aged 15-25 rather than older persons. On the other hand, an intervention that does not maintain viral suppression if the individual is exposed to re-infection could lead to an increase in HIV incidence. CONCLUSIONS: Our findings suggest that a curative intervention for HIV would have the greatest impact if the epidemic is not under control by 2030, particularly if the intervention is targeted to those who are more likely to transmit virus, and if it maintained durable viral suppression, even upon exposure to re-infection. These considerations underscore the need to carefully consider the "target product profiles" for an HIV cure in the context of how and where it would be used, and suggest that such profiles may require revision as the epidemic evolves in the coming years.

The emerging health impact of voluntary medical male circumcision in Zimbabwe: An evaluation using three epidemiological models.

BACKGROUND: Zimbabwe adopted voluntary medical male circumcision (VMMC) as a priority HIV prevention strategy in 2007 and began implementation in 2009. We evaluated the costs and impact of this VMMC program to date and in future. METHODS: Three mathematical models describing Zimbabwe's HIV epidemic and program evolution were calibrated to household survey data on prevalence and risk behaviors, with circumcision coverage calibrated to program-reported VMMCs. We compared trends in new infections and costs to a counterfactual without VMMC. Input assumptions were agreed in workshops with national stakeholders in 2015 and 2017. RESULTS: The VMMC program averted 2,600-12,200 infections (among men and women combined) by the end of 2016. This impact will grow as circumcised men are protected lifelong, and onward dynamic transmission effects, which protect women via reduced incidence and prevalence in their male partners, increase over time. If other prevention interventions remain at 2016 coverages, the VMMCs already performed will avert 24,400-69,800 infections (2.3-5% of all new infections) through 2030. If coverage targets are achieved by 2021 and maintained, the program will avert 108,000-171,000 infections (10-13% of all new infections) by 2030, costing $2,100-3,250 per infection averted relative to no VMMC. Annual savings from averted treatment needs will outweigh VMMC maintenance costs once coverage targets are reached. If Zimbabwe also achieves ambitious UNAIDS targets for scaling up treatment and prevention efforts, VMMC will reduce the HIV incidence remaining at 2030 by one-third, critically contributing to the UNAIDS goal of 90% incidence reduction. CONCLUSIONS: VMMC can substantially impact Zimbabwe's HIV epidemic in the coming years; this investment will save costs in the longer term.

An infectious way to teach students about outbreaks.

The study of infectious disease outbreaks is required to train today's epidemiologists. A typical way to introduce and explain key epidemiological concepts is through the analysis of a historical outbreak. There are, however, few training options that explicitly utilise real-time simulated stochastic outbreaks where the participants themselves comprise the dataset they subsequently analyse. In this paper, we present a teaching exercise in which an infectious disease outbreak is simulated over a five-day period and subsequently analysed. We iteratively developed the teaching exercise to offer additional insight into analysing an outbreak. An R package for visualisation, analysis and simulation of the outbreak data was developed to accompany the practical to reinforce learning outcomes. Computer simulations of the outbreak revealed deviations from observed dynamics, highlighting how simplifying assumptions conventionally made in mathematical models often differ from reality. Here we provide a pedagogical tool for others to use and adapt in their own settings.