Introduction In generalized epidemic settings, there is insufficient understanding of how the unmet HIV prevention and treatment needs of key populations (KPs), such as female sex workers (FSWs) and men who have sex with men (MSM), contribute to HIV transmission. In such settings, it is typically assumed that HIV transmission is driven by the general population. We estimated the contribution of commercial sex, sex between men, and other heterosexual partnerships to HIV transmission in South Africa (SA). Methods We developed the “Key‐Pop Model”; a dynamic transmission model of HIV among FSWs, their clients, MSM, and the broader population in SA. The model was parameterized and calibrated using demographic, behavioural and epidemiological data from national household surveys and KP surveys. We estimated the contribution of commercial sex, sex between men and sex among heterosexual partnerships of different sub‐groups to HIV transmission over 2010 to 2019. We also estimated the efficiency (HIV infections averted per person‐year of intervention) and prevented fraction (% IA) over 10‐years from scaling‐up ART (to 81% coverage) in different sub‐populations from 2020. Results Sex between FSWs and their paying clients, and between clients with their non‐paying partners contributed 6.9% (95% credibility interval 4.5% to 9.3%) and 41.9% (35.1% to 53.2%) of new HIV infections in SA over 2010 to 2019 respectively. Sex between low‐risk groups contributed 59.7% (47.6% to 68.5%), sex between men contributed 5.3% (2.3% to 14.1%) and sex between MSM and their female partners contributed 3.7% (1.6% to 9.8%). Going forward, the largest population‐level impact on HIV transmission can be achieved from scaling up ART to clients of FSWs (% IA = 18.2% (14.0% to 24.4%) or low‐risk individuals (% IA = 20.6% (14.7 to 27.5) over 2020 to 2030), with ART scale‐up among KPs being most efficient. Conclusions Clients of FSWs play a fundamental role in HIV transmission in SA. Addressing the HIV prevention and treatment needs of KPs in generalized HIV epidemics is central to a comprehensive HIV response.

IntroductionIn South Africa, the rate of HIV in the sex worker (SW) population is exceedingly high, but critical gaps exist in our understanding of SWs and the factors that make them vulnerable to HIV. This study aimed to estimate HIV prevalence among female sex workers (FSWs) in Soweto, South Africa, and to describe their sexual behavior and other factors associated with HIV infection.MethodsA cross-sectional, respondent-driven sampling (RDS) recruitment methodology was used to enroll 508 FSWs based in Soweto. Data were collected using a survey instrument, followed by two HIV rapid tests. Raw and RDS adjusted data were analyzed using a chi-squared test of association and multivariate logistic regression to show factors associated with HIV infection.FindingsHIV prevalence among FSWs was 53.6% (95% CI 47.5–59.9). FSWs were almost exclusively based in taverns (85.6%) and hostels (52.0%). Less than a quarter (24.4%) were under 25 years of age. Non-partner violence was reported by 55.5%, 59.6% of whom were HIV-infected. Advancing age, incomplete secondary schooling, migrancy and multiple clients increased the likelihood of HIV acquisition: >30 years of age was associated with a 4.9 times (95% CI 2.6–9.3) increased likelihood of HIV; incomplete secondary schooling almost tripled the likelihood (AOR 2.8, 95% CI 1.6–5.0); being born outside of the Gauteng province increased the likelihood of HIV 2.3 times (95% CI 1.3–4.0); and having more than five clients per day almost doubled the likelihood (AOR 1.9, 95% CI 1.1–3.2).ConclusionOur findings highlight the extreme vulnerability of FSWs to HIV. Advancing age, limited education and multiple clients were risk factors associated with HIV, strongly driven by a combination of structural, biological and behavioral determinants. Evidence suggests that interventions need to be carefully tailored to the varying profiles of SW populations across South Africa. Soweto could be considered a microcosm of South Africa in terms of the epidemic of violence and HIV experienced by the SW population, which is influenced by factors often beyond an individual level of control. While describing a hitherto largely undocumented population of FSWs, our findings confirm the urgent need to scale up innovative HIV prevention and treatment programs for this population.