OBJECTIVES: This thesis aims to address the evidence gap in understanding HIV epidemiology among female sex workers (FSWs) in the Middle East and North Africa (MENA) region by 1) conducting the first comprehensive assessment of HIV epidemic status among FSWs and their clients, and of other key sexually transmitted infections (STIs) among FSWs, 2) investigating the utility of herpes simplex virus type 2 (HSV-2) prevalence in predicting HIV epidemic potential in FSWs, and 3) estimating HIV incidence in heterosexual sex work networks (HSWNs) and assessing the impact of interventions on epidemiological measures of relevance to HIV response. METHODS: Methodologies include systematic reviews, meta-analyses and meta-regressions of HIV/STI prevalence data, ecological analysis of global HSV-2/HIV prevalence data among FSWs, and an individual-based mathematical model simulating HIV transmission dynamics in HSWNs. RESULTS: The median proportion of reproductive-age women reporting current/recent sex work was 0.6% (range: 0.2-2.4%), and of men reporting currently/recently buying sex was 5.7% (range: 0.3-13.8%). Risk behaviors varied widely within and across countries. The HIV epidemic was concentrated in Djibouti and South Sudan (prevalence ~20%), of intermediate intensity in North Africa and Somalia (1-5%), and limited in other countries (<1%). There was steady growth in odds of HIV prevalence since 2003 at ~15% per year (95% CI: 9-21%). STI prevalence among FSWs was substantial (relative to general population women), supporting a key role for HSWNs in STI transmission dynamics. Pooled prevalence of current infection was 12.7% (95% CI: 8.5-17.7%) for T. pallidum (syphilis), 14.4% (95% CI: 8.2-22.0%) for C. trachomatis, 5.7% (95% CI: 3.5-8.4%) for N. gonorrhoeae, and 7.1% (95% CI: 4.3-10.5%) for T. vaginalis, while that of lifetime infection was 23.7% (95% CI: 10.2-40.4%) for HSV-2. Syphilis prevalence varied by MENA subregion and has been declining by 7% per year for three decades. Analysis of 231 global paired HSV-2/HIV measures identified a strong positive association among FSWs after adjusting for confounders such as region, temporal trend, and condom use. HIV prevalence was negligible where HSV-2 prevalence was ≤20%, but HIV infection odds doubled with each 25% increase in HSV-2 prevalence indicating a threshold effect and utility of HSV-2 in predicting HIV epidemic potential. The individual-based model was developed, calibrated, tested, and applied to 12 MENA countries with sufficient input data. The estimated number of new infections in 2020 in these countries was 3,471 (range: 1,295-10,308) among FSWs, 6,416 (range: 3,144-14,223) among clients, and 4,717 (range: 3,490-7,288) among client spouses. These infections accounted for 25.1% of total HIV incidence in MENA. Incidence was distributed equally among FSWs, clients, and client spouses. The contribution of incidence in HSWNs to total incidence ranged from 3.3% in Pakistan where injecting drug use is prevalent to 71.8% in South Sudan and 72.7% in Djibouti where sex is the dominant mode of transmission. Scale-up of interventions such as antiretroviral therapy, condom use, and pre-exposure prophylaxis substantially reduced incidence among FSWs, clients, and client spouses either directly or indirectly by reducing onward transmission. CONCLUSIONS: HIV epidemics among FSWs in MENA are emerging, and some are already established. The epidemic has been growing steadily in recent years, but with strong regionalization and heterogeneity. Integrating testing for HSV-2 in HIV surveillance can be useful in predicting HIV epidemic potential particularly in countries where HIV among FSWs is still limited but has potential to grow. Substantial HIV incidence occurs in HSWNs, suggesting the need for rapidly scaling up comprehensive treatment and prevention services at least for FSWs.