Oral pre-exposure prophylaxis (PrEP) reduces HIV acquisition risk from sex by 99% and from injection drug use by ≥74% when used as recommended. The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a goal of 21.2 million persons using (initiating or continuing) PrEP globally in 2025. In 2016, CDC, with the U.S. President's Emergency Plan for AIDS Relief, joined ministries of health to implement PrEP globally. PrEP is beneficial for persons at substantial risk for acquiring HIV, including but not limited to key populations, which include female sex workers, men who have sex with men, persons in prisons and other enclosed settings, persons who inject drugs, and transgender persons. Annual country targets were used to guide scale-up. In 2023, CDC supported 856,816 PrEP initiations, which represents nearly one quarter of the 3.5 million persons globally who either initiated or continued PrEP that year. During 2017-2023, CDC supported PrEP initiations for 2,278,743 persons, 96.0% of whom were in sub-Saharan Africa. More than one half (64.0%) were female and 44.9% were aged 15-24 years. Overall, CDC achieved 118.7% of its PrEP initiation targets for the 7-year period. Among PrEP initiations for key populations, the majority in sub-Saharan Africa were female sex workers, whereas in Southeast Asia, Eurasia, and the Americas, the majority were men who have sex with men. Continued rapid scale-up is needed to meet the UNAIDS goal to end HIV as a public health threat.

INTRODUCTION: Voluntary medical male circumcision (VMMC) reduces the risk of heterosexual acquisition of HIV by 50%-60%. The Uganda Ministry of Health recommends abstinence of sex for 42 days after VMMC to allow complete wound healing. However, some men resume sex early before the recommended period. We estimated trends in prevalence and risk factors of early sex resumption (ESR) among VMMC clients in Rakai, Uganda, from 2013-2020. METHODS: Data from the Rakai Community Cohort Study (RCCS), a cross-sectional study, were analyzed. Data included consenting males aged 15-49 years in RCCS who self-reported having received VMMC between the period of 2013 to 2020. ESR prevalence and associated risk factors were assessed using modified Poisson regression to estimate adjusted prevalence ratios (aPR). RESULTS: Overall, 1,832 participants were included in this study. ESR decreased from 45.1% in 2013 to 14.9% in 2020 (p<0.001). Across the first three surveys, ESR prevalence was consistently higher among the married participants than the never married participants, aPR = 1.83, 95% CI: [1.30,2.57]; aPR = 2.46, 95% CI: [1.50,4.06]; aPR = 2.22, 95% CI: [1.22,4.03]. ESR prevalence was higher among participants who reported to have more than one sexual partner than participants with one partner, aPR = 1.59, 95% CI: [1.16,2.20]. In the fourth survey from 2018-2020, ESR prevalence was significantly higher among participants with primary education than participants with post-primary, aPR = 2.38, 95% CI: [1.31, 4.30]. However, ESR prevalence was lower among participants aged at least 45 years than participants aged 15-19 years, aPR = 0.0, 95% CI: [1.86e-07, 2.69e-06]. Overall, participants who reported primary school as their highest level of education reported ESR more often than those with post-primary education aPR = 2.38, 95% CI: [1.31, 4.30]. Occupation and known HIV status were not associated with ESR. CONCLUSIONS: Self-reported ESR after VMMC declined between 2013 and 2020. Targeted efforts for counseling focusing on married men, men who had multiple sex partners, and men with lower levels of education may decrease ESR.

BACKGROUND: Injection Drug use is associated with increased HIV risk behaviour that may result in the transmission of HIV and poor access to HIV prevention and treatment. In 2020, Uganda introduced the 'medication for opioid use disorder (MOUD) treatment' for People who inject drugs (PWID). We analysed the 12-month retention and associated factors among PWID enrolled on MOUD treatment in Kampala, Uganda. METHODS: We conducted a retrospective analysis of 343 PWID with OUD who completed 14 days of methadone induction from September 2020 to July 2022. Retention was defined as the number of individuals still in the programme divided by the total number enrolled, computed at 3-, 6-, 9-, and 12 months using lifetable and Kaplan-Meier survival analyses. Cox proportional regression analyses were conducted to assess factors associated with retention in the programme in the first 12 months. RESULTS: Overall, 243 (71%) of 343 participants stabilized at a methadone dose of 60 mg or more. The majority of participants were males (n = 284, 82.8%), and the median (interquartile range, IQR) age was 31 (26-38) years. Most participants (n = 276, 80.5%) lived 5 km or more away from the MOUD clinic. Thirty (8.8%) were HIV-positive, 52 (15.7%) had a major mental illness and 96 (27.9%) had a history of taking alcohol three months before enrollment. The cumulative retention significantly declined from 83.4% (95%CI = 79.0-87.0) at 3months to 71.9% (95%CI = 67.2-76.6) at 6months, 64% 95%CI = 58.7-68.9) at 9months, and 55.2%; 95% CI (49.8-60.3% at 12months. The 12-month retention was significantly higher for participants on methadone doses of 60 mg or more (adj.HR = 2.1, 95%CI = 1.41-3.22), while participants resident within 5 km of the MOUD clinic were 4.9 times more likely to be retained at 12 months, compared to those residing 5 km or more, (adj. HR = 4.81, 95%CI = 1.54-15). Other factors, including predisposing, need, and enabling factors, were not associated with retention. CONCLUSION: Our study demonstrates acceptable 12-month retention rates for people who inject drugs, comparable to previous studies done in both developing and developed countries. Sustaining and improving retention may require enhanced scaling up of MOUD dose to an optimal level in the first 14 days and reducing the distance between participant locale and MOUD clinics.

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.

Introduction: Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including bar work and transportation. However, data on changes in prevalence of untreated HIV infection and HIV incidence within occupations following rollout of antiretroviral therapy and voluntary medical male circumcision programs in 2004 are limited. Method(s): We evaluated 12 rounds of survey data collected between 1999-2016, from the Rakai Community Cohort Study, a population-based study of adolescents and adults 15-49 years in Uganda, to assess changes in the prevalence of untreated HIV infection and incidence by self-reported primary occupation. Adjusted prevalence risk ratios (adjPRR) for untreated HIV and incidence rate ratios for HIV incidence with 95% confidence intervals (CIs) were estimated using Poisson regression. Primary outcomes were stratified by gender and HIV incidence compared over three time periods (1999-2004; 2005-2011; 2011-2016) representing, respectively, the period prior to scale up of combined HIV prevention and treatment, the scale up period, and full implementation. Result(s): 33,866 individuals, including 19,113 (56%) women participated. Of these participants, 17,840 women and 14,244 men who were HIV-negative at their first study visit contributed 57,912 and 49,403 person-years of follow-up, respectively. Agriculture was the most common occupation at all study visits, though its prevalence declined from 39 to 29% among men and from 61 to 40% among women between 1999 and 2016. Untreated HIV infection substantially declined between 1999 and 2016 across most occupational subgroups, including by 70% among men (12 to 4.2%; adjPRR=0.30; 95%CI:0.23-0.41) and by 78% among women working in agriculture (14.7 to 4.0%; adjPRR=0.22; 95%CI:0.18-0.27), along with increasing antiretroviral therapy coverage. Exceptions included men working in transportation and women working in tailoring/laundry services. HIV incidence declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers or men working in transportation. Conclusion(s): Untreated HIV infection and HIV incidence have declined in most occupational sub-groups in Rakai, Uganda. However, women working in bars and restaurants and men working in transportation continue to have relatively high burden of untreated HIV and HIV incidence, and as such should be considered key priority populations for targeted HIV programming. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

In 2007, voluntary medical male circumcision (VMMC) was endorsed by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS after it was found to be associated with approximately a 60% reduction in the risk for female-to-male transmission of HIV (1). As a result of this endorsement, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), through partnerships with U.S. government agencies, including CDC, the U.S. Department of Defense, and the U.S. Agency for International Development, started supporting VMMCs performed in prioritized countries in southern and eastern Africa. During 2010-2016, CDC supported 5,880,372 VMMCs in 12 countries (2,3). During 2017-2021, CDC supported 8,497,297 VMMCs performed in 13 countries. In 2020, the number of VMMCs performed declined 31.8% compared with the number in 2019, primarily because of COVID-19-related disruptions to VMMC service delivery. PEPFAR 2017-2021 Monitoring, Evaluation, and Reporting data were used to provide an update and describe CDC's contribution to the scale-up of the VMMC program, which is important to meeting the 2025 Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 90% of males aged 15-59 years having access to VMMC services in prioritized countries to help end the AIDS epidemic by 2030 (4).

Beginning in March 2020, to reduce COVID-19 transmission, the US President's Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic.

BACKGROUND: Male circumcision (MC) offers men lifelong partial protection from heterosexually-acquired HIV infection. The impact of MC on HIV incidence has not been quantified in nationally-representative samples. Data from the Population-based HIV Impact Assessments (PHIAs) were used to compare incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from PHIAs conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia and Zimbabwe from 2015-2017. Incidence was measured using a recent infection testing algorithm, and analyzed by self-reported MC status distinguishing between medical and non-medical MC. Country, marital status, urban setting, sexual risk behaviors, and mean population HIV viral load among women as an indicator of treatment scale-up were included in a random effects logistic regression model using pooled survey weights. Analyses were age-stratified (15-34 and 35-59 years). Annualized incidence rates and 95% confidence intervals (CIs) and incidence differences were calculated between medically circumcised and uncircumcised men. RESULTS: Men 15-34 years reporting medical MC had lower HIV incidence than uncircumcised men (0.04% [95% CI: 0.00, 0.10%] versus 0.34% [95% CI: 0.10, 0.57%], respectively; p-value = 0.01); whereas among men 35-59 years, there was no significant incidence difference (1.36% [95% CI: 0.32, 2.39%] versus 0.55% [95% CI: 0.14, 0.67%], respectively; p-value = 0.14). DISCUSSION: Medical MC was associated with lower HIV incidence in men aged 15-34 years in nationally-representative surveys in Africa. These findings are consistent with the expected ongoing VMMC program impact and highlight the importance of VMMC for the HIV response in Africa.

BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for HIV prevention in men was demonstrated in three randomized trials. This led to the adoption of VMMC as an integral component of the President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda were followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised versus uncircumcised men. RESULTS: 3,916 non-Muslim men were followed for 17,088 person-years (py). There were 1338 newly reported VMMCs (9.8/100 py). Over the study period, the median age of men adopting VMMC declined from 28 years (IQR 21-35) to 22 years (IQR 18-29; p-trend <0.001). HIV incidence was 0.40/100 py (20/4992.8 py) among newly circumcised men and 0.98/100 py (118/12095.1 py) among uncircumcised men with an adjusted IRR of 0.47 (95%CI: 0.28-0.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV-acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) programmes have been initiated in sub-Saharan Africa to prevent HIV acquisition in key populations at increased risk. However, data on PrEP uptake and retention in high-risk African communities are limited. We evaluated PrEP uptake and retention in HIV hyperendemic fishing villages and trading centres in south-central Uganda between April 2018 and March 2019. METHODS: PrEP eligibility was assessed using a national risk screening tool. Programme data were used to evaluate uptake and retention over 12 months. Multivariable modified Poisson regression estimated adjusted prevalence ratios (aPR) and 95% Confidence intervals (CIs) of uptake associated with covariates. We used Kaplan-Meier analysis to estimate retention and multivariable Cox regression to estimate adjusted relative hazards (aRH) and 95% CIs of discontinuation associated with covariates. RESULTS AND DISCUSSION: Of the 2985 HIV-negative individuals screened; 2750 (92.1 %) were eligible; of whom 2,536 (92.2%) accepted PrEP. Male (aPR = 0.91, 95% CI = 0.85 to 0.97) and female (aPR = 0.85, 95% CI = 0.77 to 0.94) fisher folk were less likely to accept compared to HIV-discordant couples. Median retention was 45.4 days for both men and women, whereas retention was higher among women (log rank, p < 0.001) overall. PrEP discontinuation was higher among female sex workers (aRH = 1.42, 95% CI = 1.09 to 1.83) and female fisher folk (aRH = 1.99, 95% CI = 1.46 to 2.72), compared to women in discordant couples. Male fisher folk (aRH = 1.37, 95% CI = 1.07 to 1.76) and male truck drivers (aRH = 1.49, 95% CI = 1.14 to 1.94) were more likely to discontinue compared to men in discordant couples. Women 30 to 34 years tended to have lower discontinuation rates compared to adolescents 15 to 19 years (RH = 0.78 [95% CI = 0.63 to 0.96]). CONCLUSIONS: PrEP uptake was high, but retention was very low especially among those at the highest risk of HIV: fisher folk, sex workers and truck drivers and adolescent girls. Research on reasons for PrEP discontinuation could help optimize retention.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the largest bilateral funder of human immunodeficiency virus (HIV) prevention and control programs worldwide, currently supports implementation of preexposure prophylaxis (PrEP) to reduce HIV incidence among persons at substantial risk for infection, including female sex workers, men who have sex with men (MSM), and transgender women (hereafter referred to as key populations). Recent estimates suggest that 54% of all global new HIV infections in 2018 occurred among key populations and their sexual partners (1). In 2016, PEPFAR began tracking initiation of PrEP by key populations and other groups at high risk (2). The implementation and scale-up of PrEP programs across 35 PEPFAR-supported country or regional programs* was assessed by determining the number of programs reporting any new PrEP clients during each quarter from October 2016 to September 2018. As of September 2018, only 15 (43%) PEPFAR-supported country or regional programs had implemented PrEP programs; however, client volume increased by 3,351% over the assessment period in 15 country or regional programs. Scale-up of PrEP among general population clients (5,255%) was nearly three times that of key population clients (1,880%). Among key populations, the largest increase (3,518%) occurred among MSM. Factors that helped drive the success of these PrEP early adopter programs included initiation of national, regional, and multilateral stakeholder meetings; engagement of ministries of health and community advocates; revision of HIV treatment guidelines to include PrEP; training for HIV service providers; and establishment of drug procurement policies. These best practices can help facilitate PrEP implementation, particularly among key populations, in other country or regional programs to reduce global incidence of HIV infection.

BACKGROUND: Targeting combination HIV interventions to locations and populations with high HIV burden is a global priority, but the impact of these strategies on HIV incidence is unclear. We assessed the impact of combination HIV interventions on HIV incidence in four HIV-hyperendemic communities in Uganda. METHODS: We did an open population-based cohort study of people aged 15-49 years residing in four fishing communities on Lake Victoria. The communities were surveyed five times to collect self-reported demographic, behavioural, and service-uptake data. Free HIV testing was provided at each interview, with referral to combination HIV intervention services as appropriate. From November, 2011, combination HIV intervention services were rapidly expanded in these geographical areas. We evaluated trends in HIV testing coverage among all participants, circumcision coverage among male participants, antiretroviral therapy (ART) coverage and HIV viral load among HIV-positive participants, and sexual behaviours and HIV incidence among HIV-negative participants. FINDINGS: From Nov 4, 2011, to Aug 16, 2017, data were collected from five surveys. Overall, 8942 participants contributed 20 721 person-visits; 4619 (52%) of 8942 participants were male. HIV prevalence was 41% (1598 of 3870) in the 2011-12 baseline survey and declined to 37% (1740 of 4738) at the final survey (p<0.0001). 3222 participants who were HIV-negative at baseline, and who had at least one repeat visit, contributed 9477 person-years of follow-up, and 230 incident HIV infections occurred. From the first survey in 2011-12 to the last survey in 2016-17, HIV testing coverage increased from 68% (2613 of 3870) to 96% (4526 of 4738; p<0.0001); male circumcision coverage increased from 35% (698 of 2011) to 65% (1630 of 2525; p<0.0001); ART coverage increased from 16% (254 of 1598) to 82% (1420 of 1740; p<0.0001); and population HIV viral load suppression in all HIV-positive participants increased from 34% (546 of 1596) to 80% (1383 of 1734; p<0.0001). Risky sexual behaviours did not decrease over this period. HIV incidence decreased from 3.43 per 100 person-years (95% CI 2.45-4.67) in 2011-12 to 1.59 per 100 person-years (95% CI 1.19-2.07) in 2016-17; adjusted incidence rate ratio (IRR) 0.52 (95% CI 0.34-0.79). Declines in HIV incidence were similar among men (adjusted IRR 0.53, 95% CI 0.30-0.93) and women (0.51, 0.27-0.96). The risk of incident HIV infection was lower in circumcised men than in uncircumcised men (0.46, 0.32-0.67). INTERPRETATION: Rapid expansion of combination HIV interventions in HIV-hyperendemic fishing communities is feasible and could have a substantial impact on HIV incidence. However, incidence remains higher than HIV epidemic control targets, and additional efforts will be needed to achieve this global health priority. FUNDING: The National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Development, the National Cancer Institute, the National Institute for Allergy and Infectious Diseases Division of Intramural Research, Centers for Disease Control and Prevention Uganda, Karolinska Institutet, and the Johns Hopkins University Center for AIDS Research.

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged >/=10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for >/=3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).