Cost-effectiveness of voluntary medical male circumcision for HIV prevention across sub-Saharan Africa: results from five independent models.

BACKGROUND: Voluntary medical male circumcision (VMMC) has been a recommended HIV prevention strategy in sub-Saharan Africa since 2007, particularly in countries with high HIV prevalence. However, given the scale-up of antiretroviral therapy programmes, it is not clear whether VMMC still represents a cost-effective use of scarce HIV programme resources. METHODS: Using five existing well described HIV mathematical models, we compared continuation of VMMC for 5 years in men aged 15 years and older to no further VMMC in South Africa, Malawi, and Zimbabwe and across a range of setting scenarios in sub-Saharan Africa. Outputs were based on a 50-year time horizon, VMMC cost was assumed to be US$90, and a cost-effectiveness threshold of US$500 was used. FINDINGS: In South Africa and Malawi, the continuation of VMMC for 5 years resulted in cost savings and health benefits (infections and disability-adjusted life-years averted) according to all models. Of the two models modelling Zimbabwe, the continuation of VMMC for 5 years resulted in cost savings and health benefits by one model but was not as cost-effective according to the other model. Continuation of VMMC was cost-effective in 68% of setting scenarios across sub-Saharan Africa. VMMC was more likely to be cost-effective in modelled settings with higher HIV incidence; VMMC was cost-effective in 62% of settings with HIV incidence of less than 0·1 per 100 person-years in men aged 15-49 years, increasing to 95% with HIV incidence greater than 1·0 per 100 person-years. INTERPRETATION: VMMC remains a cost-effective, often cost-saving, prevention intervention in sub-Saharan Africa for at least the next 5 years. FUNDING: Bill & Melinda Gates Foundation for the HIV Modelling Consortium.

Effects of COVID-19 Pandemic on Voluntary Medical Male Circumcision Services for HIV Prevention, Sub-Saharan Africa, 2020.

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.

Defining the Global Research and Programmatic Agenda and Priority Actions for Voluntary Medical Male Circumcision for HIV Prevention.

PURPOSE OF REVIEW: Since 2007, voluntary medical male circumcision (VMMC) programs have been associated with substantially reduced HIV incidence across 15 prioritized countries in Eastern and Southern Africa. Drawing on the programmatic experience of global VMMC leaders, this report reviews progress made in the first 15 years of the program, describes programmatic and research gaps, and presents considerations to maximize the impact of VMMC. RECENT FINDINGS: Overall, key programmatic and research gaps include a lack of robust male circumcision coverage estimates due to limitations to the data and a lack of standardized approaches across programs; challenges enhancing VMMC uptake include difficulties reaching populations at higher risk for HIV infection and men 30 years and older; limitations to program and procedural quality and safety including variations in approaches used by programs; and lastly, sustainability with limited evidence-based practices. Considerations to address these gaps include the need for global guidance on estimating coverage, conducting additional research on specific sub-populations to improve VMMC uptake, implementation of responsive and comprehensive approaches to adverse event surveillance, and diversifying financing streams to progress towards sustainability. This report's findings may help establish a global VMMC research and programmatic agenda to inform policy, research, and capacity-building activities at the national and global levels.

Consolidated Overview of Notifiable Adverse Events in the U.S. President's Emergency Plan for AIDS Relief's Voluntary Medical Male Circumcision Program Through 2020.

PURPOSE OF REVIEW: Through December 2020, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supported more than 25 million voluntary medical male circumcisions (VMMC) as part of the combined HIV prevention strategy in 15 African countries. PEPFAR monitors defined adverse events (AEs) occurring within 30 days of VMMC through its notifiable adverse event reporting system (NAERS). All NAERS reports through December 2020 were reviewed to quantify AE type, severity, and relation to the VMMC procedure. Interventions to improve client safety based on NAERS findings are described. RECENT FINDINGS: Fourteen countries reported 446 clients with notifiable adverse events (NAEs); 394/446 (88%) were determined VMMC-related, representing approximately 18 NAE reports per million circumcisions. Fatalities comprised 56/446 (13%) with 24/56 (43%) of fatalities determined VMMC-related, representing 0.96 VMMC-related fatalities per million circumcisions. The remaining 390 NAEs were non-fatal with 370/390 (95%) VMMC-related. Multiple programmatic changes have been made based on NAERS data to improve client safety. Client safety is paramount in this surgical program designed for individual and population-level benefit. Surveillance of rare but severe complications following circumcision has identified pre-existing or new safety concerns and guided continuous programmatic improvement.

HIV Incidence by Male Circumcision Status From the Population-Based HIV Impact Assessment Surveys-Eight Sub-Saharan African Countries, 2015-2017.

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 were used to compare HIV incidence by MC status in countries implementing voluntary medical MC (VMMC) programs. METHODS: Data were pooled from population-based HIV impact assessments conducted in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe from 2015 to 2017. Incidence was measured using a recent infection testing algorithm and analyzed by self-reported MC status distinguishing between medical and nonmedical 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% to 0.10%) versus 0.34% (95% CI: 0.10% to 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% to 2.39%) versus 0.55% (95% CI: 0.14% to 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.

Urethrocutaneous fistulas after voluntary medical male circumcision for HIV prevention-15 African Countries, 2015-2019.

BACKGROUND: Voluntary medical male circumcision (VMMC) is an HIV prevention strategy recommended to partially protect men from heterosexually acquired HIV. From 2015 to 2019, the President's Emergency Plan for AIDS Relief (PEPFAR) has supported approximately 14.9 million VMMCs in 15 African countries. Urethrocutaneous fistulas, abnormal openings between the urethra and penile skin through which urine can escape, are rare, severe adverse events (AEs) that can occur with VMMC. This analysis describes fistula cases, identifies possible risks and mechanisms of injury, and offers mitigation actions. METHODS: Demographic and clinical program data were reviewed from all reported fistula cases during 2015 to 2019, descriptive analyses were performed, and an odds ratio was calculated by patient age group. RESULTS: In total, 41 fistula cases were reported. Median patient age for fistula cases was 11 years and 40/41 (98%) occurred in patients aged < 15 years. Fistulas were more often reported among patients < 15 compared to ≥ 15 years old (0.61 vs. 0.01 fistulas per 100,000 VMMCs, odds ratio 50.9 (95% confidence interval [CI] = 8.6-2060.0)). Median time from VMMC surgery to appearance of fistula was 20 days (interquartile range (IQR) 14-27). CONCLUSIONS: Urethral fistulas were significantly more common in patients under age 15 years. Thinner tissue overlying the urethra in immature genitalia may predispose boys to injury. The delay between procedure and symptom onset of 2-3 weeks indicates partial thickness injury or suture violation of the urethral wall as more likely mechanisms of injury than intra-operative urethral transection. This analysis helped to inform PEPFAR's recent decision to change VMMC eligibility policy in 2020, raising the minimum age to 15 years.

Case series of glans injuries during voluntary medical male circumcision for HIV prevention - eastern and southern Africa, 2015-2018.

BACKGROUND: Male circumcision confers partial protection against heterosexual HIV acquisition among men. The President's Emergency Plan for AIDS Relief (PEPFAR) has supported > 18,900,000 voluntary medical male circumcisions (VMMC). Glans injuries (GIs) are rare but devastating adverse events (AEs) that can occur during circumcision. To address this issue, PEPFAR has supported multiple interventions in the areas of surveillance, policy, education, training, supply chain, and AE management. METHODS: Since 2015, PEPFAR has conducted surveillance of GIs including rapid investigation by the in-country PEPFAR team. This information is collected on standardized forms, which were reviewed for this analysis. RESULTS: Thirty-six GIs were reported from 2015 to 2018; all patients were < 15 years old (~ 0·7 per 100,000 VMMCs in this age group) with a decreasing annual rate (2015: 0.7 per 100,000 VMMCs; 2018: 0.4 per 100,000 VMMC; p = 0.02). Most (64%) GIs were partial or complete amputations. All amputations among 10-14 year-olds occurred using the forceps-guided (FG) method, as opposed to the dorsal-slit (DS) method, and three GIs among infants occurred using a Mogen clamp. Of 19 attempted amputation repairs, reattached tissue was viable in four (21%) in the short term. In some cases, inadequate DS method training and being overworked, were found. CONCLUSION: Following numerous interventions by PEPFAR and other stakeholders, GIs are decreasing; however, they have not been eliminated and remain a challenge for the VMMC program. Preventing further cases of complete and partial amputation will likely require additional interventions that prevent use of the FG method in young patients and the Mogen clamp in infants. Improving management of GIs is critical to optimizing outcomes.

Medically, Traditionally, and Dually Circumcised Men in Lesotho: Population-Based Measurements of HIV/STI Infections, Sexual Risk Behaviors, and Service Use Patterns.

Voluntary medical male circumcision (VMMC) is an HIV prevention priority in Lesotho, but uptake remains suboptimal. We analyzed the 2014 Lesotho Demographic and Health Survey to assess population-level social, behavioral, and serological correlates of circumcision status, specifically traditional and/or medical circumcision. Among 2931 men, approximately half were traditionally circumcised, and fewer than 25% were medically circumcised. Only 4% were dually (traditionally and medically) circumcised. In multivariate analysis, only medical circumcision emerged as significantly (p < 0.05) protective against HIV infection, whereas dual circumcision was significantly associated with past-year STI symptomology. Younger (ages 15-24), lower educated, rural-dwelling, and traditionally circumcised men, including those who never tested for HIV, had significantly lower odds of medical circumcision. Our findings indicate other unmeasured behavioral factors may mitigate VMMC's protective effect against HIV and STI infections in dually circumcised men. Further research can help identify counseling and demand creation strategies for traditionally circumcised men presenting for VMMC.

Voluntary medical male circumcision service delivery in South Africa: The economic costs and potential opportunity for private sector involvement.

BACKGROUND: In 2010, the South African Government initiated a voluntary medical male circumcision (VMMC) program as a part of the country's HIV prevention strategy based on compelling evidence that VMMC reduces men's risk of becoming HIV infected by approximately 60%. A previous VMMC costing study at Government and PEPFAR-supported facilities noted that the lack of sufficient data from the private sector represented a gap in knowledge concerning the overall cost of scaling up VMMC services. This study, conducted in mid-2016, focused on surgical circumcision and aims to address this limitation. METHODS: VMMC service delivery cost data were collected at 13 private facilities in three provinces in South Africa: Gauteng, KwaZulu-Natal, and Mpumalanga. Unit costs were calculated using a bottom-up approach by cost components, and then disaggregated by facility type and urbanization level. VMMC demand creation, and higher-level management and program support costs were not collected. The unit cost of VMMC service delivery at private facilities in South Africa was calculated as a weighted average of the unit costs at the 13 facilities. KEY FINDINGS: At the average annual exchange rate of R10.83 = $1, the unit cost including training and cost of continuous quality improvement (CQI) to provide VMMC at private facilities was $137. The largest cost components were consumables (40%) and direct labor (35%). Eleven out of the 13 surveyed private sector facilities were fixed sites (with a unit cost of $142), while one was a fixed site with outreach services (with a unit cost of $156), and the last one provided services at a combination of fixed, outreach and mobile sites (with a unit cost per circumcision performed of $123). The unit cost was not substantially different based on the level of urbanization: $141, $129, and $143 at urban, peri-urban, and rural facilities, respectively. CONCLUSIONS: The private sector VMMC unit cost ($137) did not differ substantially from that at government and PEPFAR-supported facilities ($132 based on results from a similar study conducted in 2014 in South Africa at 33 sites across eight of the countries nine provinces). The two largest cost drivers, consumables and direct labor, were comparable across the two studies (75% in private facilities and 67% in public/PEPFAR-supported facilities). Results from this study provide VMMC unit cost data that had been missing and makes an important contribution to a better understanding of the costs of VMMC service delivery, enabling VMMC programs to make informed decisions regarding funding levels and scale-up strategies for VMMC in South Africa.

Progress in voluntary medical male circumcision for HIV prevention supported by the US President's Emergency Plan for AIDS Relief through 2017: longitudinal and recent cross-sectional programme data.

OBJECTIVE: This article provides an overview and interpretation of the performance of the US President's Emergency Plan for AIDS Relief's (PEPFAR's) male circumcision programme which has supported the majority of voluntary medical male circumcisions (VMMCs) performed for HIV prevention, from its 2007 inception to 2017, and client characteristics in 2017. DESIGN: Longitudinal collection of routine programme data and disaggregations. SETTING: 14 countries in sub-Saharan Africa with low baseline male circumcision coverage, high HIV prevalence and PEPFAR-supported VMMC programmes. PARTICIPANTS: Clients of PEPFAR-supported VMMC programmes directed at males aged 10 years and above. MAIN OUTCOME MEASURES: Numbers of circumcisions performed and disaggregations by age band, result of HIV test offer, procedure technique and follow-up visit attendance. RESULTS: PEPFAR supported a total of 15 269 720 circumcisions in 14 countries in Southern and Eastern Africa. In 2017, 45% of clients were under 15 years of age, 8% had unknown HIV status, 1% of those tested were HIV+ and 84% returned for a follow-up visit within 14 days of circumcision. CONCLUSIONS: Over 15 million VMMCs have been supported by PEPFAR since 2007. VMMC continues to attract primarily young clients. The non-trivial proportion of clients not testing for HIV is expected, and may be reassuring that testing is not being presented as mandatory for access to circumcision, or in some cases reflect test kit stockouts or recent testing elsewhere. While VMMC is extremely safe, achieving the highest possible follow-up rates for early diagnosis and intervention on complications is crucial, and programmes continue to work to raise follow-up rates. The VMMC programme has achieved rapid scale-up but continues to face challenges, and new approaches may be needed to achieve the new Joint United Nations Programme on HIV/AIDS goal of 27 million additional circumcisions through 2020.

Scaling Up Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention for Adolescents and Young Adult Men: A Modeling Analysis of Implementation and Impact in Selected Countries.

Background: The new World Health Organization and Joint United Nations Programme on HIV/AIDS strategic framework for voluntary medical male circumcision (VMMC) aims to increase VMMC coverage among males aged 10-29 years in priority settings to 90% by 2021. We use mathematical modeling to assess the likelihood that selected countries will achieve this objective, given their historical VMMC progress and current implementation options. Methods: We use the Decision Makers' Program Planning Toolkit, version 2, to examine 4 ambitious but feasible scenarios for scaling up VMMC coverage from 2017 through 2021, inclusive in Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Tanzania, Uganda, and Zimbabwe. Results: Tanzania is the only country that would reach the goal of 90% VMMC coverage in 10- to 29-year-olds by the end of 2021 in the scenarios assessed, and this was true in 3 of the scenarios studied. Mozambique, South Africa, and Lesotho would come close to reaching the objective only in the most ambitious scenario examined. Conclusions: Major changes in VMMC implementation in most countries will be required to increase the proportion of circumcised 10- to 29-year-olds to 90% by the end of 2021. Scaling up VMMC coverage in males aged 10-29 years will require significantly increasing the number of circumcisions provided to 10- to 14-year-olds and 15- to 29-year-olds.

Systematic review of the effect of economic compensation and incentives on uptake of voluntary medical male circumcision among men in sub-Saharan Africa.

Voluntary medical male circumcision (VMMC) prevalence in priority countries in sub-Saharan Africa, particularly among men aged ≥20 years, has not yet reached the goal of 80% coverage recommended by the World Health Organization. Determining novel strategies to increase VMMC uptake among men ≥20 years is critical to reach HIV epidemic control. We conducted a systematic review to analyze the effectiveness of economic compensation and incentives to increase VMMC uptake among older men in order to inform VMMC demand creation programs. The review included five qualitative, quantitative, and mixed methods studies published in peer reviewed journals. Data was extracted into a study summary table, and tables synthesizing study characteristics and results. Results indicate that cash reimbursements for transportation and food vouchers of small nominal amounts to partially compensate for wage loss were effective, while enrollment into lotteries offering prizes were not. Economic compensation provided a final push toward VMMC uptake for men who had already been considering undergoing circumcision. This was in settings with high circumcision prevalence brought by various VMMC demand creation strategies. Lottery prizes offered in the studies did not appear to help overcome barriers to access VMMC and qualitative evidence suggests this may partially explain why they were not effective. Economic compensation may help to increase VMMC uptake in priority countries with high circumcision prevalence when it addresses barriers to uptake. Ethical considerations, sustainability, and possible externalities should be carefully analyzed in countries considering economic compensation as an additional strategy to increase VMMC uptake.

Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected patients with cataracts in Uganda.

BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. METHODS: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. RESULTS: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively). CONCLUSION: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients.

Prevalence of protective tetanus antibodies and immunological response following tetanus toxoid vaccination among men seeking medical circumcision services in Uganda.

INTRODUCTION: Tetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV). OBJECTIVE: To determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision. METHODS: We enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response. RESULTS: Mean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35-0.53) on day 0, 3.86IU/ml (CI 3.60-4.11) on day 14, 4.05IU/ml (CI 3.81-4.29) on day 28, and 4.48IU/ml (CI 4.28-4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years. CONCLUSION: Insufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years.

Hepatitis E Virus Seroprevalence and Correlates of Anti-HEV IgG Antibodies in the Rakai District, Uganda.

A cross-sectional study was conducted of 500 human immunodeficiency virus (HIV)-infected adults frequency matched on age, sex, and community to 500 HIV-uninfected individuals in the Rakai District, Uganda to evaluate seroprevalence of anti-hepatitis E virus (HEV) IgG antibodies. HEV seroprevalence was 47%, and 1 HIV-infected individual was actively infected with a genotype 3 virus. Using modified Poisson regression, male sex (prevalence ratios [PR] = 1.247; 95% confidence interval [CI], 1.071-1.450) and chronic hepatitis B virus infection (PR = 1.377; 95% CI, 1.090-1.738) were associated with HEV seroprevalence. HIV infection status (PR = 0.973; 95% CI, 0.852-1.111) was not associated with HEV seroprevalence. These data suggest there is a large burden of prior exposure to HEV in rural Uganda.

Longitudinal household surveillance for malaria in Rakai, Uganda.

BACKGROUND: HIV and malaria exert co-pathogenic effects. Malaria surveillance data are necessary for public health strategies to reduce the burden of disease in high HIV prevalence settings. METHODS: This was a longitudinal cohort study to assess the burden of malaria in rural Rakai, Uganda. Households were visited monthly for 1 year to identify confirmed clinical malaria (CCM), or parasitaemia with temperature >37.5 °C, and asymptomatic parasitaemia (AP). Interviews of the adult or child's caregiver and clinical and laboratory assessments were conducted. Rapid diagnostic testing for malaria and anaemia was performed if participants were febrile and anti-malarial treatment given per Uganda Ministry of Health 2010 guidelines. Blood was drawn at every household visit to assess for parasitaemia, and blood smears were assessed at the Rakai Health Science Programme laboratory. RESULTS: A total of 1640 participants were enrolled, including 975 children aged 6 months up to 10 years, 393 adult caregivers, and 272 adolescent/adult household members from 393 randomly selected households in two representative communities. 1459 (89 %) participants completed all study visits. CCM was identified in 304 (19 %) participants, with the highest incidence rate for CCM of 0.38 per person-year (ppy) identified in children <5 years, and rates decreased with age; the rates were 0.27, 0.16, and 0.09 ppy for ages 5-<10 years, 10-<18 years, and adults 18+ years, respectively. AP was identified in 943 (57 %) participants; the incidence rate was 1.99 ppy for <5 years, 2.72 ppy for 5-<10 years, 2.55 ppy for 10-<18 years, and 0.86 ppy among adults, with 92 % of cases being attributed to Plasmodium falciparum by smear. 994 (61 %) individuals had at least one positive smear; 342 (21 %) had one positive result, 203 (12 %) had two, 115 (7 %) had three, and 334 (21 %) had >3 positive smears during follow-up. Seasonal rates generally followed the rains and peaked during July, then decreased through November before increasing again. CONCLUSIONS: Plasmodium falciparum infection remains high in rural Uganda. Increased malaria control interventions should be prioritized. Trial registration Clinicaltrials.gov identifier NCT01265407.

Voluntary medical male circumcision in resource-constrained settings.

Throughout East and Southern Africa, the WHO recommends voluntary medical male circumcision (VMMC) to reduce heterosexual HIV acquisition. Evidence has informed policy and the implementation of VMMC programmes in these countries. VMMC has been incorporated into the HIV prevention portfolio and more than 9 million VMMCs have been performed. Conventional surgical procedures consist of forceps-guided, dorsal slit or sleeve resection techniques. Devices are also becoming available that might help to accelerate the scale-up of adult VMMC. The ideal device should make VMMC easier, safer, faster, sutureless, inexpensive, less painful, require less infrastructure, be more acceptable to patients and should not require follow-up visits. Elastic collar compression devices cause vascular obstruction and necrosis of foreskin tissue and do not require sutures or injectable anaesthesia. Collar clamp devices compress the proximal part of the foreskin to reach haemostasis; the distal foreskin is removed, but the device remains and therefore no sutures are required. Newer techniques and designs, such as tissue adhesives and a circular cutter with stapled anastomosis, are improvements, but none of these methods have achieved all desirable characteristics. Further research, design and development are needed to address this gap to enable the expansion of the already successful VMMC programmes for HIV prevention.

Impact of Patient-Selected Care Buddies on Adherence to HIV Care, Disease Progression, and Conduct of Daily Life Among Pre-antiretroviral HIV-Infected Patients in Rakai, Uganda: A Randomized Controlled Trial.

BACKGROUND: Data are limited on effects of household or community support persons ("care buddies") on enrollment into and adherence to pre-antiretroviral HIV care. We assessed the impact of care buddies on adherence to HIV clinic appointments, HIV progression, and conduct of daily life among pre-antiretroviral therapy (pre-ART) HIV-infected individuals in Rakai, Uganda. METHODS: A total of 1209 HIV-infected pre-ART patients aged ≥15 years were randomized to standard of care (SOC) (n = 604) or patient-selected care buddy (PSCB) (n = 605) and followed at 6 and 12 months. Outcomes were adherence to clinic visits, HIV disease progression, and self-reported conduct of daily life. Incidence and prevalence rate ratios and 95% confidence intervals (CIs) were used to assess outcomes in the intent-to-treat and as-treated analyses. RESULTS: Baseline characteristics were comparable. In the intent to treat analysis, both arms were comparable with respect to adherence to CD4 monitoring visits [adjusted prevalence risk ratio (adjPRR), 0.98; 95% CI: 0.93 to 1.04; P = 0.529], and ART eligibility (adjPRR, 1.00; 95% CI: 0.77 to 1.31; P = 0.946). Good conduct of daily life was significantly higher in the PSCB than the SOC arm (adjPRR, 1.08; 95% CI: 1.03 to 1.13; P = 0.001). More men (61%) compared with women (30%) selected spouses/partners as buddies (P < 0.0001). Twenty-two percent of PSCB arm participants discontinued use of buddies. CONCLUSIONS: In pre-ART persons, having care buddies improved the conduct of daily life of the HIV-infected patients but had no effect on HIV disease progression and only limited effect on clinic appointment adherence.

Durable Suppression of HIV-1 after Virologic Monitoring-Based Antiretroviral Adherence Counseling in Rakai, Uganda.

OBJECTIVES: HIV viral load is recommended for monitoring antiretroviral treatment and identifying treatment failure. We assessed the durability of viral suppression after viral load-triggered adherence counseling among patients with HIV viremia 6 months after ART initiation. DESIGN: Observational cohort enrolled in an antiretroviral treatment program in rural Uganda. METHODS: Participants who underwent routine viral load determination every 24 weeks and had at least 48 weeks of follow-up were included in this analysis. Patients with viral loads >400 copies/ml at 24 weeks of treatment were given additional adherence counseling, and all patients were followed to assess the duration of viral suppression and development of virologic failure. RESULTS: 1,841 participants initiating antiretroviral therapy were enrolled in the Rakai Health Sciences Program between June 2005 and June 2011 and were followed with viral load monitoring every 24 weeks. 148 (8%) of patients did not achieve viral suppression at 24 weeks and were given additional adherence counseling. 85 (60%) of these patients had undetectable viral loads at 48 weeks, with a median duration of viral suppression of 240 weeks (IQR 193-288 weeks). Failure to achieve an undetectable viral load at 48 weeks was associated with age <30 years and 24 week viral load >2,000 copies/ml in multivariate logistic regression analysis. CONCLUSIONS: The majority of patients with persistent viremia who were provided adherence counseling achieved robust viral suppression for a median 4.6 years. Access to virologic monitoring and adherence counseling is a priority in resource-limited settings.

CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa.

BACKGROUND: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. METHODS: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/ml in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. RESULTS: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517­541] in North America, 494/ml (95% CI: 429­559) in West Africa, 515/ml (95% CI: 508­522) in Southern Africa, 503/ml (95% CI: 478­528) in Asia and 437/ml (95% CI: 425­449) in East Africa. CONCLUSIONS: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.