A qualitative study of influences on the uptake of contraceptive services among people of reproductive age in Uganda.

BACKGROUND: Uganda has registered an increased investment in family planning (FP) programs, which has contributed to improvement in knowledge of modern contraceptive methods being nearly universal. However, this has not matched the uptake of modern methods or the reduction in the unmet need for FP. This may be explained by the different influences which include health workers, family, and friends. Due to the limited uptake of contraceptive methods, a program on improving awareness, access to, and uptake of modern contraceptives is being implemented in selected regions in Uganda. We, therefore, conducted a formative study to determine the influences on contraceptive uptake at the onset of this program. METHODS: Using a qualitative study design, we conducted thirty-two focus group discussions and twenty-one in-depth interviews involving men and women of reproductive age. We also carried out twenty-one key informant interviews with people involved in FP service delivery. Data was collected in four districts where implementation of the program was to take place. Audio recorders were used to collect data and tools were translated into local languages. A codebook was developed, and transcripts were coded in vivo using the computer software Atlas-ti version 7 before analysis. Ethical clearance was obtained from institutional review boards and informed consent was sought from all participants. RESULTS: From the study, most married people mentioned health workers as their main influence while adolescents reported their peers and friends. Religious leaders and mothers-in-law were reported to mainly discourage people from taking up modern contraceptive methods. The cultural value attached to having many children influenced the contraceptive use decision among people in rural settings. Other influences included a person's experience and housing. CONCLUSIONS: Health workers, religious leaders, and mothers determine the uptake of contraceptive services. The study recommends the consideration of the role of these influences in the design of FP program interventions as well as more involvement of health workers in sensitization of communities about contraceptive methods.

Knowledge on voluntary medical male circumcision in a low uptake setting in northern Uganda.

BACKGROUND: Free VMMC services have been available in Uganda since 2010. However, uptake in Northern Uganda remains disproportionately low. We aimed to determine if this is due to men's insufficient knowledge on VMMC, and if women's knowledge on VMMC has any association with VMMC status of their male sexual partners. METHODS: In this cross sectional study, participants were asked their circumcision status (or that of their male sexual partner for female respondents) and presented with 14 questions on VMMC benefits, procedure, risk, and misconceptions. Chi square tests or fisher exact tests were used to compare circumcision prevalence among those who gave correct responses versus those who failed to and if p < 0.05, the comparison groups were balanced with propensity score weights in modified poisson models to estimate prevalence ratios, PR. RESULTS: A total of 396 men and 50 women were included in the analyses. Circumcision was 42% less prevalent among males who failed to reject the misconception that VMMC reduces sexual performance (PR = 0.58, 95% CI 0.38-0.89, p = 0.012), and less prevalent among male sexual partners of females who failed to reject the same misconception (PR = 0.22, 95% CI = 0.07-0.76, p = 0.016). Circumcision was also 35% less prevalent among male respondents who failed to reject the misconception that VMMC increases a man's desire for more sexual partners i.e. promiscuity (PR = 0.65, 95% CI = 0.46-0.92, p = 0.014). CONCLUSION: Misconceptions regarding change in sexual drive or performance were associated with circumcision status in this population, while knowledge of VMMC benefits, risks and procedure was not.

Randomised trial of early infant circumcision performed by clinical officers and registered nurse midwives using the Mogen clamp in Rakai, Uganda.

OBJECTIVES: To assess the safety and acceptability of early infant circumcision (EIC) provided by trained clinical officers (COs) and registered nurse midwives (RNMWs) in rural Uganda. SUBJECTS AND METHODS: We conducted a randomised trial of EIC using the Mogen clamp provided by newly trained COs and RNMWs in four health centres in rural Rakai, Uganda. The trial was registered with clinicaltrials.gov # NCT02596282. In all, 501 healthy neonates aged 1-28 days with normal birth weight and gestational age were randomised to COs (n = 256) and RNMWs (n = 245) for EIC, and were followed-up at 1, 7 and 28 days. RESULTS: In all, 701 mothers were directly invited to participate in the trial, 525 consented to circumcision (74.9%) and 23 were found ineligible on screening (4.4%). The procedure took an average of 10.5 min. Adherence to follow-up was >90% at all scheduled visits. The rates of moderate/severe adverse events were 2.4% for COs and 1.6% for RNMWs (P = 0.9). All wounds were healed by 28 days after circumcision. Maternal satisfaction with the procedure was 99.6% for infants circumcised by COs and 100% among infants circumcised by RNMWs. CONCLUSIONS: EIC was acceptable in this rural Ugandan population and can be safely performed by RNMWs who have direct contact with the mothers during pregnancy and delivery. EIC services should be made available to parents who are interested in the service.

Efficacy of knowledge and competence-based training of non-physicians in the provision of early infant male circumcision using the Mogen clamp in Rakai, Uganda.

OBJECTIVE: To assess acquisition of knowledge and competence in performing Early Infant Male Circumcision (EIMC) by non-physicians trained using a structured curriculum. SUBJECTS AND METHODS: Training in provision of EIMC using the Mogen clamp was conducted for 10 Clinical Officers (COs) and 10 Registered Nurse Midwives (RNMWs), in Rakai, Uganda. Healthy infants whose mothers consented to study participation were assigned to the trainees, each of whom performed at least 10 EIMCs. Ongoing assessment and feedback for competency were done, and safety assessed by adverse events. RESULTS: Despite similar baseline knowledge, COs acquired more didactic knowledge than RNMWs (P = 0.043). In all, 100 EIMCs were assessed for gain in competency. The greatest improvement in competency was between the first and third procedures, and all trainees achieved 80% competency and retention of skills by the seventh procedure. The median (interquartile range) time to complete a procedure was 14.5 (10-47) min for the COs, and 15 (10-50) min for the RNMWs (P = 0.180). The procedure times declined by 2.2 min for each subsequent EIMC (P = 0.005), and rates of improvement were similar for COs and RNMWs. Adverse events were comparable between providers (3.5%), of which 1% were of moderate severity. CONCLUSION: Competence-based training of non-physicians improved knowledge and competency in EIMC performed by COs and RNMWs in Uganda.

Impact of an integrated community case management programme on uptake of appropriate diarrhoea and pneumonia treatments in Uganda: A propensity score matching and equity analysis study.

INTRODUCTION: Pneumonia and diarrhoea disproportionately affect children in resource-poor settings. Integrated community case management (iCCM) involves community health workers treating diarrhoea, pneumonia and malaria. Studies on impact of iCCM on appropriate treatment and its effects on equity in access to the same are limited. The objective of this study was to measure the impact of integrated community case management (iCCM) as the first point of care on uptake of appropriate treatment for children with a classification of pneumonia (cough and fast breathing) and/or diarrhoea and to measure the magnitude and distribution of socioeconomic status related inequality in use of iCCM. METHODS: Following introduction of iCCM, data from cross-sectional household surveys were examined for socioeconomic inequalities in uptake of treatment and use of iCCM among children with a classification of pneumonia or diarrhoea using the Erreygers' corrected concentration index (CCI). Propensity score matching methods were used to estimate the average treatment effects on the treated (ATT) for children treated under the iCCM programme with recommended antibiotics for pneumonia, and ORS plus or minus zinc for diarrhoea. FINDINGS: Overall, more children treated under iCCM received appropriate antibiotics for pneumonia (ATT = 34.7%, p < 0.001) and ORS for diarrhoea (ATT = 41.2%, p < 0.001) compared to children not attending iCCM. No such increase was observed for children receiving ORS-zinc combination (ATT = -0.145, p < 0.05). There were no obvious inequalities in the uptake of appropriate treatment for pneumonia among the poorest and least poor (CCI = -0.070; SE = 0.083). Receiving ORS for diarrhoea was more prevalent among the least poor groups (CCI = 0.199; SE = 0.118). The use of iCCM for pneumonia was more prevalent among the poorest groups (CCI = -0.099; SE = 0.073). The use of iCCM for diarrhoea was not significantly different among the poorest and least poor (CCI = -0.073; SE = 0.085). CONCLUSION: iCCM is a potentially equitable strategy that significantly increased the uptake of appropriate antibiotic treatment for pneumonia and ORS for diarrhoea, but not the uptake of zinc for diarrhoea. For maximum impact, interventions increasing zinc uptake should be considered when scaling up iCCM programmes.

Male circumcision wound healing in human immunodeficiency virus (HIV)-negative and HIV-positive men in Rakai, Uganda.

OBJECTIVE: To assess completed wound healing after medical male circumcision (MMC) among human immunodeficiency virus (HIV)-negative and HIV-positive men with cluster of differentiation 4 (CD4) counts of <350 and ≥350 cells/mm(3) , as minimal data are available on the safety of MMC among HIV-positive men with low CD4 counts. PATIENTS AND METHODS: In all, 262 HIV-negative and 177 HIV-positive consenting males aged ≥12 years accepted MMC using the dorsal slit procedure and were enrolled in the study. Socio-demographic and behavioural data and blood for HIV testing and CD4 counts were collected at baseline. Participants were followed weekly to collect information on resumption of sex, condom use and both self-reported and clinically assessed wound healing. The proportions healed among HIV-positive men were compared with HIV-negative men. Time to complete wound healing was assessed by Kaplan-Meier survival analysis. RESULTS: There were no statistically significant differences in the proportion of men healed by HIV status. At 4 weeks, the proportions healed were 85.9% in HIV-negative men, 77.4% in HIV-positive men with a CD4 count of ≥350 cells/mm(3) and 87.1% in HIV-positive men with a CD4 count of <350 cells/mm(3) . The median time to healing was 4 weeks and did not vary by HIV or CD4 status. All men had certified complete wound healing at 6 weeks after MMC. In all, 1.4% of HIV-positive men with a CD4 count of <350 cells/mm(3) resumed sex before healing, compared with 8.5% among HIV-positive men with a CD4 count of ≥350 cells/mm(3) (P = 0.052) and 7.8% (P = 0.081) among HIV-negative men. CONCLUSION: Inclusion of HIV-positive men with low CD4 counts in MMC services is not deleterious to postoperative wound healing.

Family planning service disruptions in the first two years of the COVID-19 pandemic: Evidence from health facilities in seven low- and middle-income countries.

Many speculated that COVID-19 would severely restrict the delivery of essential health services, including family planning (FP), but evidence of this impact is limited, partly due to data limitations. We use cross-sectional data collected from regional and national samples of health facilities (n = 2,610) offering FP across seven low- and middle-income countries (LMICs) between 2019 and 2021, with longitudinal data from four geographies, to examine reported disruptions to the FP service environment during COVID-19, assess how these disruptions varied according to health system characteristics, and evaluate how disruptions evolved throughout the first two years of the pandemic, relative to a pre-pandemic period. Findings show significant variation in the impact of COVID-19 on facility-based FP services across LMICs, with the largest disruptions to services occurring in Rajasthan, India, where COVID-19 cases were highest among geographies sampled, while in most sub-Saharan African settings there were limited disruptions impacting FP service availability, method provision, and contraceptive supplies. Facility-reported disruptions to care were not reflected in observed changes to the number of FP clients or types of stockouts experienced in the first two years of the pandemic. Public and higher-level facilities were generally less likely to experience COVID-19-related disruptions to FP services, suggesting policy mitigation measures-particularly those implemented among government-operated health facilities-may have been critical to ensuring sustained delivery of reproductive healthcare during the pandemic.

A qualitative exploration of reproductive coercion experiences and perceptions in four geo-culturally diverse sub-Saharan African settings.

Reproductive coercion (RC) is any intentional behavior that interferes with another's reproductive decision-making or pregnancy outcome. This study aims to qualitatively examine RC experiences and perceptions among women and men in Ethiopia, Nigeria (Kano and Anambra States), and Uganda. This is a secondary analysis utilizing qualitative data from the Women's and Girls' Empowerment in Sexual and Reproductive Health study. Across sites, focus group discussions (38 groups; n=320 participants) and in-depth interviews (n=120) were conducted, recorded, and transcribed. Transcripts were loaded into Atlas.ti, and quotes describing experiences of reproductive control or abuse were coded as "reproductive coercion." RC quotes were input into a matrix for thematic analysis. Emergent RC themes included indirect reproductive pressures, direct family planning interference, concurrent experiences of violence, and responses to RC. Indirect reproductive pressures included tactics to both promote and prevent pregnancy, while direct interference centered on pregnancy promotion. Women who were not compliant with their partners' reproductive demands were often subjected to violence from multiple actors (i.e., parents, in-laws, community members) in addition to their partners. Despite concurrent forms of violence, women across sites resisted RC by using contraceptives covertly, choosing to abort, or leaving their abusive partnerships. Women and men across sites indicated that men were highly influential in fertility. RC behaviors were a mechanism of control over desired reproductive outcomes, which were often rooted in perceptions of childbearing as social status. Findings indicate a need for more nuanced community interventions targeting social norms, as well as improved RC screening and response within health services.

Epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli at the human-animal-environment interface in a farming community of central Uganda.

BACKGROUND: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) represents a significant global public health concern. The epidemiology of ESBL-Ec in Uganda is not well understood although it is harbored by humans, animals, and the environment. This study explains the epidemiology of ESBL-Ec using a one health approach in selected farming households in Wakiso district, Uganda. METHODOLOGY: Environmental, human, and animal samples were collected from 104 households. Additional data were obtained using observation checklists and through interviews with household members using a semi-structured questionnaire. Surface swabs, soil, water, human and animal fecal samples were introduced onto ESBL chromogenic agar. The isolates were identified using biochemical tests and double-disk synergy tests. To assess associations, prevalence ratios (PRs) were computed using a generalized linear model (GLM) analysis with modified Poisson and a log link with robust standard errors in R software. RESULTS: Approximately 83% (86/104) households had at least one positive ESBL-Ec isolate. The overall prevalence of ESBL-Ec at the human-animal-environment interface was approximately 25.0% (95% CI: 22.7-28.3). Specifically, humans, animals and the environment had an ESBL-Ec prevalence of 35.4%, 55.4%, and 9.2% respectively. Having visitors (adj PR = 1.19, 95% CI: 1.04-1.36), utilizing veterinary services (adj PR = 1.39, 95% CI: 1.20-1.61) and using animal waste for gardening (adj PR = 1.29, 95% CI: 1.05-1.60) were positively associated with household ESBL-Ec contamination. Covering the drinking water container with a lid (adj PR = 0.84 95% CI: 0.73-0.96) was associated with absence of ESBL-Ec in a household. CONCLUSION: There is wider dissemination of ESBL-Ec in the environment, humans, and animals, indicating poor infection prevention and control (IPC) measures in the area. Improved collaborative one health mitigation strategies such as safe water chain, farm biosecurity, household and facility-based IPC measures are recommended to reduce the burden of antimicrobial resistance at community level.

Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda.

BACKGROUND: Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. METHODS: In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878. FINDINGS: During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63-0·93, p=0·008). INTERPRETATION: Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important. FUNDING: The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

Use of a mixture of lignocaine and bupivacaine vs lignocaine alone for male circumcision under local anaesthesia in Rakai, Uganda.

OBJECTIVE: To assess self-reported pain control during and after surgery with a mixture of lignocaine and bupivacaine compared with lignocaine alone among male circumcision (MC) service recipients in Rakai, Uganda. PATIENTS AND METHODS: The two formulations of local anaesthesia for MC were used alternatively at weekly intervals in 360 patients; 179 received lignocaine alone and 181 received the lignocaine and bupivacaine mixture (LBmix). The proportions of men reporting pain during or after surgery, and the need for additional anaesthesia during surgery were determined for the LBmix vs lignocaine using Poisson adjusted rate ratios (RRs). Characteristics including age, weight, surgeon (medical officer vs clinical officer), surgical method and duration of surgery were compared between the arms using two-sample t-tests and chi-square tests. RESULTS: Patient and provider characteristics were comparable between the two anaesthetic groups. A higher proportion of patients reported pain during surgery in the lignocaine group (adjusted RR 11.6, 95% confidence interval [CI] 3.5-37.9, P < 0.001), required additional anaesthesia (adjusted RR 4.8, 95% CI 1.4-17.1, P = 0.015), and were more likely to report pain during the immediate postoperative period (adjusted RR 3.4, 95% CI 2.3-5.0, P < 0.001). These differences were particularly marked among patients with MC times longer than the median (adjusted RR 13.4, 95% CI 3.1-57.0, P < 0.001). CONCLUSION: The LBmix significantly reduced pain associated with MC and the need for additional anaesthesia during MC.

DMPA-SC stock: Cross-site trends by facility type.

Objectives: To measure trends in the supply of DMPA-SC in public and private health facilities and compare with other prominent modern methods. Study design: We used repeated cross-sectional data from service-delivery-point surveys in six settings: Burkina Faso, Democratic Republic of Congo (Kinshasa and Kongo Central), Nigeria (Kano and Lagos), and Uganda, each with 3-5 rounds of data collected between 2016 and 2020. We analyzed trends in DMPA-SC availability using percent of service delivery points offering the method and percent experiencing stockouts; trends were compared with those for DMPA-IM, IUD, implants, and other short-acting methods, by facility type. Results: All settings showed increased offering of DMPA-SC over time for both private and public facilities. Larger proportions of public facilities provided DMPA-SC compared to private facilities (66%-97% vs 16%-50% by 2019-2020). DMPA-SC was provided by fewer facilities than DMPA-IM (90%-100% public, 34%-69% private by 2019-2020), but comparable to implants (83%-100% public, 15%-52% private by 2019-2020) and IUDs (55%-91% public, 0%-44% private by 2019-2020). Trends of DMPA-SC stock varied by setting, with more consistent stock available in private facilities in the DRC and in public facilities in Burkina Faso and Nigeria. Uganda showed decreasing stock in public facilities but increasing stock in private facilities. Conclusion: DMPA-SC availability has been increasing since its introduction in sub-Saharan Africa, yet significant gaps in stock exist. Countries should consider alternative distribution models to address these issues. Implications: Our findings may help inform countries about the need to monitor DMPA-SC availability and to consider solutions that ensure contraceptive options are available to women who need them and disruptions to contraceptive use are minimized.

Do users of long-acting reversible contraceptives receive the same counseling content as other modern method users? A cross-sectional, multi-country analysis of women's experiences with the Method Information Index in six sub-Saharan African countries.

Objective: There has been a growing focus on informed choice in contraceptive research. Because removal of long-acting reversible contraception (LARC), including implants and IUDs, requires a trained provider, ensuring informed choice in the adoption of these methods is imperative. We sought to understand whether information received during contraceptive counseling differed among women using LARC and those using other modern methods of contraception. Study Design: We used cross-sectional data from Burkina Faso, Côte d'Ivoire, the Democratic Republic of Congo (DRC), Kenya, Nigeria, and Uganda collected in 2019-2020 by the Performance Monitoring for Action project. We included 7969 reproductive-aged women who reported use of modern contraception. Our outcome of interest, information received during contraceptive counseling, was measured using a binary indicator of whether respondents answered "yes" to all 4 questions that make up the Method Information Index Plus (MII+). We used modified Poisson models to estimate the prevalence ratio between method type (LARC vs. other modern methods) and the MII+, controlling for individual- and facility-level covariates. Results: Reported receipt of the full MII+ during contraceptive counseling ranged from 21% in the DRC to 51% in Kenya. In all countries, a higher proportion of LARC users received the MII+ compared to other modern method users. A greater proportion of LARC users answered "yes" to all questions that make up the MII+ at the time of counseling compared to other modern method users in DRC, Kenya, Nigeria, and Uganda. There was no significant difference in the prevalence of reporting the full MII+ between users of LARC and other modern methods in Burkina Faso (Adjusted prevalence ratio (aPR): 1.16; 95% confidence interval (CI): 0.91, 1.48) and Côte d'Ivoire (aPR: 1.13; 95% CI: 0.87, 1.45). Conclusion: Information received during contraceptive counseling was limited for all modern contraceptive users. LARC users had significantly higher prevalence of receiving the MII+ compared to other modern method users in the DRC, Kenya, and Uganda. Family planning programs should ensure that all women receive complete, unbiased contraceptive counseling. Implications: Across 6 sub-Saharan African countries, a substantial proportion reproductive-aged women using contraception did not report receiving comprehensive counseling when they received their method. Women using long-acting reversible contraception received more information compared to women using other modern methods in the DRC, Kenya, Nigeria, and Uganda after controlling for individual- and facility-level factors.

Male circumcision and anatomic sites of penile high-risk human papillomavirus in Rakai, Uganda.

Male circumcision (MC) reduces penile high-risk human papillomavirus (HR-HPV) on the coronal sulcus and urethra. HR-HPV varies by anatomic site, and it is unknown whether MC decreases HR-HPV on the penile shaft. We assessed the efficacy of MC to reduce HR-HPV on the penile shaft and compared it to known efficacy of MC to reduce HR-HPV on the coronal sulcus. HIV-negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR-HPV at 12 months postenrollment using the Roche HPV Linear Array assay. Among swabs with detectable ß-globin or HPV, year 1 HR-HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men [adjusted prevalence risk ratios (PRRs) = 0.57, 95% CI 0.39-0.84, p = 0.005]. On the shaft, year 1 HR-HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR = 0.66, 95% CI 0.39-1.12, p = 0.12). Efficacy of MC to reduce HR-HPV on the shaft was similar to efficacy on the coronal sulcus (p = 0.52). In a sensitivity analysis in which swabs without detectable ß-globin or HPV were included as HPV negative, prevalence of HR-HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%; PRR 0.57, 95% CI 0.33-0.99, p < 0.05). HR-HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs. 23.8%, respectively, p = 0.02) and circumcised men (21.5% vs. 15.5%, respectively, p = 0.24). MC reduced HR-HPV prevalence on both the coronal sulcus and shaft.

Circumcision of HIV-infected men: effects on high-risk human papillomavirus infections in a randomized trial in Rakai, Uganda.

UNLABELLED: In Rakai, Uganda, human immunodeficiency virus (HIV)-positive men were randomized to undergo either immediate circumcision (intervention arm) or delayed circumcision (control arm). Penile swab samples were assayed for high-risk human papillomavirus (HR-HPV) by Roche HPV Linear Array at enrollment and at 24 months (intervention arm, 103 subjects; control arm, 107 subjects). Rate ratios (RRs) of HR-HPV were estimated by Poisson regression. At 24 months, HR-HPV prevalence was found in 57 (55.3%) of 103 subjects in the intervention arm and in 77 (71.7%) of 107 subjects in the control arm (RR, 0.77; 95% confidence interval [CI], 0.62-0.97). Multiple HR-HPV infections were found in 19 (22.4%) of 85 subjects in the intervention arm and in 45 (42.5%) of 106 subjects in the control arm (RR, 0.53; 95% CI, 0.33-0.83). New HR-HPV genotypes were acquired by 34 (42.0%) of 81 subjects in the intervention arm and by 53 (57.0%) 85 subjects in the control arm (RR, 0.74; 95% CI, 0.54-1.01; P = .06). Multiple new HR-HPV genotypes were acquired by 8 (9.9%) of 81 subjects in the intervention arm and by 23 (24.7%) of 93 subjects in the control arm (RR, 0.40; 95% CI, 0.19-0.84; P = .01). Circumcision did not affect the acquisition of single HR-HPV infections (RR, 1.00; 95% CI 0.65-1.53) or clearance of HR-HPV infections (RR, 1.09; 95% CI 0.94-1.27). Circumcision of HIV-positive men reduced the prevalence and incidence of multiple HR-HPV infections. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00124878 .

Male circumcision decreases acquisition and increases clearance of high-risk human papillomavirus in HIV-negative men: a randomized trial in Rakai, Uganda.

METHODS: Uncircumcised human immunodeficiency virus (HIV)-negative men aged 15-49 years were randomized to immediate circumcision (intervention arm, 441 subjects) or delayed circumcision (control arm, 399 subjects). Human papillomavirus (HPV) was detected by Roche HPV Linear Array at enrollment, and at 6, 12, and 24 months. Incident high-risk HPV (HR-HPV) was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RRs) and 95% confidence intervals (CIs) of HR-HPV acquisition were estimated by Poisson multiple regression. RESULTS: Enrollment characteristics were comparable between study groups. HR-HPV incidence was 19.7 cases per 100 person-years (PYs) in the intervention arm (70 cases per 355.8 PYs) and 29.4 cases per 100 PYs (125 cases per 424.8 PYs) in the control arm (RR, 0.67; 95% CI, 0.51-0.89; P = .006). The incidence of multiple HR-HPV infections was 6.7 cases per 100 PYs in the intervention arm and 14.8 cases per 100 PYs in the control arm (RR, 0.45; 95% CI, 0.28-0.73), but there was no significant effect on single infections (RR, 0.89; 95% CI, 0.60-1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of preexisting HR-HPV infections was 215.8 cases per 100 PYs (205 cases per 95 PYs) in the intervention arm and 159.1 cases per 100 PYs (255 cases per 160.25 PYs) in the control arm (adjusted RR, 1.39; 95% CI, 1.17-1.64). CONCLUSIONS: Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00425984 .

Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial.

BACKGROUND: Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners. METHODS: 922 uncircumcised, HIV-infected, asymptomatic men aged 15-49 years with CD4-cell counts 350 cells per microL or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878. FINDINGS: The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0.36). Cumulative probabilities of female HIV infection at 24 months were 21.7% (95% CI 12.7-33.4) in the intervention group and 13.4% (6.7-25.8) in the control group (adjusted hazard ratio 1.49, 95% CI 0.62-3.57; p=0.368). INTERPRETATION: Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention. FUNDING: Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.

Effects of genital ulcer disease and herpes simplex virus type 2 on the efficacy of male circumcision for HIV prevention: Analyses from the Rakai trials.

BACKGROUND: Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC. METHODS AND FINDINGS: HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43-0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51-0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30-0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (chi(2)p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15-0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19-1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49-1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0-38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI -1.2 to 77.1). CONCLUSIONS: Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.

The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda.

OBJECTIVE: The objective of the study was to assess effects of male circumcision on female genital symptoms and vaginal infections. STUDY DESIGN: Human immunodeficiency virus (HIV)-negative men enrolled in a trial were randomized to immediate or delayed circumcision (control arm). Genital symptoms, bacterial vaginosis (BV), and trichomonas were assessed in HIV-negative wives of married participants. Adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CIs) were assessed by multivariable log-binomial regression, intent-to-treat analyses. RESULTS: A total of 783 wives of control and 825 wives of intervention arm men were comparable at enrollment. BV at enrollment was higher in control (38.3%) than intervention arm spouses (30.5%, P = .001). At 1 year follow-up, intervention arm wives reported lower rates of genital ulceration (adjPRR, 0.78; 95% CI, 0.63-0.97), but there were no differences in vaginal discharge or dysuria. The risk of trichomonas was reduced in intervention arm wives (adjPRR, 0.52; 95% CI, 0.05-0.98), as were the risks of any BV (adjPRR, 0.60; 95% CI, 0.38-0.94) and severe BV (prevalence risk ratios, 0.39; 95% CI, 0.24-0.64). CONCLUSION: Male circumcision reduces the risk of ulceration, trichomonas, and BV in female partners.

Pregnancy Incidence and Fertility Desires Among Couples by HIV Status in Rakai, Uganda.

BACKGROUND: The desire for more children and pregnancy rates are influenced by many relationship dynamics and HIV serostatus of couples. SETTING: Rakai Community Cohort Study in Uganda. METHODS: Couple data were retrospectively linked from survey rounds between 2007 and 2015 to assess drivers of fertility desire and pregnancy incidence by HIV status (M-F-; M+F+; M-F+; and M+F-). Multivariable modified Poisson regression was used to estimate prevalence ratios of fertility desire, whereas multivariable Poisson regression was used to estimate incidence rate ratios of pregnancy associated with couple characteristics. RESULTS: Six thousand six hundred forty-seven couples contributed to 7656 person-years. Approximately 40% of couples (where at least 1 HIV+) desired more children. Unmet need for family planning was evident; couples of medium or low Socioeconomic status and with coresident children had lower fertility desires but higher pregnancy rates. Older age, being in a polygamous union, and having a HIV+ spouse in care were associated with lower fertility desire while having an older male partner was associated with higher fertility desire. Pregnancy incidence was lower with older age, among women using hormonal contraception and condoms, HIV+ concordant couples and couples where the HIV+ spouse was in care while pregnancy incidence were higher among women who desired more children, and serodiscordant couples (M-F+). CONCLUSIONS: There are many drivers of fertility desires and pregnancy rates, and HIV does not diminish the desire for more children. Unmet need for family planning was evident and highlighted the need to understand and meet the contraceptive needs of couples.