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Background: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania., Methods: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688., Findings: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; p non-inferiority <0·0001 unadjusted) and -0·36% (-1·99 to 1·28; p non-inferiority <0·0001 adjusted)., Interpretation: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV., Funding: European Union Horizon 2020 and Global Alliance for Chronic Diseases., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests. NKS and EW are joint first authors.

Background: Alcohol use is common among persons living with HIV (PWH) in Uganda and associated with poor HIV care outcomes; findings regarding the relationship between alcohol use and viral suppression (VS) have been inconclusive., Methods: Data from two rounds (2017-2020) of the Rakai Community Cohort Study, an open population-based cohort study in the Rakai region, Uganda, were analyzed. Two alcohol exposures were explored: past year alcohol use and alcohol-related consequences. Multivariable models (GEE) were used to estimate associations between alcohol exposures and VS for the overall sample and stratified by sex, adjusting for repeated measurement. Causal mediation by ART use was explored., Results: Over half (55 %) of participants (n = 3823 PWH) reported alcohol use at baseline; 37.8 % of those reporting alcohol use reported alcohol-related consequences. ART use and VS at baseline significantly differed by alcohol use with person reporting alcohol use being less likely to be on ART or VS. Alcohol use was significantly associated with decreased odds of VS among women but not men (adj. OR 0.72 95 % CI 0.58-0.89, p = 0.0031). However, among males who use alcohol, experiencing alcohol-related consequences was significantly associated with decreased odds of VS (adj. OR 0.69 95 % CI 0.54-0.88, p = 0.0034). The relationships between both alcohol exposures and VS were not significant in models restricted to persons on ART., Conclusions: We provide sex-stratified estimates of associations between two alcohol measures and VS in the context of current HIV treatment guidelines. This study confirms that alcohol use is adversely associated with VS but ART use mediates this pathway, suggesting that initiation and retention on ART are critical steps to addressing alcohol-related disparities in VS., (Copyright © 2021. Published by Elsevier B.V.)

Background: Claims about what improves or harms our health are ubiquitous. People need to be able to assess the reliability of these claims. We aimed to evaluate an intervention designed to teach primary school children to assess claims about the effects of treatments (ie, any action intended to maintain or improve health)., Methods: In this cluster-randomised controlled trial, we included primary schools in the central region of Uganda that taught year-5 children (aged 10-12 years). We excluded international schools, special needs schools for children with auditory and visual impairments, schools that had participated in user-testing and piloting of the resources, infant and nursery schools, adult education schools, and schools that were difficult for us to access in terms of travel time. We randomly allocated a representative sample of eligible schools to either an intervention or control group. Intervention schools received the Informed Health Choices primary school resources (textbooks, exercise books, and a teachers' guide). Teachers attended a 2 day introductory workshop and gave nine 80 min lessons during one school term. The lessons addressed 12 concepts essential to assessing claims about treatment effects and making informed health choices. We did not intervene in the control schools. The primary outcome, measured at the end of the school term, was the mean score on a test with two multiple-choice questions for each of the 12 concepts and the proportion of children with passing scores on the same test. This trial is registered with the Pan African Clinical Trial Registry, number PACTR201606001679337., Findings: Between April 11, 2016, and June 8, 2016, 2960 schools were assessed for eligibility; 2029 were eligible, and a random sample of 170 were invited to recruitment meetings. After recruitment meetings, 120 eligible schools consented and were randomly assigned to either the intervention group (n=60, 76 teachers and 6383 children) or control group (n=60, 67 teachers and 4430 children). The mean score in the multiple-choice test for the intervention schools was 62·4% (SD 18·8) compared with 43·1% (15·2) for the control schools (adjusted mean difference 20·0%, 95% CI 17·3-22·7; p<0·00001). In the intervention schools, 3967 (69%) of 5753 children achieved a predetermined passing score (≥13 of 24 correct answers) compared with 1186 (27%) of 4430 children in the control schools (adjusted difference 50%, 95% CI 44-55). The intervention was effective for children with different levels of reading skills, but was more effective for children with better reading skills., Interpretation: The use of the Informed Health Choices primary school learning resources, after an introductory workshop for the teachers, led to a large improvement in the ability of children to assess claims about the effects of treatments. The results show that it is possible to teach primary school children to think critically in schools with large student to teacher ratios and few resources. Future studies should address how to scale up use of the resources, long-term effects, including effects on actual health choices, transferability to other countries, and how to build on this programme with additional primary and secondary school learning resources., Funding: Research Council of Norway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: As part of the Informed Health Choices project, we developed a podcast called The Health Choices Programme to help improve the ability of people to assess claims about the benefits and harms of treatments. We aimed to evaluate the effects of the podcast on the ability of parents of primary school children in Uganda to assess claims about the effects of treatments., Methods: We did this randomised controlled trial in central Uganda. We recruited parents of children aged 10-12 years who were in their fifth year of school at 35 schools that were participating in a linked trial of the Informed Health Choices primary school resources. The parents were randomly allocated (1:1), via a web-based random number generator with block sizes of four and six, to listen to either the Informed Health Choices podcast (intervention group) or typical public service announcements about health issues (control group). Randomisation was stratified by parents' highest level of formal education attained (primary school, secondary school, or tertiary education) and the allocation of their children's school in the trial of the primary school resources (intervention vs control). The primary outcome, measured after listening to the entire podcast, was the mean score and the proportion of parents with passing scores on a test with two multiple choice questions for each of nine key concepts essential to assessing claims about treatments (18 questions in total). We did intention-to-treat analyses. This trial is registered with the Pan African Clinical Trial Registry, number PACTR201606001676150., Findings: We recruited parents between July 21, 2016, and Oct 7, 2016. We randomly assigned 675 parents to the podcast group (n=334) or the public service announcement group (n=341); 561 (83%) participants completed follow-up. The mean score for parents in the podcast group was 67·8% (SD 19·6) compared with 52·4% (17·6) in the control group (adjusted mean difference 15·5%, 95% CI 12·5-18·6; p<0·0001). In the podcast group, 203 (71%) of 288 parents had a predetermined passing score (≥11 of 18 correct answers) compared with 103 (38%) of 273 parents in the control group (adjusted difference 34%, 95% CI 26-41; p<0·0001). No adverse events were reported., Interpretation: Listening to the Informed Health Choices podcast led to a large improvement in the ability of parents to assess claims about the effects of treatments. Future studies should assess the long-term effects of use of the podcast, the effects on actual health choices and outcomes, and how transferable our findings are to other countries., Funding: Research Council of Norway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Small numbers of graduates from few medical schools, and emigration of graduates to other countries, contribute to low physician presence in sub-Saharan Africa. The Sub-Saharan African Medical School Study examined the challenges, innovations, and emerging trends in medical education in the region. We identified 168 medical schools; of the 146 surveyed, 105 (72%) responded. Findings from the study showed that countries are prioritising medical education scale-up as part of health-system strengthening, and we identified many innovations in premedical preparation, team-based education, and creative use of scarce research support. The study also drew attention to ubiquitous faculty shortages in basic and clinical sciences, weak physical infrastructure, and little use of external accreditation. Patterns recorded include the growth of private medical schools, community-based education, and international partnerships, and the benefit of research for faculty development. Ten recommendations provide guidance for efforts to strengthen medical education in sub-Saharan Africa., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Archival formalin-fixed paraffin-embedded (FFPE) human tissue collections are typically in poor states of storage across the developing world. With advances in biomolecular techniques, these extraordinary and virtually untapped resources have become an essential part of retrospective epidemiological studies. To successfully use such tissues in genomic studies, scientists require high nucleic acid yields and purity. In spite of the increasing number of FFPE tissue kits available, few studies have analyzed their applicability in recovering high-quality nucleic acids from archived human autopsy samples. Here we provide a study involving 10 major extraction methods used to isolate total nucleic acid from FFPE tissues ranging in age from 3 to 13years. Although all 10 methods recovered quantifiable amounts of DNA, only 6 recovered quantifiable RNA, varying considerably and generally yielding lower DNA concentrations. Overall, we show quantitatively that TrimGen's WaxFree method and our in-house phenol-chloroform extraction method recovered the highest yields of amplifiable DNA, with considerable polymerase chain reaction (PCR) inhibition, whereas Ambion's RecoverAll method recovered the most amplifiable RNA., (2010 Elsevier Inc. All rights reserved.)

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.

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.

Background: Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men., Methods: 4996 uncircumcised, HIV-negative men aged 15-49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984., Findings: Baseline characteristics of the men in the intervention and control groups were much the same at enrollment. Retention rates were much the same in the two groups, with 90-92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16-72; p=0.006). The as-treated efficacy was 55% (95% CI 22-75; p=0.002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30-77; p=0.003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3.6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up., Interpretation: Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men.

Objective: The purpose of this study was to assess presumptive sexually transmitted disease treatment on pregnancy outcome and HIV transmission., Study Design: In a randomized trial in Rakai District, Uganda, 2070 pregnant women received presumptive sexually transmitted disease treatment 1 time during pregnancy at varying gestations, and 1963 control mothers received iron/folate and referral for syphilis. Maternal-infant sexually transmitted disease/HIV and infant outcomes were assessed. Intent-to-treat analyses estimated adjusted rate ratios and 95% confidence intervals., Results: Sexually transmitted diseases were reduced: Trichomonas vaginalis (rate ratio, 0.28; 95% CI, 0.18%-0.49%), bacterial vaginosis (rate ratio, 0.78; 95% CI, 0.69-0.87), Neisseria gonorrhoeae /Chlamydia trachomatis (rate ratio, 0.43; 95% CI, 0.27-0.68), and infant ophthalmia (rate ratio, 0.37; 95% CI, 0.20-0.70). There were reduced rates of neonatal death (rate ratio, 0.83; 95% CI, 0.71-0.97), low birth weight (rate ratio, 0.68; 95% CI, 0.53-0.86), and preterm delivery (rate ratio, 0.77; 95% CI, 0.56-1.05); but there were no effects on maternal HIV acquisition or perinatal HIV transmission., Conclusion: Reductions of maternal sexually transmitted disease improved pregnancy outcome but not maternal HIV acquisition or perinatal HIV transmission.

Background: The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various factors thought to influence infectivity., Methods: 174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively. HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners., Results: The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were 0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner., Interpretation: Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population.

Background: The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities., Methods: This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios., Findings: The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses., Interpretation: We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.

A new disease has recently been recognised in rural Uganda. Because the major symptoms are weight loss and diarrhoea, it is known locally as slim disease. It is strongly associated with HTLV-III infection (63 out of 71 patients) and affects females nearly as frequently as males. The clinical features are similar to those of enteropathic acquired immunodeficiency syndrome as seen in neighbouring Zaire. However, the syndrome is rarely associated with Kaposi's sarcoma (KS), although KS is endemic in this area of Uganda. Slim disease occurs predominantly in the heterosexually promiscuous population and there is no clear evidence to implicate other possible means of transmission, such as by insect vectors or re-used injection needles. The site and timing of the first reported cases suggest that the disease arose in Tanzania.