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Objective: We aimed to determine the effect of group support psychotherapy (GSP) compared with group HIV education (GHE) on depression and HIV treatment outcomes 24 months after treatment. We further aimed to investigate the mediating role of depression and antiretroviral therapy (ART) adherence in the relationship between GSP and viral load suppression., Methods: Thirty HIV clinics across three districts were randomly assigned to deliver either GSP or GHE for depression. Depression and optimal (≥95%) ART adherence was assessed at baseline and 6, 12, 18, and 24 months after treatment. Viral load was drawn from the medical charts at baseline and 12 and 24 months after treatment. Multilevel mixed-effects regression models and generalized structural equation modeling were used to estimate 24-month outcomes and mediation effects., Results: Participants ( N = 1140) were enrolled from HIV clinics offering either GSP ( n = 578 [51%]) or GHE ( n = 562 [49%]). Fewer GSP than GHE participants met the criteria for depression at 24 months after treatment (1% versus 25%; adjusted odds ratio [aOR] = 0.002, 95% confidence interval [CI] = 0.0002-0.018). More GSP than GHE participants reported optimal (≥95%) ART adherence (96% versus 88%; aOR = 20.88, 95% CI = 5.78-75.33) and improved viral suppression (96% versus 88%; aOR = 3.38, 95% CI = 1.02-11.02). The indirect effects of GSP through sequential reduction in depression and improvement in ART adherence at 12 months may partially explain the higher viral suppression rates at 24 months in GSP than GHE groups., Conclusion: In settings where the HIV epidemic persists, depression treatment with GSP may be critical for optimal HIV treatment outcomes.Trial Registration: The Pan African Clinical Trials Registry, number PACTR201608001738234., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Introduction: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and diabetes outcomes. A systematic inquiry of these projects will provide necessary scientific insights into the enablers and challenges in the scale up of complex NCD interventions., Methods and Analysis: We will apply systems thinking (a holistic approach to analyse the inter-relationship between constituent parts of scaleup interventions and the context in which the interventions are implemented) and adopt a longitudinal mixed-methods study design to explore the planning and early implementation phases of scale up projects. Data will be gathered at three time periods, namely, at planning (T P ), initiation of implementation (T 0 ) and 1-year postinitiation (T 1 ). We will extract project-related data from secondary documents at T P and conduct multistakeholder qualitative interviews to gather data at T 0 and T 1. We will undertake descriptive statistical analysis of T P data and analyse T 0 and T 1 data using inductive thematic coding. The data extraction tool and interview guides were developed based on a literature review of scale-up frameworks., Ethics and Dissemination: The current protocol was approved by the Monash University Human Research Ethics Committee (HREC number 23482). Informed consent will be obtained from all participants. The study findings will be disseminated through peer-reviewed publications and more broadly through the GACD network., Competing Interests: Competing interests: JvO reports Horizon2020 grants (643 692 and 825432) outside the submitted work. AGT declares funding from the National Health & Medical Research Council (NHMRC, Australia: GNT1042600, GNT1122455, GNT1171966, GNT1143155, GNT1182017), Stroke Foundation Australia (SG1807), and Heart Foundation Australia (VG102282) outside the submitted work. ML-P declares support from Fogarty International Centre, National Institutes of Health [R21TW009982], under the Global Alliance for Chronic Diseases (GACD) Diabetes ProgramProgramme. MEE reports grant funding from the Argentinian Ministry of Health (MoH) under the GACD program. AS declares funding from the Japan Agency for Medical Research & Development, as part of the GACD, outside the submitted work. FJH is partially funded by the National Institute for Health Research (NIHR) and the Medical Research Council (MRC), and is a member of the Action on Salt, and World Action on Salt, Sugar and Health (WASSH). AB declares grants from the MoH Argentina, National Institutes of Health, and World Diabetes Foundation, outside the submitted work. AP declares grant and fellowship support from the NHMRC outside the submitted work, Member of the Board of Directors, The George Institute India, and past Member of the Board of Directors, Heart Health Research Center, Beijing, PRC. RJ declares grant, outside the submitted work, from WHO Geneva, WHO South-East Asia Region (SEARO), Elrha Research for Health in Humanitarian Crises (R2HC), (Wellcome Trust, UK AID and NHS), DBT/ Wellcome Trust India Alliance and Gates Foundation. In the past 3 years, MDH has received research funding from American Heart Association, Verily, and AstraZeneca for research unrelated to this manuscript and has patents pending for heart failure polypills. The George Institute for Global Health has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. None of the others authors has any conflict of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Health policies in Africa are shifting towards integrated care services for chronic conditions, but in parts of Africa robust evidence on effectiveness is limited. We assessed the integration of vertical health services for HIV, diabetes and hypertension provided in a feasibility study within five health facilities in Uganda. From November 2018 to January 2020, we conducted a series of three in-depth interviews with 31, 29 and 24 service users attending the integrated clinics within Kampala and Wakiso districts. Ten healthcare workers were interviewed twice during the same period. Interviews were conducted in Luganda, translated into English, and analysed thematically using the concepts of availability, affordability and acceptability. All participants reported shortages of diabetes and hypertension drugs and diagnostic equipment prior to the establishment of the integrated clinics. These shortages were mostly addressed in the integrated clinics through a drugs buffer. Integration did not affect the already good provision of anti-retroviral therapy. The cost of transport reduced because of fewer clinic visits after integration. Healthcare workers reported that the main cause of non-adherence among users with diabetes and hypertension was poverty. Participants with diabetes and hypertension reported they could not afford private clinical investigations or purchase drugs prior to the establishment of the integrated clinics. The strengthening of drug supply for non-communicable conditions in the integrated clinics was welcomed. Most participants observed that the integrated clinic reduced feelings of stigma for those living with HIV. Sharing the clinic afforded privacy about an individual's condition, and users were comfortable with the waiting room sitting arrangement. We found that integrating non-communicable disease and HIV care had benefits for all users. Integrated care could be an effective model of care if service users have access to a reliable supply of basic medicines for both HIV and non-communicable disease conditions., Competing Interests: The authors declare no competing interests., (Copyright: © 2022 Bukenya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: HIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic., Objectives: To determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators., Design and Setting: Prospective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala., Intervention: Clinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments., Primary Outcome Measures: Retention in care, plasma viral load., Findings: Between 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load <100 copies/mL was 423(88.5%)/478., Conclusion: Integrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: HIV programmes in sub-Saharan Africa are well funded but programmes for diabetes and hypertension are weak with only a small proportion of patients in regular care. Healthcare provision is organised from stand-alone clinics. In this cluster randomised trial, we are evaluating a concept of integrated care for people with HIV infection, diabetes or hypertension from a single point of care., Methods and Analysis: 32 primary care health facilities in Dar es Salaam and Kampala regions were randomised to either integrated or standard vertical care. In the integrated care arm, services are organised from a single clinic where patients with either HIV infection, diabetes or hypertension are managed by the same clinical and counselling teams. They use the same pharmacy and laboratory and have the same style of patient records. Standard care involves separate pathways, that is, separate clinics, waiting and counselling areas, a separate pharmacy and separate medical records. The trial has two primary endpoints: retention in care of people with hypertension or diabetes and plasma viral load suppression. Recruitment is expected to take 6 months and follow-up is for 12 months. With 100 participants enrolled in each facility with diabetes or hypertension, the trial will provide 90% power to detect an absolute difference in retention of 15% between the study arms (at the 5% two-sided significance level). If 100 participants with HIV infection are also enrolled in each facility, we will have 90% power to show non-inferiority in virological suppression to a delta=10% margin (ie, that the upper limit of the one-sided 95% CI of the difference between the two arms will not exceed 10%). To allow for lost to follow-up, the trial will enrol over 220 persons per facility. This is the only trial of its kind evaluating the concept of a single integrated clinic for chronic conditions in Africa., Ethics and Dissemination: The protocol has been approved by ethics committee of The AIDS Support Organisation, National Institute of Medical Research and the Liverpool School of Tropical Medicine. Dissemination of findings will be done through journal publications and meetings involving study participants, healthcare providers and other stakeholders., Trial Registration Number: ISRCTN43896688., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Integration of health services might be an efficient strategy for managing multiple chronic conditions in sub-Saharan Africa, considering the scope of treatments and synergies in service delivery. Proven to promote compliance, integration may lead to increased economies-of-scale. However, evidence on the socio-economic consequences of integration for providers and patients is lacking. We assessed the clinical resource use, staff time, relative service efficiency and overall societal costs associated with integrating HIV, diabetes and hypertension services in single one-stop clinics where persons with one or more of these conditions were managed., Methods: 2273 participants living with HIV infection, diabetes, or hypertension or combinations of these conditions were enrolled in 10 primary health facilities in Tanzania and Uganda and followed-up for up to 12 months. We collected data on resources used from all participants and on out-of-pocket costs in a sub-sample of 1531 participants, while a facility-level costing study was conducted at each facility. Health worker time per participant was assessed in a time-motion morbidity-stratified study among 228 participants. The mean health service cost per month and out-of-pocket costs per participant visit were calculated in 2020 US$ prices. Nested bootstrapping from these samples accounted for uncertainties. A data envelopment approach was used to benchmark the efficiency of the integrated services. Last, we estimated the budgetary consequences of integration, based on prevalence-based projections until 2025, for both country populations., Results: Their average retention after 1 year service follow-up was 1911/2273 (84.1%). Five hundred and eighty-two of 2273 (25.6%) participants had two or all three chronic conditions and 1691/2273 (74.4%) had a single condition. During the study, 84/2239 (3.8%) participants acquired a second or third condition. The mean service costs per month of managing two conditions in a single participant were $39.11 (95% CI 33.99, 44.33), $32.18 (95% CI 30.35, 34.07) and $22.65 (95% CI 21.86, 23.43) for the combinations of HIV and diabetes and of HIV and hypertension, diabetes and hypertension, respectively. These costs were 34.4% (95% CI 17.9%, 41.9%) lower as compared to managing any two conditions separately in two different participants. The cost of managing an individual with all three conditions was 48.8% (95% CI 42.1%, 55.3%) lower as compared to managing these conditions separately. Out-of-pocket healthcare expenditure per participant per visit was $7.33 (95% CI 3.70, 15.86). This constituted 23.4% (95% CI 9.9, 54.3) of the total monthly service expenditure per patient and 11.7% (95% CI 7.3, 22.1) of their individual total household income. The integrated clinics' mean efficiency benchmark score was 0.86 (range 0.30-1.00) suggesting undercapacity that could serve more participants without compromising quality of care. The estimated budgetary consequences of managing multi-morbidity in these types of integrated clinics is likely to increase by 21.5% (range 19.2-23.4%) in the next 5 years, including substantial savings of 21.6% on the provision of integrated care for vulnerable patients with multi-morbidities., Conclusion: Integration of HIV services with diabetes and hypertension control reduces both health service and household costs, substantially. It is likely an efficient and equitable way to address the increasing burden of financially vulnerable households among Africa's ageing populations. Additional economic evidence is needed from longer-term larger-scale implementation studies to compare extended integrated care packages directly simultaneously with evidence on sustained clinical outcomes., (© 2021. The Author(s).)

Abstract: Most antiretroviral therapy (ART) programs in resource-limited settings have historically used non-nucleotide reverse transcriptase inhibitor (NNRTI)-based regimens with limited access to routine viral load (VL) testing. We examined the long-term success of these regimens in rural Uganda among participants with 1 measured suppressed VL.We conducted a prospective cohort study of participants who had been on NNRTI-based first-line regimens for ≥4 years and had a VL <1000 copies/mL at enrollment in Jinja, Uganda. We collected clinical and behavioral data every 6 months and measured VL again after 3 years. We quantified factors associated with virologic failure (VF) (VL ≥ 1000 copies/mL) using Wilcoxon Rank Sum, chi-square, and Fisher's Exact Tests.We enrolled 503 participants; 75.9% were female, the median age was 45 years, and the median duration of time on ART was 6.8 years (IQR = 6.0-7.6 years). Sixty-nine percent of participants were receiving nevirapine, lamivudine, and zidovudine regimens; 22.5% were receiving efavirenz, lamivudine, and zidovudine; and 8.6% were receiving other regimens. Of the 479 with complete follow-up data, 12 (2.5%) had VL ≥ 1000 copies/mL. VF was inversely associated with reporting never missing pills (41.7% of VFs vs 72.8% non-VFs, P = .034). There were differences in distribution of the previous ART regimens (P = .005), but no clear associations with specific regimens. There was no association between having a VL of 50 to 999 copies/mL at enrollment and later VF (P = .160).Incidence of VF among individuals receiving ART for nearly 7 years was very low in the subsequent 3 years. NNRTI-based regimens appear to be very durable among those with good initial adherence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Low-income and middle-income countries are struggling to manage growing numbers of patients with chronic non-communicable diseases (NCDs), while services for patients with HIV infection are well established. There have been calls for integration of HIV and NCD services to increase efficiency and improve coverage of NCD care, although evidence of effectiveness remains unclear. In this review, we assess the extent to which National HIV and NCD policies in East Africa reflect the calls for HIV-NCD service integration., Methods: Between April 2018 and December 2020, we searched for policies, strategies and guidelines associated with HIV and NCDs programmes in Burundi, Kenya, Rwanda, South Sudan, Tanzania and Uganda. Documents were searched manually for plans for integration of HIV and NCD services. Data were analysed qualitatively using document analysis., Results: Thirty-one documents were screened, and 13 contained action plans for HIV and NCDs service integration. Integrated delivery of HIV and NCD care is recommended in high level health policies and treatment guidelines in four countries in the East African region; Kenya, Rwanda, Tanzania and Uganda, mostly relating to integrating NCD care into HIV programmes. The increasing burden of NCDs, as well as a move towards person-centred differentiated delivery of services for people living with HIV, is a factor in the recent adoption of integrated HIV and NCD service delivery plans. Both South Sudan and Burundi report a focus on building their healthcare infrastructure and improving coverage and quality of healthcare provision, with no reported plans for HIV and NCD care integration., Conclusion: Despite the limited evidence of effectiveness, some East African countries have already taken steps towards HIV and NCD service integration. Close monitoring and evaluation of the integrated HIV and NCD programmes is necessary to provide insight into the associated benefits and risks, and to inform future service developments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In sub-Saharan Africa, the burden of non-communicable diseases (NCDs), particularly diabetes mellitus (DM) and hypertension, has increased rapidly in recent years, although HIV infection remains a leading cause of death among young-middle-aged adults. Health service coverage for NCDs remains very low in contrast to HIV, despite the increasing prevalence of comorbidity of NCDs with HIV. There is an urgent need to expand healthcare capacity to provide integrated services to address these chronic conditions., Methods and Analysis: This protocol describes procedures for a qualitative process evaluation of INTE-AFRICA, a cluster randomised trial comparing integrated health service provision for HIV infection, DM and hypertension, to the current stand-alone vertical care. Interviews, focus group discussions and observations of consultations and other care processes in two clinics (in Tanzania, Uganda) will be used to explore the experiences of stakeholders. These stakeholders will include health service users, policy-makers, healthcare providers, community leaders and members, researchers, non-governmental and international organisations. The exploration will be carried out during the implementation of the project, alongside an understanding of the impact of broader structural and contextual factors., Ethics and Dissemination: Ethical approval was granted by the Liverpool School of Tropical Medicine (UK), the National Institute of Medical Research (Tanzania) and TASO Research Ethics Committee (Uganda) in 2020. The evaluation will provide the opportunity to document the implementation of integration over several timepoints (6, 12 and 18 months) and refine integrated service provision prior to scale up. This synergistic approach to evaluate, understand and respond will support service integration and inform monitoring, policy and practice development efforts to involve and educate communities in Tanzania and Uganda. It will create a model of care and a platform of good practices and lessons learnt for other countries implementing integrated and decentralised community health services., Trial Registration Number: ISRCTN43896688; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: WHO recommends the use of psychological interventions as first-line treatment for depression in low-income and middle-income countries. However, evaluations of the effectiveness and cost-effectiveness of such interventions among people with HIV are scarce. Our aim was to establish the effectiveness of group support psychotherapy (GSP) delivered by lay health workers for depression treatment among people living with HIV in a rural area of Uganda on a large scale., Methods: In this cluster-randomised trial, we included 30 health centres offering HIV care. These were randomly assigned to deliver either GSP or group HIV education (GHE). Randomisation, in a ratio of 1:1, was achieved by health centre managers separately picking a paper containing the intervention allocation from a basket. Participants were people living with HIV, aged 19 years and older, with mild to moderate major depression assessed with the Mini International Neuropsychiatric Interview depression module, taking antiretroviral therapy, and antidepressant-naive. Group sessions were led by trained lay health workers once a week for 8 weeks. The primary outcomes were the proportion of participants with major depression and function scores at 6 months post-treatment, analysed by intention to treat by means of multilevel random effect regression analyses adjusting for clustering in health centres. This trial is registered with the Pan African Clinical Trials Registry, PACTR201608001738234., Findings: Between Sept 13 and Dec 15, 2016, we assessed 1473 individuals, of whom 1140 were recruited from health centres offering GSP (n=578 [51%]) or GHE (n=562 [49%]). Two (<1%) participants in the GSP group were diagnosed with major depression 6 months post-treatment compared with 160 (28%) in the GHE group (adjusted odds ratio=0·01, 95% CI 0·003-0·012, p<0·0001). The mean function scores 6 months post-treatment were 9·85 (SD 0·76) in the GSP group and 6·83 (2·85) in the GHE group (β=4·12; 95% CI 3·75-4·49, p<0·0001). 36 individuals had 63 serious adverse events, which included 25 suicide attempts and 22 hospital admissions for medical complications. The outcomes of these serious adverse events included 16 deaths, 4 of which were completed suicides (GSP=2; GHE=2), and 12 of which were HIV-related medical complications (GSP=8; GHE=4). Cost-effectiveness estimates showed an incremental cost-effectiveness ratio of US$13·0 per disability-adjusted life-year averted, which can be considered very cost-effective in Uganda., Interpretation: Integration of cost-effective psychological treatments such as group support psychotherapy into existing HIV interventions might improve the mental health of people living with HIV., Funding: MQ Transforming Mental Health and Grand Challenges Canada., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: HIV infection has profound clinical and economic costs at the household level. This is particularly important in low-income settings, where access to additional sources of income or loans may be limited. While several microfinance interventions have been proposed, unconditional cash grants, a strategy to allow participants to choose how to use finances that may improve household security and health, has not previously been evaluated., Methods: We examined the effect of an unconditional cash transfer to HIV-infected individuals using a 2 × 2 factorial randomized trial in two rural districts in Uganda. Our primary outcomes were changes in CD4 cell count, sexual behaviors, and adherence to ART. Secondary outcomes were changes in household food security and adult mental health. We applied a Bayesian approach for our primary analysis., Results: We randomized 2170 patients as participants, with 1081 receiving a cash grant. We found no important intervention effects on CD4 T-cell counts between groups [mean difference 35.48, 95% credible interval (CrI) -59.9 to 1131.6], food security [odds ratio (OR) 1.22, 95% CrI: 0.47 to 3.02], medication adherence (OR 3.15, 95% CrI: 0.58 to 18.15), or sexual behavior (OR 0.45 95% CrI: 0.12 to 1.55), or health expenditure in the previous 3 weeks (mean difference $2.65, 95% CrI: -9.30 to 15.69). In secondary analysis, we detected an effect of mental planning on CD4 cell count change between groups (104.2 cells, 9% CrI: 5.99 to 202.16). We did not have data on viral load outcomes., Conclusion: Although all outcomes were associated with favorable point estimates, our trial did not demonstrate important effects of unconditional cash grants on health outcomes of HIV-positive patients receiving treatment.

High rates of fertility desires, childbearing and serodiscordant partnerships among people living with HIV (PLHIV) in Uganda underscore the need to promote use of safer conception methods (SCM). Effective SCM exist but few PLHIV benefit from provider-led safer conception counseling (SCC) and comprehensive national SCC guidelines are still lacking. Providers' self-efficacy, intentions and attitudes for SCC impact provision and should inform development of services, but there are no longitudinal studies that assess these important constructs. This study reports on changes in providers' knowledge, attitudes, motivation and confidence to provide SCC among a 24-month observational cohort of Ugandan HIV providers. Compared to baseline, providers evidenced increased awareness of SCM, perceived greater value in providing SCC, saw all SCM but sperm washing as likely to be acceptable to clients, reported consistently high interest in and peer support for providing SCC, and perceived fewer barriers at the 24-month follow-up. Providers' intentions for providing SCC stayed consistently high for all SCM except manual self-insemination which decreased at 24 months. Self-efficacy for providing SCC increased from baseline with the greatest improvement in providers' confidence in advising serodiscordant couples where the man is HIV-infected. Providers consistently cite the lack of established guidelines, training, and their own reluctance to broach the issue with clients as significant barriers to providing SCC. Despite providers being more interested and open to providing SCC than ever, integration of SCC into standard HIV services has not happened. Concerted efforts are needed to address remaining barriers by establishing national SCC guidelines and implementing quality provider training.

Genetic strategies for large scale pest or vector control using modified insects are not yet operational in Africa, and currently rely on import of the modified strains to begin preliminary, contained studies. Early involvement of research teams from participating countries is crucial to evaluate candidate field interventions. Following the recommended phased approach for novel strategies, evaluation should begin with studies in containment facilities. Experiences to prepare facilities and build international teams for research on transgenic mosquitoes revealed some important organizing themes underlying the concept of "facilities readiness," or the point at which studies in containment may proceed, in sub-Saharan African settings. First, "compliance" for research with novel or non-native living organisms was defined as the fulfillment of all legislative and regulatory requirements. This is not limited to regulations regarding use of transgenic organisms. Second, the concept of "colony utility" was related to the characteristics of laboratory colonies being produced so that results of studies may be validated across time, sites, and strains or technologies; so that the appropriate candidate strains are moved forward toward field studies. Third, the importance of achieving "defensible science" was recognized, including that study conclusions can be traced back to evidence, covering the concerns of various stakeholders over the long term. This, combined with good stewardship of resources and appropriate funding, covers a diverse set of criteria for declaring when "facilities readiness" has been attained. It is proposed that, despite the additional demands on time and resources, only with the balance of and rigorous achievement of each of these organizing themes can collaborative research into novel strategies in vector or pest control reliably progress past initial containment studies.

We examined the prevalence and correlates of safer conception methods (SCM) use in HIV-affected couples with fertility intentions. A prospective cohort of 400 HIV clients in Uganda who had fertility intentions with their partner was surveyed every 6 months for 24 months. Logistic regression analysis was used to determine individual, relationship and provider level predictors of SCM use. Over one-third (35%) reported any use of timed unprotected intercourse (TUI) during the study; use of other SCM was rare. Baseline predictors of any TUI use included lower social support, greater perceived provider stigma of childbearing, greater SCM awareness, greater control over sexual decision making in the relationship, inconsistent condom use, and the belief that a desire for childbearing impedes condom use. These findings highlight the need for policy and provider training regarding integration of safer conception counselling into family planning and reproductive health services for people living with HIV.

This study aimed to examine the correlates of unintended pregnancies among young women sex workers in conflict-affected northern Uganda. Data were drawn from the Gulu Sexual Health Study, a cross-sectional study of young women engaged in sex work. Bivariable and multivariable logistic regression was used to examine the correlates of ever having an unintended pregnancy. Among 400 sex workers (median age=20 years; IQR 19-25), 175 (43.8%) reported at least one unintended pregnancy. In multivariable analysis, primarily servicing clients in lodges/brothels [Adjusted Odds Ratio (AOR= 2.24; 95% Confidence Interval: 1.03-4.84)], hormonal contraceptive usage [AOR=1.68; 95%CI 1.11-2.59] and drug/alcohol use while working [AOR= 1.64; 95%CI 1.04-2.60] were positively correlated with previous unintended pregnancy. Given that unintended pregnancy is an indicator of unmet reproductive health need, these findings highlight a need for improved access to integrated reproductive health and HIV services, catered to sex workers' needs. Sex work-led strategies (e.g., peer outreach) should be considered, alongside structural strategies and education targeting brothel/lodge owners and managers.

Background: Stable, co-habiting HIV serodiscordant couples are a key population in terms of heterosexual transmission in sub-Saharan Africa. Despite the wide availability of antiretroviral treatment and HIV educational programs, heterosexual transmission continues to drive the HIV epidemic in Africa. To investigate some of the factors involved in transmission or maintenance of serodiscordant status, we designed a study to examine participants' understanding of HIV serodiscordance and the implications this posed for their HIV prevention practices., Methods: In-depth interviews were conducted with 28 serodiscordant couples enrolled in a treatment-as-prevention study in Jinja, Uganda. Participants were asked questions regarding sexual behaviour, beliefs in treatment and prevention, participants' and communities' understanding and context around HIV serodiscordance. Qualitative framework analysis capturing several main themes was carried out by a team of four members, and was cross-checked for consistency., Results: It was found that most couples had difficulty explaining the phenomenon of serodiscordance and tended to be confused regarding prevention. Many individuals still held beliefs in pseudoscientific explanations for HIV susceptibility such as blood type and blood "strength". The participants' trust of treatment and medical services were well established. However, the communities' views of both serodiscordance and treatment were more pessimistic and wrought with mistrust. Stigmatization of serodiscordance and HIV-positive status were reported frequently., Conclusions: The results indicate that despite years of treatment and prevention methods being available, stigmatization and mistrust persist in the communities of HIV-affected individuals and may directly contribute to new cases and seroconversion. We suggest that to optimize the effects of HIV treatment and prevention, clear education and support of such methods are sorely needed in sub-Saharan African communities.

Background: Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort., Methods: We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination., Results: We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination., Conclusion: Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity., Trial Registration: Registration is not required for observational studies., Funding: This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Human immunodeficiency virus type 1 (HIV-1) prevalence and incidence in the fishing communities on Lake Victoria in Uganda are high. This population may play a role in driving the HIV epidemic in Uganda including the spread of transmitted drug resistance (TDR). We report data on TDR in this population among antiretroviral (ARV)-naive, recently infected individuals about 5 years after ARV scaling-up in Uganda. We identified phylogenetic transmission clusters and combined these with volunteer life histories in order to understand the sexual networks within this population. From a prospective cohort of 1,000 HIV-negative individuals recruited from five communities, 51 seroconverters were identified over a period of 2 years. From these, whole blood was collected and population sequencing of the HIV-1 pol gene (protease/reverse transcriptase) was performed from plasma. Drug resistance mutations (DRMs) were scored using the 2009 WHO list for surveillance of TDR. TDR prevalence categories were estimated using the WHO recommended truncated sampling technique for the surveillance of TDR for use in resource-limited settings (RLS). Of the samples 92% (47/51) were successfully genotyped. HIV-1 subtype frequencies were 15/47 (32%) A1, 20/47 (43%) D, 1/47 (2%) C, 1/47 (2%) G, and 10/47 (21%) unique recombinant forms. Nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutation K103N was identified in two individuals and V106A in one (6%) suggesting that the level of TDR was moderate in this population. No nucleoside/tide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) DRMs were detected. In this study, we identified five transmission clusters supported by high bootstrap values and low genetic distances. Of these, one pair included the two individuals with K103N. Two of the genotypic clusters corresponded with reported sexual partnerships as detected through prior in-depth interviews. The level of TDR to NNRTIs in these ARV-naive individuals was moderate by WHO threshold survey categorization. The transmission clusters suggest a high degree of sexual partner mixing between members of these communities.

Background: HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa., Methods: We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex., Results: Twenty-three cohort studies, including 216 008 participants (79 892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33-38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28-1.47)]. This was consistent across sensitivity analyses., Interpretation: The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed.

Objective: The risk of death is highest in the first few months after initiation of antiretroviral therapy (ART). We examined whether initial CD4 cell count maintains a strong prognostic value among patients with at least 6 months follow-up after the initiation of ART., Design: Observational study of HIV patients in Uganda aged 14 years or older enrolled in 10 clinics across Uganda., Methods: Baseline CD4 cell count of patients with more than 6 months of follow-up were stratified into categories (<50, 50-99, 100-149, 150-249, >250 cells/μl). A Kaplan-Meier survival analysis and Cox proportional hazards regression was used to model the associations between baseline CD4 cell count and mortality., Results: Of 22 315 patients, 20 730 (92.8%) had more than 6 months of follow-up. Six hundred and eleven (2.9%) patients died during follow-up and 737 (3.6%) were lost to follow-up. Relative to a baseline CD4 cell counts of less than 50 cells/μl, the adjusted hazard ratios for death were 0.83 [95% confidence interval (CI) 0.67-1.02], 0.71 (95% CI 0.57-0.88), 0.52 (95% CI 0.42-0.64), and 0.55 (95% CI 0.42-0.70) favouring those with baseline CD4 cell counts of 50-99, 100-149, 150-249, and at least 250 cells/μl, respectively. Differing ages and male sex increased the likelihood of mortality., Conclusion: Among patients with more than 6 months of follow-up after initiation of ART, baseline CD4 cell count at initiation still has important prognostic value. This suggests that active engagement and earlier treatment initiation is important for long-term survival.

Background: Global health research partnerships are commonly led by Northern investigators who come from resource-rich research environments, while Southern partners participate with a paucity of research skills and resources. This power asymmetry within North-South research partnerships may further exacerbate the unequal distribution of benefits from the research process., Methods: This study is designed to present the benefits and challenges of engaging in the research process from the perspective of The AIDS Support Organization (TASO), an HIV/AIDS care and treatment organization that has been involved in global health research partnerships. It uses a validated research tool entitled "Is Research Working for You?" to facilitate qualitative interviews surrounding the experienced benefits and challenges in engaging in the research partnerships as described by TASO staff., Results: Three key themes emerged from the content and thematic analysis: 1) the reported benefits of research (e.g., evidence-based management, advocacy, etc.), 2) the challenges the research committee members face in becoming more involved in the research process (e.g., lack of data analysis skill, lack of inclusion in the research process, etc.), and 3) the institutional ambition at TASO to develop a Southern-led research agenda., Conclusions: This is one of the few studies to document the development of a Southern-led research agenda in addition to the challenges of engaging in the research process. Mechanisms for moderating power dynamics within North-South partnerships can provide opportunities for improved research capacity and quality.

Objective: Although international guidelines recommend initiating antiretroviral therapy (ART) when a patient's CD4 cell count is ≤350 cells/μL, most patients in resource-limited settings present with much lower CD4 cell counts. The lowest level that their CD4 cell count reaches, the nadir, may have long-term consequences in terms of mortality. We examined this health state in a large cohort of HIV+ patients in Uganda., Design: This was an observational study of HIV patients in Uganda aged 14 years or older, who were enrolled in 10 major clinics across Uganda., Methods: We assessed the CD4 nadir of patients, using their CD4 cell count at initiation of ART, stratified into categories (,50, 50-99, 100-149, 150-249, 250+ cells/μL). We constructed Kaplan-Meier curves to assess the differences in survivorship for patients left-censored at 1 year and 2 years after treatment initiation. We used Cox proportional hazards regression to model the associations between CD4 nadir and mortality. We adjusted mortality for loss-to-follow-up., Results: Of 22,315 patients, 20,129 patients had greater than 1 year of treatment follow-up. Among these patients, 327 (1.6%) died and 444 (2.2%) were lost to follow-up. After left-censoring at one year, relative to lowest CD4 strata, patients with higher CD4 counts had significantly lower rates of mortality (CD4 150-249, hazard ratio [HR] 0.60, 95% confidence interval [CI]: 0.45-0.82, P = 0.001; 250+, HR 0.66, 95% CI, 0.44-1.00, P = -0.05). Male sex, older age, and duration of time on ART were independently associated with mortality. When left-censoring at 2 years, CD4 nadir was no longer statistically significantly associated with mortality., Conclusion: After surviving for 1 year on ART, a CD4 nadir was strongly predictive of longer-term mortality among patients in Uganda. This should argue for efforts to increase engagement with patients to ensure a higher CD4 nadir at initiation of treatment.

Background: Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda., Methods: We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up., Results: We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively)., Conclusions: In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care.

Objective: Evaluations of CD4 cell count and other prognostic factors on the survival of HIV patients in sub-Saharan Africa are extremely limited. Funders have been reticent to recommend earlier initiation of treatment. We aimed to examine the effect of baseline CD4 cell count on mortality using data from HIV patients receiving combination antiretroviral therapy (cART) in Uganda., Design: Observational study of patients aged at least 14 years enrolled in 10 clinics across Uganda for which The AIDS Support Organization (TASO) has data., Methods: CD4 cell count was stratified into categories (<50, 50-99, 100-149, 150-199, 200-249, 250-299, ≥300 cells/μl) and Cox proportional hazards regression was used to model the associations between CD4 cell count and mortality., Results: A total of 22 315 patients were included. 1498 patients died during follow-up (6.7%) and 1433 (6.4%) of patients were lost to follow-up. Crude mortality rates (CMRs) ranged from 53.8 per 1000 patient-years [95% confidence interval (CI) 48.8-58.8] among those with CD4 cell counts of less than 50, to 15.7, (95% CI 12.1-19.3) among those with at least 300 cells/μl. Relative to a baseline CD4 cell count of less than 50 cells/μl, the risk of mortality was 0.75 (95% CI 0.65-0.88), 0.60 (95% CI 0.51-0.70), 0.43 (0.37-0.50), and 0.41 (0.33-0.51) for those with baseline CD4 cell counts of 50-99, 100-149, 150-249, and ≥250 cells/μl, respectively., Conclusion: Earlier initiation of cART is associated with increased survival benefits over deferred treatment.

Objective: To examine if there is a significant difference in survival between elderly (>50 years) and nonelderly adult patients receiving combination antiretroviral therapy in Uganda between 2004 and 2010., Design: Prospective observational study., Methods: Patients 18-49 years of age (nonelderly) and 50 years of age and older enrolled in the AIDS Support Organization Uganda HIV/AIDS national programme were assessed for time to all-cause mortality. We applied a Weibull multivariable regression., Results: Among the 22 087 patients eligible for analyses, 19 657 (89.0%) were aged between 18 and 49 years and 2430 (11.0%) were aged 50 years or older. These populations differed in terms of the distributions of sex, baseline CD4 cell count and death. The age group 40-44 displayed the lowest crude mortality rate [31.4 deaths per 1000 person-years; 95% confidence interval (CI) 28.1, 34.7) and the age group 60-64 displayed the highest crude mortality rate (58.9 deaths per 1000 person-years; 95% CI 42.2, 75.5). Kaplan-Meier survival estimates indicated that nonelderly patients had better survival than elderly patients (P < 0.001). Adjusted Weibull analysis indicated that elderly age status was importantly associated (adjusted hazard ratio 1.23, 95% CI 1.08-1.42) with mortality, when controlling for sex, baseline CD4 cell count and year of therapy initiation., Conclusion: As antiretroviral treatment cohorts mature, the proportion of patients who are elderly will inevitably increase. Elderly patients may require focused clinical care that extends beyond HIV treatment.

The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We report the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 106 cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load > or =100,000 copies. Baseline characteristics did not change over time. Considerably fewer men than women presented for treatment. Both men and women presented at an advanced stage with very low median CD4 count and high plasma viral load.