Epidemiology of alcohol use and alcohol use disorders among people living with HIV on antiretroviral therapy in Northwest Tanzania: implications for ART adherence and case management.

Alcohol use disorders (AUD) among people living with HIV (PLHIV) are associated with poor health outcomes. This cross-sectional study examined current alcohol use and AUD among 300 PLHIV on ART at four HIV care centres in Northwest Tanzania. Participants' data were collected using questionnaires. Alcohol use was assessed using Alcohol Use Disorders Identification Test (AUDIT). Logistic regression was used to examine associations between each outcome (current drinking and AUD) and sociodemographic and clinical factors. Association between alcohol use and ART adherence was also studied. The median age of participants was 43 years (IQR 19-71) and 41.3% were male. Twenty-two (7.3%) participants failed to take ART at least once in the last seven days. The prevalence of current drinking was 29.3% (95% CI 24.2-34.8%) and that of AUD was 11.3% (8.2%-15.5%). Males had higher odds of alcohol use (OR 3.03, 95% CI 1.79-5.14) and AUD (3.89, 1.76-8.60). Alcohol use was associated with ART non-adherence (OR = 2.78, 1.10-7.04). There was a trend towards an association between AUD and non-adherence (OR = 2.91, 0.92-9.21). Alcohol use and AUD were common among PLHIV and showed evidence of associations with ART non-adherence. Screening patients for alcohol use and AUD in HIV clinics may increase ART adherence.

Linkage Case Management and Posthospitalization Outcomes in People With HIV: The Daraja Randomized Clinical Trial.

Importance: Despite the widespread availability of antiretroviral therapy (ART), people with HIV still experience high mortality after hospital admission. Objective: To determine whether a linkage case management intervention (named "Daraja" ["bridge" in Kiswahili]) that was designed to address barriers to HIV care engagement could improve posthospital outcomes. Design, Setting, and Participants: Single-blind, individually randomized clinical trial to evaluate the effectiveness of the Daraja intervention. The study was conducted in 20 hospitals in Northwestern Tanzania. Five hundred people with HIV who were either not treated (ART-naive) or had discontinued ART and were hospitalized for any reason were enrolled between March 2019 and February 2022. Participants were randomly assigned 1:1 to receive either the Daraja intervention or enhanced standard care and were followed up for 12 months through March 2023. Intervention: The Daraja intervention group (n = 250) received up to 5 sessions conducted by a social worker at the hospital, in the home, and in the HIV clinic over a 3-month period. The enhanced standard care group (n = 250) received predischarge HIV counseling and assistance in scheduling an HIV clinic appointment. Main Outcomes and Measures: The primary outcome was all-cause mortality at 12 months after enrollment. Secondary outcomes related to HIV clinic attendance, ART use, and viral load suppression were extracted from HIV medical records. Antiretroviral therapy adherence was self-reported and pharmacy records confirmed perfect adherence. Results: The mean age was 37 (SD, 12) years, 76.8% were female, 35.0% had CD4 cell counts of less than 100/µL, and 80.4% were ART-naive. Intervention fidelity and uptake were high. A total of 85 participants (17.0%) died (43 in the intervention group; 42 in the enhanced standard care group); mortality did not differ by trial group (17.2% with intervention vs 16.8% with standard care; hazard ratio [HR], 1.01; 95% CI, 0.66-1.55; P = .96). The intervention, compared with enhanced standard care, reduced time to HIV clinic linkage (HR, 1.50; 95% CI, 1.24-1.82; P < .001) and ART initiation (HR, 1.56; 95% CI, 1.28-1.89; P < .001). Intervention participants also achieved higher rates of HIV clinic retention (87.4% vs 76.3%; P = .005), ART adherence (81.1% vs 67.6%; P = .002), and HIV viral load suppression (78.6% vs 67.1%; P = .01) at 12 months. The mean cost of the Daraja intervention was about US $22 per participant including startup costs. Conclusions and Relevance: Among hospitalized people with HIV, a linkage case management intervention did not reduce 12-month mortality outcomes. These findings may help inform decisions about the potential role of linkage case management among hospitalized people with HIV. Trial Registration: ClinicalTrials.gov Identifier: NCT03858998.

Factors Associated with Short and Long Term Mobility and HIV Risk of Women Living in Fishing Communities Around Lake Victoria in Kenya, Tanzania, and Uganda: A Cross Sectional Survey.

Mobility is linked to negative HIV care continuum outcomes. We sought to understand factors associated with short and long term mobility among women in fishing communities in Kenya, Tanzania, and Uganda. From 2018 through 2019 we conducted a cross-sectional survey of women aged 15 years and above, randomly selected from a census of six fishing villages, around Lake Victoria. Data collected included: demographics, risky sexual behaviour on the most recent trip, and travel behaviour in the previous 4 months. Mobility was recorded as any overnight trip outside the participant's village. A two-level multinomial logistic regression model was used to determine the associated factors. A total of 901 participants were enrolled, of whom 645 (71.6%) reported travelling (53.4%; short and 18.2% long term trips). Five factors were associated with long term travel: age, travel purpose, frequency of travel, sexual behaviour while travelling, and destination. Trips made by women aged 46-75 years were less likely to be long term. Long term trips were more common if the trip was to visit, rather than to trade, and more common for women who reported one or two trips rather than three or more trips. Women who made long term trips were more likely to engage in unprotected sex while on a trip. Women who travelled to a regional town/district or another town/district were more likely to take long term trips. The factors associated with travel duration among women living in fishing communities could inform planning of future health care interventions in these communities.

Routine health check-ups for adolescents in Mwanza City, Tanzania: stakeholders' recommendations on its content, venue, and mode of delivery.

BACKGROUND: Routine adolescent health screening aiming at the detection of unnoticed medical problems may increase awareness among policy makers and contribute to improved health in this population. Research is needed to inform the World Health Organization (WHO) and national health programs to provide evidence-based guidance on whether public health systems should offer comprehensive adolescent health screening, what should be included in different contexts, and how it should be delivered. We conducted formative research to define the content and delivery strategies for health check-ups to be performed in young (10-14 years) and older (15-19 years) adolescents, and to assess whether such services are likely to be acceptable and feasible in Tanzania. METHODS: As part of a collaborative research program coordinated by WHO in Chitungwiza, Zimbabwe; Mwanza City, Tanzania; and Cape Coast, Ghana a series of key informant interviews were conducted from April to July 2020, using a semi-structured guide with purposively selected stakeholders from government departments, non-governmental and community-based organisations, schools and health facilities. Data transcripts were coded using NVivo 12 software and thematic analysis was performed. RESULTS: We report results from 31 key informant interviews to address four main domains: proposed health conditions for routine health check-ups, health interventions to be combined with such check-ups, preferable venues, and the mode for delivering such screening activities. Stakeholders were supportive of introducing routine health check-ups among adolescents. They recommended focusing on non-communicable diseases, physical disabilities, common mental health problems, reproductive health problems, specific communicable diseases, and hygiene-related problems. They also recommended combining counselling and family planning information with these check-ups. Three venues were proposed: schools, community settings (to reach out-of-school adolescents), and youth-friendly health facilities (for conditions requiring a high level of confidentiality). CONCLUSIONS: Stakeholders were supportive of the proposed routine health check-ups for adolescents, recommending specific health conditions to be screened for in both community and school settings. Based on the above, we plan to conduct implementation research to determine the number of new treatable conditions detected, and the costs of offering such services. In the longer term, evaluation of their health impact and cost-effectiveness will be required to guide policy.

Sustainability capacity and health worker normalisation of a successful non-communicable disease (NCD) health systems intervention within primary care settings in Uganda: a quantitative approach to a qualitative question.

BACKGROUND: Interventions for non-communicable diseases are increasingly implemented and evaluated in sub-Saharan Africa, but little is known about their medium- to long-term sustainability beyond the end of research funding. A cluster randomised trial conducted between 2013 and 2016 in Uganda and Tanzania showed that an intervention package to improve hypertension (HT) and type-2 diabetes mellitus (DM) care was highly effective in increasing service readiness and quality of care. The present study assesses the sustainability of the intervention 4 years after the trial in Uganda. METHODS: The study was conducted in 2020 in 22 primary care health facilities (HFs) (3 referrals and 19 lower-level units) that had received the intervention package until trial end (2016), to assess their current capacity and practice to sustain ongoing intervention activities for HT and DM care. Through a cross-sectional survey, 4 pre-defined domains (i.e., cognitive participation, coherence, collective action, and reflexive monitoring) were examined with regard to health worker (HW) normalization and 8 pre-defined domains for intervention sustainability (i.e., organisational capacity, local environment, funding stability, partnerships, communication, evaluation, adaptation, and strategic planning), using the normalisation tool and the program sustainability tool (PSAT). Summary scores were assessed by domains and facility level. RESULTS: Overall normalization strength was adequate at 4.0 (IQR: 3.8, 4.2) of a possible 5 with no evidence of association with HF level (p = 0.40); cognitive participation (buy-in) and reflexive monitoring (appraisal) were strongest at > 4 across all HF levels. All HF levels were weak (< 4) on collective action (teamwork) and coherence (sense-making). Only collective action differed by level (p < 0.002). Overall intervention sustainability was suboptimal at 3.1 [IQR: 1.9, 4.1] of a possible 7 with weak scores on funding stability (2.0), supportive partnerships (2.2), and strategic planning (2.6). Domain differences by HF level were significant for environmental support (p = 0.02) and capacity in organisation (p = 0.01). Adequate strength at a cut-off mean of ≥5 did not differ by HF level for any domain. CONCLUSIONS: Four years after their introduction, practice-dependent intervention elements e.g., local organisational context, HW knowledge or dedication were sustained, but external elements e.g., new funding support or attracting new partners to sustain intervention efforts were not. Whenever new interventions are introduced into an existing health service, their long-term sustainability including the required financial support should be ensured. The quality of services should be upheld by providing routine in-service training with dedicated support supervision.

Medium-to-long term sustainability of a health systems intervention to improve service readiness and quality of non-communicable disease (NCD) patient care and experience at primary care settings in Uganda.

BACKGROUND: With the double burden of rising chronic non-communicable diseases (NCDs) and persistent infectious diseases facing sub-Saharan Africa, integrated health service delivery strategies among resource-poor countries are needed. Our study explored the post-trial sustainability of a health system intervention to improve NCD care, introduced during a cluster randomised trial between 2013 and 2016 in Uganda, focusing on hypertension (HT) and type-2 diabetes mellitus (DM) services. In 2020, 19 of 38 primary care health facilities (HFs) that constituted the trial's original intervention arm until 2016 and 3 of 6 referral HFs that also received the intervention then, were evaluated on i) their facility performance (FPS) through health worker knowledge, and service availability and readiness (SAR), and ii) the quality-of-patient-care-and-experience (QoCE) received. METHODS: Cross-sectional data from the original trial (2016) and our study (2020) were compared. FPS included a clinical knowledge test with 222 health workers: 131 (2016) and 91 (2020) and a five-element SAR assessment of all 22 HFs. QoCE assessment was performed among 420 patients: 88 (2016) and 332 (2020). Using a pair-matched approach, FPS and QoCE summary scores were compared. Linear and random effects Tobit regression models were also analysed. RESULTS: The mean aggregate facility performance (FPS) in 2020 was lower than in 2016: 70.2 (95%CI = 66.0-74.5) vs. 74.8 (95%CI = 71.3-78.3) respectively, with no significant difference (p = 0.18). Mean scores declined in 4 of 5 SAR elements. Overall FPS was negatively affected by rural or urban HF location relative to peri-urban HFs (p < 0.01). FPS was not independently predicted but patient club functionality showed weak association (p = 0.09). QoCE declined slightly to 8.7 (95%CI = 8.4-91) in 2020 vs 9.5 (95%CI = 9.1-9.9) in 2016 (p = 0.02) while the proportion of patients receiving adequate quality care also declined slightly to 88.2% from 98.5% respectively, with no statistical difference (p = 0.20). Only the parent district weakly predicted QoCE (p = 0.05). CONCLUSIONS: Four years after the end of research-related support, overall facility performance had declined as expected because of the interrupted supplies and a decline in regular supervision. However, both service availability and readiness and quality of HT/DM care were surprisingly well preserved. Sustainability of an NCD intervention in similar settings may remain achievable despite the funding instability following a trial's end but organisational measures to prepare for the post-trial phase should be taken early on in the intervention process.

Hand hygiene intervention to optimise soil-transmitted helminth infection control among primary school children: the Mikono Safi cluster randomised controlled trial in northwestern Tanzania.

BACKGROUND: Soil-transmitted helminth (STH) infections are highly prevalent in resource-limited countries. We assessed the effect of a combination intervention aiming to enhance handwashing with soap on STH reinfection following mass drug administration among primary school children in Kagera region, Northwestern Tanzania. METHODS: We conducted a cluster randomised trial in sixteen primary schools with known high STH prevalence. Schools were randomly assigned in a 1:1 ratio to either receive the intervention or continue with routine health education. The intervention included teacher-led classroom teaching, parental engagement sessions, environmental modifications and improved handwashing stations. The evaluation involved two cross-sectional surveys in a representative sample of students, with the end-line survey conducted 12 months after the baseline survey. The primary outcome was the combined prevalence of Ascaris lumbricoides and Trichuris trichiura infections at the end-line survey. Secondary outcomes included reported handwashing behaviour, the prevalence and intensity of individual STHs, and hand contamination with STH ova and coliform bacteria. End-line STH prevalence and intensity were adjusted for baseline differences of potential confounders. RESULTS: At the end-line survey, 3081 school children (1566 from intervention schools and 1515 from control schools) provided interview data and stool specimens. More school children in the intervention group reported the use of water and soap during handwashing compared to school children in the control group (58% vs. 35%; aOR=1.76, 95%CI 1.28-2.43, p=0.001). The combined prevalence of A. lumbricoides and T. trichiura infections was 39% in both trial arms (aOR = 1.19; 95%CI 0.74-1.91). The prevalence of A. lumbricoides was 15% in the intervention and 17% in the control arm (aOR =1.24, 95%CI 0.59-2.59) and that of T. trichiura was 31% in both arms (aOR=1.17, 95%CI 0.73-1.88). No significant differences were found for STH infection intensity in both the main study and the hand contamination sub-study. CONCLUSIONS: The intervention was effective in increasing reported handwashing behaviour at school, but failed to show a similar effect in the home. The intervention had no effect on STH infection, possibly due to infection in the home environment, other transmission routes such as contaminated water or food or limited changes in school children's handwashing behaviour. TRIAL REGISTRATION: The trial was registered on June 21, 2017, by the International Standard Randomised Controlled Trial Number ( ISRCTN45013173) .

The burden of HIV, syphilis and schistosome infection and associated factors among adults in the fishing communities in northwestern Tanzania.

OBJECTIVES: To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania. METHODS: Cross-sectional study conducted between 2015 and 2016 in the selected communities. In each community, we randomly selected a sample of adults from the general population and from three putative risk groups including the following: (i) fishermen, (ii) fish processors and traders, and (iii) women working in the recreational facilities. Participants were interviewed to obtain information about potential risk factors, and venous blood was collected for detection of HIV, syphilis and schistosome infections. We used logistic regression models to quantify the associations between potential risk factors and HIV, and also between schistosome infection and HIV. RESULTS: We enrolled 1128 people from selected fishing communities. The overall prevalence of HIV, syphilis and schistosome infection was 14.2%, 15.6% and 83.1%, respectively. Female recreational facility workers had the highest prevalence of HIV (30.4%) and syphilis (24%). The odds of being HIV infected were generally higher in all age categories. Transactional sex was commonly reported and especially receiving gifts for sex was found to be strongly associated with HIV (adjusted OR = 2.50; 95% CI: 1.44-4.34, P = 0.008). Confirmed serological syphilis was associated with increased odds of having HIV infection. HIV was not associated with schistosome infection in a combined dataset and when we examined this separately for men and women alone. CONCLUSIONS: We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents.

OBJECTIFS: Quantifier la charge du VIH, de la syphilis et de l'infection à schistosomes et les facteurs de risque associés chez les adultes vivant dans sept communautés de pêcheurs du lac Victoria dans le nord-ouest de la Tanzanie. MÉTHODES: Etude transversale menée entre 2015-2016 dans les communautés sélectionnées. Dans chaque communauté, nous avons sélectionné aléatoirement un échantillon d'adultes de la population générale et de trois groupes à risque présumés, notamment: 1) les pêcheurs, 2) les transformateurs et commerçants de poisson et 3) les femmes travaillant dans les établissements de loisirs. Les participants ont été interrogés pour obtenir des informations sur les facteurs de risque potentiels, et du sang veineux a été collecté pour la détection du VIH, de la syphilis et des infections à schistosome. Nous avons utilisé des modèles de régression logistique pour quantifier les associations entre les facteurs de risque potentiels et le VIH, ainsi qu'entre l'infection à schistosome et le VIH. RÉSULTATS: Nous avons recruté 1.128 personnes dans une sélection de communautés de pêcheurs. La prévalence globale de l'infection par le VIH, la syphilis et les schistosomes était de 14,2%, 15,6% et 83,1% respectivement. Les travailleuses des établissements de loisirs avaient la prévalence la plus élevée du VIH (30,4%) et de la syphilis (24%). Les chances d'être infecté par le VIH étaient généralement plus élevées dans toutes les catégories d'âge. Les rapports sexuels transactionnels étaient fréquemment rapportés et surtout le fait de recevoir des cadeaux pour le sexe était fortement associé au VIH (OR ajusté = 2,50; IC95%: 1,44-4,34 ; P = 0,008). La syphilis sérologique confirmée était associée à une probabilité accrue d'être infecté par le VIH. Le VIH n'était pas associé à une infection à schistosome dans un ensemble de données combinées et lorsque nous avons examiné cela séparément pour les hommes et les femmes. CONCLUSIONS: Nous avons observé une charge élevée d'infections par le VIH, la syphilis et les schistosomes dans les communautés de pêcheurs. Des efforts ciblés pour traiter et contrôler les infections ont le potentiel d'améliorer la santé des résidents.

Effect of Stopping Cotrimoxazole Preventive Therapy on Microbial Translocation and Inflammatory Markers Among Human Immunodeficiency Virus-Infected Ugandan Adults on Antiretroviral Therapy: The COSTOP Trial Immunology Substudy.

BACKGROUND: Cotrimoxazole preventive therapy (CPT) in human immunodeficiency virus (HIV) infection is a World Health Organization-recommended standard of care in resource-limited settings, but the mechanism of CPT's beneficial effects is unclear. The COSTOP trial (ISRCTN44723643) evaluated the noninferiority of discontinuing CPT in stabilized patients on antiretroviral therapy. The COSTOP immunology substudy was conducted on a subset of COSTOP participants randomized to continue CPT (n = 86) or discontinue CPT (placebo, n = 86) as daily treatment for 1 year. METHODS: We evaluated whether CPT reduces microbial translocation, indicated by the presence of bacterial lipopolysaccharide (LPS) and LPS control factors such as soluble CD14 (sCD14) and endotoxin core antibody (EndoCAb immunoglobulin M [IgM]) in plasma. Intestinal barrier damage as indicated by plasma intestinal fatty acid binding protein (IFABP), T-cell activation, and the inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were also evaluated. RESULTS: We found no significant change in markers of microbial translocation (LPS, IFABP, sCD14, and T-cell activation), with decreased EndoCAb IgM. There was significant increase in inflammation markers (CRP and IL-6) after stopping CPT compared to those who continued CPT. CONCLUSIONS: These results add to the evidence of immunological benefits of CPT among HIV-infected populations in resource-limited settings. However, no evidence of reducing microbial translocation was observed.

Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania.

BACKGROUND: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. METHODS: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. RESULTS: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. CONCLUSIONS: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. CLINICAL TRIALS REGISTRATION: NCT02376400.

Experiences of capacity strengthening in sanitation and hygiene research in Africa and Asia: the SHARE Research Consortium.

The Sanitation and Hygiene Applied Research for Equity (SHARE) Research Programme consortium is a programme funded by the United Kingdom Department for International Development (DFID) that aims to contribute to achieving universal access to effective, sustainable, and equitable sanitation and hygiene worldwide. The capacity development component is an important pillar for this programme and different strategies were designed and implemented during the various phases of SHARE. This paper describes and reflects on the capacity-building strategies of this large multi-country research consortium, identifying lessons learnt and proposing recommendations for future global health research programmes. In the first phase, the strategy focused on increasing the capacity of individuals and institutions from low- and middle-income countries in conducting their own research. SHARE supported six PhD students and 25 MSc students, and organised a wide range of training events for different stakeholders. SHARE peer-reviewed all proposals that researchers submitted through several rounds of funding and offered external peer-review for all the reports produced under the partner's research platforms. In the second phase, the aim was to support capacity development of a smaller number of African research institutions to move towards their independent sustainability, with a stronger focus on early and mid-career scientists within these institutions. In each institution, a Research Fellow was supported and a specific capacity development plan was jointly developed.Strategies that yielded success were learning by doing (supporting institutions and postgraduate students on sanitation and hygiene research), providing fellowships to appoint mid-career scientists to support personal and institutional development, and supporting tailored capacity-building plans. The key lessons learnt were that research capacity-building programmes need to be driven by local initiatives tailored with support from partners. We recommend that future programmes seeking to strengthen research capacity should consider targeted strategies for individuals at early, middle and later career stages and should be sensitive to other institutional operations to support both the research and management capacities.

The validity of an area-based method to estimate the size of hard-to-reach populations using satellite images: the example of fishing populations of Lake Victoria.

BACKGROUND: Information on the size of populations is crucial for planning of service and resource allocation to communities in need of health interventions. In resource limited settings, reliable census data are often not available. Using publicly available Google Earth Pro and available local household survey data from fishing communities (FC) on Lake Victoria in Uganda, we compared two simple methods (using average population density) and one simple linear regression model to estimate populations of small rural FC in Uganda. We split the dataset into two sections; one to obtain parameters and one to test the validity of the models. RESULTS: Out of 66 FC, we were able to estimate populations for 47. There were 16 FC in the test set. The estimates for total population from all three methods were similar, with errors less than 2.2%. Estimates of individual FC populations were more widely discrepant. CONCLUSIONS: In our rural Ugandan setting, it was possible to use a simple area based model to get reasonable estimates of total population. However, there were often large errors in estimates for individual villages.

Factors associated with uptake of home-based HIV counselling and testing and HIV care services among identified HIV-positive persons in Masaka, Uganda.

We investigated uptake of home-based HIV counselling and testing (HBHCT) and HIV care services post-HBHCT in order to inform the design of future HBHCT programmes. We used data from an open-label cluster-randomised controlled trial which had demonstrated the effectiveness of a post-HBHCT counselling intervention in increasing linkage to HIV care. HBHCT was offered to adults (≥18 years) from 28 rural communities in Masaka, Uganda; consenting HIV-positive care naïve individuals were enrolled and referred for care. The trial's primary outcome was linkage to HIV care (clinic-verified registration for care) six months post-HBHCT. Random effects logistic regression was used to investigate factors associated with HBHCT uptake, linkage to care, CD4 count receipt, and antiretroviral therapy (ART) initiation; all analyses of uptake of post-HBHCT services were adjusted for trial arm allocation. Of 13,455 adults offered HBHCT, 12,100 (89.9%) accepted. HBHCT uptake was higher among men [adjusted odds ratio (aOR) 1.20, 95% confidence interval (CI) = 1.07-1.36] than women, and decreased with increasing age. Of 551 (4.6%) persons who tested HIV-positive, 205 (37.2%) were in care. Of those not in care, 302 (87.3%) were enrolled in the trial and of these, 42.1% linked to care, 35.4% received CD4 counts, and 29.8% initiated ART at 6 months post-HBHCT. None of the investigated factors was associated with linkage to care. CD4 count receipt was lower in individuals who lived ≥30 min from an HIV clinic (aOR 0.60, 95%CI = 0.34-1.06) versus those who lived closer. ART initiation was higher in older individuals (≥45 years versus <25 years, aOR 2.14, 95% CI = 0.98-4.65), and lower in single (aOR 0.60, 95% CI = 0.28-1.31) or divorced/separated/widowed (aOR 0.47, 95% CI = 0.23-0.93) individuals versus those married/cohabiting. HBHCT was highly acceptable but uptake of post-HBHCT care was low. Other than post-HBHCT counselling, this study did not identify specific issues that require addressing to further improve linkage to care.

Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: a systematic review.

BACKGROUND: Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. METHODS: Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. RESULTS: A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions. CONCLUSION: Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials.

Incidence and Persistence of Major Depressive Disorder Among People Living with HIV in Uganda.

Data on the course of major depressive disorder (MDD) among people living with HIV (PLWH) are needed to inform refinement of screening and interventions for MDD. This paper describes the incidence and persistence rate of MDD in PLWH in Uganda. 1099 ART-naïve PLWH attending HIV clinics in Uganda were followed up for 12 months. MDD was assessed using the DSM IV based Mini-International Neuropsychiatric Interview with a prevalence for MDD at baseline of 14.0 % (95 % CI 11.7-16.3 %) reported. Multivariable logistic regression was used to determine predictors of incident and persistent MDD. Cumulative incidence of MDD was 6.1 per 100 person-years (95 % CI 4.6-7.8) with significant independent predictors of study site, higher baseline depression scores and increased stress. Persistence of MDD was 24.6 % (95 % CI 17.9-32.5 %) with independent significant predictors of study site, higher baseline depression scores, and increased weight. Risks of incident and persistent MDD observed in this study were high. Potentially modifiable factors of elevated baseline depressive scores and stress (only for incident MDD) were important predictors of incident and persistent MDD.

The Association Between Cervical Human Papillomavirus Infection and Subsequent HIV Acquisition in Tanzanian and Ugandan Women: A Nested Case-Control Study.

OBJECTIVE: This study was performed to analyze the associations between cervical human papillomavirus (HPV) infection and human immunodeficiency virus (HIV) acquisition, using cervical samples from previous studies in Tanzania and Uganda. METHODS: A total of 161 adult women who acquired HIV infection during follow-up and 464 individually matched HIV-seronegative controls were selected from 5 cohorts of women working in bars and recreational facilities. Stored cervical samples were tested for 37 HPV genotypes, using a polymerase chain reaction assay (Roche Linear Array genotyping assay). Multivariate matched analysis using conditional logistic regression was performed to evaluate HPV infection, persistence, and clearance as predictors of HIV acquisition. RESULTS: HIV seroconverters were significantly more likely than controls to frequently drink alcohol and to be infected with Chlamydia trachomatis, Neisseria gonorrhoeae, or herpes simplex virus type 2. There was no evidence of an association between HIV acquisition and any detectable HPV at the visit prior to HIV seroconversion (adjusted odds ratio, 1.02; 95% confidence interval, .66-1.57) or between HIV acquisition and persistent HPV infection (defined as 2 positive HPV genotype-specific test results at least 6 months apart), cleared HPV infection (defined as a positive HPV test result followed by negative HPV genotype-specific test result), or newly acquired HPV infection, compared with HPV-negative women. CONCLUSIONS: There was no evidence of association between HPV infection status and subsequent HIV acquisition. These results stand in contrast to other observational studies.

Bacterial vaginosis among women at high risk for HIV in Uganda: high rate of recurrent diagnosis despite treatment.

OBJECTIVES: Bacterial vaginosis (BV) is associated with increased risk for sexually transmitted infections (STIs) and HIV acquisition. This study describes the epidemiology of BV in a cohort of women at high risk for STI/HIV in Uganda over 2 years of follow-up between 2008-2011. METHODS: 1027 sex workers or bar workers were enrolled and asked to attend 3-monthly follow-up visits. Factors associated with prevalent BV were analysed using multivariate random-effects logistic regression. The effect of treatment on subsequent episodes of BV was evaluated with survival analysis. RESULTS: Prevalences of BV and HIV at enrolment were 56% (573/1027) and 37% (382/1027), respectively. Overall, 905 (88%) women tested positive for BV at least once in the study, over a median of four visits. Younger age, a higher number of previous sexual partners and current alcohol use were independently associated with prevalent BV. BV was associated with STIs, including HIV. Hormonal contraception and condom use were protective against BV. Among 853 treated BV cases, 72% tested positive again within 3 months. There was no difference in time to subsequent BV diagnosis between treated and untreated women. CONCLUSIONS: BV was highly prevalent and persistent in this cohort despite treatment. More effective treatment strategies are urgently needed.

Decreased renal function and associated factors in cities, towns and rural areas of Tanzania: a community-based population survey.

OBJECTIVES: Data on renal dysfunction in sub-Saharan Africa, comparing urban and rural areas, have not yet been reported. Therefore, we aimed to determine the distribution of low estimated glomerular filtration rates (eGFRs) in urban and rural Tanzania, to describe factors associated with low eGFR and to quantify fractions attributable to common risk factors. METHODS: We conducted a community-based survey of 1095 randomly selected Tanzanian adults (≥18 years). A structured questionnaire and examinations were used to document sociodemographic characteristics, diet, physical activity, anthropomorphic measurements and blood pressure. Blood tests were performed for HIV infection, diabetes mellitus and creatinine. eGFR was calculated using two equations recommended for African adults. RESULTS: Serum creatinine was available for 1043 participants: 170 in Mwanza city, 326 in district towns and 547 in rural areas. Mean age was 35.5 years and 54% were females. The prevalence of eGFR < 60 ml/min/1.73 m(2) in these 3 strata was 2.3% (95% CI = 0.8-6.6%), 7.5% (4.7-11.8%) and 7.4% (5.1-10.6%), respectively. When age standardised to the WHO world population, prevalences were 3.8%, 10.1% and 8.1%. Factors associated with low eGFR included district town residence, older age, greater wealth, less physical activity and hypertension. Only 21% of cases with eGFR < 60 ml/min/1.73 m(2) were attributable to HIV, hypertension or diabetes. CONCLUSIONS: Decreased renal function is common in Tanzania, particularly in district towns, and unique risk factors for kidney disease may exist in this population. Population-specific strategies for prevention, early diagnosis and treatment of kidney disease are needed for Africa.

Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study.

BACKGROUND: The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX). METHODS: This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use. RESULTS: 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30. CONCLUSIONS: The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.

The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models.

In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003-2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.