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Poeple living with HIV have higher prevalence of diabetes mellitus and metabolic perturbations compared to non-HIV populations. Diabetes and metabolic syndrome co-morbidities add significant burden to HIV care. Currently, WHO recommends integrase strand transfer inhibitors (INSTIs) as the first or second line therapy in people with HIV due to overall good tolerability and safety profile. However, whether INSTI use increases the risk of incident diabetes (with or without metabolic syndrome) compared to other anti-retroviral therapies (ART) is controversial. In this systematic review and meta-analysis, we aim to examine this risk in HIV-positive populations receiving INSTIs compared to other ART regimens (not containing INSTIs). The study will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. This protocol adheres to the Standard Protocol Items for reporting systematic reviews and meta-analyses checklist. Eligibility criteria will be original peer-reviewed published articles and conference abstracts with no language or geographical restriction; that report the ocurrence of diabetes mellitus as a discrete outcome or part of metabolic syndrome, in adult PLWHIV receiving INSTIs compared to other ART regimens. PubMed/ Medline, Web of Science, Embase and Cochrane Database of Systematic Reviews will be searched from 1st- January-2000 to 31st-January-2022. Per our a priori, screening, inclusion and data extraction will be conducted separately by two investigators, and a senior researcher will be consulted in case of disagreement. The quality of included studies will be assessed by the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies and the revised Cochrane risk-of-bias tool (ROB2) for randomized controlled trials. The quantitative synthesis of the study outcomes will be explored in different subgroups and sensitivity analyses. Meta regression will also be performed to further test the predictors of the outcome. Ethical approval is waived as the study is a review of published litterature. The analyses will be presented in conferences and published as a scientific article. PROSPERO registration number is; CRD42021273040.

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Background Men in Sub-Saharan Africa are less engaged than women in accessing HIV testing and treatment and, consequently, experience higher HIV-related mortality. Reaching men with HIV testing services is challenging, thus, increasing the need for innovative ways to engage men with low access and those at higher risk. In this study, we explore men’s perceptions of drivers and barriers of workplace-based HIV self-testing in Uganda. Methods An exploratory study involving men working in private security companies employing more than 50 men in two districts, in central and western Uganda. Focus group discussions and key informant interviews were conducted. Data were analyzed using inductive content analysis. Results Forty-eight (48) men from eight private security companies participated in 5 focus group discussions and 17 key informant interviews. Of the 48 men, 14(29.2%) were ages 26–35 years. The majority 31(64.6%) were security guards. The drivers reported for workplace-based HIV self-testing included convenience, autonomy, positive influence from work colleagues, the need for alternative access for HIV testing services, incentives, and involvement of employers. The barriers reported were the prohibitive cost of HIV tests, stigma, lack of testing support, the fear of discrimination and isolation, and concerns around decreased work productivity in the event of a reactive self-test. Conclusions We recommend the involvement of employers in workplace-based HIV self-testing to encourage participation by employees. There is need for HIV self-testing support both during and after the testing process. Both employers and employees recommend the use of non-monetary incentives, and regular training about HIV self-testing to increase the uptake and acceptability of HIV testing services at the workplace.

Human resource limitations are a challenge to the delivery of antiretroviral therapy (ART) in low-resource settings. We conducted a cluster randomized trial to assess the effect of community-based peer health workers (PHW) on AIDS care of adults in Rakai, Uganda. 15 AIDS clinics were randomized 2:1 to receive the PHW intervention (n = 10) or control (n = 5). PHW tasks included clinic and home-based provision of counseling, clinical, adherence to ART, and social support. Primary outcomes were adherence and cumulative risk of virologic failure (>400 copies/mL). Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART. Analysis was by intention to treat. From May 2006 to July 2008, 1336 patients were followed. 444 (33%) of these patients were already on ART at the start of the study. No significant differences were found in lack of adherence (<95% pill count adherence risk ratio [RR] 0.55, 95% confidence interval [CI] 0.23-1.35; <100% adherence RR 1.10, 95% CI 0.94-1.30), cumulative risk of virologic failure (RR 0.81, 95% CI 0.61-1.08) or in shorter-term virologic outcomes (24 week virologic failure RR 0.93, 95% CI 0.65-1.32; 48 week, RR 0.83, 95% CI 0.47-1.48; 72 week, RR 0.81, 95% CI 0.44-1.49). However, virologic failure rates >or=96 weeks into ART were significantly decreased in the intervention arm compared to the control arm (96 week failure RR 0.50, 95% CI 0.31-0.81; 120 week, RR 0.59, 95% CI 0.22-1.60; 144 week, RR 0.39, 95% CI 0.16-0.95; 168 week, RR 0.30, 95% CI 0.097-0.92; 192 week, RR 0.067, 95% CI 0.0065-0.71). A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART, but did not affect cumulative risk of virologic failure, adherence measures, or shorter-term virologic outcomes. PHWs may be an effective intervention to sustain long-term ART in low-resource settings. ClinicalTrials.gov NCT00675389.

Background Medical schools in Sub-Saharan Africa have adopted competency based medical education (CBME) to improve the quality of graduates trained. In 2015, Makerere University College of Health Sciences (MaKCHS) implemented CBME for the Bachelor of Medicine and Bachelor of Surgery (MBChB) programme in order to produce doctors with the required attributes to address community health needs. However, no formal evaluation of the curriculum has been conducted to determine whether all established competencies are being assessed. Objective To evaluate whether assessment methods within the MBChB curriculum address the stated competencies. Methods The evaluation adopted a cross-sectional study design in which the MBChB curriculum was evaluated using an Essential Course Evidence Form (ECEF) that was developed to collect information about each assessment used for each course. Information was collected on: (1) Assessment title, (2) Description, (3) Competency domain (4) Sub-competency addressed, (5) Student instructions, and (6) Grading method/details. Data were entered into a structured Access data base. In addition, face-to-face interviews were conducted with faculty course coordinators. Results The MBChB curriculum consisted of 62 courses over 5 years, focusing on preclinical skills in years 1–2 and clinical skills in years 3–5. Fifty-nine competencies were identified and aggregated into 9 domains. Fifty-eight competencies were assessed at least one time in the curriculum. Faculty cited limited training in assessment as well as large student numbers as hindrances to designing robust assessments for the competencies. Conclusion CBME was successfully implemented evidenced by all but one of the 59 competencies within the nine domains established being assessed within the MBChB curriculum at MaKCHS. Faculty interviewed were largely aware of it, however indicated the need for more training in competency-based assessment to improve the implementation of CBME.

Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called \"Health Scouts\" to promote engagement in HIV treatment and prevention services. The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect. A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control. ClinicalTrials.gov NCT02556957.

The Prevention of Mother-to-Child Transmission of HIV (PMTCT) program in India is one of the largest in the world. It uses outreach workers (ORWs) to facilitate patient uptake of services, however, the challenges faced by the ORWs, and their views about the effectiveness of this program are unknown. The COMmunity-Home Based INDia (COMBIND) Prevention of Mother to Child Transmission of HIV study evaluated an integrated mobile health and behavioral intervention to enhance the capacity of ORWs in India. To understand the challenges faced by ORWs, and their perceptions of opportunities for program improvement, four group discussions were conducted among 60 ORW from four districts of Maharashtra, India, as part of the baseline assessment for COMBIND. Data were qualitatively analyzed using a thematic approach. Numerous personal-, social-, and structural-level challenges existed for ORW as they engaged with their patients. Personal-level challenges for ORWs included disclosure of their own HIV status and travelling costs for home visits. Personal-level challenges for patients included financial costs of travelling to ART centers, non-adherence to ART, loss of daily wages, non-affordability of infant formula, lack of awareness of the baby's needs, financial dependence on family, four time points (6weeks, 6 months, 12 months and 18 months) for HIV tests, and need for nevirapine (NVP) prophylaxis. Social-level challenges included lack of motivation by patients and/or health care staff, social stigma, and rude behavior of health care staff and their unwillingness to provide maternity services to women in the PMTCT programme. Structural-level challenges included cultural norms around infant feeding, shortages of HIV testing kits, shortages of antiretroviral drugs and infant NVP prophylaxis, and lack of training/knowledge related to PMTCT infant feeding guidelines by hospital staff. The consensus among ORWs was that there was a critical need for tools and training to improve their capacity to effectively engage with patients, and deliver appropriate care, and for motivation through periodic feedback. Given the significant challenges in PMTCT programme implementation reported by ORW, novel strategies to address these challenges are urgently needed to improve patient engagement, and access to and retention in care.

Dolutegravir is a preferred antiretroviral drug given its high resistance barrier and efficacy; however, reports from sub-Saharan Africa indicate increased hyperglycemia rates among individuals living with HIV on dolutegravir. Potential mechanisms include mitochondrial dysfunction from previous exposure to NRTIs like stavudine and zidovudine, which causes mitochondrial toxicity and predisposes patients to hyperglycemia upon switching to dolutegravir; magnesium chelation, which is borrowed from dolutegravir’s mode of action (dolutegravir inhibits the action of integrase by chelation of magnesium required as a cofactor by the HIV enzyme); and chronic inflammation, with elevated pro-inflammatory markers like IL-6, CRP, and TNF-α contributing to insulin resistance. The narrative review highlights variability in hyperglycemia among patients, influenced by genetics, lifestyle, and prior antiretroviral therapy. The exact nature of dolutegravir-associated hyperglycemia, whether due to insulin resistance or reduced insulin release, remains unclear, although insulin resistance is significant.

Background. Maternal human immunodeficiency virus (HIV) RNA load, CD4 cell count, breast-feeding, antiretroviral use, and malaria are well-established factors associated with mother-to-child transmission (MTCT) of HIV; the role of maternal tuberculosis (TB), however, has not been well established. Methods. The study population was 783 HIV-infected Indian mother-infant pair participants in randomized and ancillary HIV-infected cohorts of the Six Week Extended-Dose Nevirapine (SWEN) Study, a study comparing extended nevirapine versus single-dose nevirapine, to reduce MTCT of HIV among breast-fed infants. Using multivariable logistic regression, we assessed the impact of maternal TB occurring during pregnancy and through 12 months after delivery on risk of MTCT. Results. Of 783 mothers, 3 had prevalent TB and 30 had incident TB at 12 months after delivery. Of 33 mothers with TB, 10 (30%) transmitted HIV to their infants in comparison with 87 of 750 mothers without TB (12%; odds ratio [OR], 3.31; 95% confidence interval [CI], 1.53–7.29; P = .02). In multivariable analysis, maternal TB was associated with 2.51-fold (95% CI, 1.05–6.02; P = .04) increased odds of HIV transmission adjusting for maternal factors (viral load, CD4 cell count, and antiretroviral therapy) and infant factors (breast-feeding duration, infant nevirapine administration, gestational age, and birth weight) associated with MTCT of HIV. Conclusions. Maternal TB is associated with increased MTCT of HIV. Prevention of TB among HIV-infected mothers should be a high priority for communities with significant HIV/TB burden.

Strengthening health research is essential to inform public health policies. However, few research training programs have systematically measured their impact on capacity building and most evaluations have been limited to reporting of individual trainee metrics. Hence, we conducted an evaluation of the impact of a five-year training program focused on building both trainee and institutional research capacity at a public medical college in India. Quantitative and qualitative methods were used to assess the individual and institutional research capacity building of a five-year HIV-TB research training program at Byramjee Jeejeebhoy Government Medical College in Pune, India, supported by the US National Institutes of Health, Fogarty International Center. In addition to documentation of the number of trainee research projects initiated, the number of research papers produced by the Fogarty Scholars (FSs) available on PubMed was calculated. The institutional impact of this program was assessed by documentation of research training activities conducted by the FSs, as well as by surveys and in-depth interviews conducted at the beginning and end of the program. Twenty-one mid-level BJGMC faculty were provided training in HIV-TB research competencies. Between 1 April 2014 and 1 April 2019, 13 of these FSs designed and implemented new IRB-approved research studies and contributed to 49 PubMed listed research papers, including 11 first-authored manuscripts. FSs also conducted 36 journal club discussions, mentored 58 student research projects and conducted 5 institutional research method workshops. Pre- and-post-program surveys and in-depth interviews documented a perceived increase in institutional research capacity, particularly in TB research (epidemiology, clinical research, laboratory research). The impact of the Fogarty Training Program on institutional scientific output was perceived to be marginally improved. The Fogarty Training Program had a significant impact on building individual research capacity. To sustain this impact beyond the five years of Fogarty support, additional governmental and institutional resources, the establishment of dedicated space for faculty research and protected faculty time for research are needed. These findings can inform the design and implementation of future health research capacity building initiatives.