Integrated management of HIV, diabetes, and hypertension in sub-Saharan Africa (INTE-AFRICA): a pragmatic cluster-randomised, controlled trial.

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases.

In the era of universal test and treat in Uganda, recent intimate partner violence is not associated with subsequent ART use or viral suppression.

Intimate partner violence (IPV) has been associated with delays throughout the HIV care continuum. This study explored prospective associations between experiences of past-year IPV and two HIV care outcomes in the context of current universal test and treat guidelines using two consecutive rounds of an ongoing HIV surveillance study conducted in the Rakai region of Uganda. Longitudinal logistic regression models examined associations between IPV, use of antiretroviral therapy (ART) and viral load suppression (VS), adjusting for outcome variables at baseline. To address differences in ART retention by IPV, propensity scores were used to create inverse-probability-of-treatment-and-censoring-weighted (IPTCW) models. At baseline, of 1923 women with HIV (WWH), 34.6%, 26.5%, 13.5% reported past-year verbal, physical and sexual IPV; a lower proportion of persons who experienced physical IPV (79.4%) were VS than those who did not (84.3%; p = 0.01). The proportion VS at baseline also significantly differed by exposure to verbal IPV (p = 0.03). However, in adjusted longitudinal models, IPV was not associated with lower odds of ART use or VS at follow-up. Among WWH in the Rakai region, IPV does not appear to be a barrier to subsequent ART use or VS. However, given the prevalence of IPV in this population, interventions are needed.

Exploring HIV/AIDS investigator perceptions of equity within research partnerships between low-and middle-income and high-income countries: a pilot survey.

BACKGROUND: Recommendations for research partnerships between low- and middle-income countries (LMICs) and high-income countries (HICs) stress the importance of equity within the collaboration. However, there is limited knowledge of the practical challenges and successes involved in establishing equitable research practices. This study describes the results of a pilot survey assessing key issues on LMIC/HIC partnership equity within HIV/AIDS research collaborations and compares perspectives of these issues between LMIC- and HIC-based investigators. METHODS: Survey participants were selected using clustered, random sampling and snowball sampling. Responses were compared between LMIC and HIC respondents using standard descriptive statistics. Qualitative respondent feedback was analyzed using a combination of exploratory and confirmatory thematic analysis. RESULTS: The majority of categories within four themes (research interests and resources; leadership, trust, and communication; cultural and ethical competence; representation and benefits) demonstrated relative consensus between LMIC and HIC respondents except for 'lack of trust within the partnership' which was rated as a more pronounced challenge by LMIC respondents. However, subcategories within some of the themes had significant differences between respondent groups including: equitable setting of the research agenda, compromise within a partnership, the role of regulatory bodies in monitoring partnerships for equity, and post-study access to research technology. CONCLUSIONS: These efforts serve as a proof-of-concept survey characterizing contemporary issues around international research partnership equity. The frequency and severity of specific equity issues can be assessed, highlighting similarities versus differences in experiences between LMIC and HIC partners as potential targets for further discussion and evaluation.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Pregnancy in Sub-Saharan Africa: A 6-Country Retrospective Cohort Analysis.

BACKGROUND: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. METHODS: We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models. RESULTS: Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13). CONCLUSIONS: Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women.

A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection.

In the absence of effective antiviral therapy, HIV-1 evolves in response to the within-host environment, of which the immune system is an important aspect. During the earliest stages of infection, this process of evolution is very rapid, driven by a small number of CTL escape mutations. As the infection progresses, immune escape variants evolve under reduced magnitudes of selection, while competition between an increasing number of polymorphic alleles (i.e., clonal interference) makes it difficult to quantify the magnitude of selection acting upon specific variant alleles. To tackle this complex problem, we developed a novel multi-locus inference method to evaluate the role of selection during the chronic stage of within-host infection. We applied this method to targeted sequence data from the p24 and gp41 regions of HIV-1 collected from 34 patients with long-term untreated HIV-1 infection. We identify a broad distribution of beneficial fitness effects during infection, with a small number of variants evolving under strong selection and very many variants evolving under weaker selection. The uniquely large number of infections analysed granted a previously unparalleled statistical power to identify loci at which selection could be inferred to act with statistical confidence. Our model makes no prior assumptions about the nature of alleles under selection, such that any synonymous or non-synonymous variant may be inferred to evolve under selection. However, the majority of variants inferred with confidence to be under selection were non-synonymous in nature, and in most cases were have previously been associated with either CTL escape in p24 or neutralising antibody escape in gp41. We also identified a putative new CTL escape site (residue 286 in gag), and a region of gp41 (including residues 644, 648, 655 in env) likely to be associated with immune escape. Sites inferred to be under selection in multiple hosts have high within-host and between-host diversity although not all sites with high between-host diversity were inferred to be under selection at the within-host level. Our identification of selection at sites associated with resistance to broadly neutralising antibodies (bNAbs) highlights the need to fully understand the role of selection in untreated individuals when designing bNAb based therapies.

Patient and health provider costs of integrated HIV, diabetes and hypertension ambulatory health services in low-income settings - an empirical socio-economic cohort study in Tanzania and Uganda.

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.

Terminal Effector CD8 T Cells Defined by an IKZF2+IL-7R- Transcriptional Signature Express FcγRIIIA, Expand in HIV Infection, and Mediate Potent HIV-Specific Antibody-Dependent Cellular Cytotoxicity.

HIV-1 infection expands large populations of late-stage differentiated CD8 T cells that may persist long after viral escape from TCR recognition. In this study, we investigated whether such CD8 T cell populations can perform unconventional innate-like antiviral effector functions. Chronic untreated HIV-1 infection was associated with elevated numbers of CD45RA+CD57+ terminal effector CD8 T cells expressing FcγRIIIA (CD16). The FcγRIIIA+ CD8 T cells displayed a distinctive transcriptional profile between conventional CD8 T cells and NK cells, characterized by high levels of IKZF2 and low expression of IL7R This transcriptional profile translated into a distinct NKp80+ IL-7Rα- surface phenotype with high expression of the Helios transcription factor. Interestingly, the FcγRIIIA+ CD8 T cells mediated HIV-specific Ab-dependent cellular cytotoxicity (ADCC) activity at levels comparable with NK cells on a per cell basis. The FcγRIIIA+ CD8 T cells were highly activated in a manner that correlated positively with expansion of the CD8 T cell compartment and with plasma levels of soluble mediators of antiviral immunity and inflammation such as IP-10, TNF, IL-6, and TNFRII. The frequency of FcγRIIIA+ CD8 T cells persisted as patients initiated suppressive antiretroviral therapy, although their activation levels declined. These data indicate that terminally differentiated effector CD8 T cells acquire enhanced innate cell-like characteristics during chronic viral infection and suggest that HIV-specific ADCC is a function CD8 T cells use to target HIV-infected cells. Furthermore, as the FcγRIIIA+ CD8 T cells persist in treatment, they contribute significantly to the ADCC-capable effector cell pool in patients on antiretroviral therapy.

"I felt very small and embarrassed by the health care provider when I requested to be tested for syphilis": barriers and facilitators of regular syphilis and HIV testing among female sex workers in Uganda.

BACKGROUND: Periodic testing of female sex workers (FSW) for sexually transmitted infections (STIs) is a core component of global and national responses to achieve population-level STI elimination. We conducted a qualitative study to explore barriers and facilitators of regular syphilis and HIV testing among FSW in Uganda. METHODS: Within a quasi-experimental study among 436 FSW to assess the effect of peer education and text message reminders on uptake of regular STI and HIV testing among FSW, we conducted 48 qualitative interviews in four cities in Uganda from August-December 2018. We purposively selected FSW who tested for syphilis and HIV every 3-6 months; 12 FSW were interviewed in each city. Sex worker interviews explored: 1) reasons for periodic syphilis and HIV testing; 2) barriers and facilitators of testing; 3) experiences of testing; and 4) challenges faced while seeking testing services. Data were analyzed using thematic content analysis. RESULTS: Thematic analysis revealed individual- and health system-level barriers and facilitators of testing. For syphilis, barriers were a) interpersonal stigma, low perceived severity of syphilis and testing misconceptions (individual); and b) judgmental provider attitudes, paucity of facilities offering syphilis testing, stockouts of test kits and high cost (health system). Facilitators were c) desire to remain healthy, get married and have children, knowing the benefits of early treatment, influence of male partners/clients and normative testing behaviors (individual); and d) sex worker clinics offering dual syphilis/HIV testing (health system). For HIV, barriers included: a) internalized stigma (individual); and b) unfavorable clinic hours, stigma, discrimination, and unfriendly provider (health system). Facilitators were a) motivations to stay healthy and attract clients, habitual testing, self-efficacy, doubts about accuracy of negative test results, and use of post-exposure prophylaxis (individual); and d) availability of testing facilities (health system). Syphilis and HIV had similar testing barriers and facilitators. CONCLUSIONS: HIV programs are likely to be important entry points for syphilis testing among FSW. Multi-level interventions to address testing barriers should consider focusing on these service delivery points. Extending the dual syphilis and HIV testing approach to FSW may improve testing uptake for both infections at public health facilities and decrease population-level incidence.

Drivers and barriers to workplace-based HIV self-testing among high-risk men in Uganda: a qualitative study.

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.

Text message reminders and peer education increase HIV and Syphilis testing among female sex workers: a pilot quasi-experimental study in Uganda.

BACKGROUND: Globally, female sex workers (FSW) are disproportionately affected by HIV and other sexually transmitted infections (STIs). However, uptake of STI and HIV testing services among FSW in sub-Saharan Africa remains low. We aimed to assess the effect of FSW-led peer education and text message reminders on 3-monthly syphilis and HIV testing among FSW in Uganda. METHODS: Between September 2019 and February 2020, we implemented weekly peer education sessions and bi-monthly SMS reminders for FSW in Mbarara (intervention city). Peer education sessions were implemented by 20 FSW, who received five days of basic training as peer educators. We held monthly meetings with peer educators throughout the six-month implementation period. FSW in Mbale (control city) continued to receive standard of care consisting of HIV testing outreach campaigns, and facility-based testing. Using a quasi-experimental design in one intervention city, and one control city, we conducted pre- and post- questionnaire-based surveys on recent syphilis and HIV testing behavior among FSW in July-October 2018, and March 2020. We compared proportions and prevalence ratios at baseline and follow-up using chi-square tests and negative binomial regression. RESULTS: We conducted 436 interviews (200 before/236 after) with FSW. At baseline similar proportions reported taking an HIV test (57 % vs. 54 %; p = 0.72), and a syphilis serology test (35 % vs. 39 %; p = 0.67) in the intervention and control cities, respectively, in the prior three months. After the intervention, this proportion increased to 82 % (95 % confidence interval [CI] 74.0-88.2) for HIV, and 81 % (95 % CI: 73.0-87.0) for syphilis in the intervention city. Relative to baseline in the control city, the proportion testing for HIV was unchanged (52 %) but decreased for syphilis (26 %). CONCLUSIONS: Bi-monthly text message reminders with weekly peer education sessions increased uptake of 3-monthly syphilis and HIV testing in a Ugandan female sex work population and could help increase sex worker engagement in HIV/STI services in line with World Health Organization recommendations.

Integrating diabetes, hypertension and HIV care in sub-Saharan Africa: a Delphi consensus study on international best practice.

BACKGROUND: Although HIV continues to have a high prevalence among adults in sub-Saharan Africa (SSA), the burden of noncommunicable diseases (NCD) such as diabetes and hypertension is increasing rapidly. There is an urgent need to expand the capacity of healthcare systems in SSA to provide NCD services and scale up existing chronic care management pathways. The aim of this study was to identify key components, outcomes, and best practice in integrated service provision for the prevention, identification and treatment of HIV, hypertension and diabetes. METHODS: An international, multi stakeholder e-Delphi consensus study was conducted over two successive rounds. In Round 1, 24 participants were asked to score 27 statements, under the headings 'Service Provision' and 'Benefits of Integration', by importance. In Round 2, the 16 participants who completed Round 1 were shown the distribution of scores from other participants along with the score that they attributed to an outcome and were asked to reflect on the score they gave, based on the scores of the other participants and then to rescore if they wished to. Nine participants completed Round 2. RESULTS: Based on the Round 1 ranking, 19 of the 27 outcomes met the 70% threshold for consensus. Four additional outcomes suggested by participants in Round 1 were added to Round 2, and upon review by participants, 22 of the 31 outcomes met the consensus threshold. The five items participants scored from 7 to 9 in both rounds as essential for effective integrated healthcare delivery of health services for chronic conditions were improved data collection and surveillance of NCDs among people living with HIV to inform integrated NCD/HIV programme management, strengthened drug procurement systems, availability of equipment and access to relevant blood tests, health education for all chronic conditions, and enhanced continuity of care for patients with multimorbidity. CONCLUSIONS: This study highlights the outcomes which may form key components of future complex interventions to define a model of integrated healthcare delivery for diabetes, hypertension and HIV in sub-Saharan Africa.

Perspectives and ethical considerations for return of genetics and genomics research results: a qualitative study of genomics researchers in Uganda.

BACKGROUND: The return of genetics and genomics research results has been a subject of ongoing global debate. Such feedback is ethically desirable to update participants on research findings particularly those deemed clinically significant. Although there is limited literature, debate continues in African on what constitutes appropriate practice regarding the return of results for genetics and genomics research. This study explored perspectives and ethical considerations of Ugandan genomics researchers regarding the return of genetics and genomics research results. METHODS: This was a qualitative study that employed in-depth interviews. Thirty participants were purposively selected based on their expertise as genomics researchers in Uganda. Data were analysed through content analysis along the main themes of the study using a comprehensive thematic matrix, to identify common patterns arising from the narratives. NVivo software 12 was used to support data analysis. RESULTS: The return of genetics and genomics research results was generally acceptable to researchers, and some indicated that they had previously returned individual or aggregate results to participants and communities. The main reasons cited for sharing research results with participants included their clinical utility, actionability and overall benefit to society. Ethical considerations for appropriate return of results included a need for effective community engagement, genetic counselling prior to disclosure of the results, adequate informed consent, and proper assessment of the implications of, or consequences of returning of results. However, the approaches to return of results were perceived as unstandardized due to the lack of appropriate regulatory frameworks. CONCLUSIONS: The return of genetic and genomic research results is generally acceptable to researchers despite the lack of appropriate regulatory frameworks. Ethical considerations for return of genetics and genomics research results are highly divergent, hence the need for national ethical guidelines to appropriately regulate the practice.

A scoping review of genetics and genomics research ethics policies and guidelines for Africa.

BACKGROUND: Genetics and genomics research (GGR) is increasingly being conducted around the world; yet, researchers and research oversight entities in many countries have struggled with ethical challenges. A range of ethics and regulatory issues need to be addressed through comprehensive policy frameworks that integrate with local environments. While important efforts have been made to enhance understanding and awareness of ethical dimensions of GGR in Africa, including through the H3Africa initiative, there remains a need for in-depth policy review, at a country-level, to inform and stimulate local policy development and revision on the continent. METHODS: To identify and characterize existing ethics-related guidelines and laws applicable to GGR across much of Africa, we conducted a scoping review of English language policy documents identified through databases, repositories, and web searches. Thirty-six documents were included and coded using a framework that contained a range of themes across five analytical categories: (1) respect, (2) beneficence, (3) justice, (4) independent oversight, and (5) bans and prohibitions. Data analysis software (NVivo 12) was used to organize, code, and tabulate information according to document characteristics and topics. Illustrative examples of policy requirements were selected for inclusion. RESULTS: Documents that met inclusion criteria spanned 20 years; published between 1996 and 2018, with the majority (58%) published after 2009. About two-thirds were denoted as "guidelines," and slightly more than half were non-exclusive to GGR. Very few (six) country-level documents identified were specific to GGR. Requirements related to the principle of "respect" appeared most often across all documents, relative to other principles and processes. The most commonly stated ban was on reproductive cloning. Other prohibitions applied to germline editing, undue inducements in research, sample use for commercial purposes, employee mandatory DNA testing, fetal sex selection, stem cell use, eugenics, and research without public health benefits. CONCLUSIONS: Enforceable policies that are indispensable to the ethical conduct and review of GGR are either deficient or missing in many African countries. Existing international, GGR-specific ethics guidelines can be used to inform GGR policy development at a country-level, in conjunction with insight from country specific ethics committees and other local stakeholders.

An assessment of implementation science research capacity in Uganda.

BACKGROUND: In Uganda and other resource-poor countries, relevant research findings face a tortuous path to translation into policy and routine practice. Implementation science (ImSc) research could facilitate faster translation. Presently it is unclear what ImSc research capacity and possible training needs exist among Ugandan researchers. To assess both components, we interviewed potential trainees in Kampala, Uganda. METHODS: We used a cross-sectional design to survey potential ImSc trainees who had some research training and involvement in generating or utilizing research. Using a questionnaire, we documented eligibility for ImSc training, knowledge and interest in training, existing self-assessed confidence in initiating clinical research (SCICR) and self-assessed confidence in initiating ImSc research (SCIIR), availability for training and preferred modes of training. We developed scores from the Likert scales and used descriptive statistics, logistic regression and ordinal logistic regression to evaluate predictors of SCIIR. RESULTS: Between November 2016 and April 2017, we interviewed 190 participants; 60% were men, with a median age of 37 years. Among participants, 33% comprised faculty, 37% were graduate students and 30% were project staff. The majority of respondents knew about ImSc (73%) and were research-trained (80%). Only 9% reported any ImSc-related training. Previous ImSc training was associated with higher odds of a SCIIR score ≥ 75th percentile. Previous ImSc training compared to not having any training was associated with higher odds of reporting abilities in behaviour change theory integration (OR: 3.3, 95% CI: 1.3-8.5, p = 0.01) and framework use in intervention design and implementation (OR: 2.9, 95% CI: 1.1-7.4, p = 0.03), accounting for age, sex and current employment. In addition, 53% of participants preferred in-person (face-to-face) short ImSc courses compared to a year-long training, while 33% preferred online courses. Participants reported median availability of 6 hours per week (IQR: 4, 10) for training. CONCLUSION: Most participants had some understanding of ImSc research, had research training and were interested in ImSc training. Those with previous ImSc training had better skills and SCIIR, compared to those without previous training. A hybrid approach with modular face-to-face training and online sessions would suit the preferences of most potential trainees.

HIV Prevention Efforts and Incidence of HIV in Uganda.

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Risk and protective factors associated with BV chronicity among women in Rakai, Uganda.

OBJECTIVES: To assess risk and protective factors associated with bacterial vaginosis (BV) chronicity ascertained by Nugent score criteria. METHODS: A longitudinal cohort study included 255 sexually experienced, postmenarcheal women who provided weekly self-collected vaginal swabs for up to 2 years. Vaginal swabs were scored using Nugent criteria and classified as normal (≤3), intermediate (4-6) and Nugent-BV (≥7). Detailed behavioural/health information were assessed every 6 months. A per-woman longitudinal summary measure of BV chronicity was defined as the percentage of each woman's weekly vaginal assessments scored as Nugent-BV over a 6-month interval. Risk and protective factors associated with BV chronicity were assessed using multiple linear regression with generalised estimating equations. RESULTS: Average BV chronicity was 39% across all follow-up periods. After adjustment, factors associated with BV chronicity included baseline Nugent-BV (ß=35.3, 95% CI 28.6 to 42.0) compared with normal baseline Nugent scores and use of unprotected water for bathing (ie, rainwater, pond, lake/stream) (ß=12.0, 95% CI 3.4 to 20.5) compared with protected water sources (ie, well, tap, borehole). Women had fewer BV occurrences if they were currently pregnant (ß=-6.6, 95% CI -12.1 to 1.1), reported consistent condom use (ß=-7.7, 95% CI -14.2 to 1.3) or their partner was circumcised (ß=-5.8, 95% CI -11.3 to 0.3). CONCLUSIONS: Factors associated with higher and lower values of BV chronicity were multifactorial. Notably, higher values of BV chronicity were associated with potentially contaminated bathing water. Future studies should examine the role of waterborne microbial agents in the pathogenesis of BV.

HIV and syphilis testing behaviors among heterosexual male and female sex workers in Uganda.

BACKGROUND: In Sub-Saharan Africa where HIV disproportionately affects women, heterosexual male sex workers (HMSW) and their female clients are at risk of acquiring or transmitting HIV and other STIs. However, few studies have described HIV and STI risk among HMSW. We aimed to assess and compare recent HIV and syphilis screening practices among HMSW and female sex workers (FSW) in Uganda. METHODS: Between August and December 2019, we conducted a cross-sectional study among 100 HMSW and 240 female sex workers (FSW). Participants were enrolled through snowball sampling, and an interviewer-administered questionnaire used to collect data on HIV and syphilis testing in the prior 12 and 6 months respectively. Integrated change model constructs were used to assess intentions, attitudes, social influences, norms and self-efficacy of 3-monthly Syphilis and 6-monthly HIV testing. Predictors of HIV and syphilis recent testing behaviors were estimated using negative binomial regression. RESULTS: We enrolled 340 sex workers of whom 100 (29%) were HMSW. The median age was 27 years [interquartile range (IQR) 25-30] for HMSW and 26 years [IQR], (23-29) for FSW. The median duration of sex work was 36 and 30 months for HMSW and FSW, respectively. HMSW were significantly less likely than FSW to have tested for HIV in the prior 12 months (50% vs. 86%; p = 0.001). For MSW, non-testing for HIV was associated with higher education [adjusted prevalence ratio (aPR) 1.66; 95% confidence interval (CI) 1.09-2.50], poor intention to seek HIV testing (aPR 1.64; 95% CI 1.35-2.04), perception that 6-monthly HIV testing was not normative (aPR 1.33; 95% CI 1.09-1.67) and low self-efficacy (aPR 1.41; 95% CI 1.12-1.79). Not testing for syphilis was associated with low intention to seek testing (aPR 3.13; 95% CI 2.13-4.55), low self-efficacy (aPR 2.56; 95% CI 1.35-4.76), negative testing attitudes (aPR 2.33; 95% CI 1.64-3.33), and perception that regular testing was not normative (aPR 1.59; 95% CI 1.14-2.22). CONCLUSIONS: Non-testing for HIV and syphilis was common among HMSW relative to FSW. Future studies should evaluate strategies to increase testing uptake for this neglected sub-population of sex workers.

Lessons learned from descriptions and evaluations of knowledge translation platforms supporting evidence-informed policy-making in low- and middle-income countries: a systematic review.

BACKGROUND: Knowledge translation (KT) platforms are organisations, initiatives and networks that focus on supporting evidence-informed policy-making at least in part about the health-system arrangements that determine whether the right programmes, services and products get to those who need them. Many descriptions and evaluations of KT platforms in low- and middle-income countries have been produced but, to date, they have not been systematically reviewed. METHODS: We identified potentially relevant studies through a search of five electronic databases and a variety of approaches to identify grey literature. We used four criteria to select eligible empirical studies. We extracted data about seven characteristics of included studies and about key findings. We used explicit criteria to assess study quality. In synthesising the findings, we gave greater attention to themes that emerged from multiple studies, higher-quality studies and different contexts. RESULTS: Country was the most common jurisdictional focus of KT platforms, EVIPNet the most common name and high turnover among staff a common infrastructural feature. Evidence briefs and deliberative dialogues were the activities/outputs that were the most extensively studied and viewed as helpful, while rapid evidence services were the next most studied but only in a single jurisdiction. None of the summative evaluations used a pre-post design or a control group and, with the exception of the evaluations of the influence of briefs and dialogues on intentions to act, none of the evaluations achieved a high quality score. CONCLUSIONS: A large and growing volume of research evidence suggests that KT platforms offer promise in supporting evidence-informed policy-making in low- and middle-income countries. KT platforms should consider as next steps expanding their current, relatively limited portfolio of activities and outputs, building bridges to complementary groups, and planning for evaluations that examine 'what works' for 'what types of issues' in 'what types of contexts'.