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.

Incidence and predictors of virological failure among HIV infected children and adolescents receiving second-line antiretroviral therapy in Uganda, a retrospective study.

BACKGROUND: In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. METHODOLOGY: This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. RESULTS: Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 - 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 - 19 years (HR 3.2, 95% 1.6 - 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 - 3.1), p < 0.01) prior to second-line ART switch. CONCLUSION: Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.

Healthcare workers' informal uses of mobile phones and other mobile devices to support their work: a qualitative evidence synthesis.

BACKGROUND: Healthcare workers sometimes develop their own informal solutions to deliver services. One such solution is to use their personal mobile phones or other mobile devices in ways that are unregulated by their workplace. This can help them carry out their work when their workplace lacks functional formal communication and information systems, but it can also lead to new challenges. OBJECTIVES: To explore the views, experiences, and practices of healthcare workers, managers and other professionals working in healthcare services regarding their informal, innovative uses of mobile devices to support their work. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL and Scopus on 11 August 2022 for studies published since 2008 in any language. We carried out citation searches and contacted study authors to clarify published information and seek unpublished data. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with a qualitative component. We included studies that explored healthcare workers' views, experiences, and practices regarding mobile phones and other mobile devices, and that included data about healthcare workers' informal use of these devices for work purposes. DATA COLLECTION AND ANALYSIS: We extracted data using an extraction form designed for this synthesis, assessed methodological limitations using predefined criteria, and used a thematic synthesis approach to synthesise the data. We used the 'street-level bureaucrat' concept to apply a conceptual lens to our findings and prepare a line of argument that links these findings. We used the GRADE-CERQual approach to assess our confidence in the review findings and the line-of-argument statements. We collaborated with relevant stakeholders when defining the review scope, interpreting the findings, and developing implications for practice. MAIN RESULTS: We included 30 studies in the review, published between 2013 and 2022. The studies were from high-, middle- and low-income countries and covered a range of healthcare settings and healthcare worker cadres. Most described mobile phone use as opposed to other mobile devices, such as tablets. We have moderate to high confidence in the statements in the following line of argument. The healthcare workers in this review, like other 'street-level bureaucrats', face a gap between what is expected of them and the resources available to them. To plug this gap, healthcare workers develop their own strategies, including using their own mobile phones, data and airtime. They also use other personal resources, including their personal time when taking and making calls outside working hours, and their personal networks when contacting others for help and advice. In some settings, healthcare workers' personal phone use, although unregulated, has become a normal part of many work processes. Some healthcare workers therefore experience pressure or expectations from colleagues and managers to use their personal phones. Some also feel driven to use their phones at work and at home because of feelings of obligation towards their patients and colleagues. At best, healthcare workers' use of their personal phones, time and networks helps humanise healthcare. It allows healthcare workers to be more flexible, efficient and responsive to the needs of the patient. It can give patients access to individual healthcare workers rather than generic systems and can help patients keep their sensitive information out of the formal system. It also allows healthcare workers to communicate with each other in more personalised, socially appropriate ways than formal systems allow. All of this can strengthen healthcare workers' relationships with community members and colleagues. However, these informal approaches can also replicate existing social hierarchies and deepen existing inequities among healthcare workers. Personal phone use costs healthcare workers money. This is a particular problem for lower-level healthcare workers and healthcare workers in low-income settings as they are likely to be paid less and may have less access to work phones or compensation. Out-of-hours use may also be more of a burden for lower-level healthcare workers, as they may find it harder to ignore calls when they are at home. Healthcare workers with poor access to electricity and the internet are less able to use informal mobile phone solutions, while healthcare workers who lack skills and training in how to appraise unendorsed online information are likely to struggle to identify trustworthy information. Informal digital channels can help healthcare workers expand their networks. But healthcare workers who rely on personal networks to seek help and advice are at a disadvantage if these networks are weak. Healthcare workers' use of their personal resources can also lead to problems for patients and can benefit some patients more than others. For instance, when healthcare workers store and share patient information on their personal phones, the confidentiality of this information may be broken. In addition, healthcare workers may decide to use their personal resources on some types of patients, but not others. Healthcare workers sometimes describe using their personal phones and their personal time and networks to help patients and clients whom they assess as being particularly in need. These decisions are likely to reflect their own values and ideas, for instance about social equity and patient 'worthiness'. But these may not necessarily reflect the goals, ideals and regulations of the formal healthcare system. Finally, informal mobile phone use plugs gaps in the system but can also weaken the system. The storing and sharing of information on personal phones and through informal channels can represent a 'shadow IT' (information technology) system where information about patient flow, logistics, etc., is not recorded in the formal system. Healthcare workers may also be more distracted at work, for instance, by calls from colleagues and family members or by social media use. Such challenges may be particularly difficult for weak healthcare systems. AUTHORS' CONCLUSIONS: By finding their own informal solutions to workplace challenges, healthcare workers can be more efficient and more responsive to the needs of patients, colleagues and themselves. But these solutions also have several drawbacks. Efforts to strengthen formal health systems should consider how to retain the benefits of informal solutions and reduce their negative effects.

Exploration of clinical ethics consultation in Uganda: a case study of Uganda Cancer Institute.

INTRODUCTION: Globally, healthcare providers (HCPs), hospital administrators, patients and their caretakers are increasingly confronted with complex moral, social, cultural, ethical, and legal dilemmas during clinical care. In high-income countries (HICs), formal and informal clinical ethics support services (CESSs) have been used to resolve bioethical conflicts among HCPs, patients, and their families. There is limited evidence about mechanisms used to resolve these issues as well as experiences and perspectives of the stakeholders that utilize them in most African countries including Uganda. METHODS: This phenomenological qualitative study utilized in-depth interviews (IDIs) and focus group discussions (FGDs) to collect data from Uganda Cancer Institute (UCI) staff, patients, and caretakers who were purposively selected. Data was analyzed deductively and inductively yielding themes and sub-themes that were used to develop a codebook. RESULTS: The study revealed there was no formal committee or mechanism dedicated to resolving ethical dilemmas at the UCI. Instead, ethical dilemmas were addressed in six forums: individual consultations, tumor board meetings, morbidity and mortality meetings (MMMs), core management meetings, rewards and sanctions committee meetings, and clinical departmental meetings. Participants expressed apprehension regarding the efficacy of these fora due to their non-ethics related agendas as well as members lacking training in medical ethics and the necessary experience to effectively resolve ethical dilemmas. CONCLUSION: The fora employed at the UCI to address ethical dilemmas were implicit, involving decisions made through various structures without the guidance of personnel well-versed in medical or clinical ethics. There was a strong recommendation from participants to establish a multidisciplinary clinical ethics committee comprising members who are trained, skilled, and experienced in medical and clinical ethics.

Practices and attitudes of herbalists regarding informed consent in Uganda: a qualitative study.

BACKGROUND: Informed consent (IC) is a fundamental principle in medical ethics that upholds respect for patient autonomy. Although widely applied in healthcare, its feasibility and implementation in herbal medicine have been underexplored. This study therefore aimed to explore the practices and attitudes of herbalists regarding informed consent. METHODS: To achieve these objectives, a qualitative cross-sectional study was conducted from June to December 2020. Twenty-one in-depth interviews with herbalists and four key informant interviews with leaders of the different traditional medicine organizations were conducted. The data were analyzed thematically using NVivo version 12 software. RESULTS: Sixteen of the twenty-one participants acquired oral herbal medicine knowledge from their relatives. Although a positive inclination toward obtaining IC was evident, the focus was on disclosing basic information. Discussions of alternative treatments and herbal specifics were less frequent. Disease management decisions often involve shared responsibility within families or societies. Documented IC procedures are rare among herbalists, who deem consent forms unnecessary, although they recognize the potential benefits of IC in fostering trust and professionalism. Challenges hindering IC implementation included regulatory gaps, inadequate skills, and the absence of mechanisms to protect the intellectual property rights of herbal medicine. CONCLUSION: This study illuminates how educational, cultural, familial, and regulatory factors influence herbalists' practices and attitudes toward informed consent.

Family Psycho-Social Involvement Intervention for severe mental illness in Uganda.

Background: Treatment rates for severe mental illness (SMI) are low in low- and middle-income countries because of limited resources. Enlisting family support could be effective and low cost in improving patient outcomes. Aim: The article assess the feasibility, acceptability and estimates of efficacy of Family Psychosocial Involvement Intervention (FAPII) for patients with SMI. Setting: Masaka Regional Referral Hospital and Mityana District Hospital in Uganda. Methods: This was a controlled pilot study with two sites randomly assigned as intervention and control. Thirty patients each with one or two family members and six mental health professionals were recruited at the intervention site. Five patients, their family members and two mental health professionals met monthly for 6 months to discuss pre-agreed mental health topics. Patient outcomes were assessed at baseline, 6- and 12-months and analysed using paired t-tests. The trial was prospectively registered (ISRCTN25146122). Results: At 6 and 12 months, there was significant improvement in the QoL in the intervention group compared to the control (p = 0.001). There was significant symptom reduction in the intervention group at 6 and 12 months (p < 0.001). Family Psychosocial Involvement Intervention affected better treatment adherence at 6 and 12 months (p = 0.035 and p < 0.001, respectively) compared to the control arm. Conclusion: Family Psychosocial Involvement Intervention improved QoL, medication adherence, reduced stigma and symptoms among patients with SMI. The authors recommend involving families in the care of patients with SMI in Uganda, with FAPII employing culturally sensitive psychotherapy. Contribution: The results support involvement of family in the care of patients with SMI.

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.

Prevalence and predictors of post-stroke cognitive impairment among stroke survivors in Uganda.

BACKGROUND: Little is known about the characteristics and determinants of post-stroke cognitive impairment in residents of low- and middle-income countries. The objective of this study was to determine the frequencies, patterns, and risk factors for cognitive impairment in a cross-sectional study of consecutive stroke patients cared for at Uganda's Mulago Hospital, located in sub-Saharan Africa. METHODS: 131 patients were enrolled a minimum of 3-months after hospital admission for stroke. A questionnaire, clinical examination findings, and laboratory test results were used to collect demographic information and data on vascular risk factors and clinical characteristics. Independent predictor variables associated with cognitive impairment were ascertained. Stroke impairments, disability, and handicap were assessed using the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin scale (mRS), respectively. The Montreal Cognitive Assessment (MoCA) was used to assess participants' cognitive function. Stepwise multiple logistic regression was used to identify variables independently associated with cognitive impairment. RESULTS: The overall mean MoCA score was 11.7-points (range 0.0-28.0-points) for 128 patients with available data of whom 66.4% were categorized as cognitively impaired (MoCA < 19-points). Increasing age (OR 1.04, 95% CI 1.00-1.07; p = 0.026), low level of education (OR 3.23, 95% CI 1.25-8.33; p = 0.016), functional handicap (mRS 3-5; OR 1.84, 95% CI 1.28-2.63; p < 0.001) and high LDL cholesterol (OR 2.74, 95% CI 1.14-6.56; p = 0.024) were independently associated with cognitive impairment. CONCLUSIONS: Our findings highlight the high burden and need for awareness of cognitive impairment in post stroke populations in the sub-Saharan region and serve to emphasize the importance of detailed cognitive assessment as part of routine clinical evaluation of patients who have had a stroke.

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.

Collection and use of human materials during TB clinical research; a review of practices.

BACKGROUND: Human biological materials are usually stored for possible future use in research because they preserve valuable biological information, save time and resources, which would have been spent on collection of fresh samples. However, use of these materials may pose ethical challenges such as unauthorized disclosure of genetic information, which can result in dire consequences for individuals or communities including discrimination, stigma, and psychological harm; has biosecurity implications; and loss of control or ownership of samples or data. To understand these problems better, we evaluated the extent to which tuberculosis (TB) clinical research protocols that were used to collect and store biological materials for future use conform to the requirements stated in the Uganda national guidelines for research involving humans as participants. METHODS: This was a retrospective review of TB clinical research projects approved by the Uganda National Council for Science and Technology (UNCST) from 2011 to 2015, to examine whether they fulfilled the requirements for ethical collection and use of human materials. Data were abstracted through review of the project protocols using a template developed based on the informed consent and the Materials Transfer Agreement (MTA) requirements in the national guidelines. RESULTS: Out of 55 research protocols reviewed, most of the protocols 83.6% had been used to collect the stored samples (sputum, blood and sometimes urine), 28% had a section on specimen collection and 24% mentioned ownership of the biological materials. With respect to review of the consent forms used in the studies that stored materials for future use, only 9% of the protocols had a separate consent form for storage of materials, 4.5% of the consent forms explained the risks, 11.4% explained the purpose of the study while 6.8% mentioned the place of storage for the collected materials. CONCLUSION: Many of the studies reviewed did not meet the requirements for collection and storage of biological materials contained in the national guidelines, which indicates a need to additional training on this topic.

The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

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.

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.

"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.

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.