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Background In sub-Saharan Africa, the burdens of malaria and HIV infections overlap. In settings with moderate-to-high malaria transmission intensity, pregnant women living with HIV (PLWH) require both ART and malaria intermittent preventive treatment (IPTp). Dihydroartemisinin/piperaquine has been identified as a promising alternative to sulfadoxine/pyrimethamine for IPTp. However, another antimalarial drug, artesunate/amodiaquine, similar to dihydroartemisinin/piperaquine, was previously shown to reduce dolutegravir exposure in non-pregnant adults. Objectives To investigate the effect of dihydroartemisinin/piperaquine on dolutegravir plasma exposure in pregnant women on dolutegravir-based ART. Methods We conducted an open-label, non-randomized, fixed-sequence, pharmacokinetic study in PLWH in Malawi. Dolutegravir concentrations were measured over a 24 h period, before and after the recommended 3 day treatment dose of dihydroartemisinin/piperaquine in 12 pregnant women in their second or third trimester. Non-compartmental analysis was performed, and geometric mean ratios (GMRs) and 90% CIs were generated to compare dolutegravir pharmacokinetic parameters between the two treatment periods. Results Co-administration of dihydroartemisinin/piperaquine and dolutegravir increased dolutegravir’s overall exposure (AUC0–24) and Cmax by 30% (GMR 1.30; 90% CI 1.11–1.52) and 31% (GMR 1.31; 90% CI 1.13–1.51), respectively. The dolutegravir trough (C24) concentration increased by 42% (GMR 1.42; 90% CI 1.09–1.85). The combined treatments were well tolerated with no serious adverse events observed. Conclusions Dihydroartemisinin/piperaquine may be administered with dolutegravir-based ART in pregnant women as the modest increase in dolutegravir exposure, similar to pharmacokinetic parameter values published previously, ensures its efficacy without any clinically significant adverse events observed in this small study.

CASE PRESENTATION\ud \ud A 34-year-old man presented to Queen Elizabeth Central Hospital in Blantyre, Malawi with multiple enlarged right cervical lymph nodes. He had no associated constitutional symptoms. Fine-needle aspirate (FNA) of one of the lymph nodes was negative for acid-fast bacilli (AFB) by smear microscopy. The FNA specimen was not sent for histological examination. Mycobacterial culture and Xpert MTB/RIF were not available at the time. He tested positive for HIV but CD4 T-cell count was not requested at the time of HIV diagnosis, and he did not start antiretroviral therapy (ART) pending confirmation of the cause of lymphadenopathy. Excision biopsy of the lymph nodes was planned; however, the patient was lost to follow-up before the procedure was performed.

Background Stigma and masculinity represent persistent barriers in delivering successful HIV interventions to men. Our study examined community perceptions of HIV and anti-retroviral therapy (ART) and their implications for men on ART across the life course in Blantyre, Malawi. Methods Our qualitative study is based on 72 face-to-face semi-structured interviews. Participants were selected purposively and included men on ART (with suppressed and unsuppressed viral loads), adult male community members irrespective of HIV status and other HIV stakeholders such as health personnel and program implementers. Interviews were conducted in Chichewa and English, transcribed verbatim and analyzed thematically in NVivo 12. We applied the socio-ecological model as our theoretical framework as well as a “life-course” perspective. Results Our findings highlight lingering negative perceptions towards ART in general and towards PLHIV irrespective of viral load suppression. With intersecting notions of masculinity and stigma, men’s descriptions of anticipated stigma in their relationships and when visiting health facilities dominated. Stigma was experienced at the personal, interpersonal, facility and community level. Yet, men living with HIV were perceived differently throughout the life-course, with young sexually active men seen as the most stigmatized group and older men seen as drawing resilience from a greater range of masculine norms. Some men of all ages displayed “transformative” masculinities independent of stigma and community expectations. Conclusions We propose the “life-course” as a useful concept for studies on masculinity, HIV and stigma. Considering gendered constructions of “respectable” midlife-older age vis-à-vis younger age, and how they influence stigma as well as uptake and adherence to ART might lead to more targeted services for men that build on “transformative masculinities”.

Supplemental Digital Content is Available in the Text., Background: We constructed self-reported pre-exposure prophylaxis (PrEP) cascades and explored factors associated with and barriers to PrEP use to inform efforts to support PrEP use among young women who sell sex. Methods: Using self-reported data from HIV-negative young women who sell sex enrolled into a cohort study using respondent-driven sampling in Zimbabwe, we constructed PrEP cascades assessing knowledge of, ever offered, ever used, and current PrEP use in 2017 and 2019. We used logistic regression to examine factors associated with PrEP use by 2019. Through qualitative interviews with 43 women enrolled in the cohort, we investigated barriers to PrEP use. Results: At enrollment, 50% of women had heard of PrEP, 12% had ever been offered PrEP, and 7% ever used PrEP. Over time, all cascade domains: 96% of women had heard of and 55% reported an active offer of PrEP. Among women retained in the study in 2019 (56%; n = 538), 34% ever took PrEP by 2019. PrEP use was associated with, at enrollment, reporting more clients in the past month (10+: 45% vs 1–3: 27% adjOR = 1.71 95% CI: 1.06 to 2.76), duration of selling sex (24%

Summary: Background: Secondary distribution of HIV self-testing (HIVST) kits by patients attending clinic services to their partners could improve the rate of HIV diagnosis. We aimed to investigate whether secondary administration of HIVST kits, with or without an additional financial incentive, via women receiving antenatal care (ANC) or via people newly diagnosed with HIV (ie, index patients) could improve the proportion of male partners tested or the number of people newly diagnosed with HIV. Methods: We did a three-arm, open-label, pragmatic, cluster-randomised trial of 27 health centres (clusters), eligible if they were a government primary health centre providing ANC, HIV testing, and ART services, across four districts of Malawi. We recruited women (aged ≥18 years) attending their first ANC visit and whose male partner was available, not already taking ART, and not already tested for HIV during this pregnancy (ANC cohort), and people (aged ≥18 years) with newly diagnosed HIV during routine clinic HIV testing who had at least one sexual contact not already known to be HIV-positive (index cohort). Centres were randomly assigned (1:1:1), using a public selection of computer-generated random allocations, to enhanced standard of care (including an invitation for partners to attend HIV testing services), HIVST only, or HIVST plus a US$10 financial incentive for retesting. The primary outcome for the ANC cohort was the proportion of male partners reportedly tested, as ascertained by interview with women in this cohort at day 28. The primary outcome for the index cohort was the geometric mean number of new HIV-positive people identified per facility within 28 days of enrolment, as measured by observed HIV test results. Cluster-level summaries compared intervention with standard of care by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03705611. Findings: Between Sept 8, 2018, and May 2, 2019, nine clusters were assigned to each trial arm, resulting in 4544 eligible women in the ANC cohort (1447 [31·8%] in the standard care group, 1465 [32·2%] in the HIVST only group, and 1632 [35·9%] in HIVST plus financial incentive group) and 708 eligible patients in the index cohort (234 [33·1%] in the standard care group, 169 [23·9%] in the HIVST only group, and 305 [42·9%] in the HIVST plus financial incentive group). 4461 (98·2%) of 4544 eligible women in the ANC cohort and 645 (91·1%) of 708 eligible patients in the index cohort were recruited, of whom 3378 (75·7%) in the ANC cohort and 439 (68·1%) in the index cohort were interviewed after 28 days. In the ANC cohort, the mean proportion of reported partner testing per cluster was 35·0% (SD 10·0) in the standard care group, 73·0% in HIVST only group (13·1, adjusted risk ratio [RR] 1·71, 95% CI 1·48–1·98; p

People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen’s Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33–46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts

Objectives: Sex work sites have been hypothesised to be at the root of the observed heterogeneity in HIV prevalence in sub-Saharan Africa. We determined if proximity to sex work sites is associated with HIV prevalence among the general population in Zimbabwe, a country with one of the highest HIV prevalence in the world. Methods: In this cross-sectional study we use a unique combination of nationally representative geolocated individual-level data from 16,121 adults (age 15–49 years) from 400 sample locations and the locations of 55 sex work sites throughout Zimbabwe; covering an estimated 95% of all female sex workers (FSWs). We calculated the shortest distance by road from each survey sample location to the nearest sex work site, for all sites and by type of sex work site, and conducted univariate and multivariate multilevel logistic regressions to determine the association between distance to sex work sites and HIV seropositivity, controlling for age, sex, male circumcision status, number of lifetime sex partners, being a FSW client or being a stable partner of an FSW client. Results: We found no significant association between HIV seroprevalence and proximity to the nearest sex work site among the general population in Zimbabwe, regardless of which type of site is closest (city site adjusted odds ratio [aOR] 1.010 [95% confidence interval {CI} 0.992–1.028]; economic growth point site aOR 0.982 [95% CI 0.962–1.002]; international site aOR 0.995 [95% CI 0.979–1.012]; seasonal site aOR 0.987 [95% CI 0.968–1.006] and transport site aOR 1.007 [95% CI 0.987–1.028]). Individual-level indicators of sex work were significantly associated with HIV seropositivity: being an FSW client (aOR 1.445 [95% CI 1.188–1.745]); nine or more partners versus having one to three lifetime partners (aOR 2.072 [95% CI 1.654–2.596]). Conclusions: Sex work sites do not seem to directly affect HIV prevalence among the general population in surrounding areas. Prevention and control interventions for HIV at these locations should primarily focus on sex workers and their clients, with special emphasis on including and retaining mobile sex workers and clients into services.

Introduction Testing for recent HIV infection can distinguish recently acquired infection from long-standing infections. Given current interest in the implementation of recent infection testing algorithms (RITA), we report our experiences in implementing a RITA in three pilot studies and highlight important issues to consider when conducting recency testing in routine settings. Methods We applied a RITA, incorporating a limited antigen (LAg) avidity assay, in different routine HIV service-delivery settings in 2018: antenatal care clinics in Siaya County, Kenya, HIV testing and counselling facilities in Nairobi, Kenya, and female sex workers clinics in Zimbabwe. Discussions were conducted with study coordinators, laboratory leads, and facility-based stakeholders to evaluate experiences and lessons learned in relation to implementing recency testing. Results In Siaya County 10/426 (2.3%) of women testing HIV positive were classified as recent, compared to 46/530 (8.7%) of women and men in Nairobi and 33/313 (10.5%) of female sex workers in Zimbabwe. Across the study setting, we observed differences in acceptance, transport and storage of dried blood spot (DBS) or venous blood samples. For example, the acceptance rate when testing venous blood was 11% lower than when using DBS. Integrating our study into existing services ensured a quick start of the study and kept the amount of additional resources required low. From a laboratory perspective, the LAg avidity assay was initially difficult to operationalise, but developing a network of laboratories and experts to work together helped to improve this. A challenge that was not overcome was the returning of RITA test results to clients. This was due to delays in laboratory testing, the need for multiple test results to satisfy the RITA, difficulties in aligning clinic visits, and participants opting not to return for test results. Conclusion We completed three pilot studies using HIV recency testing based on a RITA in Kenya and Zimbabwe. The main lessons we learned were related to sample collection and handling, LAg avidity assay performance, integration into existing services and returning of test results to participants. Our real-world experience could provide helpful guidance to people currently working on the implementation of HIV recency testing in sub-Saharan Africa.

Background Despite the aging HIV epidemic, increasing age can be associated with hesitancy to test. Addressing this gap is a critical policy concern and highlights the urgent need to identify the underlying factors, to improve knowledge of HIV-related risks as well as uptake of HIV testing and prevention services, in midlife-older adults. Methods We conducted five focus group discussions and 12 in-depth interviews between April 2013 and November 2016 among rural and urban Malawian midlife-older (≥30 years) men and women. Using a life-course theoretical framework we explored how age is enacted socially and its implications on HIV testing and sexual risk behaviours. We also explore the potential for HIV self-testing (HIVST) to be part of a broader strategy for engaging midlife-older adults in HIV testing, prevention and care. Thematic analysis was used to identify recurrent themes and variations. Results Midlife-older adults (30–74 years of age) associated their age with respectability and identified HIV as “a disease of youth” that would not affect them, with age protecting them against infidelity and sexual risk-taking. HIV testing was felt to be stigmatizing, challenging age norms, threatening social status, and implying “lack of wisdom”. These norms drove self-testing preferences at home or other locations deemed age and gender appropriate. Awareness of the potential for long-standing undiagnosed HIV to be carried forward from past relationships was minimal, as was understanding of treatment-as-prevention. These norms led to HIV testing being perceived as a threat to status by older adults, contributing to low levels of recent HIV testing compared to younger adults. Conclusions Characteristics associated with age-gender norms and social position encourage self-testing but drive poor HIV-risk perception and unacceptability of conventional HIV testing in midlife-older adults. There is an urgent need to provide targeted messages and services more appropriate to midlife-older adults in sub-Saharan Africa. HIVST which has often been highlighted as a tool for reaching young people, may be a valuable tool for engaging midlife-older age groups who may not otherwise test.

Introduction Young female sex workers (FSW) are disproportionately vulnerable to HIV. Zimbabwe data show higher HIV incidence and lower engagement in services compared to older FSW. Utilizing data from a combination HIV prevention and treatment intervention, we describe engagement in the HIV services over time among FSW 18–24 years, compared to those ≥25 years of age. Materials and methods Data were collected via respondent-driven sampling (RDS) surveys in 14 communities in 2013 and 2016, with >2500 FSW per survey. They included blood samples for HIV and viral load testing. As the intervention had no significant impact on HIV care cascade outcomes, data were aggregated across study arms. Analyses used RDS-II estimation. Results Mean age in 2013 and 2016 was 31 and 33 years, with 27% and 17% aged 18–24 years. Overall HIV prevalence was 59% at each timepoint, and 35% and 36% among younger FSW. From 2013 to 2016 there was an increase in young HIV-positive FSW knowing their status (38% vs 60%, OR = 2.51, p Discussion Young FSW had improvements in care cascade outcomes, and proportionate improvements similar to older FSW, yet they remain less engaged in services overall. This implies that the dedicated FSW services in Zimbabwe are having a comparably positive impact across age groups, however more is likely required to address young FSW’s unique vulnerabilities and needs.

Background Dolutegravir (DTG)-based regimens have been recommended by the WHO as the preferred first-line and second-line HIV treatment in all populations. Evidence suggests an association with weight gain, particularly among black women. Our study investigated perceptions of weight gain from DTG-based regimen use on body image and adherence of antiretroviral therapy in women living with HIV (WLHIV) in Uganda. Methods Between April and June 2021, we conducted semi-structured interviews involving 25 WLHIV (adolescents, women of reproductive potential and post-menopausal women) and 19 healthcare professionals (clinicians, nurses, ART managers and counsellors) purposively selected from HIV clinics in Kampala. The interviews explored perceptions of body weight and image; experiences and management of weight related side effects associated with DTG; and knowledge and communication of DTG-related risks. Data was analysed thematically in NVivo 12 software. Results Our findings indicate WLHIV in Uganda commonly disliked thin body size and aspired to gain moderate to high level body weight to improve their body image, social standing and hide their sero-positive status. Both WLHIV and healthcare professionals widely associated weight gain with DTG use, although it was rarely perceived as an adverse event and was unlikely to be reported or to alter medication adherence. Clinical management and pharmacovigilance of DTG-related weight gain were hampered by the limited knowledge of WLHIV of the health risks of being over-weight and obesity; lack of diagnostic equipment and resources; and limited clinical guidance for managing weight gain and associated cardiovascular and metabolic comorbidities. Conclusions The study highlights the significance of large body-size in promoting psychosocial wellbeing in WLHIV in Uganda. Although weight gain is recognized as a side effect of DTG, it may be welcomed by some WLHIV. Healthcare professionals should actively talk about and monitor for weight gain and occurrence of associated comorbidities to facilitate timely interventions. Improved supply of diagnostic equipment and support with sufficient guidance for managing weight gain for healthcare professionals in Uganda are recommended.

Objectives: \ud \ud We sought evidence of DREAMS’ impact on uptake of services and sexual risk among adolescent-girls-and-young-women (AGYW).\ud \ud Design: \ud \ud Cohorts of AGYW aged 13–22 years were randomly selected in 2017–2018 and followed-up to 2019; 1081 in Nairobi, Kenya;1171 in Gem, western Kenya;and 2184 in uMkhanyakude, South Africa.\ud \ud Methods: \ud \ud Outcomes were knowledge of HIV status, condomless sex (past 12 months), lifetime partners, transactional sex (past 12 months), and awareness and use of condoms and pre-exposure-prophylaxis (PrEP). Using a causal inference framework, we estimated the proportions with each outcome if all vs. none were DREAMS invitees by 2018.\ud \ud Results: \ud \ud Among AGYW followed up in 2019, the percentage invited to DREAMS by 2018 was 74, 57, and 53% in Nairobi, Gem, and uMkhanyakude, respectively. By 2018, the estimated percentages of AGYW who would know their HIV status, comparing the scenarios that all vs. none were DREAMS invitees, were 86 vs. 56% in Nairobi, 80 vs. 68% in Gem, and 56 vs. 49% in uMkhanyakude. By 2019, awareness of condoms and PrEP was high among DREAMS invitees, but recent participation in condom promotion activities was less than 50% and recent PrEP use was around 0–10%. In Gem, there was evidence of a reduction attributable to DREAMS in condomless sex, and among younger AGYW in the number of lifetime partners;in Nairobi evidence of a reduction in condomless sex among sexually active older AGYW;and in uMkhanya-kude no evidence that DREAMS changed these outcomes.\ud \ud Conclusion: \ud \ud Alongside sustaining high levels of knowledge of HIV status, more is needed to link AGYW into prevention methods such as PrEP and condoms.\ud \ud Comprehensive HIV prevention promotes safer sexual partnerships, but poverty, social norms, and inequalities limit AGYW's prevention choices.

Introduction Evidence on health-related quality of life (HRQoL) outcomes is limited for new antiretroviral therapies (ART). Dolutegravir-based treatment is being rolled out as the preferred first-line treatment for HIV in many low- and middle-income countries. We compared HRQoL between treatment-naïve pregnant women randomized to dolutegravir- or efavirenz-based ART in a clinical trial in Uganda and South Africa. Methods We gathered HRQoL data from 203 pregnant women of mean age 28 years, randomized to either dolutegravir- or efavirenz-based ART. We used the medical outcomes study-HIV health survey at baseline, 24 and 48 weeks between years 2018 and 2019. Physical health summary (PHS) and mental health summary (MHS) scores were the primary study outcomes, while the 11 MOS-HIV subscales were secondary outcomes. We applied mixed model analysis to estimate differences within and between-treatment groups. Multivariate regression analysis was included to identify associations between primary outcomes and selected variables. Results At 24 weeks postpartum, HRQoL scores increased from baseline in both treatment arms: PHS (10.40, 95% CI 9.24, 11.55) and MHS (9.23, 95% CI 7.35, 11.10) for dolutegravir-based ART; PHS (10.24, 95% CI 9.10, 11.38) and MHS (7.54, 95% CI 5.66, 9.42) for efavirenz-based ART. Increased scores for all secondary outcomes were significant at p Conclusion We found no important differences in HRQoL outcomes among HIV-positive women started on dolutegravir relative to efavirenz in late pregnancy. Increases in HRQoL in the first year after delivery provide additional support for the initiation of ART in HIV-positive women presenting late in pregnancy. Trial Registration Clinical Trial Number: NCT03249181

Background Young people, aged 16–24, in southern Malawi have high uptake of HIV self-testing (HIVST) but low rates of linking to services following HIVST, especially in comparison, to older generations. The study aim is to explore the barriers and facilitators to linkage for HIV prevention and care following uptake of HIV self-testing among young Malawians. Methods We used qualitative methods. Young people aged 16–24 who had received HIVST; community-based distribution agents (CBDAs) and health care workers from the linked facilities were purposively sampled from two villages in rural southern Malawi. Results We conducted in-depth interviews with thirteen young people (9 female) and held four focus groups with 28 healthcare workers and CBDAs. Young people strongly felt the social consequences associated with inadvertent disclosure of HIV sero-status were a significant deterrent to linkage at their stage in life. They also felt communication on testing benefits and the referral process after testing was poor. In contrast, they valued encouragement from those they trusted, other’s positive treatment experiences and having a “strength of mind”. CBDAs were important facilitators for young people as they are able to foster a trusting relationship and had more understanding of the factors which prevented young people from linking following HIVST than the healthcare workers. Young people noted contextual barriers to linkage, for example, being seen on the road to the healthcare centre, but also societal gendered barriers. For example, young females and younger adolescents were less likely to have the financial independence to link to services whilst young males (aged 19–24) had the finances but lacked a supportive network to encourage linkage following testing. Overall, it was felt that the primary “responsibility” for linking to formal healthcare following self-testing is shouldered by the young person and not the healthcare system. Conclusions Young people are happy to self-test for HIV but faced barriers to link to services following a self-test. Potential interventions for improving linkage suggested by this analysis include the establishment of youth-friendly linkage services, enhanced lines of communication between young people and healthcare providers and prioritising linkage for future interventions when targeting young people following HIVST.

Background\ud Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with HIV (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events and common risk factors.\ud \ud Methods\ud This was a nationwide population-based cohort study comparing adult (≥18y) PWH with HIV-negative individuals matched on age, sex, ethnicity and location. The primary outcome was composite CVD comprising stroke, myocardial infarction (MI), peripheral vascular disease (PVD), ischaemic heart disease and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD) and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome.\ud \ud Results\ud We identified 9233 PWH and 35721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.28-1.77), stroke (aHR 1.42, 95% CI 1.08-1.86), ischaemic heart disease (aHR 1.55, 95% CI 1.24-1.94), hypertension (aHR 1.37, 95% CI 1.23-1.53), type 2 diabetes (aHR 1.28, 95% CI 1.09-1.50), CKD (aHR 2.42, 95% CI 1.98-2.94) and all-cause mortality (aHR 2.84, 95% CI (2.48-3.25).\ud \ud Conclusions\ud PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.

Background \ud HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa, highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated if HIV-exposure dysregulates HEU immunity, vaccine-antibody production and human herpes virus (HHV) amplify this effect. \ud Methods \ud 34 HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort, followed up to 6 weeks of age; and 43 HIV-infected and 61 HIV-uninfected mother-infant pairs into a longitudinal infant cohort, at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HU infants. \ud Results \ud We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HU infants. HHV infection was similar between HEU and HU infants. \ud Conclusion \ud In the era of antiretroviral therapy (ART)-mediated viral suppression, HIV-exposure may dysregulate monocyte and B cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

HIV modelling and economic analyses have had a prominent role in guiding programmatic responses to HIV in sub-Saharan Africa. We reflect critically how the HIV modelling field might develop in future. We argue for HIV modelling to be more routinely aligned with national government and ministry of health priorities, recognizing their legitimate mandates and stewardship responsibilities, for HIV and other wider health programmes. We also place importance on an environment existing in which collaboration between modellers, and joint approaches to addressing modelling questions, becomes the norm rather than exception. Such an environment can accelerate translation of modelling analyses into policy formulation because areas where models agree can be prioritized for action, whereas areas over which uncertainty prevails can be slated for additional study, data collection and analysis. We also argue the need for HIV modelling to increasingly be integrated with the modelling of health needs beyond HIV, particularly in allocative efficiency analyses, where focusing on one disease over another may lead to worse health overall. Such integration may also enhance partnership with national governments whose mandates extend beyond HIV and to all of health care. Finally, we see a need for there to be substantial and equitable investment in capacity strengthening within African countries, so that African researchers will increasingly be leading modelling exercises. Building a critical mass of expertise, strengthened through external collaboration and knowledge exchange, should be the ultimate goal.

Here we describe TZM-gfp, a novel HIV-1 reporter cell derived from the same parental clone JC.53, used previously to generate the widely-utilized indicator cell line TZM-bl. We re-engineered JC.53 cells to express GFP under regulation of HIV Tat and Rev. We characterize the new reporter cell line to show that TZM-gfp cells are equally susceptible to HIV infection, exhibit minimal background signal, and can report HIV infection in rare cells from a bulk population of experimentally-infected human monocyte-derived macrophages. We demonstrate the utility and sensitivity of the cells in detection of even a single HIV-positive macrophage by fluorescence-assisted correlative electron microscopy, using the GFP signal to guide imaging of HIV virions in primary co-culture. Finally, we used TZM-gfp cells for viral capture during co-culture with human peripheral blood mononuclear cells, showing that TZM-gfp can support outgrowth and analyses of patient-derived primary HIV-1 isolates.

Background National or regional population-based HIV prevalence surveys have small sample sizes at district or sub-district levels; this leads to wide confidence intervals when estimating HIV prevalence at district level for programme monitoring and decision making. Health facility programme data, collected during service delivery is widely available, but since people self-select for HIV testing, HIV prevalence estimates based on it, is subject to selection bias. We present a statistical annealing technique, Hybrid Prevalence Estimation (HPE), that combines a small population-based survey sample with a facility-based sample to generate district level HIV prevalence estimates with associated confidence intervals. Methods We apply the HPE methodology to combine the 2011 Uganda AIDS indicator survey with the 2011 health facility HIV testing data to obtain HIV prevalence estimates for districts in Uganda. Multilevel logistic regression was used to obtain the propensity of testing for HIV in a health facility, and the propensity to test was used to combine the population survey and health facility HIV testing data to obtain the HPEs. We assessed comparability of the HPEs and survey-based estimates using Bland Altman analysis. Results The estimates ranged from 0.012 to 0.178 and had narrower confidence intervals compared to survey-based estimates. The average difference between HPEs and population survey estimates was 0.00 (95% CI: − 0.04, 0.04). The HPE standard errors were 28.9% (95% CI: 23.4–34.4) reduced, compared to survey-based standard errors. Overall reduction in HPE standard errors compared survey-based standard errors ranged from 5.4 to 95%. Conclusions Facility data can be combined with population survey data to obtain more accurate HIV prevalence estimates for geographical areas with small population survey sample sizes. We recommend use of the methodology by district level managers to obtain more accurate HIV prevalence estimates to guide decision making without incurring additional data collection costs.

Summary Background Adolescents living with HIV face challenges to their wellbeing and antiretroviral therapy adherence and have poor treatment outcomes. We aimed to evaluate a peer-led differentiated service delivery intervention on HIV clinical and psychosocial outcomes among adolescents with HIV in Zimbabwe. Methods 16 public primary care facilities (clusters) in two rural districts in Zimbabwe (Bindura and Shamva) were randomly assigned (1:1) to provide enhanced HIV care support (the Zvandiri intervention group) or standard HIV care (the control group) to adolescents (aged 13–19 years) with HIV. Eligible clinics had at least 20 adolescents in pre-ART or ART registers and were geographically separated by at least 10 km to minimise contamination. Adolescents were eligible for inclusion if they were living with HIV, registered for HIV care at one of the trial clinics, and either starting or already on ART. Exclusion criteria were being too physically unwell to attend clinic (bedridden), psychotic, or unable to give informed assent or consent. Adolescents with HIV at all clinics received adherence support through adult counsellors. At intervention clinics, adolescents with HIV were assigned a community adolescent treatment supporter, attended a monthly support group, and received text messages, calls, home visits, and clinic-based counselling. Implementation intensity was differentiated according to each adolescent's HIV vulnerability, which was reassessed every 3 months. Caregivers were invited to a support group. The primary outcome was the proportion of adolescents who had died or had a viral load of at least 1000 copies per μL after 96 weeks. In-depth qualitative data were collected and analysed thematically. The trial is registered with Pan African Clinical Trial Registry, number PACTR201609001767322. Findings Between Aug 15, 2016, and March 31, 2017, 500 adolescents with HIV were enrolled, of whom four were excluded after group assignment owing to testing HIV negative. Of the remaining 496 adolescents, 212 were recruited at Zvandiri intervention sites and 284 at control sites. At enrolment, the median age was 15 years (IQR 14–17), 52% of adolescents were female, 81% were orphans, and 47% had a viral load of at least 1000 copies per μL. 479 (97%) had primary outcome data at endline, including 28 who died. At 96 weeks, 52 (25%) of 209 adolescents in the Zvandiri intervention group and 97 (36%) of 270 adolescents in the control group had an HIV viral load of at least 1000 copies per μL or had died (adjusted prevalence ratio 0·58, 95% CI 0·36–0·94; p=0·03). Qualitative data suggested that the multiple intervention components acted synergistically to improve the relational context in which adolescents with HIV live, supporting their improved adherence. No adverse events were judged to be related to study procedures. Severe adverse events were 28 deaths (17 in the Zvandiri intervention group, 11 in the control group) and 57 admissions to hospital (20 in the Zvandiri intervention group, 37 in the control group). Interpretation Peer-supported community-based differentiated service delivery can substantially improve HIV virological suppression in adolescents with HIV and should be scaled up to reduce their high rates of morbidity and mortality. Funding Positive Action for Adolescents Program, ViiV Healthcare.

Background The Philippines is facing a rapidly rising HIV epidemic among young men who have sex with men (MSM). Testing rates among young populations is poor. HIV self-testing (HIVST) is a promising strategy to address this testing gap. The study’s purpose was to explore the perceived acceptability, feasibility and programmatic challenges of HIVST among key informants and target users. Method A qualitative study involving semi-structured interviews and focus group discussions (FGD). We interviewed 15 key informants involved with HIV testing programs or policies and 42 target users in six FGD in Metro Manila. We held separate discussions with high socio-economic MSM (n = 12), urban poor MSM (n = 15) and transgender women (TGW) (n = 15). Results were analysed using a thematic framework approach. Results MSM and TGW welcomed the convenience and privacy HIVST could provide. They preferred an inexpensive accurate blood-based kit attained from reputable sites. Key informants at national and local level equally welcomed HIVST but identified a number of policy and regulatory issues. Both groups articulated the challenge of enrolling those who test reactive using HIVST to further testing and treatment in an environment characterised by acute stigma around HIV. Conclusions HIVST was found to be highly acceptable to target users and was welcomed as an additional testing approach at national level. Strategic alliances are now needed between stakeholders to proactively deliver a patient-centred HIVST program that could provide an effective, safe means of increasing testing coverage in this escalating context.

Background Female sex workers (FSW) in sub-Saharan Africa are disproportionately affected by HIV and are critical to engage in HIV prevention, testing and care services. We describe the design of our evaluation of the ‘AMETHIST’ intervention, nested within a nationally-scaled programme for FSW in Zimbabwe. We hypothesise that the implementation of this intervention will result in a reduction in the risk of HIV transmission within sex work. Methods The AMETHIST intervention (Adapted Microplanning to Eliminate Transmission of HIV in Sex Transactions) is a risk-differentiated intervention for FSW, centred around the implementation of microplanning and self-help groups. It is designed to support uptake of, and adherence to, HIV prevention, testing and treatment behaviours among FSW. Twenty-two towns in Zimbabwe were randomised to receive either the Sisters programme (usual care) or the Sisters programme plus AMETHIST. The composite primary outcome is defined as the proportion of all FSW who are at risk of either HIV acquisition (HIV-negative and not fully protected by prevention interventions) or of HIV transmission (HIV-positive, not virally suppressed and not practicing consistent condom use). The outcome will be assessed after 2 years of intervention delivery in a respondent-driven sampling survey (total n = 4400; n = 200 FSW recruited at each site). Primary analysis will use the ‘RDS-II’ method to estimate cluster summaries and will adapt Hayes and Moulton’s ‘2-step’ method produce adjusted effect estimates. An in-depth process evaluation guided by our project trajectory will be undertaken. Discussion Innovative pragmatic trials are needed to generate evidence on effectiveness of combination interventions in HIV prevention and treatment in different contexts. We describe the design and analysis of such a study. Trial registration Pan African Clinical Trials Registry PACTR202007818077777. Registered on 2 July 2020.

Introduction: Carbapenem-resistant Enterobacteriaceae are emerging as a global public-health threat and cause substantial challenges in clinical practice. \ud Gap Statement: There is a need for increased and continued genomic surveillance of antimicrobial resistance genes globally in order to detect outbreaks and dissemination of clinically important resistance genes and their associated mobile genetic elements in human pathogens.\ud Aim: To describe the resistance mechanisms of carbapenem-resistant Escherichia coli. \ud Methods: Rectal swabs from neonates and newly diagnosed human immunodeficiency virus (HIV) infected adults were collected between April 2017 and May 2018 and screened for fecal carriage of carbapenamases and OXA-48 producing Enterobacteriaceae. Bacterial isolates were identified using matrix assisted laser desorption ionization time of flight mass spectrometry. Antimicrobial susceptibility testing was performed by E-test. Whole genomes of carbapenem resistant E. coli were investigated using a hybrid assembly of Illumina and Oxford Nanopore Technologies sequencing reads. \ud Results: Three carbapenem-resistant E. coli were detected, two from neonates and one from an HIV infected adult. All three isolates carried blaNDM-5. Two E. coli from neonates belong to ST167 and blaNDM-5 co-existed with blaCTX-M-15 and blaOXA-01, and all were carried on IncFIA type plasmids. The E. coli from the HIV infected adult belongs to ST2083, and carried blaNDM-5 on an IncX3 type plasmid and blaCMY-42 on an IncI type plasmid. All blaNDM-5 carrying plasmids contained conjugation related genes. In addition, E. coli from the HIV infected adult carried three more plasmid types; IncFIA, IncFIB and Col(BS512). One E. coli from a neonate also carried one extra plasmid Col(BS512). All three E. coli harbored resistance genes to fluoroquinolone, aminoglycosides, sulfamethoxazole, trimethoprim, macrolides and tetracycline, carried on the IncFIA type plasmid. Furthermore, E. coli from the neonates carried a chloramphenicol resistance gene (catB3) also on the IncFIA plasmid. All three isolates were susceptible to colistin.\ud Conclusion: This is the first report from Tanzania detecting blaNDM-5 producing E. coli. The carbapenemase gene was carried on an IncFIA and IncX3 type plasmids. Our findings highlight the urgent need for a robust antimicrobial resistance (AMR) surveillance system to monitor and rapidly report on the incidence and spread of emerging resistant bacteria in Tanzania.

ObjectivePeer-to-peer (PTP) HIV self-testing (HIVST) distribution models can increase uptake of HIV testing and potentially create demand for HIV treatment and pre-exposure prophylaxis (PrEP). We describe the acceptability and experiences of young women and men participating in a cluster randomised trial of PTP HIVST distribution and antiretroviral/PrEP promotion in rural KwaZulu-Natal.MethodsBetween March and September 2019, 24 pairs of trained peer navigators were randomised to two approaches to distribute HIVST packs (kits+HIV prevention information): incentivised-peer-networks where peer-age friends distributed packs within their social network for a small incentive, or direct distribution where peer navigators distributed HIVST packs directly. Standard-of-care peer navigators distributed information without HIVST kits. For the process evaluation, we conducted semi-structured interviews with purposively sampled young women (n=30) and men (n=15) aged 18–29 years from all arms. Qualitative data were transcribed, translated, coded manually and thematically analysed using an interpretivist approach.ResultsOverall, PTP approaches were acceptable and valued by young people. Participants were comfortable sharing sexual health issues they would not share with adults. Coupled with HIVST, peer (friends) support facilitated HIV testing and solidarity for HIV status disclosure and treatment. However, some young people showed limited interest in other sexual health information provided. Some young people were wary of receiving health information from friends perceived as non-professionals while others avoided sharing personal issues with peer navigators from their community. Referral slips and youth-friendly clinics were facilitators to PrEP uptake. Family disapproval, limited information, daily pills and perceived risks were major barriers to PrEP uptake.ConclusionBoth professional (peer navigators) and social network (friends) approaches were acceptable methods to receive HIVST and sexual health information. Doubts about the professionalism of friends and overly exclusive focus on HIVST information materials may in part explain why HIVST kits, without peer navigators support, did not create demand for PrEP.

The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role of duodenal Trm CD8+ T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8+ T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69+CD103hi) cells were the predominant CD8+ T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that CD103+CD8+ T cells were localized in the intraepithelial region, while CD103-CD8+ T cells and CD4+ T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8+ T cells were enriched in the CD69+CD103-/lo population. However, the duodenal HIV-specific CD8+ Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that duodenal CD8+ Trm cells possess limited perforin-mediated cytolytic potential and are spatially separated from HIV-susceptible LP CD4+ T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies.

Selection for resistance to azithromycin (AZM) and other antibiotics such as tetracyclines and lincosamides remains a concern with long-term AZM use for treatment of chronic lung diseases (CLD). We investigated the impact of 48 weeks of AZM on the carriage and antibiotic resistance of common respiratory bacteria among children with HIV-associated CLD.Nasopharyngeal (NP) swabs and sputa were collected at baseline, 48 and 72 weeks from participants with HIV-associated CLD randomised to receive weekly AZM or placebo for 48 weeks and followed post-intervention until 72 weeks. The primary outcomes were prevalence and antibiotic resistance of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI) and Moraxella catarrhalis (MC) at these timepoints. Mixed-effects logistic regression and Fisher's exact test were used to compare carriage and resistance, respectively.Of 347 (174 AZM, 173 placebo) participants (median age 15 years (IQR 13–18), female 49%), NP carriage was significantly lower in the AZM (n=159) compared to placebo (n=153) arm for SP (18% versus 41%, pversus 16%, p=0.01) and MC (4% versus 11%, p=0.02); SP resistance to AZM (62% (18 out of 29) versus 13% (8 out of 63), pversus 21% (13 out of 63), pversus 3% (1 out of 31), pversus 13% (4 out of 31), p=0.05) and clindamycin (79% (27 out of 34) versus 3% (1 out of 31), pThe persistence of antibiotic resistance and its clinical relevance for future infectious episodes requiring treatment needs further investigation.

Introduction: 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. A scoping review mapped extant policy and evidence based literature on the feasibility of integrating NCD care with HIV in the region.\ud \ud Methods: A scoping review methodology was utilised to conduct a systematic search of peer-reviewed and grey literature published in English language and with no date limitation. A systematic search was conducted on PubMed, Embase, CINAHL, and the Cochrane library. The initial search identified 231 records considered for inclusion in this review. Twelve duplicate records were removed. The remaining 219 records were screened by title and abstract of which 165 records were excluded and 54 records were selected for full-text review. A further 16 records were excluded due to a lack of relevance or the unavailability of the full text article. Finally, 38 were charted and analysed thematically.\ud \ud Results: Thirty-eight studies were included. These comprised a range of different models to integrate NCD and HIV care in the region, reflecting differences in health system environments, and disease epidemiology. The studies provide a variety of evidence that integration of HIV and NCD care can be feasible and can improve clinical effectiveness and identify barriers and facilitators to integration and task shifting. The review confirms that integrated HIV and NCD care services is by-and-large feasible, being both clinically effective and cost-effective.\ud \ud Conclusion: The review may inform the understanding of how best to develop an integrated model of care service by reducing barriers to uptake, linkage and retention in HIV, diabetes and hypertension treatment in SSA countries.

BackgroundWe investigated risk factors for sustained virological non-suppression (viral load ≥ 1000 copies/ml on two tests 48 weeks apart) among children and adolescents accessing HIV care in public sector clinics in Harare, Zimbabwe and Blantyre, Malawi.MethodsParticipants were enrolled between 2016 and 2019, were aged 6–19 years, living with HIV, had chronic lung disease (FEV z-score ResultsAt enrolment 258 participants (64.6%) were on first-line ART and 152/347 (43.8%) had virological non-suppression. After 48 weeks 114/313 (36.4%) were non-suppressed. Participants non-suppressed at baseline had almost ten times higher odds of non-suppression at follow-up (OR = 9.9, 95%CI 5.3–18.4,p p = 0.014) and with older age. Twelve participants switched regimen in Zimbabwe and none in Malawi.ConclusionsViral non-suppression was high among this group and many with high viral load were not switched to a new regimen, resulting in continued non-suppression after 48 weeks. Further research could determine whether improved adherence counselling and training clinicians on regimen switches can improve viral suppression rates in this population.Trial registrationSecondary cohort analysis of data from BREATHE trial (Clinicaltrials.govNCT02426112).

Background Several trials of community-based HIV self-testing (HIVST) provide evidence on the acceptability and feasibility of campaign-style distribution to reach first-time testers, men and adolescents. However, we do not know how many remain unaware of HIVST after distribution campaigns, and who these individuals are. Here we look at factors associated with never having heard of HIVST after community-based campaign-style HIVST distribution in rural Zimbabwe between September 2016 and July 2017. Methods Analysis of representative population-based trial survey data collected from 7146 individuals following community-based HIVST distribution to households was conducted. Factors associated with having never heard of HIVST were determined using multivariable mixed-effects logistic regression adjusted for clustered design. Results Among survey participants, 1308 (18.3%) self-reported having never heard of HIVST. Individuals who were between 20 and 60 years old {20–29 years: [aOR = 0.74, 95% CI (0.58–0.95)], 30–39 years: [aOR = 0.56, 95% CI (0.42–0.74)], 40–49 years: [aOR = 0.50, 95% CI (0.36–0.68)], 50–59 years [aOR = 0.58, 95% CI (0.42–0.82)]}, who had attained at least ordinary level education [aOR = 0.51, 95% CI (0.34–0.76)], and who had an HIV test before [aOR = 0.30, 95% CI (0.25–0.37)] were less likely to have never heard of HIVST compared with individuals who were between 16 and 19 years old, who had a lower educational level and who had never tested for HIV before, respectively. In addition, non-household heads or household head representatives [aOR = 1.21, 95% CI (1.01–1.45)] were more likely to report never having heard of HIVST compared to household head and representatives. Conclusions Around one fifth of survey participants remain unaware of HIVST even after an intensive community-based door-to-door HIVST distribution. Of note, those least likely to have heard of self-testing were younger, less educated and less likely to have tested previously. Household heads appear to play an important role in granting or denying access to self-testing to other household members during door-to-door distribution. Differentiated distribution models are needed to ensure access to all. Trial registration PACTR, PACTR201607001701788. Registered 29 June 2016, https://pactr.samrc.ac.za/ PACTR201607001701788

Background Management of co-morbidities among persons living with HIV is an emerging priority, which may require additional medication over and above life-long antiretroviral therapy (ART). We explored factors associated with adherence to the trial drug among children and adolescents with perinatally acquired HIV taking antiretroviral therapy (ART) in the Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-Infected Children (BREATHE) trial. Methods The BREATHE trial recruited 6–19 year olds with perinatally acquired HIV and co-morbid chronic lung disease as measured by FEV1. This two-site trial was individually randomised (1:1), double-blind and placebo-controlled. Participants received a once-weekly weight-based dose of 1–5 tablets of azithromycin (AZM: 250mg) or placebo, taken orally. We used pharmacy dispensing records and count of returned pills to measure adherence to study medication. Logistic regression was used to explore factors associated with adherence coverage. Poisson regression with Lexis expansion for time was used to explore whether adherence modified the effect of azithromycin on the incidence of acute respiratory exacerbation, a secondary outcome of the trial. Trial registration: ClinicalTrials.gov NCT02426112. Results The 347 participants (median age 15.3, 51% male) consumed 14,622 doses of study medication over 16,220 person-weeks under study. Adherence was higher for those randomised to AZM (73.4%) than placebo (68.4%) and declined over the 48 weeks of the study (Score test for trend Conclusion The majority of children and adolescents tolerated the addition of a once-weekly dose of medication to their pill burden. Barriers in adhering to treatment for co-morbid conditions are likely common to barriers in adhering to ART. Control of co-morbidities will therefore present additional challenges in HIV care.

Background\ud Good patient adherence to antiretroviral (ART) medication determines effective HIV viral suppression, and thus reduces the risk of progression and transmission of HIV. With accurate methods to monitor treatment adherence, we could use simple triage to target adherence support interventions that could help in the community or at health centres in resource‐limited settings.\ud \ud Objectives\ud To determine the accuracy of simple measures of ART adherence (including patient self‐report, tablet counts, pharmacy records, electronic monitoring, or composite methods) for detecting non‐suppressed viral load in people living with HIV and receiving ART treatment.\ud \ud Search methods\ud The Cochrane Infectious Diseases Group Information Specialists searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, African‐Wide information, and Web of Science up to 22 April 2021. They also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing studies. No restrictions were placed on the language or date of publication when searching the electronic databases.\ud \ud Selection criteria\ud We included studies of all designs that evaluated a simple measure of adherence (index test) such as self‐report, tablet counts, pharmacy records or secondary database analysis, or both, electronic monitoring or composite measures of any of those tests, in people living with HIV and receiving ART treatment. We used a viral load assay with a limit of detection ranging from 10 copies/mL to 400 copies/mL as the reference standard. We created 2 × 2 tables to calculate sensitivity and specificity.\ud \ud Data collection and analysis\ud We screened studies, extracted data, and assessed risk of bias using QUADAS‐2 independently and in duplicate. We assessed the certainty of evidence using the GRADE method. The results of estimated sensitivity and specificity were presented using paired forest plots and tabulated summaries. We encountered a high level of variation among studies which precluded a meaningful meta‐analysis or comparison of adherence measures. We explored heterogeneity using pre‐defined subgroup analysis.\ud \ud Main results\ud We included 51 studies involving children and adults with HIV, mostly living in low‐ and middle‐income settings, conducted between 2003 and 2021. Several studies assessed more than one index test, and the most common measure of adherence to ART was self‐report.\ud \ud ‐ Self‐report questionnaires (25 studies, 9211 participants; very low‐certainty): sensitivity ranged from 10% to 85% and specificity ranged from 10% to 99%.\ud \ud ‐ Self‐report using a visual analogue scale (VAS) (11 studies, 4235 participants; very low‐certainty): sensitivity ranged from 0% to 58% and specificity ranged from 55% to 100%.\ud \ud ‐ Tablet counts (12 studies, 3466 participants; very low‐certainty): sensitivity ranged from 0% to 100% and specificity ranged from 5% to 99%.\ud \ud ‐ Electronic monitoring devices (3 studies, 186 participants; very low‐certainty): sensitivity ranged from 60% to 88% and the specificity ranged from 27% to 67%.\ud \ud ‐ Pharmacy records or secondary databases (6 studies, 2254 participants; very low‐certainty): sensitivity ranged from 17% to 88% and the specificity ranged from 9% to 95%.\ud \ud ‐ Composite measures (9 studies, 1513 participants; very low‐certainty): sensitivity ranged from 10% to 100% and specificity ranged from 49% to 100%.\ud \ud Across all included studies, the ability of adherence measures to detect viral non‐suppression showed a large variation in both sensitivity and specificity that could not be explained by subgroup analysis. We assessed the overall certainty of the evidence as very low due to risk of bias, indirectness, inconsistency, and imprecision.\ud \ud The risk of bias and the applicability concerns for patient selection, index test, and reference standard domains were generally low or unclear due to unclear reporting. The main methodological issues identified were related to flow and timing due to high numbers of missing data. For all index tests, we assessed the certainty of the evidence as very low due to limitations in the design and conduct of the studies, applicability concerns and inconsistency of results.\ud \ud Authors' conclusions\ud We encountered high variability for all index tests, and the overall certainty of evidence in all areas was very low. No measure consistently offered either a sufficiently high sensitivity or specificity to detect viral non‐suppression. These concerns limit their value in triaging patients for viral load monitoring or enhanced adherence support interventions.

Background People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest. Design and methods An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation. Discussion Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.

Background Many women in sub-Saharan Africa initiate antenatal care (ANC) late in pregnancy, undermining optimal prevention of mother-to-child-transmission (PMTCT) of HIV. Questions remain about whether and how late initiation of ANC in pregnancy is related to adherence to antiretroviral therapy (ART) in the era of national dolutegravir roll-out. Methods This study employed a qualitative design involving individual interviews and focus group discussions conducted between August 2018 and March 2019. We interviewed 37 pregnant and lactating women living with HIV selected purposively for early or late presentation to ANC from poor urban communities in South Africa and Uganda. Additionally, we carried out seven focused group discussions involving 67 participants in both countries. Data were analysed thematically in NVivo12. Results Women described common underlying factors influencing both late ANC initiation and poor ART adherence in South Africa and Uganda. These included poverty and time constraints; inadequate health knowledge; perceived low health risk; stigma of HIV in pregnancy; lack of disclosure; and negative provider attitudes. Most late ANC presenters reported relationship problems, lack of autonomy and the limited ability to dialogue with their partners to influence household decisions on health and resource allocation. Perception of poor privacy and confidentiality in maternity clinics was rife among women in both study settings and compounded risks associated with early disclosure of pregnancy and HIV. Women who initiated ANC late and were then diagnosed with HIV appeared to be more susceptible to poor ART adherence. They were often reprimanded by health workers for presenting late which hampered their participation in treatment counselling and festered provider mistrust and subsequent disengagement in care. Positive HIV diagnosis in late pregnancy complicated women’s ability to disclose their status to significant others which deprived them of essential social support for treatment adherence. Further, it appeared to adversely affect women’s mental health and treatment knowledge and self-efficacy. Conclusions We found clear links between late initiation of ANC and the potential for poor adherence to ART based on common structural barriers shaping both health seeking behaviours, and the adverse impact of late HIV diagnosis on women’s mental health and treatment knowledge and efficacy. Women who present late are a potential target group for better access to antiretrovirals that are easy to take and decrease viral load rapidly, and counselling support with adherence and partner disclosure. A combination of strengthened health literacy, economic empowerment, improved privacy and patient-provider relationships as well as community interventions that tackle inimical cultural practices on pregnancy and unfair gender norms may be required.

Background HIV self-testing (HIVST) has the potential to increase coverage of HIV testing, but concerns exist about intended users’ ability to correctly perform and interpret tests, especially in poor communities with low literacy rates. We assessed the clinical performance of the 2016 prototype OraQuick® HIV Self-Test in rural and urban communities in Zambia to assess the sensitivity and specificity of the test compared to the national HIV rapid diagnostic test (RDT) algorithm and a laboratory reference standard using 4th generation enzyme immunoassays and HIV RNA detection. Methods Participants were recruited from randomly selected rural and urban households and one urban health facility between May 2016 and June 2017. Participants received a brief demonstration of the self-test, and then self-tested without further assistance. The research team re-read the self-test, repeated the self-test, drew blood for the laboratory reference, and conducted RDTs following the national HIV testing algorithm (Determine™ HIV1/2 (Alere) confirmed using Unigold™ HIV1/2 (Trinity Biotech)). Selected participants (N = 85) were videotaped whilst conducting the testing to observe common errors. Results Initial piloting showed that written instructions alone were inadequate, and a demonstration of self-test use was required. Of 2,566 self-test users, 2,557 (99.6%) were able to interpret their result. Of participants who were videoed 75/84 (89.3%) completed all steps of the procedure correctly. Agreement between the user-read result and the researcher-read result was 99.1%. Compared to the RDT algorithm, user-conducted HIVST was 94.1% sensitive (95%CI: 90.2–96.7) and 99.7% specific (95%CI: 99.3–99.9). Compared to the laboratory reference, both user-conducted HIVST (sensitivity 87.5%, 95%CI: 82.70–91.3; specificity 99.7%, 95%CI: 99.4–99.9) and the national RDT algorithm (sensitivity 93.4%, 95%CI: 89.7–96.1%; specificity 100% (95%CI: 99.8–100%) had considerably lower sensitivity. Conclusions Self-testers in Zambia who used OraQuick® HIV Self-Test achieved reasonable clinical performance compared to the national RDT algorithm. However, sensitivity of the self-test was reduced compared to a laboratory reference standard, as was the national RDT algorithm. In-person demonstration, along with the written manufacturer instructions, was needed to obtain accurate results. Programmes introducing self-care diagnostics should pilot and optimise support materials to ensure they are appropriately adapted to context.

ObjectivesHIV testing is the gateway to HIV prevention and care services. Female sex workers (FSW) may benefit from HIV self-testing (HIVST), which offers greater control and confidentiality than other approaches. However, FSW also have unique vulnerabilities, making it critical to understand their perspective of HIVST to best contextualise HIVST to their needs. This study explored feasibility and acceptability of providing oral fluid-based peer-led HIVST to FSW to inform tailored HIVST delivery approaches.DesignQualitative study.SettingMalawi.ParticipantsThirty-nine FSW who had obtained a HIVST kit and eight peer distributors.ResultsPeer distributors’ accounts suggested that peer-led HIVST is feasible. Overall, FSW spoke positively about peer-led HIVST and younger FSW preferred it to facility-based HIV testing. FSW highlighted both greater control of their testing experience and that HIVST could allow them to avoid discriminatory attitudes frequently experienced in public facilities. Some also felt that HIVST kits could enable them to establish the HIV status of their sexual partners, better informing their decisions about condomless sex. Despite overall acceptance of HIVST, a few expressed doubts in the procedure. Some FSW already aware of their HIV-positive status reported using HIVST. A few accounts suggested peer pressure to self-test predominantly from peer distributors.ConclusionsThis study enabled us to explore feasibility and acceptability of peer-led HIVST among FSW, as well as potential shortcomings of the HIV testing modality. Peer distributors are a welcome additional model. However, they should avoid distribution in actual venues. Programmes should ensure a range of testing options are available and expand peer’s representation. Study findings will be used to tailor the HIVST distribution model to ensure its enhanced uptake among key populations in general and FSW, specifically.

BACKGROUND: Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality. METHODS: We established a microscopy method for direct visualisation of M. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpert® MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients predicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality. FINDINGS: M. tuberculosis was detected in 27 of 28 recruited participants; 25 (89%) by blood Xpert-ultra, 22 (79%) by DMN-Tre microscopy, and 21 (75%) by Myco/F lytic blood culture. Eight (29%) participants died by 12-week follow-up. In a combined pharmacodynamic model, predicted probabilities of negative DMN-Tre microscopy, blood Xpert-ultra, or blood culture after 72 h treatment were 0·64, 0·27, and 0·94, respectively, in those who survived, compared with 0·23, 0·06, and 0·71 in those who died (posterior probability of slower clearance of MTBBSI in those that died >0·99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolonies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0·13 log-µm/day; 95%CrI 0·10-0·16). INTERPRETATION: Pharmacodynamics of MTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert-ultra and culture. This could facilitate interventional trials in severe HIV-associated TB. FUNDING: Wellcome Trust, NIH Fogarty International Center, South African MRC, NIHR(UK), National Research Foundation of South Africa.

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

Introduction Programmes that merge management of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) aim to improve HIV/TB co-infected patients’ access to comprehensive treatment. However, several reports from sub-Saharan Africa (SSA) indicate suboptimal uptake of antiretroviral therapy (ART) even after integration of HIV and TB treatment. This study assessed ART uptake, its barriers and enablers in programmes integrating TB and HIV treatment in SSA. Method A systematic review was performed. Seven databases were searched for eligible quantitative, qualitative and mixed-methods studies published from March 2004 through July 2019. Random-effects meta-analysis was used to obtain pooled estimates of ART uptake. A thematic approach was used to analyse and synthesise data on barriers and enablers. Results Of 5139 references identified, 27 were included in the review: 23/27 estimated ART uptake and 10/27 assessed barriers to and/or enablers of ART uptake. The pooled ART uptake was 53% (95% CI: 42, 63%) and between-study heterogeneity was high (I2 = 99.71%, p Conclusions In SSA, programmes integrating treatment of TB and HIV do not, in general, achieve high ART uptake but we observe a net improvement in uptake after WHO issued the 2012 guidelines on collaborative TB/HIV activities. The recurrence of specific modifiable system-level and patient-level factors in the literature reveals key intervention points to improve ART uptake in these programmes. Systematic review registration: CRD42019131933.

OBJECTIVE\ud \ud To investigate trends in population incidence of HIV positive hospital admission and risk of in-hospital death among adults living with HIV between 2012 and 2019 in Blantyre, Malawi.\ud \ud DESIGN\ud \ud Population cohort study using an existing electronic health information system ('SPINE') at Queen Elizabeth Central Hospital and Blantyre census data.\ud \ud METHODS\ud \ud We used multiple imputation and negative binomial regression to estimate population age- and sex-specific admission rates over time. We used a log-binomial model to investigate trends in risk of in-hospital death.\ud \ud RESULTS\ud \ud Of 32,814 adult medical admissions during Q4.2012-Q3.2019, HIV status was recorded for 75.6%. HIV-positive admissions decreased substantially between 2012 and 2019. After imputation for missing data, HIV positive admissions were highest in Q3.2013 (173 per 100,000 adult Blantyre residents) and lowest in Q3.2019 (53 per 100,000 residents). An estimated 10,818 fewer than expected people living with HIV (PLHIV) (95%CI 10,068-11,568) were admitted during 2012-2019 compared to the counterfactual situation where admission rates stayed the same throughout this period. Absolute reductions were greatest for women aged 25-34 years (2,264 fewer HIV-positive admissions, 95%CI 2,002-2,526). In-hospital mortality for PLHIV was 23.5%, with no significant change over time in any age-sex group, and no association with ART use at admission.\ud \ud CONCLUSIONS\ud \ud Rates of admission for adult PLHIV decreased substantially, likely due to large increases in community provision of HIV diagnosis, treatment and care. However, HIV-positive in-hospital deaths remain unacceptably high, despite improvements in ART coverage. A concerted research and implementation agenda is urgently needed to reduce inpatient deaths among PLHIV.

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.

BackgroundHIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic.ObjectivesTo determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators.Design and settingProspective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala.InterventionClinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments.Primary outcome measuresRetention in care, plasma viral load.FindingsBetween 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load ConclusionIntegrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study.

IntroductionAntiretroviral therapy has reduced mortality and led to longer life expectancy in people living with HIV. These patients are now at an increased risk of non-communicable diseases (NCDs). Integration of care for HIV and NCDs has become a focus of research and policy. In this article, we aim to review patient perspectives on integration of healthcare for HIV, type 2 diabetes and hypertension.MethodsThe framework for scoping reviews developed by Arksey and O'Malley and updated by Peter et al was applied for this review. The databases PubMed, Web of Science and Cochrane library were searched. Broad search terms for HIV, NCDs (specifically type 2 diabetes and hypertension) and healthcare integration were used. As the review aimed to identify definitions of patient perspectives, they were not included as an independent term in the search strategy. References of included publications were searched for relevant articles. Titles and abstracts for these papers were screened by two independent reviewers. The full texts for all the publications appearing to meet the inclusion criteria were then read to make the final literature selection.ResultsOf 5502 studies initially identified, 13 articles were included in this review, of which 11 had a geographical origin in sub-Saharan Africa. Nine articles were primarily focused on HIV/diabetes healthcare integration while four articles were focused on HIV/hypertension integration. Patient’s experiences with integrated care were reduced HIV-related stigma, reduced travel and treatment costs and a more holistic person-centred care. Prominent concerns were long waiting times at clinics and a lack of continuity of care in some clinics due to a lack of healthcare workers. Non-integrated care was perceived as time-consuming and more expensive.ConclusionPatient perspectives and experiences on integrated care for HIV, diabetes and hypertension were mostly positive. Integrated services can save resources and allow for a more personalised approach to healthcare. There is a paucity of evidence and further longitudinal and interventional evidence from a more diverse range of healthcare systems are needed.

Background Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women’s heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings. Methods and findings We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years). In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period. Conclusions Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women.

Background Household contact tracing for tuberculosis (TB) may facilitate diagnosis and access to TB preventive treatment (TPT). We investigated whether household contact tracing and intensive TB/human immunodeficiency virus (HIV) screening would improve TB-free survival. Methods Household contacts of index TB patients in 2 South African provinces were randomized to home tracing and intensive HIV/TB screening or standard of care (SOC; clinic referral letters). The primary outcome was incident TB or death at 15 months. Secondary outcomes included tuberculin skin test (TST) positivity in children ≤14 years and undiagnosed HIV. Results From December 2016 through March 2019, 1032 index patients (4459 contacts) and 1030 (4129 contacts) were randomized to the intervention and SOC arms. Of intervention arm contacts, 3.2% (69 of 2166) had prevalent microbiologically confirmed TB. At 15 months, the cumulative incidence of TB or death did not differ between the intensive screening (93 of 3230, 2.9%) and SOC (80 of 2600, 3.1%) arms (hazard ratio, 0.90; 95% confidence interval [CI], .66–1.24). TST positivity was higher in the intensive screening arm (38 of 845, 4.5%) compared with the SOC arm (15 of 800, 1.9%; odds ratio, 2.25; 95% CI, 1.07–4.72). Undiagnosed HIV was similar between arms (41 of 3185, 1.3% vs 32 of 2543, 1.3%; odds ratio, 1.02; 95% CI, .64–1.64). Conclusions Household contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits. Clinical Trials Registration ISRCTN16006202.

Background A systematic review of randomised trials may be conclusive signalling no further research is needed; or identify gaps requiring further research that may then be included in review updates. In qualitative evidence synthesis (QES), the rationale, triggers, and methods for updating are less clear cut. We updated a QES on adherence to anti-retroviral treatment to examine if thematic saturation renders additional research redundant. Methods We adopted the original review search strategy and eligibility criteria to identify studies in the subsequent three years. We assessed studies for conceptual detail, categorised as ‘rich’ or ‘sparse’, coding the rich studies. We sought new codes, and appraised whether findings confirmed, extended, enriched, or refuted existing themes. Finally, we examined if the analysis impacted on the original conceptual model. Results After screening 3895 articles, 301 studies met the inclusion criteria. Rich findings from Africa were available in 82 studies; 146 studies were sparse, contained no additional information on specific populations, and did not contribute to the analysis. New studies enriched our understanding on the relationship between external and internal factors influencing adherence, confirming, extending and enriching the existing themes. Despite careful evaluation of the new literature, we did not identify any new themes, and found no studies that refuted our theory. Conclusions Updating an existing QES using the original question confirmed and sometimes enriched evidence within themes but made little or no substantive difference to the theory and overall findings of the original review. We propose this illustrates thematic saturation. We propose a thoughtful approach before embarking on a QES update, and our work underlines the importance of QES priority areas where further primary research may help, and areas where further studies may be redundant.

Introduction HIV programmes in sub-Saharan Africa are well funded but programmes for diabetes and hypertension are weak with only a small proportion of patients in regular care. Healthcare provision is organised from stand-alone clinics. In this cluster randomised trial, we are evaluating a concept of integrated care for people with HIV infection, diabetes or hypertension from a single point of care. Methods and analysis 32 primary care health facilities in Dar es Salaam and Kampala regions were randomised to either integrated or standard vertical care. In the integrated care arm, services are organised from a single clinic where patients with either HIV infection, diabetes or hypertension are managed by the same clinical and counselling teams. They use the same pharmacy and laboratory and have the same style of patient records. Standard care involves separate pathways, that is, separate clinics, waiting and counselling areas, a separate pharmacy and separate medical records. The trial has two primary endpoints: retention in care of people with hypertension or diabetes and plasma viral load suppression. Recruitment is expected to take 6 months and follow-up is for 12 months. With 100 participants enrolled in each facility with diabetes or hypertension, the trial will provide 90% power to detect an absolute difference in retention of 15% between the study arms (at the 5% two-sided significance level). If 100 participants with HIV infection are also enrolled in each facility, we will have 90% power to show non-inferiority in virological suppression to a delta=10% margin (ie, that the upper limit of the one-sided 95% CI of the difference between the two arms will not exceed 10%). To allow for lost to follow-up, the trial will enrol over 220 persons per facility. This is the only trial of its kind evaluating the concept of a single integrated clinic for chronic conditions in Africa. Ethics and dissemination The protocol has been approved by ethics committee of The AIDS Support Organisation, National Institute of Medical Research and the Liverpool School of Tropical Medicine. Dissemination of findings will be done through journal publications and meetings involving study participants, healthcare providers and other stakeholders. Trial registration number NCT43896688.

Introduction\ud Sisters with a Voice (Sisters), a programme providing community-led differentiated HIV prevention and treatment services, including condoms, HIV testing, pre-exposure prophylaxis (PrEP) and antiretroviral therapy linkage for sex workers, reached over 26,000 female sex workers (FSW) across Zimbabwe in 2020. Zimbabwe's initial Covid “lockdown” in March 2020 and associated movement restrictions interrupted clinical service provision for 6 weeks, particularly in mobile clinics, triggering the adaptation of services for the Covid-19 context and a scale up of differentiated service delivery (DSD) models. PrEP service delivery decentralized with shifts from clinical settings towards community/home-based, peer-led PrEP services to expand and maintain access. We hypothesize that peer-led community-based provision of PrEP services influenced both demand and supply-side determinants of PrEP uptake. We observed the effect of these adaptations on PrEP uptake among FSW accessing services in Sisters in 2020.\ud \ud Methods\ud New FSW PrEP initiations throughout 2020 were tracked by analysing routine Sisters programme data and comparing it with national PrEP initiation data for 2020. We mapped PrEP uptake among all negative FSW attending services in Sisters alongside Covid-19 adaptations and shifts in the operating environment throughout 2020: prior to lockdown (January–March 2020), during severe restrictions (April–June 2020), subsequent easing (July–September 2020) and during drug stockouts that followed (October–December 2020).\ud \ud Results and discussion\ud PrEP uptake in 2020 occurred at rates

Background\ud An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) prior to presentation. There is some evidence suggesting an increased two-week mortality in those receiving ART for less than 14 days compared with those on ART for more than 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or non-adherence are not well described.\ud \ud Methods\ud 678 adults with first episode of cryptococcal meningitis recruited into a randomized, non-inferiority, multicentre phase 3 trial in 4 sub-Saharan countries were analysed to compare clinical presentation and 2-and 10-week mortality outcomes between ART-naive and experienced patients, and between patients receiving ART for varying durations prior to presentation.\ud \ud Results\ud Over half (56% (381/678)) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2-weeks (17% vs 20%; HR 0.85, 95%CI 0.6-1.2, p=0.35), and 10 weeks (38% vs 36%; HR 1.03, 95%CI 0.8-1.32, p=0.82) for ART-experienced vs ART-naïve patients, respectively. Among ART-experienced patients, using different cut-off points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART.\ud \ud Conclusion\ud In this study, there were no significant differences in mortality at 2-and 10-weeks between ART- naive and experienced patients, and between ART-experienced patients according to duration on ART.

Background\ud Adolescence is a sensitive time for girls’ sexual and reproductive health (SRH), as biological changes occur concurrently with heightening pressures for sexual activity. In western Kenya, adolescent girls are vulnerable to acquiring sexually transmitted infections (STIs), such as HIV and herpes simplex virus type 2 (HSV-2), and to becoming pregnant prior to reaching adulthood. This study examines associations between individual, household, and partner-related risk factors and the prevalence of sex, adolescent pregnancy, HIV, and HSV-2.\ud \ud Methods and findings\ud We report baseline findings among 4,138 girls attending secondary school who were enrolled between 2017 and 2018 in the Cups or Cash for Girls (CCG) cluster randomized controlled trial in Siaya County, rural western Kenya. Laboratory confirmed biomarkers and survey data were utilized to assess the effects of girls’ individual, household, and partner characteristics on the main outcome measures (adolescent reported sex, prior pregnancy, HIV, and HSV-2) through generalized linear model (GLM) analysis. Complete data were available for 3,998 girls (97%) with median age 17.1 years (interquartile range [IQR] 16.3 to 18.0 years); 17.2% were HSV-2 seropositive (n = 686) and 1.7% tested positive for HIV (n = 66). Sexual activity was reported by 27.3% girls (n = 1,090), of whom 12.2% had been pregnant (n = 133). After adjustment, orphanhood (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 1.18 to 6.71, p-value [p] = 0.020), low body mass index (BMI) (aRR 2.07; CI: 1.00 to 4.30, p = 0.051), and age (aRR 1.34, 1.18 to 1.53, p < 0.001) were all associated with HIV infection. Girls reporting light menstrual bleeding (aRR 2.42, 1.22 to 4.79, p = 0.012) for fewer than 3 days (aRR 2.81, 1.16 to 6.82, p = 0.023) were over twice as likely to have HIV. Early menarche (aRR 2.05, 1.33 to 3.17, p = 0.001) was associated with adolescent pregnancy and HSV-2–seropositive girls reported higher rates of pregnancy (aRR 1.62, CI: 1.16 to 2.27, p = 0.005). High BMI was associated with HSV-2 (aRR 1.24, 1.05 to 1.46, p = 0.010) and sexual activity (aRR 1.14, 1.02 to 1.28, p = 0.016). High levels of harassment were detected in the cohort (41.2%); being touched indecently conveyed the strongest association related to reported sexual activity (aRR 2.52, 2.26 to 2.81, p < 0.001). Study limitations include the cross-sectional design of the study, which informs on the SRH burdens found in this population but limits causal interpretation of associations, and the self-reported exposure ascertainment, which may have led to possible underreporting of risk factors, most notably prior sexual activity.\ud \ud Conclusions\ud Our findings indicate that adolescent girls attending school in Kenya face frequent harassment for sex and are at high risk of pregnancy and HSV-2, with girls experiencing early menarche particularly vulnerable. Targeted interventions, such as earlier sexual education programs, are warranted to address their vulnerability to SRH harms.