Sustained high fatality during TB therapy amid rapid decline in TB mortality at population level: A retrospective cohort and ecological analysis from Shiselweni, Eswatini.

OBJECTIVES: Despite declining TB notifications in Southern Africa, TB-related deaths remain high. We describe patient- and population-level trends in TB-related deaths in Eswatini over a period of 11 years. METHODS: Patient-level (retrospective cohort, from 2009 to 2019) and population-level (ecological analysis, 2009-2017) predictors and rates of TB-related deaths were analysed in HIV-negative and HIV-coinfected first-line TB treatment cases and the population of the Shiselweni region. Patient-level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient-level and population-level predictors of deaths. RESULTS: Of 11,883 TB treatment cases, 1302 (11.0%) patients died during treatment: 210/2798 (7.5%) HIV-negative patients, 984/8443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV-status. The treatment case fatality ratio remained above 10% in most years. At patient-level, fatality risk was higher in PLHIV (aRR 1.74, 1.51-2.02), and for older age and extra-pulmonary TB irrespective of HIV-status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18-1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47-1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB-LAM testing (aRR 0.65, 0.35-0.90). At population-level, mortality rates decreased 6.4-fold (-147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (-826/100,000 vs. HIV-negative: -23/100,000), the relative population-level mortality risk remained higher in PLHIV (aRR 4.68, 3.25-6.72) compared to the HIV-negative population. CONCLUSIONS: TB-related mortality rapidly decreased at population-level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.

HIV Self-testing Among Previously Diagnosed HIV-Positive People in Khayelitsha, South Africa: No Evidence of Harm but may Facilitate Re-engagement in ART Care.

In South Africa, where an estimated 34% of nearly 7-million HIV-positive people were not on antiretroviral therapy (ART) in 2019, innovative strategies to diagnose and link people to care are needed. HIV self-testing (HIVST) is one such strategy. However, there is concern that access to HIVST might result in re-testing among people on ART, with a risk of false negative results and disengagement from care. Between November 2017 and December 2018, HIVST kits were distributed at a private pharmacy and at HIV testing outreach events. Each participant was instructed to report their result via SMS and those who did not were followed-up telephonically 10 days later. Electronic medical records of participants were searched for evidence of HIV services 6 months before and after enrollment. Of 1482 participants, 163 (11%) were previously diagnosed HIV-positive prior to taking the test. Of these, 123 reported a result, however 87% reported a negative result. Of the 163 previously diagnosed, 84 were not in ART care prior to the test, with 15 (18%) linking to care post-test. Of 79 who were in ART care prior to the test, 76 (96%) remained in care, even though 51 (67%) had reported a negative result. Overall, 29% of participants reported their result via SMS, and 48% when telephoned. Despite efforts to dissuade them, some previously diagnosed HIV-positive utilised HIVST. For those disengaged from care this may facilitate re-engagement. Self-testing among those already in care, regardless of the reported result, did not disrupt their treatment, and their reasons for doing the test remain unclear.

Delivering PrEP to Young Women in a Low-Income Setting in South Africa: Lessons for Providing Both Convenience and Support.

Daily oral pre-exposure prophylaxis (PrEP) is a key tool in addressing high HIV incidence among young women, and breaking the cycle of transmission. From 2017 to 2020, Médecins Sans Frontières (MSF) offered PrEP, in conjunction with contraception and risk-reduction counselling, to women aged 18-25, in a government-run clinic in Khayelitsha, a low income high HIV prevalence area in South Africa. Drawing on clinical, quantitative, and qualitative interview data, we describe participants' experiences and engagement with the PrEP program, participant adherence (measured by TFV-DP levels in dried blood spots) over time, and the indirect benefits of the PrEP program. Of 224 screened and eligible participants, 164 (73.2%) initiated PrEP, with no large differences between those who initiated and those who did not. Overall, 47 (29%) completed 18 months follow-up, with 15 (9.1%) attending all visits. 76 (46.9%) participants were lost to follow-up, 15 (9.1%) exited when leaving the area, and 28.7% of exits happened in the first month of the study. We identified two different trajectories of PrEP adherence: 67% of participants had, on average, consistently low TFV-DP levels, with the remaining 33% having sustained high adherence. Few baseline characteristics predicted good adherence. The main reported barrier to taking PrEP was forgetting to take or travel with the pills. Encouragement from others declined as a reported facilitator from month 6 to 18 (family: 93.1% vs 77.6%, p = 0.016, friends: 77.6% vs 41.4%, p ≤ 0.001, partners: 62.1% vs 46.6%, p = 0.096, other PrEP users: 89.7% vs 74.1%, p = 0.020). Disclosure to friends and family in some cases opened dialogue around sex, and helped to educate others about PrEP. Self-reported sex with more than one partner, and sex without a condom, decreased significantly after enrolment (p < 0.001, p = 0.063). In the individual interviews, participants credited their PrEP experience with changing their behaviour. Recognising the challenges with, but overall benefits from a package of care that includes the option of PrEP, lessons drawn from this study can help maximise persistence on PrEP within resource constraints. PrEP providers need to address participants' need for both convenience and social support.

Lay testing cadres and point-of-care diagnostic tests for HIV and other diseases: An essential combination in health service delivery.

Zibusiso Ndlovu and Tom Ellman discuss the potential value of task sharing in provision of testing for HIV and other infectious diseases.

Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Emerging priorities for HIV service delivery.

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

Tailored HIV programmes and universal health coverage.

Improvements in geospatial health data and tailored human immunodeficiency virus (HIV) testing, prevention and treatment have led to greater microtargeting of the HIV response, based on location, risk, clinical status and disease burden. These approaches show promise for achieving control of the HIV epidemic. At the same time, United Nations Member States have committed to achieving broader health and development goals by 2030, including universal health coverage (UHC). HIV epidemic control will facilitate UHC by averting the need to commit ever-increasing resources to HIV services. Yet an overly targeted HIV response could also distort health systems, impede integration and potentially threaten broader health goals. We discuss current approaches to achieving both UHC and HIV epidemic control, noting potential areas of friction between disease-specific microtargeting and integrated health systems, and highlighting opportunities for convergence that could enhance both initiatives. Examples of these programmatic elements that could be better aligned include: improved information systems with unique identifiers to track and monitor individuals across health services and the life course; strengthened subnational data use; more accountable supply chains that supply a broad range of services; and strengthened community-based services and workforces. We argue that the response both to HIV and to broader health threats should use these areas of convergence to increase health systems efficiency and mitigate the harm of any potential decrease in health funding. Further investments in implementation and monitoring of these programme elements will be needed to make progress towards both UHC and HIV epidemic control.

Les améliorations des données sanitaires géospatiales et la personnalisation du dépistage, de la prévention et du traitement du virus de l'immunodéficience humaine (VIH) ont permis de développer le micro-ciblage de la réponse au VIH, en fonction du lieu, du risque, de la situation clinique et de la charge de morbidité. Ces approches sont prometteuses pour lutter contre l'épidémie de VIH. Dans le même temps, les États membres des Nations Unies se sont engagés à atteindre des objectifs plus larges de santé et de développement d'ici 2030, notamment la couverture sanitaire universelle. Cette dernière sera facilitée par la lutte contre l'épidémie de VIH, qui réduira la nécessité de consacrer toujours plus de ressources aux services liés au VIH. Cependant, une réponse au VIH trop ciblée pourrait également distordre les systèmes de santé, empêcher leur intégration et potentiellement nuire aux objectifs de santé plus vastes. Nous abordons ici les approches actuelles en matière de couverture sanitaire universelle et de lutte contre l'épidémie de VIH, en notant les points de friction potentiels entre un micro-ciblage spécifique à certaines maladies et des systèmes de santé intégrés, ainsi que les opportunités de convergence qui pourraient être bénéfiques aux deux initiatives. Parmi les éléments de programmes qui pourraient être mieux coordonnés, nous pouvons citer: l'amélioration des systèmes d'information avec des identifiants uniques permettant de suivre les personnes dans leur parcours de soins et tout au long de leur vie; la plus grande utilisation des données infranationales; la responsabilisation des chaînes d'approvisionnement qui fournissent un grand nombre de services; et le renforcement des services et des intervenants communautaires. Nous soutenons que la réponse au VIH et à d'autres menaces sanitaires devrait exploiter ces domaines de convergence pour accroître l'efficacité des systèmes de santé et atténuer le préjudice d'une éventuelle baisse des fonds alloués à la santé. Il sera nécessaire d'investir davantage dans la mise en œuvre et le suivi de ces éléments de programmes pour avancer, aussi bien vers la couverture sanitaire universelle que dans la lutte contre l'épidémie de VIH.

Las mejoras en los datos geoespaciales de salud y las pruebas, la prevención y el tratamiento adaptados al virus de la inmunodeficiencia humana (VIH) han conducido a una mayor focalización de la respuesta al VIH, basada en la ubicación, el riesgo, el estado clínico y la carga de la enfermedad. Estos enfoques son prometedores para lograr el control de la epidemia del VIH. Al mismo tiempo, los Estados Miembros de las Naciones Unidas se han comprometido a alcanzar objetivos de salud y desarrollo de mayor alcance para 2030, incluida la cobertura universal de salud (universal health coverage, UHC). El control de la epidemia del VIH facilitará la UHC porque evitará la necesidad de comprometer recursos cada vez mayores para los servicios del VIH. Sin embargo, una respuesta al VIH demasiado específica también podría distorsionar los sistemas de salud, impedir la integración y amenazar potencialmente los objetivos de salud de mayor alcance. Se discuten los enfoques actuales para lograr tanto la atención primaria de salud como el control de la epidemia del VIH, se señalan las posibles áreas de fricción entre la focalización específica de la enfermedad y los sistemas integrados de salud, y se destacan las oportunidades de convergencia que podrían mejorar ambas iniciativas. Entre los ejemplos de estos elementos programáticos que podrían alinearse mejor se incluyen: sistemas de información mejorados con identificadores únicos para hacer un seguimiento y monitoreo de las personas a través de los servicios de salud y el curso de la vida; el fortalecimiento del uso de datos a nivel subnacional; cadenas de suministro más responsables que proveen una amplia gama de servicios; y el fortalecimiento de los servicios en la comunidad y las fuerzas de trabajo. Se argumenta que la respuesta tanto al VIH como a las amenazas para la salud en general debe utilizar estas áreas de convergencia para aumentar la eficiencia de los sistemas de salud y mitigar el daño de cualquier posible disminución en la financiación de la salud. Se necesitarán más inversiones en la ejecución y el monitoreo de estos elementos del programa para avanzar tanto en el control de la epidemia de VIH como en la UHC.

The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings.

In a Policy Forum, Peter Ehrenkranz and colleagues discuss the contribution of CD4 and viral load testing to outcomes for people with HIV in low- and middle-income countries.

Progress towards the UNAIDS 90-90-90 goals by age and gender in a rural area of KwaZulu-Natal, South Africa: a household-based community cross-sectional survey.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed an ambitious strategy to end the AIDS epidemic. After eight years of antiretroviral therapy (ART) program we assessed progress towards the UNAIDS 90-90-90 targets in Mbongolwane and Eshowe, KwaZulu-Natal, South Africa. METHODS: We conducted a cross-sectional household-based community survey using a two-stage stratified cluster probability sampling strategy. Persons aged 15-59 years were eligible. We used face-to-face interviewer-administered questionnaires to collect information on history of HIV testing and care. Rapid HIV testing was performed on site and venous blood specimens collected from HIV-positive participants for antiretroviral drug presence test, CD4 count and viral load. At the time of the survey the CD4 threshold for ART initiation was 350 cells/µL. We calculated progression towards the 90-90-90 UNAIDS targets by estimating three proportions: HIV positive individuals who knew their status (first 90), those diagnosed who were on ART (second 90), and those on ART who were virally suppressed (third 90). RESULTS: We included 5649/6688 (84.5%) individuals. Median age was 26 years (IQR: 19-40), 62.3% were women. HIV prevalence was 25.2% (95% CI: 23.6-26.9): 30.9% (95% CI: 29.0-32.9) in women; 15.9% (95% CI: 14.0-18.0) in men. Overall progress towards the 90-90-90 targets was as follows: 76.4% (95% CI: 74.1-78.6) knew their status, 69.9% (95% CI: 67.0-72.7) of those who knew their status were on ART and 93.1% (95% CI: 91.0-94.8) of those on ART were virally suppressed. By sex, progress towards the 90-90-90 targets was: 79%-71%-93% among women; and 68%-68%-92% among men (p-values of women and men comparisons were < 0.001, 0.443 and 0.584 respectively). By age, progress was: 83%-75%-95% among individuals aged 30-59 years and 64%-58%-89% among those aged 15-29 years (p-values of age groups comparisons were < 0.001, < 0.001 and 0.011 respectively). CONCLUSIONS: In this context of high HIV prevalence, significant progress has been achieved with regards to reaching the UNAIDS 90-90-90 targets. The third 90, viral suppression in people on ART, was achieved among women and men. However, gaps persist in HIV diagnosis and ART coverage particularly in men and individuals younger than 30 years. Achieving 90-90-90 is feasible but requires additional investment to reach youth and men.

Combined interventions to reduce HIV incidence in KwaZulu-Natal: a modelling study.

BACKGROUND: Combined prevention interventions, including early antiretroviral therapy initiation, may substantially reduce HIV incidence in hyperendemic settings. Our aim was to assess the potential short-term impact of combined interventions on HIV spreading in the adult population of Mbongolwane and Eshowe (KwaZulu-Natal, South Africa) using sex- and age-specific scenarios, and age-targeted interventions. METHODS: A mathematical model was used with data on adults (15-59 years) from the Mbongolwane and Eshowe HIV Impact in Population Survey to compare the effects of various interventions on the HIV incidence rate. These interventions included increase in antiretroviral therapy (ART) coverage with extended eligibility criteria, increase in voluntary medical male circumcision (VMMC), and implementation of pre-exposure prophylaxis (PrEP) among women. RESULTS: With no additional interventions to the ones in place at the time of the survey (ART at CD4 < 350 and VMMC), incidence will decrease by 24% compared to the baseline rate. The implementation of "ART at CD4<500" or "ART for all" would reduce further the incidence rate by additional 8% and 15% respectively by 4 years and 20% and 34% by 10 years. Impacts would be higher with age-targeted scenarios than without. CONCLUSIONS: In Mbongolwane and Eshowe, implementation of the new South African guidelines, recommending ART initiation regardless of CD4 count, would accelerate incidence reduction. In this setting, combining these guidelines, VMMC, and PrEP among young women could be an effective strategy in reducing the incidence to low levels.

Prospective evaluation of diagnostic accuracy of dried blood spots from finger prick samples for determination of HIV-1 load with the NucliSENS Easy-Q HIV-1 version 2.0 assay in Malawi.

HIV-1 viral load (VL) testing is not widely available in resource-limited settings. The use of finger prick dried blood spot (FP-DBS) samples could remove barriers related to sample collection and transport. Measurement of VL using DBS from EDTA venous blood (VB-DBS) in place of plasma has previously been validated using the NucliSENS Easy-Q HIV-1 v2.0 assay, but information on the accuracy of FP-DBS samples for measuring VL is limited. This prospective study, conducted at Thyolo District Hospital in southern Malawi, compared VL levels measured on FP-DBS samples and plasma using the NucliSENS Easy-Q HIV-1 v2.0 assay. Comparability was assessed by means of agreement and correlation (131 patients with VLs of ≥100 copies/ml), sensitivity, and specificity (612 patients on antiretroviral treatment [ART]). Samples of EDTA venous blood and FP-DBS from 1,009 HIV-infected individuals were collected and prepared in the laboratory. Bland-Altman analysis found good agreement between plasma and FP-DBS VL levels, with a mean difference of -0.35 log10, and 95% limits of agreement from -1.26 to 0.55 log10. FP-DBS had a sensitivity of 88.7% (95% confidence interval [CI], 81.1 to 94.4%) and a specificity of 97.8% (95% CI, 96.1 to 98.9%) using a 1,000-copies/ml cut point and a sensitivity of 83.0% (95% CI, 73.4 to 90.1%) and a specificity of 100% (95% CI, 99.3 to 100%) using a 5,000-copies/ml cut point. This study shows that FP-DBS is an acceptable alternative to plasma for measuring VL using the NucliSENS Easy-Q HIV-1 v2.0. We are conducting a second study to assess the proficiency of health workers at preparing FP-DBS in primary health care clinics.

Changes Over Time in the Proportion of Advanced HIV Disease in Two High HIV Prevalence Settings in Ndhiwa (Kenya) and Eshowe (South Africa).

BACKGROUND: The burden of advanced HIV disease remains a significant concern in sub-Saharan Africa. In 2015, the World Health Organization released recommendations to treat all people living with HIV (PLHIV) regardless of CD4 ("treat all") and in 2017 guidelines for managing advanced HIV disease. We assessed changes over time in the proportion of PLHIV with advanced HIV and their care cascade in two community settings in sub-Saharan Africa. METHODS: Cross-sectional population-based surveys were conducted in Ndhiwa (Kenya) in 2012 and 2018 and in Eshowe (South Africa) in 2013 and 2018. We recruited individuals aged 15-59 years. Consenting participants were interviewed and tested for HIV at home. All participants with HIV had CD4 count measured. Advanced HIV was defined as CD4 < 200 cells/µL. RESULTS: Overall, 6076 and 6001 individuals were included in 2012 and 2018 (Ndhiwa) and 5646 and 3270 individuals in 2013 and 2018 (Eshowe), respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 2012 (159/1376 (11.8%; 95% CI: 9.8-14.2)) to 2018 (53/1000 (5.0%; 3.8-6.6)). The proportion of individuals with advanced HIV on antiretroviral therapy (ART) was 9.1% (6.9-11.8) in 2012 and 4.2% (3.0-5.8) in 2018. In Eshowe, the proportion with advanced HIV was 130/1400 (9.8%; 8.0-11.9) in 2013 and 38/834 (4.5%; 3.3-6.1) in 2018. The proportion with advanced HIV among those on ART was 6.9% (5.5-8.8) in 2013 and 2.8% (1.8-4.3) in 2018. There was a significant increase in coverage for all steps of the care cascade among people with advanced HIV between the two Ndhiwa surveys, with all the changes occurring among men and not women. No significant changes were observed in Eshowe between the surveys overall and by sex. CONCLUSION: The proportion with advanced HIV disease decreased between the first and second surveys where all guidelines have been implemented between the two HIV surveys.

Distribution of advanced HIV disease between two time periods in Ndhiwa (Kenya) and Eshowe (South Africa)We examined changes over time in the proportion of people living with HIV (PLHIV) with advanced HIV and their care cascade in two community settings in sub-Saharan Africa: Ndhiwa (Kenya) and Eshowe (South Africa). In 2012 and 2018, a total of 6,076 and 6,001 individuals were included in Ndhiwa, and 5,646 and 3,270 individuals were included in Eshowe in 2013 and 2018, respectively. In Ndhiwa, the proportion of PLHIV with advanced HIV decreased from 11.8% in 2012 to 5.0% in 2018. The proportion of individuals with advanced HIV on antiretroviral therapy (ART) decreased from 9.1% in 2012 to 4.2% in 2018. In Eshowe, the proportion PLHIV with advanced HIV decreased from 9.8% in 2013 to 4.5% in 2018. Among those on ART, the proportion of PLHIV with advanced HIV decreased from 6.9% in 2013 to 2.8% in 2018. The results also showed a significant increase in coverage for all steps of the care cascade among people with advanced HIV in Ndhiwa in 2018 compared to 2012, with these changes observed only among men and not women. No significant changes were observed in Eshowe between the surveys, both overall and when comparing by sex.

Supporting re-engagement with HIV services after treatment interruption in South Africa: a mixed method program evaluation of MSF's Welcome Service.

Psychosocial challenges impact patients' ability to remain on antiretroviral therapy lifelong, magnified by disorganized health-systems and healthcare worker (HCW) attitudes. To address this, Médecins Sans Frontières and the Department of Health developed the Welcome Service intervention, to provide person-centered care at re-engagement after HIV treatment interruption. Implemented in Khayelitsha, South Africa, between August 2020 and February 2021, the intervention aimed to reorganize triage, optimize clinical and counselling services and address HCW attitudes. The study used a mixed-methods design, incorporating in-depth interviews, and analyses of programmatic and routine health data. Interviews demonstrated positive patient care experiences. HCWs understood the potential impact of attitudes on patient engagement, however, some continued to demonstrate judgmental attitude. Clinical objectives were variably met at re-engagement: 98% were re-initiated the same day, 50% had a CD4 done, and 45% received tuberculosis prevention. Nevertheless, 4-month retention was 66%, and 88% had a VL < 1000 c/mL. Despite HCWs' understanding of person-centered care not translating into supportive behaviors, patients had positive care experiences and the intervention ended with a high rate of VL suppression. More efforts are needed to design interventions building on Welcome Service principles to provide person-centered care and sustain retention after re-engagement.

Diabetes Care in Humanitarian Settings.

Despite the increasing prevalence of diabetes in populations experiencing humanitarian crisis, along with evidence that people living with diabetes are at higher risk for poor outcomes in a crisis, diabetes care is not routinely included in humanitarian health interventions. We here describe 4 factors that have contributed to the inequities and lack of diabetes inclusion in humanitarian programmes: (1) evolving paradigms in humanitarian health care, (2) complexities of diabetes service provision in humanitarian settings, (3) social and cultural challenges, and (4) lack of financing. We also outline opportunities and possible interventions to address these challenges and improve diabetes care among crisis-affected populations.

Outcomes of people living with HIV after hospital discharge: a systematic review and meta-analysis.

BACKGROUND: The identification and appropriate management of people with advanced HIV disease is a key component in the HIV response. People with HIV who are hospitalised are at a higher risk of death, a risk that might persist after discharge. The aims of this study were to estimate the frequency of negative post-discharge outcomes, and to determine risk factors for such outcomes in people with HIV. METHODS: Using a broad search strategy combining terms for hospital discharge and HIV infection, we searched MEDLINE via PubMed and Embase from Jan 1, 2003 to Nov 30, 2021 to identify studies reporting outcomes among people with HIV following discharge from hospital. We estimated pooled proportions of readmissions and deaths after hospital discharge using random-effects models. We also did subgroup analyses by setting, region, duration of follow-up, and advanced HIV status at admission, and sensitivity analyses to assess heterogeneity. FINDINGS: We obtained data from 29 cohorts, which reported outcomes of people living with HIV after hospital discharge in 92 781 patients. The pooled proportion of patients readmitted to hospital after discharge was 18·8% (95% CI 15·3-22·3) and 14·1% (10·8-17·3) died post-discharge. In sensitivity analyses, no differences were identified in the proportion of patients who were readmitted or died when comparing studies published before 2016 with those published after 2016. Post-discharge mortality was higher in studies from Africa (23·1% [16·5-29·7]) compared with the USA (7·5% [4·4-10·6]). For studies that reported both post-discharge mortality and readmission, the pooled proportion of patients who had this composite adverse outcome was 31·7% (23·9-39·5). Heterogeneity was moderate, and largely explained by patient status and linkage to care. Reported risk factors for readmission included low CD4 cell count at admission, longer length of stay, discharge against medical advice, and not linking to care following discharge; inpatient treatment with antiretroviral therapy (ART) during hospitalisation was protective of post-discharge mortality. INTERPRETATION: More than a quarter of patients with HIV had an adverse outcome after hospital discharge with no evidence of improvement in the past 15 years. This systematic review highlights the importance of ensuring post-discharge referral and appropriate management, including ART, to reduce mortality and readmission to hospital among this group of high-risk patients. FUNDING: Bill & Melinda Gates Foundation. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

HIV, sexual violence, and termination of pregnancy among adolescent and adult female sex workers in Malawi: A respondent-driven sampling study.

Female Sex Workers (FSWs) are a hard-to-reach and understudied population, especially those who begin selling sex at a young age. In one of the most economically disadvantaged regions in Malawi, a large population of women is engaged in sex work surrounding predominantly male work sites and transport routes. A cross-sectional study in February and April 2019 in Nsanje district used respondent driven sampling (RDS) to recruit women ≥13 years who had sexual intercourse (with someone other than their main partner) in exchange for money or goods in the last 30 days. A standardized questionnaire was filled in; HIV, syphilis, gonorrhea, and chlamydia tests were performed. CD4 count and viral load (VL) testing occurred for persons living with HIV (PLHIV). Among 363 study participants, one-quarter were adolescents 13-19 years (25.9%; n = 85). HIV prevalence was 52.6% [47.3-57.6] and increased with age: from 14.7% (13-19 years) to 87.9% (≥35 years). HIV status awareness was 95.2% [91.3-97.4], ART coverage was 98.8% [95.3-99.7], and VL suppression 83.2% [77.1-88.0], though adolescent FSWs were less likely to be virally suppressed than adults (62.8% vs. 84.4%). Overall syphilis prevalence was 29.7% [25.3-43.5], gonorrhea 9.5% [6.9-12.9], and chlamydia 12.5% [9.3-16.6]. 72.4% had at least one unwanted pregnancy, 17.9% had at least one abortion (40.1% of which were unsafe). Half of participants reported experiencing sexual violence (SV) (47.6% [42.5-52.7]) and more than one-tenth (14.2%) of all respondents experienced SV perpetrated by a police officer. Our findings show high levels of PLHIV-FSWs engaged in all stages of the HIV cascade of care. The prevalence of HIV, other STIs, unwanted pregnancy, unsafe abortion, and sexual violence remains extremely high. Peer-led approaches contributed to levels of ART coverage and HIV status awareness similar to those found in the general district population, despite the challenges and risks faced by FSWs.

High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients.

BACKGROUND: Patients hospitalized with advanced HIV have a high mortality risk. We assessed viremia and drug resistance among differentiated care services and explored whether expediting the switching of failing treatments may be justified. SETTING: Hospitals in the Democratic Republic of (DRC) Congo (HIV hospital) and Kenya (general hospital including HIV care). METHODS: Viral load (VL) testing and drug resistance (DR) genotyping were conducted for HIV inpatients ≥15 years, on first-line antiretroviral therapy (ART) for ≥6 months, and CD4 ≤350 cells/µL. Dual-class DR was defined as low-, intermediate-, or high-level DR to at least 1 nucleoside reverse transcriptase inhibitor and 1 non-nucleoside reverse transcriptase inhibitor. ART regimens were considered ineffective if dual-class DR was detected at viral failure (VL ≥1000 copies/mL). RESULTS: Among 305 inpatients, 36.7% (Kenya) and 71.2% (DRC) had VL ≥1000 copies/mL, of which 72.9% and 73.7% had dual-class DR. Among viral failures on tenofovir disoproxil fumarate (TDF)-based regimens, 56.1% had TDF-DR and 29.8% zidovudine (AZT)-DR; on AZT regimens, 71.4% had AZT-DR and 61.9% TDF-DR, respectively. Treatment interruptions (≥48 hours during past 6 months) were reported by 41.7% (Kenya) and 56.7% (DRC). Approximately 56.2% (Kenya) and 47.4% (DRC) on TDF regimens had tenofovir diphosphate concentrations <1250 fmol/punch (suboptimal adherence). Among viral failures with CD4 <100 cells/µL, 76.0% (Kenya) and 84.6% (DRC) were on ineffective regimens. CONCLUSIONS: Many hospitalized, ART-experienced patients with advanced HIV were on an ineffective first-line regimen. Addressing ART failure promptly should be integrated into advanced disease care packages for this group. Switching to effective second-line medications should be considered after a single high VL on non-nucleoside reverse transcriptase inhibitor-based first-line if CD4 ≤350 cells/µL or, when VL is unavailable, among patients with CD4 ≤100 cells/µL.

The time to act is now: pseudo-systematic review.

OBJECTIVE: To identify any medical or public health rationale for claims that the time to act is now. DESIGN: Pseudo-systematic review. DATA SOURCES: PubMed. STUDY SELECTION: Studies that included the claim "time is now" in the title, with or without exclamation marks. No language or date restriction was applied. RESULTS: 512 articles were included for review. No relationship was identified between time to act and disease burden, severity, or specialty. Claims that the time to act was Christmas were almost entirely without basis. A clustering of claims that it is time to act in the first quarter of the year suggested a possible association with New Year's resolutions. CONCLUSIONS: Now is as good a time as any.