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Introduction"Treat All" - the treatment of all people with HIV, irrespective of disease stage or CD4 cell count - represents a paradigm shift in HIV care that has the potential to end AIDS as a public health threat. With accelerating implementation of Treat All in sub-Saharan Africa (SSA), there is a need for a focused agenda and research to identify and inform strategies for promoting timely uptake of HIV treatment, retention in care, and sustained viral suppression and addressing bottlenecks impeding implementation.MethodsThe Delphi approach was used to develop consensus around research priorities for Treat All implementation in SSA. Through an iterative process (June 2017 to March 2018), a set of research priorities was collectively formulated and refined by a technical working group and shared for review, deliberation and prioritization by more than 200 researchers, implementation experts, policy/decision-makers, and HIV community representatives in East, Central, Southern and West Africa.Results and discussionThe process resulted in a list of nine research priorities for generating evidence to guide Treat All policies, implementation strategies and monitoring efforts. These priorities highlight the need for increased focus on adolescents, men, and those with mental health and substance use disorders - groups that remain underserved in SSA and for whom more effective testing, linkage and care strategies need to be identified. The priorities also reflect consensus on the need to: (1) generate accurate national and sub-national estimates of the size of key populations and describe those who remain underserved along the HIV-care continuum; (2) characterize the timeliness of HIV care and short- and long-term HIV care continuum outcomes, as well as factors influencing timely achievement of these outcomes; (3) estimate the incidence and prevalence of HIV-drug resistance and regimen switching; and (4) identify cost-effective and affordable service delivery models and strategies to optimize uptake and minimize gaps, disparities, and losses along the HIV-care continuum, particularly among underserved populations.ConclusionsReflecting consensus among a broad group of experts, researchers, policy- and decision-makers, PLWH, and other stakeholders, the resulting research priorities highlight important evidence gaps that are relevant for ministries of health, funders, normative bodies and research networks.

Patients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to a weight-banded nominal dose of 11, 14, 17, or 20 mg/kg/day levofloxacin (minimum, 750 mg) in combination with other second-line agents. A total of 101 patients were included in noncompartmental pharmacokinetic analyses. Respective median areas under the concentration-time curve from 0 to 24 h (AUC0-24) were 109.49, 97.86, 145.33, and 207.04 μg · h/ml. Median maximum plasma concentration (Cmax) were 11.90, 12.02, 14.86, and 19.17 μg/ml, respectively. Higher levofloxacin doses, up to 1,500 mg daily, resulted in higher exposures. (This study has been registered at ClinicalTrials.gov under identifier NCT01918397.).

BackgroundCurrent guidelines for treatment of multidrug-resistant tuberculosis (MDR-TB) are largely based on expert opinion and observational data. Fluoroquinolones remain an essential part of MDR-TB treatment, but the optimal dose of fluoroquinolones as part of the regimen has not been defined.Methods/designWe designed a randomized, blinded, phase II trial in MDR-TB patients comparing across levofloxacin doses of 11, 14, 17 and 20 mg/kg/day, all within an optimized background regimen. We assess pharmacokinetics, efficacy, safety and tolerability of regimens containing each of these doses. The primary efficacy outcome is time to culture conversion over the first 6 months of treatment. The study aims to determine the area under the curve (AUC) of the levofloxacin serum concentration in the 24 hours after dosing divided by the minimal inhibitory concentration of the patient's Mycobacterium tuberculosis isolate that inhibits > 90% of organisms (AUC/MIC) that maximizes efficacy and the AUC that maximizes safety and tolerability in the context of an MDR-TB treatment regimen.DiscussionFluoroquinolones are an integral part of recommended MDR-TB regimens. Little is known about how to optimize dosing for efficacy while maintaining acceptable toxicity. This study will provide evidence to support revised dosing guidelines for the use of levofloxacin as part of combination regimens for treatment of MDR-TB. The novel methodology can be adapted to elucidate the effect of other single agents in multidrug antibiotic treatment regimens.Trial registrationClinicalTrials.gov, NCT01918397 . Registered on 5 August 2013.

Our study aimed at understanding the utilization of research knowledge generated in sustainable development research. Drawing on a sample of 54 recent research projects, we investigated how and by whom the knowledge was used, what changes were achieved, and how non-academic actors were involved. As a conceptual framework we combined a concept of "stages of knowledge utilization" with a spiral model that co-creates three forms of knowledge – systems knowledge, target knowledge, and transformation knowledge, and which spans from joint problem definition to concrete sustainability transformations. We analysed questionnaires from 94 academic and non-academic actors using cross-tabulation, chi-squared tests, and qualitative content analysis. The early involvement of non-academic actors from key groups such as local enterprises was positively related to the utilization of research knowledge, as was their involvement in diverse roles. However, only little of the research knowledge generated has so far resulted in changes in policy and practice, partly because sustainability transformations are larger societal processes. Utilization of research knowledge for sustainability transformations cannot be achieved without employing a transdisciplinary approach that brings together academic and non-academic actors in a setting that enables discussions on an even footing and the empowering of actors who are often not heard. In such settings, researchers are also part of the change rather than mere observers, an additional factor that came up in our participatory results validation activities and that requires further research. For more influence on policies and practice, research for development requires active participation of non-academic actors from the outset, when the project contents are defined. • Transdisciplinary ways of doing science have become important in the co-production of knowledge to solve societal challenges. • There is a danger that non-academic actors are recipients of information rather than co-creators of knowledge. • The early involvement of non-academic actors in diverse roles in projects increases the utilization of the co-created knowledge. • Incorporating transdisciplinarity into classical research approaches adds openness – and thus uncertainty – to projects. • We recommend a more active engagement with non-academic actors especially from vulnerable groups from the start of a project. [ABSTRACT FROM AUTHOR]

Summary Background Delamanid is one of two recently approved drugs for the treatment of multidrug-resistant tuberculosis. We aimed to evaluate the safety and efficacy of delamanid in the first 6 months of treatment. Methods This randomised, double-blind, placebo-controlled, phase 3 trial was done at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa). We enrolled eligible adults (>18 years) with pulmonary multidrug-resistant tuberculosis to receive, in combination with an optimised background regimen developed according to WHO and national guidelines, either oral delamanid (100 mg twice daily) for 2 months followed by 200 mg once daily for 4 months or placebo (same regimen). Patients were centrally randomised (2:1) and stratified by risk category for delayed sputum culture conversion. Primary outcomes were the time to sputum culture conversion over 6 months and the difference in the distribution of time to sputum culture conversion over 6 months between the two groups, as assessed in the modified intention-to-treat population. The trial is registered at ClinicalTrials.gov , number NCT01424670. Findings Between Sept 2, 2011, and Nov 27, 2013, we screened 714 patients, of whom 511 were randomly assigned (341 to delamanid plus optimised background regimen [delamanid group] and 170 to placebo plus optimised background regimen [placebo group]) and formed the safety analysis population. 327 patients were culture-positive for multidrug-resistant tuberculosis at baseline and comprised the efficacy analysis population (226 in the delamanid group and 101 in the placebo group). Median time to sputum culture conversion did not differ between the two groups (p=0·0562; modified Peto-Peto), with 51 days (IQR 29–98) in the delamanid group and 57 days (43–85) in the placebo group; the hazard ratio was 1·17 (95% CI 0·91–1·51, p=0·2157). 501 (98·0%) of 511 patients had at least one treatment-emergent adverse event. 136 (26·6%) of 511 patients had at least one serious treatment-emergent adverse event; the incidence was similar between treatment groups (89 [26·1%] of 341 patients for delamanid and 47 [27·6%] of 170 for placebo). Deaths related to treatment-emergent adverse events were similar between groups (15 [4·4%] of 341 for delamanid and six [3·5%] of 170 for placebo). No deaths were considered to be related to delamanid. Interpretation The reduction in median time to sputum culture conversion over 6 months was not significant in the primary analysis. Delamanid was well tolerated with a highly characterised safety profile. Further evaluation of delamanid is needed to determine its role in a rapidly evolving standard of care. Funding Otsuka Pharmaceutical. [ABSTRACT FROM AUTHOR]

Summary: Time to liquid culture positivity (TTP) is a technically accessible and widely available measure of viable mycobacterial load in sputum samples. We describe the ability of TTP to predict colony forming unit counts of Mycobacterium tuberculosis from sputum samples collected before or during the first 14 days of antituberculosis therapy. [Copyright &y& Elsevier]

Objective: To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care., Design: Retrospective cohort study., Methods: We used data from four South African cohorts participating in the International epidemiology Databases to Evaluate AIDS Southern Africa collaboration. We included adults who started ART between 2004 and 2019. We defined a care interruption as a gap in contact longer than 180 days. Observation time prior to interruption was allocated to a 'no interruption' group. Observation time after interruption was allocated to one of two groups based on whether the first interruption started before 6 months of ART ('early interruption') or later ('late interruption'). We used Cox regression to estimate hazard ratios., Results: Sixty-three thousand six hundred and ninety-two participants contributed 162 916 person-years of observation. There were 3469 deaths. Most participants were female individuals (67.4%) and the median age at ART initiation was 33.3 years (interquartile range: 27.5-40.7). Seventeen thousand and eleven (26.7%) participants experienced care interruptions. Those resuming ART experienced increased mortality compared with those with no interruptions: early interrupters had a hazard ratio of 4.37 (95% confidence interval (CI) 3.87-4.95) and late interrupters had a hazard ratio of 2.74 (95% CI 2.39-3.15). In sensitivity analyses, effect sizes were found to be proportional to the length of time used to define interruptions., Conclusion: Our findings highlight the need to improve retention in care, regardless of treatment duration. Programmes to encourage return to care also need to be strengthened., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Of women with cervical cancer (CC) and HIV, 85% live in sub-Saharan Africa, where 21% of all CC cases are attributable to HIV infection. We aimed to generate internationally acceptable facility-based indicators to monitor and guide scale up of CC prevention and care services offered on-site or off-site by HIV clinics., Methods: We reviewed the literature and extracted relevant indicators, grouping them into domains along the CC control continuum. From February 2021 to March 2022, we conducted a three-round, online Delphi process to reach consensus on indicators. We invited 106 experts to participate. Through an anonymous, iterative process, participants adapted the indicators to their context (round 1), then rated them for 5 criteria on a 5-point Likert-type scale (rounds 2 and 3) and then ranked their importance (round 3)., Results: We reviewed 39 policies from 21 African countries and 7 from international organizations; 72 experts from 15 sub-Saharan Africa countries or international organizations participated in our Delphi process. Response rates were 34% in round 1, 40% in round 2, and 44% in round 3. Experts reached consensus for 17 indicators in the following domains: primary prevention (human papillomavirus prevention, n = 2), secondary prevention (screening, triage, treatment of precancerous lesions, n = 11), tertiary prevention (CC diagnosis and care, n = 2), and long-term impact of the program and linkage to HIV service (n = 2)., Conclusion: We recommend that HIV clinics that offer CC control services in sub-Saharan Africa implement the 17 indicators stepwise and adapt them to context to improve monitoring along the CC control cascade., Competing Interests: S.L.A. received the Swiss Government Excellence Scholarship, No 2019.0741. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Common mental disorders (CMD), which include depression and anxiety, are prevalent among people living with HIV and are associated with suboptimal antiretroviral therapy (ART) adherence., Objective: To assess the effect of a lay health worker-led psychological intervention on ART adherence, virologic suppression, and mental health symptoms., Design, Setting, and Participants: Open-label pragmatic cluster trial with 1:1 block randomization of 16 health facilities in rural Bikita, Zimbabwe. Recruitment occurred from October 2018 to December 2019, and participants were followed up for 12 months, ending in December 2020. Participants were adults aged 18 years and older, who spoke English or Shona, screened positive for CMD (Shona Symptoms Questionnaire [SSQ]-14 score ≥9), received first-line ART for 6 or more months, had no World Health Organization stage 4 disease, no psychosis, were not pregnant, and provided informed consent. Data were analyzed from March 2021 to February 2022., Intervention: The Friendship Bench, consisting of 6 lay health worker-led weekly problem-solving therapy sessions and optional peer-led group support., Main Outcomes and Measures: The primary outcome was mean adherence during 2 to 6 months of follow-up, and the secondary outcomes were mean adherence during 1 to 12 months of follow-up, change in SSQ-14 and Patient Health Questionnaire (PHQ-9) scores (3, 6, 9, and 12 months), and viral load suppression (6 and 12 months)., Results: A total of 516 participants were recruited (244 in Friendship Bench and 272 in enhanced standard care facilities); 438 (84.9%) were female and the mean (SD) age was 45.6 (10.9) years. Mean (SD) adherence between 2 to 6 months was 89.9% (18.4%) in the Friendship Bench group and 87.2% (20.1%) in the control group. The intervention had no statistically significant effect on adherence between 2 to 6 months (unadjusted mean difference, 1.93 percentage points; 95% CI, -1.20 to 5.06 percentage points; P = .23), between months 1 to 12 (mean difference 0.79 percentage points; 95% CI, -2.14 to 3.71 percentage points; P = .60), or viral suppression. Declines in SSQ-14 scores from baseline to 3 months (difference, -1.65; 95% CI, -3.07 to -0.24), 6 months (difference, -1.57; 95% CI, -2.98 to -0.15), and 9 months (difference, -1.63; 95% CI, -3.05 to -0.22) were greater in the Friendship Bench than the standard care group (P < .05). There were no differences in the decline in the SSQ-14 scores from baseline to 12 months and in declines in PHQ-9 scores from baseline to 3, 6, 9, and 12 months., Conclusions and Relevance: In this randomized trial of HIV-positive participants with CMD, the Friendship Bench intervention had no effect on adherence and viral suppression, possibly due to the absence of skill-based adherence training and a ceiling effect., Trial Registration: ClinicalTrials.gov Identifier: NCT03704805.

Introduction: Mental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders., Methods: Adolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre-screening questions followed by full screening (conditional on positive pre-screening) for depression (Patient Health Questionnaire-9 [PHQ-9]), suicide (Adolescent Innovations Project [AIP]-handbook), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), post-traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC-PTSD-5]) and substance use (CAGE Adapted to Include Drugs [CAGE-AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening., Results: Out of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre-screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ-9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD-7 ≥10), 38 (3.2%) for PTSD (PC-PTSD-5 ≥3), 18 (1.7%) for substance use (CAGE-AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load., Conclusions: ALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Young adolescents with perinatally acquired human immunodeficiency virus (HIV) are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation after care enrollment among 10-14-year-olds in 7 sub-Saharan African countries., Methods: Regression discontinuity analysis and data for 6912 patients aged 10-14-years were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) after adoption of Treat All policies in 2 groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016)., Results: There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016 than in those adopting it in 2013: 23.4 percentage points (pp) (95% confidence interval, 13.9-32.8) versus 11.2pp (2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp per year afterward., Conclusions: Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

To analyze the life situation of people with disabilities and to summarize the evidence of measures to support their participation, the World Health Assembly requested the World Health Organization to produce a World Report on Disability. This article highlights some of the main contents of the World Report on Disability, with a special focus on the rehabilitation chapter. It starts by presenting epidemiologic findings on the global disability prevalence, views on the role of rehabilitation medicine, discrepancies between met and unmet needs, and challenges for the quality of rehabilitation services and ends with an outlook on the report's recommendations and efforts toward their implementation.

The International Society for Physical and Rehabilitation Medicine has recognized the World Report on Disability as a guide for its future activities and endorsed its responsibility to disseminate, to analyze, and to implement the report's recommendations. The activities of the International Society for Physical and Rehabilitation Medicine on the global stage are embedded in a strategy that includes national and regional associations. This article reports on recent and forthcoming activities of the International Society for Physical and Rehabilitation Medicine regarding the World Report on Disability and identifies five major challenges that will impact future International Society for Physical and Rehabilitation Medicine activities. These challenges relate to (1) education and training, (2) the support of strong role models, (3) disaster management, (4) the development of innovative rehabilitation services, and (5) rehabilitation research.