Background:Recent attention has focused on the question of how quickly antiretroviral therapy (ART) should be started once HIV diagnosis is confirmed. We assessed whether rapid ART initiation improves patient outcomes.Methods:We searched five databases from inception up to August 2017. Rapid ART initiation was defined as initiation within 14 days of HIV diagnosis. Data were pooled using random effects meta-analysis.Results:Across the randomized trials, ART start on the same day increased viral suppression at 12 months [three trials: relative risk (RR) 1.17, 95% confidence interval (CI) 1.07–1.27], retention in care at 12 months (RR 1.11, 95% CI 0.99–1.26), and the likelihood of starting ART within 90 days (four trials: RR 1.35, 95% CI 1.13–1.62) and 12 months after eligibility was established (three trials: RR 1.17, 95% CI 1.07–1.27). There was a nonsignificant trend toward reduced mortality (three trials: RR 0.53, 95% CI 0.24–1.08), as well as reduced loss to follow-up at 12 months (2 trials: RR 0.66, 95% CI 0.42–1.04). In the observational studies, offering accelerated ART initiation resulted in a greater likelihood of having started ART within 3 months (two studies: RR 1.53, 95% CI 1.11–2.10). There was a trend toward an increased risk of being lost to follow-up at 6 months (three studies: RR 1.85, 95% CI 0.96–3.55).Conclusion:Accelerated ART initiation can lead to improved clinical outcomes and is likely to be of particular benefit in those settings where extensive patient preparation prior to starting ART results in long delays. These findings informed a WHO recommendation supporting accelerated ART initiation, including same day ART start.

ObjectivesTo evaluate the feasibility (population reached, costs) and effectiveness (positivity rates, linkage to care) of two strategies of community-based HIV testing and counselling (HTC) in rural Swaziland.MethodsStrategies used were mobile HTC (MHTC) and home-based HTC (HBHTC). Information on age, sex, previous testing and HIV results was obtained from routine HTC records. A consecutive series of individuals testing HIV-positive were followed up for 6 months from the test date to assess linkage to care.ResultsA total of 9 060 people were tested: 2 034 through MHTC and 7 026 through HBHTC. A higher proportion of children and adolescents (<20 years) were tested through HBHTC than MHTC (57% vs. 17%; P < 0.001). MHTC reached a higher proportion of adult men than HBHTC (42% vs. 39%; P = 0.015). Of 398 HIV-positive individuals, only 135 (34%) were enrolled in HIV care within 6 months. Of 42 individuals eligible for antiretroviral therapy, 22 (52%) started treatment within 6 months. Linkage to care was lowest among people who had tested previously and those aged 20–40 years. HBHTC was 50% cheaper (US$11 per person tested; $797 per individual enrolled in HIV care) than MHTC ($24 and $1698, respectively).ConclusionIn this high HIV prevalence setting, a community-based testing programme achieved high uptake of testing and appears to be an effective and affordable way to encourage large numbers of people to learn their HIV status (particularly underserved populations such as men and young people). However, for community HTC to impact mortality and incidence, strategies need to be implemented to ensure people testing HIV-positive in the community are linked to HIV care.ObjectifsEvaluer la faisabilité (population atteinte, coûts) et l'efficacité (taux de positivité, liaison aux soins) de deux stratégies de dépistage et conseil (DC) communautaire du VIH en zone rurale au Swaziland.MéthodesLes stratégies utilisées étaient des DC mobiles (DC-M) et le DC à domicile (DC-D). Les informations sur l’âge, le sexe, les tests précédents et les résultats VIH ont été obtenues à partir des dossiers de routine du DC. Une série d'individus séropositifs consécutifs a été suivie pendant six mois à partir de la date du test afin d’évaluer les liaisons aux soins.Résultats9.060 personnes ont été testées: 2.034 par le biais du DC-M et 7026 par le biais du DC-D. Une plus grande proportion d'enfants et d'adolescents (<20 ans) ont été testés par le biais du DC-D que par celui du DC-M (57% vs 17%; p <0,001). Le DC-M a atteint une proportion plus élevée d'hommes adultes que le DC-D (42% vs 39%; p = 0,015). Des 398 personnes séropositives, seules 135 (34%) ont été inscrites à des soins VIH dans les 6 mois. De 42 personnes admissibles à la thérapie antirétrovirale, 22 (52%) ont commencé le traitement dans les 6 mois. Les liaisons avec les soins étaient plus faibles chez les personnes qui ont effectué un dépistage auparavant et celles âgées de 20 à 40 ans. Le DC-D était 50% moins cher (11 $ US par personne testée, 797 $ par personne inscrite dans les...

Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.

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BackgroundStudies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART.Methodology/Principal FindingsWe retrospectively reviewed TB registers and clinical notes of 209 TB/HIV co-infected adults with a CD4 count <250 cells/µl and registered for TB treatment at one primary care clinic in a South African township between June 2008 and May 2009. Using Kaplan-Meier and Cox proportional hazard analysis, we compared time between initiation of TB treatment and ART for the periods before and after full, “one-stop shop” integration of TB and HIV services (in December 2009). Potential confounders were determined a priori through directed acyclic graphs. Robustness of assumptions was investigated by sensitivity analyses. The analysis included 188 patients (100 pre- and 88 post-integration), yielding 56 person-years of observation. Baseline characteristics of the two groups were similar. Median time to ART initiation decreased from 147 days (95% confidence interval [CI] 85–188) before integration of services to 75 days (95% CI 52–119) post-integration. In adjusted analyses, patients attending the clinic post-integration were 1.60 times (95% CI 1.11–2.29) more likely to have started ART relative to the pre-integration period. Sensitivity analyses supported these findings.Conclusions/SignificanceFull TB/HIV care integration is feasible and led to a 60% increased chance of co-infected patients starting ART, while reducing time to ART initiation by an average of 72 days. Although these estimates should be confirmed through larger studies, they suggest that scale-up of full TB/HIV service integration in high TB/HIV prevalence settings may shorten time to ART initiation, which might reduce excess mortality and morbidity.