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Southern and Eastern Africa is home to more than 2.1 million young people aged 15 to 24 years living with HIV. As compared with other age groups, this population group has poorer outcomes along the HIV care cascade. Young people living with HIV and the research team co-created the PEBRA (Peer Educator-Based Refill of ART) care model. In PEBRA, a peer educator (PE) delivered services as per regularly assessed patient preferences for medication pick-up, short message service (SMS) notifications, and psychosocial support. The cluster-randomized trial compared PEBRA model versus standard clinic care (no PE and ART refill done by nurses) in 3 districts in Lesotho.Individuals taking antiretroviral therapy (ART) aged 15 to 24 years at 20 clinics (clusters) were eligible. In the 10 clinics randomized to the intervention arm, participants were offered the PEBRA model, coordinated by a trained PE and supported by an eHealth application (PEBRApp). In the 10 control clusters, participants received standard nurse-coordinated care without any service coordination by a PE. The primary endpoint was 12-month viral suppression below 20 copies/mL. Analyses were intention-to-treat and adjusted for sex. From November 6, 2019 to February 4, 2020, we enrolled 307 individuals (150 intervention, 157 control; 218 [71%] female, median age 19 years [interquartile range, IQR, 17 to 22]). At 12 months, 99 of 150 (66%) participants in the intervention versus 95 of 157 (61%) participants in the control arm had viral suppression (adjusted odds ratio (OR) 1.27; 95% confidence interval [CI] [0.79 to 2.03]; p = 0.327); 4 of 150 (2.7%) versus 1 of 157 (0.6%) had died (adjusted OR 4.12; 95% CI [0.45 to 37.62]; p = 0.210); and 12 of 150 (8%) versus 23 of 157 (14.7%) had transferred out (adjusted OR 0.53; 95% CI [0.25 to 1.13]; p = 0.099). There were no significant differences between arms in other secondary outcomes. Twenty participants (11 in intervention and 9 in control) were lost to follow-up over the entire study period. The main limitation was that the data collectors in the control clusters were also young peers; however, they used a restricted version of the PEBRApp to collect data and thus were not able to provide the PEBRA model. The trial was prospectively registered on ClinicalTrials.gov (NCT03969030).Preference-based peer-coordinated care for young people living with HIV, compared to nurse-based care only, did not lead to conclusive evidence for an effect on viral suppression.clinicaltrials.gov, NCT03969030, https://clinicaltrials.gov/ct2/show/NCT03969030.

IntroductionAlthough the advanced HIV disease (AHD) care package reduces morbidity and mortality in people with AHD (defined in people living with HIV as WHO stage 3 or 4, CD4 count Methods and analysisThis two-phased study is guided by the Medical Research Council framework for evaluation of complex interventions. Stage 1 is a stakeholder consultation to define tools and indicators to assess feasibility of the AHD care package. Stage 2 is the implementation of the AHD care package during a facility-based tuberculosis diagnostic accuracy study in high-burden HIV/tuberculosis settings. Consenting adults with tuberculosis symptoms in two sites in Lesotho and South Africa are eligible for inclusion. HIV-positive participants are included in the feasibility study and are offered a CD4 test, a tuberculosis-lipoarabinomannan assay and those with CD4 count of ≤200 cells/µL a cryptococcal antigen lateral flow assay. Participants are referred for clinical management following national guidelines. The evaluation includes group discussions, participant observation (qualitative strand) and a semistructured questionnaire to assess acceptability among implementers. The quantitative strand also evaluates process compliance (process rating and process cascade) and early outcomes (vital and treatment status after twelve weeks). Thematic content analysis, descriptive statistics and data triangulation will be performed.Ethics and disseminationThe National Health Research and Ethics Committee, Lesotho, the Human Sciences Research Council Research Ethics Committee and Provincial Department of Health, South Africa and the Ethikkommission Nordwest- und Zentralschweiz, Switzerland, approved the protocol. Dissemination will happen locally and internationally at scientific conferences and in peer-reviewed journals.Trial registration numberNCT04666311.

Multi-month dispensing (MMD) of antiretroviral therapy (ART) represents one approach of differentiated service delivery (DSD) aiming to improve quality and cost-effectiveness for HIV services in resource-limited settings. However, reduction in clinic visits for people living with HIV (PLWH) should go along with out-of-clinic care tailored to PLWH`s preferences and comorbidities to maintain quality of care. eHealth supported MMD offers a potential solution.Between October 2019 and January 2020 we assessed preferences on an eHealth supported MMD package among adult PLWH attending routine ART care at a rural clinic in Lesotho using a mixed-methods approach. Participants reported their preferences among different refill and eHealth options. They were invited to test automated text messages (SMS) informing about their viral load results, an automated tuberculosis symptoms screening call and telemedical support by an expert nurse. Telemedical service comprised a call-back option if participants required any additional support and adherence counselling for closer follow-up of participants with unsuppressed viral loads. After 6 weeks, participants were followed-up to assess perception of the chosen eHealth support using a qualitative approach.Among 112 participants (median age = 43 years; 74% female), 83/112 (75%) preferred MMD for 6-12 months (median = 9 months, IQR = [5, 12]). Neither sex, age, employment, costs and time for travel to clinic, nor the duration of taking ART correlated with the MMD preference. All 17 participants attending routine viral load measurement wished to receive the result via SMS. Fifteen (19.2%) participants requested a telemedical nurse call-back during the study period. All participants with recent unsuppressed viral load (N = 13) requested telemedical adherence counselling for closer follow-up. Among 78 participants followed-up, 76 (97%) would appreciate having the call-back option in future. Seventy-five participants (67%) received and evaluated the automated symptomatic tuberculosis screening call, overall 71 (95%) appreciated it.The great majority of PLWH in this study preferred 6-12 months MMD and appreciated the additional eHealth support, including viral load results via SMS, telemedical nurse consultations and automated tuberculosis symptom screening calls. eHealth supported MMD packages appear to be a promising approach for DSD models and should be assessed for clinical endpoints and cost-effectiveness in larger studies.

Background: Community-based antiretroviral treatment (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-based refill of ART) cluster-randomised trial in rural Lesotho compared the option of ART refill by existing lay village health workers (VHW) versus clinic-based refill after home-based same-day ART initiation. Methods: In village-clusters randomised to intervention, individuals found HIV-positive during a door-to-door HIV-testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic-visits for viral load measurement at 6- and 12-months. In control-villages, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints comprised linkage and 12-month engagement in care. Analyses were intention-to-treat. Clinicaltrials.gov/NCT03630549 Findings: From August 16 th , 2018, until May 28 th , 2019, 118 individuals from 108 households in 57 clusters from intervention arm, and 139 individuals from 130 households in 60 clusters in control were enrolled (150 [58%] female, median age 36 years (interquartile range 30-48), 200 [78%] newly diagnosed). 48/118 (41%) opted for VHW-based refill. At 12 months, 46/118 (39%) and 64/139 (46%) participants in the intervention and control arm achieved viral suppression (adjusted difference -0·07[95%CI -0·20-0·06];p=0·256). Arms were similar in linkage, but engagement in care tended to be lower in intervention. Zero and seven deaths occurred in control and intervention arm. Interpretation: The offer of village-based ART refill did not amplify the effect of home-based same-day ART initiation alone. Our trial rather raises concerns regarding engagement in care and safety if follow-up is provided by existing lay health cadres for patients newly initiated on ART. Trial Registration: Clinicaltrials.gov/NCT03630549 Funding: Swiss National Science Foundation; Janggen-Pohn Foundation Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: This trial was approved by the National Health Research and Ethics Committee of the Ministry of Health of Lesotho (ID06-2018) and the Ethics committee in Switzerland (Ethikkomission Nordwest- und Zentralschweiz; 2018-00283) and registered with Clinicaltrials.gov (NCT03630549).

Background In resource-limited settings, the World Health Organization recommends enhanced adherence counseling (EAC) for individuals with an unsuppressed human immunodeficiency virus (HIV)-1 viral load (VL) and to remeasure VL after 3 months to avoid unnecessary regimen switches. In cases in which this follow-up VL remains unsuppressed, a regimen switch is indicated. We aimed to assess levels of HIV-1 drug resistance before and after the EAC period among people with ongoing viremia (≥80 c/mL) after EAC. Methods We included adult participants of the CART-1 cohort study conducted in Lesotho who had a VL ≥80 c/mL after EAC. Paired plasma samples (before and after EAC) were analyzed by next-generation sequencing. We assessed the prevalence of resistance-associated mutations and viral susceptibility scores to each participant’s antiretroviral therapy (ART) regimen (range, 0–3; 3 indicates complete susceptibility). Results Among 93 participants taking nonnucleoside reverse-transcriptase inhibitor-based ART with an initial VL ≥1000 copies/mL who received a follow-up VL test after EAC, 76 still had a VL ≥80 copies/mL after EAC, and paired samples were available for 57 of 76. The number of individuals without full susceptibility to any drug in their regimen increased from 31 of 57 (54.4%) before to 36 of 57 (63.2%) after EAC. Median susceptibility scores dropped from 0.5 (interquartile range [IQR] = 0.25–) to 0.25 (IQR = 0.25–1) during the EAC period (P = .16). Conclusions Despite high levels of resistance before EAC, we observed a slight decline in susceptibility scores after EAC. The risk of further accumulation of resistance during EAC has to be balanced against the benefit of avoiding unnecessary switches in those with spontaneous resuppression after EAC.

Objectives Emerging resistance to antiretroviral drugs may jeopardize the achievements of improved access to ART. We compared the prevalence of different resistance mutations in HIV-infected adults with virological failure in a cohort with regular routine viral load (VL) monitoring (Switzerland) and cohorts with limited access to VL testing (Uganda and Lesotho). Methods We considered individuals who had genotypic resistance testing (GRT) upon virological failure (≥1000 copies/mL) and were on ART consisting of at least one NNRTI and two NRTIs. From Lesotho, individuals with two subsequent VLs ≥1000 copies/mL despite enhanced adherence counselling (n = 58) were included in the analysis. From Uganda, individuals with a single VL ≥1000 copies/mL (n = 120) were included in the analysis. From the Swiss HIV Cohort Study (SHCS), a population without history of monotherapy or dual therapy with the first GRT upon virological failure (n = 61) was selected. Results We found that 50.8% of individuals in the SHCS, 72.5% in Uganda and 81.0% in Lesotho harboured HIV with high-level resistance to at least two drugs from their current regimen. Stanford resistance scores were higher in Uganda compared with Switzerland for all drugs used in first-line treatment except zidovudine and tenofovir (P

Summary Background In sub-Saharan Africa, home-based HIV testing is validated and accepted, but coverage is low because household members are often absent during home-based testing campaigns. We aimed to measure the effect of a secondary distribution of oral-fluid HIV self-tests on coverage during home-based testing in rural Lesotho. Methods The Home-Based Self-Testing (HOSENG) trial was a cluster-randomised, non-blinded superiority trial in rural villages in the catchment area of 20 health facilities of two districts in Lesotho (Butha-Buthe and Mokhotlong). Eligible villages had a consenting village chief and at least one registered village health worker; eligible households had a consenting representative aged 18 years or older. The HOSENG trial provided a recruitment platform for the interlinked Village-Based Refill of Antiretroviral Therapy (VIBRA) trial. Villages were randomly assigned 1:1:1:1 with block sizes of four to one of four groups: VIBRA control and HOSENG control; VIBRA control and HOSENG intervention; VIBRA intervention and HOSENG control; and VIBRA intervention and HOSENG intervention. Randomisation was stratified by district, village size, and access to the nearest health facility. An independent statistician was responsible for the computer-generated randomisation list. In the intervention group, oral-fluid HIV self-tests were left for absent or declining household members (aged ≥12 years) during a home visit from the HIV testing campaign team. One present household member was trained on self-test use. Distributed self-tests were followed up by village health workers. In control village clusters, absent or declining household members were referred to the clinic for HIV testing. The primary outcome was HIV testing coverage among all household members aged 12 years or older within 120 days, defined as a confirmed HIV test result or known status, reported in testing registers at the health facilities or on the follow-up forms of the village health worker. Adjusted random-effects logistic regression with individuals as the unit of analysis was used. This trial is registered with ClinicalTrials.gov , NCT03598686 . Findings Between July 26, 2018, and Dec 12, 2018, 3091 consenting households with 7816 household members aged 12 years or older were enrolled and randomly assigned (intervention: 57 village clusters, 1620 households, 4174 household members; control: 49 village clusters, 1471 households, 3642 household members). In the control group, 38 (3%) of 1455 initially absent or declining household members tested at a clinic within 120 days. In the intervention group, 841 (53%) of 1601 initially absent or declining household members had a confirmed status within 120 days; 12 (1%) of 841 tested at the clinic and 829 (99%) used their self-test kit. This resulted in a testing coverage of 2201 (60%) of 3642 in the control group versus 3386 (81%) of 4174 in the intervention group (odds ratio 3·00 [95% CI 2·52–3·59]; p Interpretation Secondary distribution of oral-fluid HIV self-tests during home-based testing increases testing coverage substantially and thus presents a promising add-on during testing campaigns. Funding Swiss National Science Foundation

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

Lesotho presents the second-highest adult human immunodeficiency virus (HIV) prevalence globally. Among people living with HIV, data on hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection are limited. We report HBV and HCV coinfection data from a multicentre cross-sectional study among adult and pediatric patients taking antiretroviral therapy in 10 health facilities in Lesotho. Among 1318 adults screened (68% female; median age, 44 years), 262 (20%) had immunologically controlled HBV infection, 99 (7.6%) tested anti-HBs positive and anti-HBc negative, indicating vaccination, and 57 (4.3%) had chronic HBV infection. Among the patients with chronic HBV infection, 15 tested hepatitis B envelope antigen (HBeAg) positive and eight had detectable HBV viremia (median, 2 477 400 copies/mL; interquartile range, 205-34 400 000) with a mean aspartate aminotransferase-to-platelet ratio index of 0.48 (SD, 0.40). Prevalence of HCV coinfection was 1.7% (22 of 1318), and only one patient had detectable HCV viremia. Among 162 pediatric patients screened, three (1.9%) had chronic HBV infection, whereby two also tested HBeAg-positive, and one had detectable HBV viral load (210 copies/mL). Six of 162 (3.7%) had anti-HCV antibodies, all with undetectable HCV viral loads. Overall prevalence of chronic HBV/HIV and HCV/HIV coinfection among adults and children was relatively low, comparable to earlier reports from the same region. But prevalence of immunologically controlled HBV infection among adults was high. Of those patients with chronic HBV infection, a minority had detectable HBV-DNA.

Introduction Home‐based HIV testing fails to reach high coverage among adolescents and young adults (AYA), mainly because they are often absent during the day of home‐based testing. ADORE (ADolescent ORal tEsting) is a mixed‐method nested study among AYA in rural Lesotho, measuring the effect of home‐based secondary distribution of oral HIV self‐tests (HIVST) on coverage, as well as exploring how AYA perceive this HIV self‐testing model. Methods ADORE study was nested in a cluster‐randomized trial. In intervention village‐clusters, oral HIVST were left for household members who were absent or declined testing during a testing campaign. One present household member was trained on HIVST use. Distributed HIVST were followed up by village health workers (VHW). In control clusters no self‐tests were distributed. The quantitative outcome was testing coverage among AYA (age 12 to 24) within 120 days, defined as a confirmed HIV test result or known status, using adjusted random‐effects logistic regression on the intention‐to‐treat population. Qualitatively, we conducted in‐depth interviews among both AYA who used and did not use the distributed HIVST. Results From July 2018 to December 2018, 49 and 57 villages with 1471 and 1620 consenting households and 1236 and 1445 AYA in the control and intervention arm, respectively, were enrolled. On the day of the home‐visit, a testing coverage of 37% (461/1236) and 41% (596/1445) in the control and the intervention arm, respectively, were achieved. During the 120 days follow‐up period, an additional 23 and 490 AYA in control and intervention clusters, respectively, knew their status. This resulted in a testing coverage of 484/1236 (39%) in the control versus 1086/1445 (75%) in the intervention arm (aOR 8.80 [95% CI 5.81 to 13.32]; p

Background The CASCADE trial showed that compared with usual care (UC), offering same-day (SD) antiretroviral therapy (ART) during home-based human immunodeficiency virus testing improved engagement in care and viral suppression 12 months after diagnosis. However, questions remain regarding long-term outcomes and the risk of propagating drug resistance. Methods After completion of the primary endpoint at 12 months, participants not in care in both arms were traced and encouraged to access care. At 24 months, the following outcomes were assessed in both arms: engagement in care, viral suppression, and reasons for nonengagement. Furthermore, we explored the acquisition of drug resistance mutations (DRMs) among SD arm nonlinkers. Results At 24 months, 64% (88/137) in the SD arm vs 59% (81/137) in the UC arm were in care (absolute difference [AD], 5%; 95% confidence interval [CI], −6 to16; P = .38) and 57% (78/137) vs 54% (74/137) had documented viral suppression (AD, 3%; 95% CI, −9 to 15; P = .28). Among 36 participants alive and not in care at 24 months with ascertained status, the majority rejected contact with the health system or were unwilling to take ART. Among 8 interviewed SD arm nonlinkers, 6 had not initiated ART upon enrollment, and no acquired DRMs were detected. Two had taken the initial 30-day ART supply and acquired DRMs. Conclusions SD ART resulted in higher rates of engagement in care and viral suppression at 12 months but not at 24 months. Leveling off between both arms was driven by linkage beyond 12 months in the UC arm. We did not observe compensatory long-term disengagement in the SD arm. These long-term results endorse SD ART initiation policies. Clinical Trials Registration NCT02692027.

BACKGROUND: HIV testing coverage remains below the targeted 90% despite efforts and resources invested into testing in sub-Saharan Africa. Home-based HIV testing is a key approach endorsed by the World Health Organization, especially to reach individuals who might not seek testing otherwise. Although acceptance of testing during such campaigns is high, coverage remains low due to absent house-hold members. This cluster-randomized trial aims to assess increase in testing coverage using oral HIV self-testing among individuals who are absent or decline testing during home-based HIV testing. METHODS: The HOSENG (HOme-based SElf-testiNG) trial is a cluster-randomized, parallel group, superiority trial in two districts of Lesotho, Southern Africa. Clusters are stratified by district, village size, and village access to the nearest health facility. Cluster eligibility criteria include: village is in catchment area of one of the study facilities, village authority provides consent, and village has a registered, capable and consenting village health worker. In intervention clusters, HIV self-tests are provided for eligible household members who are absent or decline HIV testing in presence of the campaign team. In control clusters, standard of care for absent and refusing individuals applies, i.e. referral to health facility. The primary outcome is HIV testing coverage among individuals ≥12 years of age within 120 days after enrolment. Secondary objectives include HIV testing coverage among other age groups, and uptake of the different testing modalities. Statistical analyses will be conducted and reported in line with CONSORT guidelines. HOSENG trial is linked to VIBRA (Village-Based Refill of ART) trial. Together, they constitute the GET ON (GETting tOwards Ninety) research project. DISCUSSION: The HOSENG trial tests if oral HIVST may be an add-on during door-to-door testing campaigns towards achieving optimal testing coverage. The provision of oral self-test kits, followed up by VHWs, requires little additional human resources, finances and logistics. If cost-effective, this approach will inform home-based HIV testing policies not only in Lesotho, but in similar international settings. TRIAL REGISTRATION: This trial has been registered at clinicaltrials.gov (NCT03598686) on July 25, 2018. More information under www.getonproject.wordpress.com. KEYWORDS: HIV, cluster randomized controlled trial, village health worker, community health worker, community-based, self-testing, HIV testing coverage, Lesotho, Southern Africa, implementation research.

Introduction : HIV-infected individuals on first-line antiretroviral therapy (ART) in resource-limited settings who do not achieve the last “90” (viral suppression) enter a complex care cascade: enhanced adherence counselling (EAC), repetition of viral load (VL) and switch to second-line ART aiming to achieve resuppression. This study describes the “failure cascade” in patients in Lesotho. Methods : Patients aged ≥16 years on first-line ART at 10 facilities in rural Lesotho received a first-time VL in June 2014. Those with VL ≥80 copies/mL were included in a cohort. The care cascade was assessed at four points: attendance of EAC, result of follow-up VL after EAC, switch to second-line in case of sustained unsuppressed VL and outcome 18 months after the initial unsuppressed VL. Multivariate logistic regression was used to assess predictors of being retained in care with viral resuppression at follow-up. Results : Out of 1563 patients who underwent first-time VL, 138 (8.8%) had unsuppressed VL in June 2014. Out of these, 124 (90%) attended EAC and 116 (84%) had follow-up VL (4 died, 2 transferred out, 11 lost, 5 switched to second-line before follow-up VL). Among the 116 with follow-up VL, 36 (31%) achieved resuppression. Out of the 80 with sustained unsuppressed VL, 58 were switched to second-line, the remaining continued first line. At 18 months’ follow-up in December 2015, out of the initially 138 with unsuppressed VL, 56 (41%) were in care and virally suppressed, 37 (27%) were in care with unsuppressed VL and the remaining 45 (33%) were lost, dead, transferred to another clinic or without documented VL. Achieving viral resuppression after EAC (adjusted odds ratio (aOR): 5.02; 95% confidence interval: 1.14–22.09; p = 0.033) and being switched to second-line in case of sustained viremia after EAC (aOR: 7.17; 1.90–27.04; p = 0.004) were associated with being retained in care and virally suppressed at 18 months of follow-up. Age, gender, education, time on ART and level of VL were not associated. Conclusions : In this study in rural Lesotho, outcomes along the “failure cascade” were poor. To improve outcomes in this vulnerable patient group who fails the last “90”, programmes need to focus on timely EAC and switch to second line for cases with continuous viremia despite EAC. Keywords 90-90-90; treatment failure; HIV; antiretroviral therapy; cascade; second line; viral load; resistance To access the supplementary material to this article please see Supplementary Files under Article Tools online. (Published: 19 July 2017) Labhardt ND et al. Journal of the International AIDS Society 2017, 20 :21803 http://www.jiasociety.org/index.php/jias/article/view/21803 | http://dx.doi.org/10.7448/IAS.20.1.21803

This survey assessed virologic outcomes of children on antiretroviral therapy and potential predictors in 10 nurse-led clinics in Lesotho. Viral suppression was achieved in 72% of the 191 children. No predictors for virologic outcome were found, underlining the need for routine viral load testing in resource-limited settings to achieve 90-90-90.

Objective In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. Methods Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. Main outcome variables: Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. Results Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32–1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83–3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83–2.84). Conclusions Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them. Objectif: En 2007, le Lesotho a lance de nouvelles directives nationales sur le traitement antiretroviral (ART), mettant en priorite le tenofovir et la zidovudine par rapport a la stavudine comme base de combinaison avec la lamivudine. Nous avons compare le taux d’adoption de ces nouvelles directives et la substitution des medicaments de premiere ligne par les centres de sante (CS) et les hopitaux dans deux circonscriptions rurales du Lesotho. Methodes: Analyse retrospective de cohorte. Les patients âges de ≥ 16 ans ont ete stratifies en groupe CS et groupe ‘hopital’. Principales variables de resultat: Type de combinaison de base a l’initiation de l’ART (1), substitutions au sein de la premiere ligne (2) et type de combinaison de base chez les patients retenus jusqu’en decembre 2010 (3). Un modele de regression logistique multiple, tenant compte de CS versus ‘hopital’, caracteristiques des patients (sexe, âge, stade de l’OMS, taux de CD4 de base, grossesse simultanee, traitement concomitant de la tuberculose) et l’annee de l’initiation de l’ART, a ete utilise. Resultats: Sur 3.936 patients adultes inities a l’ART entre 2007 et 2010, 1.971 ont commence dans les hopitaux et 1.965 dans les CS. Les hopitaux etaient plus susceptibles a suivre les nouvelles directives telles que mesurees par les prescriptions de combinaisons de base sans stavudine (odds-ratio 1,55, IC95%: 1,32 a 1,81) et avaient un taux plus eleve de substitutions de medicaments durant le traitement ART de premiere ligne (2,39; 1,83 - 3.13). En decembre 2010, les patients retenus dans les CS etaient plus susceptibles de continuer a recevoir la stavudine (2,28: 1,83 a 2,84). Conclusions: Les centres de sante ont pris plus de retard a adopter les nouvelles directives et ont substitue moins frequemment les medicaments. Les programmes ART decentralises ont besoin de soutien de proximite, la supervision et le guidage pour adopter les nouvelles directives et pour y adherer. Objetivo: En el 2007, Lesoto lanzo unas nuevas guias para el tratamiento antirretroviral (TAR), priorizando el tenofovir y la zidovudina sobre la estavudina como medicamento principal junto con la lamivudina. Hemos comparado la tasa de adopcion de estas nuevas guias y la sustitucion de los medicamentos de primera linea en los centros sanitarios (CS) y los hospitales de dos areas rurales de Lesoto. Metodos: Analisis retrospectivo de cohortes. Los pacientes, con edades ≥ 16 anos, fueron estratificados en dos grupos: CS u hospital. Las principales variables fueron: tipo de medicamento principal en el momento de iniciar el TAR (1), sustituciones dentro de la primera linea de tratamiento (2) y tipo de medicamento principal entre los pacientes retenidos a Diciembre 2010 (3). Se utilizo un modelo de regresion multiple que incluia CS vs.hospital, las caracteristicas del paciente (sexo, edad, estadio OMS, conteo CD4 de base, embarazo concurrente, tratamiento concurrente para la TB) y el ano en que comenzo a recibir TAR. Resultados: De 3,936 pacientes adultos que iniciaron TAR entre el 2007 y 2010, 1,971 lo hicieron en hospitales y 1,965 en CSs. Los hospitales tenian una mayor tendencia a seguir las nuevas guias, medido como prescripcion de medicamentos principales sin estavudina (Odds-ratio 1.55; IC 95%: 1.32 - 1.81) y tenian una mayor tasa de sustitucion del medicamento mientras que estaban en primera linea de TAR (2.39; 1.83 - 3.13). A Diciembre 2010, los pacientes retenidos en los CS tenian una mayor probabilidad de estar aun recibiendo estavudina (2.28; 1.83 - 2.84). Conclusiones: Los centros sanitarios necesitaron mas tiempo para adoptar las nuevas guias, y sustituyeron los medicamentos con menos frecuencia. Los programas descentralizados de TAR requieren de un apoyo cercano, supervision y tutelaje para poder integrar las nuevas guias y adherirse a ellas.

Background Achievement of the UNAIDS 90-90-90 targets in Sub-Sahara Africa is challenged by a weak care-cascade with poor linkage to care and retention in care. Community-based HIV testing and counselling (HTC) is widely used in African countries. However, rates of linkage to care and initiation of antiretroviral therapy (ART) in individuals who tested HIV-positive are often very low. A frequently cited reason for non-linkage to care is the time-consuming pre-ART assessment often requiring several clinic visits before ART-initiation. Methods This two-armed open-label randomized controlled trial compares in individuals tested HIV-positive during community-based HTC the proposition of same-day community-based ART-initiation to the standard of care pre-ART assessment at the clinic. Home-based HTC campaigns will be conducted in catchment areas of six clinics in rural Lesotho. Households where at least one individual tested HIV positive will be randomized. In the standard of care group individuals receive post-test counselling and referral to the nearest clinic for pre-ART assessment and counselling. Once they have started ART the follow-up schedule foresees monthly clinic visits. Individuals randomized to the intervention group receive on the spot point-of-care pre-ART assessment and adherence counselling with the proposition to start ART that same day. Once they have started ART, follow-up clinic visits will be less frequent. First primary outcome is linkage to care (individual presents at the clinic at least once within 3 months after the HIV test). The second primary outcome is viral suppression 12 months after enrolment in the study. We plan to enrol a minimum of 260 households with 1:1 allocation and parallel assignment into both arms. Discussion This trial will show if in individuals tested HIV-positive during community-based HTC campaigns the proposition of same-day ART initiation in the community, combined with less frequent follow-up visits at the clinic could be a pragmatic approach to improve the care cascade in similar settings. Trial registration NCT02692027 , registered February 21, 2016

The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with

Importance Home-based HIV testing is a frequently used strategy to increase awareness of HIV status in sub-Saharan Africa. However, with referral to health facilities, less than half of those who test HIV positive link to care and initiate antiretroviral therapy (ART). Objective To determine whether offering same-day home-based ART to patients with HIV improves linkage to care and viral suppression in a rural, high-prevalence setting in sub-Saharan Africa. Design, Setting, and Participants Open-label, 2-group, randomized clinical trial (February 22, 2016-September 17, 2017), involving 6 health care facilities in northern Lesotho. During home-based HIV testing in 6655 households from 60 rural villages and 17 urban areas, 278 individuals aged 18 years or older who tested HIV positive and were ART naive from 268 households consented and enrolled. Individuals from the same household were randomized into the same group. Interventions Participants were randomly assigned to be offered same-day home-based ART initiation (n = 138) and subsequent follow-up intervals of 1.5, 3, 6, 9, and 12 months after treatment initiation at the health facility or to receive usual care (n = 140) with referral to the nearest health facility for preparatory counseling followed by ART initiation and monthly follow-up visits thereafter. Main Outcomes and Measures Primary end points were rates of linkage to care within 3 months (presenting at the health facility within 90 days after the home visit) and viral suppression at 12 months, defined as a viral load of less than 100 copies/mL from 11 through 14 months after enrollment. Results Among 278 randomized individuals (median age, 39 years [interquartile range, 28.0-52.0]; 180 women [65.7%]), 274 (98.6%) were included in the analysis (137 in the same-day group and 137 in the usual care group). In the same-day group, 134 (97.8%) indicated readiness to start ART that day and 2 (1.5%) within the next few days and were given a 1-month supply of ART. At 3 months, 68.6% (94) in same-day group vs 43.1% (59) in usual care group had linked to care (absolute difference, 25.6%; 95% CI, 13.8% to 36.3%; P P = .007). Two deaths (1.5%) were reported in the same-day group, none in usual care group. Conclusions and Relevance Among adults in rural Lesotho, a setting of high HIV prevalence, offering same-day home-based ART initiation to individuals who tested positive during home-based HIV testing, compared with usual care and standard clinic referral, significantly increased linkage to care at 3 months and HIV viral suppression at 12 months. These findings support the practice of offering same-day ART initiation during home-based HIV testing. Trial Registration clinicaltrials.gov Identifier:NCT02692027

Introduction : In 2013, the World Health Organization (WHO) recommended scaling up of routine viral load (VL) monitoring for patients on antiretroviral therapy (ART) in resource-limited settings [1]. During the transition phase from no VL-testing at all to routine VL-monitoring, targeted VL for groups at particular risk of virologic failure (VF) may be an option [2]. We present socio-demographic and clinical risk factors for VF in a cohort in rural Lesotho with no access to VL prior to the study. Materials and Methods : Data derive from a cross-sectional study providing multi-disease screening as well as VL testing to adult patients (≥16 years old) on first-line ART ≥6 months [3]. VF was defined as VL≥1000 copies/mL. Assessed potential predictors of VF were: (1) socio-demographic (sex, age, wealth-quintile, education, employment status, disclosure of HIV status to environment, travel-time to facility); (2) treatment history (history of treatment interruption >2 days, previous drug substitution within first-line ART, time on ART, ART-base and -backbone); (3) adherence (pill count) and (4) clinical (clinical or immunological failure as defined by WHO guidelines [1], presence of papular pruritic eruption (PPE)). All variables with association to VF in univariate analysis were included in a multivariate logistic regression reporting adjusted Odds ratios (aOR). Results : Data from 1,488 patients were analyzed. Overall VF-prevalence was 6.9% (95% CI 5.7–8.3). In univariate analysis, the following were associated with VF: age

Introduction: Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART).We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods: The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count,World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results: Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women ( p =0.81) and 68.8% at HCs versus 54.7% at hospitals among men ( p

ObjectiveTo assess the positive predictive value (PPV) of a clinical score for viral failure among patients fulfilling the WHO-criteria for anti-retroviral treatment (ART) failure in rural Lesotho.MethodsPatients fulfilling clinical and/or immunological WHO failure-criteria were enrolled. The score includes the following predictors: Prior ART exposure (1 point), CD4-count below baseline (1), 25% and 50% drop from peak CD4-count (1 and 2), hemoglobin drop≥1 g/dL (1), CD4 countResultsAmong 1'131 patients on ART ≥ 6 months, 134 (11.8%) had immunological and/or clinical failure, 104 (78%) had blood drawn (13 died, 10 lost to follow-up, 7 did not show up). From 92 (88%) a result could be obtained (2 samples hemolysed, 10 lost). Out of these 92 patients 47 (51%) had viral failure (≥ 5000 copies), 27 (29%) viral suppression (40 copies (95%CI: 84-100), and of 90% to detect a VL ≥ 5000 copies (70-97). Within the score, adherenceConclusionA score ≥ 5 among patients fulfilling WHO-criteria had a PPV of 100% for a detectable VL and 90% for viral failure. In settings without regular access to VL-testing, this PPV may be considered high enough to switch this patient-group to second-line treatment without confirmatory VL-test.