Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: an open-label randomized controlled trial in Lesotho

Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment.; This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100-999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch (n = 40) or control group (n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35-51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3-8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%-50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) (p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens.; In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines.; The trial is registered at ClinicalTrials.gov, NCT03088241

PEBRA trial - effect of a peer-educator coordinated preference-based ART service delivery model on viral suppression among adolescents and young adults living with HIV: protocol of a cluster-randomized clinical trial in rural Lesotho

Despite tremendous progress in controlling the HIV epidemic in sub-Saharan Africa, HIV-related mortality continues to increase among adolescents and young people living with HIV (AYPLHIV). Globally, sub-Saharan Africa accounts for 85% of the AYPLHIV. Overall outcomes along the HIV care cascade are worse among AYPLHIV as compared to all other age groups due to various challenges in accessing and adhering to antiretroviral therapy (ART). New, innovative multicomponent packages of differentiated service delivery (DSD) models, are required to address the specific needs of AYPLHIV. This study aims to evaluate the feasibility and effectiveness of a multicomponent DSD model (PEBRA model) designed for AYPLHIV and coordinated by a peer-educator.; PEBRA (Peer-Educator Based Refill of ART) is a cluster randomized, open-label, superiority trial conducted at 20 health facilities in three districts of Lesotho, Southern Africa. The clusters (health facilities) are randomly assigned to either the PEBRA model or standard of care in a 1:1 ratio, stratified by district. AYPLHIV aged 15-24 years old in care and on ART at one of the clusters are eligible. In the PEBRA model, a peer-educator coordinates the antiretroviral therapy (ART) services - such as medication pick-up, SMS notifications and support options - according to the preferences of the AYPLHIV. The peer-educator delivers this personalized model using a tablet-based application called PEBRApp. The control clusters continue to offer standard of care: ART services coordinated by the nurse. The primary endpoint is viral suppression at 12 months. Secondary endpoints include self-reported adherence to ART, quality of life, satisfaction with care and engagement in care. The target sample size is 300 AYPLHIV. Statistical analyses are conducted and reported in line with CONSORT guidelines for cluster randomized trials.; The PEBRA trial will provide evidence on the feasibility and effectiveness of an inclusive, holistic and preference-based DSD model for AYPLHIV that is coordinated by a peer-educator. Many countries in SSA have an existing peer-educator program. If proven effective, the PEBRA model and PEBRApp have the potential to be scaled up to similar settings.; Clinicaltrials.gov, NCT03969030. Registered on 31 May 2019. More information: www.pebra.info

Stroke treatment in a low resource setting: The Motebang hospital protocol

Background: Stroke is increasingly recognized as a major cause of death and disability in low- and middle-income countries. Guidelines are available to improve stroke outcome, but are limited in their application to low-resource settings by unavailability of stroke specialists, neuroimaging, and treatment modalities. Aims:&nbsp; To contextualise and adapt guidelines for emergency, inpatient, and post-discharge stroke care for application to the Motebang Hospital in Leribe District, Lesotho and similar low-resource district hospital settings. Methods:&nbsp; Major international stroke guidelines for ischaemic and haemorrhagic stroke treatment and secondary prevention were systematically identified and reviewed, then iteratively discussed, contextualised, and adapted to the resources available at the Motebang Hospital. Results:&nbsp; Because only a subset of stroke cases can be differentiated by clinical features as ischaemic versus haemorrhagic stroke, separate guidelines were proposed for Probable Ischaemic, Probable Haemorrhagic, and Uncertain Ischaemic/Haemorrhagic Stroke presentations. The individual subgroup guidelines aimed for optimal use of antithrombotic agents and blood pressure targets according to likelihood of ischaemic or haemorrhagic stroke. Other recommended steps such as early swallowing evaluation, removal of urinary catheters, regular skin assessment and care, physiotherapy, and post-discharge blood pressure control and lifestyle changes, were similar across all stroke categories. Conclusion: The proposed Motebang Hospital Protocol offers substantial opportunities for improving stroke outcome and reducing recurrence that can be achieved without stroke specialists, acute brain imaging, or invasive stroke treatment modalities. These guidelines can serve as the basis for contextualised stroke care in similar hospital settings with limited resources. &nbsp; French title : Prise en charge de l’Accident Vasculaire Cerebral (AVC) dans un systeme de sante aux ressources limitees : Le protocole de l’hopital Motebang, Lesotho Contexte:&nbsp; L’accident vasculaire cérébral (AVC) est une cause majeure de mortalité et de handicap dans les pays à revenu faible ou modéré. De nombreuses recommandations de prise en charges de l’AVC sont disponibles, mais sont cependant d’application limitée dans des systèmes de soins aux ressources limitées par le manque d’accès aux spécialistes, à l’imagerie ou aux thérapeutiques coûteuses et invasives. Objectif:&nbsp; Adapter les recommandations pour la prise en charge de l’AVC aux phases aigue, hospitalière et post-hospitalière à l’hôpital de Motebang dans le district de Leribe, Lesotho, et aux hôpitaux possédant des ressources similaires. Méthode:&nbsp; Les recommandations internationales sur le traitement et la prévention secondaire des AVC ischémique et hémorragique ont été examinées, discutées, contextualisées puis finalement adaptées aux ressources disponibles à l’hôpital de Motebang. Résultats:&nbsp; Du fait du faible pouvoir discriminant des critères cliniques pour différencier l’AVC ischémique de l’AVC hémorragique, 3 sous-groupes de recommandations ont été établis : AVC ischémique probable, hémorragique probable et étiologie incertaine. Ces recommandations optimisaient l’usage d’agents antithrombotiques et les cibles tensionnelles à la probabilité d’une étiologie ischémique ou hémorragique. Les recommandations concernant l’évaluation précoce de la déglutition, le retrait de sonde urinaire, la prévention d’escarres, la rééducation, le contrôle tensionnel à distance et les règles hygiéno-diététiques ne différaient pas entre les sous-groupes. Conclusion: Le protocole de l’hôpital de Motebang ouvre la porte à une amélioration importante du pronostic de l’AVC et du risque de récidive qui peut être atteinte sans accès aux spécialistes, à la neuroimagerie, ou aux thérapeutiques invasives. Ces recommandations contextualisées pourront servir de support à d’autres centres soumis aux mêmes limitations de ressources. &nbsp