Effectiveness of a peer educator-coordinated preference-based differentiated service delivery model on viral suppression among young people living with HIV in Lesotho: The PEBRA cluster-randomized trial.

BACKGROUND: 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. METHODS AND FINDINGS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: clinicaltrials.gov, NCT03969030, https://clinicaltrials.gov/ct2/show/NCT03969030.

Community-based care models for arterial hypertension management in non-pregnant adults in sub-Saharan Africa: a literature scoping review and framework for designing chronic services.

BACKGROUND: Arterial hypertension (aHT) is the leading cardiovascular disease (CVD) risk factor in sub-Saharan Africa; it remains, however, underdiagnosed, and undertreated. Community-based care services could potentially expand access to aHT diagnosis and treatment in underserved communities. In this scoping review, we catalogued, described, and appraised community-based care models for aHT in sub-Saharan Africa, considering their acceptability, engagement in care and clinical outcomes. Additionally, we developed a framework to design and describe service delivery models for long-term aHT care. METHODS: We searched relevant references in Embase Elsevier, MEDLINE Ovid, CINAHL EBSCOhost and Scopus. Included studies described models where substantial care occurred outside a formal health facility and reported on acceptability, blood pressure (BP) control, engagement in care, or end-organ damage. We summarized the interventions' characteristics, effectiveness, and evaluated the quality of included studies. Considering the common integrating elements of aHT care services, we conceptualized a general framework to guide the design of service models for aHT. RESULTS: We identified 18,695 records, screened 4,954 and included twelve studies. Four types of aHT care models were identified: services provided at community pharmacies, out-of-facility, household services, and aHT treatment groups. Two studies reported on acceptability, eleven on BP control, ten on engagement in care and one on end-organ damage. Most studies reported significant reductions in BP values and improved access to comprehensive CVDs services through task-sharing. Major reported shortcomings included high attrition rates and their nature as parallel, non-integrated models of care. The overall quality of the studies was low, with high risk of bias, and most of the studies did not include comparisons with routine facility-based care. CONCLUSIONS: The overall quality of available evidence on community-based aHT care is low. Published models of care are very heterogeneous and available evidence is insufficient to recommend or refute further scale up in sub-Sahara Africa. We propose that future projects and studies implementing and assessing community-based models for aHT care are designed and described according to six building blocks: providers, target groups, components, location, time of service delivery, and their use of information systems.

Offering ART refill through community health workers versus clinic-based follow-up after home-based same-day ART initiation in rural Lesotho: The VIBRA cluster-randomized clinical trial.

BACKGROUND: Community-based antiretroviral therapy (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) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation. METHODS AND FINDINGS: The VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be 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 villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov (NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30-48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference -0.07 [95% CI -0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [-0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference -0.12 [-0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population. CONCLUSIONS: The offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community. TRIAL REGISTRATION: Registered with Clinicaltrials.gov (NCT03630549).

Engagement in Care, Viral Suppression, Drug Resistance, and Reasons for Nonengagement After Home-Based Same-Day Antiretroviral Therapy Initiation in Lesotho: A Two-Year Follow-up of the CASCADE Trial.

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.

Emerging priorities for HIV service delivery.

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

Low rates of active hepatitis B and C infections among adults and children living with HIV and taking antiretroviral therapy: A multicenter screening study in Lesotho.

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.

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.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03969030. Registered on 31 May 2019. More information: www.pebra.info.

Importance of routine viral load monitoring: higher levels of resistance at ART failure in Uganda and Lesotho compared with Switzerland.

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 < 0.01) and higher in Lesotho compared with Uganda for all drugs used in first-line treatment except zidovudine (P < 0.01). Conclusions: Frequent VL monitoring and possibly pretreatment GRT as done in the SHCS pays off by low levels of resistance even when treatment failure occurs. The high-level resistance patterns in Lesotho compared with Uganda could reflect a selection of strains with multiple resistance during enhanced adherence counselling.

Effect and cost of two successive home visits to increase HIV testing coverage: a prospective study in Lesotho, Southern Africa.

BACKGROUND: Home-based HIV testing and counselling (HB-HTC) is frequently used to increase awareness of HIV status in sub-Saharan Africa. Whereas acceptance of HB-HTC is usually high, testing coverage may remain low due to household members being absent during the home visits. This study assessed whether two consecutive visits, one during the week, one on the weekend, increase coverage. METHODS: The study was a predefined nested-study of the CASCADE-trial protocol and conducted in 62 randomly selected villages and 17 urban areas in Butha-Buthe district, Lesotho. HB-HTC teams visited each village/urban area twice: first during a weekday, followed by a weekend visit to catch-up for household members absent during the week. Primary outcome was HTC coverage after first and second visit. Coverage was defined as all individuals who knew their HIV status out of all household members (present and absent). RESULTS: HB-HTC teams visited 6665 households with 18,286 household members. At first visit, 69.2 and 75.4% of household members were encountered in rural and urban households respectively (p < 0.001) and acceptance for testing was 88.5% in rural and 79.5% in urban areas (p < 0.001), resulting in a coverage of 61.8 and 61.5%, respectively. After catch-up visit, the HTC coverage increased to 71.9% in rural and 69.4% in urban areas. The number of first time testers was higher at the second visit (47% versus 35%, p < 0.001). Direct cost per person tested and per person tested HIV positive were lower during weekdays (10.50 and 335 USD) than during weekends (20 and 1056 USD). CONCLUSIONS: A catch-up visit on weekends increased the proportion of persons knowing their HIV status from 62 to 71% and reached more first-time testers. However, cost per person tested during catch-up visits was nearly twice the cost during first visit. TRIAL REGISTRATION: NCT02692027 (prospectively registered on February 21, 2016).

Effect of Offering Same-Day ART vs Usual Health Facility Referral During Home-Based HIV Testing on Linkage to Care and Viral Suppression Among Adults With HIV in Lesotho: The CASCADE Randomized Clinical Trial.

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 < .001). At 12 months, 50.4% (69) in the same-day group vs 34.3% (47) in usual care group achieved viral suppression (absolute difference, 16.0%; 4.4%-27.2%; 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.

Same day ART initiation versus clinic-based pre-ART assessment and counselling for individuals newly tested HIV-positive during community-based HIV testing in rural Lesotho - a randomized controlled trial (CASCADE trial).

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.

Is zidovudine first-line therapy virologically comparable to tenofovir in resource-limited settings?

OBJECTIVE: To compare virologic success between adult patients on tenofovir (TDF) and zidovudine (AZT)-containing first-line antiretroviral (ART) regimens in 10 rural clinics in Lesotho, Southern Africa. METHODS: Multicentre cross-sectional study, patients ≥16 years, on first-line ART ≥6 months, receiving AZT/lamivudine (3TC) or TDF/3TC combined with efavirenz (EFV) or nevirapine (NVP). Patient characteristics and clinical/therapeutic history were collected on the day of blood draw for viral load (VL). Analysis was stratified for non-nucleoside reverse transcriptase inhibitor (EFV or NVP). A logistic regression model weighted for patients' baseline characteristics was used to assess the likelihood of virologic success (<80 copies/ml) in patients with TDF- as compared to AZT-backbones. RESULTS: In total 1539 patients were included in the analysis. Most were clinically and immunologically stable (clinical failure: 2.7% (AZT) and 2.8% (TDF); immunological failure: 4.6% (AZT) and 4.8% (TDF)). In EFV-based regimens (n = 1162), TDF was significantly associated with higher rates of virologic suppression than AZT (93.8% vs. 88.1%; weighted odds ratio: 2.15 (95% CI: 1.29-3.58; P = 0.003)). In NVP-based regimens, a similar trend was observed, but not significant (89.4% vs. 86.7%; 1.99 (0.83-4.75, P = 0.121)). CONCLUSION: These findings support the WHO recommendation to use TDF/3TC/EFV as first-line regimen. They do, however, not support the recommendation that patients who are clinically stable on AZT should continue on this first-line regimen.

Community-based management of arterial hypertension and cardiovascular risk factors by lay village health workers for people with controlled and uncontrolled blood pressure in rural Lesotho: joint protocol for two cluster-randomized trials within the ComBaCaL cohort study (ComBaCaL aHT Twic 1 and ComBaCaL aHT TwiC 2).

BACKGROUND: Arterial hypertension (aHT) is a major cause for premature morbidity and mortality. Control rates remain poor, especially in low- and middle-income countries. Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems may help to overcome the current aHT care cascade gaps. However, evidence on the effectiveness of comprehensive VHW-led aHT care models, in which VHWs provide antihypertensive drug treatment and manage cardiovascular risk factors is scarce. METHODS: Using the trials within the cohort (TwiCs) design, we are assessing the effectiveness of VHW-led aHT and cardiovascular risk management in two 1:1 cluster-randomized trials nested within the Community-Based chronic disease Care Lesotho (ComBaCaL) cohort study (NCT05596773). The ComBaCaL cohort study is maintained by trained VHWs and includes the consenting inhabitants of 103 randomly selected villages in rural Lesotho. After community-based aHT screening, adult, non-pregnant ComBaCaL cohort participants with uncontrolled aHT (blood pressure (BP) ≥ 140/90 mmHg) are enrolled in the aHT TwiC 1 and those with controlled aHT (BP < 140/90 mmHg) in the aHT TwiC 2. In intervention villages, VHWs offer lifestyle counseling, basic guideline-directed antihypertensive, lipid-lowering, and antiplatelet treatment supported by a tablet-based decision support application to eligible participants. In control villages, participants are referred to a health facility for therapeutic management. The primary endpoint for both TwiCs is the proportion of participants with controlled BP levels (< 140/90 mmHg) 12 months after enrolment. We hypothesize that the intervention is superior regarding BP control rates in participants with uncontrolled BP (aHT TwiC 1) and non-inferior in participants with controlled BP at baseline (aHT TwiC 2). DISCUSSION: The TwiCs were launched on September 08, 2023. On May 20, 2024, 697 and 750 participants were enrolled in TwiC 1 and TwiC 2. To our knowledge, these TwiCs are the first trials to assess task-shifting of aHT care to VHWs at the community level, including the prescription of basic antihypertensive, lipid-lowering, and antiplatelet medication in Africa. The ComBaCaL cohort and nested TwiCs are operating within the routine VHW program and countries with similar community health worker programs may benefit from the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05684055. Registered on January 04, 2023.

Magnitude and Determinants of Virological Failure Among Patients >15 Years on Anti-Retroviral Therapy in Rural Lesotho Between 2015 and 2019 - A Retrospective Cohort Study.

Background: Lesotho has the second-highest HIV prevalence globally at an estimated 23%, with approximately 87% of the population between 15 and 59 years of age reported to be receiving antiretroviral treatment. There is an urgent need to increase access to effective ART due to increasing rates of first- and second-line treatment failure. Sustaining successful treatment and limiting the development of virological failure is essential, hence the need for early detection of increased viral load indicating drug resistance or rapid progression of viral replication. Aim: The aim of the study was to determine the proportion of patients with HIV with virological failure and to identify factors associated with virological failure in two districts of Lesotho. Methods: A retrospective cohort study was conducted in two districts (Butha-Buthe and Mokhotlong) in Lesotho. Data for all patients (age ≥15 years) in the viral load (VL) monitoring database with at least two consecutive viral load results between December 2015 and December 2019 from 22 health facilities were extracted. Descriptive data were presented using tables and figures. Bivariate and multivariate analyses were performed. A p-value < 0.05 was considered a statistically significant association. Results: Only 4% (n = 913) of the study participants had virological failure. Longer time on treatment >65 months (AOR: 1.85 CI: 1.59-2.15) and being on second-line ART regimen (AOR: 75.23 95% CI: 75.00-99.15) were significantly (p < 0.001) associated with virological failure. Conclusion: Virological failure among the study participants is lower compared to other settings. The study identified duration on treatment, treatment regimen as high risk for virological failure. Targeted interventions should be developed for these high-risk group individuals, with continuous monitoring of virological response and appropriate drug switching to clients to achieve improved outcomes.

Prevalence and determinants of cardiovascular risk factors in Lesotho: a population-based survey.

BACKGROUND: There are no recent data on the prevalence of cardiovascular risk factors (CVDRFs) in Lesotho. This study aims to assess the prevalence of CVDRFs and their determinants. METHODS: We conducted a household-based, cross-sectional survey among adults ≥18 y of age in 120 randomly sampled clusters in two districts. RESULTS: Among 6061 participants, 52.2% were female and their median age was 39 y (interquartile range 27-58). The overall prevalence of overweight, diabetes, elevated blood pressure (BP) and tobacco use was 39.9%, 5.3%, 21.6% and 24.9%, respectively. Among participants, 34.6% had none, 45.2% had one and 20.2% had two or more CVDRFs. Women were more likely to have two or more CVDRFs (20.7% vs 12.3%). Overall, 7.5% of participants had elevated total cholesterol, 52.7% had low high-density lipoprotein cholesterol and 1.6% had elevated low-density lipoprotein cholesterol. Among younger participants (18-29 y), 16.1% reported tobacco use, 28.6% were overweight, 1.5% had diabetes and 3.5% had elevated BP. Household wealth positively correlated with the prevalence of elevated BP, overweight and diabetes, whereas tobacco use was higher among people in the lowest three wealth quintiles. CONCLUSIONS: CVDRFs are highly prevalent in Lesotho across age and sex groups, underlining the importance of strengthening prevention and care programs in Lesotho and similar settings in southern Africa.

Community-based type 2 diabetes care by lay village health workers in rural Lesotho: protocol for a cluster-randomized trial within the ComBaCaL cohort study (ComBaCaL T2D TwiC).

BACKGROUND: Type 2 diabetes (T2D) poses a growing public health burden, especially in low- and middle-income countries (LMICs). Task-shifting to lay village health workers (VHWs) and the use of digital clinical decision support systems (CDSS) are promising approaches to tackle the current T2D care gap in LMICs. However, evidence on the effectiveness of lay worker-led T2D care models, in which VHWs initiate and monitor drug treatment in addition to community-based screening and referral services, is lacking. METHODS: We are conducting a cluster-randomized trial nested within the Community-Based Chronic Disease Care Lesotho (ComBaCaL) cohort study (NCT05596773) using the trial within cohort (TwiC) design to assess the effectiveness of a VHW-led, CDSS-assisted T2D care model in rural Lesotho. Participants are non-pregnant members of the ComBaCaL cohort study with T2D. The ComBaCaL cohort study is conducted in approximately 100 villages in two rural districts in Lesotho and is managed by trained and supervised VHWs. In intervention villages, VHWs offer a community-based T2D care package including lifestyle counselling, first-line oral antidiabetic, lipid-lowering, and antiplatelet treatment guided by a tablet-based CDSS to participants who are clinically eligible, as well as treatment support to participants who prefer or clinically require facility-based T2D care. In control clusters, all participants will be referred to a health facility for T2D management. The primary endpoint is the mean glycosylated haemoglobin (HbA1c) 12 months after enrolment. Secondary endpoints include the 10-year risk for cardiovascular events estimated using the World Health Organization risk prediction tool. DISCUSSION: The trial was launched on May 13, 2023, and has enrolled 226 participants at the date of submission (October 6, 2023). To our knowledge, the trial is the first to assess task-shifting of T2D care to VHWs at the community level, including the prescription of first-line antidiabetic, lipid-lowering, and antiplatelet medication in sub-Saharan Africa, and will thus provide the missing evidence on the effectiveness of such a T2D care model in this setting. The study is operating within the established Lesotho VHW programme. Similar community health worker programmes which exist across sub-Saharan Africa may benefit from the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05743387. Registered on February 24 2023.

Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

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.

eHealth supported multi-months dispensing of antiretroviral therapy: a mixed-methods preference assessment in rural Lesotho.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Feasibility of implementing the advanced HIV disease care package as part of community-based HIV/TB activities: a mixed-methods study protocol.

INTRODUCTION: Although 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 <200 cells/µL or age <5 years), it is barely implemented in many countries. A novel point-of-care CD4 test rapidly identifies AHD. We evaluate the feasibility of implementing the AHD care package as part of community-based HIV/tuberculosis services. METHODS AND ANALYSIS: This 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 DISSEMINATION: The 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 NUMBER: NCT04666311.