Reaching absent and refusing individuals during home-based HIV testing through self-testing-at what cost?

Introduction: In the HOSENG trial (NCT03598686), the secondary distribution of oral self-tests for persons absent or refusing to test during a home-based HIV testing campaign in rural Lesotho resulted in an increase in testing coverage of 21% compared to a testing campaign without secondary distribution. This study aims to determine the per patient costs of both HOSENG trial arms. Method: We conducted a micro-costing study to estimate the cost of home-based HIV testing with (HOSENG intervention arm) and without (HOSENG control arm) secondary self-test distribution from a provider's perspective. A mixture of top-down and bottom-up costing was used. We estimated both the financial and economic per patient costs of each possible testing cascade scenario. The costs were adjusted to 2018 US$. Results: The overall provider cost for delivering the home-based HIV testing with secondary distribution was US$36,481 among the 4,174 persons enumerated and 3,094 eligible for testing in the intervention villages compared to US$28,620 for 3,642 persons enumerated and 2,727 eligible for testing in the control. The cost per person eligible for testing was US$11.79 in the intervention vs. US$10.50 in the control. This difference was mainly driven by the cost of distributed oral self-tests. The cost per person tested was, however, lower in intervention villages (US$15.70 vs. US$22.15) due to the higher testing coverage achieved through self-test distribution. The cost per person confirmed new HIV+ was US$889.79 in the intervention and US$753.17 in the control. Conclusion: During home-based HIV testing in Lesotho, the secondary distribution of self-tests for persons absent or refusing to test during the visit reduced the costs per person tested and thus presents a promising add-on for such campaigns. Trial Registration:https://ClinicalTrials.gov/, identifier: NCT03598686

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/microL 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/microL 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

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)

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

Emergence of human immunodeficiency virus-1 drug resistance during the 3-month World Health Organization-recommended enhanced adherence counseling period in the CART-1 cohort study

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

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

Assessment of a viral load result-triggered automated differentiated service delivery model for people taking ART in Lesotho (the VITAL study): study protocol of a cluster-randomized trial

INTRODUCTION: To sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving. METHODS: The VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences. EXPECTED OUTCOMES: Evidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving. TRIAL REGISTRATION: The study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020)

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

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: NCT0269202