Engagement in care, viral suppression, drug resistance and reasons for non-engagement after home-based same-day ART initiation in Lesotho: a two-year follow-up of the CASCADE trial

The CASCADE trial showed that compared to usual care (UC), offering same-day (SD) ART during home-based HIV testing improved engagement in care and viral suppression 12 months after diagnosis. However, open questions remain regarding long-term outcomes and the risk of propagating drug resistance.; 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 non-engagement. Furthermore, we explored among SD arm non-linkers the acquisition of drug resistance mutations (DRMs).; At 24 months, 64% (88/137) in the SD vs 59% (81/137) in the UC arm were in care (absolute difference 5%; 95%CI -6-16; p=0.38) and 57% (78/137) vs 54% (74/137) had documented viral suppression (3%; -9-15; p=0.28). 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 eight interviewed SD arm non-linkers, six had not initiated ART upon enrolment and no acquired DRMs were detected. Two had taken the initial 30-day ART supply and acquired DRMs.; SD ART resulted in higher rates of engagement in care and viral suppression at 12 but not 24 months. Levelling 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

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

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.; 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).; 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).; 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.; NCT02692027 (prospectively registered on February 21, 2016)

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

The viral load monitoring cascade in a resource-limited setting : a prospective multicentre cohort study after introduction of routine viral load monitoring in rural Lesotho

For HIV-positive individuals on antiretroviral therapy (ART), the World Health Organization (WHO) recommends routine viral load (VL) monitoring. We report on the cascade of care in individuals with unsuppressed VL after introduction of routine VL monitoring in a district in Lesotho.; In Butha-Buthe district 12 clinics (11 rural, 1 hospital) send samples for VL testing to the district laboratory. We included data from patients aged ≥15 years from Dec 1, 2015 to November 1, 2018. As per WHO guidelines VL <1000 copies/mL are considered suppressed, those ≥1000copies/mL unsuppressed. Patients with unsuppressed VL receive adherence counseling and follow-up VL within 8-12 weeks. Two consecutively unsuppressed VLs should trigger switch to second-line ART. For analysis of the VL monitoring cascade we defined care to be "according to guidelines" if patients with unsuppressed VL received a follow-up VL within <180 days and follow-up VL was either re-suppressed, or again unsuppressed and the individual was switched to second-line within 90 days.; For 9,949 individuals 24,948 VL tests were available. The majority were female (73%), median age 41 years (interquartile range 33-52), and 58% seen at rural clinics. Overall, 25% (260/1028) of individuals were managed according to guidelines: 40% (410/1028) had a follow-up VL within 180 days of their initial unsuppressed VL and 25% (260/1028) of those either re-suppressed or switched to second-line within 90 days. Female patients were more likely to have a follow-up VL done, (p = 0.015). In rural clinics rates of two consecutively unsuppressed VLs were higher than in the hospital (64% vs. 44%, p<0.001), and rural clinics were less likely to switch these patients to second-line (35% vs. 66%, p<0001).; Our data show that in a real-life setting availability of routine VL monitoring may not be exploited to its potential. A lack of timely follow-up after a first unsuppressed VL and reluctance to switch patients with confirmed virological failure, reduce the benefit of VL monitoring, i.e. in the rural clinics. Future studies will have to assess models of care which ensure that VL results are met with an action and make use of scalable innovative approaches

The HOSENG trial - effect of the provision of oral self-testing for absent and refusing individuals during a door-to-door HIV-testing campaign on testing coverage : protocol of a cluster-randomized clinical trial in rural Lesotho

HIV-testing coverage remains below the targeted 90% despite efforts and resources invested. Home-based HIV-testing is a key approach endorsed by the World Health Organization (WHO), 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 household members. This cluster-randomized trial aims to assess increase in testing coverage using oral HIV self-testing (HIVST) among individuals who are absent or decline testing during home-based HIV-testing.; 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 (VHW). In intervention clusters, HIV self-tests are provided for eligible household members who are absent or decline HIV-testing in the presence of the campaign team. In control clusters, standard of care for absent and refusing individuals applies, i.e., referral to a health facility. The primary outcome is HIV-testing coverage among individuals aged 12 years or older within 120 days after enrollment. 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. The HOSENG trial is linked to the VIBRA (Village-Based Refill of ART) trial. Together, they constitute the GET ON (GETting tOwards Ninety) research project.; The HOSENG trial tests whether 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 should inform home-based HIV-testing policies not only in Lesotho, but in similar high-prevalence settings.; ClinicalTrials.gov, (ID: NCT03598686 ). Registered on 25 July 2018. More information is available at www.getonproject.wordpress.com

VIBRA trial - Effect of village-based refill of ART following home-based same-day ART initiation vs clinic-based ART refill on viral suppression among individuals living with HIV : protocol of a cluster-randomized clinical trial in rural Lesotho

There is a need for evaluating community-based antiretroviral therapy (ART) delivery models to improve overall performance of HIV programs, specifically in populations that may have difficulties to access continuous care. This cluster-randomized clinical trial aims to evaluate the effectiveness of a multicomponent differentiated ART delivery model (VIBRA model) after home-based same-day ART initiation in remote villages in Lesotho, southern Africa.; The VIBRA trial (VIllage-Based Refill of ART) is a cluster-randomized parallel-group superiority clinical trial conducted in two districts in Lesotho, southern Africa. Clusters (i.e., villages) are randomly assigned to either the VIBRA model or standard care. The clusters are stratified by district, village size, and village access to the nearest health facility. Eligible individuals (HIV-positive, aged 10 years or older, and not taking ART) identified during community-based HIV testing campaigns are offered same-day home-based ART initiation. The intervention clusters offer a differentiated ART delivery package with two features: (1) drug refills and follow-ups by trained and supervised village health workers (VHWs) and (2) the option of receiving individually tailored adherence reminders and notifications of viral load results via SMS. The control clusters will continue to receive standard care, i.e., collecting ART refills from a clinic and no SMS notifications. The primary endpoint is viral suppression 12 months after enrolment. Secondary endpoints include linkage to and engagement in care. Furthermore, safety and cost-effectiveness analyses plus qualitative research are planned. The minimum target sample size is 262 participants. The statistical analyses will follow the CONSORT guidelines. The VIBRA trial is linked to another trial, the HOSENG (HOme-based SElf-testiNG) trial, both of which are within the GET ON (GETing tOwards Ninety) research project.; The VIBRA trial is among the first to evaluate the delivery of ART by VHWs immediately after ART initiation. It assesses the entire HIV care cascade from testing to viral suppression. As most countries in sub-Saharan Africa have cadres like the VHW program in Lesotho, this model-if shown to be effective-has the potential to be scaled up. The system impact evaluation will provide valuable cost estimations, and the qualitative research will suggest how the model could be further modified to optimize its impact.; Clinicaltrials.gov, NCT03630549 . Registered on 15 August 2018

When patients fail UNAIDS' last 90 - the "failure cascade" beyond 90-90-90 in rural Lesotho, Southern Africa: a prospective cohort study

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.; 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.; 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.; 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

The treatment cascade in children with unsuppressed viral load - a reality check in rural Lesotho, Southern Africa

As per the guidelines of the World Health Organization, HIV-infected children who do not achieve viral suppression while under antiretroviral therapy (ART) receive enhanced adherence counseling (EAC) with follow-up viral load (VL). A persisting unsuppressed VL after EAC triggers switch to a second-line regimen. We describe the care cascade of children with unsuppressed VL while taking ART.; Children, aged <16 years, on first-line ART for ≥6 months with unsuppressed VL (≥80 copies/mL) at first measurement were enrolled. As per guidelines, children/caregivers received EAC and a follow-up VL after 3 months, whereas those with persisting viremia despite good adherence were eligible for switching to second-line. Eighteen months after the first unsuppressed VL, outcomes were assessed.; Of 191 children receiving a first-time VL in May/June 2014, 53 (28%) had unsuppressed viremia. The care cascade of these 53 children was as follows: 49 (92%) received EAC and a follow-up VL in October 2014 (1 died, 3 lost to follow-up). 36/49 (73%) stayed unsuppressed, but only 24 were switched to second-line. At 18-months follow-up, 10 (19%) were retained in care with suppressed VL, 26 were retained with ongoing viremia (49%), 2 (4%) had died, and 15 (28%) had no VL documentation.; Only 1 of 5 children with unsuppressed initial VL under ART was retained in care and virally suppressed at 18 months of follow-up. ART programs must increase the focus onto the extremely vulnerable care cascade in children with unsuppressed VL

HIV Care Preferences among Young People Living with HIV in Lesotho: A Secondary Data Analysis of the PEBRA Cluster Randomized Trial

Introduction. Sub-Saharan Africa is home to 89% of all young people living with HIV, a key population with specific challenges and needs. In-depth knowledge of service demands is needed to tailor and differentiate service delivery for this group. We evaluated HIV care preferences among young people living with HIV who were part of the PEBRA (Peer Educator Based Refill of ART) cluster-randomized trial. Methods. The PEBRA trial evaluated a novel model of care at 20 health facilities in Lesotho, Southern Africa. In the PEBRA model, a peer educator regularly assessed participant preferences regarding antiretroviral therapy (ART) refill location, SMS notifications (for adherence, drug refill, viral load), and general care support options and delivered services accordingly over a 12-month period. We present these preferences and their changes over time. Results. At enrolment, 41 of 123 (33.3%) chose ART refill outside the health facility, compared to 8 of 123 (6.5%) after 12 months. Among those selecting clinic-based ART refill, many preferred collecting ART during the peer educator led Saturday clinic club, 45 of 123 (36.5%) at the beginning and 55 of 123 (44.7%) at the end. SMS reminders for treatment adherence and ART refill visits were chosen by 51 of 123 (41.5%) at enrolment and 54 of 123 (44.7%) at the last assessment. Support by the peer educator was popular at the beginning (110 of 123 (89.4%)) and lower but still high at the end (85 of 123 (69.1%)). Thirteen of 123 (10.6%) participants chose support by the nurse, without the involvement of any peer educator, at the first and 21 of 123 (17.1%) at the last assessment. Conclusion. Our longitudinal preference assessment among young people living with HIV in Lesotho showed a sustained interest in SMS notifications for adherence and refill visits as well as in additional support by a peer educator. ART refill outside the health facility was not as popular as expected; instead, medication pick-up at the facility, especially during Saturday clinic clubs, was favoured. The PEBRA trial was registered with clinicaltrials.gov (NCT03969030. Registered on 31 May 2019

Should viral load thresholds be lowered?

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 <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considere