Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding: A mixed-methods evaluation.

During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4≤200cells/µl. Adult participants with tuberculosis symptoms, recruited near-facility in Lesotho and South-Africa between 2021-2022, were offered HIV testing (capillary blood), Xpert MTB/RIF and Ultra, and MGIT culture (sputum). People living with HIV (PLHIV) were offered VISITECT (venous blood) and Alere tuberculosis-lipoarabinomannan (AlereLAM, urine) testing. AHD was defined as a CD4≤200cells/µl on VISITECT or a positive tuberculosis test. A CD4≤200cells/µl on VISITECT triggered Immy cryptococcal antigen (Immy CrAg, plasma) testing. Participants were referred with test results. To evaluate feasibility, we assessed i) acceptability and ii) intervention delivery of point-of-care diagnostics among study staff using questionnaires and group discussions, iii) process compliance, and iv) early effectiveness (12-week survival and treatment status) in PLHIV. Predictors for 12-week survival were assessed with logistic regression. Thematic content analysis and triangulation were performed. Among PLHIV (N = 676, 48.6% of 1392 participants), 7.8% were newly diagnosed, 81.8% on ART, and 10.4% knew their HIV status but were not on ART. Among 676 PLHIV, 41.7% had AHD, 29.9% a CD4≤200cells/µl and 20.6% a tuberculosis diagnosis. Among 200 PLHIV tested with Immy CrAg, 4.0% were positive. The procedures were acceptable for study staff, despite intervention delivery challenges related to supply and the long procedural duration (median: 73 minutes). At 12 weeks, among 276 PLHIV with AHD and 328 without, 3.3% and 0.9% had died, 84.8% and 92.1% were alive and 12.0% and 7.0% had an unknown status, respectively. Neither AHD nor tuberculosis status were associated with survival. Implementing AHD care package diagnostics was feasible during tuberculosis-case finding. AHD was prevalent, and not associated with survival, which is likely explained by the low specificity of VISITECT. Challenges with CD4 testing and preventive treatment uptake require addressing.

Impact of a multi-disease integrated screening and diagnostic model for COVID-19, TB, and HIV in Lesotho.

The surge of the COVID-19 pandemic challenged health services globally, and in Lesotho, the HIV and tuberculosis (TB) services were similarly affected. Integrated, multi-disease diagnostic services were proposed solutions to mitigate these disruptions. We describe and evaluate the effect of an integrated, hospital-based COVID-19, TB and HIV screening and diagnostic model in two rural districts in Lesotho, during the period between December 2020 and August 2022. Adults, hospital staff, and children above 5 years attending two hospitals were pre-screened for COVID-19 and TB symptoms. After a positive pre-screening, participants were offered to enroll in a service model that included clinical evaluation, chest radiography, SARS-CoV-2, TB, and HIV testing. Participants diagnosed with COVID-19, TB, or HIV were contacted after 28 days to evaluate their health status and linkage to HIV and/or TB care services. Of the 179160 participants pre-screened, 6623(3.7%) pre-screened positive, and 4371(66%) were enrolled in this service model. Of the total 458 diagnoses, only 17 happened in children. One positive rapid antigen test for SARS-CoV-2 was found per 11 participants enrolled, one Xpert-positive TB case was diagnosed per 85 people enrolled, and 1 new HIV diagnosis was done per 182 people enrolled. Of the 321(82.9%) participants contacted after 28 days of diagnosis, 304(94.7%) reported to be healthy. Of the individuals that were newly diagnosed with HIV or TB, 18/24(75.0%) and 46/51(90.1%) started treatment within 28 days of the diagnosis. This screening and diagnostic model successfully maintained same-day, integrated COVID-19, TB, and HIV testing services, despite frequent disruptions caused by the surge of COVID-19 waves, healthcare seeking patterns, and the volatile context (social measures, travel restrictions, population lockdowns). There were positive effects in avoiding diagnostic delays and ensuring linkage to services, however, diagnostic yields for adults and children were low. To inform future preparedness plans, research will need to identify essential health interventions and how to optimize them along each phase of the emergency response.

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.

Home-based versus mobile clinic HIV testing and counseling in rural Lesotho: a cluster-randomized trial.

BACKGROUND: The success of HIV programs relies on widely accessible HIV testing and counseling (HTC) services at health facilities as well as in the community. Home-based HTC (HB-HTC) is a popular community-based approach to reach persons who do not test at health facilities. Data comparing HB-HTC to other community-based HTC approaches are very limited. This trial compares HB-HTC to mobile clinic HTC (MC-HTC). METHODS AND FINDINGS: The trial was powered to test the hypothesis of higher HTC uptake in HB-HTC campaigns than in MC-HTC campaigns. Twelve clusters were randomly allocated to HB-HTC or MC-HTC. The six clusters in the HB-HTC group received 30 1-d multi-disease campaigns (five villages per cluster) that delivered services by going door-to-door, whereas the six clusters in MC-HTC group received campaigns involving community gatherings in the 30 villages with subsequent service provision in mobile clinics. Time allocation and human resources were standardized and equal in both groups. All individuals accessing the campaigns with unknown HIV status or whose last HIV test was >12 wk ago and was negative were eligible. All outcomes were assessed at the individual level. Statistical analysis used multivariable logistic regression. Odds ratios and p-values were adjusted for gender, age, and cluster effect. Out of 3,197 participants from the 12 clusters, 2,563 (80.2%) were eligible (HB-HTC: 1,171; MC-HTC: 1,392). The results for the primary outcomes were as follows. Overall HTC uptake was higher in the HB-HTC group than in the MC-HTC group (92.5% versus 86.7%; adjusted odds ratio [aOR]: 2.06; 95% CI: 1.18-3.60; p = 0. 011). Among adolescents and adults ≥ 12 y, HTC uptake did not differ significantly between the two groups; however, in children <12 y, HTC uptake was higher in the HB-HTC arm (87.5% versus 58.7%; aOR: 4.91; 95% CI: 2.41-10.0; p<0.001). Out of those who took up HTC, 114 (4.9%) tested HIV-positive, 39 (3.6%) in the HB-HTC arm and 75 (6.2%) in the MC-HTC arm (aOR: 0.64; 95% CI: 0.48-0.86; p = 0.002). Ten (25.6%) and 19 (25.3%) individuals in the HB-HTC and in the MC-HTC arms, respectively, linked to HIV care within 1 mo after testing positive. Findings for secondary outcomes were as follows: HB-HTC reached more first-time testers, particularly among adolescents and young adults, and had a higher proportion of men among participants. However, after adjusting for clustering, the difference in male participation was not significant anymore. Age distribution among participants and immunological and clinical stages among persons newly diagnosed HIV-positive did not differ significantly between the two groups. Major study limitations included the campaigns' restriction to weekdays and a relatively low HIV prevalence among participants, the latter indicating that both arms may have reached an underexposed population. CONCLUSIONS: This study demonstrates that both HB-HTC and MC-HTC can achieve high uptake of HTC. The choice between these two community-based strategies will depend on the objective of the activity: HB-HTC was better in reaching children, individuals who had never tested before, and men, while MC-HTC detected more new HIV infections. The low rate of linkage to care after a positive HIV test warrants future consideration of combining community-based HTC approaches with strategies to improve linkage to care for persons who test HIV-positive. TRIAL REGISTRATION: ClinicalTrials.gov NCT01459120. Please see later in the article for the Editors' Summary.

Clinical and socio-demographic predictors for virologic failure in rural Southern Africa: preliminary findings from CART-1.

INTRODUCTION: In 2013, the World Health Organization (WHO) recommended scaling up of routine viral load (VL) monitoring for patients on antiretroviral therapy (ART) in resource-limited settings [1]. During the transition phase from no VL-testing at all to routine VL-monitoring, targeted VL for groups at particular risk of virologic failure (VF) may be an option [2]. We present socio-demographic and clinical risk factors for VF in a cohort in rural Lesotho with no access to VL prior to the study. MATERIALS AND METHODS: Data derive from a cross-sectional study providing multi-disease screening as well as VL testing to adult patients (≥16 years old) on first-line ART ≥6 months [3]. VF was defined as VL≥1000 copies/mL. Assessed potential predictors of VF were: (1) socio-demographic (sex, age, wealth-quintile, education, employment status, disclosure of HIV status to environment, travel-time to facility); (2) treatment history (history of treatment interruption >2 days, previous drug substitution within first-line ART, time on ART, ART-base and -backbone); (3) adherence (pill count) and (4) clinical (clinical or immunological failure as defined by WHO guidelines [1], presence of papular pruritic eruption (PPE)). All variables with association to VF in univariate analysis were included in a multivariate logistic regression reporting adjusted Odds ratios (aOR). RESULTS: Data from 1,488 patients were analyzed. Overall VF-prevalence was 6.9% (95% CI 5.7-8.3). In univariate analysis, the following were associated with VF: age <30, lower wealth-quintile, no primary education, history of treatment interruption, nevirapine-base, zidovudine-backbone, history of drug substitution, travel-time to clinic ≥2 hours, disclosure of HIV status to <5 persons, clinical failure, presence of PPE and immunological failure. In multivariate analysis, 6 out of the above 12 variables were independent predictors: age <30 years (aOR: 2.4; 95% CI 1.1-5.3, p=0.029), history of treatment interruption (2.5; 1.3-4.7, p=0.005), PPE (6.9; 2.5-18.9, p<0.001), immunological failure (11.5; 5.7-23.2, p<0.001), history of drug substitution (1.9; 1.0-3.7, p=0.043), disclosure of HIV status to <5 persons (1.8; 1.1-3.1, p=0.03). CONCLUSION: In this cohort in rural Lesotho, several socio-demographic and clinical predictors were associated with VF. Particularly age <30 years, history of treatment interruption, PPE and immunological failure were strongly associated with VF. These patients may be prioritized for targeted VL-testing.