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Background: Access to antiretroviral therapy (ART) for the human immunodeficiency virus type 1 (HIV-1) has lowered morbidity and mortality in people living with HIV. Unfortunately, over time, some experience the development of viral drug resistance (DR) under therapy. Little is known about the percentages of people experiencing DR, and about the genetic patterns of DR among patients failing second-line ART in Lesotho. This study aimed to assess the prevalence of HIV-1 resistance-associated mutations (RAMs) in the viral target genes of the respective drugs in individuals with unsuppressed viral loads while taking second-line ART. Methods: In a retrospective cross-sectional study, we sequenced all available plasma samples from individuals with a viral load measurement = 1 000 copies/mL while taking second-line ART between January 2016 and October 2020. Sequencing was performed using the commercial SeqStudio™ Genetic Analyser at the Seboche Mission Hospital Laboratory. Results: Out of 55 samples meeting the eligibility criteria, 30 samples were successfully amplified and sequenced. The median age of patients was 41 years (interquartile range [IQR] 30-49), and the majority (62%) of participants were female. The median duration on a second-line ART regimen at the time of phlebotomy was 1.9 years (IQR 0.5-3.0). Most participants were taking ritonavirboosted lopinavir-based ART as their second-line therapy. Major RAMs describing those mutations in targeted gene therapy reverse transcriptase (RT) and/or protease (PR) that led to virological treatment failure, were observed in 62% of participants; one patient had major RAMs in the PR region, while 18 had RAMs in the RT region. Conclusion: In our study, we found that 31% of the included individuals (10/30) had RAMs conferring resistance to their second-line regimen during the first two years after switching to second-line ART. [ABSTRACT FROM AUTHOR]

Background: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT., Methods: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed., Findings: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study., Interpretation: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART., Funding: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation., Translations: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests NDL reports having received travel grants to conferences from Gilead Sciences and ViiV Healthcare, and his division received honoraria for consultancies from ViiV Healthcare and for participation in a data safety monitoring board from Pharming. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (© 2020 Wiley Periodicals LLC.)

Background: Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART)., Methods: GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up., Discussion: This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART., Trial Registration: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Introduction: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: NDL received travel grants from Gilead Sciences Switzerland to HIV Glasgow 2014, HIV Glasgow 2016 and the 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention 2015 in Vancouver. All other authors have no competing interests to declare.

Background: Soil-transmitted helminth (STH) infections with Ascaris lumbricoides, hookworm and Trichuris trichiura affect large parts of the world's population. For the implementation of national STH control programs, e.g. preventive chemotherapy (treatment with albendazole and mebendazole), the spatial distribution and prevalence of STH infections must be known. However, for Lesotho only little data were available and the STH distribution remains largely unknown., Methods: In early 2016, a cross-sectional parasitological STH survey was conducted including six different primary schools in the Butha-Buthe district of Lesotho. In each school stool samples were collected from 50 children (age 8-14 years) and analysed with a duplicate Kato-Katz thick smear for the presence of A. lumbricoides, hookworm and T. trichiura., Results: A total of 301 children provided a stool sample. All children were negative for A. lumbricoides and T. trichiura. Only two children from one primary school showed a light hookworm infection., Conclusion: Our data indicate a low prevalence of STH infections in the Butha-Buthe district of Lesotho. Additional parasitological surveys on the prevalence and the spatial distributions of STH infections across the entire country of Lesotho are needed.

Introduction: Due to its side effects stavudine (D4T) has been replaced by zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have been described extensively, studies from LMICs comparing metabolic profiles between patients on AZT and TDF are scarce. Given the high number of patients in LMICs still taking AZT, data on their metabolic profile are needed. We present rates of metabolic syndrome (MS) in adult patients taking either AZT- or TDF-containing first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimens., Materials and Methods: Data derived from a cross-sectional multi-disease screening conducted in ten facilities in two rural districts of Lesotho, Southern Africa [2]. Patients were eligible if aged ≥25 years and on NNRTI-containing first-line ART ≥6 months. The MS definition for Africa of the International Diabetes Federation was applied [3]. Assessed potential predictors for MS were age, time on ART, virologic suppression, body-mass index (BMI), alcohol consumption, wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz (EFV)), history of previous D4T exposure and ART-backbone (AZT or TDF). Statistical analyses - stratified for sex - comprised univariate logistic regression for each predictor variable with subsequent construction of a multivariate model including all predictors with an association to MS at a significance level<0.1 in univariate analysis., Results: Out of 1026 patients, 660 (64.3%) were female. MS prevalence was 9.8% (95% CI 6.9-13.4) in men and 22.9% (19.7-26.3) in women. In women, aged ≥35 years, AZT-backbone, NVP-base, BMI ≥25kg/m2 and taking ART for ≥4.5 years were associated with MS in univariate analysis. In the multivariate model only AZT (adjusted odds-ratio: 2.2, 95% CI 1.4-3.6; p=0.001) and BMI ≥25kg/m2 (9.8; 2.8-34.1, p<0.001) were associated with MS. For men, age, higher wealth quintile, history of D4T exposure and BMI were associated with MS in univariate analysis. In the multivariate model only a BMI ≥25kg/m2 was associated with MS (8.9; 3.8-20.9, p<0.001)., Conclusions: In rural Lesotho, Southern Africa, the use of AZT instead of TDF among women who are on ART for ≥6 months predisposes to the development of metabolic syndrome. Given that, still 38% of first-line regimens in LMIC contain AZT, this finding needs to be verified in other settings in Sub-Saharan Africa.

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.