SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa.

BACKGROUND: The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL. METHODS: In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables. DISCUSSION: The SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03088241 ), registered May 05, 2017.

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.

The state of the pediatric HIV epidemic in Lesotho.

OBJECTIVE: Lesotho does not have reliable data on HIV prevalence in children, relying on estimates generated from program data. The 2016 Lesotho Population-based HIV Impact Assessment (LePHIA) aimed to determine HIV prevalence among children 0-14 years to assess the effectiveness of the prevention of mother-to-child transmission (PMTCT) program and guide future policy. METHODS: A nationally representative sample of children under 15 years underwent household-based, two-stage HIV testing from November 2016-May 2017. Children <18 months with a reactive screening test were tested for HIV infection using total nucleic acid (TNA) PCR. Parents (61.1%) or legal guardians (38.9%) provided information on children's clinical history. Children aged 10-14 years also answered a questionnaire on knowledge and behaviors. RESULTS: HIV prevalence was 2.1% [95% confidence interval (CI): 1.5-2.6]. Prevalence in 10-14 year olds (3.2%; 95% CI: 2.1, 4.2) was significantly greater compared to 0-4 year olds (1.0%; 95% CI: 0.5, 1.6). HIV prevalence in girls and boys was 2.6% (95% CI: 1.8-3.3) and 1.5% (95% CI: 1.0-2.1), respectively. Based on reported status and/or the presence of detectable antiretrovirals, 81.1% (95% CI: 71.7-90.4) of HIV-positive children were aware of their status, 98.2% (95% CI: 90.7-100.0) of those aware were on antiretroviral therapy (ART) and 73.9% (95% CI: 62.1-85.8) of those on ART were virally suppressed. CONCLUSIONS: Despite the roll-out of Option B+ in Lesotho in 2013, pediatric HIV prevalence remains high. Further research is required to understand the greater prevalence among girls, barriers to PMTCT, and how to better achieve viral suppression in children with HIV.

High HIV prevalence and associated factors in Lesotho: Results from a population-based survey.

Despite extensive global efforts, sub-Saharan Africa remains disproportionately affected by the HIV epidemic. This generalized epidemic can be seen in Lesotho which in 2014 the HIV prevalence rate of those aged 15-49 years was 24.6%, with and incidence of 1.9 new infections per 100-person-year exposures. To better understand the impact of Lesotho's national HIV response and significant predictors associated with HIV infection, the Lesotho Population-based HIV Impact Assessment was conducted. This survey provided a nationally representative sample of individuals aged 15-59 years old in which participants were tested for HIV and given an individual questionnaire that included socio-demographic and behavioral risk questions. The association of factors between survey questions and HIV incident was assessed using logistic regression. Multivariate logistic regression models for men and women were constructed for each outcome using variables known to be or plausibly associated with recent or chronic infection. Overall annualized incidence among people aged 15-49 was 1.19% (95% CI 0.73-1.65) per year. The overall prevalence of HIV was 25.6% with women having significantly higher prevalence. Multiple variables, including decreased wealth status, lower education levels, marital status, condom use at first sex, and circumcision (men only) were identified as being significantly associated with HIV infection for both men and women. In combination with improving the awareness of HIV status, an increased focus is needed on AGYW and men 35-49 years old to prevent new infections. HIV education and prevention programs should focus heavily on younger age groups prior to and soon after sexual debut to prevent HIV transmission. The findings of the survey showed significant room for improvement in increasing awareness of HIV status and reinforcing the need for continued HIV prevention and treatment efforts in Lesotho to prevent new infections.

Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.

INTRODUCTION: The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. METHODS: We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. RESULTS: We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART. CONCLUSIONS: Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence.

Progress toward HIV epidemic control in Lesotho.

OBJECTIVE: The Lesotho Population-based HIV Impact Assessment survey was conducted nationally and designed to measure HIV prevalence, incidence, and viral load suppression (VLS). DESIGN: A nationally representative sample of 9403 eligible households was surveyed between November 2016 and May 2017; analyses account for study design. Consenting participants provided blood samples, socio-demographic, and behavioral information. METHODS: Blood samples were tested using the national rapid HIV testing algorithm. HIV-seropositive results were confirmed with Geenius supplemental assay. Screening for detectable concentrations of antiretroviral analytes was conducted on dried blood specimens from all HIV-positive adults using high-resolution liquid chromatography coupled with tandem mass spectrometry. Self-reported and/or antiretroviral biomarker data were used to classify individuals as HIV-positive and on treatment. Viral load testing was performed on all HIV-positive samples at central labs. VLS was defined as HIV RNA below 1000 copies/ml. RESULTS: Overall, 25.6% of adults aged 15-59 years were HIV-positive. Among seropositive adults, 81.0% (male 76.6%, female 84.0%) reported knowing their HIV status, 91.8% of people living with HIV (male 91.6%, female 92.0%) who reported knowing their status reporting taking antiretrovirals, and 87.7% (male and female 87.7%) of these had VLS. Younger age was significantly associated with being less likely to be aware of HIV status for both sexes. CONCLUSIONS: Findings from this population-based survey provide encouraging data in terms of HIV testing and treatment uptake and coverage. Specific attention to reaching youth to engage them in HIV-related interventions are critical to achieving epidemic control.

Correlates of HIV infection in adolescent girls and young women in Lesotho: results from a population-based survey.

BACKGROUND: HIV acquisition remains high among adolescent girls and young women (AGYW, aged 15-24 years) in sub-Saharan Africa. We aimed to estimate prevalence and incidence of HIV in AGYW and to identify correlates of HIV infection by using data from the Lesotho Population-based HIV Impact Assessment (LePHIA). METHODS: LePHIA was a nationally representative survey of adults and children based on a multistage cluster sampling method with random selection of enumeration areas and households. All adults aged 15 years and older who had slept in the household the night before were eligible for participation; participants completed an interview and HIV testing. We estimated incidence with the HIV-1 limiting antigen avidity enzyme immunoassay combined with viral load and examined the association between demographic and behavioural variables (including characteristics of cohabitating mothers and sexual partners, when available) and prevalence and incidence among AGYW using logistic regression, incorporating survey weights. FINDINGS: We interviewed 8824 households, including 2358 AGYW who were tested for HIV infection. Weighted HIV prevalence was 11·1% (95% CI 9·7-12·5) in the overall population (273 of 2358 AGYW), 5·7% (4·1-7·2) in adolescent girls aged 15-19 years (64 of 1156), and 16·7% (14·4-19·0) in women aged 20-24 years (209 of 1212). Annualised HIV incidence was 1·8% (0·8-2·8). Correlates of prevalent infection include reporting a history of anal sex (adjusted odds ratio [aOR] 3·08, 1·11-8·57), having lived outside Lesotho in the past year (1·86, 1·01-3·42), having a partner suspected or known to be HIV positive (11·7, 6·0-22·5), and having two or more lifetime sexual partners (1·84, 1·21-2·78, for 2-3 lifetime sexual partners; 2·44, 1·45-4·08, for ≥4 lifetime sexual partners). For the 570 AGYW living with their mothers, maternal education was negatively associated with HIV prevalence in their daughters (aOR 0·36, 0·15-0·82, per increase in level attended). For AGYW with a cohabitating partner, the factors associated with AGYW infection were partner age (OR 4·54, 1·30-15·80, for partners aged 35-49 years, although the OR was no longer significant when adjusted for HIV status of partner), HIV status (aOR 11·22, 4·05-31·05), lack of viral load suppression (OR 0·16, 0·04-0·66), and partner employment in the past year (aOR 3·41, 1·12-10·42). INTERPRETATION: The findings confirm the importance of improving the treatment cascade in male partners and targeting preventive interventions to AGYW who are at increased risk. A regional approach to prevention could mitigate the effect of migration on transnational spread of HIV. FUNDING: President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Evaluation of non-adherence to anti-retroviral therapy, the associated factors and infant outcomes among HIV-positive pregnant women: a prospective cohort study in Lesotho.

INTRODUCTION: Success in addressing prevention of mother-to-child transmission of HIV depends largely on good adherence to anti-retroviral therapy (ART) by pregnant women. Knowledge of the levels of ART adherence among pregnant women is essential to inform strategies to prevent or reduce HIV transmission rates, particularly in African settings. Aim: the primary objective of this study was to measure adherence to anti-retroviral therapy (ART) among pregnant women living with human immunodeficiency virus (HIV). The secondary objectives were to determine: i) the rate of new infections among children at Mabote Filter Clinic in Maseru, Lesotho whose mothers were enrolled in PMTCT, and ii) the factors associated with non-adherence to ART among pregnant women. METHODS: In this prospective cohort study, HIV-positive pregnant women receiving antiretroviral therapy (ART) for prevention of mother to child transmission (PMTCT) were followed up to delivery and their children were tested for HIV. We collected socio-demographic information, knowledge of PMTCT and adherence to ART (three-day recall and pill count) including reasons for non-adherence. We also used logistic regression to explore factors associated with non-adherence. RESULTS: One hundred and seven women were included. The mean (standard deviation) age of the participants was 28.2 (5.7) years. Most, 81.3% (87/107), were married, only 9.3% (10/107) had a postsecondary education. Two-thirds (63.6%: 68/107) of the participants started ART because of PMTCT. Only 78.5% (84/107) of the participants had adequate knowledge of the importance of PMTCT. The three-day self-reported non-adherence rate at the first visit was 7.5% (95% confidence interval (CI): 3.7, 13.1), but up to 43.4% (95% CI: 35.2, 51.9) using pill count. The most frequently reported reasons for not adhering were: running out of pills (7.5%), nausea (5.6%) and to avoid side-effects (3.7%). Women who were employed (odds ratio (OR) 4.35; 95% CI: 1.38,14.29; p = 0.012) and at a higher gestational age (OR = 1.43; 95% CI: 1.11, 1.85; p = 0.006) were more likely to be non-adherent. Only 1 of the 77 exposed infants was found to be positive for HIV at 6 weeks after birth. CONCLUSION: We found a higher non-adherence rate for participants with pill count compared to a three-day adherence self-report. However, mother to child HIV transmission was relatively low. Lack of employment and relatively high gestational age were found to be predictive factors of non-adherence.

Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials.

As a response to the human immunodeficiency virus (HIV) epidemic and part of Canadian Institutes for Health Research's mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN's Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources.