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.

24-Month HIV-free survival among HIV-exposed Infants in Lesotho: the PEAWIL cohort study.

INTRODUCTION: Following the implementation of the provision of lifelong antiretroviral therapy to all HIV-positive pregnant or breastfeeding women for prevention of mother-to-child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24-month HIV-free survival among HIV-exposed infants (HEIs). METHODS: We conducted a prospective observational cohort study that enrolled HIV-positive and HIV-negative pregnant women, with follow-up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow-up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV-free survival rates were computed using Kaplan-Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death. RESULTS: Between June 2014 and February 2016, we enrolled 653 HIV-positive and 941 HIV-negative pregnant women. Twenty-seven HIV-negative women acquired HIV during follow-up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV-unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24-month follow-up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow-up, 17 were found to be HIV-positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow-up were HIV-positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV-positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24-month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log-rank p = 0.065). HIV-free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants. CONCLUSIONS: The implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.

18-24-month HIV-free survival as measurement of the effectiveness of prevention of mother-to-child transmission in the context of lifelong antiretroviral therapy: Results of a community-based survey.

INTRODUCTION: Population-based HIV-free survival at 18-24 months of age among HIV-exposed infants in high prevalence settings in the era of treatment for all is largely unknown. We conducted a community-based survey to determine outcomes of HIV-exposed infants at 18-24 months in Lesotho. METHODS: Between November 2015 and December 2016, we conducted a survey among households with a child born 18-24 months prior to data collection. Catchment areas from 25 health facilities in Butha-Buthe, Maseru, Mohale's Hoek and Thaba-Tseka districts were randomly selected using probability proportional to size sampling. Consecutive households were visited and eligible consenting caregivers and children were enrolled. Rapid HIV antibody testing was performed on mothers of unknown HIV status (never tested or tested HIV-negative >3 months prior) and their children, and to children born to known HIV-positive mothers. Information on demographics, health-seeking behavior, HIV, and mortality were captured for mothers and children, including those who died. The difference in survival between subgroups was determined using the log-rank test. RESULTS: Of the 1,852 mothers/caregivers enrolled, 570 mothers were HIV-positive. The mother-to-child HIV transmission rate was 5.7% [95% CI: 4.0-8.0]. The mortality rate was 2.6% [95% CI: 1.6-4.2] among HIV-exposed children compared to 1.4% (95% CI: 0.9-2.3) among HIV-unexposed children. HIV-free survival was 91.8% [95% CI: 89.2-93.8] among HIV-exposed infants. Disclosure of mother's HIV status (aOR = 4.9, 95% CI: 1.3-18.2) and initiation of cotrimoxazole prophylaxis in the child (aOR = 3.9, 95% CI: 1.2-12.6) were independently associated with increased HIV-free survival while child growth problems (aOR = 0.2, 95% CI: 0.09-0.5) were independently associated with reduced HIV-free survival. CONCLUSION: Even in the context of lifelong antiretroviral therapy among pregnant and breastfeeding women, HIV has a significant effect on survival among HIV-exposed children compared to unexposed children. Lesotho has not reached elimination of HIV transmission from mother to child.

Comparison of 6-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART: Results from an observational prospective cohort study.

BACKGROUND: Lifelong antiretroviral therapy (ART) reduces mother-to-child HIV transmission (MTCT) and improves maternal health. Data on the outcomes of HIV-exposed infants (HEI) compared to their unexposed counterparts in the era of universal ART is limited. We compared birth and 6-week outcomes among infants born to HIV-positive and HIV-negative women in Lesotho. METHODS: 941 HIV-negative and 653 HIV-positive pregnant women were enrolled in an observational cohort to evaluate the effectiveness of prevention of mother-to-child HIV transmission (PMTCT) program after implementation of universal maternal ART in 14 health facilities. Pregnancy, delivery, birth, and 6-week data were collected through participant interviews and medical record review. DNA PCR testing for HEI was conducted within 2 weeks of birth and at around 6 weeks of age. Data were analysed to estimate the distribution of birth outcomes, mortality, HIV transmission and HIV-free survival at 6 weeks. RESULTS: HIV-positive women were older (mean age of 28.7 vs. 24.4 years) and presented for antenatal care earlier (mean gestational age of 23.0 weeks vs 25.3 weeks) than HIV-negative women. Prematurity was more frequent among HEI, 7.8% vs. 3.6%. There was no difference in rates of congenital anomalies between HEI (1.0%) and HIV-unexposed infants (HUI) (0.6%). Cumulative HIV transmission was 0.9% (N = 4/431) (95% CI:0.25-2.36) at birth and 1.0% (N = 6/583) (95% CI:0.38-2.23) at 6 weeks. Overall mortality, including stillbirths, was 5.2% and 6.0% by 6 weeks for HUI and HEI respectively. Among liveborn infants, 6-week HIV-free survival for HEI was 95.6% (95% CI:93.7-97.1) compared to 96.8% (95% CI:95.4-97.9) survival for HUI. CONCLUSIONS: Implementation of universal maternal ART lowers MTCT at 6 weeks of age with no differences in congenital anomalies or early mortality between HIV exposed Infants and HIV unexposed infants. However, HIV exposed infants continue to have high rates of prematurity despite improved maternal health on ART.

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.

HIV incidence among pregnant and postpartum women in a high prevalence setting.

In sub-Saharan Africa, most women who test HIV negative at the first antenatal care encounter are rarely tested again during pregnancy and postpartum, yet data suggests that pregnancy is associated with increased risk of HIV acquisition compared to non-pregnant women. We describe HIV incidence during pregnancy and postpartum in Lesotho, a high prevalence setting, and factors associated with HIV seroconversion. We enrolled a cohort of HIV negative women presenting at health facilities for antenatal care and followed them through delivery up to 24 months postpartum. Women were repeatedly tested for HIV according to the Lesotho Ministry of Health routine rapid HIV testing guidelines and responded to risk behavior questionnaire every three months. We estimated HIV incidence and associated 95% confidence intervals. We used mixed effects Cox regression models to identify independent factors associated with seroconversion accounting for repeated assessment. The estimated overall HIV incidence rate was 1.58 (95% CI: 1.05-2.28) per 100 person- years. The estimated HIV incidence rate during pregnancy (2.61 per 100 person-years, 95% CI: 1.12-5.14) was almost double the estimated HIV incidence during postpartum (1.36 per 100 person-years, 95% CI: 0.83-2.10). Women's age (14-24 years compared to 25-45 years), multiple sexual partnerships, urethral discharge and no condoms nor pre-exposure prophylaxis were independently associated with HIV infection. There is an increased need for counseling and support of HIV-uninfected pregnant and breastfeeding women to stay HIV-negative, including provision of pre-exposure prophylaxis during this high-risk period, particularly among adolescent and young women.

Characteristics of Treatment-experienced HIV-infected African Children and Adolescents Initiating Darunavir and/or Etravirine-based Antiretroviral Treatment.

BACKGROUND: Data are limited on the selection and sequencing of second-line and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program. METHODS: This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV-based and/or ETR-based ART. Descriptive statistics were used. RESULTS: Study enrolled 48 patients (45.8% women; median age = 15 years [interquartile range 17.7-10.3]) at 9 clinical sites in Zambia, Swaziland, Kenya and Lesotho. The majority (87.5%; n = 42) had received ≥2 prior ART regimens; most (81.2%) had received lopinavir/ritonavir-based ART before switch. All patients had detectable HIV RNA (median = 56,653 copies/mL). Forty seven patients (98.9%) had HIV genotype results: 41 (87.2%) had ≥1 nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistance mutation (RM), predominantly M184V (76.6%; n = 36); 31 (65.9%) had ≥1 non-NRTI-RM, including 27 (57.4%) with ≥1 ETR-RM; 30 (63.8%) had ≥3 protease inhibitor RM, including 20 (42.6%) with ≥1 DRV-RM. For new ART regimens, DRV and raltegravir were most frequently prescribed (83.3%; n = 40 on DRV and raltegravir, each). Eighteen patients (37.5%) were initiated on the NRTI-sparing ART. CONCLUSIONS: In our study, a significant proportion of treatment-experienced African children and adolescents had one or more DRV-RM and ETR-RM. For the new regimen, more than a third of pediatric patients failing second-line ART were prescribed NRTI-sparing regimens. Better understanding of the current approaches to pediatric ART sequencing in resource-limited settings is needed.