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.

Improving child tuberculosis contact identification and screening in Lesotho: Results from a mixed-methods cluster-randomized implementation science study.

BACKGROUND: Child tuberculosis (TB) contact management is recommended for preventing TB in children but its implementation is suboptimal in high TB/HIV-burden settings. The PREVENT Study was a mixed-methods, clustered-randomized implementation study that evaluated the effectiveness and acceptability of a community-based intervention (CBI) to improve child TB contact management in Lesotho, a high TB burden country. METHODS: Ten health facilities were randomized to CBI or standard of care (SOC). CBI holistically addressed the complex provider-, patient-, and caregiver-related barriers to prevention of childhood TB. Routine TB program data were abstracted from TB registers and cards for all adult TB patients aged >18 years registered during the study period, and their child contacts. Primary outcome was yield (number) of child contacts identified and screened per adult TB patient. Generalized linear mixed models tested for differences between study arms. CBI acceptability was assessed via semi-structured in-depth interviews with a purposively selected sample of 20 healthcare providers and 28 caregivers. Qualitative data were used to explain and confirm quantitative results. We used thematic analysis to analyze the data. RESULTS: From 01/2017-06/2018, 973 adult TB patients were recorded, 490 at CBI and 483 at SOC health facilities; 64% male, 68% HIV-positive. At CBI and SOC health facilities, 216 and 164 child contacts were identified, respectively (p = 0.16). Screening proportions (94% vs. 62%, p = 0.13) were similar; contact yield per TB case (0.40 vs. 0.20, p = 0.08) was higher at CBI than SOC health facilities, respectively. CBI was acceptable to caregivers and healthcare providers. CONCLUSION: Identification and screening for TB child contacts were similar across study arms but yield was marginally higher at CBI compared with SOC health facilities. CBI scale-up may enhance the ability to reach and engage child TB contacts, contributing to efforts to improve TB prevention among children.

Human Immunodeficiency Virus Infection in Adolescents and Mode of Transmission in Southern Africa: A Multinational Analysis of Population-Based Survey Data.

BACKGROUND: Adolescents aged 10-19 years living with human immunodeficiency virus (HIV) (ALHIV), both perinatally infected adolescents (APHIV) and behaviorally infected adolescents (ABHIV), are a growing population with distinct care needs. We characterized the epidemiology of HIV in adolescents included in Population-based HIV Impact Assessments (2015-2017) in Zimbabwe, Malawi, Zambia, Eswatini, and Lesotho. METHODS: Adolescents were tested for HIV using national rapid testing algorithms. Viral load (VL) suppression (VLS) was defined as VL <1000 copies/mL, and undetectable VL (UVL) as VL <50 copies/mL. Recent infection (within 6 months) was measured using a limiting antigen avidity assay, excluding adolescents with VLS or with detectable antiretrovirals (ARVs) in blood. To determine the most likely mode of infection, we used a risk algorithm incorporating recency, maternal HIV and vital status, history of sexual activity, and age at diagnosis. RESULTS: HIV prevalence ranged from 1.6% in Zambia to 4.8% in Eswatini. Of 707 ALHIV, 60.9% (95% confidence interval, 55.3%-66.6%) had HIV previously diagnosed, and 47.1% (41.9%-52.3%) had VLS. Our algorithm estimated that 72.6% of ALHIV (485 of 707) were APHIV, with HIV diagnosed previously in 69.5% of APHIV and 39.4% of ABHIV, and with 65.3% of APHIV and 33.5% of ABHIV receiving ARV treatment. Only 67.2% of APHIV and 60.5% of ABHIV receiving ARVs had UVL. CONCLUSIONS: These findings suggest that two-thirds of ALHIV were perinatally infected, with many unaware of their status. The low prevalence of VLS and UVL in those receiving treatment raises concerns around treatment effectiveness. Expansion of opportunities for HIV diagnoses and the optimization of treatment are imperative.

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.

Provider attitudes about childhood tuberculosis prevention in Lesotho: a qualitative study.

BACKGROUND: The World Health Organization estimated that 1.12 million children developed tuberculosis (TB) in 2018, and at least 200,000 children died from TB. Implementation of effective child contact management is an important strategy to prevent childhood TB but these practices often are not prioritized or implemented, particularly in low- and middle-income countries. This study aimed to explore attitudes of healthcare providers toward TB prevention and perceived facilitators and challenges to child contact management in Lesotho, a high TB burden country. Qualitative data were collected via group and individual in-depth interviews with 12 healthcare providers at five health facilities in one district and analyzed using a thematic framework. RESULTS: Healthcare providers in our study were interested and committed to improve child TB contact management and identified facilitators and challenges to a successful childhood TB prevention program. Facilitators included: provider understanding of the importance of TB prevention and enhanced provider training on child TB contact management, with a particular focus on ruling out TB in children and addressing side effects. Challenges identified by providers were at multiple levels -- structural, clinic, and individual and included: [1] access to care, [2] supply-chain issues, [3] identification and screening of child contacts, and [4] adherence to isoniazid preventive therapy. CONCLUSIONS: Given the significant burden of TB morbidity and mortality in young children and the recent requirement by the WHO to report IPT initiation in child contacts, prioritization of child TB contact management is imperative and should include enhanced provider training on childhood TB and mentorship as well as strategies to eliminate challenges. Strategies that enable more efficient child TB contact management delivery include creating standardized tools that facilitate the implementation, tracking, and monitoring of child TB contact management coupled with guidance and mentorship from the district health management team. To tackle access to care challenges, we propose delivering intensive community health education, conducting community screening more efficiently using standardized tools, and facilitating access to services in the community.

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.

Association between severe drought and HIV prevention and care behaviors in Lesotho: A population-based survey 2016-2017.

BACKGROUND: A previous analysis of the impact of drought in Africa on HIV demonstrated an 11% greater prevalence in HIV-endemic rural areas attributable to local rainfall shocks. The Lesotho Population-Based HIV Impact Assessment (LePHIA) was conducted after the severe drought of 2014-2016, allowing for reevaluation of this relationship in a setting of expanded antiretroviral coverage. METHODS AND FINDINGS: LePHIA selected a nationally representative sample between November 2016 and May 2017. All adults aged 15-59 years in randomly selected households were invited to complete an interview and HIV testing, with one woman per household eligible to answer questions on their experience of sexual violence. Deviations in rainfall for May 2014-June 2016 were estimated using precipitation data from Climate Hazards Group InfraRed Precipitation with Station Data (CHIRPS), with drought defined as <15% of the average rainfall from 1981 to 2016. The association between drought and risk behaviors as well as HIV-related outcomes was assessed using logistic regression, incorporating complex survey weights. Analyses were stratified by age, sex, and geography (urban versus rural). All of Lesotho suffered from reduced rainfall, with regions receiving 1%-36% of their historical rainfall. Of the 12,887 interviewed participants, 93.5% (12,052) lived in areas that experienced drought, with the majority in rural areas (7,281 versus 4,771 in urban areas). Of the 835 adults living in areas without drought, 520 were in rural areas and 315 in urban. Among females 15-19 years old, living in a rural drought area was associated with early sexual debut (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.43-6.74, p = 0.004), and higher HIV prevalence (OR 2.77, 95% CI 1.19-6.47, p = 0.02). It was also associated with lower educational attainment in rural females ages 15-24 years (OR 0.44, 95% CI 0.25-0.78, p = 0.005). Multivariable analysis adjusting for household wealth and sexual behavior showed that experiencing drought increased the odds of HIV infection among females 15-24 years old (adjusted OR [aOR] 1.80, 95% CI 0.96-3.39, p = 0.07), although this was not statistically significant. Migration was associated with 2-fold higher odds of HIV infection in young people (aOR 2.06, 95% CI 1.25-3.40, p = 0.006). The study was limited by the extensiveness of the drought and the small number of participants in the comparison group. CONCLUSIONS: Drought in Lesotho was associated with higher HIV prevalence in girls 15-19 years old in rural areas and with lower educational attainment and riskier sexual behavior in rural females 15-24 years old. Policy-makers may consider adopting potential mechanisms to mitigate the impact of income shock from natural disasters on populations vulnerable to HIV transmission.

Pediatric HIV Treatment Gaps in 7 East and Southern African Countries: Examination of Modeled, Survey, and Routine Program Data.

BACKGROUND: Remarkable success in the prevention and treatment of pediatric HIV infection has been achieved in the past decade. Large differences remain between the estimated number of children living with HIV (CLHIV) and those identified through national HIV programs. We evaluated the number of CLHIV and those on treatment in Lesotho, Malawi, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We assessed the total number of CLHIV, CLHIV on antiretroviral treatment (ART), and national and regional ART coverage gaps using 3 data sources: (1) Joint United Nations Programme on HIV/AIDS model-based estimates and national program data used as input values in the models, (2) population-based HIV impact surveys (PHIA), and (3) program data from the President's Emergency Plan for AIDS Relief (PEPFAR)-supported clinics. RESULTS: Across the 7 countries, HIV prevalence among children aged 0-14 years ranged from 0.4% (Uncertainty Bounds (UB) 0.2%-0.6%) to 2.8% (UB: 2.2%-3.4%) according to the PHIA surveys, resulting in estimates of 520,000 (UB: 460,000-580,000) CLHIV in 2016-2017 in the 7 countries. This compared with Spectrum estimates of pediatric HIV prevalence ranging from 0.5% (UB: 0.5%-0.6%) to 3.5% (UB: 3.0%-4.0%) representing 480,000 (UB: 390,000-550,000) CLHIV. CLHIV not on treatment according to the PEPFAR, PHIA, and Spectrum for the countries stood at 48% (UB: 25%-60%), 49% (UB: 37%-50%), and 38% (UB: 24%-47%), respectively. Of 78 regions examined across 7 countries, 33% of regions (PHIA data) or 41% of regions (PEPFAR data) had met the ART coverage target of 81%. CONCLUSIONS: There are substantial gaps in the coverage of HIV treatment in CLHIV in the 7 countries studied according to all sources. There is continued need to identify, engage, and treat infants and children. Important inconsistencies in estimates across the 3 sources warrant in-depth investigation.

The PREVENT study to evaluate the effectiveness and acceptability of a community-based intervention to prevent childhood tuberculosis in Lesotho: study protocol for a cluster randomized controlled trial.

BACKGROUND: Effective, evidence-based interventions to prevent childhood tuberculosis (TB) in high TB/HIV-burden, resource-limited settings are urgently needed. There is limited implementation of evidence-based contact management strategies, including isoniazid preventive therapy (IPT), for child contacts of TB cases in Lesotho. METHODS/DESIGN: This mixed-methods implementation science study utilizes a two-arm cluster-randomized trial design with randomization at the health facility level. The study aims to evaluate the effectiveness and acceptability of a combination community-based intervention (CBI) versus standard of care (SOC) for the management of child TB contacts. The study includes three phases: (I) exploratory phase; (II) intervention implementation and testing phase; (III) post-intervention explanatory phase. Healthcare provider interviews to inform intervention refinement (phase I) were completed in December 2015. In phase II, 10 health facilities were randomized to deliver the CBI or SOC, with stratification by facility type (i.e., hospital vs. health center). CBI holistically addresses the complex provider-related, patient-related, and caregiver-related barriers to prevention of childhood TB through nurse training and mentorship; health education for caregivers and patients by village health workers; adherence support using text messaging and village health workers; and multidisciplinary team meetings, where programmatic data are reviewed and challenges and solutions are discussed. SOC sites follow country guidelines for child TB contact management. Routine TB program data will be abstracted for all adult TB cases newly registered during the study period and their child contacts from TB registers and cards. The anticipated sample size is 1080 child contacts. Primary outcomes are yield (number) of child contacts, including children < 5 years of age and HIV-positive children < 15 years of age; IPT initiation; and IPT completion. Secondary outcomes include HIV testing; yield of active prevalent TB among child contacts; and acceptability and utilization of CBI components. Intervention implementation began in February 2016 and is ongoing. Post-intervention interviews with healthcare providers and caregivers (phase III) commenced in February 2017. DISCUSSION: The PREVENT study tests the effectiveness and acceptability of a novel combination CBI for child TB contact management in Lesotho. If effective, CBI will have important implications for addressing childhood TB in Lesotho and elsewhere. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02662829 . Registered on 15 January 2016.

Reaching the end of the line: Operational issues with implementing phone-based unannounced pill counts in resource-limited settings.

INTRODUCTION: Accurate measurement of adherence is necessary to ensure that therapeutic outcomes can be attributed to the recommended treatment. Phone-based unannounced pill counts were shown to be feasible and reliable measures of adherence in developed settings; and have been further used as part of medication adherence interventions. However, it is not clear whether this method can be implemented successfully in resource-limited settings, where cellular network and mobile phone coverage may be low. Our objective is to describe operational issues surrounding the use of phone-based unannounced pill counts in Lesotho and Ethiopia. METHODS: Phone-based monthly unannounced pill counts, using an adaptation of a standardized protocol from previous US-based studies, were utilized to measure anti-TB and antiretroviral medication adherence in two implementation science studies in resource-limited settings, START (Lesotho) and ENRICH (Ethiopia). RESULTS: In START, 19.6% of calls were completed, with 71.9% of participants reached at least once; majority of failed call attempts were due to phones not being available (54.8%) or because participants were away from the pills (32.7%). In ENRICH, 33.5% of calls were completed, with 86.7% of participants reached at least once; the main reasons for failed call attempts were phones being switched off (31.5%), participants not answering (27.3%), participants' discomfort speaking on the phone (15.4%), and network problems (13.2%). Structural, facility-level, participant-level, and data collection challenges were encountered in these settings. DISCUSSION: Phone-based unannounced pill counts were found to be challenging, and response rates suboptimal. While some of these challenges were specific to local contexts, most of them are generalizable to resource-limited settings. In a research study context, a possible solution to ease operational challenges may be to focus phone-based unannounced pill count efforts on a randomly selected sample from participants who are provided with study phones and rigorously ensure that call attempts are made for these participants.

Prevalence, patterns, and correlates of HIV disclosure among TB-HIV patients initiating antiretroviral therapy in Lesotho.

Disclosure of HIV-positive status has important implications for patient outcomes and preventing HIV transmission, but has been understudied in TB-HIV patients. We assessed disclosure patterns and correlates of non-disclosure among adult TB-HIV patients initiating ART enrolled in the START Study, a mixed-methods cluster-randomized trial conducted in Lesotho, which evaluated a combination intervention package (CIP) versus standard of care. Interviewer-administered questionnaire data were analyzed to describe patterns of disclosure. Patient-related factors were assessed for association with non-disclosure to anyone other than a health-care provider and primary partners using generalized linear mixed models. Among 371 participants, 95% had disclosed their HIV diagnosis to someone other than a health-care provider, most commonly a spouse/primary partner (76%). Age, TB knowledge, not planning to disclose TB status, greater perceived TB stigma, and CIP were associated with non-disclosure in unadjusted models (p < .1). In adjusted models, all point estimates were similar and greater TB knowledge (adjusted odds ratio [aOR] 0.59, 95% confidence interval [CI] 0.39-0.90) and CIP (aOR 0.20, 95% CI 0.05-0.79) remained statistically significant. Among 220 participants with a primary partner, 76% had disclosed to that partner. Significant correlates of partner non-disclosure (p < .1) in unadjusted analyses included being female, married/cohabitating, electricity at home, not knowing if partner was HIV-positive, and TB knowledge. Adjusted point estimates were largely similar, and being married/cohabitating (aOR 0.03, 95% CI 0.01-0.12), having electricity at home (aOR 0.38, 95% CI 0.17-0.85) and greater TB knowledge (aOR 0.76, 95% CI 0.59-0.98) remained significant. In conclusion, although nearly all participants reported disclosing their HIV status to someone other than a health-care provider at ART initiation, nearly a quarter of participants with a primary partner had not disclosed to their partner. Additional efforts to support HIV disclosure (e.g., counseling) may be needed for TB-HIV patients, particularly for women and those unaware of their partners' status.

Using mHealth for HIV/TB Treatment Support in Lesotho: Enhancing Patient-Provider Communication in the START Study.

BACKGROUND: mHealth is a promising means of supporting adherence to treatment. The Start TB patients on ART and Retain on Treatment (START) study included real-time adherence support using short-text messaging service (SMS) text messaging and trained village health workers (VHWs). We describe the use and acceptability of mHealth by patients with HIV/tuberculosis and health care providers. METHODS: Patients and treatment supporters received automated, coded medication and appointment reminders at their preferred time and frequency, using their own phones, and $3.70 in monthly airtime. Facility-based VHWs were trained to log patient information and text message preferences into a mobile application and were given a password-protected mobile phone and airtime to communicate with community-based VHWs. The use of mHealth tools was analyzed from process data over the study course. Acceptability was evaluated during monthly follow-up interviews with all participants and during qualitative interviews with a subset of 30 patients and 30 health care providers at intervention sites. Use and acceptability were contextualized by monthly adherence data. FINDINGS: From April 2013 to August 2015, the automated SMS system successfully delivered 39,528 messages to 835 individuals, including 633 patients and 202 treatment supporters. Uptake of the SMS intervention was high, with 92.1% of 713 eligible patients choosing to receive SMS messages. Patient and provider interviews yielded insight into barriers and facilitators to mHealth utilization. The intervention improved the quality of health communication between patients, treatment supporters, and providers. HIV-related stigma and technical challenges were identified as potential barriers. CONCLUSIONS: The mHealth intervention for HIV/tuberculosis treatment support in Lesotho was found to be a low-tech, user-friendly intervention, which was acceptable to patients and health care providers.

The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial.

BACKGROUND: Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. OBJECTIVE: The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. DESIGN: Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6-9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. DISCUSSION: The START Study evaluates a CIP targeting barriers to early ART implementation among TB/HIV patients. If the CIP is found effective and acceptable, this study has the potential to inform care for TB/HIV patients in high-burden, resource-limited countries in sub-Saharan Africa.

Decentralization of pediatric HIV care and treatment in five sub-Saharan African countries.

BACKGROUND: In resource-limited settings, decentralization of HIV care and treatment is a cornerstone of universal care and rapid scale-up. We compared trends in pediatric enrollment and outcomes at primary (PHFs) vs secondary/tertiary health facilities (SHFs). METHODS: Using aggregate program data reported quarterly from 274 public facilities in Kenya, Lesotho, Mozambique, Rwanda, and Tanzania from January 2008 to March 2010, we examined trends in number of children younger than 15 years of age initiating antiretroviral treatment (ART) by facility type. We compared clinic-level lost to follow-up (LTFU) and mortality per 100 person-years (PYs) on ART during the period by facility type. RESULTS: During the 2-year period, 17,155 children enrolled in HIV care and 8475 initiated ART in 182 (66%) PHFs and 92(34%) SHFs. PHFs increased from 56 to 182, whereas SHFs increased from 72 to 92 sites. SHFs accounted for 71% of children initiating ART; however, the proportion of children initiating ART each quarter at PHFs increased from 17% (129) to 44% (463) in conjunction with an increase in PHFs during observation period. The average LTFU and mortality rates for children on ART were 9.8/100 PYs and 5.2/100 PYs, respectively, at PHFs and 20.2/100 PYs and 6.0/100 PYs, respectively, at SHFs. Adjusted models show PHFs associated with lower LTFU (adjusted rate ratio = 0.55; P = 0.022) and lower mortality (adjusted rate ratio = 0.66; P = 0.028). CONCLUSIONS: The expansion of pediatric services to PHFs has resulted in increased numbers of children on ART. Early findings suggest lower rates of LTFU and mortality at PHFs. Successful scale-up will require further expansion of pediatric services within PHFs.

Pharmacokinetics of nevirapine in HIV-infected children receiving an adult fixed-dose combination of stavudine, lamivudine and nevirapine.

OBJECTIVE: To evaluate the steady state pharmacokinetics of nevirapine (NVP) in HIV-infected children receiving a fixed-dose combination of stavudine, lamivudine and NVP. METHODS: This cross-sectional study enrolled 34 children (18 girls) who had received GPO-VIR S30 (30 mg stavudine, 150 mg lamivudine and 200 mg NVP) for at least 8 weeks. Tablets were divided into quarter fractions (1/4, 1/2, 3/4 or 1 tablet) to attain the NVP dosages of 120-200 mg/m every 12 h. Plasma NVP levels were measured at predose, and at 2 and 6 h after drug administration. RESULTS: The median age was 8.4 years (range, 3-15). Median CD4 lymphocyte count and percentage at study entry was 576 x 10 cells/l and 20.25%, respectively. The median pharmacokinetics parameters were area under the curve at 12 h, 78.4 h x mug/ml; minimum plasma drug concentration, 5.98 microg/ml; plasma half-life, 25.5 h; apparent oral clearance, 0.079 l/kg per h; and volume of distribution, 2.95 l/kg. Only one child had a minimum plasma drug concentration < 3.4 microg/ml (2.57 microg/ml). Of the 13 children who received GPO-VIR as their first-line regimen, 12 had plasma HIV-1 RNA < 400 copies/ml at 6-18 months, with a median CD4 lymphocyte increase of 216 and 433 x 10 cells/l at 6 and 12 months of treatment, respectively. CONCLUSIONS: The administration of GPO-VIR S30 fixed-dose combination tablets in fractions or as a whole tablet to children resulted in appropriate NVP exposure and satisfactory virological and immunological benefit. This finding confirms the effectiveness of using a fixed-dose combination as a "transitional option" while waiting for a paediatric fixed-dose combination drug formulation.