Prevention of Mother-to-Child Transmission of HIV-1 in Lesotho

The number of new pediatric HIV-1 infections is reducing globally as services for the prevention of mother-to-child transmission of HIV-1 (PMTCT) are being scaled up. Lesotho has one of the highest HIV burdens globally with an estimated HIV prevalence of 25.7% in antenatal care (ANC). In 2013, the Ministry of Health of Lesotho adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women, regardless of clinical or immunologic status (Option B+). Although this is expected to decrease mother-to-child transmission (MTCT) in general, program effectiveness data are only starting to emerge. In this thesis, I present results of three studies: conventional early infant diagnosis (EID) turnaround time (TAT); six-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART, and 18-24-month HIV-free survival measured through community survey. The overall aim of the study was to assess the effectiveness of the PMTCT program by determining birth outcomes and HIV-free survival of a prospective cohort of HIV-exposed infants compared to HIV-unexposed infants. In addition, we assess HIV-free survival among HIV-exposed children identified in the community who were born 18-24 months prior to study initiation. This was built on a baseline evaluation where we described turnaround time for EID when conventional EID was used. Methods: The baseline study was a retrospective cohort where data were abstracted from routine clinical records in health facility. The prospective observational cohort study included HIV-positive and HIV-negative women attending ANC and their infants up to 24 months postpartum; enrolled in the study June 2014 – February 2016. Study visits for HIV-positive mothers were three-monthly until 24 months after delivery, while HIV-negative mothers had study visits every three to six months after delivery. Demographic, social, and medical data were collected from participants during clinic visits through interviews and extraction of medical record information. For the community cross-sectional study, we captured the mortality and HIV infection outcomes of HIV-exposed children who were born after the introduction of Option B+. For all studies, quantitative data analysis was performed using Stata. Categorical variables were summarized using frequencies and percentages of participants, while continuous variables were summarized using means and standard deviations or medians and interquartile ranges, as appropriate. Maternal baseline characteristics were stratified by HIV status. For the baseline study, turnaround time geometric means (with 95% CI) were calculated and compared using linear mixed models. For the prospective cohort study, we compared birth outcomes between HEIs and HIV-unexposed infants (HUIs). Categorical variables were compared using Chi-square tests and continuous variables using t-tests or Wilcoxon rank-sum tests, as appropriate. HIV-free survival was estimated as the proportion of children alive and HIV-negative among HEI. For the community cross-sectional survey, the difference in survival between subgroups was determined using the log-rank test. Results: Concerning the baseline study, of the total of 1,187 infants reviewed, the turnaround time was 61.7 days (95% CI: 55.3-68.7). The longest turnaround time was time of results from central laboratory to district hospital, 23.3 days (95% CI: 18.7-29.0). Mean times from specimen transfer to the central laboratory and for result transfer from central laboratory to district hospital were significantly shorter in the Lowlands Region (0.9 and 16.2 days, respectively), compared to Highlands Region (6.0 [p = 0.030] and 34.3 days [p = 0.0099]. Results of the cohort study showed that prematurity was more frequent among HEI, 7.8% vs. 3.6%, although there was no difference in rates of congenital anomalies between HEI (1.0%) and HUI (0.6%). For HEI, cumulative HIV-1 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 six weeks. Among liveborn infants, six-week HIV-free survival for HEI was 95.6% (95% CI: 93.7–97.1). For the cross-sectional community survey, the MTCT rate was 5.7% [95% CI: 4.0-8.0] and the reported 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. The estimated HIV-free survival was 91.8% [95% CI: 89.2-93.8] among HEI. 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: The turnaround study showed that average EID turnaround time was two months; the longest period of delay was transfer of results from central laboratory to district hospital. Meanwhile the prospective cohort study showed that implementation of universal maternal ART lowers MTCT at six weeks of age with no differences in congenital anomalies or early mortality between HEIs and HUIs. Of note, HEIs were reported to have high rates of prematurity. From the community cross-sectional survey, despite scale up of lifelong ART among pregnant and breastfeeding women, HIV has a significant effect on survival among HIV-exposed children compared to unexposed children.Doktorgradsavhandlin

Pregnant and Postpartum Women’s Experiences and Perspectives on the Acceptability and Feasibility of Copackaged Medicine for Antenatal Care and PMTCT in Lesotho

Objective. To improve PMTCT and antenatal care-related service delivery, a pack with centrally prepackaged medicine was rolled out to all pregnant women in Lesotho in 2011. This study assessed acceptability and feasibility of this copackaging mechanism for drug delivery among pregnant and postpartum women. Methods. Acceptability and feasibility were assessed in a mixed method, cross-sectional study through structured interviews (SI) and semistructured interviews (SSI) conducted in 2012 and 2013. Results. 290 HIV-negative women and 437 HIV-positive women (n=727) participated. Nearly all SI participants found prepackaged medicines acceptable, though modifications such as size reduction of the pack were suggested. Positive experiences included that the pack helped women take pills as instructed and contents promoted healthy pregnancies. Negative experiences included inadvertent pregnancy disclosure and discomfort carrying the pack in communities. Implementation was also feasible; 85.2% of SI participants reported adequate counseling time, though 37.8% felt pack use caused clinic delays. SSI participants reported improvement in service quality following pack introduction, due to more comprehensive counseling. Conclusions. A prepackaged drug delivery mechanism for ANC/PMTCT medicines was acceptable and feasible. Findings support continued use of this approach in Lesotho with improved design modifications to reflect the current PMTCT program of lifelong treatment for all HIV-positive pregnant women

Adverse Pregnancy Outcomes Among HIV-positive Women in the Era of Universal Antiretroviral Therapy Remain Elevated Compared With HIV-negative Women

Background: Without treatment, HIV infection in pregnant women is associated with adverse pregnancy outcomes. We compared adverse pregnancy outcomes among HIV-positive women on antiretroviral therapy (ART) and HIV-negative women who enrolled for antenatal care in selected health facilities in Maseru district, Lesotho. Methods: We enrolled a cohort of HIV-positive and HIV-negative women at their first antenatal visit and followed them through delivery. Study data on miscarriage, stillbirth, preterm birth, low birth weight and birth defects were collected through participant interviews and medical record abstraction. We used the Rao-Scott χ2 test and the t test to assess differences in characteristics and outcomes between HIV-positive and HIV-negative women and generalized estimating equations for multivariable analysis. Results: A total of 614 HIV-positive and 390 HIV-negative pregnant women were enrolled in the study with delivery information on 571 (93.1%) and 352 (90.3%) respectively. In the delivery cohort, the median age at enrolment was 28 years for HIV-positive women and 23 years for HIV-negative women with median gestational ages of 20 and 21 weeks, respectively. A total of 149 singleton pregnancies had documented adverse pregnancy outcomes; 33 (9.6%) HIV-negative pregnancies and 116 (20.6%) HIV-positive pregnancies. Compared with their HIV-negative counterparts, HIV-positive women were more likely to experience an adverse pregnancy outcome, adjusted odds ratio (AOR) 2.6 [95% confidence interval (CI): 1.71–3.97]; an intrauterine death (miscarriage or stillbirth), AOR 2.64 [95% CI: 1.25–5.49]; or a low birth weight delivery, AOR 1.89 [95% CI: 1.16–3.09]. Conclusion: Adverse pregnancy outcomes remained 2–3 times higher among HIV-positive women compared with HIV-negative women despite universal ART.publishedVersio

Optimizing maternal and child health outcomes through use of multidisciplinary \u27IMPROVE\u27 teams in Lesotho

The “Integrated Management Team to Improve Maternal-Child Outcomes” (IMPROVE) intervention is a comprehensive, evidence-based strategy to improve maternal and child health (MCH) outcomes through patient-centered, participatory service delivery and multidisciplinary management teams (MDT). The intervention includes three key approaches: (1) multidisciplinary, integrated management teams of facility- and community-based health care and lay workers; (2) Joint Positive Health Dignity, and Prevention (PHDP)-focused counseling for patients and skills-building training and job aids for health workers; and (3) increased early community-based counseling and support for patients. This report summarizes the key findings from the implementation of this intervention in Lesotho (under Project SOAR), a country with a generalized HIV epidemic and the second highest HIV prevalence worldwide

Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial

Background Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age. Methods Two strategies will be compared: i) The standard of care, offering pediatric TB services based on national standard of care; ii) The intervention, with pediatric TB services integrated into child healthcare services: it consists of a package of training, supportive supervision, job aids, and logistical support to the integration of TB screening and diagnosis activities into pediatric services. The design is a cluster-randomized stepped-wedge of 12 study clusters in Cameroon and Kenya. The sites start enrolling participants under standard-of-care and will transition to the intervention at randomly assigned time points. We enroll children aged less than 5 years with a presumptive diagnosis of TB after obtaining caregiver written informed consent. The participants are followed through TB diagnosis and treatment, with clinical information prospectively abstracted from their medical records. The primary outcome is the proportion of TB cases diagnosed among children < 5 years old attending the child healthcare services. Secondary outcomes include: number of children screened for presumptive active TB; diagnosed; initiated on TB treatment; and completing treatment. We will also assess the cost-effectiveness of the intervention, its acceptability among health care providers and users, and fidelity of implementation. Discussion Study enrolments started in May 2019, enrolments will be completed in October 2020 and follow up will be completed by June 2021. The study findings will be disseminated to national, regional and international audiences and will inform innovative approaches to integration of TB screening, diagnosis, and treatment initiation into child health care services.publishedVersio

Pregnant and postpartum women's experiences and perspectives on the acceptability and feasibility of copackaged medicine for antenatal care and PMTCT in Lesotho

Objective: To improve PMTCT and antenatal care-related service delivery, a pack with centrally prepackaged medicine was rolled out to all pregnant women in Lesotho in 2011. This study assessed acceptability and feasibility of this copackaging mechanism for drug delivery among pregnant and postpartum women. Methods: Acceptability and feasibility were assessed in a mixed method, cross-sectional study through structured interviews (SI) and semistructured interviews (SSI) conducted in 2012 and 2013. Results: 290 HIV-negative women and 437 HIV-positive women (n = 727) participated. Nearly all SI participants found prepackaged medicines acceptable, though modifications such as size reduction of the pack were suggested. Positive experiences included that the pack helped women take pills as instructed and contents promoted healthy pregnancies. Negative experiences included inadvertent pregnancy disclosure and discomfort carrying the pack in communities. Implementation was also feasible; 85.2% of SI participants reported adequate counseling time, though 37.8% felt pack use caused clinic delays. SSI participants reported improvement in service quality following pack introduction, due to more comprehensive counseling. Conclusions: A prepackaged drug delivery mechanism for ANC/PMTCT medicines was acceptable and feasible. Findings support continued use of this approach in Lesotho with improved design modifications to reflect the current PMTCT program of lifelong treatment for all HIV-positive pregnant women

Prevention of Mother-to-Child Transmission of HIV-1 in Lesotho

The number of new pediatric HIV-1 infections is reducing globally as services for the prevention of mother-to-child transmission of HIV-1 (PMTCT) are being scaled up. Lesotho has one of the highest HIV burdens globally with an estimated HIV prevalence of 25.7% in antenatal care (ANC). In 2013, the Ministry of Health of Lesotho adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women, regardless of clinical or immunologic status (Option B+). Although this is expected to decrease mother-to-child transmission (MTCT) in general, program effectiveness data are only starting to emerge. In this thesis, I present results of three studies: conventional early infant diagnosis (EID) turnaround time (TAT); six-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART, and 18-24-month HIV-free survival measured through community survey. The overall aim of the study was to assess the effectiveness of the PMTCT program by determining birth outcomes and HIV-free survival of a prospective cohort of HIV-exposed infants compared to HIV-unexposed infants. In addition, we assess HIV-free survival among HIV-exposed children identified in the community who were born 18-24 months prior to study initiation. This was built on a baseline evaluation where we described turnaround time for EID when conventional EID was used. Methods: The baseline study was a retrospective cohort where data were abstracted from routine clinical records in health facility. The prospective observational cohort study included HIV-positive and HIV-negative women attending ANC and their infants up to 24 months postpartum; enrolled in the study June 2014 – February 2016. Study visits for HIV-positive mothers were three-monthly until 24 months after delivery, while HIV-negative mothers had study visits every three to six months after delivery. Demographic, social, and medical data were collected from participants during clinic visits through interviews and extraction of medical record information. For the community cross-sectional study, we captured the mortality and HIV infection outcomes of HIV-exposed children who were born after the introduction of Option B+. For all studies, quantitative data analysis was performed using Stata. Categorical variables were summarized using frequencies and percentages of participants, while continuous variables were summarized using means and standard deviations or medians and interquartile ranges, as appropriate. Maternal baseline characteristics were stratified by HIV status. For the baseline study, turnaround time geometric means (with 95% CI) were calculated and compared using linear mixed models. For the prospective cohort study, we compared birth outcomes between HEIs and HIV-unexposed infants (HUIs). Categorical variables were compared using Chi-square tests and continuous variables using t-tests or Wilcoxon rank-sum tests, as appropriate. HIV-free survival was estimated as the proportion of children alive and HIV-negative among HEI. For the community cross-sectional survey, the difference in survival between subgroups was determined using the log-rank test. Results: Concerning the baseline study, of the total of 1,187 infants reviewed, the turnaround time was 61.7 days (95% CI: 55.3-68.7). The longest turnaround time was time of results from central laboratory to district hospital, 23.3 days (95% CI: 18.7-29.0). Mean times from specimen transfer to the central laboratory and for result transfer from central laboratory to district hospital were significantly shorter in the Lowlands Region (0.9 and 16.2 days, respectively), compared to Highlands Region (6.0 [p = 0.030] and 34.3 days [p = 0.0099]. Results of the cohort study showed that prematurity was more frequent among HEI, 7.8% vs. 3.6%, although there was no difference in rates of congenital anomalies between HEI (1.0%) and HUI (0.6%). For HEI, cumulative HIV-1 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 six weeks. Among liveborn infants, six-week HIV-free survival for HEI was 95.6% (95% CI: 93.7–97.1). For the cross-sectional community survey, the MTCT rate was 5.7% [95% CI: 4.0-8.0] and the reported 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. The estimated HIV-free survival was 91.8% [95% CI: 89.2-93.8] among HEI. 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: The turnaround study showed that average EID turnaround time was two months; the longest period of delay was transfer of results from central laboratory to district hospital. Meanwhile the prospective cohort study showed that implementation of universal maternal ART lowers MTCT at six weeks of age with no differences in congenital anomalies or early mortality between HEIs and HUIs. Of note, HEIs were reported to have high rates of prematurity. From the community cross-sectional survey, despite scale up of lifelong ART among pregnant and breastfeeding women, HIV has a significant effect on survival among HIV-exposed children compared to unexposed children

Assessing treatment outcomes among peer educators living with HIV in Kenya.

BACKGROUND:People living with HIV (PLHIV) often face barriers in accessing quality and comprehensive HIV care, including stigma and discrimination, which results in poor retention and viral non-suppression. Peer-led interventions can help address these barriers. In Kenya, peer educators (PEs) are PLHIV who support other PLHIV to adhere to clinic schedules and antiretroviral medication uptake. In spite of their status as role models and their key role in supporting clients receiving HIV care and treatment, little is known about the characteristics and treatment outcomes of PEs themselves, specifically viral suppression. METHODS:This is a retrospective descriptive analysis of program data on treatment outcomes of PEs engaged in active patient support activities between October 2010 and January 2017. All eligible PEs from 140 health facilities located in 23 counties of Kenya were included in the study. Data from 230 PEs were abstracted from the electronic medical records, patient files, and registers between June and August 2017. Study variables included key sociodemographic characteristics (sex, marital status, and age), duration on antiretroviral therapy (ART), WHO clinical staging, baseline CD4 count, current antiretroviral regimen and uptake of isoniazid preventive therapy (IPT). The outcome variable was viral suppression, defined as a viral load <1000 copies/ml. RESULTS:Overall, 173/230 (75%) of the PEs were female, 144/230 (63%) were married, and median age (LQ, UQ) was 38.5 (33.0, 42.0) years. The PEs had been on ART for a median (LQ, UQ) duration of 76.0 (37.0, 105.0) months. Six months IPT completion was high at 97%. Of the 222 (97%) PEs with an up-to-date viral load taken within the last one year, 211 (95%) were virally suppressed. CONCLUSION:Our study showed that peer educators actively engaged in patient support activities have achieved high viral suppression rates

Assessing Very Early Infant Diagnosis Turnaround Times: Findings from a Birth Testing Pilot in Lesotho

Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants’ HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January–June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result receipt was 76.5 days at birth and 63 and 70 days at six weeks at cohort and noncohort facilities, respectively. HIV-exposed infants tested at birth were approximately one month younger when their caregivers received results versus those tested at six weeks. Infants diagnosed at birth initiated ART about two months earlier (median 6.4 weeks old) than those identified at six weeks (median 14.8 weeks). However, the long TAT for testing at both birth and six weeks illustrates the prolonged process for specimen transport and result return that could compromise the effectiveness of adding VEID to existing overburdened EID systems