Prevention of Mother-to-Child Transmission of HIV-1 in Lesotho
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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.
Has partsPaper I: Tiam A, Gill MM, Hoffman HJ, Isavwa A, Mokone M, Foso M, Safrit JT, Mofenson LM, Tylleskär T, Guay L. Conventional early infant diagnosis in Lesotho from specimen collection to results usage to manage patients: Where are the bottlenecks? PLoS ONE 2017 12(10): e0184769. The article is available at: https://hdl.handle.net/1956/18283
Paper II: Tiam A, Kassaye SG, Machekano R, Tukei V, Gill MM, Mokone M, Letsie M, Tsietso M, Seipati I, Barasa J, Isavwa A, Tylleskär T, Guay L. 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. PLoS ONE 2019 14(12): e0226339. The article is available in the main thesis. The article is also available at: https://doi.org/10.1371/journal.pone.0226339
Paper III: Appolinaire Tiam, Michelle M. Gill, Rhoderick Machekano, Vincent Tukei, Majoalane Mokone, Shannon Viana, Mosilinyane Letsie, Mots’oane Tsietso, Irene Seipati, Cecilia Khachane, Marethabile Nei, Florence Mohai, Thorkild Tylleskär, Laura Guay. 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 communitybased survey. PLoS ONE 2020 15(10): e0237409. The accepted version is available in the thesis file. The published version is available at: https://doi.org/10.1371/journal.pone.0237409