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OBJECTIVES: Data on long-term HIV-free survival in breastfeeding, HIV-exposed infants (HEIs) are limited. The National Evaluation of Malawi's Prevention of Mother-to-Child Transmission (PMTCT) Program (NEMAPP), conducted between 2014 and 2018, evaluated mother-to-child transmission (MTCT) and infant outcomes up to 24 months postpartum. METHODS: We enrolled a nationally representative cohort of HEIs at 54 health facilities across four regional strata in Malawi and used multivariable Cox regression analysis to investigate the risk of adverse outcomes (HIV transmission, infant death and loss to follow-up) to 24 months postpartum. Models, controlling for survey design, were fitted for the total cohort (n = 3462) and for a subcohort that received maternal viral load (VL) monitoring (n = 1282). RESULTS: By 24 months, in 3462 HEIs, weighted cumulative MTCT was 4.9% [95% confidence interval (CI) 3.7-6.4%], 1.3% (95% CI 0.8-2.2%) of HEIs had died, 26.2% (95% CI 24.0-28.6%) had been lost to follow-up and 67.5% (95% CI 65.0-70.0%) were alive and HIV-free. Primiparity [weighted adjusted hazard ratio (aHR) 1.6; 95% CI 1.1-2.2; parity 2-3: weighted aHR 1.5; 95% CI 1.2-1.9], the mother not disclosing her HIV status to her partner (no disclosure: weighted aHR 1.3; 95% CI 1.1-1.6; no partner: weighted aHR 0.7; 95% CI 0.5-0.9), unknown maternal ART start (weighted aHR 2.0; 95% CI 1.0-3.9) and poor adherence (missed ≥ 2 days of ART in the last month: weighted aHR 1.7; 95% CI 1.2-2.2; not on ART: weighted aHR 1.7; 95% CI 1.0-2.7) were associated with adverse outcomes by 24 months. In the subcohort analysis, risk of HIV transmission or infant death was higher among HEIs whose mothers started ART post-conception (during pregnancy: weighted aHR 3.2; 95% CI 1.3-7.7; postpartum: weighted aHR 12.4; 95% CI 1.5-99.6) or when maternal viral load at enrolment was > 1000 HIV-1 RNA copies/mL (weighted aHR 15.7; 95% CI 7.8-31.3). CONCLUSIONS: Infant positivity and infant mortality at 24 months were low for a breastfeeding population. Starting ART pre-conception had the greatest impact on HIV-free survival in HEIs. Further population-level reduction in MTCT may require additional intervention during breastfeeding for women new to PMTCT programmes. Pre-partum diagnosis and linkage to ART, followed by continuous engagement in care during breastfeeding can further reduce MTCT but are challenging to implement.

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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.

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INTRODUCTION: the HIV-free survival rate is the gold-standard measure of the effectiveness of interventions towards prevention of mother-to-child transmission of HIV in any setting. However, data on HIV-free survival among the HIV-exposed infants followed up in most low-resource settings are lacking. We determined the HIV-free survival among breastfed infants in two tertiary facilities in a resource-poor setting in northern Uganda. METHODS: we conducted a retrospective cohort study in May 2019 and retrospectively reviewed records of HIV-exposed infants registered in 2014 through 2016 at two tertiary facilities in northern Uganda. We analyzed data using SPSS v16 software package. The chi-square and Student t-tests were used to compare factors among infant groups. Multivariate logistic regression analysis was used to determine factors independently associated with HIV-free survival. P-value <0.05 was considered for statistical significance. RESULTS: majority of the infants were males 55.6% (203/365) and 98.6% (360/365) received nevirapine prophylaxis. A total of 345 (94.5%) infants were exclusively breastfed, only 100/345 (29.0%) of whom were exclusively breastfed for at least 6 months, while the breastfeeding status of 44/345 (12.8 %) infants could not be ascertained. The overall HIV-free survival rate was 93.7% (342/365), while 2.7% (10/365) were HIV-infected and 3.6% (13/365) died. Infants´ age at enrolment in care (aOR 5.20, p=0.008) and treatment facility (aOR 3.76, p=0.027) were the independent determinants of HIV-free survival. CONCLUSION: the HIV-free survival rate among the breastfed infants in the study setting marginally falls short of the recommended standard, thus calling for more efforts to improve survival.

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In Swaziland, no data are available on the rates of HIV infection and HIV-free survival among children at the end of the breastfeeding period. We performed a national crosssectional community survey of children born 18-24 months prior to the study, in randomly selected constituencies in all 4 administrative regions of Swaziland, from April to June 2015. Mother-to-child transmission (MTCT) of HIV and HIV-free survival rates were calculated for all HIV-exposed children. The overall HIV-free survival rate at 18-24 months was 95.9% (95% CI 94.1-97.2). The estimated proportion of HIV infected children among known HIV-exposed children was 3.6% (95% CI 2.4-5.2). Older maternal age, delivering at a health facility, and receiving antenatal antiretroviral drugs were independently associated with reduced risk for child infection or death. The Swaziland program for prevention of MTCT achieved high HIV-free survival (95.9%) and low MTCT (3.6%) rates at 18-24 months of age when Option A (infant prophylaxis) of the WHO 2010 guidelines was implemented.

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BACKGROUND: Exclusive breastfeeding in the first 6 months offers protection from postnatal HIV infection but remains low in resource-poor settings. Documentation of experiences with exclusive breastfeeding is needed to strengthen infant feeding counselling by health care workers. OBJECTIVE: To explore HIV-positive mothers' experiences with exclusive breastfeeding during the first 6 months of the infant's life. DESIGN: A health facility- and community-based exploratory qualitative study was conducted among 30 HIV-positive mothers practising exclusive breastfeeding and meeting the selection criteria. In-depth interviews were conducted four times with the same participants at 6 days, 6 weeks, 12 weeks and 18 weeks after giving birth. Interviews were transcribed verbatim and files were imported into QRS NVivo Version 10 for coding, and data were analysed using the framework analysis. RESULTS: We found that mothers were aware of the risks of mother-to-child transmission of HIV through breastmilk and recognised the benefits of exclusive breastfeeding to their exposed babies. However, they were particularly concerned about achieving HIV-free survival for their exposed infants because of problems faced during the first 6 months of infant feeding. Although they reported being supported by their families and/or friends, their poor health and nutrition impacted how well they cared for their infants' well-being. CONCLUSIONS: We conclude that exclusive breastfeeding was difficult to achieve because of individual circumstances. Therefore, prevention of mother-to-child transmission interventions that adopt a once-off infant feeding counselling do not achieve adequate preparation on the part of mothers to practice exclusive breastfeeding. There is a need to provide frontline health care workers with steps for consideration during infant feeding counselling.

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OBJECTIVE: To provide estimates of HIV-free survival at 12-24 months in breastfed children by maternal ART (6 months or lifelong) to inform WHO HIV and Infant Feeding guidelines. METHODS: Eighteen studies published 2005-2015 were included in a systematic literature review (1295 papers identified, 156 abstracts screened, 55 full texts); papers were analysed by narrative synthesis and meta-analysis of HIV-free survival by maternal ART regimen in a random effects model. We also grouped studies by feeding modality. Study quality was assessed using a modified Newcastle-Ottawa Scale (NOS) and GRADE. RESULTS: The pooled estimates for 12-month HIV-free survival were 89.8% (95% confidence interval, CI: 86.5%, 93.2%) for infants of mothers on ART for 6 months post-natally (six studies) and 91.4% (95% CI 87.5%, 95.4%) for infants of mothers on lifelong ART (three studies). Eighteen-month HIV-free survival estimates were 89.0% (95% CI 83.9%, 94.2%) with 6 months ART (five studies) and 96.1% (95% CI 92.8%, 99.0%) with lifelong ART (three studies). Twenty-four-month HIV-free survival for infants whose mothers were on ART to 6 months post-natally (two studies) was 89.2% (95% CI 79.9%, 98.5%). Heterogeneity was considerable throughout. In four studies, HIV-free survival in breastfed infants ranged from 87% (95% CI 78%, 92%) to 96% (95% CI 91%, 98%) and in formula-fed infants from 67% (95% CI 35.5%, 87.9%) to 97.6% (95% CI 93.0%, 98.2%). CONCLUSION: Our results highlight the importance of breastfeeding for infant survival and of ART in reducing the risk of mother-to-child HIV transmission and support the WHO recommendation to initiate ART for life immediately after HIV diagnosis.

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