Postnatal HIV transmission in breastfed infants of HIV-infected women on ART: a systematic review and meta-analysis

Abstract

Introduction: To systematically review the literature on mother-to-child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World Health Organization infant feeding guidelines in the context of HIV and ART.

Methods: We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta-analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle-Ottawa Scale (NOS) and GRADE.

Results: Eleven studies were identified, from 1439 citations and review of 72 abstracts. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15-5.93%) and at 12 months 4.23% (95% CI: 2.97-5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32-1.85) at six and 2.93 (95% CI: 0.68-5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk.

Conclusion: There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life-long ART for all.

Keywords: Antiretroviral therapy; HIV; breast feeding; meta-analysis; prevention of mother-to-child transmission; systematic review.

Figure 1.

Flowchart of screening process.

Figure 2.

Transmission rates at age six months: (a) overall transmission rate (including peripartum) at age six months; (b) postnatal transmission rate between four and six weeks of age and age six months, with 95% confidence intervals, in children who were breastfed and whose mothers were on ART. Note: Red dashed lines represent final pooled estimate for overall (a) and postnatal (b) transmission rates. (a) Sagay et al. (2015) and Jamieson et al. (2012) did not provide a rate of transmission, but the rate was calculated on the basis of the number of children at risk provided in the paper. For Jamieson et al. (2012) transmission rate was provided at 28 weeks. For Ngoma et al. (2015) and Marazzi et al. (2009), a confidence interval was not provided in the paper but calculated using the formula¹⁸. (b) Coovadia et al. (2012), Alvarez-Uria et al. (2012), Thomas et al. (2011) and Kilewo et al. (2009) excluded positive children at six weeks. Jamieson et al. (2012) excluded transmission at two weeks and Marazzi et al. (2009) excluded four weeks. Jamieson et al. (2012), Thomas et al. (2011) and Kilewo et al. (2009) did not provide rate of transmission, but rate was calculated considering number of children at risk provided in the paper.

Figure 3.

Transmission rates at 12 months of age, with 95% confidence intervals, in children who were breastfed and whose mothers were on ART. Group 1: Overall transmission. Group 2: Postnatal transmission between four and six weeks and 12 months of age. Note: Red dashed lines represent final pooled estimate for overall (a) and postnatal (b) transmission rates. Coovadia et al (2012) excluded children HIV positive at six weeks. Jamieson et al. (2012) excluded transmission at two weeks. Marazzi et al. (2009) did not provide the confidence interval, which was thus calculated using the formula¹⁸.