Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding.

Subclinical mastitis (SCM) is an important risk factor of postnatal HIV-1 transmission that is still poorly understood. A longitudinal sub-study of the ANRS12174 trial including 270 breastfeeding mothers in Lusaka, Zambia measured sodium (Na+) and potassium (K+) in archived paired breast milk samples collected at week 14, 26 and 38 postpartum to determine cumulative incidence of SCM and the effects of recurrent severe SCM on HIV-1 shedding in breast milk. A nested retrospective cohort study including 112 mothers was also done to determine longitudinal effects of SCM on four pro-inflammatory cytokines; IL6, IL8, IP10 and RANTES. The cumulative incidence for any SCM (Na + /K + ratio > 0.6) and severe SCM (Na + /K + ratio > 1) were 58.6% (95%CI: 52.7 - 64.5) and 27.8% (95%CI: 22.5 - 33.1), respectively. In majority of affected mothers (51.4%) severe SCM was recurrent. Both breasts were involved in 11.1%, 33.3% and 70% of the mothers with a single episode, 2 and 3 episodes respectively. In affected breasts, an episode of severe SCM resulted in steep upregulation of the four cytokines considered (IL8, IP10, RANTES and IL6) compared to: before and after the episode; contralateral unaffected breasts; and SCM negative control mothers. Recurrent severe SCM significantly increased the odds of shedding cell-free HIV-1 in breast milk (OR: 5.2; 95%CI: 1.7 - 15.6) whereas single episode of severe SCM did not (OR: 1.8; 95%CI: 0.8 - 4.2). A Na+/K+ ratio > 1 indicative of severe SCM is an excellent indicator of breast inflammation characterized by a steep, localized and temporal upregulation of several pro-inflammatory cytokines that favor HIV-1 shedding in mature breast milk and may facilitate postnatal HIV-1 transmission through breastfeeding.

Prevalence and determinants of HIV shedding in breast milk during continued breastfeeding among Zambian mothers not on antiretroviral treatment (ART): A cross-sectional study.

The risk of postnatal HIV transmission exists throughout the breastfeeding period. HIV shedding in breast milk beyond six months has not been studied extensively. The aim of this study was to determine prevalence and determinants of HIV shedding in breast milk during continued breastfeedingA cross-sectional study was nested in the PROMISE-PEP trial in Lusaka, Zambia to analyze breast milk samples collected from both breasts at week 38 post-partum (mid-way during continued breastfeeding). We measured concurrent HIV deoxyribonucleic acid (DNA) and HIV ribonucleic acid (RNA) as proxies for cell-associated HIV (CAV) and cell-free HIV (CFV) shedding in breast milk respectively. Participants' socio-demographic date, concurrent blood test results, sub clinical mastitis test results and contraceptive use data were available. Logistic regression models were used to identify determinants of HIV shedding in breast milk (detecting either CAV or CFV).The prevalence of HIV shedding in breast milk at 9 months post-partum was 79.4% (95%CI: 74.0 - 84.0). CAV only, CFV only and both CAV and CFV were detectable in 13.7%, 17.3% and 48.4% mothers, respectively. The odds of shedding HIV in breast milk decreased significantly with current use of combined oral contraceptives (AOR: 0.37; 95%CI: 0.17 - 0.83) and increased significantly with low CD4 count (AOR: 3.47; 95%CI: 1.23 - 9.80), unsuppressed plasma viral load (AOR: 6.27; 95%CI: 2.47 - 15.96) and severe sub-clinical mastitis (AOR: 12.56; 95%CI: 2.48 - 63.58).This study estimated that about 80% of HIV infected mothers not on ART shed HIV in breast milk during continued breastfeeding. Major factors driving this shedding were low CD4 count, unsuppressed plasma viral load and severe sub-clinical mastitis. The inverse relationship between breast milk HIV and use of combined oral contraceptives needs further clarification. Continued shedding of CAV may contribute to residual postnatal transmission of HIV in mothers on successful ART.