Background: We assessed the association of vertical HIV transmission during breastfeeding with HIV VL and tenofovir concentrations in maternal plasma and breastmilk. Setting: A case-control study nested within the IMPAACT multi-site PROMISE trial. Methods: Each case (mother-infant pairs with infants with a positive HIV test) was matched to two controls (pairs with HIV negative infants) by infant sex, study site, PROMISE component (postpartum randomization or observational follow-up) and maternal age. Maternal plasma and breastmilk collected near the case infant’s infection date were assayed for RNA VL. Tenofovir concentrations were measured in the subset of mothers who received a tenofovir-containing regimen. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: 31 cases and 62 controls included mothers with median age of 25 years. Median infant age at HIV diagnosis was 6 (3, 14) months. Plasma and breastmilk RNA were above the lower limit of quantification (LLOQ) in 28/31 (90%) and 17/31 (55%) maternal cases vs. 25/62 (45%) and 7/62 (11%) controls. Odds of vertical transmission were 9 (95% CI: 2.67, 30.88) times higher for plasma RNA VL >LLOQ and 9.4 (95% CI: 2.73, 32.58) times higher for breastmilk RNA VL >LLOQ compared with RNA VL ≤LLOQ. Among mothers who received a tenofovir-containing regimen, only 3/14 (21%) cases had detectable tenofovir concentrations in their plasma and breastmilk vs. 31/37 (84%) in plasma and 29/37 (78%) in breastmilk for controls. In breastmilk, the odds of being a case was 90% lower (95% CI: 0.01, 0.76; p = 0.027; n = 31) for each log10 increase in TFV. Conclusion: Odds of breastmilk HIV-1 transmission is associated with higher maternal plasma and breastmilk RNA VL and lower breastmilk tenofovir concentrations.
Owor et al. (Mon,) studied this question.