Associations of Plasma and Breast Milk HIV RNA and Tenofovir Concentrations With Risk of Postnatal HIV Transmission During Breastfeeding Among Women With and Without ARV Exposure.

BACKGROUND

We assessed the association of vertical HIV transmission during breastfeeding with HIV viral load (VL) and tenofovir (TFV) concentrations in maternal plasma and breast milk.

SETTING

A case-control study nested within the IMPAACT multisite PROMISE trial.

METHODS

Each case (mother-infant pairs with infants with a positive HIV test) was matched to 2 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 breast milk collected near the case infant's infection date were assayed for RNA VL. TFV concentrations were measured in the subset of mothers who received a TFV-containing regimen. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression.

RESULTS

Thirty one 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 breast milk RNA were above the lower limit of quantification (LLOQ) in 28 of 31 (90%) and in 17 of 31 (55%) maternal cases vs. 25 of 62 (45%) and 7 of 62 (11%) controls. Odds of vertical transmission were 9.1 (95% CI: 2.67 to 30.88) times higher for plasma RNA VL > LLOQ and 9.4 (95% CI: 2.73 to 32.58) times higher for breast milk RNA VL > LLOQ compared with RNA VL ≤ LLOQ. Among mothers who received a TFV-containing regimen, only 3 of 14 (21%) cases had detectable TFV concentrations in their plasma and breast milk vs. 31 of 37 (84%) in plasma and 29 of 37 (78%) in breast milk for controls. In breast milk, the odds of being a case was 90% lower (95% CI: 0.01 to 0.76; P = 0.027; n = 31) for each log 10 increase in TFV.

CONCLUSIONS

Odds of breast milk HIV-1 transmission is associated with higher maternal plasma and breast milk RNA VL and lower breast milk TFV concentrations.