Background: While general risk factors for mother-to-child transmission (MTCT) have been well described, there are limited data on risk factors for early versus later MTCT during breastfeeding. We analyzed risk factors for both early and late transmission in a completed perinatal trial.

Methods:  Between November 1997 and April 1999, HIV-infected pregnant women identified at the Mulago National Referral hospital in Kampala, Uganda were randomized to either the nevirapine (NVP) or zidovudine (ZDV) arm of the HIVNET 012 randomized clinical trial. Clinical data and specimens were collected at pre-entry and during follow-up. Infant HIV DNA polymerase chain reaction (PCR) testing was done at birth, 6 and 14 weeks, and 12 and 18 months. Analyses assessing maternal CD4 cell count, viral load, and other risk factors for early and late transmission were performed using Cox regression. The ViroSeq HIV Genotyping System and a sensitive point mutation assay were used for detection of NVP-resistance mutations.  

Results:  Among 610 infants in this analysis, 122 were HIV infected, of whom 99 (81.1%) were infected early (first positive PCR at ≤56 days). Predictors of early MTCT included ZDV receipt compared with NVP, higher pre-entry maternal viral load and lower pre-entry CD4 cell count. Incidence of breastfeeding transmissions after 56 days was low (0.7% per month [95%CI 0.4% to 1.0%]), but continued to occur through 18 months of age. Only maternal viral load (week 6) was associated with late MTCT; 6-week NVP resistance did not predict late MTCT.

Conclusions:  In HIVNET 012, most transmission (>80%) occurred early, with a low ongoing risk of transmission during later breastfeeding. Maternal viral load was the best predictor of both early and late transmission. Maternal NVP resistance at 6 weeks did not predict late transmission.