Search

Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Short-course zidovudine (ZDV) with or without a single dose of nevirapine (sdNVP) is widely used to prevent mother-to-child HIV transmission (PMTCT). However, more data on viral load in breast milk following pMTCT regimens are needed. In a randomized PMTCT study in Botswana, in which half of the women received sdNVP in labor, stored samples from mothers assigned to breastfeed were analyzed for HIV-1 RNA in breast milk supernatant. A total of 527 samples from 282 women, collected at delivery, 2 weeks, 2 months, and 5 months postpartum were available for testing. Cell-free breast milk HIV-1 RNA was detectable (>40 copies/ml) in 44.8% (236/527) of samples analyzed. Women randomized to sdNVP + ZDV were more likely to have undetectable breast milk viral loads at 2 weeks postpartum compared with those who received ZDV alone (67.8% vs. 38.5%, p = 0.002). By 2 months postpartum the difference between study arms disappeared, and 43.8% of women who received sdNVP + ZDV had undetectable HIV-1 RNA compared to 53.8% of the ZDV alone group (p = 0.19) and 60.5% vs. 64.5%, respectively, at month 5 (p = 0.61.) The addition of sdNVP to antenatal short-course AZT resulted in significantly reduced breast milk viral loads at 2 weeks postpartum suggesting a reduced risk of MTCT during the early postpartum period. However, viral loads in both study arms were comparable at 2 and 5 months postpartum, suggesting that the receipt of sdNVP in labor may defer rather than blunt the postpartum viral load rebound seen in breast milk after the discontinuation of ZDV.