Background:  CD8⁺ T lymphocyte (CTL) responses are important for controlling HIV-1 replication. However, the development of CD8⁺ T cell escape variants may limit the effectiveness of this response. Since mothers and their infants share an HLA haplotype, the transmission of CTL escape variants may adversely affect outcome following mother-to-child transmission.

Methods:  Amino acid sequence variation in CTL epitopes were examined in five untreated mother-infant pairs. All but one infant were infected intrapartum. RNA was extracted from maternal plasma at delivery and from plasma obtained from the infants at 2 and 4 to 6 months. Gag and nef cDNAs were amplified and 10 clones per gene per patient were sequenced.  Phylogenetic analysis of all sequences confirmed the relationship between maternal-infant pair sequences. Molecular HLA class I typing was performed for each patient.

Results:  Variant sequences corresponding to epitopes restricted by maternal HLA alleles were detected in the plasma of all women. Similar variant sequences were commonly detected in the first infant plasma specimen. These variant sequences were detected again in plasma samples obtained at 4 to 6 months from infants who shared the restricting HLA allele. Reversion to wild type sequences was noted in epitopes that occurred in areas of known functional importance to the virus and which were restricted by non-shared HLA alleles. However, persistence of some variant sequences restricted by non-shared HLA alleles was noted, possibly due to low viral fitness cost of the variant sequences.

Conclusions: CTL escape variants were commonly detected in the plasma of HIV-infected women and their infants. HLA haplotype and fitness appeared to determine the stability of the escape mutants in the infant.  These findings have important implications for the design of neonatal vaccine strategies to prevent mother-to-child HIV-1 transmission.

Keywords: vertical transmission; gag and nef genes; CTL escape mutant