Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease
progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape
mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We
assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal
infection. HIV-1
gag
,
pol
and
nef
sequences were generated from a historical repository of longitudinal
specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for
each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in
nef
and
gag
vs.
pol
, and lower in infants with non-severe immunosuppression vs. severe immunosuppression
across
gag
and
nef
. Selection pressure was stronger in infants with non-severe immunosuppression
vs. severe immunosuppression across
gag
. The analysis also showed that infants with non-severe
immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in
gag
and
nef
.
Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data
indicate that infant CTLs can exert selection pressure on
gag
and
nef
epitopes in early infection and that
stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results
have implications for the development of paediatric HIV-1 vaccines.