Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

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

Subtype associations with HIV-associated neurocognitive disorder in China

Factors associated with HIV-associated neurocognitive disorders (HAND) include CD4(+) nadir and count, HIV RNA level, and HIV-1 subtype. Here, we investigated demographical and clinical markers with respect to HAND in a homogenous Chinese population. Individuals with HAND (global deficit score a parts per thousand yen0.5) had lower nadir (p < 0.01) and CD4(+) counts (p = 0.03). HAND was also associated with AIDS (p < 0.01), but subtype was not (p = 0.198). Furthermore, worse impairment correlated with higher viral diversity (r = 0.16, p < 0.01), lower nadir (r = -0.17, p < 0.01), and CD4(+) counts (r = -0.11, p = 0.01). These remained significant even when correcting for subtype. Our findings suggest that subtype does not have a major impact on HAND.NIAID NIH HHS [AI036214, AI100665, K24 AI100665, P30 AI036214]; NIDA NIH HHS [DA034978, DP1 DA034978]; NIMH NIH HHS [MH083552, K24 MH097673, MH062512, MH097520, P30 MH062512, R01 MH083552, R01 MH092225, R01 MH097520]SCI(E)[email protected]