The within-host fitness of HIV-1 increases with age in ART-naïve HIV-1 subtype C infected children

As the immune system develops with age, children combat infections better. HIV-1, however, targets an activated immune system, potentially rendering children increasingly permissive to HIV-1 infection as they grow. How HIV-1 fitness changes with age in children is unknown. Here, we estimated the within-host basic reproductive ratio, R(0), a marker of viral fitness, in HIV-1 subtype C-infected children in India, aged between 84 days and 17 years. We measured serial viral load and CD4 T cell counts in 171 children who initiated first-line ART. For 25 children, regular and frequent measurements provided adequate data points for analysis using a mathematical model of viral dynamics to estimate R(0). For the rest, we used CD4 counts for approximate estimation of R(0). The viral load decline during therapy was biphasic. The mean lifespans of productively and long-lived infected cells were 1.4 and 27.8 days, respectively. The mean R(0) was 1.5 in children aged < 5 years, increased with age, and approached 6.0 at 18 years, close to 5.8 estimated previously for adults. The tolerogenic immune environment thus compromises HIV-1 fitness in young children. Early treatment initiation, when the R(0) is small, will likely improve viral control, in addition to suppressing the latent reservoir.