Abstract
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, R0, 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 R0. For the rest, we used CD4 counts for approximate estimation of R0. 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 R0 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 R0 is small, will likely improve viral control, in addition to suppressing the latent reservoir.
Highlights
The progression of HIV-1 infection in children follows a trajectory that is different from that in a dults[1]
The interaction between HIV-1 and the host is complex in children because of the ongoing development of the immune system
The immune system undergoes a transition from being tolerogenic at birth to being more immunogenic in adolescence[6]
Summary
The progression of HIV-1 infection in children follows a trajectory that is different from that in a dults[1]. Survival is poor among perinatally-infected children compared to adults: over 50% of untreated children die within 2 years of birth[4], while untreated adults survive over 10 years after infection[5] While these observations seem to indicate that HIV-1 is more aggressive in children than in adults, evidence exists to the contrary. Whether the in vivo fitness of HIV-1 is greater or smaller in children compared to adults remains unknown. We addressed this question by estimating the within-host basic reproductive ratio, R0, in children of varying ages. We performed a similar analysis here using measurements of viral load changes in children of different ages who initiated first-line ART with the aim of understanding early viral dynamics and in vivo viral fitness in young children
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