A stable latent reservoir for HIV-1 in resting CD4(+) T lymphocytes in infected children

HIV-1 persists in a latent state in resting CD4(+)T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4(+) T cells from 21 children with perinatally acquired infection. Repli cation-competent HIV-1 was recovered from all 18 children from whom suffici ent cells were obtained. The frequency of latently infected resting CD4(+) T cells directly correlated with plasma virus levels, suggesting that in ch ildren with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1-3 yea rs on HAART, latent replication-competent HIV-1 persisted with little decay , owing to a stable reservoir of infected cells in the postintegration stag e of latency. Drug-resistance mutations generated by previous nonsuppressiv e regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that wer e part of failed regimens. Thus the latent reservoir for HIV-1 in resting C D4(+) T cells will be a major obstacle to HIV-1 eradication in children.