Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission

Abstract

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads. Unexpectedly, a subset of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3–10 months or intermittent cART adherence during 17-month loss to follow-up. We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) that was markedly stronger for males than for females. Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort, the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity. These data suggest that viremic control can occur in some infants with in utero–acquired HIV infection after early cART initiation and may be associated with innate immune sex differences.