Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission
Nomonde Bengu, Gabriela Cromhout, Emily Adland, Katya Govender, Nicholas Herbert, Nicholas Lim, Rowena Fillis, Kenneth Sprenger, Vinícius Vieira, Samantha Kannie, Jeroen van Lobenstein, Kogielambal Chinniah, Constant Kapongo, Roopesh Bhoola, Malini Krishna, Noxolo Mchunu, Giuseppe Rubens Pascucci, Nicola Cotugno, Paolo Palma, Alfredo Tagarro, Pablo Rojo, Julia Roider, Maria C. García-Guerrero, Christina Ochsenbauer, Andreas Groll, Kavidha Reddy, Carlo Giaquinto, Paolo Rossi, Seohyun Hong, Krista L. Dong, M. Azim Ansari, María C. Puertas, Thumbi Ndung’u, Edmund V. Capparelli, Mathias Lichterfeld, Javier Martínez‐Picado, John C. Kappes, Moherndran Archary, Philip Goulder
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 (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). 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.