Sustained aviraemia despite anti-retroviral therapy non-adherence in male children following in utero hiv transmission.
Bengu N., Cromhout G., Adland E., Govender K., Herbert N., Lim N., Fillis R., Sprenger K., Vieira V., Kannie S., van Lobenstein J., Chinniah K., Kapongo C., Bhoola R., Krishna M., Mchunu N., Pascucci GR., Cotugno N., Palma P., Tagarro A., Rojo P., Roider J., Garcia-Guerrero MC., Ochsenbauer C., Groll A., Reddy K., Giaquinto C., Rossi P., Hong S., Dong K., Ansari MA., Puertas MC., Ndung'u T., Capparelli E., Lichterfeld M., Martinez-Picado J., Kappes JC., Archary M., Goulder P.
Following sporadic reports of post-treatment control of HIV in children who initiated combination antiretroviral therapy (cART) early, we here prospectively studied 284 very early cART-treated children from KwaZulu-Natal, South Africa after vertical HIV transmission to assess control of viraemia. 84% of the children achieved aviraemia on cART but aviraemia persisting to >36m 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 aviraemia despite unscheduled complete discontinuation of cART lasting 3m-10m (n=4), or intermittent cART adherence during 17m 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 females (r=-0.51 versus r=-0.07 for IFNα). While 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), the viruses transmitted to the five males maintaining cART-free aviraemia had significantly lower replication capacity (p<0.0001). These data suggest that viraemic 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.