LAUSR

BACKGROUND Early antiretroviral therapy (ART) restricts the size of the HIV reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. METHODS We measured total and integrated HIV DNA, as well as the frequency of CD4 T-cells producing multiply-spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically-infected Thai infants. Eighty-five infants were followed longitudinally for up to three years. We compared the size of the reservoir in children who received continuous prophylactic ARV since birth versus those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. RESULTS Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous prophylactic ARV since birth compared to those in whom prophylactic ARV was discontinued or never initiated (p<0.020 and p<0.001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (<0.01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during three years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARV before starting ART and those who delayed ART initiation without receiving prior prophylaxis. CONCLUSIONS Neonatal prophylactic ARV with direct transition to ART durably limits the size of the HIV reservoir.