Background:  Starting ART soon after birth may improve the outcome of HIV-infected infants. However, lifelong ART is not realistic and novel therapeutic strategies are required. This prospective, randomized controlled study investigated three approaches to treatment during acute HIV infection in infancy.

Methods:  Infants born to HIV⁺ mothers in Durban, South Africa, were tested by polymerase chain reaction (PCR) on days 1 and 28. HIV-infected infants were randomized to Arm A) standard of care: deferred, continuous ART, started when CD4 ≤20%: Arm B) immediate ART for 12 months; or C) immediate ART with as many as 3 structured treatment interruptions—ART stopped at viral load <50; restarted at viral load >5000. Arm B/C infants restarted ART once CD4 ≤20% if <18 months old, or ≤15% if >18 months old. First-line ART was zidovudine/lamivudine/nelfinavir/ nevirapine. Viral load and CD4 percentage were checked monthly, or weekly during structured treatment interruptions. Infants with virologic failure changed ART regimen and had no further structured treatment interruptions. 

Results:  Of 740 infants, 75 were HIV-infected (10.3% transmission by D28) and randomized to Arms A (n = 20), B (n = 22), and C (n = 21); 12 were ineligible. In Arm A, 17 of 20 (85%) infants reached CD4 ≤20% by 12 months and started continuous ART. In Arm B, 2 infants withdrew and 4 died; 16 infants had 12-month ART, started on median day 30, and 15 stopped ART at 12 months. In Arm C, all 21 infants started ART (median day 34) and underwent 0 (n = 4), 1 (n = 5), 2 (n = 3), or 3 (n = 8) structured treatment interruptions, which lasted median 19 days, with no increase in duration with successive structured treatment interruptions. Although there was no significant difference at interim DSMB analysis, by 18 months of age, 11 of the 20 infants  (55%) in Arm C required second-line ART compared to 2 of the 16 (13%) in Arm B (p = 0.01; Fisher’s exact). After immediate ART, 23 infants (15 Arm B, 8 Arm C) stopped ART as planned; 10 of 23 (43%) reached treatment criteria within 12 months compared to 17 of 20 (85%) in Arm A (p = 0.01; Fisher’s exact). Time to restarting ART in Arms B/C correlated with CD4 percentage at birth (r = 0.74, p = 0.026).

Conclusions:  Structured treatment interruptions in acute infant HIV infection did not improve virologic control and increased regimen switches. However, continuous ART from birth, stopped at 12 months, provides a promising novel treatment strategy in infants. Immediate ART prevents the rapid disease progression that characterizes HIV in infancy and enables immune reconstitution. Stopping ART at 1 year reduces cost, toxicity, and drug resistance. Time off therapy is predictable from CD4 percentage at birth, enabling identification of eligible infants at diagnosis.