Virological and immunological responses in infants enrolled in the CHER trial

Avy Violari and colleagues from the CHER trial showed data describing response in young infants after early HAART initiation in South Africa.

Largely because of this trial, current guidelines recommend early treatment in HIV-infected infants and, where possible, infants exposed to nevirapine in prevention of mother to child transmission (PMTCT) should receive lopinavir/ritonavir (LPV/r) first line. There are few data describing virological outcomes in African infants.

In CHER, infants aged 6-12 weeks with CD4% >25% (n = 411) and CD4 <25% (n=40) started LPV/r, zidovudine (AZT), lamivudine (3TC) either immediately or when clinically or immunologically indicated.

In this analysis, the investigators defined virological response as viral load <400 copies/mL and immunological response as CD4% increase >10% from pre-treatment level, at 24 and 40 (or 48 if missing at 40) weeks after starting HAART. Using logistic regression, the investigators examined the association between age at baseline, CD4%, absolute CD4, viral load, weight for age z-score, TB and gender with virological and immunological response. By the end April 2009, 387/451 children had started HAART and had data for >1 outcome.

At baseline, the children were a median: age of 8.4 (IQR 7.111.4) weeks; weight-for-age z-score -0.8 (-1.60.0); CD4% 32% (24-38%). Over half (59%) had a viral load >750,000 copies/mL. The majority (79%) started HAART by 12 weeks.

At 24 weeks, 71% (95% CI, 6575%, 246/349) of children had a viral load <400 copies/mL; 77% (245/320) at 40/48 weeks. Assuming loss to follow up as failure, these proportions were 65% and 68% at 24 and 40/48 weeks, respectively.

The investigators found no association between virological response and age at initiation (OR at 24 weeks 1.04 per 4 weeks increase, 95%CI 0.951.14, p=0.39), CD4%, weight-for-age z-score, viral load or gender.

Only 5/15 (33%) children with active TB (diagnosed before or within 1 month after initiation) receiving concurrent TB treatment were <400 copies/mL at 24 weeks vs 241/334 (72%) of the remaining children (RR 0.47, 95%CI 0.230.96, p=0.04).

Median change in CD4% from baseline was similar at 24 weeks (7%, IQR 113%) and 40/48 weeks (7%, 1% -13%). CD4% increase >10% occurred in 33% and 32% at 24 and 40/48 weeks respectively.

CD4% increase >10% was more likely with lower CD4% at initiation. The investigators noted this was the only predictor of immunological response at both time-points.

The investigators concluded: Virological response was satisfactory in this large cohort of infants initiating lopinavir-based ART in South Africa, and similar to rates reported in infants from well-resourced settings

They plan to look at suppression in relation to adherence in this trial and resistance in children with detectable viral load.

Ref: Violari A et al. Virological and Immunological Responses in Infants Receiving a LPV/r-based Regimen. 17th CROI, 16-19 February 2010, San Francisco. Poster abstract 843.