Most children thriving after four years of HAART

After four years of HAART, the majority of a small cohort of Dutch children have continued to thrive, with most achieving and maintaining viral suppression and increased CD4 cell counts. However, unlike other paediatric studies, the researchers found that as the children aged, viral response worsened, possibly due to confounding effects of puberty-related adherence issues. The results of this study are published in the February 15^th issue of the journal of Clinical Infectious Diseases.

Between January 1997 and January 2004, 31 HIV-positive children, with a median age of 5.1 years (range 0.2 - 16.4) began HAART at a Children’s Hospital in Rotterdam. Fifteen were girls, 27 were non-white, 22 had been infected through mother-to-child transmission, four through blood products and in five, the route of HIV transmission was unknown. Fifteen were antiretroviral naive, and the other 16 had never taken protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Twenty-eight of the children began indinavir-based HAART, and three commenced with nelfinavir-based HAART. However, during the study period, anti-HIV therapy was changed 38 times for 28 children, and a median of two (range 1-5) regimens were used. A wide variety of reasons for changing treatment were given, including thirteen (41%) changing due to viral failure. Seven children moved from indinavir due to toxicity, the majority experiencing kidney toxicity, and one child experiencing skin rash.

During the four years, six children were lost to follow-up, including one death due to serious invasive opportunistic infections one year after commencing HAART. Of the remaining 25, three children’s HIV disease progressed according to CDC classification stage, although none were seriously ill. The rest were in good health, and a significant increase in growth was observed after starting HAART. In addition, CD4 counts recovered and remained stable; both the median value relative to the normal value (p=.01) and absolute T cell count (p=.025) were significantly higher after four years than at baseline.

After four years, in the intention-to-treat analysis 65% and 61% of children had viral loads below 500 copies/ml and 50 copies/ml, respectively. This increased to 80% and 76% respectively in the as-treated analysis. Seven of the 25 children still on therapy after four years had viral loads below 500 copies/ml after 12 weeks, and maintained viral suppression during the entire follow-up period; these children were all considered to have been highly adherent. Eleven of the 18 who did not have complete viral suppression throughout follow-up were considered to have been non-adherent at least once.

In binary logistic regression analysis it was found that there was no relationship between baseline viral load and response to HAART; however, the researchers found a significant negative relation between age and viral response rate (p = 0.04). They speculate that “puberty-related problems that interfere with the adherence to HAART were more likely to occur,” in this study, “because of the longer follow-up period.”

Adverse events were frequent, but usually mild and gastrointestinal, report the researchers. Several grade 3 and 4 laboratory adverse events were seen, including thrombocytopaenia in three children, increased amylase levels in two children, and increased gamma-glutamyl transpeptidase levels in one child. None of these events resulted in a change of therapy.

Lipoatrophy was suspected in two children, both of whom were taking stavudine, but different protease inhibitors. Fasting triglyceride and cholesterol levels were obtained in 17 of the 25 children on therapy; four children had triglycerides greater than the upper limit of normal (ULN), and one child had cholesterol greater than the ULN.

The authors conclude that “an excellent response to HAART was observed,” in this small study. “A high proportion of the children had undetectable HIV-1 RNA levels. CD4 T cell counts and T cell function recovered and remained stable throughout the follow-up period” and although “adverse events occurred frequently [they] were mostly mild.”