Initial growth, CD4, and viral load responses to HAART in Ugandan compared to UK/Irish HIV-positive children

Childrens responses to ART in Africa may be different from children in well-resourced settings due to non-HIV-related factors including nutritional status, exposure to infections, food scarcity and malnutrition.

Addy Kekitiinwa and coworkers compared 6 and 12-month immunological, virological and growth responses to ART in HIV-postitive children from 54 hospitals in the United Kingdom and Ireland (Collaborative HIV Paediatric Study, CHIPS) and from the Mulago Hospital, Uganda.

This study looked at predictors of viral load suppression <400 copies/mL, CD4 percentage increases >10%, and height- and weight-for-age z-score increases >+0.5, 6 months post-ART (starting >3 drugs, >2 classes).

Children in the CHIPS cohort (n=582) initiating ART naive 1997-2006 and Mulago cohort (n=876) initiating ART naive 2003-2007 were evaluated.

The investigators found at baseline, CHIPS children (76% black African) were younger than Mulago children median age 5.0 (IQR 1.6-8.9) vs 7.6 (IQR 4.4-11.6) years, with higher pre-ART CD4 percentage (14% vs 8%), lower viral load (172,491 vs 346,810 copies/mL), less stunting (0.8 vs 2.8) and wasting (0.6 vs 2.8).

After initiation of ART, the two groups showed similar changes in CD4 percentage (median +12%, +14%) and weight (+0.5, +0.4) at 12-months.

There was less change in height in the Mulago children (+0.06 vs +0.20, heterogeneity p<0.001). 16% in CHIPS vs 70% in Mulago had height <2.5th centile at ART initiation; this reduced to 11% at 12 months in CHIPS but remained at 70% in Mulago. The investigators noted that if these z-scores continued throughout childhood the average 17 year old would be 1.72 and 1.60 metres tall in CHIPS for boys and girls respectively (average UK population 1.76 and 1.64 metres) but only 1.53 and 1.47 metres tall in Mulago.

In multivariate analysis, in both cohorts, younger children had better immunological, weight and growth responses (all p<0.001) but slightly poorer viral load responses (p= 0.08) and girls had a better immunological response than boys (OR 1.55, p= 0.001).

In contrast, lower pre-ART CD4 predicted better immunological response in CHIPS but poorer response in Mulago (heterogeneity p=0.005). The investigators suggest that this may reflect poorer nutrition status and/or other environmental factors such as lower background incidence of infectious diseases in UK and Ireland.

Although 70% of the children in both cohorts had viral load <400 copies/mL at 6 months, adolescents starting ART in CHIPS had a poorer viral load responses than those in Mulago, which may reflect poorer adherence.

The investigators concluded that these findings highlight the importance of monitoring growth as well as weight gain over longer periods on ART in resource-limited settings. They suggest that investigations to evaluate the effect of nutritional support on growth in children initiating ART in resource- limited settings are urgently needed.

They wrote: Finally, this study has relevance for questions currently being raised about the timing of initiation of ART in resourcelimited settings in both adults and children. Earlier HIV diagnosis and nutritional support are clearly required for children in Africa, and initiating ART earlier in the course of the disease may well be beneficial.

Kekitiinwa A, Lee K, Walker A et al. Initial growth, CD4, and viral load responses to HAART in Ugandan compared to UK/Irish HIV-infected children. 15th CROI. February 2008. Boston, USA. Poster abstract 584.