Comparison of HAART Outcomes among HIV Positive Children in Developing and Developed Countries

By Liz Highleyman

taken by HIV positive women during pregnancy has dramatically lowered the rate of mother-to-child HIV transmission, and today vertical infection of infants in industrialized countries is quite uncommon.

Most recent research on HIV treatment in children has therefore been done in resource-poor areas. However, investigators with the European Infant Collaborative study recently reported that early treatment before babies develop symptoms of disease progression is associated with a lower risk of AIDS and death, similar to findings from the CHER study in South Africa.

At the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal, Elizabeth Peacock-Villada and colleagues from the University of Washington in Seattle reported findings from a systematic review comparing pediatric HAART treatment outcomes in developing and developed countries.

As background, the investigators explained that while they expected to observe differences in pediatric response to HAART around the world, the goal of this study was to "systematically compare and quantify differences in the major clinical endpoints between developed and developing nations as well as identify characteristics that may help decrease the treatment gaps."

The researchers searched for studies analyzing pediatric HAART cohorts in resource-limited and developed countries between 1981 and September 2008 using the PubMed, EBSCO, Global Health Host, AIDSLINE, and Cochrane Library databases.

They reviewed publications containing data on mortality, weight, CD4 cell count, or HIV viral load changes. All included studies had a sample size greater than 20 patients. HAART was defined as combination therapy consisting of 3 or more antiretroviral drugs. Countries were categorized as resource-limited or developed based on the United Nations Human Development Indices.

Out of 230 studies initially reviewed, 91 were considered relevant, and 49 met all the inclusion criteria (adequate sample size, type of therapy, etc.), 27 from resource-limited countries and 22 from developed countries. Of these, 33 studies looked at mortality, 39 included CD4 cell data, and 31 included viral load data.

Results

The mean baseline CD4 percentage was 12% in resource-limited countries, which was significantly lower than the mean 24% in developed countries (P < 0.001).

The mean baseline viral load was 5.57 log10 copies/mL in resource-limited countries compared with 4.87 log10 copies/mL in developed countries (P < 0.001).

Mortality in resource-limited countries was 2-3 times greater than in developed countries.

The mean percentage of deaths per cohort was significantly higher in resource-limited compared with developed countries (8.1 vs 4.6; P = 0.001).

The same was true for deaths per 100 person-years (8.1 vs 2.9, respectively; P < 0.001).

Most deaths occurred within 6 months after HAART initiation.

The increase in CD4 percentage after starting HAART was steeper in resource-limited countries than in developed countries.

However, the magnitude and speed (slope) of viral load suppression was comparable in both settings.

Type of HAART regimen (NNRTI vs protease inhibitor, use of a fixed-dose coformulation) was not a significant predictor of treatment success in resource-limited countries.

Overall, the investigators stated, children in resources-limited countries demonstrated "appropriate" immunological and virological response to HAART.

In fact, they continued, mortality rates in resource-limited and developed settings were similar, if not actually better in resource-limited countries considering respective mortality rates among children under age 5 in the general population.

"Significant differences in baseline CD4 percentage and viral load levels may combine with [other] infectious diseases and nutritional compromise in contributing to the differences in mortality despite adequate response to pediatric HAART," they concluded. "Earlier diagnosis of pediatric HIV in resource-limited countries would be expected to result in better HAART outcomes."

3/17/09

Reference
E Peacock-Villada, B Richardson, and G John-Stewart. Pediatric HAART Treatment Outcomes: A Comparison of Developing and Developed Countries. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 875.