HIV-positive children taking antiretroviral therapy in rural Uganda often have poor adherence, a detectable viral load and extensive resistance to anti-HIV drugs, according to a study conducted by Medecins Sans Frontieres and presented as a poster to the recent International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney.
More encouragingly, the study revealed that children taking antiretroviral drugs had a good immunological response to therapy and the overwhelming majority remained alive up to two years after starting treatment.
“Providing highly active antiretroviral therapy to children in rural areas in resource-limited-settings remains a challenge”, commented lead investigator, Dr Myrto Schaefer, who added there are limited data on medium- to long-term outcome for children who received routine HIV treatment and care in such environments.
Accordingly, Dr Schaefer and his fellow investigators designed a study to describe the clinical, virological and immunological outcomes of children who had received twelve or 24 months of potent anti-HIV therapy. The investigators also gathered data on adherence, the prevalence of resistance to antiretroviral drugs, and measured plasma concentrations of nevirapine and efavirenz.
The children enrolled in the study were receiving their care from the Arua AIDS project, which has been providing free anti-HIV therapy since July 2002.
Antiretroviral treatment was dosed according to a child’s weight. Those weighing under 10kg were prescribed treatment consisting of AZT/3TC and nevirapine syrup. Children who weighed between 10 and 24kg received half an adult fixed-dose tablet containing d4T/3TC/nevirapine, and children who weighed 25kg or above were treated with full adult fixed-dose tablets.
A total of 86 children were eligible for inclusion in the twelve month cohort. However two died, eight were lost to follow-up, five transferred their care, and eleven were excluded for analysis, providing a study population of 59.
The 24-month cohort consisted of 41 children, three of whom died, three were lost to follow-up, three transferred, and five were excluded, meaning that the study population was 27.
The median age of children who received twelve months treatment was 5.4 years, 54% were boys, 96% were HIV treatment-naïve, the median pre-treatment CD4 cell count for the over-fives was 190 cells/mm3 and the median CD4 percentage for the under-fives was 10%.
Median age for the children who received 24 months of treatment was 5.5 years, and 56% were boys. Almost all (97%) were antiretroviral-naïve, the median pre-treatment CD4 cell count was 70 cells/mm3 amongst the over-fives, and the median CD4 cell percentage prior to the initiation of HIV therapy in the under-fives was 11%.
At twelve months, 86% of children were still in care. The median weight gain at twelve months was 4kg, and median CD4 cell count at this time had increased to 504 cells/mm3 in the over-fives, with median CD4 cell percentage increasing to 25% in the under-fives. At 24 months, the median weight gain was 5kg, and median CD4 cell count amongst the over-fives was 210 cells/mm3, with median CD4 cell percentage in the under fives being 20%.
However, at neither twelve nor 24 months was adherence at optimum levels, and this was reflected in virological outcomes. At twelve months, only 59% of children had a viral load below 400 copies/ml, and this figure fell to 33% amongst children who had received 24 months of HIV therapy.
Resistance tests were performed on 33 of the 34 children who had a viral load above 1000 copies/ml. Resistance to at least one NRTI and one NNRTI was found in all but four of these children, and eight children were resistant to every drug being used in first-lined, fixed-dose therapy.
Suboptimal levels of nevirapine were found in 30% of children and 20% of those who received efavirenz also had suboptimal levels of the drug.
“Despite good long-term survival, virological outcomes at 24 months of HIV therapy were poor”, comment the investigators. They add, “this study highlights the importance of strengthening long-term adherence monitoring in children…affordable first- and second-line paediatric easy-to-use triple fixed-dose formulations are urgently needed in resource-limited settings.”
Ahoua L et al. Children’s antiretroviral treatment outcomes after 12 and 24 months of HAART in an HIV care program in North-western Uganda. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract TUPEB132, Sydney, 2007.