NNRTI-based HAART effective in Thai children

Highly active antiretroviral therapy (HAART) based on generic non-nucleoside reverse transcriptase inhibitors (NNRTIs) is feasible and effective in treated children with advanced HIV disease in resource-limited settings, according to a presentation on Wednesday at the Twelfth Annual Retrovirus Conference in Boston.

Thailand’s national programme for access to antiretroviral treatment was begun in 2002. While NNRTI-based HAART using generic drugs manufactured in Thailand is the preferred first-line therapy for use in adults, the feasibility of this approach in children had not previously been studied.

One hundred and seven HIV-positive children aged between two and 15 years of age were recruited for this study from four hospitals across Thailand. All of the children had CD4 percentages below 15% (median 3%), or evidence of an active opportunistic infection.

The children received either nevirapine or efavirenz along with d4T (stavudine) and 3TC (lamivudine) for at least 72 weeks. In place of paediatric formulations, the children were given adult pills manufactured by GPOvir. The tablets were halved or quartered as necessary to obtain doses within the correct range for each child’s weight.

Each child received help from a family member or healthcare worker to take the correct drugs at the appropriate times. This led to 86% of the children achieving adherence rates of 95% or greater. Viral loads fell from 251,000 to below 50 copies/ml in 64% of the nevirapine group and 91% of the efavirenz group. This was mirrored by an increase to a median CD4 percentage of 21% after 72 weeks.

The children also showed increased body weight and height over the course of the study.

Five (8%) of the 61 children taking nevirapine experienced severe adverse reactions within the first two weeks of the study and were switched to the efavirenz arm. Thereafter, 23% of the nevirapine group experienced rash, and 26% of the efavirenz group had central nervous system side-effects such as dizziness and nightmares, but these did not require treatment discontinuation.

Only four children died during the 72-week study, one in the nevirapine group and three in the efavirenz group. However, fifteen experienced treatment failure, with the commonest resistance pattern conferring resistance to 3TC and NNRTIs.

Thanyawee Puthanakit, presenting, concluded by emphasising the effectiveness of the use of generic drug formulations in treating children, even in areas where paediatric liquid formulations are not available or feasible for use. Her results demonstrate that HIV-positive children in other resource-limited settings may benefit from similar models of treatment, even where therapy is started during advanced HIV disease.