HIV-positive children who have a detectable viral load despite taking potent antiretroviral therapy may be able to safely simplify their HIV treatment without risking disease progression or a further increase in their viral load, according to a study published in the March 3rd edition of the Journal of Acquired Immune Deficiency Syndromes. Treatment was simplified by discontinuing therapy with a protease inhibitor whilst maintaining nucleoside reverse transcriptase inhibitor treatment, and although this led to a drop in CD4 cell percentage, in none of the children was this clinically significant.
Antiretroviral therapy can mean a longer and healthier life for HIV-positive children, but previous suboptimal treatment, side-effects, adherence issues, lack of paediatric formulations, and suboptimal or toxic drug levels, can mean that children fail to derive the full benefit of HIV treatment and continue to have a detectable viral load.
Treatment interruptions have been explored as an option for adults experiencing side-effects or ongoing HIV replication. Structured treatment interruptions guided by both CD4 cell count and viral load have been examined in clinical trials that have had disappointing results. Another strategy examined in patients with a detectable viral load has been a “partial treatment interruption” – the discontinuation of one class of drugs in a multi-class antiretroviral combination. This is also called treatment simplification.
Doctors in the United States observed that children with a detectable viral load who simplified their HIV treatment by discontinuing therapy with a protease inhibitor, but who continued to take NRTIs, remained clinically stable. They therefore conducted a retrospective study including all children who had pursued this treatment strategy. The objectives of the study were to describe the clinical, virological, and immunological outcome in the 26 children who stopped treatment with a protease inhibitor but maintained NRTI therapy.
All the children were followed for at least six months after discontinuing treatment with a protease inhibitor. Data were also available for 21 children after a year and for eleven children two years after treatment was simplified.
At baseline, the children had a median age of seven years. The median CD4 cell percentage was 27% and median viral load was 10,000 copies/ml. The most commonly used nucleoside combinations were 3TC (lamivudine, Epivir) with AZT (zidovudine, Retrovir) or 3TC with d4T (stavudine, Zerit). Resistance tests were performed on 16 children at baseline, and these indicated that 14 had extensive dual or triple-class resistance mutations.
All 26 children completed 24 weeks of follow-up and none experienced any HIV disease progression. Viral load did not change significantly, but there was a statistically significant fall in CD4 cell percentage (p = 0.028). However, in none of the children did CD4 cell percentage fall to such an extent that they were at risk of developing an AIDS-defining illness.
A total of 21 children were still included in the investigators’ analysis at week 48. Once again, none of these children experienced any HIV disease progression, and viral load was still stable at approximately 10,000 copies/ml. Although CD4 cell percentage was still significantly lower than at baseline (p = 0.01), in none of the children was it dangerously so.
Only eleven children were still taking a simplified regimen at week 96. Similar results to weeks 24 and 48 were observed at this point.
“We demonstrated that partial treatment interruption was not associated with clinical disease progression in a heterogeneous cohort of 26 children”, write the investigators, who add, “one can hypothesize that partial treatment interruption may be an acceptable option in many cases and that in those with decreasing CD4 parameters with or without increasing viral load, treatment reassessment and modification of the regimen should be considered.”
They caution that their anaylsis has “all the inherent limitations of a retrospective study” and that “further prospective studies are needed”.
Abadi J et al. Partial treatment interruption of protease inhibitor-based highly active antiretroviral therapy regimens in HIV-infected children. J Acquir Immune Defic Syndr 41: 298 – 303, 2006.