Adult fixed-dose generic antiretroviral tablets are a safe and effective emergency treatment option for HIV-positive children in resource-limited setting who lack access to specialist paediatric HIV treatment formulations, according to a study published in the October edition of AIDS. However, the investigators from the international aid agency, Medecins Sans Frontieres (MSF), caution that despite these findings, an urgent need remains for affordable paediatric HIV therapy in resource-limited settings.
There are an estimated 2.3 million HIV-positive children worldwide, most of who live in resource-limited countries. Although upwards of one million adults now have access to antiretroviral drugs in poorer countries, it is estimated that only 5% of the 660,000 children in need of anti-HIV therapy in poorer countries have actually started it.
A number of significant obstacles exist to the provision of antiretroviral drugs to children in poorer countries including, a lack of expert staff; a lack of appropriate paediatric antiretroviral formulations; a lack of fixed-dose combination tablets; cost; and, a lack of low-cost diagnostic tools.
By the end of 2005, an estimated 57,000 individuals in 30 countries were receiving antiretroviral drugs from Medecines Sans Frontieres. Although adults are the focus of these treatment programmes, an increasing number of children are receiving antiretroviral drugs from the aid agency. Due to the lack of low-cost paediatric formulations, children treated with antiretroviral therapy by Medecins Sans Frontieres have received therapy with generic fixed-dose tablets, developed for the treatment of HIV-positive adults. Investigators from the aid agency wished to determine the early outcomes of these children and the safety of adult fixed-dose therapy when used in this way.
A total of 1184 children aged under 13 years from 16 clinics in eight countries were included in the study. All the children met World Health Organization (WHO) criteria for the commencement of antiretroviral therapy and were provided with first-line anti-HIV therapy consisting of Triviro 30 or Triviro 40 (containing stavudine 30 or 40mg with lamivudine 150mg and nevirapine 200mg). These tablets were taken whole or split in half. Children who weighed under ten kilograms were ineligible for the study, so tablets were not split into quarters.
The children’s median age was 7 years, 1% were under 18 months of age, 52% were boys, and 39% had AIDS at the time antiretroviral therapy was commenced. Baseline CD4 cell counts or percentages were available for 400 children, with 85% of children aged between 18 months and five years having a CD4 cell percentage of 15% or below, and 51% of children aged between five and 13 years having a CD4 cell count of 200 cells/mm3 or less.
Antiretroviral therapy was provided for a median of six months. For children aged between 18 months and five years, the median CD4 cell percentage gain at six months was 12% and the median gain at twelve months was 15%. Children aged between 5 and 13 years had a median increase in their CD4 cell count of 277 cells/mm3 six months after initiating HIV therapy, with the twelve month gain being 277 cells/mm3.
The proportion of children with a dangerously low CD4 cell count fell significantly after the initiation of antiretroviral therapy. At baseline, 85% of children aged between 18 months and five years had a CD4 cell percentage of 15% or less, but this had fallen to 11% after a year of antiretroviral therapy. Similarly, the percentage of older children with a CD4 cell count of 200 cells/mm3 or less fell from 51% at baseline to 11% after six and twelve months of HIV therapy.
At the end of March 2005, 85% of children who started on adult, fixed-dose generic antiretroviral tablets were still alive, 3% had died, 1% had stopped therapy, 8% were lost to follow-up and 3% were of unknown outcome.
Overall probability of survival for the children was 95%. If deaths and loss to follow-up were combined, then the probability of survival was 87%.
Side-effects were reported by 4% of children, but only 26 (2%) children changed treatment because of them. No deaths were attributed to HIV therapy.
“This study shows that generic adult fixed-dose combination antiretroviral tablets can be successfully used to treat children in urgent need of antiretroviral therapy in resource-limited settings, and satisfactory short-term outcomes can be achieved under routine programme conditions”, write the investigators.
They point to a number of “operational benefits” from the use of adult fixed-dose formulations, including accessibility and cost. In addition, they suggest that children may find adult fixed-dose pills easier to take than paediatric syrup preparations which often have an unpleasant taste.
Nevertheless, they do not believe that the use of adult fixed-dose generics provides a long-term solution to the treatment needs of HIV-positive children in resource-limited countries.
They conclude, “although MSF has gone ahead and used adult fixed-dose combinations to administer life-saving antiretrovirals to children in resource-limited settings, and the primary results are very encouraging, we fell this situation is ‘far from ideal’ and does not in anyway replace the urgent need for adapted and affordable paediatric formulations, including those in fixed-dose combination form, to become available.”
O’Brian DP et al. In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy. AIDS 20: 1955 – 1959, 2006.