medwireNews: Routine laboratory monitoring for toxicity is unnecessary in children with HIV treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) plus nucleoside reverse transcriptase inhibitors (NRTIs), research shows.
Antiretroviral therapy (ART), according to the researchers, "provides enormous benefits to children and can be delivered safely with good-quality clinical care and without routine toxicity monitoring."
They note that such monitoring might only serve as a barrier to life-saving treatment, especially in developing countries like those in sub-Saharan Africa.
"Infrastructure, personnel, and supply chain constraints all affect the ability to monitor, and tests for detecting toxicity and measuring efficacy are generally unavailable, particularly at low-level facilities," write the ARROW (AntiRetroviral Research fOr Watoto) trial team in The Lancet.
ARROW was a 2x2 factorial-designed trial evaluating the long-term effect of routine efficacy and toxicity monitoring and different first-line ART strategies in 1210 treatment-naïve children with HIV from Uganda and Zimbabwe.
For patients assigned to receive routine laboratory monitoring, physicians received the results every 12 weeks. For patients assigned to undergo clinically driven monitoring, hematology and biochemistry results (toxicity) and CD4 cell counts (efficacy) were only provided if requested by clinicians or if they had a World Health Organization (WHO) stage 4 clinical event.
The primary endpoint, a new WHO stage 4 event or death, occurred in 47 (7.8%) of the 606 children assigned to clinically-driven monitoring and in 39 (6.5%) of the 600 children assigned to routine laboratory monitoring - a nonsignificant difference that met the criteria for noninferiority.
"CD4 monitoring provided a small but significant reduction in disease progression or death after the second year on ART in children, as in adults," report Diana Gibb (Medical Research Council Clinical Trials Unit, London, UK) and co-authors.
In addition, the researchers studied three first-line ART strategies based on NNRTI and NRTI combinations, including induction (four drugs) and maintenance (three drugs) strategies. The mean percentage change in CD4 cell counts did not significantly differ between the treatment groups at week 72 or week 144.
"Four-drug ART with an NNRTI plus three NRTIs provided superior short-term virologic suppression and CD4 responses, but these benefits were not sustained during maintenance three-drug ART," report Gibb and colleagues.
In children initiating ART with severe immune suppression, adding a fourth drug improved short-term immunologic and virologic responses.
In an editorial, Louise Kuhn (Columbia University, New York, USA) and Hoosen Coovadia (University of KwaZulu-Natal, Durban, South Africa) state that large, rigorous trials of pediatric HIV treatments are rare.
"ARROW, by addressing this neglected population, has greatly expanded our knowledge base to improve treatment for children with HIV," they say.