A feasibility study of immediate versus deferred antiretroviral therapy in children with HIV infection

Abstract

Objective: To evaluate the feasibility of a large immediate versus deferred antiretroviral therapy (ART) study in children.

Methods: We conducted an open-label pilot randomized clinical trial study in 43 Thai children with CD4 15 to 24% of starting generic AZT/3TC/NVP immediately (Arm 1) or deferring until CD4 < 15% or CDC C (Arm 2). Primary endpoints were recruitment rate, adherence to randomized treatment and retention in trial. Secondary endpoints were % with CDC C or CD4 < 15%. Children were in the trial until the last child reached 108 weeks. Intention to treat and on treatment analyses were performed.

Results: Recruitment took 15 months. Twenty-six of 69 (37.7%) were not eligible due mainly to low CD4%. Twenty four and 19 were randomized to arms 1 and 2 respectively. All accepted the randomized arm; however, 3 in arm 1 stopped ART and 1 in arm 2 refused to start ART. Ten/19 (53%) in arm 2 started ART. At baseline, median age was 4.8 yrs, CDC A:B were 36:7, median CD4 was 19% and viral load was 4.8 log. All in arm 1 and 17/19 in arm 2 completed the study (median of 134 weeks). No one had AIDS or death. Four in immediate arm had tuberculosis. Once started on ART, deferred arm children achieved similar CD4 and viral load response as the immediate arm. Adverse events were similar between arms. The deferred arm had a 26% ART saving.

Conclusion: Almost 40% of children were not eligible due mainly to low CD4% but adherence to randomized treatment and retention in trial were excellent. A larger study to evaluate when to start ART is feasible.

Figure 1

Study design and patient disposition. Footnote: All children in the deferred arm started ART because of protocol-defined CD4 criteria. All patients reached week 108. Some patients had additional follow up between weeks 120 to 168. Number of patients at last follow up visit in immediate/deferred arms = 21/15 at week 120, 13/11 at week 132, 8/5 week 144 and 7/4 at week 168). ART: antiretroviral therapy.

Figure 2

Intention to Treat analysis of CD4% in the immediate arm, deferred arm without ART initiation and deferred arm with ART initiation. * P-value represents difference within the three groups by by Kruskal Willis test.

Figure 3

Intention to Treat analysis of viral load in the immediate arm, deferred arm without ART initiation and deferred arm with ART initiation. * P-value represents difference within the three groups by by Kruskal Willis test.