This brief looks at the evidence from the ARROW trial, which compared a standard WHO-recommended regimen for children with a strategy of starting with a potentially more potent 4-drug regimen (induction) and then dropping to 3 drugs (maintenance), to see if this can improve outcomes for children.
Children responded very well to a standard treatment with an NRTI (non-nucleoside reverse transcriptase inhibitors) regimen with ABC (abacavir)+3TC (lamivudine); this was equally the case in children ≤3 years taking nevirapine compared with older children taking nevirapine or efavirenz. Overall, very few children died or needed to switch treatment because of first-line failure; and after nearly 4 years, 83% had suppressed viral load and only 1% had low CD4.
Children receiving an induction phase of 4 drugs had better early CD4 and viral load responses compared with those taking 3 drugs, particularly in those with low CD4 when treatment started; however, these benefits were not sustained after the fourth drug was dropped during the 3 drug maintenance phase
After an induction phase with 4 drugs (including an NNRTI), children treated with triple NRTI (nucleoside reverse transcriptase inhibitors) long-term maintenance did well clinically and immunologically even though their viral load suppression was less good than those on a regimen of 3TC/ABC/NNRTI. This suggests that 3NRTI can be used during short-term TB treatment in children who are already on ARVs, avoiding challenges of complex drug-drug interactions. In addition, young children who are on a 4 drug regimen can safely drop nevirapine if they need to start treatment for TB.
South, A.; Munderi, P.; Walker, S.; Bwakura-Dangarembizi, M.; Cook, A.; Crawley, J.; Kekitiinwa, A.; Prendergast, A.; Gibb, D. M. MRC CTU Briefing Paper, March 2013, Issue 7. (2013) 4 pp.