A randomised control trial of structured interrupted generic antiretroviral therapy versus continuous therapy in HIV-infected individuals in Southern India

Abstract

This randomised control trial, conducted in Chennai, India, compared structured interrupted therapy (SIT) and continuous therapy (CT) in relation to immunologic and virologic outcomes, adverse events (AEs) and cost of therapy. ART-naïve adult HIV1-infected participants with CD4 counts 50–350cells/mm³, and plasma viral load (PVL)>5000copies/mL were enrolled and placed on Indian-manufactured generic ART: zidovudine(AZT)/stavudine(d4T)+lamivudine(3TC)+efavirenz(EFV). After at least six months of continuous therapy, subjects were randomised to SIT (one-week-on/one-week-off cycles) or CT. The primary end-point was the proportion of subjects maintaining CD4>200cells/mm³ at six and 12 months after randomisation. Secondary end-points were effective viral suppression (PVL<400copies/mL), AEs and cost. All analyses used intention-to-treat methodology. Of 40 participants (69% male; mean age 36±7; median baseline CD4 and PVL: 162cell/mm³and 259,000copies/mL), 17 were randomised to SIT and 18 to CT. At randomisation, median CD4s for SIT and CT were 378cells/mm³ and 357cells/mm³, respectively. All participants had PVL<400 copies/mL at time of randomisation. Median CD4 six months after randomisation was 498cells/mm³ and 417cells/mm³ for SIT and CT respectively. All participants had CD4>200cells/mm³. One participant on CT and two on SIT had sustained PVL>400copies/mL. There were no serious AEs or deaths. Structured interrupted therapy cost was half of CT. Structured interrupted therapy was effective at maintaining CD4 above 200cells/mm³. Adverse events were comparable in both groups, with 50% reduction in cost for SIT. Further research on such strategies may benefit resource-constrained settings.

Acknowledgments

We are most grateful to the patients who participated in this study, to Ms Rubavathi Ranganathan, the research nurses and all the clinical staff at YRG Center for AIDS Research and Education, VHS, Chennai, India for their facilitation of the study. We would like to acknowledge Dr Sreekanth Chaguturu, Mr A. K. Srikrishnan and Mr S. Anand for their work on the project. We would like to thank Brown University's AIDS International Research and Training Program of the Fogarty International Center of the National Institutes of Health, US (Grant No. D43TW00237) and the Lifespan/Tufts/Brown Center for AIDS Research, an NIH funded program (#P30 AI42853), for supporting this study. We also acknowledge with gratitude support from the ICTU-ACTG-Chennai Site grant (5U01 AI 038858) and the Fogarty Ellison Fellowship, National Institutes of Health, US. There is no conflict of interest.