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

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- naive adult HIV1- infected participants with CD4 counts 50 - 350 cells/ mm(3), and plasma viral load ( PVL) > 5000 copies/ 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 > 200 cells/ mm 3 at six and 12 months after randomisation. Secondary end- points were effective viral suppression ( PVL < 400 copies/ mL), AEs and cost. All analyses used intention- to- treat methodology. Of 40 participants ( 69% male; mean age 3697; median baseline CD4 and PVL: 162 cell/ mm(3) and 259,000 copies/ mL), 17 were randomised to SITand 18 to CT. At randomisation, median CD4s for SITand CTwere 378 cells/ mm(3) and 357 cells/ mm(3), respectively. All participants had PVLB400 copies/ mL at time of randomisation. Median CD4 six months after randomisation was 498 cells/ mm(3) and 417 cells/ mm(3) for SIT and CT respectively. All participants had CD4 > 200 cells/ mm(3). One participant on CTand two on SIT had sustained PVL > 400 copies/ 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 200 cells/ mm(3). Adverse events were comparable in both groups, with 50% reduction in cost for SIT. Further research on such strategies may benefit resource- constrained settings.