Shift in HIV resistance genotype after treatment interruption and short-term antiviral effect following a new salvage regimen

Objective: To investigate the changes in genotypic drug-resistance pattern, plasma HIV RNA and CD4 cell count after treatment interruption and assess the short-term antiviral effect of a new salvage regimen. Design: Prospective study of 38 patients with multiple failing regimens who had completely stopped all medication for 3 months before a three to five- drug regimen was reintroduced according to clinical guidelines. Methods: Patients were tested for HIV resistance before and after treatment interruption by population-based sequencing and clonal analysis of selecte d patients. Results: Discontinuation of therapy for 3 months was associated with a medi an increase in HIV RNA of 0.4 log(10) and a median decrease in CD4 cell cou nt of 43 x 10(6)/l. Sixty-one per cent of patients had a shift from the dru g-resistant genotype to a predominantly wild-type genotype. The patients si gnificantly likely to show genotype reversion were those in Centers for Dis ease Control groups A or B, who had been exposed to few drugs, had a low pl asma HIV RNA, or a high CD4 cell count. The only independent factor predict ing genotype reversion was the clinical stage. The median change in plasma HIV RNA at month 3 after treatment reintroduction was -2.3 log(10) copies/m l in patients who had genotype reversion compared with -0.6 log(10) copies/ ml in patients without genotype reversion (P = 0.004). Conclusion: Suspending treatment for 3 months after multiple failures could be a suitable strategy for optimizing salvage therapy provided it is insti tuted early, before the HIV disease becomes too advanced. (C) 2000 Lippinco tt Williams & Wilkins.