Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure

Objective: To analyse the immunological and virological effects of treatmen t interruptions in HIV-1-infected patients with treatment failure and multi drug-resistant virus. Methods: Drug susceptibility was assessed using Antivirogram and genotypic analysis was based on population and clonal sequencing for 48 patients who had interrupted treatment (greater than or equal to 2 months). Results: Treatment interruption resulted in viral load increases (mean 0.7 log(10) copies/ml; P = 0.0001) and CD4 cell count decreases (mean 89 x 10(6 ) cells/l; P = 0.0001). A complete shift to wild-type virus at the phenotyp ic, genotypic and clonal level was observed in 28/45 patients. These patien ts differed from those that did not show a shift to wild type in baseline C D4 cell counts (192 versus 59 x 10(6) cells/I; P = 0.007) and in the relati onship between baseline viral load and CD4 cell count (no correlation versu s a significant negative correlation; P = 0.008). Response to re-initiation of treatment fell with increasing viral load [relative hazard (RH) 0.33; P = 0.001] and with increasing total number of drugs with reduced susceptibi lity (RH 0.51; P = 0.0003); it improved with the number of new drugs receiv ed (RH 2.12; P = 0.0002) and a shift to wild type (RH 5.22, P = 0.006). Conclusions: Changes in surrogate markers suggest that treatment provided b enefit in spite of virological failure and resistant virus. Although patien ts with a shift to wildtype virus responded better in the short term to tre atment re-initiation, the long-term effects are not known and the risk of i mmune deterioration needs to be carefully considered. (C) 2000 Lippincott W iIliams & Wilkins.