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

2000; Lippincott Williams & Wilkins; Volume: 14; Issue: 18 Linguagem: Inglês

10.1097/00002030-200012220-00007

1473-5571

Veronica Miller, Caroline Sabin, Kurt Hertogs, Stuart Bloor, Javier Martínez‐Picado, Richard T. D’Aquila, Brendan Larder, Thomas A. Lutz, Peter Gute, Eckhart Weidmann, Holger F. Rabenau, Andrew Phillips, Schlomo Staszewski,

Hepatitis C virus research

Objective To analyse the immunological and virological effects of treatment interruptions in HIV-1-infected patients with treatment failure and multidrug-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 (≥ 2 months). Results Treatment interruption resulted in viral load increases (mean 0.7 log10 copies/ml;P = 0.0001) and CD4 cell count decreases (mean 89 × 106 cells/l;P = 0.0001). A complete shift to wild-type virus at the phenotypic, genotypic and clonal level was observed in 28/45 patients. These patients differed from those that did not show a shift to wild type in baseline CD4 cell counts (192 versus 59 × 106 cells/l;P = 0.007) and in the relationship between baseline viral load and CD4 cell count (no correlation versus 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 susceptibility (RH 0.51;P = 0.0003); it improved with the number of new drugs received (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 benefit in spite of virological failure and resistant virus. Although patients with a shift to wild-type virus responded better in the short term to treatment re-initiation, the long-term effects are not known and the risk of immune deterioration needs to be carefully considered.