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

Veronica Miller*, Caroline Sabin, Kurt Hertogs, Stuart Bloor, Javier Martinez-Picado, Richard D'Aquila, Brendan Larder, Thomas Lutz, Peter Gute, Eckhart Weidmann, Holger Rabenau, Andrew Phillips, Schlomo Staszewski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

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/I; 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 counrs (192 versus 59 × 106 cells/I; 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.

Original languageEnglish (US)
Pages (from-to)2857-2867
Number of pages11
JournalAIDS
Volume14
Issue number18
DOIs
StatePublished - 2000

Keywords

  • Resistance
  • Salvage therapy
  • Shift to wild type
  • Treatment interruption

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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