Salvage therapy with abacavir plus a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor in heavily pre-treated HIV-1 infected patients. Swiss HIV Cohort Study

AIDS. 2000 May 5;14(7):791-9. doi: 10.1097/00002030-200005050-00004.

Abstract

Background: Highly active antiretroviral therapy (HAART) may fail, especially in pre-treated patients.

Objective: To examine retrospectively whether heavily pre-treated patients not responding to HAART at least once respond to a salvage therapy with abacavir, a nucleoside reverse transcriptase inhibitor (NRTI) plus a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) and one or two protease inhibitors (PI).

Patients: We retrospectively identified and analysed patients followed in the Swiss HIV Cohort Study with > 1000 HIV RNA copies/ml on HAART, naive to abacavir who were switched to abacavir plus one NNRTI (efavirenz or nevirapine) and one or two PI which had not been used in the previous HAART.

Results: Of 23 identified HIV-infected patients with four (median) therapy changes before salvage, 10 patients (43%) achieved a decrease of plasma HIV RNA > 0.5 log10 at 6 months of therapy. After 6 months only two patients had an HIV-1 RNA < 500 copies/ml, one of them < 50 copies/ml. Seven patients increased their CD4 cell counts by > 30% above baseline. Three patients, all with CD4 cell counts < 100 x 10(6)/l before salvage therapy had a > 30% decline in CD4 cell count. An extended number of resistance-associated mutations was found in almost all patients at baseline. One patient had two new AIDS-defining events. Five patients (22%) discontinued treatment because of side-effects, mainly occurrence of a rash.

Conclusion: Salvage therapy in intensively pre-treated patients has a low virological success rate despite usage of abacavir and NNRTI. Nevertheless, this did not correlate with immunological and clinical course. This study emphasizes the difficulty of second-line treatment in HIV-1 infection and stresses the need for new compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Dideoxynucleosides / pharmacology
  • Dideoxynucleosides / therapeutic use*
  • Disease Progression
  • Drug Resistance, Microbial / genetics
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • RNA, Viral / blood
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Salvage Therapy*

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • HIV Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • abacavir