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

Background: Highly active antiretroviral therapy (HAART) may fail, especial ly in pretreated patients. Objective: To examine retrospectively whether heavily pre-treated patients not responding to HAART at least once respond to a salvage therapy with aba cavir, a nucleoside reverse transcriptase inhibitor (NRTI) plus a non-nucle oside analogue reverse transcriptase inhibitor (NNRTI) and one or two prote ase inhibitors (PI). Patients: We retrospectively identified and analysed patients followed in t he 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 nevirap ine) 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 log(10) 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 patien ts increased their CD4 cell counts by > 30% above baseline. Three patients, all with CD4 cell counts < 100 x 10(6)/1 before salvage therapy had a > 30 % decline in CD4 cell count. An extended number of resistance-associated mu tations was found in almost all patients at baseline. One patient had two n ew 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 v irological success rate despite usage of abacavir and NNRTI. Nevertheless, this did not correlate with immunological and clinical course. This study e mphasizes the difficulty of second-line treatment in HIV-1 infection and st resses the need for new compounds. (C) 2000 Lippincott Williams & Wilkins.