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.
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).


METHODS
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.


CONCLUSIONS
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.
Khanna
N
N
Basel Center for HIV-Research, Outpatient Department of Internal Medicine, University of Basel, Switzerland.
Klimkait
T
T
Schiffer
V
V
Irigoyen
J
J
Telenti
A
A
Hirschel
B
B
Battegay
M
M
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir