Efavirenz- and adefovir dipivoxil-based salvage therapy in highly treatment-experienced patients: clinical and genotypic predictors of virologic response.
OBJECTIVE
To determine the impact of prior nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy, genotypic resistance, and other variables on response to efavirenz (EFV)- and adefovir dipivoxil (ADV)-based salvage therapy.


METHODS
Retrospective clinical cohort study.


METHODS
One university and one community-based HIV clinic.


METHODS
All 33 patients who were coenrolled in both the EFV and ADV expanded access programs.


METHODS
Patients received EFV 600 mg/day and ADV 120 mg/day in addition to other antiretroviral agents.


METHODS
HIV viral load (<500 copies/ml) at 12 and 24 weeks.


RESULTS
10 of 33 (30%) patients at 12 weeks and 8 of 33 (24%) patients at 24 weeks had viral loads <500 copies/ml. Prior NNRTI use and a history of any NNRTI-associated mutations predicted failure. Patients with Y181C or G190A single mutations had an initial greater magnitude of viral load suppression than those with K103N, but this advantage was short lived. No one with any NNRTI mutations responded with a viral load <500 copies/ml at 12 or 24 weeks.


CONCLUSIONS
EFV/ADV-based salvage yielded viral load suppression at 24 weeks in 42% (8 of 19) of patients who were highly NRTI and protease inhibitor experienced but NNRTI naive. NNRTI-experienced study subjects had a poor response regardless of the specific NNRTI resistance mutation they harbored.
Shulman
N S
NS
Stanford University School of Medicine, Division of Infectious Diseases, California 94305, USA. nshulman@earthlink.net
Zolopa
A R
AR
Passaro
D J
DJ
Murlidharan
U
U
Israelski
D M
DM
Brosgart
C L
CL
Miller
M D
MD
Van Doren
S
S
Shafer
R W
RW
Katzenstein
D A
DA
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D048588:Benzoxazines; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates; D010078:Oxazines / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D048588:Benzoxazines; D003062:Codon; D003521:Cyclopropanes; D063065:Organophosphonates; D010078:Oxazines; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000225:Adenine; C098320:efavirenz; C106812:adefovir dipivoxil