The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility: a prospective cohort analysis.
OBJECTIVE
To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI).


METHODS
Analysis of a prospective clinical trial cohort.


METHODS
NNRTI-naive patients failing a stable antiretroviral regimen.


METHODS
HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50%) of < 0.4.


RESULTS
The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 x 10(6) cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29%. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 x 10(6) cells/l greater in patients with hypersusceptible virus (P < or = 0.1).


CONCLUSIONS
NNRTI hypersusceptibility occurred in more than 20% of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.
Haubrich
Richard H
RH
University of California at San Diego, San Diego, California, USA.
Kemper
Carol A
CA
Hellmann
Nicholas S
NS
Keiser
Philip H
PH
Witt
Mallory D
MD
Forthal
Donald N
DN
Leedom
John
J
Leibowitz
Matthew
M
Whitcomb
Jeannette M
JM
Richman
Douglas
D
McCutchan
J Allen
JA
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors