A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575.
OBJECTIVE
To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy.


METHODS
A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml.


METHODS
Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures.


RESULTS
At baseline, median CD4 cell count was 277 x 10 cells/l and HIV RNA was 10 000 copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48%) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value.


CONCLUSIONS
Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.
Haubrich
Richard H
RH
University of California, San Diego, California, USA. rhaubrich@ucsd.edu
Kemper
Carol A
CA
Hellmann
Nicholas S
NS
Keiser
Philip H
PH
Witt
Mallory D
MD
Tilles
Jeremiah G
JG
Forthal
Donald N
DN
Leedom
John
J
Leibowitz
Matthew
M
McCutchan
J Allen
JA
Richman
Douglas D
DD
D000328:Adult; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral