A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy.
OBJECTIVE
To compare the effect of treatment decisions guided by phenotypic resistance testing (PRT) or standard of care (SOC) on short-term virological response.


METHODS
A prospective, randomized, controlled clinical trial conducted in 25 university and private practice centers in the United States.


METHODS
A total of 272 subjects who failed to achieve or maintain virological suppression (HIV-1-RNA plasma level > 2000 copies/ml) with previous exposure to two or more nucleoside reverse transcriptase inhibitors and one protease inhibitor.


METHODS
Randomization was to antiretroviral therapy guided by PRT or SOC.


METHODS
The percentage of subjects with HIV-1-RNA plasma levels less than 400 copies/ml at week 16 (primary); change from baseline in HIV-1-RNA plasma levels and number of "active" (less than fourfold resistance) antiretroviral agents used (secondary).


RESULTS
At week 16, using intent-to-treat (ITT) analysis, a greater proportion of subjects had HIV-1-RNA levels less than 400 copies/ml in the PRT than in the SOC arm (P = 0.036, ITT observed; P = 0.079, ITT missing equals failure). An ITT observed analysis showed that subjects in the PRT arm had a significantly greater median reduction in HIV-1-RNA levels from baseline than the SOC arm (P = 0.005 for 400 copies/ml; P = 0.049 for 50 copies/ml assay detection limit). Significantly more subjects in the PRT arm were treated with two or more "active" antiretroviral agents than in the SOC arm (P = 0.003).


CONCLUSIONS
Antiretroviral treatment guided prospectively by PRT led to the increased use of "active" antiretroviral agents and was associated with a significantly better virological response.
Cohen
Calvin J
CJ
Community Research Initiative of New England, Boston, MA 02215, USA.
Hunt
Susan
S
Sension
Michael
M
Farthing
Charles
C
Conant
Marcus
M
Jacobson
Susan
S
Nadler
Jeffrey
J
Verbiest
Werner
W
Hertogs
Kurt
K
Ames
Michael
M
Rinehart
Alex R
AR
Graham
Neil M
NM
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; 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* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors