Phenotypic testing predicts virological response in successive protease inhibitor-based regimens.
OBJECTIVE
To evaluate the importance of the number of active drugs, as determined by phenotypic resistance testing, in achieving virological response in successive salvage regimens.


METHODS
Phenotypic study of 57 plasma samples corresponding to 24 patients who had sequentially received three protease inhibitor-containing regimens. Phenotypic susceptibility to a drug (active drug) was defined as less than a four-fold-increase in the IC50 in comparison with the wild type.


METHODS
Virological response according to the number of active drugs (three versus two or fewer), HIV load, length of antiretroviral exposure, and line of protease inhibitor-based therapy (first, second and third regimen).


RESULTS
Before the first protease inhibitor-based therapy, the median time on antiretroviral treatment was 42 months, and before the second and third protease inhibitor-salvage regimens it was 10 and 8 months, respectively. The number of patients receiving three active drugs simultaneously was 24, 35 and 31% in each line of therapy. At week 12, a close correlation was found between the presence of three active drugs in the antiretroviral regimen and the rate of virological response, in comparison with those patients receiving two or fewer active drugs [76 versus 45%, relative risk (RR), 1.7; 95% confidence interval (CI) 1.1-2.6; P = 0.028]. In a multivariate analysis, the use of two or fewer active drugs was an independent predictor of lack of response, regardless of HIV load, length of previous antiretroviral exposure and line of salvage therapy (RR, 4.5; 95%CI, 1.1-18.3; P = 0.03). Of note, a higher rate of response was observed in patients receiving the first protease inhibitor-containing regimen in comparison with those in subsequent protease inhibitor-based salvage regimens (83 versus 50 versus 28%, P < 0.01), even when only those patients receiving three active drugs were included (100 versus 71 versus 60%).


CONCLUSIONS
This data confirm the usefulness of phenotypic testing in guiding antiretroviral therapy in heavily pretreated patients. The number of active drugs and the line of salvage therapy are independent predictors of virological response, regardless of HIV load and the length of antiretroviral exposure.
Pérez-Elías
M J
MJ
Infectious Diseases Service, Ramón y Cajal Hospital, Madrid, Spain. mperez@hrc.insalud.es
Lanier
R
R
Muñoz
V
V
Garcia-Arata
I
I
Casado
J L
JL
Marti-Belda
P
P
Moreno
A
A
Dronda
F
F
Antela
A
A
Marco
S
S
Moreno
S
S
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D016001:Confidence Intervals; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral