TITLE:
Darunavir Resistance in HIV Infecting Protease Inhibitor-Experienced Mexican Patients
AUTHORS:
Carlos A. Agudelo, Luis E. Soto-Ramírez, Abraham Katime-Zúñiga, Lorena Cabrera-Ruíz, Hugo Lara-Sánchez, Juan J. Calva
KEYWORDS:
Darunavir; Resistance; Risk Factors; Prevalence; Mexico
JOURNAL NAME:
World Journal of AIDS,
Vol.3 No.3,
September
5,
2013
ABSTRACT:
Background: Darunavir
(DRV) is a useful antiretroviral treatment in the salvage therapy of
multiclass-resistant HIV-infected patients. This study’s aim was to determine
the frequency and risk factors for DRV resistance-associated mutations
(DRV-RAM) among DRV-naive Mexican patients with virologic failure after extensive
antiretroviral treatment and exposure to at least one protease inhibitor (PI). Methods: HIV-infected patients with a
history of at least 2 failed regimes were included and their clinical histories
and genotype resistance tests were analyzed. Major PI resistance-associated
mutations (PI-RAM), DRV-RAM and resistance to DRV were defined according to the
IAS-USA criteria. Previous exposure to PI was compared between patients with
DRV-resistant HIV and DRV-susceptible HIV-infected controls. Results: The median number of major
PI-RAM was 2 (IQR = 0- 3). In 54.7% (95% CI = 50.0% -
59.4%) of 631 subjects, no DRV-RAM were found on viral genotyping and 6.7% (95%
CI = 4.8% - 8.6%) had 3 or more DRV-RAM. The two most frequently found DRV-RAM
were in codons I84V (in 22.7% of cases) and L33F (in 20% of cases) in the viral protease gene. The
number of major PI-RAM (as a surrogate marker of duration and number of PI
used) and previous exposure to (fos) amprenavir or tipranavir were
independently associated with DRV-resistant HIV infection. Conclusions: In this Mexican population, despite a high prior PI
exposure, HIV-DRV resistance rate is relatively low and successful viral
control with DRV-containing combined salvage therapy is expected in most
patients.