Resistance to LPV, TPV and DRV according to three different algorithms in samples from highly antiretroviral-therapy-experienced-patients in Mexico City
Background: To compare three commonly used resistance algorithms to identify resistance to lopinavir(LPV), tipranavir(TPV) and darunavir(DRV) on HIV-1 protease sequences from highly antiretroviral-therapy-experienced-patients(HARTEP) in a third-care.center.
Methods: HIV-1 protease sequences (Viroseq 2.0; Celera Diagnostics) from patients with virological failure and antiretroviral history of three or more drug combinations with at least one protease inhibitor(PI) were studied. Genotypic analysis was made using three commonly-used-resistance-algorithms: Stanford University(US), Leuven University(UL) and clinical-studies-derived-algorithms (CSDA). Agreement rates were evaluated with kappa´s coefficient.
Results: 120 HIV-1 protease sequences were included. Median of PI used was 3. The most used PIs were Indinavir 22.8%, Ritonavir 22.5%, Saquinavir 21.3%, Lopinavir 17.4%, Nelfinavir 12%, Amprenavir 3% and Atazanavir 0.6%. No patient used Tipranavir(TPV) or Darunavir(DRV). Forty-six protease sequences were identified to be resistant to at least one PI: 30 to LPV alone, 15 to TPV(14 with concomitant LPV resistance) and 1 to DRV(with concomitant LPV and TPV resistance). Resistance prevalence to LPV, TPV and DRV in at least one algorithm was 37.5%, 12.5% and 0.87%, respectively. Although sequences identified as resistant to TPV or DRV were only reported by US and not for UL or CSDA, we identified 77(64%) and 58(48%) sequences with a least one previously reported resistance-associated-mutation(RAM) to TPV or DRV, respectively, with a mean of 2.5 and 1.4 RAM. LPV resistance cases were identified by all three algorithms with a mean of 7.5 RAM. Agreement rates to LPV between algorithms were: US vs CSDA,80%; CSDA vs UL,90%; UL vs US,85% (kappa coefficient: 0.47, 0.76 and 0.59, respectively).
Conclusions: Resistance algorithms have medium to high concordance rates in PI resistance detection. Although TPV and DRV are an option for 87.5% and nearly 100% of HARTEP, respectively, RAM to these PIs are relativity common, while LPV may still be an excellent option for treatment in 62.5% of cases.
A. Campos1, R.A. Rodríguez-Díaz2, L.L. Fuentes-Romero2, L.E. Soto-Ramírez1
1Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Infectious Diseases/HIV Clinic, Mexico City, Mexico, 2Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Infectious Diseases/Clinical Virology Lab, Mexico City, Mexico