WJA  Vol.3 No.3 , September 2013
Darunavir Resistance in HIV Infecting Protease Inhibitor-Experienced Mexican Patients
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.
Cite this paper: C. Agudelo, L. Soto-Ramírez, A. Katime-Zúñiga, L. Cabrera-Ruíz, H. Lara-Sánchez and J. Calva, "Darunavir Resistance in HIV Infecting Protease Inhibitor-Experienced Mexican Patients," World Journal of AIDS, Vol. 3 No. 3, 2013, pp. 280-286. doi: 10.4236/wja.2013.33035.

[1]   A. Imaz, V. Falcó and E. Ribera, “Antiretroviral Salvage Therapy for Multiclass Drug-Resistant HIV-1-Infected Patients: From Clinical Trials to Daily Clinical Practice,” AIDS, Vol. 13, 2011, pp. 180-193.

[2]   B. Clotet, N. Bellos, J. M. Molina, et al., “Efficacy and Safety of Darunavir-ritonavir at Week 48 in Treatment-Experienced Patients with HIV-1 Infection in POWER 1 and 2: A Pooled Subgroup Analysis of Data from Two Randomized Trials,” Lancet, Vol. 369, No. 9568, 2007, pp. 1169-1178. doi:10.1016/S0140-6736(07)60497-8

[3]   K. Arastéh, P. Yeni, A. Pozniak, et al., “Efficacy and Safety of Darunavir/Ritonavir in Treatment-Experienced HIV Type-1 Patients in the POWER 1, 2 and 3 Trials at Week 96,” Antiviral Therapy, Vol. 14, 2009, pp. 859-864. doi:10.3851/IMP1301

[4]   J. V. Madruga, P. Cahn, B. Grinztejn, et al., “Efficacy and Safety of TMC125 (Etravirine) in Treatment-Experienced HIV-1-Infected Patients in DUET-1: 24-Week Results from a Randomized, Double Blind, Placebo-Controlled Trial,” Lancet, Vol. 370, No. 9581, 2007, pp. 29-38. doi:10.1016/S0140-6736(07)61047-2

[5]   A. Lazzarin, T. Campell, B. Clotet, et al., “Efficacy and Safety of TMC125 (Etravirine) in Treatment-Experienced HIV-1-Infected Patients in DUET-2: 24-Week Results from a Randomized, Double Blind, Placebo-Controlled Trial,” Lancet, Vol. 370, No. 9581, 2007, pp. 39-48. doi:10.1016/S0140-6736(07)61048-4

[6]   C. Katlama, B. Clotet, A. Mills, et al., “Efficacy and Safety of Etravirine at Week 96 in Treatment-Experienced HIV Type-1-Infected Patients in the DUET-1 and DUET-2 Trials,” Antiviral Therapy, Vol. 15, 2010, pp. 1045-1052. doi:10.3851/IMP1662

[7]   S. De Meyer, T. Vangeneugden, B. van Baelen, et al., “Resistance Profile of Darunavir: Combined 24-Week Results from the POWER Trials,” AIDS Research and Human Retroviruses, Vol. 24, No. 3, 2008, pp. 379-388. doi:10.1089/aid.2007.0173

[8]   J. E. Vidal, A. C. Freitas, A. T. W. Song, S. V. Campos, M. Dalben and A. V. Hernandez, “Prevalence and Factors Associated with Darunavir Resistance Mutations in Multi-Experienced HIV-1-Infected Patients Failing Other Protease Inhibitors in a Referral Teaching Center in Brazil,” Brazilian Journal of Infectious Diseases, Vol. 15, No. 3, 2011, pp. 245-248. doi:10.1016/S1413-8670(11)70183-0

[9]   E. Poveda, C. de Mendoza, L. Martin-Carbonero, et al., “Prevalence of Darunavir Resistance Mutations in HIV-1-Infected Patients Failing Other Protease Inhibitors,” Journal of Antimicrobial Chemotherapy, Vol. 60, No. 4, 2007, pp. 885-888. doi:10.1093/jac/dkm276

[10]   Y. Mitsuya, T. F. Liu, S. Y. Rhee, W. J. Fessel and R. W. Shafer, “Prevalence of Darunavir Resistance-Associated Mutations: Patterns of Occurrence and Association with Past Treatment,” The Journal of Infectious Diseases, Vol. 196, No. 8, 2007, pp. 1177-1179. doi:10.1086/521624

[11]   S. Bautista-Arredondo, A. Mane and S. M. Bertozzi, “Economic Impact of Antiretroviral Therapy Prescription Decisions in the Context of Rapid Scaling-Up of Access to Treatment: Lessons from Mexico,” AIDS, Vol. 20, No. 1, 2006, pp. 101-109. doi:10.1097/01.aids.0000198096.08444.53

[12]   J. J. Calva and Y. Vargas-Infante, “Cobertura Universal con la Terapia Antirretroviral Combinada. Logros y Desafios en la Secretaria de Salud de Mexico,” In: J. A. Cordova-Villalobos, S. Ponce de Leon-Rosales and J. L. Valdespino, Eds., 25 anos de SIDA en Mexico. Logros, Desaciertos y Retos, 2nd Edition, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, 2009, pp. 333-353.

[13]   V. A. Johnson, V. Calvez, H. F. Gunthard, et al., “2011 Update of the Drug Resistance Mutations in HIV-1,” Topics in Antiviral Medicine, Vol. 19, No. 4, 2011, pp. 156-164.

[14]   L. E. Wilson and J. E. Gallant, “The Management of Treatment-Experienced HIV-Infected Patients: New Drugs and Drug Combinations,” Clinical Infectious Diseases, Vol. 48, 2009, pp. 214-221.

[15]   C. Delaugerre, J. F. Buyck, G. Peytavin, et al., “Factors Predictive of Successful Darunavir/Ritonavir-Based Therapy in Highly Antiretroviral-Experienced HIV-1-Infected Patients (the DARWEST Study),” Journal of Clinical Virology, Vol. 47, No. 3, 2010, pp. 248-252. doi:10.1016/j.jcv.2009.12.022

[16]   S. De Meyer, A. Hill, G. Picchio, R. DeMasi, E. De Paepe and M. P. de Bethune, “Influence of Baseline Protease Inhibitor Resistance on the Efficacy of Darunavir/ ritonavir or Lopinavir/Ritonavir in the TITAN Trial,” Journal of Acquired Immune Deficiency Syndromes, Vol. 49, No. 5, 2008, pp. 563-564. doi:10.1097/QAI.0b013e318183ac9c

[17]   S. Y. Rhee, J. Taylor, W. J. Fessel, et al., “HIV-1 Protease Mutations and Protease Inhibitor Cross-Resistance,” Antimicrobial Agents and Chemotherapy, Vol. 54, No. 10, 2010, pp. 4253-4261.