title: Impact of the number of failed therapeutic regimes on the development of resistance mutations to HIV-1 in northeast Brazil.
abstract: Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.
authors.affiliation: Department of Pharmacology and Fisiology, Institute of Biomedicine, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. alima@ufc.br
authors.forename: Melissa Soares
authors.initials: MS
authors.lastname: Medeiros
authors.forename: Erico Antônio Gomes
authors.initials: EA
authors.lastname: Arruda
authors.forename: Richard Littleton
authors.initials: RL
authors.lastname: Guerrant
authors.forename: Christopher Cooley
authors.initials: CC
authors.lastname: Brown
authors.forename: Aldo Angelo Moreira
authors.initials: AA
authors.lastname: Lima
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase