title: Identification of key mutations in HIV reverse transcriptase gene can influence the clinical outcome of HAART.
abstract: Therapeutic failures due to in vivo loss of drug sensitivity are still a major problem in AIDS care. Currently, the role of and methods for detecting resistant mutant strains in patients before therapeutic choices are still under debate. To investigate the relevance of screening for key mutations alone the commercial INNO-LiPA HIV-1 RT method was applied retrospectively to analyzing several HIV codons correlated with resistance to RTI (reverse-transcriptase inhibitors) in sera from 62 patients before starting HAART protocols, selected on the basis of clinical parameters. INNO-LiPA detected several resistant mutant strains, which were strictly consistent with previous selective pressure in the patients. A significant correlation between genotype pattern and response to HAART was found. The presence of key mutations associated with resistance to one or two RTI included in the protocol correlated with a decrease in treatment benefits, whereas patients with wild-type or non-resistant viral strains exhibited better response to HAART. Even if this information had been available when treatment was started, 45 of the patients would not have received different treatment. When compared with the total number of patients, the subgroup receiving a treatment that was considered retrospectively as consistent with the key mutation pattern exhibited a significantly better outcome. Although the interpretation of resistance-related key mutations needs improvement, this surrogate LiPA method seems to maintain a predictive role in the management of HIV infection, and is less expensive.
authors: Department of Internal Medicine, University of Genoa, Italy. msetti@unige.it
authors: M
authors: M
authors: Setti
authors: B
authors: B
authors: Bruzzone
authors: F
authors: F
authors: Ansaldi
authors: P
authors: P
authors: Borrelli
authors: F
authors: F
authors: Indiveri
authors: G
authors: G
authors: Icardi
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004352:Drug Resistance, Microbial; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013223:Statistics as Topic; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase