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Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes.

Abstract：

BACKGROUND:Multiple resistance to nucleoside analogs mediated by the Q151M complex and/or codon 67-69 inserts/deletions represents a growing problem among HIV-infected persons, most of whom have been exposed to sequential therapies for long periods of time. PATIENTS AND METHOD:All plasma samples collected from HIV-infected patients failing antiretroviral therapy and referred for HIV genotyping to our institution during the last 3 years were examined. Genetic analysis of the reverse transcriptase (RT) and protease (PR) genes was performed using an automatic sequencer. RESULTS:Multinucleoside-resistance (MNR) genotypes were recognized in 22 (2.9%) of 761 participants. Twelve of them carried the Q151M complex and 9 harbored different codon 67-69 inserts. One participant carried a deletion at codon 67 of the RT gene. All patients with MNR viruses had been exposed to nucleoside analogs for a median of 54 months (range, 19-96). The mean plasma HIV RNA at the time MNR was first identified was 4.62 log and the mean CD4 count was 227 cells/microL. All patients with MNR viruses except two began salvage therapies based on protease inhibitors (PIs). Overall, 54.5% (12/22) of participants showed a significant virologic response (defined as >1 log reduction in plasma HIV RNA). Seven of them reached <50 copies/mL and remained with undetectable viremia for a median of 17 months (range, 8-50). No differences were found when patients with Q151M and codon 67-69 rearrangements were compared. The only predictor of response was the inclusion of ritonavir-boosted PI in the salvage regimen. In all patients with virologic failure, MNR genotypes have persisted over time. CONCLUSION:The prevalence of viruses with MNR genotypes is currently low (approximately 3%) among HIV-infected patients failing antiretroviral therapy. The expected poor prognosis of patients harboring MNR viruses may often be overcome using rescue interventions based on potent ritonavir-boosted PI combinations.

journal_name

HIV Clin Trials

journal_title

HIV clinical trials

authors

Gallego O,d Mendoza C,Labarga P,Altisent C,González J,García-Alcalde I,Valer L,Valencia E,Soriano V

doi

10.1310/X618-KWKJ-WCTQ-LQ2L

keywords:

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

372-81

issue

eissn

1528-4336

issn

1945-5771

journal_volume

pub_type

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Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes.