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Differential impact of resistance-associated mutations to protease inhibitors and nonnucleoside reverse transcriptase inhibitors on HIV-1 replication capacity.
- Source :
-
AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2013 Aug; Vol. 29 (8), pp. 1117-22. Date of Electronic Publication: 2013 May 15. - Publication Year :
- 2013
-
Abstract
- The effects of drug resistance on HIV-1 replication capacity have been studied, but data from clinical isolates are few. We accessed the patients with HIV-1 infection at the National Taiwan University Hospital who experienced virological failure. Genotypic susceptibility and replication capacity of clinical HIV-1 isolates were measured. There were 80 patients enrolled between September 2007 and August 2010. The HIV-1 replication capacity declined significantly with the increasing number of major resistance-associated mutations (RAMs) to protease inhibitors (PIs) (p<0.001); however, it did not decline significantly with the increasing RAMs to first-line nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) (p=0.098). Regarding the effects of resistance to antiretroviral drugs in salvage therapy, decreased replication capacity was noted with the increasing RAMs to darunavir/ritonavir (p<0.001) and specific RAMs (L100I, K101P, and Y181C/I/V) to etravirine (p<0.001). Although NNRTI-related RAMs have less remarkable effects, both PI- and NNRTI-related RAMs reduced replication capacity, especially RAMs to darunavir/ritonavir and etravirine, which are commonly used in salvage therapy for treatment of patients infected with highly resistant HIV. Thus, decreased viral fitness during the emergence of RAMs suggests the importance of continued optimal antiretroviral treatment even when virological failure was noted.
- Subjects :
- Adult
Anti-HIV Agents therapeutic use
Female
Genotype
HIV Infections genetics
HIV Infections virology
HIV Protease Inhibitors therapeutic use
HIV-1 genetics
HIV-1 physiology
Humans
Male
Middle Aged
Mutation
Reverse Transcriptase Inhibitors therapeutic use
Salvage Therapy
Taiwan
Virus Replication drug effects
Anti-HIV Agents pharmacology
Drug Resistance, Viral genetics
HIV Infections drug therapy
HIV Protease Inhibitors pharmacology
HIV-1 drug effects
Reverse Transcriptase Inhibitors pharmacology
Virus Replication genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1931-8405
- Volume :
- 29
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- AIDS research and human retroviruses
- Publication Type :
- Academic Journal
- Accession number :
- 23594266
- Full Text :
- https://doi.org/10.1089/AID.2013.0038