title: Differential impact of resistance-associated mutations to protease inhibitors and nonnucleoside reverse transcriptase inhibitors on HIV-1 replication capacity.
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.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. hsmaids@hotmail.com
authors.forename: Szu-Min
authors.initials: SM
authors.lastname: Hsieh
authors.forename: Sung-Ching
authors.initials: SC
authors.lastname: Pan
authors.forename: Sui-Yuan
authors.initials: SY
authors.lastname: Chang
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Hung
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.forename: Mao-Yuan
authors.initials: MY
authors.lastname: Chen
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016879:Salvage Therapy; D013624:Taiwan; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors