Genotypic and Phenotypic Cross-Resistance Patterns to Lopinavir and Amprenavir in Protease Inhibitor-Experienced Patients with HIV Viremia
In: AIDS Research and Human Retroviruses, Jg. 18 (2002-09-20), Heft 14, S. 1011-1019
serialPeriodical
Zugriff:
Genotypic correlates of reduced phenotypic susceptibility to amprenavir (APV) and lopinavir (LPV) were examined in 271 HIV isolates from 207 protease inhibitor (PI)-experienced subjects. All samples were from LPV-naive subjects; two were from APV-experienced subjects. Using a fold resistance (FR) of <2.5, 179 (66%) were APV susceptible. Using FRs of <2.5 and <10, 107 (39%) and 194 (72%), respectively, were LPV susceptible. The I84V mutation was the strongest APV resistance marker in PI-experienced subjects in both univariate and multivariate analyses, with an increased relative incidence (RI) of 6.9 with >2.5 FR. Mutations L10I (RI, 1.7), M46I (RI, 2.3), and L90M (RI, 1.9, but 65% linked with the I84V) were associated with decreased APV susceptibility in the univariate analysis (p < 0.001). Mutations L10I, G48V, I54T, I54V, and V82A were significantly associated with decreased LPV susceptibility (p < 0.001 for each) and had increased RIs of 2.2, 4.4, 13, 4.6, and 3.2, respectively. Decreased susceptibility to LPV (FR, ≥10) was significantly associated with prior exposure to the following PIs: ritonavir (RTV) (p < 0.001), saquinavir (SQV) (p < 0.001), nelfinavir (NFV) (p = 0.008), and indinavir (IDV) (p = 0.028). Decreased APV susceptibility (FR, ≥2.5) was significantly associated with prior exposure to RTV (p = 0.009), NFV (p = 0.003), and IDV (p = 0.021) but not with prior SQV (p = 0.103). These results suggest that APV and LPV have different cross-resistance mutation patterns that may help determine choice of PI therapy after therapy failure.
Titel: |
Genotypic and Phenotypic Cross-Resistance Patterns to Lopinavir and Amprenavir in Protease Inhibitor-Experienced Patients with HIV Viremia
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Autor/in / Beteiligte Person: | Paulsen, Denise ; Liao, Qiming ; Fusco, Gregory ; St. Clair, Marty ; Shaefer, Mark ; Ross, Lisa |
Zeitschrift: | AIDS Research and Human Retroviruses, Jg. 18 (2002-09-20), Heft 14, S. 1011-1019 |
Veröffentlichung: | 2002 |
Medientyp: | serialPeriodical |
ISSN: | 0889-2229 (print) ; 1931-8405 (print) |
DOI: | 10.1089/08892220260235371 |
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