期刊
AIDS
卷 20, 期 2, 页码 223-231出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.aids.0000199825.34241.49
关键词
adherence; replicative capacity; resistance; non-nucleoside reverse transcriptase inhibitors; protease inhibitors
资金
- NIAAA NIH HHS [AA015287] Funding Source: Medline
- NIAID NIH HHS [AI052745, AI058696] Funding Source: Medline
- NIMH NIH HHS [P30 MH59037, R01 MH054907, MH54907] Funding Source: Medline
- PHS HHS [A1058696] Funding Source: Medline
Objective: To compare the prevalence of resistance by adherence level ill patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTI) or protease inhibitors (PI). Also to examine the mechanism of differential class-specific adherence-resistance relationships, focusing oil the patient-derived capacity of wild-type and drug-resistant recombinant variants to replicate in vitro in the presence of variable drug levels, Methods: Participants received unannounced pill count measures to assess adherence, viral load monitoring, and genotypic resistance testing. The replicative capacity of drug-susceptible and drug-resistant recombinants was determined using a single-cycle recombinant phenotypic susceptibility assay. Drug exposure was estimated using population-averaged pharmacological measurements adjusted by participant-specific levels of adherence. Results: In the NNRTI-treated group, 69% had resistance at 0-48% adherence compared to 13% at 95-100% (P = 0.01). PI resistance was less common than NNRTI resistance at 0-48% adherence (69% versus 23%; P = 0.01). In multivariate analysis, the odds for PI resistance increased (P = 0.03) while the odds for NNRTI resistance decreased (P=0.04) with improving adherence. Individuals with drug-resistant variants were more likely to have levels of drug exposure where the resistant variant was more fit than the drug-susceptible variant in vitro, while those with drug-susceptible virus were more likely to have levels of drug exposure where the drug-susceptible virus was more fit than the drug-resistant variant (P = 0.005). Conclusions: NNRTI resistance was more common than PI resistance at low levels of adherence. Class-specific adherence-resistance relationships are associated with the relative replicative capacity of drug-resistant versus wild-type variants to replicate in the presence of clinically relevant drug levels. (C) 2006 Lippincott Williams & Wilkins.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据