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AIDS. 2006 Jan 9;20(2):223-31.

Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness.

Author information

  • 1Epidemiology and Prevention Interventions Center, Division of Infectious Diseases, San Francisco General Hospital, UCSF, San Francisco, California 94143-1372, USA. db@epi-center.ucsf.edu

Abstract

OBJECTIVE:

To compare the prevalence of resistance by adherence level in 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 on 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.

PMID:
16511415
[PubMed - indexed for MEDLINE]
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