Abstract
Objective: To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI). Design: Analysis of a prospective clinical trial cohort. Patients: NNRTI-naive patients failing a stable antiretroviral regimen. Measurements: HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50%) of < 0.4. Results: The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 × 106 cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29%. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log10 HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 × 106 cells/l greater in patients with hypersusceptible virus (P ≤ 0.1). Conclusion: NNRTI hypersusceptibility occurred in more than 20% of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.
Original language | English (US) |
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Pages (from-to) | F33-F40 |
Journal | AIDS |
Volume | 16 |
Issue number | 15 |
DOIs | |
State | Published - Oct 18 2002 |
Externally published | Yes |
Keywords
- Antiretroviral therapy
- Clinical trials
- HIV-1
- Hypersusceptibility
- Non-nucleoside reverse transcriptase inhibitor
- Phenotypic resistance
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases