Reverse transcriptase mutations in HIV-1 infected patients treated with two nucleoside analogues: the SMART study

Area of Science:

• Virology
• Infectious Diseases
• Pharmacogenomics

Background:

• Nucleoside reverse transcriptase inhibitors (NRTIs) are a cornerstone of HIV-1 treatment.
• Understanding drug resistance mechanisms is crucial for optimizing antiretroviral therapy (ART).
• Specific mutations in HIV-1 reverse transcriptase confer resistance to NRTIs.

Purpose of the Study:

• To investigate the prevalence of specific NRTI resistance mutations in HIV-1 infected patients.
• To assess the relationship between NRTI resistance mutations and clinical outcomes.
• To identify predictors of clinical failure in patients receiving NRTI-based regimens.

Main Methods:

• Retrospective analysis of 527 HIV-1 infected patients (342 responders, 185 non-responders to two NRTIs).
• Genotypic resistance testing to identify specific mutations (e.g., 215Y/F, 184V, 70R, 74V, 75T).
• Prospective follow-up of responders for one year to assess clinical failure rates; analysis of viral load at enrollment as a predictor.

Main Results:

• The 215Y/F substitution was significantly more prevalent in non-responders (33.7%) compared to responders (17%) (P = 0.0005).
• Mutations 184V and 70R showed comparable prevalence between groups; 74V was absent, and 75T was rare.
• Reduced susceptibility to zidovudine and lamivudine was observed in failing regimens, with lamivudine resistance detected in all failing subjects.
• Detectable HIV viral load at enrollment was the sole independent predictor of clinical failure over one year (P < 0.0001).

Conclusions:

• The 215Y/F mutation is associated with NRTI treatment failure in HIV-1.
• Viral load at treatment initiation is a critical factor for predicting clinical success on NRTI-based ART.
• Monitoring viral load and resistance mutations is essential for managing HIV-1 infection effectively.