Antiretroviral Efficacy and Virological Profile of a Zidovudine/Lamivudine/Tenofovir Disoproxil Fumarate Combination Therapy in Antiretroviral-Naive Patients

Abstract

Objective

To study the antiviral efficacy and the mutations selected by a triple therapy with zidovudine (AZT), lamivudine (3TC) and tenofovir disoproxil fumarate (TDF).

Methods

Antiretroviral-naive patients received 300 mg AZT/150 mg 3TC twice a day plus 300 mg TDF once a day in an open pilot study. Follow-up was assessed at baseline therapy (M0) and at months 1, 3, 6, 9 and 12. Reverse transcriptase (RT) genotypic resistance analysis and in selected cases, a recombinant drug susceptibility and replication capacity assay were performed from plasma RNA at baseline and in case of virological failure (VF); that is, rebound of viral load >50 copies/ml on therapy.

Results

Twenty-four patients were included. At baseline, the median CD4⁺ T-cell count was 443 cells/μl and the median plasma viral load (VL) was 4.38 log₁₀ copies/ml. RT resistance mutations were observed at M0 in 4 patients. At M12, the proportion of patients with a VL <50 copies/ml reached 88% using an on-treatment analysis and 67% with an intent-to-treat analysis. The median increase in CD4⁺ T cells at M12 was 94 cells/μl. Four patients had a VF on therapy: two with wild-type viruses, one with selection of M184V and thymidine analogue mutations (TAMs) on a background of TAMs, and one with selection of K65R and M184V, with a replication capacity at 2.4%.

Conclusion

The virological response in our study demonstrates the antiviral efficacy of the AZT/3TC/TDF combination therapy, which needs further evaluation. The moderate frequency of selection of K65R could be due to the presence of AZT in the regimen.