An Open-Label,Randomized Comparative Pilot Study of a Single-Class Quadruple Therapy Regimen versus a 2–Class Triple Therapy Regimen for Individuals Initiating Antiretroviral Therapy

Abstract

Objective

To examine the antiviral potency and tolerability profile of a single-class four drug (quadruple) nucleoside reverse transcriptase inhibitor (NRTI) regimen compared with a 2-class standard-of-care regimen.

Methodology

A three-centre, randomized, open-label comparative pilot study of zidovudine/lamivudine/efavirenz (triple) versus abacavir/lamivudine/zidovudine/tenofovir (quadruple) therapy in HIV-1-infected, treatment-naive individuals. Both regimens were taken without regard to food and consisted of a twice-daily regimen and 3 pills/day. The study power was based on time-weighted average changes in HIV-1 RNA load.

Results

A total of 114 individuals (56 triple, 57 quadruple) received at least one dose of medication. Patients were well matched at baseline for viral load (mean 5.26 log₁₀ versus 5.13 log₁₀, respectively) and CD4 cell count (median 193 versus 153 cells/mm³, respectively). The two regimens performed similarly with regards to all endpoints. At week 48, by intention-to-treat, missing=failure analysis, 68% of triple- and 67% of quadruple-drug treated patients had an HIV-1 RNA <50 copies/ml (P>0.05). On-treatment analysis showed 40/40 (100%) of triple- and 39/40 (97.5%) of quadruple-drug treated patients (P=0.996) had responded to <50 copies/ml. No unexpected adverse events were reported. Changes in total cholesterol and triglycerides were modest but significantly favoured the quadruple therapy regimen at multiple time points.

Conclusion

This pilot study suggests a quadruple NRTI-based regimen provides similar antiviral potency, tolerability and administrative characteristics to a 2-class triple therapy regimen. These findings should be confirmed in a more fully powered study. Potent quadruple NRTI-based regimens may have advantages for some individuals with regards to salvageability, tolerability and drug interactions.