Background:  This study compared viral decay rates VIRAL DECAY RATESof productively (1^st phase) and latently infected (2^nd phase) T cells in treatment-naïve HIV-1-infected men and women receiving either a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen or regimens that included efavirenz (EFV) plus NRTI.

Methods:  Substudy patients enrolled in A5095, a phase III, double-blind, placebo-controlled study, were randomized to receive zidovudine (ZDV)/lamivudine (3TC) /abacavir (ABC), ZDV/3TC+EFV (3-drug EFV) or ZDV/3TC/ABC+EFV (4-drug EFV). HIV-1 RNA levels were assayed at pre-entry, entry, days 2, 7, and 10 and weeks 2, 4, and 8. A nonlinear mixed-effects model was used to fit a bi-exponential viral dynamic model to on-treatment data. Non-parametric Wilcoxon tests compared the empirical Bayes estimates of first and second phase viral decay rates derived from this model between treatment and sex. Censored linear regression analyses examined treatment and sex differences in the change from baseline to day 7 and day 10 in log₁₀ viral load adjusted for baseline viral load.

Results:  We enrolled 64 patients (39 men and 25 women) with mean baseline viral load of 4.8 log₁₀ copies/mL and CD4 of 292 cells/mm³ enrolled; 25 were randomized to ZDV/3TC/ABC, 18 to 3-drug EFV, and 21 to 4-drug EFV. Following virologic rebound, 12 patients had viral load excluded from analysis. Most subjects experienced a sharp decline in viral load over days 0 to 10, with a slower decline through week 8. Median first phase viral decay rates of 0.56/day in the ZDV/3TC/ABC group was significantly slower than in the 3-drug EFV group (0.67/day, p = 0.02) but not significantly different compared to 0.59/day in the 4-drug EFV group (p = 0.19). No significant differences in second phase viral decay rates were seen (p >0.09). Censored regression analyses demonstrated an estimated mean change in viral load from baseline to day 10 of –1.60 log₁₀ copies/mL (ZDV/3TC/ABC) compared with –1.94 log₁₀ copies/mL ( 3-drug EFV) (p = 0.01) and –1.87 log₁₀ copies/mL (4-drug EFV) (p = 0.05). There were no significant sex differences in viral decay rates (p = 0.52; 0.52) or change in viral load from baseline (p = 0.91). Further analyses demonstrated an interaction between treatment group and baseline viral load (4-drug EFV [p = 0.03]; 3-drug EFV [p = 0.06]) suggesting a larger difference in the change from baseline to day 10 between the treatment groups in patients with higher viral load at baseline.

Conclusions:  First phase viral decay rates were significantly faster in patients receiving ZDV/3TC+EFV compared with a triple NRTI regimen; no other treatment differences in first or second phase viral decay rates were seen. There were no differences in viral decay rates between men and women.