Background: The relative efficacy of a regimen can be determined by comparing slopes of HIV-1 RNA decay in comparable patient (pt) populations. Stated mathematically antiviral efficacy (e) is proportional to the first phase slope of decay assuming d, the decay constant of virus-producing T-cells, is constant.

Objective: To determine e of 3 HAART regimens in 3 groups matched for pre-treatment disease stage, plasma HIV-1 RNA and CD4⁺ T-cell count.

Methods: Fifty-nine (59) subjects were treated during acute and early HIV-1 infection with ABC/3TC/APV/IND (Regimen A, n = 20), LPV/rit/EFV/TDF/3TC (Regimen B, n = 20), and TRIZIVIR/EFV (Regimen C, n = 19). Day 0 to day 7 HIV-1 RNA decay slopes were determined assuming first order exponential decay. Baseline characteristics and slopes were analyzed using Mann-Whitney test at the 0.05 level of significance.

Results:

Regimen	A	B	C
Number of subjects	20	20	19
Mean baseline log HIV-1-RNA (copies/ml)	5.4 ±0.2 (3.8–6.8)	5.6 ±0.2 (4.2–7.2)	5.8 ±0.2 (3.8–7.4)
Mean CD4+ T cell count (cells/mm3)	420 ± 26 (119–572)	444 ± 33 (259–720)	468 ± 58 (74–998)
Mean slope HIV-1 RNA decay (d-1)	-0.40 ±0.04 1	-0.52 ±0.03 2	-0.64 ±0.05
Relative efficacy (e)	0.52	0.68	1.00

¹ p < 0.01 A vs B. p < 0.001 A vs C

² p < 0.01 B vs C. All other p values not significant ( > 0.05)

 

Conclusions: The relative efficacy of TRIZIVIR/EFV is significantly greater than the 2-comparator regimens studied in nearly identical patient populations. These data suggest that the potency of standard HAART may be less than previously appreciated. Alternatively these differences may reflect some variation in time of onset of action and different mechanisms of antiviral activity. More detailed viral dynamic studies are indicated to better understand these issues. Nevertheless these data suggest that further optimization of HAART regimens may improve suppression of viral replication in vivo and allow for the further development of treatment strategies to limit long-term or indefinite drug exposure.