Four
Drugs No Better than Three for First-line Efavirenz-Based Therapy
By
Liz Highleyman Three-drug
antiretroviral regimens -
two nucleoside analog reverse transcriptase inhibitors (NRTIs) plus either
a non-nucleoside
analog reverse transcriptase inhibitor (NNRTIs) or a protease
inhibitor (PI) -- are the standard of care for first-line treatment of HIV
infection. (The small dose of ritonavir
[Norvir] used to boost levels of other PIs is not generally counted as a separate
drug.)
There has been some speculation that 4-drug combinations might prove
more potent, but new results presented at the XVI International AIDS Conference
taking place last week in Toronto, and published in the August 16, 2006 HIV/AIDS
theme issue of the Journal of the American Medical Association, showed
that adding an extra drug provides no additional benefit for treatment-naive patients.
ACTG A5095 was a randomized, double-blind, placebo-controlled trial that
enrolled 765 treatment-naive participants from other ACTG studies. Participants
had HIV RNA levels of at least 400 copies/mL (mean 4.77 log, or 58,884 copies/mL);
the mean CD4 cell count was 240 cells/mm3.
Patients were randomly assigned
to receive a 3-drug regimen consisting of AZT
(zidovudine, Retrovir), 3TC
(lamivudine, Epivir), and efavirenz
(Sustiva), or else a 4-drug regimen that included the same three agents with
the addition of abacavir (Ziagen).
Subjects in the 3-drug arm received the Combivir
(AZT/3TC) combination pill, while those in the 4-drug arm used the Trizivir
(AZT/3TC/abacavir) fixed-dose combination.
Results 
After a median three years of follow-up, 99 of 382 patients (26%) in the 3-drug
arm experienced virological failure (defined as two successive HIV RNA measurements
of 200 copies/mL or more at or after week 16).
94 of 383 patients (25%) experienced virological failure in the 4-drug arm (hazard
ratio 0.95; 97.5% CI 0.69-1.33; P = 0.73).
Efavirenz-based regimens were potent in patients with a range of baseline viral
load and CD4 cell count levels.
In a planned subgroup analysis, non-Hispanic black patients were at greater risk
for virological failure (adjusted hazard ratio 1.66; 95% CI 1.18-2.34; P = 0.003),
and blacks with poor adherence experienced more rapid treatment failure.
After three years, 152 of 169 patients (90%) had viral load below 200 copies/mL
in the 3-drug arm, compared with 143 of 156 subjects (92%) in the 4-drug arm (P
= 0.59).
For viral load below 50 copies/mL, the corresponding figures were 144 of 169 (85%)
and 137 of 156 (88%), respectively (P = 0.39).
Overall CD4 cell count increases did not differ significantly in the two arms.
The incidence of grade 3 or 4 clinical events or laboratory abnormalities was
also similar in the two groups.
Conclusion
The
researchers concluded that, "In treatment-naive patients, there were no significant
differences between the 3-drug and 4-drug antiretroviral regimens, adding that,
overall, more than 80% of patients had HIV RNA levels less than 50 copies/mL through
three years of follow-up.
"These results support current guidelines
recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection;
adding abacavir as a fourth drug provided no additional benefit," the author
wrote.
8/21/06 References H
Ribaudo, D Kuritzkes, C Lalama, and others. Efavirenz (EFV)-based regimens are
potent in treatment-naïve subjects across a wide range of pre-treatment HIV-1
RNA and CD4 cell counts: 3-year results from ACTG 5095. XVI International AIDS
Conference. Toronto, August 13-18, 2006. Abstract THLB0211. R
M Gulick, H J Ribaudo, C M Shikuma, and others. Three- vs Four-Drug Antiretroviral
Regimens for the Initial Treatment of HIV-1 Infection. Journal of the American
Medical Association 297(7): 769-781. August 16, 2006.
|
