Nevirapine
(Viramune) Has Equal Efficacy but a More Favorable Lipid Profile Compared with
Boosted Atazanavir (Reyataz)
 | ARTEN
is an international, non-inferiority study comparing ritonavir-boosted
atazanavir (Reyataz/r) versus nevirapine
(Viramune), each combined with fixed-dose tenofovir/emtricitabine
(Truvada). Week 48 results presented in a late-breaker session at the 5th
International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention
(IAS 2009) in Cape Town last week showed that nevirapine offers equal efficacy,
with a more favorable lipid profile, compared with boosted atazanavir. Although
the 2 regimens had similar rates of adverse events, discontinuations occurred
more frequently in patients taking nevirapine. |
By
Ronald Baker, PhD The
ARTEN trial included 569 treatment-naive HIV patients who were randomly assigned
to received 300/100mg once-daily (QD) atazanavir/ritonavir or nevirapine administered
either 200 mg twice-daily (BID) or 400 mg once-daily, each in combination with
the fixed-dose 300/200 mg once-daily tenofovir/emtricitabine combination pill
(Truvada). This is the first study to compare these 2 antiretroviral
drugs.
Baseline demographics characteristic and HIV-related factors
were similar in the 2 groups. The mean HIV viral load was >100,000 copies/mL
and the mean CD4 count was 183 cells/mm3.
The primary end-point was treatment
response (TR), defined as plasma HIV-RNA < 50 copies/mL at 2 consecutive visits
without subsequent rebound or change of antiretroviral drugs prior to week 48.
Results  | 67%
of the 376 patients who received nevirapine achieved the primary endpoint, compared
with 65% of the 193 patients who received atazanavir/ritonavir (P = 0.63). | | The
mean increase from baseline in high-density lipoprotein (HDL "good")
cholesterol was 9.6 mg/dL in the nevirapine arm and 4.0 mg/dL in the atazanavir/ritonavir
arm (P < 0.0001). | | The
mean increase in low-density lipoprotein (LDL "bad") cholesterol was
15 mg/dL in the nevirapine group and 10.5 mg/dL in the atazanavir/ritonavir group
(P = 0.011). | | Triglyceride
(TG) levels decreased by a mean 1.4 mg/dL from baseline in the nevirapine group,
while increasing by 26.5 mg/dL in the atazanavir/ritonavir group (P < 0.0001). |
Table
1: Week-48 results (Intent-to-treat analysis)
| Parameter |
Nevirapine (N=376)
(188
BID + 188 QD) |
Atazanavir/ritonavir (N=193) |
Comparison
(95%
CI) |
| % TR (Primary end-point) |
66.8 |
64.8 |
2.5 (-5.4
to 10.4) |
| % TR (TLOVR algorithm)* |
70.2 |
73.6 |
-2.9 (-10.4
to 4.5) |
| TC/HDL-ratio mean change from baseline |
-0.23 |
+0.13 |
P=0.0001 |
|
HDL mean change from baseline (mg/dL) |
9.6 |
4.0 |
P<0.0001 |
|
TG mean change from baseline (mg/dL) |
+1.4 |
+26.5 |
P=0.0001 |
|
% Overall adverse events (grades 3 and 4) |
85.6
(12.0 and 5.1) |
86.5 (16.1 and 3.1) |
n/a |
|
% Rash, all grades (discontinued) |
16.0
(5.6) |
12.4 (0) |
n/a |
|
% Discontinuations due to adverse events |
12.5 |
3.6 |
n/a |
BID
= once-daily; QD = once-daily;
TC = total cholesterol
*
Time to loss of virological response; HIV RNA < 50
copies/mL at wks-36 and 48 without subsequent rebound
or change of antiretroviral drugs. Based
on these findings, the investigators concluded, "Nevirapine shows non-inferior
efficacy at week-48 versus atazanavir/ritonavir (both combined with fixed-dose
[tenofovir/emtricitabine]). Despite similar rates of adverse events, discontinuations
were more frequent in nevirapine than in atazanavir/ritonavir patients. Nevirapine
demonstrated a more favourable lipid profile than atazanavir/ritonavir." Lead
investigator Vicente Soriano from Hospital Carlos III in Madrid, Spain, said,
"[This study] puts to rest the concerns over a potential lack of efficacy
of nevirapine in combination with tenofovir/emtricitabine, and confirms that the
combination of nevirapine and tenofovir/emtricitabine is a highly efficacious
combination that offers significant benefit -- even more so to patients with cardiovascular
risk." 7/28/09 Reference
V
Soriano, S Koeppe, H Mingrone, and others. Prospective comparison of nevirapine
and atazanavir/ritonavir both combined with tenofovir DF/emtricitabine in treatment-naïve
HIV-1 infected patients: ARTEN study week 48 results. 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). Cape Town,
South Africa. July 19-22, 2009. Abstract
LBPEB07.
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