Atazanavir Maintains Long-term HIV Suppression
HIV patients with suppressed viral load who switched from
ritonavir-boosted atazanavir (Reyataz) to unboosted atazanavir
in a combination antiretroviral regimen were able to maintain
undetectable HIV RNA over 120 weeks with a low risk of viral
rebound and fewer side effects, according to the latest findings
from the ARIES trial presented at the 50th Interscience Conference
on Antimicrobial Agents and Chemotherapy (ICAAC
2010) last week in Boston.
dose of ritonavir (Norvir)
interferes with drug processing in the liver and is used to "boost"
other protease inhibitors to higher concentrations in the body. This
can help ensure adequate drug levels, but even a small amount of ritonavir
can cause side effects including gastrointestinal symptoms and abnormal
blood lipid levels.
ARIES trial, Kathleen Squires from Thomas Jefferson University and colleagues
tested whether people taking boosted atazanavir
in a combination regimen could safely discontinue ritonavir.
The trial enrolled more than 500 treatment-naive participants who were
screened with the HLA-B*5701
genetic test to rule out hypersensitivity to abacavir (Ziagen).
All patients started on an induction regimen of 300/100 mg ritonavir-boosted
atazanavir plus fixed-dose abacavir/lamivudine (Epzicom) once-daily.
At week 36, a total of 419 participants with confirmed viral load <
50 copies/mL and no virological failure were randomly assigned (1:1)
to either remain on the same boosted regimen or stop ritonavir and continue
on unboosted atazanavir for an additional 48 weeks. Participants then
had the option to continue in an extension of the study through week
Baseline characteristics were similar in the 2 arms. A majority of participants
(85%) were men, the mean age was 39 years, nearly two-thirds were white,
about one-third were black, and 5% were coinfected with hepatitis C
virus (HCV). Patients had relatively advanced immune suppression with
a median CD4 cell count of about 200 cells/mm3; just over half had high
viral load (>100,000 copies/mL) at baseline.
previously reported, unboosted atazanavir demonstrated non-inferiority
to boosted atazanavir at 84 weeks. At ICAAC, researchers presented longer-term
120-week data for the 369 patients who participated in the extension
phase (189 in the unboosted atazanavir arm and 180 in the atazanavir/ritonavir
In an intent-to-treat TLOVR analysis at 120 weeks, 84% of patients
in the unboosted atazanavir arm and 83% in the atazanavir/ritonavir
arm achieved HIV suppression < 50 copies/mL.
and 90%, respectively, achieved viral load < 400 copies/mL.
participants with low baseline viral load (< 100,000 copies/mL),
86% and 82%, respectively, achieved HIV RNA < 50 copies/mL.
those with high baseline viral load ( 100,000 copies/mL) the corresponding
rates were 82% and 84%, respectively.
people in the unboosted atazanavir arm and 4 in the atazanavir/ritonavir
arm (both 2%) experienced virological failure between weeks 84 and
median CD4 cell gain from baseline to week 120 was 290 cells/mm3
in both arms.
of unboosted atazanavir recipients and 8% in the atazanavir/ritonavir
arm discontinued therapy early (1 and 2 patients, respectively,
due to adverse events).
half as many patients in the unboosted atazanavir arm experienced
moderate-to-severe (grade 2-4) treatment-related adverse events
between weeks 36 and 120 (12% vs 21%, respectively).
and 14%, respectively, developed high bilirubin levels, the only
side effect reported by >3% of participants.
arms experienced improvements in lipid profiles, but people in the
unboosted atazanavir group had larger decreases in total-to-HDL
cholesterol ratio, total cholesterol, LDL "bad" cholesterol,
person in the boosted atazanavir arm, but none in the unboosted
arm, developed a new drug-resistance mutation.
on these findings, the researchers concluded, "Atazanavir plus
[abacavir/lamivudine] confers durable virological suppression in a treatment
simplification strategy with an overall low rate (2%) of virologic failure
over 120 weeks when compared to atazanavir/ritonavir plus [abacavir/lamivudine]."
affiliations: Thomas Jefferson Univ., Philadelphia, PA; Orlando Immunology
Ctr., Orlando, FL; Southwest Infectious Disease Associates, Dallas,
TX; Dupont Circle Physicians Group, Washington, DC; Clinique Med.e L'Actuel,
Montreal, Canada; GlaxoSmithKline, Research Triangle Park, NC; ViiV
Healthcare, Research Triangle Park, NC.
K Squires, E DeJesus, N Bellos, and others. Sustained Virologic
Efficacy of Atazanavir (ATV) Versus Atazanavir/Ritonavir (ATV/r), Each
in Combination with Abacavir/Lamivudine (ABC/3TC) over 120 Weeks: The
ARIES Trial. Atazanavir Without Ritonavir Sustains Virologic Suppression
120 Weeks in ARIES. 50th Interscience Conference on Antimicrobial Agents
and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. (Abstract