SUMMARY: 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.

By Liz Highleyman

Reyataz (atazanavir) • News Articles • Full US Prescribing Information

A low 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.

In the 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 144.

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.

As 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 arm).

Results

	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.
	89% and 90%, respectively, achieved viral load < 400 copies/mL.
	Among participants with low baseline viral load (< 100,000 copies/mL), 86% and 82%, respectively, achieved HIV RNA < 50 copies/mL.
	Among those with high baseline viral load ( 100,000 copies/mL) the corresponding rates were 82% and 84%, respectively.
	3 people in the unboosted atazanavir arm and 4 in the atazanavir/ritonavir arm (both 2%) experienced virological failure between weeks 84 and 120.
	The median CD4 cell gain from baseline to week 120 was 290 cells/mm3 in both arms.
	9% of unboosted atazanavir recipients and 8% in the atazanavir/ritonavir arm discontinued therapy early (1 and 2 patients, respectively, due to adverse events).
	Approximately 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).
	6% and 14%, respectively, developed high bilirubin levels, the only side effect reported by >3% of participants.
	Both 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, and triglycerides.
	1 person in the boosted atazanavir arm, but none in the unboosted arm, developed a new drug-resistance mutation.

Based 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]."

Investigator 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.

9/21/10

Reference
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 H-204).