ICAAC 2009: Raltegravir (Isentress) plus Atazanavir (Reyataz) Maintenance Therapy Appears Safe and Effective in Small Study

A dual maintenance regimen consisting of the recently approved integrase inhibitor raltegravir (Isentress) plus the protease inhibitor atazanavir (Reyataz) was well tolerated and kept viral load below 50 copies/mL in more than 80% of patients with no prior history of treatment failure, according to a study presented at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009) last month in San Francisco.

Researchers have explored simplified maintenance regimens in an effort to improve convenience and reduce side effects and cost of treatment for patients who achieve viral suppression using a standard antiretroviral therapy (ART) regimen, typically 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

Approval of the first integrase inhibitor allows for a wider array of NRTI-sparing options, as the older NRTIs have been increasingly linked to long-term toxicities including lipoatrophy (fat loss). To date, raltegravir has demonstrated good tolerability, avoiding many of the side effects of the earlier antiretroviral drug classes.

Peter Ruane and colleagues conducted a prospective observational study to evaluate the safety and efficacy of a 2-drug regimen containing raltegravir plus atazanavir. The trial included 30 HIV patients in the Los Angeles area. All but 1 were men, 80% were white, and the median age was 47 years.

Participants had no history of treatment failure, but were experiencing poor tolerability ontheir existing regimen (primarily body shape changes or abnormal blood lipid levels). They had stable viral load < 400 copies/mL for more than 4 months, and < 50 copies/mL at study entry. The median baseline CD4 cell count was high -- about 700 cells/mm³ -- but the median CD4 nadir (lowest-ever level) was about 200 cells/mm³. Most patients (90%) had prior exposure to PIs, but none had a history of PI resistance.

All participants switched from their current regimen to 400 mg once-daily atazanavir, taken with food, plus 400 mg twice-daily raltegravir. The study is scheduled to continue through 48 weeks; preliminary 24-week data were presented at ICAAC.

Results

• As of August 2009, 27 participants were still in the study, with a median follow-up duration of 36 weeks.
• Based on pill counts, 90% of participants achieved > 85% adherence.
• At 24 weeks in an intent-to-treat, missing = failure analysis, 83% of patients had viral load < 50 copies/mL and 93% had < 400 copies/mL.
• 7 participants experienced viral load "blips," or temporary low-level (48-83 copies/mL) viral load increases through week 24.
• The mean CD4 cell count did not change.
• 2 participants discontinued the study early, 1 due to viral rebound and 1 due to elevated serum creatinine.
• 1 patient died of newly diagnosed lung cancer during the study.
• Total and low-density lipoprotein (LDL or "bad") cholesterol decreased significantly after switching to raltegravir/atazanavir.
• Triglyceride levels also fell, but the change did not reach statistical significance.
• At 24 weeks, fewer participants had blood lipid levels that fell outside the National Cholesterol Education Program (NCEP III) recommended range.

The researchers concluded that, "raltegravir/atazanavir was well tolerated and effective in maintaining viral control in this chronically suppressed population." The significance of the single blips observed in several patients is unclear, they added.

Among 14 participants who switched from a completely once-daily regimen to this regimen containing twice-daily raltegravir, there were no increased difficulties with adherence.

A dual raltegravir/atazanavir regimen may be particularly well-suited for people with high cardiovascular risk. Most maintenance regimens studied to date have included ritonavir-boosted PIs. But even a small amount of ritonavir can cause tolerability problems, including gastrointestinal symptoms and metabolic abnormalities, in some patients. People with multiple cardiovascular risk factors are often prescribed atazanavir, which is less likely than other PIs to cause unfavorable blood lipid changes; such patients may benefit from using "lipid-friendly" raltegravir and avoiding ritonavir.

Light Source Medical Group, Los Angeles, CA.

10/02/09

Reference

PJ Ruane, B Alas, and PR Wolf. Dual maintenance therapy with raltegravir BID with atazanavir qD (RAL/ATV) in patients with no prior PI resistance and intolerance to other ARV regimens: preliminary report. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. Abstract H-914.