Dual maintenance therapy with atazanavir plus raltegravir sustains viral suppression

A two-drug maintenance regimen using the protease inhibitor atazanavir (Reyataz) and the integrase inhibitor raltegravir (Isentress) was well tolerated and kept viral load suppressed, according to a small study presented this week at the 49^th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.

Researchers have explored various simplified antiretroviral regimens to maintain HIV suppression amongst patients who achieved undetectable viral load while on standard combination therapy, which typically consists of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor. Development of new drug classes such as integrase inhibitors offers a wider range of options.

Simplified maintenance therapy can potentially reduce the side-effects and cost of treatment, whilst improving convenience. However, many of the maintenance regimens studied so far include ritonavir-boosted protease inhibitors, and even a small amount of ritonavir can cause poor tolerability for some patients.

Atazanavir has been suggested as a potential partner for raltegravir because it has been shown to increase raltegravir levels by around 40%.

Peter Ruane and colleagues evaluated the safety and effectiveness of the novel maintenance regimen in a prospective observational study of 30 patients in the Los Angeles area. All but one were gay/bisexual men, 80% were white, and the median age was 47 years. The median CD4 count was high, at about 700 cells/mm³.

Participants had no history of treatment failure and had stable viral load suppression below 400 copies/ml for more than four months, and below 50 copies/ml at study entry. However, they were experiencing poor tolerability on their existing regimen, characterised by gastrointestinal symptoms, body shape changes, abnormal blood fat levels, or other side-effects.

In this single arm study, all participants switched from their current regimen to 400 mg once-daily atazanavir taken with food plus 400 mg twice-daily raltegravir; there was no placebo or control arm. Most patients (90%) had prior exposure to protease inhibitors and about 60% had previously used atazanavir, but none had prior evidence of protease inhibitor resistance.

The study is scheduled to continue through 48 weeks; Dr Ruane presented 24 week data at ICAAC. As of August 2009, 27 participants were still in the study and had accrued a median 36 weeks of follow-up data. Adherence was good, with pill counts showing that 90% took their drugs as directed more than 85% of the time.

Two participants discontinued study therapy, one due to viral rebound and another due to an elevated serum creatinine level that returned to normal after stopping therapy. One individual died of lung cancer.

At 24 weeks, 83% of participants had viral load below 50 copies/ml and 93% had less than 400 copies/ml (intent-to-treat, missing = failure analysis). However, several people experienced temporary low-level viral load increases; the researchers said the significance of these "blips" is not clear. Average CD4 cell count did not change.

Total and low-density lipoprotein (LDL) cholesterol levels decreased significantly after switching to atazanavir plus raltegravir; triglyceride levels also fell, but the change did not reach statistical significance. At 24 weeks fewer participants had blood fat levels that fell outside the recommended range for cardiovascular health.

The researchers concluded that atazanavir plus raltegravir maintenance therapy was "well tolerated and effective in maintaining viral control" in this population with stable prior virological suppression.