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Atazanavir Associated with Less HIV Treatment Failure, Illness, and Death

People with HIV who used antiretroviral regimens containing the ritonavir-boosted protease inhibitor atazanavir (Reyataz) had better outcomes than those taking lopinavir/ritonavir (Kaletra), including lower likelihood of AIDS-defining illnesses or death, less virological failure, and larger CD4 T-cell increases, according to a study published in the January 6 edition of Clinical Infectious Diseases.

Current U.S. HIV antiretroviral therapy (ART) guidelines list ritonavir-boosted atazanavir (Reyataz) or darunavir (Prezista) as the "recommended" protease inhibitors for first-line treatment. However, the older drug lopinavir/ritonavir is included as an "alternative" that may be preferable for some patients.

Lauren Cain and fellow investigators with the HIV-CAUSAL Collaboration compared boosted atazanavir and lopinavir/ritonavir ART regimens using data from prospective studies in the U.S. and Europe, looking at clinical, immunological, and virological outcomes. They used national and local death registries and medical records to establish deaths, and treating physicians provided data about AIDS-defining illnesses.

The analysis included 4301 adult participants who started a boosted atazanavir-based regimen and 6668 who started a lopinavir/ritonavir-based regimen in HIV-CAUSAL Collaboration cohort studies between 2004 and 2013. All participants were treatment-naive and did not yet have AIDS when they stared these regimens; pregnant women were excluded.

Results

• Among participants taking boosted atazanavir, 83 died and 157 developed AIDS-defining illnesses during follow-up.

• Among participants taking lopinavir/ritonavir, 213 died and 457 developed AIDS-defining illnesses.

• The adjusted hazard ratios (HR) for boosted atazanavir versus lopinavir/ritonavir in an intent-to-treat analysis at 1 year were:

o   Adjusted HR 0.70 for death, or 30% lower risk with atazanavir (95% CI 0.53, 0.91);

o   Adjusted HR 0.67 for the combined endpoint of AIDS-defining illness or death (95% CI 0.55, 0.82);

o   Adjusted HR 0.91 for virological failure (HIV RNA <50 copies/mL) at 12 months, or 9% lower risk for atazanavir (95% CI 0.84, 0.99).

• The mean 12-month increase in CD4 cell count was 8.15 cells/mm³ in favor of atazanavir.

"Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens," the study authors concluded.

However, they noted that these estimates differed somewhat according to which nucleoside/nucleotide reverse transcriptase (NRTI) "backbone" was used with boosted atazanavir or lopinavir/ritonavir.

"While we provide new evidence upon which the next set of guidelines can be based, our findings do not support changes to the current guidelines," they wrote.

2/11/15

Reference

LE Cain et al (HIV-CAUSAL Collaboration). Boosted Lopinavir- Versus Boosted Atazanavir-Containing Regimens and Immunologic, Virologic, and Clinical Outcomes: A Prospective Study of HIV-Infected Individuals in High-Income Countries. Clinical Infectious Diseases. January 6, 2015 (Epub ahead of print).