Study Supports Atazanavir-Based HIV Regimens in High-Income Countries

By C. Vidya Shankar MD

NEW YORK (Reuters Health) - Ritonavir-boosted atazanavir-based regimens are better than lopinavir-based regimens for HIV patients in high-income countries, according to a new study from Europe and the U.S.

The atazanavir-based regimens led to lower mortality, fewer treatment failures, and less progression to AIDS, researchers found.

"The current guidelines in high-income countries recommend atazanavir over lopinavir, and our findings do not support changes to the current guidelines," lead author Lauren Cain, from the Harvard School of Public Health, Boston, and the HIV-CASUAL collaboration, told Reuters Health by email.

Common first-line regimens recommended in Europe and U.S. include non-nucleoside reverse transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (lopinavir or atazanavir). In addition, all regimens have two nucleoside reverse transcriptase inhibitors as backbones. Ritonavir in combination inhibits enzymes that metabolize protease inhibitors; these protocols are termed boosted regimens.

"However, these guidelines are based on limited evidence," the researchers pointed out January 6 online in Clinical Infectious Diseases. The follow-up durations in previous studies were short and ignored clinical outcomes, they add.

The HIV-CASUAL collaboration (2004-2013) of prospective cohort studies from the U.S., UK, France, Spain, Greece, and Switzerland enrolled 6,668 treatment-naive HIV-positive adults who were started on ritonavir-boosted lopinavir and another 4,301 who started on atazanavir regimens, with the two NRTIs.

The investigators monitored clinical outcomes, including death and AIDS-defining illness, along with CD4 and HIV RNA measurements, every year. They defined treatment failure as HIV-RNA greater than 50 copies after 12 months of treatment. Patients were monitored for mortality for a median of 40 months.

The lopinavir-based regimen was associated with 213 deaths and 457 cases of AIDS-defining illness or mortality, while the corresponding figures for the atazanavir regimen were 83 and 157, respectively. The hazard ratios for atazanavir came to 0.7 and 0.67 for death and AIDS and death, respectively.

Virological failures were reported in 24% of atazanavir and 26% of lopinavir recipients, respectively. The mean 12-month increase in CD4 cell count was 8.15 cells/mm3 greater in the atazanavir group.

The choice of NRTIs also affected the outcomes. With tenofovir/emtricitabine, the most popular NRTI combination, the hazard ratio for mortality was 0.5 for atazanavir compared to lopinavir.

"Our estimates suggest benefits of atazanavir over lopinavir with respect to clinical outcomes such as death and AIDS, as well as immunologic and virologic outcomes," Dr. Cain said in her email.

"Like all observational estimates, ours rely on the untestable assumption that we have successfully measured and adjusted for all confounders," the researchers write.

Potential confounders included the use of concomitant medications and compliance issues with lopinavir, they say.

Further studies of longer duration are required, including non-AIDS defining illness in outcomes and the interactions between lopinavir and tenofovir/emtricitabine, they concluded.

This research was supported by the U.S. National Institutes of Health and the U.K. Medical Research Council.

SOURCE: https://bit.ly/1y3z7tE

Clin Infect Dis 2015.

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