Once-daily efavirenz plus tenofovir/emtricitabine (EFV/TDF/FTC) proved virologically superior to once-daily unboosted atazanavir plus didanosine/emtricitabine (ATV/DDI/FTC) and safer than EFV plus twice-daily zidovudine/lamivudine (EFV/ZDV/3TC) in a 9-country randomized trial.

As antiretroviral treatment needs remain high across the world, clinicians need stronger, safer, and more convenient first-line options for people starting their first regimen. This trial on 4 continents randomized 1571 adults to EFV/TDF/FTC once daily, ATV/DDI/FTC once daily, or EFV plus ZDV/3TC twice daily. (In high-income countries, atazanavir is usually given with a ritonavir boost.)

PEARLS trial participants lived in Brazil, Haiti, India, Malawi, Peru, South Africa, Thailand, the United States, and Zimbabwe, and 47% were women. Enrollees were at least 18 years old, had a CD4 count below 300 cells/µL, and had 7 or fewer days of cumulative antiretroviral therapy.

An independent monitoring board recommended stopping the study before 472 treatment failures occurred. After a median 184 weeks of follow-up, there were 95 failures among 526 people (18%) assigned to EFV/TDF/FTC and 98 failures among 519 participants (19%) assigned to EFV/ZDV/3TC. A hazard ratio (HR) of 0.95 (95% confidence interval [CI] 0.72 to 1.27) indicated similar efficacy with the two regimens.

But EFV/TDF/FTC was safer than EFV/ZDV/3TC with 243 safety endpoints (46%), compared with 313 safety endpoints (60%) with EFV/ZDV/3TC. That meant a safety endpoint was 36% less likely with EFV/TDF/FTC (HR 0.64, 95% CI 0.54 to 0.76, P < 0.001). Women had a greater risk of meeting a safety endpoint with EFV/ZDV/3TC than with EFV/TDF/FTC (HR 0.50, 95% CI 0.39 to 0.64) than did men (HR 0.79, 95% CI 0.62 to 1.00, P < 0.01).

Through a median follow-up of 81 weeks, EFV/TDF/FTC failed in 76 of 519 participants (15%) compared with 108 of 526 people (21%) taking ATV/DDI/FTC. Those numbers meant virologic failure was 51% more likely with ATV/DDI/FTC (HR 1.51, 95% CI 1.12 to 2.04, P = 0.007).

The researchers conclude that “superior safety [of EFV/TDF/FTC], especially in HIV-1-infected women, and once-daily dosing . . . are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries.”

They observe that ATV/DDI/FTC “had inferior efficacy and is not recommended as an initial antiretroviral regimen.”

The editors of PLoS Medicine, which published these findings, believe the results “add to the evidence that antiretroviral efficacy and safety can differ between women and men and support further development of sex-specific recommendations for antiretroviral regimen options.”

By Mark Mascolini

Source: Thomas B. Campbell, Laura M. Smeaton, N. Kumarasamy, Timothy Flanigan, Karin L. Klingman, Cynthia Firnhaber, Beatriz Grinsztejn, Mina C. Hosseinipour, Johnstone Kumwenda, Umesh Lalloo, Cynthia Riviere, Jorge Sanchez, Marineide Melo, Khuanchai Supparatpinyo, Srikanth Tripathy, Ana I. Martinez, Apsara Nair, Ann Walawander, Laura Moran, Yun Chen, Wendy Snowden, James F. Rooney, Jonathan Uy, Robert T. Schooley, Victor De Gruttola, James Gita Hakim, for the PEARLS study team of the ACTG. Efficacy and Safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings. PLoS Medicine. 2012; 9: e1001290.

Complete article provided by PLoS Medicine, an open-access journal