Boosted lopinavir- versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: a prospective study of HIV-infected individuals in high-income countries.

BACKGROUND Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience. METHODS We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes. RESULTS A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone. CONCLUSIONS 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.

[1]  M. Hernán,et al.  The effect of efavirenz versus nevirapine-containing regimens in the HIV-CAUSAL Collaboration: reply to Llibre and Podzamczer and additional results. , 2013, AIDS.

[2]  M. Johnson,et al.  A lopinavir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. , 2007, AIDS research and human retroviruses.

[3]  James M Robins,et al.  The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals , 2010, AIDS.

[4]  John W. Ward,et al.  1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. , 1993, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[5]  M. King,et al.  Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV-positive patients: a 48-week randomized clinical trial. , 2004, The Journal of infectious diseases.

[6]  R. Piso.  Can we trust the guidelines? Comparison between the data presented and the recommendations of the International Antiviral Society-USA Panel. , 2014, Journal of the International AIDS Society.

[7]  C. Leen,et al.  British HIV Association guidelines for the treatment of HIV‐1‐positive adults with antiretroviral therapy 2012 (Updated November 2013. All changed text is cast in yellow highlight.) , 2014, HIV medicine.

[8]  Jennifer F Hoy,et al.  Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. , 2014, JAMA.

[9]  O. Kirk,et al.  Atazanavir is not associated with an increased risk of cardio or cerebrovascular disease events , 2013, AIDS.

[10]  J. Bartlett,et al.  Dual HIV-1 infection associated with rapid disease progression , 2004 .

[11]  Donna Spiegelman,et al.  Easy SAS calculations for risk or prevalence ratios and differences. , 2005, American journal of epidemiology.

[12]  J. Robins,et al.  The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study , 2012, AIDS.

[13]  D. Costagliola,et al.  No evidence for a polyomavirus association or aetiology in AIDS-associated nonsmall cell lung cancer , 2010, AIDS.

[14]  J. Absalon,et al.  Once-Daily Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-Naive HIV-1–Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE Study , 2010, Journal of acquired immune deficiency syndromes.

[15]  A. Blaxhult,et al.  Lopinavir/ritonavir, atazanavir/ritonavir, and efavirenz in antiretroviral-naïve HIV-1-infected individuals over 144 weeks: An open-label randomized controlled trial , 2013, Scandinavian journal of infectious diseases.

[16]  D. Podzamczer,et al.  A Once-Daily Lopinavir/Ritonavir-Based Regimen Is Noninferior to Twice-Daily Dosing and Results in Similar Safety and Tolerability in Antiretroviral-Naive Subjects Through 48 Weeks , 2009, Journal of acquired immune deficiency syndromes.

[17]  J. Molina,et al.  Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study , 2008, The Lancet.

[18]  Amalio Telenti,et al.  Antiretroviral Treatment of Adult HIV Infection2010 Recommendations of the International AIDS Society–USA Panel , 2010 .

[19]  O. Kirk,et al.  Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. , 2010, The Journal of infectious diseases.

[20]  E. Foglia,et al.  Cost-Utility Analysis of Lopinavir/Ritonavir versus Atazanavir + Ritonavir Administered as First-Line Therapy for the Treatment of HIV Infection in Italy: From Randomised Trial to Real World , 2013, PloS one.

[21]  J. Sterne,et al.  Durability of first ART regimen and risk factors for modification, interruption or death in HIV-positive patients starting ART in Europe and North America 2002–2009 , 2012, AIDS.