title: Treatment of advanced HIV disease in antiretroviral-naïve HIV-1-infected patients receiving once-daily atazanavir/ritonavir or twice-daily lopinavir/ritonavir, each in combination with tenofovir disoproxil fumarate and emtricitabine.
abstract: Current guidelines for HIV therapy recommend initiating treatment at a CD4 cell count of 500 cells/mm(3). However, a large proportion of patients with HIV infection begin antiretroviral treatment at a more advanced stage. In the CASTLE study, patients with the most advanced HIV disease (CD4 cell count <50 cells/mm(3)) showed that 78% (45/58) vs. 58% (28/48) of the patients achieved HIV RNA <50 copies/mL in the intent-to-treat analysis at week 96 for atazanavir/ritonavir and lopinavir/ritonavir, respectively. This current sub-analysis of the CASTLE study describes demographics, virologic failure, discontinuations, safety, tolerability, immunologic response, and clinical outcomes for the following baseline strata: CD4 cell count (cells/mm(3)) <50, 50 to <100, 100 to <200, and ≥200 and HIV RNA (copies/mL) <100,000, 100,000 to <500,000, and ≥500,000. In the lowest CD4 cell count stratum (<50 cells/mm(3)), the proportion of discontinuations was 2-fold greater for the lopinavir/ritonavir arm (33%) than for the atazanavir/ritonavir arm (16%) with a similar rate of virologic failure between the two groups. Also in this CD4 cell count stratum, grades 2-4 treatment-related adverse events occurred in 25% in the atazanavir/ritonavir group and in 43% of lopinavir/ritonavir group, and the rate was also higher than in the higher CD4 cell count strata within the lopinavir/ritonavir treatment group (range: 29-34%). Grades 2-4 treatment-related diarrhea and nausea occurred in more patients receiving lopinavir/ritonavir than atazanavir/ritonavir in all strata. The atazanavir/ritonavir group had more grades 2-4 treatment-related jaundice than in the lopinavir/ritonavir group. These results highlight the importance of tolerability of antiretroviral therapy (ART) in the patients at greatest risk of morbidity and mortality when using regimens of similar potency.
authors: Bristol-Myers Squibb, Research and Development, Plainsboro, USA. jonathan.uy@bms.com
authors: Jonathan
authors: J
authors: Uy
authors: Rong
authors: R
authors: Yang
authors: Victoria
authors: V
authors: Wirtz
authors: Louise
authors: L
authors: Sheppard
authors: Awny
authors: A
authors: Farajallah
authors: Donnie
authors: D
authors: McGrath
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D063065:Organophosphonates / Q000008:administration & dosage; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage; D000068698:Tenofovir; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir