Efficacy of a nucleoside-sparing regimen of darunavir/ ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262)

• Published in: AIDS (London) Vol. 25; no. 17; pp. 2113 - 2122
• Main Authors: TAIWO, Babafemi, LU ZHENG, ERON, Joseph J, GALLIEN, Sebastien, MATINING, Roy M, KURITZKES, Daniel R, WILSON, Cara C, BERZINS, Baiba I, ACOSTA, Edward P, BASTOW, Barbara, KIM, Peter S
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 13-11-2011
• Subjects: Adolescent; Adult; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Darunavir; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - drug effects; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Medication Adherence - statistics & numerical data; Middle Aged; Odds Ratio; Pharmacology. Drug treatments; Pyrrolidinones - therapeutic use; Raltegravir Potassium; Ritonavir - therapeutic use; RNA, Viral - blood; RNA, Viral - drug effects; Sulfonamides - therapeutic use; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load - drug effects; Young Adult; Immunopathology; Antiretroviral agent; Drug combination; Darunavir; Enzyme; Ritonavir; antiretroviral therapy; nucleoside sparing; Enzyme inhibitor; Non peptide compound; AIDS; Immune deficiency; Infection; Peptidases; Chemotherapy; Integrase inhibitor; Treatment; Viral disease; Hydrolases; Antiviral; Nucleoside; Protease inhibitor; Raltegravir
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/qad.0b013e32834bbaa9

To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL) combination therapy in antiretroviral-naive patients.
Phase IIb, single-arm, open-label, multicenter study.
One hundred and twelve antiretroviral-naive, HIV-1-infected patients received DRV/r 800/100 mg once daily and RAL 400 mg twice daily. Primary endpoint was virologic failure by week 24. Virologic failure was defined as confirmed viral load of 1000 copies/ml or more at week 12, or an increase of more than 0.5 log(10) copies/ml in viral load from week 4 to 12, or a confirmed viral load of more than 50 copies/ml at or after week 24. Protease and integrase genes were sequenced in patients experiencing virologic failure.
Virologic failure rate was 16% [95% confidence interval (CI) 10-24] by week 24 and 26% (95% CI 19-36) by week 48 in an intent-to-treat analysis. Viral load at virologic failure was 51-200 copies/ml in 17/28 failures. Adjusting for age and sex, virologic failure was associated with baseline viral load of more than 100,000 copies/ml [hazard ratio 3.76, 95% CI (1.52-9.31), P = 0.004] and lower CD4 cell count [0.77 per 100 cells/μl increase (95% CI 0.61-0.98), P = 0.037]. When trough RAL concentrations were included as a time-varying covariate in the analysis, virologic failure remained associated with baseline viral load more than 100,000 copies/ml [hazard ratio = 4.67 (95% CI 1.93-11.25), P < 0.001], whereas RAL level below detection limit in plasma at one or more previous visits was associated with increased hazard [hazard ratio = 3.42 (95% CI 1.41-8.26), P = 0.006]. All five participants with integrase mutations during virologic failure had baseline viral load more than 100,000 copies/ml.
DRV/r plus RAL was effective and well tolerated in most patients, but virologic failure and integrase resistance were common, particularly in patients with baseline viral load more than 100,000 copies/ml.