Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies

• Published in: AIDS (London) Vol. 25; no. 11; pp. 1365 - 1369
• Main Authors: ROCKSTROH, Jürgen K, TEPPLER, Hedy, JING ZHAO, SKLAR, Peter, MILLER, Michael D, HARVEY, Charlotte M, STROHMAIER, Kim M, LEAVITT, Randi Y, NGUYEN, Bach-Yen T
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 17.07.2011
• Subjects: Adult; AIDS/HIV; Anti-Retroviral Agents - administration & dosage; Anti-Retroviral Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Double-Blind Method; env Gene Products, Human Immunodeficiency Virus - drug effects; env Gene Products, Human Immunodeficiency Virus - genetics; env Gene Products, Human Immunodeficiency Virus - immunology; Female; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - immunology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Pyrrolidinones - administration & dosage; Pyrrolidinones - pharmacology; Raltegravir Potassium; Treatment Outcome; United States; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; United States; Phase III trial; Immunopathology; Antiretroviral agent; Typing; HIV-1 virus; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Resistance; Symptomatology; Microbiological investigation; Integrase inhibitor; Viral disease; Antiviral; Human immunodeficiency virus; Mutation; Subtype; Raltegravir; resistance mutations; HIV-1 subtype
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e328348065a

We evaluated the long-term efficacy of raltegravir according to HIV-1 subtype (B and non-B) using data from three phase III studies in treatment-experienced (BENCHMRK-1 and 2) and treatment-naive (STARTMRK) HIV-infected patients. HIV-1 subtypes were identified from baseline plasma specimens using genotypic data of the PhenoSense GT test (Monogram Biosciences, South San Francisco, California, USA). Non-B subtypes were combined for the current analyses due to small numbers of each specific subtype. An observed failure approach was used (only discontinuations due to lack of efficacy were treated as failures). Resistance evaluation was performed in patients with documented virologic failure. Seven hundred and forty-three patients received raltegravir and 519 received comparator (efavirenz in STARTMRK; optimized background therapy in BENCHMRK). Non-B subtype virus (A, A/C, A/D, A/G, A1, AE, AG, B/G, BF, C, D, D/F, F, F1, G, and complex) was isolated at baseline in 98 (13%) raltegravir recipients and 62 (12%) comparator recipients. Subtypes AE and C were most common, isolated in 41 and 43 patients, respectively. The proportion of raltegravir recipients achieving HIV RNA less than 50 copies/ml was similar between non-B and B subtypes (STARTMRK: 94.5 vs. 88.7%; BENCHMRK-1 and 2: 66.7 vs. 60.7%); change in CD4 cell count also was similar between non-B and B subtypes (STARTMRK: 243 vs. 221 cells/μl; BENCHMRK-1 and 2: 121 vs. 144 cells/μl). Phenotypic resistance to raltegravir in non-B virus was associated with integrase mutations observed previously in subtype B virus. In phase III studies in treatment-naive and treatment-experienced patients, raltegravir showed comparable and potent clinical efficacy against B and non-B HIV-1 subtypes.