R5 Integrase Study in HIV-1 Naive Patients

Raltegravir and Maraviroc in Combination for the Treatment of Antiretroviral Naïve HIV-1 Infected Patients

This is a pilot, open-label study of raltegravir and maraviroc in combination for the treatment of antiretroviral naïve patients. The study will enroll 7 antiretroviral naïve patients with CD4 counts ≥ 350 and viral loads > 5,000. The subjects will be followed for 48 weeks. The combination of these two agents has the potential to be a potent regimen with minimal metabolic complications. However, they have not been studied in combination previously.

This pilot study proposes to evaluate this combination in antiretroviral naïve patients to document the safety and efficacy of this combination in order to provide clinicians with a treatment regimen that minimizes the risk of metabolic complications.

Seven antiretroviral naïve HIV infected participants will be treated with a combination of raltegravir and maraviroc and followed for 48 weeks to determine the time to virologic suppression of (HIV-1 viral load < 50 copies/ml).

Inclusion Criteria:

• HIV-1 infection
• CD4 count ≥ 350
• RNA > 5,000
• CCR5 tropic virus
• Baseline genotype without significant mutations known to confer antiretroviral drug resistance to currently licensed antiretroviral agents
• Antiretroviral naïve (< 7 days of experience)
• 18-75 years of age
• Subject able to provide informed consent for the study
• Women of child-bearing age agree to remain abstinent or use (or have their partner use) an acceptable method of birth control throughout the study. Acceptable method of birth control is defined as intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy.

Exclusion Criteria:

• Dual/mixed tropic virus,
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limits of normal;
• Total bilirubin >1.5 mg/dL,
• Women pregnant or breastfeeding,
• History of malignancy
• Enrollment in an experimental protocol with concomitant use of drugs known to impact or be impacted in terms of pk or drug-drug interactions with either raltegravir or maraviroc. This includes inducers of UGT1A1 ( such as rifampin, phenytoin, Phenobarbital rifabutin, St. John's wart) as well as CYP3A inhibitors (such as ketoconazole, itraconazole, clarithromycin , nefazodone and telithromycin) and CYP3A inducers (such as rifampin, carbamazepine, Phenobarbital and phenytoin)
• Enrollment in an experimental protocol having received investigational agents(antiretroviral or non-antiretroviral) within 30 days of study enrollment
• Chronic active hepatitis B infection
• Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
• Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
• Subject requires or is anticipated to require any of the prohibited medications noted in the protocol