Safety and Effectiveness of Raltegravir Plus Darunavir/Ritonavir in Treatment-Naive HIV-Infected Adults

A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects

The purpose of this study is to assess the effectiveness and safety of an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.

Despite the remarkable strides made in the treatment of HIV-1-infected persons over the last decade, current first-line ART regimens are imperfect. The ideal combination, unlike some current first-line options, would have uncompromised efficacy in the presence of transmitted drug-resistant variants. The primary purpose of this study is to estimate the cumulative proportion of ART-naive participants experiencing virologic failure at or prior to week 24 after initiating raltegravir (RAL) plus darunavir/ritonavir (DRV/RTV).

The study will last 52 weeks. All participants will follow the same treatment schedule and take RAL plus DRV/RTV orally daily for the duration of the trial.

After entry, all participants will have scheduled visits at weeks 1, 4, 12, 24, 36, 48, and 52. Medical/medication history, blood and urine collection, and liver function tests will occur at screening. A targeted physical exam and concomitant medications history will occur at all study visits. Blood and urine collection and liver function tests will occur at most study visits. For females, a pregnancy test will occur at screening and study entry.

RAL and DRV were provided by the study. RTV was not provided by the study.

Inclusion Criteria:

• HIV-1-infected
• Plasma HIV-1 RNA of at least 5,000 copies/mL within 90 days prior to study entry
• HIV genotype (for reverse transcriptase and protease) performed at any time prior to study entry. More information on this criterion can be found in the protocol.
• ARV drug-naive. More information on this criterion can be found in the protocol.
• Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry
• Agree to use one form of medically-accepted contraceptive throughout the study and for 60 days after stopping study treatment. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to study. More information on this criterion can be found in the protocol.
• Screening HIV genotype obtained any time prior to study entry with more than one DRV resistance-associated mutation [RAM] (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76V alone
• Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S
• Severe renal insufficiency requiring hemodialysis or peritoneal dialysis
• Treatment with immunomodulators within 30 days prior to study entry. More information on this criterion can be found in the protocol.
• Current medications that are prohibited with any study medications. More information on this criterion can be found in the protocol.
• Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study.
• Certain abnormal laboratory results. More information on this criterion can be found in the protocol.
• Pregnant or breastfeeding