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

• Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24 [ Time Frame: From start of study treatment to week 24 ] [ Designated as safety issue: No ]
  Virologic failure is defined as: at week 12, confirmed plasma HIV-1 RNA >= 1000 copies/ml or confirmed rebound from the week 4 value by >0.5 log10 copies/ml (for subjects with week 4 value <= 50 copies/ml, confirmed rebound to >50 copies/ml); at week 24 or later, confirmed value > 50 copies/ml. Viral load confirmation was scheduled 7-35 days after initial virologic failure. The proportion was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
  
  

• Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24 [ Time Frame: From start of study treatment to Week 24 ] [ Designated as safety issue: No ]
  The proportion of participants with virologic failure (see primary outcome measure for definition) and/or premature treatment discontinuation/modification and/or death was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
  
  
• Change in Plasma HIV-1 RNA From Baseline to Week 1 [ Time Frame: Baseline and week 1 ] [ Designated as safety issue: No ]
  Results report the week 1 change from baseline (week 1 - baseline) in HIV-1 RNA. Baseline HIV-1 RNA was computed as the mean of the log10 HIV-1 RNA values at pre-entry and study entry.
  
  
• Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24 [ Time Frame: From start of study treatment to week 24 ] [ Designated as safety issue: No ]
  Results report the percentage of participants with plasma HIV-1 RNA < 50 copies/ml or <200 copies/ml at week 24.
  
  
• Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48 [ Time Frame: From start of study treatment to week 48 ] [ Designated as safety issue: No ]
  Results report the percentage of participants with plasma HIV-1 RNA <50 copies/ml or <200 copies/ml at week 48.
  
  
• Proportion of Participants Who Experienced Signs/Symptoms or Laboratory Toxicities Grade 3 or Higher, or of Any Grade Which Led to a Permanent Change or Discontinuation of Study Treatment [ Time Frame: From start of study treatment to week 52 ] [ Designated as safety issue: Yes ]
  Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System. Results report the percentage of participants who had grade 3 or higher events, or events of any grade which led to a permanent change or discontinuation of study treatment, which occurred any time from start of treatment to end of treatment.
  
  
• Number of Participants With Pretreatment Drug Resistance [ Time Frame: At screening ] [ Designated as safety issue: No ]
  Results report the number of participants who had resistance to non-nucleoside reverse transciptase inhibitors (NNRTI), nucleoside reverse transciptase inhibitors (NRTI) and protease inbitors (PI) based on genotypic resistance testing done prior to participant's entry into the study. Participants are classified into one (and only one category) based on the maximum number of drug class resistance seen for the participant.
  
  
• Number of Participants With Integrase Drug Resistance at Virologic Failure [ Time Frame: From 12 weeks after starting study treatment to week 52 ] [ Designated as safety issue: No ]
  Results report the number of participants who had integrase resistance mutation(s) detected at the time of virologic failure.
  
  
• Number of Participants With Protease Drug Resistance at Virologic Failure [ Time Frame: From 12 weeks after starting study treatment to week 52 ] [ Designated as safety issue: No ]
  Results report the number of participants who had protease resistance mutation(s) detected at the time of virologic failure.
  
  
• Number of Participants With Perfect Overall Adherence by Self Report [ Time Frame: From one week after starting study treatment to week 52 ] [ Designated as safety issue: No ]
  At each study visit, adherence was measured in terms of the number of missed doses each participant had over a 4-day recall for each drug. Adherence for all study visit weeks were combined for an overall measure of adherence. Participants who had zero missed doses on all weeks in all drugs while on study were classified as having an overall "perfect" adherence.
  
  
• Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24 [ Time Frame: From start of study treatment through week 24 ] [ Designated as safety issue: No ]
  Results report the week 24 change from week 0 (week 24 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
  
  
• Change in Fasting Low-density Lipoprotein at Week 24 [ Time Frame: From start of study treatment through week 24 ] [ Designated as safety issue: No ]
  Results report the week 24 change from week 0 (week 24 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.
  
  
• Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48 [ Time Frame: From start of study treatment through week 48 ] [ Designated as safety issue: No ]
  Results report the week 48 change from week 0 (week 48 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.
  
  
• Change in Fasting Low-density Lipoprotein at Week 48 [ Time Frame: From start of study treatment through week 48 ] [ Designated as safety issue: No ]
  Results report the week 48 change from week 0 (week 48 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.
  
  
• Change in CD4 Count at Week 48 [ Time Frame: From start of study treatment through week 48 ] [ Designated as safety issue: No ]
  Results report the week 48 change from baseline (week 48 - baseline) in CD4 count. Baseline CD4 count was computed as the mean of CD4 count values at pre-entry and study entry.
  
  
• Plasma Trough Concentration of Raltegravir [ Time Frame: From start of study treatment to week 52 ] [ Designated as safety issue: No ]
  Plasma trough concentrations (ng/ml) of Raltegravir (RAL) below the detection limit (10 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 9-15 hours after the last RAL dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
  
  
• Plasma Trough Concentration of Darunavir [ Time Frame: From start of study treatment to week 52 ] [ Designated as safety issue: No ]
  Plasma trough concentrations (ng/ml) of Darunavir (DRV) below the detection limit (50 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 20-28 hours after the last DRV dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.
  
  

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.