Clinical trial NCT00830804: Safety and Effectiveness of Raltegravir Plus Darunavir/Ritonavir in Treatment-Naive HIV-Infected Adults
Official title: A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infections
Keywords: Treatment Naive
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2009-01-28
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24
timeFrame: From start of study treatment to week 24
Secondary outcomes:
measure: Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24
timeFrame: From start of study treatment to Week 24
measure: Change in Plasma HIV-1 RNA From Baseline to Week 1
timeFrame: Baseline and week 1
measure: Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24
timeFrame: From start of study treatment to week 24
measure: Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48
timeFrame: From start of study treatment to week 48
measure: 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
timeFrame: From start of study treatment to week 52
measure: Number of Participants With Pretreatment Drug Resistance
timeFrame: At screening
measure: Number of Participants With Integrase Drug Resistance at Virologic Failure
timeFrame: From 12 weeks after starting study treatment to week 52
measure: Number of Participants With Protease Drug Resistance at Virologic Failure
timeFrame: From 12 weeks after starting study treatment to week 52
measure: Number of Participants With Perfect Overall Adherence by Self Report
timeFrame: From one week after starting study treatment to week 52
measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24
timeFrame: From start of study treatment through week 24
measure: Change in Fasting Low-density Lipoprotein at Week 24
timeFrame: From start of study treatment through week 24
measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48
timeFrame: From start of study treatment through week 48
measure: Change in Fasting Low-density Lipoprotein at Week 48
timeFrame: From start of study treatment through week 48
measure: Change in CD4 Count at Week 48
timeFrame: From start of study treatment through week 48
measure: Plasma Trough Concentration of Raltegravir
timeFrame: From start of study treatment to week 52
measure: Plasma Trough Concentration of Darunavir
timeFrame: From start of study treatment to week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: AlabamaTherapeutics CRS
state: Alabama
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Washington
country: United States
facility: Georgetown University CRS
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Med Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp. ACTG CRS
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Rochester
country: United States
facility: AIDS Community Health Ctr. ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Durham
country: United States
facility: Duke Univ. Med. Ctr. Adult CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh CTU
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics CRS
state: Tennessee
city: Houston
country: United States
facility: Houston AIDS Research Team
state: Texas
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Joseph J. Eron, Jr., MD
role: STUDY_CHAIR
References:
citation: Capetti AF, Piconi S, Landonio S, Rizzardini G, Perno CF. Is dual therapy with raltegravir and protease inhibitors a feasible option in rescue strategy in HIV-1 infection? J Acquir Immune Defic Syndr. 2009 Feb 1;50(2):233-4. doi: 10.1097/QAI.0b013e31818c7e8e. No abstract available.
citation: Long MC, King JR, Acosta EP. Pharmacologic aspects of new antiretroviral drugs. Curr HIV/AIDS Rep. 2009 Feb;6(1):43-50. doi: 10.1007/s11904-009-0007-y.
citation: Vermeir M, Lachau-Durand S, Mannens G, Cuyckens F, van Hoof B, Raoof A. Absorption, metabolism, and excretion of darunavir, a new protease inhibitor, administered alone and with low-dose ritonavir in healthy subjects. Drug Metab Dispos. 2009 Apr;37(4):809-20. doi: 10.1124/dmd.108.024109. Epub 2009 Jan 8.
citation: Taiwo B, Zheng L, Gallien S, Matining RM, Kuritzkes DR, Wilson CC, Berzins BI, Acosta EP, Bastow B, Kim PS, Eron JJ Jr; ACTG A5262 Team. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262). AIDS. 2011 Nov 13;25(17):2113-22. doi: 10.1097/QAD.0b013e32834bbaa9.