Clinical trial NCT00525733
Conditions: HIV Infections
Keywords: HIV-1 Acute Infection Treatment Naive
Sponsor: Rockefeller University
Start date: 2007-10-01; Completion date: 2013-12-01
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest.

Hypotheses:

* Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication.
* Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa.
* Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.

Detailed description:
* DURATION: Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest.
* SAMPLE SIZE: 36 subjects randomized 2:1 multi-class versus standard antiretroviral therapy.
* POPULATION: Acutely HIV-1-infected, antiretroviral (ARV) drug-naïve (≤ 7 days of ARV treatment at anytime prior to study entry\*) men and women ≥ 18 years of age.
* REGIMEN: At entry subjects will be randomized to one of the following in a 1:2 ratio:

ARM A: FTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ritonavir 100 mg QD

ARM B: FTC 200 mg/TDF 300 mg QD + darunavir 800mg/ritonavir 100 mg QD + Raltegravir 400 mg BID + Maraviroc 150 mg BID

The three primary objectives are:

1. To assess whether a multi-class regimen could completely suppress virus replication in HIV infected individuals based on:

   * Plasma HIV-1 RNA levels at 48 weeks
   * Ultrasensitive \< 50 copy assay
   * 5 copy assay
   * 1 copy assay
   * Cell associated HIV-1RNA levels at week 48
   * Proviral DNA
   * Levels at week 48
   * Decay rates from week 12 to week 48
2. To determine whether multi-class antiviral therapy results in enhanced immune reconstitution in peripheral blood and gastrointestinal mucosa based on flow and immunohistochemistry.
3. To assess tolerability of multi-class compact antiviral therapy to that of standard compact antiviral therapy.

Arms: arm 1: FTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ +ritonavir 100 mg QD arm 2: FTC 200 mg/TDF 300 mg QD + darunavir 800 mg + ritonavir 100 mg QD + Raltegravir 400 mg BID + Maraviroc 150 mg BID
Interventions: intervention 1: darunavir 800 mg intervention 2: FTC 200 mg/TDF 300mg intervention 3: Maraviroc intervention 4: Raltegravir intervention 5: Ritonavir 100 mg
Intervention descriptions: intervention 1: darunavir 800mg tablet will be administered with 100 mg capsule of ritonavir once daily (may be taken with or without food) intervention 2: Emtricitabine/tenofovir DF fixed-dose tablet containing 200 mg of emtricitabine and 300 mg of tenofovir DF will be administered orally as one tablet once daily (may be taken with or without food) intervention 3: Maraviroc will be administered twice daily in 150 mg tablets (may be taken with or without food) intervention 4: Raltegravir will be administered twice daily as 1-400 mg tablets (to be taken with food) intervention 5: one tablet of ritonavir is taken with darunavir daily

Protocol documents: