Clinical trial NCT00734344: Pilot Study of Raltegravir/Truvada Versus Efavirenz/Truvada for Adults With Acute IV-1 Infection
Official title: Pilot Study of Raltegravir/Tenofovir/Emtricitabine Versus Efavirenz/Tenofovir/Emtricitabine for Adults With Acute HIV-1 Infection: Exploring the Role of Integrase Inhibition in Early HIV Pathogenesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute HIV Infection
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-08-14
Enrollment: 18
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single-site, investigator-initiated, open-label, randomized/controlled clinical trial to compare the viral load response in plasma (and, in a subset of subjects, in gastrointestinal lymphoid tissue reservoirs) in subjects with acute/early HIV-1 infection treated with 12 weeks of raltegravir-based versus efavirenz-based ART (each combined with tenofovir/emtricitabine). Subjects will receive a self-limited course of therapy rather than a commitment to life-long HAART, as has been the experimental approach in a variety of clinical protocols in the United States and Europe. Subjects will complete a 12 week course of therapy, and those who meet treatment-response and safety criteria will then undergo a similarly intensive period of virology and immunology monitoring to compare the timing and dynamics of any observed virologic rebound following the treatment intervention.


Eligibility criteria: Inclusion Criteria:

* Subjects 19 years of age or older who meet the NIH Acute Infection and Early Disease Research Program (AIEDRP) definition of acute or early HIV-1 infection. Briefly, acute HIV-1 infection is defined as \> 5000 copies per milliliter of HIV RNA and one of the following documented within a 7 day period of the initial positive PCR-based assay: 1) a negative HIV-1 EIA or 2) a positive EIA with a negative or indeterminant HIV-1 Western Blot test (interpreted based on current CDC guidelines). For the purposes of this protocol, early HIV-1 infection is defined as detectable HIV RNA by PCR-based assay, a positive HIV EIA, a positive HIV-1 Western blot, and one of the following: 1) a documented negative HIV EIA in the preceding 6 months or 2) an HIV detuned EIA standardized optical density measurement (defined as sample OD - negative control OD/ positive control OD) of \< 1.0 within 14 days of the positive HIV EIA (consistent with acute infection occurring in the past 120 days).

Exclusion Criteria:

* Lack consistent evidence of seroconversion or documented appropriate antibody testing for persistent HIV infection during the screening and early follow-up period.
* Prior receipt of antiretroviral therapy.
* Serum creatinine \> 2.0 x upper limit of normal or a calculated creatinine clearance at time of screening \< 30 mL/min (and 0.85X this value for females).
* Alkaline phosphatase \>5 x upper limit of normal.
* AST (SGOT) and ALT (SGPT) \> 5 x upper limit of normal. Repeat of a laboratory screening test will be allowed for test results that are unexpected based on documented prior laboratory results or to monitor declining trends that may relate to the primary retroviral syndrome.
* Have any severe medical illness that the investigators feel will interfere with the ability to take therapy or that will result in making therapy too risky for the subject. This includes active tuberculosis treatment, severe liver disease due to alcoholism or viral hepatitis, or unstable cardiovascular or cerebrovascular disease.
* Have significant psychiatric illness or ongoing substance abuse that, in the opinion of the investigators, would compromise the ability of the subject to provide adequate informed consent or to adhere to the study procedures safely and consistently.
* Women who are pregnant or actively breastfeeding at the time of screening.
* Men or women who are actively attempting to become pregnant, or who are unable or unwilling to institute adequate birth control measures during the entire course of this treatment protocol.

Primary outcomes:
measure: Mean White Blood Cell Count Between Treatment Groups at 2 Months
timeFrame: baseline to 2 months
measure: Mean White Blood Cell Count Between Treatment Groups at 4 Months
timeFrame: 4 months post baseline
measure: Mean White Blood Cell Count Between Treatment Groups at 6 Months
timeFrame: 6 months after baseline
measure: Mean White Blood Cell Count Between Treatment Groups at 8 Months
timeFrame: 8 months after baseline
measure: Mean White Blood Cell Count Between Treatment Groups at 10 Months
timeFrame: 10 months after baseline
measure: Mean White Blood Cell Count Between Treatment Groups at 12 Months
timeFrame: 12 months after baseline
measure: Mean White Blood Cell Count Between Treatment Groups at 14 Months
timeFrame: 14 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 2 Months
timeFrame: 2 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 4 Months
timeFrame: 4 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 6 Months
timeFrame: 6 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 8 Months
timeFrame: 8 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 10 Months
timeFrame: 10 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 12 Months
timeFrame: 12 months after baseline
measure: Mean Hematocrit Between Treatment Groups at 14 Months
timeFrame: 14 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 2 Months
timeFrame: 2 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 4 Months
timeFrame: 4 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 6 Months
timeFrame: 6 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 8 Months
timeFrame: 8 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 10 Months
timeFrame: 10 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 12 Months
timeFrame: 12 months after baseline
measure: Mean Platelet Count Between Treatment Groups at 14 Months
timeFrame: 4 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 1 Months
timeFrame: 1 month after baseline
measure: Mean CD4 Count Between Treatment Groups at 2 Months
timeFrame: 2 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 3 Months
timeFrame: 3 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 4 Months
timeFrame: 4 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 5 Months
timeFrame: 5 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 6 Months
timeFrame: 6 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 7 Months
timeFrame: 7 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 8 Months
timeFrame: 8 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 9 Months
timeFrame: 9 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 10 Months
timeFrame: 10 months after baseline
measure: Mean CD4 Count Between Treatment Groups at 11 Months
timeFrame: 11 months after baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB 1917 Clinic
state: Alabama
Study officials:
affiliation: Department of Medicine Divison of Infectious Disease
name: Sonya Heath, M. D.
role: PRINCIPAL_INVESTIGATOR
References: