HAART IN ACUTE/EARLY HIV INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIM: ¿¿ Within the context of a controlled clinical trial, to evaluate the benefit of a time?limited course of Highly Active Antiretroviral Therapy (TL-HAART) at different stages of acute infection/early disease due to HIV (AIED). Within the context of a three?year phase IV randomized clinical trial, we will compare two different strategies for intervention following the diagnosis of AIED. Specifically, we will examine, in a randomized fashion, whether a one?year course of HAART provides lasting benefit in patients who have recently become infected with HIV. If this is the case, we will further examine whether the benefit is limited to a subset of such individuals, based on the interval between exposure to HIV and initiation of therapy. RECRUITMENT: All patients in whom a diagnosis of AIED (i.e., duration of HIV < 12 months) can be made will be offered the opportunity to participate in the study. Over two years, we will recruit 180 patients into the protocol, including significant numbers of IDUs, including 48 in Baltimore and 132 in Canadian sites. Inclusion Criteria ¿¿ Age ? 18 years ¿¿ Ability to understand the purpose of the study (including the specific rationale for the treatment of AIED) and to read, understand and sign the informed consent document. ¿¿ No prior history of antiretroviral therapy other than post-exposure prophylaxis ¿¿ Ability to swallow significant numbers of tablets/capsules ¿¿ Negative serum Beta-HCG in women of child-bearing potential prior to initiation of therapy ¿¿ Willingness to use barrier contraception during the course of the study Exclusion Criteria ¿¿ Clinically significant medical condition that would preclude the use of HAART ¿¿ Evidence of any condition (such as uncontrolled substance abuse) that would, in the opinion of the investigator, prevent adequate adherence to the protocol, even with DOT ¿¿ Pregnancy at the time of initial presentation ¿¿ Abnormalities within two weeks of initiating HAART: Hemoglobin <90 g/L; Neutrophil count < 1,000 /mm3; Platelet count < 30,000/mm3, AST or ALT > 10X upper limit of normal (ULN); Pancreatic amylase or lipase > 3x ULN; Total bilirubin > 3x ULN ¿¿ Inability to design a study treatment regimen based on the results of genotypic resistance testing ¿¿ Plasma viral load < 5,000 copies/mL, unless it can be conclusively established that infection occurred in the previous 6 months. Randomization: Randomization will be 1:1 and stratified by acute infection (defined as infection within the last 2 months) versus early infection (defined as infection within the last 2 - 12 months). Duration: All participants will be followed monthly for the first year, then every three months for the next two years. ENDPOINTS: Primary Endpoint: ¿¿ Comparison of the plasma viral load 24 months after initial presentation in all treated vs. untreated patients.