Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease
Condition: Acquired Immune Deficiency Syndrome
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Intervention: Lopinavir 400 mg/ritonavir 100 mg; Efavirenz
Intervention description: Lopinavir 400 mg/ritonavir 100 mg fixed dose combination BID + emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD; Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
Intervention MeSH terms: Ritonavir; Lopinavir; Efavirenz
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: AIDS, HIV

Summary:

      The ideal anti-HIV medications for patients with advanced HIV disease is unknown. There is
      evidence that anti-HIV regimens that contain protease inhibitors can enhance immune function
      better than regimens that do not contain protease inhibitors. This is a study that will
      determine the difference in immune enhancement capabilities between an anti-HIV regimen that
      contains the protease inhibitor - lopinavir-ritonavir, and a regimen that contains efavirenz.
      Both medications are recommended as first line treatments for HIV-infected patients. This
      study will recruit HIV-positive patients that need to start anti-HIV treatment because their
      CD4+ T-cells are below 200. The usual threshold for starting treatment is a CD4+ T-cell less
      than 350. Subjects will be randomized to treatment with either an anti-HIV regimen that
      contains lopinavir-ritonavir or a regimen that contains efavirenz. The study will determine
      the difference in immune reconstitution over 24 weeks of treatment with study medications.
      Among the immune parameters that will be measured is the ability of each subject to respond
      to vaccination with the tetanus-diphtheria vaccine and the 23-valent pneumococcal vaccine.
      Both vaccines are also recommended for HIV-positive patients but HIV-positive patients tend
      to have a lower response rate to these vaccines.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV-1 infection

          2. The absence of exclusionary resistance mutations on a genotypic resistance assay

          3. Antiretroviral (ARV) drug-naïve

          4. Screening HIV-1 RNA >1000 copies/mL

          5. Screening CD4+ T-cell count < 200 cells/ml

          6. Laboratory values obtained within 30 days prior to study entry.

               -  Absolute neutrophil count (ANC) >500/mm3

               -  Hemoglobin >8.0 g/dL

               -  Platelet count >40,000/mm3

               -  AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 x ULN

               -  Total bilirubin <2.5 x ULN

               -  Calculated creatinine clearance ≥60 mL/min (by Cockcroft-Gault equation)

          7. For women of reproductive potential, negative serum or urine pregnancy test within 48
             hours prior to initiating study medications.

          8. Contraception requirements

          9. Men and women age >18 years and < 60 years.

         10. Ability and willingness of subject or legal guardian/representative to give written
             informed consent.

        Exclusion Criteria:

          1. Currently breast-feeding.

          2. Use of immunomodulators, vaccines, growth hormone, systemic cytotoxic chemotherapy, or
             investigational therapy within 30 days prior to study entry.

          3. Known allergy/sensitivity to study drugs, pneumococcal polysaccharide vaccine,
             tetanus-diphtheria vaccine

          4. Receipt of pneumococcal polysaccharide vaccine or tetanus-diphtheria vaccine in the
             past 5 years.

          5. Active drug or alcohol use or dependence

          6. Serious illness requiring systemic treatment and/or hospitalization until candidate
             either completes therapy or is clinically stable on therapy, in the opinion of the
             site investigator, for at least 14 days prior to study entry.

          7. Requirement for any current medications that are prohibited with any study treatment.

          8. Evidence of any major resistance-associated mutation on any genotype or evidence of
             significant resistance on any phenotype performed at any time prior to study entry

          9. Current or anticipated imprisonment or involuntary incarceration in a medical facility
             for psychiatric or physical (e.g., infectious disease) illness

         10. History of, or current bipolar disorder, major depression, schizophrenia or other
             psychotic disorders