Randomized Placebo-Controlled Trial of Atorvastatin in HIV-Positive Patients Not on Antiretroviral Therapy
Condition: HIV
MeSH terms: HIV Seropositivity
Intervention: Atorvastatin; Placebo
Intervention description: 80 mg atorvastatin oral daily; patients will be administered placebo
Intervention MeSH terms: Atorvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Viremia; Statin; HIV Replication; Cholesterol; Lipid Raft; HIV Infection; HIV Positive

Summary:

      This study will examine the effects of atorvastatin, a statin (drug that lowers cholesterol)
      on the human immunodeficiency virus (HIV). If not treated, HIV infection causes an incurable,
      progressive deficiency in the immune system that leads to death, usually from disease that
      takes advantage of weakened immunity. Previous studies, however, have suggested that if the
      amount of cholesterol in infected cells is reduced, multiplication of HIV is also reduced. In
      this study, researchers will examine the HIV viral loads, that is, amount of the virus in the
      blood. They will evaluate the composition of the strain of the virus that patients carry (HIV
      genotype), response of the immune system to the virus, and how genes may determine the way in
      which the drug may or may not work against the strain of virus. Researchers plan to enroll 22
      participants, anticipating a study to last 30 weeks for each participant.

      Patients ages 18 or older with HIV infection, who are not pregnant or breastfeeding, who do
      not have a known allergy to atorvastatin use, and who have not had a serious illness or
      infection that required hospitalization within the 30 days before entering the study may be
      eligible for this study. They will be assigned to random groups: one that to receive
      atorvastatin and the other to receive a placebo, which has no effect on cholesterol or
      ability of the HIV infection to multiply. Patients will remain in their groups and treatments
      for 8 weeks. At the completion of 8 weeks, no matter the study group, all patients will be
      required to discontinue all study-related medications for 4 weeks. After that period, the
      study assignments will be switched, so that those previously taking the placebo will take
      atorvastatin, and vice versa. The study will proceed for another 8 weeks, followed by a
      period of stopping study-related medications and patients being observed for 4 weeks.
      Throughout the study, patients will have regularly scheduled visits at the clinic. At those
      visits there will be collection of blood samples, assessments of symptoms, physical
      examinations, and questionnaires to complete. Blood tests may require fasting beforehand, and
      blood samples will be used in standard tests, including those regarding the liver, kidneys,
      muscles, blood cells, and pregnancy status. Specialized blood tests will determine viral
      load, effects of the drug on the immune cells, and genetic influence on the drug's
      effectiveness.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Adults 18 years of age or older.

          -  Human Immunodeficiency Virus -1 (HIV-1) infection, as documented by a licensed
             Enzyme-Linked Immunosorbent Assay (ELISA) test kit and confirmed by a Western blot
             assay at any time point prior to study entry or at study entry (May do after informed
             consent if no test results are available).

        Off all antiretroviral (ARV) for greater than or equal to three months prior to study
        entry, no documented evidence of viral resistance, and no evidence of acute HIV infection.

          -  Willingness to use a method of contraception during the study period.

          -  Willingness to have blood drawn.

          -  No known allergy or contraindication to atorvastatin use.

          -  Ability to understand and willingness to sign the informed consent.

          -  Willingness to have blood stored for future phenotyping and genotyping.

          -  Cluster of differentiation 4 (CD4) cell count greater than 350 cells/ml.

          -  3 viral loads that average greater than 1000 copies/ml within a 4-week period.

          -  The viral loads will be done using the branched deoxyribonucleic acid (bDNA) method in
             the National Institutes of Health (NIH) laboratory and must be within 20% (log10bDNA
             of each other).

          -  A fasting total cholesterol lower than 240mg/dl and an Low-density lipoprotein (LDL)
             cholesterol lower than 130mg/dl.

          -  Liver function tests (aspartate aminotransferase (AST) or alanine aminotransferase
             (ALT)) not greater than 1.5 times the upper limit of normal.

          -  Creatine phosphokinase elevations (CPK) not greater than 3 times the upper limit of
             normal (ULN) on two sequential determinations and, in the opinion of the investigator,
             without clear association with exercise.

          -  Laboratory values:

        Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3).

        Hemoglobin greater than or equal to 11.0 g/dL.

        Platelet count greater than or equal to 100,000/mm(3).

        Creatinine less than or equal to 2 x ULN.

        Serum amylase and lipase less than or equal to 1.25 x ULN.

          -  Negative serum pregnancy test at randomization.

        EXCLUSION CRITERIA:

          -  Pregnancy or breast feeding.

          -  Active drug use or alcohol abuse/dependence, which in the opinion of the
             investigators, will interfere with the patient's ability to participate in the study.

          -  Serious illness requiring systemic treatment and/or hospitalization within 30 days of
             entry.

          -  Evidence of active opportunistic infections or neoplasms that require chemotherapy
             during the study period except cutaneous Kaposi Sarcoma.

          -  Allergy or hypersensitivity to atorvastatin or any of its components.

          -  History of myositis or rhabdomyolysis with use of any statins.

          -  History of inflammatory muscle disease such as poly or dermatomyositis.

          -  Concomitant use of fibric acid derivatives or other lipid lowering agents including
             patients on statins and Ezetimibe.

          -  Concomitant use of drugs that have significant interactions with atorvastatin. Please
             see appendix II for a listing.

          -  Concomitant use of St.Johns wort.

          -  Concomitant use of Valproic acid.

          -  Patients who are on concurrent immunomodulatory agents, including systemic
             corticosteroids, will be ineligible for 3 months after completion of therapy with the
             immunomodulating agents. Topical, nasal or inhaled corticosteroids use is not an
             exclusion criterion.

          -  Serum LDL cholesterol less than 40 mg/dl.

          -  Vaccinations within 6 weeks of study entry.

          -  Vaccinations within 6 weeks of study entry.