Randomized Placebo-Controlled Trial of Atorvastatin in HIV-Positive Patients Not on Antiretroviral Therapy

NCT00367458 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 06019706-I-0197
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

HIV

Keywords

Viremia; Statin; HIV Replication; Cholesterol; Lipid Raft; HIV Infection; HIV Positive

Outcome Measures

Primary Outcomes (1)

• Change in Human Immunodeficiency Virus 1 (HIV-1) Ribonucleic Acid (RNA) Levels

  The change in HIV viral RNA level in plasma in response to lipid lowering agents was measured as log10 plasma RNA copy number, and the change in the log10 viral RNA level is included in table.

  Baseline and 8 weeks

Secondary Outcomes (4)

• Change in Percentage of Cluster of Differentiation 4 (CD4+) Human Leukocyte Antigen DR (HLA-DR+) in Peripheral Blood

  Baseline and 8 weeks

• Number of Participants With Serious and Non-Serious Adverse Events

  Date treatment consent signed to date off study, approximately 26 weeks.

• Change in Percentage of Cluster of Differentiation 8 (CD8+) Human Leukocyte Antigen DR (HLA-DR+) in Peripheral Blood

  Baseline and 8 weeks

• Change in Percentage of Cluster of Differentiation 8 (CD8+) Human Leukocyte Antigen DR (HLA-DR+), CD8+(CD8+HLADR+CD38+) in Peripheral Blood

  Baseline and 8 weeks

Study Arms (2)

Atorvastatin, then Placebo

EXPERIMENTAL

Patients were randomized to receive Atorvastatin first for 8 weeks, followed by 4 weeks wash out, and then cross over to placebo for 8 weeks.

Drug: Atorvastatin; Drug: Placebo

Placebo, Then Atorvastatin

EXPERIMENTAL

Patients were randomized to receive placebo first for 8 weeks, followed by 4 weeks wash out, and then cross over to 80 mg atorvastatin daily for 8 weeks.

Drug: Atorvastatin; Drug: Placebo

Interventions

Atorvastatin DRUG

80 mg atorvastatin oral daily

Also known as: lipitor

Atorvastatin, then Placebo; Placebo, Then Atorvastatin

Placebo DRUG

patients will be administered placebo

Also known as: no other name for placebo

Atorvastatin, then Placebo; Placebo, Then Atorvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• Serum LDL cholesterol less than 40 mg/dl.
• Vaccinations within 6 weeks of study entry.
• Vaccinations within 6 weeks of study entry.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Naval Medical Center, San Diego

San Diego, California, 92134-5000, United States

Location

National Naval Medical Center

Bethesda, Maryland, 20889, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.

  PMID: 9516219 BACKGROUND

• Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet. 2000 Oct 21;356(9239):1423-30. doi: 10.1016/S0140-6736(00)02854-3.

  PMID: 11052597 BACKGROUND

• Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. 1999 Jun 19;353(9170):2093-9. doi: 10.1016/S0140-6736(98)08468-2.

  PMID: 10382692 BACKGROUND

MeSH Terms

Conditions

Viremia; HIV Infections; HIV Seropositivity

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Virus Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Frank Maldarelli
• Organization: National Cancer Institute

fmalli@mail.nih.gov

301-435-8019

Study Officials

• Frank Maldarelli, M.D. Ph.D.

  National Cancer Institute (NCI), National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Study Record Dates

• First Submitted: August 22, 2006
• First Posted: August 23, 2006
• Study Start: October 18, 2006
• Primary Completion: June 19, 2008
• Study Completion: June 19, 2008
• Last Updated: February 26, 2020
• Results First Posted: February 26, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)