Phase 2 N=24 Randomized Quadruple-blind Basic Science

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

HIV

Bottom Line

View on ClinicalTrials.gov: NCT00367458 ↗

Enrolled (actual)

Serious AEs

8.3%

Results posted

Feb 2020

Primary outcome: Primary: Change in Human Immunodeficiency Virus 1 (HIV-1) Ribonucleic Acid (RNA) Levels — 0; 0; -0.03; -0.08 Log10 copies/ml plasma

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Atorvastatin (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Jun 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Human Immunodeficiency Virus 1 (HIV-1) Ribonucleic Acid (RNA) Levels	0; 0; -0.03; -0.08	—
SECONDARY Change in Percentage of Cluster of Differentiation 4 (CD4+) Human Leukocyte Antigen DR (HLA-DR+) in Peripheral Blood	0; 0; -2; -1.8	—
SECONDARY Number of Participants With Serious and Non-Serious Adverse Events	12; 12	—
SECONDARY Change in Percentage of Cluster of Differentiation 8 (CD8+) Human Leukocyte Antigen DR (HLA-DR+) in Peripheral Blood	0; 0; -3.8; -3.5	—
SECONDARY Change in Percentage of Cluster of Differentiation 8 (CD8+) Human Leukocyte Antigen DR (HLA-DR+), CD8+(CD8+HLADR+CD38+) in Peripheral Blood	0; 0; -3.75; -3.3	—

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.

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Data sourced from ClinicalTrials.gov (NCT00367458). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.