Influence of Atorvastatin on Viral Replication During Antiretroviral Treatment Interruption

This study has been terminated.
(On the basis of published results of SMART study, it has been observed that the results are worse in patients who have interrupted their treatments.)
Sponsor:
Collaborator:
Fundacio Lluita Contra la SIDA
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00355251
First received: July 19, 2006
Last updated: March 19, 2014
Last verified: February 2014
  Purpose

To determine the influence of atorvastatin on plasma viral replication when the latter is given before and during highly active anti-retroviral therapy (HAART) in patients with HIV infection and viral suppression.


Condition Intervention Phase
HIV Infections
Drug: Atorvastatin 40 mg/Atorvastatin 80 mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of the Influence of Atorvastatin in Plasma Viral Replication Given Prior to Antiretroviral Treatment Interruption in Patients With HIV-1 Infection and Viral Suppression.

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • The primary endpoint is viral load (HIV RNA) in plasma. [ Time Frame: at 12 and 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CD4 and CD8, absolute value, percentage and activation. [ Time Frame: during the 32 weeks of follow-up ] [ Designated as safety issue: No ]
  • Total cholesterol, HDL and LDL in serum. [ Time Frame: during the 32 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Cholesterol in cell membrane. [ Time Frame: during the 32 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Symptoms reported by the patient following the interruption of the HAART therapy or signs detected by the clinician (classification according to the WHO), mainly those which may indicate acute antiretroviral symptoms. [ Time Frame: during the 32 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Creatinine, urea, creatine kinase (CK), hepatic tests, (AST, ALT, GGT) [ Time Frame: during the 32 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Proviral load. [ Time Frame: during the 32 weeks of follow-up ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: July 2006
Study Completion Date: February 2007
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
4 semanas manteniendo el tratamiento antirretroviral e iniciar atorvastatina 40 mg/día. A la semana 4 interrupción HAART y aumentar a 80 mg/día de atorvastatina hasta la semana 32 de seguimiento
Drug: Atorvastatin 40 mg/Atorvastatin 80 mg
Atorvastatin 40 mg/80 mg
No Intervention: B
4 semanas manteniendo el tratamiento antirretroviral. A la semana 4 interrupción HAART hasta la semana 32 de seguimiento

Detailed Description:

Recently, the inhibitory effect of the statins on the replication of the human immunodeficiency virus Type 1 (HIV-1) through two independent mechanisms of action has been described: the blockade of Rho guanosine triphosphatase that intervenes in the entry and exit of the virus and the blockade of the interaction between LFA-1 (leukocyte function antigen 1) and its ICAM 1 ligand (intercellular adhesion molecule 1) that intervenes in the process through which the virus binds to the target cell.

These initial data have led to the study of the effect of atorvastatin on the plasma replication of HIV in HIV+ patients that interrupt antiretroviral therapy (Ator Study 3) developed in our unit. The data of this study indicate that baseline plasma cholesterol determines viral load rebound on interrupting antiretroviral treatment. However, the introduction of atorvastatin on the day of interruption provided no virological or immunological benefit in comparison with an interruption of antiretrovirals without statins. This may be due to the fact that the potent inhibitory effect of atorvastatin is unable to compensate their activating effect on the production of HIV also described in our study.

Overall, our results pose a possible usefulness of atorvastatin in the control of viral replication if given before the interruption of antiretroviral therapy due to:

  • Their capacity to reduce serum cholesterol at the time of interruption and consequently the cholesterol of the cell membrane.
  • Their potent capacity to purge the HIV reservoir

Therefore, in this study we aim to investigate the impact of atorvastatin on viral replication when it is given 8 weeks before the interruption of the antiretroviral treatment and determine whether this impact is due to the reduction in serum and/or membrane cholesterol, or whether, on the other hand, there is a contribution by atorvastatin's capacity to induce the expression of viral products.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >= 18 years.
  2. Patients with chronic infection by HIV-1 in stable highly active antiretroviral treatment (>= 6 months).
  3. Undetectable plasma viral load (<50 copies/mL) in the last 3 determinations over the last 6 months.
  4. CD4 > 500 cells/mm>=3 in the last two determinations.
  5. Documented prior viral load at some time of >15,000 copies/mL.
  6. Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
  7. Signature of the informed consent

Exclusion Criteria:

  1. CD4 nadir <= 200 cells/mm3.
  2. Background of infections or other AIDS-defining pathology.
  3. Intercurrent infections in the last 6 months.
  4. Creatine kinase (CK) >= 500 U/L.
  5. AST or ALT >= 3 times higher than the upper limit of normality.
  6. Treatment with others statins, fibrates, macrolides or fluconazole in the last 3 months.
  7. Pregnancy or breastfeeding
  8. Patients participating in another clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00355251

Locations
Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Investigators
Principal Investigator: Bonaventura Clotet, MD,PhD LLuita contra la Sida Foundation-HIV Unit
  More Information

No publications provided

Responsible Party: Fundació Lluita contra la Sida
ClinicalTrials.gov Identifier: NCT00355251     History of Changes
Other Study ID Numbers: PRE-ATOR, 2005-005356-41
Study First Received: July 19, 2006
Last Updated: March 19, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Atorvastatin
Viral replication
HIV-1
plasma cholesterol
Cell membrane cholesterol

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014