Atorvastatin for HAART Suboptimal Responders

Acquired Immune Deficiency Syndrome Virus Clinical Trial

Official title:

Use of Atorvastatin as Adjuvant Therapy Among Suboptimal Responders to Antiretroviral Therapy in an African Cohort of HAART-treated Adults: A Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01766076
• Other study ID #: HS1258
• Status: Completed
• Phase: Phase 3
• First received: December 10, 2012
• Last updated: May 20, 2015
• Start date: January 2013
• Est. completion date: March 2014

Study information

• Verified date: May 2015
• Source: Makerere University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: National Council for Science and Technology
• Study type: Interventional

Clinical Trial Summary

We hypothesise that atorvastatin changes immune activation among HAART-treated adults with suboptimal cluster cell differentiation 4 (CD4) recovery by 25%

Description:

The investigators have previously shown that up to 40% of HAART-treated adults have suboptimal CD4 recovery despite viral suppression. The investigators have also shown that immune activation and exhaustion are significantly higher among patients that do not exhibit satisfactory rise in CD4 counts despite viral suppression (suboptimal responders); when compared with their counterparts with viral suppression and satifactory CD4 count recovery (optimal responders). Given that atorvastatin changes immune activation in this pilot study, then larger studies can be done to understand its effect on CD4 count increase among suboptimal responders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

List of inclusion Criteria: HIV-infected adults on antiretroviral therapy for at least 6 years with sustained viral suppression (viral load<400 copies), and CD4 increase below 300 cells (difference between current and baseline CD4 count).

List of exclusion Criteria: History of an opportunistic infection within the previous six months, Pregnancy, History of myositis, History of ingestion of lipid-lowering agents at the baseline visit, Use of therapeutic agents known to have substantial drug-drug interactions with statins, and individuals on PI-containing HAART

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immune Deficiency Syndrome Virus
• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Other:
• atorvastatin, Lipitor®
PBMC collected for immune activation assays using flowcytometry

Drug:
• Placebo
PBMC collected for immune activation assays using flowcytometry

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Makerere University	Vaccine and Gene Therapy Institute, Florida

References & Publications (2)

Ganesan A, Crum-Cianflone N, Higgins J, Qin J, Rehm C, Metcalf J, Brandt C, Vita J, Decker CF, Sklar P, Bavaro M, Tasker S, Follmann D, Maldarelli F. High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. J Infect Dis. 2011 Mar 15;203(6):756-64. doi: 10.1093/infdis/jiq115. Epub 2011 Feb 15. — View Citation

Nakanjako D, Ssewanyana I, Mayanja-Kizza H, Kiragga A, Colebunders R, Manabe YC, Nabatanzi R, Kamya MR, Cao H. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infect Dis. 2011 Feb 8;11:43. doi: 10.1186/1471-2334-11-43. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Change in Immune Activation Levels After 12 Weeks of Atorvastatin 80mg Daily	Immune activation was measured by co-expression of CD38 and HLADR on CD4 T-cells (CD4+CD38+HLADR+) Mean percentage change at 12 weeks was calculated	12 weeks	Yes