Raltegravir Therapy for Women With HIV and Fat Accumulation

NCT00656175 | Completed Phase 2 Results

• 1 other identifier: IISP-Raltegravir
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 5

Brief Summary

Ritonavir-boosted protease inhibitor (PI) regimens have become a backbone for treatment of people with HIV. However, adverse drug effects, particularly lipodystrophy/lipoatrophy are closely associated with these regimens. Therefore, there is a need for a drug with comparable effectiveness to the ritonavir boosted PIs without the side effects of dyslipidemia, which has been associated with elevated cholesterol and cardiovascular disease Raltegravir is an HIV integrase inhibitor in phase III clinical development. To date there are no approved drugs that target the same stage of the HIV-1 lifecycle. However, data from studies indicate that raltegravir is generally safe and well tolerated and has strong antiretroviral activity when used in combination with licensed antiretroviral medications. This study aims to demonstrate that patients substituting raltegravir for a PI or NNRTI based antiretroviral regimen will be associated with a 10% reduction in body fat over 24 weeks. The study will consist of a total of 10 subject visits over a period of 48 weeks. Approximately 40 female patients will participate in this study (approximately 10 at UCLA).

Conditions

HIV Infections; Lipodystrophy

Keywords

lipodystrophy; fat; visceral fat; HIV; women; raltegravir; ART; anti HIV therapy; NNRTI; Protease inhibitor; integrase inhibitor; treatment experienced

Outcome Measures

Primary Outcomes (1)

• Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)

  Adipose tissue volumes were measured via single slice L4-L5 CT scan, and volumes were calculated using cm\^2, not cm\^3, as is standard protocol at the Tufts University Body Composition Reading Center. The authors acknowledge that cm\^2 uses area as a surrogate for volume, but this protocol is well-accepted in our field.

  Baseline and 24 weeks

Study Arms (2)

Immediate

ACTIVE COMPARATOR

Immediate switch of PI or NNRTI to Raltegravir

Drug: raltegravir

Delayed

ACTIVE COMPARATOR

Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir

Drug: raltegravir

Interventions

raltegravir DRUG

raltegravir

Also known as: Isentress

Delayed; Immediate

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry or plasma HIV-1 RNA \> 2000 on two occasions,
• Female subjects 18 years or older
• Documented central fat accumulation (defined by waist circumference of \> 94 cm or a waist to hip ratio of \> 0.88).
• Documented HIV RNA \<50 copies/mL at screening and \<400 copies/mL in the past 6 months.
• Current antiretroviral therapy with two nucleoside analogues and either a non-nucleoside analogue (nevirapine, efavirenz or TMC125) or an approved protease inhibitor. Patients on NNRTI+PI at study entry will be excluded. Study participants do not need to be on their first regimen. No changes in ART in the 12 weeks prior to screening. The nucleoside backbone must include either tenofovir or abacavir and either lamivudine or emtricitabine. Fixed dose combinations with emtricitabine or abacavir are allowed.
• For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation), will need a negative serum or urine pregnancy test within 48 hours prior to entry.
• Ability and willingness of subject to provide informed consent.

You may not qualify if:

• Pregnancy: current or within the past 6 months or breast feeding
• Prior treatment history that would preclude the use of emtricitabine or abacavir as the nucleoside backbone during study treatment
• Current use of metformin or thiazolidinediones.
• Use of growth hormone or growth hormone releasing factor in the last 6 months before screening.
• Change or initiation of anti-hyperlipemic regimen within 3 months prior to randomization; Use of stable anti-hyperlipemic regimen during the study is allowed.
• Current use of androgen therapy.
• Intent to modify diet, exercise habits or to enroll in a weight loss intervention during the study period.
• Current or projected need to use rifampin, dilantin or phenobarbital during the 48-week study period.
• Laboratory values at screening of
• ANC \>500 cells/mm3
• Hemoglobin \<10 gm/dl
• CrCl \> 60 ml/min (estimated by Cockcroft-Gault equation)
• AST or ALT \> 3 x ULN

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Merck Sharp & Dohme LLC: collaborator
• Case Western Reserve University: collaborator
• Vanderbilt University: collaborator
• Tufts University: collaborator
• University Health Network, Toronto: collaborator

Study Sites (5)

UCLA CARE Center

Los Angeles, California, 90035, United States

Location

Tufts University School of Medicine

Boston, Massachusetts, 02111, United States

Location

Case School of Medicine

Cleveland, Ohio, 44106, United States

Location

Vanderbilt University

Nashville, Tennessee, 37203, United States

Location

University Health Network, Toronto

Toronto, Ontario, Canada

Location

Related Publications (2)

• Lake JE, McComsey GA, Hulgan TM, Wanke CA, Mangili A, Walmsley SL, Boger MS, Turner RR, McCreath HE, Currier JS. A randomized trial of Raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in HIV-infected women with lipohypertrophy. AIDS Patient Care STDS. 2012 Sep;26(9):532-40. doi: 10.1089/apc.2012.0135. Epub 2012 Jul 23.

  PMID: 22823027 RESULT

• Offor O, Utay N, Reynoso D, Somasunderam A, Currier J, Lake J. Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy. PLoS One. 2018 May 10;13(5):e0196395. doi: 10.1371/journal.pone.0196395. eCollection 2018.

  PMID: 29746485 DERIVED

MeSH Terms

Conditions

HIV Infections; Lipodystrophy; Platelet Glycoprotein IV Deficiency

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

High prevalence of generalized obesity; small sample size; short follow-up; not designed to assess the potential contribution of NRTIs to lipohypertrophy, nor could we exclude the NRTI backbone as a confounding factor.

Results Point of Contact

• Title: Dr. Jordan Lake
• Organization: UCLA CARE Center

jlake@mednet.ucla.edu

310-557-9679

Study Officials

• Judith S. Currier, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Grace McComsey, M.D.

  Case School of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: April 2, 2008
• First Posted: April 10, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 19, 2012
• Results First Posted: December 19, 2012

Record last verified: 2012-12

Locations

CA (1); US (4)