Raltegravir Therapy for Women With HIV and Fat Accumulation

NCT ID: NCT00656175

Last Updated: 2012-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2011-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immediate

Immediate switch of PI or NNRTI to Raltegravir

Group Type: ACTIVE_COMPARATOR

raltegravir

Intervention Type: DRUG

raltegravir

Delayed

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

Group Type: ACTIVE_COMPARATOR

raltegravir

Intervention Type: DRUG

raltegravir

Interventions

raltegravir

raltegravir

Intervention Type: DRUG

Other Intervention Names

Isentress

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Case Western Reserve University

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

Tufts University

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Judith S. Currier

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Judith S. Currier, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Grace McComsey, M.D.

Role: STUDY_CHAIR

Case School of Medicine

Locations

UCLA CARE Center

Los Angeles, California, United States

Tufts University School of Medicine

Boston, Massachusetts, United States

Case School of Medicine

Cleveland, Ohio, United States

Vanderbilt University

Nashville, Tennessee, United States

University Health Network, Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 22823027 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29746485 (View on PubMed)

Other Identifiers

IISP-Raltegravir

Identifier Type: -

Identifier Source: org_study_id

NCT00755612

Identifier Type: -

Identifier Source: nct_alias