Raltegravir Therapy for Women With HIV and Fat Accumulation

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).

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

University Health Network, Toronto, Toronto, Ontario, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

raltegravir

Drug

raltegravir

Other names: Isentress

Primary outcomes

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

Time frame: Baseline and 24 weeks

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.

Sponsors and collaborators

Lead sponsor

University of California, Los Angeles

Other

Collaborators

Case Western Reserve University
Merck Sharp & Dohme LLC
Tufts University
University Health Network, Toronto
Vanderbilt University

Registry information

Official study title

Phase II Study of Raltegravir as Replacement for Protease Inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Based Antiretroviral Therapy in Women With Fat Accumulation

Important dates

Study start: 2008
Primary completion: 2011
Study completion: 2011
First posted: Apr 10, 2008
Registry last updated: Dec 19, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed