Clinical trial NCT00656175: Raltegravir Therapy for Women With HIV and Fat Accumulation
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lipodystrophy
Keywords: lipodystrophy
fat
visceral fat
HIV
women
raltegravir
ART
anti HIV therapy
NNRTI
Protease inhibitor
integrase inhibitor
treatment experienced
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Case Western Reserve University
name: Vanderbilt University
name: Tufts University
name: University Health Network, Toronto
First posted: 2008-04-10
Enrollment: 39
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)
timeFrame: Baseline and 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center
state: California
city: Boston
country: United States
facility: Tufts University School of Medicine
state: Massachusetts
city: Cleveland
country: United States
facility: Case School of Medicine
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Toronto
country: Canada
facility: University Health Network, Toronto
state: Ontario
Study officials:
affiliation: University of California, Los Angeles
name: Judith S. Currier, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Case School of Medicine
name: Grace McComsey, M.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.