Raltegravir Therapy for Women With HIV and Fat Accumulation

• ClinicalTrials.gov Identifier: NCT00656175
• Recruitment Status: Completed
• First Posted: April 10, 2008
• Results First Posted: December 19, 2012
• Last Update Posted: December 19, 2012
• Sponsor: University of California, Los Angeles
• Collaborators: Merck Sharp & Dohme LLC; Case Western Reserve University; Vanderbilt University; Tufts University; University Health Network, Toronto
• Information provided by (Responsible Party): Judith S. Currier, University of California, Los Angeles

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: HIV Infections; Lipodystrophy
• Intervention: Drug: raltegravir
• Enrollment: 39

Participant Flow

Recruitment Details	61 subjects were screened, 39 enrolled, and 37 completed the Week 24 primary endpoint at 5 sites in North America. Of the 37 subjects included in the as-treated analysis, 17 were randomized to immediate-switch (Immediate Group), and 20 to delayed-switch (Delayed Group).
Pre-assignment Details

Arm/Group Title	Immediate	Delayed
Arm/Group Description	Immediate switch of PI or NNRTI to Raltegravir (400 mg twice daily)	Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir (400mg twice daily)
Period Title: Overall Study
Started	18	21
Completed	17	20
Not Completed	1	1
Reason Not Completed
Adverse Event	1	0
Transportation issues	0	1

Baseline Characteristics

Arm/Group Title		Immediate	Delayed	Total
Arm/Group Description		Immediate switch of PI or NNRTI to Raltegravir	Continue current therapy unchanged for 24 weeks then switch PI or NNRTI to Raltegravir	Total of all reporting groups
Overall Number of Baseline Participants		18	21	39
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants	21 participants	39 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	18 100.0%	21 100.0%	39 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	18 participants	21 participants	39 participants
		39 (47)	36 (51)	37 (49)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants	21 participants	39 participants
	Female	18 100.0%	21 100.0%	39 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	18 participants	21 participants	39 participants
African-American		9	13	22
Hispanic		5	3	8
White		3	5	8
Asian		1	0	1
		[1] Measure Description: Subjects were recruited from 5 centers in North America between September 2008 and July 2010. Age 18 or older, documented HIV-1 infection, central fat accumulation at screening and <400 copies/mL for the 6 months prior to entry, current ART with a nucleoside (NRTI) backbone of tenofovir or abacavir AND emtricitabine or lamivudine PLUS either a PI or NNRTI, no change in ART for 12 weeks prior to screening, and ability and willingness to provide informed consent.
Region of Enrollment [1]; Measure Type: Number; Unit of measure: Participants
North America	Number Analyzed	18 participants	21 participants	39 participants
		18	21	39
		[1] Measure Description: Subjects were recruited from 5 centers in North America between September 2008 and July 2010.

Outcome Measures

1. Primary Outcome

Title	Baseline to 24-week Change in Visceral Adipose Tissue Volume (cm^2)
Description	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.
Time Frame	Baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immediate	Delayed
Arm/Group Description:	Immediate switch of PI or NNRTI to Raltegravir	Continue current therapy unchanged for 24 weeks, then switch PI or NNRTI to Raltegravir
Overall Number of Participants Analyzed	17	20
Median (Inter-Quartile Range); Unit of Measure: cm^2
	-6.6; (-15.5 to 17.6)	1.8; (-9.3 to 8.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Immediate, Delayed
	Comments	Wilcoxon sign-rank test used for statistical significance.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.52
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Immediate	Delayed
Arm/Group Description	Immediate switch of PI or NNRTI to Raltegravir	Continue current therapy unchanged for 24 weeks then switch PI or NNRTI to Raltegravir
All-Cause Mortality
	Immediate	Delayed
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Immediate	Delayed
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/17 (0.00%)	0/20 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Immediate	Delayed
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/17 (0.00%)	0/20 (0.00%)

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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Jordan Lake
• Organization: UCLA CARE Center
• Phone: 310-557-9679
• EMail: jlake@mednet.ucla.edu

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Judith S. Currier, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00656175
• Obsolete Identifiers: NCT00755612
• Other Study ID Numbers: IISP-Raltegravir
• First Submitted: April 2, 2008
• First Posted: April 10, 2008
• Results First Submitted: June 12, 2012
• Results First Posted: December 19, 2012
• Last Update Posted: December 19, 2012