Metabolic Effects of Non-Thymidine Analogue Anti-HIV Medications
Study Details
Study Description
Brief Summary
The purpose of this study is to observe the effects of certain anti-HIV medications on mitochondrial activity and fat cell death. This study will enroll participants from another study, ACTG A5202, who are on treatment regimens that do not include zidovudine, stavudine, or other thymidine-containing anti-HIV medications.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Detailed Description
The main objective of this study is to observe the effects of anti-HIV medication lacking thymidine on mitochondrial metabolism and adipocyte apoptosis (fat cell death). Changes in mitochondrial metabolism and increases in adipocyte apoptosis are associated with lipoatrophy. Lipoatrophy is a common condition characterized by loss of subcutaneous fat and can be caused by many anti-HIV medications. This study will examine the metabolic consequences of the use of thymidine analogue-sparing treatment regimens.
This study will evaluate HIV infected patients who are enrolled in ACTG A5202, starting their first nucleoside reverse transcriptase inhibitor (NRTI)-containing regimen. This regimen will include either tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC), which are thymidine-sparing regimens. The changes in mitochondrial activity and fat cell death will be compared between participants taking thymidine-sparing regimens (TDF/FTC or ABC/3TC) and thymidine-containing regimens.
This study will last for 96 weeks, with two study visits occurring at entry and another visit at Week 96. During each visit, a dual energy x-ray absorptiometry (DEXA) scan and blood collection will occur, and a fat biopsy will be performed in the lower abdomen under local anesthetic.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| ABC/3TC HIV-infected subjects were given Abacavir-Lamuvidine |
|
| TDF/FTC HIV-infected patients were given tenofovir DF-emtricitabine |
Outcome Measures
Primary Outcome Measures
- Change in Mitochondrial Activity [Entry, Week 96]
mtDNA content in adipose tissue was measured by quantitative real-time polymerase chain-reaction.
Secondary Outcome Measures
- Change in Fat Apoptosis [Entry, Week 48]
Changes in limb fat from 0 to 48 weeks measured with whole-body dual-energy x-ray absorptiometry
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HIV-infected
-
Enrolling in ACTG A5202 and its metabolic substudy ACTG A5224
Exclusion Criteria:
-
Bleeding problems
-
Cannot undergo fat biopsies
-
Require aspirin anytime in the 7-day period prior to each biopsy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Case School of Medicine | Cleveland | Ohio | United States | 44106 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Grace McComsey, MD, Case School of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 1R01AI065348-01A2
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | ABC/3TC | TDF/FTC |
|---|---|---|
| Arm/Group Description | HIV-infected subjects taking abacavir-lamivudine (ABC/3TC) | HIV-infected subjects taking tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-lamivudine (ATV-r) |
| Period Title: Overall Study | ||
| STARTED | 28 | 28 |
| COMPLETED | 19 | 20 |
| NOT COMPLETED | 9 | 8 |
Baseline Characteristics
| Arm/Group Title | ABC/3TC | TDF/FTC | Total |
|---|---|---|---|
| Arm/Group Description | HIV-infected subjects taking abacavir-lamivudine (ABC/3TC) | HIV-infected subjects taking tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-lamivudine (ATV-r) | Total of all reporting groups |
| Overall Participants | 28 | 28 | 56 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
28
100%
|
28
100%
|
56
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
10.7%
|
4
14.3%
|
7
12.5%
|
| Male |
25
89.3%
|
24
85.7%
|
49
87.5%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
8
28.6%
|
4
14.3%
|
12
21.4%
|
| White |
10
35.7%
|
12
42.9%
|
22
39.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
10
35.7%
|
12
42.9%
|
22
39.3%
|
Outcome Measures
| Title | Change in Mitochondrial Activity |
|---|---|
| Description | mtDNA content in adipose tissue was measured by quantitative real-time polymerase chain-reaction. |
| Time Frame | Entry, Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ABC/3TC+EFV | TDF/FTC+EFV | ATV/r +TDF/FTC | ATV/r +ABC/3TC |
|---|---|---|---|---|
| Arm/Group Description | HIV-infected subjects taking abacavir-lamivudine (ABC/3TC) with Efavirenz at baseline | HIV-infected subjects taking tenofovir DF-emtricitabine (TDF/FTC) with Efavirenz at baseline | HIV infected subjects taking atazanavir-ritonavir with tenofovir DF-emtricitabine at baseline | HIV-infected subjects taking atazanavir-ritonavir with abacavir-lamivudine at baseline |
| Measure Participants | 15 | 13 | 15 | 13 |
| Median (Inter-Quartile Range) [copies/cell] |
1250
|
1312
|
1150
|
1125
|
| Title | Change in Fat Apoptosis |
|---|---|
| Description | Changes in limb fat from 0 to 48 weeks measured with whole-body dual-energy x-ray absorptiometry |
| Time Frame | Entry, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | ABC/3TC | TDF/FTC |
|---|---|---|
| Arm/Group Description | HIV-infected subjects taking abacavir-lamivudine (ABC/3TC) | HIV-infected subjects taking tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-lamivudine (ATV-r) |
| Measure Participants | 19 | 20 |
| Median (Inter-Quartile Range) [g] |
906
|
1479
|
Adverse Events
| Time Frame | the adverse event data was collected over the duration of the study of 96 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | ABC/3TC | TDF/FTC | ||
| Arm/Group Description | HIV-infected subjects taking abacavir-lamivudine (ABC/3TC) | HIV-infected subjects taking tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-lamivudine (ATV-r) | ||
All Cause Mortality |
||||
| ABC/3TC | TDF/FTC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 1/28 (3.6%) | ||
Serious Adverse Events |
||||
| ABC/3TC | TDF/FTC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/28 (7.1%) | 0/28 (0%) | ||
| Psychiatric disorders | ||||
| Depression | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/28 (3.6%) | 1 | 0/28 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| ABC/3TC | TDF/FTC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 0/28 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Grace McComsey |
|---|---|
| Organization | Case Western Reserve University |
| Phone | 216-844-2739 |
| mccomsey.grace@clevelandactu.org |
- 1R01AI065348-01A2