HIV Infections
Conditions
Keywords
Mitochondria, Fat apoptosis, Lipoatrophy, Lipodystrophy, Thymidine, Treatment experienced
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.
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.
Interventions
None listed
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mitochondrial Activity | Entry, Week 96 | mtDNA content in adipose tissue was measured by quantitative real-time polymerase chain-reaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABC/3TC HIV-infected subjects taking abacavir-lamivudine (ABC/3TC) | 28 |
| TDF/FTC HIV-infected subjects taking tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-lamivudine (ATV-r) | 28 |
| Total | 56 |
Baseline characteristics
| Characteristic | ABC/3TC | TDF/FTC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 28 Participants | 56 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 12 Participants | 22 Participants |
| Race (NIH/OMB) White | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 25 Participants | 24 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 1 / 28 |
| other Total, other adverse events | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 2 / 28 | 0 / 28 |
Outcome results
Primary
Change in Mitochondrial Activity
mtDNA content in adipose tissue was measured by quantitative real-time polymerase chain-reaction.
Time frame: Entry, Week 96
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABC/3TC+EFV | Change in Mitochondrial Activity | 1250 copies/cell |
| TDF/FTC+EFV | Change in Mitochondrial Activity | 1312 copies/cell |
| ATV/r +TDF/FTC | Change in Mitochondrial Activity | 1150 copies/cell |
| ATV/r +ABC/3TC | Change in Mitochondrial Activity | 1125 copies/cell |
Secondary
Change in Fat Apoptosis
Changes in limb fat from 0 to 48 weeks measured with whole-body dual-energy x-ray absorptiometry
Time frame: Entry, Week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABC/3TC+EFV | Change in Fat Apoptosis | 906 g |
| TDF/FTC+EFV | Change in Fat Apoptosis | 1479 g |