HIV Infection
Conditions
Keywords
lipodystrophy, Lipoatrophy, antiretroviral treatment
Brief summary
The purpose of this study is to compare the body fat distribution in Human Immunodeficiency Virus-1 (HIV-1) infected patients receiving, since the beginning and for at least two years, an antiretroviral therapy based on efavirenz or lopinavir/ritonavir and a combination of tenofovir plus emtricitabine (or lamivudine).
Detailed description
Lipodystrophy (also called abnormal fat redistribution) associated with HIV infection is characterized by loss of subcutaneous adipose tissue (lipoatrophy) that is more apparent in the limbs, face, and buttocks, or by accumulation of adipose tissue (lipohypertrophy) in the intra-abdominal cavity, the mid, upper back, and breasts. Lipodystrophy may also occur in a mixed form (lipoatrophy and lipohypertrophy in the same patient). Participants made a single study visit. Dual energy X-ray absorptiometry (DEXA) was performed within 30 days of this study visit. In addition, routine visit clinical results, demographic data, disease data, comorbidities and concomitant medications were collected.
Interventions
None listed
Sponsors
Demométrica
AbbVie (prior sponsor, Abbott)
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women aged ≥ 18 years with HIV-1 infection who are clinically stable and who were invited to participate in the study at a routine follow-up visit. * HIV-1 infected patients receiving since the beginning and continuously, for at least two years, initial antiretroviral therapy (ART) based on efavirenz (EFV) and a combination of tenofovir (TDF) + emtricitabine (FTC) \[or lamivudine (3TC)\] or HIV-1 infected patients receiving since the beginning and continuously, for at least two years, initial ART based on lopinavir/ritonavir (LPV/r) and a combination of TDF +FTC (or 3TC). * Patients with an undetectable viral load, in response to the detection limit of each participating hospital defined in the last 6 months. * Patients who have given written informed consent to participate in this study \[personal data collection and performance of dual energy X-ray absorptiometry (DEXA)\].
Exclusion criteria
* Patients who have received at some point both efavirenz (EFV) and lopinavir/ritonavir (LPV/r) in combination regimen or thereafter. * Patients who have had structured treatment interruptions (therapeutic holidays). * Patients with a body mass index \<16 kg/m\^2. * Patients with metallic prostheses or prosthetic material that could interfere with the measurement of dual energy X-ray absorptiometry (DEXA). * Patients with a history of plastic or repair surgery in the buttocks and breasts. * Patients with a diagnostic test with barium or radionucleotides, performed during the last month. * Pregnant women. * Patients treated with other agents under investigational phase. * Patients on current treatment with systemic corticosteroids or chemotherapy. * Diabetes mellitus and hypoglycaemic treatment. * Transsexualism (though implicit in prostheses and drugs). * Any drug taken chronically, which may alter the distribution of fat or adipocyte biology (insulin, non-steroidal anti-inflammatory drugs, etc). * Patient has undergone liposuction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Limb Fat Mass | Study visit | Total limb fat mass was assessed by dual energy X-ray absorptiometry (DEXA) scan. DEXA uses a whole body scanner and two different low-dose x-rays to read bone mass and soft tissue mass. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Body Fat Mass | Study visit | Body fat mass was assessed by dual energy X-ray absorptiometry (DEXA) scan. |
| Lipodystrophy Severity Grading Scale (LSGS) Scores | Study visit | Perception of body fat was assessed by the Lipodystrophy Severity Grading Scale (LSGS), a standardized measurement of subjective lipoatrophy (fat loss) and lipoaccumulation (fat gain) perceived by the participant and by the physician. The degree of lipoatrophy and diffuse fat accumulation at each region was rated by both the participant and the physician as: Score 0=absent; Score 1=mild or noticeable on close inspection; Score 2=moderate or readily noticeable by patient/physician; Score 3=severe or readily noticeable to a casual observer. Score A reflects the lipoatrophy or fat loss perception at the face, arms, buttocks and legs and ranges from 0-12. Score B reflects the perception of fat gain at the abdomen, neck, and breasts and ranges from 0-9. The overall score is the sum of the scores A+B, and ranges from 0-21. Higher numbers indicate more fat loss (Score A) or gain (Score B). An average overall patient/physician score \>7 indicates a clinical diagnosis of lipodystrophy. |
| Change Over Time in Body Fat Distribution | DEXA performed at the study visit and more than 6 months prior to the study visit (the period of time between the DEXA recorded at the study visit and the previous DEXA ranged from 6 to 36 months). | Change over time in total body fat and fat in the limbs and trunk was assessed by dual X-ray absorptiometry (DEXA) in participants for whom a DEXA measurement performed at least 6 months before participation in this study was available. A negative change score indicates fat loss over time and a positive change score indicates fat gain over time. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Efavirenz Human Immunodeficiency Virus 1 (HIV-1)-infected patients on initial and continuous antiretroviral therapy for at least two years with efavirenz (Sustiva®; EFV) with a combination of tenofovir (TDF) plus emtricitabine (FTC) or lamivudine (3TC). | 237 |
| Lopinavir / Ritonavir HIV-infected patients on initial and continuous antiretroviral therapy for at least two years with lopinavir/ritonavir (Kaletra®; LPV/r) with a combination of tenofovir (TDF) plus emtricitabine (FTC) or lamivudine (3TC). | 109 |
| Total | 346 |
Baseline characteristics
| Characteristic | Lopinavir / Ritonavir | Total | Efavirenz |
|---|---|---|---|
| Age Continuous | 44.3 years STANDARD_DEVIATION 9.46 | 42.8 years STANDARD_DEVIATION 9.69 | 42.2 years STANDARD_DEVIATION 9.74 |
| CD4+ T-cell count nadir | 169.94 cells/µL STANDARD_DEVIATION 153.84 | 202.00 cells/µL STANDARD_DEVIATION 134.39 | 216.85 cells/µL STANDARD_DEVIATION 121.88 |
| Cluster of differentiation 4 (CD4)+ T-cell count | 592.75 cells/µL STANDARD_DEVIATION 258.77 | 587.82 cells/µL STANDARD_DEVIATION 250.31 | 585.56 cells/µL STANDARD_DEVIATION 246.87 |
| Hepatitis C Virus (HCV) Co-infection HCV negative | 76 participants | 272 participants | 196 participants |
| Hepatitis C Virus (HCV) Co-infection HCV positive | 33 participants | 74 participants | 41 participants |
| Previous acquired immunodeficiency syndrome (AIDS) diagnosis No | 74 participants | 272 participants | 198 participants |
| Previous acquired immunodeficiency syndrome (AIDS) diagnosis Yes | 34 participants | 73 participants | 39 participants |
| Region of Enrollment Spain | 109 participants | 346 participants | 237 participants |
| Sex: Female, Male Female | 17 Participants | 55 Participants | 38 Participants |
| Sex: Female, Male Male | 92 Participants | 291 Participants | 199 Participants |
| Time on current antiretroviral regimen 2 - 3 years | 27 participants | 102 participants | 75 participants |
| Time on current antiretroviral regimen 3 - 4 years | 32 participants | 108 participants | 76 participants |
| Time on current antiretroviral regimen More than 4 years | 50 participants | 136 participants | 86 participants |
| Undetectable HIV-1 RNA (< 50 copies/mL) | 109 participants | 345 participants | 236 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 237 | 0 / 109 |
| serious Total, serious adverse events | 0 / 237 | 0 / 109 |
Outcome results
Primary
Total Limb Fat Mass
Total limb fat mass was assessed by dual energy X-ray absorptiometry (DEXA) scan. DEXA uses a whole body scanner and two different low-dose x-rays to read bone mass and soft tissue mass.
Time frame: Study visit
Population: All participants for whom data were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efavirenz | Total Limb Fat Mass | 8.84 kg | Standard Deviation 4.45 |
| Lopinavir / Ritonavir | Total Limb Fat Mass | 9.13 kg | Standard Deviation 6.26 |
Secondary
Change Over Time in Body Fat Distribution
Change over time in total body fat and fat in the limbs and trunk was assessed by dual X-ray absorptiometry (DEXA) in participants for whom a DEXA measurement performed at least 6 months before participation in this study was available. A negative change score indicates fat loss over time and a positive change score indicates fat gain over time.
Time frame: DEXA performed at the study visit and more than 6 months prior to the study visit (the period of time between the DEXA recorded at the study visit and the previous DEXA ranged from 6 to 36 months).
Population: Participants for whom a dual X-ray absorptiometry measurement performed at least 6 months before participation in this study was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz | Change Over Time in Body Fat Distribution | Trunk fat mass | 0.32 kg | Standard Deviation 2.23 |
| Efavirenz | Change Over Time in Body Fat Distribution | Upper limb fat mass | 0.39 kg | Standard Deviation 0.69 |
| Efavirenz | Change Over Time in Body Fat Distribution | Limb fat mass | 0.16 kg | Standard Deviation 2.43 |
| Efavirenz | Change Over Time in Body Fat Distribution | Lower limb fat mass | 0.12 kg | Standard Deviation 2.13 |
| Efavirenz | Change Over Time in Body Fat Distribution | Total fat mass | -0.05 kg | Standard Deviation 4.02 |
| Lopinavir / Ritonavir | Change Over Time in Body Fat Distribution | Lower limb fat mass | 0.13 kg | Standard Deviation 2.8 |
| Lopinavir / Ritonavir | Change Over Time in Body Fat Distribution | Total fat mass | -0.06 kg | Standard Deviation 7.34 |
| Lopinavir / Ritonavir | Change Over Time in Body Fat Distribution | Trunk fat mass | -0.05 kg | Standard Deviation 4.04 |
| Lopinavir / Ritonavir | Change Over Time in Body Fat Distribution | Limb fat mass | 0.10 kg | Standard Deviation 3.37 |
| Lopinavir / Ritonavir | Change Over Time in Body Fat Distribution | Upper limb fat mass | -0.03 kg | Standard Deviation 0.66 |
Secondary
Distribution of Body Fat Mass
Body fat mass was assessed by dual energy X-ray absorptiometry (DEXA) scan.
Time frame: Study visit
Population: All participants for whom data were available. The number of participants included in the analysis of each category for each group of participants is shown as N (EFV and then LPV/r).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz | Distribution of Body Fat Mass | Total body fat mass [N=231, 106] | 20.13 kg | Standard Deviation 7.56 |
| Efavirenz | Distribution of Body Fat Mass | Trunk fat mass [N=232, 106] | 10.77 kg | Standard Deviation 4.84 |
| Efavirenz | Distribution of Body Fat Mass | Upper limb fat mass [N=232, 106] | 2.11 kg | Standard Deviation 1.07 |
| Efavirenz | Distribution of Body Fat Mass | Lower limb fat mass [N=232, 106] | 6.72 kg | Standard Deviation 3.68 |
| Lopinavir / Ritonavir | Distribution of Body Fat Mass | Lower limb fat mass [N=232, 106] | 7.04 kg | Standard Deviation 5.72 |
| Lopinavir / Ritonavir | Distribution of Body Fat Mass | Total body fat mass [N=231, 106] | 20.24 kg | Standard Deviation 8.6 |
| Lopinavir / Ritonavir | Distribution of Body Fat Mass | Upper limb fat mass [N=232, 106] | 2.08 kg | Standard Deviation 1.14 |
| Lopinavir / Ritonavir | Distribution of Body Fat Mass | Trunk fat mass [N=232, 106] | 10.76 kg | Standard Deviation 5.24 |
Secondary
Lipodystrophy Severity Grading Scale (LSGS) Scores
Perception of body fat was assessed by the Lipodystrophy Severity Grading Scale (LSGS), a standardized measurement of subjective lipoatrophy (fat loss) and lipoaccumulation (fat gain) perceived by the participant and by the physician. The degree of lipoatrophy and diffuse fat accumulation at each region was rated by both the participant and the physician as: Score 0=absent; Score 1=mild or noticeable on close inspection; Score 2=moderate or readily noticeable by patient/physician; Score 3=severe or readily noticeable to a casual observer. Score A reflects the lipoatrophy or fat loss perception at the face, arms, buttocks and legs and ranges from 0-12. Score B reflects the perception of fat gain at the abdomen, neck, and breasts and ranges from 0-9. The overall score is the sum of the scores A+B, and ranges from 0-21. Higher numbers indicate more fat loss (Score A) or gain (Score B). An average overall patient/physician score \>7 indicates a clinical diagnosis of lipodystrophy.
Time frame: Study visit
Population: All participants for whom data were available. The number of participants included in the analysis of each score for each group of participants is shown as N (EFV and then LPV/r).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efavirenz | Lipodystrophy Severity Grading Scale (LSGS) Scores | Patient Score A (fat loss) [N=233, 105] | 1.02 units on a scale | Standard Deviation 1.92 |
| Efavirenz | Lipodystrophy Severity Grading Scale (LSGS) Scores | Patient Score B (fat gain) [N=235, 103] | 0.98 units on a scale | Standard Deviation 1.5 |
| Efavirenz | Lipodystrophy Severity Grading Scale (LSGS) Scores | Patient Overall Score [N=233, 102] | 2.01 units on a scale | Standard Deviation 2.68 |
| Efavirenz | Lipodystrophy Severity Grading Scale (LSGS) Scores | Physician Score A (fat loss) [N=233, 105] | 0.70 units on a scale | Standard Deviation 1.27 |
| Efavirenz | Lipodystrophy Severity Grading Scale (LSGS) Scores | Physician Score B (fat gain) [N=235, 103] | 0.60 units on a scale | Standard Deviation 1.1 |
| Efavirenz | Lipodystrophy Severity Grading Scale (LSGS) Scores | Physician Overall Score [N=233, 102] | 1.31 units on a scale | Standard Deviation 1.8 |
| Lopinavir / Ritonavir | Lipodystrophy Severity Grading Scale (LSGS) Scores | Physician Score B (fat gain) [N=235, 103] | 0.76 units on a scale | Standard Deviation 1.35 |
| Lopinavir / Ritonavir | Lipodystrophy Severity Grading Scale (LSGS) Scores | Patient Score A (fat loss) [N=233, 105] | 1.12 units on a scale | Standard Deviation 2 |
| Lopinavir / Ritonavir | Lipodystrophy Severity Grading Scale (LSGS) Scores | Physician Score A (fat loss) [N=233, 105] | 1.04 units on a scale | Standard Deviation 1.76 |
| Lopinavir / Ritonavir | Lipodystrophy Severity Grading Scale (LSGS) Scores | Patient Score B (fat gain) [N=235, 103] | 1.17 units on a scale | Standard Deviation 1.86 |
| Lopinavir / Ritonavir | Lipodystrophy Severity Grading Scale (LSGS) Scores | Physician Overall Score [N=233, 102] | 1.83 units on a scale | Standard Deviation 2.43 |
| Lopinavir / Ritonavir | Lipodystrophy Severity Grading Scale (LSGS) Scores | Patient Overall Score [N=233, 102] | 2.33 units on a scale | Standard Deviation 3 |