Trial Outcomes & Findings for Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada (NCT NCT00324649)
NCT ID: NCT00324649
Last Updated: 2015-08-17
Results Overview
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
COMPLETED
PHASE4
80 participants
Baseline to Week 48
2015-08-17
Participant Flow
Participant milestones
| Measure |
Truvada
Truvada + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).
|
Zidovudine/Lamivudine
Zidovudine/lamivudine + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).
|
|---|---|---|
|
Overall Study
STARTED
|
39
|
41
|
|
Overall Study
COMPLETED
|
37
|
36
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
Reasons for withdrawal
| Measure |
Truvada
Truvada + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).
|
Zidovudine/Lamivudine
Zidovudine/lamivudine + nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI).
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
4
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Noncompliance
|
1
|
0
|
Baseline Characteristics
Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada
Baseline characteristics by cohort
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
44 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
44 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
15.0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
65.0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
36 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
74.0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black, of African heritage
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3.0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1.0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2.0 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
39 participants
n=5 Participants
|
41 participants
n=7 Participants
|
80.0 participants
n=5 Participants
|
|
HIV-1 RNA Level
< 50 copies/mL
|
38 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
77.0 Participants
n=5 Participants
|
|
HIV-1 RNA Level
50 to < 400 copies/mL
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3.0 Participants
n=5 Participants
|
|
Cluster determinant 4 (CD4) cell count
|
655.0 cells/mm^3
n=5 Participants
|
504.0 cells/mm^3
n=7 Participants
|
600.5 cells/mm^3
n=5 Participants
|
|
Total limb fat
|
3565 grams (g)
n=5 Participants
|
3589 grams (g)
n=7 Participants
|
3589 grams (g)
n=5 Participants
|
|
Years on zidovudine (AZT)/lamivudine (3TC)
|
5.8 Years
n=5 Participants
|
6.2 Years
n=7 Participants
|
5.9 Years
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Number of participants analyzed is those with baseline and post-baseline DEXA data. Last post-baseline observation carried forward (LOCF) method was used if the Week 48 limb fat value was missing.
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=38 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=38 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Limb Fat at Week 48
|
392 grams (g)
Interval -102.0 to 1056.0
|
-257 grams (g)
Interval -751.0 to 148.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=34 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=35 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa)
|
62.0 Ratio
Interval 20.0 to 212.0
|
97.0 Ratio
Interval 20.0 to 197.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=36 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=35 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes)
|
36.0 Ratio
Interval 2.0 to 89.5
|
43.0 Ratio
Interval 1.0 to 72.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=27 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=30 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Lactate Concentration
|
-0.23 mmol/L
Interval -0.55 to 0.0
|
0.09 mmol/L
Interval -0.12 to 0.43
|
SECONDARY outcome
Timeframe: Baseline to Week 72Population: Treated participants.
Compliance = \[1 - \[(sum of days with a missed dose \[per Question 6 study medication assessment questionnaire (SMAQ)\])/(sum of days between SMAQ visits)\]\] \*100 for visits with SMAQ data. An assessable visit is one where the number of missed days was reported \[Question 6\] and the number of days between SMAQ visits could be calculated.
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percentage of Days for Which Participants Were Compliant With Study Drug
|
100.0 Percentage of days with compliance
Interval 99.8 to 100.0
|
100.0 Percentage of days with compliance
Interval 99.6 to 100.0
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Treated participants. Missing values were treated as failure (i.e., as HIV-1 RNA greater than or equal to 50 copies/mL).
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL
|
92.3 Percentage of participants
|
78.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Treated participants.
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL
|
0 Percentage of participants
|
5 Percentage of participants
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Treated participants.
Virologic failure was defined as two consecutive HIV RNA values \> 400 copies/mL.
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percentage of Participants With Virologic Failure
|
0 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=36 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=34 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count
|
60.5 cells/mm^3
Interval -6.5 to 159.0
|
9.0 cells/mm^3
Interval -61.0 to 106.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=34 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=31 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Fasting Serum Triglycerides
|
1.5 mg/dL
Interval -31.0 to 17.0
|
4.0 mg/dL
Interval -44.0 to 40.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=34 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=31 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Fasting Total Cholesterol
|
4.5 mg/dL
Interval -12.0 to 12.0
|
1.0 mg/dL
Interval -19.0 to 21.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=29 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=27 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL)
|
7.0 mg/dL
Interval -9.4 to 15.6
|
5.0 mg/dL
Interval -14.0 to 16.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=31 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=28 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL)
|
-2.0 mg/dL
Interval -7.0 to 2.0
|
2.0 mg/dL
Interval -7.0 to 7.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=36 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=33 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Hemoglobin
|
0.9 g/dL
Interval 0.0 to 1.2
|
0.3 g/dL
Interval -0.5 to 0.7
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded.
Change = Week 48 value minus baseline value expressed as median percent change.
Outcome measures
| Measure |
Truvada
n=36 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=33 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percent Change From Baseline in Hematocrit
|
2.7 Percent change in hematocrit
Interval 1.5 to 4.3
|
1.0 Percent change in hematocrit
Interval -0.9 to 2.0
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: Treated participants. Missing values were excluded. Assessment of waist and hip circumference was added to the study schedule via protocol amendment part way through the study. This resulted in small numbers of subjects having data available for this analysis.
Change = Week 48 value minus baseline value.
Outcome measures
| Measure |
Truvada
n=28 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=25 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Change From Baseline in Waist Circumference/Hip Circumference Ratio
|
-0.01 Ratio
Interval -0.03 to 0.02
|
0.01 Ratio
Interval -0.01 to 0.04
|
SECONDARY outcome
Timeframe: 72 weeksPopulation: Treated participants.
Participants with treatment-emergent adverse events were analyzed. Adverse events were defined as any untoward medical occurrence in a clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with study treatment, and were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Version 11. Treatment-emergent adverse events were events that met one of the following criteria: * Began or worsened in severity or relationship to study drug, on or after the date of the first dose of study drug and on or before the date of the last dose of study drug plus 30 days. * Had no recorded start date.
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percentage of Participants With Any Adverse Event
|
77 Percentage of participants
|
85 Percentage of participants
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Treated participants.
Outcome measures
| Measure |
Truvada
n=39 Participants
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
n=41 Participants
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events.
|
3 Percentage of participants
|
10 Percentage of participants
|
Adverse Events
Truvada
Zidovudine/Lamivudine
Serious adverse events
| Measure |
Truvada
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/39
|
2.4%
1/41
|
|
Cardiac disorders
Prinzmetal angina
|
0.00%
0/39
|
2.4%
1/41
|
|
Gastrointestinal disorders
Diarrhoea
|
2.6%
1/39
|
0.00%
0/41
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/39
|
2.4%
1/41
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
2.6%
1/39
|
0.00%
0/41
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/39
|
2.4%
1/41
|
|
Nervous system disorders
Cauda equina syndrome
|
2.6%
1/39
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/39
|
2.4%
1/41
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
2.6%
1/39
|
0.00%
0/41
|
Other adverse events
| Measure |
Truvada
Truvada + NNRTI or PI.
|
Zidovudine/Lamivudine
Zidovudine/lamivudine + NNRTI or PI.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.6%
1/39
|
7.3%
3/41
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/39
|
7.3%
3/41
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
3/39
|
4.9%
2/41
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.1%
2/39
|
0.00%
0/41
|
|
General disorders
Pyrexia
|
5.1%
2/39
|
0.00%
0/41
|
|
Infections and infestations
Bronchitis
|
5.1%
2/39
|
0.00%
0/41
|
|
Investigations
Gamma-glutamyltransferase increased
|
28.2%
11/39
|
24.4%
10/41
|
|
Investigations
Alanine aminotransferase increased
|
20.5%
8/39
|
24.4%
10/41
|
|
Investigations
Aspartate aminotransferase increased
|
10.3%
4/39
|
14.6%
6/41
|
|
Investigations
Blood amylase increased
|
10.3%
4/39
|
19.5%
8/41
|
|
Investigations
Lipase increased
|
2.6%
1/39
|
7.3%
3/41
|
|
Investigations
Blood creatine phosphokinase increased
|
7.7%
3/39
|
7.3%
3/41
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.1%
2/39
|
9.8%
4/41
|
|
Metabolism and nutrition disorders
Hyperlactacidaemia
|
5.1%
2/39
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.6%
1/39
|
7.3%
3/41
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/39
|
7.3%
3/41
|
|
Investigations
Blood lactic acid increased
|
5.1%
2/39
|
9.8%
4/41
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other scholarly media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years.
- Publication restrictions are in place
Restriction type: OTHER