This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine \[FTC, 200 mg\] and tenofovir disoproxil fumarate \[TDF, 300 mg\]) or who remained on a zidovudine- plus lamivudine-containing regimen. Subjects continued their protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).
Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (PI or NRTI). The use of nucleoside analogues, especially stavudine and zidovudine, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances. As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the European Medicines Agency (EMA) in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection". In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing zidovudine and lamivudine were randomized to switch to Truvada or to stay on their zidovudine- plus lamivudine-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).
Study Type
INTERVENTIONAL
Allocation
Truvada once daily with continuation of the current NNRTI or PI at randomization.
Continuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization.
Gilead Sciences, S.L.
Madrid, Spain
Change From Baseline in Limb Fat at Week 48
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa)
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes)
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in Lactate Concentration
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Percentage of Days for Which Participants Were Compliant With Study Drug
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.
Time frame: Baseline to Week 72
Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL
Time frame: 48 weeks
Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL
Time frame: 48 weeks
Percentage of Participants With Virologic Failure
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RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Virologic failure was defined as two consecutive HIV RNA values \> 400 copies/mL.
Time frame: 48 weeks
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in Fasting Serum Triglycerides
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in Fasting Total Cholesterol
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL)
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL)
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Change From Baseline in Hemoglobin
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Percent Change From Baseline in Hematocrit
Change = Week 48 value minus baseline value expressed as median percent change.
Time frame: Baseline to Week 48
Change From Baseline in Waist Circumference/Hip Circumference Ratio
Change = Week 48 value minus baseline value.
Time frame: Baseline to Week 48
Percentage of Participants With Any Adverse Event
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.
Time frame: 72 weeks
Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events.
Time frame: 48 weeks