Open AccessRandomized, crossover, double‐blind, placebo‐controlled trial to assess the lipid lowering effect of co‐formulated TDF/FTC
Author(s) -
Ramón Santos José,
Saumoy María,
Curran Adrian,
Bravo Isabel,
Navarro Jordi,
Estany Carla,
Podzamczer Daniel,
Ribera Esteban,
Negredo Eugenia,
Clotet Bonaventura,
Paredes Roger
Publication year - 2014
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.17.4.19550
Subject(s) - medicine , placebo , randomized controlled trial , randomization , double blind , crossover study , lipid profile , cholesterol , clinical trial , clinical endpoint , gastroenterology , alternative medicine , pathology
Previous studies have described improvements on lipid parameters when switching from other antiretroviral drugs to tenofovir (TDF) and impairments in lipid profile when discontinuing TDF. [1–3] It is unknown, however, if TDF has an intrinsic lipid‐lowering effect or such findings are due to the addition or removal of other offending agents or other reasons. Materials and Methods This was a randomized, crossover, double‐blind, placebo‐controlled clinical trial (NCT 01458977). Subjects with HIV‐1 RNA <50 copies/mL during at least 6 months on stable DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy, with confirmed fasting total cholesterol ≥200 or LDL‐cholesterol ≥130 mg/dL and not taking lipid‐lowering drugs were randomized to (A) adding TDF/FTCduring 12 weeks followed by 24 weeks without TDF/FTC, or (B) continuing without TDF/FTC for 12 weeks, adding TDF/FTC for 12 weeks and then withdrawing TDF/FTC for 12 additional weeks. Randomization was stratified by DRV/r or LPV/r use at study entry. All subjects received a specific dietary counselling. Primary endpoints were changes in median fasting total, LDL and HDL‐cholesterol 12 weeks after TDF/FTC addition. Analyses were performed by ITT. Results 46 subjects with a median age of 43 (40–48) years were enrolled in the study: 70% were male, 56% received DRV/r and 44% LPV/r. One subject withdrew the study voluntarily at week 4 and another one interrupted due to diarrhoea at week 24. Treatment with TDF/FTC decreased total, LDL and HDL‐cholesterol from 235.9 to 204.9 (p<0.001), 154.7 to 127.6 (p<0.001) and 50.3 to 44.5 mg/dL (p<0.001), respectively. In comparison, total, LDL and HDL‐cholesterol levels remained stable during placebo exposure. Week 12 total cholesterol (p<0.001), LDL‐cholesterol (p<0.001) and HDL‐cholesterol (p=0.011) levels were significantly lower in TDF/FTC versus placebo. Treatment with TDF/FTC reduced the fraction of subjects with abnormal fasting total‐cholesterol (≥200 mg/dL) from 86.7% to 56.8% (p=0.001) and LDL‐cholesterol (≥130 mg/dL) from 87.8% to 43.9% (p<0.001), which was not observed with placebo. There were no virological failures, and CD4 and triglyceride levels remained stable regardless of exposure. Conclusion Coformulated TDF/FTC has an intrinsic lipid‐lowering effect, likely attributable to TDF.