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Changes in lipid profiles after switching to a protease inhibitor-containing cART - unfavourable effect of fosamprenavir in obese patients

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Objective One focus in the medical care of HIV-infected patients today is cardiovascular risk reduction. Metabolic disturbances occur frequently in patients taking protease inhibitors (PI) and are a major risk factor for atherosclerosis. With few published head-to head studies substance-specific differences concerning metabolic effects are insufficiently defined. Therefore this cohort study directly compared the metabolic profiles of boosted atazanavir (ATV/r), fosamprenavir (FPV/r) and saquinavir (SQV/r). Methods Data from a cohort of 124 HIV patients initiating a boosted regimen with one of the PIs at the University of Munich (LMU) infectious diseases outpatient clinic were retrospectively analyzed. The main outcome measures were median absolute total cholesterol levels and median relative change of total cholesterol levels after six months of PI-therapy. A multivariate linear regression model was built to identify and control for potential confounders of the association between PI-therapy and serum cholesterol level. Results 84 patients were treated with ATV/r, 23 patients received FPV/r and 17 patients SQV/r. Demographically the cohort constituted a representative sample of HIV-infected patients in Germany. There were no statistically significant differences between the comparison groups at baseline. After six months of therapy median serum cholesterol in the ATV/r group dropped significantly from 204 mg/dl to 186 mg/dl, while in the FPV/r and SQV/r groups a rise in serum cholesterol levels was observed from 179 mg/dl to 204 mg/dl and from 173 mg/ddl to 209 mg/dl respectively. The multivariate linear regression model identified a significant interaction between BMI at baseline and treatment with FPV/r: patients with higher BMI showed more prominent increases in serum cholesterol while taking FPV/r compared to patients with lower BMI. Conclusion This cohort study demonstrated the most favourable impact on serum cholesterol levels and thus cardiovascular risk for ATV/r compared to FPV/r and SQV/r under real-life conditions. Given the statistical interaction detected between FPV/r and BMI further studies assessing metabolic profiles of different antiretroviral drugs in specific patient populations are urgently needed.

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Published 01 January 2011
Reads 15
Language English
feBruàry 24, 2011
Eur J MeD ReS (2011) 16: 85-92
EURoPEan JoURnaL of MEdICaL REsEaRCH
85 © I. HOlzàpFel PuBliSherS 2011
CHangEs InLIPIdPRofILEs aftERswItCHIng to aPRotEasE InHIbItoR-ContaInIng CaRt – UnfavoURabLEEffECt of fosaMPREnavIR InobEsEPatIEnts
M. gyàlrONG-sTeur, J. R. bOGNer, U. seyBOlD
INFekTiONSàBTeiluNG Der MeDiziNiScheN POlikliNik, CàmpuS INNeNSTàDT, LuDWiG-MàximiliàNS-UNiVerSiTäT, MüNcheN, germàNy
Abstract Objective:HIv-iN-oNe FOcuS iN The meDicàl càre OF FecTeD pàTieNTS TODày iS càrDiOVàSculàr riSk reDucTiON. MeTàBOlic DiSTurBàNceS Occur FrequeNTly iN pàTieNTS TàkiNG prOTeàSe iNhiBiTOrS (PI) àND àre à màjOr riSk Fàc-TOr FOr àTherOSclerOSiS. wiTh FeW puBliSheD heàD-TO-heàD STuDieS SuBSTàNce-SpeciFic DiFFereNceS cONcerNiNG meTàBOlic eFFecTS àre iNSuFFicieNTly DeFiNeD. thereFOre ThiS cOhOrT STuDy DirecTly cOmpàreD The meTàBOlic prO-FileS OFBOOSTeD àTàzàNàVir (atv/r), FOSàmpreNàVir (fPv/r) àND SàquiNàVir (sQv/r). Methods:124 HIv pàTieNTS iNi-dàTà FrOm à cOhOrT OF TiàTiNG à BOOSTeD reGimeN WiTh ONe OFThe PIS àT The UNiVerSiTy OFMuNich (LMU) iNFecTiOuS DiSeàSeS OuT-pàTieNT cliNic Were reTrOSpecTiVely àNàlyzeD. the màiN OuTcOme meàSureS Were meDiàN àBSOluTe TOTàl chOleS-TerOl leVelS àND meDiàN relàTiVe chàNGe OFTOTàl chOleS-TerOl leVelS àFTer Six mONThS OFPI-Theràpy. a mulTi-VàriàTe liNeàr reGreSSiON mODel WàS BuilT TO iDeNTiFy àND cONTrOl FOr pOTeNTiàl cONFOuNDerS OFThe àSSOcià-TiON BeTWeeN PI-Theràpy àND Serum chOleSTerOl leVel. Results:84 pàTieNTS Were TreàTeD WiTh atv/r, 23 pà-TieNTS receiVeD fPv/r àND 17 pàTieNTS sQv/r. demO-Gràphicàlly The cOhOrT cONSTiTuTeD à repreSeNTàTiVe Sàmple OFHIv-iNFecTeD pàTieNTS iN germàNy. there Were NO STàTiSTicàlly SiGNiFicàNT DiFFereNceS BeTWeeN The cOmpàriSON GrOupS àT BàSeliNe. aFTer Six mONThS OFTheràpy meDiàN Serum chOleS-TerOl iN The atv/r GrOup DrOppeD SiGNiFicàNTly FrOm 204 mG/Dl TO 186 mG/Dl, While iN The fPv/r àND sQv/r GrOupS à riSe iN Serum chOleSTerOl leVelS WàS OBSerVeD FrOm 179 mG/Dl TO 204 mG/Dl àND FrOm 173 mG/Dl TO 209 mG/Dl reSpecTiVely. the mulTiVàriàTe liN-eàr reGreSSiON mODel iDeNTiFieD à SiGNiFicàNT iNTeràcTiON BeTWeeN bMI àT BàSeliNe àND TreàTmeNT WiTh fPv/r: pàTieNTS WiTh hiGher bMI ShOWeD mOre prOmiNeNT iN-creàSeS iN Serum chOleSTerOl While TàkiNG fPv/r cOm-pàreD TO pàTieNTS WiTh lOWer bMI. Conclusion:thiS cOhOrT STuDy DemONSTràTeD The mOST FàVOuràBle impàcT ON Serum chOleSTerOl leVelS àND ThuS càrDiOVàSculàr riSk FOr atv/r cOmpàreD TO fPv/r àND sQv/r uNDer reàl-liFe cONDiTiONS. giVeN The STàTiSTicàl iNTeràcTiON DeTecTeD BeTWeeN fPv/r àND bMI FurTher STuDieS àSSeSSiNG meTàBOlic prOFileS OF DiFFereNT àNTireTrOViràl DruGS iN SpeciFic pàTieNT pOpu-làTiONS àre urGeNTly NeeDeD.
Key words:HIv, caRt, prOTeàSe iNhiBiTOr, àTàzàNàVir, FOSàmpreNàVir, SàquiNàVir, lipiDS, chOleSTerOl, TriGlyc-eriDeS, GlucOSe, meTàBOliSm, BODy màSS iNDex, DySlipi-Demià, OBeSiTy, càrDiOVàSculàr riSk, mulTiVàriàTe liNeàr reGreSSiON, STàTiSTicàl iNTeràcTiON
Abbr eviations: atv/r BOOSTeDàTàzàNàVir bMI BODymàSS iNDex caRt cOmBiNàTiONàNTireTrOViràl Theràpy fPv/r BOOSTeDFOSàmpreNàVir LPv/r BOOSTeDlOpiNàVir PI prOTeàSeiNhiBiTOr PLHa peOpleliViNG WiTh HIv/aIds Rtv riTONàVir sQv/r BOOSTeDSàquiNàVir
IntRodUCtIon andobJECtIvEs
MeTàBOlic àND càrDiOVàSculàr heàlTh iSSueS àre BecOm-iNG àN iNcreàSiNG prOBlem iN germàNy àND OTher iN-DuSTriàlizeD cOuNTrieS. CàrDiOVàSculàr cOmplicàTiONS [1-8] NOW àre àmONG The leàDiNG càuSeS OFmOrTàliTy iN TheSe cOuNTrieS [9-12]. siNce The iNTrODucTiON OFcOmBiNàTiON àNTireTrOVi-ràl Theràpy (caRt) mOrTàliTy Due TO aIds-DeFiNiNG ill-NeSSeS hàS cONSiDeràBly DecreàSeD àmONG peOple liViNG WiTh HIv/aIds (PLHa), reSulTiNG iN àN iNcreàSe OF liFe expecTàNcy TO àlmOST ThàT OFThe GeNeràl pOpulà-TiON [13, 14]. thereFOre NON-HIv-relàTeD càuSeS OF DeàTh, àmONG Them càrDiOVàSculàr DiSeàSeS, àre Be-cOmiNG mOre releVàNT àmONG PLHa [14-17]. IN àDDi-TiON, BOTh HIv-iNFecTiON iTSelF[18-21] àND VàriOuS àN-TireTrOViràl DruGS àre àlSO àSSOciàTeD WiTh iNcreàSeD càrDiOVàSculàr riSk [22-24]. EleVàTeD Serum chOleSTerOl hàS BeeN ShOWN TO Be à màjOr càuSe FOr àTherOSclerO-SiS iN NumerOuS STuDieS [3-5, 8] àND ThiS àSSOciàTiON hàS àlSO BeeN cONFirmeD iN PLHa [25]. wiTh à BrOàD SpecTrum OFàNTireTrOViràl DruGS àVàil-àBle, The FOcuS OFHIv Theràpy TODày lieS ON màNàGiNG The pàTieNTS’ OVeràll heàlTh SiTuàTiON, iNcluDiNG meTà-BOlic àND càrDiOVàSculàr àS Well àS quàliTy OFliFe iSSueS [26]. ChOOSiNG àNTireTrOViràl DruGS WiTh à FàVOuràBle meTàBOlic prOFile iS The primàry SpeciFic iNTerVeNTiON recOmmeNDeD TO miNimize The càrDiOVàSculàr riSk Bur-DeN iN HIv-pàTieNTS eVeN BeFOre iDeNTiFicàTiON OFOTh-