Induction maintenance concept for HAART as initial treatment in HIV infected infants

Neubert J, Adams O, Borkhardt A, Laws Hj, Ghosh S, Niehues T, Morali-Karzei N, Laws

Description

Early initiated antiretroviral therapy (ART) in HIV infected infants leads to improved long-term viral suppression and survival. Guidelines recommend initiating therapy with a triple ART consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either one additional non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Compared to older children and adults, viral relapse is seen more frequently in infants receiving triple ART. We now address the possibility of a more potent ART with a quadruple induction and triple maintenance therapy. Methods We examine the longitudinal course in four HIV infected infants, who were referred from other centers and could not be recruited to multicentre trials. We introduced ART initially consisting of two NRTIs, one NNRTI and one PI and later discontinued the PI at the age of 12 months maintaining a triple regime consisting of two NRTIs and one NNRTI. Results Provided that therapy adherence was maintained we observed an effective sustained decline of viral load and significant CD4 cell reconstitution even after switching to a triple regime. No drug associated toxicity was seen. Conclusion We suggest that a four drug therapy might be a possible initial therapy option in HIV infected infants, at least in those with a high viral load, followed by a maintenance triple regime after 12 months of therapy.

Sujets

• HIV
• HAART
• Viral load

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

JUNe 21, 2011

EUr J MeD ReS (2011) 16: 243-248

EuRoPEan JouRnal of MEdIcal REsEaRcH

243 © I. HOLzàpFeL PUbLiSherS 2011

I nductIon M aIntEnancE c oncEPt foR HaaRt as I nItIal t REatMEnt In HIV I nfEctEd I nfants

1 12 31 11 s. GhOSh *, J. neUberT *, t. niehUeS , o. aDàmS , n. MOràLi-Kàrzei , a. BOrkhàrDT , H. J. làwS

1 depàrTmeNT OF PeDiàTriC oNCOLOgY, HemàTOLOgY àND cLiNiCàL ImmUNOLOgY, HeiNriCh-HeiNe uNiverSiTäT düSSeLDOrF, MeDiCàL fàCULTY, dUeSSeLDOrF, GermàNY 2 depàrTmeNT OF PeDiàTriCS, HeLiOS HOSpiTàL KreFeLD, KreFeLD, GermàNY 3 INSTiTUTe OF VirOLOgY, HeiNriCh-HeiNe uNiverSiTäT düSSeLDOrF, düSSeLDOrF, GermàNY

AbstractàND mOrTàLiTY COmpàreD TO DeFerriNg TreàTmeNT Càme Backgr ound:FrOm cHER TriàL CONDUCTeD iN sOUTh aFriCà [3] àNDEàrLY iNiTiàTeD àNTireTrOviràL TheràpY (aRt) iN HIV iNFeCTeD iNFàNTS LeàDS TO imprOveD LONg-FrOm The EUrOpeàN INFàNT cOLLàbOràTiON grOUp [4]. IN Term viràL SUppreSSiON àND SUrvivàL. GUiDeLiNeS reCOm-The cHER TriàL eàrLY HIV DiàgNOSiS àND eàrLY TreàT- meND iNiTiàTiNg TheràpY wiTh à TripLe aRt CONSiSTiNg OF meNT reDUCeD eàrLY iNFàNT mOrTàLiTY bY 76%. TwO NUCLeOSiDe reverSe TràNSCripTàSe iNhibiTOrS (nR-VirOLOgiCàL FàiLUre CONTiNUeS TO be à màjOr ChàLLeNge tIS) àND eiTher ONe àDDiTiONàL NON-NUCLeOSiDe reverSeàFTer iNiTiàTiNg eàrLY aRt iN iNFàNTS. PEnPact-1 TràNSCripTàSe iNhibiTOr (nnRtI) Or à prOTeàSe iN-ShOweD reCeNTLY ThàT iN ChiLDreN FOLLOwiNg The reCOm- hibiTOr (PI). cOmpàreD TO OLDer ChiLDreN àND àDULTS,meNDeD iNiTiàL regimeN wiTh TwO NUCLeOSiDe reverSe viràL reLàpSe iS SeeN mOre FreqUeNTLY iN iNFàNTS reCeiv-TràNSCripTàSe iNhibiTOrS (nRtI) àND ONe prOTeàSe iN- iNg TripLe aRt. We NOw àDDreSS The pOSSibiLiTY OFà hibiTOr(PI) Or NON-NUCLeOSiDe reverSe TràNSCripTàSe iN- mOre pOTeNT aRt wiTh à qUàDrUpLe iNDUCTiON àNDhibiTOr (nnRtI) 71% were ON FirST-LiNe aRt àFTer à TripLe màiNTeNàNCe TheràpY. meDiàN FOLLOw-Up Time OF5 YeàrS, NeverTheLeSS ONLY Methods:We exàmiNe The LONgiTUDiNàL COUrSe iN FOUr 56% hàD CONTiNUeD viràL LOàD SUppreSSiON [5]. Previ- HIV iNFeCTeD iNFàNTS, whO were reFerreD FrOm OTher OUS STUDieS eveN ShOw ThàT CONSiSTeNT LONg Term viràL CeNTerS àND COULD NOT be reCrUiTeD TO mULTiCeNTre TriàLS. SUppreSSiON wiTh HIV-1 Rna beLOw DeTeCTiON LimiT iS We iNTrODUCeD aRt iNiTiàLLY CONSiSTiNg OFTwO nRtIS, àChieveD iN LeSS ThàN 50% OFThe ChiLDreN wiTh FirST ONe nnRtI àND ONe PI àND LàTer DiSCONTiNUeD The PI LiNe TripLe aRt.. chiLDreN wiTh àN iNCreàSeD viràL LOàD àT The àge OF12 mONThS màiNTàiNiNg à TripLe regime àre àT riSk FOr à ràpiD prOgreSSiON OFDiSeàSe àND Therà- CONSiSTiNg OFTwO nRtIS àND ONe nnRtI. pY FàiLUre [6, 7]. WhiLe ThiS DrUg COmbiNàTiON FOLLOwS Results: OFFiCiàL reCOmmeNDàTiONS [1, 2], SeveràL STUDieS hàve PrOviDeD ThàT TheràpY àDhereNCe wàS màiN- TàiNeD we ObServeD àN eFFeCTive SUSTàiNeD DeCLiNe OFàDDreSSeD The pOSSibiLiTY OFiNTrODUCiNg à mOre àg- viràL LOàD àND SigNiFiCàNT cd4 CeLL reCONSTiTUTiON eveNgreSSive iNiTiàL regime CONSiSTiNg OFFOUr àNTireTrOviràL àFTer SwiTChiNg TO à TripLe regime. nO DrUg àSSOCiàTeDDrUgS [8-13]. TOxiCiTY wàS SeeN.lUzUriàgà eT àL STUDieD 52 iNFàNTS reCeiviNg DiFFereNT Conclusion:TheràpY regimeS àND DemONSTràTeD àN imprOveD LONg-We SUggeST ThàT à FOUr DrUg TheràpY mighT be à pOSSibLe iNiTiàL TheràpY OpTiON iN HIV iNFeCTeD iN-Term viràL SUppreSSiON iN pàTieNTS wiTh à qUàDrUpLe FàNTS, àT LeàST iN ThOSe wiTh à high viràL LOàD, FOLLOweDTheràpY iNiTiàTeD beFOre The àge OF3 mONThS [9]. a TOL- bY à màiNTeNàNCe TripLe regime àFTer 12 mONThS OFeràbiLiTY àND SàFeTY STUDY ShOweD LOw àDverSe eveNTS iN TheràpY. ChiLDreNreCeiviNg à 4- àND 5- DrUg regimeN [10]. BàSeD ON TheSe FiNDiNgS àND OUr OwN experieNCe wiTh STàN- Key words:HIV, HaaRt, àNTi HIV àgeNTS, iNFàNTS, vi-DàrD TripLe aRt we repOrT ON FOUr verTiCàLLY HIV iN- ràL LOàDFeCTeD ChiLDreN, iN whOm à qUàDrUpLe àNTireTrOviràL DrUg SCheme wàS iNTrODUCeD CONSiSTiNg OFTwO nRtIS, B acKGRound ONe nnRtI àND ONe PI. We FUrThermOre àDDreSS The pOSSibiLiTY OFSTàrTiNg wiTh à qUàDrUpLe TheràpY iN The EUrOpeàN [1] àND us gUiDeLiNeS [2] reCOmmeND TOFirST Yeàr OFLiFe àND LàTer màiNTàiNiNg à TripLe regime STàrT wiTh aRt iN àLL HIV iNFeCTeD iNFàNTS beLOw TheCONSiSTiNg OFTwO nRtIS àND ONe nnRtI. àge OF12 mONThS irreSpeCTive OFCLiNiCàL Or immUNO- LOgiCàL STàge. IN pàrTiCULàr, iN iNFàNTS iNFeCTeD DeSpiTe M EtHods àTTempTeD mOTher TO ChiLD TràNSmiSSiON prOphYLàxiS, P atIEnts aRt ShOULD be COmmeNCeD àS SOON àS The DiàgNOSiS iS CONFirmeD. EviDeNCe ThàT eàrLY TheràpY iN àLL iNFeCTeDBeTweeN 2004 àND 2009 FOUr iNFàNTS were iNiTiàLLY iNFàNTS LeàDS TO à SigNiFiCàNT reDUCTiON OFmOrbiDiTY TreàTeD wiTh à qUàDrUpLe TheràpY àT OUr HIV OUTpà- TieNT CLiNiC. aLL were reFerreD TO US FrOm OTher CeNTerS. aLL mOTherS UNDerweNT à CàeSàreàN SeCTiON. IN TwO pà- * BOTh àUThOrS CONTribUTeD eqUàLLY TO ThiS wOrk. TieNTS, màTerNàL HIV DiàgNOSiS wàS màDe àT à LàTe STàge