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J Infect Dis. 2008 Dec 1;198(11):1599-608. doi: 10.1086/593022.

Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children.

Collaborators (195)

Oleske J, Bettica L, Dieudonne A, Johnson J, Pelton S, Cooper ER, Kay L, Regan AM, Church JA, Dunaway T, Deveikis A, Batra J, Marks S, Fineanganofo I, Gaur S, Whitley-Williams P, Malhotra A, Carrachio L, Keller M, Redjal N, Wettgen S, Sullivan S, Hutton N, Griffith B, Joyner M, Kiefner C, Farley J, Watson D, Minglana F, Paul ME, Shearer WT, Jackson CD, Boyer KM, Martinez J, McAuley JB, Haak M, Brady M, Koranyi K, Hunkler J, Callaway C, Johnson DC, Kowalski D, Wolfe B, Ryan D, Higgins A, Foca M, LaRussa P, Gershon A, Scott GB, Mitchell CD, Florez C, Gamber C, Wara DC, Tilton N, Muscat M, Petru A, Courville T, Gold K, Eng K, Spector SA, Viani RM, Caffery M, Norris K, Donnelly M, McGann K, Mathison C, Swetnam J, Piatt JP, Foti J, Clarke-Steffen L, Belhorn T, Pitkin B, Eddleman J, Bonagura VR, Schuval SJ, Kaplan B, Colter C, Abrams EJ, Frere M, Calo D, Borkowsky W, Deygoo N, Minter M, Aklem S, Dobbins D, Wimbley D, D'Angelo L, Spiegel H, Melvin AJ, Mohan KM, Acker M, Phelps S, Rich KC, Hayani K, Camacho J, Handelsman E, Moallem HJ, Swindell DM, Kaye JM, Chin M, Dorio K, Wiznia A, Donovan M, Acevedo M, Gonzalez M, Fabregas L, Texidor ME, Andiman WA, Hurst L, de Jesus J, Schroeder D, Weiner LB, Contello KA, Holz WA, Famigletti MJ, Nachman S, Ferraro D, Perillo J, Kelly M, Rana S, Finke H, Yu PH, Roa JC, Kovacs A, Homans J, Neely M, Spencer L, Rathore MH, Merza A, Thoma T, Mendoza A, Puga AM, Talero G, Blood J, Inman A, Weinberg GA, Murante B, Laverty S, Gigliotti F, Lavoie SR, Smith TY, Flynn PM, Gauer A, Knapp K, Patel N, Donohoe M, Febo IL, Lugo L, Santos R, Heyer I, Wilson G, McGann KA, Pickering L, Storch GA, Douglas SD, Rutstein RM, Vincent CA, Coburn C, Foster J, Chen J, Conway D, Laguerre R, Stuard E, Nubel C, Hagmann S, Purswani M, Bamji M, Pathak I, Manwani S, Patel E, Luzuriaga K, Moriarty R, Silio M, Alchediak T, Borne C, Bradford S, Wilcox RD, Stechenberg BW, Fisher DJ, Johnston AM, Toye M, Salazar JC, Fullerton K, Karas G, Mani CS, Foshee S, Murrray D, White C, Mancao MY, Estrada B, Heckman BE, Kraimer J, Tryon NS, Traite SE, Bohlin P.

Abstract

BACKGROUND:

Human immunodeficiency virus (HIV) therapy includes a backbone of nucleoside reverse-transcriptase inhibitors (NRTIs). Toxicities associated with NRTIs are not fully defined in children.

METHODS:

We studied 2233 children < or =13 years of age who were perinatally infected with HIV and were receiving > or =2 NRTIs, to determine the relative toxicities of the 5 most common NRTI pairs: zidovudine (ZDV)/lamivudine (3TC), ZDV/didanosine (ddI), stavudine (d4T)/3TC, d4T/ddI, and ddI/3TC. Incidence rates for clinical and laboratory toxicities were estimated, and NRTI pairs were compared with regard to the time to the first toxicity.

RESULTS:

The most common clinical toxicities noted were hepatitis, peripheral neuropathy, lipodystrophy/lipoatrophy, and pancreatitis, whereas the most common laboratory toxicities were an elevated anion gap, an increased total amylase level, neutropenia, and thrombocytopenia. Overall, regimens containing ZDV were associated with a significantly lower rate of clinical toxicities than were those containing d4T (adjusted hazard ratio [HR], 0.49; P = .02) ); regimens containing ddI were associated with a significantly lower rate of laboratory toxicities than were those containing 3TC (adjusted HR, 0.78; P = .04). ZDV/3TC was associated with a lower rate of clinical toxicities than were d4T/ddI and ddI/3TC and with a higher rate of laboratory toxicities than was ZDV/ddI. ZDV/ddI was associated with a lower rate of clinical toxicities than was d4T/3TC.

CONCLUSIONS:

In children, regimens containing ZDV have less toxicity than do those containing d4T, thereby supporting their use in first-line regimens. D4T/3TC, d4T/ddI, and ddI/3TC have similar toxicity rates and are appropriate for second-line therapy.

PMID:
19000014
[PubMed - indexed for MEDLINE]
PMCID:
PMC2737265
Free PMC Article
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