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Clin Infect Dis. 2008 Jun 1;46(11):1751-60. doi: 10.1086/587900.

Long-term effects of highly active antiretroviral therapy on CD4+ cell evolution among children and adolescents infected with HIV: 5 years and counting.

Collaborators (254)

Paul ME, Jackson CD, Minglana F, Schwarzwald H, Rathore MH, Mirza A, Champion K, Mendoza A, Yogev R, Chadwick E, Febo IL, Lugo L, Santos R, Heyer I, Purswani M, Baksi S, Stuard E, Dummit M, Acevedo M, Gonzalez M, Fabregas L, Texidor ME, Scott GB, Mitchell CD, Florez C, Gamber J, Bardeguez A, Dieudonne A, Bettica L, Johnson J, Silio M, Alchediak T, Boe C, Cowie M, Van Dyke R, Spector SA, Viani RM, Caffery M, Norris K, Rana S, Finke H, Yu P, Roa J, Donovan M, Serrano R, Burey M, Auguste R, Chen J, Foster J, Stechenberg BW, Fisher D, Johnston AM, Toye M, Homans J, Neely M, Spencer LS, Kovacs A, Burchett S, Karthas N, Moore E, Cromer C, Gaur A, Knapp K, Patel N, Donohoe M, Minter M, Hastings T, Akleh S, Borkowsky W, Handelsman E, Moallem HJ, Swindell DM, Kaye JM, Higgins A, Foca M, LaRussa P, Gershon A, Douglas SD, Rutstein RM, Vincent CA, Coburn PC, Petru A, Courville T, Eng K, Gold K, Wara DW, Tilton N, Muscat M, McFarland E, Salbenblatt C, Hutton N, Griffith B, Joyner M, Kiefner C, Acker M, Melvin AJ, Mohan KM, Phelps S, Bamji M, Pathak I, Manwani S, Patel E, Dobbins D, Wimbley D, Perron T, Spiegel H, Luzuriaga K, Moriarty R, Pass R, Crain M, Watson D, Farley J, Klipner K, Hilyard C, Bonagura VR, Schuval SJ, Colter C, Campbell L, Pelton SI, Cooper ER, Kay L, Regan AM, Rich KC, Hayani K, Bicchinella M, Camacho J, Nachman S, Ferraro D, Perillo J, Kelly M, Puga AM, Talero G, Blood J, Juliano S, Mathison C, Whitfield K, Wiley F, Donnelly M, Champion S, Frere M, DiGrado M, Abrams EJ, McAuley JB, Boyer KM, Haak M, Martinez J, Mancao M, Estrada B, Salazar JC, Karas G, Belhorn T, Eddleman J, Pitkin B, Figueroa W, Reyes E, Weiner LB, Contello KA, Holz WA, Famiglietti MJ, Ramilo O, Lawrence R, Lew J, Delany C, Duff C, Fernandez AD, Hughes PA, Wade N, Adams ME, Piatt JP, Foti J, Clarke-Steffen L, Sleasman J, Delaney C, Foshee S, Mani CS, Murray DL, White C, Andiman WA, Hurst L, de Jesus J, Schroeder D, Wilson G, Weinberg GA, Gigliotti F, Murante B, Laverty S, Hutchcon N, Townley A, Nesheim S, Dennis R, Emmanuel P, Lujan-Zilberman J, Graisberry C, Moore S, Fisher RG, Cunnion KM, Rubio TT, Sandifer D, Johnson GM, Gay H, Sadler S, Keller MA, Redjal N, Wettgen S, Sullivan S, Johnson D, Church J, Dunaway T, Salata C, Marks S, Elkins K, Batra J, Deveikis A, Gaur S, Whitley-Williams P, Malhotra A, Cerracchio L, Dolan M, D'Agostino J, Posada R, Mani C, Cobb S, Lavoie SR, Smith TY, Feingold A, Burrows-Clark S, Mrus J, Beiting R, Brady M, Hunkler J, Koranyi K, Albritton W, Warford R, Arpadi S, Gershon A, Miller P, Rubinstein A, Krienik G, Kovacs A, Operskalski E, Wara D, Kamrin A, Farrales S, Tilton N, Muscat M, Johan-Liang R, O'Keefe K, McGann KA, Pickering L, Storch GA, Pahwa S, Rodriquez L, Lewis P, Croteau R.

Author information

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.



Lower percentages of CD4(+) T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4(+) lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4(+) cell percentage are maintained and whether they lead to normal CD4(+) cell percentages in children with severe immunosuppression.


The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4(+) cell percentage, using marginal structural models to account for confounding by severity.


Initiation of any type of HAART increased CD4(+) cell percentage by 2.34% (95% confidence interval, 1.35%-3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4(+) cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4(+) cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4(+) cell percentage after 5 years of HAART did not reach normal levels.


Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4(+) cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy.

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