. 2008 Dec 1;198(11):1599-608.

doi: 10.1086/593022.

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

Russell B Van Dyke¹, Lu Wang, Paige L Williams; Pediatric AIDS Clinical Trials Group 219C Team

Collaborators, Affiliations

Collaborators

Pediatric AIDS Clinical Trials Group 219C Team:
J Oleske, L Bettica, A Dieudonne, J Johnson, S Pelton, E R Cooper, L Kay, A M Regan, J A Church, T Dunaway, A Deveikis, J Batra, S Marks, I Fineanganofo, S Gaur, P Whitley-Williams, A Malhotra, L Carrachio, M Keller, N Redjal, S Wettgen, S Sullivan, N Hutton, B Griffith, M Joyner, C Kiefner, J Farley, D Watson, F Minglana, M E Paul, W T Shearer, C D Jackson, K M Boyer, J Martinez, J B McAuley, M Haak, M Brady, K Koranyi, J Hunkler, C Callaway, D C Johnson, D Kowalski, B Wolfe, D Ryan, A Higgins, M Foca, P LaRussa, A Gershon, G B Scott, C D Mitchell, C Florez, C Gamber, D C Wara, N Tilton, M Muscat, A Petru, T Courville, K Gold, K Eng, S A Spector, R M Viani, M Caffery, K Norris, M Donnelly, K McGann, C Mathison, J Swetnam, J P Piatt, J Foti, L Clarke-Steffen, T Belhorn, B Pitkin, J Eddleman, V R Bonagura, S J Schuval, B Kaplan, C Colter, E J Abrams, M Frere, D Calo, W Borkowsky, N Deygoo, M Minter, S Aklem, D Dobbins, D Wimbley, L D'Angelo, H Spiegel, A J Melvin, K M Mohan, M Acker, S Phelps, K C Rich, K Hayani, J Camacho, E Handelsman, H J Moallem, D M Swindell, J M Kaye, M Chin, K Dorio, A Wiznia, M Donovan, M Acevedo, M Gonzalez, L Fabregas, M E Texidor, W A Andiman, L Hurst, J de Jesus, D Schroeder, L B Weiner, K A Contello, W A Holz, M J Famigletti, S Nachman, D Ferraro, J Perillo, M Kelly, S Rana, H Finke, P H Yu, J C Roa, A Kovacs, J Homans, M Neely, L Spencer, M H Rathore, A Merza, T Thoma, A Mendoza, A M Puga, G Talero, J Blood, A Inman, G A Weinberg, B Murante, S Laverty, F Gigliotti, S R Lavoie, T Y Smith, P M Flynn, A Gauer, K Knapp, N Patel, M Donohoe, I L Febo, L Lugo, R Santos, I Heyer, G Wilson, K A McGann, L Pickering, G A Storch, S D Douglas, R M Rutstein, C A Vincent, C Coburn, J Foster, J Chen, D Conway, R Laguerre, E Stuard, C Nubel, S Hagmann, M Purswani, M Bamji, I Pathak, S Manwani, E Patel, K Luzuriaga, R Moriarty, M Silio, T Alchediak, C Borne, S Bradford, R D Wilcox, B W Stechenberg, D J Fisher, A M Johnston, M Toye, J C Salazar, K Fullerton, G Karas, C S Mani, S Foshee, D Murrray, C White, M Y Mancao, B Estrada, B E Heckman, J Kraimer, N S Tryon, S E Traite, P Bohlin

Affiliation

¹ Department of Pediatrics, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. vandyke@tulane.edu

PMID: 19000014
PMCID: PMC2737265
DOI: 10.1086/593022

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

Russell B Van Dyke et al. J Infect Dis. 2008.

. 2008 Dec 1;198(11):1599-608.

doi: 10.1086/593022.

Authors

Russell B Van Dyke¹, Lu Wang, Paige L Williams; Pediatric AIDS Clinical Trials Group 219C Team

Collaborators

Pediatric AIDS Clinical Trials Group 219C Team:
J Oleske, L Bettica, A Dieudonne, J Johnson, S Pelton, E R Cooper, L Kay, A M Regan, J A Church, T Dunaway, A Deveikis, J Batra, S Marks, I Fineanganofo, S Gaur, P Whitley-Williams, A Malhotra, L Carrachio, M Keller, N Redjal, S Wettgen, S Sullivan, N Hutton, B Griffith, M Joyner, C Kiefner, J Farley, D Watson, F Minglana, M E Paul, W T Shearer, C D Jackson, K M Boyer, J Martinez, J B McAuley, M Haak, M Brady, K Koranyi, J Hunkler, C Callaway, D C Johnson, D Kowalski, B Wolfe, D Ryan, A Higgins, M Foca, P LaRussa, A Gershon, G B Scott, C D Mitchell, C Florez, C Gamber, D C Wara, N Tilton, M Muscat, A Petru, T Courville, K Gold, K Eng, S A Spector, R M Viani, M Caffery, K Norris, M Donnelly, K McGann, C Mathison, J Swetnam, J P Piatt, J Foti, L Clarke-Steffen, T Belhorn, B Pitkin, J Eddleman, V R Bonagura, S J Schuval, B Kaplan, C Colter, E J Abrams, M Frere, D Calo, W Borkowsky, N Deygoo, M Minter, S Aklem, D Dobbins, D Wimbley, L D'Angelo, H Spiegel, A J Melvin, K M Mohan, M Acker, S Phelps, K C Rich, K Hayani, J Camacho, E Handelsman, H J Moallem, D M Swindell, J M Kaye, M Chin, K Dorio, A Wiznia, M Donovan, M Acevedo, M Gonzalez, L Fabregas, M E Texidor, W A Andiman, L Hurst, J de Jesus, D Schroeder, L B Weiner, K A Contello, W A Holz, M J Famigletti, S Nachman, D Ferraro, J Perillo, M Kelly, S Rana, H Finke, P H Yu, J C Roa, A Kovacs, J Homans, M Neely, L Spencer, M H Rathore, A Merza, T Thoma, A Mendoza, A M Puga, G Talero, J Blood, A Inman, G A Weinberg, B Murante, S Laverty, F Gigliotti, S R Lavoie, T Y Smith, P M Flynn, A Gauer, K Knapp, N Patel, M Donohoe, I L Febo, L Lugo, R Santos, I Heyer, G Wilson, K A McGann, L Pickering, G A Storch, S D Douglas, R M Rutstein, C A Vincent, C Coburn, J Foster, J Chen, D Conway, R Laguerre, E Stuard, C Nubel, S Hagmann, M Purswani, M Bamji, I Pathak, S Manwani, E Patel, K Luzuriaga, R Moriarty, M Silio, T Alchediak, C Borne, S Bradford, R D Wilcox, B W Stechenberg, D J Fisher, A M Johnston, M Toye, J C Salazar, K Fullerton, G Karas, C S Mani, S Foshee, D Murrray, C White, M Y Mancao, B Estrada, B E Heckman, J Kraimer, N S Tryon, S E Traite, P Bohlin

Affiliation

¹ Department of Pediatrics, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. vandyke@tulane.edu

PMID: 19000014
PMCID: PMC2737265
DOI: 10.1086/593022

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.

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Conflict of interest statement

Potential conflicts of interest: none reported.

Figures

**Figure 1**
Kaplan-Meier estimates of the probability of remaining event free for each of 5 dual nucleoside reverse-transcriptase inhibitor (NRTI) regimens, where the event is a targeted clinical diagnosis *(A)* or laboratory toxicity *(B)*. d4T, stavudine; ddI, didanosine; 3TC, lamivudine; ZDV, zidovudine.

**Figure 2**
Pairwise comparison of dual nucleoside reverse-transcriptase inhibitor (NRTI) regimens containing both zidovudine (ZDV) and stavudine (d4T) (A and B) and pairwise comparison of dual NRTI regimens containing both didanosine (ddI) and lamivudine (3TC) (C and D), with Kaplan-Meier estimates of the probability of remaining event free and associated P values (by log-rank test). The event is a targeted clinical diagnosis (A and C) or a targeted abnormal laboratory test result (B and D).

See this image and copyright information in PMC

References

1. Brogly S, Williams P, Seage G, Oleske J, Van Dyke R, MacIntosh K for the PACTG 219C. Antiretroviral treatment in pediatric HIV in the United States: from clinical trials to clinical practice. JAMA. 2005;293:2213–2220. - PubMed
1. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. 2008. Feb 28 [Accessed 22 April 2008]. Available at: http://aidsinfo.nih.gov/ContentFiles/PediatricGuidelines.pdf. - PubMed
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Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children

Collaborators

Affiliation

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

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Conflict of interest statement

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