PEDIATRICS Vol. 97 No. 6 June 1996, pp. 886-890
This Article
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kline, M. W.
Right arrow Articles by Dunkle, L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kline, M. W.
Right arrow Articles by Dunkle, L. M.

Combination Therapy With Stavudine and Didanosine in Children With Advanced Human Immunodeficiency Virus Infection: Pharmacokinetic Properties, Safety, and Immunologic and Virologic Effects

Mark W. Kline MD1, Courtney V. Fletcher PharmD2, Marianne E. Federici MS3, Alice T. Harris RN1, Kim D. Evans RN, MSN, CPNP1, Victoria L. Rutkiewicz MS3, William T. Shearer MD, PhD1, and Lisa M. Dunkle MD3

1 Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston
2 College of Pharmacy, University of Minnesota, Minneapolis
3 Bristol-Myers Squibb Company, Wallingford, Connecticut

Objectives. To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection.

Methods. Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 42 cells/µL; range, 8 to 553 cells/µL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter.

Results. Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4+ lymphocyte counts greater than 50 cells/µL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4+ lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively.

Conclusions. Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.

Submitted on December 8, 1995
Accepted on March 1, 1996




This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
C. Rongkavilit, P. Thaithumyanon, T. Chuenyam, B. D. Damle, S. Limpongsanurak, C. Boonrod, A. Srigritsanapol, E. A. M. Hassink, R. M. W. Hoetelmans, D. A. Cooper, et al.
Pharmacokinetics of Stavudine and Didanosine Coadministered with Nelfinavir in Human Immunodeficiency Virus-Exposed Neonates
Antimicrob. Agents Chemother., December 1, 2001; 45(12): 3585 - 3590.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
T. Abreu, K. Plaisance, V. Rexroad, S. Nogueira, R. H. Oliveira, L. A. Evangelista, R. Rangel, I. S. Silva, C. Knupp, and J. S. Lambert
Bioavailability of Once- and Twice-Daily Regimens of Didanosine in Human Immunodeficiency Virus-Infected Children
Antimicrob. Agents Chemother., May 1, 2000; 44(5): 1375 - 1376.
[Abstract] [Full Text]

Home page
 Antimicrob. Agents Chemother.Home page
C. V. Fletcher, R. C. Brundage, R. P. Remmel, L. M. Page, D. Weller, N. R. Calles, C. Simon, and M. W. Kline
Pharmacologic Characteristics of Indinavir, Didanosine, and Stavudine in Human Immunodeficiency Virus-Infected Children Receiving Combination Therapy
Antimicrob. Agents Chemother., April 1, 2000; 44(4): 1029 - 1034.
[Abstract] [Full Text]

Home page
 PediatricsHome page
M. W. Kline, R. B. Van Dyke, J. C. Lindsey, M. Gwynne, M. Culnane, C. Diaz, R. Yogev, R. E. McKinney Jr, E. J. Abrams, L. M. Mofenson, et al.
Combination Therapy With Stavudine (d4T) Plus Didanosine (ddI) in Children With Human Immunodeficiency Virus Infection
Pediatrics, May 1, 1999; 103(5): 62e - 62.
[Abstract] [Full Text]

Home page
 PediatricsHome page
Antiretroviral Therapy and Medical Management of Pediatric HIV Infection
Pediatrics, October 1, 1998; 102(4): 1005 - 1062.
[Full Text]

Home page
 PediatricsHome page
B. U. Mueller, R. P. Nelson Jr, J. Sleasman, J. Zuckerman, M. Heath-Chiozzi, S. M. Steinberg, F. M. Balis, P. Brouwers, A. Hsu, R. Saulis, et al.
A Phase I/II Study of the Protease Inhibitor Ritonavir in Children With Human Immunodeficiency Virus Infection
Pediatrics, March 1, 1998; 101(3): 335 - 343.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
M. W. Kline, R. B. Van Dyke, J. C. Lindsey, M. Gwynne, M. Culnane, R. E. McKinney Jr, S. Nichols, W. G. Mitchell, R. Yogev, N. Hutcheon, et al.
A Randomized Comparative Trial of Stavudine (d4T) Versus Zidovudine (ZDV, AZT) in Children With Human Immunodeficiency Virus Infection
Pediatrics, February 1, 1998; 101(2): 214 - 220.
[Abstract] [Full Text] [PDF]