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Preliminary experiences with ritonavir in children with advanced HIV infection

  • Clinical and Epidemiological Studies
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Summary

The aim of this study was to obtain information on the feasibility (tolerance, safety) of antiretroviral combination therapy, including ritonavir, in children. In eight children (median age 8.9 years; range 3 to 13 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 80 cells/μl;range 0 to 280 cells/μl), drug combinations including ritonavir (approximately 300 mg/m2 b.i.d.) were administered. In seven children, previous therapy using a combination of at least two nucleoside reverse transcriptase inhibitors (NRTI) had failed. Four patients had ritonavir added to an already existing regimen of two NRTI; two patients had one NRTI replaced by a new one; and in two patients two new NRTI were initiated. The number of CD4 T cells, plasma HIV RNA concentration, CBC and blood chemistry profile were monitored. Medication had to be discontinued in two children because of severe nausea and vomiting. In the remaining six children, ritonavir was tolerated and treatment was maintained for at least 6 months. The number of CD4 cells increased in five of six patients. The median number of CD4 cells increased from 66+/−110 cells/μl at baseline to 92+/−99 cells/μl, 161+/−88 cells/μl, and 252+/−25 cells/μl after 1,3 and 6 months of therapy, respectively. The plasma HIV RNA concentration decreased below the detection limit of 500 copies/ml in three children. In the remaining children a maximum reduction of 0.8, 1.0 and 1.8 log10 was observed. In one child the HIV RNA concentration reincreased after 6 months by 0.7 log10 above the nadir. Antiretroviral combinations including ritonavir were tolerated by six of eight children and produced substantial benefits with respect to increased numbers of CD4 cells and a decline in plasma viral RNA concentration. It can be concluded that the administration of ritonavir is possible in a significant proportion of HIV-infected children, and leads to improvement of the CD4 cell count and viral load.

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References

  1. Carpenter, C. C. J., Fischl, M. A., Hammer, S. M., Hirsch, M. S., Jacobsen, D. M., Katzenstein, D. A., Montaner, J. S. G., Richman, D. D., Saag, M. S., Schooley, R. T., Thompson, M. A., Vella, S., Yeni, P. G., Violberding, P. A.: Antiretroviral therapy for HIV infection in 1997. JAMA 277 (1997) 1962–1969.

    Article  PubMed  CAS  Google Scholar 

  2. Mueller, B. U., Nelson, R. P., Jr., Sleasman, J., Zuckerman, J., Heath-Chiozzi, M., Steinberg, S. M., Balis, F. M., Brouwers, P., Hsu, A., Saulis, R., Sei, S., Wood, L. V., Zeichner, S., Katz, T. T. K., Higham, C., Aker, D., Edgerly, M., Jarosinski, P., Serchuck, L., Whitcup, S. M., Pizzuti, D., Pizzo, P. A.: A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection. Pediatrics 103 (1998) 335–343.

    Article  Google Scholar 

  3. Luzuriaga, K., Bryson, Y., Krogstad, P., Robinson, J., Stechenberg, B., Lamson, M., Cort, S., Sullivan, J. L.: Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection. N. Engl. J. Med. 336 (1997) 1343–1349.

    Article  PubMed  CAS  Google Scholar 

  4. Katzenstein, D. A., Winters, M., Bubp, J., Israelski, D., Winger, E., Merigan, T. C.: Quantification of human immunodeficiency virus by culture and polymerase chain reaction in response to didanosine after long-term therapy with zidovudine. J. Infect. Dis. 169 (1994) 416–419.

    PubMed  CAS  Google Scholar 

  5. Rutstein, R. M., Feingold, A., Meislich, D., Word, B., Rudy, B.: Protease inhibitor therapy in children with perinatally acquired HIV infection. AIDS 11 (1997) F107-F111.

    Article  PubMed  CAS  Google Scholar 

  6. Centers for Disease Control: 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR 43 (1994) 1–10.

    Google Scholar 

  7. Piscitelli, S. C., Flexner, C., Minor, J. R., Polis, M. A., Masur, H.: Drug interactions in patients infected with human immunodeficiency virus. Clin. Infect. Dis. 23 (1996) 685–693.

    PubMed  CAS  Google Scholar 

  8. Englund, J. A., Baker, C. J., Raskino, C., McKinney, R. E., Petrie, B., Fowler, M. G., Pearson, D., Gershon, A., McSherry, G. D., Abrams, E. J., Schliozberg, J., Sullivan, J. L.: Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. N. Engl. J. Med. 336 (1997) 1704–1712.

    Article  PubMed  CAS  Google Scholar 

  9. Husson, R. N., Mueller, B. U., Farley, M., Woods, L., Kovacs, A., Goldsmith, J. C., Ono, J., Lewis, L. L., Balis, F. M., Brouwers, P., Avramis, V. I., Chrich, J. A., Butler, K. M., Rasheed, S., Jarosinski, P., Venzon, D., Pizzo, P. A.: Zidovudine and didanosine combination therapy in children with human immunodeficiency virus infection. Pediatrics 93 (1997) 316–322.

    Google Scholar 

  10. Kline, M. W., Fletcher, C. V., Federici, M. E., Harris, A. T., Evans, K. D., Rutkiewicz, V. L., Shearer, W. T., 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. Pediatrics 97 (1996) 889–890.

    Google Scholar 

  11. Sölder, B., Wintergerst, U., Notheis, G., Eberle, J., Gürtler, L., Beloradski, B. H.: Effect of antiretroviral combination therapy (zidovudine/didanosine or zidovudine/lamivudine) on quantitative plasma human immunodeficiency virus-ribonucleic acid in children and adolescents infected with human immunodeficiency virus. J. Pediatr. 130 (1997) 293–299.

    Article  PubMed  Google Scholar 

  12. Horneff, G., Adam, O., Wahn, V.: Pilot study of zidovudine/lamivudine combination therapy in vertically infected children not previously treated with antiretroviral drugs. AIDS 12 (1998) 489–494.

    Article  PubMed  CAS  Google Scholar 

  13. Melvin, A. J., Mohan, K. M., Arcuino, L. A., Edlestein, R. E., Frenkel, L. M.: Clinical, virologic and immunologic responses of children with advanced human immunodeficiency virus type 1 disease treated with protease inhibitors. Pediatr. Infect. Dis. J. 16 (1997) 968–974.

    Article  PubMed  CAS  Google Scholar 

  14. Danner, S. A., Carr, A., Leonard, J. M., Lehman, L. M., Gudiol, F., Gonzalez, J., Raventos, A., Rubio, R., Bouza, E., Pintado, V., Aguado, A. G., De Lomas, J. G., Delgado, R., Borleffs, J. C. C., Hsu, A., Valdes, J. M., Boucher, C. A. B., Cooper, D. A.: A short term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. N. Engl. J. Med. 333 (1995) 1528–1533.

    Article  PubMed  CAS  Google Scholar 

  15. Yogev, R., Stanley, K., Nachman, S. A.: LB-6 virologic efficacy of ZDV+3TC vs. d4T+ritonavir (RTV) vs. ZDV+3TC+RTV in stable antiretroviral experienced HIV-infected children (pediatric ACTG Trial 338). 37th ICAAC, Toronto, Canada, 1997 (abstr.)

  16. Markowitz, M., Saag, M., Powderly, W. G., Hurley, A. M., Hsu, A., Valdes, J. M., Henry, D., Sattler, F., La Marca, A., Leonard, J. M., Ho, D. D.: A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N. Engl. J. Med. 333 (1995) 1535–1539.

    Article  Google Scholar 

  17. Wintergerst, U., Hoffmann, F., Solder, B., Notheis, G., Petropoulou, T., Eberle, J., Gürtler, L., Belohradsky, B. H.: Comparison of two antiretroviral triple combinations including the protease inhibitor indinavir in children infected with human immunodeficiency virus. Pediatr. Infect. Dis. J. 17 (1998) 495–499.

    Article  PubMed  CAS  Google Scholar 

  18. Cameron, D. W., Heath-Chiozzi, M., Danner, S., Cohen, C., Kravcik, S., Maurath, C., Sun, E., Henry, D., Rode, R., Potthoss A., Leonard, J.: Randomized placebo-controlled trial of ritonavir in advanced HIV-1 disease. The advanced HIV disease ritonavir study group. Lancet 351 (1998) 543–549.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Universitäts-Kinderklinik Halle, Ernst-Grube-Str. 40, D-06120, Halle

    G. Horneff

  2. Institut der Medizinischen Mikrobiologie und Virologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225, Düsseldorf, Germany

    O. Adams

  3. Zentrum für Kinderheilkunde, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225, Düsseldorf, Germany

    V. Wahn

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  1. G. Horneff
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  2. O. Adams
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  3. V. Wahn
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Horneff, G., Adams, O. & Wahn, V. Preliminary experiences with ritonavir in children with advanced HIV infection. Infection 27, 103–107 (1999). https://doi.org/10.1007/BF02560507

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  • DOI: https://doi.org/10.1007/BF02560507

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