Abstract
Although monotherapy with available antiretroviral agents has proved useful in terms of delaying disease progression and improving the survival of persons with AIDS, the utility of these compounds as single agents is limited by several factors, including incomplete suppression of viral replication, the emergence of resistant virus, and a gradual increase in viral burden over time.1,2 As the benefit of antiretroviral monotherapy wanes, immune function decreases, leading to disease progression and ultimately death.
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References
I. O’Brien WA. The predictive value of CD4, p2 microglobulin and HIV RNA by PCR in VACSP #298, a placebo controlled zidovudine trial. Presented at: Surrogate Markers of HIV: Strategies and Issues for Selection and Use. Arlington, VA, October 1994.
Wei X, Ghosh SK, Taylor ME et al. Viral dynamics in human immunodeficiency type 1 infection. Nature 1995; 373: 117–122.
Eron J, Benoit S, Jemsek J et al. A randomized, double-blind multicenter comparative trial of lamivudine (3TC) monotherapy vs zidovudine (ZDV) monotherapy vs 3TC + ZDV combination in naive patients CD4+ 200–500mm3. Latebreaker abstract 34. 2nd National Conference of Human Retroviruses and Related Infections, Washington, DC, February 1995.
Larder BA, Kemp SD, Harrigan PR et al. Antiviral potency of AZT plus 3TC combination therapy supports virological observations. Latebreaker abstract 33. 2nd National Conference of Human Regtroviruses and Related Infections, Washington, DC, February 1995.
Caliendo AM, Hirsch MS. Combination therapy for infection due to human immunodeficiency virus type 1. Clin Inf Dis 1994; 18: 516–524.
St. Clair MH, Pennington KN, Rooney J et al. In vitro comparison of selected triple drug combinations for suppression of HIV-1 replication. J Acquir Immune Defic Syndr Hum Retrovirol (in press).
Schafer RW, Kozal MJ, Winter MA et al. Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J Infect Dis 1994; 169: 722–729.
Schooley RT, Ramirez-Ronda C, Lavelle J et al. Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared to didanosine monotherapy. Manuscript in preparation.
Gao W, Shirasaka T, Johns DG et al. Differential phosphorylation of azidothymidine, dideoxycytidine, dideoxyinosine in resting and activated peripheral blood mononuclear cells. J Clin Invest 1993; 91: 2326 2333.
Dudley MN. Clinical pharmacokinetics of nucleoside antiretroviral agents. J Infect Dis 1995; 171 (Suppl 2): S99 - S112.
Collier AC. Clinical effects of combination chemotherapy. Antiviral Chemotherapy; New Directions for Clinical Application and Research, Vol 4 this volume. Edited by Mills J, Volberding P, Corey L. Plenum Press 1995 (in press).
Coombs R. Virologic outcomes of combination chemotherapy. Antiviral Chemotherapy; New Directions for Clinical Application and Research, Vol 4 this volume. Edited by Mills J, Volbending P, Corey L. Plenum Press 1995 (in press).
Medical Section of the American Lung Association. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis 1986; 134: 355–363.
WHO Study Group. Chemotherapy of leprosy for control programmes. WHO Tech Rep Ser 1982; 675: 7.
Rivera GK, Pinkel D, Simone N et al. Treatment of acute lymphoblastic leukemia–30 years’ experience at St. Jude Children’s Research Hospital. N Engl J Med 1993; 329: 1289–1295.
Mohri H, Singh MK, Ching WT et al. Quantitation of zidovudine-resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients. Proc Natl Acad Sci USA 1993; 90 (1): 25–29.
Welles SL. Issues of internal and external validity in retrospective studies of virus load and clinical outcome. Presented at: Surrogate Markers of HIV: Strategies and Issues for Selection and Use. Arlington, VA, October 1994.
Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis and therapy. Science 1995; 267: 483–489.
CaoY, Qin L, Zhang L et al. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med 1995; 332: 259–260.
Parry NR, Tisdale M. Wellcome Research Laboratories, Beckenham, Kent, UK, personal communication.
Bassett R, Schoenfeld D, Collier A for the ACTG 229 Protocol Team. ACTG 229 Executive Summary. Bethesda, MD: National Institutes of Health, National Institute of Allergy and Infectious Diseases: May 26, 1994.
ACTG 241 Protocol Team. ACTG 241 Executive Summary. Bethesda, MD: National Institutes of Health, National Institute of Allergy and Infectious Diseases; November 16 1994.
Drews J. Presentations on barriers to AIDS drug development. US Department of Health and Human Services National Task Force on AIDS Drug Development, Arlington, VA, April 1994.
Daluge SM, Purifoy DJ, Savina PM et al. 5-Chloro-2’,3’-dideoxy-3’-fluorouridine (935U83), a selective anti-human immunodeficiency virus agent with an improved metabolic and toxicological profile. Antimicrob Agents Chemother 1994; 38: 1590–1603.
Gosselin G, Schinazi RF, Sommadossi JP et al. Anti-human immunodeficiency virus activities of the beta-L enantiomer of 2’,3’-dideoxycytidine and its 5-fluoroderivative in vitro. Antimicrob Agents Chemother 1992; 36: 2423–2431.
Condreay LD, Jansen RW, Powdrill TF et al. Evaluation of the potent anti-hepatitis B virus agent (-) cis 5-fluoro-1-[2–9hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in a novel in vivo model. Antimicrob Agents Chemother 1992; 38 (3); 616–619.
Tisdale M, Parry NR, Cousens D et al. Anti-HIV activity of (IS,4R)-4-[2-amino-6-(cyclopropylamino)9H-purin-9-yl]-2-cyclopentene-l-methanol(1592U89). Poster session 43, number 182. 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, FL, October 1994.
Painter GR, St. Clair MH, DeMiranda P et al. An overview of the preclinical development of the HIV protease inhibitor VX-478 (141 W94). Latebreaker abstract 5. 2nd National Conference of Human Retroviruses and Related Infections, Washington, DC, January 1995.
Rolan PE, Parker JE, Gray SJ et al. The pharmacokinetics, tolerability, and pharmacodynamics of tucaresol (589C80);4[2-formyl-3-hydroxyphenoxymethyllbenzoic acid), a potential anti-sickling agent, following administration to healthy subjects. Br J Clin Pharmacol 1993; 35: 419–425.
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Rooney, J.F., Warwick, J.C., Elkins, M.M., St. Clair, M.H., Barry, D.W. (1996). New Initiatives in Combination Antiretroviral Chemotherapy. In: Mills, J., Volberding, P.A., Corey, L. (eds) Antiviral Chemotherapy 4. Advances in Experimental Medicine and Biology, vol 394. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9209-6_34
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DOI: https://doi.org/10.1007/978-1-4757-9209-6_34
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