Human Immunodeficiency Virus Type 1 (HIV-l) Viremia Changes and Development of Drug-Related Mutations in Patients with Symptomatic HIV-l Infection Receiving Alternating or Simultaneous Zidovudine and Didanosine Therapy

Abstract

The changes in viremia levels and the development of drug-related mutations were examined in 26 patients with symptomatic human immunodeficiency virus type 1 (HIV-1) infection participating in a randomized trial comparing alternating (A) and simultaneous (S) regimens of zidovudine and didanosine therapy. Patients on both arms had significant reduction in serum RNA copies from baseline throughout the 2 years of study. Significant differences between the two arms were demonstrated over the first 2-3 months of therapy. Analyses with nested polymerase chain reaction revealed that the emergence of the didanosine-related position 74 Leu-->Val mutation was significantly blocked in both regimens, while the zidovudine-related mutation at codon 215 was not affected. Determination of the overall durability of the antiviremic effect of the A and S regimens of zidovudine and didanosine and clinical implications of the results require further research.

Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

“…L74V is sufficient to cause virologic failure in patients receiving didanosine monotherapy (202) but additional mutations may be required to cause virologic failure to abacavir monotherapy. L74V causes hypersensitivity to zidovudine and possibly also to stavudine (368) and is consequently rarely observed in patients receiving dual nucleoside therapy with didanosine/zidovudine or didanosine/stavudine (49,200,285,335,338). L74V has also been shown to be cause decreased RT processivity in enzymatic studies and decreased replication in cell culture (347,348).…”

Optimal Switching In Structured Treatment Interruption For Hiv Therapy

“…However, the reduction of total drug intake is limited if only RTI is used. In addition, the use of RTI alone may increase the risk of the emergence of drug resistant viral strains and other side effects [21]. Antiretroviral therapy that switches classes of drugs has been recently proposed as a potential strategy for treating metabolic complications [22][23][24].…”

Fluorometric Determination of 2′-β-Fluoro-2′,3′-dideoxyadenosine 5′-Triphosphate, the Active Metabolite of a New Anti-Human Immunodeficiency Virus Drug, in Human Lymphocytes

“…Dideoxynucleosides (ddN) 4 remain an integral part of current therapies for the treatment of individuals infected with the human immunodeficiency virus (HIV) (1,2). The emergence of drug-resistant HIV strains, however, poses serious problems for the use of these agents in effective combination regimens and new drugs are urgently needed (3)(4)(5).…”

“…The emergence of drug-resistant HIV strains, however, poses serious problems for the use of these agents in effective combination regimens and new drugs are urgently needed (3)(4)(5). 2Ј-␤-Fluoro-2Ј,3Ј-dideoxyadenosine (lodenosine, F-ddA), a new purine 1 This work was supported in part under a Cooperative Research and Development Agreement between the National Cancer Institute and U.S. Bioscience, Inc. 2 Present address: Liposome, 600 College Road, Princeton, NJ 08540.…”