Drug resistance and Sl phenotype; implications for chemotherapy.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Drug resistance and Sl phenotype; implications for chemotherapy.

Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:22 (abstract no. FPI-2). Unique Identifier : AIDSLINE ASHM5/94348938
Richman DD; University of California San Diego 92093-0679.

Abstract: The clinical and therapeutic significance of the emergence of diminished drug susceptibility has been difficult to elucidate. Two recent studies, one with nucleosides and one with a non-nucleoside reverse transcriptase inhibitor (NNRTI) address this issue. A multicenter virologic analysis of ACTG 116B/117 documented that the acquisition of AZT resistance was a highly negative prognostic marker although the implications for therapeutic decisions between AZT and ddl are unclear. A study of the NNRTI, nevirapine, more clearly provides compelling evidence that loss of drug activity can be attributed to the acquisition of drug resistance. In addition when drug doses were increased to generate plasma levels that exceeded the susceptibility of the resistant virus, sustained antiviral activity was observed. This may have important implications for the development of many antiretroviral drugs, including protease inhibitors. Moreover, the combination of nevirapine with AZT resulted in a dramatic shift in the patterns of drug resistance mutations utilised by the virus. The syncytium-inducing (S.I.) phenotype of HIV evolves in just over one-half of patients during their course of HIV infection, with the proportion progressively increasing as CD4 cells decline. The acquisition of the SI phenotype accelerates the rate of CD4 cell decline 3 fold, thus shortening the natural history of HIV infection in those patients. Of note however, the SI phenotype does not increase the relative risk of mortality per se independent of its effort on CD4 cell decline. The relative risk of the SI phenotype exceeds the relative benefits of any antiretroviral drugs identified to date. It is thus essential that this viral phenotype be considered in the assessment of chemotherapeutic or immunologic interventions.

Keywords: Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC USE Clinical Trials CD4-Positive T-Lymphocytes/IMMUNOLOGY Didanosine/ADVERSE EFFECTS/THERAPEUTIC USE Drug Therapy, Combination Human HIV Infections/*DRUG THERAPY/IMMUNOLOGY/MICROBIOLOGY Leukocyte Count/DRUG EFFECTS Prognosis Pyridines/ADVERSE EFFECTS/THERAPEUTIC USE RNA-Directed DNA Polymerase/*ANTAGONISTS & INHIB Zidovudine/ADVERSE EFFECTS/THERAPEUTIC USE ABSTRACT
941230
M94C4289

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1994. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1994. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .