Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Antiretroviral therapy of HIV: a virologists perspective.
Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:19 (abstract no. TPI-4). Unique Identifier : AIDSLINE ASHM5/94348934 Corey L; University of Washington, Seattle.
Abstract:
While the availability of nucleoside reverse transcriptase (RT) inhibitors have revolutionised care of HIV infected persons, controversy exists about the overall utility of these medications. When should therapy be initiated? With what agent? When should alternative therapy be utilised, what alternative should be given and when should antiretrovirals be stopped? Much of this controversy exists (in this persons opinion) because the expectations and questions asked in often quoted studies have differed. RT inhibitors differ from most other antimicrobials in that they inhibit the frequency of newly infected cells, and do not inhibit production from persistently infected cells. Moreover, they are all prodrugs with the active triphosphate derivative requiring intracellular metabolism. For AZT and D4T this is dependent upon cell cycle activation. As such, in vivo inhibition of HIV is only partial. All clinical trials of RT inhibitors have stratified patients by CD4 cell count. However, a variety of virologic assays indicate that viral load whether measured in plasma or PBMCs may differ by as much as 4 logs among persons with similar CD4 cell counts. In addition, RT inhibitors alone inhibit replication by about 1/2 log and in combination by 1-1.5 log. As such, the varied effects of these compounds in large scale trials is not unexpected. It appears that whether one uses monotherapy, combination therapy or sequential therapy, the duration of effectiveness is greatest the earlier one initiates therapy. In addition, adding or switching to alternative therapy after AZT appears to be most effective when CD4 counts are > 150 cells/mm3. In AZT treated patients, the effectiveness of any of these current nucleosides (ddl or ddC) in those with < 100 CD4 cells is unclear. In these patients prophylaxis of opportunistic infections should be optimised. The data leading to the above observations will be discussed.
Keywords: Antiviral Agents/*THERAPEUTIC USE CD4-Positive T-Lymphocytes/DRUG EFFECTS Drug Therapy, Combination Human HIV Infections/*DRUG THERAPY Leukocyte Count/DRUG EFFECTS Prodrugs/THERAPEUTIC USE RNA-Directed DNA Polymerase/*ANTAGONISTS & INHIB Virus Replication/DRUG EFFECTS Zidovudine/THERAPEUTIC USE ABSTRACT 941230
M94C4293
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
