Abstract:
A specific rationale exists for the use of 'immunosupportive' drugs in patients (pts) infected with HIV. Even the most effective antiviral drug will not eliminate the need for such a treatment because the elective target of viral attack is the CD4+ lymphocyte. Numerous immunomodulators have been tested in HIV infection, including interleukin-2, granulocyte-macrophage colony-stimulating factor, IMREG-1, isoprinosine, sodium diethyldithiocarbamate (imuthiol), thymic hormones, and interferons (IFNs). The use of the last two of these agents in therapy for HIV-infected pts is reviewed. Studies on the effect of IFNs on retroviral replication in vitro showed that they reduce the production of new virions and lead to the formation of defective, noninfectious viral particles. The severe and profound dysfunction of the IFN system in HIV-infected pts led to the development of therapeutic regimens including alpha, beta, or gamma IFN. IFNs have been applied in AIDS and related syndromes as: (1) antiproliferative agents and (2) antivirals/immunomodulators. In one recent report, a dramatic fall in HIV p24 antigen was seen in 4/5 HIV+ homosexuals treated for chronic B hepatitis with 5-20 MU of alpha-IFN thrice weekly. Even more promising, though only preliminary, are results in which a synergistic inhibition of HIV has been observed when alpha-IFN and azidodeoxythymidine were combined in vitro. IFNs may be more effective with less toxicity if they can be delivered more directly (for example, intralymphatic administration) to the immune cells rather than administered conventionally. A role in the treatment of HIV infection may also be played by IFN inducers, such as mismatched double-stranded RNA (ampligen). Thymostimulin (TP-1) has been employed in clinical trials dating to 1984. In a randomized, comparative study, 58 pts with AIDS-related complex (ARC) received 6-mo of TP-1 therapy and were followed for 12 mo. Among the significant differences in immune parameters between these pts and controls were improved cutaneous delayed hypersensitivity (Multitest) and amelioration of clinical problems, such as weight loss, asthenia, and fever. In a multicenter trial, 100 pts with ARC were treated with TP-1 for 6 mo and followed for 2 yr; the CD3 subset was increased in treated pts, as were the CD8+ lymphocytes. Clinical improvement also was observed only in treated pts. (38 Refs)
Keywords: Adjuvants, Immunologic/*THERAPEUTIC USE Antiviral Agents/THERAPEUTIC USE Comparative Study Human HIV/*DRUG EFFECTS HIV Infections/*THERAPY Interferon Inducers/THERAPEUTIC USE Interferons/THERAPEUTIC USE Thymus Hormones/THERAPEUTIC USE Virus Replication/DRUG EFFECTS JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL 900530
M9051000
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