Implications of the discovery of HTLV-III for the treatment of AIDS.
The recent discovery of HTLV-III, a cytopathic member of the family of human T-cell lymphotropic viruses (HTLV), and its identification as the etiological agent of acquired immunodeficiency syndrome (AIDS) have important implications for the treatment of this disorder. The pathogenesis of AIDS involves the destruction of helper/inducer T-lymphocytes by active viral infection, and drugs which inhibit the replication of HTLV-III or monoclonal antibodies directed at viral antigens may be important components of future therapeutic strategies. There are a number of steps in the replication of HTLV-III which might potentially be susceptible to antiviral agents. One drug, suramin, which was originally developed as an antitrypanosomal agent, has been found to be an inhibitor of reverse transcriptase. This drug has been shown to block the infectivity and cytopathic effect of HTLV-III [Mitsuya, H., Popovic, M., Yarchoan, R., Matsushita, S., Gallo, R. C., and Broder, S. Science (Wash. DC), 266: 172-174, 1984]; in addition, it is able to block the in vitro replication of another member of the HTLV family, HTLV-I, at concentrations of 25 to 75 micrograms/ml. Lymphocyte proliferation in vitro is minimally inhibited at these concentrations of suramin, and the ratios of helper/inducer to cytotoxic/suppressor T-lymphocytes are not affected. Clinical trials are being initiated to study the effect of suramin on patients with AIDS. Evaluation of this and other antiviral treatments for AIDS will optimally involve direct assessment of its effects on HTLV-III replication in vivo. Recent evidence, however, suggests that these patients have a low level of viral replication in lymphoid tissue which may spontaneously fluctuate, making such evaluation complex.
Yarchoan
R
R
Mitsuya
H
H
Matsushita
S
S
Broder
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000382:microbiology; D002986:Clinical Trials as Topic; D004279:DNA, Viral / Q000378:metabolism; D017977:Deltaretrovirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D011995:Recombination, Genetic; D012192:Retroviridae Infections / Q000188:drug therapy*; D018894:Reverse Transcriptase Inhibitors; D013498:Suramin / Q000494:pharmacology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D013498:Suramin