Human T-lymphotropic virus type III is susceptible to attack at various sites during its replicative cycle. Inhibitors of reverse transcriptase activity, including suramin, antimoniotungstate (HPA-23), and trisodium phosphonoformate, have shown in-vitro activity against the virus in early clinical trials. Other significant antiviral agents are recombinant interferon alpha-A, ribavirin, and ansamycin. Double-blind, placebo-controlled clinical trials of interferon alpha, which inhibits viral replication at easily achievable serum levels, are underway. The development of optimal therapeutic regimens will require carefully controlled, multicenter collaborative trials with standardized criteria for evaluating responses. Prolonged treatment with combinations of antiviral and immunomodulating agents may be necessary for control of HTLV-III replication and for effective treatment of the acquired immunodeficiency syndrome.

PIP: This article outlines steps in the development of antiviral drugs, with particular emphasis on therapeutic regimens for infections with human T-lymphotropic virus type III (HTLV-III). Inhibitors of reverse transcriptase activity, including suramin, antimoniotungstate (HPA-23), and trisodium phosphonorformate have shown in vitro activity against HTLV-III in early clinical trials. Other significant antiviral agents are recombinant interferon alpha-A, ribavirin, and ansamycin. Recent evidence suggests that antibodies to envelope protein, gp120, may be essential for neutralization. Combinations of antiviral agents may prove additive or synergistic, eg, interferons plus reverse transcriptase inhibitors or interferons plus ribavirin. Alternating, sequential antiviral regimens may be useful in reducing resistance and toxicity. However, antiviral agents will not be effective without additonal immunostimulatory therapy for viral control and immune reconstitution.