Several approaches are being utilized to identify drugs that can block human immunodeficiency virus type-1 (HIV-1) replication in cell culture. Our studies show that combination therapy with two or more drugs interfering with different stages of the virus life cycle may be more useful in the treatment of acquired immunodeficiency syndrome (AIDS). Antisense oligonucleotides with or without modification of the phosphate residues can effectively block HIV-1 replication in cell culture. Combination of oligonucleotides defining the different sites show some synergistic affect. The antisense oligomers with the thiophosphate or cholesterol residues have been found to inhibit HIV-1 replication in chronically infected cells. Recent studies with ribozymes indicate that some of the structures can block HIV-1 replication in cell culture. A human T lymphotropic virus type-I (HTLV-I) strain has been isolated from the cerebrospinal fluid of a patient with tropical spastic paraparesis (TSP) and this virus isolate appears to be similar to but not identical to HTLV-I from adult T-cell leukemia (ATL). These HTLV-I isolates obtained from TSP patients show the release of high levels of interleukin-6 (II-6) and TNF-beta, as well as p55 and p75 subunits of II-2 receptor. Cloning and sequence analysis of one of the TSP isolates shows about 1% variation in nucleotide sequence from the prototype HTLV-L from ATL patients.
