AIDS TREATMENT NEWS Issue #183, September 17, 1993
John S. James
The BHAP compounds are part of a class of drugs called non- nucleoside reverse transcriptase (RT) inhibitors. Unfortunately, a major problem with all the known drugs which work this way is that HIV can quickly become resistant to them. But different kinds of resistance (different mutations on the virus) develop with different non-nucleoside drugs; the different drugs of this class are not interchangeable. This suggests that useful combination treatments including these drugs may be possible. (Also, low-level drug resistance can sometimes be overcome by increasing the dose.)
The recent Ateviridine article reported that:
* Ateviridine was found to be effective against a number of clinical isolates (HIV taken from patients), regardless of whether or not the virus strains are AZT resistant or ddI resistant. No virus tested was resistant to both ateviridine and AZT, or to both ateviridine and ddI. The authors suggested that such cross resistance might not occur. (However, only a few different strains were tested and reported in this paper.)
* Laboratory tests showed that the combination of ateviridine and AZT might be useful against AZT-resistant viruses. This combination was synergistic against AZT-resistant viruses (meaning that the combination worked better than would be expected by adding how well the drugs worked separately). But against AZT-susceptible virus, the combination was only additive. With ddI the result was different; the combination was additive whether or not the virus was resistant to ddI.
The authors conclude that ateviridine might be useful in combination with AZT -- especially in the common case where patients have already been using AZT alone for some time, and are likely to have developed strains of AZT-resistant virus.
[Campbell TB, Young RK, Eron JJ, D'Aquila RT, Tarpley WG, and Kuritzkes DR. Inhibition of human immunodeficiency virus type 1 replication in vitro by the bisheteroarylpiperzine ateviridine (U-87201E) in combination with zidovudine or didanosine. JOURNAL OF INFECTIOUS DISEASES. August 1993; volume 168, pages 318-326.]
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