4.1. AIDS General Treatment Information: Newer Classes of Drugs
Description
This article is from the AIDS FAQ, by Dan Greening with numerous contributions by others.
4.1. AIDS General Treatment Information: Newer Classes of Drugs
Along with new data on existing therapies, more information is
available now on newer classes of drugs. These include nucleoside
analogs, non-nucleoside reverse transcriptase inhibitors, protease
inhibitors, and the tat inhibitor.
Nucleoside Analogs. New nucleoside analogs in clinical investigation
include d4T (stavudine) and 3TC. d4T has been much more extensively
studied and appears effective in raising CD4 count and lowering HIV
p24 antigen in a number of Phase 1 trials. It appears safe. Although
cases of pancreatitis have been reported, they seem to be extremely
rare. Neuropathy is the main toxicity but, again, it appears to be
somewhat less than with ddI or ddC. d4T may not be suitable for
combination with zidovudine as the two drugs have a negative
interaction limiting their activation within the cell. On the other
hand, d4T is a well-tolerated drug and may prove to be an alternative
to one or more of the existing nucleosides. 3TC also appear safe and
may be able to help restore sensitivity to zidovudine when the
patient's HIV has become resistant.
Reverse Transcriptase Inhibitors. The non-nucleoside reverse
transcriptase inhibitors, including nevirapine and the Merck "L" drug,
were recently thought to have limited value because they induce
high-level drug resistance so rapidly. At the Berlin conference,
however, one report showed that by increasing the dosage of nevirapine
to 400 mg daily, a dose well above the level of resistance, prolonged
benefit might be achieved. Also, it was shown that combining
zidovudine with nevirapine delays the onset of nevirapine
resistance. Thus, these drugs may still find a place in clinical
medicine. At the same time, convergent therapy, using three drugs
together, was disappointing because of simultaneous resistance to
zidovudine, ddI and non-nucleoside reverse transcriptase inhibitors.
Protease Inhibitors. Protease inhibitors seem to be gaining some
ground. In Phase 1 trials, several of these compounds have evident
antiretroviral activity, which was reflected in decreasing HIV p24 and
increasing CD4 cell counts. Clinical benefits have not been
established nor has the activity of these drugs used in combination
with zidovudine been described. Because several structurally different
protease inhibitors are being developed by different drug companies,
it is hoped that at least one of these compounds will become more
widely available soon for clinical use. Tat. While the protease
inhibitors appear encouraging, tat inhibitors appear to be clinically
inactive. In Phase 1 trials of the Hoffman LaRoche tat inhibitor,
little or no antiretroviral activity was seen and it is probably that
this class of drugs will not be developed further.
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