Facts and Issues [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Bolstering the Immune System
Immunomodulator therapies act by restoring the body's impaired immune functions rather
than attacking the virus.This may be done by replacing depleted immune system cells, such
as CD4 or CD8 cells, or by stimulating normal immune functions.Therapeutic vaccines which
are believed to have this activity are currently being tested around the world.
Antiretroviral Therapies
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
The most widely used drugs in HIV treatment are the (dideoxy) nucleoside reverse
transcriptase inhibitors (NRTIs).These molecules closely resemble the nucleotides that serve
as the building blocks of DNA and RNA. A number of these drugs are licensed in North
America for HIV/AIDS including:
* zidovudine (azidothymidine, AZT; ZDV; Retrovir:T" GlaxoWellcome)
* zalcitabine (dideoxycytidine, ddC; Hivid:TM' Roche)
* didanosine (dideoxyinosine, ddl;Videx:TM Bristol-Myers Squibb)
* stavudine (D4T, Zerit:T Bristol-Myers Squibb)
* lamivudine (3TC, Epivir:TM GlaxoWellcome).
While all of these drugs have been approved for use, they all provide toxic effects in some
people. While they each have different profiles, diarrhea, nausea and vomiting have been
associated with all five drugs.The common side-effects are summarised below:
Drug Major side effects
AZT Hematologic toxicity (bone marrow disorders), such as
granulocytopenia (reduction in white blood cells) and anemia
ddC Peripheral neuropathy (disorder of the nerves of the hands and feet)
Pancreatitis (inflammation of the pancreas)
Oral ulcers
ddl Pancreatitis
Peripheral neuropathy
D4T Peripheral neuropathy
Pancreatitis
3TC Hematologic toxicity, such as anemia and neutropenia (reduction in a
type of white blood cell)
Protease Inhibitors
Protease inhibitors act at a different stage of the viral life cycle than NRTIs.They prevent the
creation of viral proteins late in the development of HIV, which results in the production of
non-infectious viral particles. Many companies are investigating this promising area of HIV
therapyThe most advanced of the protease inhibitors are:
* indinavir (Crixivan,T" Merck)
* nelfinavir (Viracept,TM Agouron)
* ritonavir (Norvir,' Abbott Laboratories)
* saquinavir (Invirase," Roche)
Other protease inhibitors under development include VX-478 (also known as 141W94;
Vertex and GlaxoWellcome) and SC-5215 I 1 (Searle/Monsanto).
Protease inhibitors appear to be far more potent and effective than any other type of
antiretroviral drug. In combination with NRTIs, they can lead to such large reductions in viral
load that the virus is sometimes no longer detectable by the assay used to measure it.This
does not necessarily mean that all the virus has been cleared from the bloodstream, but just
that there is too little of it to be detected by the test.