2005 has been a relatively quiet year on the anti-HIV drug front with only one new anti-HIV drug -- tipranavir (Aptivus) -- approved by the Food and Drug Administration (FDA). Fortunately, a look into the HIV drug development pipeline shows a handful of new and hopefully promising candidates in the later stages of clinical testing.
In July 2005, the FDA approved tipranavir, in combination with other anti-HIV drugs, for people with detectable viral loads and whose virus has developed resistance to other protease inhibitors (PIs). Tipranavir is taken as two 250mg capsules (500mg total) twice a day (total daily dose 1,000mg). It must be taken along with 200mg of ritonavir (Norvir) twice a day (total daily dose 400mg). This is twice the boosting dose of ritonavir typically used with other drugs, and it may increase the toxicity of the overall regimen. Tipranavir should be taken along with a meal. In clinical trials, tipranavir was effective in many people with PI-resistant virus, with most people experiencing significant drops in viral load and increases in CD4+ cell counts.
Some severe liver complications were seen in the same studies. People with chronic hepatitis B or C virus should exercise caution when taking tipranavir. Everyone taking tipranavir should have their doctors monitor their liver because liver problems were seen in some people without hepatitis. Other commonly reported side effects were nausea, vomiting, diarrhea and headache.
There is concern about tipranavir's lengthy list of drug interactions, which is further complicated by the required large ritonavir boost. People taking tipranavir should work closely with their medical provider and pharmacist to manage any drug possible drug interactions. More information can be found in Project Inform's publication, Drug Interactions.
For more information about tipranavir, read the publication, Tipranavir.
The FDA granted Tibotec Pharmaceuticals accelerated approval review for its new PI, TMC-114. It could be available in pharmacies sometime in late 2006. The company is launching an expanded access program for the drug that will begin in October 2006. For more information about how to apply for this program, call Project Inform's Infoline or watch for the announcement on www.projectinform.org.
TMC-114 is taken as 600mg once a day, along with 100mg of ritonavir. TMC-114 must be taken together with other anti-HIV drugs. Like tipranavir, TMC-114 has been shown to work in people whose virus has developed resistance to other PIs. Although it is too early to know all of the possible side effects for this drug, diarrhea and numbness in the mouth have been reported in trials.
Another important area of research right now is in a new class of anti-HIV drugs, called CCR5 antagonists, or entry inhibitors. This class of drugs attempts to stop HIV from using the receptor called CCR5 to get inside the cell. Three pharmaceutical companies have CCR5 drugs entering the final phase of clinical testing. However, one drug has encountered a severe liver toxicity problem, and it is unclear whether this drug has a future.
Looking a bit further into the future, there are some other approaches being studied. There are other kinds of entry inhibitors, integrase inhibitors and maturation inhibitors. There are also new drugs in the current classes, such as NRTIs and NNRTIs. For a list of clinical trials in your area, call 1-800-TRIALS-A (1-800-874-2572).
These new drugs may prove particularly vital for people who have taken many anti-HIV drugs and whose virus has developed resistance. These people (heavily pre-treated or salvage patients) stand to benefit the most from new strategies to block HIV from replicating. It is encouraging to see studies being done to benefit this group of people.