OTHER ANTIRETROVIRAL DRUGS IN DEVELOPMENT

NOTE: Several fact sheets describe drugs that are being tested against HIV: These drugs have not been approved by the Food and Drug Administration (FDA) for use against HIV.
GENE THERAPIES
Several products are being developed to interfere with genes used by HIV. One of them, mifepristone (VGX410, also known as RU486) by Viral Genomix, interferes with the viral protein vpr. It is in a Phase I/II trial. BI-201 by BioInvent is an antibody designed to block HIV's tat gene. It is in Phase I/II trials.
INTEGRASE INHIBITORS
After HIV's genetic code is changed from a single strand to a double strand by the reverse transcriptase enzyme, it gets inserted (integrated) into the genetic code of the infected cell. Then the HIV genetic code gets "read", producing new viruses. Scientists hope that integration will be another point in the HIV life cycle that can be targeted by drugs.

Elvitegravir (also known as Gilead 9137 and JTK-303) has completed a Phase II study. The drug is used boosted with ritonavir. It is eliminated almost entirely via the feces so no dose adjustments are needed for patients with kidney problems.

GSK364735 by GlaxoSmithKline and Shionogi is in Phase I trials.

Raltegravir (Isentress, MK-0518) by Merck is being studied in Phase III trials. It is available through an expanded access program. An FDA decision on approval of raltegravir is expected in mid October 2007.
MATURATION INHIBITORS
A new type of drug inhibits the development of HIV?s internal structures in a new virus. The first ?maturation inhibitor? being tested is bevirimat (PA457) by Panacos Pharmaceuticals. It is currently in Phase II trials. Early results show strong antiretroviral activity. Side effects are mild. PA457 will probably be a once-a-day drug.
ZINC FINGER INHIBITORS
The inner core of HIV is called the nucleocapsid. It is held together by structures called "zinc fingers". Zinc finger inhibitors (or zinc ejectors) are drugs that can break apart these structures and prevent the virus from functioning.

Scientists believe that the nucleocapsid core cannot mutate very easily, so a drug that works against zinc fingers might be effective for a long time. Unfortunately, zinc fingers are not only used by the HIV virus. Drugs that attack them could have serious side effects.

One zinc finger inhibitor - azodicarbonamide (ADA) - has been tested in a Phase I/II trial, but there are no recent reports on its development.
ANTISENSE DRUGS
These are a "mirror image" of part of the HIV genetic code. The drug locks onto the virus to prevent it from functioning. One antisense drug, HGTV43 by Enzo Therapeutics, is starting Phase II trials.

VIRxSYS is testing a gene therapy product, VRX496, in a Phase II trial. The product involves modifying a patient?s own CD4 cells with an ?antisense? factor and then reintroduced to the patient.

DRUGS NO LONGER IN DEVELOPMENT
The following drugs are no longer being developed for use against HIV:
  • L870810 integrase inhibitor by Merck
  • S-1360 (GW810781) (integrase inhibitor) by Shionogi and GlaxoSmithKline