Fact Sheet 470

Other Antiretroviral Drugs in Development

GENE THERAPIES
INTEGRASE INHIBITORS
MATURATION INHIBITORS
ZINC FINGER INHIBITORS
VIRAL DECAY ACCELERATOR
DRUGS NO LONGER IN DEVELOPMENT
 

NOTE: several fact sheets describe drugs that are being tested against HIV:
Fact sheet 410: nucleoside analog reverse transcriptase inhibitors (nukes)
Fact sheet 430: non-nucleoside analog reverse transcriptase inhibitors (NNRTIs or non-nukes)
Fact sheet 440: protease inhibitors
Fact sheet 460: attachment and fusion inhibitors
Fact sheet 480: immune therapies

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.

• HGTV43 by Enzo Biochem is an “antisense” therapy designed to produce CD4 cells (T-cells) that resist infection by HIV. It is in Phase I trials.

• M87o by EUFETS AG is a gene therapy that makes CD4 cells resist infection by HIV. It is being studied in a Phase I trial.

• Mifepristone (VGX410, also known as RU486) by Viral Genomix, interferes with the viral protein vpr. It is in a Phase I/II trial.

• Modified CD4 and CD8 cells by Cell Genesys are genetically modified to block attachment by HIV.

• RRz2 by Johnson & Johnson is a ribozyme that attacks HIV’s tat gene. It is in Phase II trials.

• VRX496 by VIRxSYS is in Phase II trials. It appears to bind to the RNA (genetic code) of HIV and disrupt it.

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) is now in a phase III study. The drug is used boosted with ritonavir or with Gilead's new booster GS9350. It is eliminated almost entirely via the feces so no dose adjustments are needed for patients with kidney problems.

S/GSK1349572 by ViiV Healthcare* is a once-daily integrase inhibitor. It is going into Phase III trials. It does not require boosting.

S/GSK1265744 by ViiV Healthcare* is an integrase inhibitor. It is in a Phase IIa study.
 

MATURATION INHIBITORS

A new type of drug inhibits the development of HIV’s internal structures in a new virus. The first “maturation inhibitor” was bevirimat by Myriad Pharmaceuticals. A backup compound was also in development. Early results showed good antiretroviral activity and tolerability. However, in 2010, Myriad announced that it was stopping development of maturation inhibitors. 

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.
 
SB-728-T by Sangamo BioSciences is a zinc finger gene therapy. It started Phase I clinical trials in 2009.

VIRAL DECAY ACCELERATOR

A new type of drug under development encourages mutations in HIV to the point that the virus is no longer functional. Unfortunately, development of the only drug of this type was discontinued in 2008.
 

DRUGS NO LONGER IN DEVELOPMENT

Bevirimat (PA457) by Myriad Genetics
BI201 by BioInvent
KP-1461 by Koronis
L870810 integrase inhibitor by Merck
S-1360, GW810781 (integrase inhibitor) by Shionogi and GlaxoSmithKline
Vivecon (MPC9055) by Myriad Genetics

 

 *ViiV Healthcare is a new HIV company. It is a joint venture of Pfizer and GlaxoSmithKline.