A new generation of anti-HIV drugs

Over 30 million people globally are estimated to be infected with HIV. The only means to reduce virus transmission and replication is prevention and antiretroviral (ARV) drugs. Currently, there are 27 licensed drugs that interfere with the normal function of HIV enzymes required to complete the viral replication cycle in infected cells.

However, the inherent ability of the virus to mutate its enzymes and escape immune attack has resulted in the emergence of drug-resistant strains. This clearly necessitates the continuous development of new drugs with a completely different mode of action.

In this context, the EU-funded 'Generation of a new class of antiretrovirals targeting HIV-cellular cofactors interactions' (HIVINNOV) project proposes a new class of ARV drugs that specifically target the virus–host interaction. Scientists will base their strategy on two molecules, cofactors of the integrase enzyme and capsid protein (CA).

Partners have contributed significantly to the discovery of these cofactors and the elucidation of their importance in the HIV life cycle. Small molecules that inhibit the integrase–LEDGF interaction have been developed and exhibit high ARV activity. Initially, they will be tested in vivo in a humanised mouse model of HIV infection and ultimately in phase I/IIa clinical trials. Results so far are promising, indicating that these molecules work both at the integration of the virus in target cells and during production of infectious particles.

With respect to the cofactor transportin, the consortium plans to delineate its structure, and through a high-throughput screen to identify compounds capable of blocking its interaction with CA. Promising hits have been obtained and these molecules will be further explored for their antiviral capacity.

HIVINNOV's new generation of antiviral drugs promises to overcome the current resistance problems associated with HIV treatment. Equally significant is the consortium's contribution to drug release in SSA through its active participation in phase II trials.