Anti-infectives: clinical progress of HIV-1 integrase inhibitors.
BACKGROUND
HIV-1 integrase (IN) represents a therapeutically advantageous viral target to treat HIV/AIDS in the clinic. Over a decade of progress in the field has resulted in IN inhibitor chemical classes that display specificity for strand transfer catalysis of the enzyme, thus blocking viral DNA integration into host cell nuclear DNA, an essential step for viral infectivity.


OBJECTIVE
In this manuscript we provide an update on recent HIV-1 IN inhibitors that have been clinically evaluated, which include MK-0518, MK-2048, GS-9137, GS-9160, GS-9224, GSK-364735, and BMS-707035. The information presented here can aid in the IN drug developmental process.


METHODS
We have limited the scope of this review to information available on the clinical evaluation of promising strand transfer-specific IN inhibitors and their potential drug-drug interaction profiles with other antiretroviral agents.


CONCLUSIONS
The development of strand transfer-specific inhibitor classes is an important achievement for the IN drug design and development field. However, continued drug development is needed given that the ability of HIV to replicate under therapeutic pressure will undoubtedly lead to the emergence of IN drug-resistant viral strains.
Al-Mawsawi
Laith Q
LQ
University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Los Angeles, California 90089, USA.
Al-Safi
Rasha I
RI
Neamati
Nouri
N
D044966:Anti-Retroviral Agents / Q000494:pharmacology; D002986:Clinical Trials as Topic; D015195:Drug Design; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans
D044966:Anti-Retroviral Agents; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase