Mechanisms for HIV-1 Entry: Current Strategies to Interfere with This Step

Striking reductions in HIV replication, in vivo, by potent combinations of antiretroviral therapies (ART) are the most significant contributor to the decline in HIV morbidity and mortality. Unfortunately, HIV is not eradicated and rebounds quickly when therapy is stopped. Drug toxicity and the emergence of resistant virus cause virologic treatment failure in 40% to 60% of patients, underscoring the need for improved therapeutic modalities. Recent advances regarding the mechanisms and molecules involved in HIV entry have stimulated development of novel therapeutics. A phase I/IIB trial of an HIV-1 fusion inhibitor demonstrated potent inhibition of virus replication, providing proof of the concept that HIV entry can be blocked in vivo. The development of entry inhibitors and their addition to the armamentarium of HIV therapeutics will likely lead to more efficacious cocktails of antiretroviral agents for salvage therapy of antiretroviral-experienced patients, as well as for treatment of antiretroviral-naive patients.