HIV-1 is the causative agent of AIDS and presently infects approximately 33 million persons worldwide with approximately 1.9 million infected persons in North America alone. Recent studies have shown that HIV/AIDS has become a global epidemic that is not under control in developing nations. The rapid emergence of drug-resistant strains of HIV throughout the world has placed a priority on innovative approaches for the identification of novel drug targets that may lead to a new class of anti-retroviral therapies.
The virus contains a 10-kb single-stranded RNA genome that encodes three major classes of gene products that include: (i) structural proteins (Gag, Pol and Env); (ii) essential trans-acting proteins (Tat, Rev); and (iii) “auxiliary” proteins that are not required for efficient virus replication in permissive cells (Vpr, Vif, Vpu, Nef) [reviewed in (1)]. There has been a heightened interest in Vif as an antiviral target because of the discovery that the primary function of Vif is to overcome the action of a cellular antiviral protein known as APOBEC3G or A3G (2).
In 1984, it was determined that HIV was the virus that causes AIDS and researchers declared that a vaccine would be available within two years. Nearly three decades later, there is still no vaccine available and the primary focus remains on developing therapeutics for those already infected. Currently, the primary HIV preventative is the combination treatment known as STRIBILD™. This medication contains 3 components of the highly active anti-retroviral therapy (HAART) regimen (i.e., one integrase (IN) and two reverse transcriptase (RT) inhibitors). However, HIV strains with resistance to some or all of these components had already emerged prior to the availability of STRIBILD™, thus rendering it ineffective against such strains. Furthermore, not only has HIV developed resistance to STRIBILD™ components, but it also has developed resistance to all HAART medications to date, including inhibitors of all HIV enzymatic and viral entry targets. In fact, it is common to see drug resistance even among treatment-naïve individuals worldwide, emphasizing that at least some of the current drugs have limited efficacy in a subset of untreated, infected individuals. The barrier to developing resistance to HIV drugs is low and often a single codon change in the targeted protein is sufficient to cause resistance to more than one inhibitor of the same class (i.e., M46I/L/V in the HIV protease confers resistance to 7 out of 8 inhibitors). The ever-present problem of drug resistance together with the lack of success in developing a vaccine accentuate the need for novel HIV prevention and treatment strategies that are unlikely to develop resistance.
The present invention is directed toward overcoming these and other deficiencies in the art.