Emergence of Drug Resistance in a Senegalese cohort of HIV-2 Infected Individuals Receiving Protease Inhibitor-based Therapy

Although rare worldwide, HIV-2 is endemic in West Africa. HIV-2 infection is characterized by lower transmission rates, a longer asymptomatic stage, lower plasma viral loads, slower decrease in CD4 cell count, and decreased mortality rate associated with AIDS compared to HIV-1. Nonetheless, a considerable number of untreated individuals will progress to clinical AIDS without antiretroviral therapy (ART). However, intrinsic resistance to many FDA-approved antiretrovirals complicates anti-HIV-2 therapy, and resistance pathways may differ from HIV-1. We undertook a study to identify common amino acid changes in protease from subjects failing protease inhibitor (PI)-based ART.

We PCR-amplified and analyzed HIV-2 protease consensus sequences from HIV-2 infected Senegalese subjects failing PI-based ART. These sequences were examined from amino acid changes known to confer PI-resistance in HIV-1.

The majority of subjects were on boosted lopinavir regimens. We observed a number of amino acid changes, which correspond to major HIV-1 resistance to lopinavir and other PIs. In particular, V47A, I54M, and I82F were found frequently. Accessory or minor mutations were also quite common, particularly at amino acid positions 10, 84, and 90. Where longitudinal samples were available, accumulation of putative PI resistance mutations was uncommon.

While the effect of these mutations on PI efficacy is known in HIV-1, it remains unclear in HIV-2. An understanding of the mutations that occur in the HIV-2 strains of individuals receiving ART and the effect of these mutations on ART efficacy is a first step in improving ART regimens for HIV-2 infected individuals to prevent progression to AIDS.