Effectiveness of current anti-HIV regimen in low-and middle-income countries
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Nevirapine (NVP) is a first-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). However, with the emergence of resistance mutations due to a low genetic barrier under NVP pressure, new (second generation) NNRTIs have been approved. Rilpivirine (RPV), a second generation NNRTI, is not frequently used in low- and middle- income countries (LMICs) that bear the major HIV burden. RPV has been co-formulated with tenofovir (TDF) and emtricitabine (FTC) and has been recommended for patients with viral loads <100,000 copies/mL, inhibiting viruses that are resistant to NVP. It is now being considered in many LMICs. To understand RPV efficacy in HIV-1 subtypes prevalent in LMICs, we cloned RT genes from patients infected with four different HIV-1 subtypes: subtype B (HIV-1B), subtype C (HIV-1C), and recombinant forms CRF01_AE and CRF02_AG. HIV-1B is most prevalent in western countries and accounts for only ~12% of all infections. However, HIV-1C, which accounts for ~52% of all HIV infections, is most prevalent in LMICs. In vitro inhibition assays were performed with the four patient-derived RTs. Our results show that overall, NVP binds RTs with lower affinity than RPV, suggesting that NVP has lower effectiveness than RPV. However, NV binds 02_AG RT with better affinity than RPV. Hence, NVP may still be effective for patients infected with 02_AG. Furthermore, RPV binding affinity with HIV-1C is lower than other subtypes. This result is consistent with clinical results, showing less efficacy of RPV among HIV-1C infected patients.