Impact of gag genetic determinants on virological outcome to boosted lopinavir-containing regimen in HIV-2-infected patients

Abstract

Objective: This study investigated the impact on virological outcome of the gag cleavage sites and the protease-coding region mutations in protease inhibitor-naive and protease inhibitor-experienced patients infected with HIV-2 receiving lopinavir (LPV) containing regimen. Design: Baseline gag and protease-coding region were sequenced in 46 HIV-2 group A-infected patients receiving lopinavir. Virological response was defined as plasma viral load less than 100 copies/ml at month 3. Associations between virological response and frequencies of mutations in gag [matrix/capsid (CA), CA/p2, p2/nucleocapsid (NC), NC/p1, p1/p6] and gag-pol (NC/p6) cleavage site and protease-coding region, with respect to the HIV-2ROD strain, were tested using Fisher's exact test. Results: Virological response occurred in 14 of 17 (82%) protease inhibitor-naive and 17 of 29 (59%) protease inhibitor-experienced patients. Virological failure was associated with higher baseline viral load (median: 6765 versus 1098 copies/ml, P=0.02). More protease-coding region mutations were observed in protease inhibitor-experienced compared with protease inhibitor-naive patients (median: 8 versus 5, P=0.003). In protease inhibitor-naive patients, T435A (NC/p6), V447M (p1/p6), and Y14H (protease-coding region) were associated with virological failure (P=0.011, P=0.033, P=0.022, respectively). T435A and V447M were associated with Y14H (P=0.018, P=0.039, respectively). In protease inhibitor-experienced patients, D427E (NC/p1) was associated with virological response (P=0.014). A430V (NC/p1) and I82F (protease-coding region) were associated with virological failure (P=0.046, P=0.050, respectively). Mutations at position 430 were associated with a higher number of mutations in protease-coding region (median: 10 versus 7, P=0.008). Conclusion: We have demonstrated, for the first time, an association between gag, gag-pol cleavage site and protease-coding region mutations, with distinct profiles between protease inhibitor-naive and protease inhibitor-experienced patients. These mutations might impact the virological outcome of HIV-2-infected patients receiving LPV-containing regimen. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.