Journal of Antivirals & Antiretrovirals
Open Access

Abstract

The Prediction of Integrase Inhibitors Efficacy in Third Line Regimen after First and Second Line Antiretroviral Therapy Failure in Senegal

Edmond Tchiakpe, Abou Abdallah Malick Diouara, Moussa Thiam,

The optimal efficacy of the INI depends on the backbone of nucleoside inhibitors, which seems to be challenged in a context of late switch and drug resistance mutations accumulations. It is also known that before using the 3rd line regimen, a drug resistance testing is recommended. This paper aims to predict the efficacy of integrase inhibitors in third line regimen after 1st and 2nd line failure and to describe the HIV-1 genetic diversity. A cross sectional study was conducted in 52 Senegalese HIV-1 infected patients. After viral load (VL) quantification, a drug resistance testing was performed for patients with VL ≥ 3log10 copies/ml. ART combinations and DRM for each patient were considered to predict possible future regimens. The phylogenetic analysis was done using Seaview v4.4.2 and Simplot v3.5.1 software’s. The medians of virological failure (VL) and treatment follow up duration in 1st and 2nd line ART were respectively 4.09 vs 1.6 log10 copies/ml and 55 vs 32 months. The most common therapeutic combinations were 2 NRTI (D4T/AZT+3TC)+1NNRTI (EFV/NVP) and 2 NRTI (TDF+3TC/FTC)+1 PI (LPVr) respectively at 1st and 2nd line. A number of 29 and 13 in VF (VL ≥ 3log10 copies/ml) were genotyped on Protease and partial RT genes at 1st and 2nd line ART; and 12 among the 13 were genotyped in integrase gene. The TAMs (85.5 vs 90.9%), M184V (32.9 vs 27.3%) and K103N (24.2 vs 33.3%) were predominant both for the 1st and 2nd line therapy. No major DRM was found in integrase gene. The phylogenetic analysis shows a predominance of CRF_02AG both in protease-partial RT and integrase genes. Third line regimen including NRTI and new generation of NNRTI is possible only for 6/12 patients failing in second line ART. These findings highlighted the importance to reinforce virological monitoring of HIV-1 infected patients and to consider the drug resistance results for a third line regimen.