HIV-1 GP41 genetic diversity, glycosylation and drug resistance associated mutations among enfuvirtide naïve patients in Kisii County, Kenya

Abstract

Objective: To determine the HIV-1 genetic diversity, glycosylation and drug associated mutations with aim in optimizing highly active  antiretroval therapy (HAART) treatment.

Design: A cross-sectional study

Setting: comprehensive HIV care clinics of Kisii Teaching and Referral Hospital, Kenya

Subjects: All HIV -1 patients

Method: A total of 21 plasma samples systematically collected among ENF drug
naïve HIV-1 patients from Kisii Teaching and Referral Hospital (KTRH). HIV1 gp41 gene was directly sequenced and sequences HIV-1 subtypes, glycosylation and drug resistance mutations determined using insilico tools.

Results: Phylogenetic analysis revealed A1 10(47.6%) as the most predominant HIV subtype followed by subtype C 5(23.8%) and 3  circulating recombinant forms (CRFs): A/C 2(9.5%), A/D 2(9.5%) and A2/D 2(9.5%). No major drug resistances associated mutations were  detected with minor intermediate resistance mutations; N42S and Q36K to Enfuvirtide (T20) being detected. However, accessory  mutations with varied proportions that are not associated with any drug resistance were detected. Viral glycosylation showed all sequences had glycosylation occurring at positions N611, N616, N637 except one with N625 mutations.

Conclusion: The detected  recombinants indicate possible mixed infections with detected mutation in gp41 gene likely to be associated with immunological and drug pressures. In addition, gp41 glycans plays a significant role in viral infectivity with pre-dominant N-glycan depending on viral strain.  Nevertheless, ENF remains effective against HIV-1 but this could be confirmed among drug experienced populations.