Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaoundé, Cameroon

• Published in: Scientific reports Vol. 7; no. 1; pp. 14136 - 14
• Main Authors: Teto, Georges, Tagny, Claude T., Mbanya, Dora, Fonsah, Julius Y., Fokam, Joseph, Nchindap, Emilienne, Kenmogne, Léopoldine, Njamnshi, Alfred K., Kanmogne, Georgette D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.10.2017; Nature Publishing Group
• Subjects: 38/77; 38/90; 38/91; 45/23; 45/29; 631/208/727; 692/699/255/1901; 82; Adolescent; Adult; Anti-HIV Agents - pharmacology; Antiretroviral drugs; Cameroon; CD4 antigen; CD4-Positive T-Lymphocytes - virology; Cross-Sectional Studies; Drug resistance; Drug Resistance, Viral - genetics; Female; gag Gene Products, Human Immunodeficiency Virus - genetics; Gene polymorphism; Genetic diversity; Genetic Variation; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - genetics; HIV-1 - pathogenicity; Humanities and Social Sciences; Humans; Male; Middle Aged; multidisciplinary; Mutation; Phylogeny; pol Gene Products, Human Immunodeficiency Virus - genetics; Polymorphism, Genetic; Protease inhibitors; Science; Science (multidisciplinary); Thymidine; Viral Load; Zidovudine; Cameroon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-14095-4

In HIV-1 subtype-B, specific mutations in Gag cleavage sites (CS) are associated with treatment failure, with limited knowledge among non-B subtypes. We analyzed non-B HIV-1 gag and pol (protease/reverse-transcriptase) sequences from Cameroonians for drug resistance mutations (DRMs) in the gag P2/NC CS, and pol major DRMs. Phylogeny of the 141 sequences revealed a high genetic diversity (12 subtypes): 67.37% CRF02_AG versus 32.6% non-CRF02_AG. Overall, 7.3% transmitted and 34.3% acquired DRMs were found, including M184V, thymidine analogue mutations (T215F, D67N, K70R, K219Q), NNRTIs (L100I, Y181C, K103N, V108I, Y188L), and PIs (V82L). Twelve subjects [10 with HIV-1 CRF02_AG, 8 treatment-naïve and 4 on 3TC-AZT-NVP] showed 3 to 4 mutations in the Gag P2/NC CS: S373Q/T/A, A374T/S/G/N, T375S/A/N/G, I376V, G381S, and R380K. Subjects with or without Gag P2/NC CS mutations showed no significant difference in viral loads. Treatment-naïve subjects harboring NRTI-DRMs had significantly lower CD4 cells than those with NRTI-DRMs on ART (p = 0.042). Interestingly, two subjects had major DRMs to NRTIs, NNRTIs, and 4 mutations in the Gag P2/NC CS. In this prevailing CRF02_AG population with little exposure to PIs (~3%), mutations in the Gag P2/NC CS could increase the risk of treatment failure if there is increased use of PIs-based therapy.