Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon
Autoři:
Henry Dilonga Meriki aff001; Kukwah Anthony Tufon aff001; Damian Nota Anong aff001; Pascal Nji Atanga aff004; Irene Ane Anyangwe aff001; Fidelis Cho-Ngwa aff005; Theresa Nkuo-Akenji aff001
Působiště autorů:
Department of Microbiology and Parasitology, University of Buea, Buea, SW Region, Cameroon
aff001; BioCollections Worldwide Inc., Regional Office, Buea, SW Region, Cameroon
aff002; Department of Biochemistry and Molecular Biology, University of Buea, Buea, SW Region, Cameroon
aff003; Cameroon Baptist Convention Health Service, Mutengene, South West Region, Cameroon
aff004; Laboratory Department, Buea Regional Hospital, Buea, SW Region, Cameroon
aff005
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0225575
Souhrn
Background
Antiretroviral therapy (ART) has improved the survival of HIV infected persons. However, rapid scale-up of ART and the high HIV-1 genetic variability, has greatly influenced the emergence of drug-resistant strains. This constitutes a potential threat to achieving the UNAIDS’ 90-90-90 goals by 2020. We investigated the prevalent HIV-1 genotypes, drug resistance-associated mutations and assessed some predictors of the occurrence of these mutations.
Methods
This was a hospital-based cross-sectional study conducted between October 2010 and June 2012. Participants were consecutively enrolled from selected HIV treatment centers of the Southwest and Northwest regions of Cameroon. Viral load was determined with the automated Abbott Real-time HIV-1 m2000rt System. HIV genotyping and antiretroviral resistance mutations analysis were performed using Bayer’s HIV-1 TRUGENE™ Genotyping Kit and OpenGene DNA Sequencing system. The drug resistance mutation was interpreted with the Stanford HIV database. Epidemiological data were obtained using pre-tested semi-structured questionnaires.
Results
Of the 387 participants, 239 were successfully genotyped. The median age of these participants was 33 years (interquartile range, IQR: 28–40 years), and a majority (65.7%) were female. A total of 29.3% of the participants were receiving ART. The median duration of ART was 10.5 months (IQR: 4–17.25 months). The median CD4 count and log10 viral load of study participants were 353.5 cells/ml (IQR:145–471) and 4.89 copies/ml (IQR: 3.91–5.55) respectively. CRF02 (A/G) (69%) was the most prevalent subtype followed by G (8.2%) and F (6.7%). Overall, resistance mutations were present in 37.1% of ART-experienced and 10.7% of ART-naive patients. Nucleoside reverse transcriptase inhibitors (NRTI) mutations occurred in 30% of ART-experienced and 2.4% of ART-naïve patients, while non-nucleoside reverse transcriptase inhibitors (NNRTI) mutations occurred in 34.2% of ART-experienced and 10.1% of -naïve patients. M184V (8.4%, 20/239) and K103N (5.4%, 13/239) were the most prevalent mutations. Major protease inhibitor mutations occurred in 3 (1.3%) out of the 239 sequences. The duration of ART independently predicted the occurrence of resistance mutation among ART-experienced patients.
Conclusion
The high resistance to NNRTIs, which are the main support to the backbone (NRTIs) first-line antiretroviral regimen in Cameroon, has prompted the need to rollout an integrase strand transfer inhibitor regimen (containing Dolutegravir) with a higher genetic barrier to resistance as the preferred first line regimen.
Klíčová slova:
Viral load – HIV-1 – Antiretrovirals – Antimicrobial resistance – Mutation databases – Reverse transcriptase inhibitors
Zdroje
1. World Health Organisation. HIV/AIDS: Key facts. In: World Health Organisation [Internet]. 2018 [cited 20 Aug 2018]. Available: http://www.who.int/news-room/fact-sheets/detail/hiv-aids
2. Castro-Nallar E, Crandall KA, Pérez-Losada M. Genetic diversity and molecular epidemiology of HIV transmission. Future Virol. 2012;7: 239–252. doi: 10.2217/fvl.12.4
3. Arimide DA, Abebe A, Kebede Y, Adugna F, Tilahun T, Kassa D, et al. HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003–2013. Blackard J, editor. PLoS One. Public Library of Science; 2018;13: e0205446. doi: 10.1371/journal.pone.0205446 30304061
4. Maldarelli F, Kearney M, Palmer S, Stephens R, Mican J, Polis MA, et al. HIV Populations Are Large and Accumulate High Genetic Diversity in a Nonlinear Fashion. J Virol. American Society for Microbiology (ASM); 2013;87: 10313–10323. doi: 10.1128/JVI.01225-12 23678164
5. Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency virus (HIV)-2 infection. Clin Infect Dis. 2011;52: 780–7. doi: 10.1093/cid/ciq248 21367732
6. Lal RB, Chakrabarti S, Yang C. Impact of genetic diversity of HIV-1 on diagnosis, antiretroviral therapy & vaccine development. Indian Journal of Medical Research. 2005. pp. 287–314. 15817945
7. Shao Y, Williamson C. The HIV-1 epidemic: Low- to middle-income countries. Cold Spring Harb Perspect Med. 2012;2: 1–17. doi: 10.1101/cshperspect.a007187 22393534
8. Robertson DL. HIV-1 Nomenclature Proposal. Science (80-). 2000;288: 55d – 55. doi: 10.1126/science.288.5463.55d 10766634
9. Gao F, Vidal N, Li Y, Trask SA, Chen Y, Kostrikis LG, et al. Evidence of Two Distinct Subsubtypes within the HIV-1 Subtype A Radiation. AIDS Res Hum Retroviruses. Mary Ann Liebert, Inc; 2001;17: 675–688. doi: 10.1089/088922201750236951 11429108
10. Lihana RW, Ssemwanga D, Abimiku A, Ndembi N. Update on HIV-1 diversity in Africa: A decade in review. AIDS Rev. 2012;14: 83–100. 22627605
11. Akrim M, Lemrabet S, Elharti E, Gray RR, Tardy JC, Cook RL, et al. HIV-1 Subtype distribution in morocco based on national sentinel surveillance data 2004–2005. AIDS Res Ther. 2012;9: 5. doi: 10.1186/1742-6405-9-5 22333070
12. Bouzeghoub S, Jauvin V, Recordon-Pinson P, Garrigue I, Amrane A, Belabbes el H, et al. High diversity of HIV type 1 in Algeria. AIDS Res Hum Retroviruses. 2006;22: 367–372. doi: 10.1089/aid.2006.22.367 16623641
13. El Sayed NM, Gomatos PJ, Beck-Sague CM, Dietrich U, von Briesen H, Osmanov S, et al. Epidemic transmission of human immunodeficiency virus in renal dialysis centers in Egypt. J Infect Dis. 2000;181: 91–97. doi: 10.1086/315167 10608755
14. Vallari A, Holzmayer V, Harris B, Yamaguchi J, Ngansop C, Makamche F, et al. Confirmation of Putative HIV-1 Group P in Cameroon. J Virol. 2011;85: 1403–1407. doi: 10.1128/JVI.02005-10 21084486
15. Vallari A, Bodelle P, Ngansop C, Makamche F, Ndembi N, Mbanya D, et al. Four New HIV-1 Group N Isolates from Cameroon: Prevalence Continues to Be Low. AIDS Res Hum Retroviruses. 2010;26: 109–115. doi: 10.1089/aid.2009.0178 20059396
16. Plantier J-C, Leoz M, Dickerson JE, De Oliveira F, Cordonnier F, Lemée V, et al. A new human immunodeficiency virus derived from gorillas. Nat Med. Nature Publishing Group; 2009;15: 871–872. doi: 10.1038/nm.2016 19648927
17. Carr JK, Wolfe ND, Torimiro JN, Tamoufe U, Mpoudi-Ngole E, Eyzaguirre L, et al. HIV-1 recombinants with multiple parental strains in low-prevalence, remote regions of Cameroon: Evolutionary relics? Retrovirology. 2010;7: 39. doi: 10.1186/1742-4690-7-39 20426823
18. Ndembi N, Takehisa J, Zekeng L, Kobayashi E, Ngansop C, Songok EM, et al. Genetic diversity of HIV type 1 in rural eastern Cameroon. J Acquir Immune Defic Syndr. 2004;37: 1641–1650. doi: 10.1097/00126334-200412150-00019 15577423
19. Powell RLR, Urbanski MM, Burda S, Kinge T, Nyambi PN. High frequency of HIV-1 dual infections among HIV-positive individuals in Cameroon, West Central Africa. J Acquir Immune Defic Syndr. 2009;50: 84–92. doi: 10.1097/QAI.0b013e31818d5a40 19295338
20. Zhong P, BUrda S, Konings F, Urbanski M, Ma L, Zekeng L, et al. Genetic and biological properties of HIV type 1 isolates prevalent in villagers of the Cameroon equatorial rain forests and grass fields: further evidence of broad HIV type 1 genetic diversity. AIDS Res Hum Retroviruses. 2003;19: 1167–78. doi: 10.1089/088922203771881284 14717120
21. Lessells RJ, Katzenstein DK, de Oliveira T. Are subtype differences important in HIV drug resistance? Curr Opin Virol. Elsevier B.V.; 2012;2: 636–43. doi: 10.1016/j.coviro.2012.08.006 23006584
22. Skhosana L, Steegen K, Bronze M, Lukhwareni A, Letsoalo E, Papathanasopoulos MA, et al. High prevalence of the k65r mutation in hiv-1 subtype c infected patients failing tenofovir-based first-line regimens in south africa. PLoS One. 2015;10. doi: 10.1371/journal.pone.0118145 25659108
23. Kiepiela P, Manasa J, Moosa MY, Moodley P, Gordon M, Parikh UM, et al. HIV drug resistance patterns at the epicentre of the HIV-1 epidemic in Kwazulu-Natal, South Africa 2003–2013 [Internet]. Journal of AIDS and Clinical Research. 2014. p. 299. doi: 10.4172/2155-6113.1000299
24. Bunupuradah T., Ananworanich J., Chetchotisakd P., Kantipong P., Jirajariyavej S., Sirivichayakul S., Munsakul W., Prasithsirikul W., Sungkanuparph S., Bowonwattanuwong C., Klinbuayaem V., Petoumenos S., Hirschel B. BS and RK. Etravirine and rilpivirine resistance in HIV-1 subtype CRF01-AE-infected adults failing non-nucleoside reverse transcriptase inhibitor-based regimens. Antivir Ther. 2011;16: 1113–1121. doi: 10.3851/IMP1906 22024527
25. Carvajal-Rodríguez A, Crandall KA, Posada D. Recombination favors the evolution of drug resistance in HIV-1 during antiretroviral therapy. Infect Genet Evol. NIH Public Access; 2007;7: 476–483. doi: 10.1016/j.meegid.2007.02.001 17369105
26. Joint United Nations Programme on HIV/AIDS (UNAIDS). 90-90-90 An ambitious treatment target to help end the AIDS epidemic [Internet]. http://www.Unaids.Org/Sites/Default/Files/Media_Asset/90-90-90_En_0.Pdf. 2014. doi: 10.7448/IAS.16.4.18751
27. Falagas ME, Zarkadoulia E a, Pliatsika P a, Panos G. Socioeconomic status (SES) as a determinant of adherence to treatment in HIV infected patients: a systematic review of the literature. Retrovirology. 2008;5: 13. doi: 10.1186/1742-4690-5-13 18241330
28. Reda AA, Biadgilign S. Determinants of Adherence to Antiretroviral Therapy among HIV-Infected Patients in Africa. AIDS Res Treat. 2012;2012: 574656. doi: 10.1155/2012/574656 22461980
29. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol. 2018; doi: 10.1093/molbev/msy096 29722887
30. WHO, CDC, TheGlobalFund. HIV Drug Resistance Report 2017 Trends Quality Action [Internet]. HIV Drug Resistance Report 2017 Trends Quality Action. 2017. Available: https://apps.who.int/iris/bitstream/handle/10665/255896/9789241512831-eng.pdf?sequence=1
31. Ragupathy V, Zhao J, Wood O, Tang S, Lee S, Nyambi P, et al. Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon. Virol J. 2011;8: 185. doi: 10.1186/1743-422X-8-185 21513545
32. Agyingi L, Barengolts D, Mayr L, Kinge T, MBida M, Nyambi P. Genetic variability and drug resistance mutations in HIV-1 infected individuals on HAART or drug naïve in Limbe, Cameroon. Retrovirology. BioMed Central Ltd; 2012;9: 158. doi: 10.1186/1742-4690-9-S2-P158
33. Ceccarelli L, Salpini R, Moudourou S, Cento V, Santoro MM, Fokam J, et al. Characterization of drug resistance mutations in na??ve and ART-treated patients infected with HIV-1 in Yaounde, Cameroon. J Med Virol. 2012;84: 721–727. doi: 10.1002/jmv.23244 22431019
34. Ndongmo CB, Pieniazek D, Holberg-Petersen M, Holm-Hansen C, Zekeng L, Jeansson SL, et al. HIV genetic diversity in Cameroon: possible public health importance. AIDS Res Hum Retroviruses. 2006;22: 812–816. doi: 10.1089/aid.2006.22.812 16910839
35. Teto G, Tagny CT, Mbanya D, Fonsah JY, Fokam J, Nchindap E, et al. 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. Sci Rep. 2017;7. doi: 10.1038/s41598-017-14095-4 29074854
36. Nanfack AJ, Redd AD, Bimela JS, Ncham G, Achem E, Banin AN, et al. Multimethod Longitudinal HIV Drug Resistance Analysis in Antiretroviral-Therapy-Naive Patients. J Clin Microbiol. 2017;55: 2785–2800. doi: 10.1128/JCM.00634-17 28659324
37. Mondinde Ikomey G, Claire M, Assoumou O, Gichana JO, Njenda D, Mikasi SG, et al. Observed HIV drug resistance associated mutations amongst naïve immunocompetent children in Yaoundé, Cameroon [Internet]. www.germs.ro • GERMS. 2017. Available: www.germs.ro doi: 10.18683/germs.2017.1124 29264355
38. Medeiros MS, Arruda EAG, Guerrant RL, Brown C, Hammarskjold M-L, Rekosh D, et al. Genotype testing and antiretroviral resistance profiles from HIV-1 patients experiencing therapeutic failure in northeast Brazil. Brazilian J Infect Dis. 2007;11: 390–4. Available: http://www.ncbi.nlm.nih.gov/pubmed/17873990
39. Torimiro JN, Takou D, Salpini R, Nanfack A, Fokam J, Cappelli G, et al. Population Level Drug Resistance Mutations in HIV Type 1 Protease and Reverse Transcriptase in Cameroon: 1995 to 2010 Review. JAIDS J Acquir Immune Defic Syndr. 2011;56: 83. doi: 10.1097/QAI.0b013e3181fdc928 21084997
40. Kurt Yilmaz N, Swanstrom R, Schiffer CA. Improving Viral Protease Inhibitors to Counter Drug Resistance. Trends Microbiol. NIH Public Access; 2016;24: 547–557. doi: 10.1016/j.tim.2016.03.010 27090931
41. Mata-Munguía C, Escoto-Delgadillo M, Torres-Mendoza B, Flores-Soto M, Vázquez-Torres M, Gálvez-Gastelum F, et al. Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis. BMC Bioinformatics. BioMed Central; 2014;15: 72. doi: 10.1186/1471-2105-15-72 24629078
42. Coffin J, Swanstrom R. HIV Pathogenesis: Dynamics and Genetics of Viral Populations and Infected Cells. Cold Spring Harb Perspect Med. 2013;3: a012526–a012526. doi: 10.1101/cshperspect.a012526 23284080
43. Delaugerre C. Genetic barrier to antiretroviral drug-resistance. Focus on raltegravir, the first integrase inhibitor. Médecine Mal Infect. 2010;40: S1–S10. doi: 10.1016/S0399-077X(10)70001-9
44. d’Aquin Toni T, Masquelier B, Minga A, Anglaret X, Danel C, Coulibaly A, et al. HIV-1 antiretroviral drug resistance in recently infected patients in Abidjan, Côte d’Ivoire: A 4-year survey, 2002–2006. AIDS Res Hum Retroviruses. 2007;23: 1155–1160. doi: 10.1089/aid.2007.0072 17919113
45. Brooks K, Diero L, DeLong A, Balamane M, Reitsma M, Kemboi E, et al. Treatment failure and drug resistance in hiv-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya. J Int AIDS Soc. 2016;19: 1–10. doi: 10.7448/IAS.19.1.20798 27231099
46. Aghokeng AF, Kouanfack C, Eymard-Duvernay S, Butel C, Edoul GE, Laurent C, et al. Virological outcome and patterns of HIV-1 drug resistance in patients with 36 months’ antiretroviral therapy experience in Cameroon. J Int AIDS Soc. 2013;16: 1–8. doi: 10.7448/IAS.16.1.18567 24008177
47. Lin B, Sun X, Su S, Lv C, Zhang X, Lin L, et al. HIV drug resistance in HIV positive individuals under antiretroviral treatment in Shandong Province, China. PLoS One. Public Library of Science; 2017;12: e0181997. doi: 10.1371/journal.pone.0181997 28750025
48. Semvua SK, Orrell C, Mmbaga BT, Semvua HH, Bartlett JA, Boulle AA. Predictors of non-adherence to antiretroviral therapy among HIV infected patients in northern Tanzania. PLoS One. Public Library of Science; 2017;12: e0189460. doi: 10.1371/journal.pone.0189460 29252984
49. Siefried KJ, Mao L, Kerr S, Cysique LA, Gates TM, McAllister J, et al. Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression. PLoS One. Public Library of Science; 2017;12: e0174613. doi: 10.1371/journal.pone.0174613 28369066
50. Parienti J-J, Massari V, Descamps D, Vabret A, Bouvet E, Larouze B, et al. Predictors of Virologic Failure and Resistance in HIV-Infected Patients Treated with Nevirapine- or Efavirenz-Based Antiretroviral Therapy. Clin Infect Dis. 2004;38: 1311–1316. doi: 10.1086/383572 15127346
51. Lehman JS, Carr MH, Nichol AJ, Ruisanchez A, Knight DW, Langford AE, et al. Prevalence and public health implications of state laws that criminalize potential HIV exposure in the United States. AIDS Behav. Springer New York LLC; 2014;18: 997–1006. doi: 10.1007/s10461-014-0724-0 24633716
52. Meriki HD, Tufon K a, Afegenwi MH, Nyindem B a, Atanga PN, Anong DN, et al. Immuno-haematologic and virologic responses and predictors of virologic failure in HIV-1 infected adults on first-line antiretroviral therapy in Cameroon. Infect Dis poverty. 2014;3: 5. doi: 10.1186/2049-9957-3-5 24479873
53. Silverman RA, Beck IA, Kiptinness C, Levine M, Milne R, McGrath CJ, et al. Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013–2014. J Infect Dis. 2017;216: 1569–1578. doi: 10.1093/infdis/jix544 29040633
54. Soria A, Porten K, Fampou-Toundji JC, Galli L, Mougnutou R, Buard V, et al. Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-1infected patients. Antivir Ther. 2009;14: 339–347. 19474468
55. Moradigaravand D, Kouyos R, Hinkley T, Haddad M, Petropoulos CJ, Engelstädter J, et al. Recombination Accelerates Adaptation on a Large-Scale Empirical Fitness Landscape in HIV-1. PLoS Genet. 2014;10: 1004439. doi: 10.1371/journal.pgen.1004439 24967626
56. Santoro MM, Perno CF. HIV-1 Genetic Variability and Clinical Implications. ISRN Microbiol. 2013;2013: Article ID 481314. doi: 10.1155/2013/481314 23844315
57. Santos AFA, Tebit DM, Lalonde MS, Abecasis AB, Ratcliff A, Camacho RJ, et al. Effect of natural polymorphisms in the HIV-1 CRF02-AG protease on protease inhibitor hypersusceptibility. Antimicrob Agents Chemother. 2012;56: 2719–2725. doi: 10.1128/AAC.06079-11 22330918
58. Santos AF, Soares MA. HIV genetic diversity and drug resistance. Viruses. 2010;2: 503–531. doi: 10.3390/v2020503 21994646
59. Xing H, Wang X, Liao L, Ma Y, Su B, Fu J, et al. Incidence and associated factors of HIV drug resistance in Chinese HIV-infected patients receiving antiretroviral treatment. PLoS One. 2013;8: e62408. doi: 10.1371/journal.pone.0062408 23638072
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