Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study

BMC Microbiology - 2020
Chika Onwuamah1, Jonathan Okpokwu2, Rosemary Audu1, Godwin Imade2, Seema Meloni3, Azuka Okwuraiwe1, Philippe Chebu4, Adesola Z. Musa1, Beth Chaplin3, Ibrahim Dalhatu5, Oche Agbaji2, Jay Osi Samuels4, OC Ezechi1, Ahmed Mukhtar5, Georgina N. Odaibo6, David O. Olaleye6, Prosper Okonkwo4, Babatunde Lawal Salako1, Elliot Raizes7, Chunfu Yang7, Phyllis J. Kanki3, Emmanuel O. Idigbe1
1Microbiology Department, Centre for Human Virology and Genomics, Nigerian Institute of Medical Research, Lagos, Nigeria
2Jos University Teaching Hospital, Jos, Nigeria
3Harvard T.H. Chan School of Public Health, Boston, USA
4APIN Public Health Initiative Nigeria, Abuja, Nigeria
5Centers for Disease Control-Nigeria, Abuja, Nigeria
6University of Ibadan, Ibadan, Nigeria
7Centers for Disease Control and Prevention, Atlanta, USA

Tóm tắt

Abstract Background We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. Result Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. Conclusion This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance.

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Tài liệu tham khảo

Federal Ministry of Health Nigeria. National Guidelines for HIV Prevention, Treatment and Care. In: (NASCP) NAaSsCP, editor. ISBN: 978–978–954-309-0 ed. Abuja, Nigeria: Federal Ministry of Health, Nigeria; 2016.

Sethi AK, Celentano DD, Gange SJ, Moore RD, Gallant JE. Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance. Clin Infect Dis. 2003;37(8):1112–8.

Meresse M, March L, Kouanfack C, Bonono RC, Boyer S, Laborde-Balen G, et al. Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon. HIV Med. 2014;15(8):478–87.

Reda AA, Biadgilign S. Determinants of adherence to antiretroviral therapy among HIV-infected patients in Africa. AIDS Res Treat. 2012;2012:574656.

Lyimo RA, van den Boogaard J, Msoka E, Hospers HJ, van der Ven A, Mushi D, et al. Measuring adherence to antiretroviral therapy in northern Tanzania: feasibility and acceptability of the medication event monitoring system. BMC Public Health. 2011;11:92.

O'Connor JL, Gardner EM, Esser S, Mannheimer SB, Lifson AR, Telzak EE, et al. A simple self-reported adherence tool as a predictor of viral rebound in people with viral suppression on antiretroviral therapy. HIV Med. 2016;17(2):124–32.

Turner BJ. Adherence to antiretroviral therapy by human immunodeficiency virus-infected patients. J Infect Dis. 2002;185(Suppl 2):S143–51.

de Truchis P, Lê MP, Daou M, Madougou B, Nouhou Y, Moussa Saley S, et al. High efficacy of first-line ART in a west African cohort, assessed by dried blood spot virological and pharmacological measurements. J Antimicrob Chemother. 2016;71(11):3222–7.

Edessa D, Sisay M, Asefa F. Second-line HIV treatment failure in sub-Saharan Africa: a systematic review and meta-analysis. PLoS One. 2019;14(7):e0220159.

Lucas GM. Antiretroviral adherence, drug resistance, viral fitness and HIV disease progression: a tangled web is woven. J Antimicrob Chemother. 2005;55(4):413–6.

Hoffmann CJ, Maritz J, van Zyl GU. CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone. Tropical Med Int Health. 2016;21(2):219–23.

Muri L, Gamell A, Ntamatungiro AJ, Glass TR, Luwanda LB, Battegay M, et al. Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern. AIDS. 2017;31(1):61–70.

Abreu JC, Vaz SN, Netto EM, Brites C. Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy. Braz J Infect Dis. 2017;21(3):219–25.

Oku AO, Owoaje ET, Ige OK, Oyo-Ita A. Prevalence and determinants of adherence to HAART amongst PLHIV in a tertiary health facility in south-South Nigeria. BMC Infect Dis. 2013;13:401.

McDonald HP, Garg AX, Haynes RB. Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA. 2002;288(22):2868–79.

World Health Organization, World Health Organization. Department of HIV/AIDS. In: Antiretroviral therapy for HIV infection in adults and adolescents : recommendations for a public health approach. Geneva: World Health Organization; 2010. Available from: http://www.ncbi.nlm.nih.gov/books/NBK138540/.

Johnston V, Cohen K, Wiesner L, Morris L, Ledwaba J, Fielding KL, et al. Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch. J Infect Dis. 2014;209(5):711–20.

Mills EJ, Nachega JB, Bangsberg DR, Singh S, Rachlis B, Wu P, et al. Adherence to HAART: a systematic review of developed and developing nation patient-reported barriers and facilitators. PLoS Med. 2006;3(11):e438.

Heestermans T, Browne JL, Aitken SC, Vervoort SC, Klipstein-Grobusch K. Determinants of adherence to antiretroviral therapy among HIV-positive adults in sub-Saharan Africa: a systematic review. BMJ Glob Health. 2016;1(4):e000125.

Meloni ST, Onwuamah CK, Agbaji O, Chaplin B, Olaleye DO, Audu R, et al. Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options. Open Forum Infect Dis. 2017;4(4):ofx233.

Chaplin B, Meloni S, Eisen G, Jolayemi T, Banigbe B, Adeola J, et al. Scale-up of networked HIV treatment in Nigeria: creation of an integrated electronic medical records system. Int J Med Inform. 2015;84(1):58–68.

Zhou Z, Wagar N, DeVos JR, Rottinghaus E, Diallo K, Nguyen DB, et al. Optimization of a low cost and broadly sensitive genotyping assay for HIV-1 drug resistance surveillance and monitoring in resource-limited settings. PLoS One. 2011;6(11):e28184.

Gifford RJ, Liu TF, Rhee SY, Kiuchi M, Hue S, Pillay D, et al. The calibrated population resistance tool: standardized genotypic estimation of transmitted HIV-1 drug resistance. Bioinformatics. 2009;25(9):1197–8.

Liu TF, Shafer RW. Web resources for HIV type 1 genotypic-resistance test interpretation. Clin Infect Dis. 2006;42(11):1608–18.

Frentz D, Boucher CA, Assel M, De Luca A, Fabbiani M, Incardona F, et al. Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time. PLoS One. 2010;5(7):e11505.

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