HIV-1 Subtype C, Tenofovir, and the Relationship With Treatment Failure and Drug Resistance

Günthard, Huldrych F.; Scherrer, Alexandra U.

doi:10.1093/infdis/jiw214

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…However, when other factors that lead to differential non-adherence, such as demographics and clinical characteristics, are present then subtype C viruses have a greater propensity to develop a K65R mutation. 31 …”

Section: Discussionmentioning

confidence: 99%

An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs

Smit

White

Clark

et al. 2017

Journal of Antimicrobial Chemotherapy

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Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients (n = 3410) were mostly MSM (78%) and those with subtype C (n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55–2.62, P < 0.001). Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated.

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Section: Discussionmentioning

confidence: 99%

An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs

Smit

White

Clark

et al. 2017

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

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“…The increased clinical use of combination antiretroviral treatment for HIV-1 infection has led to the selection of viral strains resistant to multiple drugs, including strains resistant to all licensed nucleoside analog RT inhibitors and protease inhibitors [28,[36][37][38][39][40][41][42]. Although research continues to improve our understanding of drug resistance leading to re ned treatment strategies and, in some cases, improved outcome, resistance to antiretroviral therapy remains a major cause of treatment failure among patients living with HIV-1 [43][44][45].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of minority Human Immunodeficiency virus multi-drug resistant mutations among patients failing a Nucleoside Reverse Transcriptase Inhibitor based regimen in Uganda

Nankya¹,

Nabulime²,

Kyeyune³

et al. 2021

Preprint

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Objective To determine the prevalence of multi-drug resistant variants among patients failing on a nucleoside reverse transcriptase inhibitor (NRTI) based regimen with a detectable viral load ≥ 1000 copies/ml among patients harboring HIV subtype A, C and D. Methods Samples were obtained from patients who were failing on an NRTI based regimen. Sanger based sequencing was performed as part of the standard of care. Mutation analysis was performed using the Stanford HIV drug Resistance database. A subset of these patient samples was further analyzed using the Next Generation Sequencing (NGS) technology and analysis of the drug resistance mutations was performed at the 20% and 1% cut off Results Analysis of the Non-nucleoside reverse transcriptase inhibitor (NNRTI) coding region revealed that the K101 and the Y181 mutations were more predominant among subtype C than subtype A and D. Although Thymidine analog mutations (TAMs) were prevalent in all subtypes, our analyses showed that these mutations occurred in significantly less proportions among subtype C infections when compared with the subtype A and D counterparts. Furthermore, the Q151M mutation complex which involves mutations in multiple domains was significantly more prominent among patients harboring subtype C variants. Analysis using NGS revealed that minority drug resistant mutations that confer multi-drug resistance (MDR) were present even in patients who exhibited a susceptible genotype based on the Sanger sequencing technique. Conclusion Although HIV-1 MDR variants occur in all subtypes, their predominance is subtype specific with TAMs being significantly more predominant among subtype A and D while the Q151M complex being significantly more predominant among patients harboring subtype C viruses. Even in patients with a susceptible genotype based on Sanger technology, minority variants are present and their evolution to full blown MDR occurs over time such that by the time they are detectable, cross resistance to other drugs has occurred in some cases.

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HIV-1 Subtype C, Tenofovir, and the Relationship With Treatment Failure and Drug Resistance

Cited by 2 publications

References 21 publications

An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs

An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs

Prevalence of minority Human Immunodeficiency virus multi-drug resistant mutations among patients failing a Nucleoside Reverse Transcriptase Inhibitor based regimen in Uganda

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