Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure

Balduin, Melanie; Oette, Mark; Däumer, Martin; Hoffmann, Daniel; Pfister, Herbert; Kaiser, Rolf

doi:10.1016/j.jcv.2009.03.002

Cited by 45 publications

(34 citation statements)

References 26 publications

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“…13 The impact of pre-existing minority drug-resistant HIV-1 variants on first-line ART remains unresolved. [14][15][16][17][18][19][20] Contradictory results in treatment-naïve patients might be due to differences in the patient populations and the antiretroviral regimens, which differ in respect to their genetic resistance barriers. 21 In this study within the German Truvada Cohort, we wanted to investigate the prevalence of the key drug resistance mutations K65R, K103N, and M184V at low frequencies and their possible impact on the clinical outcome of first-line ART in chronically HIV-1 infected patients.…”

mentioning

confidence: 99%

Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naïve patients

Metzner

Rauch

Braun

et al. 2011

Journal of Clinical Virology

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confidence: 99%

Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naïve patients

Metzner

Rauch

Braun

et al. 2011

Journal of Clinical Virology

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“…These undetected resistant associated mutations may cause suboptimal response to ART and lead to rapid emergence of HIV drug resistance, and can be implicated in early treatment failures. [116][117][118][119][120] Unequal exposure to antiretrovirals and treatment interruptions are thought to underlie the development of resistance in some patients. [121][122][123][124][125] Different rates of adherence to medications within a regimen (discordant adherence) combined with varied pharmacokinetics of the agents can lead to viral replication, and subsequent exposure to sub-optimal treatment regimens.…”

Section: Resistancementioning

confidence: 99%

Issues in resistance, adherence, and comparative efficacy of the single-tablet regimen combination of tenofovir, emtricitabine, and efavirenz in the management of HIV-1 infection

Rebick¹,

Walmsley²

2012

VAAT

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Abstract:Atripla is the first once-daily, single-tablet, triple-combination antiretroviral therapy. It is recommended for the initial treatment of the naïve patient with human immunodeficiency virus-1 (HIV-1) infection in all current guidelines, based on its proven efficacy in numerous head-to-head randomized clinical trials. Not only has it proven efficacy, but the fixed-dose combination, Atripla, has resulted in an improvement in adherence, quality of life, and satisfaction among naïve as well as virally suppressed patients switching from another regimen. Despite the advantages, tolerability issues can arise that are related primarily to the efavirenz component, which is known to cause central nervous side effects such as dizziness, abnormal dreams, and anxiety. Although generally self-limited, these side-effects can lead to treatment discontinuation in the short-or long-term. Based on the observation of neural tube defects in macaque models, and isolated case reports in human fetuses with first trimester exposure, it is rated as Food and Drug Administration pregnancy category D, and considered as contraindicated in the first trimester of pregnancy where alternatives are available. Given the low genetic barrier of each of the individual components, resistance remains an important issue for patients with poor adherence, but is balanced in part by the long half-life of the drugs. Transmitted resistance is described in up to 16% of newly infected patients in population surveys, and is particularly prevalent in men who have sex with men. Minority variants that may impart resistant to efavirenz are not detected with currently used HIV-1 genotype assays, but nonetheless may also be implicated in patients who fail initial treatment. Several single-tablet regimens are recently licensed or in development that will challenge Atripla as the single-tablet first-line option, but none have shown superior efficacy to date.

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“…This phenomenon has been addressed in a number of studies in recent years [2,3,4,5,6,7,8,9,10,11]. Different analyses showed reduced efficacy of ART in cases with primary drug resistance in bulk sequencing or as a minority strain [12,13,14,15,16,17,18]. Epidemiology of transmitted resistance varies according to the investigated population, the applied methods, and the geographic region.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Transmitted Drug Resistance in Chronically HIV-Infected Patients in Germany: The RESINA Study 2001–2009

Oette

Reuter²,

Kaiser³

et al. 2012

Intervirology

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Objectives: Transmitted HIV drug resistance may impair treatment efficacy of combination antiretroviral therapy (ART). This study describes the epidemiology of transmitted resistance in chronically infected patients. Methods: In a prospective multicenter trial in Nordrhein-Westfalen, Germany, transmitted drug resistance was determined by genotypic resistance testing in patients on initiation of first-line ART. Results: From 2001 to 2009, 2,078 patients were enrolled in the study. 79.9% were male, 81.2% were Caucasians, and a homosexual transmission mode was found in 51.3%. Of these patients, 41.5% were at the stage of AIDS, median CD4 cell count was 230/µl, and median viral load was 64.466 copies/ml. Transmitted drug resistance mutations were seen in 9.2% (95% CI, 7.9–10.4). Resistance in the nucleoside reverse transcriptase inhibitor class was found in 5.8% (4.8–6.8), in the nonnucleoside reverse transcriptase inhibitor class in 2.8% (2.1–3.6), and in the protease inhibitor class in 2.7% (2.0–3.4). After a continuous increase to a level above 10% in the years 2006 and 2007, a decline of drug resistance prevalence followed in 2008 and 2009. Conclusions: Transmitted HIV drug resistance was found in around 10% of chronically infected patients in Germany who started their ART. We showed a moderate decline of the prevalence of mutant virus strains in recent years. Further surveillance of this phenomenon is mandatory.

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Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure

Cited by 45 publications

References 26 publications

Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naïve patients

Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naïve patients

Issues in resistance, adherence, and comparative efficacy of the single-tablet regimen combination of tenofovir, emtricitabine, and efavirenz in the management of HIV-1 infection

Epidemiology of Transmitted Drug Resistance in Chronically HIV-Infected Patients in Germany: The RESINA Study 2001–2009

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