Improved virological and immunological efficacy of resistance-guided switch in antiretroviral therapy: a Frankfurt HIV cohort analysis

Wolf, Timo; Fuß, Bernhard; Khaykin, Pavel; Berger, Annemarie; Knecht, Gaby; Gute, Peter; Brodt, Hans-Reinhard; Goepel, Siri; Bickel, Markus; Stuermer, M.; Stephan, Christoph

doi:10.1007/s00430-014-0350-5

Cited by 5 publications

(2 citation statements)

References 18 publications

(19 reference statements)

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“…This study was performed as retrospective subanalysis of the ongoing Frankfurt HIV Cohort Study, for which patient data and serum samples are being collected prospectively since 1987. 53 It was approved by the data protection officer of the state of Hesse and the Frankfurt University Ethics Committee (Umbrella-Vote-No. 270/09), including special subproject Approval No.…”

Section: Methodsmentioning

confidence: 99%

Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller

Ringel

Müller

Koch

et al. 2018

AIDS Research and Human Retroviruses

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The analysis of patient derived HIV neutralizing antibodies (nAbs) and their target epitopes in the viral envelope (Env) protein provides important basic information for vaccine design. In this study we optimized an epitope, EC26-2A4, that is targeted by neutralizing antibodies from an elite controller (EC26) and localizes in the membrane-proximal external region from the gp41 transmembrane protein. Due to its overlap with the epitope of the first generation broadly neutralizing monoclonal Ab (mAb) 2F5 associated with autoreactivity, we first defined the minimal core epitope reacting with antibodies from EC26 plasma, but not with mAb 2F5. The optimized minimal epitope, EC26-2A4ΔM, was able to induce neutralizing antibodies in vaccinated mice. We further analyzed the frequency of antibodies against the EC26-2A4ΔM peptide in HIV-positive patient sera from a treated cohort and an untreated long-term nonprogressor (LTNP) cohort. Interestingly, 27% of the LTNP sera reacted with the peptide, whereas only 9% showed reactivity in the treated cohort. Although there was no association between the presence of antibodies against the EC26-2A4ΔM epitope and viral load or CD4 count in these patients, the CD4 nadir in the treated cohort was higher in patients positive for EC26-2A4ΔM antibodies, in particular in patients having such antibodies at an early and a late timepoint after infection.

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Section: Methodsmentioning

confidence: 99%

Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller

Ringel

Müller

Koch

et al. 2018

AIDS Research and Human Retroviruses

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“…been shown to improve the treatment outcome following ART [36]. Anti-HIV drugs have become broadly available for the treatment of HIV-positive patients in Turkey, and the genetic diversity of HIV-1 has been analysed in recent studies showing that besides subtype B, the CRFs 02_AG, 01_AE and 03_AB are circulating [2,22,37].…”

mentioning

confidence: 99%

HIV-1 subtypes and drug resistance profiles in a cohort of heterosexual patients in Istanbul, Turkey

Köksal

Beka

Lübke

et al. 2015

Med Microbiol Immunol

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Turkey is seeing a steady rise in rates of HIV infection in the country. The number of individuals with HIV/AIDS was greater than 7000 in 2014 according to data released by the Ministry of Health, and heterosexual contacts were reported to be the main transmission routes. Istanbul has the highest number of reported cases of HIV infection. The aim of the study was to determine the prevalence of HIV-1 drug resistance in 50 heterosexual patients from Istanbul. The most prevalent subtype was found to be subtype B (56.2 %). Resistance-associated mutations were found in 14 patients with 6/14 patients being therapy-experienced and 8/14 therapy naive at the time point of analysis. With increasing number of patients who require treatment and the rapid up-scaling of the antiretroviral therapy in Turkey, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.

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Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD)

Reinheimer

Wesner

Keppler

et al. 2016

Med Microbiol Immunol

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Mutations in the genome of HIV-1 can compromise the success of antiretroviral treatments (ARTs) in HIV-1-infected individuals. The Frankfurt HIV Cohort Study Resistance Database (FHCS-RD) has previously documented a decline in the burden of resistance-associated mutations (RAMs) following the implementation of several new antiretroviral therapy regimens in 2007. In the current study, the annual burden of RAMs documented in the FHCS-RD in 2005-2013 was set in relation to the annual number of all cohort patients, drug regimens, available resistance tests, and prevalence for each RAM on relevant codons of reverse transcriptase (RT) and protease (PR) genes. A specific focus was put on the prevalence of the tenofovir disoproxil fumarate (TDF) signature mutation K65R in HIV-1 RT in relation to the application of TDF within ART. Between 2005 and 2012, a total of 4423 HIV genotyping data sets from 4509 patients were analysed. All mutations show a consistent decline, and the most impressive decrease was observed for thymidine analogue mutations (TAMs). The frequency of non-TAMs and PR mutations also decreased, but generally to a lower extent. The prevalence of K65R decreased from 2.6 % in 2005 to 0.2 % in 2012 despite increased use of TDF-containing ART. Both the improved strategic use of TDF in ARTs and generally more effective ART regimens may have resulted in decreasing RAM prevalences in FHCS-RD since 2007. These trends challenge the cost-effectiveness of resistance testing prior to failing ART.

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Improved virological and immunological efficacy of resistance-guided switch in antiretroviral therapy: a Frankfurt HIV cohort analysis

Cited by 5 publications

References 18 publications

Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller

Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller

HIV-1 subtypes and drug resistance profiles in a cohort of heterosexual patients in Istanbul, Turkey

Prevalence of K65R in patients treated with tenofovir disoproxil fumarate: recommendations based on the Frankfurt HIV Cohort Study Resistance Database (FHCS-RD)

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