Prevalence in the Usa of Rilpivirine Resistance-Associated Mutations in Clinical Samples and Effects on Phenotypic Susceptibility to Rilpivirine and Etravirine

  title={Prevalence in the Usa of Rilpivirine Resistance-Associated Mutations in Clinical Samples and Effects on Phenotypic Susceptibility to Rilpivirine and Etravirine},
  author={Gaston Picchio and Laurence T. Rimsky and Veerle van Eygen and Mojgan Haddad and Laura Napolitano and Johan Vingerhoets},
  journal={Antiviral Therapy},
  pages={819 - 823}
Background The prevalence of rilpivirine resistance-associated mutations (RAMs) in the USA, and their effect on phenotypic susceptibility to rilpivirine and etravirine, was evaluated in clinical samples from HIV-1-infected patients. Methods In total, 15,991 samples submitted to Monogram Biosciences (South San Francisco, CA, USA) for routine resistance testing between January 2010 and June 2011 were assessed for the presence of known rilpivirine RAMs K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V… 

Tables from this paper

Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV‐1: Analysis from a national drug‐resistance database (ARCA)

In Italian HIV‐positive HAART‐naïve patients, prevalence of the main RAMs for RPV is low except for E138A (present in 5.1% of subjects), and a previous exposure to NVP might increase the risk to develop RPV‐associated RAMs.

Prevalence of Pretreatment and Acquired HIV-1 Mutations Associated with Resistance to Lamivudine or Rilpivirine: A Systematic Review

This review suggests low risk of lamivudine- or rilpivirine-resistant mutations in treatment-naive, HIV-1-infected individuals.

Factors influencing the efficacy of rilpivirine in HIV-1 subtype C in low- and middle-income countries.

The clinical and biochemical findings indicate that the usefulness of rilpivirine has limitations in HIV-1C-dominated epidemics in LMICs, but the drug could still be beneficial in patients failing first-line therapy if genotypic resistance testing is performed.

In Vitro Resistance Selection with Doravirine (MK-1439), a Novel Nonnucleoside Reverse Transcriptase Inhibitor with Distinct Mutation Development Pathways

Results suggest that mutant viruses selected by DOR are susceptible toRPV and EFV and mutants selected by RPV andEFV are susceptibility to DOR.

Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa

The frequently observed cross-resistance of HIV-1 suggests that the preventive efficacy of TMC278LA pre-exposure prophylaxis could be compromised by transmission of HIV -1 from individuals with failure of first-line non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy.

APOBEC3 selects V179I in HIV-1 reverse transcriptase to provide selective advantage for non-nucleoside reverse transcriptase inhibitor-resistant mutants

Evidence is provided that V179I in HIV-1 RT can arise due to APOBEC-mediated G to A hypermutation and can confer a selective advantage to drug-resistant HIV- 1 isolates in the presence of some NNRTIs.

Prevalence and Evolution of Transmitted Human Immunodeficiency Virus Drug Resistance in Belgium Between 2013 and 2019

The TDR prevalence in Belgium remained stable between 2013 and 2019 and is comparable to the prevalence in other Western European countries, and the high frequency of NNRTI mutations requires special attention and follow-up.

HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006–2022

Investigation of patterns and temporal trends in HIV DR as well as the prevalence of genetic variants in treatment-naïve patients from 2006 to 2022, using data from the Russian database showed high viral diversity, with the predominance of A6, which was the most common in all transmission risk groups.

An unusual case of underlying rilpivirine resistance in an antiretroviral-naïve man with AIDS

The patient went on to develop rifamycin-induced neutropenia during treatment of his opportunistic infection but later recovered his counts, and remains well on an integrase-based HIV regimen, illustrating the growing importance of archived resistance mutations including the less common E138A mutation.

Transmitted Drug Resistance among HIV-1 drug-naïve patients in Greece.

Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses.

The prevalence of rilpivirine, emtricitabine and tenofovir resistance mutations was very low in antiretroviral-naive patients and was not statistically different from the prevalence of efavirenz and nevirapine resistance in the population.

Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database.

Short communication prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV type 1 resistance testing in the United States.

A high proportion of samples with first-generation NN RTI resistance was susceptible to etravirine by genotype and phenotype, and a higher proportion of NNRTI-resistant samples with K103N than without was susceptible.

The HIV-1 Reverse Transcriptase M184I Mutation Enhances the E138K-Associated Resistance to Rilpivirine and Decreases Viral Fitness

The higher frequency of E138K and M184I among RPV + FTC/TDF virologic failures is due to reduced susceptibility of the single mutants toRPV and FTC and the enhanced resistance to RPV for the double mutant at the cost of decreased viral fitness.

Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies

RPV resistance is overall recognized in nearly 20% of patients failing other NNRTIs, and is more common following ETR or NVP failures than EFV (14.5%).

Etravirine and Rilpivirine Resistance in HIV-1 Subtype Crf01_Ae-Infected Adults Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens

The role of ETR in second-line therapy is limited in late NNRTI failure settings, and cross-resistance between ETR and RVP was high.

96-Week Resistance Analyses of Rilpivirine in Treatment-Naive, HIV-1-Infected Adults from the Echo and Thrive Phase Iii Trials

During the second year of treatment in ECHO/THRIVE, few VFs with emerging NNRTI RAMs (no new RPV RAMs) occurred, and less phenotypic resistance to RPV and other NN RTIs than in patients with baseline VL>100,000 copies/ml.

Genotypic and Phenotypic Characterization of HIV-1 Isolates Obtained From Patients on Rilpivirine Therapy Experiencing Virologic Failure in the Phase 3 ECHO and THRIVE Studies: 48-Week Analysis

VF and treatment-emergent reverse transcriptase RAMs were similar at low baseline VL but more frequent at high baselineVL in rilpivirine-treated than in efavirenz-treated patients, and the frequent emergence of E138K, especially in combination with M184I, is a unique finding of these trials.

Effect of Mutations at Position E138 in HIV-1 Reverse Transcriptase on Phenotypic Susceptibility and Virologic Response to Etravirine

E138G, K, and Q were added to the existing etravirine-weighted genotypic score including 17 etravIRine resistance-associated mutations, andVirologic response was observed in six of 12 and eight of 10 patients with E138A and E138Q, respectively.

TMC278, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), Active against Wild-Type and NNRTI-Resistant HIV-1

In vitro analyses demonstrate that TMC278 is a potent next-generation NNRTI, with a high genetic barrier to resistance development, and efavirenz- and/or nevirapine-resistant HIV-1 recombinant clinical isolates.