scholarly journals Successful establishment of third-line antiretroviral therapy in Malawi: lessons learned

2019 ◽  
Vol 9 (4) ◽  
pp. 169-173
Author(s):  
T. Heller ◽  
P. Ganesh ◽  
J. Gumulira ◽  
L. Nkhoma ◽  
C. Chipingu ◽  
...  
Keyword(s):  
Expert Knowledge ◽  
Lessons Learned ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
African Countries ◽  
Genotypic Resistance ◽  
Treatment Regimens ◽  
Art Program ◽  
Genotypic Resistance Testing ◽  
Third Line

Setting: Malawi has an extensive national antiretroviral treatment (ART) program, and although less than 2% of all patients receive second-line ART, there are increasingly more patients failing on these regimens.Objective: To establish a virtual ART committee using limited available local facilities and expertise to recommend third-line regimens based on genotype resistance of samples sent abroad.Design: A secretariat and a laboratory sample hub were established. The committee started work after locally organizing training courses. Decisions about ART regimens were mainly based on a relatively simple, previously described algorithm, which allowed decisions to be taken without extensive expert knowledge.Results: Of the 25 applications assessed, 23 samples were sent for resistance testing from June 2017 to April 2018. Major protease inhibitor (PI) resistance was detected in 65% of the samples. PI resistance was found even in patients exposed to PIs for short periods. In particular, patients who received co-administration of PIs and rifampicin frequently showed resistance mutations.Conclusion: Third-line ART using genotypic resistance testing and algorithm-based treatment regimens are feasible in low-resource settings. Our model can serve as a base for similar programs initiating programmatic third-line ART in other African countries.

scholarly journals Distribution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Mutation Patterns in 4,183 Persons Undergoing Genotypic Resistance Testing

2004 ◽  
Vol 48 (8) ◽  
pp. 3122-3126 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Tommy Liu ◽  
Jaideep Ravela ◽  
Matthew J. Gonzales ◽  
Robert W. Shafer
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Drug Resistance Mutations ◽  
Genotypic Resistance Testing ◽  
Immunodeficiency Virus

ABSTRACT In a sample of 6,156 sequences from 4,183 persons, the top 30 patterns of protease inhibitor, nucleoside reverse transcriptase (RT) inhibitor, and nonnucleoside RT inhibitor mutations accounted for 55, 46, and 66%, respectively, of sequences with drug resistance mutations. Characterization of the phenotypic and clinical significance of these common patterns may lead to improved treatment recommendations for a large proportion of patients for whom antiretroviral therapy is failing.

scholarly journals Genetic Consequences of Antiviral Therapy on HIV-1

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Miguel Arenas
Keyword(s):  
Enzyme Inhibitors ◽  
Resistance Testing ◽  
Evolutionary Analysis ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Antiviral Therapies ◽  
Genotypic Resistance Testing ◽  
Before And After ◽  
Emergence Of Resistance ◽  
Hiv 1

A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the viral genetic diversity and molecular adaptation. The role of recombination in the generation of drug resistance is also analyzed. Besides the investigation and discussion of published works, an evolutionary analysis of protease-coding genes collected from patients before and after treatment with different protease inhibitors was included to validate previous studies. Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments design.

scholarly journals HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0145772 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Michael R. Jordan ◽  
Elliot Raizes ◽  
Arlene Chua ◽  
Neil Parkin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Point Of Care ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Drug Resistance Mutations ◽  
Genotypic Resistance Testing ◽  
Potential Applications ◽  
Hiv 1

scholarly journals Differentiation between Polymorphisms and Resistance-Associated Mutations in Human Cytomegalovirus DNA Polymerase

2010 ◽  
Vol 54 (12) ◽  
pp. 5004-5011 ◽  
Author(s):  
Meike Chevillotte ◽  
Ina Ersing ◽  
Thomas Mertens ◽  
Jens von Einem
Keyword(s):  
Drug Resistance ◽  
Dna Polymerase ◽  
Human Cytomegalovirus ◽  
Antiviral Drug ◽  
Drug Susceptibility ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Drug Resistance Testing ◽  
Genotypic Resistance Testing

ABSTRACT Specific mutations in the human cytomegalovirus (HCMV) DNA polymerase (pUL54) are known to confer resistance against all currently licensed drugs for treatment of HCMV infection and disease. Following the widespread use of antivirals, the occurrence of HCMV drug resistance is constantly increasing. Recently, diagnostic laboratories have started to replace phenotypic drug resistance testing with genotypic resistance testing. However, the reliability and success of genotypic testing highly depend on the availability of high-quality phenotypic resistance data for each individual mutation and for combinations of mutations, with the latter being increasingly found in patients' HCMV isolates. We performed clonal marker transfer experiments to investigate the impacts of 7 different UL54 point mutations and also of combinations of these mutations on drug susceptibility and viral replicative fitness. We show that several mutations—S695T, A972V, K415R, S291P, and A692V—of suspected but uncertain drug susceptibility phenotype, either alone or in combination, were not relevant to antiviral drug resistance. In contrast, the combination of two mutations individually characterized previously—E756K and D413E—conferred high-grade loss of susceptibility to all three antivirals. Our results have been added to the newly available database of all published HCMV resistance mutations (http://www.informatik.uni-ulm.de/ni/mitarbeiter/HKestler/hcmv/index.html ). These data will allow better interpretation of genotypic data and further improve the basis for drug resistance testing.

Application of HIV-1 genotypic-resistance testing prevents the evolution of further resistance mutations in heavily pretreated patients

2001 ◽  
Vol 21 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Bernhard Zöllner ◽  
Heinz-Hubert Feucht ◽  
Lutwin Weitner ◽  
Axel Adam ◽  
Matthias Schröter ◽  
...  
Keyword(s):  
Resistance Testing ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Hiv 1

scholarly journals Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

2011 ◽  
Vol 9 (1) ◽  
pp. 14 ◽  
Author(s):  
Jan Fehr ◽  
Tracy R Glass ◽  
S�verine Louvel ◽  
Fran�ois Hamy ◽  
Hans H Hirsch ◽  
...  
Keyword(s):  
Cohort Study ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing

Response to Waters et al. ‘Successful use of genotypic resistance testing in HIV-1-infected individuals with detectable viraemia …’

AIDS ◽  
2006 ◽  
Vol 20 (15) ◽  
pp. 1991-1992 ◽  
Author(s):  
Virginia L Kan ◽  
Howard B Gale ◽  
Rebecca C Shinol
Keyword(s):  
Resistance Testing ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing ◽  
Hiv 1

scholarly journals Genotypic Resistance Testing Creates New Treatment Challenges: Two Cases of Oxacillin-Susceptible Methicillin-Resistant Staphylococcus aureus

2012 ◽  
Vol 50 (12) ◽  
pp. 4151-4153 ◽  
Author(s):  
K. A. Sharff ◽  
S. Monecke ◽  
S. Slaughter ◽  
G. Forrest ◽  
C. Pfeiffer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Methicillin Resistant ◽  
Genotypic Resistance Testing ◽  
New Treatment
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