Fitness of drug resistant HIV-1: methodology and clinical implications.

Recent studies of human immunodeficiency virus type 1 (HIV-1) fitness have examined the potential relationship with plasma viral load, drug resistance, and disease progression. For example, treatment of HIV-1 infected individuals with antiretroviral drugs may result in the selection and emergence of inhibitor-resistant variants with reduced replicative capacity. However, it is still unclear whether in vitro HIV-1 fitness has any direct relationship to in vivo disease progression or treatment success. A related question is which in vitro assay of viral fitness is the most appropriate for comparison with in vivo HIV-1 fitness. Characterization of the relative viral fitness of drug-resistant HIV-1 strains may lead to a better understanding of whether or not less fit viruses pose a clinical benefit to the patient.

[1]  F. Brun-Vézinet,et al.  Switch to Unusual Amino Acids at Codon 215 of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Gene in Seroconvertors Infected with Zidovudine-Resistant Variants , 1998, Journal of Virology.

[2]  J. Mellors,et al.  A recombinant retroviral system for rapid in vivo analysis of human immunodeficiency virus type 1 susceptibility to reverse transcriptase inhibitors , 1997, Antimicrobial agents and chemotherapy.

[3]  M. Lederman,et al.  Altered Viral Fitness of HIV‐1 Following Failure of Protease Inhibitor‐Based Therapy , 2000, Journal of acquired immune deficiency syndromes.

[4]  F. Maggiolo,et al.  Discordant immunological response in HIV-positive patients on non-nucleoside reverse transcriptase inhibitor-based regimens. , 2002, AIDS (London).

[5]  F. Mammano,et al.  HIV drug resistance and viral fitness. , 2000, Advances in pharmacology.

[6]  E. Arts,et al.  A Dual Infection/Competition Assay Shows a Correlation between Ex Vivo Human Immunodeficiency Virus Type 1 Fitness and Disease Progression , 2000, Journal of Virology.

[7]  Arthur J. Olson,et al.  Viral Evolution in Response to the Broad-Based Retroviral Protease Inhibitor TL-3 , 2001, Journal of Virology.

[8]  D. Montefiori,et al.  Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. D. de Boer,et al.  Establishment of New Transmissible and Drug-Sensitive Human Immunodeficiency Virus Type 1 Wild Types due to Transmission of Nucleoside Analogue-Resistant Virus , 2001, Journal of Virology.

[10]  R. Swanstrom,et al.  A multiple-site-specific heteroduplex tracking assay as a tool for the study of viral population dynamics. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Jacques Izopet,et al.  Changes in Human Immunodeficiency Virus Type 1 Populations after Treatment Interruption in Patients Failing Antiretroviral Therapy , 2001, Journal of Virology.

[12]  C. Sabin,et al.  Substantial correlation between HIV type 1 drug-associated resistance mutations in plasma and peripheral blood mononuclear cells in treatment-experienced patients. , 2000, AIDS research and human retroviruses.

[13]  Brendan Larder,et al.  A Rapid Method for Simultaneous Detection of Phenotypic Resistance to Inhibitors of Protease and Reverse Transcriptase in Recombinant Human Immunodeficiency Virus Type 1 Isolates from Patients Treated with Antiretroviral Drugs , 1998, Antimicrobial Agents and Chemotherapy.

[14]  J. Martinez-Picado,et al.  Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants. , 2000, Virology.

[15]  C. Boucher,et al.  Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. , 1999, AIDS.

[16]  E. Domingo,et al.  Viruses at the edge of adaptation. , 2000, Virology.

[17]  John M. Leonard,et al.  Genotypic Changes in Human Immunodeficiency Virus Type 1 Associated with Loss of Suppression of Plasma Viral RNA Levels in Subjects Treated with Ritonavir (Norvir) Monotherapy , 1998, Journal of Virology.

[18]  D. Lamarre,et al.  Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors , 1997, Journal of virology.

[19]  B Clotet,et al.  Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society--USA Panel. , 1998, JAMA.

[20]  F. Mammano,et al.  Resistance-Associated Loss of Viral Fitness in Human Immunodeficiency Virus Type 1: Phenotypic Analysis of Protease andgag Coevolution in Protease Inhibitor-Treated Patients , 1998, Journal of Virology.

[21]  D. Ho,et al.  Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor , 1995, Journal of virology.

[22]  P. Harrigan,et al.  Relative Replicative Fitness of Zidovudine-Resistant Human Immunodeficiency Virus Type 1 Isolates In Vitro , 1998, Journal of Virology.

[23]  H. Mitsuya,et al.  Comparative Fitness of Multi-Dideoxynucleoside-Resistant Human Immunodeficiency Virus Type 1 (HIV-1) in an In Vitro Competitive HIV-1 Replication Assay , 1999, Journal of Virology.

[24]  M. Rayner,et al.  Population dynamics studies of wild-type and drug-resistant mutant HIV in mixed infections. , 1997, Virology.

[25]  S. Deeks.  Nonnucleoside Reverse Transcriptase Inhibitor Resistance , 2001 .

[26]  S. Deeks.  Determinants of virological response to antiretroviral therapy: implications for long-term strategies. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  R. Myers,et al.  HIV type 1 protease cleavage site mutations and viral fitness: implications for drug susceptibility phenotyping assays. , 2000, AIDS research and human retroviruses.

[28]  M. Kazatchkine,et al.  Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. , 2001, The Journal of infectious diseases.

[29]  R. Swanstrom,et al.  Patterns of Changes in Human Immunodeficiency Virus Type 1 V3 Sequence Populations Late in Infection , 2000, Journal of Virology.

[30]  B. Berkhout.  HIV-1 Evolution under Pressure of Protease Inhibitors: Climbing the Stairs of Viral Fitness , 1999, Journal of Biomedical Science.

[31]  D. Kuritzkes,et al.  A novel recombinant marker virus assay for comparing the relative fitness of hiv-1 reverse transcriptase variants. , 2001 .

[32]  H. Schuitemaker,et al.  In vitro replication kinetics of human immunodeficiency virus type 1 (HIV-1) variants in relation to virus load in long-term survivors of HIV-1 infection. , 1998, The Journal of infectious diseases.

[33]  D. Venzon,et al.  Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance. , 1998, The Journal of infectious diseases.

[34]  C. Boucher,et al.  Implications of antiretroviral resistance on viral fitness , 2001, Current opinion in infectious diseases.

[35]  R. Swanstrom,et al.  Nelfinavir-Resistant, Amprenavir-Hypersusceptible Strains of Human Immunodeficiency Virus Type 1 Carrying an N88S Mutation in Protease Have Reduced Infectivity, Reduced Replication Capacity, and Reduced Fitness and Process the Gag Polyprotein Precursor Aberrantly , 2002, Journal of Virology.

[36]  A. Monforte,et al.  Reduced levels of CD4 cell spontaneous apoptosis in human immunodeficiency virus-infected patients with discordant response to protease inhibitors. , 2002, The Journal of infectious diseases.

[37]  B. Yip,et al.  "Discordant" increases in CD4 cell count relative to plasma viral load in a closely followed cohort of patients initiating antiretroviral therapy. , 2002, Journal of acquired immune deficiency syndromes.

[38]  C. Loveday,et al.  Nucleoside Reverse Transcriptase Inhibitor Resistance , 2001, Journal of acquired immune deficiency syndromes.

[39]  J. Mullins,et al.  Genetic analysis of HIV-1 isolates from Brazil reveals presence of two distinct genetic subtypes. , 1994, AIDS research and human retroviruses.

[40]  R Hoh,et al.  Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. , 2001, The New England journal of medicine.

[41]  Christos J. Petropoulos,et al.  A Novel Phenotypic Drug Susceptibility Assay for Human Immunodeficiency Virus Type 1 , 2000, Antimicrobial Agents and Chemotherapy.

[42]  D. Lamarre,et al.  Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors , 1996, Journal of virology.

[43]  A. Telenti,et al.  Individual Contributions of Mutant Protease and Reverse Transcriptase to Viral Infectivity, Replication, and Protein Maturation of Antiretroviral Drug-Resistant Human Immunodeficiency Virus Type 1 , 2001, Journal of Virology.

[44]  R. Siliciano,et al.  Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. , 2000, Annual review of immunology.

[45]  Carrie Dykes,et al.  Mutants of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase Resistant to Nonnucleoside Reverse Transcriptase Inhibitors Demonstrate Altered Rates of RNase H Cleavage That Correlate with HIV-1 Replication Fitness in Cell Culture , 2000, Journal of Virology.

[46]  A S Perelson,et al.  Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase , 1996, Journal of virology.

[47]  B. Clotet,et al.  Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity , 2002, AIDS.

[48]  M. Urdea,et al.  Comparison of selective polymerase chain reaction primers and differential probe hybridization of polymerase chain reaction products for determination of relative amounts of codon 215 mutant and wild-type HIV-1 populations. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[49]  A. Sönnerborg,et al.  Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy , 2001, AIDS.

[50]  S. Paulous,et al.  Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug. , 1996, The Journal of general virology.

[51]  V. Miller.  Structured treatment interruptions in antiretroviral management of HIV-1 , 2001, Current opinion in infectious diseases.

[52]  M. Markowitz,et al.  Origin of Human Immunodeficiency Virus Type 1 Quasispecies Emerging after Antiretroviral Treatment Interruption in Patients with Therapeutic Failure , 2002, Journal of Virology.

[53]  V. Trouplin,et al.  Retracing the Evolutionary Pathways of Human Immunodeficiency Virus Type 1 Resistance to Protease Inhibitors: Virus Fitness in the Absence and in the Presence of Drug , 2000, Journal of Virology.

[54]  J. Holland,et al.  Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses , 1991, Journal of virology.

[55]  E. Domingo,et al.  RNA virus mutations and fitness for survival. , 1997, Annual review of microbiology.

[56]  J. Martinez-Picado,et al.  Replicative Fitness of Protease Inhibitor-Resistant Mutants of Human Immunodeficiency Virus Type 1 , 1999, Journal of Virology.

[57]  E. Yuste,et al.  In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. , 2002, The Journal of general virology.

[58]  J. Metcalf,et al.  Relative Replication Fitness of a High-Level 3′-Azido-3′-Deoxythymidine-Resistant Variant of Human Immunodeficiency Virus Type 1 Possessing an Amino Acid Deletion at Codon 67 and a Novel Substitution (Thr→Gly) at Codon 69 , 2000, Journal of Virology.

[59]  C. Crumpacker,et al.  Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation , 1997, Journal of virology.

[60]  C. Crumpacker,et al.  Decreased Processivity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) Containing Didanosine-Selected Mutation Leu74Val: a Comparative Analysis of RT Variants Leu74Val and Lamivudine-Selected Met184Val , 1999, Journal of Virology.

[61]  C. Verhofstede,et al.  Interruption of reverse transcriptase inhibitors or a switch from reverse transcriptase to protease inhibitors resulted in a fast reappearance of virus strains with a reverse transcriptase inhibitor-sensitive genotype. , 1999, AIDS.

[62]  R. Grant,et al.  Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. , 2000, The Journal of infectious diseases.

[63]  B. Berkhout.  Proposed alternatives for the use of anti-HIV drugs. , 1999, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[64]  H. Lane,et al.  Amino Acid Deletion at Codon 67 and Thr-to-Gly Change at Codon 69 of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Novel Drug Resistance Profiles , 2001, Journal of Virology.

[65]  E. Domingo,et al.  Memory in Viral Quasispecies , 2000, Journal of Virology.

[66]  W. Heneine,et al.  Evidence of a Role for the Q151L Mutation and the Viral Background in Development of Multiple Dideoxynucleoside-Resistant Human Immunodeficiency Virus Type 1 , 2000, Journal of Virology.

[67]  E. Domingo,et al.  Origin and Evolution of Viruses , 2010, Virus Genes.

[68]  R de Boer,et al.  Broad spectrum of in vivo fitness of human immunodeficiency virus type 1 subpopulations differing at reverse transcriptase codons 41 and 215 , 1997, Journal of virology.

[69]  R. Bambara,et al.  The P236L Delavirdine-Resistant Human Immunodeficiency Virus Type 1 Mutant Is Replication Defective and Demonstrates Alterations in both RNA 5′-End- and DNA 3′-End-Directed RNase H Activities , 1999, Journal of Virology.

[70]  A. Perelson,et al.  Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. , 1999, The New England journal of medicine.

[71]  V. Miller.  Resistance to Protease Inhibitors , 2001 .

[72]  David J. Livingston,et al.  Kinetic Characterization of Human Immunodeficiency Virus Type-1 Protease-resistant Variants* , 1996, The Journal of Biological Chemistry.

[73]  E. Domingo,et al.  Viral Quasispecies and Fitness Variations , 1999 .

[74]  J. Coffin,et al.  HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy , 1995, Science.

[75]  D Norbeck,et al.  Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor , 1994, Journal of virology.

[76]  D. Richman,et al.  Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients , 1996, Journal of virology.

[77]  B. Larder,et al.  Recombinant virus assay: a rapid, phenotypic assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates , 1994, Antimicrobial Agents and Chemotherapy.

[78]  C. Perno,et al.  Drug-resistant mutants of HIV-1 in patients exhibiting increasing CD4 cell count despite virological failure of highly active antiretroviral therapy. , 2001, AIDS.

[79]  R. Grant,et al.  Impaired replication of protease inhibitor-resistant HIV-1 in human thymus , 2001, Nature Medicine.

[80]  M. Johnson,et al.  Replicative fitness in vivo of HIV‐1 variants with multiple drug resistance‐associated mutations , 2001, Journal of medical virology.