High Prevalence of Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Antiretroviral Treatment-Experienced Patients from Pune, India

ABSTRACT Among 16 human immunodeficiency virus-infected (subtype C) Batswana patients who failed nelfinavir (NFV)-containing regimens, the most prevalent mutation observed was D30N (54%), followed by L90M (31%). L89I, K20T/I, and E35D polymorphic changes were also identified. These findings suggest that subtype C viruses in Botswana may develop resistance to NFV via subtype-specific pathways.

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Biological characterization of human immunodeficiency virus type 1 subtype C protease carrying indinavir drug-resistance mutations

Journal of General Virology ◽

10.1099/vir.0.81517-0 ◽

2006 ◽

Vol 87 (5) ◽

pp. 1303-1309 ◽

Cited By ~ 6

Author(s):

Luis M. F. Gonzalez ◽

Renato S. Aguiar ◽

Adriana Afonso ◽

Patricia A. Brindeiro ◽

Mônica B. Arruda ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Resistance Mutations ◽

Subtype C ◽

Drug Resistance Mutations ◽

Subtype B ◽

Immunodeficiency Virus

Human immunodeficiency virus type 1 subtype C isolates belong to one of the most prevalent strains circulating worldwide and are responsible for the majority of new infections in the sub-Saharan region and other highly populated areas of the globe. In this work, the impact of drug-resistance mutations in the protease gene of subtype C viruses was analysed and compared with that of subtype B counterparts. A series of recombinant subtype C and B viruses was constructed carrying indinavir (IDV)-resistance mutations (M46V, I54V, V82A and L90M) and their susceptibility to six FDA-approved protease inhibitor compounds (amprenavir, indinavir, lopinavir, ritonavir, saquinavir and nelfinavir) was determined. A different impact of these mutations was found when nelfinavir and lopinavir were tested. The IDV drug-resistance mutations in the subtype C protease backbone were retained for a long period in culture without selective pressure when compared with those in subtype B counterparts in washout experiments.

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Discordant Human Immunodeficiency Virus Type 1 Drug Resistance Mutations, Including K103N, Observed in Cerebrospinal Fluid and Plasma

Clinical Infectious Diseases ◽

10.1086/340865 ◽

2002 ◽

Vol 35 (1) ◽

pp. 82-83 ◽

Cited By ~ 10

Author(s):

K. T. Tashima ◽

T. P. Flanigan ◽

J. Kurpewski ◽

S. M. Melanson ◽

P. R. Skolnik

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Cerebrospinal Fluid ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Immunodeficiency Virus

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Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

Clinical Microbiology Reviews ◽

10.1128/cmr.15.2.247-277.2002 ◽

2002 ◽

Vol 15 (2) ◽

pp. 247-277 ◽

Cited By ~ 176

Author(s):

Robert W. Shafer

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Immunodeficiency Virus ◽

Rt Inhibitors ◽

Hiv 1

SUMMARY There are 16 approved human immunodeficiency virus type 1 (HIV-1) drugs belonging to three mechanistic classes: protease inhibitors, nucleoside and nucleotide reverse transcriptase (RT) inhibitors, and nonnucleoside RT inhibitors. HIV-1 resistance to these drugs is caused by mutations in the protease and RT enzymes, the molecular targets of these drugs. Drug resistance mutations arise most often in treated individuals, resulting from selective drug pressure in the presence of incompletely suppressed virus replication. HIV-1 isolates with drug resistance mutations, however, may also be transmitted to newly infected individuals. Three expert panels have recommended that HIV-1 protease and RT susceptibility testing should be used to help select HIV drug therapy. Although genotypic testing is more complex than typical antimicrobial susceptibility tests, there is a rich literature supporting the prognostic value of HIV-1 protease and RT mutations. This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs.

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