Multiple drug resistance mutations in human immunodeficiency virus in semen but not blood of a man on antiretroviral therapy

ABSTRACT AIDS dementia complex (ADC) in human immunodeficiency virus (HIV)-infected patients continues to be a problem in the era of highly active antiretroviral therapy (HAART). A better understanding of the drug resistance mutation patterns that emerge in the central nervous system (CNS) during HAART is of paramount importance as these differences in drug resistance mutations may explain underlying reasons for poor penetration of antiretroviral drugs into the CNS and suboptimal concentrations of the drugs that may reside in the brains of HIV-infected individuals during therapy. Thus, we provide a detailed analysis of HIV type 1 (HIV-1) protease and reverse transcriptase (RT) genes derived from different regions of the brains of 20 HIV-1-infected patients (5 without ADC, 2 with probable ADC, and 13 with various stages of ADC) on antiretroviral therapy. We show the compartmentalization and independent evolution of both primary and secondary drug resistance mutations to both RT and protease inhibitors in diverse regions of the CNS of HIV-infected patients, with and without dementia, on antiretroviral therapy. Our results suggest that the independent evolution of drug resistance mutations in diverse areas of the CNS may emerge as a consequence of incomplete suppression of HIV, probably related to suboptimal drug levels in the CNS and drug selection pressure. The emergence of resistant virus in the CNS may have considerable influence on the outcome of neurologic disease and also the reseeding of HIV in the systemic circulation upon failure of therapy.

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Interactions Between Drug Resistance Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Journal of General Virology ◽

10.1099/0022-1317-75-5-951 ◽

1994 ◽

Vol 75 (5) ◽

pp. 951-957 ◽

Cited By ~ 99

Author(s):

B. A. Larder

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Reverse Transcriptase ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Immunodeficiency Virus

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Single Base Primer Extension Assay (SNaPshot) for Rapid Detection of Human Immunodeficiency Virus - 1 Drug Resistance Mutations

Journal of Molecular Biomarkers & Diagnosis ◽

10.4172/2155-9929.1000271 ◽

2016 ◽

Vol 7 (2) ◽

Author(s):

Arpan A ◽

Salil V

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Rapid Detection ◽

Primer Extension ◽

Resistance Mutations ◽

Primer Extension Assay ◽

Single Base ◽

Drug Resistance Mutations ◽

Immunodeficiency Virus ◽

Human Immunodeficiency Virus 1

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Dramatic Activation of Antibiotic Production in Streptomyces coelicolor by Cumulative Drug Resistance Mutations

Applied and Environmental Microbiology ◽

10.1128/aem.02800-07 ◽

2008 ◽

Vol 74 (9) ◽

pp. 2834-2840 ◽

Cited By ~ 100

Author(s):

Guojun Wang ◽

Takeshi Hosaka ◽

Kozo Ochi

Keyword(s):

Drug Resistance ◽

Multiple Drug Resistance ◽

Antibiotic Production ◽

Streptomyces Coelicolor ◽

Strain Improvement ◽

Multiple Drug ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Order Of Magnitude

ABSTRACT We recently described a new method to activate antibiotic production in bacteria by introducing a mutation conferring resistance to a drug such as streptomycin, rifampin, paromomycin, or gentamicin. This method, however, enhanced antibiotic production by only up to an order of magnitude. Working with Streptomyces coelicolor A3(2), we established a method for the dramatic activation of antibiotic production by the sequential introduction of multiple drug resistance mutations. Septuple and octuple mutants, C7 and C8, thus obtained by screening for resistance to seven or eight drugs, produced huge amounts (1.63 g/liter) of the polyketide antibiotic actinorhodin, 180-fold higher than the level produced by the wild type. This dramatic overproduction was due to the acquisition of mutant ribosomes, with aberrant protein and ppGpp synthesis activity, as demonstrated by in vitro protein synthesis assays and by the abolition of antibiotic overproduction with relA disruption. This new approach, called “ribosome engineering,” requires less time, cost, and labor than other methods and may be widely utilized for bacterial strain improvement.

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Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa026 ◽

2020 ◽

Vol 221 (12) ◽

pp. 1962-1972 ◽

Cited By ~ 1

Author(s):

Philip L Tzou ◽

Diane Descamps ◽

Soo-Yon Rhee ◽

Dana N Raugi ◽

Charlotte Charpentier ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Amino Acid ◽

Meta Analysis ◽

Multiple Comparisons ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Immunodeficiency Virus ◽

Hiv 1

Abstract Background HIV-1 and HIV-2 differ in their antiretroviral (ARV) susceptibilities and drug resistance mutations (DRMs). Methods We analyzed published HIV-2 pol sequences to identify HIV-2 treatment-selected mutations (TSMs). Mutation prevalences were determined by HIV-2 group and ARV status. Nonpolymorphic mutations were those in <1% of ARV-naive persons. TSMs were those associated with ARV therapy after multiple comparisons adjustment. Results We analyzed protease (PR) sequences from 483 PR inhibitor (PI)-naive and 232 PI-treated persons; RT sequences from 333 nucleoside RT inhibitor (NRTI)-naive and 252 NRTI-treated persons; and integrase (IN) sequences from 236 IN inhibitor (INSTI)-naive and 60 INSTI-treated persons. In PR, 12 nonpolymorphic TSMs occurred in ≥11 persons: V33I, K45R, V47A, I50V, I54M, T56V, V62A, A73G, I82F, I84V, F85L, L90M. In RT, 9 nonpolymorphic TSMs occurred in ≥10 persons: K40R, A62V, K70R, Y115F, Q151M, M184VI, S215Y. In IN, 11 nonpolymorphic TSMs occurred in ≥4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, R231 5-amino acid insertions. Nine of 32 nonpolymorphic TSMs were previously unreported. Conclusions This meta-analysis confirmed the ARV association of previously reported HIV-2 DRMs and identified novel TSMs. Genotypic and phenotypic studies of HIV-2 TSMs will improve approaches to predicting HIV-2 ARV susceptibility and treating HIV-2–infected persons.

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