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

2020 ◽  
Vol 221 (12) ◽  
pp. 1962-1972 ◽  
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.

scholarly journals Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana

Medicine ◽  
2019 ◽  
Vol 98 (6) ◽  
pp. e14313 ◽  
Author(s):  
Christopher Z. Abana ◽  
Kwamena W.C. Sagoe ◽  
Evelyn Y. Bonney ◽  
Edward K. Maina ◽  
Ishmael D. Aziati ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Viral Load ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Emergence of Drug Resistance Mutations in Human Immunodeficiency Virus Type 2-Infected Subjects Undergoing Antiretroviral Therapy

2000 ◽  
Vol 38 (4) ◽  
pp. 1370-1374 ◽  
Author(s):  
Berta Rodés ◽  
Africa Holguín ◽  
Vincent Soriano ◽  
Manuela Dourana ◽  
Kamal Mansinho ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Amino Acid ◽  
Protease Inhibitors ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1

The reverse transcriptase (RT) and protease genes from 12 human immunodeficiency virus type 2 (HIV-2)-infected individuals who had been exposed to antiretroviral drugs for longer than 6 months were examined for the presence of mutations which could be involved in drug resistance. Four individuals carried virus genotypes with amino acid substitutions potentially associated with resistance to nucleoside analogues: two at codon 70 (K→R) and two at codon 184 (M→V). Moreover, the latter two patients harbored a codon Q151M mutation which is associated to multidrug resistance in HIV-1, and one of these subjects carried some of the typically linked mutations at codons 65 and 69. With regard to the protease inhibitors, substitutions associated with resistance to protease inhibitors at codon 46 were observed in all individuals. Moreover, minor resistance mutations, as well as new ones of unknown meaning, were often seen in the protease gene. In conclusion, amino acid changes in the HIV-2 RT and protease genes which could be associated with drug resistance seem to occur at positions identical to those for HIV-1.

scholarly journals Human Immunodeficiency Virus type 1 Drug Resistance Mutations in Patients Failing Antiretroviral Therapy in Lebanon from 2009 to 2013

2021 ◽  
Vol 1 (1) ◽  
pp. 113-123
Author(s):  
Ahmad A. Hachem ◽  
Essa H. Hariri ◽  
Anthony Mansour ◽  
Jacques Mokhbat
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Transcriptase Inhibitor ◽  
Resistance Mutations ◽  
Therapy Failure ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1

Background: Antiretroviral drug resistance remains a significant problem in the clinical management of patients infected with the Human Immunodeficiency Virus type-1. Aim: This study investigates and reports data on the molecular characterization of HIV-1 isolates from patients who are in a state of therapy failure. Methods: This is a retrospective study conducted on 65 patients in therapy failure. Inclusion criteria included patients diagnosed as being in therapy failure between the years 2009 and 2013. We defined ART failure as either a failure to achieve viral suppression or a failure to detect viral loads below 500 copies/mL after virological suppression in at least two plasma samples.  We used the published WHO list for surveillance of transmitted resistance and the Stanford HIV Drug Resistance Database to identify drug resistance mutations. Results: 65% of the participants had at least one drug resistance mutation (DRM). 12% of the population sampled had resistance to only one ART class, 32% presented with resistance to two classes of antiretroviral drugs, and 20% had resistance to all three classes of drugs. The prevalence of nucleoside transcriptase inhibitor (NRTI) mutations was 55%, the most common DRM being M184V. The prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations was 58%, with the most common mutation being the K103N mutation. The prevalence of protease inhibitors drug resistance mutations was 23%, with mutations V82A and I47V being present in 10% of the study population. Conclusion: Our study is the first molecular characterization of DRM emergence in HIV-1 strains from patients failing antiretroviral therapy in Lebanon. Continuous monitoring of resistance patterns for HIV in the country is necessary to tackle the emergent drug resistance.

scholarly journals Combination of Drugs and Drug-Resistant Reverse Transcriptase Results in a Multiplicative Increase of Human Immunodeficiency Virus Type 1 Mutant Frequencies

2002 ◽  
Vol 76 (18) ◽  
pp. 9253-9259 ◽  
Author(s):  
Louis M. Mansky ◽  
Dennis K. Pearl ◽  
Lisa C. Gajary
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Mutant Frequency

ABSTRACT Replication of drug-resistant human immunodeficiency virus type 1 (HIV-1) in the presence of drug can lead to the failure of antiretroviral drug treatment. Drug failure is associated with the accumulation of drug resistance mutations. Previous studies have shown that 3′-azido-3′-deoxythymidine (AZT), (−)2′,3′-dideoxy-3′-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT) can increase the virus in vivo mutation rate. In this study, the combined effects of drug-resistant RT and antiretroviral drugs on the HIV-1 mutant frequency were determined. In most cases, a multiplicative effect was observed with AZT-resistant or AZT/3TC dually resistant RT and several drugs (i.e., AZT, 3TC, hydroxyurea, and thymidine) and led to increases in the odds of recovering virus mutants to over 20 times that of the HIV-1 mutant frequency in the absence of drug or drug-resistance mutations. This observation indicates that HIV-1 can mutate at a significantly higher rate when drug-resistant virus replicates in the presence of drug. These increased mutant frequencies could have important implications for HIV-1 population dynamics and drug therapy regimens.

scholarly journals Effects of Drug Resistance Mutations L100I and V106A on the Binding of Pyrrolobenzoxazepinone Nonnucleoside Inhibitors to the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Catalytic Complex

2004 ◽  
Vol 48 (5) ◽  
pp. 1570-1580 ◽  
Author(s):  
Giada A. Locatelli ◽  
Giuseppe Campiani ◽  
Reynel Cancio ◽  
Elena Morelli ◽  
Anna Ramunno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Wild Type ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have previously described a novel class of nonnucleoside reverse transcriptase (RT) inhibitors, the pyrrolobenzoxazepinone (PBO) and the pyridopyrrolooxazepinone (PPO) derivatives, which were effective inhibitors of human immunodeficiency virus type 1 (HIV-1) RT, either wild type or carrying known drug resistance mutations (G. Campiani et al., J. Med. Chem. 42:4462-4470, 1999). The lead compound of the PPO class, (R)-(−)-PPO464, was shown to selectively target the ternary complex formed by the viral RT with its substrates nucleic acid and nucleotide (G. Maga et al., J. Biol. Chem. 276:44653-44662, 2001). In order to better understand the structural basis for this selectivity, we exploited some PBO analogs characterized by various substituents at C-3 and by different inhibition potencies and drug resistance profiles, and we studied their interaction with HIV-1 RT wild type or carrying the drug resistance mutations L100I and V106A. Our kinetic and thermodynamic analyses showed that the formation of the complex between the enzyme and the nucleotide increased the inhibition potency of the compound PBO354 and shifted the free energy (energy of activation, ΔG#) for inhibitor binding toward more negative values. The V106A mutation conferred resistance to PBO 354 by increasing its dissociation rate from the enzyme, whereas the L100I mutation mainly decreased the association rate. This latter mutation also caused a severe reduction in the catalytic efficiency of the RT. These results provide a correlation between the efficiency of nucleotide utilization by RT and its resistance to PBO inhibition.

Subtype Classification by Polymerase and Gag Genes of HIV-1 Iranian Sequences Registered in the NCBI GenBank

2020 ◽  
Vol 17 ◽  
Author(s):  
Behzad Dehghani ◽  
Zahra Hasanshahi ◽  
Tayebeh Hashempour ◽  
Parvin Afsar Kazerooni
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Human Immunodeficiency Virus Type ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Online Tools ◽  
Immunodeficiency Virus ◽  
Reliable Software ◽  
Hiv 1

Background: The rate of Human Immunodeficiency Virus type 1 (HIV-1) infection in Iran has increased dramatically in the last few years. Objective: The aim of this study was to investigate the HIV subtype amongst all Iranian HIV sequences, using 8 online websites. Methods: In this study, 637 sequences of polymerase, and gag genes of HIV-1 were obtained from NCBI. HIV-1 subtyping was done, using 8 reliable software. Results: The final results of the 8 online tools indicated that the majority of sequences were HIV-1 subtype CRF35 AD. However, it appeared that in some genes a few programs could not determine specific subtypes and in some cases they described different subtypes. Conclusion: Considering the CRF35 AD diagram, it was clear that integrase was not an appropriate region to define this subtype. Also the full length of gag gene should be used for subtyping. For CRF1, AE envelop gene is a reliable region to define this subtype. Stanford software was used to determine the drug resistance prevalence and in 5.7% of the sequences, drug resistance mutations were found.

scholarly journals Near Real-Time Identification of Recent Human Immunodeficiency Virus Transmissions, Transmitted Drug Resistance Mutations, and Transmission Networks by Multiplexed Primer ID–Next-Generation Sequencing in North Carolina

2020 ◽  
Author(s):  
Shuntai Zhou ◽  
Sabrina Sizemore ◽  
Matt Moeser ◽  
Scott Zimmerman ◽  
Erika Samoff ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
North Carolina ◽  
Drug Resistance ◽  
Next Generation Sequencing ◽  
Resistance Mutations ◽  
Recent Infection ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Generation Sequencing ◽  
Hiv 1

Abstract Background The identification of recent human immunodeficiency virus (HIV) 1 infections among people with new HIV diagnoses is important to both tailoring and assessing the impact of HIV-1 prevention strategies. Methods We developed a multiplexed Primer ID–next-generation sequencing approach to identify recent infections by measuring the intrahost viral diversity over multiple regions of the HIV-1 genome, in addition to detecting drug resistance mutations (DRMs) and phylogenetically linked clusters. We summarize the field implementation of this all-in-one platform among persons with newly diagnosed HIV-1 by the North Carolina State Laboratory of Public Health in 2018. Results Overall, recent infection was identified in 94 (35%) of 268 patients with new HIV diagnoses. People <30 years old, and people who inject drugs were more likely to have diagnoses of recent infection. The reverse-transcriptase region K103N was the most commonly detected DRM (prevalence, approximately 15%). We found a total of 28 clusters, and persons with recent infection were more likely to be cluster members than were those with chronic infections (P = .03). Conclusions We demonstrate the rapid identification of recent infection and pretreatment DRMs coupled with cluster analysis that will allow prioritization of linkage to care, treatment, and prevention interventions to those at highest risk of onward transmission.

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