scholarly journals Characterisation of HIV-1 transmission clusters and drug-resistant mutations in Denmark, 2004 to 2016

2018 ◽  
Vol 23 (44) ◽  
Author(s):  
Andreas Petersen ◽  
Susan A Cowan ◽  
Jens Nielsen ◽  
Thea K Fischer ◽  
Jannik Fonager
Keyword(s):  
Drug Resistance ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Transmission Networks ◽  
Late Presenters ◽  
Drug Resistance Mutations ◽  
Hiv Epidemic ◽  
Immunodeficiency Virus ◽  
Sex With Men ◽  
Hiv 1

This study describes the prevalence of human immunodeficiency virus (HIV) drug resistance mutations among 1,815 patients in Denmark from 2004 to 2016 and characterises transmission clusters. POL sequences were analysed for subtype, drug resistance mutations and phylogenetic relationship. The prevalence of surveillance drug resistance mutations (SDRM) was 6.7%, while the prevalence of drug resistance mutations (DRM) with a clinical impact was 12.3%. We identified 197 transmission clusters with 706 patients. Patients 40 years or older were less likely to be members of a transmission cluster and patients in transmission clusters were less likely to be infected abroad. The proportion of late presenters (LP) was lower in active compared with inactive clusters. Large active clusters consisted of more men who have sex with men (MSM), had members more frequently infected in Denmark and contained a significantly lower proportion of LP and significantly fewer patients with DRM than small active clusters. Subtyping demonstrated that the Danish HIV epidemic is gradually becoming more composed of non-B subtypes/circulating recombinant forms. This study shows that active HIV-1 transmission has become increasingly MSM-dominated and that the recent increase in SDRM and DRM prevalence is not associated with more sustained transmission within identified transmission networks or clusters.

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 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 Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure

2016 ◽  
Vol 60 (6) ◽  
pp. 3380-3397 ◽  
Author(s):  
Fred Kyeyune ◽  
Richard M. Gibson ◽  
Immaculate Nankya ◽  
Colin Venner ◽  
Samar Metha ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Sanger Sequencing ◽  
Antiretroviral Treatment ◽  
Low Frequency ◽  
Drug Resistant ◽  
Viral Quasispecies ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.

scholarly journals Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Zhang ◽  
Bingyu Liang ◽  
Xu Liang ◽  
Zhaosen Lin ◽  
Yuan Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Injection Drug Users ◽  
Drug Users ◽  
Resistance Mutations ◽  
Related Factors ◽  
Transmission Networks ◽  
Drug Resistance Mutations ◽  
Two Cities ◽  
Viral Subtypes ◽  
Hiv 1

IntroductionPretreatment drug resistance (PDR) is becoming an obstacle to the success of ART. This study investigated the prevalence of PDR and the transmission clusters (TCs) of drug resistance mutations (DRMs) in two cities where drug abuse used to be high to describe the local HIV-1 transmission dynamics.MethodsPlasma samples were obtained from 1,027 ART-naïve patients in Guangxi. Viral subtypes and DRMs were identified. Transmission network and related factors were also determined.ResultsA total of 1,025 eligible sequences were obtained from Qinzhou (65.8%) and Baise (34.2%) cities. The predominant HIV-1 genotype was CRF08_BC (45.0%), followed by CRF01_AE (40.9%). The overall prevalence of PDR was 8.3%, and resistance to NNRTI was the most common. Putative links with at least one other sequence were found in 543/1,025 (53.0%) sequences, forming 111 clusters (2–143 individuals). The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). Clusters related to shared DRMs were more frequent and larger in CRF08_BC. The prevalence of shared DRMs increased with time, while the proportion of PDR gradually decreased. Age > 50 years was associated with clustering. Subtype CRF08_BC was more likely to have DRMs, PDR propagation, and DRM sharing.ConclusionPDR prevalence is moderate in this region. The association between PDR and subtype CRF08_BC suggested that DRMs spreading from injection drug users (IDUs) to heterosexuals (HETs) might be the major source of PDR in this region. Our findings highlight the significance of continuous surveillance of PDR.

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.

Short Communication: Discordance in Drug Resistance Mutations Between Blood Plasma and Semen or Rectal Secretions Among Newly Diagnosed HIV-1-Infected Thai Men Who Have Sex with Men

2018 ◽  
Vol 34 (7) ◽  
pp. 626-628
Author(s):  
Akarin Hiransuthikul ◽  
Rapeeporn Wongkanya ◽  
Sunee Sirivichayakul ◽  
Deondara Trachunthong ◽  
Thanthip Sungsing ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Plasma ◽  
Short Communication ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Sex With Men ◽  
Hiv 1

scholarly journals Validation of publicly-available software used in analyzing NGS data for HIV-1 drug resistance mutations and transmission networks in a Washington, DC, Cohort

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0214820 ◽  
Author(s):  
Kamwing Jair ◽  
Chase D. McCann ◽  
Harrison Reed ◽  
Amanda D. Castel ◽  
Marcos Pérez-Losada ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Washington Dc ◽  
Resistance Mutations ◽  
Transmission Networks ◽  
Drug Resistance Mutations ◽  
Ngs Data ◽  
Hiv 1

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 Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease

2007 ◽  
Vol 81 (6) ◽  
pp. 2887-2898 ◽  
Author(s):  
Sandra M. Mueller ◽  
Birgit Schaetz ◽  
Kathrin Eismann ◽  
Silke Bergmann ◽  
Michael Bauerle ◽  
...  
Keyword(s):  
Drug Resistance ◽  
T Cells ◽  
Immune Responses ◽  
Hla Class I ◽  
Class I ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT To determine the influence of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells on the development of drug resistance mutations in the HIV-1 protease, we analyzed protease sequences from viruses from a human leukocyte antigen class I (HLA class I)-typed cohort of 94 HIV-1-positive individuals. In univariate statistical analyses (Fisher's exact test), minor and major drug resistance mutations as well as drug-associated polymorphisms showed associations with HLA class I alleles. All correlations with P values of 0.05 or less were considered to be relevant without corrections for multiple tests. A subset of these observed correlations was experimentally validated by enzyme-linked immunospot assays, allowing the definition of 10 new epitopes recognized by CD8+ T cells from patients with the appropriate HLA class I type. Several drug resistance-associated mutations in the protease acted as escape mutations; however, cells from many patients were still able to generate CD8+ T cells targeting the escape mutants. This result presumably indicates the usage of different T-cell receptors by CD8+ T cells targeting these epitopes in these patients. Our results support a fundamental role for HLA class I-restricted immune responses in shaping the sequence of the HIV-1 protease in vivo. This role may have important clinical implications both for the understanding of drug resistance pathways and for the design of therapeutic vaccines targeting drug-resistant HIV-1.

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