scholarly journals Simple PCR Assays Improve the Sensitivity of HIV-1 Subtype B Drug Resistance Testing and Allow Linking of Resistance Mutations

PLoS ONE ◽  
2007 ◽  
Vol 2 (7) ◽  
pp. e638 ◽  
Author(s):  
Jeffrey A. Johnson ◽  
Jin-Fen Li ◽  
Xierong Wei ◽  
Jonathan Lipscomb ◽  
Diane Bennett ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Drug Resistance Testing ◽  
Subtype B ◽  
Pcr Assays ◽  
Hiv 1

Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains

2020 ◽  
Vol 75 (6) ◽  
pp. 1567-1574
Author(s):  
Daniela Sánchez ◽  
Solange Arazi Caillaud ◽  
Ines Zapiola ◽  
Silvina Fernandez Giuliano ◽  
Rosa Bologna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Current Knowledge ◽  
Phylogenetic Analyses ◽  
Genotypic Diversity ◽  
Resistance Testing ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Middle Income ◽  
Subtype B ◽  
Hiv 1

Abstract Background Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate. Materials and methods HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses. Results Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs. Conclusions Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs.

scholarly journals Monitoring of HIV Drug Resistance Mutations in Newly Diagnosed Patients in Cyprus (2010–2012)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S424-S424
Author(s):  
Ioannis Demetriades
Keyword(s):  
Drug Resistance ◽  
Phylogenetic Trees ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
High Rate ◽  
Resistance Testing ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Subtype B ◽  
Hiv 1

Abstract Background A molecular epidemiology study of HIV-1 infection was conducted in 100 HIV-1 diagnosed and untreated patients in Cyprus representing 65.4 percent of all the reported HIV-1 infections in Cyprus between 2010 and 2012. Methods Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and 18 patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Results Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other CRFs (7.0%) and unknown recombinant forms, URFs (12%). Most of newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33–48) reporting having sex with other men, MSM (51%). Conclusion A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM. Twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are subtype A1 and three subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with subtype A2 strain, both with the PI drug resistance mutation M46L and one patient from Greece with subtype A1 strain with the NNRTI drug resistance mutation K103N. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of the HIV-1 drug resistance to elsulfavirine and the effectiveness of it among Russian treatment-naïve patients

2021 ◽  
Vol 12 (5) ◽  
pp. 29-39
Author(s):  
A. A. Kirichenko ◽  
D. E. Kireev ◽  
A. V. Kravchenko ◽  
A. V. Pokrovskaya ◽  
U. A. Kuimova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Virological Failure ◽  
Resistance Testing ◽  
Study Group ◽  
Resistance Mutations ◽  
Drug Resistance Testing ◽  
The Third ◽  
Treatment Naïve ◽  
Hiv 1

The aim of the study: to analyze the prevalence of resistance mutations to elsulfavirine and to evaluate the effectiveness of it among HIV-infected treatment-naïve patients in real clinical practice.Materials and methods. The study included 578 patients with HIV infection, which divided into 3 groups. The first group is 354 HIV-infected treatment-naïve patients for whom HIV-1 nucleotide sequences were obtained as part of routine drug resistance testing. The second study group included 111 HIV-infected treatment-naïve patients, tested for drug resistance before the antiretroviral therapy containing elsulfavirine. The third study group included 113 HIV-infected treatment-naïve patients, each of whom was assigned a treatment regimen containing elsulfavirine without prior drug resistance testing. The observation period for patients of the second and third groups who received treatment was 24 weeks. To assess the effectiveness of antiretroviral therapy in patients, viral load, CD4+ T-cell counts, and adherence to therapy were assessed. HIV-1 subtypes and drug resistance mutations were determined using the Stanford HIV Resistance Database (v. 8.9-1). To clarify the results of subtyping, phylogenetic analysis of nucleotide sequences was carried out using the MEGA program (v. 6.0).Results. The prevalence of mutations associated with decreased susceptibility to elsulfavirine among HIV-infected treatment-naïve patients was 1.7% and 4.5% for the first and second groups of patients, respectively. All of the patients have only single resistance mutations which, according to the results of preclinical studies, cannot cause drug resistance. The use of elsulfavirine in real clinical practice among treatment-naïve patients has demonstrated good virological and immunological efficacy of the drug. As a result of 24 weeks of therapy in patients of the second group, no treatment ineffectiveness, and the development of drug resistance were observed. Among the patients of the third group, 6 patients (5.3%) have the virological failure of therapy associated with the resistance to the used drugs. All patients with virological failure had a resistance mutation profile associated with a high level of drug resistance to one of the drugs in the treatment regimen, lamivudine. Additionally, 1 patient had a combination of mutations that reduce susceptibility to elsulfavirine, and 4 patients had mutations that can reduce susceptibility to elsulfavirine in combination with other mutations.Conclusion. The low prevalence of mutations associated with a decrease in susceptibility to elsulfavirine and the absence of combinations of mutations make it possible to predict the successful use of this drug for Russian treatment-naïve patients. Reported cases of virological failure of antiretroviral therapy are difficult to interpret in the context of elsulfavirine due to the lack of an exact list of mutations and their combinations, and associations with the degree of resistance to it. This study describes for the first time the mutation profiles in patients with virological failure of therapy containing elsulfavirine and demonstrates the necessity of the further study of drug resistance profile to drug in vitro and in vivo.

scholarly journals Transmitted Drug Resistance in Treatment-naïve HIV-Infected VCT clients in Taiwan, 2007–2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S423-S424
Author(s):  
Hung-Chin Tsai ◽  
I-Tzu Chen ◽  
Susan Shin-Jung Lee ◽  
Yao-Shen Chen
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Resistance Mutation ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Drug Resistance Testing ◽  
Subtype B ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Level Resistance

Abstract Background The transmission of drug-resistant HIV-1 strains might compromise the efficacy of antiretroviral treatment. The aim of this study was to monitor the prevalence of transmitted drug resistance (TDR) in Taiwan, where free highly active antiretroviral therapy (HAART) was provided since 1997. Methods A cohort study on TDR was conducted in antiretroviral therapy -naïve HIV-1 ¡Vinfected voluntary counseling and testing (VCT) clients from 2007 to 2016 in southern Taiwan. Genotypic drug resistance testing to PR/RT (pol gene) were determined by ViroSeqTM system and drug resistance testing to integrase inhibitors (INSTI) was done by in house PCR. Antiretroviral resistance was interpreted using the HIVdb program of the Stanford University HIV Drug Resistance Database. The patients classified as having low-level resistance, intermediate resistance and high-level resistance were defined as having drug resistance. Resistance-associated mutations were defined by the presence of at least one mutation included in the 2017 drug resistance mutation list of the International AIDS Society-USA consensus guidelines. Results A total of 29384 individuals received a free HIV anonymously screening test during 2007 to 2016. The positive rate for HIV-1 infection was 2%. Sequences were obtained from 407 individuals, of whom 90% were infected by MSM, and 10% were infected by heterosexually. Subtype B HIV-1 strains were found in 97%, subtype C in 0.3% and subtype CRF01_AE in 2.7%. A total of 6% was found to harbor drug resistance strains. The most common NRTI resistance associated mutation was D67N, M184V, K219N, Y118I and T215S/P. The most common NNRTI resistance associated mutation was Y181C, K103N, V179D and Y318F. No any one harbored resistance to INSTI inhibitors (n = 188). Conclusion The resistance prevalence (6%) in this study supported the WHO guideline to prescribe pol resistance testing before initiation of HAART therapy in the treatment naïve patients. Disclosures All authors: No reported disclosures.

scholarly journals A2 Phylogenetic investigation of transmitted HIV-1 drug resistance mutations in Denmark, 2009–17

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
J Fonager ◽  
T K Fischer
Keyword(s):  
Drug Resistance ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Sequence Alignments ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Genotypic Resistance Testing ◽  
Hiv 1

Abstract Transmission of HIV-1 resistance mutations among therapy-naïve patients impairs the efficiency of antiretroviral therapy (ART). Therefore, genotypic resistance testing of patients is recommended at baseline, as this both allows for the selection of the correct ART regimen and for surveillance of transmitted drug resistance mutations (TDRM) among therapy naive HIV-1 patients. In Denmark, the occurrence of TDRM in newly diagnosed and therapy naïve HIV-1 patients is monitored through the SERO project. Here, we investigated if the prevalence of TDRM differed between patients within and outside of phylogenetically identified transmission clusters. Samples from 1,227 newly diagnosed HIV-1 patients were sent along with epidemiological information to the Virological Surveillance and Research group at Statens Serum Institut. HIV-1 RNA extraction, RT-PCR and Sanger sequencing of the pol gene was performed using an in-house assay. The sequences were analyzed using BioNumerics v. 6.6 and manually checked for the presence of mixed mutations and analyzed for mutations using the HIVDB 8.4 algorithm implemented at the Stanford database. Sequence alignments were performed in Mafft, and phylogenetic analysis was performed using Mega 6.0 using the Maximum likelihood general time reversible model with 100 bootstrap replicates. Clusters were identified with ClusterPicker at default settings (cluster support = 90%, genetic distance 4.5%). Active clusters contained newly diagnosed patients from the 2015 to 2017 period. HIV-1 sequences from 588 patients belonged to one of 154 clusters, and sequences from 639 patients did not belong to a cluster. Patients in clusters were significantly more likely to be men who have sex with men and subtype B and significantly less likely to be late presenters (Fisher’s test P < 0.05). The TDRM prevalence was significantly higher for patients outside of clusters than within clusters, 16.6 per cent versus 12.1 per cent, respectively (Fisher’s test P < 0.05); however, no significant differences were found in the TDRM prevalence between the 75 active and 79 inactive clusters, nor between small (<3 patients) and large (≥3 patients) clusters. E138A, V179D, and K103N were the three most prevalent TDRMs for both patient groups, whereas M41L differed between them. In Denmark, the TDRM prevalence is lower within clusters than outside, indicating that TDRM cases are either imported and/or belong to yet unidentified clusters.

scholarly journals Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010–2018

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Tali Wagner ◽  
Neta S. Zuckerman ◽  
Tami Halperin ◽  
Daniel Chemtob ◽  
Itzchak Levy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Subtype C ◽  
Reverse Transcriptase Inhibitors ◽  
Subtype B ◽  
Hiv 1

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.

Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China

2020 ◽  
Vol 18 (3) ◽  
pp. 210-218
Author(s):  
Guolong Yu ◽  
Yan Li ◽  
Xuhe Huang ◽  
Pingping Zhou ◽  
Jin Yan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Phylogenetic Analyses ◽  
Resistance Mutations ◽  
Protease Inhibition ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

scholarly journals Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Bin Zhao ◽  
Minghui An ◽  
Wei Song ◽  
Xue Dong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Northeast China ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Shenyang City ◽  
Subtype B ◽  
Recent Hiv Infection ◽  
Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

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