scholarly journals Characteristics of HIV-1 Molecular Transmission Networks and Drug Resistance Among Men Who Have Sex with Men in Tianjin, China (2014-2018)

2020 ◽  
Author(s):  
Minna Zheng ◽  
Maohe Yu ◽  
Shaohui Chen ◽  
Ning Zhou ◽  
Tielin Ning ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Transmission ◽  
Transmitted Disease ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Bootstrap Support ◽  
Resistance Mutations ◽  
Sexually Transmitted ◽  
Sex With Men ◽  
Hiv 1

Abstract BackgroundIn Tianjin, China, there is a relatively high prevalence of HIV in men who have sex with men (MSM). The number of cases of HIV in Tianjin is also increasing. We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. MethodsBlood samples were collected from 510 newly diagnosed antiretroviral therapy (ART)-naïve HIV-1-infected subjects among MSM in Tianjin. Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. Molecular clusters were identified with 1.5% genetic distance and 90% bootstrap support.ResultsAmong the 436 HIV-1 pol sequences obtained from the study participants, various genotypes were identified, including CRF01_AE (56.9%), CRF07_BC (27.8%), B (7.3%), CRF55_01B (4.1%), unique recombinant forms (URFs) (3.7%), and CRF59_01B (0.2%). A higher prevalence of X4 viruses was observed in individuals infected with CRF55_01B (56.3%) and CRF01_AE (46.2%) than with other subtypes. Of all 110 sequences in the 36 clusters, 62 (56.4%) were observed in 23 CRF01_AE clusters and 18 (16.4%) in four CRF07_BC clusters. Nine sequences clustered with at least one other shared the same drug resistance mutation (DRM). In different cluster sizes, the distributions of individuals by age, presence of sexually transmitted disease, and presence of DRMs, were significantly different. ConclusionWe revealed the characteristics of HIV molecular transmission, tropism, and DRMs of ART-naïve HIV-infected individuals among the MSM population in Tianjin. Identifying infected persons at risk of transmission is necessary for proposing counseling and treating these patients to reduce the risk of HIV transmission.

scholarly journals Characteristics of HIV-1 molecular transmission networks and drug resistance among men who have sex with men in Tianjin, China (2014–2018)

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Minna Zheng ◽  
Maohe Yu ◽  
Shaohui Cheng ◽  
Ning Zhou ◽  
Tielin Ning ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Transmission ◽  
Transmitted Disease ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Bootstrap Support ◽  
Resistance Mutations ◽  
Sexually Transmitted ◽  
Sex With Men ◽  
Hiv 1

Abstract Background In Tianjin, China, there is a relatively high prevalence of HIV in men who have sex with men (MSM). The number of HIV cases in Tianjin is also increasing. We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. Methods Blood samples were collected from 510 newly diagnosed antiretroviral therapy (ART)-naïve HIV-1-infected subjects among MSM in Tianjin. Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. Molecular clusters were identified with 1.5% genetic distance and 90% bootstrap support. Results Among the 436 HIV-1 pol sequences obtained from the study participants, various genotypes were identified, including CRF01_AE (56.9%), CRF07_BC (27.8%), B (7.3%), CRF55_01B (4.1%), unique recombinant forms (URFs) (3.7%), and CRF59_01B (0.2%). A higher prevalence of X4 viruses was observed in individuals infected with CRF55_01B (56.3%) and CRF01_AE (46.2%) than with other subtypes. Of all 110 sequences in the 36 clusters, 62 (56.4%) were observed in 23 CRF01_AE clusters and 18 (16.4%) in four CRF07_BC clusters. Eight sequences clustered with at least one other shared the same drug resistance mutation (DRM). In different cluster sizes, the distributions of individuals by age, presence of sexually transmitted disease, and presence of DRMs, were significantly different. Conclusion We revealed the characteristics of HIV molecular transmission, tropism, and DRMs of ART-naïve HIV-infected individuals among the MSM population in Tianjin. Identifying infected persons at risk of transmission is necessary for proposing counseling and treating these patients to reduce the risk of HIV transmission.

scholarly journals Characteristics of HIV-1 molecular transmission networks and drug resistance among men who have sex with men in Tianjin, China (2014-2018)

2020 ◽  
Author(s):  
Minna Zheng ◽  
Maohe Yu ◽  
Shaohui Chen ◽  
Ning Zhou ◽  
Tielin Ning ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Transmission ◽  
Transmitted Disease ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Bootstrap Support ◽  
Resistance Mutations ◽  
Sexually Transmitted ◽  
Sex With Men ◽  
Hiv 1

Abstract Background In Tianjin, China, there is a relatively high prevalence of HIV in men who have sex with men (MSM). The number of HIV cases in Tianjin is also increasing. We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. Methods Blood samples were collected from 510 newly diagnosed antiretroviral therapy (ART)-naïve HIV-1-infected subjects among MSM in Tianjin. Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. Molecular clusters were identified with 1.5% genetic distance and 90% bootstrap support.Results Among the 436 HIV-1 pol sequences obtained from the study participants, various genotypes were identified, including CRF01_AE (56.9%), CRF07_BC (27.8%), B (7.3%), CRF55_01B (4.1%), unique recombinant forms (URFs) (3.7%), and CRF59_01B (0.2%). A higher prevalence of X4 viruses was observed in individuals infected with CRF55_01B (56.3%) and CRF01_AE (46.2%) than with other subtypes. Of all 110 sequences in the 36 clusters, 62 (56.4%) were observed in 23 CRF01_AE clusters and 18 (16.4%) in four CRF07_BC clusters. Eight sequences clustered with at least one other shared the same drug resistance mutation (DRM). In different cluster sizes, the distributions of individuals by age, presence of sexually transmitted disease, and presence of DRMs, were significantly different. Conclusion We revealed the characteristics of HIV molecular transmission, tropism, and DRMs of ART-naïve HIV-infected individuals among the MSM population in Tianjin. Identifying infected persons at risk of transmission is necessary for proposing counseling and treating these patients to reduce the risk of HIV transmission.

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 Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap–Core Interface of HIV-1 Protease

ACS Omega ◽  
2018 ◽  
Vol 3 (9) ◽  
pp. 12132-12140 ◽  
Author(s):  
Andres Wong-Sam ◽  
Yuan-Fang Wang ◽  
Ying Zhang ◽  
Arun K. Ghosh ◽  
Robert W. Harrison ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Nucleic Acid Template and the Risk of a PCR-Induced HIV-1 Drug Resistance Mutation

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10992 ◽  
Author(s):  
Vici Varghese ◽  
Elijah Wang ◽  
Farbod Babrzadeh ◽  
Michael H. Bachmann ◽  
Rajin Shahriar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nucleic Acid ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

2011 ◽  
Vol 203 (8) ◽  
pp. 1174-1181 ◽  
Author(s):  
Vivek Jain ◽  
Maria C. Sucupira ◽  
Peter Bacchetti ◽  
Wendy Hartogensis ◽  
Ricardo S. Diaz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Dolutegravir-Selected HIV-1 Containing the N155H and R263K Resistance Substitutions Does Not Acquire Additional Compensatory Mutations under Drug Pressure That Lead to Higher-Level Resistance and Increased Replicative Capacity

2015 ◽  
Vol 89 (20) ◽  
pp. 10482-10488 ◽  
Author(s):  
Kaitlin Anstett ◽  
Robert Fusco ◽  
Vincent Cutillas ◽  
Thibault Mesplède ◽  
Mark A. Wainberg
Keyword(s):  
Drug Resistance ◽  
Rescue Therapy ◽  
Resistance Mutation ◽  
Viral Infectivity ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Subtype B ◽  
Compensatory Mutations ◽  
Hiv 1 ◽  
Level Resistance

ABSTRACTWe have previously shown that the addition of the raltegravir/elvitegavir (RAL/EVG) primary resistance mutation N155H to the R263K dolutegravir (DTG) resistance mutation partially compensated for the fitness cost imposed by R263K while also slightly increasing DTG resistancein vitro(K. Anstett, T. Mesplede, M. Oliveira, V. Cutillas, and M. A. Wainberg, J Virol89:4681–4684, 2015, doi:10.1128/JVI.03485-14). Since many patients failing RAL/EVG are given DTG as part of rescue therapy, and given that the N155H substitution often is found in combination with other compensatory resistance mutations in such individuals, we investigated the effects of multiple such substitutions within integrase (IN) on each of integrase function, HIV-1 infectivity, and levels of drug resistance. To this end, each of the L74M, E92Q, T97A, E157Q, and G163R substitutions were introduced into NL4.3 subtype B HIV-1 vectors harboring N155H and R263K in tandem [termed NL4.3IN(N155H/R263K)]. Relevant recombinant integrase enzymes also were expressed, and purified and biochemical assays of strand transfer efficiency as well as viral infectivity and drug resistance studies were performed. We found that the addition of T97A, E157Q, or G163R somewhat improved the affinity of INN155H/R263Kfor its target DNA substrate, while the presence of L74M or E92Q had a negative effect on this process. However, viral infectivity was significantly decreased from that of NL4.3IN(N155H/R263K)after the addition of each tertiary mutation, and no increases in levels of DTG resistance were observed. This work shows that the compensatory mutations that evolve after N155H under continued DTG or RAL/EVG pressure in patients are unable to improve either enzyme efficiency or viral infectivity in an N155H/R263K background.IMPORTANCEIn contrast to other drugs, dolutegravir has not selected for resistance in HIV-positive individuals when used in first-line therapy. We had previously shown that HIV containing the primary raltegravir/elvitegravir resistance substitution N155H could select for R263K under dolutegravir pressure and that this virus was fit and displayed low-level resistance to dolutegravir (Anstett et al., J Virol89:4681–4684). Therefore, the current study aimed to uncover whether accessory mutations that appear after N155H in response to raltegravir/elvitegravir were compatible with N155H and R263K. We found, however, that the addition of a third mutation negatively impacted both the enzyme and the virus in terms of activity and infectivity without large shifts in integrase inhibitor resistance. Thus, it is unlikely that these substitutions would be selected under dolutegravir pressure. These data support the hypothesis that primary resistance against DTG cannot evolve through RAL/EVG resistance pathways and that the selection of R263K leads HIV into an evolutionary dead-end.

scholarly journals Deep Sequencing of HIV-1 RNA and DNA in Newly Diagnosed Patients with Baseline Drug Resistance Showed No Indications for Hidden Resistance and Is Biased by Strong Interference of Hypermutation

2016 ◽  
Vol 54 (6) ◽  
pp. 1605-1615 ◽  
Author(s):  
Kenny Dauwe ◽  
Delfien Staelens ◽  
Leen Vancoillie ◽  
Virginie Mortier ◽  
Chris Verhofstede
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Deep Sequencing ◽  
Resistance Mutation ◽  
Wild Type Virus ◽  
Multiple Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Hiv 1 ◽  
Rna And Dna

Deep sequencing of plasma RNA or proviral DNA may be an interesting alternative to population sequencing for the detection of baseline transmitted HIV-1 drug resistance. Using a Roche 454 GS Junior HIV-1 prototype kit, we performed deep sequencing of the HIV-1 protease and reverse transcriptase genes on paired plasma and buffy coat samples from newly diagnosed HIV-1-positive individuals. Selection was based on the outcome of population sequencing and included 12 patients with either a revertant amino acid at codon 215 of the reverse transcriptase or a singleton resistance mutation, 4 patients with multiple resistance mutations, and 4 patients with wild-type virus. Deep sequencing of RNA and DNA detected 6 and 43 mutations, respectively, that were not identified by population sequencing. A subsequently performed hypermutation analysis, however, revealed hypermutation in 61.19% of 3,188 DNA reads with a resistance mutation. The removal of hypermutated reads dropped the number of additional mutations in DNA from 43 to 17. No hypermutation evidence was found in the RNA reads. Five of the 6 additional RNA mutations and all additional DNA mutations, after full exclusion of hypermutation bias, were observed in the 3 individuals with multiple resistance mutations detected by population sequencing. Despite focused selection of patients with T215 revertants or singleton mutations, deep sequencing failed to identify the resistant T215Y/F or M184V or any other resistance mutation, indicating that in most of these cases there is no hidden resistance and that the virus detected at diagnosis by population sequencing is the original infecting variant.

scholarly journals Genetic Diversity and Drug Resistance Mutations in HIV-1 from Untreated Patients in Niamey, Niger

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Saïdou Mamadou ◽  
Yahayé Hanki ◽  
Amadou Roufaï Ali Maazou ◽  
Balki Aoula ◽  
Sanata Diallo
Keyword(s):  
Drug Resistance ◽  
Genetic Variants ◽  
Care Center ◽  
Rna Extraction ◽  
Resistance Mutation ◽  
Capital City ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Drug Naïve ◽  
Hiv 1

The objective of the study was to estimate the prevalence of transmitted resistance to antiretroviral of HIV-1 circulating in Niger. We collected plasmas from 96 drug-naive patients followed up in the main HIV/AIDS Care Center of Niamey, the capital city of Niger. After RNA extraction and retrotranscription to proviral DNA, nested PCR was performed to amplify PR (codons 1–99) and RT (codons 1–240) fragments for sequencing. Sequences were analysed for phylogeny, then for resistance-associated mutations according to IAS-USA and Stanford's lists of mutations. We characterized six HIV-1 genetic variants: CRF02-AG (56.3%), CRF30_0206 (15.6%), subtype G (15.6%), CRF06_cpx (9.4%), CRF11_cpx (2.1%), and CRF01_AE (1%). About 8.3% of HIV strains had at least 1 resistance mutation: 4 strains with at least 1 mutation to NRTI, 5 for NNRTI, and 1 for PI, respectiveley 4.2%, 5.2%, and 1.0%. These preliminary results gave enough information for the need of instauring HIV drug resistance national surveillance.

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