scholarly journals Transmitted HIV drug resistance and subtype patterns among blood donors in Poland

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miłosz Parczewski ◽  
Ewa Sulkowska ◽  
Anna Urbańska ◽  
Kaja Scheibe ◽  
Karol Serwin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Donors ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv Protease ◽  
Resistance Mutations ◽  
Subtype B ◽  
Interpretation Algorithm ◽  
First Time ◽  
Hiv Diversity

AbstractSurveillance on the HIV molecular variability, risk of drug resistance transmission and evolution of novel viral variants among blood donors remains an understudied aspect of hemovigilance. This nationwide study analyses patterns of HIV diversity and transmitted resistance mutations. Study included 185 samples from the first time and repeat blood donors with HIV infection identified by molecular assay. HIV protease, reverse transcriptase and integrase were sequenced using population methods. Drug resistance mutation (DRM) patterns were analyzed based on the Stanford Interpretation Algorithm and standardized lists of transmitted mutations. Phylogeny was used to investigate subtyping, clustering and recombination patterns. HIV-1 subtype B (89.2%) followed by subtype A6 (7.6%) were predominant, while in three (1.6%) cases, novel recombinant B/A6 variants were identified. Non-B variants were more common among repeat donors (14.5%) compared to the first time ones (1.8%), p = 0.011, with higher frequency (9.9%) of A6 variant in the repeat donor group, p = 0.04. Major NRTI DRMs were observed in 3.8%, NNRTI and PI in 0.6% and INSTI 1.1% of cases. Additionally, E157Q polymorphism was observed in 9.8% and L74I in 11.5% of integrase sequences. Transmission of drug resistance among blood donors remains infrequent. Subtype patters increase in complexity with emergence of novel intersubtype A6B recombinants.

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 Transmitted drug resistance mutations and subtype diversity among HIV-1 sero-positive voluntary blood donors in Accra, Ghana

2020 ◽  
Author(s):  
Billal Musah Obeng ◽  
Evelyn Yayra Bonney ◽  
Lucy Asamoah-Akuoko ◽  
Nicholas Israel Nii-Trebi ◽  
Gifty Mawuli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Donors ◽  
Transmitted Drug Resistance ◽  
Nucleotide Sequencing ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Major Drug ◽  
Hiv 1

Abstract Background: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of ART among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations and subtype diversity among HIV-1 sero-positive blood donors in Accra, Ghana was characterized.Methods: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by serology as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbor-joining tree with the Kimura’s 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0).Results: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 50% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. Conclusion: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis suggest possible subtype importation. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.

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 Immediate pools of malaria infections at diagnosis combined with targeted deep sequencing accurately quantifies frequency of drug resistance mutations

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11794
Author(s):  
Ozkan Aydemir ◽  
Benedicta Mensah ◽  
Patrick W. Marsh ◽  
Benjamin Abuaku ◽  
James Leslie Myers-Hansen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Testing ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Sub Saharan Africa ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Antimalarial Resistance ◽  
Sample Pooling ◽  
Sub Saharan

Antimalarial resistance surveillance in sub-Saharan Africa is often constrained by logistical and financial challenges limiting its breadth and frequency. At two sites in Ghana, we have piloted a streamlined sample pooling process created immediately by sequential addition of positive malaria cases at the time of diagnostic testing. This streamlined process involving a single tube minimized clinical and laboratory work and provided accurate frequencies of all known drug resistance mutations after high-throughput targeted sequencing using molecular inversion probes. Our study validates this method as a cost-efficient, accurate and highly-scalable approach for drug resistance mutation monitoring that can potentially be applied to other infectious diseases such as tuberculosis.

scholarly journals Transmitted drug resistance mutations and subtype diversity amongst HIV-1 sero-positive voluntary blood donors in Accra, Ghana

2020 ◽  
Author(s):  
Billal Musah Obeng ◽  
Evelyn Yayra Bonney ◽  
Lucy Asamoah-Akuoko ◽  
Nicholas Israel Nii-Trebi ◽  
Gifty Mawuli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Donors ◽  
Transmitted Drug Resistance ◽  
Nucleotide Sequencing ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Major Drug ◽  
Hiv 1

Abstract Background: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of antiretroviral therapy (ART) among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations (DRMs) and SD amongst HIV-1 sero-positive blood donors in Accra, Ghana were characterized.Methods: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by INNO-LIA as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbour-joining tree with the Kimura’s 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0).Results: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 47% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. Conclusion: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis may suggest possible subtype importation. However, a more prospective and detailed analysis is needed to establish this phenomenon. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.

scholarly journals Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1238
Author(s):  
Marta Pingarilho ◽  
Victor Pimentel ◽  
Isabel Diogo ◽  
Sandra Fernandes ◽  
Mafalda Miranda ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Transmitted Drug Resistance ◽  
Reverse Transcriptase Inhibitors ◽  
Genotypic Resistance ◽  
Acquired Drug Resistance ◽  
Subtype B ◽  
Number Of Patients

Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.

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 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.

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