scholarly journals Detection of Mutations Resistant to Lamivudine or Adefovir in HBV and Its Management

2013 ◽  
Vol 2 (4) ◽  
pp. 183-186
Author(s):  
De-xing Jia ◽  
Jing Feng ◽  
Ping Li ◽  
Xiu-ying Lun ◽  
Xian-jie Yu
Keyword(s):  
Drug Resistance ◽  
Rescue Therapy ◽  
Resistance Mutation ◽  
The Other ◽  
Resistance Mutations ◽  
Lamivudine Resistance ◽  
Drug Resistance Mutations ◽  
Antiviral Effects ◽  
Before And After ◽  
Detection Of Mutations

Abstract Objective Nucleos(t)ide analogues (NAs) naïve chronic hepatitis B(CHB) patients were given rescue combination therapy after drug resistance to lamivudine or adefovir. Evolution of HBV mutation patterns and its impact on antiviral effects were studied. Methods Total of 142 naïve CHB patients treated with lamivudine were randomly divided into two groups when lamivudine resistance occurred. One group was added with adefovir, the other was switched to entecavir and adefovir. Seventy-two naïve CHB patients treated with adefovir were randomly divided into two groups when adefovir resistance occurred. One group was added with lamivudine, the other was added with entecavir. HBV polymerase reverse transcriptase mutations associated with resistance were analyed before and after 48 weeks of rescue therapy, respectively. Results The mutation patterns of M204V/I, M204V+L180M were predominantly found in CHB patients after lamivudine resistance. Meanwhile, the entecavir resistance mutation patterns were also detected. Therefore, patients with lamivudine resistance could develop more diverse drug resistance mutations if they were switched to entecavir and adefovir. The mutation patterns of rtA181 were predominantly found in CHB patients after adefovir resistance and rescure therapy with add-on entecavir was more effective than with add-on lamivudine Conclusions Resistance mutation analysis chould help to choose NAs, reduce resistance and ehance antiviral effects.

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 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.

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 Detectable viral load among HIV -1 positive pregnant women on ART (Option B +) in northern Tanzania: Baseline results from the HIVDR study

2021 ◽  
Vol 3 (1) ◽  
pp. 44-50
Author(s):  
Nicholaus Steven Mazuguni ◽  
Festo Mazuguni ◽  
Eva Prosper Muro
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Virological Failure ◽  
Virologic Failure ◽  
Resistance Mutation ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1 ◽  
Level Resistance

Introduction: In Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDEC) has implemented the Option B+ as one of the strategies to facilitate achievement of elimination of mother to child transmission of HIV. To prevent emergence of drug resistance mutations early identification of option B+ failure is critical. The emergence of drug resistance mutation and subsequent treatment failure poses a major concern for HIV program in low- and middle-income resource settings where treatment options are limited. Methodology: We recruited treatment naïve, treatment experienced HIV-1 positive pregnant women and those who had prophylaxis in their previous pregnancy in Kilimanjaro, northern Tanzania August 2016 to February 2017. Whole blood (2ml) for biochemistry, viral load and drug resistance testing were taken at baseline. ARV drug resistance testing was done on women with VL ≥ 1000 copies/ml. We used descriptive statistic and logistic regression to determine the strength of association between virologic outcome (virologic failure) and independent predictors. Results: One hundred and forty eight (148) pregnant HIV-positive women were enrolled in the study with mean age of 29.82 years (SD=6.17) from August, 2016 to February, 2017. Virologic failure was demonstrated in 34 (23%) with viral load   ≥ 1,000 copies/ml. Genotyping results were available from 26 women, mutations associated with ARV resistance were detected in 23.1% (n = 6/26). Among the six women with ARV resistance mutation 4(66.7%) had high level resistance and 2(33.3%) had low level resistance. Among the 26 samples genotyped 15(58%) viruses were subtype A, while eight were subtype C (31%) and three subtypes D (11%). The most dominant drug resistance mutations against the reverse transcriptase inhibitors for the women with high level resistance were K103N, Y188L, D67N, K70R, M184V, T215F, K219EQ, and the low-level resistance was E138A. The older age was associated with virological failure compared to those who were < 20 year of age. Conclusion: Viral load testing should be done on women who were already on antiretroviral treatment on their first antenatal visit to ensure early detection of virological failure and enable clinicians to take an appropriate course of action on their management. Educational intervention on adherence should be targeted at an early stage to women with virological failure during pregnancy to reduce the emergence of HIV-1 drug resistance mutations.

scholarly journals The frequency of HIV-1 infection and surveillance drug-resistant mutations determination among Iranians with high-risk behaviors, during 2014 to 2020

2021 ◽  
Author(s):  
Saba Garshasbi ◽  
Arezoo Marjani ◽  
Ali Alipour ◽  
Khadijeh Khanaliha ◽  
Maryam Esghaei ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Risk ◽  
Reverse Transcriptase ◽  
Risk Behaviors ◽  
Resistance Mutation ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
High Risk Behaviors ◽  
Drug Resistance Mutations ◽  
Hiv 1

Background and Objectives: Human immunodeficiency virus (HIV) has various transmission routes. Instant antiretroviral therapy (ART) is the recommended treatment for HIV infection. Highly active antiretroviral therapy (HAART) significantly decreases the acquired immunodeficiency syndrome (AIDS) and AIDS-related co-morbidities. Notwithstanding the suit- ability of HAART, the antiretrovirals (ARVs) have adverse effects and antiretroviral drug resistance mutations are reported among those who receive ARVs. In this survey, the abundance of HIV-1 infection in Iranians with high-risk behaviors, and detection of the surveillance drug-resistant mutations (SDRMs) were evaluated. Materials and Methods: This cross-sectional study was conducted on 250 individuals with high-risk behaviors from Sep- tember 2014 to February 2020. HIV-1 Ag/Ab in plasma samples was detected using enzyme immunoassay (EIA) kits. The conserved region of HIV-1 was detected in the plasma samples by real-time polymerase chain reaction (PCR) assay. Further- more, in individuals with positive HIV-1 RNA, HIV-1 viral load testing was performed. After amplification and sequencing of the HIV-1 protease, reverse transcriptase, and integrase genes, surveillance drug resistance mutation (SDRM) and phylo- genetic analysis were determined. Results: Out of the 250 participants with high-risk behaviors, six (2.4%) were infected with HIV-1. According to the phy- logenetic analysis, the CRF35_AD (83.3% or 5/6) was the dominant subtype, followed by CRF01_AE (16.7% or 1/6). In this research, in none of the HIV-1 infected patients, SDRM for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase inhibitors (INs) were observed. Nevertheless, in one of the patients, V179L mutation was detected which is a rare non-polymorphic mutation and is listed as a rilpivirine (RPV) -associated resistance mutation. Conclusion: The results of the current survey revealed that 2.4% of people with high-risk behaviors are infected with HIV and the level of drug resistance mutations (DRMs) in these people is very low.

scholarly journals Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals

2021 ◽  
Vol 18 (5) ◽  
pp. 2719
Author(s):  
Pablo López ◽  
Grissell Tirado ◽  
Andrea Arias ◽  
Raphael Sánchez ◽  
Elliott R. Rodríguez-López ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Puerto Rico ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Therapeutic Procedures ◽  
Treatment Naïve ◽  
High Level

The HIV-1 integrase viral protein is responsible for incorporating the viral DNA into the genomic DNA. The inhibition of viral integration into host cell DNA is part of recent therapeutic procedures. Combination therapy with protease and reverse transcriptase inhibitors has demonstrated good synergistic results in reducing viral replication. The purpose of this study is to assess the occurrence of integrase drug resistance mutations from the period comprising 2013 through 2018 in Puerto Rico (PR). We analyzed 131 nucleotide sequences available in our HIV genotyping database, and we performed drug resistance mutation analyses using the Stanford HIV Drug Resistance Database. Twenty-one sequences (16.03%) harbored major or resistance-associated mutations. We identified the Q148HKR, G140S, Y143R, N155H, S147G, and E138EA major drug resistance mutations and the D232DN, T97TA, E157Q, G163GART accessory mutations. We detected high-level drug resistance to Elvitegravir and Raltegravir (76.19% and 85.71%). Moreover, we identified sequences harboring drug resistance mutations that could provide resistance to Dolutegravir. The transmission of strains with integrase antiretroviral resistance has been previously documented in treatment naïve patients. Given the increase of patients treated with integrase inhibitors, surveillance of drug resistance mutations is an essential aspect of PR’s clinical management of HIV infection.

scholarly journals Independent Evolution of Human Immunodeficiency Virus (HIV) Drug Resistance Mutations in Diverse Areas of the Brain in HIV-Infected Patients, with and without Dementia, on Antiretroviral Treatment

2004 ◽  
Vol 78 (18) ◽  
pp. 10133-10148 ◽  
Author(s):  
Theresa K. Smit ◽  
Bruce J. Brew ◽  
Wallace Tourtellotte ◽  
Susan Morgello ◽  
Benjamin B. Gelman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Resistance Mutation ◽  
Antiretroviral Drugs ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Independent Evolution ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT AIDS dementia complex (ADC) in human immunodeficiency virus (HIV)-infected patients continues to be a problem in the era of highly active antiretroviral therapy (HAART). A better understanding of the drug resistance mutation patterns that emerge in the central nervous system (CNS) during HAART is of paramount importance as these differences in drug resistance mutations may explain underlying reasons for poor penetration of antiretroviral drugs into the CNS and suboptimal concentrations of the drugs that may reside in the brains of HIV-infected individuals during therapy. Thus, we provide a detailed analysis of HIV type 1 (HIV-1) protease and reverse transcriptase (RT) genes derived from different regions of the brains of 20 HIV-1-infected patients (5 without ADC, 2 with probable ADC, and 13 with various stages of ADC) on antiretroviral therapy. We show the compartmentalization and independent evolution of both primary and secondary drug resistance mutations to both RT and protease inhibitors in diverse regions of the CNS of HIV-infected patients, with and without dementia, on antiretroviral therapy. Our results suggest that the independent evolution of drug resistance mutations in diverse areas of the CNS may emerge as a consequence of incomplete suppression of HIV, probably related to suboptimal drug levels in the CNS and drug selection pressure. The emergence of resistant virus in the CNS may have considerable influence on the outcome of neurologic disease and also the reseeding of HIV in the systemic circulation upon failure of therapy.

scholarly journals Microdrop HIV sequencing for incidence and drug resistance surveillance

2021 ◽  
Author(s):  
Sung Yong Park ◽  
Gina Faraci ◽  
Gary Murphy ◽  
Christopher Pilcher ◽  
Michael P Busch ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Resistance Mutation ◽  
Hiv Incidence ◽  
Resistance Mutations ◽  
Blood Draw ◽  
Recent Infection ◽  
Survey Tool ◽  
Drug Resistance Mutations

Abstract Background Precise and cost-efficient HIV incidence and drug resistance surveillances are in high demand for the advancement of 90-90-90: Treatment for All. Methods We developed microdrop HIV sequencing for HIDA (HIV incidence and drug resistance assay), a single blood draw surveillance tool for incidence and drug resistance mutation detection. We amplified full-length HIV envelope and pol gene sequences within micro-droplets and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences. Results We achieved a greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and 262 days of mean duration of recent infection (average timespan of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked drug resistance mutations. By screening all 93 WHO surveillance drug resistance mutations (SDRMs), we detected six pretreatment drug resistance mutations with 2.6% – 13.2% prevalence and cross-linked mutations. Conclusions HIDA via microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for other pathogen surveillances.

scholarly journals Prevalence and Genotypic Characterization of Hbv In Hiv- Infected Patients From Kwazulu-Natal, South Africa

2020 ◽  
Author(s):  
Lorato Mosetsanagape Modise
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Resistance Mutation ◽  
Pcr Amplification ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Kwazulu Natal ◽  
Genotype A

Abstract Introduction: The co-infection of HIV with HBV is very common due to shared mode of transmission. HBV/HIV co-infection impact on low HBeAg expression, high HBV replication, causes progressive liver disease, cirrhosis, liver cancer and high mortality. Co-infection may lead to cross-resistance of HBV and HIV drugs due to drug-related immune therapeutic pressure or hepatotoxicity. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to aid patient treatment management. Hence we conducted this study to characterise HBV among HIV infected patients in Durban, KwaZulu-Natal of South Africa. Methods: Serum was screened for HBsAg using ELISA, followed by DNA extraction from all samples. Genotyping of HBV was done through PCR amplification, Sanger sequencing and phylogenetic analysis. Results: Of the 50 samples in this study 100% (n = 50/50) were HBsAg positive. HBV/HIV co-infection was 82% (n = 41/50) based on PCR amplification of the HBV partial surface gene and 63% (n = 26/41) of the amplicons were successfully sequenced. Phylogenetic and sequence analyses identified patients nucleotide sequence as genotype A. Mutations prevalence in the HBsAg region was 43% (n = 18/26); including mutations associated with diagnostic failure (K122R and T143S) and 7 vaccines escape mutations (P127T, G145R, S207N, Y200T, E164D, Y206H and L209V). Mutations were determined within the polymerase region of HBV and the amino acid substitutions were identified at 54% (14/26) in different positions within the reverse transcriptase (RT) region The prevalence of mutations associated with drug resistance was 43% (n = 6/14) within the RT region. Drug resistance mutations was 67% (n = 4/6) for both lamivudine (LMV) and telbivudine (LdT) resistance, 17% (n = 1/6) for entecavir (ETV) and 33% (n = 2/6) for adefovir (ADV) resistance. Mutations causing resistance to lamivudine and telbivudine were M204V, L180M, V163I, and S202K; with S202K also causing resistance to entecavir and adefovir resistance mutation were I253Y and M250I. Multiple drug resistance mutations within a single sample contained L180M, M204V, S202K and M250I mutations. Conclusion: This study shows the predominance of HBV genotype A in HIV-infected patients and the HBV mutations present in HBV/HIV co-infected individuals. HBV mutations associated with drug resistance suggest the need for continuous HBV screening and use of tenofovir ART regimen among HBV/HIV co-infected individuals.

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