Accumulation of HIV-1 Drug Resistance Mutations and Methamphetamine Use

Background: Antiretroviral therapy (ART) non-adherence and methamphetamine use are associated with higher HIV drug resistance prevalence. How they affect drug resistance mutation accumulation is less studied. Objective: We assessed factors associated with drug resistance mutation accumulation. Methods: We evaluated HIV chronically-infected patients from a clinic-based research cohort on first-line ART regimens with genotype results within 30 days of baseline. Methamphetamine use and ART adherence were self-reported at each study visit. High ART adherence was defined as 0-5% missed doses in the prior 30 days. Results: One-hundred twenty-five patients contributed 496 study visits. At baseline, 81% of patients reported high ART adherence; 90% reported no methamphetamine use in the prior 4 months, 8% used monthly or less and 2% used daily or weekly. Methamphetamine users and non-users had similarly high ART adherence (p=0.93). Adjusted incidence rate ratio (aIRR) of drug resistance mutations accumulation was 2.04 (95% CI 0.64, 6.46) for daily/weekly users and 1.71 (95% CI 0.66, 4.42) for patients with monthly or less users, compared to non-users. aIRR was 0.71 (95% CI 0.44, 1.15) with >5-10% missed ART doses and 1.21 (95% CI 0.80, 1.83) with >10% missed doses compared to 0-5% missed doses. Conclusions: We found no strong evidence for the effect of methamphetamine use and ART adherence on drug resistance mutation accumulation. Research cohort patients may have been more engaged in care and treatment adherence than non-cohort patients. Our findings suggest methamphetamine use might not lead to treatment failure among HIV patients who are otherwise engaged in care.

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

PeerJ ◽

10.7717/peerj.11794 ◽

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.

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052719 ◽

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.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.1066 ◽

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.

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

ISRN Microbiology ◽

10.5402/2011/797463 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 3

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

East Africa Science ◽

10.24248/easci-d-20-00009 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-021-92210-2 ◽

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.

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

Virology Journal ◽

10.1186/s12985-020-01441-8 ◽

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.

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

Infection International ◽

10.1515/ii-2017-0063 ◽

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.

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

Iranian Journal of Microbiology ◽

10.18502/ijm.v13i6.8094 ◽

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.

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

10.21203/rs.3.rs-34185/v1 ◽

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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