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.

Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients

AIDS ◽  
2011 ◽  
Vol 25 (17) ◽  
pp. 2183-2188 ◽  
Author(s):  
Avelin F. Aghokeng ◽  
Charles Kouanfack ◽  
Christian Laurent ◽  
Eugenie Ebong ◽  
Arrah Atem-Tambe ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Treatment ◽  
Scale Up ◽  
Sub Saharan Africa ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Drug Naïve ◽  
Sub Saharan ◽  
Hiv 1

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.

Accumulation of HIV-1 Drug Resistance Mutations and Methamphetamine Use

2021 ◽  
Vol 19 ◽  
Author(s):  
Hong-Ha M. Truong ◽  
Robin Fatch ◽  
Steven G. Deeks ◽  
Melissa Krone ◽  
Jeffrey N. Martin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Mutation Accumulation ◽  
Art Adherence ◽  
Resistance Mutations ◽  
Methamphetamine Use ◽  
Drug Resistance Mutations ◽  
Adjusted Incidence Rate ◽  
Adjusted Incidence

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.

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 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 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.

Drug Resistance Mutations of HIV Type 1 Non-B Viruses to Integrase Inhibitors in Treatment-Naive Patients from Sub-Saharan Countries and Discordant Interpretations

2012 ◽  
Vol 28 (9) ◽  
pp. 1157-1160 ◽  
Author(s):  
Marjorie Monleau ◽  
Avelin F. Aghokeng ◽  
Benedicte A. Nkano ◽  
Marie-Laure Chaix ◽  
Martine Peeters, and the AC11/AC12 ANRS Wor
Keyword(s):  
Drug Resistance ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
Hiv Type 1 ◽  
Sub Saharan

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 Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes

2020 ◽  
Author(s):  
Kara A. Moser ◽  
Rashid A. Madebe ◽  
Ozkan Aydemir ◽  
Mercy G. Chiduo ◽  
Celine I. Mandara ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Population Structure ◽  
Genetic Relatedness ◽  
Sub Saharan Africa ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Molecular Inversion Probes ◽  
Parasite Populations ◽  
The Impact

ABSTRACTHigh-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programs, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania country-wide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, roughly separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from geographically close districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts, and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared.SIGNIFICANCEDocumenting dynamics of malaria parasite genomics in high-transmission settings at scale in sub-Saharan Africa is critical for policy and decision making to support ongoing malaria elimination initiatives. Using molecular inversion probes, we genotyped over 1,000 Tanzanian Plasmodium falciparum samples collected country-wide in 2017 at hundreds of variable polymorphic positions across the genome. Frequencies of known drug resistance mutations were higher in northern districts of the country compared to the south. Results also showed a distinct isolation-by-distance pattern (whereby increasing geographic distance was correlated with decreasing genetic relatedness), as well as signals of higher genetic sharing between several southern districts. These results provide, for the first time, a picture of current within-country diversity of Tanzanian P. falciparum populations.

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