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| 5. |
- Magiorkinis, G, et al.
(författare)
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The global spread of HIV-1 subtype B epidemic
- 2016
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Ingår i: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. - : Elsevier BV. - 1567-7257. ; 46, s. 169-179
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Schlosser, M, et al.
(författare)
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HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia
- 2020
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology for the systematisation of A6 identification and to describe the HIV epidemiology in the Russian Southern Federal District. Drug consumption (32.0%) and heterosexual contact (27.1%) were the major reported transmission risks. This study successfully established the settings for systematic identification of A6 samples. Low frequency of subtype B (3.3%) and large prevalence of sub-subtype A6 (69.6%) and subtype G (23.4%) were detected. Transmitted PI- (8.8%) and NRTI-resistance (6.4%) were detected in therapy-naive patients. In therapy-experienced patients, 17.3% of the isolates showed resistance to PIs, 50.0% to NRTI, 39.2% to NNRTIs, and 9.5% to INSTIs. Multiresistance was identified in 52 isolates, 40 corresponding to two-class resistance and seven to three-class resistance. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. This study establishes the conditions for a systematic annotation of sub-subtype A6 to normalise epidemiological studies. Accurate knowledge on South Russian epidemiology will allow for the development of efficient regional frameworks for HIV-1 infection management.
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- Oette, M, et al.
(författare)
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Efficacy of antiretroviral therapy switch in HIV-infected patients: a 10-year analysis of the EuResist Cohort
- 2012
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Ingår i: Intervirology. - : S. Karger AG. - 1423-0100 .- 0300-5526. ; 55:2, s. 160-166
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Tidskriftsartikel (refereegranskat)abstract
- <i>Introduction:</i> Highly active antiretroviral therapy (HAART) has been shown to be effective in many recent trials. However, there is limited data on time trends of HAART efficacy after treatment change. <i>Methods:</i> Data from different European cohorts were compiled within the EuResist Project. The efficacy of HAART defined by suppression of viral replication at 24 weeks after therapy switch was analyzed considering previous treatment modifications from 1999 to 2008. <i>Results:</i> Altogether, 12,323 treatment change episodes in 7,342 patients were included in the analysis. In 1999, HAART after treatment switch was effective in 38.0% of the patients who had previously undergone 1–5 therapies. This figure rose to 85.0% in 2008. In patients with more than 5 previous therapies, efficacy rose from 23.9 to 76.2% in the same time period. In patients with detectable viral load at therapy switch, the efficacy rose from 23.3 to 66.7% with 1–5 previous treatments and from 14.4 to 55.6% with more than 5 previous treatments. <i>Conclusion:</i> The results of this large cohort show that the outcome of HAART switch has improved considerably over the last years. This result was particularly observed in the context after viral rebound. Thus, changing HAART is no longer associated with a high risk of treatment failure.
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| 19. |
- Zazzi, M, et al.
(författare)
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Predicting response to antiretroviral treatment by machine learning: the EuResist project
- 2012
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Ingår i: Intervirology. - : S. Karger AG. - 1423-0100 .- 0300-5526. ; 55:2, s. 123-127
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Tidskriftsartikel (refereegranskat)abstract
- For a long time, the clinical management of antiretroviral drug resistance was based on sequence analysis of the HIV genome followed by estimating drug susceptibility from the mutational pattern that was detected. The large number of anti-HIV drugs and HIV drug resistance mutations has prompted the development of computer-aided genotype interpretation systems, typically comprising rules handcrafted by experts via careful examination of in vitro and in vivo resistance data. More recently, machine learning approaches have been applied to establish data-driven engines able to indicate the most effective treatments for any patient and virus combination. Systems of this kind, currently including the Resistance Response Database Initiative and the EuResist engine, must learn from the large data sets of patient histories and can provide an objective and accurate estimate of the virological response to different antiretroviral regimens. The EuResist engine was developed by a European consortium of HIV and bioinformatics experts and compares favorably with the most commonly used genotype interpretation systems and HIV drug resistance experts. Next-generation treatment response prediction engines may valuably assist the HIV specialist in the challenging task of establishing effective regimens for patients harboring drug-resistant virus strains. The extensive collection and accurate processing of increasingly large patient data sets are eagerly awaited to further train and translate these systems from prototype engines into real-life treatment decision support tools.
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- Elén, S, et al.
(författare)
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Low-level HIV viraemia during antiretroviral therapy : Longitudinal patterns and predictors of viral suppression
- 2024
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Ingår i: HIV Medicine. - 1468-1293. ; 25:1, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Our objective was to characterize longitudinal patterns of viraemia and factors associated with viral suppression in people with HIV and low-level viraemia (LLV) during antiretroviral therapy (ART).METHODS: We included people with HIV in the EuResist Integrated Database with LLV following ART initiation after 2005. LLV was defined as two or more consecutive viral load (VL) measurements of 51-199 copies/mL 30-365 days apart after >12 months of ART. Viraemia patterns were analyzed over 24 months. Factors associated with viral suppression at 12 months after LLV episodes were identified using univariable and multivariable logistic regression.RESULTS: Of 25 113 people with HIV, 2474 (9.9%) had LLV. Among 1387 participants with 24 months of follow-up after LLV, 406 (29%) had persistent suppression, 669 (48%) had transient viraemic episodes, 29 (2%) had persistent LLV, and 283 (20%) had virological failure. Following LLV episodes, the proportion with detectable viraemia declined (p for trend <0.001 and 0.034, in the first and second year, respectively). At 12 months, 68% had undetectable VL, which was associated with suppression before LLV (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.2-2.4) and ART modification after LLV (aOR 1.6; 95% CI 1.0-2.4). The following factors were negatively associated with undetectable VL at 12 months: higher VL during LLV (aOR 0.57 per log 10 copies/mL; 95% CI 0.37-0.89), injecting drug use (aOR 0.67; 95% CI 0.47-0.96), and regimens with protease inhibitors (aOR 0.65; 95% CI 0.49-0.87) or combined anchor drugs (aOR 0.52; 95% CI 0.32-0.85). CONCLUSION: Most people with LLV did not experience sustained viral suppression during 24-month follow-up, supporting the association between LLV and inferior treatment outcome.
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| 26. |
- Kuo, NIH, et al.
(författare)
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The Health Gym: synthetic health-related datasets for the development of reinforcement learning algorithms
- 2022
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 9:1, s. 693-
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, the machine learning research community has benefited tremendously from the availability of openly accessible benchmark datasets. Clinical data are usually not openly available due to their confidential nature. This has hampered the development of reproducible and generalisable machine learning applications in health care. Here we introduce the Health Gym - a growing collection of highly realistic synthetic medical datasets that can be freely accessed to prototype, evaluate, and compare machine learning algorithms, with a specific focus on reinforcement learning. The three synthetic datasets described in this paper present patient cohorts with acute hypotension and sepsis in the intensive care unit, and people with human immunodeficiency virus (HIV) receiving antiretroviral therapy. The datasets were created using a novel generative adversarial network (GAN). The distributions of variables, and correlations between variables and trends in variables over time in the synthetic datasets mirror those in the real datasets. Furthermore, the risk of sensitive information disclosure associated with the public distribution of the synthetic datasets is estimated to be very low.
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| 30. |
- Rhee, SY, et al.
(författare)
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Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations
- 2022
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non-subtype B viruses. A total of 264 (18%) sequences had a PI drug-resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non-subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high-level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low-level darunavir resistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymorphic mutation occurring primarily in non-B sequences. Atazanavir-selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second-line and potentially later line therapy in LMICs.
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| 31. |
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| 33. |
- van de Klundert, MAA, et al.
(författare)
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Molecular Epidemiology of HIV-1 in Eastern Europe and Russia
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the protease and reverse transcriptase genes of HIV-1 from 812 people living with HIV from Ukraine (n = 191), Georgia (n = 201), and Russia (n = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the integrase gene sequence was also determined. The most reported route of transmission was heterosexual contact, followed by intravenous drug use, and men having sex with men (MSM). Several pre-existing drug resistance mutations were found against non-nucleoside reverse transcriptase inhibitors (RTIs) (n = 103), protease inhibitors (n = 11), and nucleoside analogue RTIs (n = 12), mostly polymorphic mutations or revertants. In the integrase gene, four strains with accessory integrase strand transfer inhibitor mutations were identified. Sub-subtype A6 caused most of the infections (713/812; 87.8%) in all three countries, including in MSM. In contrast to earlier studies, no clear clusters related to the route of transmission were identified, indicating that, within the region, the exchange of viruses among the different risk groups may occur more often than earlier reported.
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| 44. |
- Eden, M, et al.
(författare)
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Pulse-assisted homonuclear dipolar recoupling of half-integer quadrupolar spins in magic-angle spinning NMR
- 2005
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 410:1-3, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate numerically and experimentally that zero-quantum homonuclear dipolar recoupling techniques employing rotor-synchronized 180 degrees pulses, previously introduced for spin-1/2 applications, are useful also for magnetization transfers between half-integer quadrupolar nuclei in rotating solids. The recoupling sequences are incorporated as mixing periods in two-dimensional experimental protocols, that correlate either single-quantum coherences of coupled spins, or triple-quantum with single-quantum coherences for improving spectral resolution. We present Na-23 and Al-27 NMR experiments on powders of sodium sulphite [Na2SO3], YAG [Y3Al5O12] and a synthetic chlorite mineral [Mg4.5Al3Si2.5O10(OH)(8)].
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| 45. |
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| 46. |
- Eriksson, M., et al.
(författare)
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2R, 3S)-2,3-dibromosuccinic acid
- 2006
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Ingår i: Acta Crystallographica Section E. - : International Union of Crystallography (IUCr). - 1600-5368. ; 62, s. O200-O201
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Tidskriftsartikel (refereegranskat)abstract
- Crystals of the title compound, C4H4Br2O4, were grown from an aqueous solution. The structure features centrosymmetric molecules, each of which forms hydrogen bonds with two adjacent acid molecules, yielding long chains.
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| 47. |
- Eriksson, M, et al.
(författare)
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(RS)-2,3-Dibromosuccinic acid (vol E62, pg o200, 2006)
- 2006
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Ingår i: ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS. - Royal Inst Technol, Sch Chem Sci & Engn, S-10044 Stockholm, Sweden. : INT UNION CRYSTALLOGRAPHY. - 2056-9890. ; 62, s. E5-E5
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Tidskriftsartikel (refereegranskat)
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