scholarly journals Susceptibility Score Mutations Indicator

2020 ◽  
Author(s):  
Keyword(s):  
2019 ◽  
Vol 74 (10) ◽  
pp. 3035-3043
Author(s):  
M H W Huibers ◽  
C Kityo ◽  
R S Boerma ◽  
E Kaudha ◽  
K C E Sigaloff ◽  
...  

Abstract Objectives To evaluate long-term virological failure (VF) and drug resistance among HIV-infected Ugandan children on first-line ART. Methods In a multicentre prospective cohort study, viral load (VL) and drug resistance mutations (DRMs) were investigated at baseline and 6 monthly intervals in children (age ≤ 12 years). VF (two consecutive VLs >1000 copies/mL or death after 6 months of ART) was defined as early VF (0–24 months of ART) or late VF (25–48 months of ART). An active regimen was defined as partially active if the genotypic susceptibility score (GSS) was <3. Results Between 2010 and 2011, 316 children were enrolled. Viral suppression was achieved in 75.8%, 71.5%, 72.6% and 69.2% at 12, 24, 36 and 48 months. VF occurred in 111/286 (38.8%), of which 67.6% was early and 32.4% late VF. Early VF was associated with a partially active regimen at baseline (OR 6.0, 95% CI 1.9–18.5), poor adherence (OR 3.1, 95% CI 1.3–7.4) and immunodeficiency (OR 3.3, 95% CI 1.1–10.2). Late VF was associated with age >3 years (OR 2.5, 95% CI 1.0–6.6) and WHO stage 3/4 (OR 4.2, 95% CI 1.4–13.4). Acquired DRMs were detected in 27.0% before 24 months, versus 14.4% after 24 months (P < 0.001). A total of 92.2% of the children with early VF, versus 56.2% with late VF, had a partially active regimen (P < 0.001). Conclusions VF rates were high, occurred predominantly in the first 24 months and appeared to increase again in year four. Risk factors and patterns of early VF/DRMs were different from those of late VF/DRMs. Virological control may improve by close monitoring and prompt switching to second-line therapy in the first 24 months. Late VF may be prevented by early start of ART.


2002 ◽  
Vol 13 (4) ◽  
pp. 231-240 ◽  
Author(s):  
Kristien Van Vaerenbergh ◽  
Sabina De Geest ◽  
Inge Derdelinckx ◽  
Herman Bobbaers ◽  
An Carbonez ◽  
...  

The relationship between adherence, virological response to highly active antiretroviral therapy (HAART) and the presence and development of genotypic resistance was assessed in 41 HIV-infected patients on HAART. Four adherence parameters (drug taking adherence, dosing adherence, timing adherence and drug holidays) were scored prospectively using electronic event monitoring. Genotypic resistance at baseline and after therapy failure was scored retrospectively and a genotype-based susceptibility score was calculated. Overall median adherence rates were high. All adherence parameters were better in virological responders ( n=31) compared to non-responders ( n=10), drug taking adherence and number of drug holidays being significantly different. Responders had a significantly higher susceptibility score. Stepwise logistic regression showed that the number of drug holidays and a low susceptibility score were highly predictive for therapy failure. Despite the presence of a limited number of baseline resistance mutations, perfectly adherent patients can control virus replication for a prolonged period.


1983 ◽  
Vol 56 (2) ◽  
pp. 627-631 ◽  
Author(s):  
Ralph L. Piedmont

This study examined the relationship between hypnotic susceptibility and thermal regulation using biofeedback. 30 subjects were given the Stanford Hypnotic Susceptibility Scale, Form C Immediately after the susceptibility score was determined, all subjects were given instructions to lower the peripheral skin temperature on the right middle finger. Subjects remained under hypnosis while they performed this task. A significant negative correlation (—.38) was found, in that the higher subjects' susceptibility, the better they were able to maintain a lower dermal temperature over trials. A 2 × 6 analysis of variance for low and high susceptibility with repeated measures yielded a significant main effect for subjects and a significant interaction of group × trials; highly susceptible subjects maintained a lower mean temperature over trials than subjects of low susceptibility. Issues for future research concerning the role of susceptibility in research on hypnosis are outlined.


2020 ◽  
Vol 75 (5) ◽  
pp. 1301-1310 ◽  
Author(s):  
D Armenia ◽  
D Di Carlo ◽  
P Flandre ◽  
Y Bouba ◽  
V Borghi ◽  
...  

Abstract Objectives To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. Methods Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). Results Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P &lt; 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P &lt; 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P &lt; 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. Conclusions A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.


2019 ◽  
Vol 91 (10) ◽  
pp. 1891-1895
Author(s):  
Andrea Giacomelli ◽  
Massimiliano Fabbiani ◽  
Ilaria Benedetto ◽  
Silvia Nozza ◽  
Emanuele Focà ◽  
...  

2010 ◽  
Vol 54 (4) ◽  
pp. 1520-1525 ◽  
Author(s):  
Philip M. Grant ◽  
Jonathan Taylor ◽  
Andrew B. Nevins ◽  
Vincent Calvez ◽  
Anne-Geneviève Marcelin ◽  
...  

ABSTRACT A K65R mutation in HIV-1 reverse transcriptase can occur with the failure of tenofovir-, didanosine-, abacavir-, and, in some cases, stavudine-containing regimens and leads to reduced phenotypic susceptibility to these drugs and hypersusceptibility to zidovudine, but its clinical impact is poorly described. We identified isolates with the K65R mutation within the Stanford Resistance Database and a French cohort for which subsequent treatment and virological response data were available. The partial genotypic susceptibility score (pGSS) was defined as the genotypic susceptibility score (GSS) excluding the salvage regimen's nucleoside reverse transcriptase inhibitor (NRTI) component. A three-part virologic response variable was defined (e.g., complete virologic response, partial virologic response, and no virologic response). Univariate, multivariate, and bootstrap analyses evaluated factors associated with the virologic response, focusing on the contributions of zidovudine and tenofovir. Seventy-one of 130 patients (55%) achieved a complete virologic response (defined as an HIV RNA level of <200 copies/ml). In univariate analyses, pGSS and zidovudine use in the salvage regimen were predictors of the virologic response. In a multivariate analysis, pGSS and zidovudine and tenofovir use were associated with the virologic response. Bootstrap analyses showed similar reductions in HIV RNA levels with zidovudine or tenofovir use (0.5 to 0.9 log10). In the presence of K65R, zidovudine and tenofovir are associated with similar reductions in HIV RNA levels. Given its tolerability, tenofovir may be the preferred agent over zidovudine even in the presence of the K65R mutation.


Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1314
Author(s):  
George A. Yendewa ◽  
Sulaiman Lakoh ◽  
Sahr A. Yendewa ◽  
Khadijah Bangura ◽  
Andrés Tabernilla ◽  
...  

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.


2019 ◽  
Author(s):  
Musharib Gull ◽  
Parvaze A. Sofi ◽  
R. R. Mir ◽  
Asmat Ars ◽  
S. M. Zargar

This paper reports the usefulness of a new method for identification of productive and resilient cowpea genotypes. The new indices called as Yield Susceptibility Score Index (YSSI) and Yield Production Score Index (YPSI) are based on a scoring scales, offer simple and easy visualization and identification of genotypes that possess resilience, productivity, both or none. A set of 40 cowpea genotypes was evaluated and stress indices were combined in terms of new indices based on a combination of stress susceptibility index, the stress tolerance index, the mean productivity index and the tolerance index, which have been previously used either in isolation or together for understanding water stress adaptation. This new selection method could help breeders and researchers by defining clear and strong criteria to identify genotypes with high resilience and high productivity and provide a clear visualization of contrasts in terms of grain yield production under stress. The approach is highly useful in initial evaluation of large germplasm sets for identification of resilient and productive cowpea genotypes.


2018 ◽  
Vol 73 (6) ◽  
pp. 1665-1671 ◽  
Author(s):  
Charlotte Charpentier ◽  
Gilles Peytavin ◽  
Minh P Lê ◽  
Véronique Joly ◽  
Ornella Cabras ◽  
...  

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