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A Short-Term Assessment of Nascent HIV-1 Transmission Clusters Among Newly Diagnosed Individuals Using Envelope Sequence-Based Phylogenetic Analyses.

ABSTRACT: The identification of transmission clusters (TCs) of HIV-1 using phylogenetic analyses can provide insights into viral transmission network and help improve prevention strategies. We compared the use of partial HIV-1 envelope fragment of 1,070 bp with its loop 3 (108 bp) to determine its utility in inferring HIV-1 transmission clustering. Serum samples of recently (n = 106) and chronically (n = 156) HIV-1-infected patients with status confirmed were sequenced. HIV-1 envelope nucleotide-based phylogenetic analyses were used to infer HIV-1 TCs. Those were constructed using ClusterPickerGUI_1.2.3 considering a pairwise genetic distance of ≤10% threshold. Logistic regression analyses were used to examine the relationship between the demographic factors that were likely associated with HIV-1 clustering. Ninety-eight distinct consensus envelope sequences were subjected to phylogenetic analyses. Using a partial envelope fragment sequence, 42 sequences were grouped into 15 distinct small TCs while the V3 loop reproduces 10 clusters. The agreement between the partial envelope and the V3 loop fragments was significantly moderate with a Cohen's kappa (κ) coefficient of 0.59, p < .00001. The mean age (<38.8 years) and HIV-1 B subtype are two factors identified that were significantly associated with HIV-1 transmission clustering in the cohort, odds ratio (OR) = 0.25, 95% confidence interval (CI, 0.04-0.66), p = .002 and OR: 0.17, 95% CI (0.10-0.61), p = .011, respectively. The present study confirms that a partial fragment of the HIV-1 envelope sequence is a better predictor of transmission clustering. However, the loop 3 segment may be useful in screening purposes and may be more amenable to integration in surveillance programs.

SUBMITTER: Kafando A

PROVIDER: S-EPMC6806616 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We aimed to elucidate the characteristics of HIV molecular epidemiology and identify transmission hubs in eastern China using genetic transmission network and lineage analyses. HIV-TRACE was used to infer putative relationships. Across the range of epidemiologically-plausible genetic distance (GD) thresholds (0.1–2.0%), a sensitivity analysis was performed to determine the optimal threshold, generating the maximum number of transmission clusters and providing reliable resolution without merging different small clusters into a single large cluster. Characteristics of genetically linked individuals were analyzed using logistic regression. Assortativity (shared characteristics) analysis was performed to infer shared attributes between putative partners. 1,993 persons living with HIV-1 were enrolled. The determined GD thresholds within subtypes CRF07_BC, CRF01_AE, and B were 0.5%, 1.2%, and 1.7%, respectively, and 826 of 1,993 (41.4%) sequences were linked with at least one other sequence, forming 188 transmission clusters of 2–80 sequences. Clustering rates for the main subtypes CRF01_AE, CRF07_BC, and B were 50.9% (523/1027), 34.2% (256/749), and 32.1% (25/78), respectively. Median cluster sizes of these subtypes were 2 (2–52, n = 523), 2 (2–80, n = 256), and 3 (2–6, n = 25), respectively. Subtypes in individuals diagnosed and residing in Hangzhou city (OR = 1.423, 95% CI: 1.168–1.734) and men who have sex with men (MSM) were more likely to cluster. Assortativity analysis revealed individuals were more likely to be genetically linked to individuals from the same age group (AIage = 0.090, P<0.001) and the same area of residency in Zhejiang (AIcity = 0.078, P<0.001). Additionally, students living with HIV were more likely to be linked with students than show a random distribution (AI student = 0.740, P<0.01). These results highlight the importance of Hangzhou City in the regional epidemic and show that MSM comprise the population rapidly transmitting HIV in Zhejiang Province. We also provide a molecular epidemiology framework for improving our understanding of HIV transmission dynamics in eastern China.

Project description:ImportanceTolerability is a key determinant of the effectiveness of epilepsy treatment. It is important to evaluate whether the overall tolerability has improved.ObjectiveTo identify factors associated with poor tolerability of antiseizure medications (ASMs) and examine temporal changes in tolerability.Design, setting, and participantsThis was a longitudinal cohort study at a specialist clinic in Glasgow, Scotland. Patients with newly diagnosed and treated epilepsy between July 1982 and October 2012 were included from 2282 eligible individuals. They were followed up until April 2016 or death. Data analysis was completed in August 2019.ExposuresAntiseizure medications.Main outcomes and measuresUnivariable and multivariable survival analyses were performed to examine associations between potential risk factors and development of intolerable adverse effects (AEs). Intolerable AE rates of the ASMs as the initial monotherapy were compared between 3 epochs (July 1982-June 1992, July 1992-June 2002, and July 2002-April 2016).ResultsOf 1795 patients, 969 (54.0%) were male, and the median (interquartile range) age was 33 (21-50) years. A total of 3241 ASMs were prescribed during the period, of which 504 (15.6%) were discontinued within 6 months owing to intolerable AEs. Children younger than 18 years had lower intolerable AE rates than adults (vs aged 18-64 years: adjusted hazard ratio [aHR], 1.58; 95% CI, 1.07-2.32; vs aged ≥65 years: aHR, 1.90; 95% CI, 1.19-3.02) while female individuals (aHR, 1.60; 95% CI, 1.30-1.96) and those who had more than 5 pretreatment seizures (aHR, 1.24; 95% CI, 1.03-1.49) were associated with having higher risk. For each ASM trial, the risk of intolerable AEs increased with the number of previous drug withdrawals due to AEs (aHR, 1.18; 95% CI, 1.09-1.28) and the number of concomitant ASMs (aHR, 1.31; 95% CI, 1.04-1.64). The proportion of second-generation ASMs prescribed as the initial monotherapy increased from 22.3% (33 of 148) in the first epoch to 68.7% (645 of 939) in the last (P < .001). Although differences in intolerable AE rates and types of AEs were found between the ASMs, there was no difference in the overall intolerable AEs rates to the initial monotherapy across the 3 epochs (first: 10.1% [15 of 148]; second: 13.8% [98 of 708]; third: 14.0% [131 of 939]; P = .41).Conclusions and relevanceIn this cohort study, the increased use of the second-generation ASMs had not improved overall treatment tolerability. Greater effort to improve tolerability in ASM development is needed.

Project description:BACKGROUND:Newly diagnosed HIV-positive individuals are 35 to 100-fold more susceptible to Streptococcus pneumoniae infection compared to non-infected individuals. Therefore, the 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been recommended, though efficacy and effectiveness of vaccination remains controversial. Early severe B cell dysfunction is a central feature of HIV infection. The specific nature of the immune cells involved in the production of protective antigen-specific antibodies in HIV-positive individuals remains to be elucidated. OBJECTIVES:Evaluate the antibody and antigen-specific B cell response to the 23-valent pneumococcal polysaccharide vaccine in newly diagnosed HIV-positive patients. Moreover, determine if newly diagnosed patients with CD4<200 cells/?l benefit from 6-12 months of HAART, allowing partial viral suppression and immune reconstitution, prior to immunization. METHODS:Newly diagnosed HIV-positive patients with CD4>200 cells/?l and CD4<200 cells/?l were immunized with PPV23. Patients with CD4<200 cells/?l received either immediate or delayed immunization following 6-12 months of HAART. Antibody responses, opsonophagocytic activity and phenotypic analysis of pneumococcal polysaccharide-specific B cells were studied. RESULTS:Newly diagnosed HIV-positive patients demonstrated CD4-dependent increases in antibody and opsonophagocytic titers thought to be commensurate with protection. Functional opsonophagocytic titers of patients with CD4<200 cells/?l immunized immediately compared to patients with CD4<200 cells/?l receiving HAART for 6-12 months were not significantly different. Pneumococcal polysaccharide-specific B cells were distributed evenly between IgM memory and switched memory B cells for all groups, but IgM memory B cells were significantly lower than in HIV-negative individuals. CONCLUSIONS:Despite CD4-dependent pneumococcal polysaccharide-specific deficiencies in newly diagnosed HIV-positive patients, vaccination was beneficial based on opsonophagocytic titers for all newly diagnosed HIV-positive groups. In HIV-positive patients with CD4<200 cells/?l, 6-12 months of HAART did not improve opsonophagocytic titers or antibody concentrations. Based on these findings, immunization with the 23-valent pneumococcal polysaccharide vaccine should not be delayed in newly diagnosed HIV-positive patients with CD4<200 cells/?l.

Project description:BACKGROUND:Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients' functioning. METHODS:Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders. RESULTS:Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5-10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (≥10 points difference) physical, role, and social functioning (betas ranged from -11.3 to -15.9, all P < 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of -12.3, P < 0.001), independent of other factors. CONCLUSIONS:Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients' functioning as measured with a self-report questionnaire.

Project description:Background and objectivesPublic health officials faced with a large number of transmission clusters require a rapid, scalable and unbiased way to prioritize distribution of limited resources to maximize benefits. We hypothesize that transmission cluster prioritization based on phylogenetically derived lineage-level diversification rates will perform as well as or better than commonly used growth-based prioritization measures, without need for historical data or subjective interpretation.Methodology9822 HIV pol sequences collected during routine drug resistance genotyping were used alongside simulated sequence data to infer sets of phylogenetic transmission clusters via patristic distance threshold. Prioritized clusters inferred from empirical data were compared to those prioritized by the current public health protocols. Prioritization of simulated clusters was evaluated based on correlation of a given prioritization measure with future cluster growth, as well as the number of direct downstream transmissions from cluster members.ResultsEmpirical data suggest diversification rate-based measures perform comparably to growth-based measures in recreating public heath prioritization choices. However, unbiased simulated data reveals phylogenetic diversification rate-based measures perform better in predicting future cluster growth relative to growth-based measures, particularly long-term growth. Diversification rate-based measures also display advantages over growth-based measures in highlighting groups with greater future transmission events compared to random groups of the same size. Furthermore, diversification rate measures were notably more robust to effects of decreased sampling proportion.Conclusions and implicationsOur findings indicate diversification rate-based measures frequently outperform growth-based measures in predicting future cluster growth and offer several additional advantages beneficial to optimizing the public health prioritization process.

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A Short-Term Assessment of Nascent HIV-1 Transmission Clusters Among Newly Diagnosed Individuals Using Envelope Sequence-Based Phylogenetic Analyses.

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