The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be ...elucidated.
Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models.
2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p = 0.361).
Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.
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The presence and severity of pelvic inflammatory disease (PID) symptoms are thought to vary by microbiological etiology but there is limited empirical evidence. We sought to estimate and compare the ...rates of hospitalisation for PID temporally related to diagnoses of gonorrhoea and chlamydia.
All women, aged 15-45 years in the Australian state of New South Wales (NSW), with a diagnosis of chlamydia or gonorrhoea between 01/07/2000 and 31/12/2008 were followed by record linkage for up to one year after their chlamydia or gonorrhoea diagnosis for hospitalisations for PID. Standardised incidence ratios compared the incidence of PID hospitalisations to the age-equivalent NSW population.
A total of 38,193 women had a chlamydia diagnosis, of which 483 were hospitalised for PID; incidence rate (IR) 13.9 per 1000 person-years of follow-up (PYFU) (95%CI 12.6-15.1). In contrast, 1015 had a gonorrhoea diagnosis, of which 45 were hospitalised for PID (IR 50.8 per 1000 PYFU, 95%CI 36.0-65.6). The annual incidence of PID hospitalisation temporally related to a chlamydia or gonorrhoea diagnosis was 27.0 (95%CI 24.4-29.8) and 96.6 (95%CI 64.7-138.8) times greater, respectively, than the age-equivalent NSW female population. Younger age, socio-economic disadvantage, having a diagnosis prior to 2005 and having a prior birth were also associated with being hospitalised for PID.
Chlamydia and gonorrhoea are both associated with large increases in the risk of PID hospitalisation. Our data suggest the risk of PID hospitalisation is much higher for gonorrhoea than chlamydia; however, further research is needed to confirm this finding.
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Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and ...hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood.
In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections.
We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified.
SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.
Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of ...pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0-45, 46-365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM.
SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron ...breakthrough infection.
The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR 95% CI for BA.2: 0.83 0.73–0.95, p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR 95% CI for BA.2 spike-specific IgG: 0.65 0.48–0.88, p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 0.30–0.69, p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.
High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.
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•High antibody levels are associated with low odds of Omicron breakthrough infection•Vaccine-induced antibodies are an immune marker of protection against infection•Sex stratification revealed a clear association for females in particular
Immunology; Molecular medicine; Immune response
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Results of routine maternal antenatal hepatitis B (HBV) screening have been recorded in the New South Wales (NSW) Perinatal Data Collection (PDC) since January 2011. We evaluated the accuracy of this ...reporting in 2012, the first year that comprehensive data were available, by linking the PDC to HBV notifications.
PDC records of mothers giving birth in 2012 were probabilistically linked to HBV notifications recorded in the NSW Notifiable Conditions Information Management System (NCIMS). Sensitivity and specificity of the PDC record of HBV status were determined using a linked HBV notification from the NCIMS database as the gold standard. Results were also examined according to health service (area health service, hospital level, public or private) and individual factors (maternal age, country of birth, Aboriginality, parity, timing of first antenatal visit).
Among 99 510 records of women giving birth in NSW in 2012, positive HBV status was recorded for 0.69% of the women according to the PDC record and 0.90% from linked NCIMS records. The overall sensitivity of the HBV status variable in the PDC data was 65.5% (95% confidence interval CI 62.4, 68.7) and positive predictive value was 85.3% (95% CI 82.6, 87.9). In general, the low prevalence of HBV meant we had limited statistical power to assess differences between health service factors and maternal factors; however, sensitivity was significantly lower in PDC data for HBV in Australian-born non-Aboriginal women (37.0%; 95% CI 27.5, 46.7) than in overseas-born women (69.9%; 95% CI 66.6, 73.1; p < 0.001).
PDC records of HBV status for women giving birth in 2012 had high specificity but poor sensitivity. Sensitivity varied across area health services and levels of maternal services, and by various maternal factors. Because the results of maternal HBV screening can be used to monitor HBV prevalence in adults, analysis of the PDC records in subsequent years is necessary to track whether sensitivity improves over time.
State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV ...patients based on four key indicators.
Four indicators of health care were assessed: Compliance with current guidelines on initiation of: 1) combination antiretroviral therapy (cART); 2) chemoprophylaxis; 3) frequency of laboratory monitoring; and 4) virological response to cART (proportion of patients with HIV-RNA < 500copies/ml for >90% of time on cART).
7097 EuroSIDA patients were included from Northern (n = 923), Southern (n = 1059), West Central (n = 1290) East Central (n = 1366), Eastern (n = 1964) Europe, and Argentina (n = 495). Patients in Eastern Europe with a CD4 < 200cells/mm(3) were less likely to initiate cART and Pneumocystis jiroveci-chemoprophylaxis compared to patients from all other regions, and less frequently had a laboratory assessment of their disease status. The proportion of patients with virological response was highest in Northern, 89% vs. 84%, 78%, 78%, 61%, 55% in West Central, Southern, East Central Europe, Argentina and Eastern Europe, respectively (p < 0.0001). Compared to Northern, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for Eastern Europe and Argentina (adjusted OR 0.16 95%CI 0.11-0.23, p < 0.0001; 0.200.14-0.28, p < 0.0001 respectively).
This assessment of HIV health care utilization revealed pronounced regional differences in adherence to guidelines and can help to identify gaps and direct target interventions. It may serve as a tool for the assessment and benchmarking of the clinical management of HIV patients in any setting worldwide.
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Abstract
Gonorrhea and chlamydia are important causes of pelvic inflammatory disease. Chlamydia also causes long-term sequelae, but the role of gonorrhea is unclear. We followed 300 000 ...reproductive-aged women for 10 years for ectopic pregnancy and tubal infertility; our findings suggest both infections confer similar increases in risk of these outcomes.
We examined the association between vitamin D 25(OH)D level and disease progression in HIV infection.
Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored ...plasma samples closest to study entry. 25(OH)D results were stratified into tertiles. Factors associated with 25(OH)D levels and associations of 25(OH) levels with subsequent risk of all-cause mortality, AIDS and non-AIDS events were analyzed.
Of 1985 persons with 25(OH)D levels available, 23.7% had 25(OH)D below 10, 65.3% between 10 and 30, and 11% above 30 ng/ml. At the time of 25(OH)D measurement, older persons, persons of black ethnic origin, living outside Southern Europe/Argentina, sampled during winter, and infected with HIV through nonhomosexual exposure were at higher odds of having low 25(OH)D levels, whereas persons receiving protease inhibitors were at lower odds. Compared to those in the lowest 25(OH)D tertile (<12 ng/ml), those in the middle (12-20) and higher (>20) tertiles had a significantly lower risk of clinical progression during subsequent follow-up. Adjusted incidence rate ratios for all-cause mortality were 0.68 (95% CI 0.47-0.99, P = 0.045) and 0.56 (95% CI 0.37-0.83, P = 0.0039), and for AIDS events were 0.58 (95% CI 0.39-0.87, P = 0.0086) and 0.61 (95% CI 0.40-0.93, P = 0.020), for the middle and higher tertiles, respectively. There was a similar, nonsignificant reduced incidence of non-AIDS events in the middle and higher tertiles.
25(OH)D deficiency was frequent in HIV-infected persons (83% on combined antiretroviral therapy), and was independently associated with a higher risk of mortality and AIDS events. Causality relationships should be examined, because of potential public health consequences.
To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and the durability of vaccine-induced antibodies.
Adults without history of SARS-CoV-2 infection ...from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase 4 study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90, and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 after first vaccination. Nondurable vaccine response was defined as day-90 responders who no longer had significant responses by day 180.
Of 6544 participants completing two vaccine doses (median age 64 years; interquartile range: 54–75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by an mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hyporesponsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG and 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type, and number of comorbidities were associated with all four outcomes. Additionally, age ≥75 years was associated with hyporesponsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds ratio: 1.59; 95% confidence interval: 1.25–2.01) but not for Spike IgG.
Comorbidity, male sex, and vaccine type were risk factors for hyporesponsiveness and nondurable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-second-vaccination levels for most individuals after 6 months.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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