Safety and immunogenicity of the third and fourth doses of vaccine against SARS-CoV-2 following a 2-dose regimen of inactivated whole-virion SARS-CoV-2 vaccine.

This study followed healthcare personnel (HCP) who had completed a primary series of CoronaVac and then received the third and fourth doses of COVID-19 vaccine. The primary objective was to determine the seroconversion rate of neutralizing antibodies against wild-type SARS-CoV-2 and VOCs at day 28 after the third dose of vaccine and day 28 after the fourth dose of vaccine. This prospective cohort study was conducted at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital affiliated to Chiang Mai University from July 2021 to February 2022. Two hundred and eighty-three participants were assessed for eligibility; 142 had received AZD1222 and 141 BNT162b2 as the third dose. Seroconversion rates using a 30% inhibition cutoff value against wild-type SARS-CoV-2 were 57.2%, 98.6%, 97.8%, and 98.9% at points before and after the third dose, before and after the fourth dose, respectively among those receiving AZD1222 as the third dose. Frequencies were 31.9%, 99.3%, 98.9%, and 100% among those receiving BNT162b2 as the third dose, respectively. The seroconversion rates against B.1.1.529 [Omicron] were 76.1% and 90.2% (p-value 0.010) at 4 weeks after the third dose in those receiving AZD1222 and BNT162b2 as the third dose, respectively. After a booster with the mRNA vaccine, the seroconversion rates increased from 21.7 to 91.3% and from 30.4 to 91.3% in those receiving AZD1222 and BNT162b2 as the third dose, respectively. No serious safety concerns were found in this study. In conclusion, antibody responses waned over time regardless of the vaccine regimen. The booster dose of the vaccine elicited a humoral immune response against SARS-CoV-2 including SARS-CoV-2 variants of concern, including B.1.1.529 [Omicron], which was circulating during the study period. However, the results might not be extrapolated to other Omicron sublineages.

Cryptococcal Meningitis: Differences between Patients with and without HIV-Infection.

Background: Cryptococcal meningitis is one of the most devastating infections, particularly in HIV-infected individuals. The increased use of immunosuppressants led to an increase in the incidence of cryptococcosis in HIV-uninfected individuals. This study aimed to compare the characteristics between groups. Methods: This retrospective cohort study was conducted from 2011 to 2021 in northern Thailand. Individuals diagnosed with cryptococcal meningitis aged ≥15 years were enrolled onto the study. Results: Out of 147 patients, 101 were individuals infected with HIV and 46 were non-infected. Factors associated with being infected with HIV included age < 45 years (OR 8.70, 95% CI 1.78-42.62), white blood cells < 5000 cells/cu.mm. (OR 7.18, 95% CI 1.45-35.61), and presence of fungemia (OR 5.86, 95% CI 1.17-42.62). Overall, the mortality rate was 24% (18% in HIV-infected vs. 37% in HIV-uninfected individuals, p-value = 0.020). Factors associated with mortality included concurrent pneumocystis pneumonia (HR 5.44, 95% CI 1.55-19.15), presence of alteration of consciousness (HR 2.94, 95% CI 1.42-6.10), infection caused by members of C. gattii species complex (HR 4.19, 95% CI 1.39-12.62), and anemia (HR 3.17, 95% CI 1.17-8.59). Conclusions: Clinical manifestations of cryptococcal meningitis differed between patients with and without HIV-infection in some aspects. Increasing awareness in physicians of this disease in HIV-uninfected individuals may prompt earlier diagnosis and timely treatment.

Diagnostic performance between in-house and commercial SARS-CoV-2 serological immunoassays including binding-specific antibody and surrogate virus neutralization test (sVNT).

This study aimed to evaluate the correlation between in-house and commercial binding-specific IgG antibodies and between in-house and commercial SARS-CoV-2 surrogate virus neutralization tests (sVNT). Samples from healthcare workers who received vaccines against SARS-CoV-2 were tested for RBD-specific antibody, S-specific antibody, and in-house ELISA, commercial sVNT, and in-house sVNT, against wild-type SARS-CoV-2. Three hundred and five samples were included in the analysis. The correlation between S-specific binding antibodies and in-house ELISA was 0.96 (95% CI 0.96-0.97) and between RBD-specific antibodies and in-house ELISA was 0.96 (95% CI 0.95-0.97). The Cohen's kappa between in-house sVNT and the commercial test was 0.90 (95% CI 0.80, 1.00). If using 90% inhibition of sVNT as the reference standard, the optimal cut-off value of RBD-specific antibodies was 442.7 BAU/mL, the kappa, sensitivity, and specificity being 0.99, 99%, and 100%, respectively. The optimal cut-off value of S-specific antibodies was 1155.9 BAU/mL, the kappa, sensitivity, and specificity being 0.99, 100%, and 99%, respectively. This study demonstrated a very strong correlation between in-house ELISA and 2 commercial assays. There was also a very strong correlation between in-house and commercial SARS-CoV-2 sVNT, a finding of particular interest which will inform future research.

Hospital-Wide Protocol Significantly Improved Appropriate Management of Patients with Staphylococcus aureus Bloodstream Infection.

Background:Staphylococcus aureus bloodstream infection (SA-BSI) causes morbidity and mortality. We established a management protocol for patients with SA-BSI aimed at improving quality of care and patient outcomes. Methods: A retrospective pre−post intervention study was conducted at Maharaj Nakorn Chiang Mai Hospital from 1 October 2019 to 30 September 2020 in the pre-intervention period and from 1 November 2020 to 31 October 2021 in the post-intervention period. Results: Of the 169 patients enrolled, 88 were in the pre-intervention and 81 were in the post-intervention periods. There were similar demographic characteristics between the two periods. In the post-intervention period, evaluations for metastatic infections were performed more frequently, e.g., echocardiography (70.5% vs. 91.4%, p = 0.001). The appropriateness of antibiotic prescription was higher in the post-intervention period (42% vs. 81.5%, p < 0.001). The factors associated with the appropriateness of antibiotic prescription were ID consultation (OR 15.5; 95% CI = 5.9−40.8, p < 0.001), being in the post-intervention period (OR 9.4; 95% CI: 3.5−25.1, p < 0.001), and thorough investigations for metastatic infection foci (OR 7.2; 95% CI 2.1−25.2, p = 0.002). However, the 90-day mortality was not different (34.1% and 27.2% in the pre- and post-intervention periods, respectively). The factors associated with mortality from the multivariate analysis were the presence of alteration of consciousness (OR 11.24; 95% CI: 3.96−31.92, p < 0.001), having a malignancy (OR 6.64; 95% CI: 1.83−24.00, p = 0.004), hypoalbuminemia (OR 5.23; 95% CI: 1.71−16.02, p = 0.004), and having a respiratory tract infection (OR 5.07; 95% CI: 1.53−16.84, p = 0.008). Source control was the only factor that reduced the risk of death (OR 0.08; 95% CI: 0.01−0.53, p = 0.009). Conclusion: One-third of patients died. Hospital-wide protocol implementation significantly improved the quality of care. However, the mortality rate did not decrease.

Cardio-ankle vascular index of increased arterial wall stiffness is associated with neurocognitive impairment in well-controlled HIV.

OBJECTIVES: HIV-associated neurocognitive disorders (HAND) remain prevalent in people living with HIV (PLWH) despite widespread use of combined antiretroviral therapy (ART). Vascular disease contributes to the pathogenesis of HAND, but traditional vascular risk factors do not fully explain the relation between vascular disease and HAND. A more direct measure of vascular dysfunction is needed. This cross-sectional study tested whether the cardio-ankle vascular index (CAVI), a novel method to assess arterial stiffness, is associated with HAND among PLWH. METHODS: Participants included 75 non-diabetic adults with well-controlled HIV from an outpatient HIV clinic. We assessed the relation between CAVI and neurocognitive impairment (NCI). The latter was primarily characterized by the Frascati criteria and secondarily (post hoc) using the Global Deficit Score (GDS). Logistic regression models tested whether high CAVI (≥ 8) was independently associated with NCI when controlling for potential confounders. RESULTS: Participants (Mage  = 45.6 ± 8.3 years; 30.1% male) had few traditional cardiovascular disease (CVD) risk factors (hypertension, n = 7; dyslipidaemia, n = 34; body mass index ≥ 25 kg/m2 , n = 12; smoking history, n = 13; 2.2% mean 10-year risk of CVD or stroke). Twelve (16%) participants had high CAVI, which was independently associated with meeting Frascati criteria for NCI [n = 39, odds ratio (OR) = 7.6, p = 0.04], accounting for age, education, gender, income, CD4 nadir, recent CD4 and traditional CVD risk factors. High CAVI was also associated with NCI as reflected by higher GDS (OR = 17.4, p = 0.02). CONCLUSIONS: Cardio-ankle vascular index is a promising measure of vascular dysfunction that may be independently associated with NCI in relatively healthy PLWH. Larger studies should test the utility of CAVI in predicting NCI/decline in PLWH.

Psychometric utility of the international HIV dementia scale and Montreal Cognitive Assessment in HIV-associated asymptomatic neurocognitive impairment.

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Drug-drug interaction between itraconazole capsule and efavirenz in adults with HIV for talaromycosis treatment.

OBJECTIVES: To assess the pharmacokinetic of itraconazole capsule formulation and its active metabolite, hydroxyitraconazole, in adults with HIV diagnosed with talaromycosis in an endemic area, and to evaluate the drug-drug interaction between itraconazole/hydroxyitraconazole (ITC/OH-ITC) and efavirenz. METHODS: Open-label, single arm, sequential pharmacokinetic study. Eligible subjects were adults with HIV, ≥18 years old, with confirmed talaromycosis, initiating itraconazole capsule as part of standard talaromycosis treatment, in whom efavirenz-based ART was anticipated. Steady-state pharmacokinetic assessments (pre-dose and at 1, 3, 4, 5, 6, 8 and 12 h post dose) were performed for itraconazole/hydroxyitraconazole without and with efavirenz use. Mid-dose efavirenz concentrations were also assessed. Pharmacokinetics parameters were calculated using non-compartmental analysis. RESULTS: Ten subjects (70% male) were enrolled. At entry, median (range) age was 29.5 years (22-64), and CD4 cell count was 18.0 (1-39) cells/mm3. Geometric mean (95% CI) of itraconazole and hydroxyitraconazole AUC0-12 without efavirenz were 9097 (6761-12 239) and 11 705 (8586-15 959) ng·h/mL, respectively, with a median metabolic ratio of OH-ITC : ITC of 1.3 (95% CI 0.9-1.9). Intra-subject comparison revealed that both itraconazole and hydroxyitraconazole exposures were significantly reduced with concomitant efavirenz use, with the mean AUC0-12 of itraconazole and hydroxyitraconazole being 86% (71%-94%) and 84% (64%-97%) lower, respectively. With efavirenz, itraconazole trough concentrations were also below the recommended therapeutic level (0.5 µg/mL). All subjects had mid-dose efavirenz concentrations >1000 ng/mL. CONCLUSIONS: Concomitant administration of itraconazole capsule with efavirenz significantly reduced itraconazole and hydroxyitraconazole exposures. The clinical impact of this drug-drug interaction on talaromycosis treatment or prophylaxis in the era of potent ART needs further evaluation.