Safety and immunogenicity of heterologous COVID-19 vaccine regimens to deal with product shortage: A randomised clinical trial in an elderly population.

Objectives: In a context of COVID-19 vaccine shortages, this study sought to evaluate the safety and efficacy of receiving one dose of Gam-COVID-Vac rAd26 followed by a second COVID-19 vaccine dose of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV in a cohort of older adults. Study design: Single-centre, randomised, open label, non-inferiority trial. Methods: Adults aged ≥65 years who had received one dose of Gam-COVID-Vac rAd26 were randomised in a 1:1:1 ratio to receive a second-dose COVID-19 vaccination of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV. The primary outcome was the assessment of the humoral immune response to vaccination (i.e. antibody titres of SARS-CoV-2 spike protein at 28 days after second-dose vaccination). In addition, neutralising antibody titres at day 28 for the three schedules were measured. Results: Of 85 participants who were enrolled in the study between 26 and July 30, 2021, 31 individuals were randomised to receive Gam-COVID-Vac rAd5, 27 to ChAdOx1 nCoV-19 and 27 to BBIBP-CorV. The mean age of participants was 68.2 years (SD 2.9) and 49 (57.6%) were female. Participants who received Gam-COVID-Vac rAd5 and ChAdOx1 nCoV1-19 showed significantly increased anti-S titres at 28 days after second-dose vaccination, but this magnitude of difference was not observed for those who received BBIBP-CorV. The ratio between the geometric mean at day 28 and baseline within each group was 11.8 (6.98-19.89) among patients assigned to Gam-COVID-Vac rAd26/rAd5, 4.81 (2.14-10.81) for the rAd26/ChAdOx1 nCoV-19 group and 1.53 (0.74-3.20) for the rAd26/BBIBP-CorV group. All of the schedules were shown to be safe. Conclusions: The findings in this study contribute to the scarce information published on the safety and immunogenicity of Gam-COVID-Vac heterologous regimens and will help the development of guidelines and vaccine programme management.

Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina.

OBJECTIVE: Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). METHODS: Retrospective study in a cohort of 40 naïve HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. RESULTS: TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were <2.3% of viral population and ML was <350 c/mL for 77.8% of them. CONCLUSIONS: NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.

Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients.

Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103 IU/ml (group A) or > 103 IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9 × 10-4 ±â€¯1.3 × 10-4) than group B (2.7 × 10-4 ±â€¯7.4 × 10-5 substitution/site/year, p < .001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.

Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014-15.

BACKGROUND: In Argentina, current national guidelines recommend starting with NNRTI-based regimens. Recently, there have been some local reports regarding concerning levels of NNRTI-transmitted resistance, but surveillance has never been carried out at a national level. OBJECTIVES: To determine the prevalence of HIV drug resistance in people starting ART in Argentina using a WHO-proposed methodology. METHODS: This was a cross-sectional, nationally representative study. Twenty-five antiretroviral-dispensing sites throughout the country were randomly chosen to enrol at least 330 persons starting ART, to generate a point prevalence estimate of resistance-associated mutations (RAMs) with a 5% CI (for the total population and for those without antiretroviral exposure). All consecutive patients older than 18 years starting or restarting ART in the chosen clinics were eligible. Samples were processed with Trugene and analysed using the Stanford algorithm. RESULTS: Between August 2014 and March 2015, we obtained 330 samples from people starting ART. The mean ±â€ŠSD age was 35 ±â€Š11 years, 63.4% were male, 16.6% had prior antiretroviral exposure and the median (IQR) CD4 count was 275 cells/mm3 (106-461). The prevalence of RAMs found was 14% (±4%) for the whole population (3% NRTI-RAMs; 11% NNRTI-RAMs and 2% PI-RAMs) and 13% (±4%) for those without prior antiretroviral exposure (3%, 10% and 2%, respectively). The most common mutation was K103N. CONCLUSIONS: This surveillance study showed concerning levels of HIV drug resistance in Argentina, especially to NNRTIs. Due to this finding, Argentina's Ministry of Health guidelines will change, recommending performing a resistance test for everyone before starting ART. If this is taken up properly, it also might function as a continuing surveillance tool.

Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation.

HSV can cause oral lesions that exacerbate chemotherapy-related mucositis. Intravenous acyclovir is effective in preventing HSV reactivations, but expensive. Valacyclovir has good bioavailability and has not been studied for prophylaxis of HSV among PCT patients. We compared the efficacy and costs of valacyclovir in preventing HSV reactivation among HSV seropositive autologous progenitor cell transplantation (APCT) patients with historical controls in whom intravenous acyclovir or no HSV prophylaxis were used. Valacyclovir group: From October 1997 to April 1999 108 adult patients received valacyclovir 500 mg twice daily from day -3 of APCT until neutropenia recovery or day +30. Valacyclovir was switched to intravenous acyclovir in cases of oral intolerance (17 patients) or suspected HSV reactivation (five patients). Intravenous acyclovir group: From January 1996 to October 1997 43 patients received 5 mg/kg twice-daily intravenous acyclovir from day -3 until recovery from neutropenia. No prophylaxis group: 38 patients from January 1996 to October 1997 did not receive HSV prophylaxis. HSV reactivations were seen in 2.7%, 2% and 45% of patients in the valacyclovir, intravenous acyclovir, and no prophylaxis groups, respectively. Valacyclovir was well tolerated and was the least expensive strategy. Oral valacyclovir was as effective as intravenous acyclovir for the prophylaxis of HSV reactivation in APCT patients.

Toronto Alexithymia Scale in outpatients with sexual disorders.

The Toronto Alexithymia Scale (TAS-26) was administered to patients with sexual disorders (n = 112) and to healthy control subjects (n = 94). The clinic sample was divided into three subgroups according to DSM-III-R criteria: patients with hypoactive sexual desire disorder (n = 41), patients with orgasm disorders (n = 51) and patients with male erectile disorder (n = 20). TAS scores were significantly higher for male and female patients with hypoactive sexual desire disorder, and with male erectile disorder than controls. The TAS scores in the orgasm disorder patients were not significantly different from those of controls. These results are interesting because they show an association betweeen alexithymia and some sexual symptoms.

Prospective randomized trial of single clamp technique versus intermittent ischaemic arrest: myocardial and neurological outcome.

OBJECTIVE: To explore the hypothesis that intermittent ischaemic arrest (IIA) provides better myocardial preservation but generates a larger number of cerebral microemboli (ME) and consequently a higher incidence of post-operative cerebral dysfunction compared with the single clamp technique (SCT). METHODS: Ninety-one patients with stable angina undergoing elective CABG with no clinical evidence of aortic or cerebro-vascular or neurological disease were prospectively randomized to: IIA (n = 43) or SCT with intermittent anterograde cold blood cardioplegia (n = 48). Myocardial preservation was assessed by measuring serum CK-MB, Troponin-T (TnT) and Troponin-I (TnI) and from pre- and post-operative ECGs and left ventricular (LV) function by echocardiography. Intra-operative cerebral ME were counted by transcranial Doppler of the right middle cerebral artery. All patients completed the Luria Nebraska Neuropsychological Battery (LNNB) tests for motor, visual, reading, memory and intellectual processes the day before surgery and at 1 week and 6 months post-operatively. Serum levels of the neuro-specific protein S-100 were measured. RESULTS: The two groups were comparable for age, sex, extent of coronary disease, previous myocardial infarction, diabetes, hypertension and number of arterial and venous grafts. The median number of ME detected per patient was 34 (range 4-208) and was similar in both groups. Protein S-100 levels remained normal and similar in both groups at all times except in one patient with SCT who had an operative stroke. LNNB scores were similarly depressed at 1 week and recovered in all cases at 6 months. There was no correlation between the number of ME and LNNB scores. Median peak TnI levels were 0.64 microg/l with IIA vs. 0.87 microg/l with SCT (P = NS) and TnT 0.8 microg/l vs. 1.08 microg/l (P < 0.03). SCT was however associated with longer mean ischaemic (67.6 +/- 16.1 vs. 34.5 +/- 16.5 min, P < 0.001) and mean bypass time (88.5 +/- 18.2 vs. 74.6 +/- 26.3 min, P < 0.004) than IIA. Four patients with SCT and none with IIA had ECG changes suggestive of MI (P = 0.04). CONCLUSION: During elective CABG in patients with no clinical evidence of aortic or cerebro-vascular disease the incidence of peri-operative ME and post-operative neuropsychological disturbances are comparable with both techniques of myocardial preservation. Biochemical analysis suggests that IIA provides more effective myocardial preservation.