Hepatitis B and HIV coinfection in Northern Uganda: Is a decline in HBV prevalence on the horizon?

BackgroundThe available data concerning hepatitis B virus (HBV) infection in Uganda are limited, particularly in the case of people living with HIV/AIDS (PLWH). HBV is not routinely tested when starting antiretroviral therapy (ART). We aimed to determine the prevalence, the correlates of the risk of HBV infection, and the association with outcomes of ART among PLWH attending a busy HIV clinic in a referral hospital in Northern Uganda.Patients and methodsFrom April to June 2016, a random sample of 1000 PLWH attending the outpatients' clinic of St. Mary's Hospital, Gulu, Uganda were systematically selected to undergo a rapid hepatitis B surface antigen (HBsAg) test after administering a questionnaire in this cross-sectional study. HIV care parameters were obtained from client files. Multivariate logistic regression and general linear model were used for the analysis.Results950 of the 985 evaluable patients (77% females; mean age 42.8 years) were receiving ART. The overall prevalence of HBsAg was 7.9% (95% confidence interval [CI] 6.2-9.6%), and was significantly lower among the females (6.8% vs 11.7%; p = 0.020). The factors independently associated with higher HBV infection were having lived in an internally displaced persons' camp (adjusted odds ratio [aOR] 1.76, 95% CI 1.03-2.98; p = 0.036) and having shared housing with HBV-infected people during childhood (aOR 3.30, 95% CI 1.49-7.32; p = 0.003). CD4+ T cell counts were significantly lower in HBV patients (p = 0.025), and co-infection was associated with a poorer CD4+ T cell response to ART (AOR 0.88; 95% CI 0.79-0.98; p = 0.030).ConclusionsThe observed prevalence of HBV among the PLWH may be underestimated or a signal of HBV decline in the region. The factors favouring horizontal HBV transmission identified suggest extending HBV screening and vaccine prophylaxis among PLWH

Differences in the Prevalence of SARS-CoV-2 Infection and Access to Care between Italians and Non-Italians in a Social-Housing Neighbourhood of Milan, Italy

The northern Italian region of Lombardy has been severely affected by the COVID-19 pandemic since its arrival in Europe. However, there are only a few published studies of the possible influence of social and cultural factors on its prevalence in the general population. This cross-sectional study of the San Siro social-housing neighbourhood of Milan, which was carried about between 23 December 2020 and 19 February 2021, found that the prevalence of anti-SARS-CoV-2 nucleocapsid antibodies in the population as a whole was 12.4% (253/2044 inhabitants), but there was a more than two-fold difference between non-Italians and Italians (23.3% vs. 9.1%). Multivariable analyses showed that being more than 50 years old, living in crowded accommodation, being a non-Italian, and having a low educational level were associated with higher odds of a positive SARS-CoV-2 test, whereas a higher level of education, retirement, and being a former or current cigarette smoker were inversely associated with SARS-CoV-2 infection. Our findings are in line with previous observations indicating that a lower socio-economic status may be a risk factor for COVID-19 and show that non-Italians are disproportionately affected by SARS-CoV-2 infection. This suggests that public health policies should focus more on disadvantaged populations

SARS-CoV-2 viremia and COVID-19 mortality: A prospective observational study.

BackgroundSARS-CoV-2 viremia has been found to be a potential prognostic factor in patients hospitalized for COVID-19.ObjectiveWe aimed to assess the association between SARS-CoV-2 viremia and mortality in COVID-19 hospitalized patients during different epidemic periods.MethodsA prospective COVID-19 registry was queried to extract all COVID-19 patients with an available SARS-CoV-2 viremia performed at hospital admission between March 2020 and January 2022. SARS-CoV-2 viremia was assessed by means of GeneFinderTM COVID-19 Plus RealAmp Kit assay and SARS-CoV-2 ELITe MGB® Kit using ResultsFour hundred and forty-five out of 2,822 COVID-19 patients had an available SARS-CoV-2 viremia, prevalently males (64.9%) with a median age of 65 years (IQR 55-75). Patients with a positive SARS-CoV-2 viremia (86/445; 19.3%) more frequently presented with a severe or critical disease (67.4% vs 57.1%) when compared to those with a negative SARS-CoV-2 viremia. Deceased subjects (88/445; 19.8%) were older [75 (IQR 68-82) vs 63 (IQR 54-72)] and showed more frequently a detectable SARS-CoV-2 viremia at admission (60.2% vs 22.7%) when compared to survivors. In univariable analysis a positive SARS-CoV-2 viremia was associated with a higher odd of death [OR 5.16 (95% CI 3.15-8.45)] which was confirmed in the multivariable analysis adjusted for age, biological sex and, disease severity [AOR 6.48 (95% CI 4.05-10.45)]. The association between positive SARS-CoV-2 viremia and death was consistent in the period 1 February 2021-31 January 2022 [AOR 5.86 (95% CI 3.43-10.16)] and in subgroup analysis according to disease severity: mild/moderate [AOR 6.45 (95% CI 2.84-15.17)] and severe/critical COVID-19 patients [AOR 6.98 (95% CI 3.68-13.66)].ConclusionsSARS-CoV-2 viremia resulted associated to COVID-19 mortality and should be considered in the initial assessment of COVID-19 hospitalized patients

Comparing the efficacy and safety of a first-line regimen with emtricitabine/tenofovir alafenamide fumarate plus either bictegravir or dolutegravir: Results from clinical practice

Background: First-line integrase strand transfer inhibitor-based regimens have become commonly used in clinical practice over the last decade. This study aimed to analyse and compare the efficacy and safety of bictegravir (BIC) and dolutegravir (DTG) when prescribed in association with emtricitabine/tenofovir alafenamide (FTC/TAF) as part of a first-line regimen for the treatment of human immunodeficiency-1 (HIV-1) infection. Methods: Treatment-naïve people living with HIV (PLWHIV) starting a first-line regimen with either BIC/FTC/TAF (BIC group) or FTC/TAF+DTG (DTG group) were analysed. Snapshot analyses were performed after 24 and 48 weeks to evaluate virological efficacy. In addition, differences in the rate of treatment discontinuation (TD) between the two groups were evaluated using the Kaplan-Meier method and the log rank test. Results: Data from 327 PLWHIV were analysed: 140 in the DTG group and 187 in the BIC group. At 48 weeks, 90.0% of individuals in the DTG group and 86.7% of those in the BIC group achieved HIV-RNA <50 copies/mL. In total, 88 and 38 cases of TD were observed in the DTG group and BIC group, respectively. The estimated probability of maintaining the study regimen at week 48 was 59.5% in the DTG group and 84.2% in the BIC group. Analysing changes in immunological parameters after 48 weeks, median improvements of +169 cell/mm3 (P<0.001) and +233 cell/mm3 (P<0.001) were observed in the DTG group and the BIC group, respectively. Conclusions: Both BIC and DTG, in combination with FTC/TAF, show promising efficacy and safety as first-line strategies in clinical practice, with favourable immunological recovery even in the short term

Clinical and genetic determinants of nevirapine plasma trough concentration

Background: Only few data are available on the influence of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations in the Caucasian population. Our aim was to assess the impact of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations consecutively collected. Methods: We retrospectively analyzed clinical data of all HIV-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan between January 2000 and December 2015. All patients with at least one nevirapine plasma trough concentration (NVP C min ) determination were tested for CYP2B6 c.516 G>T, CYP3A4*22C>T and CYP3A5*3 A>G polymorphisms. Univariate and multivariate regression analyses were carried out considering NVP C min as the dependent variable and genetic polymorphisms and clinical characteristics as independent variables. Results: A total of 143 patients were evaluated. Most of them were males (61.5%) and Caucasian (92.3%). Overall, NVP C min varied from 1571 to 14,189  ng/mL (median  =  5063  ng/mL, interquartile range  =  3915–6854). The median NVP C min significantly differed in patients with different CYP2B6 genotypes, but did not vary in those with different CYP3A phenotypes. In the final general linear model, factors significantly associated with a higher NVP C min were each extra unit of T alleles of CYP2B6 rs3745274 (β  =  0.328, 95% confidence interval  =  0.172–0.484; p   <  0.0001), older age (β  =  0.362, 95% confidence interval  =  0.193–0.532; p   <  0.0001) and hepatitis C virus coinfection (β  =  0.161, 95% confidence interval  =  0.006–0.315; p   <  0.041). Conclusion: Our study, conducted in a prevalent Caucasian population, highlighted the importance of CYP2B6 genetic variants in influencing nevirapine plasma trough concentration. Furthermore, older age and hepatitis C virus coinfection significantly increase exposure to nevirapine

Impact of prior infection status on antibody response to the BNT162b2 mRNA COVID-19 vaccine in healthcare workers at a COVID-19 referral hospital in Milan, Italy

In Italy, SARS-CoV-2 vaccination campaign prioritized healthcare workers (HCWs) to receive two doses of BNT162b2 vaccine, irrespective of a previous SARS-CoV-2 infection. In this real-life study, we compared the humoral response to BNT162b2 vaccine in HCWs with and without a previous SARS-CoV-2 infection. Of the 407 HCWs enrolled, 334 (82.1%) were SARS-CoV-2-naive and 73 (17.9%) SARS-CoV-2-experienced. Post-vaccine humoral response was detectable in more than 98% of HCWs. Overall, the median level of anti-S IgG in SARS-COV-2-experienced HCWs was twice as high as those of SARS-CoV-2-naive subjects (24641.0 AU/mL [IQR: 15273.0–>40000.0] versus 13053.8 [IQR: 7303.3–20105.8]; p < .001), irrespective of the time elapsed from SARS-CoV-2 previous infection. In a subgroup of SARS-CoV-2-naive and -experienced subjects who received only one dose of the vaccine, the latter showed 32 times higher levels of anti-S IgG compared to the former. Although no serious adverse events have been reported, mild to moderate side effects occurred more frequently after the first dose in the SARS-CoV-2-experienced than in naive subjects (67% versus 42%, respectively; p < .001). Notably, post-vaccination anti-SARS-CoV-2 spike IgG levels ≥20,000 AU/mL were independently associated with the risk of fever ≥38°C (adjusted odds ratio [aOR] 5.122, 95% CI 2.368–11.080, p < .0001). Our study showed high responsiveness of BNT162b2 vaccine and a relationship between levels of antibody response and reactogenicity. It suggests that a single dose of mRNA vaccine might evoke effective protection in SARS-CoV-2-experienced subjects

Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p p p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction

Logistic regression analysis of factors associated with death restricted to the 3rd and 4th epidemic period.

Logistic regression analysis of factors associated with death restricted to the 3rd and 4th epidemic period.</p