Consequences of the COVID-19 pandemic on the continuum of care in a cohort of people living with HIV followed in a single center of Northern Italy.

INTRODUCTION: During the COVID-19 pandemic, hospitals faced increasing pressure, where people living with HIV risked to either acquire SARS-CoV-2 and to interrupt the HIV continuum of care. METHODS: This is a retrospective, observational study. We compared the numbers of medical visits performed, antiretroviral drugs dispensed and the number of new HIV diagnosis and of hospitalizations in a cohort of people living with HIV (PLWH) followed by the Spedali Civili of Brescia between the bimester of the COVID-19 pandemic peak and the bimester of October-November 2019. Data were retrieved from administrative files and from paper and electronic clinical charts. Categorical variables were described using frequencies and percentages, while continuous variables were described using mean, median, and interquartile range (IQR) values. Means for continuous variables were compared using Student's t-tests and the Mann-Whitney test. Proportions for categorical variables were compared using the χ2 test. RESULTS: As of December 31st, 2019, a total of 3875 PLWH were followed in our clinic. Mean age was 51.4 ± 13 years old, where 28% were females and 18.8% non-Italian. Overall, 98.9% were on ART (n = 3834), 93% were viro-suppressed. A total of 1217 and 1162 patients had their visit scheduled at our out-patient HIV clinic during the two bimesters of 2019 and 2020, respectively. Comparing the two periods, we observed a raise of missed visits from 5 to 8% (p < 0.01), a reduction in the number of new HIV diagnosis from 6.4 in 2019 to 2.5 per month in 2020 (p = 0.01), a drop in ART dispensation and an increase of hospitalized HIV patients due to COVID-19. ART regimens including protease inhibitors (PIs) had a smaller average drop than ART not including PIs (16.6 vs 21.6%, p < 0.05). Whether this may be due to the perception of a possible efficacy of PIs on COVID19 is not known. CONCLUSIONS: Our experience highlights the importance of a resilient healthcare system and the need to implement new strategies in order to guarantee the continuum of HIV care even in the context of emergency.

Coxiella burnetii outbreak, Northern Italy 2021.

Objective: We report an outbreak of 14 cases of Q fever among tourists caused by an infected calf and characterized by respiratory transmission and a high attack rate in humans. Materials and methods: Following the identification of an index case of Q fever in September 2021, an epidemiological investigation was conducted in collaboration with local Health and Veterinary authorities and an unknown outbreak was discovered and terminated. Results: The outbreak originated from the delivery by an infected cow, with spread of C. burnetii by air and infection via the respiratory route. The transmission period was calculated, and 25 potentially exposed tourists were identified: 14 were infected (56%) based on serological investigations, four were hospitalized, there were no deaths. All the 22 cows were tested by PCR for C. burnetii: 3 cows (14%) were positive on milk samples and one, the index animal, was also positive on blood. Conclusions: Timely diagnosis in a human patient was pivotal to identify the outbreak since involved animals were asymptomatic. The close collaboration between veterinary and human Public Health services in six different geographical areas of two countries was crucial for the rapid termination of the outbreak.

Immunological Evolution of a Cohort of HIV-2 Infected Patients: Peculiarities of an Underestimated Infection.

Background: Human Immunodeficiency Virus type 2 (HIV-2) affects a minority of patients in Italy; nevertheless, the increasing migratory flow from higher prevalence areas led to the spread of this virus into our Country. We evaluate clinical, viro-immunological, and therapeutic characteristics of patients with HIV-2 infection and HIV-1/HIV-2 dual-infection and the early treatment impact on overall survival and incidence of AIDS events. Methods: We retrospectively analyzed all HIV-2, and HIV-1/HIV-2 positive patients followed in a large Italian clinic from January 1987 to December 2020. We recorded demographic, viro-immunological, clinical, and therapeutic data. We performed a descriptive analysis followed by a longitudinal analysis to explore the factors associated with the CD4+ lymphocyte trend; lastly, we studied the possible predictors of death and AIDS in our cohort in a multivariable model. Results: 32 subjects were enrolled, 17 (53%) HIV-2 infected and 15 (46.8%) HIV-1/HIV-2 dual-infected; 12 patients were lost to follow up, while 3 died. We found a lack of HIV-2 viremia in 12/32 subjects (37.5%). Most of the patients at baseline had a good viro-immunological profile with HIV-2 RNA <200 copies/ml and CD4+ lymphocyte >200 cell/mcl. We found a CD4+ lymphocyte improvement over time, both in the absolute number (ß 472.61, 95%CI 383.05-562.18, p<0.001) and in percentage (ß 25.28, 95%CI 21.91 - 28.66, p<0.001). Nevertheless, subjects taking cART had CD4+ lymphocyte percentage increase over time, and this trend appeared significantly better than those who did not receive therapy. Lastly, in the multivariable model CD4+, T-cell count increase was negatively associated with AIDS (HR 0.34 95%CI 0.13-0.91, p=0.032). Conclusion: We found a higher prevalence of HIV-1/2 dual infection than in previous observations. Subjects with HIV-2 infection showed a favorable immunological condition at diagnosis, and the benefits of cART in those who received treatment are undiscussed. Moreover, our data suggest a different disease course based on age at diagnosis, as in HIV-1 infections. We encourage starting cART at diagnosis in HIV-2 patients, regardless of CD4+ lymphocyte, because even in the new cART era, CD4+ lymphocyte decrease remains the strongest predictor of death and AIDS also in this population.

Durability of Integrase STrand Inhibitor (InSTI)-based regimen in geriatric people living with HIV in the GEPPO cohort.

OBJECTIVE: To investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation. DESIGN: This is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more. METHODS: The analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level (Kruskal-Wallis test, Chi-squared test, log-rank test and a Cox Proportional Hazard model). The proportion of participants discontinuing the three regimens was displayed using cumulative curves. RESULTS: Among 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p 0.05) or both, DTG and RAL (p<0.001). Among participants who discontinued their regimen we found 0 virological failure and 56.7% simplification/deprescription. CONCLUSIONS: The three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen.

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

BACKGROUND: The 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 METHODS: From 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. RESULTS: 950 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). CONCLUSIONS: The 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.

Low prevalence of symptomatic thyroid diseases and thyroid cancers in HIV-infected patients.

Thyroid diseases (TDs) have been widely associated with HIV infection. However, data about TDs prevalence and distribution are controversial, and few published studies are available. The aim of our study was to assess prevalence and risk factors of symptomatic thyroid disturbances, including thyroid cancers, in a large cohort of HIV-infected patients. A retrospective cohort study was performed at the Department of Infectious and Tropical Diseases of the University of Brescia, Italy, in the period 2005-2017. We identified all HIV-positive patients with a diagnosis of symptomatic TD in the electronic database of our Department (HIVeDB); we also operated a record-linkage between our data and the Health Protection Agency database (HPADB) of Brescia Province. Multivariate logistic regression analysis was used to determine risk factors associated with TDs onset; an incidence rate analysis was also performed. During the study period, 6343 HIV-infected patients have been followed at our Department; 123 received a diagnosis of symptomatic TD (1.94% of the entire cohort). In the TDs group, almost half of patients were females (n = 59, 48%), mean age was 47.15 years (SD: 11.56). At TD diagnosis, mean T CD4+ cell count was 491 cell/uL and most patients showed undetectable HIV-RNA (n = 117, 95.12%). Among them, 81 patients were found to have hypothyroidism (63 with Hashimoto's thyroiditis), 21 hyperthyroidism (17 suffered from Graves' disease), while 11 subjects were diagnosed with a primitive thyroid cancer. Papillary thyroid cancer was the most frequent histotype (n = 7, 63.63%), followed by medullary (n = 2, 18.18%) and follicular thyroid cancer (n = 1, 9.1%). Male gender was a protective factor for TDs development, especially for hypothyroidism (p < 0.001); age emerged as a variable associated with both hypothyroidism (p = 0.03) and thyroid cancer (p = 0.03), while CD4+ cell nadir <200 cell/mm3 was associated with symptomatic hyperthyroidism (p = 0.005). To conclude, symptomatic thyroid dysfunctions rate in well-treated HIV-infected patients is low. Age and gender are crucial elements in the onset of thyroid abnormalities, together with T CD4+ cell nadir. Interestingly, medullary thyroid cancer seems to be much more frequent in HIV-infected patients compared to the general population.