Association between markers of hepatitis B virus infection and risk of virological rebound in people with HIV receiving antiretroviral therapy.

OBJECTIVES: The aim of this analysis was to investigate the impact of hepatitis B virus (HBV) coinfection on the risk of HIV viral rebound (VR) after achieving suppression for the first time following initiation of antiretroviral therapy (ART) in the real-world setting. DESIGN: Patients living with HIV (PLWH) who were enrolled in the ICONA Foundation Study cohort and achieved viral suppression ≤50 copies/mL for the first time after starting ART were prospectively evaluated and divided in three exposure groups according to serology test results: (a) HIV-monoinfected; (b) HIV-positive/HBcAb-positive/HBsAg-negative; (c) HIV-positive/HBsAg-positive. The occurrence of VR, defined as two consecutive HIV-RNA values >50 copies/mL after achieving viral suppression for the first time (baseline), was investigated. METHODS: Standard survival analysis by means of Kaplan-Meier curves and Cox regression analysis with the serology exposure fitted as a time-fixed covariate measured at baseline was employed after controlling for key confounding factors. RESULTS: Of a total of 5657 patients included, 4090 (72%) were HIV-monoinfected, 1342 (23.7%)were HBcAb-positive, and 225 (3.9%) were HbsAg-positive coinfected. Overall, 654 (11.5%) PLWH experienced VR > 50 copies/mL during follow-up. After controlling for all sources of measured confounding, coinfected PLWH showed an increased risk of experiencing VR compared with those who were HIV-monoinfected. In particular, the strongest associations were seen for the HIV/HBsAg-positive participants [adjusted hazard ratio (aHR) = 1.56, 95% confidence interval (CI): 1.03-2.38, p = 0.037] but an excess of risk was also seen in those who were HIV-positive/HBcAb-positive/HBsAg-negative (aHR = 1.25, 95% CI: 1.00-1.55, p = 0.047). CONCLUSIONS: Coinfection with HBV seems to have an impact on the probability of maintaining HIV viral suppression achieved for the first time after ART initiation. Of note, even PLWH positive for HBcAb, a marker of inactive HBV infection, appeared to be at higher risk of VR compared with those who were HIV-monoinfected and their HIV-RNA should be carefully monitored.

Immunomodulation for the management of severe SARS-CoV2 infections. State of the art and review of the literature.

This Mini Review of the literature aimed to assess the role of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Based on the available scientific evidence, it is not clear to date what is the best therapeutic strategy for the treatment of COVID-19. Since SARS-CoV-2 infection stimulates a vigorous proinflammatory response and may cause the so-called "cytokine storm", immunomodulator drugs have been investigated as potential treatment for severe COVID-19 pneumonia. Among immunomodulators, tocilizumab, a recombinant humanized monoclonal antibody directed against IL-6 receptor, seems to be promising. An increasing number of clinical trials are exploring the role of tocilizumab in COVID-19, focusing on outcomes like mortality, risk of intensive care unit admission and the need for mechanical ventilation. At the moment, there is no conclusive evidence that tocilizumab would be proper outright in all patients with COVID-19 pneumonia, but some studies suggest that its use may be beneficial in selected categories of patients.

Ceftazidime/avibactam and ceftolozane/tazobactam for the treatment of extensively drug-resistant Pseudomonas aeruginosa post-neurosurgical infections: three cases and a review of the literature.

PURPOSE: Post-neurosurgical infection caused by extensively drug resistant Pseudomonas aeruginosa (XDR-PA) are becoming a matter of great concern due to limited therapeutic options. Although not approved for these indications, the new BetaLactam-BetaLactamase Inhibitor combinations (BLBLIs) could represent a valid salvage treatment. We describe one nosocomial meningitis and two cervical osteomyelitis due to an XDR-PA who were treated with ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) and review the literature. METHODS: The first and the third patients developed an osteomyelitis following cervical stabilization surgery due to an XDR-PA. Although the first patient started treatment with a high dose of C/T, resistance to C/T occurred, so therapy was switched to CZA plus aztreonam. The third patient switched to aztreonam plus CZA due to development of acute kidney injury during therapy with colistin. The second patient had an XDR-PA meningitis following the insertion of an external ventricular catheter and he was treated with C/T plus meropenem and amikacin. RESULTS: All three cases reported were successfully conservatively treated thanks to the use of the new BLBLIs with different combinations. Only few experiences demonstrated an equally favorable outcome: one patient treated with C/T plus fosfomycin for otogenic meningitis caused by an XDR-PA and another case of XDR-PA post-surgical meningitis with CZA in combination with colistin. Finally, the combination of CZA plus aztreonam has proven to be effective on XDR-PA only in limited mostly in vitro studies. CONCLUSION: These recently developed antibiotics, C/T and CZA are promising and complementary therapy options against post-neurosurgical hard-to-treat P. aeruginosa infections. Further prospective real-life studies are required to validate these findings in this special setting.

Incidence, risk factors and outcome of acute kidney injury (AKI) in patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and case-fatality rate of AKI in patients with COVID-19. METHODS: We reviewed the health medical records of 307 consecutive patients with COVID-19 hospitalized at the University Hospital of Modena, Italy. RESULTS: AKI was diagnosed in 69 out of 307 (22.4%) COVID-19 patients. Stages 1, 2, or 3 AKI accounted for 57.9%, 24.6% and 17.3%, respectively. AKI patients had a mean age of 74.7 ± 9.9 years. These patients showed higher serum levels of the main markers of inflammation and higher rate of severe pneumonia than non-AKI patients. Kidney injury was associated with a higher rate of urinary abnormalities including proteinuria (0.44 ± 0.85 vs 0.18 ± 0.29 mg/mg; P = < 0.0001) and microscopic hematuria (P = 0.032) compared to non-AKI patients. Hemodialysis was performed in 7.2% of the subjects and 33.3% of the survivors did not recover kidney function after AKI. Risk factors for kidney injury were age, male sex, CKD and higher non-renal SOFA score. Patients with AKI had a mortality rate of 56.5%. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (hazard ratio [HR] = 4.82; CI 95%, 1.36-17.08) compared to non-AKI patients. CONCLUSION: AKI was a common and harmful consequence of COVID-19. It manifested with urinary abnormalities (proteinuria, microscopic hematuria) and conferred an increased risk for death. Given the well-known short-term sequelae of AKI, prevention of kidney injury is imperative in this vulnerable cohort of patients.

Hypokalemia in Patients with COVID-19.

BACKGROUND: Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19. METHODS: A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020. RESULTS: Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients. CONCLUSIONS: Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

Acute human herpes virus 7 (HHV-7) encephalitis in an immunocompetent adult patient: a case report and review of literature.

We report a case of an acute HHV-7 encephalitis involving the nucleus of the VI cranial nerve in an immunocompetent host. The patient was an adult male admitted to our Clinic with headache, diplopia, fever, nausea, vertigo, asthenia and general malaise. PCR for viral and bacterial genomes was run on both serum and cerebral spinal fluid (CSF) after performing lumbar puncture, resulting positive only for HHV-7 DNA on CSF. MRI showed hyperintensity in FLAIR signal in the dorsal pons, in the area of the VI cranial nerve nucleus. Empirical therapy with Acyclovir and Dexamethasone was started at the time of admission and was continued after the microbiology results. After three days of therapy diplopia, fever and other previous clinical manifestations improved and the patient recovered normal sight. Our case report contributes to a better understanding of the presentation, diagnosis and treatment of HHV-7 encephalitis in immunocompetent patients due to reactivation in adult age.

A Machine Learning Approach to Predict Weight Change in ART-Experienced People Living With HIV.

INTRODUCTION: The objective of the study was to develop machine learning (ML) models that predict the percentage weight change in each interval of time in antiretroviral therapy-experienced people living with HIV. METHODS: This was an observational study that comprised consecutive people living with HIV attending Modena HIV Metabolic Clinic with at least 2 visits. Data were partitioned in an 80/20 training/test set to generate 10 progressively parsimonious predictive ML models. Weight gain was defined as any weight change >5%, at the next visit. SHapley Additive exPlanations values were used to quantify the positive or negative impact of any single variable included in each model on the predicted weight changes. RESULTS: A total of 3,321 patients generated 18,322 observations. At the last observation, the median age was 50 years and 69% patients were male. Model 1 (the only 1 including body composition assessed with dual-energy x-ray absorptiometry) had an accuracy greater than 90%. This model could predict weight at the next visit with an error of <5%. CONCLUSIONS: ML models with the inclusion of body composition and metabolic and endocrinological variables had an excellent performance. The parsimonious models available in standard clinical evaluation are insufficient to obtain reliable prediction, but are good enough to predict who will not experience weight gain.

Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial.

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR). Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders. Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm3; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12. Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04054089.

Bone Mineral Density and Trabecular Bone Score Changes throughout Menopause in Women with HIV.

OBJECTIVE: The objectives of this study were to describe the trajectories of bone mineral density (BMD) and trabecular bone score (TBS) changes throughout pre-menopause (reproductive phase and menopausal transition) and post-menopause (early and late menopause) in women with HIV (WWH) undergoing different antiretroviral therapies (ARTs) and explore the risk factors associated with those changes. METHODS: This was an observational longitudinal retrospective study in WWH with a minimum of two DEXA evaluations comprising BMD and TBS measurements, both in the pre-menopausal and post-menopausal periods. Menopause was determined according to the STRAW+10 criteria, comprising four periods: the reproductive period, menopausal transition, and early- and late-menopausal periods. Mixed-effects models were fitted to estimate the trajectories of the two outcomes (BMD and TBS) over time. Annualized lumbar BMD and TBS absolute and percentage changes were calculated in each STRAW+10 time window. A backward elimination procedure was applied to obtain the final model, including the predictors that affected the trajectories of BMD or TBS over time. RESULTS: A total of 202 WWH, all Caucasian, were included. In detail, 1954 BMD and 195 TBS data were analyzed. The median number of DEXA evaluations per woman was 10 (IQR: 7, 12). The median observation periods per patient were 12.0 years (IQR = 8.9-14.4) for BMD and 6.0 years (IQR: 4.3, 7.9) for TBS. The prevalence of osteopenia (63% vs. 76%; p < 0.001) and osteoporosis (16% vs. 36%; p < 0.001) increased significantly between the pre-menopausal and post-menopausal periods. Both BMD (1.03 (±0.14) vs. 0.92 (±0.12) g/cm2; p < 0.001) and TBS (1.41 (IQR: 1.35, 1.45) vs. 1.32 (IQR: 1.28, 1.39); p < 0.001) decreased significantly between the two periods. The trend in BMD decreased across the four STRAW+10 periods, with a slight attenuation only in the late-menopausal period when compared with the other intervals. The TBS slope did not significantly change throughout menopause. The delta mean values of TBS in WWH were lower between the menopausal transition and reproductive period compared with the difference between menopause and menopausal transition. CONCLUSIONS: Both BMD and TBS significantly decreased over time. The slope of the change in BMD and TBS significantly decreased in the menopausal transition, suggesting that this period should be considered by clinicians as a key time during which to assess bone health and modifiable risk factors in WWH.

HIV and syphilis: incidence rate of coinfection and syphilis reinfection in a cohort of newly diagnosed HIV patients.

BACKGROUND: Syphilis represents a major public health concern disproportionately affecting HIV positive patients and, in many cases, both infections are newly diagnosed at the same time. To date, limited studies are available on syphilis incidence in patients with a new HIV diagnosis. METHODS: Patients newly diagnosed with HIV in 2010-2018 were included in the study and screening tests for syphilis were performed at baseline and at least once a year. Primary aims were to analyze the incidence rate of HIV-syphilis coinfection and syphilis reinfection. Secondary objective was to identify characteristics independently associated with coinfection and reinfection. RESULTS: Of 500 newly diagnosed HIV patients, 20% presented a concomitant positive syphilis serology. Among them, 54 patients had a serology indicative for an active syphilis requiring therapy, while 46 had a history of prior treatments. The independent factors for syphilis acquisition were: MSM contact (OR=2.64; 95% CI: 1.48-4.72; P<0.001), male gender (OR=2.43; 95% CI: 1.08-5.48; P=0.032), and age (OR=1.03; 95% CI: 1.01-1.05; P=0.005 per year increasing). Presence of syphilis at the time of HIV diagnosis remained fairly stable during the study period (P for trend, P=0.689). We observed 52 syphilis reinfections related to 37 people. Patients with at least one reinfection were all males and 86.5% MSM. CONCLUSIONS: Males and MSM with HIV presented high rates of syphilis coinfection and reinfection suggesting persistent high-risk sexual behaviors and the need for appropriate intervention strategies in order to early detect and treat syphilis avoiding life-threatening complications and the spread of the infection in the community.

Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome.

BACKGROUND: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. METHODS: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. RESULTS: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. CONCLUSIONS: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

First and second waves among hospitalised patients with COVID-19 with severe pneumonia: a comparison of 28-day mortality over the 1-year pandemic in a tertiary university hospital in Italy.

OBJECTIVE: The first COVID-19-19 epidemic wave was over the period of February-May 2020. Since 1 October 2020, Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients. DESIGN: Observational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of HRs with 95% CIs. A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed. SETTING: University Hospital of Modena, Italy. Patients admitted to the hospital for severe COVID-19 pneumonia during the first (22 February-31 May 2020) and second (1 October-31 December 2020) waves were included. RESULTS: During the two study periods, a total of 1472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1023 during the second. Median age was 70 years (IQR 56-80), 37% women, 49% with PaO2/FiO2 <250 mm Hg, 82% with ≥1 comorbidity, median duration of symptoms was 6 days. 28-day mortality rate was 20.0% (95% CI 16.3 to 23.7) during the first wave vs 14.2% (95% CI 12.0 to 16.3) in the second (log-rank test p value=0.03). After including key predictors of death in the multivariable Cox regression model, the data still strongly suggested a lower 28-day mortality rate in the second wave (aHR=0.64, 95% CI 0.45 to 0.90, p value=0.01). CONCLUSIONS: In our hospitalised patients with COVID-19 with severe pneumonia, the 28-day mortality appeared to be reduced by 36% during the second as compared with the first wave. Further studies are needed to identify factors that may have contributed to this improved survival.

Acid base disorders in patients with COVID-19.

PURPOSE: Acid-base derangement has been poorly described in patients with coronavirus disease 2019 (COVID-19). Considering the high prevalence of pneumonia and kidneys injury in COVID-19, frequent acid-base alterations are expected in patients admitted with SARS-Cov-2 infection. The study aimed to assess the prevalence of acid-base disorders in symptomatic patients with a diagnosis of COVID-19. METHODS: The retrospective study enrolled COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Baseline arterial blood gas (ABG) analysis was collected in 211 patients. In subjects with multiple ABG analysis, we selected only the first measurement. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.43 was categorized as alkalemia. RESULTS: ABG analyses revealed a low arterial partial pressure of oxygen (PO2, 70.2 ± 25.1 mmHg), oxygen saturation (SO2, 92%) and a mild reduction of PO2/FiO2 ratio (231 ± 129). Acid-base alterations were found in 79.7% of the patient. Metabolic alkalosis (33.6%) was the main alteration followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%), respiratory acidosis (3.3%), metabolic acidosis (2.8%) and other compensated acid-base disturbances (3.6%). All six patients with metabolic acidosis died at the end of the follow-up. CONCLUSION: Variations of pH occurred in the majority (79.7%) of patients admitted with COVID-19. The patients experienced all the type of acid-base disorders, notably metabolic and respiratory alkalosis were the most common alterations in this group of patients.

Adherence to Lipid-Lowering Medication in People Living with HIV: An Outpatient Clinic Drug Direct Distribution Experience.

OBJECTIVE: Adherence to lipid-lowering drugs could be challenging in our patients as it is in the general population, which is described as low as 25%. Our aim was to evaluate adherence to statins and to investigate clinical event impact on it. METHODS: This retrospective study on HIV+ patients attending to Clinic of Modena (Italy) was conducted in order to evaluate characteristics, clinical events, and adherence on lipid-lowering drugs. All drugs for comorbidities are distributed by the hospital pharmacy and recorded in an electronical database. Adherence was also evaluated in patients who were supplied with antilipemics in external pharmacies through phone calls. Patients were considered adherent if the percentage of correct time of drug refill was >80%. FINDINGS: Totally 1123 patients were evaluated. Lipid-lowering drugs (statins, fenofibrate, and omega-3 oil) were prescribed in 242 patients (21.5%). Prescription occurred mainly in those who were older, males, and Italians. Two hundred of them (82.6%) used statins alone, 23 (9.5%) only fenofibrate or omega-3 oil, and 19 (7.8%) a combination of both drugs. The median adherence was 90% while patients with adherence >80% resulted 153 (63.2%). Forty-six (19%) had a clinical history of cardiovascular events; 59% of them, placed in secondary prophylaxis, and 76%, already in treatment, continued to adhere. No differences in terms of adherence according to the type of drug distribution (hospital pharmacy or outside pharmacies) were found. CONCLUSION: Linking the supply of these drugs to that of antiretrovirals led to a good level of adherence higher than that described in the general population. The majority of the patients who experienced a cardiovascular event remain adherent to the prescribed therapy.

HBcAb Positivity Increases the Risk of Severe Hepatic Fibrosis Development in HIV/HCV-Positive Subjects From the ICONA Italian Cohort of HIV-Infected Patients.

BACKGROUND: The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). METHODS: All patients with FIB-4 <3.25 at baseline were evaluated prospectively: 6966 people with HIV (PWH) were screened and classified based on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology. RESULTS: Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8-13.64). CONCLUSIONS: HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients.

Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus.

OBJECTIVES: Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. DESIGN: We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. METHODS: We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. RESULTS: During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/µl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline. CONCLUSION: Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.

The Impact of COVID-19 on UNAIDS 90-90-90 Targets: Calls for New HIV Care Models.

We compared 90-90-90 targets in 2020, during the coronavirus disease 2019 (COVID-19) pandemic, with the targets across the period 2017-2019 in people with HIV. We observed a significant loss in the 90-90-90 objectives in 2020 when compared with 2017-2019 that might be attributable to the COVID-19 crisis.

Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator.

OBJECTIVES: Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. METHODS: This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death according to sex. Interaction was formally tested to compare the risk difference by sex in sub-populations. Mediation analysis with a binary endpoint IMV or death (yes/no) by day 28 of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. RESULTS: Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs. 191 mmHg; p 0.023). By 28 days from admission, 49.2% (95% CI 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank p < 0.0001) and this amounted to a difference in terms of HR of 0.40 (0.26-0.63, p 0.0001). The area under the curve in C-reactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex. DISCUSSION: Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. Specifically, CRP showed a predominant role to mediate the difference in risk by sex.

Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV.

OBJECTIVE: Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men. DESIGN: Prospective, cross-sectional, observational study. METHODS: HIV-infected men aged <50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively. RESULTS: A total of 316 HIV-infected men aged 45.3 ± 5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/testosterone (TS) ratio. Patients with MM had lower cFT (P < 0.0001) and TT (P = 0.036), and higher E1 (P < 0.0001) and E2/TS ratio (P = 0.002). Frailty was inversely related to cFT (R2 = 0.057, P < 0.0001) and TT (R2 = 0.013, P = 0.043), and directly related to E1 (R2 = 0.171, P < 0.0001), E2 (R2 = 0.041, P = 0.004) and E2/TS ratio (R2 = 0.104, P < 0.0001). CONCLUSIONS: Lower TT and cFT, higher E1, E2/TS ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.