Hospital distribution, seasonality, time trends and antifungal susceptibility profiles of all Aspergillus species isolated from clinical samples from 2015 to 2022 in a tertiary care hospital.

BACKGROUND: Aspergillus species cause a variety of serious clinical conditions with increasing trend in antifungal resistance. The present study aimed at evaluating hospital epidemiology and antifungal susceptibility of all isolates recorded in our clinical database since its implementation. METHODS: Data on date of isolation, biological samples, patients' age and sex, clinical settings, and antifungal susceptibility tests for all Aspergillus spp. isolated from 2015 to 2022 were extracted from the clinical database. Score test for trend of odds, non-parametric Mann Kendall trend test and logistic regression analysis were used to analyze prevalence, incidence, and seasonality of Aspergillus spp. isolates. RESULTS: A total of 1126 Aspergillus spp. isolates were evaluated. A. fumigatus was the most prevalent (44.1%) followed by A. niger (22.3%), A. flavus (17.7%) and A. terreus (10.6%). A. niger prevalence increased over time in intensive care units (p-trend = 0.0051). Overall, 16 (1.5%) were not susceptible to one azole compound, and 108 (10.9%) to amphotericin B, with A. niger showing the highest percentage (21.9%). The risk of detecting A. fumigatus was higher in June, (OR = 2.14, 95% CI [1.16; 3.98] p = 0.016) and reduced during September (OR = 0.48, 95% CI [0.27; 0.87] p = 0.015) and October as compared to January (OR = 0.39, 95% CI [0.21; 0.70] p = 0.002. A. niger showed a reduced risk of isolation from all clinical samples in the month of June as compared to January (OR = 0.34, 95% CI [0.14; 0.79] p = 0.012). Seasonal trend for A. flavus showed a higher risk of detection in September (OR = 2.7, 95% CI [1.18; 6.18] p = 0.019), October (OR = 2.32, 95% CI [1.01; 5.35] p = 0.048) and November (OR = 2.42, 95% CI [1.01; 5.79] p = 0.047) as compared to January. CONCLUSIONS: This is the first study to analyze, at once, data regarding prevalence, time trends, seasonality, species distribution and antifungal susceptibility profiles of all Aspergillus spp. isolates over a 8-year period in a tertiary care center. Surprisingly no increase in azole resistance was observed over time.

Comparison of different microbiological procedures for the diagnosis of Pneumocystis jirovecii pneumonia on bronchoalveolar-lavage fluid.

BACKGROUND: The current diagnostic gold standard for Pneumocystis jirovecii is represented by microscopic visualization of the fungus from clinical respiratory samples, as bronchoalveolar-lavage fluid, defining "proven" P. jirovecii pneumonia, whereas qPCR allows defining "probable" diagnosis, as it is unable to discriminate infection from colonization. However, molecular methods, such as end-point PCR and qPCR, are faster, easier to perform and interpret, thus allowing the laboratory to give back the clinician useful microbiological data in a shorter time. The present study aims at comparing microscopy with molecular assays and beta-D-glucan diagnostic performance on bronchoalveolar-lavage fluids from patients with suspected Pneumocystis jirovecii pneumonia. Bronchoalveolar-lavage fluid from eighteen high-risk and four negative control subjects underwent Grocott-Gomori's methenamine silver-staining, end-point PCR, RT-PCR, and beta-D-glucan assay. RESULTS: All the microscopically positive bronchoalveolar-lavage samples (50%) also resulted positive by end-point and real time PCR and all, but two, resulted positive also by beta-D-glucan quantification. End-point PCR and RT-PCR detected 10 (55%) and 11 (61%) out of the 18 samples, respectively, thus showing an enhanced sensitivity in comparison to microscopy. All RT-PCR with a Ct < 27 were confirmed microscopically, whereas samples with a Ct ≥ 27 were not. CONCLUSIONS: Our work highlights the need of reshaping and redefining the role of molecular diagnostics in a peculiar clinical setting, like P. jirovecii infection, which is a rare but also severe and rapidly progressive clinical condition affecting immunocompromised hosts that would largely benefit from a faster diagnosis. Strictly selected patients, according to the inclusion criteria, resulting negative by molecular methods could be ruled out for P. jirovecii pneumonia.

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.

The Lisbon patient: exceptional longevity with HIV suggests healthy aging as an ultimate goal for HIV care.

In the context of global aging, HIV infection has become a new chronic disease and requires innovative models of care. Treating isolated comorbidities represents a useless and potentially harmful practice at advanced age. Therefore, a patient-centered approach, in which the interventions are focused on the biology and function of the individual, with understanding of the importance of securing social and home environment that provides psychosocial support, better suits unmet health needs. We present a paradigmatic case of healthy aging: the first reported HIV-infected patient who achieved 100th of life - the Lisbon patient. The construct of healthy aging, recently introduced by the World Health Organization, is the best example of this comprehensive model and could represent the fourth target of UNAIDS agenda of the end of AIDS.

Compression of frailty in adults living with HIV.

BACKGROUND: Contemporary HIV care may reduce frailty in older adults living with HIV (OALWH). Objective of the study was to estimate prevalence of frailty at the age of 50 and 75 years, and build a model to quantify the burden of frailty in the year 2030. METHODS: This study included OALWH attending Modena HIV Metabolic Clinic between 2009 and 2015. Patients are referred from more than 120 HIV clinics well distributed across Italy, therefore being country representative. Our model forecasts the new entries on yearly basis up to 2030. Changes in frailty over a one-year period using a 37-variable frailty index (FI) and death rates were modelled using a validated mathematical algorithm with parameters adjusted to best represent the changes observed at the clinic. In this study, we assessed the number of frailest individuals (defined with a FI > 0.4) at the age of 50 and at the age 75 by calendar year. RESULTS: In the period 2015-2030 we model that frailest OALWH at age 50 will decrease from 26 to 7%, and at the age of 75 years will increase from 43 to 52%. This implies a shift of the frailty prevalence at an older age. CONCLUSION: We have presented projections of how the burden of frailty in older adults, living with HIV will change. We project fewer people aged 50+ with severe frailty, most of whom will be older than now. These results suggest a compression of age-related frailty.

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.

In Vitro Susceptibility Tests in the Context of Antifungal Resistance: Beyond Minimum Inhibitory Concentration in Candida spp.

Antimicrobial resistance is a matter of rising concern, especially in fungal diseases. Multiple reports all over the world are highlighting a worrisome increase in azole- and echinocandin-resistance among fungal pathogens, especially in Candida species, as reported in the recently published fungal pathogens priority list made by WHO. Despite continuous efforts and advances in infection control, development of new antifungal molecules, and research on molecular mechanisms of antifungal resistance made by the scientific community, trends in invasive fungal diseases and associated antifungal resistance are on the rise, hindering therapeutic options and clinical cures. In this context, in vitro susceptibility testing aimed at evaluating minimum inhibitory concentrations, is still a milestone in the management of fungal diseases. However, such testing is not the only type at a microbiologist's disposal. There are other adjunctive in vitro tests aimed at evaluating fungicidal activity of antifungal molecules and also exploring tolerance to antifungals. This plethora of in vitro tests are still left behind and performed only for research purposes, but their role in the context of invasive fungal diseases associated with antifungal resistance might add resourceful information to the clinical management of patients. The aim of this review was therefore to revise and explore all other in vitro tests that could be potentially implemented in current clinical practice in resistant and difficult-to-treat cases.

Candida parapsilosis sensu stricto Antifungal Resistance Mechanisms and Associated Epidemiology.

Fungal diseases cause millions of deaths per year worldwide. Antifungal resistance has become a matter of great concern in public health. In recent years rates of non-albicans species have risen dramatically. Candida parapsilosis is now reported to be the second most frequent species causing candidemia in several countries in Europe, Latin America, South Africa and Asia. Rates of acquired azole resistance are reaching a worrisome threshold from multiple reports as in vitro susceptibility testing is now starting also to explore tolerance and heteroresistance to antifungal compounds. With this review, the authors seek to evaluate known antifungal resistance mechanisms and their worldwide distribution in Candida species infections with a specific focus on C. parapsilosis.

Paradigm Shift: Candida parapsilosis sensu stricto as the Most Prevalent Candida Species Isolated from Bloodstream Infections with Increasing Azole-Non-Susceptibility Rates: Trends from 2015-2022 Survey.

Candidemia is the fourth most common healthcare-related bloodstream infection. In recent years, incidence rates of Candida parapsilosis have been on the rise, with differences in prevalence and antifungal susceptibility between countries. The aim of the present study was to evaluate temporal changes in prevalence and antifungal susceptibility of C. parapsilosis among other species causing candidemia. All candidemia episodes from January 2015 to August 2022 were evaluated in order to depict time trends in prevalence of C. parapsilosis sensu stricto among all Candida species recovered from blood cultures as well as fluconazole- and voriconazole-non-susceptibility rates. Secondary analyses evaluated time trends in prevalence and antifungal non-susceptibility according to clinical settings. The overall prevalence of C. parapsilosis was observed to increase compared to the prevalence of other Candida species over time (p-trend = 0.0124). From 2019, the number of C. parapsilosis sensu stricto isolates surpassed C. albicans, without an increase in incidence rates. Overall rates of fluconazole- and voriconazole-non-susceptible C. parapsilosis sensu stricto were both 3/44 (6.8%) in 2015 and were 32/51 (62.7%) and 27/51 (52.9%), respectively, in 2022 (85% cross-non-susceptibility). The risk of detecting fluconazole- or voriconazole-non-susceptibility was found to be higher in C. parapsilosis compared to other Candida species (odds ratio (OR) = 1.60, 95% CI [1.170, 2.188], p-value < 0.0001 and OR = 12.867, 95% CI [6.934, 23.878], p-value < 0.0001, respectively). This is the first study to report C. parapsilosis sensu stricto as the most prevalent among Candida spp. isolated from blood cultures, with worrisome fluconazole- and voriconazole-non-susceptibility rates, unparalleled among European and North American geographical regions.

Rapid and Accurate Identification of Nontuberculous Mycobacteria Directly from Positive Primary MGIT Cultures by MALDI-TOF MS.

Over the last years, nontuberculous mycobacteria (NTM) have emerged as important human pathogens. Accurate and rapid mycobacterial species identification is needed to successfully diagnose, treat, and manage infections caused by NTM. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS, was demonstrated to effectively identify mycobacteria isolates subcultured from solid or liquid media rather than new positive cultures. The present study aims to develop a new extraction protocol to yield rapid and accurate identification of NTM from primary MGIT cultures by MALDI-TOF MS. A total of 60 positive MGIT broths were examined by the Bruker Biotyper system with Mycobacteria Library v. 2.0 (Bruker Daltonics GmbH & Co. KG., Bremen, Germany). The results were compared with those obtained by the molecular method, line probe assay GenoType Mycobacterium CM/AS/NTM-DR. All samples were concordantly identified by MALDI-TOF MS and the molecular test for all the tested mycobacteria. Fifty-seven (95%) MGIT positive cultures for NTM from clinical samples had a MALDI-TOF MS analysis score S ≥ 1.8. Although a small number of strains and a limited diversity of mycobacterial species were analysed, our results suggest that MALDI-TOF MS could represent a promising routine diagnostic tool for identifying mycobacterial species directly from primary liquid culture.

Synergistic Activity of the Human Lactoferricin-Derived Peptide hLF1-11 in Combination with Caspofungin against Candida Species.

Candida species are the main fungal opportunistic pathogens causing systemic infections that are often associated with drug resistance and biofilm production on medical devices. The pressing need for new antifungal agents led to an increased interest in the use of combination therapies. The present study was aimed at investigating potential synergistic activity of the human lactoferrin-derived hLF1-11 peptide with caspofungin against caspofungin-resistant or -susceptible C. albicans, C. parapsilosis, and C. glabrata strains. Synergism was evaluated by the checkerboard assay, measuring cellular metabolic activity against Candida planktonic and sessile cells. A fractional inhibitory concentration (FIC) index of ≤0.5 was interpreted as synergy. Synergism was evaluated by killing assays on planktonic cells. A cell viability assay was performed with biofilm formation inhibition and preformed biofilm. Synergy for killing and viability assays was defined as a ≥2-log-CFU/mL reduction in comparison with the most active constituent. hLF1-11 and caspofungin exerted (i) synergistic effects against planktonic cells of all the tested strains, yielding drastic caspofungin MIC reduction, (ii) synergistic effects on the inhibition of biofilm formation against biofilm producer strains, yielding caspofungin BIC reduction, and (iii) synergistic effects on preformed biofilm assessed by measuring metabolic activity (FIC range, 0.28 to 0.37) against biofilm-producing strains and by cell viability assay in C. albicans SC5314. The synergistic effect observed between caspofungin and hLF1-11 against Candida spp. is of potential clinical relevance, representing a promising novel approach to target caspofungin-resistant Candida species infections. Further studies elucidating the mechanisms of action of such a synergistic effect are needed. IMPORTANCE The present study describes a synergistic effect between a conventional antifungal drug, caspofungin, and a synthetic peptide derived from human lactoferrin, hLF1-11, against Candida species. These yeasts are able to cause severe systemic fungal infections in immunocompromised hosts. In addition, they can form biofilms in medical implanted devices. Recently, caspofungin-resistant Candida strains have emerged, thus highlighting the need to develop different therapeutic strategies. In in vitro studies, this drug combination is able to restore sensitivity to caspofungin in caspofungin-resistant strains of Candida species, both in free-living cells and in cells organized in biofilms. This synergism could represent a promising novel approach to target infections caused by caspofungin-resistant Candida species.

Contribution of integrase inhibitor use, body mass index, physical activity and caloric intake to weight gain in people living with HIV.

Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up.Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present.Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27-59, p < 0.001), followed by high CD4/CD8 ratio (41%, 21-57, p < 0.001) and lower physical activity (32%, 95% CI 5-52, p = 0.03). PAF was not significant for daily caloric intake (-1%, -9-13, p = 0.45), smoking cessation during follow-up (5%, 0-12, p = 0.10), INSTI switch (11%, -19-36; p = 0.34).Conclusions: WG in PLWH on ART is mostly influenced by pre-existing weight and low physical activity, rather than switch to INSTI.

Liver steatosis and nonalcoholic fatty liver disease with fibrosis are predictors of frailty in people living with HIV.

OBJECTIVE: The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association [nonalcoholic fatty liver disease (NAFLD) with fibrosis] to frailty as a measure of biological age in people living with HIV (PLWH). DESIGN: This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019. METHODS: Patients with hazardous alcohol intake and viral hepatitis coinfection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP ≥248 dB/m), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM at least 7.1 kPa. Frailty was assessed using a 36-Item frailty index. Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates. RESULTS: We analysed 707 PLWH (mean age 53.5 years, 76.2% men, median CD4 cell count 700 cells/µl, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9 and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment [odds ratio (OR) = 5.1, 1.6-15], vitamin D insufficiency (OR = 1.94, 1.2-3.2), obesity (OR = 8.1, 4.4-14.6), diabetes (OR = 3.2, 1.9-5.6), metabolic syndrome (OR = 2.41, 1.47-3.95) and osteoporosis (OR = 0.37, 0.16-0.76) were significantly associated with NAFLD with fibrosis. Predictors of frailty index included steatosis (OR = 2.1, 1.3-3.5), fibrosis (OR = 2, 1-3.7), NAFLD with fibrosis (OR = 9.2, 5.2-16.8), diabetes (OR = 1.7, 1-2.7) and multimorbidity (OR = 2.5, 1.5-4). CONCLUSION: Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.

The Interplay Between Age and Frailty in People Living With HIV: Results From an 11-Year Follow-up Observational Study.

Between 2006 and 2017, frailty prevalence decreased in HIV-positive individuals aged 50 years but presented a 3-fold increase among those 75 years of age. This dynamic relationship, defined as the frailty compression ratio, represents the net result of gero-inducing and gero-protective competing forces, described in the cohort.

Migration and health: A retrospective study about the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infections amongst newly arrived migrants screened at the Infectious Diseases Unit of Modena, Italy.

INTRODUCTION: Aim of the study is to evaluate the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infection among immigrants assigned to the immigrant centre of the province of Modena. METHODS: At the time of arrival all immigrant were tested for: HBsAg, HBsAb, HBcAb, Ag p24/HIVAb, HCVAb, RPR, TPPA, Mantoux test (>10mm diameter of induration was considered to be positive), Chest X-rays. In case of positive samples, second level tests were performed (HbeAg, HBeAb, HDVAb, and baseline management and treatment of the infection detected). RESULTS: A total of 304 immigrant people were enrolled in the study. HBsAg positivity was 12.2%, HCVAb 3.3%, HIVAb 1.6%, TPPA+RPR positivity in the 0.7%; 10.2% had a positive Mantoux test; 5.6% had Chest X-rays positive for signs of infection and 6 patients had an active tuberculosis. 83.8% HBsAg were HBeAb positive/HBeAg negative. HDVAb resulted positive in 1 patient (2.7%). Previous HBV infection was detected in 28.6% of cases, isolated HBcAb in 2.3%; 5.6% of patients resulted to be positive to HbsAb alone (probable vaccinated). CONCLUSION: Our study confirms the high prevalence of HBsAg positivity and latent tuberculosis among immigrants, underlying the importance of screening for infections in this special population.

Pneumocystosis as a Complication of H1N1 Influenza A Infection in an HIV-Positive Patient on Effective cART.

H1N1 influenza A virus can affect the immune system, causing lymphopenia. This might be of great concern for HIV individuals undergoing effective antireroviral therapy (cART). We report the first confirmed case of H1N1-induced AIDS and Pneumocystis jiroveci pneumonia in an HIV-positive woman on effective cART since 2006.

Thymus Imaging Detection and Size Is Inversely Associated With Metabolic Syndrome and Frailty in People With HIV.

BACKGROUND: People with HIV (PWH) may experience accentuating aging in relation to immuno-activation. Little is known regarding thymus (THY) involution in this process. We sought to investigate the relationship between THY imaging detection/size and clinically relevant aging outcomes such as metabolic syndrome (MetS), multimorbidity (MM), and frailty in PWH. METHODS: This was a cross-sectional observational study including 665 HIV patients (81% males; median age, 53 years) attending Modena HIV Metabolic Clinic from 2014 to 2017. They underwent thoracic computed tomography scan as part of the medical assessment for cardiovascular disease, in which THY detection and size were reported using a semiquantitative score. Outcome measures were MetS, MM, and frailty. RESULTS: THY was detected in 27.0% of subjects; 71.1% showed THY size of grade 1-2, and 28.9% exhibited grade ≥3. Covariates that inversely correlated with THY detection were age, male gender, body mass index (BMI), and HIV duration. Covariates that inversely correlated with MetS were age, HIV duration, BMI, and THY grade 1-2. Covariates that inversely correlated with MM were age, HIV duration, and CD4 nadir. Covariates that inversely correlated with frailty were age, HIV duration, CD4 nadir, BMI, and THY detection. CONCLUSIONS: THY is inversely associated with MetS and frailty in PWH.

Pre-exposure Prophylaxis for HIV Infection in the Older Patient: What can be Recommended?

Over the past 15 years, a significant increase in new HIV/AIDS diagnoses has been observed in the elderly population. This new epidemiological shift has been attributed to a longer sex life, lifestyle and changes in sexual behavior, poor sexual health education, and misconceptions about the absence of sexually transmitted disease in later life. Although many biomedical and behavioral interventions have proven useful to prevent sexually transmitted infections and HIV, pre-exposure prophylaxis (PrEP) has been shown to be the most successful biomedical intervention to prevent HIV in high-risk individuals. This approach is based on delivering a fixed dose of tenofovir disoproxil fumarate (300 mg), alone or combined with emtricitabine (300/200 mg) daily or on demand, before and after sexual intercourse. Despite the consistent number of clinical trials proving the effectiveness and safety of this strategy, no studies have focused specifically on elderly people. These individuals, who may benefit substantially from (PrEP), are at a higher risk of experiencing side effects secondary to tenofovir exposure. This review critically discusses the efficacy and safety of PrEP in people aged over 50 years and translates the knowledge of tenofovir management in patients with HIV into monitoring and stopping rules to be used in this special population. We provide practical recommendations to properly identify PrEP candidates among older adults. Furthermore, we define correct case management before and during PrEP  delivery, and we suggest stopping rules and alternative sexually transmitted infection prevention strategies.

Construct validation of a Frailty Index, an HIV Index and a Protective Index from a clinical HIV database.

BACKGROUND: Standard care for HIV clinical practice has started focusing on age-related problems, but despite this recent change physicians involved in HIV care do not often screen HIV patients for frailty. Our aim was to construct three indexes from an HIV clinical database (i.e. Frailty Index, (FI), HIV Index, (HIVI), and Protective Index (PI)) and to assess levels of frailty, HIV severity and demographic and protective lifestyle factors among HIV patients. METHODS AND FINDINGS: We included data from 1612 patients who attended an Italian HIV clinic between September 2016 and December2017 (mean±SD age: 53.1±8 years, 73.9% men).We used 92 routine variables collected by physicians and other health care professionals to construct three indexes: a 72-item FI (biometric, psychiatric, blood test, daily life activities, geriatric syndromes and nutrition data), a 10-item HIVI (immunological, viral and therapeutics) and a 10-item PI (income, education, social engagement, and lifestyle habits data)(the lower the FI and HIVI scores, and the higher the PI scores, the lower the risk for participants).The FI, HIVI and PI scores were 0.19±0.08, 0.48±0.17 and 0.62±0.13, respectively. Men had higher FI (0.19±0.08 vs 0.18±0.08; p = 0.010) and lower HIVI (0.47±0.18 vs 0.50±0.15; p = 0.038) scores than women. FI and HIVI scores both increased 1.9% per year of age (p < 0.001), whereas the PI decreased 0.2% per year (p<0.050). In addition, the FI score increased 1.6% and the PI score decreased 0.5% per year of HIV infection (p < 0.001). CONCLUSION: It is feasible to assess levels of frailty, HIV severity and protective lifestyle factors in HIV patients using data from a clinical database. Frailty levels are high among HIV patients and even higher among older patients and those with a long duration of HIV. Future studies need to examine the ability of the three indices to predict adverse health outcomes such as hospitalization and mortality.