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Nicola Squillace,1 Elena Ricci,2 Elisa Colella,1 Paolo Bonfanti1 1Infectious Diseases Unit ASST-Monza, San Gerardo Hospital-University of Milano-Bicocca, Monza, Italy; 2Fondazione ASIA Onlus, Milan, ItalyCorrespondence: Nicola SquillaceInfectious Diseases Unit ASST-Monza, San Gerardo Hospital-University of Milano-Bicocca, via G.B. Pergolesi 33, Monza, 20900, ItalyEmail n.squillace@asst-monza.it; nicolasquillace74@gmail.comAbstract: The dramatic increase of the global pandemic of SARS-CoV-2 infection represents a critical issue that needs to be investigated to evaluate the associated risk factors for acquisition and worse outcome. The interplay between immune activation and immune depression during SARS-CoV-2 infection is an intriguing topic that still needs to be clarified. The role of HIV in SARS-CoV-2 infection is not well defined. Chronic inflammation linked to HIV infection could be a driver for a worse prognosis in people living with HIV (PLWH). We explored the role of HIV as a risk factor for SARS-CoV-2 infection and severity and which factors contributed to a worse prognosis when HIV infection was present. PubMed/MEDLINE was searched for “COVID-19” or “SARS-CoV2” and “HIV” or “AIDS” and (“hospitalization” or “intensive care” or “mechanical ventilation” or “death” OR “mortality”), both in MeSH and as free text in all fields. Our review focused on 21 studies that enrolled at least 40 PLWH. In most studies, HIV infection did not represent a risk factor for SARS-CoV-2 infection. On the contrary, the risk of severe COVID-19 and hospitalization was higher in PLWH. Low CD4 cell count consistently emerged as a risk factor for severe COVID-19. Comorbidities, either in people with or without HIV diagnosis, played a key role, especially because of their early development in PLWH.Keywords: HIV, SARS, CoV-2, COVID-19

Nicola Squillace,1 Giorgio Bozzi,2 Elisa Colella,1 Andrea Gori,2 Alessandra Bandera1 1Infectious Diseases Unit, Azienda Socio Sanitaria Territoriale di Monza, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy; 2Infectious Disease Unit, Department of Internal Medicine, Fondazione IRCCS Ca’Granda, Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milano, Milan, Italy Abstract: A fixed-dose combination consisting of darunavir (Drv), cobicistat (Cobi), emtricitabine (2',3'-dideoxy-5-fluoro-3'-thiacytidine [FTC]), and tenofovir alafenamide (Taf) has been recently approved by the European Medicines Agency for the treatment of HIV infection, and is the first ever protease-inhibitor-based single-tablet regimen. This article provides a detailed description of its pharmacokinetic, efficacy, and safety profile. The pharmacokinetics of single compounds were analyzed, with a special focus on contrasts between Drv/Cobi and Drv/ritonavir (Rtv). When comparing Cobi and Rtv, multiple interactions must be taken into account: in comparison to Rtv, Cobi is a more selective CYP3A4 inhibitor and has no clinical effect on other isoenzymes inhibited by Rtv (eg, 2C8 and 2C9). Moreover, unlike Cobi, Rtv shows in vivo induction activity on some CYP isoenzymes (eg, 1A2, 2C19, 2C8, 2C9, and 2B6), glucuronyltransferases (eg, UGT1A4), and Pgp. Drv-Cobi-FTC-Taf has recently been demonstrated to be of equal efficacy to Drv-Rtv and other protease inhibitors in both experienced (EMERALD study) and naïve (AMBER study) patients. Moreover, kidney and bone safety profiles have been shown to be good, as has central nervous system tolerance. Total cholesterol:low-density-lipoprotein cholesterol and total cholesterol:high-density-lipoprotein cholesterol ratios are generally high in Drv-Cobi-FTC-Taf vs Rtv-Drv-FTC + tenofovir disoproxil fumarate. An unlikely role of Drv in influencing cardiovascular risk in HIV infection has also been reported. Kidney safety profile is influenced by Cobi, with an increase in creatinine plasma concentration of 0.05–0.1 mg/dL and a parallel glomerular filtration-rate reduction of 10 mL/min within the first 4 weeks after Cobi introduction, which remains stable during treatment. Bone and central nervous system safety profiles were found to be good in randomized clinical trials of both experienced and naïve patients. The efficacy and safety of Drv/Cobi/FTC/Taf are comparable to other drug regimens recommended for HIV treatment. Keywords: protease inhibitors, darunavir/cobicistat, emtricitabine/tenofovir alafenamide, HIV

Andrea Antinori,1 Paola Meraviglia,2 Antonella d’Arminio Monforte,3,4 Antonella Castagna,5,6 Cristina Mussini,7 Teresa Bini,4 Nicola Gianotti,5 Stefano Rusconi,8 Elisa Colella,8 Giuseppe Airoldi,9 Daniela Mancusi,10 Roberta Termini10 1Clinical Department, National Institute for Infectious Diseases “L. Spallanzani”, Rome, 2Department of Infectious Disease, “L. Sacco” University Hospital, 3Department of Health Sciences – University of Milan, 4Clinic of Infectious Diseases, “San Paolo” Hospital, 5Infectious Diseases, San Raffaele Scientific Institute, 6Università Vita-Salute San Raffaele, Milan, 7Institute of Infectious Diseases, University of Modena and Reggio Emilia, Modena, 8Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, 9Studio Associato Airoldi, Cicogna, Ghirri, 10Janssen-Cilag SpA, Medical Affairs, Cologno Monzese, Milan, Italy Abstract: Current antiretroviral (ARV) therapy for the treatment of human immunodeficiency virus (HIV-1)-infected patients provides long-term control of viral load (VL). Darunavir (DRV) is a nonpeptidomimetic protease inhibitor approved for use with a ritonavir booster (DRV/r). This study evaluated the effectiveness of DRV/r in combination with other ARV agents in routine clinical practice in Italy. In this descriptive observational study, data on utilization of DRV/r, under the conditions described in the marketing authorization, were collected from June 2009 to December 2012. Effectiveness (VL