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Is a step-down antiretroviral therapy necessary to fight severe acute respiratory syndrome coronavirus 2 in HIV-infected patients?

2020; Lippincott Williams & Wilkins; Volume: 34; Issue: 12 Linguagem: Italiano

10.1097/qad.0000000000002630

1473-5571

Antonio Di Biagio, Lucia Taramasso, Chiara Dentone, Antonio Vena, Daniele Roberto Giacobbe, Andrea De Maria, Małgorzata Mikulska, Matteo Bassetti,

SARS-CoV-2 detection and testing

At present, no evidence exists that people living with HIV (PLWHIV) are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with the general population or experiencing a worse outcome. There is also no evidence that PLWHIV receiving a protease inhibitor-based regimen have a lower incidence of coronavirus disease 2019 (COVID-19) compared with PLWHIV receiving other regimens. At the time of writing, COVID-19 management and outcome have been described in nine PLWHIV, all treated with protease inhibitors [1–3]. The first case has been described in Asia and was a naïve patient who received lopinavir/ritonavir (LPV/r)-containing first-line therapy [1]. A few days later, Blanco et al.[2] reported a case series of five HIV and SARS-CoV-2 coinfected patients in Spain, of whom four were already on antiretroviral therapy (ART) and one was an ART naive AIDS presenter. Also in this case, they were all treated with protease inhibitors: one patient maintained a darunavir/ritonavir (DRV/r)-based treatment; two replaced dolutegravir with LPV/r; one replaced DRV/r with LPV/r; while the naïve patient started a first-line ART with cobicistat boosted DRV (DRV/c). Finally, also Riva et al. described a case series of PLWHIV in Italy, who were all already treated with DRV/c, and in which the protease inhibitor treatment failed to prevent COVID-19, despite adequate DRV plasma levels. In two of them, the authors replaced DRV/c with LPV/r [3]. All these reported cases were discharged alive from hospital [1–3], but their follow-up is too short to evaluate the efficacy of their new antiretroviral strategies. The use of LPV/r is not supported by evidence in the current COVID-19 epidemic but is only considered as a potential treatment of SARS, based on previous observations in the first SARS-CoV epidemic in 2003 [4]. DRV is the most recent protease inhibitor, sharing the same mechanism of action with LPV, but is better tolerated and more efficacious for HIV treatment [5]. In the only randomized trial comparing LPV/r with placebo for the treatment of SARS-CoV-2, no benefit was observed in the protease inhibitor arm [6]. Based on these results, do we really have reasons to support the use of protease inhibitors in PLWHIV with COVID-19? Are we forgetting the successes achieved in PLWHIV in recent years overcoming protease inhibitors use? Can we abandon therapies based on modern, better tolerated single-tablet regimens (STR) and go back 15 years to the LPV/r era? In our centre, we follow about 1500 PLWHIV, and have managed four cases of symptomatic HIV/SARS-CoV-2 coinfection so far. All of them maintained their current ART regimens and one was taking DRV/c, while all the others were on rilpivirine/tenofovir alafenamide/emtricitabine. Our patients did not experience different COVID-19 outcomes compared with those reported in the literature and at our single-centre experience in the general population (Table 1). The reasons for maintaining unchanged ART regimen were multiple. First, they all had undetectable HIV-RNA and a CD4+ T-cell count of more than 500; second, three out of them were on STR, and last, no virological study has ever demonstrated an advantage of switching ART from rilpivirine to protease inhibitors. On the contrary, many studies have demonstrated how switching from protease inhibitors to nonnucleoside reverse transcripatse inhibitors ameliorates tolerability and adherence to ART [7]. The same is also true for switching from protease inhibitors to integrase inhibitors (INSTIs) [7]. Despite this, in some of the COVID-19 cases described in PLWHIV, the inverse and unjustified strategy of interrupting a successful INSTI treatment in favour of protease inhibitor has been made, or that of switching from DRV to LPV [1–3]. The choice of switching to a protease inhibitor could be even worse, if the protease inhibitor used is LPV/r, a drug characterized by a well known gastrointestinal intolerance, often causing diarrhoea and vomiting at onset of treatment [8], which also represent symptoms of COVID-19, and are difficult to manage in the setting of social distancing. Moreover, PLWHIV are becoming older and data of LPV/r use in the elderly are not available. Finally, LPV/r is not coformulated with other antiretrovirals in STR and it is administered in two capsules twice daily, while a multitude of evidences support the use of STR, and none show the utility of switching from STR to multitablet regimens, unless justified by virological failure or intolerance [9].Table 1: Demographics and baseline characteristics of HIV-severe acute respiratory syndrome coronavirus 2 coinfected patients in Genoa Cohort.Notably, the US Department of Health and Human Services treatment guidelines for the management of HIV-infected patients only report protease inhibitor as alternative drugs, while no guidelines recommend them, unless particular conditions are present [10]. In conclusion, PLWHIV and COVID-19 are safely treated without switching to protease inhibitor. The SARS-CoV-2 epidemics should not erase past therapeutic failures and the lessons learned from the history of HIV. Acknowledgements GECOVID Working Group: Anna Alessandrini, Marco Camera, Emanuele Delfino, Andrea De Maria, Chiara Dentone, Antonio Di Biagio, Ferdinando Dodi, Antonio Ferrazin, Giovanni Mazzarello, Malgorzata Mikulska, Laura Ambra Nicolini, Federica Toscanini, Daniele Roberto Giacobbe, Antonio Vena, Lucia Taramasso, Elisa Balletto, Federica Portunato, Eva Schenone, Nirmala Rosseti, Federico Baldi, Marco Berruti, Federica Briano, Silvia Dettori, Laura Labate, Laura Magnasco, Michele Mirabella, Rachele Pincino, Chiara Russo, Giovanni Sarteschi, Chiara sepulcri, Stefania Tutino (Clinica di Malattie Infettive); Roberto Pontremoli; Valentina Beccati; Salvatore Casciaro; Massimo Casu; Francesco Gavaudan; Maria Ghinatti; Elisa Gualco; Giovanna Leoncini; Paola Pitto; Kassem Salam (Clinica di Medicina interna 2); Angelo Gratarola; Mattia Bixio; Annalisa Amelia; Andrea Balestra; Paola Ballarino; Nicholas Bardi; Roberto Boccafogli; Francesca Caserza; Elisa Calzolari; Marta Castelli; Elisabetta Cenni; Paolo Cortese; Giuseppe Cuttone; Sara Feltrin; Stefano Giovinazzo; Patrizia Giuntini; Letizia Natale; Davide Orsi; Matteo Pastorino; Tommaso Perazzo; Fabio Pescetelli; Federico Schenone; Maria Grazia Serra; Marco Sottano (Anestesia e Rianimazione; Emergenza Covid padiglione 64 'Fagiolone'); Roberto Tallone; Massimo Amelotti; Marie Jeanne Majabò; Massimo Merlini; Federica Perazzo (Cure intermedie); Nidal Ahamd; Paolo Barbera; Marta Bovio; Paola Campodonico; Andrea Collidà; Ombretta Cutuli; Agnese Lomeo; Francesca Fezza Nicola Gentilucci; Nadia Hussein; Emanuele Malvezzi; Laura Massobrio; Giula Motta; Laura Pastorino; Nicoletta Pollicardo; Stefano Sartini; Paola Vacca Valentina Virga (Dipartimento di Emergenza ed accettazione); Italo Porto; Giampaolo Bezante; Roberta Della Bona; Giovanni La Malfa; Alberto Valbusa; Vered Gil Ad (Clinica Malattie Cardiovascolari); Emanuela Barisione; Michele Bellotti; Aloe' Teresita; Alessandro Blanco; Marco Grosso; Maria Grazia Piroddi; (Pneumologia ad Indirizzo Interventistico); Paolo Moscatelli; Paola Ballarino; Matteo Caiti; Elisabetta Cenni; Patrizia Giuntini Ottavia Magnani (Medicine d'Urgenza); Samir Sukkar; Ludovica Cogorno; Raffaella Gradaschi; Erica Guiddo; Eleonora Martino; Livia Pisciotta (Dietetica e nutrizione clinica); Bruno Cavaliere; Rossi Cristina; Farina Francesca (Direzione delle Professioni sanitarie); Giacomo Garibotto; Pasquale Esposito (Clinica nefrologica, dialisi e trapianto); Giovanni Passalacqua; Diego Bagnasco; Fulvio Braido; Annamaria Riccio; Elena Tagliabue (Clinica Malattie Respiratorie ed Allergologia); Claudio Gustavino; Antonella Ferraiolo (Ostetricia e Ginecologia); Salvatore Giuffrida; Nicola Rosso (Direzione Amministrativa); Alessandra Morando; Riccardo Papalia; Donata Passerini; Gabriella Tiberio (Direzione di presidio); Giovanni Orengo; Alberto Battaglini (Gestione del rischio clinico); Silvano Ruffoni; Sergio Caglieris; (servizio emergenza 118 e 112). Transparency declarations: none to declare. Conflicts of interest There are no conflicts of interest.