PRESTIGIO RING "a 59-year-old man with multidrug resistant HIV-1 infection failing a regimen including dolutegravir, rilpivirine, atazanavir/cobicistat: successful treatment tailoring based on genotypic and phenotypic resistance tests".

Management of virological failure in heavily treatment-experienced people with multidrug-resistant (MDR) HIV infection is a serious clinical challenge. New drugs with novel mechanisms of action have recently been approved, and their use has improved the outcome of subjects with limited treatment options (LTO). In this setting, the choice of antiretroviral therapy (ART) should be tailored based on the pattern of resistance, treatment history and patients' individual characteristics. While genotypic resistance testing is the reference method for analysing residual drug susceptibility, phenotypic resistance testing can provide additional support when facing LTO. Herein, we present the case of a patient with MDR HIV-1 infection on virological failure enrolled in the PRESTIGIO Registry. The salvage ART regimen, which included drugs with novel mechanisms of action (MoA), was tailored to the patient's clinical characteristics and on the resistance pattern explored with genotypic and phenotypic investigation, allowing the achievement of viro-immunological success. The use of recently approved drugs with novel MoA, combined with an optimized background regimen, may also achieve virological suppression in people with LTO.

Does Nirmatrelvir/Ritonavir Influence the Immune Response against SARS-CoV-2, Independently from Rebound?

Recurrence of coronavirus disease 19 (COVID-19) symptoms and SARS-CoV-2 viral load relapse have been reported in people treated with nirmatrelvir/ritonavir (NM/r). However, little is understood about the etiology of this phenomenon. Our aim was to investigate the relation between the host's immune response and viral rebound. We described three cases of COVID-19 rebound that occurred after treatment with nirmatrelvir/ritonavir (group A). In addition, we compared spike-specific antibody response and plasma cytokine/chemokine patterns of the rebound cases with those of (i) control patients treated with nirmatrelvir/ritonavir who did not show rebound (group B), and (ii) subjects not treated with any anti-SARS-CoV-2 drug (group C). The anti-spike antibodies and plasma cytokines/chemokines were similar in groups A and B. However, we observed a higher anti-BA.2 spike IgG response in patients without antiviral treatment (group C) [geometric mean titer 210,807, 5.1- and 8.2-fold higher compared to group A (p = 0.039) and group B (p = 0.032)]. Moreover, the patients receiving antiviral treatment (groups A-B) showed higher circulating levels of platelet-derived growth factor subunit B (PDGF-BB) and vascular endothelial growth Factors (VEGF) and lower levels of interleukin-9 (IL-9), interleukine-1 receptor antagonist (IL-1 RA), and regulated upon activation normal T cell expressed and presumably secreted chemokine (RANTES) when compared to group C. In conclusion, we observed lower anti-spike IgG levels and different cytokine patterns in nirmatrelvir/ritonavir-treated patients compared to those not treated with anti-SARS-CoV-2 drugs. This suggests that early antiviral treatment, by reducing viral load and antigen presentation, could mitigate the immune response against SARS-CoV-2. The clinical relevance of such observation should be further investigated in larger populations.

Primary Cutaneous Cryptococcosis in an Immunocompetent Patient: Diagnostic Workflow and Choice of Treatment.

Cryptococcosis is an opportunistic infection in immunocompromised patients, involving mainly the lungs and central nervous system; however, the skin, eyes and genitourinary tract could also be involved as secondary sites of infection. Primary cutaneous cryptococcosis (PCC) is a distinct clinical entity that can occur in both immunocompetent and -compromised patients, usually trough skin injury. In immunocompetent patients, it is a very rare infection, presenting with non-specific clinical pictures and being challenging to diagnose. Herein, we present the case of an immunocompetent man with PCC due to Cryptococcus neoformans on his right forearm. PCC was diagnosed by a histological and cultural examination. Causes of concomitant immunosuppression were ruled out. A secondary cutaneous cryptococcosis was excluded with careful investigations. Therapy with oral fluconazole for three months was successfully performed, without evidence of recurrence in the following six months. Complete clinical recovery was achieved after three months of oral antifungal therapy, suggesting that longer courses of treatment could be avoided when faced with PCC in immunocompetent patients.

Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients.

BACKGROUND: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. METHODS: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. RESULTS: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). CONCLUSIONS: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.