Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon.

In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged between 25 and 49 years (63.4%); the probable route of transmission was heterosexual contact in 37.5% of cases, injecting drug use in 28.1%, and male-to-male contact in 27.9%. Among people in care, 20.1% had less than 350 CD4 cells/μl, 87.6% received antiretroviral therapy, and among these, 62.4% had a CD4 cell count higher than 350 cells/μl. The overall estimated prevalence of individuals diagnosed and linked to care in 2012 in Italy was 0.16 per 100 residents (all ages). Adding the estimated proportion of undiagnosed people, the estimated HIV prevalence would range between 0.19 and 0.26 per 100 residents. In Italy, the majority of people diagnosed and linked to care receive antiretroviral therapy. A higher prevalence of individuals diagnosed and linked to care was observed in Northern Italy and among males. More information for developing the HIV care continuum is necessary to improve the entire engagement in care, focusing on test-and-treat strategies to substantially reduce the proportion of people still undiagnosed or with a detectable viral load.

Dear Sirs:The aim of anti-HIV treatment in pregnancy is the suppression of the HIV-1 RNA viral load in the plasma before delivery [1] to prevent mother-to-child transmission of the infection. The achievement of this outcome may be complicated in pregnant women who have been treated with multiple drugs by the lack of active drugs available. Although there are limited data on the use of the integrase inhibitor raltegravir in pregnancy, the availability of this drug is important in the management of multidrug-resistant virus in pregnant women.We describe a case of a 22-year-old woman who acquired the infection via vertical transmission and who has been followed up at our Centre since March 2009. Past antiretroviral treatments include numerous drugs; the historical genotypic resistance test showed mutations in the regions of reverse transcriptase (41L, 74V, 101Q, 103N, 103S, 108I, 115F, 179I, 184V, 215D, 215N, 215S, 215Y) and protease (36I, 63P). These mutations confer resistance or poor efficacy to all the nucleoside/nucleotide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors except etravirine.Since April 2009 the patient has received treatment with tenofovir/emtricitabine (fixed dose combination) plus darunavir/ritonavir (600/100 mg twice daily) plus raltegravir (400 mg twice daily). At the time of conception she presented HIV-RNA <20 cp/mL. Despite safety and pharmacokinetics data of raltegravir in pregnancy being insufficient to recommend its use during pregnancy, it was decided to continue the treatment with tenofovir/emtricitabine (fixed dose combination) plus raltegravir (400 mg twice daily); only darunavir/ ritonavir had been discontinued since the 4th week of pregnancy and substituted with lopinavir/ritonavir (400/100 mg twice daily), the gold standard for protease inhibitors in pregnant women [2]. Therapeutic drug monitoring was performed by a validated HPLC-UV method [3] in the third trimester, which demonstrated good adherence; at that time lopinavir, ritonavir and raltegravir plasma levels were 9.59 μg/mL (minimum target trough concentration 1 μg/mL) [3], 0.81 μg/mL and 0.21 μg/mL (median trough concentration from clinical trials 0.029-0.118 μg/mL) [2].At 39 weeks' gestation a 2.4-kg neonate was delivered by elective caesarean section without complications; at the time of delivery the HIV-RNA viral load in plasma was <20 cp/mL. Despite the low birth weight the infant was healthy; the Apgar scores were 9 and 10 at 1 and 5 min respectively. The mother received zidovudine intravenous prophylaxis during labour and the newborn received 4 weeks of oral zidovudine; the HIV-RNA was undetectable at birth and at 1 and 3 months of age. At delivery the raltegravir level in cord and in maternal plasma was the same (0.19 μg/mL) with a cord/maternal plasma ratio of 1. The lopinavir levels were 1.3 μg/mL and 8.05 μg/mL and the ritonavir levels were 0.26 μg/mL and 0.94 μg/mL, corresponding to a ratio of 0.16 and 0.28 respectively.The low plasma cord concentration of lopinavir can be ex...

Mesalazine therapy for ulcerative colitis has been reported to be effective and safe. Rare cases of mesalazine-induced renal, pancreatic, myo-pericardial, pleuro-pulmonary and haematological toxicity have been described separately. We report a case characterized by the simultaneous presence of fever, pericarditis, peripheral eosinophilia, eosinophilic pneumonia, anaemia and haematuria (together with proteinuria and leukocyturia) due to mesalazine treatment in a patient with ulcerative colitis. No clinical response had been obtained with corticosteroids and various antibacterial agents. When mesalazine treatment was suspended, all symptoms rapidly and totally disappeared, confirming the direct responsibility of this drug in causing these adverse events. We conclude that mesalazine can induce multi-organ hypersensitivity, which must always be considered as a possible adverse effect during treatment with this drug. To resolve this adverse event it is essential to discontinue mesalazine treatment.