We prospectively evaluated 28 triple-class experienced HIV-1-infected patients harbouring R5 virus, who received maraviroc, raltegravir and etravirine. By on-treatment analysis, 26 (92%) had less than 50 copies HIV-RNA/ml at week 48. The median (interquartile range) 48-week increase in CD4 cell counts was 267 (136-355) cells/microl. Three serious adverse events occurred: one recurrence of mycobacterial spondylodiscitis, one anal cancer, one Hodgkin lymphoma. Although long-term safety needs further study, this protease inhibitor and nucleoside analogue-sparing regimen showed sustained efficacy.

Background During the Coronavirus disease 2019 (COVID-19) pandemic, advanced health systems have come under pressure by the unprecedented high volume of patients needing urgent care. The impact on mortality of this “patients’ burden” has not been determined. Methods and findings Through retrieval of administrative data from a large referral hospital of Northern Italy, we determined Aalen-Johansen cumulative incidence curves to describe the in-hospital mortality, stratified by fixed covariates. Age- and sex-adjusted Cox models were used to quantify the effect on mortality of variables deemed to reflect the stress on the hospital system, namely the time-dependent number of daily admissions and of total hospitalized patients, and the calendar period. Of the 1225 subjects hospitalized for COVID-19 between February 20 and May 13, 283 died (30-day mortality rate 24%) after a median follow-up of 14 days (interquartile range 5–19). Hospitalizations increased progressively until a peak of 465 subjects on March 26, then declined. The risk of death, adjusted for age and sex, increased for a higher number of daily admissions (adjusted hazard ratio [AHR] per an incremental daily admission of 10 patients: 1.13, 95% Confidence Intervals [CI] 1.05–1.22, p = 0.0014), and for a higher total number of hospitalized patients (AHR per an increase of 50 patients in the total number of hospitalized subjects: 1.11, 95%CI 1.04–1.17, p = 0.0004), while was lower for the calendar period after the peak (AHR 0.56, 95%CI 0.43–0.72, p<0.0001). A validation was conducted on a dataset from another hospital where 500 subjects were hospitalized for COVID-19 in the same period. Figures were consistent in terms of impact of daily admissions, daily census, and calendar period on in-hospital mortality. Conclusions The pressure of a high volume of severely ill patients suffering from COVID-19 has a measurable independent impact on in-hospital mortality.

Purpose of the studyWith the availability of new drug classes, the full suppression is a realistic goal even for heavily pre-treated patients. We prospectively evaluated the magnitude of CD4 recovery (CR) in this setting. MethodsWe decided to simultaneously screen triple class failing patients (pts) followed at San Raffaele Hospital in three Expanded Access Programs: raltegravir (MK0518-023), maraviroc (A4001050), etravirine (TMC125-C214). Salvage therapy was prescribed according to: viral tropism, screening genotype and previous resistance tests. Data were collected at baseline (BL) and at 4, 12, 24, 36 and 48 weeks. Generalized linear regression model was applied. Results are reported as median (Q1-Q3). Summary of resultsUp to date, 68 pts reached week 24 (W24) without modification of the initial regimen; age 44.5 (41.7-49.9) years, 17 (25%) women, 10 (17.2%) IVDU, infected since 15.0 (12.5-18.4) years, ARV exposure of 13.0 (11.6-15.4) years, CDC C stage 32 (47%). At BL: CD4 195 (87-306) cells//μL; CD4% 11.8 (7.0-17.5), HIV-RNA 4.2 (3.8-5.0) log10 copies/mL and CD4 nadir 73 (22-178) cells/μL. No difference in BL characteristics were found according to the group regimen prescribed. (Table 1.) At week 24, 14 (93%), 13 (76%), 14 (74%), 15 (94%) had HIV-RNA <50 copies/mL in group A, B, C, D, respectively (p = 0.238).At multivariable analysis, a significantly different CR was related to therapy group (p = 0.035) and positively related to BL HIV-RNA (p = 0.049). CR was higher in group A (adjusted mean: 214.8 ± 37.3) than group B (129.2 ± 33.5, p = 0.062) or group C (115.7 ± 30.5, p = 0.023) or group D (91.7 ± 33.3, p = 0.005). No independent effect of age (p = 0.834), gender (p = 0.392), HIV risk factor (p = 0.522), CD4% (p = 0.297) and CD4 nadir (p = 0.195) was observed. Despite the high pill number, RAL +MVC+ETR were very well tolerated; serious adverse events were diagnosed in two pts: spondylodiscitis (one), anal cancer (one). ConclusionSalvage therapy with RAL+ MVC+ETR showed an excellent short-term CD4 recovery. Reasons for this success could include: presence of active drugs blocking consecutive targets of viral replication, high doses of MVC required with this regimen, avoidance of ritonavir and NRTI toxicity.

Factors associated with CCR5 coreceptor usage are not yet extensively evaluated; in some studies high CD4 and low viremia have been considered predictive [1,2]. We evaluated factors predicting the viral tropism in failing patients with long exposure to HIV, screened for Maraviroc Expanded Access Program (A4001050) at San Raffaele Hospital. MethodsViral tropism was determined in 98/116 (84%) (ViroLogic PhenoSense assay). Viral tropism was classified as R5, D/M or X4 for virus that used CCR5 coreceptor, CCR5 and CXCR4 coreceptors or CXCR4 coreceptor, respectively. Variables evaluated for the association with the R5 virus (outcome variable) were: age, gender, CDC stage (C vs. A and B), screening CD4 percentage, CD4+ cells, HIV-1 plasma RNA level, nadir CD4+, risk factor (IVDU vs. other), time since HIV infection. All these characteristics were considered at univariable and multivariable analysis. Logistic regression was applied at multivariable analysis. Data were described as median (Q1-Q3) or frequency (%), as appropriate. Summary of results 56 ConclusionOur study underlines the possibility for gender to influence not only the initial viral set-point as previously shown [3], but also the probability of harbouring R5 viruses.

Internet e i new media rappresentano un nuovo strumento potenzialmente alleato di chi vuole adescare minori per compiere reati sessuali. Gli studi epidemiologici disponibili confermano che il fenomeno č in crescita, cosě come il numero di arresti ad esso correlati, e che le vittime spesso agiscono consenzienti, consapevoli di comunicare con adulti estranei, mentre raramente parlano di ciň con gli adulti di riferimento (genitori/insegnanti). Il rischio di vittimizzazione cresce con l'etŕ della vittima e per le femmine. Strategie preventive efficaci devono comprendere non solo interventi normativi, ma anche programmi educativi volti ad aiutare gli adolescenti a costruire competenze che li rendano capaci di affrontare le esigenze ed i cambiamenti propri dell'etŕ evolutiva, in linea con il modello delle life skills proposto dall'OMS.