Background: Monkeypox virus (mpxv) started to spread to Europe and North America at the beginning of the current outbreak in May 2022, and the World Health Organization (WHO) declared Human Monkeypox (mpox) as a public health emergency of international concern (PHEIC) in July 2022. The aim of this observational analysis is to describe demographical data, symptoms presentation and clinical course till outcome of individuals diagnosed with mpox, between May and October 2022, at our open-access Sexual Health Clinic in IRCCS San Raffaele Hospital in Milan, Italy. Methods: Among people who accessed our Sexual Health Clinic, we considered, as suspected diagnosis of mpox, individuals with consistent symptoms and epidemiological criteria. Following the physical examination, oropharyngeal, anal, genital and cutaneous swabs, plus plasma, urine and seminal fluid were collected as biological materials to detect mpxv DNA. We also performed a screening for sexually transmitted infections (STIs). Results: Overall, 140 individuals with mpox were included in this study. Median age was 37 (interquartile, IQR 33, 43) years old. Males were 137 (98%) and men who have sex with men (MSM) were 134 (96%). As risk factors, we detected travels abroad in 35 (25%) individuals and close contact with mpox cases in 49 (35%). There were 66 (47%) people living with HIV (PLWH). Most frequent symptoms were fever (59%), lymphadenopathy (57%), cutaneous (77%), genital (42%), anal (34%) and oral (26%) lesions, proctitis (39%), sore throat (22%) and generalized rash (5%). At mpox diagnosis, we also observed N. gonorrhoeae in 18 (13%) cases, syphilis in 14 (10%) and C. trachomatis in 12 (9%). Two (1%) people received a concomitant diagnosis of HIV infection. We attended to 21 (15%) complications, with nine (6%) cases of hospitalization including six (IQR 3,7) median hospital days. Forty-five (32%) patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs), 37 (26%) with antibiotics and eight (6%) with antiviral drugs. Conclusions: Similarly to other international cohorts, sexual transmission was most frequently present, and concomitant STIs were common. Symptoms were heterogenous, self-resolving and responsive to therapy. Hospitalization was necessary in few patients. There is uncertainty about the future development of mpox and further studies (e.g., potential disease reservoirs, other possible means of transmission, predictors of severe disease) are still needed.

It is currently debated whether patients with residual viraemia are at higher risk of virological failure than those attaining <1 HIV RNA copy/mL. We therefore investigated the effect of residual viraemia on virological rebound. We used a prospective, non-interventional, single-centre, study. This analysis was based on HIV-infected patients with two consecutive HIV RNA viral loads (VLs) of <50 copies/mL as tested by Versant bDNA, followed by two HIV RNA VLs of 50 copies/mL after baseline, and the time to virological rebound was calculated using the Kaplan–Meier method. There were 739 eligible patients; 446 (60.4%) had HIV RNA <1 copy/mL (group A) and 293 (39.6%) had residual viraemia (1–49 HIV RNA copies/mL; group B). After a follow-up (median 48.9 weeks), virological rebound occurred in four patients in group A (0.9%) and six patients in group B (2%); the time to virological rebound was similar in the two groups (log-rank test P = 0.231). CD4+ cell recovery (slope) was significantly less in the patients with residual viraemia; +14.3 (−7.7, 43.9) cells/mm³ per year versus +21.2 (−2.5, 53.2) cells/mm³ per year; P = 0.036. Residual viraemia assessed by kPCR was not associated with virological rebound during 1 year of follow-up. However, the patients attaining <1 HIV RNA copy/mL showed a small but statistically significant improvement in CD4+ cell recovery.

Background: The effect of the HIV reverse transcriptase K65R mutation on virological response to salvage therapy has not been clearly defined. Methods: From six Italian clinical centres, all consecutive patients starting salvage antiretroviral therapy after virological failure in the presence of the K65R mutation identified by a genotypic resistance test were selected. Results: Among 145 subjects included over a 197 person-year follow-up, the estimated probability of virological response (VR, defined as reaching HIV RNA <50 copies/ml after salvage therapy) at 24 and 48 weeks was 36% and 60%, respectively. The strongest independent predictor of VR was the inclusion of a thymidine analogue (TA) in the salvage regimen. The presence of M184V and the introduction of lopinavir/ritonavir as new drug were both marginally associated with better outcome. After 24 weeks of salvage therapy, the median reduction in HIV-1 RNA was -1.36 log ₁₀ copies/ml (interquartile range [IQR] 0.10–2.46): at multivariable regression analysis, salvage regimens containing a TA (β=+0.80; P=0.02) and lamivudine (β=+1.21; P=0.02) as new drug had a positive effect on the reduction of HIV-1 RNA. Conclusions: Development of the K65R mutation does not preclude a high rate of virological response to rescue therapy. Inclusion of a TA in the salvage regimen and the presence of a M184V mutation could have a favourable effect on virological outcome.

Objectives The aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients. Methods An adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the χ² test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses. Results Among 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 ± 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019). Conclusions In this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status.

Despite a substantial reduction in virological failures following introduction of new potent antiretroviral therapies in the latest years, drug resistance remains a limitation for the control of HIV-1 infection. We evaluated trends and correlates of resistance in treatment failing patients in a comprehensive database over a time period of relevant changes in prescription attitudes and treatment guidelines. We analyzed 6,796 HIV-1 pol sequences from 49 centres stored in the Italian ARCA database during the 2003–2012 period. Patients (n = 5,246) with viremia > 200 copies/mL received a genotypic test while on treatment. Mutations were identified from IAS-USA 2013 tables. Class resistance was evaluated according to antiretroviral regimens in use at failure. Time trends and correlates of resistance were analyzed by Cochran-Armitage test and logistic regression models. The use of NRTI backbone regimens slightly decreased from 99.7% in 2003–2004 to 97.4% in 2010–2012. NNRTI-based combinations dropped from 46.7% to 24.1%. PI-containing regimens rose from 56.6% to 81.7%, with an increase of boosted PI from 36.5% to 68.9% overtime. In the same reference periods, Resistance to NRTIs, NNRTIs and PIs declined from 79.1% to 40.8%, from 77.8% to 53.8% and from 59.8% to 18.9%, respectively (p < .0001 for all comparisons). Dual NRTI + NNRTI and NRTI + PI resistance decreased from 56.4% to 33.3% and from 36.1% to 10.5%, respectively. Reduced risk of resistance over time periods was confirmed by a multivariate analysis. Mutations associated with NRTIs, NNRTIs and PIs at treatment failure declined overtime regardless of specific class combinations and epidemiological characteristics of treated population. This is likely due to the improvement of HIV treatment, including both last generation drug combinations and prescription guidelines.