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Objectives: The aim of the study was to assess the feasibility of a national pre‐exposure prophylaxis (PrEP) programme using smartphone‐compatible data collection. Methods: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone‐compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV‐negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow‐up (number with first follow‐up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. Results: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52–137]. Retention at first follow‐up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33–47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. Conclusions: In a national PrEP programme using smartphone‐compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort. [ABSTRACT FROM AUTHOR]

Background: Changes in mental and sexual health among men having sex with men (MSM) due to the SARS-CoV-2 pandemic remain unclear., Methods: Design: Longitudinal analysis of an ongoing, multicentre, pre-exposure prophylaxis (PrEP) cohort (NCT03893188) in Switzerland. Participants: HIV-negative MSM aged ≥18 who completed at least one questionnaire before and one after the start of the SARS-CoV-2 pandemic. Outcomes: Primary: mental health, defined as anxiety and depression scores assessed by the Patient Health Questionnaire-4. Secondary: sexual behaviour, well-being, PrEP use and disruption of care. Outcomes were assessed over seven periods corresponding to different SARS-CoV-2 prevention measures in Switzerland. We performed pairwise comparisons between periods (Wilcoxon signed rank test)., Results: Data from 1,043 participants were included. Whilst anxiety scores remained stable over time, depression scores worsened in the second wave and the second lockdown period compared to pre-pandemic scores. This was confirmed by pairwise comparisons (pre-SARS-CoV-2/second wave and pre-SARS-CoV-2/second lockdown: p <0.001). Downward trends in sexual activity,sexualized substance use, and a switch from daily to "event-driven" PrEP were found. Disruption of care affected 42.6% (790/1856) of daily PrEP users' follow-up visits., Conclusion: In this longitudinal analysis of a PrEP cohort enrolling MSM, depression scores worsened in the second wave and the second lockdown compared to the pre-pandemic period.

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.

In 2008, Mr Brown, an HIV positive patient was healed of acute myeloid leukemia, after receiving an hematopoietic stem cell transplantation from a donor homozygous for the CCR5 gene variant delta32. He was able to recover a normal CD4 T cell count and his HIV viral load has remained undetectable, despite discontinuing antiviral therapy. This extraordinary case is a proof of concept that HIV can be cured and has boosted the research, especially in the field of gene therapy. Several groups are working on blocking the expression of the CCR5 and CXCR4 co-receptors, by using either RNA interference or zinc-finger nuclease tools. The aim of this article is to describe their actual stage of development.

Because of increasing migration, European countries are facing new pathogens and diseases, such as human herpes virus-8 (HHV-8). We assessed the prevalence of HHV-8 using a new ELISA test in 140 pregnant women delivering in Geneva (Switzerland). The prevalence of HHV-8 was 7.9% globally and up to 33.3% in the African subpopulation. Seropositive women were more frequently older (≥32 years old) than seronegative ones: 81.8% vs. 43%; p = 0.023, respectively. In conclusion, HHV-8 infection is present in European pregnant women. Attention should be given to the emergence of infectious diseases, such as HHV-8, and their impact on health in nonendemic countries.

Upper respiratory tract infections are frequent in athletes. Mainly of viral origin, they are treated symptomatically. Infectious mononucleosis is associated with an estimated 2% per hundred risk of splenic rupture, which occurs between day four and twenty one of the illness. Therefore return to play guidelines recommend avoiding, exercice during the first twenty one days. Physical exercise seems to influence the immune system, depending on the intensity and length of it. But the relationship between physical exercise and risk of infections remains controversial: some articles showing an increase in risk, whereas others suggesting a certain degree of protection, in athletes. The actual generally accepted working theory is the J-curve proposed by Nieman. This model remains to be formally proven.

Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) were enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal Chlamydia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic patients and patients having >20 sexual partners. These results support routine anorectal Chlamydia screening in HIV-infected MSM who report unprotected anal intercourse.

Hodgkin lymphoma (HL) risk is elevated among persons infected with HIV (PHIV) and has been suggested to have increased in the era of combined antiretroviral therapy (cART). Among 14,606 PHIV followed more than 20 years in the Swiss HIV Cohort Study (SHCS), determinants of HL were investigated using 2 different approaches, namely, a cohort and nested case-control study, estimating hazard ratios (HRs) and matched odds ratios, respectively. Forty-seven incident HL cases occurred during 84,611 person-years of SHCS follow-up. HL risk was significantly higher among men having sex with men (HR vs intravenous drug users = 2.44, 95% confidence interval [CI], 1.13-5.24) but did not vary by calendar period (HR for 2002-2007 vs 1995 or earlier = 0.65, 95% CI, 0.29-1.44) or cART use (HR vs nonusers = 1.02, 95% CI, 0.53-1.94). HL risk tended to increase with declining CD4(+) cell counts, but these differences were not significant. A lower CD4(+)/CD8(+) ratio at SHCS enrollment or 1 to 2 years before HL diagnosis, however, was significantly associated with increased HL risk. In conclusion, HL risk does not appear to be increasing in recent years or among PHIV using cART in Switzerland, and there was no evidence that HL risk should be increased in the setting of improved immunity.

It is important to identify the optimal dosage and best method of infusion of parenteral vancomycin to be used over a several week period for the treatment of osteomyelitis. A retrospective study was undertaken to compare a high dose vancomycin treatment (HD: 40 mg/kg/d) with a standard dose treatment (SD: 20 mg/kg/d), and also to compare the modality of infusion using either intermittent vancomycin infusion (IVI) or continuous vancomycin infusion (CVI). 89 patients with Gram-positive cocci osteomyelitis requiring vancomycin treatment were followed, and the outcome and therapeutic safety were compared. There were significantly more adverse drug reactions (acute renal failure) in the IVI subgroup (HD-IVI vs SD-IVI, p-value 0.007). No cases of renal failure were found in the HD-CVI subgroup. The best outcome was found in the subgroup of patients who received HD-CVI (HD-CVI vs SD-IVI, overall log rank p-value 0.02). HD-CVI treatment appears to provide an improved outcome with fewer adverse drug reactions.

It remains controversial whether combination therapy, given empirically or as definitive treatment, for Pseudomonas aeruginosa bacteremia is associated with a better outcome than monotherapy. The aim of the present study was to compare the rates of survival among patients who received either combination therapy or monotherapy for P. aeruginosa bacteremia. We assembled a historical cohort of 115 episodes of P. aeruginosa bacteremia treated with empirical antipseudomonal therapy between 1988 and 1998. On the basis of susceptibility testing of the bacteremic P. aeruginosa isolate, we defined categories of empirical treatment, including adequate combination therapy, adequate monotherapy, and inadequate therapy, as well as corresponding categories of definitive therapy. Neither the adequacy of the empirical treatment nor the use of combination therapy predicted survival until receipt of the antibiogram. However, the risk of death from the date of receipt of the antibiogram to day 30 was higher for both adequate empirical monotherapy (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.0 to 14.1) and inadequate empirical therapy (aHR, 5.0; 95% CI, 1.2 to 20.4) than for adequate empirical combination therapy. Compared to adequate definitive combination therapy, the risk of death at 30 days was also higher with inadequate definitive therapy (aHR, 2.6; 95% CI, 1.1 to 6.7) but not with adequate definitive monotherapy (aHR, 0.70; 95% CI, 0.30 to 1.7). In this retrospective analysis the use of adequate combination antimicrobial therapy as empirical treatment until receipt of the antibiogram was associated with a better rate of survival at 30 days than the use of monotherapy. However, adequate combination antimicrobial therapy given as definitive treatment for P. aeruginosa bacteremia did not improve the rate of survival compared to that from the provision of adequate definitive monotherapy.