Introduction. Low levels of nasal NO have been associated with increased propensity to rhinosinusitis and respiratory tract infections. Our objective was to describe nasal NO levels in HIV-infected ...individuals versus healthy controls and determine possible risk factors for reduced nasal NO levels. Materials and Methods. HIV-infected individuals and healthy controls were recruited. Participants underwent nasal NO testing by standardized methods using a CLD88 chemiluminescence analyzer and completed the Sinonasal Outcome Test-20 (SNOT-20) on symptoms of rhinosinusitis. Results. Participants included 41 HIV-infected individuals with suppressed VL on antiretroviral therapy (ART group), 5 HIV-infected individuals with detectable VL off ART (viremic group), and 12 healthy controls (HC group). Mean nasal NO level was 253 (±77) nL/min in the ART group, 213 (±48) nL/min in the viremic group, and 289 (±68) nL/min in the HC group (p=0.133; ANOVA). There was no correlation between nasal NO level and VL in viremic individuals (r=-0.200; p=0.747). Differences were observed in mean total points on the SNOT-20 which were 19 (±16)/100, 18 (±26)/100, and 4 (±4)/100 in the ART, viremic, and HC groups, respectively (p=0.013; ANOVA). Conclusion. Healthy individuals, HIV patients on ART, and viremic individuals off ART display similar nasal NO levels. However, rhinosinusitis symptoms remain prominent despite ART-treatment.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. HIV-infected persons without viral hepatitis are at increased risk of NAFLD. Nevertheless, data on ...NAFLD in HIV monoinfection are scarce.
We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography and associated controlled attenuation parameter (CAP) in unselected HIV-infected adults without significant alcohol intake or viral hepatitis coinfection. NAFLD was defined as CAP at least 238 dB/m. Significant liver fibrosis and cirrhosis were defined as transient elastography measurement at least 7.1 and 13 kPa, respectively. Predictors of NAFLD and significant liver fibrosis were determined using logistic regression analysis.
A total of 300 consecutive patients (mean age 50 years, 77% men; mean CD4 cell count 570 cells/μl, 90% on antiretrovirals) were included as a part of a routine screening program. Transient elastography with CAP identified NAFLD and significant liver fibrosis in 48 and 15% of cases, respectively. NAFLD was independently associated with BMI more than 25 kg/m adjusted odds ratio (aOR) 4.86, 95% confidence interval (CI) 2.55-9.26 and elevated alanine aminotransferase (ALT) (aOR 3.17, 95% CI 1.43-7.03). Independent predictors of significant liver fibrosis were diabetes (aOR 5.84, 95% CI 1.91-17.85), elevated ALT (aOR 3.30, 95% CI 1.27-8.59) and current use of protease inhibitors (aOR 3.96, 95% CI 1.64-9.54).
NAFLD and significant liver fibrosis diagnosed by transient elastography with CAP are major comorbidities in unselected HIV monoinfected persons on antiretroviral therapy, particularly if metabolic conditions and elevated ALT coexist. Noninvasive screening for NAFLD should be implemented in this population to establish early interventions and prevent complications.
Use of illicit substances during sex (chemsex) may increase transmission of HIV and other STIs. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV transmission, providing an ...important prevention tool for those who practise chemsex. However, it does not prevent acquisition of other STIs. We aim to examine the impact of chemsex on STI incidence among gay, bisexual and other men who have sex with men (gbMSM), and transgender women using PrEP in Montréal, Canada.
We linked baseline sociodemographic and behavioural data with follow-up STI testing from 2013 to 2020 among PrEP users in the l'Actuel PrEP Cohort (Canada). Focusing on the 24 months following PrEP initiation, we estimated the effect of chemsex reported at baseline on cumulative incidence of gonorrhoea and chlamydia using Kaplan-Meier curves and survival analyses. We investigated the role of polysubstance use and effect modification by sociodemographic factors.
There were 2086 clients (2079 cisgender gbMSM, 3 transgender gbMSM, 4 transgender women) who initiated PrEP, contributing 1477 years of follow-up. There were no incident HIV infections among clients on PrEP. Controlling for sociodemographic confounders, clients reporting chemsex at baseline had a 32% higher hazard of gonorrhoea/chlamydia diagnosis (adjusted HR=1.32; 95% CI: 1.10 to 1.57), equivalent to a risk increase of 8.9 percentage points (95% CI: 8.5 to 9.4) at 12 months. The effect was greater for clients who reported polysubstance use (adjusted HR=1.51; 95% CI: 1.21 to 1.89). The strength of the effect of chemsex on STI incidence varied by age, education and income.
Among PrEP users, chemsex at baseline was linked to increased incidence of gonorrhoea and chlamydia. This effect was stronger for people reporting multiple chemsex substances. The high STI incidence among gbMSM who report chemsex highlights the importance of PrEP for this population and the need for integrated services that address the complexities of sexualised substance use.
HIV-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among ...HIV-infected patients remain unknown.
Single-centre, phase IV, open-label, single arm clinical trial.
HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) at least 248 dB/m and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) greater than 130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks postdiscontinuation. Generalized linear mixed effects models were used to evaluate changes in alanine aminotransferase (ALT), CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pretreatment trends.
A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared with baseline, 24 weeks of vitamin E treatment improved ALT -27 units/l; 95% confidence interval (CI) -37 to -17, CAP scores (-22 dB/m; 95% CI -42 to -1) and CK-18 (-123 units/l; 95% CI -201 to -46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up.
In this first clinical trial, we showed that vitamin E is an effective and well tolerated treatment for NASH in HIV-infected patients.
Integrase strand transfer inhibitors (INSTIs) are recommended for first-line HIV therapy based on their relatively high genetic barrier to resistance. Although raltegravir (RAL) and elvitegravir ...(EVG) resistance profiles are well-characterized, resistance patterns for dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) remain largely unknown. Here, in vitro drug selections compared the development of resistance to DTG, BIC, CAB, EVG and RAL using clinical isolates from treatment-naïve primary HIV infection (PHI) cohort participants (n = 12), and pNL4.3 recombinant strains encoding patient-derived Integrase with (n = 5) and without (n = 5) the E157Q substitution.
Patient-derived viral isolates were serially passaged in PHA-stimulated cord blood mononuclear cells in the presence of escalating concentrations of INSTIs over the course of 36-46 weeks. Drug resistance arose more rapidly in primary clinical isolates with EVG (12/12), followed by CAB (8/12), DTG (8/12) and BIC (6/12). For pNL4.3 recombinant strains encoding patient-derived integrase, the comparative genetic barrier to resistance was RAL > EVG > CAB > DTG and BIC. The E157Q substitution in integrase delayed the advent of resistance to INSTIs. With EVG, T66I/A, E92G/V/Q, T97A or R263K (n = 16, 3, 2 and 1, respectively) arose by weeks 8-16, followed by 1-4 accessory mutations, conferring high-level resistance (> 100-fold) by week 36. With DTG and BIC, solitary R263K (n = 27), S153F/Y (n = 7) H51Y (n = 2), Q146 R (n = 3) or S147G (n = 1) mutations conferred low-level (< 3-fold) resistance at weeks 36-46. Similarly, most CAB selections (n = 18) resulted in R263K, S153Y, S147G, H51Y, or Q146L solitary mutations. However, three CAB selections resulted in Q148R/K followed by secondary mutations conferring high-level cross-resistance to all INSTIs. EVG-resistant viruses (T66I/R263K, T66I/E157Q/R263K, and S153A/R263K) retained residual susceptibility when switched to DTG, BIC or CAB, losing T66I by week 27. Two EVG-resistant variants developed resistance to DTG, BIC and CAB through the additional acquisition of E138A/Q148R and S230N, respectively. One EVG-resistant variant (T66I) acquired L74M/G140S/S147G, L74M/E138K/S147G and H51Y with DTG CAB and BIC, respectively.
Second generation INSTIs show a higher genetic barrier to resistance than EVG and RAL. The potency of CAB was lower than BIC and DTG. The development of Q148R/K with CAB can result in high-level cross-resistance to all INSTIs.
Monkeypox, a viral zoonotic disease, is causing a global outbreak outside of endemic areas.
To characterize the outbreak of monkeypox in Montréal, the first large outbreak in North America.
...Epidemiologic and laboratory surveillance data and a phylogenomic analysis were used to describe and place the outbreak in a global context.
Montréal, Canada.
Probable or confirmed cases of monkeypox.
Epidemiologic, clinical, and demographic data were aggregated. Whole-genome sequencing and phylogenetic analysis were performed for a set of outbreak sequences. The public health response and its evolution are described.
Up to 18 October 2022, a total of 402 cases of monkeypox were reported mostly among men who have sex with men (MSM), most of which were suspected to be acquired through sexual contact. All monkeypox genomes nested within the B.1 lineage. Montréal Public Health worked closely with the affected communities to control the outbreak, becoming the first jurisdiction to offer 1 dose of the Modified Vaccinia Ankara-Bavarian Nordic vaccine as preexposure prophylaxis (PrEP) to those at risk in early June 2022. Two peaks of cases were seen in early June and July (43 and 44 cases per week, respectively) followed by a decline toward near resolution of the outbreak in October. Reasons for the biphasic peak are not fully elucidated but may represent the tempo of vaccination and/or several factors related to transmission dynamics and case ascertainment.
Clinical data are self-reported. Limited divergence among sequences limited genomic epidemiologic conclusions.
A large outbreak of monkeypox occurred in Montréal, primarily among MSM. Successful control of the outbreak rested on early and sustained engagement with the affected communities and rapid offer of PrEP vaccination to at-risk persons.
None.
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