Identifying risk factors for prevalent anal human papillomavirus type 16 infection in women living with HIV.

BACKGROUND: Women living with HIV (WLHIV) have a high risk of anal cancer. Identifying risk factors for anal HPV 16 infection, the most significant risk factor for anal cancer, is essential for prevention and screening strategies. METHODS: In the EVVA Cohort study, 151 WLHIV had cervical and anal HPV testing with genotyping every 6 months for 2 years, while demographic and clinical data were collected via questionnaires and chart reviews. Here, we present results of baseline data analyzed using multivariable logistic regression. RESULTS: Among 150 women with adequate HPV test results at baseline, HPV 16 DNA was detected anally in 23 (15.3%; 95%CI:10.4-22.1) and cervically in 5 (3.3%; 95%CI:1.4-7.8). In multivariable analysis, current smoking (OR = 6.0; 95%CI: 1.5-23.9), nadir CD4 count ≤ 200 cells/µL (OR = 8.4; 95%CI: 2.0-34.3), prevalent cervical HPV 16 (OR = 14.7; 95%CI: 1.0-222.5) and anogenital herpes in previous 6 months (OR = 9.8, 95%CI: 1.7-56.8) were associated with prevalent anal HPV 16. CONCLUSIONS: Knowledge of risk factors can help identify WLHIV at greatest risk of anal HPV 16 infection and, potentially, developing subsequent anal cancer. Identification of the subgroup of these women in whom HPV 16 persists could be an early step in the algorithm of anal cancer screening.

Chemsex and incidence of sexually transmitted infections among Canadian pre-exposure prophylaxis (PrEP) users in the l'Actuel PrEP Cohort (2013-2020).

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Characteristics of new HIV diagnoses over 1995-2019: A clinic-based study in Montréal, Canada.

BACKGROUND: Characterization of populations at risk of acquiring HIV is required to inform the public health response to HIV. To identify potential changing needs in HIV prevention and care cascade, we aim to describe how the demographic profiles and exposure categories of newly diagnosed HIV positive individuals attending a large sexual health clinic in Montréal (Canada) evolved since the beginning of the antiretroviral therapy era in the mid-1990s. METHODS: Using diagnosis data from participants of the Clinique médicale l'Actuel cohort of HIV-positive patients, we examined the distribution of exposure categories (sexual orientation, sexual behaviours, injection drug use, being born in an HIV-endemic country) by gender and year of diagnosis. Time trends in mean age and in the proportion of patients with late (CD4 <350 cells/µL) or advanced stage (CD4 <200 cells/µL) of HIV infection at diagnosis were assessed through meta-regressions. RESULTS: A total of 2,612 patients diagnosed with HIV between January 1st, 1995 and December 31st, 2019 were included. Overall, mean age was 35 years (standard deviation: 10 years) and remained stable over time. The proportion of patients with advanced stage of HIV infection decreased from 16% in 1995 to 4% in 2019. Although men who have sex with men (MSM) consistently accounted for the highest proportion of new diagnoses (77%, 2,022/2,612 overall), their proportion decreased since 2013. There was also a concomitant decrease in the proportion of people who inject drugs, with none of the newly diagnosed participants reporting injection drug use since 2017, and an important increase in the proportion of patients born in an HIV-endemic country (24%, 7/29 in 2019), especially among women. Compared to patients from non-endemic countries, those from HIV-endemic countries were characterized by higher proportions of heterosexuals (88% vs 17%) and of women (52% vs 7%), and were twice likely to get diagnosed at an advanced stage of HIV infection (32% vs 15%). CONCLUSIONS: In absolute numbers, MSM continue to account for the largest exposure category. However, patients from HIV-endemic countries, who tend to be diagnosed at later stages of HIV infection, constitute an increasing proportion of newly diagnosed individuals. These persons could face distinct barriers to rapid diagnosis. Tailoring HIV testing strategies and other prevention interventions to the specific unmet prevention needs of these individuals is warranted.

Pre-exposure Prophylaxis Uptake Among Men Who Have Sex With Men Who Used nPEP: A Longitudinal Analysis of Attendees at a Large Sexual Health Clinic in Montréal (Canada).

BACKGROUND: Reducing HIV transmission using pre-exposure prophylaxis (PrEP) requires focussing on individuals at high acquisition risk, such as men who have sex with men with a history of nonoccupational post-exposure prophylaxis (nPEP). This study aims to characterize longitudinal trends in PrEP uptake and its determinants among nPEP users in Montréal. METHODS: Eligible attendees at Clinique médicale l'Actuel were recruited prospectively starting in October 2000 (nPEP) and January 2013 (PrEP). Linking these cohorts, we characterized the nPEP-to-PrEP cascade, examined the determinants of PrEP uptake after nPEP consultation using a Cox proportional-hazard model, and assessed whether PrEP persistence differed by nPEP history using Kaplan-Meier curves. RESULTS: As of August 2019, 31% of 2682 nPEP cohort participants had 2 or more nPEP consultations. Subsequent PrEP consultations occurred among 36% of nPEP users, of which 17% sought nPEP again afterward. Among 2718 PrEP cohort participants, 46% reported previous nPEP use. Among nPEP users, those aged 25-49 years [hazard ratio (HR) = 1.3, 95% confidence interval (CI): 1.1 to 1.7], with more nPEP episodes (HR = 1.4, 95% CI: 1.3 to 1.5), who reported chemsex (HR = 1.3, 95% CI: 1.1 to 1.7), with a sexually transmitted infection history (HR = 1.5; 95% CI: 1.3 to 1.7), and who returned for their first nPEP follow-up visit (HR = 3.4, 95% CI: 2.7 to 4.2) had higher rates of PrEP linkage. There was no difference in PrEP persistence between nPEP-to-PrEP and PrEP only participants. CONCLUSION: Over one-third of nPEP users were subsequently prescribed PrEP. However, the large proportion of men who repeatedly use nPEP calls for more efficient PrEP-linkage services and, among those who use PrEP, improved persistence should be encouraged.

Asymptomatic urethral lymphogranuloma venereum: a case report.

Since 2003, there has been a resurgence of lymphogranuloma venereum (LGV), a variant of Chlamydia trachomatis (CT), among men who have sex with men (MSM) in several urban areas of Europe and North America. LGV infection occurs most often at anal sites causing proctitis. Urethral and oropharyngeal infections are rare. In Quebec, LGV incidence has been increasing exponentially in recent years and the current guidelines support systematic LGV genotype testing among anorectal CT-positive samples only. This case report describes a patient with a urethral LGV infection, remarkable due to its prolonged asymptomatic development prior to the manifestation of an inguinal bubo. Physicians should be vigilant of potential cases of LGV and forward CT-positive samples occurring among individuals with LGV risk factors for genotype testing.

Incidence of sexually transmitted infections before and after preexposure prophylaxis for HIV.

OBJECTIVE: Use of preexposure prophylaxis (PrEP) for HIV raises concerns about sexually transmitted infection (STI) incidence because of decreased condom use among MSM. This study examines whether PrEP is associated with STIs in the 12 months following PrEP prescription relative to the 12 months prior to PrEP and if STI rates are higher among PrEP users relative to individuals receiving postexposure prophylaxis (PEP). DESIGN: Retrospective cohort study including PrEP users with more than 12 months of follow-up before PrEP prescription and individuals receiving PEP from 2010 to 2015 at Clinique l'Actuel (Montréal, Canada). METHODS: Incidence of chlamydia, gonorrhoea, syphilis and hepatitis C virus over 12 months was compared before and after PrEP; and for PrEP versus PEP users using Poisson models to generate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted IRRs (aIRRs) controlling for frequency of STI-screening visits. Models comparing PrEP and PEP users were further adjusted for age and education. RESULTS: One hundred and nine PrEP and 86 PEP users were included. Increased rates of STIs were observed in the 12 months after PrEP relative to the 12 months prior (IRR: 1.72, CI: 1.22-2.41; aIRR: 1.39, CI 0.98-1.96). PrEP users were also at higher STI risk relative to PEP users (IRR: 2.18, CI: 1.46-3.24; aIRR: 1.76, CI: 1.14-2.71). CONCLUSION: Increased rates of STIs among individuals after initiation of PrEP may suggest greater risk behaviours during the first year on PrEP. Further studies are needed to measure long-term trends in STI acquisition following PrEP initiation.

The EVVA Cohort Study: Anal and Cervical Type-Specific Human Papillomavirus Prevalence, Persistence, and Cytologic Findings in Women Living With HIV.

Background: The risk of anal cancer due to high-risk human papillomavirus (HR-HPV) is higher in women living with human immunodeficiency virus (HIV) than in the general population. We present findings of cervical and anal HPV and cytologic tests at baseline in the EVVA cohort study and HPV persistence data 6 months after baseline. Methods: Semiannual visits included questionnaires, chart reviews, cervical/anal cytologic and cervical/anal HPV testing for 2 years. Genotyping for 36 HPV genotypes was performed using the Roche Linear Array HPV genotyping test. Results: A total of 151 women living with HIV were recruited. At baseline, 75% had anal HPV, 51% had anal HR-HPV, 50% had cervical HPV, and 29% had cervical HR-HPV. Anal HPV-16 and HPV-51 were more frequent in women born in Canada (31% and 29%, respectively, compared with ≤16% for other women). Most anal HR-HPV types detected at 6 months (57%-93%) were persistent from baseline. Findings of anal cytologic tests were abnormal for 37% of women. Conclusions: Anal HPV is highly prevalent in women living with HIV, and type distribution varies by place of birth. High-resolution anoscopy was indicated in more than one third of results. As anal cancer is potentially preventable, these important findings need to be considered when selecting the best approach for anal cancer screening programs.

Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort.

BACKGROUND: There is limited evidence on the efficacy of post-exposure prophylaxis (PEP) for sexual exposures. We sought to determine the factors associated with adherence to treatment and describe the incidence of PEP failures in a Montreal clinic. METHODS: We prospectively assessed all patients consulting for PEP following sexual exposures from October 2000 to July 2014. Patients were followed at 4 and 16 weeks after starting PEP. Treatment adherence was determined by self-report at week 4. Multivariable logistic regression was used to estimate the factors predicting adherence to treatment. RESULTS: 3547 PEP consults were included. Patients were mainly male (92%), MSM (83%) and sought PEP for anal intercourse (72%). Seventy-eight percent (n = 2772) of patients received a prescription for PEP, consisting of Tenofovir/Emtracitabine (TVD) + Lopinavir/Ritonavir (LPV) in 74% of cases, followed by Zidovudine/Lamivudine (CBV) + LPV (10%) and TVD + Raltegravir (RAL) (8%). Seventy percent of patients were adherent to treatment. Compared to TVD+LPV, patients taking CBV+LPV were less likely to adhere to treatment (OR 0.58, 95% CI 0.44-0.75), while no difference was observed for patients taking TVD+RAL (OR 1.15, 95% CI 0.83-1.59). First-time PEP consults, older and male patients were also more adherent to treatment. Ten treated patients seroconverted (0.37%) during the study period, yet only 1 case can be attributed to PEP failure (failure rate = 0.04%). CONCLUSION: PEP regimen was associated with treatment adherence. Patients were more likely to be adherent to TVD-based regimens. Ten patients seroconverted after taking PEP; however, only 1 case was a PEP failure as the remaining patients continued to engage in high-risk behavior during follow-up. One month PEP is an effective preventive measure to avoid HIV infection.

Tolerability is more important than simplicity for treatment durability.

INTRODUCTION: Many studies have shown the superiority of single tablet regimens (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy, adherence and rate of hospitalisation as they offer a low pill burden and once daily dosing. Our objective was to compare the duration of first-line STRs to multi-tablet regimens. METHODS: From our clinical database, we selected patients initiating any of the major first-line regimens between 2007 and 2013. Two STRs, Atripla (ATP) and Complera (CPLR), were compared to three non-STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r). The primary outcome was time to discontinuation of the first-line regimen. The association between regimen type and duration was estimated using Cox proportional hazards models adjusted for age, gender, baseline CD4, baseline viral load, risk factor, site and year of treatment initiation. RESULTS: A total of 743 patients (281 on STRs and 462 on non-STRs) were included. 693 (93%) were male and median age was 43 years. Median length of follow-up was 3.2 years. 56% of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR were less likely to be IDU (p<0.024) and have a baseline HIV-RNA ≥100,000 copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen during the study period. The rate of discontinuation one year after starting ARV depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on 2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model, durability for STR and non-STR was equivalent (aHR=0.83, p=0.108). Compared to patients on ATP, patients on CPLR were less likely to discontinue (HR=0.58, p=0.070). No difference between ATP and the other regimens was observed: HR for 2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11 (p=0.46). CONCLUSIONS: Our findings suggest that STRs do not necessarily result in a more durable treatment. Even with a higher pill burden and/or twice daily dosing, patients initiating therapy with RAL or boosted-PI based regimens were not more likely to discontinue the first-line regimen compared to patients on an STR. Among the STR subgroups, the regimen with better known tolerability conferred more durable treatment. Limitations included our inability to adjust for the patient's adherence to a given regimen.