This study presents the PrEP experience in one of the largest Canadian sexual health clinics evaluating treatment uptake, adherence and behavioral changes in a high-risk population. We prospectively assessed patients receiving TDF-FTC at Clinique l'Actuel from 2011 to August 2015. Patients were evaluated at baseline (BL) and at 3-month follow-up intervals (FU). Treatment adherence and behavioral data were measured by self-report. Risk behavior was defined in terms of condom use and number of sexual partners. Behavioral changes were analyzed by chi-square. 355 patients were prescribed PrEP. Patients were male (99%) and MSM (97%) with a median age of 36 (Range = 18-66y). The main indication for PrEP was regular unprotected anal intercourse (69%). 80% of patients had a history of STIs and 73% reported having >10 sexual partners in the last 12 months. Mean condom use was 49% for both receptive and insertive anal intercourse. 33 patients (9%) never started PrEP; 3/33 seroconverted within 8 months of the consultation. Among patients taking PrEP (n = 322), 69% reported daily use, while 10% took PrEP as needed. No seroconversion was observed. The mean duration of PrEP was 6.5 months. 49 patients (21%) stopped PrEP with 49% of discontinuations occurring in the first 3 months of FU. 39% of discontinuations were due to patients feeling that PrEP was no longer needed and 23% were due to adverse events. Increases in high-risk behavior following PrEP use were observed in 25% of cases, while 43% of patients reported no change in behavior and 32% had improved behavior (p = 0.018). Patients with improved behavior were those that were most at risk to acquire HIV at baseline.

BackgroundThere 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.MethodsWe 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.Results3547 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%).ConclusionPEP 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.

Background: Despite the benefit of maintaining inactive Nucleotide/side reverse transcriptase inhibitors (NRTIs) in salvage regimens, they are associated with increased toxicity and treatment costs. Current evidence suggests that NRTI-sparing regimens in patients failing ART are non-inferior to NRTI-including regimens. This study aimed to evaluate the impact of removing at least one inactive NRTI on virologic, safety, and financial outcomes.Methods: Drug-resistant, virologically suppressed patients with CD4 > 250 cells/ml on a stable regimen of four or more antiretrovirals (ARVs) were enrolled in a 48-week prospective, open-label pilot trial. One inactive NRTI was removed at baseline. Patients taking over five ARVs had a second inactive NRTI removed at 24 weeks. Viral load, CD4 count, and adverse events were assessed at baseline, 24, and 48 weeks.Results: Thirty-one male patients participated. Twenty-nine (94%) patients had lamivudine (3TC) or emtricitabine (FTC) removed and four patients had an additional NRTI removed. One patient was excluded at week 26 for discontinuing an active NRTI. All patients maintained undetectable viral loads at weeks 24 (100%) and 48 [PP=100%; Intent-to-treat (ITT)=97%]. At 48 weeks, patients had a median gain of 20 CD4 (IQR: -50, +133; mean +39) compared to baseline. Three patients exhibited Grade III bilirubin elevation (two Grade II and one Grade III at baseline), which returned to baseline levels. No serious adverse events were observed. Removal of one or two ARVs equated to a mean annual savings of $3319 CDN (11%) and $8630 CDN (24%), respectively.Conclusion: Removing inactive NRTIs in patients with a controlled viral load appears to be safe, maintains virological suppression, and reduces treatment costs.

IntroductionIn HIV+ patients exhibiting multidrug resistance (MDR), NRTIs often have little activity, increased toxicity, drug interactions and add unnecessary treatment costs. The 48 week VERITAS study demonstrated that these patients can have a safe and effective simplification of salvage regimen by removing inactive NRTIs as determined by genotypic data. Virological, immunological, clinical and financial outcomes were evaluated at an additional 96 weeks of follow‐up.Materials and MethodsMDR patients with an undetectable viral load (VL) on a stable regimen containing at least four ARVs (including one inactive NRTI) were enrolled in an open‐label, prospective simplification trial, where one inactive NRTI was removed at baseline (BL). A second NRTI could be removed at week 24 if the regimen contained at least five ARVs at enrolment.Results31 male patients participated. The mean length of treatment was 14 years, with a median CD4 count of 525. The BL regimen consisted of 4 ARVs in 22 patients (71%) and 5 ARVs in 9 patients (29%). 3TC or FTC was removed in 29 patients (94%), and either AZT or TDF was interrupted in 2 others. Four patients had a second NRTI stopped. One patient was removed at W26 as an active NRTI was removed for creatinine elevation. 30 well‐controlled patients continued follow‐up after W48. At W144, six patients had additional changes in their ARV regimen. Half were due to toxicity (jaundice, neuropathy and nephrotoxicity) while the other half were the result of treatment simplification. None of the patients exhibited virologic failure at the time of treatment change and maintained undetectable VLs throughout the entire follow‐up. These six patients had a mean gain of 79 CD4 (p=0.17) compared to baseline. 22 of the 24 patients (92%) with no changes in ARV therapy after W48 had undetectable VLs. The other two had confirmed virologic failure, one with genotypic resistance. All 24 had elevated CD4 counts (mean +118 CD4, p<0.0001). No deaths or serious adverse events were observed. One or two ARV removals translated to a mean annual saving of $3319 CDN (11%) and $8630 (24%) respectively.ConclusionsFinal results indicate that removing one or two inactive NRTIs from a regimen in patients taking four or more ARVs with controlled VL appears to be safe, maintains virological suppression through 144 weeks and significantly reduces treatment costs.

IntroductionMany 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.MethodsFrom 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.ResultsA 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).ConclusionsOur 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.

BACKGROUND:Depression related to interferon-alpha (IFN-α) is common, may reduce adherence, and can be treatment limiting. HIV-HCV coinfected persons experience lower sustained virologic response rates and commonly have psychiatric comorbidities, thus they may benefit from prevention of depression.OBJECTIVE:The aim of the study was to determine whether prophylactic citalopram can increase HCV treatment adherence and reduce the incidence of moderate depression in HIV-HCV coinfected patients initiating PEG-IFN-α/ribavirin therapy.METHODS:This was an investigator-initiated Canadian multicenter randomized, double-blind placebo-controlled trial. HIV-HCV coinfected patients were randomized in a 1:1 ratio to receive citalopram or placebo 3 weeks prior to starting PEG-IFN-α2b/ribavirin, stratified by study center and HCV genotype. The protocol design permitted the comparison of prophylaxis with the treatment of emergent depression. The primary outcomes were adherence (assessed through questionnaire and returned medication) and time to moderate depression measured by Beck Depression Inventory-II (BDI- II) score greater than 15, confirmed 2 weeks apart.RESULTS:Seventy-six patients (36 citalopram/40 placebo) were randomized. Overall adherence was high, ranging from 95% (week 12) to 91% (week 48). There was no difference between arms with respect to mean or median adherence at any study time point. Cumulative incidence of moderate depression did not differ significantly by group (log rank P = .32). The hazard ratio for moderate depression was 0.81 (95% CI, 0.26 to 2.54) for citalopram compared with placebo when adjusted for baseline BDI-II score.CONCLUSIONS:A strategy of prophylactic citalopram compared to treatment of emergent depression was not associated with higher adherence or a reduction in treatment-limiting depression nor did it significantly reduce depressive symptoms among HIV-HCV coinfected persons during treatment for HCV.

BACKGROUND:Current treatment guidelines recommend the use of tenofovir (TDF) and emtricitabine (FTC) along with a third agent to treat HIV-positive adults. However, other treatment options, including the use of abacavir (ABC) and lamivudine (3TC) when used with ritonavir-boosted darunavir (DRV/r), have rarely been studied.OBJECTIVE:We evaluated the safety and efficacy of the coformulation of ABC/3TC administered with DRV/r in treatment-naïve and treatment-experienced patients.METHODS:HIV-infected adults who received an open-label combination of ABC/3TC/ DRV/r were followed in a community clinic in Montréal. Patients had no resistance to any of the compounds in their regimen. Viral load (VL), CD4 cell count, AST, ALT, and creatinine levels were examined throughout the 48 weeks of follow-up.RESULTS:Sixty-seven patients with a mean age of 45 years were enrolled. Two did not return for follow-up and were excluded. Thirty-five (52%) were treatment- experienced and the remaining were treatment-naïve. HLA-B*5701 test results were available for 56 patients and none were positive. At baseline, mean VL was 4.8 log for treatment-naïve and 2.3 log for experienced patients. Twelve patients discontinued the study regimen prior to reaching the endpoint. At week 48, 79% had a VL <50. Median CD4 cell gain was higher among treatment-naïve patients (273 cells) than among treatment-experienced patients (102 cells) (P = .002). No patient experienced any grade 2 or higher liver enzyme elevation throughout the study.CONCLUSIONS:The new combination of ABC/3TC/DRV/r demonstrates a high rate of antiviral activity with no major toxicity. The drug combination appears to be generally safe and well tolerated.

Background In Québec it is estimated that 1/3 of those infected do not know their HIV status, that HIV is diagnosed late in 41%, and that sex during primary infection is an important driver of the epidemic. In late 2008 Clinique l'Actuel launched a testing campaign tailored to MSM in Montréal using free rapid tests with the goal of increasing early diagnosis of HIV. In this study we evaluated the feasibility of and potential impact of facilitated access to rapid HIV-testing. Methods Rapid HIV-tests offered through dedicated clinics were widely advertised in Montréal's MSM community. Patients calling for testing deemed at high risk were given appointments within 2 weeks, where they filled out a short questionnaire, received medical consultation routine STI screening, pre- and post-test counselling and their HIV test results within the hour. Ongoing support, care, and treatment were offered to those testing positive. Results Over 9 months 2500 received HIV testing. 98% were men and median age was 34 (IQR=26–41). Of these patients, 42% were new to the clinic, 10% had never been tested previously, and 29% had not been tested within the past 2 years. 93% reported they were more likely to undergo repeat screening because of rapid testing. 2% were found to be HIV positive. Of these, 60% cited the rapid test as the primary reason for undergoing screening. 33% of those testing positive were in primary infection, as compared to 18% the previous year at Clinique l'Actuel (p=0.062) and 11% in Québec. Conclusion Facilitated access to rapid HIV testing can increase uptake in high-risk patients. This may increase early HIV diagnosis and intervention to decrease transmission.

BACKGROUND:Human immunodeficiency virus (HIV)-seropositive men who have sex with men (MSM) are at risk for anal intraepithelial neoplasia (AIN) and cancer. The goal of this study was to identify risk factors associated with high-grade AIN (AIN-2,3) in HIV-positive MSM, including the receipt of highly active antiretroviral therapy (HAART). METHODS:A cohort study involving 247 HIV-seropositive MSM receiving HAART or initiating HAART was followed up every 6 months for 3 years with human papillomavirus (HPV) testing and high-resolution anoscopy to identify predictors of AIN-2,3 by Cox regression analysis and period prevalence logistic regression. RESULTS:AIN-2,3 was observed during the study in 132 (53%) of 247 participants. The progression rate to AIN-2,3 from a lesser abnormality at baseline was 12.8 cases per 1000 person-months (95% confidence interval [CI], 9.8-16.5 cases per 1000 person-months). The risk of AIN-2,3 increased with age (odds ratio [OR], 3.09 [95% CI, 1.12-8.52] for men 40-49 years of age and 4.78 [95% CI, 1.29-17.73] for men >50 years of age, compared with men <40 years of age) and for men whose CD4+ cell counts were <50 cells/mm(3) before starting HAART (OR, 14.40 [95% CI, 1.45-143.58]). Men who had been receiving their current HAART regimen for >4 years had a marginally significant lower risk of AIN-2,3 after adjustment for HPV (OR, 0.28 [95% CI, 0.07-1.06]) compared with those treated for <4 years. Anal HPV type 16 (HPV16) or type 18 (HPV18) infections (OR, 14.18; [95% CI, 3.51-57.32]) and HPV16 and HPV18 co-infection (OR, 31.03 [ 95% CI, 5.68-169.60]) were strongly associated with progression to AIN-2,3. CONCLUSION:HPV16 and HPV18 infections and a low nadir CD4+ cell count increase the risk of AIN-2,3. Receiving the same HAART regimen for >4 years may contribute some benefit against AIN-2,3.

Background Often STIs are not diagnosed and not treated because people don't have access to appropriate healthcare screening facilities and to care. At Clinique l'Actuel (Montreal, Canada) we developed Gay Screen Clinic (GSC) as a new concept giving rapid access to men who have sex with men (MSM) to an appointment for STI screening. We then assessed the extend and risk factors of STIs in a population of men having sex with men (MSM) attending the GSC. Methods We did a retrospective analysis of the last 1000 attendees to the GSC at Clinique l'Actuel in 2009−2010. Multivariable analyses were conducted to identify the factors associated with history of STIs. Results Participants were all MSM with a mean age of 32 years (ranged from 18 to 70 y). In total, 50% (n=506) of them self reported history of STIs and 236(24%) of them had a positive sexual health screen at this visit. STI diagnoses included genital herpes (n=105, 14 %), condylomes (n=79, 8%), syphilis (n=43, 5%), chlamydia infection (n=32, 3%), HIV (n=10, 1%), Gonorrhoea (n=9, 1%) and HCV (n=5, 1%). 32% of the attendees had sexual relations in bath houses and 43% with anonymous contacts. In multivariate analyses, past history of STI was significantly associated with higher age (OR=1.02, p=0.001), higher number of sexual partners in the last 12 months (OR=1.02, p=0.015), having sexual contact in bath houses (OR=1.46, p=0.021) and with unknown partners met through internet or in backrooms (OR=1.53, p=0.004), using recreational drugs (OR=2.01, p=0.001) and having only male partners (OR=1.60, p=0.023) rather than male and female sexual partners. Conclusions STIs were common among non HIV MSM attending the GSC in Montreal. Even after many years of prevention campaign MSM still have high risk sexual behaviour. Physician should routinely enquire about drug use of their patients in order to prevent new STIs. Targeting specific sexual networks is needed to be more effective.

Background It was estimated in 2005 that 13% of men who have sex with men (MSM) in Montréal were HIV-positive, and that 23% of these were not aware of their diagnosis. Clinique l'Actuel introduced a pilot rapid HIV testing program using the MedMira kit in 2008. The objective of this study was to describe the sensitivity and specificity of rapid HIV tests in a community based, high HIV risk setting. Methods An advertising campaign encouraged MSM and others at risk for HIV to undergo testing through dedicated clinics offering rapid HIV tests. Patients calling for testing deemed at high risk were given appointments within 2 weeks, where they filled out a short questionnaire, received medical consultation routine STI screening, pre- and post- test counselling and their HIV test results within the hour. Those consenting received with a MedMira or and INSTI rapid test and regular HIV screening. Any positive result was confirmed by Western blot. Results 2500 individuals were tested: 98% men with a median age of 34 (IQR: 26–41). For the MedMira test there were 43 true positives, 2295 true negatives, 13 false positives and four false negatives. 145 patients received the finger-prick INSTI test giving two true positives and 143 true negatives. For MedMira, sensitivity was 91.5% and specificity 99.5% while both figures were 100% for INSTI. The four false negatives were also negative by standard ELISA but positive for P24 antigen. Patients testing positive for HIV had significantly more history of previous STI than those testing negative (p=0.041). Conclusion In this setting sensitivity and specificity of the rapid tests used was comparable to standard testing. Acute seroconversion likely explains the four false negatives. As with conventional testing, rapid testing requires adequate counselling about the possibilities of a false negative test. In high-risk populations, routine STI screening should always be performed together with HIV screening.

Methods A retrospective analysis of the clients who attend the “Gay Screening Clinic” (GSC) at Clinique medical l'Actuel (Montreal, Canada) between May 2009 and April 2010 was conducted. Results Among the 1010 patients included in the analyses we found five cases of new HCV infection which seems to be acquired by sexual transmission. All of them were male and MSM, none of the cases had previous history of IDU, but three reported having had sexual relation with IDU partners. All of them were previously vaccinated for Hepatitis A and B and screened for HIV. None of them were coinfected with HIV, but one was coinfected with Syphilis and one with Gonorrhoea. Patients infected with HCV were older than non HCV patients (37 years vs 32 years) and had a higher number of sexual partners during the last 12 months (16 part. vs 9 for the non HCV patients). One of the HCV cases reported not having anal intercourse, two reported having had occasional unprotected anal intercourse and two reported always using condom for anal intercourse. Conclusions As in other urban centers, cases of sexually transmitted HCV had also been found in Montreal. This prevalence of 0.5% is very low compared to our HIV population in which the prevalence of sexually transmitted HCV is 3%. The particularity of MSM with recently acquired HCV by sexual transmission seems to be related to their engagement in sexual relation with high number of concurrent partners.

Recently HIV-infected individuals have virus-specific responses characterized by IFN-gamma/IL-2 secretion and proliferation rarely seen in chronic infection. To investigate the timing of loss of HIV-specific T-cell function, we screened cells from 59 treatment-naïve HIV-infected individuals with known dates of infection for proteome-wide responses secreting IFN-gamma/IL-2 and IFN-gamma alone by ELISPOT. HIV peptide-specific proliferation was assessed by carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution. The contribution of IFN-gamma/IL-2 and IFN-gamma-only secretion to the total HIV-specific response was compared in subjects infected <6, 6-12, and 12-36 mo earlier. The frequency of IFN-gamma/IL-2-secreting cells fell, while that of IFN-gamma-only secretion rose with time from infection. HIV peptide-specific proliferative responses were almost exclusively mediated by CD8(+) T cells, and were significantly lower in cells obtained from the 12-36 mo versus < 6 mo post-infection groups. By the second year of infection there was a significant difference in these functions compared to those assessed within 6 mo.

Objectives:To assess levels of episomal and integrated human papillomavirus type 16 (HPV-16) loads in HIV-seropositive men who have sex with men (MSM) in anal infection and to study the association between episomal and integrated HPV-16 loads and anal intraepithelial neoplasia (AIN). Study design:A cohort study of 247 HIV-positive MSM followed each 6 months for 3 years. Overall, 135 (54.7%) men provided 665 HPV-16-positive anal samples. Methods:Episomal and integrated HPV-16 loads were measured with quantitative real-time PCR assays. HPV-16 integration was confirmed in samples with a HPV-16 E6/E2 of 1.5 or more with PCR sequencing to demonstrate the presence of viral–cellular junctions. Results:The HPV-16 DNA forms in anal samples were characterized as episomal only in 627 samples (94.3%), mixed in 22 samples (3.3%) and integrated only in nine samples (1.4%). HPV-16 episomal load [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1–2.1], number of HPV types (OR = 1.4, 95% CI 1.1–1.8) and current smoking (OR = 4.8, 95% CI 1.3–18.6) were associated with high-grade AIN (AIN-2,3) after adjusting for age and CD4 cell counts. Integrated HPV-16 load was not associated with AIN-2,3 (OR = 0.7, 95% CI 0.4–1.1). Considering men with AIN-1 at baseline, four (16.7%) of the 24 men who progressed to AIN-2,3 had at least one sample with integrated HPV-16 DNA compared with three (23.1%) of 13 men who did not progress (OR = 0.7, 95% CI 0.2–3.8; P = 0.64). Integration was detected in similar proportions in samples from men without AIN, with AIN-1 or AIN-2,3. Conclusion:High episomal HPV-16 load but not HPV-16 integration load measured by real-time PCR was associated with AIN-2,3.