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Background Lenacapavir (LEN), a potent first-in-class inhibitor of HIV-1 capsid function, is in development as a long-acting agent for treatment and prevention of HIV-1. Methods CAPELLA is an ongoing, phase 2/3 study in heavily treatment-experienced (HTE) people with HIV-1 (PWH) with multidrug-resistance. 36 participants were randomized (2:1) to add oral LEN or placebo to their failing regimen. At D15, those on oral LEN received subcutaneous (SC) LEN 927 mg (Q6M); those on placebo started the oral LEN lead-in, followed by SC Q6M. All randomized participants initiated an investigator-selected, optimized background regimen (OBR) at D15. An additional 36 participants started OBR concurrent with LEN (oral lead-in → SC) in a non-randomized cohort. We report the Week (W) 52 efficacy and safety results from both cohorts. Results Of 72 participants enrolled, 25% were female, 38% Black, median age 52 years, 64% had CD4 < 200 cells/µL, 46% had HIV-1 resistant to all 4 major classes (NRTI, NNRTI, PI, INSTI), and 53% had OBR with 1 or no fully active agents. At W52, 78% (56/72) achieved VL< 50 c/mL and 82% (59/72) achieved VL< 200 c/mL via FDA Snapshot algorithm. CD4 count increased by a median 84 cells/µL (Q1 to Q3: 21 to 153) and the proportion of participants with CD4 count ≥200 cells/ul increased from 36% at baseline to 68% at W52. Ten participants had emergent LEN resistance (8 previously reported); 4 of 10 subsequently suppressed. The median (range) duration of follow up on LEN was 71 (13–111) weeks. One participant discontinued due to injection site nodule (Grade 1). The most common injection site reaction (ISR) was swelling (28% [20/72] and 17% [12/70] after the 1st and 2nd SC doses, respectively). Most ISRs were mild or moderate. The most common AEs (excluding injection site reactions) were nausea and diarrhea (14% each). Conclusion In HTE PWH, subcutaneous LEN was well tolerated and in combination with OBR led to high and sustained rate of virologic suppression at W52. These results support the potential role for LEN for treatment of multi-drug resistant HIV-1 infection. Disclosures Sorana Segal-Maurer, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|JANSSEN THERAPEUTICS: Honoraria|ViiV: Honoraria Benoit Trottier, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Jason Brunetta, M.D., Gilead Canada: Advisor/Consultant|Gilead Canada: Honoraria|Gilead Canada: Conference Attendance Sponsorship|Viiv Canada: Advisor/Consultant Hui Wang, PhD, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds Nicolas A. Margot, MA, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds Hadas Dvory-Sobol, PhD, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds Martin S Rhee, MD, Gilead Sciences: Stocks/Bonds Jared Baeten, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Jean-Michel Molina, MD; PhD, GIlead: Board Member|GIlead: Grant/Research Support|Merck: Board Member|Merck: Expert Testimony|ViiV: Board Member.

Summary Background In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov , number NCT02842086 . Findings Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p Interpretation Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Funding Gilead Sciences.

Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan–Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30–45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4–5.4], baseline log10viral load [VL]=4.6 [IQR = 4.1–5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217–440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan–Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p 10of baseline VL (aHR = 1.94; 95%CI = 1.58–2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.

We assessed renal and metabolic changes associated with switching from tenofovir disoproxil fumarate (TDF)– to tenofovir alafenamide (TAF)–containing regimens among patients with HIV at the Maple Leaf Medical Clinic, Toronto, Canada. Using an electronic medical records retrospective chart review from July 2005 to December 2019, 651 patients aged ≥16 years taking TDF-containing regimens for ≥6 months who switched to TAF-containing regimens for ≥6 months were included. Change in estimated glomerular filtration rate (eGFR) was examined at 12-month follow-up. Secondary outcomes included change in urine albumin-to-creatinine ratio, serum phosphate, alkaline phosphatase (ALP), cholesterol markers, HbA1C, and weight. After 12 months, eGFR increased in 63% of the baseline eGFR 2 group (mean change [SD] = +5.1 [10.8], p = 0.002), 52% for the baseline eGFR = 60–90 mL/min/1.73 m2 group (+0.5 [10.4], p = 0.490), and 26% for baseline eGFR >90 mL/min/1.73 m2 group (−7.2 [11.2], p 2).

Background: In DISCOVER, a multinational randomized controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate demonstrated noninferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. Here, we report outcomes analysed after all participants had completed 96 weeks of follow up. Methods: Adult cisgender men and transgender women who have sex with men with a high risk of acquiring HIV were randomly assigned (1:1) to either of two study arms. This trial is registered with ClinicalTrials.gov, NCT02842086. Findings: 5,387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2,694) or emtricitabine and tenofovir disoproxil fumarate (n=2,693), contributing 10,081 person-years (PY) of follow-up. There were eight HIV infections in emtricitabine and tenofovir alafenamide users (0·16 infections/100 PY [95% CI 0·07–0·31]), and 15 in emtricitabine and tenofovir disoproxil fumarate users (0·30 infections/100 PY [0·17–0·49]). Emtricitabine and tenofovir alafenamide was noninferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the infection rate ratio (IRR) was less than the prespecified noninferiority margin of 1·62 (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78% to 82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across arms (21 per 100 PYs for rectal gonorrhea and 28 per 100 PY for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to demonstrate superiority over emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarkers. There was more weight gain among emtricitabine and tenofovir alafenamide users (median weight gain 1·7 kg vs. 0·5 kg, p

Following cardiovascular events (CVE) among people living with HIV (PLWH) is essential. Abacavir (ABC)'s impact on CVE challenges clinicians. We characterized CVE at our HIV clinic associated with ABC versus tenofovir disoproxil fumarate (TDF). This was a retrospective study of PLWH who started combination antiretroviral therapy with no prior CVE. Patients were evaluated as antiretroviral naive or antiretroviral experienced. Regimens included the following: always-ABC, always-TDF, first-ABC-switched-to-TDF, and first-TDF-switched-to-ABC regimens. Frequencies, rates, and Poisson regression were used to analyze CVE (cardiovascular/cerebrovascular) and were stratified with an

Background Rates of bacterial sexually transmitted infections (STIs) continue to rise among gay, bisexual, and other men who have sex with men (GBMSM) globally. Testing and treatment can prevent morbidity and transmission. However, testing rates remain suboptimal. Methods In 2018, we conducted an online cross-sectional survey to explore STI testing ordering practices, 14 potential barriers for testing and 11 possible ways to improve testing from the perspective of health care providers in Toronto, Ontario. An estimated 172 providers were invited from primary care and sexual health clinic settings. Providers were eligible to complete the survey if they provided care for ≥1 GBMSM per week and were involved in the decision-making process in providing STI tests. We used descriptive statistics to summarize survey responses. Results Ninety-five providers (55% response rate) participated, of whom 68% worked in primary care and 32% in sexual health settings. Most (66%) saw ≤10 GBMSM clients per week. In primary care (65%) and sexual health (40%) clinic settings, insufficient consultation time was the most common barrier to STI testing. In primary care, other common barriers included difficulty introducing testing during unrelated consultations (53%), forgetting (47%), and patients being sexually inactive (31%) or declining testing (27%). The following were most likely to improve testing: express/fast-track testing services (89%), provider alerts when patients are due for testing (87%), patient-collected specimens (84%), nurse-led STI testing (79%), and standing orders (79%). Conclusions Promising interventions to improve bacterial STI testing included initiatives that simplify and expedite testing and expand testing delivery to other health care professionals.

Men who have sex with men (MSM) are disproportionately affected by anal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection. Currently, the nonavalent HPV vaccine provides coverage against nine HPV genotypes, including seven HR-HPV genotypes. Here, we characterize anal HR-HPV genotype distribution and associated risk factors in MSM from Toronto, Canada recruited between September 2010 and June 2012. Wilcoxon–Mann–Whitney test was used for continuous variables, Chi-square test was performed for categorical variables, and a multivariable model using logistic regression was created to assess for correlates of anal HR-HPV infection. A total of 442 MSM were recruited, with a median age of 45 (IQR 38–50) and an overall HPV prevalence of 82%. The prevalence of any HR-HPV infection was 65.3% and 50.7% in the HIV-positive and HIV-negative MSM, respectively. No participant tested positive for all genotypes covered by the nonavalent vaccine. HIV status (aOR 1.806; 95% CI 1.159–2.816), smoking (aOR 2.176; 95% CI 1.285–3.685) and the number of lifetime sexual partners (aOR 2.466; 95% CI 1.092–5.567) were independent risk factors for anal HR-HPV infection. Our findings will be useful to inform HPV vaccine rollout and HPV prevention strategies in Canadian MSM.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL

Background Bacterial STI testing is a necessary component of sexual health care for MSM living with and at risk for HIV. Guidelines recommend testing at least once a year or more often if at ongoing risk. As part of a larger mixed methods study with the overall goal to prioritize new STI testing interventions, our aim was to determine barriers and facilitators to offering bacterial STI testing to MSM according to healthcare providers in Toronto, Canada. Methods In 06/2018–07/2018, we circulated invitations for an online, anonymous survey to an estimated 172 providers in Toronto. Providers were eligible if they provided care for ≥1 MSM per week and were involved in the decision-making process in providing a STI test (e.g., taking sexual histories, ordering tests). Results Of 93 respondents, 68% worked in primary care, 32% worked in public health/sexual health clinics, 70% were physicians and 30% were nurses or other allied health professionals. Most (67%) saw between 1–10 MSM clients per week. Among respondents working in primary care (n=63), barriers to offering testing ‘sometimes’ or more often were: insufficient consultation time (64%), difficulty introducing testing during unrelated consultations (52%), forgetting to offer testing (46%), patient reporting no sexual activity (30%) and patient refusal (25%). Among all respondents, preferred practice changes to improve testing were: express testing/fast-track testing services (89%), provider alerts when patients are due for testing (87%), selfcollected specimen sampling by patients (84%), standing orders for tests (79%), and nurse-led STI testing (78%). Primary care providers were more in favour of provider alerts whereas providers at sexual health clinics favoured patient reminders. Conclusion Among those whose practice incorporated sexual health care for MSM, providers were in favour of initiatives to simplify and expedite bacterial STI testing (including self-collection of samples), prompts/reminders for testing, and expanding testing delivery to other healthcare professionals. Disclosure No significant relationships.

Background: HIV-positive and HIV-negative (gay, bisexual, and other) men who have sex with men (MSM) have experienced a dramatic increase in bacterial sexually transmitted infections (STIs)—syphilis, gonorrhea, and chlamydia. STI testing and treatment mitigate adverse health outcomes and substantially reduce transmission; yet, testing rates remain below recommended levels. Innovation is needed to produce the required increases in testing levels, frequency, and the use of appropriate testing technologies in ways that are engaging, nonstigmatizing, and acceptable to men. Objective: The aim of this study is to build consensus with regard to interventions with the greatest potential for improving local STI testing services for MSM communities in Toronto, Canada. Methods: Following a literature review of evidence regarding the effectiveness of novel testing interventions, and focus groups, and surveys to describe local barriers and facilitators of testing among MSM, we will conduct a Web-based, modified Delphi study (e-Delphi). We will form expert panels of community members and STI test providers. Panelists will rate potential interventions in terms of their priority, using a 7-point Likert scale from definitely not a priority to definitely a priority. They will also rank their preferences by selecting their top 3 preferred interventions. Surveys will be distributed in 3 rounds, with feedback on the distribution of responses from preceding rounds provided in rounds 2 and 3. We will define consensus as having ≥60% (18/30) members indicate a preference within 2 adjacent response points. Qualitative data on disagreements will be obtained using open-ended text responses to explain for ratings and rankings that are different from the majority. Results: On the basis of a literature review and identification of barriers and facilitators to STI testing among community members and test providers in Toronto, we have selected 8 potential interventions for inclusion in the e-Delphi panel surveys. These include 4 interventions that streamline STI testing for asymptomatic individuals, 2 interventions that are targeted at clients and 2 interventions that are targeted at providers. Conclusions: Findings will provide community direction for informed decision making regarding the implementation of STI testing interventions in this setting. They will characterize the intervention climate for innovation to STI testing services, including perceived needs for changes to test delivery, relative priorities for change, and readiness for implementation. These methods may be transferable to other urban jurisdictions experiencing similar epidemics and for other contexts where stakeholder input is needed to manage sensitive areas of concern. International Registered Report Identifier (IRRID): PRR1-10.2196/13801

BACKGROUND HIV-positive and HIV-negative (gay, bisexual, and other) men who have sex with men (MSM) have experienced a dramatic increase in bacterial sexually transmitted infections (STIs)—syphilis, gonorrhea, and chlamydia. STI testing and treatment mitigate adverse health outcomes and substantially reduce transmission; yet, testing rates remain below recommended levels. Innovation is needed to produce the required increases in testing levels, frequency, and the use of appropriate testing technologies in ways that are engaging, nonstigmatizing, and acceptable to men. OBJECTIVE The aim of this study is to build consensus with regard to interventions with the greatest potential for improving local STI testing services for MSM communities in Toronto, Canada. METHODS Following a literature review of evidence regarding the effectiveness of novel testing interventions, and focus groups, and surveys to describe local barriers and facilitators of testing among MSM, we will conduct a Web-based, modified Delphi study (e-Delphi). We will form expert panels of community members and STI test providers. Panelists will rate potential interventions in terms of their priority, using a 7-point Likert scale from definitely not a priority to definitely a priority. They will also rank their preferences by selecting their top 3 preferred interventions. Surveys will be distributed in 3 rounds, with feedback on the distribution of responses from preceding rounds provided in rounds 2 and 3. We will define consensus as having ≥60% (18/30) members indicate a preference within 2 adjacent response points. Qualitative data on disagreements will be obtained using open-ended text responses to explain for ratings and rankings that are different from the majority. RESULTS On the basis of a literature review and identification of barriers and facilitators to STI testing among community members and test providers in Toronto, we have selected 8 potential interventions for inclusion in the e-Delphi panel surveys. These include 4 interventions that streamline STI testing for asymptomatic individuals, 2 interventions that are targeted at clients and 2 interventions that are targeted at providers. CONCLUSIONS Findings will provide community direction for informed decision making regarding the implementation of STI testing interventions in this setting. They will characterize the intervention climate for innovation to STI testing services, including perceived needs for changes to test delivery, relative priorities for change, and readiness for implementation. These methods may be transferable to other urban jurisdictions experiencing similar epidemics and for other contexts where stakeholder input is needed to manage sensitive areas of concern. INTERNATIONAL REGISTERED REPOR PRR1-10.2196/13801

Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF) has high efficacy and improved renal and bone safety in multiple phase 3 trials; TAF single agent is being studied in 2 phase 3 trials in patients with chronic hepatitis B. We report the results of an open-label, noncomparative switch study evaluating the efficacy and safety of E/C/F/TAF in HIV/hepatitis B virus (HBV)–coinfected adults. At 48 weeks, 91.7% of the 72 participants maintained or achieved virologic suppression (HIV-1 RNA

The resistance profiles for patients on first-line antiretroviral therapy (ART) regimens after viremia have not been well studied in community clinic settings in the modern treatment era.To determine time to viremia and the ART resistance profiles of viremic patients.HIV-positive patients aged ≥16 years initiating a three-drug regimen were retrospectively identified from 01/01/06 to 12/31/12. The regimens were a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs) and a third agent: a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (II). Time to viremia was compared using a proportional hazards model, adjusting for demographic and clinical factors. Resistance profiles were described in those with baseline and follow-up genotypes.For 653 patients, distribution of third-agent use and viremia was: 244 (37%) on PIs with 80 viremia, 364 (56%) on NNRTIs with 84 viremia, and 45 (7%) on II with 11 viremia. Only for NNRTIs, time to viremia was longer than PIs (p = 0.04) for patients with a CD4 count ≥200 cells/mm(3). Of the 175 with viremia, 143 (82%) had baseline and 37 (21%) had follow-up genotype. Upon viremia, emerging ART resistance was rare. One new NNRTI (Y181C) mutation was identified and three patients taking PI-based regimens developed NRTI mutations (M184 V, M184I, and T215Y).Time to viremia for NNRTIs was longer than PIs. With viremia, ART resistance rarely developed without PI or II mutations, but with a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimens.

BACKGROUND: Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate. METHODS: In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA

Background Patient-reported outcomes (PROs) can provide important information about treatment tolerability in HIV-1-infected patients. Objective The aim of this study was to evaluate PROs following switching from a boosted protease inhibitor-based regimen to the single-tablet regimen (STR) of rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in the 48-week open-label Switching Boosted PI to Rilpivirine in Combination with Truvada as a Single-Tablet Regimen (SPIRIT) trial. Methods In the open-label SPIRIT trial, patients were randomized to receive an STR of RPV/FTC/TDF (n = 317) for 48 weeks or stay on their baseline regimen of a ritonavir-boosted protease inhibitor and two nucleoside/nucleotide analog reverse transcriptase inhibitors (PI + RTV + 2NRTIs, n = 159) for 24 weeks before switching to RPV/FTC/TDF for another 24 weeks. PRO assessments included the HIV Treatment Satisfaction Questionnaire (TSQ) and the HIV Symptom Index Questionnaire (SIQ). Results At week 24, the mean HIV TSQ improvement from baseline was significantly greater in the RPV/FTC/TDF group than the PI + RTV + 2NRTIs group (p

Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate.EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917.The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2·5%] of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI -1·5 to 2·2; p0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 [SD 1·1] vs 0·1 [1·1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen.Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression.Janssen.

Objective(s): To systematically review literature on brief screening tools used to detect and differentiate between normal cognition and neurocognitive impairment and HIV-associated neurocognitive disorders (HANDs) in adult populations of persons with HIV. Design: A formal systematic review. Methods: We searched six electronic databases in 2011 and contacted experts to identify relevant studies published through May 2012. We selected empirical studies that focused on evaluating brief screening tools (0.70); however, none of the tools differentiated HAND conditions well enough to suggest broader use. There were significant methodological shortcomings noted in most studies. Conclusion: HDS and IHDS perform well to screen for HAD but poorly for milder HAND conditions. Further investigation, with improved methodology, is required to understand the utility of newer screening tools for HAND; further tools may need to be developed for milder HAND conditions.

Background Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may persist in the gut mucosa and elsewhere in individuals on long-term HAART. Objective We conducted a double-blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4(+) T cells in blood and the sigmoid colon (gut). Methods Long-term (>4 years) virologically suppressed HIV-infected individuals on standard HAART were randomized 1 : 1 in a double-blind fashion to receive raltegravir (400 mg twice/day) or placebo for 48 weeks. After week 48, all participants were treated with raltegravir to week 96. Blood and sigmoid biopsies were sampled and the frequency of CD4(+) T cells carrying HIV-1 proviral DNA was determined. Results Twenty-four study patients were recruited. At 48 weeks, no difference was apparent between participants receiving raltegravir or placebo in blood HIV-1 proviral levels (P = 0.62), CD4(+) T-cell counts (P = 0.25) and gut proviral loads (P = 0.74). Similarly, prolonged raltegravir intensification up to week 96 had no further effect on both blood and gut HIV-1 proviral loads and blood CD4(+) T-cell counts. Conclusion In long-term virologically suppressed patients on standard HAART, intensification with raltegravir did not result in further decay of CD4(+) T cells carrying HIV-1 proviral DNA in either the blood or gut after 48 or 96 weeks of therapy, or in any increase in CD4(+) T-cell counts.

Objective: To compare the immunologic effectiveness of raltegravir–maraviroc (R+M+)-based regimens with raltegravir-based regimens that do not include maraviroc (R+M−) in treatment-experienced patients in clinical practice. Methods: We conducted a retrospective study of treatment-experienced HIV-infected adults receiving either R+M+- or R+M−-based therapy. Longitudinal CD4 counts were analyzed using a linear mixed model. Results: One hundred and fifty-six patients were included in the analysis, of whom 32 were receiving R+M+ and 124 R+M−. Mean baseline CD4 counts in patients on R+M+ and R+M− were 463.8 and 442.3 cells/mm3, respectively ( P = .67). In multivariable mixed models, a baseline viral load ≥50 copies/mL was significantly associated with CD4 change during follow-up ( P < .0001). No difference between R+M+ and R+M− was observed during follow-up ( P = .81). Conclusion: CD4 cell recovery was similar among patients receiving either R+M+- or R+M−-based therapy during a 24-month period of follow-up.

Background: Although both tipranavir and darunavir are important options for the management of patients with multidrug resistant HIV, there are at present no studies comparing the effectiveness and safety of these 2 antiretroviral drugs in this population of patients. Objective: To compare the effectiveness and safety of ritonavir (TPV/r)- and darunavir/ritonavir (DRV/ r)-based therapies in treatment-experienced patients (n = 38 and 47, respectively). Methods: Multicenter, retrospective cohort study. Results: The median baseline viral load and CD4 count were 4.7 copies/mL (interquartile range [IQR] 4.3, 5.2) and 168 cells/mm 3 (IQR 80, 252) for TPV/r patients and 4.7 copies/mL (IQR 3.7, 5.1) and 171 cells/mm3 (IQR 92, 290) for DRV/r patients. The median number of years on antiretroviral therapy (ART) prior to starting DRV/r or TPV/r were 12.7 (10.2-15.5) and 10.5 (8.4-12.6), respectively (P < .01). Current raltegravir (RAL) use (odds ratio [OR] 5.53, 95% CI 1.08-28.34) was significantly associated with virologic suppression at week 24 in multivariable logistic regression models, whereas the use of TPV/r was not significantly associated with virologic suppression compared to DRV/r (OR 0.93, 95% CI 0.27-3.18, P = .91). Conclusion: No significant difference was observed between DRV/r and TPV/r in terms of virologic suppression.

Background Non-disclosure criminal prosecutions among gay, bisexual and other men who have sex with men (MSM) are increasing, even though transmission risk is low when effective antiretroviral treatment (ART) is used. Reduced HIV testing may reduce the impact of HIV “test and treat” strategies. We aimed to quantify the potential impact of non-disclosure prosecutions on HIV testing and transmission among MSM. Methods MSM attending an HIV and primary care clinic in Toronto completed an audio computer-assisted self-interview questionnaire. HIV-negative participants were asked concern over non-disclosure prosecution altered their likelihood of HIV testing. Responses were characterized using cross-tabulations and bivariate logistic regressions. Flow charts modelled how changes in HIV testing behaviour impacted HIV transmission rates controlling for ART use, condom use and HIV status disclosure. Results 150 HIV-negative MSM were recruited September 2010 to June 2012. 7% (9/124) were less or much less likely to be tested for HIV due to concern over future prosecution. Bivariate regression showed no obvious socio/sexual demographic characteristics associated with decreased willingness of HIV testing to due concern about prosecution. Subsequent models estimated that this 7% reduction in testing could cause an 18.5% increase in community HIV transmission, 73% of which was driven by the failure of HIV-positive but undiagnosed MSM to access care and reduce HIV transmission risk by using ART. Conclusions Fear of prosecution over HIV non-disclosure was reported to reduce HIV testing willingness by a minority of HIV-negative MSM in Toronto; however, this reduction has the potential to significantly increase HIV transmission at the community level which has important public health implications.

The long-term safety and efficacy of products used in the correction of HIV-associated facial lipoatrophy (FLA) are largely unknown. The purpose of this study was to describe the long-term efficacy and safety of polyalkylimide gel (PAIG) in the treatment of HIV-associated FLA. In this open-label, randomized, single-center study, 31 HIV-positive individuals (median age 48 years (interquartile ranges (IQR) 45, 55, 97% male) with FLA were randomized to immediate (week 0 and six) or delayed (week 12 and 18) PAIG injections. Week 96 endpoints included change in FLA severity scores (FLSS) (five-point scale), proportion of patients with adverse events, and changes in quality of life, depression and anxiety using validated surveys. Results at week 96 were available for 28 patients. Adverse events, including swelling, redness, bruising and pain, were mild, and resolved after a median of three days following the injection. At week 96, median changes in physician and patient FLSS scores were -2 (IQR -3, -1; p

Direct comparison of the efficacy and safety of different agents is needed to guide selection of optimal treatment regimens for therapy-naive HIV-1-infected patients.: Gemini was a 48-week, multicenter, open-label, noninferiority trial in treatment-naive HIV-1-infected adults randomized to either saquinavir/ritonavir (SQV/r) 1000 mg/100 mg twice a day or lopinavir/ritonavir (LPV/r) 400 mg/100 mg twice a day, each with emtricitabine/tenofovir 200 mg/300 mg every day.: A similar proportion of participants in the SQV/r (n = 167) and LPV/r (n = 170) arms had HIV-1 RNA levels50 copies per milliliter at week 48: 64.7% vs 63.5% and estimated difference in proportion for noninferiority: 1.14%, 96% confidence interval: -9.6 to11.9 (P0.012), confirming that SQV/r was noninferior to LPV/r treatment. There were no significant differences in week 48 CD4 counts between arms. The rate and severity of adverse events were similar in both groups. There were no significant differences in the median change from baseline between arms in plasma lipids except for triglyceride levels, which were significantly higher in the LPV/r at week 48.: In treatment-naive, HIV-1-infected patients, SQV/r treatment was noninferior in virologic suppression at 48 weeks to LPV/r treatment and offered a better triglyceride profile.

Summary Outbreaks of skin and soft tissue infections mediated by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are being reported with increasing frequency among men who have sex with men (MSM). However, the potential role of asymptomatic colonization with this organism in perpetuating these infections is unclear. The purpose of this cross-sectional study was to determine the prevalence of colonization with CA-MRSA among a cohort of 500 MSM recruited from two inner city clinics in Toronto, Canada. Following the provision of informed consent, subjects completed a questionnaire capturing demographic and clinical variables, which may be associated with MRSA colonization. A nasal swab for MRSA was collected from each subject, and instructions were provided regarding the self-collection of a rectal swab. Cultured MRSA underwent pulsed-field gel electrophoresis and virulence testing for Panton-Valentine leukocidin gene expression. The prevalence of CA-MRSA colonization was 1.6% (95% CI: 0.5–2.6%).

BACKGROUND: The purpose of the present study was to describe the clinical characteristics and management of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) infections among a cohort of men who have sex with men.PATIENTS AND METHODS: A retrospective chart review was conducted of patients with culture-proven MRSA at Maple Leaf Medical Clinic (Toronto, Ontario) between November 2004 and December 2005. Cases were identified by individual physicians and by queries in the clinical management system. A standard data collection form was used to record patient demographics, potential risk factors for MRSA and course of illness. When available, antimicrobial sensitivities were recorded. DNA fingerprinting using pulsed-field gel electrophoresis, and genetic analysis for SCCmectyping and detection of the Panton-Valentine leukocidin cytotoxin were performed on six available isolates.RESULTS: Seventeen patients with MRSA infection were identified, 12 (71%) of whom were HIV-positive. The most common clinical presentation was abscess (35%), followed by furuncle (17%), folliculitis (17%), cellulitis (17%) and sinusitis (12%). The majority of MRSA isolates were resistant to ciprofloxacin (92%) and levofloxacin (77%). All isolates were susceptible to trimethoprim-sulfamethoxazole, rifampin, linezolid, gentamicin and clindamycin, while the majority were susceptible to tetracycline (80%). All six isolates tested were SCCmectype IVa-positive and Panton-Valentine leukocidin-positive, and had fingerprint patterns consistent with the CMRSA-10 (USA300) clone.CONCLUSION: The present study describes the clinical presentation and management of CA-MRSA infections occurring in Toronto among men who have sex with men. The infections appear to have been caused by CMRSA-10, which has caused the majority of CA-MRSA outbreaks elsewhere.

Background We sought to determine the pharmacokinetic disposition of raltegravir in the blood and seminal plasma of HIV-infected men. Methods We conducted a pharmacokinetic study using a staggered sampling approach. A total of 16 HIV-infected men receiving raltegravir-based therapy were recruited into the study. Each participant provided six blood plasma and six seminal plasma samples for quantification of drug concentrations in both compartments. Blood and semen samples were obtained within 1 h of each other and were collected prior to the morning dose and at 1, 2, 4, 8 and 12 h post-ingestion. Drug concentrations were determined by liquid chromatography tandem mass spectrometry. Results A total of 96 semen samples and 96 blood samples were obtained from all participants during the study period. The median age and baseline CD4+ T-cell count of the study participants were 48 years (IQR 42–53) and 450 cells/mm3 (IQR 289–585). Virological suppression to 0–12 h seminal plasma-to-blood plasma ratios of raltegravir were 3.25 (IQR 1.46–5.37) and 2.26 (IQR 1.05– 4.45), respectively. Conclusions Concentrations of raltegravir in seminal plasma are several fold higher than those attained in blood plasma and those required to inhibit viral replication in this compartment. Further research examining the therapeutic and prophylactic implications of these findings is warranted.

BACKGROUND Herpes simplex virus type 2 (HSV-2) reactivations are associated with increased HIV load, but whether HSV-2 coinfection accelerates HIV disease is unclear. We compared rates of CD4 count decline according to HSV-2 status in untreated HIV-infected adults. METHODS HIV-infected patients with a past period of antiretroviral therapy (ART)-untreated follow-up with initial CD4 count of 400-900 cells/mm(3) and no chronic anti-HSV therapy were included. HSV-2 status was determined by HerpeSelect enzyme-linked immunosorbent assay. Rates of CD4 count change were compared by HSV-2 status using mixed linear regression models, and time to the first of ART initiation or CD4

Etravirine (ETV) has been approved for use in treatment-experienced patients based on results of the Duet clinical trials [1]. Less experience exists with ETV in earlier stages of treatment. ETV has a favorable genetic barrier, lipid profile, and little associated CNS toxicity. These characteristics make ETV attractive as a switch strategy for simplification and/or management of side effects. A retrospective chart review was conducted at a large urban HIV clinic in Toronto. All patients who were switched to ETV plus 2 nucleosides and whose viral load (VL) was

This study evaluated the 12-month retention rate of third agents in HAART (highly active anti-retroviral therapy) regimens in routine clinical practice in a Canadian HIV clinic. This is a descriptive retrospective database analysis of HIV-positive patients naive to antiretroviral therapy (ART). The study included male and female HIV patients ≥18 years of age at HAART initiation date, seen in routine consultation at the Maple Leaf Medical Clinic (MLMC), Toronto, Ontario, Canada. Data were extracted from the MLMC database for the period of September 1st, 2003 to August 31st, 2010 for patients who commenced a protease inhibitor (PI), a non-nucleoside reverse-transcriptase inhibitor (NNRTI), or an integrase inhibitor (II) -based regimen in combination with two nucleoside reverse transcriptase inhibitors (NRTI). Demographic and baseline disease characteristics were extracted and include age, gender, disease duration, baseline HIV-1 RNA count, CD4 cell count, and hepatitis B and C co-infection status at baseline. A total of 722 patients were included in the analysis. The primary outcome of the study was the proportion of HIV patients remaining on their initial third agent (PI, NNRTI, or II) at one year post-treatment initiation. For therapies used by more than 10% of patients (efavirenz [EFV]=315, atazanavir [ATV]=104, lopinavir [LPV]=162, as other agents were used but in limited numbers), the percentage of patients still on the initial third agents at one year was 77%, 64% and 62%, respectively. In addition, viral load (VL) was less than 50 copies/mL in 95% of EFV, 79% of ATV and 76% of LPV patients at one year. The rate of discontinuation at 12 months from EFV, ATV, and LPV due to efficacy (i.e. lack of virologic suppression) or safety (i.e. adverse events) were 15.56%, 19.23%, and 19.75% respectively. In a clinical practice setting, the majority of patients treated with HAART regimens were maintained on therapy at one year and were able to suppress their viral load consistently. Of those reported here, EFV resulted in the best retention rate and viral suppression overall. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Crouzat F et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18242 http://www.jiasociety.org/index.php/jias/article/view/18242 | http://dx.doi.org/10.7448/IAS.15.6.18242

To evaluate polyalkylamide gel (PAIG) use in treating HIV-associated facial lipoatrophy (FLA) 4 years after its injection in an open-label, randomized controlled trial (RCT).Five patients were treated with PAIG in a pilot study, and 31 patients were subsequently enrolled in the RCT of immediate or delayed (12 weeks later) PAIG injections. Endpoints included proportion of participants with complications; changes in FLA severity score (FLSS); and quality of life (QoL), depression, anxiety, and satisfaction scores. Infections were classified as "confirmed" if purulent material was extracted and/or an organism cultured. Infections were classified as "possible" if only clinical signs were present without purulent discharge or microbiologic confirmation.Year 4 results were available for 5 pilot and 27 full-scale study participants. Delayed complications included 5 confirmed infections (15.6%), 3 possible infections (9.4%), nodules (25%), and bleeding (3%). No significant changes were observed between years 2 to 4 in patient-graded FLSS, QoL, depression, and anxiety scores. Whereas 94% of participants were satisfied with their overall treatment, only 69% were satisfied with PAIG treatment specifically.Even though PAIG treatment was associated with delayed complications including high rates of infection and nodules, most patients were satisfied with the treatment.

Introduction : The resistance profiles of first-line antiretroviral therapy (ART) regimens after virologic failure have yet to be studied in a clinic setting in the modern treatment era. Time to virologic failure among three standard first-line regimens and the resistance profiles of these failures were compared. Materials and Methods : All HIV-positive persons aged 16 and over starting a three-drug first-line ART regimen were retrospectively identified at a Toronto community clinic (1 January 2006–1 January 2013). The regimens included a backbone of two NRTIs and a third agent; a PI, an NNRTI, or an II. Patients must have been on treatment for at least 14 days and have at least one VL test within 6 months after starting treatment. The primary outcome was virologic failure defined as either: no suppression by 6 months, or after suppression, two consecutive, detectable VL200 copies/mL at least 14 days apart or one VL>200 copies/mL. Time to failure was compared using a proportional hazards model adjusting for demographic and clinical factors. Resistance profiles of NRTIs and third agents are described in patients with virologic failure who had both baseline and virologic failure genotypes. Results : Six hundred sixty patients (93% male) were included with a mean age of 38.9 and a median follow-up period of 35.3 (32.2–39.3) months. Distribution of third agent use was: PI 37.3% (n=246), NNRTI 55.9% (n=369) and II 6.8% (n=45). Virologic failures occurred in 81/246 (33%) with PI, 87/369 (24%) with NNRTI and 11/45 (24%) with II. Compare to PIs, time to failure was longer with NNRTIs (p=0.0013) and similar for IIs (p=0.1562). No evidence that failure with NNRTIs was different from IIs (p=0.9139). Of the 660 patients, 567 (86%) had a baseline genotype. Of the 567 patients, 179 had virological failure. Of the 179, 145(81%) had a baseline genotype and only 37 (21%) had both a baseline and follow-up genotype. Upon failure, emerging ART resistance was rare. No new PI or II mutations were identified and one new NNRTI (Y181C) mutation was identified. Three patients taking PI-based regimens developed NRTI mutations (M184V, M184I, T215Y). Conclusions : Time to virologic failure was significantly greater in the NNRTI group compared to the PI group. If failure did occur, ART resistance rarely developed with no PI mutations but a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimen. (Published: 2 November 2014) Citation: Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Crouzat F et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19757 http://www.jiasociety.org/index.php/jias/article/view/19757 | http://dx.doi.org/10.7448/IAS.17.4.19757