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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.

Background Prior studies have reported improved adherence, persistency, virologic outcomes and lower risk of hospitalizations with single tablet (STR) vs. multi-tablet regimens (MTR) in HIV treatment. However, most studies were conducted using prescription and medical claims data limited to EFV-based therapies. In this study, we utilized EMR, prescription, and pharmacy dispensing data to assess STR and MTR adherence and persistency as observed in a network of clinical practices. Methods Data were collected for HIV-infected patients in care at six US-based HIV treatment centers. Patients eligible for the study initiated their first ARV between January 2015 and December 2016. First ARV regimen was assigned based on absence of prior ARV prescriptions and a 30-day pre-treatment period with no ARV dispensed or for rapid starts, a high baseline viral load (≥10,000 copies/mL). Adherence was assessed using proportion of days covered (PDC). Follow-up was ≥365 days with duration capped at 365 days for persistency comparisons. Results A total of 1,499 patients met the criteria for the study; 66% (982/1,499) received STR and 34% (517/1,499) MTR. Top STRs were EVG/c/TDF/FTC (265/982, 27%), EVG/c/TAF/FTC (250/982, 26%), and DTG/ABC/3TC (171/982, 17%). Top MTRs were DTG + TDF/FTC (69/517, 13%), DRV + RTV + TDF/FTC (60/517, 12%), and DRV/c + TDF/FTC (40/517, 8%). Average persistency for STRs was significantly longer at 252 days vs. 233 days for MTRs (P = 0.002). Average PDC adherence rates were significantly higher for STRs at 91% vs. 83% for MTRs (P < 0.001). Within the STR group, older age was significantly associated with greater adherence (average age: 45 in 80%+ adherent group vs. 42 in

Established and emerging tickborne infections are significant causes of human illness in the southern United States. Rocky Mountain spotted fever, human monocytic ehrlichiosis, human ewingii ehrlichiosis and tularemia are known pathogens in this geographic distribution. Rickettsia parkeri and novel ehrlichioses are more recently described tickborne infections reviewed in this article. An understanding of the tick vectors, pathogenesis, epidemiology, clinical presentation, diagnosis and treatment is useful for the clinician treating patients potentially infected with any of these pathogens. Prevention measures, the optimal method for removing an attached tick and current and future vaccine development conclude this review.