title: Dolutegravir with tenofovir disoproxil fumarate-emtricitabine as HIV postexposure prophylaxis in gay and bisexual men.
abstract: Completion rates for HIV postexposure prophylaxis (PEP) are often low. We investigated the adherence and safety of dolutegravir (DTG; 50 mg daily) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC; 300/200 mg, respectively) as three-drug PEP in gay and bisexual men.
  
  
  
  Open-label, single-arm study at three sexual health clinics and two emergency departments in Australia.
  
  
  
  In total, 100 HIV-uninfected gay and bisexual men requiring PEP received DTG and TDF-FTC for 28 days. The primary end point was PEP failure (premature PEP cessation or primary HIV infection through week 12). Additional end points were adherence by self-report (n = 98) and pill count (n = 55), safety, and plasma drug levels at day 28.
  
  
  
  PEP completion was 90% (95% confidence interval 84-96%). Failures (occurring at a median 9 days, interquartile range 3-16) comprised loss to follow-up (9%) and adverse event resulting in study drug discontinuation (headache, 1%). No participant was found to acquire HIV through week 12. Adherence to PEP was 98% by self-report and in the 55 participants with corresponding pill count data. The most common clinical adverse events were fatigue (26%), nausea (25%), diarrhoea (21%), and headache (10%). There were only four grade 3-4 subjective adverse events. The most common laboratory adverse event was raised alanine aminotransferase (22%), but there was no case of clinical hepatitis. At day 28, the mean estimated glomerular filtration rate decrease was 14 ml/min/1.73m (SD 17, P = 0.001); an estimated glomerular filtration rate of less than 60 ml/min/1.73m occurred in 3%.
  
  
  
  DTG with TDF-FTC is a well tolerated option for once-daily PEP.
authors.affiliation: aHIV, Immunology & Infectious Diseases Unit and Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales bMelbourne Sexual Health Centre cCentral Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria dSydney Sexual Health Centre, Sydney, New South Wales eDepartment of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria fClinic 16, Northern Sydney Sexual Health, Sydney, New South Wales, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: McAllister
authors.forename: Janet M
authors.initials: JM
authors.lastname: Towns
authors.forename: Anna
authors.initials: A
authors.lastname: Mcnulty
authors.forename: Anna B
authors.initials: AB
authors.lastname: Pierce
authors.forename: Rosalind
authors.initials: R
authors.lastname: Foster
authors.forename: Robyn
authors.initials: R
authors.lastname: Richardson
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D000068679:Emtricitabine / Q000008:administration & dosage* / Q000009:adverse effects; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D055118:Medication Adherence; D010078:Oxazines; D010879:Piperazines; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D011728:Pyridones; D000072339:Sexual and Gender Minorities; D000068698:Tenofovir / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D000068679:Emtricitabine; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000068698:Tenofovir; D000099226:Dolutegravir