Adherence, HIV-1 Infection, Resistance, and Renal and Skeletal Adverse Event in Individuals Taking Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF, Truvada®) for HIV Pre-Exposure Prophylaxis (PrEP): A Pooled Observational Study

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Medical condition to be studied:
  Prophylaxis against HIV infection

Population studied

• Short description of the study population:
  HIV-1 negative adults or adolescents (any sex/gender, including transgender) who had at least one measurement of adherence of TFV-DP in DBS or of TFV in plasma available while taking Truvada for PrEP.; ; Inclusion Criteria; To be eligible for study participation, an HIV-1 uninfected individual was required to satisfy the following criteria:; 1. Participant in a Truvada PrEP observational or clinical study.; 2. HIV-1 negative individual at the time of enrollment in a demonstration project or clinical study.; 3. Participants with at least one measurement of TFV-DP in DBS or TFV in plasma.; ; Exclusion Criteria; This observational study collected HIV-1 infection and resistance information along with renal or skeletal adverse events without intervention. In the pooled analysis, only available TFV-DP or TFV measurements were analyzed. Individuals with no TFV-DP or TFV measurements within 48 weeks after PrEP initiation, with HIV-1 infection tested positive before PrEP initiation date or before the first adherence measurement, and with PrEP initiation date later than PrEP end date were excluded. Adherence measurements with laboratory test date prior to the Truvada for PrEP initiation date, and with extreme values of TFV-DP in DBS over 4,000 femtomole/punch (fmol/punch) were excluded, based on communication with from , whose laboratory conducted all the tests for adherence of the individual; studies.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  7302

Study design details

• Main study objective:
  The study assessed level of adherence as measured by drug level and its relationship to renal and bone adverse events, risk of seroconversion, and resistance development in subjects taking Truvada for PrEP.
• Outcomes:
  The objectives of the study were to assess levels of adherence, evaluate the association between levels of adherence, and measure a gradient of adherence levels using available data on drug levels as the measure of adherence in participants taking Truvada for PrEP.
• Data analysis plan:
  GS-US-276-0104 conducted an analysis of data from ongoing and planned demonstration projects (trials) including at least 7000 uninfected individuals taking Truvada® for a preexposure prophylaxis (PrEP) indication with the objective of examining the association between levels of adherence to the once-daily dosing regimen and risk of seroconversion, resistance development, and renal and skeletal adverse events. Levels of adherence measured a gradient of adherence levels rather than the simple dichotomy of ‘adherent’ versus ‘nonadherent’ using any available data on drug levels as the measure of adherence. Seroconversion was assessed every three months, and, upon each seroconversion, resistance testing was performed. Assessment for renal and skeletal adverse events was performed every three months, including evaluation of available laboratory data. Analyses was performed by geographic region.