Comparing Weight Gain on F/TAF and Placebo Using DISCOVER and iPrEx Study Data

Study type

• Study topic:
  Disease /health condition

  Human medicinal product

  Other
• Study topic, other:
  Research method
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  DESCOVY

  TRUVADA
• Medicinal product name, other:
  emtricitabine/tenofovir alafenamide ; Emtricitabine/tenofovir Disoproxil Fumarate
• Study drug International non-proprietary name (INN) or common name:
  EMTRICITABINE

  TENOFOVIR ALAFENAMIDE

  TENOFOVIR DISOPROXIL FUMARATE
• Anatomical Therapeutic Chemical (ATC) code:
  (J05AR17) emtricitabine and tenofovir alafenamide

  emtricitabine and tenofovir alafenamide

  (J05AR03) tenofovir disoproxil and emtricitabine

  tenofovir disoproxil and emtricitabine
• Medical condition to be studied:
  HIV infection
• Additional medical condition(s):
  Pre-Exposure Prophylaxis of HIV-1 Infection

Population studied

• Short description of the study population:
  Individuals not living with HIV, all of whom were adults aged at least 18 years, and with 1 or more ; behavioral risk factors for contracting HIV-1. All iPrEx study participants were born male, and were recruited from North and South America, South Africa, and Thailand. All DISCOVER study ; participants were born male or were TGW, and were recruited from North America, 8 European Union (EU) countries, and the UK. Study start and randomized-primary completion dates were as ; follows, iPrEx: June 2007 to February 2011; DISCOVER: September 2016 to January 2019.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Study design details

• Study design:
  This study utilized existing data collected during 2 large Phase 3 clinical studies of FTC/TDF and F/TAF to conduct an indirect comparison of F/TAF (DISCOVER) and placebo treatment groups (iPrEX), using the common FTC/TDF treatment groups as negative controls.
• Main study objective:
  To compare weight change/trajectory distributions between F/TAF and placebo cohorts from the DISCOVER and iPrEx studies
• Setting:
  Both studies used for this study recruited individuals not living with HIV, all of whom were adults aged at least 18 years, and with 1 or more behavioral risk factors for contracting HIV-1. ; All iPrEx study participants were born male, and were recruited from North and South America, South Africa, and Thailand. ; All DISCOVER study participants were born male or were TGW, and were recruited from North America, 8 European Union (EU) countries, and the UK. ; ;
• Outcomes:
  - weight change trajectories/distributions ; - weight gain; - incidence of weight-related comorbidities
• Data analysis plan:
  To compare mean weight changes between individuals assigned to F/TAF and placebo over time, we used linear mixed models adjusting for potential confounders. Data from the two FTC/TDF groups were pooled and analyzed as a single group to facilitate an overall estimate of average TDF-associated weight change. ; ; To investigate whether F/TAF selectively caused excessive weight change in only a small fraction of individuals or otherwise shifted the shape of the distribution of weight change over time relative to placebo, we compared top percentiles of weight change at Week 48 between individuals assigned to F/TAF and placebo using quantile regression adjusted by the same set of covariates as the linear mixed model. To adjust for differential patterns of missing information between the source studies, we estimated the probability of having complete data at Week 48 with logistic regression and weighted each individual by the inverse probability in the quantile regression model. ; ; In the sensitivity analysis, we repeated the primary analyses after excluding individuals with suboptimal adherence to their assigned study drug. ; ; Incidence of adverse events related to weight (cardiovascular events, diabetes and ; hypertension) were reported for each source study.
• Summary results:
  Leveraging data from two large, randomized, double‑blind Phase 3 PrEP studies in PWoH, we observe no statistically or clinically meaningful differences in mean weight change between individuals receiving F/TAF and those receiving placebo. Observed weight changes with F/TAF were small relative to normal inter‑individual variability and consistent ; with background physiological weight trends.