Background: As efficacy of triple-drug antiretroviral therapy remains high, patient wellbeing (e.g., patient-reported outcomes) has become an important differentiator among regimens. Bictegravir, a novel, unboosted integrase strand transfer inhibitor, coformulated with emtricitabine and tenofovir alafenamide (B/F/TAF), demonstrated high efficacy and was well tolerated through week (W) 48, with no resistance in two phase 3 studies of treatment-naïve adults. We aimed to characterize change in symptoms of adult patients with HIV-1-infection after initiating or switching to B/F/TAF versus ABC/DTG/3TC.
Methods: Treatment-naïve adults were randomized (1:1) to receive blinded treatment with B/F/TAF or ABC/DTG/3TC (study 1489). Virologically suppressed adults were randomized (1:1) to switch to B/F/TAF or continue ABC/DTG/3TC in blinded fashion (study 1844). Across studies, HIV Symptoms Distress Module (HIV-SI) was administered at baseline (BL), W4, W12, and W48. Responses were dichotomized as bothersome/not. Treatment differences were assessed using logistic regression models adjusted for BL HIV-SI count, age, sex, BL Veterans Aging Cohort Study Index, medical history of serious mental illness, BL Short Form [SF]-36 Physical Component Summary [PCS], BL SF-36 Mental Component Summary [MCS], and years since HIV diagnosis (study 1844 only). Longitudinal modeling of bothersome symptoms was conducted using generalized, mixed model including treatment, time, time-by-treatment, and additional covariates. Pittsburgh Sleep Quality Index (PSQI) was administered with same frequency as HIV-SI, and total score was dichotomized as good/poor sleep quality. Similar models to HIV-SI were applied using BL sleep quality and BL SF-36 MCS as covariates.
Results: Bothersome symptoms were reported by fewer participants on B/F/TAF than ABC/DTG/3TC in both studies (figure). For treatment-naïve adults, fatigue/loss of energy, nausea/vomiting, dizzy/lightheadedness, and difficulty sleeping significantly favored B/F/TAF at ≥2 timepoints (table). Fatigue and nausea were significantly less common for B/F/TAF in longitudinal models. For virologically suppressed participants, nausea/vomiting, sad/down/depressed, nervous/anxious, and poor sleep quality (from the PSQI) significantly favored B/F/TAF at ≥2 timepoints and in longitudinal models. No symptom favored ABC/DTG/3TC at ≥2 timepoints in either study.
Conclusions: Results suggest that patient-reported wellbeing may be better with B/F/TAF compared to ABC/DTG/3TC. B/F/TAF was associated with significantly lower prevalence of multiple bothersome symptoms across gastrointestinal disorders, neuropsychiatric events, and sleep. No symptoms favored ABC/DTG/3TC.

 Treatment-naïve adults (study 1489)Virologically suppressed adults (study 1844)
Bothersome SymptomWeek 4Week 12Week 48Longitudinal ModelWeek 4Week 12Week 48Longitudinal Model
Fatigue/loss of energyXXXXX   
Dizzy/lightheadednessX X X  X
Nausea/vomitingXX X XXX
Sad/down/depressed    X XX
Nervous/anxious    XXXX
Difficulty sleeping XX  X X
Poor sleep quality (PSQI) X  XX X
X = statistically significant favoring the B/F/TAF group Statistical significance was assessed using p<0.05 Note: Only symptoms where at least two or more timepoints showed significance in either study were included. No symptom favored ABC/DTG/3TC at two or more timepoints for either study
[Comparison of patient-reported outcomes (B/F/TAF vs ABC/DTG/3TC) from adjusted logistic regression analyses and longitudinal analyses]

Prevalence of bothersome symptoms over time by treatment group
[Prevalence of bothersome symptoms over time by treatment group]

Download the e-Poster