Increase in pro-atherogenic apolipoprotein B in people living with HIV (PLWH) following switch from tenofovir disoproxil fumarate to tenofovir alafenamide

Objectives: Tenofovir alafenamide (TAF) has been associated with weight gain and adverse lipid profiles compared to tenofovir disoproxil fumarate (TDF). The impact of TAF on apolipoprotein (Apo) composition is largely unknown. We compared Apo and lipids between PLWH who switched from TDF to TAF (TDF-TAF) compared to those continuing TDF (TDF-TDF). Methods: Retrospective analysis on PLWH enrolled in the UPBEAT study who were on TDF at baseline and with available data and follow-up samples. ApoA1, ApoB and Lp (a) were measured on plasma by immunoturbidimetry at baseline (T0) and between year 3 and 5 of study follow-up (T1), following switch to TAF in TDF-TAF group. Subjects with exposure to TDF of 2–5 years between the two time points were included. Within- and between-group differences in Apo and lipids were compared using Wilcoxon signed rank test and linear regression, adjusting for T0 values and socio-demographic/clinical variables. Values are n (%) or median (IQR). Results: 52 PLWH (36 TDF-TDF, 16 TDF-TAF) were included. Differences between TDF-TAF and TDF-TDF groups included: male sex 12 (75%) versus 19 (52.8%); age (46 [41–55] versus 38 [34–47] years); Caucasian ethnicity 12 (75%) versus 21 (58.3%); diabetes 3 (18.8%) versus 2 (5.6%); hypertension 6 (37.5%) versus 6 (16.7%); cardiovascular disease (CVD) 0 (0%) versus 3 (8.3%); duration of ART at T0 (years, 8.13 [6.13–13.35] versus 2.78 [1.03–6.72]). Exposure (years) to TDF between T0 and T1 was 2.86 (2.58–3.48) in TDF-TAF versus 2.43 (2.15–3.62) in TDF-TDF. Exposure to TAF (years) in TDF-TAF was 1.1 (0.54–1.72). Observation time between T0 and T1 (years) was longer in TDF-TAF than in TDF-TDF (4.01 [3.59–4.59] versus 2.42 [2.15–3.62]). Virological suppression at T1 was 16 (100%) in TDF-TAF versus 34 (94.4%) in TDF-TDF. Third agent use at T1 in TDF-TAF versus TDF-TDF was: NNRTI 3 (18.8%) versus 18 (50%); PI 1 (6.3%) versus 12 (33.3%); INSTI 12 (75%) versus 6 (16.7%). Values of Apo and lipids did not change significantly between T0 and T1 within each group, except for ApoB which showed a small (0.17 g/l) but significant increase in the TDF-TAF group (P=0.007), and a non-significant decrease in the TDF-TDF group (Table 1). TDF-TAF switch remained associated with higher levels of ApoB at T1 (B coefficient 0.199, 95% CI [0.53, 0.345]; P=0.009), after adjustment for values at T0 and demographic/clinical confounders. Conclusions: Despite no change in other lipid and lipoprotein parameters, PLWH switching to T