CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

667

Transaminase Decrease Upon Switch From TDF to TAF in PWH Is Modulated by HBV Status Alessandro Soria 1 , Giuseppe Lapadula 2 , Nicola Squillace 3 , Elisa Colella 1 , Francesca Sabbatini 1 , Alban Rugova 1 , Luca Mezzadri 2 , Silvia Limonta 1 , Anna Cappelletti 1 , Alice Ranzani 1 , Paolo Bonfanti 2 1 Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, 2 University of Milano–Bicocca, Milan, Italy, 3 San Gerardo Hospital, Monza, Italy Background: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has been associated with a reduction in transaminase level among people with hepatitis B virus (HBV) and in people with HIV (PWH), with or without HBV. It is unclear whether such reduction is due to a lower hepatotoxicity of TAF or to an enhanced suppression of HBV in people with overt or occult HBV. Methods: We conducted a longitudinal study on PWH switching from TDF to TAF between 2016 and 2023, whose HBsAg/HBcAb status was known. A mixed effects model with random intercepts at the patient level was used to assess the effect of the switch on transaminase levels. An interaction term between the switch and HBV status was included to evaluate whether the effect of the switch varied across three mutually exclusive HBV categories: chronic hepatitis B (CHB), defined by HBsAg+; occult HBV infection (OBI), defined as HBsAg-/HBcAb+; no HBV infection, defined as HBsAg-/HBcAb-. Results: Among 648 PWH switching from TDF to TAF, 7.4% had CHB and 34.9% OBI. Table 1 summarizes other patient characteristics. Switching to TAF was associated with a significant transaminase (ALT) decrease (beta [b] -3.2 UI/ml, 95%CI -4.9 to -1.5, P<0.001). Compared with patients without HBV, a significantly steeper ALT decrease upon switch was observed among those with CHB (b -7.6, 95%CI -12.3 to -2.8; P=0.002), while OBI was associated with a non-significant reduction (b -1.6; 95%CI -4.3 to 1.1; P=0.252). In the final multivariable model, male gender (b +10.3, 95%CI 6.4 to 14.2, P<0.001) and diabetes (b +5.1, 95%CI 0.2 to 10, P=0.042) were associated with higher ALT, while older age (b -0.2 per year increase, 95%CI -0.3 to -0.1, P=0.021) and later calendar years ( versus 2016-2017, b -7.1, 95%CI -13 to -1.5, P=0.012 for 2020-2023 and b -3.7, 95%CI -7.2 to -0.2, P=0.037 for 2018-2019) were associated with lower ALT. Again, a significant interaction was found between the switch and CHB versus no HBV infection (b -7.6, 95%CI -12.4 to -2.9, P=0.002) but not for OBI (b -1.5, 95%CI -4.2 to 1.2, P=0.276). Consistent results with AST were obtained. Conclusions: Switching from TDF to TAF is associated with significant transaminase decrease in PWH. Such effect is partially dependent of HBV status, suggesting that, among those with CHB, enhanced viral suppression, not captured by plasma HBVDNA measurement, plays a role. Further studies are warranted to explore the underlying mechanisms and the long-term clinical implications of these findings.

668

Impact of Switching From DTG/3TC to BIC/FTC/TAF on Weight, Cholesterol, and Inflammation in HIV Sergio Serrano-Villar 1 , Laura Martín Pedraza 1 , Daniel Podzamczer 2 , José Sanz 3 , Luis López-Cortés 4 , Alfonso Cabello 5 , Carmen Busca 6 , Miguel Torralba 7 , Maria J. Crusells 8 , Carmen Hidalgo-Tenorio 9 , Vicente Estrada 10 , Alberto Díaz De Santiago 11 , Ana del Amo 1 , Marta De Miguel 12 , Santiago Moreno 1 1 Hospital Universitario Ramon y Cajal, Madrid, Spain, 2 Bellvitge University Hospital, Barcelona, Spain, 3 Hospital Universitario Príncipe de Asturias, Madrid, Spain, 4 Hospital Universitario Virgen del Rocio, Sevilla, Spain, 5 Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, 6 Hospital La Paz Institute for Health Research, Madrid, Spain, 7 Hospital Universitario de Guadalajara, Guadalajara, Spain, 8 Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, 9 Hospital Universitario Virgen de las Nieves, Granada, Spain, 10 Hospital Universitario Clínico San Carlos, Madrid, Spain, 11 Hospital Puerta de Hierro, Madrid, Spain, 12 Fundación SEIMC-GeSIDA, Madrid, Spain Background: DTG/3TC and BIC/FTC/TAF are recommended ART regimens in major HIV guidelines. However, data on the metabolic and inflammatory effects of switching from DTG/3TC to BIC/FTC/TAF are scarce. We investigated the impact of this switch on metabolic parameters and systemic inflammation in virologically suppressed individuals. Methods: This randomized, open-label, multicenter INSTINCT study (GESIDA10918) assessed the impact of switching from DTG/3TC to BIC/FTC/TAF vs. continuing DTG/3TC on weight, cholesterol and systemic inflammation up to 96 weeks. Adults with virologically suppressed HIV, stable on DTG/3TC for at least 48 weeks were enrolled. Exclusions included previous virological failure, drug resistance, and autoimmune conditions. For inflammation, we focused on IL-6 changes from baseline to week 96 using high-sensitivity ELISA. We estimated treatment effects using linear mixed models in Stata v.18. Results: We included 141 participants, with 135 completing follow-up; 14% women, mean age 45 ± 11 years; 78% were white; 58% MSM; 11% had a previous AIDS diagnosis, and the median nadir CD4 was 368 cells/uL. Baseline CD4 count was 789/uL, the mean duration of HIV suppression 6.5 years, mean weight at baseline 77 kg, and mean IL6 levels within normal range (1.72 pg/mL 95% CI [1.46-1.99]). No differences were observed in baseline characteristics between groups. At 96-week, there were no differences in the rates of virological efficacy between DTG/3TC and BIC/FTC/TAF (risk difference 0.01%, 95% CI -0.07 to 0.04). The overall mean weight gain of 1.22 kg, (95% CI 0.31 2.13), with no significant differences between regimens ( Fig. A ). Changes in total cholesterol (-4.7 mg/dL), HDL cholesterol (0.9 mg/dL), and LDL cholesterol (-2.3 mg/dL) were similar in both groups. Adjusted IL-6 changes were not significantly different (median fold change: DTG/3TC 2.0 [1.3-2.7]; BIC/FTC/TAF 1.2 [1.0-1.4], P = 0.106)( Fig. B ). Conclusions: Switching from DTG/3TC to BIC/FTC/TAF in virologically suppressed individuals showed comparable effects on weight, cholesterol levels, and systemic inflammation (IL-6) compared to continuing DTG/3TC. Ongoing analyses of additional inflammatory markers are needed to determine if either regimen may lead to differential effects on systemic inflammation.

Poster Abstracts

CROI 2025 187