To Tenofovir Alafenamide Research Articles

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA<20IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. This study included 309 patients with a median age of 59years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6months after switching (74.8%-83.5%; P=0.008). Adjusted eGFR significantly improved at 6months (+5.55±10.52mL/min/1.73m2; P<0.001) and 12months (+6.02±10.70mL/min/1.73m2; P<0.001) after switching. In the subgroup of patients with renal impairment (eGFR<60mL/min/1.73m2), significant improvement in renal function was observed at 6months (+0.6±10.5mL/min/1.73m2; P<0.001) and 12months (+1.0±10.7mL/min/1.73m2; P<0.001) after switching to TAF. In patients with osteoporosis (n=182), switching to TAF resulted in significant improvement in spine and hip BMD at 12months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids.

Tenofovir disoproxil fumarate (TDF) compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. People living with HIV, without significant gastrointestinal symptoms, receiving TDF (n=12) or TAF (n=12) containing regimen underwent esophagogastroduodenoscopies with duodenal biopsies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty-acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. COX/SDH histochemical staining and electron microscopy (EM) were conducted to evaluate mitochondria. Five patients in TDF (celiac disease (excluded from further analyses), helicobacter gastritis, and three esophagitis) and two in TAF group (two esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 (59) vs. 397 (42) μm, p=0.016), crypts non-significantly deeper (200 (46) vs. 176 (27) μm, p=0.2), and villus to crypt ratio lower (1.5 (0.42) vs. 2.5 (0.51), p=0.009) in TDF vs. TAF group. I-FABP concentration was higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically but not statistically significantly lower concentrations of folate, vitamins A, B1, D, and E. COX/SDH staining showed signs of mitochondrial damage in 10 participants in TDF and 11 in TAF group. EM studies showed similar mitochondrial damage in both groups. Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.

Atherosclerotic cardiovascular disease risk profile of patients with chronic hepatitis B treated with tenofovir alafenamide or tenofovir disoproxil fumarate for 96 weeks.

Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles. To evaluate how these changes affect cardiovascular risk. This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks. Patients who fulfilled the American College of Cardiology criteria (age 40-79 years, high-density lipoprotein [HDL] 20-100 mg/dL, total cholesterol [TC] 130-320 mg/dL and systolic blood pressure 90-200 mmHg) required to assess 10-year atherosclerotic cardiovascular disease (ASCVD) risk with baseline lipid data and at least one post-baseline measurement were included in the ASCVD-risk population. The 10-year ASCVD risk was calculated for patients in this population, and changes from baseline to Week 96 were assessed using intermediate- (≥7.5%) and high-risk (≥20%) cut-offs. Among 1632 patients, 620 (38%) met the criteria for the ASCVD-risk population. At Week 96, fasting levels of all lipids, except TC:HDL ratio, were lower with TDF than TAF. No significant increase was observed in overall ASCVD risk or in any ASCVD-risk categories during the 96-week treatment period compared with baseline. A similar proportion of patients in the TAF and TDF treatment groups (1.3% and 2.3%, respectively; p = 0.34) reported cardiovascular events. Despite on-treatment differences in lipid profiles with TAF and TDF, predicted cardiovascular risk and clinical events were similar for both groups after 96 weeks.

Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.

Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. To assess the treatment and renal/bone safety outcomes following the switch to TAF. We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.

Switching from entecavir to tenofovir alafenamide for maintaining complete virological response in chronic hepatitis B.

Hepatocellular carcinoma development can be decreased by achieving and maintaining complete virological response (CVR) in chronic hepatitis B. However, it is unclear whether switching from entecavir (ETV) to tenofovir alafenamide (TAF) could achieve and maintain CVR in patients with low-level viremia (LLV; HBV DNA ≤ 3.3 log IU/mL) or occasional detectable HBV DNA during ETV treatment. Therefore, we aimed to examine whether the switching from ETV to TAF is effective in achieving CVR in patients with LLV or occasional detectable HBV DNA. This study comprised 45 patients who switched from ETV to TAF. All patients received ETV and TAF for >2 years, and the HBV DNA levels were measured every 3 months. Maintaining undetectable HBV DNA during 2-year period is defined as CVR. The primary endpoint is the CVR rate during ETV and TAF treatment. The CVR rate for each of the 2 years of ETV and TAF therapy was 33.3% (15/45) and 68.9% (31/45, P < 0.01), respectively, and the CVR rate increased by switching from ETV to TAF. In patients with occasional detectable HBV DNA during ETV treatment (22 patients), 15 achieved CVR and 7 maintained occasional detectable HBV DNA. In patients with LLV during ETV treatment (eight patients), three achieved CVR and five had occasional detectable HBV DNA. Switching from ETV to TAF increases the CVR rate in patients with LLV or occasional detectable HBV DNA and could be an alternative treatment option.

Long-term health and economic benefits of switching to tenofovir alafenamide versus continuing on entecavir in chronic hepatitis B patients with low-level viremia in Saudi Arabia.

Despite the success of current treatments, many chronic hepatitis B (CHB) patients still live with low-level viremia [LLV] resulting in liver disease progression. This study evaluated the long-term health and economic impact of switching to tenofovir alafenamide (TAF) from entecavir (ETV) in Saudi Arabia (SA) in chronic hepatitis B (CHB) LLV patients. A hybrid decision tree Markov state-transition model was developed to simulate a cohort of patients with CHB LLV treated with ETV and switched to TAF over a lifetime horizon in SA. While on treatment, patients either achieved complete virologic response (CVR) or maintained LLV. CVR patients experienced slower progression to advanced liver disease stages as compared to LLV patients. Demographic data, transition probabilities, treatment efficacy, health state costs, and utilities were sourced from published literature. Treatment costs were sourced from publicly available databases. Base case analysis found that over a lifetime horizon, switching to TAF versus remaining on ETV increased the proportion of patients achieving CVR (76% versus 14%, respectively). Switching to TAF versus remaining on ETV resulted in a reduction in cases of compensated cirrhosis (-52%), decompensated cirrhosis (-5%), hepatocellular carcinoma (-22%), liver transplants (-12%), and a 37% reduction in liver-related deaths. Switching to TAF was cost-effective with an incremental cost-effectiveness ratio of $57,222, assuming a willingness-to-pay threshold of three times gross national income per capita [$65,790/QALY]. This model found that switching to TAF versus remaining on ETV in SA CHB LLV patients substantially reduced long-term CHB-related morbidity and mortality and was a cost-effective treatment strategy.

Effectiveness and safety of tenofovir amibufenamide and its comparison with tenofovir alafenamide in patients with chronic hepatitis B: results from a retrospective real-world study.

Background/aim: Tenofovir amibufenamide (TMF) has shown potent antiviral efficacy in randomized clinical studies. This study aimed to reveal the effectiveness and safety of tenofovir amibufenamide in the real world and compared tenofovir amibufenamide to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). Methods: In this retrospective study, tenofovir amibufenamide-treated chronic hepatitis B patients were divided into treatment-naive (TN) and treatment-experienced (TE) groups. Furthermore, tenofovir alafenamide-treated patients were enrolled using the propensity score matching method (PSM). We assessed the virological response (VR, HBV DNA < 100IU/mL) rate, renal function, and blood lipid changes during 24weeks of treatment. Results: Virologic response rates at week 24 were 93% (50/54) in the treatment-naive group and 95% (61/64) in the treatment-experienced group. The ratios of alanine transaminase (ALT) normalization were 89% (25/28) in the treatment-naive group and 71% (10/14) in the treatment-experienced group (p = 0.306). Additionally, serum creatinine decreased in both the treatment-naive and treatment-experienced groups, (-4.44 ± 13.55μmol/L vs. -4.14 ± 9.33μmol/L, p = 0.886), estimated glomerular filtration rate (eGFR) increased (7.01 ± 12.49ml/min/1.73m2 vs. 5.50 ± 8.16ml/min/1.73m2, p = 0.430), and low-density lipoprotein cholesterol (LDL-C) levels increased (0.09 ± 0.71mmol/L vs. 0.27 ± 0.68mmol/L, p = 0.152), whereas total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) levels decreased continuously from 3.26 ± 1.05 to 2.49 ± 0.72 in the treatment-naive group and from 3.31 ± 0.99 to 2.88 ± 0.77 in the treatment-experienced group. Using propensity score matching, we further compared virologic response rates between the tenofovir amibufenamide and tenofovir alafenamide cohorts. Virologic response rates in treatment-naive patients were higher in the tenofovir amibufenamide cohort [92% (35/38) vs. 74% (28/38), p = 0.033]. Virologic response rates in treatment-experienced patients showed no statistical difference between the tenofovir amibufenamide and tenofovir alafenamide cohorts. Conclusion: Tenofovir amibufenamide had profound antiviral effectiveness and no adverse effects on renal function or blood lipids. Additionally, tenofovir amibufenamide was more efficient than tenofovir alafenamide in inhibiting viral replication, which needs to be demonstrated in future studies.

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study.

The impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART. HIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate. A total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF. A bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity.

Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide.

Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.

Pregnancy Outcomes in Pregnant Women with HIV on Tenofovir Disoproxil Fumarate (TDF) Compared to Tenofovir Alafenamide (TAF)

Our objective was to assess the safety, efficacy, and pregnancy outcomes of Tenofovir Disoproxil Fumarate (TDF) compared to Tenofovir Alafenamide (TAF) use in pregnant women with HIV (PWLHIV). This retrospective cohort study of all women who received prenatal care at a single academic center between January 1st 2015 and June 30th, 2020 compared outcomes in PWLHIV using TDF compared to TAF. The primary outcome was weight-gain during pregnancy. Secondary outcomes included CD4 count, viral-load, gestational age at delivery, fetal and neonatal outcomes. Outcomes were analyzed using standard statistical tests. Multivariable linear-regression analysis models accounting for potential confounders were created for primary and secondary outcomes, with beta coefficients (β) and associated 95% confidence intervals as the primary measure of effect. Statistical analysis was done with STATA 16. There were 66 women in the TDF group and 34 women in the TAF group. In the overall cohort, the median (interquartile range, IQR) gestational age at delivery for PWLHIV on TDF and TAF were 38.6 (IQR 37.5-39.4) and 38.1 (31.1-39.1) weeks respectively; and most women (85%) were Black/African American. Compared to PWLHIV on a TDF regimen, women on TAF, on average, gained over 3 kg more weight in the 3rd trimester of pregnancy (β=3.20, 95% CI 1.64, 7.97; p=0.03). Women in the TAF arm were also more likely to have higher median CD4-count (470 cells/mm3 versus 669 cells/mm3, p=0.035) in the third trimester compared to women on TDF. There were no cases of neonatal/infant HIV or death. Although TAF use was associated with more weight gain compared to TDF, both regimens appear safe and effective during pregnancy. PWLHIV should be counseled about the potential for weight gain with TAF based regimens during pregnancy.

Improved treatment response and bone density in patients with chronic hepatitis B (CHB) switched to tenofovir alafenamide (TAF) from other nucleos (t)ide analogue: 96-week results from a prospective multinational study

Improved treatment response and bone density in patients with chronic hepatitis B (CHB) switched to tenofovir alafenamide (TAF) from other nucleos (t)ide analogue: 96-week results from a prospective multinational study

Switching from tenofovir alafenamide to tenofovir disoproxil fumarate improves lipid profile and protects from weight gain

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) increases low-density lipoprotein cholesterol (LDL-C) and body weight. Metabolic effects of the opposite TAF-to-TDF switch are unknown. To investigate the effect of TAF-to-TDF switch on plasma lipids, body weight, and atherosclerotic cardiovascular disease (ASCVD) risk score. A retrospective chart review. One hundred and forty-six patients with TAF-to-TDF switch (Switch group) were compared with 146 patients matched for sex, age, and third antiretroviral agent class who continued unchanged TAF-containing regimen (Control group). Data were collected at approximately 1 year (follow-up FU-1) and 2 years (follow-up FU-2) after baseline values. In Switch group at FU-1, total cholesterol (TC) and LDL-C decreased 12.1% and 12.4% ( P < 0.001 in both), respectively. High-density lipoprotein cholesterol (HDL-C) also decreased 8.2% ( P < 0.001) in Switch group, but TC/HDL-C ratio did not change. No statistically significant changes were observed in Control group in any lipid values. TC remained similarly decreased through FU-2 in Switch group, but LDL-C increased from FU-1 to FU-2 in both groups. ASCVD risk score decreased from 6.3% at baseline to 6.0% at FU-2 ( P = 0.012) in Switch group but increased from 8.4 to 9.1% ( P = 0.162) in Control group. Body weight increased from 83.4 kg at baseline to 84.9 kg at FU-2 ( P = 0.025) in Control group but remained stable in Switch group (83.1-83.7 kg, P = 0.978). TAF-to-TDF switch improved plasma lipid profile and ASCVD risk score, as well as prevented weight gain, when compared with ongoing TAF-based antiretroviral therapy.

One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor.

BackgroundWe determined the frequency of and factors associated with ≥10% weight gain and its metabolic effects in virally suppressed people with human immunodeficiency virus (PWH) from the Dutch national AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort switching to tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI).MethodsWe identified antiretroviral therapy–experienced but TAF/INSTI-naive PWH who switched to a TAF and/or INSTI-containing regimen while virally suppressed for >12 months. Individuals with comorbidities/comedication associated with weight change were excluded. Analyses were stratified by switch to only TAF, only INSTI, or TAF + INSTI. Factors associated with ≥10% weight gain were assessed using parametric survival models. Changes in glucose, lipids, and blood pressure postswitch were modeled using mixed-effects linear regression and compared between those with and without ≥10% weight gain.ResultsAmong 1544 PWH who switched to only TAF, 2629 to only INSTI, and 918 to combined TAF + INSTI, ≥10% weight gain was observed in 8.8%, 10.6%, and 14.4%, respectively. Across these groups, weight gain was more frequent in Western and sub-Saharan African females than Western males. Weight gain was also more frequent in those with weight loss ≥1 kg/year before switching, age <40 years, and those discontinuing efavirenz. In those with ≥10% weight gain, 53.7% remained in the same body mass index (BMI) category, while a BMI change from normal/overweight at baseline to obesity at 24 months postswitch was seen in 13.9%, 11.7%, and 15.2% of those switching to only TAF, only INSTI, and TAF + INSTI, respectively. PWH with ≥10% weight gain showed significantly larger, but small increases in glucose, blood pressure, and lipid levels. Lipid increases were limited to those whose switch included TAF, whereas lipids decreased after switching to only INSTI.ConclusionsWeight gain of ≥10% after switch to TAF and/or INSTI was common in virally suppressed PWH, particularly in females and those starting both drugs simultaneously. Consequent changes in metabolic parameters were, however, modest.

Weight changes in patients with sustained viral suppression switching tenofovir disoproxil fumarate to tenofovir alafenamide.

Switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing antiretroviral therapy may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease risk. The extent of these changes and their association with TAF remain unclear. This retrospective cohort evaluated metabolic changes in virologically suppressed patients with HIV infection who switched from TDF to TAF without switching other antiretroviral therapy medications. Adult patients on TDF and with no HIV viral load values >200 copies/mL for ≥2 years prior to and following a TAF switch were included. Weight and other variables were collected for 2 years before and after the switch. Longitudinal linear mixed-effects models evaluated changes at 1 and 2 years after the switch. In the unadjusted analysis, there were increases in weight, BMI, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, fasting glucose, and atherosclerotic cardiovascular disease risk scores 2 years after switching to TAF (each p ≤ 0.03). However, only increases in total and low-density lipoprotein cholesterol were associated with TAF and were significantly different from expected changes predicted in the adjusted longitudinal models. Despite observing significant unadjusted metabolic changes after switching to TAF, only changes in cholesterol were associated with TAF and were different from changes expected in time-trend adjusted models.

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on estimated glomerular filtration rate slope in patients with HIV: A retrospective observational study

IntroductionThere is limited data on the effects of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on estimated glomerular filtration rates (eGFR) slope in patients with human immunodeficiency virus (HIV) infection. This study aimed to compare the eGFR slope when administering TDF and TAF and to investigate the predictors of improvement in eGFR slope after switching from TDF to TAF. MethodsWe conducted a single-center, retrospective, observational study in Japanese patients with HIV infection who switched the antiretroviral drug from TDF to TAF. eGFR was calculated using serum cystatin C. The eGFR slope was defined as the regression coefficient between eGFR and time. Differences between eGFR slope during TDF and TAF administration were compared using Wilcoxon signed rank test. A stepwise logistic regression model was used to examine the associations between improvement of eGFR slope after switching from TDF to TAF and various parameters. ResultsOverall, 63 patients (656 eGFR) were included in the analysis. The median analyzed durations of TDF and TAF exposures were 1.6 and 1.5 years, respectively. There were no significant differences between eGFR slope during TDF and TAF periods (median: 0.6 vs. 4.0 mL/min/1.73 m2/year, p = 0.165). The eGFR slopes during the TDF period and while switching from TDF to TAF were independent predictors of improvement in eGFR slope after switching from TDF to TAF. ConclusionsThe results suggest that patients with poor renal function and those with progressive worsening during TDF administration would benefit from switching to TAF.

Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides.

BackgroundIncreases in lipids have been observed in people with HIV (PWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF.MethodsAdults with ≥1 lipid measure before and after switch from TDF to TAF were identified in the OPERA cohort. Multivariable linear regression using generalized estimating equations was used to estimate predicted changes in lipids over time on TAF, modeled flexibly with linear splines.ResultsA total of 6451 PWH switched from TDF to TAF, of whom 4328 maintained all other agents. LDL-C increased significantly by 1.40 mg/dL/mo over the first 3 months on TAF, by 0.33 mg/dL/mo between 3 and 9 months and then plateauing beyond 9 months. TG increased significantly by 3.52 mg/dL/mo over the first 3 months of TAF, by 0.91 mg/mL/mo between 3 and 9 months and by 0.72 mg/mL/mo between 9 and 16 months, but decreased thereafter. Similar patterns were observed in analyses restricted to PWH who switched from TDF to TAF but maintained all other agents.ConclusionsTDF-to-TAF switch was associated with LDL-C and TG increases over the first 9 to 16 months on TAF. The dynamic patterns observed cannot be attributed to changes in other agents.

828. Short- and Long-Term Metabolic Changes in Virologically Suppressed Patients Switching from TDF to TAF Containing Antiretroviral Therapy

BackgroundSwitching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) containing antiretroviral therapy (ART) may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease (ASCVD) risk. The timing, duration, and extent of these changes and their definitive associations with TAF remain unclear. MethodsThis retrospective observational study evaluated weight, body mass index (BMI), cholesterol, and ASCVD risk score changes in virologically suppressed patients living with HIV infection (PLWH) who switched from TDF to TAF without switching any other ART regimen components. Adult patients on TDF and no HIV viral load values > 200 copies/mL for ≥ 2 years prior to and following a TAF switch were included. Body weight, BMI, cholesterol and other variables were collected for the 2 years before and after the switch. The Wilcoxon signed-rank test compared median values for each measurement pre and post switch in a univariate analysis. Longitudinal linear mixed effects models evaluated changes for each outcome measure at 1 and 2 years after the switch. Models were built with random effects for patients and included covariates such as time on TAF, age, sex, race, time with HIV, diabetes, smoking status, and concomitant medications associated with weight gain or loss. ResultsA total of 86 patients met study criteria (table 1). In the univariate analysis, there were significant increases in weight, BMI, total cholesterol, LDL, HDL, triglycerides, and ASCVD risk scores 2 years after switching to TAF (each p ≤ 0.05, table 2). However, after controlling for covariates, only the increases in total and LDL cholesterol were associated with switching to TAF and significantly different from expected changes predicted in the linear model. In terms of weight gain with TAF, patients gained an average of 4.3 pounds in year 1 and 3.8 pounds in year 2 after the switch. Neither of these increases were statistically different from the expected changes in weight predicted in the linear model (3.1 pounds/year, 95% CI: 1.6-4.6). ConclusionDespite observing significant increases in weight, BMI, cholesterol and ASCVD risk scores after switching to TAF, only the changes in cholesterol were significantly associated with TAF and different from changes expected in PLWH over time.Disclosures Jason J. Schafer, PharmD, MPH, Gilead (Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)ViiV (Advisor or Review Panel member)

S1127 Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) in Virally Suppressed Chronic Hepatitis B (CHB) Patients With Renal Impairment: Week 48 Results From a Phase 2 Open-Label Study

Introduction: Switching to TAF, a novel tenofovir prodrug, has shown maintenance of viral suppression with stable or improved bone and renal safety at Week 24 in CHB patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault [eGFRCG] < 60 mL/min) and ESRD patients on HD. We evaluated the safety and efficacy in these virally suppressed patients with renal impairment 1 year after switching to TAF in a Phase 2 study. Methods: CHB patients with renal impairment receiving TDF and/or other OAVs for ≥48 weeks and virally suppressed for ≥6 months with HBV DNA < 20 IU/mL at screening were enrolled into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG 15 to < 60 mL/min) and 2) ESRD (eGFRCG < 15 mL/min) on chronic HD. All patients were switched to TAF 25 mg QD for 96 weeks (given post-HD on days of dialysis for ESRD patients). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed in all patients at Week 48. Results: 93 patients (moderate-severe impairment 78; ESRD 15) were enrolled from 26 sites in 8 countries; 89% of patients remained on study at Week 48. At baseline, 74% were male, 77% Asian, 68% ≥60 y, 83% HBeAg-negative and median ALT was 17 U/L. Up to 25% overall (both cohorts) had osteoporosis at hip and/or spine, and a high proportion had comorbidities (60% HTN, 24% DM). Key efficacy/safety results at Week 48 are summarized in the Table. Efficacy (HBV DNA< 20 IU/mL) was maintained in nearly all patients on treatment at Week 48 and a high proportion had normal ALT levels. Five patients discontinued study drug early (withdrew consent) with last available HBV DNA < 20 U/mL; 1 patient had HBV DNA ≥20 IU/mL and 1 patient died. Relative to baseline levels, switching to TAF resulted in stable hip/spine BMD in moderate to severe renal impairment patients, with a slight decrease in hip BMD in ESRD patients. Slight improvements were observed in renal parameters including eGFRCG and markers of renal tubular function in moderate to severely impaired patients. TAF was well tolerated, with no Grade 3/4 or serious adverse events related to study drug. Conclusion: In renally-impaired CHB patients, including ESRD patients on HD, viral suppression was well maintained, and the bone and renal safety were stable or improved 48 weeks after switching to TAF.Table 1.: Study outcomes comparing EUS-guided liver biopsy and percutaneous liver biopsy.

Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization.

Background and ObjectiveMany people living with HIV (PLWH) on stable tenofovir disoproxil fumarate (TDF)-containing regimens have switched to tenofovir alafenamide (TAF), despite the potential lipid-lowering effect of TDF. We aimed to assess the impact of switching from TDF to TAF on lipids in real-world clinical practice.MethodsPLWH prescribed TDF for ≥ 4 weeks who switched to TAF were identified in the OPERA cohort. Patterns of dyslipidemia were compared before and after switch based on NCEP ATPIII guidelines. Elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD ≥ 7.5%) and statin use were assessed.ResultsAmong 6423 PLWH switched from TDF to TAF, the proportion with dyslipidemia/severe dyslipidemia observed after switch from TDF to TAF increased statistically significantly (p < 0.0001) with total cholesterol (5–10%), low-density lipoprotein cholesterol (16–23%), and triglycerides (21–27%), but decreased statistically significantly with high-density lipoprotein cholesterol (35–30%, p < 0.0001). These patterns of dyslipidemia persisted in sensitivity analyses restricted to PLWH who maintained all other antiretrovirals (N = 4328) or stratified by pharmaco-enhancer use before and after switch. An elevated ASCVD risk was detected in 29% before and 31% after switch. As many as 59% of PLWH with an elevated ASCVD risk were not prescribed a statin after switch from TDF to TAF.ConclusionsIn this large, diverse population of PLWH in the USA, the switch from TDF to TAF was associated with development of less favorable lipid profiles, regardless of pharmaco-enhancers or third-agent use. Statins remained underutilized after a switch from TDF to TAF.

Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV

BackgroundAs cardiovascular diseases represent the main cause of non-AIDS related death in people living with HIV (PLWH) with undetectable viral load, we evaluated lipid profile, weight gain and calculated cardiovascular risk change after switching from tenofovir disoproxil fumarate (TDF)-based regimens to tenofovir alafenamide (TAF)-based regimens.MethodsFor this retrospective study, we selected HIV-infected patients with suppressed viral load who fitted in one of the two groups below: First group (TDF/TDF): Patients treated continuously with TDF-based regimens. Second group (TDF/TAF): Patients treated with TDF-regimens during at least 6 months then switched to TAF-regimens while maintaining other drugs unchanged. Available data included date of birth, gender, ethnicity, lymphocyte T CD4+ count, weight, height, blood pressure, current/ex/non-smoker, diabetes mellitus, familial cardiovascular event, lipid profile, duration and nature of antiretroviral therapy. Lipid parameters, weight and calculated cardiovascular risk using 5-year reduced DAD score algorithm [Friis-Møller et al. in Eur J Cardiovasc Prev Rehabil 17:491–501, 2010] were analyzed in each groups.ResultsSwitching from TDF to TAF resulted in a significant increase in triglycerides levels, total cholesterol and HDL cholesterol. LDL cholesterol and total cholesterol/HDL ratio did not show significant changes. Calculated cardiovascular risk increased after switch from TDF- to TAF-based therapy.ConclusionsTogether with favorable outcomes at the bone and kidney levels, potential negative impact of TAF on lipid profile should be included in the reflection to propose the most appropriate and tailored ARV treatment.