Therapeutic effectiveness analysis of tenofovir alafenamide and tenofovir disoproxil fumarate on the treatment for chronic hepatitis B.

To explore the therapeutic effectiveness of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on the treatment for chronic hepatitis B (CHB). Retrospectively analyzing 241 cases of chronic hepatitis B patients admitted to our hospital from January 2020 to December 2021, they were divided into a TAF group of 180 cases and a TDF group of 61 cases. The liver function, serum virus markers, clinical efficacy, adverse reactions and cost-effectiveness ratio (CER) analysis of 2 groups were compared. Two groups of patients had no statistically significant difference in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) before treatment. After treatment, the levels of ALT, AST and TBIL were lower than before treatment in both groups (P < .05), but the inter-group difference was not statistically significant (P > .05). After treatment, Hepatitis B surface antigen (HBsAg) conversion rate and Hepatitis B virus DNA (HBV-DNA) conversion rate in the 2 groups had no statistically significant difference. After treatment, the difference in total clinical cure rate between the 2 groups has no statistical significance (P > .05), adverse reactions rate of TAF group was lower than that of TDF group (P < .05). The drug cost median of TAF group was higher than that of TDF (P < .05), but Cost-effectiveness analysis showed the CER of TAF group was similar of TDF group. TAF or TDF therapy can both improve liver function and promote recovery in patients with CHB, achieving the goal of treatment. TAF have more cost but have similar CER to TDF. Moreover, TAF therapy has a higher safety profile.

Assessment of weight gain in adult patients living with HIV receiving first-line dolutegravir-based or efavirenz-based ART regimens in routine care clinics in Tshwane district, South Africa: An observational study.

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

Is urinary ß2-microglobulin a reliable marker for assessment of renal tubular dysfunction in chronic hepatitis B patients receiving tenofovir therapy?

BACKGROUND AND AIM: Urinary ß2-microglobulin (ß2-M) is a marker for renal tubular dysfunction. The current study aimed to assess urinary ß2-M as a reliable marker for early prediction of tenofovir disoproxil fumarate (TDF)-related nephrotoxicity among hepatitis B virus (HBV) patients. METHODS: Forty-two HBV patients who were a candidate for TDF therapy or have recently started it (for less than 6 months) were enrolled and subjected to demographic, clinical, laboratory assessment, abdominal ultrasound and transient elastography. The glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Also, urinary ß2-M was measured by the ELISA method within 6 months after the introduction of TDF treatment and 6 months later. RESULTS: Mean age was 41.8 (9.55) years, 27 were males and 59.5% of patients have elevated urinary ß2-M after 6 months follow-up of TDF therapy. Urinary ß2-M was 0.07 ± 0.07 µg/ml at baseline and insignificantly increased up to 0.09 ± 0.08 µg/ml after 6 months follow-up. Despite the insignificant increase in serum creatinine from 0.85 ± 0.23 mg/dl at baseline to 0.9 ± 0.21 mg/dl after 6 months and the insignificant decrease in eGFR from 126.2 ± 39.72 ml/min at baseline and 117.64 ± 42.23 ml/min at 6 months follow-up. No correlation was found between the changes in urinary ß2-M and the changes in other renal function indices at baseline and 6 months follow-up. CONCLUSIONS: Short-term TDF therapy is associated with nonsignificant changes either in eGFR or urinary ß2-M; these changes are not clinically relevant that indicates disease progression. Therefore, the suitability of urinary ß2-M as a screening tool for tenofovir induced tubular dysfunction should be further.

Update on HIV prevention and preexposure prophylaxis.

HIV preexposure prophylaxis (PrEP) is an opportunity for clinicians to curb the 40,000 HIV infections occurring annually in the United States. PrEP is medication used by HIV-negative patients to reduce their risk of acquiring the virus. This article provides a baseline understanding of PrEP indications, prescribing, and monitoring, including a review of previously approved medication and an update on newly approved drugs, including emtricitabine/tenofovir alafenamide (F/TAF). Sexual and gender minorities are often underrepresented in the literature about PrEP, but clinicians should address risk focused on specific behaviors rather than population-level characteristics. As one of few professions with prescriptive authority, PAs have an obligation to understand and manage PrEP.

Adverse events in Chinese human immunodeficiency virus (HIV) patients receiving first line antiretroviral therapy.

BACKGROUND: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. METHODS: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. RESULTS: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. CONCLUSION: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m2, pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.

Assessment of Drug Interaction Potential Between the Hepatitis C Virus Direct-Acting Antiviral Agents Elbasvir/Grazoprevir and the Nucleotide Analog Reverse-Transcriptase Inhibitor Tenofovir Disoproxil Fumarate.

Treatment of individuals coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) requires careful consideration of potential drug-drug interactions. We evaluated the pharmacokinetic interaction of the direct-acting antiviral agents elbasvir and grazoprevir coadministered with the nucleotide reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF). Three open-label, multidose studies in healthy adults were conducted. In the first study (N = 10), participants received TDF 300 mg once daily, elbasvir 50 mg once daily, and elbasvir coadministered with TDF. In the second study (N = 12), participants received TDF 300 mg once daily, grazoprevir 200 mg once daily, and grazoprevir coadministered with TDF. In the third study (N = 14), participants received TDF 300 mg once daily and TDF 300 mg coadministered with coformulated elbasvir/grazoprevir 50 mg/100 mg once daily. Pharmacokinetics and safety were evaluated. Following coadministration, the tenofovir area under the plasma concentration-time curve to 24 hours and maximum plasma concentration geometric mean ratios (90% confidence intervals) for tenofovir and coadministered drug(s) versus tenofovir were 1.3 (1.2, 1.5) and 1.5 (1.3, 1.6), respectively, when coadministered with elbasvir; 1.2 (1.1, 1.3) and 1.1 (1.0, 1.2), respectively, when coadministered with grazoprevir; and 1.3 (1.2, 1.4) and 1.1 (1.0, 1.4), respectively, when coadministered with the elbasvir/grazoprevir coformulation. TDF had minimal effect on elbasvir and grazoprevir pharmacokinetics. Elbasvir and/or grazoprevir coadministered with TDF resulted in no clinically meaningful tenofovir exposure increases and was generally well tolerated, with no deaths, serious adverse events (AEs), discontinuations due to AEs, or laboratory AEs reported. No dose adjustments for elbasvir/grazoprevir or TDF are needed for coadministration in HCV/HIV-coinfected people.

Assessment of bone mineral density in patients with cirrhosis treated with third-generation nucleos(t)ide analogues: comparison between tenofovir and entecavir.

BACKGROUND AND AIM: Tenofovir and entecavir are nowadays the first-line treatment in hepatitis B virus (HBV)-related cirrhosis. Both drugs were shown to be effective in HBV suppression and well tolerated. The effects of tenofovir on bone mineral density (BMD), however, were shown to worsen the rate of osteoporosis, which is already a common feature in cirrhosis. In contrast, entecavir seems to have no effect on mineral metabolism. The aim of our study was to compare the effects of nucleos(t)ide analogs on bone density in HBV-related cirrhosis. PATIENTS AND METHODS: Fourty-eight patients were treated with tenofovir and 22 patients were treated with entecavir, and were followed prospectively from 2008 to 2013. To evaluate BMD, laboratory examinations, dual-X-ray absorptiometry, and Fracture Risk Assessment Tool were assessed. RESULTS: During the study, no difference was found between the two groups in the plasmatic concentration of calcium, phosphate, vitamin D, parathyroid hormone, or creatinine. Dual-X-ray absorptiometry showed no difference in the T-score and Fracture Risk Assessment Tool showed no significant difference in the 10-year risk of osteoporotic fractures in the two groups. On univariate and multivariate analyses, the only predictors of osteoporosis development were the prognostic scores of liver disease and BMI. CONCLUSION: Both tenofovir and entecavir are effective in treating HBV in cirrhotic patients. The known effects of tenofovir on BMD do not worsen osteoporotic fractures risk compared with entecavir in these patients.

Switching to a rilpivirine/emtricitabine/tenofovir single-tablet regimen in RNA-suppressed patients infected with human immunodeficiency virus 1: Effectiveness, safety and costs at 96 weeks.

OBJECTIVES: This study evaluates the effectiveness, safety and costs of switching to a rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) regimen in treatment-experienced HIV-1-infected patients with sustained virological suppression. METHODS: Observational, prospective study. Study population included all treatment-experienced patients with sustained virological suppression who switched to RPV/FTC/TDF during 2013 in a tertiary hospital. Patients were followed until they completed 96 weeks of treatment. The effectiveness end-point was defined as the proportion of patients who maintained virological suppression at week 96 by intention-to-treat analysis (discontinuation=failure). The safety of RPV/FTC/TDF (incidence of adverse events leading to discontinuation and laboratory abnormalities) and adherence to this regimen were evaluated, and the cost of switching was analysed. RESULTS: One-hundred forty-six patients were included. At week 96, 71.9% of patients remained virologically suppressed; 6.8% experienced virological failure. During follow-up, 25.3% of patients discontinued RPV/FTC/TDF (14.4% because of adverse events, mainly renal impairment). Throughout the 96 weeks, there were significant decreases in total cholesterol (TC) (14.0 mg/dL, P<.001), TC/HDL cholesterol ratio (0.4 mg/dL, P=.019) and triglycerides (42.0 mg/dL, P<.001). A slight decrease in glomerular filtration rate was observed (4.3 mL/min/1.73 m2 , P<.001). Switching to RPV/FTC/TDF improved adherence in the subgroup of patients whose previous treatment was based on a twice-daily schedule, although differences did not reach statistical significance. Switching to RPV/FTC/TDF reduced the annual per-patient antiretroviral cost by €1744 (P<.001). CONCLUSIONS: In virologically suppressed patients, the switch to a RPV/FTC/TDF regimen was associated with a mild but maintained improvement in lipid parameters and a significant reduction in costs. However, the relatively high rates of virological failure and treatment discontinuation because of adverse events make this combination a less favourable choice over other regimens currently available.

Tenofovir disoproxil fumarate-associated renal tubular dysfunction: noninvasive assessment of mitochondrial injury.

OBJECTIVE: To determine whether tenofovir disoproxil fumarate (TDF)-associated renal tubular dysfunction is associated with evidence of mitochondrial injury in urine. DESIGN: Single-centre cross-sectional observational study of HIV-positive outpatients. METHODS: Biochemistry was performed on paired serum and urine samples. Mitochondrial DNA (mtDNA) was studied by real-time PCR and long-range PCR on cellular fractions of urine. RESULTS: In total, 48 study participants were enrolled of whom half were TDF treated. Mean age was 43 years. 58% had estimated glomerular filtration rate at least 90, with no differences between ART treatment groups. Urinary phosphate wasting was common and independently associated with TDF exposure (P = 0.02). No study participants had low molecular weight proteinuria. Cellular mtDNA content in urine was heavily influenced by the cellularity of the sample. The mtDNA 'common deletion' mutation was detectable significantly more commonly in the urine of TDF exposed study participants compared with unexposed (13/22 TDF study participants (59%), 4/21 TDF (19%), P = 0.01). Common deletion levels were not associated with age, estimated glomerular filtration rate, or urinary phosphate wasting. No mtDNA measures were associated with current or nadir CD4 lymphocyte counts, duration of disease or antiretroviral therapy, or historical exposure to nucleoside analogue reverse transcriptase inhibitors with systemic mitochondrial toxicity. CONCLUSION: The presence of mtDNA mutations in the context of TDF exposure adds weight to the hypothesis that TDF-associated renal damage is at least in part mitochondrially mediated. The assessment of mtDNA markers in urine may be a feasible noninvasive investigation for TDF-treated patients.

Longitudinal Assessment of Proximal Tubular Dysfunction in HIV Seropositive and Seronegative Persons: Correlates and Implications.

BACKGROUND: Proximal tubular dysfunction (PTD) is common in HIV-positive persons and has been associated with tenofovir disoproxil fumarate (TDF). However, few studies have assessed the natural history PTD in HIV-positive and -negative individuals, or the association of PTD with the subsequent trajectory of directly measured glomerular filtration rate (mGFR). METHODS: We followed 192 HIV-positive and 100 HIV-negative, nondiabetic participants for 3 years. We measured 3 PTD markers (normoglycemic glycosuria, fractional excretion of phosphorus, and tubular proteinuria) and mGFR (by iohexol disappearance from serum) annually. We used univariate and multivariate generalized estimating equation logistic regression to identify factors associated with PTD across all visits and linear mixed effects models to assess the association between baseline PTD and mGFR slope. RESULTS: Compared with HIV-negative participants, HIV-positive persons that were not taking antiretroviral therapy were at increased risk of PTD (adjusted odds ratio 3.33; 95% confidence interval: 1.65 to 6.71), whereas those taking a TDF-based or a TDF-sparing regimen were not at significantly increased risk of PTD. Among HIV-positive participants, uncontrolled viremia was a strong correlate of PTD. Forty-nine of 55 (89%) participants with PTD at baseline had at least 1 subsequent visit without PTD. There was no association between baseline PTD and rate of decline in mGFR over time. CONCLUSIONS: Poorly controlled HIV may be a stronger risk factor for PTD than TDF use. The individual-level variability of the PTD markers over time was high, potentially limiting their usefulness for routine screening in unselected patients. Baseline PTD was not associated with subsequent mGFR slope.

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs). METHODS: This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs). RESULTS: We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD -3.96; 95% CI: -7.31, -1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD -3.85; 95% CI: -5.02, -2.78). CONCLUSIONS: In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower or similar to those for all HIV patients, with the lowest IRs observed among patients receiving EFV/FTC/TDF. Compared with all HIV patients, the observed IR for fracture was higher with EVG/COBI/FTC/TDF, comparable with RPV/FTC/TDF, and lower with EFV/FTC/TDF.

Preexposure Prophylaxis (PrEP) for HIV Prevention: The Primary Care Perspective.

Until recently there have been few primary care office-based strategies to reduce the transmission of HIV. In May 2014 the Centers for Disease Control and Prevention published updated practice guidelines recommending the use of preexposure prophylaxis (PrEP) with daily oral dosing of tenofovir/emtricitabine to help prevent HIV infection in high-risk individuals (strength of recommendation, A). Knowledge of PrEP among primary care providers is low, however, and this intervention is likely reaching only a small fraction of eligible patients. PrEP is recommended for certain injection drug users, nonmonogamous men who have sex with men, heterosexual women who have sex with men who have sex with men or injection drug users, and those in HIV serodiscordant relationships. Providers should obtain baseline laboratory values and provide initial counseling before prescribing PrEP. Regular office visits are necessary to ensure adherence, provide ongoing counseling, and monitor for side effects, including nausea, abdominal pain, headache, and, less commonly, increased creatinine. Guidelines and toolkits have been developed to assist in incorporating PrEP into primary care practice. PrEP is gaining widespread acceptance and has become a crucial tool in the fight to stop the spread of HIV.

The Epi-TAF for Tenofovir Disoproxil Fumarate?

Approximately 84% of human immunodeficiency virus (HIV)-infected US residents on antiretroviral therapy currently receive some form of tenofovir disoproxil fumarate (TDF) as part of their HIV treatment regimen. The TDF analogue tenofovir alafenamide (TAF) has demonstrated equal efficacy but with decreased renal injury and bone mineral density loss compared with TDF. We examine how much more society ought to be willing to pay for TAF over TDF, in exchange for its improved toxicity profile. Using cost-effectiveness methods, we find that current conditions warrant an annual premium of up to $1000 over the average wholesale price (AWP) of TDF. Once generic coformulations of tenofovir/lamivudine become accessible, however, the appropriate premium for TAF will likely merit a downward adjustment, using generic TDF-based costs as the benchmark.