TDF-based Antiretroviral Therapy Research Articles

Kidney disease among adults on tenofovir-based second-line antiretroviral therapy in Dar es Salaam, Tanzania

Background: Kidney disease is a growing non-AIDS-related comorbidity among people living with HIV (PLWH). Tenofovir disoproxil fumarate (TDF) can result in proximal tubulopathy and acute tubular injury, whereas atazanavir/ritonavir (ATV/r) can cause interstitial nephritis and renal stones, both of which can lead to chronic kidney disease.Objectives: To examine the relationship between second-line combination antiretroviral therapy (ART) and the risk of kidney disease and morphological changes among PLWH in Dar es Salaam, Tanzania.Method: A cross-sectional study of adult PLWH receiving TDF-based second-line ART. Socio-demographic and clinical data were gathered, and laboratory tests were conducted to determine the estimated glomerular filtration rate (eGFR). Ultrasonography was performed to visualise the kidneys.Results: A total of 323 patients were enrolled (67.8% women), with a median age of 44 (interquartile range [IQR]: 39–51) years. Patients were on second-line ART for a median of 49 [IQR: 25–73] months, and 60% received ATV/r. Low eGFR ( 90 mL/min per 1.73 m2) was found in 22% of patients, proportionately higher among patients on ATV/r compared to those on a lopinavir/ritonavir (LPV/r) (P 0.05). Nearly one-third (32.2%) of patients had a triad of renal calcinosis, renal calculi, and nephritis on ultrasonography. Patients using ATV/r had significantly smaller kidney volumes and greater proportions of renal calculi and nephritis compared to those on LPV/r (P 0.05).Conclusion: Adults on second-line ART containing TDF were found to have a high prevalence of renal kidney disease in the Tanzanian context. Predictors of kidney disease were older age, proteinuria, and ATV/r-based regimen as compared to LPV/r.

Hepatitis B virus (HBV) viremia despite tenofovir disoproxil fumarate-containing antiretroviral therapy in persons with HBV/HIV coinfection

BackgroundThe goal of treatment of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is suppression of both viruses; yet incomplete HBV suppression on tenofovir (TFV) disoproxil fumarate (TDF)-based antiretroviral therapy (ART) is common. This study investigated TFV resistance-associated mutations (RAMs) in individuals with HBV/HIV coinfection with viremia on TDF/lamivudine (3TC)-containing ART. MethodsSamples from individuals with HBV DNA levels ≥20 IU/mL in a cross-sectional study of 138 persons with HBV/HIV coinfection in Ghana were analyzed in the present study. HBV was sequenced for RAM analysis. TFV-diphosphate (TFV-DP) concentration in peripheral blood mononuclear cells (PBMCs) was used to assess ART adherence level. ResultsNine of 138 participants (6.5 %) had detectable HBV DNA levels ≥20 IU/mL while on ART. Seven of the nine participants had TFV-DP concentrations commensurate with 7 doses per week, and six had suppressed HIV RNA. Phylogenetic analysis revealed that eight sequences were HBV genotype E, with one genotype E/A recombinant. Ten previously-reported TFV RAMs were present in the study samples; eight were wild-type for HBV genotype E. The non-genotype-E-wild-type point mutations M267L and K333Q were found in two and one patients, respectively. No 3TC RAMs were found. ConclusionHBV viremia despite high adherence to TDF/3TC-based ART may be associated with the presence of TFV RAMs. These findings highlight the need for enhanced resistance monitoring and further research to examine the clinical significance of reported TFV RAMs. Individuals with HBV/HIV coinfection and TFV resistance on TDF-based ART may need alternative treatment strategies.

Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy.

Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy is limited. We evaluated metabolic markers in pregnant women with HIV after starting TAF- vs TDF-based ART. We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC+DTG; n=217) or TDF/FTC+DTG (n=215). We measured non-fasting plasma concentrations of glucose, total-cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), lipoprotein (a), and triglycerides from samples collected eight weeks after enrollment. We employed linear regression models to estimate by-arm mean differences. 219 participants enrolled in the DTG arms in Zimbabwe and Uganda: 109 in the TAF/FTC+DTG and 110 in the TDF/FTC+DTG arms. At study entry, mean gestational age was 22.6 weeks, median HIV-1 RNA was 711 copies/mL, and mean age was 25.8 years. By eight weeks, mean total cholesterol was 12 mg/dL higher in women randomized to TAF/FTC+DTG versus TDF/FTC+DTG (95% CI 3.8, 21.1). Pregnant women in the TAF/FTC+DTG arm had higher mean LDL-C (7.1 mg/dL, 95% CI 0.2, 14.0), triglycerides (12.3 mg/dL, 95% CI 1.8, 22.7), lipoprotein (a) (7.3 mg/dL, 95% CI 1.1, 13.6), and lower mean HDL-C (2.8 mg/dL, 95% CI 0.1, 5.6) compared to the TDF/FTC+DTG arm. Pregnant women randomized to start TAF/FTC+DTG had higher lipids than those randomized to TDF/FTC+DTG within eight weeks of ART initiation. However, lipid levels were within normal reference ranges.

Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir-based antiretroviral therapy.

We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia. Cross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART). We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia at least 1000 copies/ml using logistic regression models. In exploratory analyses, we used receiver operating curves (ROCs) to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia. Among 124 participants, 68 (54.8%) were women, median age was 39 years [interquartile range (IQR) 34-45] and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV [1000 ng/ml increase, odds ratio (OR) 0.97 95% CI 0.94-0.99, P = 0.005] and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95% CI 0.67-0.86, P < 0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV, P = 0.072; DBS TFV-DP, P = 0.003). Nagelkerke pseudo- R2 for the DBS TFV-DP models was higher for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥1000 copies/ml. Among PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.

Tenofovir-Induced Renal Dysfunction Among HIV-Infected Patients: A Systematic Review.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug widely used as part of antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV-1) infection. Negative effects of tenofovir include impaired kidney function, especially with long-term use. In studies conducted among HIV-positive individuals, we found evidence of extensive kidney damage associated with TDF use. Despite the therapeutic importance of this consequence, its continued use in ART regimens was not contraindicated. The therapeutic and long-term effects of TDF are a major concern. However, in countries or settings where resources are limited and renal function monitoring cannot be ensured, screening methods to detect ART-related renal failure are still supported by data. Therefore, it is safe to re-evaluate the use of TDF-based ART. However, adherence to guidelines may be hampered by insufficient laboratory testing in low- and middle-income countries. More research is also needed among people under 18 years of age and pregnant and breastfeeding mothers.

Blood immune cells from people with HIV on antiviral regimens that contain tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) have differential metabolic signatures

BackgroundMitochondria regulate immune and organ function. It is unknown whether higher intracellular drug levels observed in peripheral blood mononuclear cells (PBMCs) treated with tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) may alter mitochondrial function and energy production in immune cells in HIV(+) patients. MethodsCellular bioenergetics were determined in PBMCs from HIV-1(−) participants exposed to TAF versus TDF in vitro, at a comparable concentration to a clinically relevant plasma exposure. A decrease in cellular oxygen consumption rate (OCR) at baseline (basal-OCR) and under cellular stress (max-OCR) may suggest mitochondrial dysfunction. We also assessed the in vivo impact of TAF vs TDF on OCR in PBMCs from 26 people with HIV (PWH) interchanged from TDF-based to TAF-based antiretroviral therapy (ART) over a 9-month period in the setting of an open label clinical trial. The Wilcoxon and Mann Whitney tests were used for comparison of continuous variables. ResultsPBMCs from HIV-1(−) participants exposed in vitro to a concentration of 0.12–3.3 μM for TAF and TDF at 2 and 24 h, reduced basal and maximal OCR compared to vehicle control. Switch studies of antivirals (TAF vs TDF) within the same PWH showed that TAF-based ART was associated with reduced OCR compared to TDF-based ART in PBMCs. We observed that TAF-treated PBMCs selectively relied more on glucose/pyruvate supply rather than fatty acid to fuel their mitochondria. ConclusionsCompared to TDF, TAF may alter bioenergetics in immune cells from PWH in vitro and in vivo. The clinical significance in terms of the differential impact caused by TAF versus TDF on mitochondrial function and energy production in immune cells, a regulator of immune function, requires further studied in HIV, preexposure prophylaxis and hepatitis B.

Serial changes in renal indices in chronic HCV patients with and without HIV co-infection receiving sofosbuvir and tenofovir-based therapies.

Sofosbuvir (SOF) is authorized for hepatitis C virus (HCV) patients. The nephrotoxicity of SOF on HCV mono-infected and HCV-human immunodeficiency virus (HIV) individuals receiving antiretroviral therapy (ART) remains controversial. A prospective study including 159 HCV mono-infected and 124 HCV-HIV individuals (47 were ART naïve and 77 were tenofovir [TDF]-based ART) who presented with an estimated glomerular filtration rate (eGFR) ≥30ml/min/1.73m2 at baseline and were treated with SOF-daclatasvir for 12weeks. The eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation over the study period. HCV patients had a progressive decline in median levels of eGFR compared with HCV-HIV patients who were ART naïve and those receiving TDF-based ART during and after discontinuing SOF-DAC treatment (96, 109 and 114 at baseline vs 94, 117 and 108 at the end of treatment [EOT]) vs 95, 114 and 115ml/min/1.73m2 at 12weeks after treatment [SVR12], respectively). Moreover, the rate of eGFR stage worsening was more pronounced in HCV mono-infected compared with HCV-HIV individuals who were ART naïve and those receiving TDF-based ART (21.4% vs 8.5% and 14.3% at EOT; 21.4% vs 2.1% and 6.5% at SVR12, respectively). Multivariable regression analysis showed that baseline variables were not independent predictors of eGFR stage worsening either at EOT or SVR12. Because the changes in eGFR were minimal and not of clinical significance, and TDF was not associated with an increase in renal dysfunction, SOF-based direct-acting antivirals could be safely used in HCV mono-infected and HCV-HIV individuals, even in those on TDF-based ART.

Evolution of estimated glomerular filtration rate in human immunodeficiency virus and hepatitis C virus-coinfected patients receiving sofosbuvir-based direct-acting antivirals and antiretroviral therapy.

The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)-coinfected patients receiving antiretroviral therapy (ART) remains controversial. We prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF-based direct-acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)-based (n=116) and TFV-free ART (n=51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV-based ART had a higher eGFR decline than those on TFV-free ART (slope coefficient difference: -0.82ml/min/1.73m2 /month [95% CI: -1.21 to -0.43]; p<0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13ml/min/1.73m2 /month [95% CI: -0.32 to 0.58]; p=0.42) after discontinuing DAAs. Participants on TFV TDF-based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)-based ART (slope coefficient difference: -0.31ml/min/1.73m2 /month [95% CI: -0.50 to -0.12]; p=0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06ml/min/1.73m2 /month [95% CI: -0.98 to 1.10]; p=0.91). In conclusion, HIV/HCV-coinfected patients on TFV-based ART had a slight eGFR decline compared to those on TFV-free ART during SOF-based DAA therapy. A similar trend between TDF-based and TAF-based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF-based DAAs in HIV-positive patients on TFV-based ART.

Detectable HIV RNA in late pregnancy associated with low tenofovir hair levels at time of delivery among women living with HIV in the United States.

We evaluated peripartum tenofovir (TFV) exposure via hair measures among women living with HIV in the United States. Observational cohort study. Hair samples were collected at or shortly after childbirth among mothers enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study of the Pediatric HIV/AIDS Cohort Study between 6/2014 and 7/2016. Among mothers receiving TFV disoproxil fumarate (TDF)-based regimens during pregnancy, TFV hair concentrations were analyzed using liquid chromatography/tandem mass spectrometry. Weight-normalized TFV concentrations were log10 transformed. Multivariable linear regression assessed correlates of TFV concentrations. Overall, 121 mothers on TDF-based antiretroviral therapy during pregnancy had hair specimens tested for TFV concentrations and were included in the analysis. Median age at delivery was 31 years [interquartile range (IQR) 26-36]; 71% self-identified as non-Hispanic black, and 10% had unsuppressed viral loads in late pregnancy (HIV RNA ≥ 400 copies/ml). Median time from birth to hair collection was 3 days (IQR 1-14) and median TFV hair concentration was 0.02 ng/mg (IQR 0.01-0.04). In multivariable models, an unsuppressed viral load in late pregnancy was associated with 80% lower adjusted mean peripartum TFV concentrations than pregnancies with viral suppression (95% confidence interval: -90% to -59%, P < 0.001). Use of TDF only in the first trimester and attaining high school graduation were also associated with lower TFV hair concentrations. Unsuppressed viral load during late pregnancy was strongly associated with lower maternal TFV hair concentrations at birth, though viremia was rare. Efforts to improve maternal virological outcomes and eliminate vertical HIV transmission could incorporate drug exposure monitoring using hair or other metrics.

Prevalence of kidney injury in patients taking tenofovir based antiretroviral therapy at a primary health care clinic, in East Rand,Gauteng Province

ABSTRACT Background: Tenofovir disoproxil fumarate (TDF) is currently one of the key medicines in the management of HIV-1 infection across the globe. Conversely, various studies indicate that TDF is associated with an increased risk of kidney injury. Furthermore, data from different studies indicate that clinically significant TDF-related kidney toxicity is uncommon, with an estimated incidence of reduction in creatinine clearance to below 50 ml/min ranging from 3% to 8%. Objective: This study investigated the prevalence of TDF-induced kidney injury, risk factors associated with the exacerbation of kidney injury, and reversibility of TDF-induced kidney injury in a South African cohort. Methods: A retrospective cross-sectional descriptive study was conducted, where quantitative data were collected through patient file reviews. Files of 600 patients initiated on TDF-based antiretroviral therapy (ART) were reviewed. The degree of kidney function was monitored using the eGFR at baseline, 3, 6, 12, and 36 months of TDF therapy. eGFR after TDF discontinuation was monitored to determine its reversibility. HIV parameters (CD4 count and viral load) were monitored to determine patients’ immune response to treatment throughout the study. Comorbidities and other factors that affect kidney function were extracted from the patients’ files. Results: Final sample comprised 413 files, 272 (65.9%) were females. Significant variability in the eGFR overtime was observed; 20 (5.9%) experienced mild-moderate kidney injury, four (1.2%) developed moderate-severe kidney injury and three (1%) had severe kidney injury. Significant association with decline in eGFR included high viral load, low CD4 count and long duration of treatment. Six (1.5%) patients were discontinued from TDF treatment and five patients of those fully recovered. Conclusions: TDF-induced kidney injury was uncommon in this setting and where it occurred was associated with full reversibility after discontinuation. Therefore, lack of resources in health-care settings in terms of frequent monitoring of renal function should not prevent prescribing TDF-based therapy.

Association between Nonalcoholic Fatty Liver Disease and Bone Mineral Density in HIV-Infected Patients Receiving Long-term TDF-Based Antiretroviral Therapy.

Tenofovir (TDF) has a detrimental effect on bone mineral density (BMD), while nonalcoholic fatty liver disease (NAFLD) is associated with a lower BMD. To help understand the mutual effects of NAFLD and TDF on BMD, this study was designed to explore the potential association between NAFLD and BMD in HIV-infected patients receiving long-term TDF-based antiretroviral therapy (ART). A total of 89 HIV-infected patients who received TDF-based ART for more than three years were enrolled in this cross-sectional study. We measured BMD using an ultrasonic bone density apparatus, and liver ultrasonography was performed to determine the severity of the fatty liver. The association of NAFLD with BMD was examined using multiple logistic regression analyses. Patients with NAFLD showed a worse BMD status than those without NAFLD. The incidence rates of osteopenia (42.86% versus 25.93%) and osteoporosis (17.14% versus 3.70%) were significantly higher in HIV-infected patients with NAFLD than in those without NAFLD. After multivariate adjustment, the odds ratio (OR) for patients with NAFLD exhibiting a worse BMD status compared with those without NAFLD was 4.49 (95% confidence interval [CI] 1.42, 14.15). Based on our results, NAFLD was significantly associated with a worse BMD status, including osteopenia and osteoporosis, in HIV patients after receiving long-term TDF-based ART. Furthermore, we may want to avoid using TDF for ART in HIV-infected patients with NAFLD.

Longitudinal change in bone mineral density among Chinese individuals with HIV after initiation of antiretroviral therapy.

Persons living with HIV (PLWH) are at increased risk for osteoporosis and fracture. Tenofovir disoproxil fumarate (TDF) has been associated with higher rates of bone mineral density (BMD) loss, osteoporosis, and fracture. Few studies have studied the impact among PLWH in Asia. We analyzed retrospectively patients from the outpatient HIV clinic of a large tertiary hospital in Beijing, China, from March 2007 to May 2016. Patients who had dual-energy X-ray absorptiometry testing prior to antiretroviral initiation and at 48 and/or 96weeks after initiation were included in this analysis. A total of 136 patients were included (mean age 36.0 ± 10.6years) and over 90% participants were male and Han Chinese ethnicity. We observed greater declines in BMD at the spine from baseline to week 48 (-2.94% vs. -0.74%) and at the hip from baseline to week 96 (-4.37% vs. -2.34%) in the TDF group compared with the non-TDF group. With regard to HIV-specific parameters, longer duration since HIV diagnosis and undetectable viral load over time were associated with lower BMD at the hip [relative risk (RR) 0.97, 95% confidence index (CI) (0.95, 0.99) per 1year increase and RR 0.96, 95%CI (0.94, 0.99), respectively] and femoral neck [RR 0.97, 95%CI (0.95, 0.99) per 1year increase and RR 0.97, 95%CI (0.95, 0.998), respectively] over 96weeks. This is the first study to report changes in BMD among PLWH after initiation of TDF-based antiretroviral therapy in China. Our findings provide important knowledge for the long-term clinical management of PLWH from this region.

Long-Term TDF-Inclusive ART and Progressive Rates of HBsAg Loss in HIV-HBV Coinfection-Lessons for Functional HBV Cure?

Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection. Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years. 12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (<15 IU/mL) and 91.4% had undetectable HIV RNA (<20 copies/mL). HBsAg loss was high and ongoing over 5 years of follow-up in HIV-HBV coinfected individuals on TDF-containing ART and undetectable HBV was almost universal. Although the pattern of HBsAg loss temporarily parallels immune reconstitution, we could not identify predictive immune markers. The high rate of HBsAg loss in HIV-HBV coinfection may offer valuable insights into the search for a functional HBV cure.

Brief Report: Kidney Dysfunction Does Not Contribute Significantly to Antiretroviral Therapy Modification in Treatment-Naive PLWH Receiving Initial ART.

Antiretroviral therapy (ART) durability, time to modification or cessation, has declined. The study objective was to determine whether kidney dysfunction is contributing to reduced durability. This retrospective follow-up study of CNICS evaluated treatment-naive PLWH initiating ART between 2007 and 2014. Regimen modification was defined as cessation/modification of any part of the 3-drug ART regimen. We evaluated the role of kidney dysfunction in initial regimen modification as both a mediator and effect measure modifier. Associations of the variables with the ART modification were examined using univariable and multivariable Cox proportional hazard models. Of 4515 PLWH included in the analysis, 1967 modified their ART. Of those receiving TDF-based ART (n = 3888), 1580 (41%) modified their regimen compared with 387 (62%) receiving other regimens. Overall, the median eGFR decreased by 5 mL/min/1.73 m (quartiles: first = -16, third = 0) from baseline to follow-up. Of the 128 patients with low baseline eGFR (<60 mL/min/1.73 m), the final eGFR remained low in 73% while it increased to above 60 mL/min/1.73 m in 27%. Of the 4387 with normal baseline eGFR, only 135 (3%) had a final eGFR <60 mL/min/1.73 m. Those with low eGFR at the baseline and/or final visits were more likely to modify ART than others (hazards ratio = 1.75, 95% confidence interval: 1.39 to 2.19, P < 0.001). Relative to other regimens, TDF-based ART was less likely to be modified when accounting for numerous clinical and demographic traits. For patients in our study initiated on ART, including TDF-based ART, in the last decade, kidney dysfunction is not a major factor leading to regimen modification.

Lipid profile and renal safety of tenofovir disoproxil fumarate-based anti-retroviral therapy in HIV-infected Chinese patients

BackgroundTenofovir disoproxil fumarate (TDF) is an important component of antiretroviral therapy (ART) that has been widely used. The aim of this study was to observe the long-term impact of TDF-based ART on lipid metabolism profiles and renal functions in Chinese patients. Methods414 and 124 HIV-infected, ART-naïve patients who initiated TDF-based regimens and non-TDF regimens respectively were retrospectively included. Demographic characteristics and clinical information of each patient was collected. Changes of lipid profiles and renal function, as well as the risk factors of hyperlipidemia and renal dysfunction were analyzed. ResultsAfter 96 weeks of ART, HIV viral loads were undetectable in 97.34% (403/414) of patients exposed to TDF. The plasma total cholesterol (TCH) increased from 3.97 ± 0.83 mmol/L to 4.53 ± 0.87 mmol/L (P < 0.001), which did not show a significant difference comparing with non-TDF exposed group. By contrast, the plasma triglyceride (TG) levels increased, but were still lower than that in the non-TDF exposed group (0.26 ± 1.24 vs. 0.89 ± 1.78, P < 0.001). The mean estimated glomerular filtration rate (eGFR) decreased from 127.29 ± 24.04ml∙min−1∙1.73 m−2 at baseline to 118.84 ± 22.74 ml∙min−1∙1.73 m−2(P < 0.001) in the TDF exposed group, while it increased in the non-TDF exposed group. In the TDF group, high body mass index (BMI) (OR = 1.13, P = 0.01), high baseline TG (OR = 2.33, P<0.001) and receiving protease inhibitors (PIs) (OR = 7.58, P < 0.001) were associated with hypertriglyceridemia after ART, while high baseline TCH predicted hypercholesterolemia (OR = 3.58, P < 0.001). MSM (OR = 0.22, P = 0.02) and baseline eGFR (OR = 0.90, P < 0.001) was associated with renal dysfunction after ART. ConclusionsTDF-based regimens are of good therapeutic effect among Chinese people. These regimens showed a better plasma lipid profile but mild renal dysfunction as compared to non-TDF based regimens. Patients with high BMI, high baseline TG, high baseline TCH and low baseline eGFR should be closely monitored when using TDF-based ART.

Long Term Exposure to Tenofovir Disoproxil Fumarate-Containing Antiretroviral Therapy Is Associated with Renal Impairment in an African Cohort of HIV-Infected Adults.

Objectives and Method:There are growing concerns of tenofovir disoproxil fumarate (TDF)–associated renal toxicity. We evaluated the effect of long-term TDF exposure on renal function in a cohort of HIV-1-infected Nigerians between 2006 and 2015. Multivariate logistic regression was used to identify predictors of renal impairment at different time over 144 weeks of antiretroviral therapy (ART).Results:Data of 4897 patients, median age 42 years (interquartile range: 36-49), and 61% females were analyzed. The prevalence of renal impairment increased from 10% at week 24 to 45% at 144 weeks in TDF-exposed participants compared to an increase from 8% at 24 weeks to 14% at 144 weeks in TDF-unexposed participants. Tenofovir disoproxil fumarate exposure predicted the risk of renal impairment at 144 weeks of ART (odds ratio: 2.36; 95% confidence interval: 1.28-4.34).Conclusion:Long-term exposure to TDF-based ART significantly increases the likelihood of renal impairment. The continued use of TDF-based regimen in our setting should be reviewed. We recommend the urgent introduction of tenofovir alafenamide–based regimen in the HIV treatment guidelines of Nigeria and other resource-limited countries.

Adherence, virological outcome, and drug resistance in Chinese HIV patients receiving first-line antiretroviral therapy from 2011 to 2015.

Stavudine (D4T), zidovudine (AZT), and tenofovir (TDF) along with lamivudine (3TC) are the most widely used HIV treatment regimens in China. China's National Free Antiretroviral Treatment Programme (NFATP) has replaced D4T with AZT or TDF in the standard first-line regimens since 2010. Few studies have evaluated the adherence, virological outcome, and drug resistance in HIV patients receiving first-line antiretroviral therapy (ART) from 2011 to 2015 due to changes in ART regimen.From 2011 to 2015, 2787 HIV patients were examined, with 364, 1453, and 970 patients having initiated D4T-, AZT-, and TDF-based first-line ART regimens, respectively. The Cochran–Armitage test was used to examine the trends in clinical and virological outcomes during 2011 to 2015. Logistic regression was used to examine the effects of different regimens after 9 to 24 months of ART.From 2011 to 2014–2015, adverse drug reactions decreased from 18.9% to 6.7%, missed doses decreased from 9.9% to 4.6%, virological failure decreased from 16.2% to 6.4%, and drug resistance rates also significantly decreased from 5.4% to 1.1%. These successes were strongly associated with the standardized use of TDF- or AZT-based regimens in place of the D4T-based regimen. Poor adherence decreased from 11.3% in patients who initiated D4T-based regimens to 4.9% in those who initiated TDF-based regimens, adverse drug reactions decreased from 32.4% to 6.7%, virological failure reduced from 18.7% to 8.6%, and drug resistance reduced from 5.8% to 2.9%. Compared with patients who initiated AZT-based regimens, patients who initiated TDF-based regiments showed significant reductions in adherence issues, adverse drug reactions, virological outcomes, and drug resistance. Significant differences were also observed between those who initiated D4T- and AZT-based regimens.The good control of HIV replication and drug resistance was attributed to the success of China's NFATP from 2011 to 2015. This study provided real world evidence for further scaling up ART and minimizing the emergence of drug resistance in the “Three 90” era.

Incidence of Acute Kidney Injury in Patients Coinfected with HIV and Hepatitis C Virus Receiving Tenofovir Disoproxil Fumarate and Ledipasvir/Sofosbuvir in a Real-World, Urban, Ryan White Clinic.

Ledipasvir/sofosbuvir (LDV/SOF), an antiviral treatment for hepatitis C virus (HCV), and tenofovir disoproxil fumarate (TDF), an antiretroviral for treating human immunodeficiency virus (HIV), may be coadministered in patients coinfected with these viruses. A drug interaction between LDV and TDF could increase TDF-associated nephrotoxicity rates; however, there is minimal clinical evidence describing acute kidney injury (AKI) rates in this population. This study was conducted at a Ryan White-funded facility in Atlanta, Georgia, that cares for over 5,000 patients with AIDS. This retrospective cohort used chart review to assess occurrence of and risk factors for AKI in HIV/HCV-coinfected patients receiving LDV/SOF and antiretroviral therapy (ART). AKI rates were compared between TDF-containing and non-TDF-containing ART groups according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Additional evaluated risk factors for AKI included chronic kidney disease and use of boosted protease inhibitor-based ART. In the 117 included patients, the overall incidence of AKI was 27.3%. AKI occurred more frequently in the non-TDF group (13/86, 15.1% vs. 19/31, 61.3%, p < .001). All AKI was KDIGO stage 1. From multivariable logistic regression, the only independent predictor of AKI was treatment with non-TDF relative to TDF (adjusted odds ratio 6.51, 95% confidence interval 2.34-18.10, p < .001). In this real-world cohort of HIV/HCV-coinfected patients, KDIGO-defined AKI was common, but occurred less frequently in patients receiving TDF-based ART. Our study suggests that patients with normal baseline renal function can be safely treated with TDF and LDV/SOF without significant nephrotoxicity if renal function is closely monitored.

Bone density, microarchitecture, and tissue quality after 1 year of treatment with tenofovir disoproxil fumarate.

Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health in HIV patients. DXA measures the amount of mineral, but not other key aspects of bone strength such as bone microarchitecture or bone quality. Trabecular bone score (TBS) and in-vivo microindentation directly measure trabecular microarchitecture and bone tissue quality, respectively. The aim of this study is to measure bone strength properties using these techniques. Forty naive HIV patients who were going to start antiretroviral therapy (ART), a single pill treatment with elvitegravir/cobicistat, tenofovir disoproxil fumarate (TDF), emtricitavine (FTC) were included. A significant reduction in BMD at spine (-3.25%, P < 0.001) and in femoral neck (-3.82%, P = 0.016) between baseline and 48 weeks of treatment were found. Bone microarchitecture score at the spine, as measured by TBS, also significantly decreased from 1.357 (0.09) to 1.322 (0.09) (-2.5%, P = 0.011) between baseline to 48 weeks of treatment. Microindentation (BMSi) values were significantly higher than at baseline [89.04 (4.2) versus 86.07 (6.1); 3.49%, P < 0.001] after 48 weeks of TDF-based ART treatment, indicating improved bone material properties CONCLUSION:: A significant decrease in BMD and TBS were observed after 1 year of TDF therapy. However, tissue quality significantly improved after 1 year of treatment, suggesting a recovery of bone material properties following the control of the infection despite the significant reduction of BMD. These techniques provide additional and necessary information to DXA about bone health in treated HIV patients, and because of its convenience and feasibility they could be routinely apply to assess bone in clinical practice.

Incidence and risk factors for tenofovir-associated nephrotoxicity among human immunodeficiency virus-infected patients in Korea.

Background/AimsLittle is known about tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in Korea. The objective of this study was to evaluate the incidence and risk factors of TDF-associated nephrotoxicity among HIV-infected patients in Korea.MethodsA single-center retrospective cohort study was conducted on HIV-infected patients in Korea. We included patients who had started TDF or abacavir (ABC)-based antiretroviral therapy (ART) between October 2006 and December 2014. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Renal dysfunction was defined as > 25% decrease of baseline eGFR. A propensity matched case-control study was conducted to compare renal dysfunction rates between the two groups. The risk factors of nephrotoxicity were analyzed by Cox regression analysis.ResultsA total of 210 HIV-infected patients were included in the study, of which, 108 were TDF-based ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16 patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and 5.14 per 100 PYs, respectively (p = 0.176). In propensity-score-matched analysis, renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In multivariable analysis, Centers for Disease Control and Prevention clinical category C was a significant risk factor for renal dysfunction.ConclusionsApproximately, 13% of HIV-infected patients treated with TDF had renal dysfunction. Advanced stage of HIV infection was a significant risk factor for renal dysfunction.