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

Abstract

Background: Tenofovir 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. Methods: 414 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. Results: After 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 AE 0.83 mmol/L to 4.53 AE 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 AE 1.24 vs. 0.89 AE 1.78, P < 0.001). The mean estimated glomerular filtration rate (eGFR) decreased from 127.29 AE 24.04mlÁmin À1 Á1.73 m À2 at baseline to 118.84 AE 22.74 mlÁmin À1 Á1.73 m À2 (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. Conclusions: TDF-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.

<p>Dyslipidemia and Associated Factors in Tenofovir Disoproxil Fumarate-Based Regimen Among Human Immunodeficiency Virus-Infected Ethiopian Patients: A Hospital-Based Observational Prospective Cohort Study</p>

“…This disparity of results might be due to the difference in proportion of male and female, duration of follow-up, definition of dyslipidemia, 21 genetics and life style of participants. 22,23 Concerning TC, the present study showed 42.9% had raised TC, higher than the findings of other studies done in China, 19.3%, 14 and Zimbabwe, 15.9%. 21 In a study in China, there was 96.6% male participants, lower baseline TC (153.52 mg/dL), lower baseline raised TC (6.5%), and 24 months follow-up whereas the Ethiopian patients had 31.7% male participants, higher baseline TC (180 mg/dL), higher baseline raised TC (38.1%) and 6 months followup.…”

“…21 In a study in China, there was 96.6% male participants, lower baseline TC (153.52 mg/dL), lower baseline raised TC (6.5%), and 24 months follow-up whereas the Ethiopian patients had 31.7% male participants, higher baseline TC (180 mg/dL), higher baseline raised TC (38.1%) and 6 months followup. 14 Thus, the difference of the findings might be attributed at least in part to these differences. In contrast, it is lower than the findings of other studies done in China of 50% and 55.1%.…”

“…[8][9][10] However, in some trials and most studies in routine clinical practice, increased lipid parameters and dyslipidemia was found in a TDF-based regimen. [11][12][13][14][15] Worldwide, including Ethiopia, TDF-based regimen is now the preferred first line ART due to its more favorable efficacy and safety compared to other ARTs. But it is not without risk of adverse effects as evidenced by studies in routine care.…”

“…However, in practical patients have been taking TDF-based regimen without monitoring lipid profiles. 13,14 Especially, lack of monitoring lipid profiles in TDF-based regimen is a major problem in low income countries like Ethiopia. In Ethiopia, TDF-based regimen is the preferred first line therapy and more patients are more likely to be exposed to this regimen but there is no data regarding prevalence and associated factors of dyslipidemia in the country, particularly in the study setting.…”

Efficacy and safety of lower dose tenofovir disoproxil fumarate and efavirenz versus standard dose in HIV-infected, antiretroviral-naive adults: a multicentre, randomized, noninferiority trial

“…It has also shown to occur in non-PI containing regimens. This AE has been partially explained by increased TDF concentration due to drug-drug interactions and resultant tenofovir accumulation in proximal renal tubular cells [19][20][21][22][23]. As a result, reducing the TDF dose should result in decreased TDF concentrations in renal proximal tubular cells and subsequently lower nephrotoxicity.…”