Tenofovir Disoproxil Fumarate Not Linked to Renal Damage
Zahra Masoud
Patients infected with HIV and receiving tenofovir disoproxil fumarate (TDF) as antiretroviral therapy (ART) have a greater risk for estimated glomerular filtration rate reduction if they have a lower body weight; however, this risk is not significant according to a study published in the Journal of Infection.
Current World Health Organization recommendations suggest using TDF as a part of initial ART for patients with HIV. TDF is also commonly used in combination for pre-exposure prophylaxis of HIV infection and monotherapy for the treatment of hepatitis B virus infection. Although the high potency of ART has dramatically improved survival of patients with HIV, chronic kidney disease remains one of the major comorbidities of HIV infection. The TDF regimen appears safe for short-term use in people with HIV, but has been associated with a broad spectrum of kidney tubular dysfunction.
Further, when combined with a boosted protease inhibitor, TDF is associated with a higher risk for estimated glomerular filtration rate reduction, which could increase the long-term risk for chronic kidney disease. However, the risk for eGFR reduction in Asian adults with HIV who initiate ART containing TDF remains unclear. Therefore, this study compared the long-term evolution of estimated glomerular filtration rate in Thai patients receiving TDF and zidovudine (AZT) and analyzed the role of body weight in the risk for estimated glomerular filtration rate reduction.
In total, data collected from a multicenter clinical trial in Thailand of 640 patients were included (ClinicalTrials.gov identifier: NCT00162682). Of these included patients, 461 (72%) patients received a TDF-containing regimen for a median of 6.7 years, and 179 (28%) patients received an AZT-containing regimen for 6.5 years. The estimated glomerular filtration rate was estimated for each patient before initiation of ART, and quarterly thereafter. The primary outcome measure was the time to >25% reduction in estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease equation with Thai racial factor during the follow-up period. Using proportional hazard regression models, the risk for a >25% estimated glomerular filtration rate reduction in HIV-naive patients initiating TDF of AZT-containing nonprotease inhibitor regimen were compared.
Results showed that the risk for a >25% estimated glomerular filtration rate reduction was not higher on TDF-based vs AZT-based nonprotease inhibitor regimens, and therefore was not associated with treatment (hazard ratio [HR], 1.11; P =.46). Multivariate analysis showed that the risk for >25% estimated glomerular filtration rate reduction from baseline was associated with body weight at baseline (HR, 2.12; P <.001); this was also true for patients with hypertension (HR, 4.03; P <.001). However, the effect on baseline weight on >25% estimated glomerular filtration rate reduction did not vary significantly with treatment (P =.27).
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Overall, the study authors concluded that, “HIV infected-patients initiating TDF-containing antiretroviral combinations without protease inhibitors did not have a higher risk of [estimated glomerular filtration rate] reduction or [chronic kidney disease] compared with AZT containing regimens in Thailand.”
Reference
Liegeon G, Harrison L, Nechba A, et al. Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors [published online August 8, 2019]. J Infect. doi:10.1016/j.jinf/2019.08.006 作者: StephenW 时间: 2019-10-2 15:44
结果显示，与基于AZT的非蛋白酶抑制剂相比，基于TDF的肾小球滤过率降低> 25％的风险并不更高，因此与治疗无关（危险比[HR]，1.11； P = .46 ）。多变量分析显示，估计的肾小球滤过率从基线降低> 25％的风险与基线时的体重相关（HR，2.12； P <.001）；与基线时的体重相关。高血压患者也是如此（HR，4.03； P <.001）。但是，估计基线重量> 25％的肾小球滤过率降低对治疗的影响并没有显着变化（P = .27）。
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