Changes in renal function with long‐term exposure to antiretroviral therapy in HIV‐infected adults in Asia

Abstract

Introduction: Renal disease is common amongst people living with HIV. However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. Methods: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy (ART) during or after 2003, had a serum creatinine measurement at ART initiation (baseline) and had at least two follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60ml/min/1.73m2 were excluded. Chronic kidney disease was defined as two consecutive eGFR values ≤60ml/min/1.73m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative_incidence plots were used to evaluate factors associated with CKD. Results: Of 2,547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage and low nadir CD4 were associated with a decrease in eGFR during follow up. CKD occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. Conclusions: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Tenofovir nephrotoxicity among Asians living with HIV: review of the literature

“…(90) country study and it still showed the increasing loss in eGFR in the TDF group compared to the non-TDF group (41). On the other hand, a single-center study from Montreal, Canada reported that among 1043 patients mostly comprised of Whites, there was no trend between the years of exposure and the loss in eGFR in the TDF group relative to non-TDF group (15).…”

“…Although evidence is still limited to draw any firm conclusions, it is interesting that two observational studies from Asia showed that the loss in eGFR among the patients who started TDF-containing ART relative to that in those who started non-TDF-containing ART continued to increase over time (20,41), whereas one cohort study from Canada did not show such finding and concluded that most of the loss in eGFR was acquired during the first year of exposure and stabilized after that (15) (Figure 2). In the Japanese cohort study, the loss in eGFR in the TDF group relative to the ABC group continuously increased over time, and reached -10.3 mL/min/1.73 m 2 at 5 years of TDF exposure (20) (Figure 2).…”

“…In the Japanese cohort study, the loss in eGFR in the TDF group relative to the ABC group continuously increased over time, and reached -10.3 mL/min/1.73 m 2 at 5 years of TDF exposure (20) (Figure 2). Another multi-country observational study from East and South-East Asia reported that among 2547 patients with median body weight of 56 kg (703 on TDF-containing ART, 1844 on non-TDF-containing ART), the loss in eGFR in the TDF group relative to the non-TDF group increased over time and reached -7.1 mL/min/1.73 m 2 at 5 years of TDF exposure (41). It is notable that whereas in the Japanese study 85% of the study patients were on PI/r, one of the risk factors for TFV nephrotoxicity, it was only 18.7% for the multi- Whereas two studies from Asia (Joshi et al and Nishijima et al) showed that the loss in eGFR among the patients who started TDF containing ART relative to those who started non-TDF containing ART continued to increase over time, the study from Canada (Laprise et al) showed that most of the loss in eGFR was acquired during the first year of exposure and stabilized after that (15,20,41).…”

“…To date, TFV nephrotoxicity is generally regarded as mild and tolerable (17,18); severe tubulopathy such as Fanconi syndrome or acute tubular necrosis is rare (8), and a TDF-related eGFR decrement is generally modest (17). However, it is notable that low body weight is one of the risk factors for TFV nephrotoxicity and that Asians are generally of smaller body stature and can be susceptible to such nephrotoxicity, as shown in several cohort studies (19,20,41). Creatinine is transported through tubular cells on the basolateral side by organic anion transporters (OAT) 2 and 3, and organic cation transporters (OCT) 2 and 3.…”

<p>Longitudinal Progression of Estimated GFR in HIV-1-Infected Patients with Normal Renal Function on Tenofovir-Based Therapy in China</p>

“…7,8 Studies have consistently demonstrated that TDF is associated with a decline of eGFR and renal dysfunction in a subpopulation. [9][10][11][12][13][14] Delineating exactly the eGFR progression trajectories on TDF therapy through routine screening is undoubtedly helpful in this scenario. Since a linear figure seems convenient to interpret, most of the relevant studies so far considered the decline of eGFR to be approximately linear.…”