Renal events among women treated with tenofovir/emtricitabine in combination with either lopinavir/ritonavir or nevirapine

Abstract

Objectives Tenofovir disoproxil fumarate (TDF) has been associated with renal insufficiency. Co-administration with boosted protease inhibitors (PIs), which increases its exposure, may further increase the risk of renal insufficiency. Methods We compared the incidence of renal events among women taking TDF co-administered with lopinavir/ritonavir (LPV/r) versus those co-administering TDF with nevirapine (NVP). Renal events were defined as a confirmed drop in creatinine clearance associated with a serum creatinine grade 2 or higher, or that leading to treatment modification. Results Overall, 741 HIV-infected women were enrolled into the study. Of these, 24 (3.2%) had reportable renal events (18 in LPV/r arm, 6 in NVP arm). In multivariate analysis, renal events were significantly associated with the LPV/r arm (odds ratio [OR]=3.12, 95% confidence interval [CI] 1.21, 8.05]; p=0.019), baseline HIV-1 RNA (OR=2.65, 95% CI: 1.23, 5.69 per 1 log10 copies/mL higher; p=0.013) and baseline creatinine clearance (OR=0.83, 95% CI 0.70–0.98 per 10 mL/min higher; p=0.030). In multivariate analysis evaluating renal events requiring treatment modification, only baseline HIV-1 RNA and creatinine clearance were significantly associated (OR=4.41, 95% CI 1.65, 11.78 per 1 log10 copies/mL higher; p= 0.003 and OR=0.80, 95% CI 0.64, 0.99 per 10 mL/min higher; p= 0.040, respectively). Conclusion The rates of renal events were relatively low in the two treatment arms. However, patients taking TDF co-administered with LPV/r had significantly more renal events compared to those co-administered with NVP. Furthermore, higher baseline HIV RNA and lower creatinine clearance were associated with the development of renal insufficiency requiring treatment modification.

Changes in estimated glomerular filtration rate over time in South African HIV‐1‐infected patients receiving tenofovir: a retrospective cohort study

“…In our study, older patients and those with lower baseline eGFR, lower CD4 count, lower body weight and concomitant protease inhibitor use were at increased risk of kidney toxicity, which concurs with previous studies [4,5,9,14–18]. Baseline eGFR <60 mL/min was one of the strongest predictors of at least one eGFR <30 mL/min on treatment, supporting the current South African guideline recommendation to avoid tenofovir in those with baseline eGFR <60 mL/min.…”

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

“…Therefore, Chinese HIV patients with these concerns could still receive TDF-base therapy. Several studies had claimed that PLWH exposed to TDF and LPV/r were strongly associated with chronic kidney disease (Mizushima et al, 2018;Mwafongo et al, 2014). A similar result was observed in our study in univariate analysis, but it lost correlation in multivariate analysis.…”

Low body weight and tenofovir use are risk factors for renal dysfunction in Vietnamese HIV-infected patients. A prospective 18-month observation study

“…This discrepancy could be explained by the fact that patients who could be affected by these factors were already excluded according to the study design, which excluded patients with renal dysfunction. With regard to the use of LPV/r, which is known as a risk for renal dysfunction [14,17], especially in cases of co-use with TDF, a number of patients with LPV/r were excluded from the study since most of the patients with LPV/r were cotreated with TDF at baseline. Thus, the impact of co-use of LPV/r and TDF on renal function could be underestimated in this study.…”