Lamivudine or emtricitabine (XTC)/protease inhibitor dual therapy as a harm-reduction strategy in patients with tenofovir-related renal toxicity: A case-control study
ABSTRACT Tenofovir disoproxil fumarate (TDF) is widely used in HIV-infected patients. It is associated with tubular toxicity, but its management is controversial. A possible strategy is to switch to a dual therapy based on lamivudine or emtricitabine (XTC) and protease inhibitors (PIs). A case-control study was designed to evaluate the switch to XTC + PI therapy in patients with TDF-related renal toxicity. A case was defined as a patient who was on TDF/XTC + PI and who switched to XTC + PI. A control was defined as a patient with the same clinical features who remained on TDF/XTC + PI. Twenty-one cases and 21 controls were included. After 48 weeks, no differences in efficacy were observed. No improvement in the glomerular filtration rate as estimated with the Cockroft-Gault formula (eGFR) was seen, but the number of times that patients had values below 60 ml/min was higher with standard TDF/XTC 1 PI treatment than with dual XTC + PI treatment. A switch to dual therapy could be an option for patients at risk of TDF-related renal damage with no relevant risk of virological or immunological failure.
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ABSTRACT: Impaired renal function caused by tenofovir disoproxil fumarate (TDF) is considered reversible by discontinuing TDF administration, but there are occasional cases of incomplete recovery. We investigated the recovery of renal function after the discontinuation of TDF. Subjects comprised patients who had been started on TDF but in whom it was later discontinued because of impaired renal function. We investigated renal function until 96 weeks after the discontinuation of TDF, and the duration of TDF administration, up to May 2010. TDF was discontinued because of impaired renal function in 21 of 766 patients (2.7%). Following discontinuation, a significant recovery was seen in eGFR (p = 0.003). The median duration of administration was 28 days (6-941 days) in 9 patients whose eGFR recovered to pre-administration levels, 405 days (250-1,379) in 7 patients in whom mild recovery was seen, and 1,110 days (421-1,470) in 5 patients in whom eGFR was much lower than at the time of discontinuation. A significant correlation was seen between the eGFR recovery rate and the duration of TDF administration. TDF administration was discontinued because of renal impairment in 2.7% of patients. The duration of TDF administration was short in patients whose renal function recovered to pre-administration levels, but patients in whom sufficient recovery was not seen after discontinuation had received TDF over long periods and included many whose renal function gradually declined, even after discontinuation. Recovery of renal function after discontinuation of TDF is likely affected by the duration of TDF administration.Journal of Infection and Chemotherapy 10/2011; 18(2):169-74. DOI:10.1007/s10156-011-0310-6 · 1.38 Impact Factor
- HIV Clinical Trials 09/2009; 10(5):337-40. DOI:10.1310/hct1005-337 · 2.14 Impact Factor
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ABSTRACT: Plasma concentration of atazanavir (ATV) may be reduced when coadministered with tenofovir (TDF) or proton pump inhibitors. Boosting ATV exposure with ritonavir (r) may make it possible to overcome these drug interactions. However, jaundice and loss of the metabolic advantages of ATV are more frequent using ATV/r than ATV alone. Herein, we assessed whether therapeutic drug monitoring (TDM) could make it possible to identify the subset of patients in whom removal of ritonavir could be attempted without risk of suboptimal plasma ATV exposure and subsequent virological failure. A total of 56 patients with undetectable plasma HIV-RNA under a stable triple regimen containing ATV 300/100 mg qd were switched to ATV 400 mg qd. Plasma ATV concentrations were measured using a reliable high-performance liquid chromatography method. Median plasma ATV C(min) fell from 880 to 283 ng/ml (p = 0.03) after removal of ritonavir. While all patients on ATV/r showed ATV plasma concentrations within therapeutic values (IC(min) above 150 ng/ml) before switching, four patients (7%) fell below this threshold after switching to ATV 400 mg qd. However, only one of this group experienced virological failure at week 24 of follow-up. TDF was part of the antiretroviral regimen in all four cases. From a total of 29 (52%) patients on ATV/r showing grade 3-4 hyperbilirubinemia, only 7 (12%) remained on it upon switching to ATV 400 mg qd (p < 0.001). Patients with complete viral suppression under ATV/r 300/100 mg qd may benefit from switching to ATV 400 mg qd guided by TDM, which may make it possible to minimize adverse events without compromising antiviral efficacy in most cases.AIDS research and human retroviruses 07/2008; 24(6):821-5. DOI:10.1089/aid.2007.0276 · 2.46 Impact Factor