We report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally HIV-infected adolescents. The first case, a 16-year-old African American male with an absolute CD4+ cell count of 314 cells/mm(3), presented with an abrupt rise in serum creatinine leading to irreversible renal failure while on TDF-containing highly active antiretroviral therapy (HAART). While the patient had evidence of underlying kidney disease, the timing of his renal failure indicates that TDF played a central role. The second case, a 16-year-old African-American male with an absolute CD4+ cell count of 895 cells/mm3, presented with rickets and hypophosphatemia while receiving TDF-based HAART. To our knowledge, these cases represent the first reports of TDF-associated irreversible renal failure and rickets in pediatric patients. We believe these cases highlight important and potentially irreversible side effects of this agent and emphasize the need for further studies of the renal safety of TDF in pediatric patients.
[Show abstract][Hide abstract] ABSTRACT: Adherence to antiretroviral regimens continues to be a significant problem in HIV-infected individuals facing a lifetime of therapy. Youth who were infected through perinatal transmission enter into adolescence often with a history of multiple medication regimens. Thus, adherence can be a particularly important issue in these young people, as medication options can often be limited. This was a cross-sectional, observational study to determine the prevalence of personal barriers to adherence and to identify associations among the following barriers in subjects 12 to 24 years old: mental health barriers, self-efficacy and outcome expectancy, and structural barriers. Among the 368 study participants, 274 (74.5%) were adherent and 94 (25.5%) were nonadherent to highly active antiretroviral therapy (HAART). No significant differences were found between adherent and nonadherent subjects according to mental health disorders. Adherence was associated with some but not all structural barriers. Both self-efficacy and outcome expectancy were significantly higher in adherent versus nonadherent subjects (p < 0.0001). In subjects with low self-efficacy and outcome expectancy, adherence differed according to the presence or absence of either mental health or structural barriers, similar to findings in behaviorally- infected adolescents. Interventions that address the breadth and clustering of adherence barriers in adolescents are needed to have the maximum chance for positive effects.
AIDS patient care and STDs 02/2010; 24(2):97-104. DOI:10.1089/apc.2009.0198 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Significant nephrotoxicity develops in 1%-2% of HIV-infected adults receiving tenofovir (TDF). This nephrotoxicity is said to resolve rapidly, but this assessment is based on short follow-up, very few patients and use of serum creatinine, an insensitive measure of renal function.
We determined the reversibility of TDF-related nephrotoxicity in 24 HIV-infected male outpatients who ceased TDF for renal impairment by retrospective assessment of estimated glomerular filtration rate (eGFR) using the Modified Diet in Renal Disease equation.
Median (interquartile range) eGFR pre-TDF was 74 (61-88) mL.min.1.73 m, fell to 51 (39-61) mL.min.1.73 m at TDF cessation and increased to 58 (48-70) mL.min.1.73 m a median 13 months after TDF cessation (most recent vs pre-TDF eGFR; P = 0.0008). Results were similar with the Cockcroft-Gault equation and after exclusion of patients who had shorter follow-up after TDF cessation. Only 10 (42%) patients reached their pre-TDF eGFR. Greater eGFR improvement was significantly associated with more rapid decline in eGFR on TDF therapy and in those who received TDF with a protease inhibitor, with a trend for shorter duration of TDF therapy.
In this population, TDF-related renal toxicity was not always fully reversible.
[Show abstract][Hide abstract] ABSTRACT: One of most important functions of the kidney concerns the clearance of endogenous waste products, exogenously administered drugs as well as environmental exposures. In addition to glomerular filtration, active tubular secretion is an efficient mechanism for extracting compounds from the circulation and excreting them into the urinary compartment, and it presents one of the determinants of a drug's pharmacokinetic behavior. The renal proximal tubules are equipped with a range of transporters, which can be roughly divided into a system for organic anions and one for organic cations, each consisting of multiple carriers with overlapping substrate specificities that cooperate in basolateral drug uptake and luminal excretion. Drug transporters are often involved in clinically significant drug-drug interactions, leading to unexpected changes in drug plasma levels. Similar effects may be observed for the interaction of drugs with endogenous substrates and food components. Furthermore, disease states could affect the expression and/or function of transport systems as well, mainly through regulation of gene transcription. Finally, inter-individual variability and gender differences exist in the expression of drug transporters, which affect overall renal drug handling. This review highlights recent knowledge of the renal organic anion system with special reference to the therapeutic implications associated with variations in transporter activity and drug interactions.
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