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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to assess the pharmacokinetic behavior of atazanavir-ritonavir when it is coadministered with tenofovir disoproxil fumarate (DF) in human immunodeficiency virus (HIV)-infected patients. Eleven patients enrolled in Agence Nationale de Recherche sur le SIDA (National Agency for AIDS Research, Paris, France) trial 107 were included in this pharmacokinetic study. They received atazanavir at 300 mg and ritonavir at 100 mg once a day (QD) from day 1 to the end of study. For the first 2 weeks, their nucleoside analog reverse transcriptase inhibitor (NRTI) treatments remained unchanged. Tenofovir DF was administered QD from day 15 to the end of the study. Ongoing NRTIs were selected according to the reverse transcriptase genotype of the HIV isolates from each patient. The values of the pharmacokinetic parameters for atazanavir and ritonavir were measured before (day 14 [week 2]) and after (day 42 [week 6]) initiation of tenofovir DF and are reported for the 10 patients who completed the study. There was a significant decrease in the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for atazanavir with the addition of tenofovir DF (AUC(0-24) ratio, 0.75; 90% confidence interval, 0.58 to 0.97; P = 0.05). There was a trend for a decrease in the minimum concentrations of atazanavir and ritonavir in plasma when they were combined with tenofovir, but none of the differences reached statistical significance. The median decreases in the HIV RNA loads at week 2 and week 6 were 0.1 and 0.2 log copies/ml, respectively. In summary, our data are consistent with the existence of a significant interaction between atazanavir and tenofovir DF.
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PMID:Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients. 1515 5

The first association between HIV-1 infection and kidney disease was made in 1984 and much has been learned over the past 20 years. In recent years, more effective therapies for HIV-1 infection and its associated opportunistic infections have led to improved patient survival. However, with prolonged survival, morbidity associated with renal disease has also increased. Among the multiple glomerulopathies that can affect patients with HIV, focal segmental glomerulosclerosis (FSGS) is most common and frequently leads to end-stage renal disease. Although the precise mechanisms of HIV-associated FSGS remain to be elucidated, it appears that host genetic susceptibility, direct infection of the renal epithelium, and toxicity of one or more viral accessory protein contribute. Therapy for HIV-associated FSGS includes control of blood pressure and the use of angiotensin antagonist therapy. A randomized trial of angiotensin receptor blocker will be initiated shortly. Drug-related nephropathies are also common, manifesting as acute renal failure, nephrolithiasis, and interstitial nephritis. Tenofovir, a newer nucleoside analogue, has recently been implicated in causing tubular toxicity, although the incidence is low. Appropriate screening for renal dysfunction can minimize the likelihood of progressive renal injury in all patients with HIV-1 infection.
Curr HIV/AIDS Rep 2004 Sep
PMID:HIV and the kidney: a status report after 20 years. 1609 Dec 30

Tenofovir has significant activity against hepatitis B virus (HBV), but clinical data about its utility for treatment of hepatitis B in patients coinfected with HBV and HIV are limited. We report the long-term safety and efficacy of tenofovir in 6 HBV-HIV-coinfected persons who received tenofovir as part of their antiretroviral regimen and were followed up for an average of 26.8 months (range, 19 to 33 months). Four of 6 patients were positive for hepatitis B e antigen (HBeAg), and all 6 had initial HBV DNA levels greater than 7 log10 copies/mL. HBV DNA levels dropped by a mean (median) of 2.83 (3.40) and 3.92 (4.63) log10 after 12 and 24 months of treatment, respectively. After 24 months, 3 patients had HBV DNA levels below the limit of detection and 5 had HIV RNA levels below the limit of detection (less than 400 copies/mL). The sixth patient had stopped treatment and had a 0.14-log10 decrease in HIV RNA level at 36 months of follow-up. The CD4+ lymphocyte count increased by a mean (median) value of 47/microL (177/microL). No significant adverse events attributable to tenofovir therapy were reported.
AIDS Read 2006 Apr
PMID:Tenofovir for chronic hepatitis B virus infection in HIV-coinfected patients. 1661 31

Tenofovir (Viread) is a nucleotide reverse transcriptase inhibitor introduced into the United States in 2001. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleoside analogs. It is now increasingly recognized as a cause of acquired Fanconi's syndrome (FS) in human immunodeficient individuals. We describe a case of a patient with AIDS, who, after starting tenofovir therapy, developed myalgias, renal failure, and profound electrolyte abnormalities compatible with the classic features of FS. On discontinuation of tenofovir and replacement of electrolytes, the individual improved clinically with normalization of his renal failure and electrolyte abnormalities. With the success of tenofovir in the anti-HIV drug market, practitioners should remain alert to the possibility of the development of FS. Frequent urine, renal, and electrolyte parameters should be measured at regular intervals following initiation of tenofovir therapy.
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PMID:Acquired Fanconi's syndrome associated with tenofovir therapy. 1702 23

To evaluate tenofovir-related nephropathy, we quantified calculated glomerular filtration rates (GFR) and renal tubular function in 46 tenofovir-treated patients and 25 without tenofovir. We also analysed patients who stopped tenofovir for drug-related nephrotoxicity at our clinic. Tenofovir use combined with non-nucleoside reverse transcriptase inhibitors, but not with protease inhibitors, resulted in a significant increase in calculated GFR. Tenofovir use was associated with significantly lower phosphatemia and a marginally increased fractional excretion of uric acid, but no other signs of tubulopathy.
AIDS 2007 Jul 11
PMID:Effect of tenofovir on renal glomerular and tubular function. 1758 97

Thai patients enrolled in STACCATO with HIV/hepatitis B virus (HBV) co-infection and tenofovir/emtricitabine-based antiretroviral therapy (ART) were randomly assigned to continuous treatment or CD4 cell count-guided interruptions. HBV replication was suppressed below detection in 15/16 patients. Structured treatment interruption increased transaminases and HBV viraemia in five of six patients; one flare was severe. Conversion to anti-hepatitis Be occurred with continuous treatment only. Tenofovir/emtricitabine-containing ART is highly effective in controlling chronic HIV/HBV co-infection but treatment should not be interrupted.
AIDS 2008 Jan 02
PMID:Interruptions of tenofovir/emtricitabine-based antiretroviral therapy in patients with HIV/hepatitis B virus co-infection. 1809 Apr 5

Tenofovir disoproxil fumarate (TDF) is an analog of adenosine monophosphate that inhibits HIV reverse transcriptase in HIV/AIDS. Despite its therapeutic success, renal tubular side effects are reported. The mechanisms and targets of tenofovir toxicity were determined using '2 x 2' factorial protocols, and HIV transgenic (TG) and wild-type (WT) littermate mice with or without TDF (5 weeks). A parallel study used didanosine (ddI) instead of TDF. At termination, heart, kidney, and liver samples were retrieved. Mitochondrial DNA (mtDNA) abundance, and histo- and ultrastructural pathology were analyzed. Laser-capture microdissection (LCM) was used to isolate renal proximal tubules for molecular analyses. Tenofovir increased mtDNA abundance in TG whole kidneys, but not in their hearts or livers. In contrast, ddI decreased mtDNA abundance in the livers of WTs and TGs, but had no effect on their hearts or kidneys. Histological analyses of kidneys showed no disruption of glomeruli or proximal tubules with TDF or ddI treatments. Ultrastructural changes in renal proximal tubules from TDF-treated TGs included an increased number and irregular shape of mitochondria with sparse fragmented cristae. LCM-captured renal proximal tubules from TGs showed decreased mtDNA abundance with tenofovir. The results indicate that tenofovir targets mitochondrial toxicity on the renal proximal tubule in an AIDS model.
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PMID:Tenofovir renal toxicity targets mitochondria of renal proximal tubules. 1927 46

Renal failure developed after a prolonged course of vancomycin therapy in 2 patients who were receiving tenofovir disoproxil fumarate as part of an antiretroviral regimen. Tenofovir has been implicated in the development of Fanconi syndrome and renal insufficiency because of its effects on the proximal renal tubule. Vancomycin nephrotoxicity is infrequent but may result from coadministration with a nephrotoxic agent. Clinicians should be aware that tenofovir may raise the risk of renal failure during prolonged administration of vancomycin.
AIDS Read
PMID:Acute renal failure in patients with AIDS on tenofovir while receiving prolonged vancomycin course for osteomyelitis. 1964 44

The widespread introduction of highly active antiretroviral therapy (HAART) in the mid-1990s dramatically altered the course of human immunodeficiency virus (HIV) infection, with improvements in survival and reductions in the incidence of AIDS-defining illnesses. Although antiretroviral therapy has been shown to reduce the incidence of both AIDS-defining and non-AIDS conditions, long-term exposure to HAART may also be associated with significant toxicity. This article reviews the potential nephrotoxicity of specific antiretroviral agents and the impact of antiretroviral therapy on related metabolic disorders. The antiretroviral agents most strongly associated with direct nephrotoxicity include the nucleotide reverse transcriptase inhibitor, tenofovir, and the protease inhibitor indinavir, although other agents have been implicated less frequently. Tenofovir and related nucleotide analogs have primarily been associated with proximal tubular dysfunction and acute kidney injury, whereas indinavir is known to cause nephrolithiasis, obstructive nephropathy, and interstitial nephritis. Kidney damage related to antiretroviral therapy is typically reversible with early recognition and timely discontinuation of the offending agent, and nephrologists should be familiar with the potential toxicity of these agents to avoid delays in diagnosis.
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PMID:Antiretroviral medications: adverse effects on the kidney. 2000 91

Tenofovir is an acyclic phosphonate analog of deoxyadenylate used in AIDS and hepatitis B therapy. We find that tenofovir diphosphate, its active form, can be produced by human nucleoside diphosphate kinase (NDPK), but with low efficiency, and that creatine kinase is significantly more active. The 1.65 A x-ray structure of NDPK in complex with tenofovir mono- and diphosphate shows that the analogs bind at the same site as natural nucleotides, but in a different conformation, and make only a subset of the Van der Waals and polar interactions made by natural substrates, consistent with their comparatively low affinity for the enzyme.
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PMID:Nucleoside diphosphate kinase and the activation of antiviral phosphonate analogs of nucleotides: binding mode and phosphorylation of tenofovir derivatives. 2018 17


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