Disease relevance of Apropovir

• The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency virus (HIV) [1].
• Two examples of crystal structures of HIV-1 RT with bound inhibitors have been published recently, one with the non-nucleoside CP94707 and the second with the nucleotide analogue drug tenofovir [2].
• Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections [3].
• These results suggest a low potential for increased toxicity upon co-administration of tenofovir DF with RBV in patients [4].
• In vitro susceptibility of lamivudine-resistant hepatitis B virus to adefovir and tenofovir [5].
• The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection [6].

Psychiatry related information on Apropovir

• Tenofovir-containing nucleoside/nucleotide-only antiretroviral maintenance therapy: decision making and virological outcome [7].

High impact information on Apropovir

• The HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir (TFV), abacavir, didanosine and stavudine can select for K65R, whereas zidovudine (AZT) and stavudine can select for thymidine analogue mutations (TAMs) in HIV-1 reverse transcriptase (RT) [8].
• In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine [9].
• BACKGROUND: Tenofovir (TDF) exposure has been associated with renal dysfunction [10].
• Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients [11].
• The combination of tenofovir (TDF) and efavirenz (EFV) has not been associated with any pharmakokinetic interaction or with enhancement of neuropsychiatric disturbances [12].

Chemical compound and disease context of Apropovir

• In vitro combination studies of tenofovir and other nucleoside analogues with ribavirin against HIV-1 [4].
• A rare HIV reverse transcriptase mutation, K65N, confers reduced susceptibility to tenofovir, lamivudine and didanosine [13].
• Patients with phenotypic susceptibility to tenofovir within 4-fold of wild-type responded durably to tenofovir DF 300 mg therapy with a decline in plasma HIV-1 RNA of > or = 0.5 log10 copies/ml; few patients had a more than 4-fold reduced susceptibility to tenofovir at baseline [14].
• Improvement of dyslipidemia in patients switching from stavudine to tenofovir: preliminary results [15].
• In addition, several novel anti-HBV agents recently evaluated in phase II clinical trials, such as tenofovir, clevudine, telbivudine, pradefovir, and valtorcitabine, appear to be promising agents for the treatment of chronic hepatitis B [16].

Biological context of Apropovir

• The steady-state pharmacokinetics of nelfinavir in combination with tenofovir in HIV-infected patients [17].
• Drug interactions between tenofovir and RBV were studied in vitro in order to provide insights into the safety of co-administration of tenofovir disoproxil fumarate (DF) and RBV in HCV/HIV-1-coinfected patients [4].
• Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine [18].
• Except for the epidydimis, the tissues with the lowest rates of proviral replacement by tenofovir-resistant genotypes differed between animals [19].
• To overcome the low oral bioavailability of the highly potent and selective antiretroviral agent (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), a new lipophilic ester derivative, i.e., the bis(isopropyloxycarbonyloxymethyl)-ester [bis(POC)-PMPA], was prepared [20].

Anatomical context of Apropovir

• METHODS: Intracellular anabolism of combinations of FTC and tenofovir (TFV) were studied in the human T leukaemic cell line CEM and human peripheral blood mononuclear cells (PBMCs) [9].
• Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine [21].
• Enfuvirtide did not cross the blood-testis barrier, whereas tenofovir accumulated in semen [22].
• Treatment with tenofovir (3 to 300 microM) for up to 3 weeks produced no significant changes in mitochondrial DNA (mtDNA) levels in human hepatoblastoma (HepG2) cells, skeletal muscle cells (SkMCs), or renal proximal tubule epithelial cells [23].
• Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue [24].

Associations of Apropovir with other chemical compounds

• METHODS: HIV-infected antiretroviral-naive patients with viral load > or =30 000 copies/ml were enrolled in a pilot randomized trial of tenofovir/didanosine (250 mg)/ efavirenz with (arm A) or without (arm B) lopinavir/r for the first 12 weeks [25].
• Thus, although tenofovir and ddl are both adenosine analogues, their in vitro interactions with RBV are markedly different [4].
• Identified risk factors included concomitant ritonavir or didanosine use, a lower weight and longer duration of tenofovir use [26].
• Efavirenz treatment was stopped, but lamivudine and tenofovir treatment for two other macaques was continued [27].
• Four cynomolgus macaques were infected with SIV(mac251.) Six months after infection the monkeys received a 7-day course of subcutaneous, quadruple antiretroviral therapy with zidovudine, lamivudine, tenofovir, and ritonavir-boosted lopinavir [28].
• At baseline patients on tenofovir plus lamivudine (n = 25) had a median HBV DNA of 5.9 x 10(7) copies/ml compared to 1.37 x 10(8) copies/ml in the tenofovir arm (n = 50; P = 0.32) [29].

Gene context of Apropovir

• The kidney accumulation of adefovir and tenofovir was significantly greater in Mrp4 knockout mice (130 versus 66 and 191 versus 87 pmol/g tissue, respectively); thus, the renal luminal efflux clearance was estimated to be 37 and 46%, respectively, of the control [30].
• Renal Transport of Adefovir, Cidofovir, and Tenofovir by SLC22A Family Members (hOAT1, hOAT3, and hOCT2) [31].
• In conclusion, MRP2 appeared to have no modulatory effect on the intestinal disposition of tenofovir and tenofovir (mono)ester [32].
• Although less effectively, PMEG and (R)-PMPA also increase production of TNF-alpha and NO by the IFN-gamma- but not LPS-co-stimulated macrophages from C3H/HeJ mice, which are otherwise hypo-responsive to major immune stimuli provided by IFN-gamma and LPS [33].
• Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir [34].

Analytical, diagnostic and therapeutic context of Apropovir

• HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture [35].
• A cross-sectional study was conducted to compare patients treated with tenofovir with patients never treated with tenofovir [36].
• The ability of tenofovir to suppress viremia in simian immunodeficiency virus (SIV)-infected macaques for years despite the presence of virulent viral mutants with reduced in vitro susceptibility is unprecedented in this animal model [37].
• The results from these controlled clinical trials provide guidance for the use of tenofovir DF for treatment-experienced patients [38].
• Tenofovir (TFV) undergoes renal elimination by a combination of glomerular filtration and active tubular secretion [39].

References