Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The short-term effects of stavudine (d4T) plus lamivudine (3TC) were evaluated among 48 human immunodeficiency virus-infected patients for whom zidovudine therapy had failed or who could not tolerate zidovudine. Patients were followed for 8 weeks after initiation of open-label d4T plus 3TC. Four patients discontinued therapy, because of neutropenia (1), hepatitis (1), or neuropathy (2). Reduction in virus load was -0.86 (+0.3 to -3.4) log10 copies/mL and CD4 cell increase was 30 (-100 to +290) cells/mm3. Virologic response was associated with a higher CD4 cell count, no prior exposure to d4T and 3TC, and no previous AIDS-defining illness. Virus load reduction for patients naive to 3TC and d4T was -1.47 (-0.14 to -3.37) log10 copies/mL. Short-term use of d4T plus 3TC is safe, well-tolerated, and associated with virologic and substantial immunologic benefits. Further evaluation of d4T and 3TC in combination is warranted.
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PMID:Stavudine plus lamivudine in advanced human immunodeficiency virus disease: a short-term pilot study. 935 13

Reports at the 5th Conference on Retroviruses and Opportunistic Infections addressed new anti-HIV agents in primary phases of development that offer treatment alternatives to people with little or no treatment history and individuals with few treatment choices. FTC, a new nucleoside analog produced by Triangle Pharmaceuticals, is an alternative to 3TC. F-ddA (lodenosine), a nucleoside analog licensed by US Bioscience, is structurally similar to ddI and is reported to have good bioavailability, once-a-day dosing, and no bone marrow suppression. F-ddA has also shown in vitro activity against multidrug-resistant strains of HIV. Adult and pediatric studies are currently being conducted by the National Cancer Institute (NCI) and US Bioscience. Oral versus IV PMPA shows promising results as a possible alternative for 3TC- and AZT-experienced patients. Further testing is being done by Gilead Sciences and HIV Network for Prevention Trials (HIVNET). Abbott Laboratories is developing a second-generation protease inhibitor, ABT-378, which has a ten-fold greater antiviral activity in vitro than the original, ritonavir. It is administered with ritonavir to increase ABT-378 levels in the blood, but has no food requirements, and less severe side effects. Two trials are being conducted: one for patients who are treatment-naive and the second for patients who are failing other protease inhibitors. Immune-based therapies, such as Leukine (GM-CSF), are used to handle neutropenia and offset bone marrow toxicities from drugs. Concerns that GM-CSF may increase viral replication may be balanced by using highly active antiretroviral therapy. FP-21399, developed by Lexigen Pharmaceuticals, is being tested as an HIV fusion inhibitor.
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PMID:Looking down the drug pipeline. 1136 93

In vitro and in vivo prophylactic and therapeutic efficacy of AZT/3TC treatment was evaluated against feline immunodeficiency virus (FIV) infection. In vitro studies utilized FIV-infected peripheral blood mononuclear cells (PBMCs) or FIV-infected T-cell lines treated with AZT (azidothymidine) alone, 3TC alone, or AZT/3TC combination and tested for anti-FIV activity and drug toxicity. AZT/3TC combination had additive to synergistic anti-FIV activities in primary PBMC but not in chronically infected cell lines. In vivo studies consisted of four treatment groups (n=15) of SPF cats receiving AZT/3TC combination (5-75 mg/kg/drug PO BID for 8 or 11 weeks) and one control group (n=9) receiving oral placebo. Group I (n=6, 150 mg/kg/drug/day) was treated starting 3 days pre-FIV inoculation, whereas Group II (n=3, 150 mg/kg/drug/day) and Group III (n=3, 100 mg/kg/drug/day) treatments were simultaneous with FIV inoculation. Group IV treatment (n=3, 100 mg/kg/drug/day) was initiated 2 weeks post-FIV inoculation. All cats were monitored for drug toxicity and FIV infection. Eighty-three percent of cats in Group I and 33% of cats in Groups II and III were completely protected from FIV infection. A significant delay in infection and antibody seroconversion was observed in all unprotected cats from Groups I, II and III. Group IV cats had only a slight delay in FIV antibody seroconversion. Adverse drug reactions (anemia and neutropenia) were observed at high doses (100-150 mg/kg/drug/day) were reversible upon lowering the dose (20 mg/kg/drug/day). In contrast, AZT/3TC treatment had no anti-FIV activity in chronically infected cats. Furthermore, severe clinical symptoms caused by adverse drug reactions were observed in some of these cats. Overall, AZT/3TC treatment is effective for prophylaxis but not for therapeutic use in chronically FIV-infected cats.
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PMID:Is AZT/3TC therapy effective against FIV infection or immunopathogenesis? 1194 20

For the treatment of HBV/HIV-co-infection, study data on interferon-based therapy are very limited and insufficient to draw any specific conclusions. In contrast, data on HBV-polymerase inhibitors (lamivudine, adefovir, tenofovir) are available from controlled trials. Lamivudine is well tolerated and safe, however, development of HBV-resistance is frequent. Adefovir has a nephrotoxic potential and may at least theoretically induce antiretroviral resistance in HBV/HIV-patients treated with adefovir. Tenofovir has gastrointestinal side effects, is associated with hypophospatemia, which has not induced serious osteopenia so far and may have a nephrotoxic potential. For HCV/HIV-co-infection pegylated interferon alpha plus ribavirin is standard of care. Flu-like symptoms, fatigue and depressive mood changes are frequent. In patients with a history of neurotic or minor depression initiation of treatment with antidepressants before the start of interferon-based therapy should be considered. Weight loss may be pronounced in individual cases. A marked decrease in absolute, but not relative CD4 +/- cells is the rule, but no relevant increase in opportunistic infection was observed, and anaemia (<10 g/dl) is reported in up to 30% of patients. Neutropenia (< 1,000 cells/microl) is observed in up to 50% of the patients. Adverse events specific to the HCV/HIV-patient population as compared to HCV-mono-infected patients are the occurrence of hyperlactataemia/lactic acidosis and hepatic decompensation.
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PMID:Treatment of viral hepatitis in HIV-coinfected patients-adverse events and their management. 1635 79

The adverse effects of antiviral drugs are dose dependent and often reversible. The major side effects include influenza-like symptoms, hematologic abnormalities and neuropsychiatric symptoms. The influenza-like syndrome can be prevented by paracetamol taken at the time of the injection. Psychiatric adverse effects range from irritability to a severe depressive syndrome. Antidepressants, such as selective serotonin reuptake inhibitors, may be useful in the management. Adverse hematologic effects can occur very early during treatment. The platelet count often stabilizes rapidly, but neutropenia can deteriorate throughout treatment. In selected patients treatment with hematopoietic growth factor (filgrastim) may be useful. Ribavirin therapy may result in a dose-dependent reversible intravascular hemolytic anemia in 10% of patients. Adjunctive therapy with erythropoietin for ribavirin-induced anemia is currently under evaluation. Interferons and ribavirin are contraindicated in pregnancy. Contraception must be continued for 4 months (women) and 7 months (men) after ribavirin cessation. Lactic acidosis may be a rare complication of combination therapy in patients undergoing therapy for HIV and HCV. Any sign of mitochondrial DNA depletion syndrome calls for blood lactate measurement and, possibly, a modification of antiretroviral treatment. Lamivudine is well tolerated but the emergence of lamivudine-resistant (YMDD) HBV mutants is associated with the loss of clinical response. Adefovir dipivoxil effectively suppresses lamivudine-resistant HBV in chronic hepatitis B.
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PMID:[Treatment of the side effects of antiviral therapy]. 1638 Dec 45

The adverse effects of antiviral drugs are dose dependent and often reversible. The major side effects include influenza-like symptoms, hematologic abnormalities and neuropsychiatric symptoms. The influenza-like syndrome can be prevented by paracetamol taken at the time of injection. Psychiatric adverse effects range from irritability to severe depressive syndrome. Antidepressants such as selective serotonin reuptake inhibitors may be useful. Adverse hematologic effects can occur very early during treatment. The platelet count often stabilizes rapidly, but neutropenia can deteriorate throughout the treatment. In selected patients, treatment with hematopoietic growth factor (filgrastim) may be useful. Ribavirin therapy may result in a dose-dependent reversible intravascular hemolytic anemia in 10% of patients. Therapy with erythropoietin for ribavirin induced anemia can be useful; however, are insufficient data to recommend its routine use in all patients. Interferon and ribavirin are contraindicated in pregnancy. Contraception must be continued for 4 months (women) and 7 months (men) after ribavirin cessation. Lactic acidosis may be a rare complication of combination therapy in patients undergoing therapy for HIV and HCV. Any sign of mitochondrial DNA depletion syndrome calls for blood lactate measurement and, possibly, a modification of antiretroviral treatment. Lamivudine is well tolerated but the emergence of lamivudine-resistant (YMDD) HBV mutants is associated with the loss of clinical response. Adefovir, entecavir, telbivudin and tenofovir effectively suppress lamivudine-resistant HCV in chronic hepatitis B.
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PMID:[Management of side effects during antiviral therapy]. 2019 9