Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combined antiviral effects of various 2',3'-dideoxynucleosides and ribavirin on the replication of human immunodeficiency virus type 1 in MT-4 cells have been examined. Ribavirin antagonized the antiviral activity of the pyrimidine 2',3'-dideoxynucleosides (3'-azido-2',3'-dideoxythymidine, 2',3'-dideoxythymidin-2'-ene, 2',3'-dideoxycytidine, and 2',3'-dideoxycytidin-2'-ene), but enhanced the antiviral activity of the purine 2',3'-dideoxynucleosides (2',3'-dideoxyadenosine and 2',3'-dideoxyguanosine). Combinations of the 2',3'-dideoxynucleosides with each other were also examined. These combinations resulted in an additive to subsynergistic effect.
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PMID:Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro. 343 8

The current epidemic of acquired immunodeficiency syndrome (AIDS) poses a major threat to our population. Urgently needed are both a vaccine to prevent infection with the etiologic retrovirus, human immunodeficiency virus (HIV), and safe, effective antiviral agents to treat those individuals already infected. The elucidation of viral replicative mechanisms has allowed the development and testing of several agents active against HIV in vitro. Inhibitors of reverse transcriptase that have demonstrated activity include azidothymidine, phosphonoformate, antimoniotungstate (HPA-23), and suramin. Ribavirin and recombinant interferon alpha-A (IFN-alpha-A) also inhibit HIV replication, although their mechanisms of action are less clear. All of these compounds are undergoing early clinical trials in patients with HIV infection. The identification of immunogenic viral proteins may allow the development of one or more subunit vaccines against HIV. Studies are underway to clone appropriate viral genes and incorporate the expressed proteins into vectors for administration. Laboratory models, e.g., chimpanzees, will be inoculated with candidate vaccines and, if successful, this will be followed by clinical trials for safety and efficacy in appropriate human populations seronegative for HIV. Although important problems, such as virus envelope protein variability, need to be addressed, efforts to develop effective vaccines may well prove successful in the years ahead.
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PMID:Prospects for the prevention and therapy of infections with the human immunodeficiency virus. 354 Nov 31

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.
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PMID:Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome. 356 39

Persistent viral infections have been postulated to be trigger factors for the development of autoimmune disease. We report the development of vitiligo in four patients with human immunodeficiency virus (HIV)-related conditions and in one patient with hepatitis who later developed both psoriasis and acquired immunodeficiency syndrome (AIDS). Other common features were hepatitis and multiple other viral infections. Ribavirin was associated with repigmentation in one patient. Vitiligo may be an example of an autoimmune disease triggered by viral infection in a genetically predisposed host.
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PMID:Human immunodeficiency virus-associated vitiligo: expression of autoimmunity with immunodeficiency? 366 11

Respiratory syncytial virus (RSV) lower respiratory tract and febrile upper respiratory tract illnesses were prospectively assessed in cohorts of 83 infants born to human immunodeficiency virus (HIV)- and of 48 infants born to non-HIV-infected mothers. Of the infants born to HIV-infected mothers, 18 were themselves infected with HIV, 26 were indeterminant and 39 were free from HIV. Ten RSV illnesses occurred in 8 HIV-infected, 2 illnesses in 2 indeterminant and 17 illnesses occurred in 17 non-HIV-infected children. RSV shedding was prolonged in HIV class P2- vs. non-HIV-infected children, at medians of 30 days (range, 1 to 199 days) and 6 days (range, 1 to 21 days), respectively (P = 0.02). Ribavirin and intravenous immunoglobulin failed to eradicate RSV from one child who shed virus for 199 days. Wheezing occurred in 1 of 4 vs. 9 of 10 episodes of lower respiratory tract illness in HIV-infected and non-HIV-infected children, respectively (P = 0.04). No differences were noted in duration of illness, temperature, respiratory rate or oxygen saturation between HIV- and non-HIV-infected children. Infection control and public health concerns regarding prolonged shedding of RSV in HIV-infected children must be recognized.
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PMID:Respiratory syncytial virus illnesses in human immunodeficiency virus- and noninfected children. 841

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 mg and 800 mg) and placebo was conducted at six medical centers. Two hundred fifteen adults were enrolled over a 5-month period and randomized to receive ribavirin 800 mg daily (74 subjects), ribavirin 600 mg (71 subjects), or placebo (70 subjects). Active treatment was administered for 24 weeks followed by a 4-week wash-out period. Fifteen patients receiving placebo, 10 receiving ribavirin 600 mg, and 18 receiving ribavirin 800 mg developed AIDS during the 28-week study period. Ribavirin at daily doses of 600 mg or 800 mg for 24 weeks did not significantly affect the rate of progression to AIDS as defined by the Centers for Disease Control, in univariate analysis, Kaplan-Meier survival analysis, or Cox proportional hazards modeling. Although in the proportional hazards analysis, the dose-response regression coefficients indicated a reduction of 43% in the hazard of progression to AIDS among patients on active treatment, it was not statistically significant (p = 0.19). Furthermore, there was no evidence that ribavirin had a significant effect upon any immunologic or virologic parameter measured, including CD4 count, CD4:CD8 ratio, lymphocyte proliferative response, skin test reactivity, interferon-gamma production, peripheral blood mononuclear cell culture for human immunodeficiency virus (HIV), or level of HIV p24 antigen in serum. The most prominent adverse effect of ribavirin was induction of a mild reversible hemolytic anemia (mean fall in hematocrit, 5%). No severe or unremitting drug reaction was documented.
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PMID:Multicenter clinical trial of oral ribavirin in symptomatic HIV-infected patients. The Ribavirin ARC Study Group. 841 72

Nucleotide heterodimers were synthesized and examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1), including HIV-1 reverse transcriptase (RT) inhibitor-resistant mutants. 3'-Azido-3'-deoxythymidilyl-(5')-phospho-(5')-6-[(3', 5'-dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]uracil (AZT-P-E-HEPU-dM) and 3'-azido-3'-deoxythymidilyl-(5')-phospho-(5')-2', 3'-dideoxyinosine (AZT-P-ddI) proved to be highly potent and selective inhibitors of HIV-1 (IIIB strain) in MT-4 cells. The mechanism of inhibition by these heterodimers may be attributed to their degradation and the formation of each constituent. AZT-P-E-HEPU-dM was also markedly inhibitory to an AZT-resistant mutant (HIV-1-IIIB/AZT) and an E-HEPU-dM-resistant mutant (HIV-1-IIIB-R). However, AZT-P-ddI was found to have a less inhibitory effect on HIV-1-IIIB/AZT than on HIV-1-IIIB. The heterodimers of (5',5') AZT and ribavirin (AZT-P-Ribavirin) and (5',5') ddI and ribavirin (ddI-P-Ribavirin) were also synthesized: AZT-P-Ribavirin inhibited HIV-1 replication, but ddI-P-Ribarvirin did not.
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PMID:Antiviral activities of nucleotide heterodimers against human immunodeficiency virus type 1 in vitro. 879 15

The efficacy and toxicity of ribavirin (25 or 125 mg/kg/day), 2',3'-dideoxyinosine (ddI) (200 mg/kg/day) and a combination of both drugs at these doses given for 6 weeks were investigated in the murine acquired immunodeficiency syndrome model. Our results showed a significant protection against splenomegaly, lymphadenopathy and hypergammaglobulinemia in mice treated with ribavirin at 25 mg/kg/day alone or in combination with ddI at 200 mg/kg/day. A good synergistic effect was observed with the drug combination, whereas ddI alone (200 mg/kg/day) did not give any protection. Ribavirin/ddI combination protected against the loss of CD8 T cells in spleen and restored the capacity of splenocytes to proliferate after activation with a mitogenic agent. Moreover, the drug combination resulted in a protection of the spleen and cervical lymph node architectures and a regression of germinal centers. Hematotoxicity appeared at a dose of 125 mg/kg of ribavirin alone and increased when used concomitantly with ddI. In conclusion, ribavirin and ddI at low doses are synergistic and effective in the murine acquired immunodeficiency disease model, but at high doses they are toxic.
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PMID:Ribavirin potentiates the efficacy and toxicity of 2',3'- dideoxyinosine in the murine acquired immunodeficiency syndrome model. 893 Feb 11

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).
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PMID:Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients. 1200 Oct 34

Ribavirin in combination with alpha 2 interferon is the consensus treatment for chronic hepatitis C. However, recent preliminary pharmacological studies have suggested that the bioavailability of ribavirin displays great interindividual variability. In order to monitor serum ribavirin levels during combination treatment, we developed and validated a quantitative assay using an approach adaptable for routine hospital laboratories. The method involved solid-phase extraction on phenyl boronic acid cartridges followed by high-performance liquid chromatography with a C(18)-bonded silica column and a mobile phase containing 10 mM ammonium phosphate buffer (with the pH adjusted to 2.5) and UV detection (207 nm). The sensitivity, recovery, linearity of the calibration curve, intra- and interassay accuracies, precision, and stability at 4 degrees C were consistent with its use in the laboratory routine. In addition, other nucleoside analogues sometimes used with ribavirin in patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus did not interfere with the quantification of ribavirin levels. The ribavirin concentration was quantified in 24 serum samples from patients with chronic hepatitis C treated with a combination of ribavirin and alpha 2 interferon. The mean serum ribavirin concentration was 2.67 +/- 1.06 micro g/ml (n = 24) at week 12 of treatment (W12) and 3.24 +/- 1.35 micro g/ml (n = 24) at week 24 of treatment (W24). In addition, ribavirin concentrations displayed high interindividual variabilities: the coefficients of variation of the serum ribavirin concentrations adjusted to the administered dose were 44 and 48% at W12 and W24, respectively. Moreover, the ribavirin concentration was higher in patients with a sustained virological response (n = 11) than in patients with treatment failure (n = 13), with significant intergroup differences at W12 (P = 0.030) and W24 (P = 0.049). The present study describes a simple analytical method for the quantification of ribavirin in human serum that could be a useful tool for the monitoring of ribavirin concentrations in HCV-infected patients in order to improve the efficacy and safety of therapy with ribavirin plus interferon.
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PMID:Ribavirin quantification in combination treatment of chronic hepatitis C. 1249 79


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