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 pharmacokinetics of zidovudine (ZDV) are established in patients with various stages of human immunodeficiency virus (HIV) disease. This study was conducted to determine the pharmacokinetic parameters of ZDV in patients with asymptomatic HIV infection and liver disease. HIV-infected volunteers with normal renal function were stratified according to the severity of liver disease (seven of eight were classified as mild). Each subject received a single intravenous dose of ZDV (120 mg) on the first day, followed by a single oral dose of ZDV (200 mg) on the second day. Blood samples were obtained over a 8-h collection interval, and concentrations of ZDV and its glucuronidated metabolite (GZDV) were determined by high-performance liquid chromatography. The following pharmacokinetic parameters were obtained after oral administration of ZDV to HIV-infected patients with mild hepatic disease; these values were compared with previously reported data in healthy volunteers. The area under the curve (AUC) (1,670 +/- 192 ng.h/ml), maximum concentration of drug in serum (1,751 +/- 180 ng/ml), and half-life (2.04 +/- 0.38 h) of ZDV were increased, while the apparent oral clearance (1.57 +/- 0.31 liter/h/kg of body weight) was decreased; AUC (7,685 +/- 1,222 ng.h/ml) and maximum concentration of drug in serum (5,220 +/- 1,350 ng/ml) of GZDV and the AUC ratio of GZDV to ZDV (2.79 +/- 0.43) after oral administration were decreased. ZDV absolute bioavailability was 0.75 +/- 0.15 in HIV-infected patients with hepatic disease. Although the ZDV apparent oral clearance was not impaired as significantly as in patients with biopsy-proven cirrhosis, our results suggest that ZDV, could accumulate in HIV-infected patients with mild hepatic disease because of impaired formation of GZDV. Patients with mild hepatic disease may require dosage adjustment to avoid accumulation of ZDV after extended therapy.
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PMID:Pharmacokinetics and bioavailability of zidovudine and its glucuronidated metabolite in patients with human immunodeficiency virus infection and hepatic disease (AIDS Clinical Trials Group protocol 062). 859 10

Chronic liver disease due to hepatitis C virus (HCV) infection is a major problem in hemophiliacs. Recent reports suggested that hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus (HIV) have an increased incidence of liver failure but the mechanism of accelerated liver injury is not clear. We tested plasma from 100 hemophiliacs for anti-HCV by second generation ELISA, anti-HIV by EIA, and HCV RNA and HIV RNA by branched DNA and polymerase chain reaction assays to determine if hemophiliacs coinfected with HCV and HIV have higher HCV RNA levels and more active liver disease. Seventy-nine (79%) patients were anti-HCV positive, of whom 85% were HCV RNA positive. None of the anti-HCV-negative patients had detectable HCV RNA in plasma. Forty-two (42%) patients were anti-HIV positive, of whom 47% had detectable HIV RNA. All the anti-HIV-positive patients were also anti-HCV positive. The prevalence of both anti-HCV and anti-HIV increased significantly with age. There was no difference in HCV RNA levels between anti-HIV-positive and anti-HIV-negative patients (mean: 21 +/- 4 vs 18 +/- 5 Meq/ml), although HCV RNA levels were significantly higher in anti-HIV-positive patients with CD4 counts < 200/mm3 (P = 0.008). There was an inverse correlation between HCV RNA levels and CD4 counts but no correlation was found between HCV RNA and serum aminotransferase levels. We found a high prevalence of HCV and HIV coinfection in our hemophiliacs. Hepatitis C virus replication appears to be increased in patients with severe immunodeficiency secondary to progressive HIV infection. However, there was no correlation between HCV RNA and serum ALT level, suggesting that HCV is not directly cytopathic.
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PMID:Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs. 865 62

Although liver test abnormalities are frequently identified in patients with acquired immunodeficiency syndrome (AIDS), the causes, evaluation, and outcome of jaundice in these patients have not been systematically evaluated. From August 1, 1990 through September 1, 1994, all human immunodeficiency virus (HIV)-infected patients with liver test abnormalities seen by the gastroenterology service at a large, inner-city hospital were prospectively identified. Jaundice was defined as a serum bilirubin concentration > or = 3 mg/dL. The etiology of jaundice was determined by the pattern of liver biochemistry test abnormalities, radiographic studies, liver biopsy, clinical follow-up, and autopsy. During the study period, 541 HIV-infected patients (511 with AIDS) were evaluated for liver disease by our service; 36 of these patients had jaundice (7 percent). The most common causes of jaundice were drug-induced hepatitis, occurring in 11 patients (31 percent), and alcoholic liver disease, occurring in 5 (13 percent). Opportunistic infections or neoplasms were identified as the cause of jaundice in 11 patients (30 percent), with 4 having intrahepatic disease and 7 having extrahepatic disease. Multiple potential causes were seen in 3 patients. Abdominal ultrasonography (US) and computed tomography (CT) were helpful in suggesting the underlying cause of disease. The short-term mortality was high, with 9 patients dying during the hospitalization (25 percent) and 7 patients dying within 6 months of evaluation. Liver disease was the cause of death in 7 of these patients. In conclusion, jaundice is uncommon in AIDS and may result from a variety of both opportunistic and non-opportunistic etiologies. Drug-induced hepatitis is the most common cause and may be fatal. Long-term survival was poor.
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PMID:Etiology, evaluation, and outcome of jaundice in patients with acquired immunodeficiency syndrome. 866 25

A retrospective analysis of 99 hepatitis B-positive homosexual men with known human immunodeficiency virus (HIV) status was conducted to study the interaction of concurrent HIV infection on the course of their chronic hepatitis B virus (HBV) infection. All 99 subjects had chronic hepatitis B, 43 of whom were HIV antibody negative and 56 of whom were HIV antibody positive at the time of their initial presentation. Serial serum aminotransferase levels were used as an indirect estimate of the severity of hepatic inflammation. Factors that may influence the course of hepatitis B, HIV status, hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) status, alcohol intake, and zidovudine (AZT) therapy were correlated with aminotransferase values. Overall, there was no difference in mean serum alanine aminotransferase (ALT) levels between HIV antibody-negative and HIV antibody-positive patients. There is a higher prevalence rate of HBeAg in HIV antibody-positive patients (p < 0.05), and the seroconversion rate from HBeAg to HBeAb was lower in HIV antibody-positive patients compared with HIV antibody-negative patients (p < 0.05). However, reactivation rates from HBeAb to HBeAg were no different in the HIV antibody-positive and negative hepatitis B carriers. With mild, moderate, or heavy alcohol intake, we observed no statistically significant difference in mean serum alanine aminotransferase levels and no mean serum aspartate aminotransferase levels between HIV antibody-negative patients versus HIV antibody-positive patients. Similarly, there was no significant difference in the pattern of serum aminotransferase in those subjects treated with or without AZT. The mortality rates were higher in HIV antibody-positive patients (n = 8) compared with in HIV antibody-negative patients (n = 2). Seventy-five percent (n = 6) of the HIV antibody-positive patients died from acquired immunodeficiency syndrome (AIDS), and overall only two patients died of liver disease, one in each group. We conclude that there is no overt influence by HIV or the treatment thereof on the course of chronic HBV infection in a population of homosexual men. In HIV-infected patients, death from AIDS predominated; hence, the main target for therapy should be HIV rather than HBV.
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PMID:The interaction of human immunodeficiency virus infection and hepatitis B virus infection in infected homosexual men. 877 27

It is generally agreed that hepatitis B virus (HBV) replication is reduced by hepatitis delta virus infection (HDV) and augmented by human immunodeficiency virus (HIV) infection. However, the precise nature of the interactions between HBV, HDV and HIV is controversial. The aim of this study was to evaluate the impact of HIV infection on HBV and HDV replication, and on histological scores during delta virus superinfection in HDV-positive, chronic carriers of hepatitis B surface antigen (HBsAg). We studied 38 men and six women, 15 of whom were HIV-positive and all of whom had at least one marker of HDV infection. Serum hepatitis B e antigen (HBeAg), HBV DNA, HDV RNA, anti-delta antigen antibodies (anti-HD) IgM, anti-HD IgG and hepatitis delta antigen (HDAg) were tested for in the serum and liver, respectively; anti-hepatitis C virus (HCV) antibodies were detected using a second-generation recombinant immunoblot assay. Histological specimens were scored blindly according to Knodell's classification for periportal and intralobular necrosis, portal inflammation and fibrosis. HBV DNA was detected more frequently in the HIV-positive patients than in those who were HIV-negative (25 vs 0%; P = 0.01), while markers of HDV replication (serum anti-HD IgM, serum HDV RNA and liver HDAg) were as frequent in the HIV-positive patients (69%, 40% and 50%, respectively) as in those who were HIV-negative (75%, 52% and 30%, respectively; P > 0.05). By contrast, 31% of the HIV-positive patients were serum HDAg-positive compared to only 6% of the HIV-negative patients (P = 0.001). HDV antigenaemia and anti-HD antibodies usually fluctuated in the HIV-positive patients during follow-up. The mean Knodell score was similar in the HIV-positive (11.5 +/- 3.2) and HIV-negative (10.7 +/- 2) subgroups, as was the mean semi-quantitative index of hepatic necrosis, inflammation and fibrosis. Our results provide evidence that in HDV-positive patients: (1) HIV infection counters the inhibitory effect of HDV superinfection on HBV replication; (2) serum anti-HD IgM. HDV RNA and liver HDAg are not more frequent in HIV-positive than in HIV-negative patients, suggesting that HIV infection has no effect on HDV replication (although the significance of the increased frequency of HD antigenaemia remains unclear); (3) the histological severity of liver disease is not influenced by HIV status.
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PMID:Influence of human immunodeficiency virus infection on hepatitis delta virus superinfection in chronic HBsAg carriers. 879 May 68

The natural history of hepatitis C is complex and still poorly known. Hepatitis C virus (HCV) replication can be detected very soon after exposure and, at least in the transfusional setting, it persists indefinitely in up to 90% of the cases. While liver damage during the acute phase of hepatitis is almost invariably mild (fulminant cases are exceptions), chronic sequelae of HCV infection may be severe in the long run. Chronic hepatitis C, in fact, is a long-lasting indolent process which leads to cirrhosis in approximately 20% of all infected patients. Hepatocellular carcinoma is a well-recognized complication of old infections, as are a number of extrahepatic manifestations, including type II cryoglobulinaemia. The determinants of the severity of the liver disease are still unclear. However, the risk of cirrhosis seems to be greater for patients with old infections, those infected with the genotype 1b and those with associated conditions. The latter are a heterogeneous and increasing group of 'problem' patients, including patients who are co-infected with the human immunodeficiency virus (HIV1), or who are being treated with cytotoxic or immunomodulating drugs. Data suggest that the natural history of hepatitis C is altered in patients with associated conditions, and this might have an impact on strategies of patient management and treatment.
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PMID:The natural history of hepatitis C. 886 34

Liver disease secondary to hepatitis C virus (HCV) infection is a rising cause of morbidity and mortality among individuals who have been infected parenterally with human immunodeficiency virus (HIV) such as injection drug users, hemophiliacs, and transfused patients. We analyzed both the efficacy of interferon (IFN) alpha therapy in these patients and the predictors of response to this agent. A total of 119 patients with chronic hepatitis C (90 of whom were infected with HIV and 29 of whom were not) were included in a multicenter, prospective, open, nonrandomized observational study. IFN-alpha was given subcutaneously in a dosage of 5 million units three times a week during a 3-month period; those patients who responded received a dose of 3 million units given subcutaneously three times a week for an additional 9 months. One hundred seven patients completed the study; the level of aminotransferases returned to normal and sera became negative (complete response) for HCV RNA in 26 (32.5%) of 80 HIV-infected patients and 10 (37.0%) of 27 non-HIV-infected patients (P = .666) after completion of the treatment. Two variables were independently associated with a response in HIV-infected patients: a CD4+ T lymphocyte count of > 500 x 10(6)/L and a baseline HCV viremia level of < 10(7) copies/mL. In the 12 months following treatment, relapses occurred in 30.8% of the HIV-infected patients and 12.5% of non-HIV-infected patients (P = .403).
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PMID:Interferon alpha for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Hepatitis-HIV Spanish Study Group. 887 84

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same routes of transmission, which explains the high rate of HCV and HIV coinfection (approximately 9%). HIV/HCV coinfection leads to high rates of indeterminate recombinant immunoblot assay patterns and seroreversion; high levels of viral replication; and a more severe histopathologic course. By contrast, HCV infection does not seem to accelerate the progression of HIV infection. Interferon alpha (IFN-alpha) in coinfected patients leads to a similar rate of primary responses, but sustained responses are less frequent. The potential severity of hepatitis C virus infection evidences the need for early diagnosis. Liver biopsy should be performed for all HCV RNA-positive patients in order to evaluate the activity of the liver disease. Given the poor efficiency of IFN-alpha in terms of sustained response in HIV-infected patients, reinforced therapeutic procedures (long-term administration of IFN-alpha or combined ribavirin/IFN-alpha) should be proposed, at least for those patients with severe liver disease.
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PMID:Reciprocal interactions between human immunodeficiency virus and hepatitis C virus infections. 892 12

The genomes of both bacteria and eukaryotic organisms are known to encode selenoproteins, using the UGA codon for seleno-cysteine (SeC), and a complex cotranslational mechanism for SeC incorporation into polypeptide chains, involving RNA stem-loop structures. These common features and similar codon usage strongly suggest that this is an ancient evolutionary development. However, the possibility that some viruses might also encode selenoproteins remained unexplored until recently. Based on an analysis of the genomic structure of the human immunodeficiency virus HIV-1, we demonstrated that several regions overlapping known HIV genes have the potential to encode selenoproteins (Taylor et al. [31], J. Med. Chem. 37, 2637-2654 [1994]). This is provocative in the light of overwhelming evidence of a role for oxidative stress in AIDS pathogenesis, and the fact that a number of viral diseases have been linked to selenium (Se) deficiency, either in humans or by in vitro and animal studies. These include HIV-AIDS, hepatitis B linked to liver disease and cancer, Coxsackie virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which Se is a potent chemoprotective agent. There are also established biochemical mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic effect, suggesting that hemorrhagic fever viruses should also be examined for potential virally encoded selenoproteins. In addition to the RNA stem-loop structures required for SeC insertion at UGA codons, genomic structural features that may be required for selenoprotein synthesis can also include ribosomal frameshift sites and RNA pseudoknots if the potential selenoprotein module overlaps with another gene, which may prove to be the rule rather than the exception in viruses. One such pseudoknot that we predicted in HIV-1 has now been verified experimentally; a similar structure can be demonstrated in precisely the same location in the reverse transcriptase coding region of hepatitis B virus. Significant new findings reported here include the existence of highly distinctive glutathione peroxidase (GSH-Px)-related sequences in Coxsackie B viruses, new theoretical data related to a previously proposed potential selenoprotein gene overlapping the HIV protease coding region, and further evidence in support of a novel frameshift site in the HIV nef gene associated with a well-conserved UGA codon in the 1-reading frame.
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PMID:Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. 915 12

This paper reviews our current understanding of hepatitis C infection in tropical countries. Since its discovery in 1989, hepatitis C has been recognized as an important disease in many tropical countries. In Egypt the prevalence in some sections of the population may-exceed 20%. In most tropical areas, however, the epidemiology of hepatitis C infection is poorly defined. There are clear variations in the distribution of genotypes in different areas and this may be one of the factors which influence the natural history of infection in different regions of the world. Routes of infection in tropical countries are poorly defined, most carriers having no clear risk factors for infection. There is some speculation that inadequate sterilization of medical equipment may be a route of infection in some areas. A combination of factors may result in an increased risk of hepatocellular carcinoma developing in patients from the tropics infected with hepatitis C and the prognosis may be worse due to co-infection with hepatitis B and human immunodeficiency virus, both of which may lead to accelerated liver disease. Prospects for disease control are poor due to the difficulty of developing a vaccine to the virus.
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PMID:Tropical aspects of viral hepatitis. Hepatitis C. 919 45


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