Does active hepatitis C virus infection increase the risk for infection due to Staphylococcus aureus?

Infections with Staphylococcus aureus may be more frequent in subjects with active hepatitis C virus (HCV) infection. In this retrospective dual-cohort study, we sought to determine whether persons with active HCV infection (positive HCV antibody, detectable blood HCV RNA) were at greater risk of S. aureus infection than those with spontaneously resolved HCV infection (positive HCV antibody, negative blood HCV RNA). Based on prestudy power calculation, we included 231 subjects with active HCV and 116 subjects with resolved HCV infection. The two groups were well matched at baseline, except that subjects with active HCV had a higher mean Charlson's comorbidity index (2.2 vs. 1.3; p < 0.0001). Cohorts were followed for a mean of 3.67 years. Thirty-one of the 231 (13%) subjects with active HCV infection developed ≥1 S. aureus infection(s) as compared to 4/116 (3.4%) subjects with resolved HCV (p = 0.004), with a trend towards more recurrent S. aureus infections in subjects with active HCV infection. The S. aureus infections were mostly serious, necessitating hospitalization and intravenous antibiotics. In the logistic regression, factors that independently predicted S. aureus infection were active HCV and Charlson's comorbidity index. Our regression models confirmed that the enhanced susceptibility to S. aureus infections was related to active HCV infection and not attributable solely to the increased number of comorbidities [adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI) 1.1-9.8; p = 0.03]. This study shows that subjects with active HCV infection have a significantly higher incidence of serious S. aureus infections than those with spontaneously resolved HCV, even after adjustment for comorbidities.

Which factors predict the behavior of ventricular extrasystoles in athletes over time?

Spontaneous behavior of ventricular extrasystoles (VE) was analysed. From a database containing 578 athletes with VE, 84 males and 11 females (29.9 ± 18.1 years) having ≥ 100 VE or repetitive VE [ventricular couplets (VC) or ventricular tachycardias (VT)] at first 24-hour Holter electrocardiographic monitoring (24-h-HM) (baseline) and at least 1-year of follow-up (3.1 ± 2.2 years) over the past 10 years were selected. The baseline was compared with the last 24-h-HM to establish DVE (VE reduction of at least 98%/24 h in the absence of VC or VT). SDVE was calculated as standard deviation of the number of VE on serial 24-h-HMs. DVE and SDVE were considered as dependent variables. Independent variables were: age, sex, type of sport, symptoms, baseline VE rate (BVE), baseline VC and VT, VE morphology, VE behavior during the baseline training session, disqualification from competitive sports, echocardiographic abnormalities. DVE occurred in 32 athletes (34%). SDVE varied from 0 to 12,658 VE/24 h (1916 ± 2649.9). Disappearance of VE during the baseline training session (DVET) correlated to DVE (P = 0.0319). BVE directly correlated to SDVE (P = 0.0008). Athletes' VE are highly variable over time, their variability depending on BVE, and they not infrequently tend to disappear. The only useful variable for predicting DVE is DVET.

Comparison of peginterferon pharmacokinetic and pharmacodynamic profiles.

The pharmacokinetics and in dosing regimens of the currently available pegylated interferon (peginterferon) alfa molecules differ greatly, depending on the size and nature of their polyethylene glycol (PEG) moiety. Peginterferon alfa-2a has a branched 40 kDa PEG chain covalently attached to lysine residues and circulates as an intact molecule. On the other hand, peginterferon alfa-2b has a linear 12 kDa PEG chain covalently attached to interferon-a-2b via an unstable urethane bond that is hydrolysed after injection, releasing native interferon alfa-2b. The difference in pegylation between the two peginterferons has a significant impact on their pharmacokinetic properties. Data from comparative and non-comparative studies indicate that peginterferon alfa-2b has a shorter half-life in serum than peginterferon alfa-2a, and a significant proportion of patients receiving peginterferon alfa-2b may have trough concentrations below the limit of detection during the latter part of the 7-day dosing schedule. However, the pharmacodynamic parameters of the two drugs appear to be similar.

Pharmacodynamics of peginterferon alpha-2a and peginterferon alpha-2b in interferon-naïve patients with chronic hepatitis C: a randomized, controlled study.

BACKGROUND: Peginterferon alpha-2a and alpha-2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus. AIM: To compare the pharmacodynamics of peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive patients with chronic hepatitis C. METHODS: Patients were randomized to receive peginterferon alpha-2a, 180 microg (n = 10) or peginterferon alpha-2b 1.0 microg/kg (n = 12) once weekly. The enzymatic activity of 2'5'-oligoadenylate synthetase and levels of neopterin and beta(2)-microglobulin were measured at baseline and at 24, 48, 120 and 168 h. RESULTS: Oligoadenylate synthetase activity and serum neopterin and beta(2)-microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration-time curve of either peginterferon and the area under the concentration-time curve for 2',5'-oligoadenylate synthetase, neopterin and beta(2)-microglobulin. The area under the concentration-time curves calculated for these three markers did not correlate with body mass index stratified at <25 and >or=25 kg/m(2) for either peginterferon. CONCLUSIONS: Despite pharmacokinetic differences between peginterferon alpha-2a and peginterferon alpha-2b, the pharmacodynamic profiles of the two formulations appear to be comparable.

The impact of rifaximin in the prevention of bacterial infections in cirrhosis.

OBJECTIVE: Bacterial infections are a leading factor in the progression from compensated to decompensated cirrhosis, with consequent worsening of the prognosis, and concerted efforts have been made to reduce infections and improve the survival rate of these patients. We retrospectively investigated the rate of infections in hospitalized cirrhotic patients under treatment with rifaximin. PATIENTS AND METHODS: We enrolled 649 patients whose clinical and personal data, prescribed therapy, microbiological findings and laboratory tests were collected from previous discharge letters and our institution database. The efficacy of rifaximin in preventing several types infection was evaluated by comparing outcomes for rifaximin-treated patients vs patients receiving no antibiotic treatment. RESULTS: The risk of developing selected bacterial infections was significantly lower in patients treated with rifaximin (OR 0.29; 95% CI 0.20-0.40, p < 0.001). CONCLUSIONS: Continuous treatment with rifaximin may prevent bacterial infections in cirrhotic patients.

Hepatotoxicity and antiretroviral therapy with protease inhibitors: A review.

Highly active antiretroviral therapy including protease inhibitors has led to dramatic decrease in the morbidity and mortality resulting from infection with human immunodeficiency virus-1. However, this combination regimen can be associated with the occurrence of serious toxicities, which may reduce patient compliance. In particular, human immunodeficiency virus-1 protease inhibitors and nevirapine among nonnucleoside reverse transcriptase inhibitors, have the potential for producing hepatotoxicity. We summarise current knowledge of the hepatotoxic effects associated with the commercially available human immunodeficiency virus-1 protease inhibitors based on a literature review of the major retrospective and prospective clinical studies designed to elucidate risk factors for developing hepatotoxicity among human immunodeficiency virus-1-infected patients receiving antiretroviral therapy containing protease inhibitors. Coinfection with chronic hepatitis, a common occurrence in human immunodeficiency virus-1-infected patients, is identified as an independent risk factor for developing hepatotoxicity in antiretroviral-treated human immunodeficiency virus-1-infected patients treated with antiretroviral regimens containing protease inhibitors. The importance of other risk factors for developing protease inhibitor-associated hepatotoxicity and the mechanism underlying the drug-related hepatotoxicity are discussed. The data indicate that the potential for producing hepatotoxicity is variable among the protease inhibitors and suggest that based on differences in drug-related hepatotoxicity, certain protease inhibitors may be preferred for the treatment of human immunodeficiency virus-hepatitis C virus coinfected patients.

Nosocomial febrile illnesses in patients on an internal medicine service.

Febrile illnesses commonly arise in hospitalized patients after admission, but most previous studies have been of specific subsets of febrile illnesses. To provide practical information about the problem as a whole, we studied febrile illnesses arising after admission (nosocomial febrile illnesses [NFls]) in 123 inpatients of an internal medicine service who had been afebrile for the preceding week. We compared them with 123 randomly selected patients without NFl. Causes of NFl included infections in 83 cases; noninfectious, inflammatory states in 15; malignancy in 12; ischemia in eight; and procedures in three. Evidence for the cause of the NFl was present at onset in at least 110 of the 123 patients. Despite this, antimicrobial agents were administered to 23 (58%) of 40 patients without infections. Thirty-four patients with NFl died; the NFl contributed to death in 26. In contrast, only eight comparison patients died. "Do not resuscitate" status was present in 32 patients with NFl compared with only 12 comparison patients, and 19 (59%) of the former died. The data from this study provide a comprehensive description of NFl arising in hospitalized internal medicine patients, indicate that the occurrence of a new febrile illness signifies a poor prognosis, and provide a rational basis for management.

General issues on microbial translocation in HIV-infected patients.

The lumen of the gastrointestinal tract is home to an enormous quantity of different bacterial species that thrive in an often symbiotic relationship with the host. It is the principal source of microbial products because of its massive bacterial load. Injury to the immune component of the gastrointestinal mucosal surface, along with damage to the intestinal epithelial microenvironment with its antimicrobial functions, may affect systemic immune activation during the chronic phase of HIV infection through the increased translocation of luminal microbial products. Moreover, microbial translocation, which is defined as "the passage of both viable and nonviable microbes and microbial products such as endotoxin across anatomically intact intestinal barrier", may be a fundamental mechanism through which HIV accelerates progression of chronic viral hepatitis. Improvements in the tools available to microbiota research, and especially advancement of our knowledge in this area may help us in controlling the evolution of HIV disease, although population complexity and diversity between individuals make this challenging.

Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients.

OBJECTIVE: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment. METHODS: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points. RESULTS: Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9-28.9] due to toxicity and 7.6% (95% CI, 4.9-1 0.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74-5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04-1.26 versus hard-gell saquinavir). CONCLUSIONS: If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

Infection in the myelodysplastic syndromes.

PURPOSE: To determine the incidence, characteristics, and outcome of infection in patients with myelodysplastic syndromes (MDS) and risk factors that may lead to infection. PATIENTS AND METHODS: We reviewed infections that occurred in 86 consecutive patients with MDS who received care from 1968 to 1986 at a university-affiliated Veterans Affairs Medical Center. Time lines charting the course of each patient with MDS were created and included infections, MDS subgroup at the time of presentation and at the time of each infection, peripheral neutrophil counts, and therapies for MDS. RESULTS: Infections occurred at a rate of nearly one per patient year of observation. Infection rates were associated with MDS subgroup as follows: refractory anemia with or without ringed sideroblasts (RA +/- RS) less than refractory anemia with excess blasts (RAEB) less than RAEB in transformation (RAEB-T). The group of RA +/- RS patients who had erythroid abnormalities but minimal or no dyspoiesis of other cell lines had the lowest rate of infections. Infection rates were higher in patients with less than or equal to 1,000 neutrophils/microL blood than in patients with greater than 1,000 neutrophils/microL blood for each classifiable MDS subgroup. Neutrophil concentration and MDS subgroup were independent risk factors for infection in patients with MDS. Bacterial pneumonias and skin abscesses were the most common infections. Infection was the most common cause of death during MDS, accounting for 64% of deaths, and was more common than transformation to acute leukemia as a cause of death. CONCLUSION: Infection is a common, life-threatening problem in patients with MDS. Neutropenia and MDS subgroup are each risk factors for infection. Clinicians should aggressively evaluate patients with fever and MDS for infection, especially pneumonia and skin infections.

Diagnosis and outcome of 100 consecutive patients with extreme granulocytic leukocytosis.

PURPOSE: To determine the clinical features, causes, and prognostic significance of extreme leukocytosis in adults. PATIENTS AND METHODS: Medical records of 100 consecutive patients who presented at the Minneapolis Veterans Affairs Medical Center between March 1993 and January 1994 with more than 25,000 leukocytes/microL blood and with more than 50% granulocytes were reviewed. Demographic, clinical, and outcome information was recorded, and a cause of extreme leukocytosis was sought in each case. RESULTS: Extreme leukocytosis was attributed to infection in 48 cases, advanced malignancy in 13 cases, hemorrhage in 9 cases, glucocorticoids in 8 cases, and other causes in 22 cases. Four patients had previously diagnosed conditions resulting in chronic leukocytosis. Higher leukocyte counts were associated with malignancy (chi2 for trend=12.5, P <0.002). Fever was more common in patients with infection (weighted rate ratio=3.7, 95% Confidence interval [CI]=2.2 to 6.2). Mortality was high overall (31%), and was greater in patients with noninfectious diagnoses compared with infected patients, an association which persisted after stratification by leukocyte count (weighted rate ratio=2.5, 95% CI=1.2 to 4.9). CONCLUSION: Clinicians should be aware that extreme leukocytosis with a predominance of granulocytes is associated with infection in only 48% of cases. The presence of fever increases the likelihood that infection is the cause. Mortality is high, particularly in patients without infection.

Comparison of the plasma pharmacokinetics of lamivudine during twice and once daily administration in patients with HIV.

OBJECTIVE: To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection. DESIGN: Nonblind, sequential, pharmacokinetic study. PARTICIPANTS: 13 patients with HIV-1 infection (median age 36 years). METHODS: Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after > or =7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration,. RESULTS: 12 patients completed the study. Lamivudine pharmacokinetic parameters (mean +/- SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077+/-816 microg/L; trough plasma concentration (Cmin) 332+/-219 microg/L; elimination half-life (t 1/2beta) 6.1+/-1.9h; time to Cmax (t(max)) 1.6+/-0.7h; average concentration over the dosage interval (Cav) 711+/-269 microg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17085+/-6464 microg x h/L. Corresponding values after administration of 300mg once daily were: Cmax 3461+/-854 microg/L; Cmin 146+/-87 microg/L; t1/2 7.9+/-3.4h; t(max) 2.2+/-1.3h; Cav 705+/-177 microg/L; and AUC over 1 dosage interval (24h) 16644+/-4150 microg x h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters. CONCLUSIONS: Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.

HIV type 1 intraperitoneal infection of rabbits permits early detection of serum antibodies to Gag, Pol, and Env proteins, neutralizing antibodies, and proviral DNA from peripheral blood mononuclear cells.

The aim of this study is the development of an animal model useful for studying HIV-1 pathogenesis, candidate vaccines, and antiviral drugs. Aseptic thioglycolate peritonitis was induced in six rabbits. After 4 days, four rabbits were infected with 1 ml of HIV-1 stock containing 100 times the MID50. Blood samples were collected every 2 weeks for 8 months. Serum antibodies were tested by ELISA, using as antigen the recombinant protein p24; synthetic peptides of highly conserved regions of p31, gp41, and gp120; and a synthetic peptide of gp120 at the V3 loop region of HIV-1 strains IIIB and MN. Furthermore, neutralizing antibodies were tested by a microscale neutralization assay. Proviral DNA was detected by PCR, and virus isolation was performed by a cocultivation technique using primary rabbit peripheral blood mononuclear cells (PBMCs). All infected rabbits produced antibodies to HIV-1 proteins within 2 weeks and up to 8 months after virus infection. Serum antibodies were directed against the Env (gp120 and gp41), Gag (p24), and Pol (p31) proteins and against two synthetic peptides whose sequence corresponds to gp120 at the V3 loop region of HIV-1 strains IIIB and MN. Neutralizing antibodies were also detected in the sera of infected animals. Proviral DNA was detected in PBMCs by PCR within 4 weeks and up to 8 months after HIV-1 infection. HIV-1 was also isolated from PBMCs of infected animals at 30, 60, and 120 days after infection. Results obtained indicate that HIV-1 intraperitoneal infection of the rabbit permits the early detection of serum antibodies to Gag, Pol, and Env proteins, neutralizing antibodies, and proviral DNA sequences from PBMCs.

Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in 'real world' patients with chronic hepatitis C.

BACKGROUND: Interferon-alpha plus ribavirin therapy for chronic hepatitis C is associated with adverse effects that lead to therapy discontinuation in up to 27% of patients in randomized controlled trials. AIM: To examine the causes and predictive factors for therapy discontinuation in patients treated in current clinical practice. METHODS: We retrospectively enrolled 441 consecutive patients, scheduled to receive interferon-alpha + ribavirin for chronic hepatitis C, in five centres. Patients had been treated with 3 or 6 MU interferon-alpha three times a week plus ribavirin, 800-1200 mg daily, for 6 or 12 months. RESULTS: One hundred and eight [24.5%; confidence interval (CI), 20.5-28.8%] patients failed to finish combination therapy because of adverse events. The discontinuation rate was higher during the first 6 months of treatment; anaemia was an important cause (36.1% of discontinuations); unexplained lipothymia resulted in discontinuation in 11 patients. Female gender [hazard ratio (HR) = 1.85; CI, 1.17-2.92], an interferon-alpha dose > 15 MU/week (HR = 1.79; CI, 1.12-2.86) and no previous interferon-alpha treatment (HR = 1.63; CI, 1.04-2.57) were independent factors associated with discontinuation. The simultaneous presence of these factors identified patients at high risk for discontinuation [odds ratio (OR) = 10; CI, 3.98-25.13]. CONCLUSIONS: The study identified some predictive factors for adverse event-related discontinuation, which may improve the safety profile and effectiveness of interferon-alpha + ribavirin combination therapy in chronic hepatitis C.

Human immunodeficiency virus type 1-related nucleic acids and papillomavirus DNA in cervicovaginal secretions of immunodeficiency virus-infected women.

OBJECTIVE: To evaluate simultaneous human immunodeficiency virus (HIV)-related nucleic acids and human papillomavirus (HPV)-DNA in cervicovaginal secretions of HIV-seropositive women. METHODS: We collected 47 paired blood and cervicovaginal lavage samples from 124 known HIV-1-seropositive women. Proviral HIV-1 DNA, cell-associated, and cell-free HIV-1 RNA in cervicovaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (PCR) and reverse transcription PCR. Polymerase chain reaction and subsequent restriction fragment length polymorphism analysis of PCR products were used to detect HPV types 6, 11, 16, 18, 31, 33, 35, and 56. RESULTS: Proviral HIV-1 DNA, cell-associated, and cell-free HIV-1 RNA were detected in 52.4% (65 of 124), 38.7% (48 of 124), and 33.9% (42 of 124) of lavage samples, respectively. Human papillomavirus-DNA in cervicovaginal secretions was detected in 64% (79 of 124) of participants. The rate of detection of HPV types of intermediate to high oncogenic risk was higher in HIV-positive women who tested positive for cell-associated (odds ratio [OR] 3.57, 95% confidence interval [CI] 1.17, 11.12) or cell-free (OR 4.63, 95% CI 1.42, 15.51) HIV-1 RNA in cervicovaginal secretions than their counterparts who tested negative. Logistic regression analysis showed that the association between HPV infection and the detection of HIV-1 RNA in cervicovaginal secretions persisted after adjustment for potential confounders such as CD4+ cell counts, HIV-1 RNA in plasma, use of antiretroviral drugs, vaginal infection, and regular condom use. In univariable and multivariable analysis, HPV-DNA detection was associated with amounts of cell-free and cell-associated HIV-1 RNA in cervicovaginal secretions (chi(2) for trend 10.35, and 9.84, P =.001 and.002, respectively). CONCLUSIONS: The rate of HPV detection in the genital tract of HIV-1-seropositive women is associated with the amount of cell-associated and cell-free HIV-1 RNA present in cervicovaginal secretions. The association does not appear to be attributable entirely to the effect of HIV-related immunodepression.

Lack of observed association between armadillo contact and leprosy in humans.

In 1971 it was discovered that the nine-banded armadillo (Dasypus novemcinctus) could be infected in the laboratory with Mycobacterium leprae, and would manifest disease similar to the lepromatous form of leprosy in man. In 1975 several wild armadillos captured in Louisiana were found to have a disease identical to the M. laprae infection in laboratory animals. To determine if there is a significant association between contact with armadillos and presence of leprosy in humans, the armadillo contact of persons with indigenous leprosy in Louisiana was compared to the contact of matched controls. No difference in the nature or frequency of contact was found. If this infection of wild armadillos is of recent onset, an association with human leprosy in enzootic areas may not be detectable for several years.

Quantitative assessment of cell-associated and cell-free virus in cervicovaginal samples of HIV-1-infected women.

OBJECTIVE: To examine the amount of cell-free and cell-associated virus in cervicovaginal secretions (CVS) of HIV-infected women. METHODS: Paired cervicovaginal and blood samples from 61 seropositive women were quantitatively evaluated by competitive polymerase chain reaction (cPCR) and reverse transcription-PCR (cRT-PCR) for: (1) genomic RNA from plasma and cell-free CVS, and (2) unspliced (u/s) RNA transcripts and proviral DNA in cells from secretions. RESULTS: HIV DNA was detected in 42.6%, u/s transcripts in 32.7% and cell-free HIV RNA in 31.1% of 61 cervicovaginal samples. The median copy numbers of HIV DNA, u/s transcripts, and cell-free RNA were 125 copies/10(5) cells, 40 copies/10(5) cells, and 300 copies/mL of secretion, respectively. Nineteen of 26 (73.1%) and 17 of 26 (65.3%) women positive for DNA were also positive for RNA transcripts and cell-free RNA, respectively (P<0.001). A significant correlation between the amounts of cell-free and u/s transcripts was also found (Spearman Rho 0.618, P=0.014). The prevalences of u/s transcripts and cell-free RNA were 42.6% and 53.8% respectively among patients with detectable blood RNA, and 22.9% (P=0.09) and 14.3% (P=0.0017) among patients with undetectable blood RNA. In stepwise logistic regression, cell-free RNA was independently associated with the presence of detectable blood viremia. The amount of HIV DNA was lower among subiects currently under treatment (50 copies/10(5) cells) than in untreated subjects (250 copies/10(5) cells) (P=0.037). CONCLUSIONS: Both cell-free and cell-associated HIV could be detected and quantitated in CVS, providing a means to examine the level of viral activity in the female genital tract.

Transfusion-transmitted virus infection in HIV-1-seropositive patients.

OBJECTIVES: To investigate the prevalence, persistence and genome heterogeneity of transfusion-transmitted (TTV) in HIV-1-infected patients, a group at high risk both of contracting blood-borne viruses and having viral persistence relating to immunodepression. METHODS: Plasma samples from 238 HIV-1 seropositive subjects and 226 healthy blood donors were examined for TTV-DNA both by polymerase chain reaction (PCR) using primers from the conserved regions in the N22 clone and PCR using primers deduced from the untranslated region (UTR). Direct DNA sequencing and phylogenetic analysis were used to characterize 27 TTV isolates from HIV-1 patients or healthy controls. RESULTS: Using PCR with the UTR primers, TTV DNA was detected in a very high percentage (> 80%) of samples both from HIV-1 seropositive subjects and from blood donors. Using PCR with N22 primers, shown to detect viral strains associated with hepatitis of unknown etiology, TTV DNA was found in 103 of 238 (43.3%) HIV-1-infected patients and in 22 of 226 (9.7%) blood donors. There was no difference in the prevalence of the TTV DNA in HIV seropositive subjects with regard to clinical features related to immunosuppression, markers of HCV infection or intravenous drug use; presence of TTV DNA was associated significantly only with male gender (P = 0.003). Persistent or intermittent viremia was detected in plasma samples taken up over a period of 19 months in all (15 of 15) HIV-infected patients tested. CONCLUSIONS: The persistence and high frequency of infection detected by PCR with N22 primers in HIV-1 seropositive patients suggest that further clinical investigation of immunocompromised hosts will provide information to clarify the pathogenic role of TTV.

Management of hepatitis C in human immunodeficiency virus-infected patients.

Hepatitis C virus-related liver disease and its associated complications are steadily emerging health concerns in persons co-infected with human immunodeficiency virus. The increasing number of liver-related deaths in human immunodeficiency virus-hepatitis C virus co-infected individuals supports the compelling argument for more aggressive treatment in these patients. The safety and efficacy of interferon/ribavirin in human immunodeficiency virus/hepatitis C virus co-infected patients is currently under evaluation. Despite well-documented concern over highly active antiretroviral therapy-associated hepatotoxicity human immunodeficiency virus/hepatitis C virus co-infected patients should be offered antiretroviral therapy. Since management of co-infected patients is complex a multidisciplinary approach is needed in order to facilitate care and help patients to achieve a positive outcome.

Prevalence and histologic features of transfusion transmitted virus and hepatitis C virus coinfection in a group of HIV patients.

BACKGROUND: A recently identified DNA transfusion-transmitted virus has been associated with post-transfusion non-A to G hepatitis. AIM: To determine the prevalence of transfusion-transmitted virus in patients with human immunodeficiency virus infection. Its clinical role in the pathogenesis of liver disease was also evaluated in patients with transfusion-transmitted-virus hepatitis C virus coinfection compared with those with hepatitis C Virus infection alone. PATIENTS AND METHODS: We evaluated 312 HIV-hepatitis C virus coinfected patients (225 males, 87 females). All underwent screening for transfusion-transmitted virus DNA using a nested polymerase chain reaction technique. In some transfusion transmitted virus-DNA positive patients, we performed a phylogenetic analysis. In 56 patients (20 transfusion-transmitted-virus-hepatitis C virus and 36 hepatitis C virus alone), liver biopsy was collected. RESULTS: The prevalence of transfusion-transmitted virus was 113/312 (36%). The genotype distribution was similar to that reported in other studies. No difference in liver histology was found between the two groups. CONCLUSION: Transfusion-transmitted virus infection is common in human immunodeficiency virus patients. We found no histologic differences between liver biopsy specimens from patients coinfected with transfusion-transmitted virus plus hepatitis C virus compared with those infected with hepatitis C virus alone. Transfusion-transmitted virus is not clearly associated with a distinct liver injury.