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Biomedical subjects

L Morand-Joubert

Publications and source records attributed to L Morand-Joubert.

17 recordsLinked to original sources

Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually transmitted viruses: evidence of sexual and parenteral transmission.

BACKGROUND: The first epidemiologic evidence of GB virus type C (GBV-C)/hepatitis G virus (HGV) infection showed a high prevalence of asymptomatic carriers in blood donors and in populations at risk for blood-borne viruses. However, by using only viral RNA polymerase chain reaction, those studies underestimated the true spread of GBV-C/HGV infection. The combined detection of GBV-C/HGV RNA and of anti-E2 (which reflects recovery from infection) is necessary to define accurately the prevalence of GBV-C/HGV. STUDY DESIGN AND METHODS: The presence of both anti-E2 and GBV-C/HGV RNA was searched for in 1438 serum samples collected from various groups of individuals at low or high risk for blood-borne or sexually transmitted viruses (blood donors, organ donors, unselected pregnant women, immunocompetent or immunodepressed multiply transfused patients, HIV-positive or HIV-negative homosexual men, intravenous drug addicts). RESULTS: The presence of GBV-C/HGV RNA and/or anti-E2 (exposure to GBV-C/HGV) was frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV appeared also to be sexually transmitted, with transmission from male to female more efficient than vice versa. A particularly elevated level of exposure to GBV-C/HGV was observed in homosexual men. In immunocompetent individuals, the prevalence of anti-E2 was about twice that of GBV-C/HGV RNA, which suggests the frequency of recovery from GBV-C/HGV infection. Most of the GBV-C/HGV RNA-positive individuals had no biochemical evidence of liver damage. CONCLUSIONS: GBV-C/HGV is frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV is not a hepatitis virus, and it seems appropriate to rename it.

Alanine Transaminase

The risk of disease progression is determined during the first year of human immunodeficiency virus type 1 infection.

A cohort of 103 human immunodeficiency virus type 1 (HIV-1)-infected persons with well-defined dates of seroconversion were studied to determine whether baseline plasma HIV RNA loads 6-12 months after seroconversion have prognostic value. Baseline plasma virus loads had predictive value for the disease-free survival rate and for the survival rate. The level of baseline HIV RNA also had a strong negative predictive value for the CD4+ T cell count during the fifth year of infection: A baseline load >5 log was predictive of a CD4+ T cell count <500/mm3 5 years after infection. Baseline HIV RNA load was a CD4+ T cell-independent predictor of progression to death. The major finding was that the disease outcome for HIV-1-infected persons is already determined during the first year of infection.

Adult

[Factors predictive of early virologic response after a first treatment with an protease inhibitor in the course of HIV infection].

As many factors may be involved in therapeutic response to triple therapy with protease inhibitor (PI), the aim of this study was to determine the influence of epidemiological factors (sex, risk factors), clinical status (previous number of AIDS defining events), immunological status (baseline CD4 T cells count), virological factor (baseline viral load), previous antiretroviral therapy and duration of AZT therapy (> or < 6 months), number of prescribed reverse transcriptase inhibitors (RTI), therapeutic strategy (switch to different RTI or only addition of PI) and compliance, on early virological response (M2-M3) after initiation of triple therapy with PI. These results concerned 167 patients treated with triple therapy including PI. A viral load response was defined in three types: complete response (undetectable: < 500 copies/ml) for 100 patients; partial response (significant decrease: > 0.5 log from baseline) for 30 patients and no response for 37 patients. Only two parameters were associated of good virological response: no previous antiretroviral therapy (p < 0.001) and good compliance (p < 0.001). No significant difference was observed between patients with no prior therapy and pretreated patients, in terms of median baseline CD4 count and observance. The baseline median viral load was higher in naive patients despite a better response. In pretreated patients, the type of response appeared to be dependent on the duration of AZT treatment (p = 0.06) and good compliance (p = 0.06). Among the 100 patients with initial complete response, only 23/81 were still undetectable after a median of 13 months of therapy.

Adult

Natural history of GBV-C/hepatitis G virus infection through the follow-up of GBV-C/hepatitis G virus-infected blood donors and recipients studied by RNA polymerase chain reaction and anti-E2 serology.

The aims of this study were to determine the outcome and the natural history of GBV-C/hepatitis G virus (HGV) infection and to establish the frequency of acute or persistent infections in multiply-transfused individuals and blood donors. We used a GBV-C/HGV RNA polymerase chain reaction (PCR) and an assay evidencing antibodies to the envelop protein E2, which is considered a marker for virus clearance. Among 16 PCR-positive recipients, 11 were still positive for GBV-C/HGV RNA at the end of the study period; six of the 16 recipients were GBV-C/HGV infected during the study period and thus had a well-defined date of infection. The 16 patients were shown to carry GBV-C/HGV RNA over a mean period of 4.4 years, for a mean observational period (defined as the follow-up period since the first sample positive for GBV-C/HGV RNA) of 5.3 years. Within the limits of the study period, the patients with a well-defined date of infection were positive for GBV-C/HGV RNA during a mean period of 4.7 years. If defined by the presence of GBV-C/HGV RNA for at least 6 months, the persistent infection rate was 100% in this recipient cohort. Serum anti-E2 antibody was evidenced at least once in five (31.2%) recipients and, except in one case, became detectable after the loss of GBV-C/HGV RNA. Among the 11 blood donors, all were still positive for GBV-C/HGV RNA after a mean follow-up period of 7.7 months. The persistent infection rate was 100% in this donor cohort. Once acquired, the infection to GBV-C/HGV generally tends to persist in immunocompetent patients.

Adenovirus E2 Proteins

Even individuals considered as long-term nonprogressors show biological signs of progression after 10 years of human immunodeficiency virus infection.

Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/microL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, beta-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.

Adult

Risk factors for cirrhosis in patients with chronic hepatitis C virus infection: results of a case-control study.

The role of the viral genotype, especially genotype 1b, in the severity of liver injury induced by chronic hepatitis C virus (HCV) infection is unclear, probably because of confounding factors such as the date and mode of contamination. Host genetic or environmental factors such as heterozygous MZ alpha1-antitrypsin deficiency or alcoholism, could also be potential risk factors for the development of cirrhosis. The aim of this study was to compare the prevalence of genotypes, alpha1-antitrypsin phenotype, past hepatitis B virus infection, and alcohol consumption in cirrhotic and noncirrhotic patients with chronic hepatitis C. We conducted a case-control study comparing 84 consecutive cirrhotic patients with chronic hepatitis C (cases) with 84 noncirrhotic patients with chronic hepatitis C (controls) selected from a cohort of 464 patients hospitalized during the same period. Controls were paired with cases according to age, sex, risk factors, and date of infection. HCV genotypes were determined using the InnoLiPA technique (Innogenetics, Zwijnaarde, Belgium) and classified according to the method of Simmonds. Patients were divided in three groups according to alcohol consumption: <30 g/d (light), 30 to 80 g/d (moderate), and >80 g/d (heavy). Cirrhotic and noncirrhotic patients were not significantly different in terms of genotype distribution (1a/1b/2a/3a/others/undetermined: 10/48/7/17/0/2 versus 11/43/10/10/5/5), alpha1-antitrypsin phenotype distribution (MM/MS/MZ: 84%/14%/2% vs. 87%/11%/2%, respectively), and prevalence of antibody to hepatitis B core antigen positivity (29% vs. 23%). Alcohol consumption was significantly different between cases and controls (L/M/H: 58%/27%/16% vs. 76%/15%/9%, respectively; P < .05). Two conclusions regarding patients with chronic hepatitis C virus infection can be drawn from this study: 1) viral genotype, especially 1b, past hepatitis B virus infection, and heterozygous MZ alpha1-antitrypsin deficiency are not risk factors for cirrhosis; and 2) alcohol consumption, even moderate, is a risk factor for cirrhosis.

Adult

Virological and immunological data of AIDS patients treated by passive immunotherapy (transfusions of plasma rich in HIV-1 antibodies).

BACKGROUND AND OBJECTIVES: In human immunodeficiency virus (HIV) infections, passive immunotherapy can be carried out through infusions of virus-inactivated plasma from symptomless HIV-infected persons with abundant HIV antibodies. MATERIALS AND METHODS: We carried out a prospective, randomized, double-blind, controlled, passive immunotherapy study, which compared two groups. One received plasma rich in HIV antibodies, the other a standard seronegative plasma. RESULTS: Measurement of the plasma HIV RNA load showed in both groups a significant decrease in the mean viral copy number at the end of the first month, followed by an increase at the third month. Beyond the third months, a significant decrease in viral load was observed only in the treatment group. A significant difference in favor of the treatment group was observed for plasma viremia by HIV culture. For the cytokines involved in the viral replication and for the immune activation markers such as neopterin and beta 2-microglobulin, the biological analysis in plasma failed to show a significant difference in either group. Clinically, the treatment group benefited by delay in the appearance of the first AIDS-defining event and reduction in the cumulative incidence of such events. CONCLUSION: One possible interpretation is that passive immunotherapy affects plasma viral load, but there is no evidence that HIV-specific antibodies are exclusively responsible for the observed effects.

Acquired Immunodeficiency Syndrome

Full or partial seroreversion in patients infected by hepatitis C virus.

Cases of partial seroreversion have been reported in hemodialyzed or immunodepressed patients, but spontaneous clearance of viremia associated with a disappearance of specific antibodies or clearance while receiving therapy has not been precisely documented in immunocompetent hepatitis C virus (HCV)-infected persons. A longitudinal study of markers of HCV infection in a cohort of 178 multitransfused patients followed over an 8-year period was done to establish well-documented cases of partial or full seroreversion. Thirty (16.8%) of 178 patients were HCV-infected; among them, 5 had partial or full seroreversion. Seroreversion to an anti-HCV-negative state is characterized by a quantitative decrease in antibody. A seroreversion may be observed in three circumstances: spontaneously, induced by therapy, and in conjunction with human immunodeficiency virus infection. Long-term follow-up of seroreverters will establish whether they have definitively eradicated HCV from their systems.

Alanine Transaminase

Human T-lymphotropic virus type I excretion and specific antibody response in paired saliva and cervicovaginal secretions.

Paired sera, salivas, and cervicovaginal secretions from 17 HTLV-I-infected women (10-75 years) were evaluated for total IgA, IgG, IgM, for IgA and IgG to whole HTLV-I lysate, for albumin, and for tax-rex proviral HTLV-DNA. IgG to HTLV-I were constantly detected, with much higher titers in serum (mean titer: 97,800) than in saliva (53) or in cervicovaginal secretions (216). IgA to HTLV-I were detected in only 12 (70%) sera, 6 (35%) salivas, and 8 (53%) cervicovaginal secretions, with higher titers in serum (75) than in saliva (8). Using the relative coefficient of excretion by reference to albumin, as well as the comparison of specific activities, the HTLV-I-specific IgG appeared primarily originating from serum, whereas IgA to HTLV-I were primarily locally produced. Salivary synthesis of IgG to HTLV-I occurred in both patients with a sicca syndrome attesting salivary glands impairment. Local excretions of total IgA, IgG, and IgM evaluated in body fluids were normal. HTLV DNA was detected in 4 (24%) salivas and in 3 (20%) cervicovaginal secretions, always in patients demonstrating local synthesis of HTLV-I-specific IgA or IgG. HTLV-I excretion elicits a weak local immune response to HTLV-I in saliva as well as in cervicovaginal secretions, which could be relevant for HTLV-I transmission via body fluids.

Adolescent

Quantitation of passively acquired human immunodeficiency virus (HIV) antibodies in AIDS patients transfused with a plasma that is rich in HIV antibodies.

BACKGROUND: Passive immunotherapy in human immunodeficiency virus (HIV) infection is based on transfusions of plasma that is rich in HIV antibodies. STUDY DESIGN AND METHODS: To verify whether the clearance of transfused antibodies will maintain an elevated titer of specific antibodies between biweekly transfusions of plasma, the titers of anti-HIV-1 in plasma and in transfusion recipients were measured. Samples from 12 recipients were analyzed by automated scanning of Western blot, before transfusion and at Days 2, 7, and 14 after transfusion. RESULTS: The p24 antibody became detectable or higher than the baseline after transfusion and remained detectable until the second transfusion. Anti-p24 titers were variable and dependent on the antibody titer of the transfused plasma and the baseline p24 antigen titer. CONCLUSION: Biweekly transfusion of plasma with a high anti-HIV titer maintains a high anti-p24 titer between transfusions in AIDS patients treated with passive immunotherapy.

Acquired Immunodeficiency Syndrome

Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma.

A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.

Acquired Immunodeficiency Syndrome

Correlation between viral DNA load and serum anti p19 antibody concentration in symptomless human T-lymphotropic virus type-I (HTLV-I)-infected individuals.

In order to determine whether serum anti-human T-cell lymphotropic virus type I (HTLV-I) antibody concentration is correlated with cellular viral DNA load, these 2 biological parameters were established in 22 symptomless HTLV-I carriers. The proviral copy (PVC) number was determined through quantificative polymerase chain reaction. Specific antibody titers were determined by Western blot with the end-point dilution method; the quantification of each antibody was performed through ScanBlot by determination of the peak height of each Western-blot band. A positive correlation was observed between the PVC number and the titer of total antibodies. When the association between the peak height of each antibody and the PVC number was studied, a significant positive correlation was observed only with anti-p 19. Further evaluation through follow-up studies of symptomless HTLV-I individuals is needed to clarify the value of anti-HTLV-I antibody titer as a predictor of disease progression.

Adult

Serum anti-p24 antibody concentration has a predictive value on the decrease of CD4 lymphocyte count higher than acid-dissociated p24 antigen.

We studied the prognostic value on the decrease of CD4 lymphocyte count of anti-p24 antibody (ab) titer and compared this value with that of polyclonal and monoclonal p24 (ag) titer before and after immune complex dissociation (ICD); 53 human immunodeficiency virus (HIV)-infected patients having CD4+ counts above 400/mm3 when first examined were followed up over a 3-year period including at least four visits; HIV disease progressors (n = 18) were defined as having CD4+ counts below 200/mm3 and non-progressors (n = 35) as having CD4+ counts still above 400/mm3 at the end of follow-up. Sera were collected at each visit and assayed for p24 ag with and without ICD and for anti-p24 ab titer. The mean anti-p24 ab titer of progressors and of non-progressors at entry was significantly different. A threshold of anti-p24 ab titer indicating a HIV progression was determined at 1/300. The proportion of individuals with an anti-p24 ab titer lower than 1/300 at least once during the study period was 34% in non-progressors and 94% in progressors. The difference between progressors and non-progressors at entry was significant with monoclonal p24 ag without ICD and more significant with monoclonal p24 ag after ICD. The marker having the highest predictive value was the anti-p24 ab titer, then monoclonal p24 ag with ICD, then polyclonal p24 ag with ICD. Anti-p24 ab is an earlier and stronger marker of the decrease of CD4 lymphocyte count than p24 ag even after ICD.

Acids

Analysis of BCR/ABL transcripts in chronic myeloid patients by nested PCR using an immunoassay-like detection format.

We describe an 'immunoassay-like' detection format, based on the AMPLICIS technique for the routine detection of BCR/ABL transcripts in leukaemic patients. The AMPLICIS technique is characterized as a nested PCR coupled to solid phase isotopic or non-isotopic detection of PCR products. Comparison between this assay and a conventional PCR technique using Southern-blot analysis provided a good correlation between the two procedures. The assay, easier and faster than the conventional one, gives access to automation and therefore appears well suited for the routine screening of BCR/ABL chimaeric mRNAs.

Base Sequence

Predicting progression of HIV disease: usefulness of acid-dissociated p24 antigen.

To ascertain whether immune complex dissociation (ICD) improves the value of p24 antigen as a prognostic marker for progression of HIV infection, 53 patients were followed over a 3-year period, including at least one visit per year. All had CD4+ counts at entry > 400/mm3; progressors (n = 18) were defined as having CD4+ counts < 200/mm3 and nonprogressors (n = 35) as having CD4+ counts still > 400/mm3 at the end of follow-up. Serum specimens were collected at each annual visit and assayed for p24 antigen with and without ICD treatment. At entry, the percentage of progressors positive for ICD p24 antigen was significantly higher than the percentage of positive nonprogressors (39% versus 3%, p < 0.01). The sensitivity of p24 antigen over all visits in terms of predicting the progression increased from 61% before ICD to 83% after. The specificity of p24 antigen in terms of predicting progression decreased from 97% before ICD to 89% after. The relative risk of progression in individuals positive for p24 antigen was 6.7 before ICD and increased after ICD to 12.7. When evaluating the respective prognostic value of the p24 antigen and of the ICD p24 antigen, only ICD p24 was significant (RR 10.2, 95% CI 2.2-46.9). ICD p24 antigen appears to be a marker of progression that may be detected earlier than p24 antigen without ICD.

Adult