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Biomedical subjects

C Rouzioux

Publications and source records attributed to C Rouzioux.

At least 73 records · Page 4Linked to original sources

Apparent enhancement of perinatal transmission of human immunodeficiency virus type 1 by high maternal anti-gp160 antibody titer.

The presence of antibodies able to enhance infection in vitro in sera from human immunodeficiency virus (HIV)-1-infected patients raises the possibility that antibodies exert a deleterious activity during natural infection. The anti-HIV-1 humoral response and plasma HIV-1 RNA were measured in a cohort of 98 infected mothers, included in the French Prospective Study on Pediatric HIV Infection, 49 of whom transmitted HIV to their children. Transmission from mother to child was associated with antibody responses to the envelope gp160 (P = .009 for serum dilution of 1/400) and to a highly conserved domain of the transmembrane glycoprotein (P = .055 for serum dilution of 1/400) and with plasma HIV-1 RNA levels (P < .0001). Multivariate logistic regression indicated that a high anti-gp160 response and a high plasma virus load are independent risk factors for perinatal transmission of HIV-1 (odds ratio, 3.4; 95% confidence interval, 1.1-9.9 for anti-gp160; odds ratio, 2.8; 95% confidence interval, 1.6-5.0 for virus load).

Amino Acid Sequence↗

Tritherapy for human immunodeficiency virus infection does not modify replication of hepatitis C virus in coinfected subjects.

Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis for human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. In an attempt to evaluate the impact of anti-HIV triple combination therapy on the course of hepatitis C virus (HCV)-related chronic hepatitis and on HCV replication, we studied the biological and virological characteristics of 22 HCV/HIV-coinfected patients who were given triple combination therapy. In comparison with baseline values, there was (1) a significant increase in the CD4 and CD8 cell counts and a decrease in the HIV RNA load and (2) no significant variation in aminotransferase activities or the HCV RNA load at 3, 6, or 9 months of tritherapy. Antiretroviral tritherapy seems to modify neither the biological activity of HCV-related chronic hepatitis nor the HCV load, despite immune restoration. Hepatic histopathologic analysis is warranted to assess the impact of immune restoration on liver lesions.

Adult↗

Predictive value of viral load and other markers for progression to clinical AIDS after CD4+ cell count falls below 200/microL. SEROCO & HEMOCO Study Group.

BACKGROUND: To assess the predictive value of biological and clinical events for progression to AIDS (1993 European classification) when the CD4+ cell count falls below 200/microL (CD4 threshold) in different exposure groups. To investigate whether such markers remain predictive independently of the serum HIV-1 RNA level at the CD4 threshold. METHODS: The predictive value of biological and clinical events occurring during the 24 months prior to the occurrence of CD4 threshold (n = 333) was quantified in a Cox model. Another Cox model was carried out in a subset of 77 patients in whom viral load from stored sera was available. Furthermore, changes in viral load during the 24 months preceding the CD4 threshold were assessed in a mixed model according to subsequent development of AIDS. RESULTS: Among the 333 patients, the slope of the CD4+ cell counts, the emergence of p24 antigen, persistent thrush, and age at the CD4 threshold were independent predictors of progression to clinical AIDS (44.7%). Among the subset of 77 patients, the HIV-1 RNA level at the CD4 threshold, persistent thrush and age remained independent predictors of progression to AIDS (45.5%). The increase of the HIV-1 RNA level was moderate, both in non-progressors (24.0% per year) and in those who subsequently developed AIDS (27.1% per year), (P = 0.93). Viral load was consistently higher in the latter group (P = 0.002). CONCLUSION: At a late stage of infection, age and persistent thrush remain predictive of progression to AIDS, independently of viral load.

Acquired Immunodeficiency Syndrome↗

Longitudinal study of plasma HIV-1 RNA concentrations during the asymptomatic stage of HIV infection measured using AMPLICOR HIV monitor and NASBA HIV-1 RNA QT tests. ACCTES Association.

The predictive value of two methods for measuring HIV RNA concentration in plasma was assessed in relation to CD4 lymphocyte counts during the asymptomatic period of infection. The design was a retrospective longitudinal case-control study for a mean period of 60 months involving 20 asymptomatic patients included in the French National prospective survey. The CD4 counts in these patients during the last 36 months of the study were stable (non-progressors) or declined (progressors). Plasma RNA concentrations were determined in each subject annually using the AMPLICOR and NASBA techniques. Only AMPLICOR gave RNA titers above the cut-off value for all the patients. The techniques agreed satisfactorily, although there was a difference, median 0.4 log10, between the AMPLICOR and NASBA values. The non-progressors had low and stable RNA concentrations. The concentration was higher in the progressors, according to the AMPLICOR technique, from their inclusion in the study, and according to the NASBA technique, from 1 year after inclusion. However, only four of ten individual progressors had stable plasma HIV RNA concentrations significantly above those of the non-progressors before the decline in their CD4 counts. These were all and only the patients with a decline in lymphocyte counts more than 100 CD4/mm3/year. In each of the other progressors, the RNA concentration was not significantly different from those of the non-progressors. Thus, when making decisions about therapy, plasma HIV RNA determinations cannot be used in place of CD4 counts and may provide valuable additional information.

CD4 Lymphocyte Count↗

HIV-1 RNA detection in plasma for the diagnosis of infection in neonates. The French Pediatric HIV Infection Study Group.

The objective of this study was to assess the frequency of detection of HIV-1 RNA in plasma of neonates born to HIV-1-seropositive mothers and to determine the diagnostic value of this method in the neonatal period. The study involved 96 infants among those enrolled in the French National Prospective Study. HIV-1 RNA was detected in the first 10 days of life by nucleic acid sequence-based amplification (NASBA) in 12 of 48 plasma samples of infected infants and in 39 of 39 of the second samples taken before the age of 3 months. On the same samples, peripheral blood mononuclear cell (PBMC) DNA polymerase chain reaction (PCR) or viral culture that had been routinely performed were found to be positive in 11 of 48 samples taken in the first 10 days of life and 39 of 39 second samples. For the noninfected infants, HIV-1 RNA was never detected in the 48 samples taken in the first 10 days of life and was detected in one of the 48 samples taken before the age of 3 months. HIV-1 RNA detection in plasma by NASBA has sensitivity and specificity equal to those of DNA PCR and culture on PBMC for the diagnosis of infection in infants with the clade B virus. This standardized method gives rapid results on a small volume of plasma and seems well suited for diagnosis on a large scale.

CD4 Lymphocyte Count↗

Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study.

Based on 392 infected children enrolled in two European prospective studies of infants born to HIV-infected women, with similar standard protocols, HIV disease progression in the first 6 years of life is described, using the 1994 CDC paediatric HIV classification. Most children had developed minor (A) or moderately severe (B) illness in the first 4 years of life, although usually it was transient in nature. Progression to U.S. Centers for Disease Control and Prevention (CDC) group C disease or HIV-related death is an estimated 20% (95% confidence interval 16-24%) during the first year of life, and 4.7% (3.3-6.5%) per year thereafter, giving a cumulative incidence of 36% (30-43%) by 6 years. The mortality rate at 6 years is 26% (20-32%). Two thirds of the children alive at 6 years had only minor symptoms, and one third had a CD4+ cell distribution of > 25% despite previous clinical manifestations and a transient period of moderate immune deficiency. Differences in zidovudine monotherapy between the two cohorts were not associated with the mortality rate. However, the risk of severe bacterial infections was lower in the French cohort, in which the use of antibacterial prophylaxis was more common. The early, severe form of HIV disease affects approximately 20% of infants, and after 6 years 75% of infected children are still alive. This has important implications for health-care planning.

Adult↗

Acceptability and impact of zidovudine for prevention of mother-to-child human immunodeficiency virus-1 transmission in France.

We studied the propagation and the impact of zidovudine prevention on the human immunodeficiency virus-1 transmission rate from infected mothers to their infants in the French nationwide prospective cohort. Infection was diagnosed in the children on the basis of at least two positive human immunodeficiency virus-1 polymerase chain reaction tests, culture, or both. The transmission rate among treated women was compared with that among untreated women during the same period and with that among women enrolled in the cohort since 1986. The impact of zidovudine was analyzed according to the women's clinical and biologic characteristics, the mode of delivery, and use of zidovudine therapy before the pregnancy. Nearly 90% of women were treated as soon as the second half of 1994. In 1994 and 1995, 80% of mother-child pairs received at least one of the three phases of preventive treatment. Among the 663 mothers enrolled during these 2 years, only six refused the treatment. Zidovudine treatment was associated with a reduction in the transmission rate of nearly two-thirds, from 14% +/- 6% to 5% +/- 2% (p < 0.01). The degree of reduction was not influenced by the maternal CD4+ cell count or p24 antigenemia at delivery. Zidovudine treatment of the mother before the pregnancy considerably reduced the impact of preventive therapy; the transmission rate was significantly higher among pretreated mothers (20% versus 5%, p < 0.01) even after adjusting for maternal CD4+ cell count. Zidovudine prevention is now widely used in France and has had a major impact on the epidemiology of mother-child human immunodeficiency virus transmission. This justifies a policy of offering human immunodeficiency virus screening to all women before or shortly after the diagnosis of pregnancy.

Acquired Immunodeficiency Syndrome↗

Early protective effect of CCR-5 delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load. The SEROCO Study Group.

OBJECTIVE: To determine the influence of heterozygosity for the delta 32 mutant CCR-5 allele on HIV-1 disease progression. DESIGN: HIV-1 disease progression and serum viral load were analysed according to the C-C chemokine receptor (CCR)-5 genotype in 412 Caucasian patients (319 men and 93 women) with a known date of seroconversion, who were enrolled in the SEROCO cohort (median follow-up, 74 months). RESULTS: The frequency of heterozygosity for the mutant allele was 17% and did not differ according to sex or risk factor of HIV infection. Heterozygotes were significantly less likely than patients with two functional alleles to have symptomatic primary infection. Their serum viral load was lower during the 6- to 24-month plateau phase after seroconversion. This difference persisted afterwards, although the rate of decline in CD4+ cells was similar. Kaplan-Meier survival curves showed slower progression to clinical AIDS in heterozygotes during the first 7 years following infection (P < 0.02), the two curves tending to join thereafter (overall log-rank test, P = 0.17). However, the interaction term with time did not reach significance in a Cox model. The overall relative risk of progression was 0.67 (95% confidence interval, 0.38-1.18) and was not influenced by adjustment for age at seroconversion or symptomatic primary infection. After adjustment for early viral load the relative risk was 0.83. Pneumocystis carinii pneumonia and toxoplasmosis were less likely to be the first AIDS-defining illness in heterozygotes than in the other patients (0 versus 24.7% of AIDS cases, P = 0.04), despite similar management. CONCLUSION: Deletion of one CCR-5 gene allele appears to protect against HIV-1 disease progression, mainly during the early years of the infection. Heterozygosity for the deletion leads to persistently lower viral load, and also seems to protect against some opportunistic infections.

AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus-1 infection in neonates: correlation of plasma and cellular viremia and clinical outcome. French Pediatric Cohort Study Group.

Among human immunodeficiency virus-1 (HIV-1) vertically infected children, two patterns of disease progression have been observed: about 25% develop a severe immunodeficiency within the first 2 years of life; the rest experience a slower progression, like adults. We have assessed infectious viral burden in infected neonates through the French National Prospective Study. Plasma and cell-associated viremia were assayed by endpoint-dilution cultures in samples from 46 infants followed prospectively from birth. Plasma and cell-associated viral burden were found to be significantly higher in rapid progressing infants than in non-progressing infants in the first months of life: before the age of 2 months, between 2 and 4 months of age and by the age of 6 months. Moreover, among the non-progressing children, the infectious viral burden before the age of 4 months was predictive of the viral burden measured after the age of 12 months. In conclusion, this work demonstrates that infectious viral load is a reliable predictive marker for rapid progression to AIDS in infants and could be useful for initiating antiretroviral therapy.

Age Factors↗

Varicella and zoster in children after kidney transplantation: long-term results of vaccination.

OBJECTIVE: To determine the long-term prevalence of varicella infection and herpes zoster after kidney transplantation and to assess the effectiveness of varicella immunization with the Oka attenuated strain. METHODS: This study involved 704 children and adolescents who received a kidney graft in our institution from 1973 to 1994 and had routinely been given varicella vaccine beginning in 1980 in preparation for transplantation. RESULTS: After vaccination 62% of these patients still had varicella/zoster (VZ) antibodies at 1 year and 42% after 10 years. After transplantation the incidence of varicella was significantly lower, 26/212 (12%), in patients who received immunization than in those who did not and had no history of varicella, 22/49 (45%). The disease was also significantly less severe in the vaccinated patients (three deaths among naive patients vs none among vacciness). In the vaccinees, varicella infection was observed only in those who did not develop or lost VZ antibodies; in addition, 21 patients of this subgroup had an asymptomatic seroconversion. Four of the 415 patients with a history of varicella had another episode of benign varicella after grafting. Herpes zoster was observed in 76 of the 704 patients included in the study. The prevalence differed according to VZ status at the time of grafting: 13% in patients with a history of varicella, 7% in the vacciness, and 38% in the naive patients at grafting who developed varicella. Three rejection episodes occurred in association with a varicella episode and four with a zoster episode, but graft function was only transiently impaired, and as a whole varicella or zoster did not significantly affect graft function or survival. CONCLUSION: Naive VZ patients with a kidney graft are at risk to develop severe varicella and this may be effectively prevented by available immunization.

Adrenal Cortex Hormones↗

Influenza and influenza-like illness in general practice: drawing lessons for surveillance from a pilot study in Paris, France.

BACKGROUND: There are two types of inflenza surveillance techniques: qualitative laboratory-based surveillance and quantitative medical practice-based surveillance. The former is of great importance in isolating new strains of the virus, which helps in the decision-making process concerning the composition of the vaccine, and the latter provides estimates of morbidity, mortality or economic impact as a result of infection from the influenza virus. Rapid methods such as immunoflourescence (IF) or immunocapture assays (ICA) are now available for diagnosis of influenza infections. However, little is known about the use of these methods for influenza surveillance purposes. AIMS: To evaluate the feasibility of a rapid influenza diagnosis in ambulatory conditions, and to investigate the therapeutical outcomes of patients suffering from influenza-like illness (ILI) in relation to the virological diagnoses. METHOD: During the 1994-1995 influenza season, 130 patients presenting with ILI symptoms (< 36 hours) to 33 general practitioners (GPs) were included in a prospective study. Two nasal swabs and one throat swab per patient were collected and sent to the laboratory within 12 hours. Information concerning therapeutical outcomes was recorded during examination. Specimens were analysed using the immunofluorescence (IF) method and antigen immunocapture assay (ICA). RESULTS: Sixteen influenza A (12%) and 19 influenza B (15%) infections were diagnosed. The overall rate of influenza positive specimens was 17% in the pre-epidemic period and 31% during the epidemic (P = 0.1). The rates of usable specimens for IF assay, nasal ICA and throat ICA were 46%, 100% and 99% respectively. The combination of these three collections ensured a highly sensitive influenza virological diagnosis. There were no differences in therapeutical outcomes between the influenza positive and negative cases. The GPs prescribed antibiotics in 60% of the cases for a mean duration of 7 days (+/- 1.2). The mean duration of sick leave was 3.4 days (+/- 1.6). Twelve patients (four influenza positive, eight influenza negative) had been vaccinated at the beginning of the winter. The practitioner's intuition concerning 'which patient should be tested for influenza virus' did not prove useful in improving the aptness of virological diagnoses in the field of influenza surveillance. CONCLUSION: The only way to estimate the true impact of influenza is to carry out a systematic virological sampling based on a sensitive clinical definition and using sensitive laboratory methods.

Adult↗

Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.

BACKGROUND AND METHODS: A placebo-controlled trial has shown that treatment with zidovudine reduces the rate at which human immunodeficiency virus type 1 (HIV-1) is transmitted from mother to infant. We present data from that trial showing the number of infected infants at 18 months of age and the relation between the maternal viral load, the risk of HIV-1 transmission, and the efficacy of zidovudine treatment. Viral cultures were obtained, and HIV-1 RNA was measured by two assays in samples of maternal blood obtained at study entry and at delivery. RESULTS: In 402 mother-infant pairs, the rate of transmission of HIV-1 was 7.6 percent (95 percent confidence interval, 4.3 to 12.3 percent) with zidovudine treatment and 22.6 percent (95 percent confidence interval, 17.0 to 29.0 percent) with placebo (P<0.001). In the placebo group, a large viral burden at entry or delivery or a positive culture was associated with an increased risk of transmission (the transmission rate was greater than 40 percent in the highest quartile of the RNA level). In both groups, transmission occurred at a wide range of maternal plasma HIV-1 RNA levels. Zidovudine reduced plasma RNA levels somewhat (median reduction, 0.24 log). Zidovudine was effective regardless of the HIV-1 RNA level or the CD4+ count at entry. In the zidovudine group, however, after we adjusted for the base-line HIV-1 RNA level and CD4+ count, the reduction in viral RNA from base line to delivery was not significantly associated with the risk of transmission of HIV-1. CONCLUSIONS: A high maternal plasma concentration of virus is a risk factor for the transmission of HIV-1 from an untreated mother to her infant. The reduction in such transmission after zidovudine treatment is only partly explained by the reduction in plasma levels of viral RNA. To prevent HIV-1 transmission, initiating maternal treatment with zidovudine is recommended regardless of the plasma level of HIV-1 RNA or the CD4+ count.

Anti-HIV Agents↗

Delayed virus-specific CD8+ cytotoxic T lymphocyte activity in an HIV-infected individual with high CD4+ cell counts: correlations with various parameters of disease progression.

This 4-year longitudinal study monitored the temporal association between the HIV-specific cytotoxic T lymphocyte (CTL) response and the control viremia in an individual infected with human immunodeficiency virus type (HIV-1). At the beginning of the study, this asymptomatic individual with a high CD4+ cell count showed no HIV-specific cytotoxic activity after polyclonal in vitro restimulation with autologous PHA-blasts, unlike most HIV-seropositive individuals. Anti-HIV CTLs were detected only in the last year of the study, both after in vitro restimulation and directly ex vivo. This was correlated with the inversion of the CD4+/CD8+ ratio, essentially due to increased numbers of CD8+CD28- T lymphocytes. The HIV-specific cytolytic activity was mediated by this CD28+CD28- subpopulation. The amount of HIV-1 provirus in peripheral blood mononuclear cells (PBMCs) did not change during the study, but the HIV RNA in plasma increased and virus was isolated from PBMCs only at the time when HIV-specific CTL activity was detected. This suggests overall that the HIV-1 replication was low in this individual, with a transient increase that could have reached the threshold for CTL reactivation, and was perhaps controlled thereby.

CD28 Antigens↗

Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease. The French Pediatric HIV Infection Study Group.

OBJECTIVE: To identify clinical and laboratory parameters at birth that are associated with the rapidly progressive form of human immunodeficiency virus type 1 (HIV-1) disease in children born to infected mothers. DESIGN: Multicenter, prospective study of infants born to HIV-seropositive mothers. SETTING: A total of 62 obstetric and pediatric centers in France. PARTICIPANTS: Of 1386 children born to HIV-1-seropositive mothers at least 18 months before the cutoff date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before the age. MAIN OUTCOME MEASURE: Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific encephalopathy, and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention classification during the first year of life, according to clinical, immunological, and virological findings at birth. RESULTS: The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1% vs 15.1%; relative risk [RR], 2.5; 95% confidence interval [CI], 1.4 to 6.0; P<.02) or a low proportion (<30%) of CD4+ cells at birth (45.5% vs 15.0%; RR, 3.0; 95% CI, 1.4 to 6.4; P<.005). Similarly, HIV-1 culture and/or polymerase chain reaction positivity during the first week of life was associated with a higher risk of the early, severe form of HIV infection (26.4% vs 9.3%; RR, 2.8; 95% CI, 1.3 to 6.1; P<.006). In case of positive antigenemia at birth, the risk was 50.0% vs 14.4% (RR, 3.5; 95% CI, 1.9 to 6.2; P<.001). These parameters, determined at birth, were strongly interrelated and could reflect active disease onset in utero in some cases of early, severe HIV-1 disease in childhood. CONCLUSIONS: These prognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention.

AIDS Serodiagnosis↗