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Biomedical subjects

C Rouzioux

Publications and source records attributed to C Rouzioux.

At least 91 records · Page 5Linked to original sources

High risk of HIV disease progression after infection through a sexual partner with AIDS.

OBJECTIVE: To investigate whether HIV-1 infection acquired through a severely immunodepressed sexual partner increases the risk of disease progression. DESIGN: A prospective cohort of patients infected through sexual contact at a known date and enrolled a few months (median, 2 months) after their first HIV-positive test. At enrolment, 12 subjects stated having had unprotected intercourse (anal or vaginal penetration) with a partner with AIDS within the 6 months prior to their first HIV-positive test. For the same period, 60 subjects stated having had unprotected intercourse with a partner, known to be HIV-positive, but who had not developed AIDS. METHOD: The endpoint was the first occurrence of an HIV-related illness (group IV or AIDS, 1987 Centers for Disease Control and Prevention revised classification). Event-free survival curves since infection were constructed using the Kaplan-Meier method and compared by the log-rank test. The Cox model was used for multivariate analysis. RESULTS: Disease progression was more rapid among the 12 subjects who stated having sex with a person with AIDS at a time close to infection, than among the other subjects (P = 0.03). Homosexuality and age at infection were also related to HIV disease progression. The adjusted relative risk of developing an HIV-related illness among those 12 subjects was 3.9 (95% confidence interval, 1.5-9.9). CONCLUSION: Our results confirm the influence of virus-related factors on the onset of immunodepression in subjects infected through sexual contact.

Acquired Immunodeficiency Syndrome↗

Separation between HIV-positive women and their children: the French prospective study, 1986 through 1993.

OBJECTIVES: We studied the risk and circumstances of separation (due to either maternal death or drug use) between women infected by human immunodeficiency virus (HIV) type 1 and their children. METHODS: This analysis was based on the French Prospective Study of Infants Born to HIV-seropositive Women (1986 through 1993). Data recorded at each follow-up visit included the mother's effective presence with the child and the child's care after separation. RESULTS: A child's cumulative risk of long-term or permanent separation from his or her mother was 37% at 60 months. Maternal drug use was associated with an added risk during the child's first years (adjusted relative risk [RR]=3.4, 95% confidence interval [CI]=2.3, 5.0). The risk among drug users was even higher when the mother used injection drugs during pregnancy (adjusted RR=2.9, 95% CI=1.9, 4.3). Risk of early separation related to drug use tended to diminish since survey initiation. After separation, 57% of the children were placed through child welfare services and 43% were cared for by relatives. CONCLUSIONS: In the French Prospective Study, 2% to 3% of HIV-infected children were separated each year from their mothers as a result of the mothers death from acquired immunodeficiency syndrome (AIDS). Separations related to drug use have decreased over the years, and the family is becoming the most frequent carer after separation.

Actuarial Analysis↗

Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission by use of a Markov model. The HIV Infection in Newborns French Collaborative Study Group.

It has been shown that mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission can occur both during pregnancy and at delivery, but the respective frequencies in these periods are unknown. Moreover, it is difficult to determine the timing of mother-to-child HIV-1 transmission by direct sampling. The use of an elaborate statistical method is therefore necessary. The authors studied 495 consecutive infants born between May 1988 and August 1991 who were included, at birth, in the French Prospective Study on Pediatric HIV Infection. At least one blood sample was obtained from every infant during the first 14 days of life. All samples obtained within 3 months of birth were tested by at least two of the following methods: viral culture, polymerase chain reaction (PCR), and antigenemia, as well as by Western blot test. Data for the 95 infected infants (those seropositive at 18 months and those who died of HIV disease before this age), and who were exclusively bottle-fed, were analyzed in a Markov model to estimate the timing of viral transmission, the time from birth to the emergence of detectable virus, and the time from birth to seroconversion. The model indicated that one-third of the infants were infected in utero, less than 2 months before delivery (95th percentile). In the remaining 65% of cases (95% confidence interval (CI) 22-92), the date of infection was estimated as the day of birth. The estimated median period between birth and the emergence of viral markers was 10 days (95% CI 6-14) and the 95th percentile was estimated at 56 days. These results support the view that HIV infection can be diagnosed during the first 3 months of life. The authors conclude that mother-to-child HIV-1 transmission appears to occur late in pregnancy or at delivery.

Adult↗

Maternal factors associated with perinatal HIV-1 transmission: the French Cohort Study: 7 years of follow-up observation. The French Pediatric HIV Infection Study Group.

A nationwide, longitudinal study of infants born to human immunodeficiency virus-seropositive mothers has been under way in France since 1986. After 7 years of follow-up observations, we will update our assessment of the transmission rate in France and analyze, on a larger number of mother-infant pairs, the influence of maternal factors. Among the 848 pairs included in this analysis, the transmission rate was 20.2 +/- 2.7%. The transmission rate has remained stable with time and was not influenced by the mode of delivery, the mode of maternal infection, or the mother's ethnic origin. It was twice as high among the breast-fed infants as among the bottle-fed infants (40 vs. 19%, p < 0.04). Two factors were identified in a multivariate analysis (that did not include lymphocyte subset counts and the mode of feeding) as being associated with an increased risk of maternofetal transmission: p24 antigenemia (odds ratio = 3.1, confidence interval, = 1.5-6.2; p < 0.003) and elevated maternal age (p < 0.05). In the subgroup of 277 women whose absolute CD4+ lymphocyte counts at the time of delivery were available, the risk of transmission increased gradually from 15% of counts of > 600 CD4+ cells to 43% at counts of < 200. The risk of transmission was also related to the percentage of CD8+ cells, but each of the two factors seemed to play an independent role: the risk was lowest (12%) when the CD4+ cell count was > 500 and the proportion of CD8+ cells was < or = 40%, and was highest (50%) for values < 200 and > 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

How much would the safety of blood transfusion be improved by including p24 antigen in the battery of tests?

BACKGROUND: Because p24 antigen may be detectable during seroconversion, before antibodies, some of the infected blood undetected by antibody screening could be identified through antigen screening. STUDY DESIGN AND METHODS: The potential benefit of antigen screening was evaluated in a simulation model incorporating present knowledge of the time sequence from antigen exposure to antibody development during seroconversion and the incidence of seroconversion among repeat donors. The model was designed so that the results were consistent with the observed rate of antibody-positive blood donations and the CIs of surveys that did not find any antibody-negative/antigen-positive donated blood. RESULTS: In the United States in 1990, the number of expected, undetected, contaminated blood components was estimated at 68; of these 8 to 17 could have been identified by antigen screening, depending on the hypothesis explored. (In 1992, 20 undetected, contaminated blood components were expected according to this model, of which 2 to 5 could have been identified by antigen screening.) In France, the comparable figures were 1 to 4 of 13 in 1990 and 1 to 2 of 7 in 1992. CONCLUSION: The projected benefit must be weighted against possible negative consequences, including 1) an increase in recently infected persons seeking p24 antigen screening at blood banks (assuming this test is not incorporated into screening in non-blood bank settings) and 2) the need for additional quality assurance procedures to avoid operational flaws associated with the increase in the donor screening test battery. In any case, the best way of increasing the safety of blood is improvement in the selection of donors, which can diminish the residual risk of transmission of any viruses.

Biomarkers↗

Hepatic toxicity associated with 2'-3' dideoxyinosine in children with AIDS.

Among 34 children with AIDS enrolled in a trial with 2'-3' dideoxyinosine (ddI), six (aged 1-6 years) developed liver abnormalities within 2-18 months after institution of ddI. Two children died of fulminant hepatic failure (one had also an adenovirus infection), and four had a striking elevation of alkaline phosphatases (AP: 1120-7000 IU/L). All of them received sulfa drugs and antifungic treatment with ketoconazole or fluconazole. Three had a serology positive for hepatitis C virus. The evolution of liver enzymes following withdrawal and rechallenge with ddI in the children with elevated AP was an indication of drug-induced toxicity in two patients. In both of the others, readministration of ddI did not cause any subsequent problems. Liver histology in the patients with fulminant hepatitis showed an extensive hepatic necrosis. Liver biopsy done in two other patients revealed a mild granulomatous hepatitis in one and nonspecific changes (i.e., steatosis and a mild inflammation) in the other. Hepatic toxicity has been described with ddI and other nucleoside analogs in adult patients. These six children had many potential causes of liver disease. It may be that ddI is not hepatotoxic per se but that it precipitates liver disease in predisposed patients. We recommend that liver functions be carefully monitored when using this drug.

Acquired Immunodeficiency Syndrome↗

Molecular identification of viruses in sudden infant death associated with myocarditis and pericarditis.

A subset of infants dying suddenly and unexpectedly have myocarditis with or without pericarditis found at autopsy. To address whether viruses known to cause infantile myocarditis and pericarditis might be present in such infants, we examined myocardium, liver and skeletal muscle for the presence of genomic sequences from adenovirus, cytomegalovirus, enterovirus and echovirus 22/23 in infants enrolled in a comprehensive evaluation protocol. We studied eight infants who died suddenly and unexpectedly with histologic evidence of myocarditis and/or pericarditis detected at postmortem examination. One infant with myocarditis and pericarditis had adenovirus genome detected in the myocardium. In an additional infant with severe pericarditis alone, enterovirus genome was detected in the liver. Although echovirus 22/23 has been associated with myopericarditis in young infants, no previous studies have used molecular methods to search for the genomic sequences of these viruses in clinical samples. No echovirus 22/23 genome was detected in the patients reported here. The significance of enterovirus and adenovirus genome in the tissues of two patients dying suddenly and unexpectedly remains speculative but raises the possibility that pathogenic viruses may cause little or no clinical symptoms and yet be contributory to sudden death in young infants.

Adenoviridae↗

Prevention of maternal HIV transmission. Practical guidelines.

The recently published Protocol 076 study (ACTG 076/ANRS 024) showed that zidovudine significantly decreased the relative risk of maternal HIV transmission by 71.5% compared with placebo. Oral zidovudine 100 mg five times daily until the onset of labour, followed by intravenous zidovudine 2 mg/kg over 1 hour then 1 mg/kg.h until delivery, or an identical placebo regimen were administered to HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ counts > 200 cells/microliters. 400 babies born to these women received zidovudine syrup 2 mg/kg or placebo administered 6-hourly for 6 weeks. The zidovudine regimens were well tolerated by both mothers and infants. Further studies should aim to determine the mechanism by which zidovudine reduces the risk of maternal HIV transmission, the timing of HIV transmission, the efficacy of zidovudine in women not meeting the entry criteria for Protocol 076 and the long term effects of zidovudine during pregnancy on both mother and infant, and should examine the possibility of developing a simplified zidovudine regimen. Following recent guidelines from the US and French public health services, the full Protocol 076 regimen should be given to all women fulfilling that study's entry criteria. This regimen should also be considered in women with more severe disease or in later stages of gestation. Clinical efficacy of zidovudine should be monitored closely in women and infants, who should also be followed up for long term adverse effects. Unblinded screening for HIV in pregnant women in the USA is facing extreme opposition; nevertheless, guidelines on HIV counselling and HIV testing of pregnant women are currently being developed there in light of the Protocol 076 findings.

Drug Administration Schedule↗

[Multicenter French cohort of adults with HIV infection. Description and course after 4 years of follow-up. SEROCO].

OBJECTIVES: A prospective multicentric epidemiological study (SEROCO) of subjects with a diagnosis of human immunodeficiency virus (HIV) infection was started on January 1, 1988 in order to better understand the natural history of HIV infection and factors related to outcome. Observations after 4 years of follow-up are reported here. METHODS: After authorization by the French national ethics committee and the national commission for personal freedom, 18 French centres included non-haemophiliac volunteers who were asymptomatic, had had non anti-HIV treatment and whose HIV positivity had been known less than 1 year at inclusion. These last three criteria were not required for patients whose precise date of contamination was known within a range of +/- 3 months. RESULTS: On July 15, 1992, there were 1453 infected subjects in the cohort (1063 males, 417 females; age range at inclusion 18-75 years; mean age 31.3 +/- 9.4). Globally, 2.7% of the subjects were symptomatic at inclusion. Mean CD4 lymphocyte count at inclusion was 508/mm3. Clinically, 51.5% of the patients had a history of sexually transmitted disease at inclusion. After 4 years (on July 15, 1992) mean follow-up was 28 +/- 12.9 months for a total of 3428 patient-years. Disease progression to stage IV was observed in 439 patients including 202 who developed the acquired immuno-deficiency syndrome (AIDS). Among these 202 patients, 113 had died at the end-point of this report. The first manifestation of AIDS was Kaposi sarcoma in 44, pulmonary pneumocystosis in 38 and cerebral toxoplasmosis in 27. The probability of developing AIDS was calculated at 13.9% at 5 years, 27.7% at 7 years and 33.7% at 10 years. The probability of a CD4 count below 200/mm3 was 32.7, 55.6 and 67% at 5, 7 and 10 years respectively. For patients with a CD4 count below 200, the probability of developing AIDS was 18% at 1 year, 39% at 2 years and 51% at 3 years. CONCLUSIONS: SEROCO has been a most useful prospective epidemiological tool due to the diversity of the subjects included. The observed natural history of HIV infection will lead to specific research projects aimed at better understanding the disease process.

Acquired Immunodeficiency Syndrome↗

Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery.

BACKGROUND: Among infants with maternally transmitted human immunodeficiency virus (HIV) infection, there are two patterns of disease progression. In about a fifth of these infants there is a rapid progression to profound immunodeficiency, whereas in the majority the disease progresses much more slowly. METHODS: We studied the clinical and biologic characteristics of the mothers of infants infected with HIV type 1 (HIV-1) in the French Prospective Multicenter Cohort. Infection in the children was confirmed by serologic tests at the age of 18 months or by death from the acquired immunodeficiency syndrome at an earlier age. Only the 162 infected infants who could be followed for at least 18 months or until death were included in the analysis. RESULTS: The risk of opportunistic infections or encephalopathy in the first 18 months was 50 percent in the infants of mothers with class IV disease, according to the Centers for Disease Control and Prevention classification, and 14 percent in the infants of mothers with class II or III disease (relative risk, 3.6; 95 percent confidence interval, 1.8 to 7.3; P < 0.002). Forty-four percent of the former infants and 9 percent of the latter died before 18 months (relative risk, 4.7; 95 percent confidence interval, 2.1 to 10.4; P < 0.002). The risk of death correlated inversely with the mother's CD4+ cell count and directly with her HIV-1 p24 antigen level at delivery. There was also a direct correlation between the mother's CD4+ cell count and that of the infant at one, three, and nine months of age (correlation coefficient at nine months [n = 44], 0.48; P < 0.002). HIV-1 p24 antigen was detected more often in the infants whose mothers also had the antigen. CONCLUSIONS: In infants whose HIV infection is maternally acquired, the rate of disease progression varies directly with the severity of the disease in the mother at the time of delivery.

AIDS Dementia Complex↗

Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV-infected patients. SEROCO Study Group.

OBJECTIVE: To analyse the influence of age at seroconversion and sexual exposure group on the progression of HIV disease. DESIGN: This multicentre prospective cohort study involved 443 subjects whose date of HIV infection was known to within +/- 1 year. Individuals whose sexual behaviour was exclusively heterosexual after HIV infection constituted the heterosexual group (n = 131). AIDS-free survival was compared with that of men (n = 312) infected through homosexual sex and who continued homosexual activity after HIV infection. They constituted the homosexual group. METHODS: The end-point was the onset of an AIDS-defining illness listed in the 1987 revised Centers for Disease Control and Prevention (CDC) criteria. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for three age categories (< 20, 20-39, > or = 40 years). A Cox model was used to quantify the effect of age and to assess the influence of exposure group on AIDS onset after adjustment for age. Because of the high incidence of Kaposi's sarcoma (KS) among homosexual men, a disease that can be an early AIDS-defining illness, multivariate analysis was performed with and without consideration of the occurrence of KS. RESULTS: Patients aged > or = 40 years at seroconversion progressed more rapidly to AIDS than younger patients (P < 0.006). When age was fitted as a continuous variable and adjusted for exposure group, the relative risk of developing AIDS by any time after seroconversion was 1.34 for a 10-year increase difference [P = 0.03; 95% confidence interval (CI), 1.03-1.77]. After adjustment for age, the relative risk of developing AIDS (CDC criteria) was 2.42 (P = 0.008; 95% CI, 1.18-4.97) among the homosexual men (AIDS cases, n = 56). All cases of KS (n = 19) involved the homosexual group. Excluding KS as a first manifestation of AIDS, homosexual or bisexual subjects had a risk of AIDS of 1.92 (P = 0.07; 95% CI, 0.92-4.03) compared with heterosexual subjects. CONCLUSIONS: The risk of AIDS increases with age at seroconversion. The more rapid progression towards AIDS in the homosexual group than in the heterosexual group persisted after adjustment for age. Further studies are required to determine the possible role of repeated exposure to HIV or other pathogens acquired sexually.

Acquired Immunodeficiency Syndrome↗

Acyclovir in preventing cytomegalovirus infection in kidney transplant recipients: a case-controlled study.

High dose oral acyclovir has been reported to be effective in preventing both cytomegalovirus (CMV) infection and disease in renal transplant recipients. We conducted a case-controlled study in which 42 cadaveric kidney transplant recipients were prophylactically treated with high dose oral acyclovir for 3 months and compared to historical controls matched for donor/recipient CMV serological status, age, sex, and immunosuppressive therapy. Before transplantation, study group patients received acyclovir intravenously (500 mg/m2 over 1 hour) which was subsequently given orally (basal dose--800 mg four times daily) from day 2 post-transplantation according to renal function. All patients received 14-day induction immunosuppressive therapy with either a polyclonal or a monoclonal antibody together with low dose steroids and azathioprine, cyclosporin being introduced at day 10 post-transplantation. Blood viral cultures as well as CMV antibody titers were performed in study group and control patients in the same laboratory, before transplantation, weekly until 3 months and then monthly until 6 months. CMV infection was defined as a positive blood or bronchoalveolar lavage viral culture or presence of CMV IgM or CMV IgG in a previously seronegative patient. Diagnosis of CMV disease also required the presence of at least one concomitant febrile illness, with or without other clinical symptoms, not attributable to another pathogen. All patients were followed for 3 months. Incidence of both CMV infection and disease was compared in the two groups using the log-rank test. With regard to CMV infection, we found significantly less CMV infection in CMV seropositive patients (regardless of donor CMV serological status) in the study group compared to historical controls (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Randomized study of two doses of didanosine in children infected with human immunodeficiency virus.

2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability.

Adolescent↗

Timing of mother-to-child HIV-1 transmission depends on maternal status. The HIV Infection in Newborns French Collaborative Study Group.

OBJECTIVES: To estimate when mother-to-child transmission occurs and investigate the possible role of maternal factors. DESIGN: We studied virological data obtained in the first 3 months of life of 95 infected newborns born to HIV-1-seropositive mothers included in the French Prospective Cohort Study who did not breast-feed. METHODS: Comparative Western blot analysis of sequential blood specimens from neonates and mothers with incomplete antibody patterns enabled us to detect antibody production in some infants. The results of viral investigation of neonate specimens enabled us to describe the acute phase of infection in newborns. Because the process between infection and antibody production is irreversible, we chose a Markov modelling technique, which is well suited for staged clinical processes. RESULTS: About two-thirds (65%) of the infants were considered to have been contaminated during delivery. In the remaining infants, the contamination was estimated to have occurred in utero and 95% of them had been infected less than 59 days before delivery. The association between the mother's immunological and virological status and the time of transmission was examined. The greater the degree of maternal immunodeficiency at delivery (in terms of p24 antigen and Western blot pattern) the higher the risk of in utero transmission, showing that vertical transmission is dependent on the mother's immunological status. CONCLUSIONS: These estimates should be considered when designing strategies to prevent mother-to-child transmission.

Cohort Studies↗

[Quantitative viremia and p24 antigenemia in short-term follow-up of the treatment with zidovudine in twenty HIV infected patients].

The authors emphasize the interest of detecting HIV p24 antigen after immune complexes dissociation as well as changes in cellular viremia titers in the therapeutic follow-up of HIV infected patients. A significant decline of cell virus titers was found in 4-8 weeks among 13 of 20 zidovudine treated patients. A significant decrease of immune complexes dissociated p24 antigenemia was noted in 11 out of 17 patients.

Acquired Immunodeficiency Syndrome↗