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A Krivine

Publications and source records attributed to A Krivine.

15 recordsLinked to original sources
PubMed2000

Interventions to prevent vertical transmission of HIV-1: effect on viral detection rate in early infant samples.

OBJECTIVE: To determine whether mode of delivery or the use of maternal or neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be detected in infected infants, particularly the probability of detection at birth. METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1 infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14 days of age were analysed. Weibull mixture models were used to estimate the cumulative proportion of infants with detectable levels of HIV-1 according to use of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were first tested, at a median age of 2 days. At birth, it was estimated that 36% [95% confidence interval (CI), 31-41%] of infants have levels of virus that can be detected by DNA PCR or cell culture. This percentage was not associated with either mode of delivery (35% for vaginal delivery versus 40% for cesarean section delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis. Among infants with undetectable levels of HIV-1 at birth, the median time to viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were exposed to antiretroviral therapy postnatally compared with infants who were not exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of an early virological test for HIV-1 is thought to be related directly to the timing of transmission and cesarean section delivery primarily reduces the risk of intrapartum transmission. The absence of an association between mode of delivery and viral detectability at birth was therefore unexpected. There was no evidence that foetal or neonatal exposure to prophylactic zidovudine delays substantially the diagnosis of infection, although this cannot be inferred for combination antiretroviral therapy.

Age Factors↗
PubMed1999

Measuring HIV-1 RNA and interferon-alpha in the cerebrospinal fluid of AIDS patients: insights into the pathogenesis of AIDS Dementia Complex.

The aim of this work was to study the role of HIV replication and the role of endogenous secretion of interferon-alpha in the pathogenesis of AIDS Dementia Complex (ADC). To accurately establish the diagnosis of ADC, 39 consecutive HIV-positive patients who presented with immune and intellectual deficiency underwent an extensive neurological evaluation. This included magnetic resonance imaging, neuropsychological testing and a lumbar puncture. The levels of HIV-1 RNA were measured in the cerebrospinal fluid (CSF) and blood by HIV Monitor (Roche Diagnostics) and those of interferon-alpha by an in-house biological assay. The diagnosis of ADC was established in 22 cases, which included nine out of the ten patients who had a high CSF viral load (above 4 log HIV-1 RNA copy per ml). Patients receiving highly active antiretroviral therapy had low viral loads in blood and CSF. In all 22 ADC patients, viral load in the CSF correlated with the staging of ADC (r=0.46, P=0.03), the CSF level of interferon-alpha (r=0.42, P=0.05) and with the bicaudate ratio (r=0.43, P=0.06), a measure of cerebral atrophy in the region of the caudate nucleus. No correlation was observed between CSF and plasma HIV-1 RNA. These results show that HIV may play a role in the neurological impairment of ADC patients possibly in part through the deleterious effect of interferon-alpha on the central nervous system and that highly active combination therapy should reduce or prevent these complications.

AIDS Dementia Complex↗
PubMed1998

Adjuvant is required when using Env lipopeptide construct to induce HIV type 1-specific neutralizing antibody responses in mice in vivo.

Extensive immunological studies on HIV-1 infection, the causative agent of AIDS in humans, have led to the conclusion that efficient protection against this infection should require early elicitation of neutralizing antibodies as well as cellular immune and particularly cytotoxic T lymphocyte responses. The use of synthetic peptides modified at one end by introduction of a lipidic tail is now well known to be an effective means of eliciting virus-specific cytotoxic T lymphocyte responses in vivo, both in mouse and humans. To ascertain that such a strategy can be used for vaccinal purposes, particularly against HIV-1 infection, it remains to be determined whether these molecules can also act as effective inducers of antibody responses, most of all of the neutralizing type. The present study set out to address this question by using a synthetic HIV-1 ENV lipopeptide construct, previously identified as a potent immunogen for in vivo induction of ENV-specific CTL responses in BALB/c mice. We first showed that V3 peptide-specific antibodies were effectively induced by the lipopeptide construct. However, we provided evidence that the biological activity of these antibodies, i.e., their ability to neutralize HIV-1 infectivity in vitro, was strongly influenced by the immunizing conditions and protocol, in that only those antibodies generated by the use of adjuvanted lipopeptide formulations were effective. Albeit at a slightly lower efficacy than by the intraperitoneal route, neutralizing antibodies could also be induced using the subcutaneous route. With the prospect of a human peptide vaccine in mind, we then studied the properties of different known or possibly clinically relevant adjuvants. We found that alum, the only relevant adjuvant for human use, not only provides inefficient help to the lipopeptide construct in generating neutralizing antibodies, but tends to have deleterious effects on the ability of the construct to induce CTL responses. The only protocol that gave satisfactory results in terms of the magnitude of the neutralizing antibody responses was a mineral oil-based lipopeptide formulation. When induced under those conditions, strong neutralizing activities were still present up to 8 months after the last injection.

Adjuvants, Immunologic↗
PubMed1996

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↗
PubMed1996

Testing for in utero human immunodeficiency virus infection with fetal blood sampling.

OBJECTIVE: Our purpose was to evaluate the potential of midtrimester fetal blood sampling to detect in utero human immunodeficiency virus type 1 infection. STUDY DESIGN: Ultrasonographically guided fetal blood sampling was performed before pregnancy termination in 28 women infected with human immunodeficiency virus type 1. Mean gestational age was 22 weeks (range 15 to 29 weeks). Samples were tested for human immunodeficiency virus with undissociated p24 antigen and deoxyribonucleic acid polymerase chain reaction or viral isolation by cell culture. After terminations fetal thymuses were also tested for human immunodeficiency virus infection by polymerase chain reaction. Polymerase chain reaction was also performed on maternal cells to confirm that the primer pairs used were able to detect human immunodeficiency virus type 1 strains present. RESULTS: All fetal blood samples had negative results by p24 antigen and polymerase chain reaction or virus culture and all fetal thymuses were negative by polymerase chain reaction. CONCLUSION: Early in utero human immunodeficiency virus infection appears infrequent, supporting the hypothesis that mother-to-child transmission predominantly occurs late in pregnancy. Therefore midtrimester prenatal diagnosis is not currently of use to women in making reproductive decisions.

Antigens, Viral↗
PubMed1995

The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission.

OBJECTIVE: To derive reliable estimates of the sensitivity of HIV-1 DNA polymerase chain reaction (PCR) in the neonatal period and to quantify the relative contributions of intra-uterine and intra-partum transmission. METHODS: After reviewing studies on the early diagnosis of HIV-1 infection, investigators were asked to provide published and unpublished PCR test results on prospectively followed, non-breastfed, vertically infected children. Age-specific estimates of the sensitivity of PCR were derived using distribution-free methods for interval-censored data. RESULTS: Data on 271 infected children were combined for analysis. PCR detected HIV-1 DNA in an estimated 38% [90% confidence interval (CI), 29-46] of HIV-infected children tested on the day of, or day after, birth. Sensitivity was observed to rise rapidly in the second week of life, reaching 93% (90% CI, 76-97) by 14 days of age. CONCLUSION: The sensitivity of PCR in the neonatal period is higher than previously reported. This affects the clinical interpretation of an early negative test result and encourages the use of PCR as an endpoint for trials to evaluate interventions to reduce vertical transmission in non-breastfed populations. Approximately one-third of vertically acquired HIV-1 infection could be attributable to intra-uterine transmission.

DNA, Viral↗
PubMed1993

Antibody avidity measurement and immune complex dissociation for serological diagnosis of vertically acquired HIV-1 infection.

Differences in avidity between HIV-1 antibodies transmitted passively and antibodies synthesized by children born to HIV-1-positive mothers can be measured using a commercially available competitive enzyme immunoassay kit. The avidity determination method is based on the competition between an anti-HIV-1-peroxidase-labeled antibody at a stable and known concentration and the anti-HIV-1 antibodies (IgA, IgG, IgM) present in the child's serum at various and increasing dilutions. The shift in the competition/dilution curves between serum samples taken at the third and the sixth month of the child's life showed either the loss or the synthesis of anti-HIV-1 antibodies. The antibody avidity determination combined with a test detecting free or complexed p24 antigen is a workable and inexpensive serological method for the follow-up of children born to seropositive mothers. Combining these two complementary methods, HIV-1 infection has been established at 6 months of age in 13 of 13 infants, and positive results were confirmed by coculture and by PCR. An HIV-1 infection was excluded at 6 months of age in 17 of 17 infants, results otherwise confirmed by virological and clinical follow-up. These new and convenient approaches to the diagnosis of vertically acquired HIV-1 could be used worldwide, including in developing countries.

AIDS Serodiagnosis↗
PubMed1992

HIV replication during the first weeks of life.

Diagnosis of HIV infection among children born to HIV-positive mothers can be made in the first 12 months, but few studies have examined HIV status during the first weeks of life. In a prospective longitudinal study of 50 infants born to HIV-1 seropositive women, blood samples were obtained at birth and at 4-9 weeks and 5-9 months of age, and were tested for HIV-1 by the polymerase chain reaction (PCR), viral culture, and p24 antigen measurements. 16 were diagnosed as HIV-infected by the age of 4-9 weeks according to both PCR and culture; by contrast, infection could be detected in only 5 children at birth. No changes in HIV status were observed between 4-9 weeks and 5-9 months in the 44 children who could be retested. Perinatal HIV-1 infection can therefore be diagnosed in the first 2 months of life, either by PCR or viral culture. Our inability to detect HIV-1 infection at birth in almost 70% of babies subsequently found infected suggests an active replication of HIV during the first weeks of life. Our results might favour the hypothesis that transmission of HIV-1 takes place either at the end of pregnancy or at delivery.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Frequent identification of HIV-1 DNA in bronchoalveolar lavage cells obtained from individuals with the acquired immunodeficiency syndrome.

Tissue macrophages are recognized as a cellular target for infection with the human immunodeficiency virus type 1 (HIV-1). To characterize the nature of this cell-retrovirus interaction within the lower respiratory tract we analyzed fluid and cells obtained by bronchoalveolar lavage (BAL) of eight individuals with acquired immunodeficiency syndrome (AIDS) who were undergoing diagnostic fiberoptic bronchoscopy. Of these eight individuals, seven had active infection with Pneumocystis carinii; one had suspected cytomegalovirus pneumonitis. At the time of study two were receiving the antiretroviral drug zidovudine (azidothymidine [AZT]). HIV-1 could not be isolated from any of the eight samples of BAL fluid concentrated by ultracentrifugation through 20% sucrose. HIV-1 antigen (p24) was detected in one of eight samples of concentrated BAL fluid but could not be found in eight samples of media conditioned by overnight incubation with adherent BAL cells. Despite the infrequent detection of HIV-1 antigen it was possible to identify HIV-1 genomic sequences by the use of a DNA amplification technique, the polymerase chain reaction, in all eight BAL cell preparations. In BAL cells adherent for up to 5 days in culture this method detected retroviral DNA that hybridized to a complementary pair of primers located in the env and gag gene regions of HIV-1. These studies demonstrate the uniform presence of HIV-1 harboring cells within the airways of the lung in individuals with AIDS and active respiratory infection and may have implications for local organ defense.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

A comparative study of virus isolation, polymerase chain reaction, and antigen detection in children of mothers infected with human immunodeficiency virus.

We report on an investigation designed to compare the polymerase chain reaction (PCR) with culture and p24 measurement for the diagnosis of human immunodeficiency virus (HIV) infection in infants and children. Forty-five children born of mothers with antibodies to HIV type 1 were studied; P24 antigen was measured in plasma, and HIV-1 proviral DNA was sought in peripheral blood mononuclear cells after amplification by PCR. In 26 cases, blood specimens were cultured for HIV; in all but two instances cultures were established at the same time that the PCR test was performed. Primer pairs in three regions of the proviral genome were used for the PCR test. There was good agreement between the results obtained from PCR tests and from cultures; of 24 children in whom both tests were done at the same time, 10 had positive results on both the culture and the PCR test, 1 had positive results on the PCR test but negative culture results, and 13 had negative results on both tests (concordance 96%). Measurement of p24 antigen in plasma was, in contrast, an insensitive marker of infection: 6 of 12 infants with positive cultures had positive p24 test results, and 8 of 18 infants had positive PCR test results. Sixteen children with subsequent seronegativity for HIV-1 had negative PCR results. This study provides further evidence that the PCR test is a valid alternative to viral culture for the diagnosis of pediatric HIV infection.

Blotting, Western↗