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

Dunn, David; Simonds, R. J.; Bulterys, Marc; Kalish, Leslie A.; Moye, John; Maria, Arti; Kind, Christian; Rudin, Christoph; Denamur, Erick; Krivine, Anne; Loveday, Clive; Newell, Marie‐Louise

doi:10.1097/00002030-200007070-00016

Cited by 36 publications

(29 citation statements)

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“…We tested 109 specimens from infants of 0 to 7 days of age and 151 specimens from infants of 8 to 30 days of age and had only four false positives. Sensitivity increased with age (Table 1), similar to the increased sensitivity observed in both HIV nucleic acid assays and HIV cultures (3,7,8). Given limited resources, the most useful time for using virologic assays to diagnose pediatric HIV infection is between 6 and 14 weeks of age, which corresponds to regularly scheduled immunization visits and allows early diagnosis for entry into treatment.…”

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confidence: 58%

Ultrasensitive p24 Antigen Assay for Diagnosis of Perinatal Human Immunodeficiency Virus Type 1 Infection

et al. 2007

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Ultrasensitive p24 Antigen Assay for Diagnosis of Perinatal Human Immunodeficiency Virus Type 1 Infection

et al. 2007

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“…110 In some studies, detection of virus with DNA PCR assays has been reported not to vary according to receipt of maternal or infant antiretroviral prophylaxis. 111 However, a study by Prasitwattanaseree et al 112 suggested that the age at which HIV-1 infection was detectable (by using a DNA PCR assay) among 98 HIV-1-infected infants depended on the duration of exposure to zidovudine by the mother and the infant. Detectable infection at birth was less frequent among children with a longer maternal duration of zidovudine receipt.…”

Section: Antiretroviral Exposure History Of the Mother And Childmentioning

confidence: 99%

Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States

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2007

Pediatrics

115

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The objectives of this technical report are to describe methods of diagnosis of HIV-1 infection in children younger than 18 months in the United States and to review important issues that must be considered by clinicians who care for infants and young children born to HIV-1–infected women. Appropriate HIV-1 diagnostic testing for infants and children younger than 18 months differs from that for older children, adolescents, and adults because of passively transferred maternal HIV-1 antibodies, which may be detectable in the child's bloodstream until 18 months of age. Therefore, routine serologic testing of these infants and young children is generally only informative before the age of 18 months if the test result is negative. Virologic assays, including HIV-1 DNA or RNA assays, represent the gold standard for diagnostic testing of infants and children younger than 18 months. With such testing, the diagnosis of HIV-1 infection (as well as the presumptive exclusion of HIV-1 infection) can be established within the first several weeks of life among nonbreastfed infants. Important factors that must be considered when selecting HIV-1 diagnostic assays for pediatric patients and when choosing the timing of such assays include the age of the child, potential timing of infection of the child, whether the infection status of the child's mother is known or unknown, the antiretroviral exposure history of the mother and of the child, and characteristics of the virus. If the mother's HIV-1 serostatus is unknown, rapid HIV-1 antibody testing of the newborn infant to identify HIV-1 exposure is essential so that antiretroviral prophylaxis can be initiated within the first 12 hours of life if test results are positive. For HIV-1–exposed infants (identified by positive maternal test results or positive antibody results for the infant shortly after birth), it has been recommended that diagnostic testing with HIV-1 DNA or RNA assays be performed within the first 14 days of life, at 1 to 2 months of age, and at 3 to 6 months of age. If any of these test results are positive, repeat testing is recommended to confirm the diagnosis of HIV-1 infection. A diagnosis of HIV-1 infection can be made on the basis of 2 positive HIV-1 DNA or RNA assay results. In nonbreastfeeding children younger than 18 months with no positive HIV-1 virologic test results, presumptive exclusion of HIV-1 infection can be based on 2 negative virologic test results (1 obtained at ≥2 weeks and 1 obtained at ≥4 weeks of age); 1 negative virologic test result obtained at ≥8 weeks of age; or 1 negative HIV-1 antibody test result obtained at ≥6 months of age. Alternatively, presumptive exclusion of HIV-1 infection can be based on 1 positive HIV-1 virologic test with at least 2 subsequent negative virologic test results (at least 1 of which is performed at ≥8 weeks of age) or negative HIV-1 antibody test results (at least 1 of which is performed at ≥6 months of age). Definitive exclusion of HIV-1 infection is based on 2 negative virologic test results, 1 obtained at ≥1 month of age and 1 obtained at ≥4 months of age, or 2 negative HIV-1 antibody test results from separate specimens obtained at ≥6 months of age. For both presumptive and definitive exclusion of infection, the child should have no other laboratory (eg, no positive virologic test results) or clinical (eg, no AIDS-defining conditions) evidence of HIV-1 infection. Many clinicians confirm the absence of HIV-1 infection with a negative HIV-1 antibody assay result at 12 to 18 months of age. For breastfeeding infants, a similar testing algorithm can be followed, with timing of testing starting from the date of complete cessation of breastfeeding instead of the date of birth.

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“…Although it is generally agreed that molecular methods, such as the detection of viral RNA or proviral DNA, are the most sensitive methods for HIV type 1 (HIV-1) diagnosis in infants (7,14), these methods involve complex and expensive technologies and thus have remained largely unavailable in resource-poor settings in the developing world, where the majority of pediatric HIV infections continue to occur (3,5). While affordable intervention strategies are now available to prevent vertical transmission (4,5,8,13,16), early diagnosis of HIV infection in exposed infants remains a major obstacle and challenge both to assessing the efficacy of these strategies and to providing early appropriate care to infected infants.…”

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confidence: 99%

“…Further analysis with alternative cutoff values indicated that the 3A11-LS had a sensitivity of 12 to 44% and a specificity of 90 to 100% for infants between 4-6 months of age. This data suggest that a diagnosis of HIV infection in some of the infants could be made after 4 months of age by the 3A11-LS assay, although a negative 3A11-LS test result may not rule out infection and may require a further followup.Considerable efforts have been devoted to developing and assessing new approaches for the early diagnosis of human immunodeficiency virus (HIV) infection in infants (1,6,7,12,14,17). Although it is generally agreed that molecular methods, such as the detection of viral RNA or proviral DNA, are the most sensitive methods for HIV type 1 (HIV-1) diagnosis in infants (7,14), these methods involve complex and expensive technologies and thus have remained largely unavailable in resource-poor settings in the developing world, where the majority of pediatric HIV infections continue to occur (3, 5).…”

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Efficacy of a Less-Sensitive Enzyme Immunoassay (3A11-LS) for Early Diagnosis of Human Immunodeficiency Virus Type 1 Infection in Infants

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Bulterys

Abrams

et al. 2001

Clin Diagn Lab Immunol

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We evaluated a less-sensitive enzyme immunoassay (3A11-LS) for its possible use for early diagnosis of human immunodeficiency virus type 1 (HIV-1) infection in infants. The results were compared with those from the immunoglobulin G-capture enzyme immunoassay. A total of 239 sera from 77 infants were tested. All 25 sera from the 10 infants born to seronegative mothers were found to be negative by both assays. Forty-one seroreverting infants showed a complete decay of maternal antibodies by 4 months by the 3A11-LS assay. However, the assay detected HIV antibodies in only 9 (36%) of 25 sera collected from infected infants between 4 and 6 months and in 27 (63%) of 43 sera collected after 6 months of age. Further analysis with alternative cutoff values indicated that the 3A11-LS had a sensitivity of 12 to 44% and a specificity of 90 to 100% for infants between 4-6 months of age. This data suggest that a diagnosis of HIV infection in some of the infants could be made after 4 months of age by the 3A11-LS assay, although a negative 3A11-LS test result may not rule out infection and may require a further followup.Considerable efforts have been devoted to developing and assessing new approaches for the early diagnosis of human immunodeficiency virus (HIV) infection in infants (1,6,7,12,14,17). Although it is generally agreed that molecular methods, such as the detection of viral RNA or proviral DNA, are the most sensitive methods for HIV type 1 (HIV-1) diagnosis in infants (7,14), these methods involve complex and expensive technologies and thus have remained largely unavailable in resource-poor settings in the developing world, where the majority of pediatric HIV infections continue to occur (3, 5). While affordable intervention strategies are now available to prevent vertical transmission (4,5,8,13,16), early diagnosis of HIV infection in exposed infants remains a major obstacle and challenge both to assessing the efficacy of these strategies and to providing early appropriate care to infected infants. Identification of a simple and inexpensive laboratory tool for early diagnosis in infants would have great implications, especially in developing countries (11).In 1998 Janssen et al. (9) described a modified, less-sensitive enzyme immunoassay (3A11-LS) which, when used in conjunction with the sensitive enzyme immunoassay (EIA), identifies recent HIV-1 infection and is useful for estimating incidence in a population. This method detects increasing antibody levels during the early phase of infection and thus is quite sensitive to various levels of HIV-1 antibodies. We postulated that this method may also be useful in diagnosing HIV infection in perinatally exposed infants who are making their own antibodies in the background of decaying maternal antibodies. Our previous work (15), using an immunoglobulin G-capture EIA (IgG-CEIA), had shown that the decay of maternal antibodies was observed over a period of 6 months and that most infected infants (Ͼ90%) developed their own HIV-specific antibodies which were detectable after...

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

Cited by 36 publications

References 26 publications

Ultrasensitive p24 Antigen Assay for Diagnosis of Perinatal Human Immunodeficiency Virus Type 1 Infection

Ultrasensitive p24 Antigen Assay for Diagnosis of Perinatal Human Immunodeficiency Virus Type 1 Infection

Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States

Efficacy of a Less-Sensitive Enzyme Immunoassay (3A11-LS) for Early Diagnosis of Human Immunodeficiency Virus Type 1 Infection in Infants

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