Early diagnosis of paediatric HIV-1 infection among African breast-fed children using a quantitative plasma HIV RNA assay

118

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.

Section: Hiv-1 Naatsmentioning

confidence: 97%

Section: Hiv-1 Naatsmentioning

confidence: 99%

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

Read¹

2007

118

“…34 It gave extremely concordant results in this pediatric population with the above-mentioned HIV-1 DNA PCR designed to allow a reliable amplification of both B and non-B subtypes. 35 This property is particularly suitable in Cô te d'Ivoire, where the CRF02 recombinant form AG is predominant. 36 The use of the bDNA assay in a pediatric context was possible using 0.2-mL specimens and correcting the threshold of the assay to 250 (instead of 50) copies/mL.…”

Section: Laboratory Assaysmentioning

confidence: 99%

Pediatric Viral Human Immunodeficiency Virus Type 1 RNA Levels, Timing of Infection, and Disease Progression in African HIV-1-Infected Children

Raffi

Sakarovitch²,

Msellati³

et al. 2003

Self Cite

ABSTRACT. Objective. To describe plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in African HIV-1-infected children in relation to the timing of infection and disease progression.Methods. A retrospective cohort study was conducted of 80 children who were born to HIV-1-positive mothers and clinically followed from birth to 18 months of age in the ANRS 049 Ditrame project, Abidjan, Cô te d'Ivoire (West Africa). The diagnosis and timing of pediatric HIV-1 infection were determined prospectively according to HIV-1 DNA polymerase chain reaction results. A total of 364 HIV-1 RNA viral load (VL) measurements were assessed retrospectively. Kaplan-Meier analyses and proportional hazards models were used to evaluate the prognostic value of pediatric VL and covariates for HIV disease progression or death.Results. Mean initial positive VL was significantly lower among children who were infected in utero (4.94 log 10 /mL, n ‫؍‬ 12) than in children who were infected later (5.6 -6.1 log 10 /mL, n ‫؍‬ 68). In the first 6 months after diagnosis, HIV-1 RNA levels peaked (>6 log 10 /mL), regardless of timing of infection. Then, a slow decline (overall slope, ؊0.076 log 10 copies/mL/mo) was observed until 18 months of age. A 1 log 10 higher value of the pediatric peak VL (risk ratio [

“…The sensitivity of both DNA and RNA testing is high, 39,40 so either can be used for the diagnosis of HIV-1 infection in infancy. 41 False-positive results with low-level viral copy numbers have been described by using HIV-1 RNA assays, 38,42,43 reinforcing the importance of repeating any positive assay result to confirm the diagnosis of HIV-1 infection in infancy. 16 False-negative results are also possible, and even infants with multiple negative HIV-1 NAAT results should be retested (perhaps by using a different test) if clinical findings suggest the presence of HIV-1 infection.…”

Section: Testing To Determine the Infant's Hiv-1 Infection Statusmentioning

confidence: 99%

Evaluation and Management of the Infant Exposed to HIV-1 in the United States

Havens¹,

Mofenson²

2009

The pediatrician plays a key role in the prevention of mother-to-child transmission of HIV-1 infection. For infants born to women with HIV-1 infection identified during pregnancy, the pediatrician ensures that antiretroviral prophylaxis is provided to the infant to decrease the risk of acquiring HIV-1 infection and promotes avoidance of postnatal HIV-1 transmission by advising HIV-1–infected women not to breastfeed. The pediatrician should perform HIV-1 antibody testing for infants born to women whose HIV-1 infection status was not determined during pregnancy or labor. For HIV-1–exposed infants, the pediatrician monitors the infant for early determination of HIV-1 infection status and for possible short- and long-term toxicity from antiretroviral exposures. Provision of chemoprophylaxis for Pneumocystis jiroveci pneumonia and support of families living with HIV-1 by providing counseling to parents or caregivers are also important components of care.