HIV Tests in Children

“maternal HIV antibody crosses the placenta and will be detectable in all HIV-exposed infants up to 18 months of age. Therefore, standard antibody tests should not be used for HIV diagnosis in newborns…NAT assays [i.e. ‘viral load’] can yield qualitative (i.e., positive or negative) or quantitative (copy number per mL of plasma) results for HIV infection. Methods used for qualitative detection of HIV DNA are laboratory-specific, because no commercially available assays have been approved for clinical use. Methods used to quantitate plasma HIV RNA levels, commonly referred to as viral load tests, utilize a variety of technologies such as conventional and real-time reverse transcriptase (RT)-PCR, as well as amplification methods known as branched chain DNA amplification (bDNA), and nucleic acid sequence-based amplification (NASBA). The intended use of viral load tests is to assess prognosis of disease progression and monitor the effectiveness of ART, rather than diagnosis of HIV infection in HIV-exposed infants…[but, despite documenting that neither antibody tests nor NAT tests should be used with infants]…The NYSDOH strongly recommends that all New York State birth facilities use the pediatric HIV testing services at the Wadsworth Center. The laboratory performs rapid turnaround NAT in addition to assays capable of detecting HIV-2 infection”

“When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive.”

“PCR results were positive for HIV virus in 3 neonates. These infants on follow up were asymptomatic and 4 have been tested at 18 months using HIV ELISA with two different antigen tests and one rapid test to confirm the diagnosis. Surprisingly, all 3 PCR positive neonates were nonreactive to ELISA.”

“The [new] Genscreen Plus HIV Antigen–Antibody is an EIA [Enzyme Immuno-Assay or ELISA] for the detection of HIV infection based on the detection (sandwich technique) of antibodies to HIV-1 and HIV-2, as well as the HIV-1 p24 antigen in human serum or plasma…Using this assay in 18 infants with three consecutive negative HIV-DNA PCR we found that eight were antibody negative (age range 18–24 months), and 10 were positive (age range 19–20 months). Of the 10 infants positive by the fourth generation assay, nine were negative by our previous third-generation HIV assay (performed simultaneously). Repeat fourth-generation EIA testing was negative for nine infants within a few months, confirming waning levels of maternal antibody and not emerging infection. In one infant it was not possible to obtain a repeat sample but it shows no clinical evidence of HIV infection [although a positive HIV test with no symptoms is usually accepted as a genuine infection].”

“According to a number of physicians at Princess Marina Hospital [in Botswana], the main public hospital in the capital of Gabarone, even with mass education most women refuse to be tested…50% of adult Tanzanian women know where they could be HIV tested, yet only 6% have been tested. In Zimbabwe, only 11% of adult women have been tested for HIV…Mandatory HIV testing, and when necessary, mandatory treatment of all pregnant women in Botswana is both a necessary and a vital part of a broader comprehensive strategy for preventing the spread of AIDS in sub-Saharan Africa.”

“the not infrequent occurrence of borderline quantitative HIV RNA results can confuse the diagnostic status of the child.”

“At the present time, if a newborn tests positive at birth, the baby may only be showing passive antibodies, passed along by the mother. As notted earlier, only a small percentage of infants born to HIV positive women will turn out to be infected. Infants who test positive will have their blood retested using a more sophisticated technique called PCR. The State recommends that newborns with a positive HIV test should have the first of two or three PCR tests beginning at one month of age. PCR detects small amounts of genetic material in the blood and produces a definitive HIV diagnosis by the time the infant is two months old…One potential drawback to voluntary testing [why would involuntary testing be any different?] is the unknown toxicity affect AZT use can have on infants who are born without HIV [and what about the toxicity on children who will later be found to be HIV-positive?] and the pregnant women who take it. There are no long-term studies on the efficacy of AZT use on healthy children [how could AZT be effective in HIV-negative children?]. Most clinical studies have excluded women. Moreover, a report prepared by the Institute of Medicine indicated that PCP prophylaxis or antiviral therapy for those who were HIV positive but asymptomatic had serious ramifications, especially regarding toxicity…Convincing pregnant women, especially African Americans, to use AZT or other anti-viral drugs may be difficult. One study showed that African American women hold disturbing views towards AZT use. For instance, some respondents said that AZT could harm them [shocking!], others said the drug was indiscriminately prescribed, while others were unwilling to use it because AZT had not been tested on women of color. A number of respondents indicated that AZT use was a way for pharmaceutical companies to make money”

“Physicians should determine whether the infant is at low, moderate, or high risk for acquiring HIV. After risk-stratification the physician may proceed with 2 PCR tests, 3 PCR tests, or PCR testing and serologic follow-up. Infants of mothers who are on highly active antiretroviral therapy (HAART) at delivery, whose mothers have a low or undetectable viral load at delivery, and who do not breast-feed, should be considered low-risk. These low-risk infants should have 2 PCR tests, 1- and 4-months post partum. Infants whose mothers have an unknown or high viral load at delivery and who do not breast-feed should be considered moderate-risk. These infants should have 3 negative PCR tests, 1 during the first month of life, 1 after the first month of life, and 1 after 4 months of life. Infants who breastfeed should be considered high-risk and require at least 3 negative PCR tests, PCR testing every 3 months until breast-feeding stops, and serologic follow-up. Any positive PCR test requires virologic confirmation and serologic followup.”

“The positive predictive value of a single [rapid HIV] test (i.e., the probability that a positive test represents true infection) will be low among populations with low prevalence. Therefore, a reactive rapid test must be confirmed by a supplemental test (e.g., Western blot). However, necessary peripartum interventions to reduce the risk for perinatal transmission might need to be based on the preliminary results of rapid testing at labor and delivery [i.e. it’s okay to give toxic antiviral drugs to babies that are uninfected]”

“A total of 2474 samples were obtained from 742 children and were tested at the University of North Carolina laboratory; 19 of 2472 were classified as indeterminate. The sensitivity of the test rose rapidly from 54.5% for infants who were younger than 48 hours to 75% for infants who were between 48 hours and 1 week, to greater than 95% for infants who were older than 1 month.”

“Twenty-three (72%) of 32 symptomatic HIV-1-exposed neonates recruited at a mean of 15.2 days were HIV-1-infected [i.e. 28% of infants with AIDS symptoms with uninfected]. HIV-1 infection was detected in 5 patients who were tested within 48 h of birth, confirming congenital infection.”

“[the definition of HIV-uninfected in babies was] two negative enzyme-linked immunosorbent assay results at 9 months or older among those either not breastfed or who had stopped breastfeeding more than 3 months before their last sample”

“Although DNA and RNA PCR and cell culture can detect very low concentrations of HIV-1, these assays yield a positive result in only 20-40% of vertically- infected infants who are tested shortly after birth”

“We cared for a woman initially seen because of Rhe[s]us isoimmunization who consented to routine HIV screening at 20 weeks’ gestation. The initial EIA result was reactive, as was the result of a repeat test 2 weeks later, at which time a supplemental EIA test (nonreactive) and Western blot analysis (indeterminate) were requested. One week later, the result of a third screening EIA test was nonreactive. A month later, another screening EIA test gave a reactive result, a supplemental EIA test result was nonreactive, and a Western blot analysis result was indeterminate for all 3 determinants of HIV-1; the patient’s HIV viral load was < 500 copies/mL. At 34 weeks’ gestation (when all results were finally to hand) the patient was reassured that she was HIV negative. Twelve weeks had passed since the first positive test result. Understandably, the patient was under considerable stress during this time…We had been unaware that multiparity, multiple previous transfusions and auto-immume disorders are all risk factors for false-positive reactions (in non-pregnant populations) because of anti-HLA-DR or other antibodies. Pregnant women are often multiparous, may have a prior history of ante- or post-partum hemorrhage requiring transfusion, and belong to the gender and age groups in which auto-autoimmune phenomena are most common”

“Infants were considered to be HIV-1 infected if they had detectable HIV RNA on two separate blood draws, or a reactive EIA [ELISA antibody test] and confirmed by Western blot for HIV-1 antibody at 18 months of age. Infants who had a single positive plasma HIV-1 RNA test were considered to have probable infection. Where possible, HIV culture...was also performed to confirm the HIV-1 infection in the infants...At birth, one of 22 infants was HIV-1 infected. One infant, who tested negative, died the day after birth leaving 21 evaluable infants for subsequent testing. At 6 months of age four of 21 infants were HIV-1 infected (one in cohort 1 and three in cohort 2). One of the four HIV-infected infants was initially positive for plasma HIV RNA at birth, two were initially HIV RNA positive at 6 weeks of age, and one was initially HIV RNA positive at 6 months of age. Two of the infants with positive plasma HIV RNA tests (one positive at birth and the other positive at 6 weeks of age) also had a confirmatory positive HIV culture; one infant had a confirmatory HIV RNA test. One of these four infants had a single positive plasma HIV RNA test, but died before a confirmatory test and was therefore considered as probably HIV-1 infected.”

“The standard diagnostic test for HIV infection [ELISA] is based on the detection of HIV immunoglobulin class G (IgG) antibody. However, all children born to infected mothers initially test HIV antibody positive since maternal IgG antibody crosses the placenta.”

“6 (2%) specimens from uninfected children tested positive by NASBA and one specimen had an indeterminate result [four of these were blamed on lab errors, but there was no direct evidence of this]…Of the 131 specimens from infected children, 106 (81%) tested positive and 25 (19%) tested negative by qualitative NASBA. Of the 106 specimens testing positive, 100 (94%) also had detectable RNA by quantitative NASBA, 5 (5%) did not, and one (1%) test was invalid…The sensitivity of qualitative NASBA was 38% in the first week…and 95% between 6 weeks and 3 months of life.…By DNA PCR, 92 (70%) specimens from infected children tested positive, 36 (28%) tested negative, and three (2%) tested indeterminate. The sensitivity of DNA PCR was 29% in the first week…and 92% between 6 weeks and 3 months of life. For 15 of the 128 specimens with definitive PCR results, qualitative NASBA results were discordant.”

“47 samples from uninfected children between the age of 10 days and 3 months were negative; all were initially negative by viral culture or DNA PCR on PBMC [peripheral blood mononuclear cells]. One sample was found to be repeatedly positive when it was negative by viral culture and DNA PCR on PBMC. This child was considered definitely non-infected because he was repeatedly seronegative after 18 months of age [This sounds good, but is consistent with a 2% false positive rate. In a low risk population this would mean that false positives drastically outnumber true. If the rate of HIV infection is 1/1000, there would be 1 true positive and 20 false positives for each group of 1000]”

“[the results of this study include] specimens (1 each obtained during weeks 2 and 5 and month 3 of life) from [an infant] who was DNA-PCR-negative and viral RNA-negative in all tests during [the] first 5 months of life but DNA PCR-positive after age 9 months; infant remained HIV antibody-positive in year 2 (infant was not breast-fed…)”

“Blood-draw specimens (108) obtained…from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants less than 28 days of age. Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative [but note that the small sample size makes this study unable to detect quite high rates of false positives (e.g. 10%) and other anomalies]”

“[our studies suggest that] the result of a single PCR test is not sufficient to diagnose or exclude HIV infection and that PCR is more informative when delayed until after the first month of life. These findings also suggest that initial PCR results should be confirmed on samples drawn after a delay of a month or more. This strategy will reduce (but not eliminate) false-positive and false-negative test results. Although sequential testing will provide further evidence for or against infection, the posttest probability of disease will not increase or decrease as much as sequential application of the Bayes theorem would indicate unless test errors (false-positive and false-negative results) are independent between the tests. Sequential and combination test strategies have been evaluated recently. PCR results during the first month of life are of value primarily if the test is negative...In conclusion, our analysis confirms that although PCR is one of the most useful tests for diagnosis of HIV infection in neonates and infants, it is not definitive. Therefore, PCR should be interpreted with the aid of careful clinical follow-up examinations, preferably lasting until the HIV antibody status of the infant is resolved [usually considered to be after 18 months, although it is unlikely that most doctors would consider withholding antiretroviral therapy until that point]. The sensitivity and specificity of PCR in neonates [newborns] is lower than in older infants, which results in a low positive predictive value; however, negative tests are informative [negative test results are much more likely to be accurate than positive test results]. Delaying the use of PCR until after the neonatal period or repeating PCR on independent samples obtained 30 to 60 days later will reduce test errors [but not eliminate them]”

“for 100 neonates [newborns] with positive PCR [‘viral load’] test results...44 will prove to be uninfected. For older infants, the probability of true HIV infection after a positive PCR test result is 83% [although earlier the authors admit that there is no ‘gold standard’ for evaluating the tests]”

“A diagnosis of infection was based on the development of an AIDS-defining illness or seropositivity beyond 15 months of age...Incorrect and indeterminate diagnoses by various rules are summarized in table 3...In uninfected infants, misdiagnoses [false positives] were more common in rule B [positive by at least two of PCR, antibody or culture on one sample] and rule C [positive by at least two samples using one of: PCR, antibody or culture tests] with PCR...mainly because of the occurrence of false-positive PCR results”

“Most infected infants lack specific signs, symptoms or characteristic laboratory abnormalities at birth that distinguish them from uninfected seropositive infants...[In this study] Group 1 consisted of 105 subjects confirmed to be infected as documented by the presence of at least two of the following: positive HIV culture, persistent antibody after 15 months of age, positive p24 antigen, or the presence of AIDS as defined by the CDC surveillance definition...Overall, 96 of 105 initial PCRs in infected subjects were positive [4 of the false positive PCR occurred during the first week of life, but the other 5 occurred in children more than 1 year old]”

“Data were available on 271 HIV-infected children [in 12 different studies]…At the initial assessment, 175 children tested PCR-positive…All children who initially tested negative subsequently tested PCR-positive…An estimated 38% of infected children tested on the day of birth or day after birth are PCR-positive…At 28 days the estimated sensitivity was 96%…7 children had negative test results…between 65 and 183 days. As information was not sought on children who were subsequently found to be HIV-uninfected, conclusions about the specificity of PCR cannot be drawn.”

“3 uninfected infants [out of 14] have had one abnormal laboratory test (virus isolated at age 3 weeks and low levels of HIV antigen in two at ages 1 and 9 months, respectively). A fourth uninfected infant had a weak positive result by HIV-1 polymerase chain reaction assay at age 3 months, and virus was isolated [i.e. cell culture, not isolation] at 12 months. These children have had multiple negative tests subsequently, are now 3.7, 6.8, 3.5 and 2.5 years old, respectively, and remain well. 2 infected infants are symptomatic (CDC class P-2A [mildly symptomatic, moderate immune suppression, this is not AIDS]). The third, a breast-fed infant, seroconverted at about 5 months of age, on the basis of the appear of and subsequent rise in HIV p24 antigen levels and HIV antibody titers; he remains asymptomatic”

“HIV-1-specific CTL [cyto-toxic/cell-killing lymphocyte] activity in PBMC [peripheral blood mononuclear cells] could be evaluated in 23 children [out of 42 originally in the study]…All children had seroreverted [gone from HIV-positive to HIV-negative] at the time of the study, and no HIV-1 proviral DNA had been detected in their PBMC…The presence of CTL indicates that the subjects were exposed to HIV-1 or its products. It is unclear whether infection actually occurred, since no evidence of HIV-1 proviral DNA could be detected…Furthermore, all subjects remained seronegative…the presence of HIV-1-specific CTL is certainly suggestive that some degree of viral replication had occurred and was successfully contained and cleared by this HIV-1-specific immune response.”

“The probability of having a positive PCR [Polymerase Chain Reaction or ‘viral load’ test]…among [47] children with unequivocal evidence of infection, was 30.5% on cord blood and 80.6% at 3 months…Among 117 HIV-1-uninfected children born to HIV-1-infected mothers, 6 (5%) had a false-positive PCR on cord blood…[after excluding 6(5%) of the samples because of the possibility of maternal blood contamination] an estimate of the specificity of our PCR technique applied to the diagnosis of perinatal HIV-1 infection is 98.0%…our study showed also that cord blood is probably not suitable for early diagnosis of HIV-1 infection in newborns because a probable contamination of the newborn blood sample by maternal blood…was observed in 6 of 117 cord blood samples from newborns further shown to be uninfected.”

“The results of this work indicate that certain anti-HIV antibodies cross-react with endogenous placental proteins. Anti-gp120/160 was generally reactive with villus cytotrophoblast cells from second trimester placenta and with limited regions of syncytium in third trimester placental tissue samples. Reactivity was mostly cytoplasmic, although some extravillus trophoblast cells stained in a manner suggesting surface membrane-related expression. This was also the case with anti-p17 staining of extravillus trophoblast. In villus placental tissue sections from the second and third trimester, anti-p17 reactivity was strongly associated with the cytotrophoblast layer. Limited syncytial areas also displayed an apical band of reactivity. These data demonstrate that HIV-1 cross-reactive protein epitopes are expressed within trophoblast of normal human placentae. In additional studies, it was observed that placental ERV particle isolates are cross-reactive with these antibodies and that these antibodies also cross-react with human choriocarcinoma cell lines BeWo, JAr, and JEG-3 that are not infected with HIV-1 (data not shown). These data suggest that human placental endogenous retroviral proteins may have antigenic similarity with exogenous HIV-1 and that expression of these proteins is a normal feature of trophoblast differentiation.”

“potential causes of indeterminate Western blots for HIV-1...included...HLA antibody cross-reactivity, and current pregnancy...All but one of the cases who demonstrated anti-class I HLA reactivity were multiparous women [pregnant more than once]”

“Some of the large cohort studies of children born to infected mothers have identified a small population (2.5-4.7%) of seronegative children in whom viral markers have been or continue to be positive. The longterm outlook of such children is unknown, but studies suggest that they have a good prognosis.”

“An infant was considered to be infected if anti-HIV-1 antibodies persisted beyond 18 months of age or if the infant died of AIDS [although all AIDS-defining diseases can occur without HIV, so at least some of these deaths could be unrelated to HIV infection]...60 of the 162 infants with negative cultures at birth were retested before the age of 3 months, and 11 were positive...Of the 181 infants tested for HIV p24 antigen at birth, 7 were positive...Of the 174 infants negative for p24 antigen at birth, 81 were tested again before the age of three months, and 4 were positive”

“[HIV co-culture] was positive in 32 of 41 (78%) [HIV-positive] children”

“In 1990, of 20.2 million HIV tests done in Russia only 112 were confirmed and about 20,000 were false positives, 1991 saw some 30,000 false positives out of 29.4 million tests, with only 66 confirmations...in 1991 alone some 8000 false-positive results were reported in pregnant women, with only 6 confirmations [presumably with the Western Blot test]”

“At birth, 5 babies had a positive PCR...and 3 of them had detectable p24 antigenaemia...Among the 45 babies who were negative by PCR, 20 were tested by HIV culture and all were negative. By 4-9 weeks of age, 16 infants had a positive PCR; 13 with the three primer sets, and 3 with two primer sets. HIV culture could be done in 14 of these cases and was positive in 11, negative in 1, and indeterminate in 2...By the age of 5-9 months...34 children previously found negative and 10 the 16 found positive [were retested]. The results remained unchanged for PCR, and culture was positive in the 2 children who had indeterminate results at 4-9 weeks. In addition, p24 antigenaemia became positive in 1 child previously found infected...The negative results obtained at birth by PCR and culture indicate that the viral load in PBMC is not sufficient to be detected.”

“4 children who became seronegative but who were repeatedly virus [culture] positive were excluded from the analysis”

“PCR performed before the age of 1 month identified only 55% of the truly infected infants”

“The presence of anti-HIV antibodies [in young children] is not a useful marker of infection because of the passive transmission of maternal antibodies, which may persist for several months...up to 15 months. Tests for p24 antigen are often negative in newborns and therefore are not helpful for diagnosis. Moreover, it has been reported that some children could remain seronegative...[In this study of 24 newborns and young children] HIV was isolated [sic] from PBMC [Peripheral Blood Mononuclear Cell] cultures in 8 of the 24 cases studied...16/24 harbored HIV DNA sequences in their PBMCs using PCR...HIV RNA sequences were amplified using gag primers in cells from 10 [out of the 24, 20 were eventually defined as HIV-positive by antibodies after 15 months]...[in summary] 67% of newborns were found to be infected by HIV using PCR”

“Infants were defined as infected by a positive [i.e. p24 antigen present] HIV-1 culture or by increasing anti-p24 or gp41/gp120 antibody titers after delivery...Infants were defined as not infected if HIV-1 cultures were negative, a sequential decline or loss of antibody to both p24 and gp41/gp120 proteins was measured, and immunoglobulin levels and T lymphocyte subset counts were comparable to those of control infants [no word on whether some infants were indeterminate, or whether all were arbitrarily placed in one category or the other]”

“A recent analysis of several published studies involving 172 infants of seropositive mothers concluded that the sensitivity [of DNA PCR (‘viral load’)] in the newborn period (0-30 days) was around 55%, and in all infected children was only 73%”

“Among the 8 newborns…born to HIV1-infected mothers, 6 had detectable HIV1 DNA sequences…In group II [babies], 17 of 23 sera were available…HIV1 DNA was detected in PBL [peripheral blood leukocytes] of 14 of 23 babies. Among the 14 babies positive by PCR, 10 had positive or incomplete and 2 had negative Western blots. Among the nine babies negative by PCR, 3 had positive or incomplete and two had negative Western blots. Therefore, 2 of 4 babies, who were seronegative at the time of PCR test, had HIV1 DNA in PBL…8 (including the 4 with symptoms consistent with AIDS) of the 14 HIV1 DNA-positive and 1 of 9 HIV DNA-negative babies had clinical features likely to be related to HIV infection. The results obtained with the three sets of primers markedly differed; indeed 7 of 31 samples yielded positive results with all three sets of primers as compared to 7 of 31 which were positive with two sets of primers but negative with the third, and the remaining six of 31 samples were only positive with one set.”

“Of 1954 women screened at delivery, 12% were seropositive for HIV-1...At labour none of the 109 seropositive mothers for whom follow up was possible had AIDS...during two years of follow up, 4% developed AIDS, 28% had AIDS related complex, 46% had generalized lymphadenopathy, and the remaining 25% had no symptoms...Of 61 children who became seronegative at 8 months, antibodies to HIV-1 reappeared in nine at 12 months. By comparison none of of the nine children who became seronegative at 12 months showed a reappearance of antibodies. On the other hand, 18% of children who were seropositive up to 12 months became negative at 18 months and were free of symptoms after 24 months...of 13 neonates who were seronegative at birth, four converted to become seropositive at different ages...HIV-1 serology is unreliable among children under 18 months of life”

“The detection of conventional IgG antibodies to HIV-1 during the first year of life may result from the passive transfer of maternal antibodies...Our inability to detect these antibodies in 10 of the 11 infants who were without evidence of AIDS in the first year of life but who had positive cord-blood cultures highlights the difficulty of diagnosing perinatal HIV-1 infection. The absence of detectable antibodies in children with obvious clinical disease has also been noted in previous studies”

“30 of the infants born to seropositive mothers reverted from seropositive to seronegative. The median age of these 30 infants at seroreversion...was 9 months (range 1 to 16)”

“proviral [HIV] sequences [of DNA] were detected in 9 of the 10 infants tested whose illness met the CDC case definition for HIV infection, this definition includes infants with AIDS, positive culture, positive serum antigen [p24] test, or persistent antibody beyond 15 months of age. In addition, proviral sequences were detected in one infant with nonspecific findings who was negative on culture and serum antigen testing and less than 15 months of age”

“HIV proviral sequences were detected in 1 or more serum specimens obtained during the postnatal period from all of the 6 infants tested who later had AIDS and from 4 of the 14 infants who had nonspecific findings”

“In four of five infants who had signs or symptoms of HIV infection after becoming seronegative, we detected evidence of HIV infection with use of hybridization studies carried out after the genome was amplified with the polymerase-chain-reaction method. One infant who became seronegative was totally free of symptoms but carried the HIV genome”

“9 infants (8%) were [HIV] seronegative [at 18 months] but had persistent or transient clinical signs [of HIV infection]…In 4 of 5 infants who had signs or symptoms of HIV infection after becoming seronegative, we detected evidence of HIV infection with use of hybridization studies carried out after the genome was amplified with the PCR method. 1 infant who became seronegative was totally free of symptoms but carried the HIV genome”

“Infection was defined by persistence of antibody...beyond the age of 15 months, clinical AIDS or AIDS-related complex (ARC), or the presence of virus [actually culture] or p24 antigen...[but]...53% [of children HIV-antibody-positive at birth] lost antibody by 1 year. By 15 months, 69% would be expected to have lost antibody...6 [of 107 eventually determined to be HIV-negative] have lost antibody after 15 months; one had been antibody positive at 18.1 months...No child has lost antibody and then become, and remained, antibody-positive”

“Of 85 children with human-immuno-deficiency-virus (HIV) infection based on clinical (opportunistic infection), epidemiological (mother a drug addict or known to be HIV infected), and immunological (helper-T-cell deficiency and impaired proliferative response to pokeweed mitogen) features, 9 were found to lack antibody to HIV as measured by a commercial enzyme-linked immunoassay (ELISA). All 9 children had detectable levels of HIV antigen in simultaneous plasma specimens, measured by a sensitive antigen-capture ELISA. The use of the western blot assay and an ELISA with recombinant HIV antigens was able to identify HIV infection in 4 of the 9 children.”

“IgM [Immunoglobulin M] antibodies were present in 4 [of 27] children who were aged over 3 months. These antibodies were found only against p41, p55 and p31 viral antigens but not against p120, p24 and p15. These patterns were completely different from their mothers’ or those of 30% of adult patients recently infected with persistent lymphadenopathy who had anti-HIV IgM”

“We have seen an infant, born to seropositive parents, who was persistently seronegative for HIV antibody before the onset of severe immunodeficiency..The diagnosis of AIDS in this child rests on the opportunistic infections, decreased T4/T8 [immune cell] ratios, impaired T-cell immunity, loss of functional antibody, and seropositivity in the parents”

“In neonates, presence of antibodies to HIV-1 is indicative of exposure to HIV-1, but not necessarily of HIV-1 infection, due to the acquisition of maternal antibodies which persist for up to 6 months.”