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Volume 328:297-302 February 4, 1993 Number 5 Next

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ABSTRACT

Background Serologic detection of human immunodeficiency virus (HIV) infection in neonates is complicated by the presence of immune complexes, consisting of passively transferred maternal antibodies and HIV antigens. A new, rapid assay has been designed to disrupt these immune complexes in order to permit the detection of a specific HIV antigen. We evaluated the efficacy of this assay in detecting HIV infection in neonates.

Methods We measured p24 antigen in blood samples from both infected and uninfected children of HIV-infected mothers. The samples were treated with glycine hydrochloride to dissociate the immune complexes, followed by neutralization with TRIS-hydrochloric acid. A commercial HIV p24 antigen assay was then used, with an optical density greater than 0.120 at a wavelength of 450 nm defined as indicating a positive result.

Results Of eight cord-blood samples from neonates with proved HIV infection, five were positive for immune-complex-dissociated p24 antigen. For two other neonates the first postnatal sample, obtained on days 12 and 18, was positive. There was no follow-up sample for the eighth neonate. Of 22 uninfected neonates, 20 were negative on the cord-blood assay. Two neonates had positive cord-blood samples, but the first postnatal sample was negative. Thus, the tests with early postnatal samples identified the HIV-infection status correctly for all 29 children who could be evaluated. In a separate group of 78 children (median age, 188 weeks), the specificity of the test was 100 percent and the sensitivity 81 percent.

Conclusions The immune-complex-dissociated HIV p24 antigen assay is a rapid, simple serologic test that may be of value in diagnosing HIV infection in neonates born to HIV-infected women.

Currently, there are several techniques for detecting HIV infection in adults and children. The most commonly used technique relies on the detection of antibodies to HIV in serum or plasma. Unfortunately, this assay is of little value in neonates, because maternal IgG antibodies readily cross the placental barrier to enter the cord blood and are detected in the serum and plasma of newborns^4,5. Thus, the detection of antibodies to HIV in the cord blood or in neonatal serum samples does not necessarily indicate HIV infection. Moreover, these antibodies can persist for a variable period (up to 12 months or more), thereby delaying diagnosis. Other diagnostic methods include the detection of HIV-specific IgA antibodies in early-childhood serum samples^6,7 and that of integrated HIV DNA with the polymerase chain reaction and HIV-specific primers in blood samples^{8,9,10,11,12,13,14}. In addition, a culture of lymphocytes in cord blood or neonatal blood for HIV can demonstrate HIV infection¹⁰. The isolation of HIV by lymphocyte cocultures of replicate samples and the persistence of HIV antibodies after 15 months are the gold standards for the identification of neonatal HIV infection. However, these diagnostic techniques are time-consuming, require a sophisticated laboratory, and are expensive.

Recently, a technique has been described for dissociating HIV antibodies from their bound antigens. In this assay, the serum is treated with hydrochloric acid and then neutralized with sodium hydroxide^15,16. The technique was subsequently modified by the substitutions of glycine hydrochloride for hydrochloric acid and of TRIS-hydrochloric acid for the sodium hydroxide neutralization buffer. This method yields what is referred to as immune-complex-dissociated HIV p24 antigen¹⁷. The assay has been investigated in a variety of clinical settings. Preliminary data suggest that it can detect immune-complex-dissociated HIV antigen in the majority of patients with symptomatic HIV infection and to a lesser extent in patients without clinical symptoms (unpublished data). This assay has greater sensitivity than does routine HIV p24 antigen testing¹⁶.

We hypothesized that the circulating cells of HIV-infected neonates could produce large amounts of HIV, as in acute infection,^18,19 and that they shed HIV p24 antigen into the circulation. This antigen could form complexes with maternally transferred HIV antibodies and circulate as immune complexes. We also hypothesized that for the majority of infants maternal antibody would remain in excess. If these hypotheses were correct, free HIV p24 antigen should be infrequently detected in HIV-infected neonates, and immune-complex-dissociated antigen should be detected frequently. Neither free nor bound HIV p24 antigen would be detected in neonates who were not infected with HIV. As a result, we should be able to use the detection of immune-complex-dissociated HIV p24 antigen as a reliable indicator of neonatal HIV infection. To test this hypothesis, we investigated the frequency with which immune-complex-dissociated p24 antigen was detected in cord-blood plasma and serum samples from neonates born to mothers with HIV infection.

Methods

Forty-one children and their mothers, along with 54 children exposed to HIV in utero who were followed by the Southern California Pediatric AIDS Consortium, were studied with consent obtained under the guidelines of the Human Subjects Protection Committee of the University of California, Los Angeles. Samples of plasma, serum, and lymphocytes were obtained from cord blood, neonatal blood, and postnatal blood collected at various times after delivery from children born to mothers with HIV infection. Maternal samples were obtained at the time of delivery or as close to that time as possible. An additional 24 samples of blood from children serving as controls or of cord blood from newborns of mothers not infected with HIV were anonymously obtained from residual laboratory specimens. Unless otherwise specified, the plasma and serum samples were stored at -70 °C, and the lymphocytes in liquid nitrogen.

Assays for Immune-Complex-Dissociated HIV p24 Antigen

We used a modification of a commercially available kit (Coulter Immunology, Hialeah, Fla.) to detect immune-complex-dissociated p24 antigen. The standard dissociation solution was 1.5 M glycine hydrochloride (pH 1.8) (Sigma Chemical, St. Louis). In 96-well flat-bottomed plates (Corning Plastics, Fisher Scientific, Irvine, Calif.), a mixture of 70 microl of this solution with 70 microl of the plasma or serum sample to be tested was incubated at 37 °C for 90 minutes. To each well was added 70 microl of a neutralization solution of 1.5 M TRIS-hydrochloric acid (pH 7.4) (Sigma Chemical), and the mixture was incubated for two hours. Two hundred microls of this mixture was transferred to the 96-well plates (Coulter) used in the HIV p24 antigen assay and was incubated overnight (>18 hours) at 37 °C. The plates were then assayed for HIV p24 antigen with the standard antigen-capture enzyme-linked immunosorbent assay (Coulter). A standard curve was prepared with use of the HIV p24 antigen solution supplied with the HIV p24 antigen kit (Coulter). Standards ranging from 16 to 250 pg of HIV p24 antigen per milliliter of solution were prepared. The plates were read in a kinetic microplate reader. The cutoff for a positive value was calculated as the mean of all the values for normal human serum samples in each plate (three normal samples per plate) plus two times the standard deviation, or 0.0416 + (2 x 0.0392). In these assays, the cutoff was an optical density of 0.120 at the 450-nm wavelength. Samples with an optical density above this value were considered to be positive for immune-complex-dissociated HIV p24 antigen. Samples with an optical density within 10 percent of the cutoff value were tested again, but only the initial value was used in the analysis.

Isolation of HIV from Cocultures of Peripheral-Blood Lymphocytes

Lymphocytes from cord blood and neonatal blood were isolated as a mononuclear fraction after Ficoll-Hypaque density-gradient separation. The mononuclear cells were washed twice in Hanks' balanced salt solution (HBSS, Sigma Chemical) and counted. Lymphocyte cocultures were performed according to the standard methods of the AIDS Clinical Trials Group for the bulk isolation of HIV²⁰. Neonates were considered to be infected with HIV if two cultures were positive on separate occasions, if HIV antibodies persisted after 15 months, or if clinical complications developed that met the clinical definition of the acquired immunodeficiency syndrome (AIDS).

Results

A total of 282 samples of serum or plasma were analyzed in seven assays for immune-complex-dissociated p24 antigen. In each assay a standard curve, negative samples, and known positive samples were assayed to serve as controls. The intraassay coefficient of variation was 2.3 percent, and the interassay variation was 11 percent.

Samples from a group of 78 children (median age, 188 weeks; range, 6 days to 13 years) were analyzed for sensitivity and specificity in a single assay. This group included 19 samples of plasma from cord blood from neonates born to mothers without HIV infection and 5 serum samples from healthy children, 14 serum samples from asymptomatic HIV-infected children, 28 serum samples from symptomatic HIV-infected infants, and 12 serum samples from seroreverting children born to HIV-infected mothers who were not receiving antiretroviral therapy (Figure 1). When the cutoff value of 0.120 was used, all 19 neonates born to mothers without HIV infection were negative, and all 12 seroreverting children were negative. In addition, 9 of the 14 asymptomatic HIV-infected children and 25 of the 28 symptomatic HIV-infected children had detectable immune-complex-dissociated antigen. When the standard curve for HIV p24 antigen was used, the mean (±SD) level of antigen recovered after dissociation by acid in the samples from symptomatic children was 989 ±924 pg per milliliter (range, 0 to 2865). The mean level of antigen recovered after dissociation by acid in asymptomatic children was 825 ±1004 pg per milliliter (range, 0 to 2832). In the two groups combined, the overall sensitivity of the assay was 81 percent (34 of 42; 95 percent confidence interval, 69 to 93 percent), and the specificity was 100 percent.

View larger version (27K): [in this window] [in a new window]   Figure 1. Detection of Immune-Complex-Dissociated HIV p24 Antigen in the Serum of HIV-Infected Children and Control Samples. Each point represents one child. The control samples are from children not at risk for HIV infection. "Symptomatic" and "asymptomatic" refer to the classification of pediatric HIV infection by the Centers for Disease Control and Prevention. "Seroreverting" children are those who were born to HIV-infected mothers but who have lost all antibody to HIV and are not infected with HIV. Absorbance is expressed as the optical density at a wavelength of 450 nm. The solid line represents the cutoff value above which results were considered positive. The sensitivity was 81 percent (34 of 42; 95 percent confidence interval, 69 to 93 percent), and the specificity was 100 percent (36 of 36).

 
Cord-blood plasma samples from a second group of 41 children born to HIV-infected mothers were analyzed to determine the predictive value of the assay for neonatal HIV infection (Figure 2). Eight children were found to be infected with HIV and 22 children were not, when two positive lymphocyte cocultures for HIV isolation were used as the standard for classification²¹. Ten children had negative lymphocyte cocultures for HIV but had not been followed for 15 months. They could not be definitively categorized as either infected or uninfected according to our criteria, and they were excluded from this analysis. For one child there was no cord-blood sample, and therefore the child could not be evaluated.

View larger version (35K): [in this window] [in a new window]   Figure 2. Detection of Immune-Complex-Dissociated HIV p24 Antigen in the Cord-Blood Plasma from Newborns of Mothers Infected with HIV. Each point represents one child. The children are classified as infected or uninfected according to the standard criteria of the Centers for Disease Control and Prevention. Absorbance is expressed as the optical density at a wavelength of 450 nm. The short line represents the mean in each group, and the wide solid line the cutoff value above which results were considered positive. The sensitivity was 63 percent (5 of 8; 95 percent confidence interval, 29 to 97 percent), and the specificity was 91 percent (20 of 22; 95 percent confidence interval, 79 to 100 percent).

 
Five of the eight HIV-infected neonates had detectable immune-complex-dissociated p24 antigen in their cord-blood plasma. All these children had rapidly rising levels of dissociated antigen in follow-up postnatal samples. An additional two neonates who were infected with HIV did not have immune-complex-dissociated p24 antigen in their cord-blood plasma, but dissociated antigen was found in the first sample available on follow-up (at 12 and 18 days of age, respectively) (Figure 3). One neonate was known to have symptomatic HIV disease, but there was no follow-up sample available for this child.

View larger version (32K): [in this window] [in a new window]   Figure 3. Detection of Immune-Complex-Dissociated HIV p24 Antigen in Serum Samples from Two Children Born to Mothers Infected with HIV, after Samples of Cord-Blood Plasma Tested Negative. Each line represents one child. Absorbance is expressed as the optical density at a wavelength of 450 nm. The solid line represents the cutoff value above which results were considered positive.

 
Of the 22 neonates without HIV infection, 20 were negative for immune-complex-dissociated p24 antigen on testing of their cord-blood plasma. Two neonates had cord-blood plasma samples that were repeatedly positive, though close to the cutoff value; these neonates were negative on testing of the first available follow-up serum sample. Their cord-blood plasma samples could be neutralized with serum specific for HIV p24 antigen, suggesting that these were true positive results. Overall, the sensitivity of the assay in the original cord-blood samples was 63 percent (5 of 8; 95 percent confidence interval, 29 to 97 percent), and the specificity was 91 percent (20 of 22; 95 percent confidence interval, 79 to 100 percent). By testing a single follow-up serum sample from each neonate for immune-complex-dissociated p24 antigen, we correctly identified the HIV-infection status of all 29 children who could be evaluated within the first three weeks of life (for 1 patient there was no follow-up sample) (Figure 4).

View larger version (31K): [in this window] [in a new window]   Figure 4. Detection of Immune-Complex-Dissociated HIV p24 Antigen in Samples of Cord-Blood Plasma and in the First Serum Sample Obtained during Follow-up from Infants Born to Mothers Infected with HIV. Each line represents one child. Absorbance is expressed as the optical density at a wavelength of 450 nm. The solid line represents the cutoff value above which results were considered positive. The follow-up serum samples were obtained at a median age of 3.9 weeks (range, 2 days to 145 weeks).

 
One possible explanation of these results is the passive transfer of immune complexes from mother to child. To investigate this possibility, we studied the 41 prospectively followed mother-child pairs for immune-complex-dissociated p24 antigen (Figure 5). There were 28 such pairs for whom both a cord-blood plasma sample and a maternal serum sample were available from around the time of delivery. Sixteen of these pairs had no detectable immune-complex-dissociated HIV p24 antigen. Among the 12 pairs for whom at least one of the two samples contained detectable dissociated HIV p24 antigen, there were 5 mothers in whom the antigen level was lower than that of the offspring. This finding made the passive transfer of immune complexes appear unlikely. The discordance in results does not appear to be an effect of maternal antiviral therapy, because none of the mothers who had lower antigen levels than their offspring were receiving antiviral therapy at the time of delivery.

View larger version (54K): [in this window] [in a new window]   Figure 5. Relation between Maternal and Neonatal Levels of Immune-Complex-Dissociated HIV p24 Antigen. Each line represents one pair of samples. The 18 mother-neonate pairs with no detectable antigen are not represented. Absorbance is expressed as the optical density at a wavelength of 450 nm. The solid line represents the cutoff value above which results were considered positive.

 
As seen with standard HIV p24 antigen testing,²² mothers who had detectable levels of dissociated p24 antigen in their perinatal-blood samples appeared more likely to transmit HIV to their offspring. Among the 28 pairs of mothers and infants who could be evaluated, 9 mothers were positive for immune-complex-dissociated p24 antigen. In four of these nine pairs, there was transmission of HIV. Of the 19 mothers without detectable levels of dissociated HIV p24 antigen, 4 also transmitted HIV to their offspring. Among mothers with dissociated p24 antigen the relative risk of transmitting HIV to their offspring was approximately 2.5 (P = 0.08).

Discussion

Establishing a diagnosis of HIV infection with confidence in newborns is difficult for a variety of reasons. These include the passive transfer of maternal antibodies across the placenta into the serum of the neonate, the immaturity of the neonate's developing immune system, and the altered immunologic function that results from HIV infection. Nonetheless, the anxiety of parents who want to find out whether their child is infected and the clinical benefit that accrues from early intervention make a rapid, accurate diagnosis of neonatal HIV infection important.

A variety of techniques have been developed to address this problem. In large part, tests such as the HIV DNA polymerase chain reaction^{8,9,10,11,12,13,14} and HIV coculture are expensive, time-consuming,^10,23 and impractical for screening large populations of newborns. For these reasons, it is unlikely that they will be widely used. Today, only the detection of HIV-specific IgA in early childhood offers any realistic hope of becoming a widely used assay with a reasonable sensitivity^6,7. However, this assay appears to be less sensitive in the important period of the first three months after birth.

In this study, we used a modification of immune-complex dissociation to disrupt HIV antigen-antibody complexes and a commercial assay to detect the released antigen. Although the numbers of infected children are small, we correctly ascertained the ultimate virologic status of all 29 children who could be evaluated who were born to HIV-infected mothers. When we used the cord-blood sample alone, only five children were incorrectly categorized. All these misclassifications were corrected when a follow-up serum sample was tested.

This technique may also be of value in delineating the pathogenesis of pediatric HIV infection. For example, children who are infected intrapartum are thought to have a different course of disease than those who are infected in utero. Since none of these children were breast-fed, it is possible that the two neonates who were negative on cord-blood testing but positive on all subsequent samples could have been infected intrapartum. This assay would not be capable of detecting antigen in such children and would give true negative results. The rapid increase in antigen levels after birth may represent primary HIV infection¹⁸. Indeed, other virologic data on these children and their clinical course suggest that this may be correct. If the observation is confirmed by others, this assay may be useful in helping to distinguish intrapartum from in utero HIV infection. In addition, the high frequency of free-antigen detection in neonates as compared with older children and adults with HIV infection, together with the rapidly rising levels of immune-complex-dissociated antigen in the neonatal period, suggests that we may be observing the earliest phase of primary infection in these neonates¹⁸. We anticipate that later samples from these children may show declines in antigen levels independent of antiretroviral therapy as HIV-specific immunity occurs^18,19. Long-term studies of more children will be necessary to see whether this is so.

This technique is rapid, simple, and relatively accurate as compared with other methods of neonatal diagnosis of HIV infection. Because a large number of laboratories in the United States already measure HIV p24 antigen routinely with commercial assays, this technique can be readily implemented in most centers where children are born to mothers infected with HIV. Although the performance of the assay in this small cohort was excellent, these results should be considered preliminary. Additional testing of the technique and confirmation of the initial results in other laboratories are necessary before the technique is adopted widely in neonatal HIV diagnosis. As was suggested by the inaccurate identification of cord-blood samples and the potential problem of specimens that have undergone hemolysis, there may be other circumstances in which plasma or serum samples from neonates give inaccurate results when a single sample is used. Given the tremendous medical and psychological impact of the diagnosis of HIV infection, it is important to have additional confirmatory testing. Nonetheless, this technique appears to be a step forward in the rapid diagnosis of neonatal HIV infection and thus in the care of HIV-infected neonates.

Supported in part by a grant (HD26621) from the National Institute of Child Health and Human Development, grants (AI27660, AI28697, AI27550) from the National Institute of Allergy and Infectious Diseases, grants (R90LA121, R91LA161) from the UniversityWide Task Force on AIDS, and the Pediatric AIDS Foundation.

Dr. Miles is a paid consultant for the Coulter Corporation.

We are indebted to Pamela Selveraj of the Coulter Corporation for her technical assistance, to Victor Redula and Dorkus Wang for technical assistance, and to Mary Anne Dillion, Audra Devekis, Doug Heiner, Margaret Keller, and Carol Berkowitz, without whose samples this study would not be possible.

Source Information

From the Center for AIDS Research and Education (S.A.M., L.M., A.L.) and the Department of Pediatrics (E.B., L.A.W., E.R.S., Y.B.), the University of California, Los Angeles, and the Coulter Corporation, Hialeah, Fla. (D.H., G.T.).

Address reprint requests to Dr. Miles at the UCLA CARE Center, Rm. BH-412C, CHS, Los Angeles, CA 90024-1793.

References

1. Gwinn M, Pappaioanou M, George JR, et al. Prevalence of HIV infection in childbearing women in the United States: surveillance using newborn blood samples. JAMA 1991;265:1704-1708. [Free Full Text]
2. Pizzo PA, Butler K, Balis F, et al. Dideoxycytidine alone and in an alternating schedule with zidovudine in children with symptomatic human immunodeficiency virus infection. J Pediatr 1990;117:799-808. [Medline]
3. Brouwers P, Moss H, Wolters P, et al. Effect of continuous-infusion zidovudine therapy on neuropsychologic functioning in children with symptomatic human immunodeficiency virus infection. J Pediatr 1990;117:980-985. [CrossRef][Medline]
4. De Rossi A, Ades AE, Mammano F, et al. Antigen detection, virus culture, polymerase chain reaction, and in vitro antibody production in the diagnosis of vertically transmitted HIV-1 infection. AIDS 1991;5:15-20. [Medline]
5. Rakusan TA, Parrott RH, Sever JL. Limitations in the laboratory diagnosis of vertically acquired HIV infection. J Acquir Immune Defic Syndr 1991;4:116-121.
6. Martin NL, Levy JA, Legg H, Weintrub PS, Cowan MJ, Wara DW. Detection of infection with human immunodeficiency virus (HIV) type 1 in infants by an anti-HIV immunoglobulin A assay using recombinant proteins. J Pediatr 1991;118:354-358. [CrossRef][Medline]
7. Quinn TC, Kline RL, Halsey N, et al. Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies. JAMA 1991;266:3439-3442. [Free Full Text]
8. Krivine A, Yakudima A, Le May M, Pena-Cruz V, Huang AS, McIntosh K. A comparative study of virus isolation, polymerase chain reaction, and antigen detection in children of mothers infected with human immunodeficiency virus. J Pediatr 1990;116:372-376. [CrossRef][Medline]
9. Williams P, Simmonds P, Yap PL, et al. The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection. AIDS 1990;4:393-398. [Medline]
10. Edwards JR, Ulrich PP, Weintrub PS, et al. Polymerase chain reaction compared with concurrent viral cultures for rapid identification of human immunodeficiency virus infection among high-risk infants and children. J Pediatr 1989;115:200-203. [CrossRef][Medline]
11. Weintrub PS, Ulrich PP, Edwards JR, et al. Use of polymerase chain reaction for the early detection of HIV infection in the infants of HIV-seropositive women. AIDS 1991;5:881-884. [Medline]
12. Rudin C, Senn HP, Berger R, Kuhne T, Erb P. Repeated polymerase chain reaction complementary to other conventional methods for early detection of HIV infection in infants born to HIV-infected mothers. Eur J Clin Microbiol Infect Dis 1991;10:146-156. [CrossRef][Medline]
13. Cassol SA, Lapointe N, Salas T, et al. Diagnosis of vertical HIV-1 transmission using the polymerase chain reaction and dried blood spot specimens. J Acquir Immune Defic Syndr 1992;5:113-119.
14. Brandt CD, Rakusan TA, Sison AV, et al. Detection of human immunodeficiency virus type 1 infection in young pediatric patients by using polymerase chain reaction and biotinylated probes. J Clin Microbiol 1992;30:36-40. [Free Full Text]
15. Nishanian P, Huskins KR, Stehn S, Detels R, Fahey JL. A simple method for improved assay demonstrates that HIV p24 antigen is present as immune complexes in most sera from HIV-infected individuals. J Infect Dis 1990;162:21-28. [Medline]
16. Palomba E, Gay V, de Martino M, Fundaro C, Perugini L, Tovo PA. Early diagnosis of human immunodeficiency virus infection in infants by detection of free and complexed p24 antigen. J Infect Dis 1992;165:394-395. [Medline]
17. Kageyama S, Yamada O, Mohammad SS, et al. An improved method for the detection of HIV antigen in the blood of carriers. J Virol Methods 1988;22:125-131. [CrossRef][Medline]
18. Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 1991;324:961-964. [Abstract]
19. Alimenti A, Luzuriaga K, Stechenberg B, Sullivan JL. Quantitation of human immunodeficiency virus in vertically infected infants and children. J Pediatr 1991;119:225-229. [Medline]
20. Miles SA, Mitsuyasu RT, Moreno J, et al. Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine. Blood 1991;77:2109-2117. [Free Full Text]
21. Arpadi S, Caspe WB. Diagnosis and classification of HIV infection in children. Pediatr Ann 1990;19:409, 412-403, 417. 
22. Scarlatti G, Lombardi V, Plebani A, et al. Polymerase chain reaction, virus isolation and antigen assay in HIV-1-antibody-positive mothers and their children. AIDS 1991;5:1173-1178. [Medline]
23. Bryson Y, Chen I, Miles S, et al. A prospective evaluation of HIV co-culture for early diagnosis of perinatal HIV infection. In: Abstracts of the Seventh International Conference on AIDS, Florence, Italy, June 16-21, 1991. Vol. 7, Suppl 2. Rome: Istituto Superiore di Sanita, 1991:185. abstract.

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