Correspondence
Viral Culture of HIV in Neonates
N Engl J Med 1993; 328:814-815March 18, 1993
- Article
To the Editor:
Burgard et al. (Oct. 22 issue)1 are to be congratulated on their use of very sensitive assays to detect infection with human immunodeficiency virus type 1 (HIV-1) in neonates and infants. However, in their Discussion the authors state that the frequency of transmission of this virus from infected women to their fetuses is not known and that there is an apparent absence of the viral genome in fetal tissues. The authors take this as evidence that vertical transmission occurs at birth and not prenatally. To support these conclusions, they cite three papers. However, other studies that do not substantiate their claims are not cited.
With respect to maternal-fetal transmission of HIV-1 during the first and second trimesters of pregnancy, studies have shown that the frequency of transmission during this period ranges from approximately 15 percent to 70 percent2-4. Although one might argue with the exact number, to give the impression that nothing is known in this regard is not consistent with the evidence. The second claim by Burgard et al., that the HIV-1 genome is absent in fetal tissues, is also not supported by the literature. We4,5 and others3,6 have demonstrated that HIV-1 DNA can be detected in human fetal tissues before 24 weeks of gestation.
The authors imply strongly that their findings, in conjunction with other studies, indicate that maternal-fetal transmission of HIV-1 occurs at birth. However, neither in utero nor peripartum transmission can be excluded on the basis of their data. Until there is definitive knowledge of when and how vertical transmission occurs, it is of the utmost importance to strategies for care and treatment that all available evidence be considered.
6 ReferencesWilliam D. Lyman, Ph.D.
Ruy Soeiro, M.D.
Arye Rubinstein, M.D.
Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 104611
Burgard M ,Mayaux M-J ,Blanche S , et al. The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. N Engl J Med 1992;327:1192-1197
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European Collaborative Study
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Courgnaud V ,Laure F ,Brossard A , et al. Frequent and early in utero HIV-1 infection. AIDS Res Hum Retroviruses 1991;7:337-341
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Soeiro R ,Rubinstein A ,Rashbaum WK ,Lyman WD . Maternofetal transmission of AIDS: frequency of human immunodeficiency virus type 1 nucleic acid sequences in human fetal DNA. J Infect Dis 1992;166:699-703
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Lyman WD ,Kress Y ,Kure K ,Rashbaum WK ,Rubinstein A ,Soeiro R . Detection of HIV in fetal central nervous system tissue. AIDS 1990;4:917-920
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Mano H ,Chermann JC . Fetal human immunodeficiency virus type 1 infection of different organs in the second trimester. AIDS Res Hum Retroviruses 1991;7:83-88
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To the Editor:
Burgard and colleagues suggest that the diagnosis of vertically acquired HIV infection can be made at birth with the use of viral culture in 48 percent of the cases. This rate is slightly higher than that observed in two previous studies1,2. Using viral culture and the polymerase chain reaction (PCR) in a prospective study started in January 1990, we identified at birth 5 children with infection among 16 (31 percent) who were positive by four to nine weeks of age1. More recently, De Rossi et al. detected 4 children with infection at birth among 11 positive children (36 percent), using the same techniques2. The detection of HIV-1 proviral DNA in mononuclear cells with PCR has been shown to be as sensitive as viral culture in the diagnosis of perinatal HIV-1 infection1-4. In the study of Burgard et al., it would have been interesting to perform both tests to see whether the higher rate of detection at birth was due to a greater sensitivity of these authors' viral-culture technique.
4 ReferencesAnne Krivine, M.D.
Pierre Lebon, M.D.
Hopital Saint-Vincent de Paul, 75014 Paris, France1
Krivine A ,Firtion G ,Cao L ,Francoual C ,Henrion R ,Lebon P . HIV replication during the first weeks of life. Lancet 1992;339:1187-1189
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De Rossi A ,Ometto L ,Mammano F ,Zanotto C ,Giaquinto C ,Chieco-Bianchi L . Vertical transmission of HIV-1: lack of detectable virus in peripheral blood cells of infected children at birth. AIDS 1992;6:1117-1120
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Krivine A ,Yakudima A ,LeMay 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
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Borkowsky W ,Krasinski K ,Pollack H ,Hoover W ,Kaul A ,Ilmet-Moore T . Early diagnosis of human immunodeficiency virus infection in children <6 months of age: comparison of polymerase chain reaction, culture, and plasma antigen capture techniques. J Infect Dis 1992;166:616-619
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Author/Editor Response
The authors reply:
To the Editor: Drs. Krivine and Lebon suggest that our viral-culture technique may be more sensitive than PCR. In fact, our sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) is not significantly different from their figure of 31 percent (95 percent confidence interval, 8 to 54 percent; P = 0.27) or from the 36 percent obtained by De Rossi et al. (95 percent confidence interval, 8 to 64 percent; P = 0.75). The comparison of the confidence intervals for the three methods shows that the values are largely superimposable. Krivine and Lebon also propose that we compare our method with PCR. However, we consider serologic testing the gold standard for diagnosing HIV infection, and we believe that the results at 18 months are the best end point for determining the sensitivity of a diagnostic method in the neonatal period.
We agree with Dr. Lyman et al. that vertical transmission of HIV occurs either in utero or during delivery. Indeed, we stated that transmission late in pregnancy was one possibility. We think that the incidence of transmission in early pregnancy is probably low. In the study by Soeiro et al.,1 the viral genome was detected in 7 of 23 fetuses (30 percent). These results would suggest that all cases of vertical transmission occur in early pregnancy, since the rate of transmission is on the order of 16 to 30 percent2. The question thus arises, Why have several teams using PCR or viral culture failed to identify all infected infants at birth? The answer to this and other questions will be known only when the rates of vertical transmission of HIV have been determined in each of the potential periods -- early pregnancy, late pregnancy, and delivery.
2 ReferencesMarianne Burgard, M.D.
Hopital Necker-Enfants Malades, 75015 Paris, FranceMarie-Jeanne Mayaux, B.A.
Hopital de Bicetre, 94270 Kremlin-Bicetre, FranceChristine Rouzioux, Ph.D.
Hopital Necker-Enfants Malades, 75015 Paris, France1
Soeiro R ,Rubinstein A ,Rashbaum WK ,Lyman WD . Maternofetal transmission of AIDS: frequency of human immunodeficiency virus type 1 nucleic acid sequences in human fetal DNA. J Infect Dis 1992;166:699-703
CrossRef | Web of Science | Medline2
Maternal factors involved in mother-to-child transmission of HIV-1: report of a Consensus Workshop, Siena, Italy, January 17-18, 1992. J Acquir Immune Defic Syndr 1992;5:1019-1029
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