Correspondence
Mode of Delivery and the Risk of Vertical Transmission of HIV-1
N Engl J Med 1999; 341:205-207July 15, 1999
- Article
To the Editor:
The meta-analysis reported by the International Perinatal HIV Group (April 1 issue)1 provides convincing evidence that the risk of transmission of human immunodeficiency virus type 1 (HIV-1) may be further reduced by elective cesarean delivery in women who are receiving either no antiretroviral agents or zidovudine alone. The authors advise caution, pointing out the shortcomings of this analysis, including potential morbidity. They also note, as do Riley and Greene in their editorial,2 the lack of data on viral load and on women receiving highly active antiretroviral therapy.
We are concerned that the use of cesarean delivery may become the rule rather than the exception. At many centers, including ours, more than 80 percent of pregnant women infected with HIV are treated with highly active antiretroviral therapy, have undetected viral loads, and rarely transmit HIV to their infants. In addition, at least two groups of investigators have presented data on 137 HIV-infected women, without a single reported case of transmission among women receiving highly active antiretroviral therapy.3,4
In developing countries, the morbidity associated with cesarean section may preclude the safe use of this intervention, and the high rate of prematurity would further diminish its effectiveness. In Ribeirao Preto, Brazil, for example, a metropolitan area with many HIV-infected women, 41 percent of infants infected by HIV are delivered before 37 weeks' gestation, so prevention methods such as cesarean section at term would be ineffective. Among severely immunocompromised pregnant women — those most likely to transmit HIV — the rate of preterm delivery is 73 percent (unpublished data).
We believe cesarean section should not be performed for this indication, except in unusual circumstances — for example, when there is a lack of prenatal care, inadequate HIV therapy, or the failure of therapy to reduce the viral load. There remains no evidence that women receiving optimal treatment for HIV infection (highly active antiretroviral therapy) will benefit their infants by opting for cesarean delivery. It would be a travesty to repeat our experience with neonatal herpes, in which thousands of needless cesarean deliveries were performed, with associated morbidity and mortality and little or no benefit to the neonate.
4 ReferencesDaniel V. Landers, M.D.
Magee–Women's Hospital, Pittsburgh, PA 15213Geraldo Duarte, M.D.
School of Medicine of Ribeirao Preto of São Paulo University, 14049-900 Ribeirao Preto, Brazil1
The International Perinatal HIV Group
Full Text | Web of Science | Medline2
Riley LE ,Greene MF . Elective cesarean delivery to reduce the transmission of HIV. N Engl J Med 1999;340:1032-1033
Full Text | Web of Science | Medline3
Morris A, Zorrilla C, Vajaranant M, et al. A review of protease inhibitors (PI) use in 89 pregnancies. In: Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31–February 4, 1999.
4
Stek A, Khoury M, Kramer F, Homans J, Rother C, Kovacs A. Maternal and infant outcomes with highly active antiretroviral therapy during pregnancy. In: Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31–February 4, 1999.
To the Editor:
We agree that randomized studies of the role of routine elective cesarean delivery for HIV-infected women receiving combination antiretroviral therapy are not likely to be performed. Still, it is quite likely that a retrospective examination of the experience to date will be very relevant to clinical decision making regarding the mode of delivery for HIV-infected women.
Our preliminary data from three independent series of women receiving combination antiretroviral therapy during pregnancy have already been reported in the form of abstracts. Together, these three reports1-3 describe more than 180 HIV-exposed infants whose mothers received combination therapy during pregnancy and whose infection status is known. The mothers received routine obstetrical care. There was a single infected infant, delivered by cesarean section. In addition, there has been a case report of vertical transmission of multidrug-resistant virus.4 In both cases, the mothers had received antiretroviral therapy but with low adherence to the regimen and incomplete suppression of maternal plasma HIV-1 RNA.
Providing comprehensive perinatal and HIV care, which includes access to state-of-the-art HIV therapies, is not easy, nor is it inexpensive. It requires considerable coordination among public health, obstetrical, pediatric, and medical services; intensive monitoring of viral replication; and extensive counseling, education, and social support, along with ongoing funding for expensive combination antiretroviral therapies. In contrast, zidovudine monotherapy coupled with elective abdominal delivery appears to be a comparatively simple intervention. However, our collective experience suggests that, regardless of the route of delivery, optimal and aggressive treatment of maternal HIV disease (which will almost certainly result in prolonged maternal survival and improved maternal health) may reduce rates of vertical transmission to levels below those associated with elective cesarean section used with zidovudine prophylaxis alone.
4 ReferencesKaren P. Beckerman, M.D.
University of California, San Francisco, San Francisco, CA 94141-9100Anne B. Morris, M.D.
Baystate Medical Center, Springfield, MA 01199Alice Stek, M.D.
University of Southern California School of Medicine, Los Angeles, CA 900331
Beckerman KP, Benson M, Dahud S, Shannon M, Wara D. Control of maternal HIV-1 disease during pregnancy. In: Conference supplement of the 12th World AIDS Conference, Geneva, June 28–July 3, 1998:41. abstract.
2
Morris A, Zorrilla C, Vajaranant M, et al. A review of protease inhibitors (PI) use in 89 pregnancies. In: Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31–February 4, 1999.
3
Stek A, Khoury M, Kramer F, Homans J, Rother C, Kovacs A. Maternal and infant outcomes with highly active antiretroviral therapy during pregnancy. In: Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31–February 4, 1999.
4
Johnson VA, Woods C, Hamilton CD, Fiscus SA. Vertical transmission of an HIV-1 variant resistant to multiple reverse transcriptase and protease inhibitors. In: Abstracts of the 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31–February 4, 1999.
To the Editor:
The definition of elective cesarean section used in the meta-analysis by the International Perinatal HIV Group could lead to overly optimistic estimates of the treatment effect associated with this intervention. Specifically, elective cesarean section was performed before the rupture of membranes and the onset of labor. However, infants born prematurely are at higher risk for HIV infection than infants born at term.1 Therefore, the risk of transmission was higher for women who had an early onset of labor (which precluded their classification as candidates for elective cesarean section) than for women whose pregnancies were maintained long enough for them to be candidates for elective cesarean section in the 15 cohorts included in the meta-analysis. Among the women in the meta-analysis who received prenatal and intrapartum antiretroviral therapy and whose infants received antiretroviral therapy, much or all of the observed difference between a 2.0 percent rate of transmission (4 HIV-1–infected children of a total of 196) for elective cesarean section and a 7.3 percent rate of transmission (92 HIV-1–infected children of a total of 1255) for other known modes of delivery could be due to the bias associated with the exclusion of premature births from the elective-cesarean-section group.
Only by conducting a randomized trial or at least declaring early during pregnancy the intention to perform an elective cesarean section and analyzing the results according to this declaration (as is being done in the ongoing Pediatric AIDS Clinical Trials Group Study 316) can one control this bias.
1 ReferencesRichard D. Gelber, Ph.D.
David E. Shapiro, Ph.D.
Harvard School of Public Health, Boston, MA 021151
Simonds RJ ,Steketee R ,Nesheim S , et al. Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV. AIDS 1998;12:301-308
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Read replies:
To the Editor: Drs. Gelber and Shapiro suggest that our definition of elective cesarean section could have resulted in an overestimate of the effect of this intervention because preterm births were excluded from the elective-cesarean-section group. Our logistic-regression analyses indicated that the association between vertical transmission and elective cesarean section did not differ between term and preterm infants, and the inclusion of gestational age in the final model did not alter our findings. As we noted in our report, an intention-to-treat analysis was not possible. However, a recent randomized clinical trial demonstrated an even lower risk of transmission among women assigned to undergo elective cesarean section.1
Our results indicate that the risk of vertical transmission is higher among women in whom labor begins, membranes rupture, or both events occur before the cesarean section is performed. Drs. Landers and Duarte suggest that this intervention should be considered only in unusual circumstances, as when there is a lack of prenatal care. However, women without prenatal care often present in labor, which precludes an elective cesarean section as we defined it.
As we noted, the potential risks associated with elective cesarean section in less developed countries could outweigh the potential benefit. Such risks include neonatal morbidity and mortality related to preterm birth in settings where the gestational age cannot be assessed accurately or routinely.
Drs. Landers and Duarte and Dr. Beckerman and colleagues reiterate issues that we acknowledged our study could not address. The role of elective cesarean section should continue to be evaluated as new information, including more precise estimates of the risk of vertical transmission among HIV-infected women receiving combination antiretroviral therapy, becomes available. Recent data suggest that the effect of elective cesarean section persists even among women with low viral loads.2
One must weigh the risks and benefits of any intervention. Although operative delivery is associated with risks, it is important to quantify their incidence and severity. There were few complications and no serious adverse events after elective procedures among HIV-infected women in a large European trial.1 Along with the benefits, the potential problems associated with combination therapy will need to be considered, including the problem of adherence to relatively complex therapeutic regimens, the development of viral resistance, and the uncertain short- and long-term safety of therapy for the fetus and infant.3 HIV-infected pregnant women deserve the opportunity to make informed decisions about all the potential interventions, including elective cesarean section, to prevent vertical transmission.
3 ReferencesJennifer S. Read, M.D., M.P.H.
National Institute of Child Health and Human Development, Bethesda, MD 20892for the International Perinatal HIV Group
1
The European Mode of Delivery Collaboration
CrossRef | Web of Science | Medline2
The European Collaborative Study. Maternal viral load and vertical transmission of HIV-1: an important factor but not the only one. AIDS (in press).
3
Lorenzi P ,Spicher VM ,Laubereau B , et al. Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. AIDS 1998;12:F241-F247
CrossRef | Web of Science | Medline
- Citing Articles (9)
Citing Articles
1
Tessa Goetghebuer, Edwige Haelterman, Isabelle Marvillet, Patricia Barlow, Marc Hainaut, Assaad Salameh, Roberta Ciardelli, Michele Gerard, Jack Levy. (2009) Vertical transmission of HIV in Belgium: a 1986–2002 retrospective analysis. European Journal of Pediatrics 168:1, 79-85
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Marisa T. GILLES, Jan E. DICKINSON, Alison CAIN, Kate A. TURNER, Rosemary MCGUCKIN, Richard LOH, Susan L. PRESCOTT, Martyn A. FRENCH. (2007) Perinatal HIV transmission and pregnancy outcomes in indigenous women in Western Australia. Australian and New Zealand Journal of Obstetrics and Gynaecology 47:5, 362-367
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(2005) Mother-to-Child Transmission of HIV Infection in the Era of Highly Active Antiretroviral Therapy. Clinical Infectious Diseases 40:3, 458-465
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Ana Ceballos, Guadalupe Andreani, Silvia E. Gonzalez Ayala, Yamila Romer, Isabel Rimoldi, María Rosa Agosti, Liliana Martinez Peralta. (2004) Epidemiological and Molecular Evidence of Two Events of Father-to-Child HIV Type 1 Horizontal Transmission. AIDS Research and Human Retroviruses 20:8, 789-793
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Leslie E. Wolf, Bernard Lo, Lawrence O. Gostin. (2004) Legal Barriers to Implementing Recommendations for Universal, Routine Prenatal HIV Testing. The Journal of Law, Medicine & Ethics 32:1, 137-147
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Ana Ceballos, María de Los Angeles Pando, Diana Liberatore, Mirna Biglione, Patricia Coll Cárdenas, Marina Martínez, María Luisa Celadilla, María M. Avila, Liliana Martínez Peralta. (2002) Efficacy of Strategies to Reduce Mother-to-Child HIV-1 Transmission in Argentina, 1993–2000. JAIDS Journal of Acquired Immune Deficiency Syndromes 31:3, 348-353
CrossRef7
Antonia L Moore, Sara Madge, Margaret A Johnson. (2002) HIV and pregnancy. The Obstetrician & Gynaecologist 4:4, 197-200
CrossRef8
MARY GLENN FOWLER. (2000) Prevention of Perinatal HIV Infection: What Do We Know? Where Should Future Research Go?. Annals of the New York Academy of Sciences 918:1, 45-52
CrossRef9
Mg Brook, Gp Taylor, A Dale, Egh Lyall, D Tomlinson. (2000) Management of HIV and pregnancy in England's North Thames Region 1999: a survey of practice in 21 hospitals. HIV Medicine 1:3, 143-147
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