Maternal Levels of Plasma Human Immunodeficiency Virus Type 1 RNA and the Risk of Perinatal Transmission
Patricia M. Garcia, M.D., M.P.H., Leslie A. Kalish, D.Sc., Jane Pitt, M.D., Howard Minkoff, M.D., Thomas C. Quinn, M.D., Sandra K. Burchett, M.D., Janet Kornegay, Ph.D., Brooks Jackson, M.D., John Moye, M.D., Celine Hanson, M.D., Carmen Zorrilla, M.D., Judy F. Lew, M.D., for The Women and Infants Transmission Study Group
Background The importance of plasma levels of human immunodeficiencyvirus type 1 (HIV-1) RNA in pregnant women in relation to theother factors known to influence the risk of transmission ofinfection to their infants is incompletely defined. We studiedthe relation of maternal plasma HIV-1 RNA levels to the riskof perinatal transmission and the timing of transmission.
Methods We measured plasma HIV-1 RNA serially in 552 women withHIV-1 infection who had singleton pregnancies. The status ofinfection in their infants was assessed by culture of bloodand further classified as early (if a culture of blood obtainedwithin the first two days of life was positive) or late (ifa culture of blood obtained in the first seven days of lifewas negative but subsequent cultures were positive). The ratesof transmission at various levels of maternal plasma HIV-1 RNAwere analyzed by tests for trend, with adjustment for covariatesby stratification and logistic regression.
Results Increasing geometric mean levels of plasma HIV-1 RNAwere associated with increasing rates of transmission: the ratewas 0 percent among women with less than 1000 copies per milliliter(0 of 57), 16.6 percent among women with 1000 to 10,000 copiesper milliliter (32 of 193), 21.3 percent among women with 10,001to 50,000 copies per milliliter (39 of 183), 30.9 percent amongwomen with 50,001 to 100,000 copies per milliliter (17 of 54),and 40.6 percent among women with more than 100,000 copies permilliliter (26 of 64, P<0.001). The treatment status of onewoman was unknown. The highest rate of transmission was amongwomen whose plasma HIV-1 RNA levels exceeded 100,000 copiesper milliliter and who had not received zidovudine (19 of 30women, 63.3 percent). Neither higher HIV-1 RNA levels earlyin pregnancy nor higher levels late in pregnancy were associatedwith the timing of infection in the infants.
Conclusions In pregnant women with HIV-1 infection, the levelof plasma HIV-1 RNA predicts the risk but not the timing oftransmission of HIV-1 to their infants.
Source Information
From the Department of Obstetrics and Gynecology, Northwestern University, Chicago (P.M.G.); New England Research Institutes, Watertown, Mass. (L.A.K.); the Department of Pediatrics, Columbia College of Physicians and Surgeons, New York (J.P.); the Department of Obstetrics and Gynecology, State University of New York Health Science Center, Brooklyn (H.M.); Johns Hopkins University, Baltimore (T.C.Q., B.J.); the National Institute of Allergy and Infectious Diseases, Bethesda, Md. (T.C.Q., J.F.L.); the Department of Pediatrics, Harvard Medical School, Boston (S.K.B.); Roche Molecular Systems, Alameda, Calif. (J.K.); the National Institute of Child Health and Human Development, Bethesda, Md. (J.M.); the Section of Allergy and Immunology, Baylor College of Medicine, Houston (C.H.); and the Department of Obstetrics and Gynecology, University of Puerto Rico, San Juan (C.Z.). Presented in part at the meeting of the Society of Perinatal Obstetricians, Miami, February 5, 1998.
Address reprint requests to Dr. Garcia at Rm. 410, Prentice Women's Hospital, 333 E. Superior St., Chicago, IL 60611, or at p-garcia{at}nwu.edu.
Pandrea, I., Onanga, R., Souquiere, S., Mouinga-Ondeme, A., Bourry, O., Makuwa, M., Rouquet, P., Silvestri, G., Simon, F., Roques, P., Apetrei, C.
(2008). Paucity of CD4+ CCR5+ T Cells May Prevent Transmission of Simian Immunodeficiency Virus in Natural Nonhuman Primate Hosts by Breast-Feeding. J. Virol.
82: 5501-5509
[Abstract][Full Text]
Babaahmady, K., Oehlmann, W., Singh, M., Lehner, T.
(2007). Inhibition of Human Immunodeficiency Virus Type 1 Infection of Human CD4+ T Cells by Microbial HSP70 and the Peptide Epitope 407-426. J. Virol.
81: 3354-3360
[Abstract][Full Text]
Ayele, W., Schuurman, R., Messele, T., Dorigo-Zetsma, W., Mengistu, Y., Goudsmit, J., Paxton, W. A., de Baar, M. P., Pollakis, G.
(2007). Use of Dried Spots of Whole Blood, Plasma, and Mother's Milk Collected on Filter Paper for Measurement of Human Immunodeficiency Virus Type 1 Burden. J. Clin. Microbiol.
45: 891-896
[Abstract][Full Text]
Drake, A. L., John-Stewart, G. C., Wald, A., Mbori-Ngacha, D. A., Bosire, R., Wamalwa, D. C., Lohman-Payne, B. L., Ashley-Morrow, R., Corey, L., Farquhar, C.
(2007). Herpes Simplex Virus Type 2 and Risk of Intrapartum Human Immunodeficiency Virus Transmission. Obstet Gynecol
109: 403-409
[Abstract][Full Text]
Manigart, Y., Rozenberg, S., Barlow, P., Gerard, M., Bertrand, E., Delvigne, A.
(2006). ART outcome in HIV-infected patients. Hum Reprod
21: 2935-2940
[Abstract][Full Text]
Benatar, D.
(2006). Reproductive freedom and risk. Hum Reprod
21: 2491-2493
[Abstract][Full Text]
Parry, S., Zhang, J., Koi, H., Arechavaleta-Velasco, F., Elovitz, M. A.
(2006). Transcytosis of Human immunodeficiency virus 1 across the placenta is enhanced by treatment with tumour necrosis factor alpha.. J. Gen. Virol.
87: 2269-2278
[Abstract][Full Text]
Wilson, N. A., Reed, J., Napoe, G. S., Piaskowski, S., Szymanski, A., Furlott, J., Gonzalez, E. J., Yant, L. J., Maness, N. J., May, G. E., Soma, T., Reynolds, M. R., Rakasz, E., Rudersdorf, R., McDermott, A. B., O'Connor, D. H., Friedrich, T. C., Allison, D. B., Patki, A., Picker, L. J., Burton, D. R., Lin, J., Huang, L., Patel, D., Heindecker, G., Fan, J., Citron, M., Horton, M., Wang, F., Liang, X., Shiver, J. W., Casimiro, D. R., Watkins, D. I.
(2006). Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239.. J. Virol.
80: 5875-5885
[Abstract][Full Text]
Rychert, J., Lacour, N., Amedee, A. M.
(2006). Genetic Analysis of Simian Immunodeficiency Virus Expressed in Milk and Selectively Transmitted through Breastfeeding.. J. Virol.
80: 3721-3731
[Abstract][Full Text]
Chen, K. T., Segu, M., Lumey, L. H., Kuhn, L., Carter, R. J., Bulterys, M., Abrams, E. J., for the New York City Perinatal AIDS Collaborative,
(2005). Genital Herpes Simplex Virus Infection and Perinatal Transmission of Human Immunodeficiency Virus. Obstet Gynecol
106: 1341-1348
[Abstract][Full Text]
Riley, L. E., Yawetz, S.
(2005). Case records of the Massachusetts General Hospital. Case 32-2005. A 34-year-old HIV-positive woman who desired to become pregnant.. NEJM
353: 1725-1732
[Full Text]
Chou, R., Smits, A. K., Huffman, L. H., Fu, R., Korthuis, P. T.
(2005). Prenatal Screening for HIV: A Review of the Evidence for the U.S. Preventive Services Task Force. ANN INTERN MED
143: 38-54
[Abstract][Full Text]
Scott, G. B.
(2005). Perinatal Exposure to Antiretroviral Agents: Risks and Benefits. Am. J. Neuroradiol.
26: 689-692
[Full Text]
Sudhakaran, S., Ghabrial, H., Nation, R. L., Kong, D. C. M., Gude, N. M., Angus, P. W., Rayner, C. R.
(2005). Differential Bidirectional Transfer of Indinavir in the Isolated Perfused Human Placenta. Antimicrob. Agents Chemother.
49: 1023-1028
[Abstract][Full Text]
Nettles, R. E., Kieffer, T. L., Kwon, P., Monie, D., Han, Y., Parsons, T., Cofrancesco, J. Jr, Gallant, J. E., Quinn, T. C., Jackson, B., Flexner, C., Carson, K., Ray, S., Persaud, D., Siliciano, R. F.
(2005). Intermittent HIV-1 Viremia (Blips) and Drug Resistance in Patients Receiving HAART. JAMA
293: 817-829
[Abstract][Full Text]
Ling, B., Apetrei, C., Pandrea, I., Veazey, R. S., Lackner, A. A., Gormus, B., Marx, P. A.
(2004). Classic AIDS in a Sooty Mangabey after an 18-Year Natural Infection. J. Virol.
78: 8902-8908
[Abstract][Full Text]
Havens, P. L., Committee on Pediatric AIDS,
(2003). Postexposure Prophylaxis in Children and Adolescents for Nonoccupational Exposure to Human Immunodeficiency Virus. Pediatrics
111: 1475-1489
[Abstract][Full Text]
Peters, V., Liu, K.-L., Dominguez, K., Frederick, T., Melville, S., Hsu, H.-W., Ortiz, I., Rakusan, T., Gill, B., Thomas, P.
(2003). Missed Opportunities for Perinatal HIV Prevention Among HIV-Exposed Infants Born 1996-2000, Pediatric Spectrum of HIV Disease Cohort. Pediatrics
111: 1186-1191
[Abstract][Full Text]
Minkoff, H.
(2003). Human Immunodeficiency Virus Infection in Pregnancy. Obstet Gynecol
101: 797-810
[Abstract][Full Text]
Andreoletti, L., Gresenguet, G., Chomont, N., Matta, M., Quiniou, Y., Si-Mohamed, A., Belec, L.
(2003). Comparison of Washing and Swabbing Procedures for Collecting Genital Fluids To Assess Shedding of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in Asymptomatic HIV-1-Infected Women. J. Clin. Microbiol.
41: 449-452
[Abstract][Full Text]
DeVange Panteleeff, D., Emery, S., Richardson, B. A., Rousseau, C., Benki, S., Bodrug, S., Kreiss, J. K., Overbaugh, J.
(2002). Validation of Performance of the Gen-Probe Human Immunodeficiency Virus Type 1 Viral Load Assay with Genital Swabs and Breast Milk Samples. J. Clin. Microbiol.
40: 3929-3937
[Abstract][Full Text]
(2002). HIV in Women: An Update. AIDS Clin Care
2002: 1-1
[Full Text]
Dybul, M., Fauci, A. S., Bartlett, J. G., Kaplan, J. E., Pau, A. K.
(2002). Guidelines for Using Antiretroviral Agents among HIV-Infected Adults and Adolescents: The Panel on Clinical Practices for Treatment of HIV. ANN INTERN MED
137: 381-433
[Abstract][Full Text]
Tang, J., Tang, S., Lobashevsky, E., Myracle, A. D., Fideli, U., Aldrovandi, G., Allen, S., Musonda, R., Kaslow, R. A.
(2002). Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1. J. Virol.
76: 8276-8284
[Abstract][Full Text]
Watts, D. H.
(2002). Management of Human Immunodeficiency Virus Infection in Pregnancy. NEJM
346: 1879-1891
[Full Text]
Katz, M. H., Schwarcz, S. K., Kellogg, T. A., Klausner, J. D., Dilley, J. W., Gibson, S., McFarland, W.
(2002). Impact of Highly Active Antiretroviral Treatment on HIV Seroincidence Among Men Who Have Sex With Men: San Francisco. Am. J. Public Health
92: 388-394
[Abstract][Full Text]
Bucceri, A.M., Somigliana, E., Matrone, R., Ferraris, G., Rossi, G., Grossi, E., Vignali, M.
(2002). Combination antiretroviral therapy in 100 HIV-1-infected pregnant women. Hum Reprod
17: 436-441
[Abstract][Full Text]
Tang, J., Shelton, B., Makhatadze, N. J., Zhang, Y., Schaen, M., Louie, L. G., Goedert, J. J., Seaberg, E. C., Margolick, J. B., Mellors, J., Kaslow, R. A.
(2002). Distribution of Chemokine Receptor CCR2 and CCR5 Genotypes and Their Relative Contribution to Human Immunodeficiency Virus Type 1 (HIV-1) Seroconversion, Early HIV-1 RNA Concentration in Plasma, and Later Disease Progression. J. Virol.
76: 662-672
[Abstract][Full Text]
Wolf, L. E., Lo, B., Beckerman, K. P., Dorenbaum, A., Kilpatrick, S. J., Weintrub, P. S.
(2001). When Parents Reject Interventions to Reduce Postnatal Human Immunodeficiency Virus Transmission. Arch Pediatr Adolesc Med
155: 927-933
[Abstract][Full Text]
Englert, Y., Van Vooren, J.-P., Place, I., Liesnard, C., Laruelle, C., Delbaere, A.
(2001). ART in HIV-infected couples: Has the time come for a change of attitude?. Hum Reprod
16: 1309-1315
[Abstract][Full Text]
Lo, J. C., Schambelan, M.
(2001). Reproductive Function in Human Immunodeficiency Virus Infection. J. Clin. Endocrinol. Metab.
86: 2338-2343
[Full Text]
de Baar, M. P., Timmermans, E. C., Bakker, M., de Rooij, E., van Gemen, B., Goudsmit, J.
(2001). One-Tube Real-Time Isothermal Amplification Assay To Identify and Distinguish Human Immunodeficiency Virus Type 1 Subtypes A, B, and C and Circulating Recombinant Forms AE and AG. J. Clin. Microbiol.
39: 1895-1902
[Abstract][Full Text]
Gayle, H. D., Hill, G. L.
(2001). Global Impact of Human Immunodeficiency Virus and AIDS. Clin. Microbiol. Rev.
14: 327-335
[Abstract][Full Text]
de Baar, M. P., van Dooren, M. W., de Rooij, E., Bakker, M., van Gemen, B., Goudsmit, J., de Ronde, A.
(2001). Single Rapid Real-Time Monitored Isothermal RNA Amplification Assay for Quantification of Human Immunodeficiency Virus Type 1 Isolates from Groups M, N, and O. J. Clin. Microbiol.
39: 1378-1384
[Abstract][Full Text]
Shetty, A. K., Maldonado, Y.
(2001). Preventing Mother-to-Child Transmission of HIV-1: An International Perspective. NeoReviews
2: e75-82
[Full Text]
Shetty, A. K., Maldonado, Y.
(2001). HIV transmission Prevention of Perinatal HIV-1 Transmission in the United States. NeoReviews
2: e83-93
[Full Text]
Shetty, A. K., Maldonado, Y.
(2001). Changing Epidemiology of Perinatal HIV-1 Infection in the United States. NeoReviews
2: e94-99
[Full Text]
Dickover, R. E., Garratty, E. M., Plaeger, S., Bryson, Y. J.
(2001). Perinatal Transmission of Major, Minor, and Multiple Maternal Human Immunodeficiency Virus Type 1 Variants In Utero and Intrapartum. J. Virol.
75: 2194-2203
[Abstract][Full Text]
CHEN, K. T., SELL, R. L., TUOMALA, R. E.
(2001). Cost-Effectiveness of Elective Cesarean Delivery in Human Immunodeficiency Virus-Infected Women. Obstet Gynecol
97: 161-168
[Abstract][Full Text]
Behbahani, H., Popek, E., Garcia, P., Andersson, J., Spetz, A.-L., Landay, A., Flener, Z., Patterson, B. K.
(2000). Up-Regulation of CCR5 Expression in the Placenta Is Associated with Human Immunodeficiency Virus-1 Vertical Transmission. Am. J. Pathol.
157: 1811-1818
[Abstract][Full Text]
Mofenson, L. M., the Committee on Pediatric AIDS,
(2000). Technical Report: Perinatal Human Immunodeficiency Virus Testing and Prevention of Transmission. Pediatrics
106: 88e-88
[Abstract][Full Text]
McGowan, J. P., Shah, S. S.
(2000). Prevention of perinatal HIV transmission during pregnancy. J Antimicrob Chemother
46: 657-668
[Abstract][Full Text]
Barouch, D. H., Santra, S., Schmitz, J. E., Kuroda, M. J., Fu, T.-M., Wagner, W., Bilska, M., Craiu, A., Zheng, X. X., Krivulka, G. R., Beaudry, K., Lifton, M. A., Nickerson, C. E., Trigona, W. L., Punt, K., Freed, D. C., Guan, L., Dubey, S., Casimiro, D., Simon, A., Davies, M.-E., Chastain, M., Strom, T. B., Gelman, R. S., Montefiori, D. C., Lewis, M. G., Emini, E. A., Shiver, J. W., Letvin, N. L.
(2000). Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination. Science
290: 486-492
[Abstract][Full Text]
Luzuriaga, K., McManus, M., Catalina, M., Mayack, S., Sharkey, M., Stevenson, M.
(2000). Early Therapy of Vertical Human Immunodeficiency Virus Type 1 (HIV-1) Infection: Control of Viral Replication and Absence of Persistent HIV-1-Specific Immune Responses. J. Virol.
74: 6984-6991
[Abstract][Full Text]
Hu, J., Gardner, M. B., Miller, C. J.
(2000). Simian Immunodeficiency Virus Rapidly Penetrates the Cervicovaginal Mucosa after Intravaginal Inoculation and Infects Intraepithelial Dendritic Cells. J. Virol.
74: 6087-6095
[Abstract][Full Text]
Visconti, E., Celentano, L. P., Tamburrini, E., Villa, P., Oliva, G., Genovese, O., Fundaro, C., McGowan, J. P., Crane, M., Wiznia, A. A., Blum, S.
(2000). COMBINATION ANTIRETROVIRAL THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PREGNANT WOMEN. Obstet Gynecol
95: 636-637
[Full Text]
Quinn, T. C., Wawer, M. J., Sewankambo, N., Serwadda, D., Li, C., Wabwire-Mangen, F., Meehan, M. O., Lutalo, T., Gray, R. H., The Rakai Project Study Group,
(2000). Viral Load and Heterosexual Transmission of Human Immunodeficiency Virus Type 1. NEJM
342: 921-929
[Abstract][Full Text]
De Cock, K. M., Fowler, M. G., Mercier, E., de Vincenzi, I., Saba, J., Hoff, E., Alnwick, D. J., Rogers, M., Shaffer, N.
(2000). Prevention of Mother-to-Child HIV Transmission in Resource-Poor Countries: Translating Research Into Policy and Practice. JAMA
283: 1175-1182
[Abstract][Full Text]
(1999). Prevention of Perinatal HIV Infection: Cause For Optimism. AIDS Clin Care
1999: 1-1
[Full Text]
Ioannidis, J. P.A., Contopoulos-Ioannidis, D. G., Mofenson, L. M., Lambert, J. S., Stiehm, E. R., Garcia, P. M., Moye, J., Lew, J. F.
(1999). Maternal Viral Load and the Risk of Perinatal Transmission of HIV-1. NEJM
341: 1698-1700
[Full Text]
(1999). Viral Load and Perinatal Transmission. AIDS Clin Care
1999: 3-3
[Full Text]