Zidovudine administered to women infected with human immunodeficiency virus type 1 and to their neonates reduces pediatric infection independent of an effect on levels of maternal virus,☆☆,

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Abstract

Objective: To determine whether zidovudine, administered to reduce vertical transmission of human immunodeficiency virus type 1 (HIV-1), impacts the level of maternal viral DNA within the lymphocytes of infected pregnant women.

Study design: A prospective, nonrandomized study of 42 HIV-1 infected pregnant women. Nineteen women received zidovudine therapy to reduce HIV-1 perinatal transmission, and 23 were untreated. HIV-1 DNA was determined by polymerase chain reaction amplification of lymphocyte DNA from maternal blood samples obtained at the time of delivery. Treated and untreated, transmitting and nontransmitting groups were compared for clinical, virologic, and immunologic parameters with a t test or a Fisher Exact Test, and for copies of HIV-1 DNA per 10 6 CD4 + T cells with a Mann-Whitney rank sum test.

Results: Untreated pregnant women who transmitted HIV-1 to their infants had lower CD4 + T-cell counts and a greater degree of immune complex dissociated p24 antigenemia than did the untreated nontransmitting group ( p <0.01) but did not differ significantly with respect to age, race, or mode of delivery. The level of HIV-1 proviral DNA within lymphocytes was significantly greater in the untreated transmitting group than in the nontransmitting mothers ( p = 0.003). Zidovudine treatment resulted in a 78% decrease in maternal transmission ( p = 0.017). However, there was not a significant difference in DNA copy numbers in CD4 + T cells in the treated compared with the untreated groups.

Conclusion: Zidovudine reduces HIV-1 maternal transmission independent of its effect on the level of the maternal peripheral blood proviral load (J Pediatr 1997;130:906-14).

Section snippets

Subjects

Study subjects were 42 HIV-infected pregnant women who were enrolled between October 1989 and December 1995 in an ongoing study of HIV-1 genetic variability according to a protocol approved by the institutional review board of the University of Florida. Forty-one women were enrolled at the University of Florida in Gainesville and one at the University of South Florida in Tampa. Nineteen women in the study and their neonates received ZDV according to ACTG protocol 076, which was initiated in

Characteristics of study population

Clinical and demographic characteristics of the 42 individual women enrolled in the study are shown in Table I.

. Clinical data for the cohort of HIV-infected mothers

Patient No.AgeRaceTransmission statusCDC stageMode of deliveryp24 AgCD4 + /T cells/μlCD4/CD8 ratio
Untreated
56423BTA1VD8821.03
18423BTA1VD7500.67
21117BTA1VD+3960.43
56719WTA1VD5500.54
05127BTC3VD+2960.28
25029BTC3VD+390.07
140031HTA2VD+680.07
40230BTC3CD+70.03
55932BTC3CD+1330.12
31326BTC3VD+1020.12
17929BTC3VD380.01
56623BNTA1VD9951.33
369

DISCUSSION

In the absence of antiviral therapy for HIV-1 infected mothers and their infants, a significant relationship between maternal immunologic and virologic parameters and the risk of HIV-1 infection for the infant was detected in our study. An increased likelihood of transmission within our cohort of untreated HIV-1 infected women was inversely related to maternal CD4 + T-cell counts and CD4/CD8 ratios and was directly associated with levels of HIV-1 DNA copies found in CD4 + T cells in maternal

Acknowledgements

The 8E5 cell line was received from Dr. Thomas Folks through the National Institute of Allergy and Infectious Diseases AIDS Research and Reference Reagent Program. We are grateful to Drs. Robert Nelson and Patricia Emmanuel for providing maternal samples, to Cynthia Anders for plasma virus determinations, to Mabel Rojas for sample preparation, and to Dr. David Burchfield for his helpful discussion.

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    0022-3476/97/$5.00 + 0 9/21/79178

    ☆☆

    Supported by Public Health Service award HD32259 from the National Institute of Child Health and Human Development (Drs. Goodenow and Sleasman), by Pediatric AIDS Foundation award 50335-14-PG (Dr. Sleasman), by the Children's Miracle Network, and by the Conselho Nacional de Desenvolvimento Cientfaifico e Tecnológico (CNPq) award 202732-91-6 of Brazil (Dr. Aleixo).

    Reprint requests: John W. Sleasman, MD, University of Florida College of Medicine, Box 100296, Room R1-118, 1600 SW Archer Rd., Gainesville, FL 32610.

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