Abstract
Humoral immunity is thought to play an important role in the natural history of HIV infection. It has been hypothesised that the presence of high titre neutralising antibody may protect against the maternal-fetal transmission of HIV-1 infection. HIV-Ig is a passive antibody preparation consisting of highly purified immune globulin containing high titres of antibody to HIV structural proteins. It contains considerable functional antibody in virus neutralisation and antibody dependent cytotoxicity assays. This product (and others) have undergone extensive investigation in preclinical (in vitro and animal models) and clinical trials. In a randomised, double-blind trial, pregnant women with HIV infection who were receiving antiretroviral therapy received either HIV-Ig or control intravenous Ig. While transmission rate was 5 to 6% in both treatment and control arms (sample size was too small to show a difference), infected infants who received HIV-Ig had a delayed time to culture positivity versus those receiving intravenous Ig, suggesting that HIV-Ig may have the ability to modify disease but not prevent infection. While this study did not prove an effect of HIV-Ig it did prove an effect of antiretroviral therapy in a population of women with prior zidovudine experience. Passive antibody preparations (HIV-Ig and monoclonal antibodies) may have the potential to decrease perinatal transmission in combination with antiretroviral agents, to levels less than 5%. Special niches where immunoglobulins and HIV vaccines may play a role, include treatment of infants born to women who do not receive prenatal care, or where the diagnosis of HIV in mother and infant is made only following delivery: a post-exposure prophylaxis strategy.
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References
United Nations Development Programme. Young women: silence, susceptibility and the HIV epidemic. Pediatr AIDS HIV Infection 1994; 5: 1–9
European Collaborative Study: Risk factors for mother-to-child transmission of HIV-1. Lancet 1992; 339: 1007
Gabiano C, Tovo PA, de Martino M, et al. Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission. Pediatrics 1992; 90: 369
Goedert JJ, Mendez H, Drummond JE, et al. Mother-to-infant transmission of human immunodeficiency virus type 1: association with prematurity or low anti-gp120. Lancet 1989; 2: 1351–4
Lindgren S, Angen B, Bohlin A, et al. HIV and child-bearing: clinical outcome and aspects of mother-to-infants transmission. AIDS 1991; 5: 1111
Blanche S, Mayaux MJ, Rouzioux C, et al: Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery. N Engl J Med 1994; 330: 308
Rouzioux C, Costagliola D, Burgard M, et al. Timing of mother-to-child HIV-1 transmission depends on maternal status. AIDS 1993; 7Suppl. 2: S49–52
St Louis M, Kamenga M, Brown C, et al. Risk for perinatal HIV-1 transmission according to maternal immunologic, virologic, and placental factors. JAMA 1993; 269: 2853
Tovo P, Martino M, Gabiano C, et al. Prognostic factors and survival in children with perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 1996; 11: 84
Lepage P, Msellati P, Van de Perre P, et al. Mother-to-child transmission of human immunodeficiency virus type 1 and its determinants. A cohort study in Kigali, Rwanda. Am J Epidemiol 1993; 137: 589
Abrams EJ, Matheson P, Thomas P, et al. Neonatal predictors of infection status and early death among 322 infants at risk of HIV-1 infection monitored prospectively from birth. Pediatrics 1995; 96: 451
Thea DM, Steketee RW, Pliner V, et al. The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group. AIDS 1997 March; 11(4): 437–44
Contopoulos-Ioannidis DG, Ioannidis JPA. Maternal cell-free viremia in the natural history of perinatal HIV-1 transmission: a meta-analysis. J Acquir Immune Defic Syndr Hum Retrovirol 1998 Jun; 18(2): 126–35
Nair P, Alger L, Hines S, et al. Maternal and neonatal characteristics associated with HIV infection in infants of seropositive women. J Acquir Immune Defic Syndr Hum Retrovirol 1993; 6: 298
Burns DN, Landesman S, Muenz LR, et al. Cigarette smoking, premature rupture of membranes and vertical transmission of HIV-1 among women with low CD4+ levels. J Acquir Immune Defic Syndr 1994; 7: 718
Landesman SH, Kalish LA, Burns DN, et al. Obstetrical factors and the transmission of human immunodeficiency virus type 1 from mother to child. N Engl J Med 1996; 334: 1617
Mandelbrot L, Mayaux MJ, Bongain A, et al. Obstetrical factors and mother-to-child transmission of HIV-1. Am J Obstet Gynecol 1996; 175: 661
Minkoff H, Burns DN, Landesman S, et al. The relationship of the duration of ruptured membranes to vertical transmission of HIV. Am J Obstet Gynecol 1995; 173: 585
Dunn DT, Newell M, Mayaux MJ, et al. Mode of delivery and vertical transmission of HIV-1: A review of prospective studies. J Acquir Immune Defic Syndr 1994; 7: 1064
Thomas P, Weedon J, Krasinki K, et al. Maternal predictors of perinatal human immunodeficiency virus transmission. Pediatr Infect Dis J 1994; 13: 489
Semba RD, Miotti PG, Chiphangwi JD, et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 1994; 343: 1593
Bulterys M, Chao A, Dushimimana A, et al. Multiple sexual partners and mother-to-child transmission of HIV-1. AIDS 1993; 7: 1639
Beasley RP, Hwang LY, Stevens CE, et al. Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of hepatitis B virus carrier state: final report of a randomized, double-blind, placebo-controlled trial. Hepatology 1983; 3: 135–41
St Louis M, Pau CP, Nsuami M, et al. Lack of association between anti-V3 loop antibody and perinatal HIV-1 transmission in Kinshasa, Zaire, despite use of assays based on local HIV-1 strains. J Acquir Immune Defic Syndr Hum Retrovirol 1994; 7: 63
Rodriquez E, Mofenson L, Chang B, et al. Association of maternal drug use during pregnancy with maternal HIV culture positivity and perinatal HIV transmission. AIDS 1996; 10: 273
Boyer P, Dillon M, Navaie M, et al. Factors predictive of maternal-fetal transmission of HIV-1. JAMA 1994; 271: 1925
Lambert, J, Mofenson L, Stiehm ER, et al. Risk factors for perinatal HIV transmission in women/infants receiving standard zidovudine prophylaxis [oral session #467]. 12th World AIDS Conference; 1998 Jun 28–Jul 3; Geneva, Switzerland
Mofenson L. Mother-to-child HIV-1 transmission: timing and determinants. Obstet Gynecol Clin North Am 1997. In press
Parekh BS, Shaffer N, Pau CP, et al. Lack of correlation between maternal antibodies to V3 loop peptides of gp120 and perinatal HIV-1 transmission. AIDS 1991; 5: 1179–84
Geffin RB, Lai SH, Hutto C, et al. Quantitative analysis of human immunodeficiency virus type 1 antibody reactivity by western immunoblots: evaluation of relative antibody levels in seropositive individuals and mothers. J Infect Dis 1992; 165: 111–8
Ugen KE, Boedert JJ, Boyer J, et al. Vertical transmission of HIV infection: correlation with reactivity of maternal sera with glycoprotein 120 and gp41 peptides from HIV type 1. J Clin Invest 1992; 89: 1923–30
Khouri YF, McIntosh K, Cavacini L, et al. Vertical transmission of HIV-1. Correlation with maternal viral load and plasma levels of CD4 binding site anti-gp120 antibodies. J Clin Invest 1995; 95: 732–7
Rossi P, Moschese V, Broliden PA, et al. Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the noninfective status of children born to seropositive mothers. Proc Natl Acad Sci USA 1989; 86: 8055–8
Brolinden PA, Moschese V, Ljunggrenn K, et al. Diagnostic implication of specific immunoglobulin G patterns of children born to HIV-infected mothers. AIDS 1989; 3: 577–82
Devash Y, Calvelli T, Wood DG, et al. Vertical transmission of HIV is correlated with absence of high affinity/avidity maternal antibodies to the gp120 principal neutralizing domain. Proc Natl Acad Sci USA 1990; 87: 3445–9
Erb P, Krauchi S, Burgin D, et al. Quantitative anti-p24 determinations can predict the risk of vertical transmission. J Acquir Immune Defic Syndr 1994; 7: 261–4
Scarletti G, Leitner T, Halapi E, et al. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. Proc Natl Acad Sci USA 1993; 90: 1721
Bryson Y, Lehman D, Garratty E, et al. The role of maternal autologous neutralizing antibody in prevention of maternal fetal HIV-1 transmission [abstract QZ005]. J Cell Biochem 1993; Suppl. 17E: 95
Kliks SC, Wara DW, Landers DV, et al. Features of HIV-1 that could influence maternal-child transmission. JAMA 1994; 272: 467–74
Mofenson LM. Epidemiology and determinants of vertical HIV transmission. Sem Pediatr Infect Dis 1994; 5: 252–65
Husson RN, Lan Y, Kojima E, et al. Vertical transmission of human immunodeficiency virus type 1: autologous neutralizing antibody, virus load, and virus phenotype. J Pediatr 1995; 126: 865–71
Pantaleo G, Demarest JF, Vaccarezza M, et al. Effect of anti-V3 antibodies on cell-free and cell-to-cell human immunodeficiency virus transmission. Eur J Immunol 1995; 25: 226–31
Jenkins M, Landers D, Williams-Herman D, et al. Association between anti-human immunodeficiency virus type 1 (HIV-1) antibody-dependent cellular cytotoxicity antibody titers at birth and vertical transmission of HIV-1. J Infect Dis 1994; 170: 308–12
Ljunggren K, Moschese V, Borliden PA, et al. Antibodies mediating cellular cytotoxicity and neutralization correlate with better clinical stage in children born to human immunodeficiency virus infected mothers. J Infect Dis 1990;161: 198–202
Conner EM, Sperling RS, Gelbert R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 1994; 331: 1173–80
Sperling RS, Shapiro DE, Coombs RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med 1996; 335(22): 1621–9
Jackson GG, Rubenic M, Knigge M, et al. Passive immunoneutralization of HIV patients with advanced AIDS. Lancet 1989; 2: 647–51
Karpas A, Hill F, Youle M, et al. Effects of passive immunization in patients with AIDS related complex and AIDS. Proc Natl Acad Sci USA 1988; 85: 9234–7
Osther K, Wiik A, Black F, et al. PASSHIV-1 treatment of patients with HIV-1 infection. A preliminary report of a phase 1 trial of hyperimmune porcine immunoglobulin to HIV-1. AIDS 1992; 6: 1457–64
Levy J, Youvan T, Lee ML. Passive hyperimmune plasma therapy in the treatment of acquired immunedeficiency syndrome: results of a 12-month multicenter double-blind controlled trial. The Passive Hyperimmune Therapy Study Group. Blood 1994; 84: 2130–5
Vittecoq D, Chevret S, Morand-Joubert L, et al. Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma. Proc Natl Acad Sci USA 1995; 92: 1195–9
Fletcher CV, Goodroad BK, Cummins L, et al. Pharmacokinetics of hyperimmune anti-human immunodeficiency virus immunoglobulins in persons with AIDS. Antimicrob Agents Chemother 1997; 41(7): 1571–4
Wong VK, Gillette SG, Roth MJ, et al. Passive immunotherapy in a child with acquired immunedeficiency syndrome. Pediatr Infect Dis J 1993; 12: 947–51
Cummins LM, Weinholt KJ, Matthews TJ, et al. Preparation and characterization of an intravenous solution of IgG from human immunodeficiency virus-seropositive donors. Blood 1991; 77: 1111–7
Lambert JS, Mofenson LM, Fletcher CV, et al. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. JID 1997; 175: 283–91
Stiehm ER, Lambert JS, Mofenson LM, et al. Efficacy of zidovudine and hyperimmune HIV immunoglobulin for reducing perinatal disease: results of Pediatric AIDS Clinical Trials Group protocol 185. J Infect Dis 1998. In press
Guay L, Musoke P, Mrniro F, et al. Phase I/II Trial of HIVIG for the prevention of HIV-1 vertical transmission in Uganda. 5th Conference on Global Strategies for the Prevention of HIV Transmission from Mothers to Infants [abstract]. 1997 Sept; Washington, DC
Mascola JR, Louder MK, VanCott TC, et al. Potent and synergistic neutralization of human immunodeficiency virus (HIV) type 1 primary isolates by hyperimmune anti-HIV immunoglobulin combined with monoclonal antibodies 2F5 and 2G12. J Virol 1997; 71(10): 7198–206
Li A, Baba TW, Sodroski J, et al. Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations of human anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins. AIDS Res Hum Retroviruses 1997; 13(8): 647–56
Borkowsky W, Wara D, MacNamara J, et al. Lymphoproliferative responses to rec. HIV-1 envelope antigens in neonates and infants receiving gpl20 vaccines [abstract]. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1–5: Chicago (IL)
McFarland EJ, Borkowsky W, Wara D, et al. Humoral immune responses to recombinant HTV- envelope antigens in newborns receiving gp120 vaccines [abstract]. 5th Conference on Retroviruses and Opportunistic Infections, 1998 Jan; Chicago (IL)
Cunningham CK, Wara DW, Fenton T, et al. Safety of recombinant HIV-1 envelope vaccines in neonates born to HIV-1 infected women [abstract]. 5th Conference on Retroviruses and Opportunistic Infections; 1998 Feb 1-5: Chicago (IL)
Wright PF, Lambert JS, Hsieh RH, et al. Safety and Immunogenicity of Envelope MN rgp120 vaccine in HIV-1 infected pregnant women. In press
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Lambert, J.S., Moye, J. Current Issues in the Immunoprophylaxis of Vertical Transmission of HIV. BioDrugs 11, 31–41 (1999). https://doi.org/10.2165/00063030-199911010-00004
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DOI: https://doi.org/10.2165/00063030-199911010-00004