Immunoprophylaxis against Mother-to-Child Transmission of HIV-1

I n resource-limited settings, there is a high risk of mother-to-child-transmission (MTCT) of HIV-1. The rate of MTCT without specifi c intervention and with an extended time of breast-feeding is about 35%– 40% [1], a fi gure that results in the infection of about 750,000 children every year worldwide [2]. A single dose of nevirapine can reduce the rate of MTCT by 42%, but it selects for drug-resistant variants in as many as 75% of mothers receiving this treatment [3]. As multiple-drug treatment is rarely available in developing countries, and breast-feeding often continues for at least two years after delivery, the concept of preventing MTCT transmission by passive administration of antibodies, by the use of antibodies and drugs, or by the use of combined active–passive immunization is attracting increasing attention [4]. Passive immunization experiments have proven that antibodies can protect against HIV-1 infection in animal models. Polyclonal or monoclonal antibodies (mAbs) against simian immunodefi ciency virus (SIV) or HIV-1 have mediated protection of chimpanzees from HIV-1 infection [5] and protection of juvenile and neonatal macaques from infection with SIV or with chimeric simian/human immunodefi ciency virus (SHIV) [6–10]. In several experiments with SHIV89.6P, broadly neutralizing human mAbs b12, 2G12, 2F5, and 4E10 were tested [6,7,9,10]. These mAbs were generated from subtype-B-infected individuals. Although HIV-1 subtype B is the predominant subtype in North America, Western Europe, and Australia, HIV-1 subtype B viruses account for only about 12% of the global HIV pandemic [11]. The mAbs tested in these experiments react with epitopes in the CD4 binding domain of gp120 (mAb b12), with gp120 glycans (mAb 2G12), and with epitopes in the membrane proximal region of gp41 (mAbs 2F5 and 4E10). A combination of these mAbs provided a stronger protective effect than any of the single mAbs, which individually mediated only partial protection at best against chimeric simian/human immunodefi ciency virus [6]. The evidence for the function of anti-HIV-1 antibodies in preventing MTCT in humans is less conclusive than in animal models. Early studies showed a positive correlation between the presence of neutralizing antibodies in mothers and lower incidence of MTCT [12,13], although more recently these fi ndings have not been replicated [14]. Moreover, there are few data on the effectiveness of passive immunization in the prevention of MTCT in humans. Only one study reported the use in HIV-infected pregnant women of HIVIG, an immune globulin preparation from HIV-infected individuals containing high …