PERINATAL TRANSMISSION OF HIV TYPE-1 - ASSOCIATIONS WITH MATERNAL ANTI-HIV SEROLOGICAL REACTIVITY

As a hypothesis-generating study of large regions of the human immunodeficiency virus type 1 (HIV-1) envelope, we collaborated with several laboratories to test sera from subgroups of 65 HIV-1-positive pregnant women, 18 (28%) of whom transmitted the virus to their infants. Assays included neutralizing antibodies to HIVLAI and reactivity to 102 HIV-1 Env peptides with sequences based on strains LAI, MN, SC, RF, and WMJ-2 as well as several clinical isolates, spanning about 65% of gp120 and about 80% of gp41. Results for the V3 loop and for neutralizing activity were conflicting and for the most part did not reach statistical significance. Transmission risk appeared lower with reactivity to a few gp41 epitopes (amino acids 571-585, 736-750, and perhaps 650-663), whereas risk appeared higher with reactivity to two gp120 epitopes (amino acids 466-480 and 475-486) and one gp41 epitope (amino acids 547-576). However, these associations could have occurred simply by chance because such a large number of peptides was tested. With independently synthesized peptides, results between laboratories often were inconsistent. However, reproducibility was good (rank correlation coefficient greater than or equal to 0.78) when the same protocols and peptides were used. Although this study could not identify a humoral immune response to linear Env peptides that consistently and broadly protected against perinatal transmission of HIV-1, there were regions of gp120 and gp41 that should be evaluated in larger cohorts and with techniques to investigate potential conformational epitopes and neutralization to autologous or clinical isolates of HIV-1 from the community.