Heterosexual transmission accounts for the majority of human immunodeficiency virus-1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encoding compact, glycan-restricted envelope glycoproteins. These viruses were also uniquely sensitive to neutralization by antibody from the transmitting partner. Thus, the exposure of neutralizing epitopes, which are lost in chronic infection because of immune escape, appears to be favored in the newly infected host. This reveals characteristics of the envelope glycoprotein that influence HIV-1 transmission and may have implications for vaccine design.

Joint VCT prompted sustained but imperfect condom use in HIV discordant couples. Biological markers were insensitive but provided evidence for a significant under-reporting of unprotected sex. Strategies that encourage truthful reporting of sexual behavior and sensitive biological markers of exposure are urgently needed. The impact of prevention programs should be assessed with both behavioral and biological measures.