Biological correlates of HIV-1 heterosexual transmission

Abstract

HIV-1 infection is a sexually transmitted disease but HIV transmission efficiency by sexual contacts appears to be highly variable; this is probably due to the influence that several behavioural, clinical and biological factors exert on the transmission event. Here we focused on possible biological correlates of HIV sexual transmission, with emphasis on the host antibody response towards HIV and the virus biological characteristics.

The seroreactivity against peptides resembling the V3 loop as well as the autologous and heterologous neutralizing activity in sera from infected men that had or had not transmitted the infection to the heterosexual partner were analysed. The results from these studies indicate that a broad cross-recognition of HIV by host antibodies may exert a protective role with respect to male to female heterosexual transmission. In fact, sera from non-transmitting index cases more frequently revealed a reactivity also against V3 loop peptides derived from viruses phylogenetically distant from those commonly circulating in our geographical areas. In line with this finding, sera from these individuals also showed a broad cross neutralizing activity against heterologous HIV-1 primary isolates derived from the same group of patients. Taken together, these results highlight the role of the host antibody response in possible protection from transmission and may be relevant in view of possible vaccine-based preventive measures.

The pathogenic potential of the virus, that is the combination of cytopathogenicity, cell tropism and replicative activity "in vitro" and the extent of "in vivo" replication reflected by viral load, also plays a key role in transmission. We analysed the biological phenotype and the replicative activity of the viruses harboured by patients from the same groups and also determined the plasma viral load of such patients. Viruses of the syncytium.inducing (SI) phenotype and/or with highest "in vitro" replicative activity were isolated from transmitting index cases, that also showed higher plasma viral laods. Thus, a narrow HIV antibody recognition/neutralization, higher plasma viral loads and virus variants more cytopathic and with highest replication potential generally marks individuals at high risk to sexually transmit the infection.

Analysis of the newly infected individuals showed no selection for specific viral variants (SI vs NSI) during transmission. Infected individuals, in fact, generally retain the virus phenotype of the transmitting index case. The results have important prognostic consequences. We retrospectively analysed the CD4+ cell decline and the progression to full-blown disease of women that acquired the infection from men harbouring SI variants: they experienced a significantly faster progression with respect to women that acquired the infection from men carrying non-syncytium inducing (NSI) viruses.

Finally, we approached the problem of the possible sexual transmission of viral variants resistant to antiretroviral drugs, by analysing virus isolates obtained at the time of seroconversion from women from the same group and whose index cases harboured viruses resistant to Zidovudine. Transmission of a resistant variant was documented in one out of four cases: we should then take into consideration this event when starting an antiretroviral treatment in patients at risk to have sexually acquired a resistant strain. Our findings call for further studies on the complex interplay between the host and the virus occurring in the course of HIV-1 heterosexual transmission.