Repeated exposure to HIV during oral sex elicits HIV-neutralising antibodies in HIV-negative men

Some HIV-negative men in long-term relationships with HIV-positive men have an antibody response in saliva that may inhibit HIV infection, report Swedish researchers in an article published online (ahead of print) in AIDS. This is the first time that such a response has been described in saliva, and may help explain why infection through oral sex is somewhat infrequently reported even in serodiscordant couples.

While it is well established that HIV infection during fellatio and other types of oral sex can and does happen, the number of infections that can be attributed to oral sex is relatively small in comparison with the number of times that unprotected oral sex is practiced. One reason is that saliva contains enzymes that partially inhibit HIV infection.

Moreover, a number of studies, most famously among commercial sex workers in Kenya, have identified individuals who have had unprotected vaginal sex on many occasions and are likely to have been repeatedly exposed to HIV, but who have not been infected. It is thought that, through repeated exposure, these individuals have acquired a stronger immune response which makes HIV infection less likely. Different researchers have investigated a number of different markers of this immune response, including the presence of specific antibodies (IgA1), which may neutralise HIV, and HIV-specific CD4 cell responses.

Klara Hasselrot and colleagues from the Karolinska Institutet in Stockholm wished to investigate whether, in long-term relationships where one partner has HIV, the HIV-negative partner develops IgA1 antibodies in saliva that would help inhibit HIV infection during oral sex.

They recruited 25 HIV-negative men who were in a relationship of at least six-months duration with an HIV-positive man. In addition, 22 HIV-negative men who were not in a serodiscordant relationship were recruited at a blood donor clinic to act as controls.

Klara Hasselrot told aidsmap.com that the study participants’ questionnaires showed that 24 of the 25 men had performed unprotected receptive oral sex in the previous six months. For 21 men, this was with their HIV-positive partner, but for three men it was with casual partners of unknown HIV status. Just three men also reported unprotected receptive anal intercourse.

Moreover, analysis of the medical records of the HIV-positive partners showed that, whilst most were on treatment at the time of the study, only two had been on antiretroviral treatment with undetectable viral loads for the entire length of their relationship. The researchers judge that this means that, with two exceptions, all HIV-negative partners have probably been exposed to HIV at some point.

Analysis of whole saliva samples showed that saliva from 15 of the men in serodiscordant relationships had HIV neutralising capacity. This was also the case for six of the control group, which confirms saliva’s usual HIV inhibiting activity.

Further tests were performed on samples of the IgA1 antibodies only. In these tests, antibodies from 13 of the serodiscordant partners, but none of the control samples, neutralised HIV.

The researchers believe that repeated exposure to HIV during oral sex produces this specific immune response in saliva. Moreover they argue that the inhibitory effect of IgA1 is likely to be a significant contributor to neutralisation in the whole-saliva samples. Looking at the 13 men whose IgA1 was able to neutralise HIV, they re-tested saliva samples from which IgA1 had been removed. Only five of these samples had neutralising activity.

Two years after enrolment into the study, new samples were taken and tested. The situation was unchanged for almost all serodiscordant partners (although one man’s saliva showed neutralising capacity for the first time, and another man lost this ability). Moreover, they all remained HIV-negative.

The researchers also found that men who had neutralising capacity in their saliva tended to have partners with a higher viral load than men who did not have this capacity. This would suggest that neutralising capacity is determined by the amount of exposure to virus.

The researchers conclude that “unprotected oral sex evokes a salivary IgA1-mediated HIV-neutralizing response that persists over time during continuous exposure in uninfected male partners of infected men”.