HIV and Herpes, together forever

What we know, in terms of herpes and HIV, and everybody can mostly agree upon:
1) Co-infection with herpes simplex virus increases the risk of transmission of HIV, mostly from the decreased mucosal damage from herpes ulcers.
2) Acyclovir, our preferred antiviral for herpes simplex, reduces HSV levels in blood.
3) Acyclovir also has effects on HIV, with both in vitro and in vivo activity, either indirectly through HSV or directly on HIV replication itself.
4) An exacerbation of HSV is associated with worsening HIV disease.

So, it makes sense that co-infected people who are on acyclovir, take it well, and get subsequent suppression of their herpes would have lower transmissibility of their HIV. Unfortunately, as this trial in this week's New England Journal of Medicine shows, this isn't the case.

It's probably the best-done, largest study that can be done looking at the issue, effectively closing the door on being able to reduce HIV transmission solely through HSV treatment. Finding 3400 willing couples where one partner is HIV and HSV positive and the other is negative for both must have been incredibly difficult. Also, the strict, but necessary, inclusion criteria, such as not yet being on antiretroviral treatment and being otherwise well, must have limited recruitment.

In the end, they reduced blood HIV levels and the incidence of genital ulcers, but, sadly, couldn't reduce HIV transmission, their primary outcome. The ultimate goal of bringing down HIV blood levels, through antiretrovirals or the treatment of other concomitant infections and illnesses, might use acyclovir as part of a multi-factorial approach. By itself, however, it doesn't seem to work, at least to the degree hoped for.

One point is that those enrolled in the study received fairly intensive counseling regarding safe sexual practices for serodiscordant couples, meaning that the overall transmission rate was lower than for the general population, increasing the numbers needed to find a difference in transmission rate. Everybody, however, should be receiving this support, and that can't be taken as a criticism of the study itself. In addition, almost 30% of the new infections in the study were with different viruses than their partners, meaning they were infected by somebody else's virus, reinforcing the need for effective counselling and support.

In the end, managing serodiscordant couples will continue to be a challenge, and will likely involve more aggressive use of antiretrovirals and counselling, similar to that in this study.



Celum, C., Wald, A., Lingappa, J., Magaret, A., Wang, R., Mugo, N., Mujugira, A., Baeten, J., Mullins, J., Hughes, J., Bukusi, E., Cohen, C., Katabira, E., Ronald, A., Kiarie, J., Farquhar, C., Stewart, G., Makhema, J., Essex, M., Were, E., Fife, K., de Bruyn, G., Gray, G., McIntyre, J., Manongi, R., Kapiga, S., Coetzee, D., Allen, S., Inambao, M., Kayitenkore, K., Karita, E., Kanweka, W., Delany, S., Rees, H., Vwalika, B., Stevens, W., Campbell, M., Thomas, K., Coombs, R., Morrow, R., Whittington, W., McElrath, M., Barnes, L., Ridzon, R., Corey, L., & , . (2010). Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2 New England Journal of Medicine DOI: 10.1056/NEJMoa0904849