Vaccine and Infectious Disease Division

Herpes drug fails to reduce HIV transmission

The complex interplay between infections with herpes virus HSV-2 and HIV is only recently coming to light.  Epidemiologic studies in the last few years have shown that HSV-2 infection increases a person’s chances of both acquiring and transmitting HIV.  Because HSV-2 is so common, and antiviral drugs exist that keep the infection in check, medical researchers hoped that treating HSV-2 might go a long way in controlling HIV infection and transmission in that large population that carries both infections.

The Partners in Prevention HSV/HIV Study, led by University of Washington Professor of Global Health and Medicine, Dr. Connie Celum, and Associate Professor of Global Health and Medicine, Dr. Jairam Lingappa, along with VIDI co-directors Drs. Julie McElrath and Larry Corey, VIDI affiliate investigators Drs. Anna Wald and Rhoda Morrow, and others, showed that unfortunately, twice daily suppressive doses of the HSV-2 drug acyclovir does not decrease HIV transmission in persons infected with both viruses.  The study looked at nearly 3,400 couples from 14 sites in Africa in which one partner was HIV and HSV-2 positive and the other partner HIV negative.  Half of the HIV positive partners in the study received acyclovir, and the other half a placebo.  The rates of HIV transmission, that is, how often the originally uninfected partner contracted HIV over the course of the year-long study, were the same in both groups.

This result was somewhat surprising, as the study also found that daily acyclovir reduces plasma HIV viral load, the amount of HIV present in the bloodstream, by approximately half (or 0.25 log10 reduction) as compared to participants taking the placebo. The researchers conclude that even greater reductions in viral load will be needed to make a substantial dent in HIV transmission. While the initial results of this study were disappointing with regards to stemming HIV transmission from HSV-2 co-infected persons, the massive scale of the study has led to a repository of epidemiologic data and biologic samples that can inform future studies on HIV transmission.

Some immediate good news did come out of the study. In a separate publication, the authors show that daily acyclovir slows progression of HIV disease by 16 percent in people infected with both HIV and HSV-2. While the reduction is not dramatic, the drug is cheap and readily accessible, and thus may be used to slow HIV progression and delay initiating antiretroviral therapy.   

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.  Celum C, Wald A, Lingappa JR, Magaret AS, Wang RS, Mugo N, Mujugira A, Baeten JM, Mullins JI, Hughes JP, Bukusi EA, Cohen CR, Katabira E, Ronald A, Kiarie J, Farquhar C, Stewart GJ, Makhema J, Essex M, Were E, Fife KH, de Bruyn G, Gray GE, McIntyre JA, 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 MS, Thomas KK, Coombs RW, Morrow R, Whittington WL, McElrath MJ, Barnes L, Ridzon R, Corey L; Partners in Prevention HSV/HIV Transmission Study Team.  N Engl J Med. 2010 Feb 4;362(5):427-39.

Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial. Lingappa JR, Baeten JM, Wald A, Hughes JP, Thomas KK, Mujugira A, Mugo N, Bukusi EA, Cohen CR, Katabira E, Ronald A, Kiarie J, Farquhar C, Stewart GJ, Makhema J, Essex M, Were E, Fife KH, de Bruyn G, Gray GE, McIntyre JA, Manongi R, Kapiga S, Coetzee D, Allen S, Inambao M, Kayitenkore K, Karita E, Kanweka W, Delany S, Rees H, Vwalika B, Magaret AS, Wang RS, Kidoguchi L, Barnes L, Ridzon R, Corey L, Celum C; Partners in Prevention HSV/HIV Transmission Study Team. Lancet. 2010 Mar 6;375(9717):824-33.