Vaccine and Infectious Disease Division

Herpes therapy does not select for HIV-1 resistance

Herpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected persons, and co-infection has been linked to increased risk of HIV transmission.  A number of recent clinical trials have assessed the effect of herpes-suppressive therapy on HIV-1 in dually-infected persons, and found that anti-HSV drugs reduce levels of HIV virus in the bloodstream of co-infected people, but do not significantly reduce HIV transmission.  However, in vitro studies have raised concerns that the drug used in these studies, acyclovir, can directly inhibit replication of HIV-1, in turn potentially leading to selection in the human host for a specific resistance mutation (V75I) within the HIV-1 reverse transcriptase protein and loss of acyclovir’s anti-HIV-1 effect.  To assess this concern in a clinically relevant setting, UW researcher Dr. Jared Baeten and colleagues, including VIDD member Dr. Anna Wald and Center President and Director Dr. Larry Corey, tested for the presence of this resistance mutation in 168 HIV-1- and HSV-2-infected persons who participated in clinical trials of acyclovir or valacyclovir therapy, some for up to two years of continuous therapy.  They found no instances of the V75I mutation in this cohort, indicating that at standard clinical dosing acyclovir or valacyclovir treatment does not select for this particular HIV-1 resistance mutation.

Baeten JM, Lingappa J, Beck I, Frenkel LM, Pepper G, Celum C, Wald A, Fife KH, Were E, Mugo N, Sanchez J, Essex M, Makhema J, Kiarie J, Farquhar C, Corey L. Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons. J Infect Dis. 2011 Jan 1;203(1):117-21.