Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of genital herpes simplex virus type 2 in HIV-infected patients

Christine Johnston, MD, MPH
Anna Wald, MD, MPH
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Genital herpes is a common sexually transmitted virus infection that is found worldwide. Genital herpes is usually secondary to herpes simplex virus type 2 (HSV-2); the remainder of infections is related to HSV-1, which also causes herpes labialis ("cold sores") [1]. The seroprevalence of HSV-2 infections in HIV-infected patients is high (50 to 90 percent) and genital ulcer disease can be more frequent, severe, and of longer duration than in HIV-seronegative patient populations [1].

This topic will review the treatment of genital herpes in HIV-infected patients. The natural history, clinical manifestations, and prevention of genital HSV infection in the HIV-infected patient and important viral interactions between HIV and HSV-2 are discussed elsewhere. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus in HIV-infected patients" and "Effect of herpes simplex virus on HIV infection: Implications for HIV prevention".)


There are three classification categories for genital herpes, as noted below.

Primary HSV infection — An HSV outbreak is defined as "primary" if the patient was HSV-seronegative for both HSV-1 and HSV-2 at the onset of genital lesions.

Nonprimary HSV infection — Nonprimary first episode infection refers to: a) the acquisition of genital HSV-1 infection in a patient with preexisting antibodies to HSV-2 or b) the acquisition of genital HSV-2 infection in a patient with preexisting antibodies to HSV-1 (eg, an individual with prior orolabial herpes). Most HIV-infected adults with a new diagnosis of HSV infection have nonprimary disease due to prior acquisition of HSV-1 infection.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Dec 11, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Gupta R, Warren T, Wald A. Genital herpes. Lancet 2007; 370:2127.
  2. Bagdades EK, Pillay D, Squire SB, et al. Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection. AIDS 1992; 6:1317.
  3. Aumakhan B, Gaydos CA, Quinn TC, et al. Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers. PLoS One 2010; 5:e9973.
  4. Warren T, Harris J, Brennan CA. Efficacy and safety of valacyclovir for the suppression and episodic treatment of herpes simplex virus in patients with HIV. Clin Infect Dis 2004; 39 Suppl 5:S258.
  5. Conant MA, Schacker TW, Murphy RL, et al. Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials. Int J STD AIDS 2002; 13:12.
  6. Romanowski B, Aoki FY, Martel AY, et al. Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group. AIDS 2000; 14:1211.
  7. Schacker T, Hu HL, Koelle DM, et al. Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial. Ann Intern Med 1998; 128:21.
  8. DeJesus E, Wald A, Warren T, et al. Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects. J Infect Dis 2003; 188:1009.
  9. Lingappa JR, Celum C. Clinical and therapeutic issues for herpes simplex virus-2 and HIV co-infection. Drugs 2007; 67:155.
  10. Bell WR, Chulay JD, Feinberg JE. Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore) 1997; 76:369.
  11. Patel R, Stanberry L, Whitley RJ. Review of recent HSV recurrent-infection treatment studies. Herpes 2007; 14:23.
  12. Corey L, Bodsworth N, Mindel A, et al. An update on short-course episodic and prevention therapies for herpes genitalis. Herpes 2007; 14 Suppl 1:5A.
  13. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  14. Mujugira A, Magaret AS, Celum C, et al. Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial. J Infect Dis 2013; 208:1366.
  15. Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med 2010; 362:427.
  16. Ioannidis JP, Collier AC, Cooper DA, et al. Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. J Infect Dis 1998; 178:349.
  17. Van Wagoner N, Geisler WM, Bachmann LH, Hook EW. The effect of valacyclovir on HIV and HSV-2 in HIV-infected persons on antiretroviral therapy with previously unrecognised HSV-2. Int J STD AIDS 2015; 26:574.
  18. Yi TJ, Walmsley S, Szadkowski L, et al. A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy. Clin Infect Dis 2013; 57:1331.
  19. Ratnam I, Chiu C, Kandala NB, Easterbrook PJ. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis 2006; 42:418.
  20. Fox PA, Barton SE, Francis N, et al. Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease. HIV Med 1999; 1:10.
  21. Couppié P, Sarazin F, Clyti E, et al. Increased incidence of genital herpes after HAART initiation: a frequent presentation of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients. AIDS Patient Care STDS 2006; 20:143.
  22. Tobian AA, Grabowski MK, Serwadda D, et al. Reactivation of herpes simplex virus type 2 after initiation of antiretroviral therapy. J Infect Dis 2013; 208:839.
  23. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguideline s/adult_oi.pdf (Accessed on November 04, 2015).
  24. Graham SM, Masese L, Gitau R, et al. Increased risk of genital ulcer disease in women during the first month after initiating antiretroviral therapy. J Acquir Immune Defic Syndr 2009; 52:600.
  25. Murdoch DM, Venter WD, Feldman C, Van Rie A. Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study. AIDS 2008; 22:601.
  26. Fife KH, Crumpacker CS, Mertz GJ, et al. Recurrence and resistance patterns of herpes simplex virus following cessation of > or = 6 years of chronic suppression with acyclovir. Acyclovir Study Group. J Infect Dis 1994; 169:1338.