Treatment of genital herpes simplex virus type 2 in HIV-infected patients
- Christine Johnston, MD, MPH
Christine Johnston, MD, MPH
- Assistant Professor of Medicine
- University of Washington
- Anna Wald, MD, MPH
Anna Wald, MD, MPH
- Professor of Medicine, Epidemiology, and Laboratory Medicine
- University of Washington
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") . 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 .
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.
- Gupta R, Warren T, Wald A. Genital herpes. Lancet 2007; 370:2127.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Lingappa JR, Celum C. Clinical and therapeutic issues for herpes simplex virus-2 and HIV co-infection. Drugs 2007; 67:155.
- 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.
- Patel R, Stanberry L, Whitley RJ. Review of recent HSV recurrent-infection treatment studies. Herpes 2007; 14:23.
- 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.
- Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- Primary HSV infection
- Nonprimary HSV infection
- Reactivation (recurrent) disease
- AVAILABLE AGENTS
- TREATMENT OF FIRST EPISODE HSV INFECTION
- TREATMENT STRATEGIES FOR RECURRENT DISEASE
- Episodic therapy
- Suppressive therapy
- CLINICAL TRIAL DATA
- General background
- Limitations of clinical trial data
- Suppressive therapy trials
- Episodic therapy trials
- DRUG INTERACTIONS
- WHICH STRATEGY TO SELECT
- DOSING GUIDELINES FOR ANTIVIRAL THERAPY
- Suppressive therapy
- Episodic therapy
- IMMUNE RECONSTITUTION SYNDROME
- DURATION OF THERAPY
- WHEN TO SUSPECT HSV DRUG RESISTANCE
- SUMMARY AND RECOMMENDATIONS