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This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >18 years) and adolescents (i.e., persons aged 13–17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States.

Prepared by
Jonathan E. Kaplan, MD (CDC, Atlanta, Georgia)
Constance Benson, MD (University of California San Diego, San Diego, California)
King K. Holmes, MD, PhD (University of Washington, Seattle, Washington)
John T. Brooks, MD (CDC, Atlanta, Georgia)
Alice Pau, PharmD (National Institutes of Health, Bethesda, Maryland)
Henry Masur, MD (National Institutes of Health, Bethesda, Maryland)

Published by the Coordinating Center for Health Information and Service, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30333.

Sample

Herpes Simplex Virus Disease
Epidemiology
Infections with human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are common, with a seroprevalence of HSV-1 among adults of approximately 60% and a seroprevalence of HSV-2 among persons aged >12 years in the United States of 17% (731). Approximately 70% of HIV-infected persons are HSV-2 seropositive and 95% are seropositive for either HSV-1 or HSV-2 (732). In most HSV-infected persons, HSV infections are unrecognized clinically. However, regardless of the clinical severity of infection, reactivation on mucosal surfaces occurs intermittently and can result in transmission. HSV-2 is a risk factor for HIV acquisition, and HSV-2 reactivation results in increases in HIV RNA levels in coinfected patients.

Clinical Manifestations
Orolabial herpes is the most common manifestation of HSV-1 infection. Classic manifestations include a sensory prodrome in the affected area, rapidly followed by the evolution of lesions from papule to vesicle, ulcer, and crust stages on the lips. The course of illness in untreated subjects is 7–10 days. Lesions recur 1–12 times per year and can be triggered by sunlight or physiologic stress.

Genital herpes is the most common manifestation of HSV-2 infection. Genital mucosal or skin lesions are similar to external orolabial lesions in appearance and evolution. Local symptoms might include a sensory prodrome consisting of pain and pruritis. Ulcerative lesions are usually the only stage observed on mucosal surfaces. Mucosal disease is occasionally accompanied by dysuria or vaginal or urethral discharge; inguinal lymphadenopathy, particularly in primary infection, is common with genital herpes (733). These classic manifestations occur in certain patients, but most persons with genital herpes have mild and atypical lesions that are not brought to medical attention and that cannot be diagnosed by physical examination. In profoundly immunocompromised patients, extensive, deep, nonhealing ulcerations might occur. These lesions have been reported most often in those with CD4+ counts of <100 cells/µL and also might be more commonly associated with acyclovir-resistant virus (734).

The episodes of genital HSV-1 infection are indistinguishable from genital HSV-2 infection but genital HSV-1 infection recurs less frequently than genital HSV-2 infection.

Nonmucosal HSV infections, such as HSV keratitis, HSV encephalitis, HSV hepatitis, and herpetic whitlow, are similar in presentation to those manifestations observed in HIV-seronegative persons; disseminated HSV infection is rare. HSV retinitis manifests as acute retinal necrosis (ARN) and can lead rapidly to loss of vision.

Diagnosis
Because mucosal HSV infections cannot be diagnosed accurately without laboratory confirmation, especially in HIV-seropositive patients, a laboratory diagnosis should be pursued in all cases (529). Viral culture, HSV DNA PCR, and HSV antigen detection are available methods for diagnosis of mucocutaneous HSV lesions caused by HSV. PCR is the most sensitive method, but is not widely available. The virus detected in genital lesions should be typed, because HSV-1 recurs less frequently than HSV-2 in the genital area. Type-specific serologic assays are commercially available and can be used in asymptomatic persons or those with atypical lesions. Because of the poor sensitivity and specificity of clinical diagnosis, extensive interactions between HIV and HSV-2, and the availability of effective therapy for HSV-2, routine type-specific serologic testing for HSV-2 should be considered in persons who seek HIV care. Diagnosis of HSV-2 should be accompanied by counseling that discusses the risk for transmission of infection to sex partners. Guidelines for counseling are provided in the 2006 CDC STD treatment guidelines (http://www.cdc.gov/std/treatment).

Preventing Exposure
The majority of HIV-infected persons have HSV-1 and -2 infections. However, prevention of acquisition of HSV is important for those who are uninfected. HSV-2-seronegative HIV-infected persons should ask their partners to be tested using type-specific serology before initiating sexual activity, because disclosure of HSV-2 in heterosexual HSV-2-discordant couples was associated with reduced risk for transmission of HSV-2 (BII) (735). Consistent use of latex condoms reduced HSV-2 acquisition from women to men and from men to women, and their use should be encouraged for prevention of transmission of HSV-2 and other sexually transmitted pathogens (AII) (736). HIV-infected persons should specifically avoid sexual contact when their partners have overt (genital or orolabial) herpetic lesions (AII). However, sexual transmission of HSV can occur during asymptomatic shedding. The use of suppressive antiviral therapy (valacyclovir 500 mg once daily) in persons with genital herpes reduced HSV-2 transmission to susceptible heterosexual partners by 50% (737); the effectiveness of this approach in reducing HSV-2 transmission from HIV-seropositive persons or to HIV-seropositive persons has not been evaluated.

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