Chapter 21. Sexually Transmitted Diseases in HIV-Infected Persons

• • Because new sexually transmitted diseases (STDs) are common in HIV-infected patients, regular screening and timely treatment are essential.
• • Counseling of HIV-positive patients should include discussion of HIV-STD interactions and risks.
• • Both genital ulcer–causing diseases and non–ulcer-causing STDs increase HIV transmission.
• • Clinical and laboratory findings of syphilis in HIV-infected patients can be challenging to interpret, and these patients require close follow up.
• • Prevention of human papillomavirus (HPV)– associated malignancies requires active surveillance in HIV-infected persons.
• • Genital herpes and syphilis may increase HIV viral load, lower CD4 count, and hasten HIV disease progression.

Symptomatic Assessment

At the initial evaluation of a patient with HIV infection, the clinician should actively screen for typical symptoms and signs of STDs. These include the presence of genital, oral, or anal lesions; pain or burning with urination; new or unusual skin rash; lymphadenopathy and rectal symptoms of discharge, burning, or itching. In addition, men should be screened for urethral discharge or groin pain and women for bloody or foul-smelling vaginal discharge, itching, lower abdominal pain, missed menses, and pregnancy status. Any patient reporting symptoms and signs of STDs should have appropriate diagnostic testing regardless of reported sexual behavior or other risk factors.

Routine Laboratory Assessment

All HIV-infected patients should undergo serologic testing for syphilis, herpes simplex virus type 2 (HSV-2), and hepatitis as well as gonorrhea and chlamydia testing at all exposed anatomic sites (urogenital, anal, oral) at the initial visit. HSV-2 serologic testing should utilize newer, glycoprotein G–specific tests (see Table 21–1). HIV-infected women should undergo speculum-guided pelvic examination with microscopic evaluation of vaginal fluid (wet mount) and Papanicolaou (Pap) smear. Pap smears should be repeated at 6 months and then annually thereafter. Although no national guidelines exist, some experts recommend that HIV-infected men should also undergo regular anal cancer screening (anal Pap smear). Newly diagnosed HIV-infected patients should also receive a broad medical evaluation, which is beyond the scope of discussion in this chapter.

Repeat testing should be based on reported sexual risk behavior and may need to occur as often as every 3 months (see Table 21–2). Given recent increases in syphilis in HIV-infected men who have sex with men (MSM), most experts recommend syphilis testing for sexually active HIV-infected persons at 3- to 6-month intervals along with routine laboratory studies.

Strategies for Effective Assessment of STD Risks in HIV-Infected Patients

Discussing sexual practices with patients can be challenging, but it is essential to providing comprehensive care to HIV-infected patients. When discussing these topics, the mnemonic “Know the CODES” (Confidentiality; Open-minded approach and open-ended questions; Direct questions about specific behaviors; Explanation of implications of the elicited information; Specific informations and advice) is a helpful guide.

Specific terms such as “men who have sex with men” should be used, rather than “gay.” Assumptions about sexual behaviors and risk-taking should be avoided, including monogamy or heterosexuality among married people. Explanation of unfamiliar practices should be requested: “I don’t know what you mean, could you explain ...?” Clinicians should ask about sex partners, including questions about number, where the patient meets sex partners, how well the patient knows the sex partners, HIV status (infected, not infected, or unknown) of sex partners, and any possible STD-related symptoms among sex partners. Questions should also focus on sexual activities and protection methods, use of condoms (and with what type of activities), use of drugs or alcohol, and sexual assault or coercion.

For patients acknowledging the use of drugs or alcohol, discussion of their impact on decision making and risk for further STDs or HIV transmission is appropriate and the responsibility of every treating medical provider. Use of drugs for enhanced erectile function (eg, sildenafil [Viagra]) may likewise be markers for sexual risk-taking behavior.

For injection drug users, discussion should include options to help with cessation or harm reduction, and advice regarding use of only sterile equipment and how to obtain such materials via needle exchange, local pharmacies, or harm reduction centers. Clinicians should ask the patient if all sex and needle-sharing partners have been informed of their possible exposure to HIV. Patients can be referred to appropriate services for facilitation of partner notification.

In women of childbearing age, clinicians should ask about pregnancy-related issues; these include possible current pregnancy (if so, test), past history of pregnancies and terminations, interest in future pregnancy, sexual activity, and contraception use.

Risk Reduction Counseling

The diagnosis of a new STD in a patient with HIV-infection should initiate a discussion about sexual risk behavior and the spread of STDs and HIV. The prevention of HIV transmission can be promoted during the patient visit by discussing safer behaviors to protect both the patient’s own health and the health of sex and needle-sharing partners. Patients should be advised that there can be an significant adverse impact on their own health (increased HIV viral load or decreased CD4 T cell count, or both) as well as on the health of others should they practice high-risk sexual or injection behaviors.

The risk of HIV transmission to partners should also be discussed (see Table 21–3). Risks can be reduced in the following ways: abstinence from sexual or injection drug use; alteration of specific sexual behaviors for harm reduction (oral sex versus anal or vaginal sex; no ejaculation versus ejaculation); safer sex or injection practices (consistent and correct condom or barrier method use, bleaching or not sharing injection equipment); and sexual or injection activity only with others who are also HIV-infected (although as discussed later, this practice is not without risk).

Although effective highly active antiretroviral therapy (HAART) decreases plasma viral load and is thought to decrease risk of HIV transmission from the HIV-infected person taking HAART to an HIV-uninfected sex partner (see Table 21–4), it should be emphasized that even patients who are highly adherent to HAART regimens should not be thought of as unable to transmit HIV to others. HIV viral particles can be detected in the genital and rectal secretions of patients with an undetectable plasma viral load, and factors controlling viral load and infectivity in those anatomic compartments are currently being investigated.

In addition, patients should be counseled that antiretroviral drug interruptions, whether intentional or unintentional, increase both the risk of developing resistance to antiretroviral therapy and the risk of HIV transmission to sex or injection partners. Ultimately, virologic failure of HAART regimens can lead to asymptomatic increases in viral load and further increased infectivity among patients.

Finally, there is evidence of transmission of drug-resistant HIV strains from infected patients with histories of antiretroviral therapy to HIV-uninfected persons who “inherit” the drug-resistance patterns of the person from whom they acquired their HIV infection. Numerous studies now demonstrate that a rising proportion of newly diagnosed cases of HIV infection are caused by viruses resistant to one or more antiretroviral drugs. Studies of the dynamics of transmission and clinical implications of drug-resistant HIV strains are ongoing.

Syphilis

Syphilis and HIV affect similar at-risk populations, including MSM, injection drug users, and people who exchange sex for drugs or money. Many patients are dually infected. For example, among primary and secondary syphilis cases reported to the Centers for Disease Control and Prevention (CDC) in 2002, 25% occurred in HIV-infected persons. Among MSM, rates of syphilis and HIV coinfection may be as high as 60%.

Clinical and laboratory findings of syphilis can differ in HIV-infected patients in several ways. Multiple chancres and atypical or florid skin manifestations are more common. HIV-infected patients are more likely to have chancres of primary syphilis at the same time as they manifest symptoms of secondary syphilis. In addition, more protracted and malignant constitutional symptoms and greater organ involvement have been reported. Studies also have demonstrated that HIV-infected persons appear to have a greater risk of central nervous system involvement at all stages of syphilis infection. Neurosyphilis presentations include meningitis and cranial nerve deficits, such as optic neuritis and deafness. Syphilitic uveitis, and particularly bilateral eye involvement, has been reported more frequently among HIV-infected patients than among those without HIV infection.

Because of the specific immune disturbances of B-cell function in HIV infection, antibody-based syphilis testing results in HIV-infected patients may be different in seemingly paradoxical ways (see Table 21–5). For example, HIV-infected patients in the early stages of HIV disease who have syphilis tend to have higher titers of antibodies than HIV-uninfected patients with syphilis. Also related to overexpression of B-cell activity in early HIV disease have been rare reports of falsely reactive nontreponemal test results. However, before defining a positive nontreponemal test as falsely positive (because a simultaneous treponemal test was negative), the clinician should repeat treponemal testing at least 1 week after the initial tests were performed. In cases where clinical suspicion is high in the face of negative serologic test results, alternative tests (eg, biopsy of skin lesions with silver staining) may be useful to confirm the diagnosis.

The rate of decline of nontreponemal titers following successful therapy may also be influenced by early HIV disease. In a large, randomized, prospective study of patients with early syphilis, HIV-coinfected patients had higher rates of serologically defined treatment failure, although patients had equal clinical responses to therapy, suggesting that the expected decline in titer in HIV-infected patients may be delayed.

Standard indications for lumbar puncture in HIV-infected patients with syphilis are as follows: neurologic, ocular, or auditory symptoms or signs; latent syphilis of unknown duration or late latent syphilis (>1 year); tertiary syphilis; or suspected treatment failure. However, some authorities recommend lumbar puncture in all HIV-infected patients with syphilis. Surveillance data from the CDC suggest neurosyphilis is two to three times more common in HIV-infected patients than in uninfected patients. In one study of 326 patients, many of whom had early syphilis, 20% who underwent cerebrospinal fluid (CSF) analysis had neurosyphilis. Those with serum rapid plasma reagin (RPR) titers of 1:32 or higher were 7.6 times as likely to have laboratory evidence of central nervous system involvement. A serum RPR titer of 1:32 or higher combined with a peripheral blood CD4 cell count of 350 cells/μL or lower conferred still higher odds of neurosyphilis in HIV-infected patients. Thus, a possible strategy to use in deciding whether to perform lumbar puncture in an HIV-infected syphilis patient without signs or symptoms of neurosyphilis might be to factor in serum RPR titer and a recent CD4 count.

The interpretation of CSF laboratory results in patients with syphilis and HIV infection requires careful consideration. Because mild pleocytosis (5–15 white blood cells [WBCs]/μL) can be attributed to HIV infection alone, especially when CD4 counts are higher than 500 cells/μL, most experts would consider more than 20 WBCs/μL to be indicative of a secondary process (ie, syphilis). Elevated CSF protein concentrations are highly nonspecific findings in HIV infection and should not be used alone to make a diagnosis of neurosyphilis. The CSF VDRL is not sensitive and may only be positive in 25–50% of patients with neurosyphilis. In the absence of inflammation (<5 WBCs/μL), the significance of a reactive CSF VDRL result is even less clear (see Chapter 20).

If available, the CSF fluorescent treponemal antibody absorbed (FTA-ABS) test may be helpful, because it is likely to be positive in HIV-positive patients with neurosyphilis who have falsely negative CSF VDRL results, as well as in many patients without other evidence of neurosyphilis. A negative CSF FTA-ABS test essentially excludes neurosyphilis, but a positive CSF FTA-ABS is nonspecific and the diagnosis should not be made if this is the only abnormal CSF result. If CSF evaluation is equivocal and neurosyphilis cannot be excluded, some experts would opt to treat patients for neurosyphilis while others would not. Such decisions are based in part on differing interpretations of the same data. Patient preferences, the likelihood of reliable follow-up, and other factors should also be incorporated in this decision-making process.

Similar treatment regimens are recommended for syphilis in both HIV-infected and uninfected patients; however, because of concerns about a modest increase in risk for treatment failure, closer follow-up is recommended for HIV-infected patients at 3, 6, 9, 12, and 24 months. All patients with neurosyphilis, regardless of HIV status, require repeat CSF analysis at 6 months to document improvement.

Among HIV-infected patients who contract syphilis, several studies have reported that CD4 concentration drops and HIV plasma viral load rises from previous levels. In studies where changes were observed, both markers tended to return toward baseline levels following syphilis treatment. The magnitude of CD4 and viral load changes was largest in patients not receiving HAART, and most of those data are drawn from patients with CD4 concentrations greater than 200 cells/μL. In the medical care of HIV-infected patients, an increase in HIV viral load or decrease in CD4 T cell count should prompt an evaluation for syphilis infection. The effect of advanced syphilis on HIV disease progression or of early syphilis on patients with advanced AIDS is less well characterized.

Human Papillomavirus–Associated Genital Warts & Malignancies

HPV-associated genital warts may be more extensive and more difficult to treat in HIV-infected patients. Precancerous cervical lesions are much more common in HIV-infected women, and studies have reported up to ninefold increases in rates of cervical cancer in women with HIV. Among HIV-infected women with dysplasia, the severity of cervical disease correlates with the degree of immune compromise. Persistence of cervical cancer-causing HPV strains is also more common in women with HIV infection and correlates with the level of immunosuppression.

Anal cancer is similar to cervical cancer; it is associated with the same HPV strains, characterized by a predictable progression through stages of dysplasia to frank neoplasm, and can be detected by Pap smear techniques. The prevalence of HPV in MSM is 60–75%, and the frequency of anal carcinoma in men with HIV infection is 80 times that of the general population and increases with decreasing CD4 count. Some experts recommend regular anal cytology at three-year intervals for all HIV-infected men regardless of history of receptive anal intercourse. Patients with abnormal anal Pap smears should be referred for anoscopy and biopsy. The role of the new HPV vaccine in management of HIV-infected patients is being investigated and is currently unclear.

Herpes Simplex Virus Type 2

Much recent work has focused on the role of genital ulcer disease caused by HSV-2 in the sexual transmission of HIV infection. HSV-2 infection (with symptomatic genital ulcers or with positive HSV-2 serology) in an HIV-uninfected sex partner of an HIV-infected person increases the likelihood that the HIV-negative partner will acquire HIV. Similarly, HSV-2 infection (with or without a history of symptomatic genital ulcers) in an HIV-infected person also increases the risk that he or she will transmit HIV to uninfected partners. The mechanism of enhanced HIV transmission between an asymptomatic HSV-2–positive, HIV-coinfected person and his or her HSV-2–negative, HIV-uninfected sex partner may be related to the increased HIV viral loads observed in HSV-2– and HIV-coinfected individuals.

HIV-infected, HSV-2–positive patients experience both more frequent symptomatic herpetic outbreaks and more frequent and prolonged asymptomatic HSV-2 viral shedding than persons without HIV infection. At present, determinants of HSV-2 asymptomatic viral shedding are unknown. Clinical trials of chronic suppressive anti–HSV-2 therapy to decrease HIV transmission (from a coinfected partner to an HIV-uninfected partner) and HIV acquisition (by an HIV-uninfected person with HSV-2 from his or her HIV-infected partner) are ongoing.

Symptomatic HSV-2 lesions are more common in HIV-infected persons and may be more severe, numerous, painful, prolonged, or atypical. In fact, chronic HSV-2 ulcers of more than 1 month’s duration are considered an AIDS-defining illness in HIV-infected individuals. HSV-2 ulcers appear frequently in the perianal area of HIV-infected people. In severely immunocompromised patients, HSV-2 may present as hyperkeratotic verrucous lesions that mimic condylomata.

Disseminated lesions, refractory disease, and acyclovir-resistant HSV disease are also more common in patients with advanced HIV infection. Neurologic complications of HSV-2 infection are rare, occur mostly in advanced AIDS, and develop rapidly. These complications can include aseptic meningitis, sacral radiculopathy, and transverse myelitis. If herpes is unresponsive to acyclovir or related agents, viral culture with testing of isolates for thymidine-kinase mutations should be undertaken and treatment using foscarnet or cidofovir should be considered. In HIV-infected patients, the treatment of HSV-2 infection can require higher doses and prolonged courses of therapy.

Among HIV- and HSV-2–coinfected patients treated with high-dose acyclovir therapy to suppress HSV reactivation, plasma HIV-1 RNA levels at a given CD4 cell count were decreased by about half, suggesting that HSV reactivation is associated with increased HIV replication in vivo. HIV-infected individuals who develop HSV-2 recurrences have a median HIV viral load increase of 3.4-fold, and increased viral load is sustained for 30–45 days following appearance of genital lesions.

HSV-2 has been shown to upregulate HIV replication at a cellular level. HSV-2 also likely plays a role in determining the steady-state HIV viral load of patients in the early stages of HIV disease following acute infection (the so-called viral set-point). HSV-2–seropositive patients with acute HIV infection have been found to have higher HIV viral loads more than 1 year following their estimated date of HIV acquisition than HSV-2–seronegative patients. Because of the role of HSV-2 in enabling HIV transmission, as well as its potential role in driving HIV disease progression, the overlapping global phenomena of HIV and HSV-2 can truly be considered a “syndemic.”

We recommend routine, type-specific serologic testing for HSV-2 in all HIV-infected persons. Only tests that detect HSV glycoprotein G are truly type-specific and suitable for HSV-2 serologic screening. Patients with positive results should be informed of the increased risk of transmitting HIV during both symptomatic herpes episodes and phases of asymptomatic viral shedding. Such patients should be counseled regarding recognition of symptoms of early HSV-2 outbreaks, and may benefit from keeping anti-HSV-2 medications on hand to take when symptoms first develop. Consistent and correct condom use even when HSV symptoms are absent is advisable for maximal protection against transmission of HSV-2 or HIV to uninfected sex partners. Patients with negative HSV-2 serologic results should be counseled about measures to avoid HSV-2 exposure, and their sex partners should be offered serologic testing and counseling regarding chronic suppressive anti–HSV-2 therapy.

Consideration should be given to chronic suppressive anti-HSV therapy for HIV- and HSV-2-coinfected patients who experience recurrent symptomatic outbreaks. If a coinfected patient has an HIV-negative, HSV-2–negative, or dual-negative sex partner, the clinician could also consider chronic HSV-2 suppressive therapy for the patient to decrease the likelihood of HSV-2 and HIV transmission to the uninfected partner. Regimens recommended for chronic suppressive therapy of HSV-2 are acyclovir, 400 mg orally twice daily, or valacyclovir, 500 mg or 1000 mg orally daily (for further discussion, see Chapter 14). At this time, there is no direct clinical evidence to support recommending chronic HSV-2 suppressive therapy for HIV-infected patients to slow HIV disease progression; however, clinical trials addressing this question are now being performed.

Gonorrhea, Chlamydia, & Pelvic Inflammatory Disease

According to the CDC’s 2006 STD treatment guidelines, whether the management of immunodeficient HIV-infected women with pelvic inflammatory disease requires more intensive treatment has not been determined. Such women were more likely to have tubo-ovarian abscesses but responded equally well to standard parenteral and oral antibiotic regimens when compared with HIV-uninfected women.

Similarly, gonococcal and chlamydial infections do not seem to cause differing illness or require different treatment in HIV-infected individuals. However, HIV-infected women more often have multiple concomitant reproductive tract infections, a fact that bears remembering when assessing and treating such patients.

Bacterial Vaginosis & Trichomoniasis

The clinical presentation and recommended treatment of these infections do not differ in HIV-infected patients. The reader is referred to detailed discussion of these diseases elsewhere in this text (see Chapters 11 and 18).

Vulvovaginal Candidiasis

Presentations of candidal vulvovaginitis are generally similar in HIV-infected and uninfected patients but are by definition considered “complicated” when occurring in immunosuppressed patients. Episodes may be more common and more severe among HIV-infected patients and may require longer duration of therapy (7–14 days or more) if standard courses are not effective for individual patients.

Lymphogranuloma Venereum

This infection is rare in developed countries but more common currently in HIV-infected people than in those without HIV infection. The manifestations and treatment of lymphogranuloma venereum are described elsewhere in this text (see Chapter 17), but the infection bears mentioning here because of its strong epidemiologic association with HIV-infected MSM, in whom outbreaks in urban areas have recently been reported.

Scabies & Norwegian Scabies

Norwegian (or crusted) scabies, a severe form of scabies that occurs in patients with advanced immunosuppression, is much more common in HIV-infected patients than in uninfected patients and, like all scabies, is highly contagious. It is best treated with oral ivermectin, 200 mcg/kg as a single dose, followed by a repeat dose 2 weeks later in conjunction with topical permethrin.

Molluscum Contagiosum

This skin and genital condition caused by a poxvirus is much more common in HIV-infected persons and has no apparent long-term adverse effects. It presents as scattered umbilicated papules, usually in the genital area, but can be disseminated in patients with advanced HIV infection. Treatment consists of ablative cryotherapy, as needed.

• • The diagnosis of a new STD in a patient with HIV-infection should initiate a broad screening evaluation as well as a discussion about sexual risk behavior and the spread of STDs and HIV.
• • In the medical care of HIV-infected patients, an increase in HIV viral load or decrease in CD4 T cell count should prompt an evaluation for syphilis infection.