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Case 3: Discussion

Rationale for STD Screening in HIV-Infected Persons

Although many HIV-infected individuals consistently practice safe sex, a significant proportion engage in high-risk sexual behaviors, placing themselves at risk for sexually transmitted diseases (STDs).Indeed, HIV-infected persons are more likely than the general population to develop a STD, and some STDs may have atypical presentations or cause significant morbidity in HIV-infected individuals[1]. Promptly identifying and treating STDs can both limit a patient's long-term sequelae from these infections and prevent them from transmitting STDs to their sexual partners.Furthermore, available data suggest the presence of an STD in an HIV-infected person increases the likelihood of transmitting HIV to their sexual partners; for more detailed information regarding this issue, see STDs and HIV Transmission in this same Prevention for Positives Module[2,3]. Thus, prompt treatment of STDs in HIV-infected individuals may reduce their risk of transmitting HIV to others[4]. Finally, detecting a new STD in an HIV-infected patient indicates ongoing high-risk behavior and should prompt an appropriate intervention to eliminate or minimize this high-risk behavior.As part of the initiative for incorporating HIV prevention into the medical care of persons living with HIV, the Centers for Disease Control and Prevention (CDC), Health Resources Services Administration (HRSA), and HIV Medicine Association (HIVMA) strongly emphasize routine periodic STD screening in HIV-infected individuals[5,6].

Incidence and Prevalence of STDs Among HIV-Infected Individuals

The overall incidence and prevalence of STDs in HIV-infected individuals in the United States are difficult to estimate. Incidence varies both by local prevalence of the STD and by the HIV-infected population under consideration. For example, the incidence and prevalence of STDs may vary considerably when comparing men who have sex with men (MSM), women, or heterosexual men. In addition, most studies of STD incidence in HIV-infected patients have been limited to a relatively small number of clinics providing HIV and/or STD-related care, and there have been no published studies of longitudinal STD screening in asymptomatic HIV-infected men. Not surprisingly, individuals are often diagnosed with an STD at the same time they receive an initial diagnosis of HIV. One retrospective cohort study of men and women who sought care at an STD clinic in Baltimore revealed particularly high rates of STDs in both women and men at the time of HIV diagnosis (Figure 1); approximately one-third of them were symptomatic[7]. Nonetheless, even after receiving a diagnosis of HIV, the incidence of STDs in the cohort remained high at follow-up (7.0 STD cases/100 person years in men and 5.6 STD cases /100 person years in women) (Figure 2)[7]. In a separate study that involved HIV-infected women living in 14 cities in the United States, a baseline examination found evidence of an STD in 13% of the women, with more than 80% of these STD cases consisting of a diagnosis of trichomoniasis (Figure 3)[8]. Subsequent periodic STD screening of these women during a mean of 2.1 years revealed that 19% had infection or re-infection with Trichomonas vaginalis, and 2-3% acquired chlamydia, gonorrhea, or syphilis (Figure 4). Risk factors for STD acquisition were African-American ethnicity, sex with an injection-drug user, report of a previous STD, and detection of an STD at baseline. Other studies have also shown HIV-infected women to have a particularly high risk for trichomoniasis[9].

The resurgence of gonorrhea and syphilis among HIV-infected MSM in the United States (Figure 5 and Figure 6) clearly illustrates continued risk behavior in this group[10,11]. Depending on sexual practices, HIV-infected patients may also be at risk for STDs at non-genital sites. A recent cross-sectional study that predominantly involved male HIV-infected patients in San Francisco (most of whom were MSM) found that asymptomatic pharyngeal and rectal infections were significantly more common than asymptomatic urethral infections (Figure 7)[12]. Taken together, these data from multiple studies highlight the ongoing risk behavior that places HIV-infected persons at increased risk for acquiring and transmitting STDs and HIV.

Screening Guidelines

Because of the high prevalence of asymptomatic STDs in HIV-infected persons and the potential impact of STDs on both these individuals and their partners, the CDC, HRSA, and HIVMA issued guidelines in 2003 recommending routine periodic STD screening of asymptomatic HIV-infected individuals[5]. These guidelines advise that medical providers should make STD screening a high priority during the initial clinic visit with an HIV-infected patient. At this initial visit, all HIV-infected women should undergo screening for syphilis and trichomoniasis (Figure 8 STD Screening Recommendations for HIV-Infected IndividualsSTD Screening Recommendations for HIV-Infected Individuals). Screening for genital gonorrhea and chlamydia should also be considered in most sexually active HIV-infected women, and performed routinely in all HIV-infected women aged 25 years or younger (regardless of whether condom use was reported). Screening in women older than 25 years should be based on risk assessment, and would be indicated in a patient such as the one in the case presented here, who reports no condom use and has a partner who has other partners. Furthermore, HIV-infected women who report receptive oral or anal sex should undergo testing for pharyngeal gonorrhea (for oral sex) and rectal gonorrhea, and rectal chlamydia (for anal sex). Similarly, all HIV-infected men should be screened for syphilis at the initial visit. These STD screening guidelines also recommend consideration of testing for urethral chlamydia and gonorrhea at the initial visit. Among HIV-infected men who report receptive oral or anal sex (regardless of whether condom use was reported), testing for pharyngeal gonorrhea (for oral sex) and rectal gonorrhea and chlamydia (for anal sex) should be performed. Some experts also recommend routine serologic testing for herpes simplex virus type-2 (HSV-2), which causes most genital herpes in HIV-infected individuals[5]. Subsequent to the initial STD screening, further screening should be performed at least annually for all sexually active patients and as frequently as every 3 to 6 months for patients at higher risk for STDs (Figure 9). Finally, any patient who reports any symptoms consistent with an STD should receive immediate and appropriate clinical testing.

Preferred Tests for Screening

The 2003 CDC, HRSA, and HIVMA 2003 recommendations regarding STD screening in HIV-infected individuals provides a listing of preferred and alternative STD tests based on the suspected STD, the anatomic site of exposure, and the gender of the individual undergoing testing (Figure 10). Although a detailed account of the specific aspects of all tests available for STD screening is beyond the scope of this discussion, a few key points should be highlighted. First, screening for asymptomatic syphilis requires serologic testing, typically with a non-treponemal test (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]) test; a positive RPR or VDRL test should then be quantified as a titer. If the patient has a positive non-treponemal test, it should be followed by a confirmatory treponemal antigen test (fluorescent treponemal antibody absorbed [FTA-ABS] or Treponema pallidum particle agglutination [TP-PA]). Second, several modalities are available to test for trichomoniasis, including microscopic examination of wet mount, culture of vaginal fluid, and rapid (point-of-care) antigen detection testing[13]. Third, nucleic acid amplification testing (NAAT) of first-catch urine (the initial 10-30 ml when starting to void) has greatly simplified testing for urogenital gonorrhea and chlamydia, and is generally considered as sensitive as NAAT of cervical or urethral swab specimens[14]. Although NAAT is not yet FDA-approved for pharyngeal or rectal specimens, some local laboratories have validated this approach (local STD programs can offer guidance in this rapidly evolving area). Otherwise, most providers use culture for rectal and pharyngeal gonorrhea screening; rectal chlamydia screening requires culture (if available) or direct fluorescent antibody testing. Chlamydial infection of the pharynx is rare and unlikely to be persistent or to cause symptoms; for this reason, pharyngeal screening is generally not recommended. Finally, for serologic screening for HSV-2, providers should use assays that detect glycoprotein G-based antibody (commonly termed "type-specific antibody"). Non-glycoprotein G-based antibody tests, while commonly used[15], have poor performance characteristics and are not recommended.

Case Summary

Saline microscopy of this patient's vaginal fluid performed in the clinic revealed motile trichomonads consistent with vaginal trichomoniasis. The provider obtained a pharyngeal swab for N. gonorrhoeae culture, a rectal swab for N. gonorrhoeae, C. trachomatis cultures, and a first-catch urine for NAAT for N. gonorrhoeae and C. trachomatis. Blood was drawn and sent to the lab for an RPR. A pregnancy test was also performed, and was negative. The patient's cultures were negative, but her RPR was positive at a titer of 1:16 (confirmed by FTA). She was treated appropriately for trichomoniasis and syphilis, and her partner was also tested and treated for syphilis and trichomoniasis. After she received the results of the positive STD tests, the patient stated that she was more motivated to use condoms, but was unsure if she would be able to use them 100% of the time. After a discussion of additional birth control options, she was prescribed oral contraceptive pills. Follow-up STD screening was planned within the next 3 to 6 months.

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    Figure 1. Prevalence of STDs at the Time of HIV Diagnosis

    The prevalence of STDs in a cohort of patients testing positive for HIV at two STD clinics in Baltimore. Syphilis = either primary or secondary syphilis; GC = Neisseria gonorrhoeae; NGU = non-gonococcal urethritis (in men); and Trichomonas = Trichomonas vaginalis (in women).

    Data from: Erbelding EJ, Chung SE, Kamb ML, Irwin KL, Rompalo AM. New sexually transmitted diseases in HIV-infected patients: markers for ongoing HIV transmission behavior. J Acquir Immune Defic Syndr. 2003;33:247-52.


    Figure 1
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    Figure 2. Incidence of STDs in HIV-Infected Patients Tested at an STD Clinic

    The incidence of STDs seen in passive follow-up of the HIV-infected patients represented in Figure 1. Syphilis = either primary or secondary syphilis; GC = Neisseria gonorrhoeae; NGU = non-gonococcal urethritis (in men); and Trichomonas = Trichomonas vaginalis (in women).

    Data from: Erbelding EJ, Chung SE, Kamb ML, Irwin KL, Rompalo AM. New sexually transmitted diseases in HIV-infected patients: markers for ongoing HIV transmission behavior. J Acquir Immune Defic Syndr. 2003;33:247-52.


    Figure 2
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    Figure 3. Prevalence of STDs in HIV-Infected Women at 14 HIV Care Facilities in the United States

    Prevalence of STDs in a group of HIV-infected women at 14 HIV care facilities in the United States upon entry into a fluconazole prophylaxis trial. Trichomonas = Trichomonas vaginalis; CT = Chlamydia trachomatis; GC= Neisseria gonorrhoeae; and PID= pelvic inflammatory disease.

    Data from: Capps L, Peng G, Doyle M, El-Sadr W, Neaton JD. Sexually transmitted infections in women infected with the human immunodeficiency virus. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Sex Transm Dis. 1998;25:443-7.


    Figure 3
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    Figure 4. Incidence of STDs in HIV-infected Woman and 14 HIV Care Facilities in the United States

    Incidence of STDs in a group of HIV-infected women at 14 HIV care facilities in the United States during a mean of 2.1 years of active follow-up. The proportion of asymptomatic versus symptomatic infections was not published. Cumulative incidence of any STD after 24 months was 26%. Trichomonas = Trichomonas vaginalis; CT = Chlamydia trachomatis; GC= Neisseria gonorrhoeae; and PID = pelvic inflammatory disease.

    Data from: Capps L, Peng G, Doyle M, El-Sadr W, Neaton JD. Sexually transmitted infections in women infected with the human immunodeficiency virus. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Sex Transm Dis. 1998;25:443-7.


    Figure 4
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    Figure 5. Prevalence of Gonorrhea and Chlamydia in MSM by HIV Status

    This graph represents 2004 data from the MSM Prevalence Monitoring Project, a CDC funded project that includes data from culture and non-culture tests collected during routine care at participating STD clinics in 9 cities in the United States.

    Data from: Centers for Disease Control. Sexually Transmitted Disease Surveillance 2004. Atlanta, GA: U.S. Department of Health and Human Services, September 2005. http://www.cdc.gov/std/stats/toc2004.htm


    Figure 5
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    Figure 6. Incidence of Primary and Secondary Syphilis by HIV Status in MSM in California

    These figures highlight that more than 50% of individuals with newly diagnosed primary and secondary syphilis in California are HIV-infected. Only patients in whom HIV status was known are included. The number of individuals with primary or secondary syphilis in whom HIV-status was unknown was 86 in 2002, 94 in 2003, and 102 in 2004.

    Adapted from: 2004 California STD Surveillance Slides. California Department of Health Services, STD Control Branch, 2006. http://www.dhs.ca.gov/ps/dcdc/STD/datatables.htm


    Figure 6
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    Figure 7. Prevalence of Gonorrhea and Chlamydia in Asymptomatic HIV-Infected Patients in San Francisco, by Anatomic Site

    Prevalence of rectal, pharyngeal, and urethral chlamydia and gonorrhea in a cohort of asymptomatic HIV-infected patients in San Francisco. Individuals were tested at each anatomic site for which they reported sexual exposure. The sample was 75% male, and no women had urinary or rectal infections. Of note, nucleic acid amplification testing (NAAT) was used for gonorrhea and chlamydia detection at all anatomic sites. Syphilis was identified in 1.8% of patients.

    Data from: Phipps W, Stanley H, Kohn R, Stansell J, Klausner JD. Syphilis, chlamydia, and gonorrhea screening in HIV-infected patients in primary care, San Francisco, California, 2003. AIDS Patient Care STDS. 2005;19:495-8.


    Figure 7
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    Figure 8. Image 1: STD Screening Recommendations for HIV-Infected Individuals
    Figure 8
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    Figure 9. Indications to Perform STD Screening Every 3-6 Months

    HIV-infected individuals with the above risk factors should be considered for more frequent periodic screening for asymptomatic STDs. A minimum screening interval of every 3 to 6 months is recommended.

    From: Centers for Disease Control and Prevention (CDC); Health Resources and Services Administration; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Incorporating HIV prevention into the medical care of persons living with HIV. Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2003;52 (RR-12):8 (Box 2).


    Figure 9
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    Figure 10. Diagnostic Testing Available for Detection of STDs

    Diagnostic tests for STDs are listed in order of preference for recommendation, with the most highly recommended test listed first.

    DFA= direct fluorescent antibody, RPR=rapid plasma reagin, VDRL=Venereal Disease Research Laboratory, FTA-ABS= fluorescent treponemal antibody absorbed, TP-PA= Treponema pallidum particle agglutination, GU=genitourinary, NAAT =nucleic acid amplification test.

    *First catch urine (i.e. first 10-30 ml of void) should be used; advise patient not to self-cleanse prior to collection and ideally, patients should not have urinated in prior 1-2 hours. > Local STD Program staff can provide guidance regarding status of NAAT validation for performance at rectum and pharynx + Chlamydia trachomatis major outer membrane protein (MDMP)-specific stain should be used.

    From: Centers for Disease Control and Prevention (CDC); Health Resources and Services Administration; National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Incorporating HIV prevention into the medical care of persons living with HIV. Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2003;52(RR-12):9 (Table 3).


    Figure 10