2006 STD Treatment Guidelines Forum: Implications for HIV Care Providers

1. 2006 STD Treatment Guidelines Forum: Implications for HIV Care Providers Jeffrey Beal, M.D. Clinical Director Florida/Caribbean AIDS Education and Training Center Please include the title of your presentation, your full name and affiliations (including your role within the AETC, if applicable).Please include the title of your presentation, your full name and affiliations (including your role within the AETC, if applicable).

2. Disclosure of Financial RelationshipsThis speaker has the no significant financial relationships with commercial entities to disclose. Use this slide if you have any significant financial relationships with any commercial entities. If you use this slide, please delete slide 2. Use this slide if you have any significant financial relationships with any commercial entities. If you use this slide, please delete slide 2.

3. STD Prevention Accurate identification of STDs and effective clinical management are important strategies to improve HIV prevention efforts CDC has published guidance for STD prevention and management for 20 yrs Guidelines development- evidence based systematic review- public/private sectors; professional organizations

4. CDC STD Treatment Guidelines Authoritative source of STD treatment and management Screening, prevention and vaccination strategies, treatment regimens Order hard copies http://www.cdc.gov/ std/treatment Pocket guides, wall charts

5. Clinical Prevention Guidance Education/counseling to reduce risk of STD acquisition Detection of asymptomatic infection and/or symptomatic persons unlikely to seek services Effective diagnosis and treatment Evaluation, treatment, counseling of sexual partners Pre-exposure vaccination of persons at risk - hepatitis A, B The guidelines focus on 5 issues to reduce the occurrence of STDs and thus also decrease the incidence of HIV The guidelines focus on 5 issues to reduce the occurrence of STDs and thus also decrease the incidence of HIV

6. STD/HIV Prevention Counseling Routine discussion of sex behaviors- client centered counseling # partners, serostatus, type of activity, condom use (barriers), pregnancy prevention Specific actions necessary to avoid acquisition or transmission of STDs Abstinence, condom use, limiting sex partners, modifying sex behaviors, vaccines Culturally appropriate client-centered counseling: Abstinence, ? sexual partners, mutually monogamous relationship with both STD screened prior to sex, male/female condom education, specific counseling regarding sex act and risk Culturally appropriate client-centered counseling: Abstinence, ? sexual partners, mutually monogamous relationship with both STD screened prior to sex, male/female condom education, specific counseling regarding sex act and risk

7. Prevention Methods - Male Condoms Correct and consistent male latex condom use is highly effective in preventing the sexual transmission of HIV; can reduce risk of CT, GC, trichomoniasis May reduce the risk of transmission of HSV-2 May reduce risk of HPV-associated genital warts, cervical cancer Higher rates of regression of CIN, HPV clearance (women), penile lesions in men Protective effect on HPV acquisition among newly sexually active women (70%?) Condom use might reduce the risk for HPV-associated diseases (e.g., genital warts and cervical cancer [17]) and mitigate the adverse consequences of infection with HPV, as their use has been associated with higher rates of regression of cervical intraepithelial neoplasia (CIN) and clearance of HPV infection in women (18), and with regression of HPV-associated penile lesions in men (19). one recent prospective study among newly sexually active college women demonstrated that consistent condom use was associated with a 70% reduction in risk for HPV transmission (20). When used consistently and correctly, male latex condoms are highly effective in preventing the sexual transmission of HIV infection (i.e., HIV-negative partners in heterosexual serodiscordant relationships in which condoms were consistently used were 80% less likely to become HIV-infected compared with persons in similar relationships in which condoms were not used) 2006 CDC GuidelinesCondom use might reduce the risk for HPV-associated diseases (e.g., genital warts and cervical cancer [17]) and mitigate the adverse consequences of infection with HPV, as their use has been associated with higher rates of regression of cervical intraepithelial neoplasia (CIN) and clearance of HPV infection in women (18), and with regression of HPV-associated penile lesions in men (19). one recent prospective study among newly sexually active college women demonstrated that consistent condom use was associated with a 70% reduction in risk for HPV transmission (20). When used consistently and correctly, male latex condoms are highly effective in preventing the sexual transmission of HIV infection (i.e., HIV-negative partners in heterosexual serodiscordant relationships in which condoms were consistently used were 80% less likely to become HIV-infected compared with persons in similar relationships in which condoms were not used) 2006 CDC Guidelines

8. Prevention Methods - Spermicides Spermicides (N-9 ) not effective in preventing cervical GC, CT, HIV frequent use -disruption of vaginal, anal epithelium may increase risk of HIV transmission with vaginal intercourse (IC) Condoms lubricated with N-9 no more effective than other lubricated condoms in protection against HIV, STDs

9. STD Screening Strategies STD screening for MSM or HIV+ at initial visit Syphilis serology Trichomonas, pap smear (women) GC/CT (Urethral culture or NAAT) Pharyngeal culture, GC (oro-genital) Rectal culture, GC/CT (receptive anal IC) Type specific HSV2 serology (some specialists) Hepatitis A, B serology; C (HIV + or risk factors) Periodic screening- as indicated q3-6 mo What is the argument for HSV-2 screening? Note older assays that do not accurately distinguish HSV-1 from HSV-2 antibody (despite claims to the contrary) remain on the market. Therefore, the serologic type-specific glycoprotein G (gG)-based assays should be specifically requested when serology is performed What is the argument for HSV-2 screening? Note older assays that do not accurately distinguish HSV-1 from HSV-2 antibody (despite claims to the contrary) remain on the market. Therefore, the serologic type-specific glycoprotein G (gG)-based assays should be specifically requested when serology is performed

10. Emerging Issues STD/HIV in MSM Syphilis Increases in US and Western Europe 40-60% HIV co-infected Methamphetamine use, internet partnering Gonorrhea Increase in Flouroquinolone-resistant Neisseria gonorrhea (QRNG) Chlamydia- LGV proctitis Acute hepatitis C- high risk sexual behavior (fisting) HIV - drug resistance, superinfection

11. MSM Prevalence Monitoring Project � Median Test Positivity for GC, CT, HIV,and Syphilis Seroreactivity among MSM by Race/Ethnicity, STD Clinics, 2005 2005 increased incidence of GC and Syphilis in Black Hispanic2005 increased incidence of GC and Syphilis in Black Hispanic

12. Median Test Positivity for GC, CT, Syphilis among MSM, by HIV Status, STD Clinics, 2005 MSM Prevalence Monitoring Project And more common in the HIV infected � prevention efforts not working. And more common in the HIV infected � prevention efforts not working.

13. Both syphilis chancers Primary syphilis Consider using to introduce historical factors of ulcers: Note number of lesions, depth of lesion, presence of vesicles, induration, necrotic material on the ulcer bed, presence or absence of pain, associated lymphadenopathy, change over time, history of trauma, does the ulcer invade under the superficial edges or is it well demarcated. An incorrect diagnosis frequently results from a purely clinical approach to genital ulcers. Both syphilis chancers Primary syphilis Consider using to introduce historical factors of ulcers: Note number of lesions, depth of lesion, presence of vesicles, induration, necrotic material on the ulcer bed, presence or absence of pain, associated lymphadenopathy, change over time, history of trauma, does the ulcer invade under the superficial edges or is it well demarcated. An incorrect diagnosis frequently results from a purely clinical approach to genital ulcers.

14. Genital UlcerEvaluation History and physical examination often inaccurate Serologic test for syphilis Diagnostic evaluation for HSV Haemophilus ducreyi culture (chancroid prevalent) Biopsy may be useful Treat for diagnosis most likely - clinical/epidemiology 25% have no lab confirmed dx Treat for most likely which in US would be HSV, syphilis or chancroid Treat for most likely: genital HSV, syphilis, chancroid most common in the USTreat for most likely: genital HSV, syphilis, chancroid most common in the US

15. Genital herpes � Initial visits to physicians� offices: US, 1966�2004

16. HSV-2 / HIV Infection Lesions may be severe, prolonged, and atypical HSV shedding increased despite ARV Antiviral suppressive or episodic therapy effective in decreasing clinical manifestations; may need higher doses or more frequent dosing Extent to which suppressive therapy decreases HIV transmission is unknown Suppressive therapy can ? recurrence by 70-80% Persistent lesions on antivirals - foscarnet 40 mg/kg q8 or topical cidofovir gel 1% Suppressive therapy does reduce the frequency of genital HSV recurrences by 70-80% in patients with frequent recurrences (= 6/yr).Suppressive therapy does reduce the frequency of genital HSV recurrences by 70-80% in patients with frequent recurrences (= 6/yr).

17. The classical painful multiple vesicular or ulcerative lesions are absent in many infected persons. The classical painful multiple vesicular or ulcerative lesions are absent in many infected persons.

19. Primary and secondary syphilis � Rates: Total and by sex: United States, 1986�2005 and the Healthy People 2010 target The 2000 re-emergence of syphilis � MSM related?The 2000 re-emergence of syphilis � MSM related?

20. Painless ulcer on genitalia, perianal area, pharynx, tongue, lips � appears 10-90 days after infection, spontaneously heals in 5-6 wk. May have associated nontender, rather firm, unilateral regional lymphadenitis.Painless ulcer on genitalia, perianal area, pharynx, tongue, lips � appears 10-90 days after infection, spontaneously heals in 5-6 wk. May have associated nontender, rather firm, unilateral regional lymphadenitis.

21. Secondary syphilitic rash � wide variety of skin lesion � macular, papular, maculopapular, pustular, ulcerative, follicular or nodular, mucous patches (highly infectious lesions of the mucous membrane with �snail-track ulcers�, condylomata lata. 90% have generalized lymphadenopathy. 99% will have + VDRL and FTA-ABS or TPHASecondary syphilitic rash � wide variety of skin lesion � macular, papular, maculopapular, pustular, ulcerative, follicular or nodular, mucous patches (highly infectious lesions of the mucous membrane with �snail-track ulcers�, condylomata lata. 90% have generalized lymphadenopathy. 99% will have + VDRL and FTA-ABS or TPHA

22. Syphilis Laboratory Testing Darkfield or Direct Flourescent Antibody (DFA) test of lesion exudate or tissue � definitive for early syphilis Presumptive diagnosis: Nontreponemal (VDRL or RPR) � false + occur in other medical conditions Treponemal tests (FTA-ABS or TP-PA) - confirmatory Quantitative non-treponemal (RPR, VDRL) testing to guide treatment (= 4-fold change is significant) False + RPR: HIV/Lyme Ds./certain types of pneumonia/ Malaria/ SLE 4 fold change; 1:16 � 1:4 or 1:8 � 1:32 VDRL/RPR usually revert to negative over time, may remain low titre �serofast� FTA-ABS/TP-PA � usually remain + for life (15-25% treated will become nonreactive after 2-3 yrs) Sonicated treponemes � recombinant proteins of Treponema pallidum used as antigen. FTA-ABS (flourescent treponemal antibody-absorption test) as second treponemal test; TP-PA Treponemal Pallidum particle agglutination EIA�s more expensive. Ready for use today?False + RPR: HIV/Lyme Ds./certain types of pneumonia/ Malaria/ SLE 4 fold change; 1:16 � 1:4 or 1:8 � 1:32 VDRL/RPR usually revert to negative over time, may remain low titre �serofast� FTA-ABS/TP-PA � usually remain + for life (15-25% treated will become nonreactive after 2-3 yrs) Sonicated treponemes � recombinant proteins of Treponema pallidum used as antigen. FTA-ABS (flourescent treponemal antibody-absorption test) as second treponemal test; TP-PA Treponemal Pallidum particle agglutination EIA�s more expensive. Ready for use today?

23. Syphilis Drug of choice remains penicillin PCN allergy- doxycycline (100 mg BID x 14 d if primary or secondary), ceftriaxone - optimal dose not defined (1 gm IV/IM x 8-10 d for early disease) Azithromycin 2 gm may be effective; resistance and treatment failure reported PCN alternatives - not well studied in HIV+ Cef try ax oneCef try ax one

24. Primary/Secondary SyphilisResponse to Therapy/HIV Infection Most respond to benzathine penicillin G 2.4 million units IM single dose No regimens more effective in preventing neurosyphilis � majority respond to above Some increased risk of treatment failure/neurologic complications not precisely defined Benzathine pen x 3 wkly (some specialists) CSF exam - neurologic signs/sx; CSF exam if RPR >1:32 or CD4 <350 (some specialists) Clinical/serologic evaluation at 3, 6, 9, 12, 24 mo Tx/serologic failure (6-12 mo after tx) - CSF exam, retreat with benzathine penicillin wkly x 3 Bullet 3?Bullet 3?

25. Latent Syphilis - HIV Infection CSF exam before treatment WBC > 5cells/mm3, ?Pro., + VDRL-CSF, if FTA-ABS negative may exclude neurosyphilis CSF exam for RPR >1:32 or HIV+ CD4 <350 regardless of stage (some specialists) Benzathine PCN 2.4 MU IM weekly x 3 Doxycycline 100 mg BID x 28d, or TCN 500 mg QID x 28d Evaluation at 6,12,18, 24 mo after tx CSF exam - no 4x decline by 12-24 mo CSF FTA-ABS highly sensitive but less specific. And if PCN allergic? Doxycycline 100 mg orally BID or TCN 500 mg QID X 28 days. Last bullet 4 fold decline in titre based on CSF, or on Serum RPRCSF FTA-ABS highly sensitive but less specific. And if PCN allergic? Doxycycline 100 mg orally BID or TCN 500 mg QID X 28 days. Last bullet 4 fold decline in titre based on CSF, or on Serum RPR

26. Neurosyphilis Treatment LP recommended to rule out neurosyphilis in all HIV-infected patients with syphilis Recommended regimen Aqueous crystalline penicillin G, 18-24 million units administered 3-4 mu IV q4h for 10-14 days (may be given via continuous infusion) Alternative regimen Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg orally qid for 10-14 days Some experts give benzathine penicillin G 2.4 million units IM wkly x 3 after completion of these regimens to provide comparable duration of treatment for late latent syphilis CDC MMWR 2006; Vol 55 (RR11)

27. Chlamydia � Rates: Total and by sex: US, 1986�2005

28. Chlamydia trachomatis Most frequently reported infectious disease in US 3-4 million cases per year Properties of both viruses and bacteria Requires material from host cells for replication Coinfection with chlamydia occurs in 60% of cases of gonorrhea

29. Lymphogranuloma venereum Proctitis presentation among HIV(+) MSM Diagnosis Genital or lymph node aspirates-culture, DFA Caused by Chlamydia trachomatis serovars L1, L2, L3 Serology can support (CF > 1:64), not validated for proctitis Empiric Rx warranted for appropriate clinical syndrome Doxycycline 100 mg PO bid x 21 d ?? Azithromycin 1 g PO q wk x 3 wks LGV caused by serovars L1, L2, or L3 DFA Direct Flourescent Antibody Compliment fixation titre >1:64 can support the diagnosis in the appropriate clinical context. LGV caused by serovars L1, L2, or L3 DFA Direct Flourescent Antibody Compliment fixation titre >1:64 can support the diagnosis in the appropriate clinical context.

30. A self limiting genital ulcer or papule occurs at the site of infection. Tender inguinal and or femoral lymphadenopathy, typically unilateral may A self limiting genital ulcer or papule occurs at the site of infection. Tender inguinal and or femoral lymphadenopathy, typically unilateral may

31. LGV Proctocolitis Rectal ulcers or lesions Mucoid anal discharge Rectal bleeding Tenesmus or constipation Rectal scarring and fistulas

32. Detection of CT/GC using NAATRectal Specimens NAAT (nucleic acid amplification test) not FDA cleared- rectal/pharyngeal NAAT urine for GC/Chlamydia CDC/FDA/manufacturers - NAAT rectal indication PCR assays for LGV serovars Culture specimens for GC/Chlamydia DNA probes for GC/Chlamydia Bullet 2? 3/ Why is bullet 4 on this slideBullet 2? 3/ Why is bullet 4 on this slide

33. Chlamydia Treatment Same treatment regimens for HIV+ Equivalent efficacy and tolerance of azithromycin 1g po single dose or doxycycline 100 mg BID x 7d Retest 3-4 mo after therapy - high prevalence of repeat infection (women) Azithromycin recommended in pregnancy

34. Other Diseases CausingGenital Ulcers/HIV Chancroid (H. Ducreyi) Painful genital ulcers heal slowly, lymphnodes may need drained some specialists prefer erythromycin 500 mg tid x 7 d ceftriaxone 250 mg IM, or azithromycin 1 g po single dose therapies, or cipro 500 BID X 3d Granuloma inguinale (Donovanosis) (Klebsiella granulomatis) Rare in us, painless progressive ulcerative lesions, no ? nodes Doxycycline for 3 wks or until all lesions healed No cipro if PG or lactating H Ducreyi � Chancroid - painful genital ulcer and tender supperative inguinal adenopathy. 10% in US coinfected with HIV or syphilis. Probable diagnosis made if all the following criteria met: 1)one or more painful genital lesions 2) No evidence of T. pallidum by darkfield or negative serologic test for syphilis at least 7 days after onset of lesion 3) Appearance of lesion oand regional lymphadenopathy are typical for chancroid 4) HSV testing on the ulcer exudate is negative Klebsiella granulomatis � Granuoma inguinale (Donovanosis) � rare in US; painless, progressive ulcerative lesions without regional lymphadenopathy, highly vascular, beefy red appearance and bleed easily on contact.No cipro if PG or lactating H Ducreyi � Chancroid - painful genital ulcer and tender supperative inguinal adenopathy. 10% in US coinfected with HIV or syphilis. Probable diagnosis made if all the following criteria met: 1)one or more painful genital lesions 2) No evidence of T. pallidum by darkfield or negative serologic test for syphilis at least 7 days after onset of lesion 3) Appearance of lesion oand regional lymphadenopathy are typical for chancroid 4) HSV testing on the ulcer exudate is negative Klebsiella granulomatis � Granuoma inguinale (Donovanosis) � rare in US; painless, progressive ulcerative lesions without regional lymphadenopathy, highly vascular, beefy red appearance and bleed easily on contact.

35. Gonorrhea � Rates: Total and by Sex: US, 1986�2005

36. Treatment of Gonorrhea Recommended regimens Ceftriaxone 125 mg IM x 1 Cefixime 400 mg PO x 1 Quinolone (ciprofloxacin 500 mg, or ofloxacin 400 mg, or levofloxacin 250 mg po x 1) Quinolones should not be used in MSM If cefixime unavailable cefpodoxime 400 mg cefuroxime axetil 1 g (marginal) azithromycin 2 g (possible emergence of resistance) Quinolones should not be used in MSM in areas of HIGH prevalence QRNG or if infected while traveling abroad Quinolones should not be used in MSM in areas of HIGH prevalence QRNG or if infected while traveling abroad

37. GC Treatment - Spectinomycin Discontinuation of distribution in US 11/05- inventory expired 5/06 Preferred - PCN/cephalo allergy in pregnancy, high prevalence of QRNG, or MSM Options- desensitize; azithromycin 2 gm effective GI side effects Potential emergence of resistance TREAT ALL FOR CHLAMYDIA AS WELL

38. Cervicitis CT, GC, TV, HSV; M genitalium, BV Evaluation - CT/GC NAAT, trichomonas culture if smear neg., BV; vaginal WBC >10 may indicate endocervical CT or GC Cervicitis increases HIV shedding Same treatment regimen for HIV+ Presumptive tx: Azithromycin 1 g po x 1 or Doxy 100 mg BID x 7d

39. Tinidazole Second generation 5-nitromidazole Long duration of action ( t1/2 12-14 hr) One of the recommended regimens for trichomoniasis (2g po single dose) Effective in metronidazole resistant trichomonas Lower tinidazole MLC in MTZ-resistant isolates MTZ 2 g po single dose WHAT IS MLethalC? Tye ni da zoleMTZ 2 g po single dose WHAT IS MLethalC? Tye ni da zole

40. Genital warts � Initial visits to physicians� offices: US, 1966�2004

41. Genital Warts-Male

42. Genital Warts-Female

43. HPV/HIV Infection May have larger or numerous warts, might not respond as well to tx, more frequent recurrences Same treatment regimens recommended Anal cancer screening (some specialists) natural history of anal intraepithelial neoplasia reliability of screening methods response to treatments programmatic considerations

44. Sexually Transmitted GI Syndromes History of receptive anal intercourse or analingus Proctitis Anorectal pain, tenesmus, or rectal disch. N. gonorrhea, C. Trachomatis, T. pallidum, HSV Proctocolitis Sxs. of proctitis + diarrhea, abd. Cramps Campylobacter, shigella, entamoeba histolytica, & rarely LGV Most common infectious causesMost common infectious causes

45. Sexually Transmitted GI Syndromes Enteritis Diarrhea and abd. cramping without signs of proctitis or proctocolitis Associated with analingus Giardia lamblia most frequently implicated Emperic therapy while workup in progress: Cefriaxone 125 mg IM + Doxycycline 100 mg BID x 7d

46. Summary STD Treatment Guidelines MMWR 2006; Vol. 55 (No. RR-11) Critical importance of open dialogue Routine screening Diagnostic studies better than clinical diagnosis Match treatment to the patient Partner assessment and treatment Advancing HIV prevention

47. Acknowledgement Kimberly A Workowski, MD, FACP Associate Professor of Medicine, Emory University, Division of Infectious Diseases Epidemiology and Surveillance Branch, Division of STD Prevention, CDC John F. Toney, M.D. and Joanne Orrick, PharmD, with the Florida/Caribbean AETC