2010 CDC STD Treatment Guidelines – Implications for the HIV Provider John F. Toney, MD, FACP, FIDSA Professor of Medicine, Division of Infectious Diseases and International Medicine, University of South Florida College of Medicine Disclosure of Financial Relationships This speaker has the following significant financial relationships with commercial entities to disclose: • Consultant/speaker – Pfizer • Consultant – Graceway • Grant/speaker - Merck This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation. 2010 CDC STD Treatment Guidelines Answer the “Key Questions” Enlistment of Subject Matter Expert Key Questions Systematic Review of Evidence Guidelines Meeting, April 2009 Rate the quality of the evidence Identify critical gaps in knowledge (research agenda) Background papers; Tables of evidence Write the Guidelines document Special Populations • • • • • • • Adolescents Children STD in pregnancy HIV MSM Women who have sex with women (WSW) Persons in correctional facilities • CT/GC adolescent females (juvenile detention/jail), females <35 • Syphilis (local/institutional prevalence) Clinical Prevention Guidance • High-intensity behavioral counseling (USPSTF) • Risk assessment, interventions, suggestions for practice, screening • Vaccination – hepatitis A virus (HAV), hepatitis B virus (HBV), human papillomavirus (HPV) (bivalent/quadrivalent) • Condoms • CDC fact sheet; female nitrile condom • Microbicides • www.microbicide.org • Pre-exposure prophylaxis for HIV/STD • Male circumcision • Reduced acquisition of HPV, genital HSV USPSTF = US Preventive Services Task Force Ann Intern Med 2008 149:491-496 Prevention Methods - Male Condoms • Correct/consistent latex condom use - highly effective in preventing sexual transmission of HIV; reduced risk - CT, GC, trichomoniasis • May reduce risk of HSV-2 transmission • May reduce risk of genital warts, cervical cancer • Higher rates of CIN regression, HPV clearance, penile lesions • Protective - HPV acquisition (newly sexually active women) Question One Which of the following screening tests should be performed at least annually for sexually active MSM? 1. 2. 3. 4. 5. 6. 7. CT/GC Syphilis Trichomonas HIV if not positive 1, 2, and 3 1, 2, and 4 All should be included Screening Tests Performed at Least Annually for Sexually Active MSM • HIV serology, if HIV negative or not tested within the previous year • Syphilis serology • Urine nucleic acid amplification testing (NAAT) testing for gonorrhea (GC) and chlamydia (CT) • Receptive anal intercourse during the preceding year – screening for GC and CT (regardless of condom history use; rectal swab NAAT is preferred) • GC pharyngeal infection screening in men who have had receptive oral intercourse during the preceding year (NAAT is preferred); CT testing not recommended • Screen more frequently with multiple/anonymous partners NAAT Testing • NAATs perform better than culture (rectum, pharynx) • Extragenital Sites • Commercial laboratories validated NAATs • Most infections asymptomatic • Self-collected vaginal swabs preferred specimen in females; urine OK • Urine preferred specimen in men; urethral swabs OK NAAT Laboratory Ordering and Billing Codes For information on specimen collection and transportation, clinicians should contact the local reference laboratory representative. CPT Billing Codes CT detection by NAAT 87491 GC detection by NAAT 87591 *CDC does not endorse these laboratories, however, they represent the largest laboratories nationally. There may be other private laboratories that have verified rectal and pharyngeal testing with NAATs. Many PHLs have also verified rectal and pharyngeal testing. Question Two • 28yo male MSM sees you for persistent dysuria and a meager mucoid urethral discharge present for a week. He nearly always uses a condom except with oral sex, where he never uses them. He has a new partner beginning two weeks ago, and three partners in the last 5 months. His exam is remarkable only for a scant urethral discharge. He is HIV negative by rapid testing. NAAT testing of the oropharyngeal, rectal, and urine are sent to the lab, as well as syphilis serology. • He is treated with ceftriaxone 125mg IM x 1 dose and doxycycline 100mg orally twice daily for 7 days. He returns 10 days later with slightly improved but persistent dysuria. His NAAT testing is negative as is his syphilis serology. Which of the following answers is correct regarding a potential cause of treatment failure in this case? 1. Mycoplasma genitalium 2. Trichomonas vaginalis 3. Ureaplasma sp. 4. HSV 5. All are potential causes Urethritis • Bacterial STDs: GC (5-20%), CT (15-40%) • Nongonococcal urethritis (NGU) • Mycoplasma genitalium 15-25% • Trichomonas vaginalis 5-20% • Ureaplasma 0-20%; data inconsistent, biovars differ • HSV 15-30%; urethritis in primary infection • Adenovirus, enterics, Candida, anaerobes Mycoplasma genitalium (MG) • Association with acute or persistent NGU • No role in male infertility (limited data) • Conflicting/insufficient evidence for cervicitis, PID, infertility, ectopic pregnancy, adverse birth outcomes • Azithromycin superior to doxycycline for MG urethritis • Moxifloxacin for persistent NGU NGU Treatment • Current drug regimens are adequate for majority of bacterial NGU • Azithromycin > doxycycline for M. genitalium (82% vs 39%) • Cost considerations and lack of public health impact data for MG insufficient to demote doxycycline to alternative agent • Recurrence • Re-exposure from untreated partners • T. vaginalis and M. genitalium • U. urealyticum may account for some failures Epididymitis • Chronic infectious epididymitis (consider Mycobacterium tuberculosis) • Ceftriaxone + doxycycline for initial treatment • quinolone if GC negative (cx or NAAT) or infection likely caused by enteric organism • Ceftriaxone + quinolone • Risk for both sexually transmitted and enteric organisms (MSM-insertive anal intercourse) Cervicitis • CT/GC NAATs-vaginal, cervical, urine • No new antimicrobial treatment trial information • Research is needed on the etiology of persistent cervicitis including the potential role of Mycoplasma genitalium Chlamydia • Primary focus of screening efforts to detect and prevent complications in women • Selective male screening - (adolescent clinics, corrections, national job training program, < 30 yrs, STD, military) • Retest women/men 3 mo post tx • Chlamydia testing in pregnancy – first and third trimester (latter for reinfection) Gonorrhea • Screen sexually active women at increased risk <25 years, previous GC or other STDs, new or multiple partners, inconsistent condoms, CSW, drug use (USPSTF) • No screening in men or women at low risk of infection (USPSTF) • Retest women/men 3 mo after treatment USPSTF = US Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/uspstf/uspsgono.htm Gonorrhea • NAAT sensitivity in genital/non-genital sites superior to culture (variation in NAATs, crossreaction) • Co-treatment might hinder the development of antimicrobial resistance • GC dual treatment (oral cephalosporin + azithromycin) may enhance oropharyngeal tx response Gonorrhea Treatment Efficacy • Anogenital • Ceftriaxone • 125 mg = 98.8% • 250 mg = 99.2% • Geographic distribution in vitro decreased susceptibility, ceftriaxone failures, enhanced pharyngeal efficacy, consistent guidance at all anatomic sites • Oropharyngeal • Ceftriaxone • 125 mg = 94.1% • 250 mg = 98.9% • Oral cephalosporins limited (poor penetration) • Azithromycin 2 gm = 95% • Oral exposure - regimen with enhanced pharygneal efficacy Oropharyngeal GC Treatment • Ceftriaxone efficacy for oropharyngeal GC acceptable • 125 mg = 94.1% ( L95%CI = 85.6%) • 250 mg = 98.9% ( L95%CI = 94.0%) • Limited efficacy of oral cephalosporins (poor penetration) • Cefpodoxime 400 mg = 70.3%, 26/37 patients (Hall) • Cefixime 400 mg = 88.9%, 8/9 (McMillan) • Cefixime + azithro 1 g = 100%, 36/36 (McMillan) • Azithromycin 2 gm = 95%, 20/21 (L95%CI=76.2%) (Dan) • + oral exposure - regimen with enhanced pharygneal efficacy Anogenital GC Treatment • Recommended regimens • Ceftriaxone 250 mg IM (preferred) • PLUS azithromycin 1 gm or doxycycline 100 mg bid x 7d • Cefixime 400 mg PO (if ceftriaxone is not an option) • PLUS azithromycin 1 gm or doxycycline 100 mg bid x 7d • Alternatives • Cefpodoxime 400 mg or Cefuroxime axetil 1 g • Azithromycin 2 g (PCN allergy) Oropharyngeal GC Treatment • Recommended • Ceftriaxone 250 mg IM (preferred) • PLUS azithromycin 1 gm or doxycycline 100 mg bid x 7d • Alternatives • Azithromycin 2 g (PCN allergy) Cephalosporin GC Rx Failures • Suspected treatment failure (oral and injectable) • Treatment failure or in vitro resistance • • • • • Infectious disease consultation Culture and susceptibility Rx ceftriaxone 250 mg IM Ensure partner tx Report to CDC via state or local public health authorities PID • Some association with MG • Insufficient data to support testing/tx MG • Emergence of QRNG • Quinolones not recommended • Parenteral tx not feasible - • Levofloxacin +/- metronidazole may be considered if prevalence/individual risk low • Azithromycin 2 gm + quinolone +/- metronidazole • Ceftriaxone 250 mg IM + azithromycin 1gm qwk x2 (short term success) • Insufficient evidence to warrant removal of IUD Genital, Perianal, Anal Ulcers • History and physical examination often inaccurate • Majority due to HSV or syphilis • Less common chancroid • Noninfectious (yeast, aphthi, fixed drug eruption, psoriasis) • Serologic test for syphilis • Diagnostic evaluation for HSV (culture, PCR) • Treat for diagnosis most likely based on clinical/epidemiology • If syphilis is suspected, treat empirically as initial tests may be negative in primary syphilis • Biopsy if uncertain Syphilis • Definitive diagnosis for early syphilis • darkfield microscopy; PCR • No commercially available Treponema pallidum detection tests • Nontreponemal / treponemal serologic testing • Reverse serologic screening • Management principles for HIV+ similar • Frequent clinical/serologic monitoring • Neurosyphilis can occur at any stage Which of the following is the recommendation for lumbar puncture in HIV positive patients with positive syphilis serology and neurologic symptoms? 1. CD4 count ≤ 350 and RPR ≥ 1:32 2. CD4 count ≥ 350 and RPR ≤ 1:32 3. Treatment failure with benzathine penicillin 4. Late latent syphilis Evaluation of CNS Involvement • Neurologic, ocular, auditory signs/symptoms • CNS invasion occurs in early syphilis regardless of HIV or neurologic symptoms (protein, pleocytosis) • Clinical significance unknown (HIV+/-) • Neurosyphilis diagnosis - combination of tests • CSF: neuro/ocular symptoms, tertiary, serologic treatment failure • Some studies - clinical and CSF consistent with neurosyphilis are associated with RPR ≥ 1:32 and/or CD4 ≤350 • Unless neurologic symptoms present, CSF exam has not been associated with improved clinical outcomes Treatment Recommendations Primary, Secondary, Early Latent • Penicillin treatment of choice +/-HIV • Benzathine penicillin 2.4 mu IM x 1 • No benefit of additional therapy • Enhanced treatment (IM + oral) • Penicillin alternatives • Doxycycline, ceftriaxone • Azithromycin 2 gm (resistance/treatment failure) • Use only when penicillin or doxycycline not feasible • Do not use in MSM or pregnancy Azithromycin • Macrolide resistance associated with A2058G mutation in 23S rRNA gene • Canada, Ireland, Czech Republic, China • Prevalence of mutation US • A2058G found in 9/11 US sites (Su, ISSTDR 2009) • MSM>MSW; no association with US region, race • Treatment failure • US, Czech Republic, China Syphilis - Monitoring in HIV+ • Jarisch-Herxheimer reaction in HIV+ • Early syphilis, high RPR, prior penicillin treatment • Immune reconstitution inflammatory syndrome uncommon • ART use in HIV+ with syphilis • Reduced risk of serologic treatment failure • Lower risk of neurosyphilis • Normalization of CSF parameters with improvement in serum RPR Syphilis Serology and HIV • For most, serologic tests are accurate and reliable for the diagnosis and treatment management • Atypical syphilis serologic test results (i.e., unusually high, unusually low, or fluctuating titers) can occur in HIV-infected persons • When serologic tests do not correspond with clinical findings suggestive of early syphilis, use of other tests (e.g., biopsy, darkfield microscopy, PCR of lesion material) should be considered Syphilis in Pregnancy and Congenital Syphilis • Treponemal screening performed with reflex nontreponemal test • Oral step-wise penicillin dose challenge or skin testing may be helpful in identifying women at risk for acute allergy • Erythromycin or azithromycin does not reliably cure maternal infection or infected fetus • Insufficient data on ceftriaxone for treatment of maternal infection and prevention of CS HSV • IgM testing not useful • Antiviral efficacy • Acyclovir, valacyclovir, famciclovir equally effective • Higher dosing with HIV infection • No change in management recommendations • Acyclovir resistance • Topical cidofovir or imiquimod; intravenous foscarnet • Less likely to develop resistance using suppressive therapy (data in bone marrow transplant patients may correlate with HIV +) • HSV suppressive therapy and HIV infection controversies • HPTN 039: no impact of ACV (400 mg bid) on HIV acquisition despite high compliance • Partners in Prevention: trial of suppressive ACV on HIV positives to prevent HIV transmission failed Chancroid • Prevalence in US/worldwide has declined • No ongoing antimicrobial resistance surveillance as culture not routine • Primary risk factors for treatment failure are HIV+ and lack of circumcision • Single dose tx may be less effective in HIV+ (poor response to ceftriaxone) Lymphogranuloma venereum • Proctitis presentation among HIV+ MSM • Diagnosis • Genital or lymph node aspirates-culture, DFA, nucleic acid detection (CLIA validation) • Genotyping required for determining LGV strains • Serology not validated for proctitis presentation • Empiric Rx for appropriate clinical syndrome • Doxycycline 100 mg PO bid x 21 d • Azithromycin 1 g PO q wk x 3 wks (limited data) Proctitis • HSV/LGV presumptive treatment - painful perianal or mucosal ulceration • Consider LGV treatment in MSM with anorectal chlamydia and either proctitis (by anoscopy) with >10 WBCs/high-power field or HIV + Scabies/Pediculosis • Permethrin superior to crotamiton • Combined treatment for crusted scabies oral/ topical scabicide • Emerging resistance to all pediculicides except malathion Bacterial Vaginosis • Fastidious/uncultivated anaerobes • Reoccurs with higher frequency in HIV-positive women • Alternative regimen • Tinidazole 2 g daily x 2 or 1 g daily x 5 • Management of recurrences • Metronidazole gel 2x weekly x 4-6 mo • Oral nitroimidazole followed by intravaginal boric acid and suppressive metronidazole gel • USPSTF • Insufficient evidence to support screening high risk pregnant women • Against screening in low risk Trichomoniasis • Diagnostic evaluation • Aptima TV analyte specific reagents • Consider rescreen women ( HIV-/HIV+) at 3 mo • NAAT preferred diagnostic in men • Antimicrobial resistance • 5-10% estimated prevalence • No data to guide treatment of male partners of treatment failure • Metronidazole 500 mg bid x 7 or tinidazole 2 gm • Interaction of HIV and trichomoniasis in women • Screening at entry into HIV care; rescreen • Treatment metronidazole 500 mg bid x 7 days (2g single dose failures) • Rescreening 3 months after completion of therapy with HIV(+) women HPV/Genital Warts • Counseling messages • Oral transmission • Clarification on use of HPV testing (should not be used for men, for women <20 years of age, or as general test for STDs) • HIV-infected are more likely to develop genital warts and more recalcitrant to therapy • Genital wart treatment • Sinecatechins ointment (15%) as a patient-applied • Not recommended for HIV(+) persons, immunocompromised persons, or persons with clinical genital herpes as safety/efficacy not established • HPV vaccine • Bivalent/quadrivalent vaccine (70% cervical cancer) • Quadrivalent vaccine (90% genital warts) • Quadrivalent recommended in women, permissive in men Cervical Cancer Screening • Clarify indication for high risk HPV testing • High-risk (HR) HPV testing not indicated • • +/- vaccinate; STD screening for HPV • Triage of LSIL • Age <21 yr • Primary cervical cancer screening only Counseling messages • Purpose of screening • Normal pap/+HR HPV test • Disclosure to sex partner • Prevention measures - condoms, vaccine Anal Cancer Screening • Increased anal cancer incidence in HIV-infected MSM • Screening for anal cytologic abnormalities can be considered • Evidence is limited concerning the natural history of anal intraepithelial neoplasias • Reliability of screening methods • Safety and response to treatments • Programmatic support needed for screening activity Hepatitis A • Hepatitis A - international travelers, household/sex contacts, non-household contacts (e.g., play, daycare), IVDA • Post exposure - hepatitis A vaccine or IG (0.02 mL/kg) based on limited comparative data (no data >40 yr, medical conditions) Hepatitis B • Premastication as source of infection • HBV vaccine should be offered to all unvaccinated persons attending STD clinics and persons seeking STD tx (other settings) • HBV vaccine (hemodialysis dose) recommended in HIV+ OI Guidelines Hepatitis C • Sexual transmission of HCV (syphilis, LGV) • HCV serology at baseline HIV visit • Acute HCV- monitor LFTs • Unprotected sexual contact may facilitate spread of HCV (semen); barrier precautions discussed STD Screening with HIV+ • Periodic retesting for all sexually active patients • Annually for all, more frequent (every 3-6 months) depending on risk: • Multiple or anonymous sex partners • Unprotected vaginal or anal intercourse with partner with negative or unknown HIV status • Sex or needle-sharing partner with above risks • “Life changes” associated with increased risk Points to Remember • Screen more frequently rather than less • Screen at all anatomic sites exposed (rectum, pharynx, cervix, urethra) • Remember report of condom use does not always predict absence of STDs • Reinforce the consistent and correct use of condoms with patients Disclosure of Financial Relationships This speaker has the following significant financial relationships with commercial entities to disclose: • Consultant/speaker – Pfizer • Consultant – Graceway • Grant/speaker - Merck This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.