Document

Report
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.

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