Mountain West AIDS Education and Training Center

Trichomonas and HIV

Hillary Liss, MD Clinical Associate Professor Harborview Medical Center University of Washington

Presentation prepared by: Hillary Liss, MD Presenter: Hillary Liss, MD Last Updated: November 30, 2016

This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice related to any specific patient. Courtesy of John Alderete, Ph.D. Case: Trichomonas—Sometimes Tricky to Find

• 45 year old African American woman with HIV, last CD4 642 with suppressed viral load, presents with vaginal itching, malodorous vaginal discharge and mild dysuria. She denies abdominal pain and says she has not been sexually active for several years. • Pelvic exam is significant for yellow-green frothy discharge, pH>5, positive whiff test, no cervical motion tenderness. • Her wet mount reveals copious WBC >5 per HPF, no clue cells, no trichomonads, KOH prep negative for fungal elements. • Could she have trichomoniasis? How can we find out? Typical frothy, yellowish vaginal discharge of trichomoniasis Cervicitis due to Trichomonas vaginalis

Strawberry cervix “Colpitis macularis” Saline microscopy of Trichomonas vaginalis, with PMN’s Trichomoniasis: The “Neglected STD”

• Under appreciated in its importance—most prevalent nonviral STD in US (~4-8 million new cases/yr estimated) • Not reportable in the US • Wider age distribution of 20-45 y • Prevalence 3% in US, 15-20% in US black women 30-50 y • Very high rates in incarcerated women (9-32%) and men (2-9%) screened • Rare in MSM • 70-85% asymptomatic, may persist for years • Can lead to pre-term delivery, LBW, PID • Worldwide—MAJOR implications –multiple studies show increased acquisition of HIV if T. vaginalis infection (2-3 fold)

Meites E, Infect Dis Clin North Am 2013;Muzny C, CID 2015; Soper D, AJOG 2004; NHANES, Sutton, CID 2007. Seeing Trich on Wet Mount is a Coin Flip

Sensitivity Specificity

Wet mount 55 100

Culture 75 100

Nye, AJOG 2009 “Decreasing Shelf-Life” of Wet Mounts for Trichomonas 100%

80%

65% Survival(%)

22%

0 10 30 120 Time (minutes)

Kingston MA, Int J STD and AIDS 2003; 14:28-29 Stoner KA, Sex Transm Infect 2013;89:485-8. New Testing Options for Trich

• Rapid antigen test (OSOM; Genzyme) - Significantly better than wet mount (P = 0.004) - Results in 10 minutes Test Sensitivity Specificity OSOM 83.3% 98.8% Wet prep 71.4% 100% • APTIMA TMA Trichomonas Vaginalis Analyte Specific Reagent (ASR; Gen-Probe) - Nucleic Acid Amplification Test - Utilizes same technology as APTIMA Combo 2 (for GC/CT) - May use same specimen type as used with APTIMA Combo 2 (i.e. vaginal swab, endocervical swab, urine) - FDA approved spring 2011 in women - Can be used with urethral swabs or urine in men if validated

Huppert JS. J Clin Microbiol. 2005;43(2):684-7. NAAT for Trichomonas

• APTIMA TMA (Gen-Probe) in 933 women - 12.7% prevalence of trichomonas - No differences in performance for symptomatic vs. asymptomatic women Sensitivity Specificity Urine 95.2 98.9 Vaginal swab 100 99 Endocervical swab 100 99.4 ThinPrep 100 99.6

Schwebke, JR. J Clin Micro. 2011;49(12):4106-11. 2015 CDC STD Treatment Guidelines: Trichomoniasis

• Metronidazole 2.0 gm PO, single dose (84-98% cure) or • Tinidazole 2.0 gm PO, single dose (92-100% cure) • Alternative Regimen: - Metronidazole 500 mg PO BID x 7 d • Metronidazole is safe at all stages of pregnancy; Tinidazole Category C • Vaginal therapy is ineffective (<50%) • Treat sex partner(s): male and female • Test for other STDs

CDC. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR. 2015;64: 1-137. Trichomonas and HIV

• Up to 53% women with HIV also infected with TV

• TV increases genital shedding of HIV - Increased risk of preterm birth, PID, vertical HIV transmission - Treatment of TV decreases HIV genital shedding

• Routine screening of HIV infected women - At entry to care - Then annually if sexually active - At first prenatal visit if pregnant - Rescreen 3 months after therapy

CDC. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR. 2015;64: 1-137. Cu-Uvin S, Clin Infect Dis 2002;34:1406–11. Miller M, Sex Transm Dis 2008;35:696–702. KissingerJ, Acquir Immune Defic Syndr 2010;55:565–71. Treatment of Trichomonas in HIV

• RCT of 270 HIV+/TV+ women, mean age 40, 92.2% AA • Treatment arms similar age, race, CD4, viral load, ARV status, site, loss to follow-up • Treated with 2 g MTZ v. 7 days MTZ 500 mg BID • Tested at 6-12 d after treatment completed and at 3 months with culture

TV+ Rate 7-day dose Single dose RR P value % (n) % (n) % (n) (95% CI) Test of cure 12.5 8.5 (11/130) 16.8 (21/125) 0.50 (0.25- 0.045 (6-12 d) (32/255) 1.0) 3 months 17.8 11.0 (8/73) 24.1 (19/79) 0.46 (0.21- 0.030 (27/152) 0.98) • Treatment issues - MTZ 2 gm PO not as effective as 500 mg PO BID x 7 days

KissingerJ, Acquir Immune Defic Syndr 2010;55:565–71. Recurrent Infection is Common

• Up to 17% at 3 months

• Reinfection from untreated partner: most important!

• Noncompliance with MTZ therapy: less relevant with single- dose observed therapy

• Infection with MTZ-resistant strain: ~4-10%

- Tinidazole-resistant ~1%

• Rescreen women at 3 months (no <2 weeks), unclear in men

• Ensure partner treatment and avoid sex until all cured

• Consider Expedited Partner Therapy (EPT)

Peterman TA, Ann Intern Med 2006;145:564–72. Additional Issues in the 2015 Guidelines

• Follow-up - High rate of reinfection (up to 17% at 3 months) - Consider rescreening women at 3 months - If treatment failure, see next slides - Ensure partner treatment and avoid sex until all cured • Allergy or intolerance to the regimen - Metronidazole desensitization - Paromomycin cream (may cause ulcers and poor efficacy) • Pregnancy - Complicated - Metronidazole class B - Tinidazole class C - Pump and dump with breastfeeding for 12-24 hours after last dose MTZ, 3 days after Tinidazole

CDC. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR. 2015;64: 1-137. Management of Persistent or Recurrent Trich

• Assure partner treatment • Then MTZ 500 mg PO bid x 7 d • Then MTZ or TDZ 2 gm PO x 7 d • Consider TDZ 2-3 gm PO x 14 d with topical TDZ • Consider involving a specialist - Options may include Paromomycin, Boric Acid, Nitazoxanide • Then, susceptibility testing - CDC: (404) 718-4141

CDC. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR. 2015;64: 1-137. Key Points

• Trichomonas is common and often found in an older population than other STDs • Consider NAAT testing if saline microscopy is unrevealing • Screen for trichomonas in women with HIV at entry to care and annually thereafter • Women with HIV should be treated with 7 days of metronidazole rather than single dose therapy • Consider expedited partner therapy and follow-up testing in 3 months • Reinfection is the most common cause of ongoing infection, but there is emerging nitroimidazole resistance—contact CDC if resistance is suspected