Co-Occurrence of \u3ci\u3eTrichomonas vaginalis\u3c/i\u3e and Bacterial Vaginosis and Vaginal Shedding of HIV-1 RNA

Background Trichomonas vaginalis (TV) and bacterial vaginosis (BV) are independently associated with increased risk of vaginal shedding in HIV-positive women. Because these 2 conditions commonly co-occur, this study was undertaken to examine the association between TV/BV co-occurrence and vaginal shedding of HIV-1 RNA. Methods HIV-positive women attending outpatient HIV clinics in 3 urban US cities underwent a clinical examination; were screened for TV, BV, Neisseria gonorrhoeae, Chlamydia trachomatis, and vulvovaginal candidiasis; and completed a behavioral survey. Women shedding HIV-1 RNA vaginally (\u3e= 50 copies/mL) were compared with women who had an undetectable (/mL) vaginal viral load to determine if women who were TV positive and BV positive or had co-occurrence of TV/BV had higher odds of shedding vaginally when compared with women who did not have these conditions. Results In this sample of 373 HIV-positive women, 43.1% (n = 161) had co-occurrence of TV/BV and 33.2% (n = 124) were shedding HIV-1 RNA vaginally. The odds of shedding HIV vaginally in the presence of TV alone or BV alone and when TV/BV co-occurred were 4.07 (95% confidence interval [CI], 1.78-9.37), 5.65 (95% CI, 2.64-12.01), and 18.63 (95% CI, 6.71-51.72), respectively, when compared with women with no diagnosis of TV or BV, and after adjusting for age, antiretroviral therapy status, and plasma viral load. Conclusions T. vaginalis and BV were independently and synergistically related to vaginal shedding of HIV-1 RNA. Screening and prompt treatment of these 2 conditions among HIV-positive women are important not only clinically but for HIV prevention, as well

P2.33 Co-occurrence of trichomonas vaginalis and bacterial vaginosis among women; prevalence and treatment outcomes

IntroductionBoth Trichomonas vaginalis (TV) and bacterial vaginosis (BV) cause vaginitis and place women at higher risk for HIV infection. Both are treated with metronidazole (Mtz) but at different doses. The purpose of this study was to examine the co-occurrence of these infections and BV treatment outcomes among TV+/BV+ women multi-dose Mtz for the treatment of TV.MethodsWomen attending three sexually transmitted disease clinics in the southern US who had a diagnosis of TV (culture or NAAT confirmed) were interviewed and examined for BV using a Nugent score ≥7. Women were randomised to either 2 g single dose or 500 mg Mtz BID for 7 days multi-dose for the treatment of TV and followed 3–12 weeks post TV treatment and retested for both TV and BV. Medical records were abstracted for Amsel criteria for a subset of the cohort. ResultsOf 528 TV+ women at baseline, 49.8% also had BV per Nugent score, 44.3% reported a history of BV and 5.9% also had yeast. Of 289 women whose medical records were abstracted, 23.5% had a vaginal discharge consistent with BV (i.e. thin and white/grey), and 34.1% were BV+ per Amsel at baseline. Of the 46 women who were BV+ at baseline per Amsel (i.e. diagnosed at point of care) and per Nugent (i.e. lab diagnosed) and were treated with multi-dose Mtz, 96% reported taking all their medicine. While 36% of these women reported condomless sex during follow-up, there was no association between sexual exposure and BV status at TOC. Of these 46 women, 42.9% remained BV+ at TOC and 19.4% reported BV-related symptoms. BV status at TOC was not associated with TV cure rates (p>0.56).ConclusionA high rate of BV co-infection (49.8%) was found among women with TV, much of which was asymptomatic. The rate of BV persistence post multi-dose Mtz was also high both microbiologically (42.9%) and clinically (19.4%) and did not appear to be influenced by TV treatment status. Additional research and development of novel therapeutics (i.e. biofilm disruptors) are urgently needed for women with BV, particularly among TV+ women where BV rates are high

Optimal timing for Trichomonas vaginalis test of cure using nucleic acid amplification testing

BackgroundThe optimal timing for nucleic acid amplification testing (NAAT) posttreatment for Trichomonas vaginalis has not been fully established. Testing too soon posttreatment may detect remnant nucleic acid that is not from viable organisms, falsely misclassifying person as infected. The purpose of this study was to examine how long T. vaginalis nucleic acid is detectable postmetronidazole (MTZ) treatment.MethodsWomen diagnosed with T. vaginalis treated with MTZ (2 g single-dose or 500 mg twice daily for 7 days multidose) self-collected a vaginal swab for NAAT at baseline and each week postcompletion of treatment through test of cure (TOC) at week 4, when a culture was also performed. Women who reported interim sexual exposure or who were culture positive at 4 weeks were excluded. Time to first negative NAAT was examined using Kaplan Meier analysis.ResultsAll women receiving multidose metronidazole were NAAT-negative by 21 days and those receiving single dose by 28 days postcompletion of treatment. Though over half (60.7%) of the cohort reinitiated sex during follow-up¸ all reported using condoms during sex or that they and their partner were treated before sex. Six (6.7%) of 89 had a positive NAAT following their first negative NAAT.ConclusionsThe optimal timing for T. vaginalis retesting after completion of treatment is 3 weeks for those receiving multidose MTZ and 4 weeks for those receiving single-dose, though sexual reexposure and false negatives should be considered

P790 Determining the origins of repeat trichomonas vaginalis infections using clinical versus genotype-informed criteria

BackgroundHigh rates of repeat T. vaginalis infections post-treatment have been reported. It is essential to understand the origin of these infections (i.e. treatment failure or reinfection) to determine the best secondary prevention measures. Self-reported sexual behavior and medication adherence can be subject to bias. The purpose of this study is to examine the origins of early repeat T. vaginalis infections in women using clinical versus genotype-informed criteria.MethodsWomen with T. vaginalis confirmed by culture or nucleic acid amplification test (NAAT), who were randomized to receive 2 g or 7-day 500 mg BID metronidazole (MTZ), were retested 3–12 weeks post treatment at test-of-cure (TOC). Viable isolates from women who were TOC TV+ were genotyped (baseline and TOC isolates) and MTZ susceptibility (TOC only) was evaluated. Sexual and treatment adherence histories were elicited by computer-assisted self-administered survey. Treatment failure was defined using two criteria: 1) clinical (a combination of MTZ adherent per self-report+ no follow-up sexual exposure per self-report + no MTZ resistance), and 2) genotype-informed (concordant baseline and TOC genotype with no follow-up sexual exposure per self-report).ResultsOf 80 repeat positives, 78 were evaluated using clinical and 49 using genotype-informed criteria. Per clinical criteria, 87.2% were treatment failure, 7.7% were reinfection and 5.1% were new infection. Per genotype-informed criteria, 51.0% were treatment failure, 10.2% were reinfection and 38.3% were new infection. In subset analysis, comparing the 49 with both clinical and genotype-informed assessments, 61.2% agreed and 38.8% disagreed (kappa 0.29 indicating poor reliability). Of 44 women who denied having a new partner during follow-up, 14 (31.8%) had a discordant genotype.ConclusionUsing either criteria, most TOC T. vaginalis positives were treatment failure rather than re-infections. Clinical and genotype-informed classification were not well correlated. Possible explanations for this will be discussed.DisclosureNo significant relationships

O01.5 Origin and predictors of early repeat infections among hiv negative women with trichomonas vaginalis receiving a 2 g dose of metronidazole

IntroductionA recent meta-analysis demonstrated superiority of multi-dose metronidazole (MTZ) over the CDC and WHO recommended 2 g dose for the treatment of T. vaginalis (TV). Another study among HIV+ women with TV found higher test-of-cure (TOC)+ rates among women who had asymptomatic bacterial vaginosis (BV) than those without BV. The purpose of this study was to measure the TOC TV+ rate and to examine if the presence of BV influenced that rate. MethodsHIV-/TV+ women treated with 2 g oral directly observed MTZ and who completed their TOC visit 3–12 weeks post treatment were included. Women were tested for TV using NAAT and surveyed via computer at baseline and TOC. Nugent scores≥7, calculated from vaginal gram stain, were considered BV+. MTZ susceptibility testing was performed on TOC TV+ specimens.ResultsOf 227 TV+ women included baseline the mean age was 31.3 (S.D. 9.9), 95.2% were African American, 39.3% had multiple male partners in the prior 3 months, 32.3% regularly smoked, 19.4% were binge drinkers, 48.9% had BV and 5.4% had yeast on the gram stain. At TOC, 19.8% were NAAT TV+. Of the 45 TOC-TV+ women, 44 provided sexual exposure information and 10/44 (24.4%) reported sexual re-exposure to baseline partner or sexual exposure to a new partner. Two of 26 (7.7%) TOC+ specimens that underwent susceptibility testing had low to moderate MTZ resistance (50–100 ug/ml). There were no differences in TOC NAAT+ rates by BV, sexual re-exposure to a baseline partner, sexual exposure to a new partner, regular smoking, binge drinking, or by the presence of yeast (p>0.22).ConclusionTOC NAAT+ rate after 2 g MTZ dose was high (19.8%) and isolates from these women were susceptible to MTZ (94.3%). Most TOC+ women (75.6%) reported no sexual exposure/re-exposure during follow-up suggesting that most cases were treatment failures. Selected behavioural factors and BV did not did not appear to influence TV treatment. The 2 g MTZ dose for TV recommended by CDC and WHO, should be reevaluated in light of more sensitive NAAT

Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial

Among women, trichomoniasis is the most common non-viral sexually transmitted infection worldwide, and is associated with serious reproductive morbidity, poor birth outcomes, and amplified HIV transmission. Single-dose metronidazole is the first-line treatment for trichomoniasis. However, bacterial vaginosis can alter treatment efficacy in HIV-infected women, and single-dose metronidazole treatment might not always clear infection. We compared single-dose metronidazole with a 7-day dose for the treatment of trichomoniasis among HIV-uninfected, non-pregnant women and tested whether efficacy was modified by bacterial vaginosis. In this multicentre, open-label, randomised controlled trial, participants were recruited at three sexual health clinics in the USA. We included women positive for Trichomonas vaginalis infection according to clinical screening. Participants were randomly assigned (1:1) to receive either a single dose of 2 g of metronidazole (single-dose group) or 500 mg of metronidazole twice daily for 7 days (7-day-dose group). The randomisation was done by blocks of four or six for each site. Patients and investigators were aware of treatment assignment. The primary outcome was T vaginalis infection by intention to treat, at test-of-cure 4 weeks after completion of treatment. The analysis of the primary outcome per nucleic acid amplification test or culture was also stratified by bacterial vaginosis status. This trial is registered with ClinicalTrials.gov, number NCT01018095, and with the US Food and Drug Administration, number IND118276, and is closed to accrual. Participants were recruited from Oct 6, 2014, to April 26, 2017. Of the 1028 patients assessed for eligibility, 623 women were randomly assigned to treatment groups (311 women in the single-dose group and 312 women in the 7-day-dose group; intention-to-treat population). Although planned enrolment had been 1664 women, the study was stopped early because of funding limitations. Patients in the 7-day-dose group were less likely to be T vaginalis positive at test-of-cure than those in the single-dose group (34 [11%] of 312 vs 58 [19%] of 311, relative risk 0·55, 95% CI 0·34-0·70; p<0·0001). Bacterial vaginosis status had no significant effect on relative risk (p=0·17). Self-reported adherence was 96% in the 7-day-dose group and 99% in the single-dose group. Side-effects were similar by group; the most common side-effect was nausea (124 [23%]), followed by headache (38 [7%]) and vomiting (19 [4%]). The 7-day-dose metronidazole should be the preferred treatment for trichomoniasis among women. National Institutes of Health