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Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

Objective: Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. Methods: Four cohortswith participantswhoinitiatedARTduring acute infection or during chronic infectionwere enrolled in a cross-sectional, noninterventional study.Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIVDNA Assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. Results: Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. Conclusion: Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity, and high susceptibility to bNAbs, and would be an optimal target population for proof-of-concept HIV cure trials.

Summary These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11–14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.

OBJECTIVE Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis. DESIGN A nested substudy within a longitudinal observational cohort. METHODS We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis. RESULTS Mean age of participants was 56.3 years, mean CD4+ cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r = 0.250, P = 0.005) and APRI (r = 0.262, P = 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r = 0.333, P = 0.0001) and APRI (r = 0.457, P

Sexually transmitted infections (STIs) caused by the bacteria Neisseria gonorrhoeae (gonococcal infections) have increased 63% since 2014 and are a cause of sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility and can facilitate transmission of human immunodeficiency virus (HIV) (1,2). Effective treatment can prevent complications and transmission, but N. gonorrhoeae's ability to acquire antimicrobial resistance influences treatment recommendations and complicates control (3). In 2010, CDC recommended a single 250 mg intramuscular (IM) dose of ceftriaxone and a single 1 g oral dose of azithromycin for treatment of uncomplicated gonococcal infections of the cervix, urethra, and rectum as a strategy for preventing ceftriaxone resistance and treating possible coinfection with Chlamydia trachomatis (4). Increasing concern for antimicrobial stewardship and the potential impact of dual therapy on commensal organisms and concurrent pathogens (3), in conjunction with the continued low incidence of ceftriaxone resistance and the increased incidence of azithromycin resistance, has led to reevaluation of this recommendation. This report, which updates previous guidelines (5), recommends a single 500 mg IM dose of ceftriaxone for treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydial infection has not been excluded, concurrent treatment with doxycycline (100 mg orally twice a day for 7 days) is recommended. Continuing to monitor for emergence of ceftriaxone resistance through surveillance and health care providers' reporting of treatment failures is essential to ensuring continued efficacy of recommended regimens.

Progressive antimicrobial resistance in Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis has created a pressing need for treatment optimisations for sexually transmitted infections (STIs). In this Review, we aim to highlight urgent needs in global STI management, including: (1) improved surveillance to monitor antimicrobial resistance and clinical outcomes; (2) systematic pharmacokinetic and pharmacodynamic evaluations to ensure resistance suppression and bacterial eradication at all sites of infection; (3) development of novel, affordable antimicrobials; and (4) advancements in new molecular and point-of-care tests to detect antimicrobial resistance determinants. Antimicrobial resistance among STIs is a global public health crisis. Continuous efforts to develop novel antimicrobials will be essential, in addition to other public health interventions to reduce the global STI burden. Apart from prevention through safer sexual practices, the development of STI vaccines to prevent transmission is a crucial research priority.

BACKGROUND With increasing rates of sexually transmitted infections in the United States, there is a critical need to educate health professionals on the prevention, diagnosis, and treatment of sexually transmitted infections. The National Sexually Transmitted Disease Curriculum (NSTDC, https://www.std.uw.edu) is a free, online curriculum, funded by the Centers for Disease Control and Prevention. The purpose of this article is to evaluate the reach, utilization, and engagement of users with the curriculum. METHODS Data on NSTDC utilization was collected for 24 months after the February 1, 2017 launch. For all users, Google Analytics was used to determine total number of users, geographic location, age and sex, and average session duration. For registered users, additional data analysis included work-role, demographics, and completion of self-study modules, check-on-learning questions, and question banks. User satisfaction was measured on a 5-point Likert scale. RESULTS During the evaluation period, 136,270 individual users accessed the NSTDC, including 24,652 registered users. Among all registered users, 10,660 (43.2%) were registered nurses, 2810 (11.4%) physicians, 4942 (20.1%) Advanced Practice Nurses and Physician Assistants, and 6213 (25.2%) nonclinicians. Among registered users, 18,533 (75.2%) completed at least 1 module, 7898 (32.0%) completed all 7 modules, and 19,804 (80.4%) answered optional check-on-learning questions. Median satisfaction with the content was (5) very satisfied (interquartile range, 4-5). CONCLUSIONS The NSTDC is a free, guideline-based, online curriculum with novel dual functionality that has achieved extensive reach with a broad array of health professionals who engage deeply with the material. The wide usage of NSTDC demonstrates the need for high-quality, unbiased, free content in user-focused formats.

OBJECTIVE To identify factors associated with testing for and diagnosis of trichomoniasis in pregnancy and to describe patterns of treatment and tests of reinfection or persistence. METHODS We conducted a retrospective cohort study of women who delivered from July 2016 to June 2018 at one institution. Testing for Trichomonas vaginalis infection was done by wet mount microscopy or by nucleic acid amplification testing for routine prenatal testing or symptomatic visits. Poisson regression was used to identify factors associated with testing for trichomoniasis and testing positive in pregnancy. Treatment and re-testing patterns also were assessed. RESULTS Among 3,265 pregnant women, 2,489 (76%) were tested for T vaginalis infection. Of the total sample, 1,808 (55%) were tested by wet mount microscopy, 1,661 (51%) by nucleic acid amplification testing, and 980 (30%) by both modalities. The sensitivity for microscopy compared with nucleic acid amplification testing was 26%, with a specificity of 99%. Factors associated with increased likelihood of being tested included younger age (adjusted risk ratio [aRR] 0.99, 95% CI 0.99-1.00) and bacterial vaginosis (aRR 1.17, 95% CI 1.01-1.37). Prevalence of trichomoniasis was 15% among those tested by any modality (wet mount or nucleic acid amplification testing). Risk factors for trichomoniasis included younger age (aRR 0.97, P

The articles in this supplement address key questions on syphilis diagnostics, provide reference tables of test performances, and discuss optimal specimens and knowledge gaps. Laboratory-developed genetic direct detection tests could be most useful at the point of care and add to the currently available serologic methods of nontreponemal and treponemal tests.

Summary This report (hereafter referred to as STD QCS) provides CDC recommendations to U.S. health care providers regarding quality clinical services for sexually transmitted diseases (STDs) for primary care and STD specialty care settings. These recommendations complement CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2015 (hereafter referred to as the STD Guidelines), a comprehensive, evidence-based reference for prevention, diagnosis, and treatment of STDs. STD QCS differs from the STD Guidelines by specifying operational determinants of quality services in different types of clinical settings, describing on-site treatment and partner services, and indicating when STD-related conditions should be managed through consultation with or referral to a specialist. These recommendations might also help in the development of clinic-level policies (e.g., standing orders, express visits, specimen panels, and reflex testing) that can facilitate implementation of the STD Guidelines. CDC organized the recommendations for STD QCS into eight sections: 1) sexual history and physical examination, 2) prevention, 3) screening, 4) partner services, 5) evaluation of STD-related conditions, 6) laboratory, 7) treatment, and 8) referral to a specialist for complex STD or STD-related conditions. CDC developed the recommendations by synthesizing relevant, evidence-based guidelines and recommendations issued by other experts; reviewing current practice in the United States; soliciting Delphi ratings by subject matter experts on STD care in primary care and STD specialty care settings; discussing the scientific evidence supporting the proposed recommendations at a consultation meeting of experts and institutional stakeholders held November 20, 2015, in Atlanta, Georgia; conducting peer reviews of draft recommendations and supporting evidence; and discussing draft recommendations and supporting evidence during meetings of the CDC/Health Resources and Services Administration Advisory Committee on HIV, Viral Hepatitis, and STD Prevention and Treatment STD Work Group. These recommendations are intended to help health care providers in primary care or STD specialty care settings offer STD services at their clinical settings and to help the persons seeking care live safer, healthier lives by preventing and treating STDs and related complications.

Downstream next generation sequencing (NGS) of the syphilis spirocheteTreponema pallidumsubspeciespallidum(T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for theT. pallidumgenome, and the capture and removal of CpG-methylated host DNA using the NEBNext®Microbiome DNA Enrichment Kit followed by MDA with the REPLI-g Single Cell Kit as enrichment methods to improve the yields ofT. pallidumDNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93-98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit propagated isolates, containing >14T. pallidumgenomic copies/μl of sample for SWGA and >129 genomic copies/μl for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens, showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole genome sequencing (WGS) of specimens containing very low numbers ofT. pallidum, which have been challenging until now.ImportanceSyphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogenTreponema pallidumsubspeciespallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions, and if left untreated, can progress through multiple stages with varied clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past two decades, WGS data is needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of a SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers ofT. pallidum.

Background Ocular syphilis cases continue to be identified in the United States since two clusters were reported in late 2014 into early 2015. Ocular syphilis (OS) is an inflammatory eye condition that can occur at any stage of syphilis with vision loss and blindness reported in some patients. We performed genotyping and whole genome sequencing (WGS) on Treponema pallidum strains from OS cases as part of molecular surveillance activities. Methods A total of 79 specimens from 57 patients with suspected or confirmed OS were received from 14 states between February 2016 and November 2020. Specimens included CSF, whole blood, serum, plasma, vitreous fluid, and a throat swab. T. pallidum DNA was detected with a real-time PCR assay targeting the polA gene. Genotyping was done using the four-component typing scheme (tpr E, G, & J; arp, tp0548, and tp0279). T. pallidum genomic DNA was enriched by selective whole genome amplification (SWGA) using Multiple Displacement Amplification (MDA) with custom oligonucleotides followed by WGS on an Illumina MiSeq v2 500 cycle platform. Results Twenty-three patients (40.4%) were MSM and HIV positive, respectively; 41 (71.9%) identified as White race, 4 (7%) Hispanic, and 3 (5.3%) Black. Twenty-three specimens from 18 (31.6%) patients tested positive for T. pallidum DNA. Thirteen of 23 (56.5%) specimens were CSF, while the remaining 10 included whole blood, serum, vitreous fluid, and a throat swab. Specimens from 3 patients were fully typed, revealing strain types 14b9g, 14d10g, and 14e9f. Six patients had partial genotypes. WGS was successful on 1 CSF and 2 vitreous fluid specimens from 2 cases resulting in 87% – 98% genome coverage with at least 5 reads/site. Phylogenetic analysis showed that the 2 strains belonged to the Street 14 clade. Conclusions Our findings show that multiple strain types are responsible for ocular syphilis in the United States.

Background The Centers for Disease Control and Prevention (CDC) recommends specific regimens for chlamydia and dual therapy for gonorrhea to mitigate antimicrobial-resistant gonorrhea in the CDC 2015 sexually transmitted disease treatment guidelines. Only limited studies examining adherence to these recommendations have been conducted at private practices in the United States. Methods We used the OptumLabs Data Warehouse, a comprehensive, longitudinal data asset with deidentified persons with linked commercial insurance claims and clinical information, to identify persons aged 15 to 60 years who had valid nucleic acid amplification testing results demonstrating urogenital or extragenital gonorrhea or chlamydia in 2016 to 2018. We defined valid laboratory results as positive or negative. We then assessed the time of their first positive test result and the type of treatment within 30 days to determine if there was evidence in the claims record that the CDC-recommended treatment was provided. We defined presumed treatment if the date of treatment was before the date of the positive test result within 30 days. Results Among 6476 patients with positive gonorrhea test results and 26,847 patients with positive chlamydia test results only, 34.8% and 64.2% had evidence of receiving the CDC-recommended therapy, respectively. Approximately 11.6% of patients with positive gonorrhea test results with recommended dual treatment and 7.1% of patients with positive chlamydia test results only with recommended chlamydia treatment were presumptively treated. Conclusion Analysis of treatment claims and medical records from private settings indicated low rates of recommended gonorrhea and chlamydia treatment. Validation of treatment claims is needed to support further quality of care interventions based on these data.

Purpose Trichomoniasis is the most prevalent non-viral sexually transmitted infection in the United States. It can present with vaginitis in women and urethritis in men, but is most often asymptomatic or occurs with minimal symptoms. It is associated with other sexually transmitted infections (STIs), adverse pregnancy outcomes and pelvic inflammatory disease. For these reasons, healthcare provider awareness of trichomoniasis is of public health importance. Methods To assess practitioner knowledge, attitudes, and practices concerning trichomoniasis management, the American College of Obstetricians and Gynecologists (ACOG) conducted an online survey in 2016 of its members, and we analyzed results from 230 respondents. Results We note discrepancies between practice and recommendations amongst surveyed providers: a minority of respondents routinely screen HIV positive patients for trichomoniasis (10.7% “most of the time” 95% confidence interval [CI]: 6.7-15.8, 33.0% “always” 95% CI: 26.5%-40.0%), treat trichomoniasis in HIV positive patients with the recommended dose of metronidazole 500 mg twice a day for 7 days (25.8% 95% CI: 20.0%-32.3%), or retest patients diagnosed with trichomoniasis 3 months after treatment (9.6% 95% CI: 6.1%-14.3R). Only 29.0% (95% CI: 23.0%-35.5%) retreat with metronidazole 500 mg twice a day for 7 days in patients who have failed prior treatment. Conclusions Screening for and treatment of trichomoniasis in HIV positive patients, as well as retesting and retreatment for trichomoniasis in the general population appear to be suboptimal. Continuing education for providers is needed for this common but “neglected” STI.

Gonorrhea, the sexually transmitted disease (STD) caused by Neisseria gonorrhoeae, is the second most common notifiable disease in the United States after chlamydia; 468,514 cases were reported to state and local health departments in 2016, an increase of 18.5% from 2015 (1). N. gonorrhoeae has progressively developed resistance to most antimicrobials used to treat the infection (2). As a result, CDC recommends two antimicrobials (250 mg of ceftriaxone [IM] plus 1 g of azithromycin [PO]) for treating uncomplicated gonorrhea to improve treatment efficacy and, potentially, to slow the emergence and spread of antimicrobial resistance. To monitor adherence to the current CDC-recommended regimen for uncomplicated gonorrhea, CDC reviewed enhanced data collected on a random sample of reported cases of gonorrhea in seven jurisdictions participating in the STD Surveillance Network (SSuN) and estimated the proportion of patients who received the CDC-recommended regimen for uncomplicated gonorrhea, by patient characteristics and diagnosing facility type. In 2016, the majority of reported patients with gonorrhea (81%) received the recommended regimen. There were no differences in the proportion of patients receiving the recommended regimen by age or race/ethnicity; however, patients diagnosed with gonorrhea in STD (91%) or family planning/reproductive health (94%) clinics were more likely to receive this regimen than were patients diagnosed in other provider settings (80%). These data document high provider adherence to CDC gonorrhea treatment recommendations in specialty STD clinics, indicating high quality of care provided in those settings. Local and state health departments should monitor adherence with recommendations in their jurisdictions and consider implementing interventions to improve provider and patient compliance with gonorrhea treatment recommendations where indicated.

In this phase 2 study, single oral doses of gepotidacin were ≥95% effective for bacterial eradication in culture-proven uncomplicated urogenital gonorrhea. New antibiotics for drug-resistant Neisseria gonorrhoeae are urgently needed. With additional evaluation, gepotidacin may provide an alternative therapeutic option., Background In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea. Methods Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4–8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose. Conclusions This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration NCT02294682.

This article lays out the research priorities for Mycoplasma genitalium research agreed upon by the participants in a 2016 National Institutes of Allergy and Infectious Diseases–funded Technical Consultation focused on this organism. The state of current knowledge concerning the microbiology, epidemiology, clinical manifestations of infection, treatment, and public health significance of M. genitalium reviewed at the meeting is described in detail in the individual articles included in this supplemental edition of the Journal of Infectious Diseases. Here we summarize the points made in these articles most relevant to the formulation of the research priorities listed in this article. The most important recommendation resulting from this Technical Consultation is the initiation of clinical trials designed to determine definitively whether screening for and treatment of M. genitalium infections in women and their sexual partners improve reproductive health in women and/or prevent human immunodeficiency virus transmission.

Although Mycoplasma genitalium is increasingly recognized as a sexually transmitted pathogen, at present there is no defined public health response to this relatively newly identified sexually transmitted infection. Currently available data are insufficient to justify routinely screening any defined population for M. genitalium infection. More effective therapies, data on acceptability of screening and its impact on clinical outcomes, and better information on the natural history of infection will likely be required before the value of potential screening programs can be adequately assessed. Insofar as diagnostic tests are available or become available in the near future, clinicians and public health agencies should consider integrating M. genitalium testing into the management of persons with sexually transmitted infection (STI) syndromes associated with the infection (ie urethritis, cervicitis, and pelvic inflammatory disease) and their sex partners. Antimicrobial-resistant M. genitalium is a significant problem and may require clinicians and public health authorities to reconsider the management of STI syndromes in an effort to prevent the emergence of ever more resistant M. genitalium infections.

Summary Hepatitis C (HCV) infection prevalence estimates have been unavailable for all US states. We demonstrate a new approach that synthesizes national seroprevalence and state-level mortality data, yielding first estimates of HCV prevalence for all states, and interpret geographic patterns., Background. Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States and a leading cause of morbidity and mortality. Previous analyses of the US National Health and Nutrition Examination Survey (NHANES) indicated approximately 3.6 million noninstitutionalized persons with antibody to HCV (anti-HCV). However, state-level prevalence remains less understood and cannot be estimated reliably from NHANES alone. Methods. We used 3 publicly available government data sources to estimate anti-HCV prevalence in each US state among noninstitutionalized persons aged ≥18 years. A small-area estimation model combined indirect standardization of NHANES-based prevalence with logistic regression modeling of mortality data, listing acute or chronic HCV infection as a cause of death, from the National Vital Statistics System during 1999–2012. Model results were combined with US Census population sizes to estimate total number and prevalence of persons with antibody to HCV in 2010. Results. National anti-HCV prevalence was 1.67% (95% confidence interval [CI], 1.53–1.90), or 3 911 800 (95% CI, 3 589 400– 4 447 500) adults in 2010. State-specific prevalence ranged from 0.71% (Illinois) to 3.34% (Oklahoma). The West census region had the highest region-specific prevalence (2.14% [95% CI, 1.96–2.48]); 10 of 13 states had rates above the national average. The South had the highest number of persons with anti-HCV (n = 1561600 [95% CI, 1 427 700–1 768 900]). The Midwest had the lowest region-specific prevalence (1.14% [95% CI, 1.04%–1.30%]). Conclusions. States in the US West and South have been most impacted by hepatitis C. Estimates of HCV infection burden are essential to guide policy and programs to optimally prevent, detect, and cure infection.

Background A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1. Methods This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis. All patients received sofosbuvir-velpatasvir once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Efficacy and safety were assessed in all patients receiving at least 1 dose of treatment. Results Of 106 patients, 91 (86%) were men, 48 (45%) were black, and 19 (18%) had cirrhosis. SVR12 was achieved by 101 of 106 (95% [95% confidence interval {CI}, 89%-99%]) patients: 74 of 78 (95% [95% CI, 87%-99%]) with genotype 1; all 11 (100% [95% CI, 72%-100%]) with genotype 2; 11 of 12 (92% [95% CI, 62%-100%]) with genotype 3; and all 5 (100% [95% CI, 48%-100%]) with genotype 4. All 19 patients with cirrhosis had SVR12. Two patients relapsed, 2 were lost to follow-up, and 1 withdrew consent. Two discontinued treatment due to adverse events and 2 had serious adverse events. The most common adverse events were fatigue (25%), headache (13%), upper respiratory tract infection (8%), and arthralgia (8%). Conclusions Sofosbuvir-velpatasvir for 12 weeks was safe and provided high rates of SVR12 in patients coinfected with HCV and HIV-1. Clinical Trials Registration NCT02480712.

Orolabial lymphogranuloma venereum was diagnosed for a man in Michigan, USA, who had sex with men, some infected with HIV. High index of suspicion for lymphogranuloma venereum led to accurate diagnosis, successful therapy, and description of an L2b variant with a unique genetic mutation.

Background Expedited partner therapy (EPT) is an intervention for patients with gonorrhea or chlamydia, providing index patients with prescriptions or medication to give to their partners. Expedited partner therapy is recommended for heterosexuals but not for men who have sex with men (MSM), partially due to concerns about overtreatment of uninfected partners and missed opportunities for human immunodeficiency virus (HIV) diagnosis. Methods We extended our stochastic network-based mathematical model of HIV, gonorrhea, and chlamydia among MSM to include EPT. The EPT implementation was simulated for 10 years. Counterfactual scenarios varied EPT coverage, provision, uptake, and partnership window duration. We estimated sexually transmitted infection (STI) incidence, proportion of infections averted, and process outcomes under each scenario. Results Delivery of EPT to 20% of eligible MSM index patients (coverage) reduced cumulative STI incidence by 27% (interquartile range, 13%-39%) over 10 years compared with current estimated STI screening levels. A 20% increase in providing medication to non-index partners (provision) averted 32% (interquartile range, 20%-41%) of STI infections compared with estimated STI screening levels. When targeted by partnership type, EPT solely to casual partners maximized the population-level infections averted. The proportion of partners given medication who had no current STI varied from 52% to 63%, depending on coverage level. The proportion of partners given medication with undiagnosed HIV infection was 4% across scenarios. Conclusions Expedited partner therapy could reduce bacterial STI incidence for MSM. However, this intervention could result in missed opportunities for HIV/STI prevention and a substantial increase in use of antimicrobials by STI-uninfected MSM, raising concerns about cost and antimicrobial resistance.

BackgroundThe incidence of bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) has increased substantially despite availability of effective antibiotics. The US Centers for Disease Control and Prevention (CDC) recommends annual screening for all sexually active (SA) MSM and more frequent screening for high-risk (HR) MSM. The population-level benefits of improved coverage vs increased frequency of STI screening among SA vs HR MSM are unknown.MethodsWe used a network transmission model of gonorrhea (NG) and chlamydia (CT) among MSM to simulate the implementation of STI screening across different scenarios, starting with the CDC guidelines at current coverage levels. Counterfactual model scenarios varied screening coverage and frequency for SA MSM and HR MSM (MSM with multiple recent partners). We estimated infections averted and the number needed to screen to prevent 1 new infection.ResultsCompared with current recommendations, increasing the frequency of screening to biannually for all SA MSM and adding some HR screening could avert 72% of NG and 78% of CT infections over 10 years. Biannual screening of 30% of HR MSM at empirical coverage levels for annual SA screening could avert 76% of NG and 84% of CT infections. Other scenarios, including higher coverage among SA MSM and increasing frequency for HR MSM, averted fewer infections but did so at a lower number needed to screen.ConclusionsThe optimal screening scenarios in this model to reduce STI incidence among MSM included more frequent screening for all sexually active MSM and higher coverage of screening for HR men with multiple partners.

Background The Centers for Disease Control and Prevention (CDC) recommends specific regimens for treatment of chlamydia and gonorrhea. Dual therapy is recommended for gonococcal infection to mitigate antimicrobial resistant gonorrhea (250 mg ceftriaxone plus 1g azithromycin). Previous studies examining adherence to these recommendations have had limited information on medical claims, prescription claims, and laboratory data in private practices in the United States. Methods We used the OptumLabs® Data Warehouse (OLDW) a comprehensive, longitudinal, real-world data asset with de-identified lives with linked private insurance claims and clinical information to identify persons aged 15–60 years who had valid nucleic acid amplified testing results demonstrating gonorrhea or chlamydia in 2016–2017. We defined valid lab results as positive or negative, but did not include lab records with indeterminate or missing results in our analysis. We then assessed the time of their first positive test and the type of treatment within 30 days to determine if there was evidence in the claims record that the CDC recommended treatment was provided. Results 4,972 patients were identified as having gonorrhea only. Of this group, 77% were male, and 70% were 15–35 years of age. Additionally among this group, 35% had evidence of receiving the CDC recommended combination therapy for gonorrhea, 26% had evidence of receiving 250 mg ceftriaxone without evidence of receiving 1g azithromycin, and 16% had evidence of receiving 1g azithromycin without ceftriaxone. A separate group of 24,044 patients were identified as having chlamydia only. Among this group, 40% were male, and 88% were 15–35 years of age. Additionally among this group, 65% had evidence of receiving a CDC-recommended chlamydia treatment, and 11% also had evidence of receiving 250 mg ceftriaxone. Conclusion There is variation in claims data regarding the treatment regimens administered for gonorrhea and chlamydia treatment. Further studies are needed to evaluate treatment claims data against medical record reviews. Disclosure No significant relationships.

Background Expedited partner therapy (EPT) is an intervention for patients with gonorrhea (NG) or chlamydia (CT), through which index patients are provided with medication to give to their partner. While EPT is recommended for heterosexuals, EPT is not recommended for men who have sex with men (MSM), partially due to concerns about overtreatment of uninfected partners and missed opportunities for HIV diagnosis. In this study, we used modeling to investigate the potential impact of EPT implementation on STI incidence among MSM in the United States. Methods We extended our stochastic network-based mathematical model of HIV, NG, and CT among MSM to include partner-delivered EPT for NG and CT. EPT implementation was simulated for 10 years. Counterfactual scenarios varied EPT coverage, provision, uptake, and partnership window duration. We estimated STI incidence, percent of infections averted (PIA), and process outcomes under each scenario, compared to a reference scenario that included routine and symptoms-based STI screening at current empirical levels among US MSM. Results Delivery of EPT to 20% of eligible MSM index patients (coverage) was projected to reduce cumulative STI infections among MSM by 22% over 10 years compared to current estimated STI screening levels. A 20% increase in providing medication to non-index partners (provision) averted 29% of STI infections compared to STI screening. By partnership type, intervention benefits were greatest when EPT was restricted to casual partners. The proportion of partners given medication who had no current STI varied from 55% to 65%, depending on coverage. The proportion of partners given medication with undiagnosed HIV infection was 4%. Conclusion EPT could substantially reduce bacterial STI incidence for MSM. However, this intervention could result in a substantial increase in unnecessary use of antibiotic medication by STI-uninfected MSM, raising concerns about cost and antimicrobial resistance in absence of additional medical evaluation. Disclosure No significant relationships.

Background Disseminated gonococcal infections (DGI) are uncommon; occurring in an estimated 0.5–3% of Neisseria gonorrhoeae (GC) cases. DGI surveillance is limited and case reports are often analyzed retrospectively or in case clusters. We describe the population-level burden of laboratory culture confirmed DGI using an established surveillance infrastructure, the Active Bacterial Core surveillance (ABCs) system of CDC’s Emerging Infections Program. Methods During 2017–2018, prospective surveillance was conducted among residents in three ABCs areas (3-counties in the Bay Area in California (CA), the 20-county Atlanta metropolitan area in Georgia [GA-MSA], and Georgia outside of the 20-county metropolitan area [GA-DPH]); retrospective surveillance was conducted during 2015–2016 in CA and GA-MSA. A DGI case was defined as isolation of GC from a normally sterile site; a case report form was completed for each case. Isolates collected during prospective surveillance underwent antimicrobial susceptibility testing (AST). Results During 2015–2018, 53 DGI cases were identified (12 in CA, 6 in GA-DPH, and 41 in GA-MSA) for an overall rate of 0.11 cases per 100,000 population (0.08 per 100,000 in CA, 0.06 in GA-DPH, 0.16 in GA-MSA). DGI cases accounted for 0.06% of all reported cases of GC in the three surveillance areas. Most DGI cases were male (60%), aged 15–29 years (34%) or ≥ 45 years (34%), and were Black, non-Hispanic (58%). Clinical presentation was bacteremia (23%) or monoarticular septic arthritis (26%); 11% were immunocompromised. Of the 37 cases identified during 2017–2018, 18 viable isolates had AST completed. All were susceptible to Azithromycin, Ceftriaxone, and Cefixime; 6 (33%) were Penicillin and/or Ciprofloxacin resistant. Conclusion DGI is an infrequent complication of GC. The ABCs infrastructure is a viable platform for DGI surveillance. As GC can quickly develop antimicrobial resistance, continued surveillance, including monitoring trends in antimicrobial susceptibility of DGI isolates and molecular epidemiology, could help inform DGI treatment recommendations. Disclosure No significant relationships.

The recommended regimen for treating uncomplicated gonorrhea has changed over time, due to the emergence of antimicrobial resistance. We assessed physician knowledge of the recommendation for treating uncomplicated urogenital gonorrhea in adolescents and adults using ceftriaxone and azithromycin dual therapy.We analyzed DocStyles 2015 survey data from 1357 primary care physicians practicing for at least 3 years who provided screening, diagnosis, or treatment for sexually transmitted diseases to one or more patients in an average month. Logistic regression and χ analyses were used to identify factors associated with knowledge of dual therapy.Among the options of treatment with ceftriaxone alone, azithromycin alone, both of these, or spectinomycin plus levofloxacin, 64% of physicians correctly preferred ceftriaxone plus azithromycin. Knowledge of the recommended dual therapy decreased with increasing years of practice, ranging from 74% among physicians with 3-9 years of practice to 57% among those practicing for ≥24 years (adjusted odds ratio, ORa, for ≥24 vs 3-9 years of practice, 0.50; 95% confidence interval [CI], 0.35-0.70). Knowledge of dual therapy decreased with higher socioeconomic status of patients (ORa for high income vs poor/lower middle income patients, 0.47; 95% CI, 0.32-0.69). Physicians who pursued continuing medical education using journals, podcasts, and government health agencies were more likely to report dual therapy than those who did not use these sources (ORa, 2.09; 95% CI, 1.31-3.33).Knowledge of the recommended regimen for treating gonorrhea decreased with increasing years of practice and with higher socioeconomic status of patients.

Introduction: Couples’ voluntary HIV counseling and testing (CHTC) is an HIV risk reduction strategy not widely available in the US. Methods: We assessed willingness to participate in CHTC among US HIV-infected clinic patients via tablet-based survey and among HIV-negative persons with HIV-infected partners in care via mixed-method phone interviews. Results: Most of the N=64 HIV-infected partners surveyed were men (89%), on antiretroviral treatment (ART) (92%), and many self-identified homosexual (62%). We observed high levels of willingness to participate in CHTC (64%) among HIV-infected partners. Reasons for not wanting to participate included perceived lack of need (26%), desire to self-disclose their status (26%), and fear of being asked sensitive questions with their partner present (17%). HIV-infected partners were interested in discussing ART (48%), other sexually transmitted infections (STIs) (44%), and relationship agreements like monogamy (31%) during CHTC sessions. All N=15 HIV-negative partners interviewed were men, most identified as homosexual (73%), and about half (54%) reported consistent condom use with HIV-infected partners. We observed high levels of willingness to participate in CHTC (87%) among HIV-negative partners, who were also interested in discussing ART (47%), other STIs (47%), mental health services (40%), and relationship agreements (33%). Most negative partners (93%) indicated that they believed their HIV-infected partner was virally suppressed, but in the event that they were not, many (73%) were willing to take pre-exposure prophylaxis (PrEP). Conclusion: These results indicate that CHTC for serodiscordant couples is acceptable and should emphasize aspects most pertinent to these couples, such as discussion of ART/PrEP, STIs, and relationship agreements.

PURPOSE To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis. METHODS Case report Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1 month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. The patient denied history of genital lesions or rash, but did complain of difficulty hearing bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512 dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was made based on the clinical and laboratory findings. The patient was admitted for systemic intravenous antibiotic therapy, but was noted to have a penicillin allergy. Intravitreal ceftazidime was promptly administered bilaterally to achieve treponemacidal levels of antibiotic therapy. After penicillin desensitization protocol, the patient received 14 days of intravenous penicillin with clinical resolution. CONCLUSIONS There are increasing reports of ocular syphilis in the United States and delay in diagnosis and management can lead to severe visual impairment and blindness. We report the first case of adjunct intravitreal antibiotic therapy in a penicillin allergic patient. As ocular syphilis is a form of bacterial endophthalmitis, combination intravitreal and systemic antibiotics may be considered.

Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance’s scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society’s governing board.

Background The National Sexually Transmitted Diseases Curriculum (NSTDC) is an online, guideline-based, interactive curriculum developed at the University of Washington in Seattle with funding from the Centers for Disease Control and Prevention (CDC) National Network of STD Clinical Prevention Training Centers (NNPTC). The NSTDC has dual-functionality to provide users with the option of engaging in (1) sequential, longitudinal learning and/or (2) quick access to specific content. We describe the first evaluation of the reach, utilization and effectiveness of the NSTDC. Methods We evaluated user data collected from survey completion, Google Analytics, and the Health Professional Application for Training (HPAT) between the launch of NSTDC in February 1, 2017 through August 31, 2018. Chi-square and ANOVA tests were used to determine significant differences between prescribers, nurses, and non-clinicians. Results month period and 54,910 hours of CE awarded. Registered users were mostly women (16,133, 84%), and 8,476 (44%) were registered nurses, with an additional 6,052 (34%) prescribing providers (physicians, nurse practitioners, physician assistants, and dentists). The most common programmatic focus was primary care (4,886, 25%). While 18,175 (95%) of users were in the United States, users were located around the world (Figure 1). Referral patterns differed significantly by occupation (Figure 2). Users engaged deeply with the curriculum. Average site session time was 28 minutes for registered users and 14 minutes for all users. Registered users completed an average of 4.37 out of 7 total modules. Nurses were more likely to complete all modules, (48% vs. 34% of prescribers and 30% of non-clinicians, P < 0.0001). Over 15,000 users answered at least one optional check-on-learning (COL) question. On average, 77% of COL questions were answered in modules where COL questions were initiated. Over 60% of the users found the content and experience highly satisfying. Overall 39% of users intended to change practice following completion of the modules. Conclusion The NSTDC has a broad reach, leads to high user engagement and satisfaction, and fosters intent to change practice. This web-based curriculum is a novel and effective strategy to disseminate recommendations from CDC Guidelines. Disclosures All authors: No reported disclosures.

Black patients chronically infected with genotype 1 hepatitis C virus (HCV) have historically had lower rates of response to interferon‐based treatment than patients of other races. In the phase 3 ION program, the single‐tablet regimen of the NS5A inhibitor ledipasvir and NS5B nucleotide polymerase inhibitor sofosbuvir was shown to be safe and highly effective in the general population. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir in black patients using data from the three open‐label ION clinical trials, which evaluated the safety and efficacy of 8, 12, and 24 weeks of ledipasvir/sofosbuvir with or without ribavirin for the treatment of treatment‐naïve and treatment‐experienced patients with genotype 1 HCV, including those with compensated cirrhosis. The primary endpoint was sustained virologic response at 12 weeks after the end of therapy (SVR12). For our analysis, rates of SVR12, treatment‐emergent adverse events, and graded laboratory abnormalities were analyzed in black versus non‐black patients. Of the 1949 patients evaluated, 308 (16%) were black. On average, black patients were older, had higher body mass index, were more likely to be IL28B non‐CC, and had a lower serum alanine aminotransferase at baseline than non‐black patients. Overall, 95% of black and 97% of non‐black patients achieved SVR12. The rate of relapse was 3% in black patients as compared with 2% in non‐black patients. The most common adverse events included fatigue, headache, nausea, and insomnia. The majority of adverse events occurred more frequently in the ribavirin‐containing arms of the studies. No differences were observed in overall safety by race. Conclusion: A once‐daily dosage of ledipasvir/sofosbuvir was similarly effective in black and non‐black patients with genotype 1 HCV infection. The addition of ribavirin did not appear to increase SVR12 but was associated with higher rates of adverse events. (Hepatology 2016;63:437–444)

Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need.We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events.Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).

Clinical diagnosis of neurosyphilis is challenging since patient presentation varies. Persons with clinical signs of neurosyphilis (eg, cranial nerve dysfunction, auditory or ophthalmic abnormalities, loss of vibration sense, altered mental status, meningitis, and stroke) warrant further laboratory investigation. Although no single laboratory test can be used to diagnose neurosyphilis, a variety of laboratory parameters in cerebrospinal fluid (CSF) can aid in the diagnosis, yet there are caveats in different patient groups1 and those coinfected with human immunodeficiency virus (HIV).2 A definitive diagnosis of neurosyphilis can be performed by identifying Treponema pallidum in CSF by polymerase chain reaction (PCR), detecting treponemes in brain tissue by silver staining, immunohistochemistry, or direct fluorescent antiNormal, but these test modalities and samples are not available in many clinical settings. In a person with neurologic signs or symptoms, a reactive CSF–Venereal Disease Research Laboratory (VDRL) (in a specimen not contaminated with blood) is considered diagnostic of neurosyphilis, while probable cases include patients with clinical signs suggestive of neurosyphilis or suggestive of other syphilis stages with negative CSF-VDRL but reactive serologic treponemal and nontreponemal tests and alterations in the CSF protein or leukocyte counts.3 Because the CSF-VDRL test has high specificity but lacks sensitivity,4 serum T pallidum–specific or treponemal tests such as T pallidum particle agglutination (TP-PA) or fluorescent treponemal antiNormal absorption (FTA-ABS) have been used to test CSF to improve neurosyphilis diagnosis.5-9 However, TP-PA and FTA-ABS are manual tests performed in reference laboratories, and their use in serum has been supplanted by treponemal enzyme immunosorbent assays (EIAs) and chemiluminescent immunoassays (CIAs), which are automated and interfaced to electronic medical records.10 When using serum, the agreement of treponemal EIAs and CIAs with FTA-ABS is above 95%.11 Added advantages of using automated instrumentation to detect treponemal-specific antibodies on CSF specimens include requiring low specimen volume and quick turnaround time. The goal of this study was to evaluate the use of serum treponemal immunoassays on CSF specimens and define their potential use for diagnosis of neurosyphilis.

A patient who never resided in an endemic area for dimorphic fungi was diagnosed with Histoplasma capsulatum endocarditis. His diagnosis was suggested by yeast and hyphae on cardiac valve tissue pathology. Isavuconazole was an optimal therapeutic option due to renal dysfunction and anticoagulation with warfarin for mechanical valve replacement.

A 47-year-old man with HIV infection presented 10 years after initial secondary syphilis diagnosis and treatment for routine follow-up. His HIV was well controlled on antiretroviral therapy. Rapid plasma reagin was 1:1, and TP-PA was reactive. Physical examination revealed a wide pulse pressure, a systolic murmur, and an early diastolic decrescendo murmur. Echocardiogram revealed moderate to severe aortic regurgitation, and subsequent computed tomography angiogram showed a 6.8-cm fusiform aneurysm of the proximal ascending aorta. Aortic valve and ascending hemiarch replacement were performed. Pathology showed adventitial inflammation with plasma cells, gumma-like amorphous areas surrounded by histiocytes, and giant cells with calcified plaques. Cardiovascular syphilis, while rare, remains a relevant cause of aortic aneurysm, even in previously treated patients. The physical exam can be critical in identifying this potentially fatal complication.

International audience; Integrase strand transfer inhibitors (INSTIs) coadministered with two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are recommended as first-line treatment for HIV, and coformulated fixed-dose combinations are preferred to facilitate adherence. We report 48-week results from a study comparing initial HIV-1 treatment with bictegravir-a novel INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug interactions-coformulated with the NRTI combination emtricitabine and tenofovir alafenamide as a fixed-dose combination to dolutegravir administered with coformulated emtricitabine and tenofovir alafenamide.METHODS:In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were screened and enrolled at 126 outpatient centres in 10 countries in Australia, Europe, Latin America, and North America. Participants were previously untreated adults (HIV-1 RNA ≥500 copies per mL) with estimated glomerular filtration rate of at least 30 mL/min. Chronic hepatitis B virus or hepatitis C co-infection was allowed. We randomly assigned participants (1:1) to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo, once a day for 144 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received at least one dose of study drug were included in primary efficacy and safety analyses. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of -12%. This study is registered with ClinicalTrials.gov, number NCT02607956.FINDINGS:Between Nov 11, 2015, and July 15, 2016, 742 participants were screened for eligibility, of whom 657 were randomly assigned to treatment (327 with bictegravir, emtricitabine, and tenofovir alafenamide fixed-dose combination [bictegravir group] and 330 with dolutegravir plus emtricitabine and tenofovir alafenamide [dolutegravir group]). 320 participants who received the bictegravir regimen and 325 participants who received the dolutegravir regimen were included in the primary efficacy analyses. At week 48, HIV-1 RNA

Background & Aims Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). Methods In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the noninferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a noninferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups with a performance goal of 83%. Results In POLARIS-2, 95% (95% confidence interval [CI], 93%–97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish noninferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%–99%; difference in the stratum-adjusted Mantel–Haenszel proportions of -3.2%; 95% CI, -6.0% to -0.4%). The difference in the efficacy was owing primarily to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%–99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by patients receiving voxilaprevir. In both trials, the proportion of patients who discontinued treatment because of adverse events was low (range, 0%–1%). Conclusions In phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was noninferior to sofosbuvir-velpatasvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis. Mild gastrointestinal adverse events were associated with treatment regimens that included voxilaprevir. ClinicalTrials.gov numbers: POLARIS-2, NCT02607800; and POLARIS-3, NCT02639338.