Reduced Odds of Mpox-Associated Hospitalization Among Persons Who Received JYNNEOS Vaccine - California, May 2022-May 2023.

The effectiveness of 1 dose of JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic) against hospitalization for mpox (caused by Monkeypox virus), has been demonstrated; however, the impact of 2 doses on hospitalization risk, especially among persons infected with HIV, who are at higher risk for severe disease, is an important factor in evaluating vaccine effectiveness against mpox disease severity and Monkeypox virus infection. Surveillance data collected by the California Department of Public Health were used to evaluate whether receipt of 2 doses of JYNNEOS vaccine reduced the odds of hospitalization among persons with mpox. The odds of hospitalization among persons with mpox who had received 1 or 2 JYNNEOS doses were 0.27 (95% CI = 0.08-0.65) and 0.20 (95% CI = 0.01-0.90), respectively, compared with unvaccinated mpox patients. In mpox patients with HIV infection, the odds of hospitalization among those who had received 1 JYNNEOS vaccine dose was 0.28 (95% CI = 0.05-0.91) times that of those who were unvaccinated. No mpox-associated hospitalizations were identified among persons infected with HIV who had received 2 JYNNEOS vaccine doses. To optimize durable immunity, all eligible persons at risk for mpox, especially those infected with HIV, should complete the 2-dose JYNNEOS series.

Implementation and Evaluation of a Collaborative, Pharmacy-Based Hepatitis C and HIV Screening Program.

INTRODUCTION: Pharmacy-based HIV and hepatitis C virus (HCV) screening services developed in conjunction with state and local health departments can improve public health through increased access to testing and a linkage-to-care strategy. The objective of this study was to evaluate the impact of implementing HIV and HCV screening in community pharmacies. METHODS: This prospective, multicenter implementation project was conducted from July 2015 through August 2018. Sixty-one pharmacies participated in 3 US regions. We assessed the effectiveness of point-of-care testing, counseling, and disease education for populations at increased risk for HIV and HCV infection through screening programs offered in community pharmacies. Pharmacy customers were offered screening with point-of-care HIV and/or HCV tests. Reactive test results were reported to state or local health departments for disease surveillance. RESULTS: A total of 1,164 patients were screened for HIV, HCV, or both at the 61 participating pharmacies; the average number of patients screened per pharmacy was 19. Pharmacists conducted 1,479 HIV or HCV tests among the 1,164 patients. Five of 612 (0.8%) HIV tests yielded a reactive result, and 181 of 867 (20.9%) of HCV tests yielded a reactive result. CONCLUSION: Patients at increased risk of HIV or HCV can benefit from screening for infection at community pharmacies. Ease of accessibility to testing coupled with a strategy for linkage to care designed for the local community can improve patient care and improve the course of treatment for HIV and HCV.

HIV and Sexually Transmitted Infections Among Persons with Monkeypox - Eight U.S. Jurisdictions, May 17-July 22, 2022.

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

The CDC HIV Outbreak Coordination Unit: Developing a Standardized, Collaborative Approach to HIV Outbreak Assessment and Response.

The Centers for Disease Control and Prevention (CDC) and state, territorial, and local health departments have expanded efforts to detect and respond to HIV clusters and outbreaks in the United States. In July 2017, CDC created the HIV Outbreak Coordination Unit (OCU) to ensure consistent and collaborative assessment of requests from health departments for consultation or support on possible HIV clusters and outbreaks of elevated concern. The HIV OCU is a multidisciplinary, cross-organization functional unit within CDC's Division of HIV/AIDS Prevention. HIV OCU members have expertise in areas such as outbreak detection and investigation, prevention, laboratory services, surveillance and epidemiology, policy, communication, and operations. HIV OCU discussions facilitate problem solving, coordination, and situational awareness. Between HIV OCU meetings, designated CDC staff members communicate regularly with health departments to provide support and assessment. During July 2017-December 2019, the HIV OCU reviewed 31 possible HIV clusters and outbreaks (ie, events) in 22 states that were detected by CDC, health departments, or local partners; 17 events involved HIV transmission associated with injection drug use, and other events typically involved sexual transmission or overall increases in HIV diagnoses. CDC supported health departments remotely or on site with planning and prioritization; data collection, management, and analysis; communications; laboratory support; multistate coordination; and expansion of HIV prevention services. The HIV OCU has augmented CDC's support of HIV cluster and outbreak assessment and response at health departments and had important internal organizational benefits. Health departments may benefit from developing or strengthening similar units to coordinate detection and response efforts within and across public health agencies and advance the national Ending the HIV Epidemic initiative.

Evaluation of the Abbott ARCHITECT HIV Ag/Ab combo assay for determining recent HIV-1 infection.

BACKGROUND: Given the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States. METHODS: In this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs. RESULTS: The MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination. CONCLUSION: Dual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.

Infective Endocarditis Among Persons Aged 18-64 Years Living with Human Immunodeficiency Virus, Hepatitis C Infection, or Opioid Use Disorder, United States, 2007-2017.

BACKGROUND: Infective endocarditis (IE) is a life-threatening bacterial infection of the heart valves, most often diagnosed in older persons and persons with prior cardiac surgery. It is also associated with injection drug use, a behavior that has increased in recent years along with the US opioid crisis. METHODS: We conducted a retrospective cohort analysis of commercial and Medicaid health insurance databases to estimate incident cases of IE in the United States in 2017, stratified by persons living with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and opioid use disorder (OUD). We also estimated annual percentage changes (EAPCs) in IE from 2007-2017 among persons with commercial insurance. RESULTS: The weighted incidence rate of IE was 13.8 cases per 100 000 persons among persons with commercial insurance, and 78.7 among those with Medicaid. The incidence rate of IE among commercially insured persons increased slightly from 2007-2017 (EAPC, 1.0%). It decreased among commercially insured persons living with HIV, from 148.0 in 2007 to 112.1 in 2017 (EAPC, -4.3%), and increased among those with HCV infection, from 172.4 in 2007 to 238.6 in 2017 (EAPC, 3.2%). Among persons aged 18-29 years with HCV infection, IE increased from 322.3 in 2007 to 1007.1 in 2017 (EAPC, 16.3%), and among those with OUD it increased from 156.4 in 2007 to 642.9 in 2017 (EAPC, 14.8%). CONCLUSIONS: The incidence rate of IE increased markedly among young persons with HCV infections or OUD. This increase appears to parallel the ongoing national opioid crisis. Harm reduction with syringe services programs, medications for opioid use disorder, and safe injection practices can prevent the spread of HIV, HCV, and IE.

Benchmarks for HIV Testing: What Is Needed to Achieve Universal Testing Coverage at U.S. Ambulatory Healthcare Facilities.

BACKGROUND: Black and Hispanic men have the highest rates of HIV diagnoses. To decrease the number of U.S. men who are unaware of their HIV status, they should be tested at least once. Our objective was to estimate the increases needed in HIV testing rates at ambulatory health care visits to achieve universal coverage. METHODS: We analyzed nationally representative medical record abstraction data to estimate the number of visits per person to physician offices, emergency departments, and outpatient clinics among men aged 18-39 years during 2009-2016, and the percentage of visits with an HIV test. We calculated the increase in the percentage of visits with an HIV test needed to achieve universal testing coverage of men by age 39 years. RESULTS: Men had a mean of 75.3 million ambulatory visits per year and 1.67 visits per person. An HIV test was performed at 0.9% of the ambulatory visits made by white men, 2.5% by black men, and 2.4% by Hispanic men. A 3-fold increase in the percentage of visits with an HIV test would result in coverage of 46.2% of white, 100% of black, and 100% of Hispanic men; an 11-fold increase would be needed to result in coverage of 100% of white men. CONCLUSIONS: HIV testing rates of men at ambulatory health care visits were too low to provide HIV testing coverage of all men by aged 39 years. A 3-fold increase in the percentage of visits with an HIV test would result in universal testing coverage of black and Hispanic men by age 39 years.

Trends in Indicators of Injection Drug Use, Indian Health Service, 2010-2014 : A Study of Health Care Encounter Data.

OBJECTIVES: Hepatitis C virus (HCV) and HIV transmission in the United States may increase as a result of increasing rates of opioid use disorder (OUD) and associated injection drug use (IDU). Epidemiologic trends among American Indian/Alaska Native (AI/AN) persons are not well known. METHODS: We analyzed 2010-2014 Indian Health Service data on health care encounters to assess regional and temporal trends in IDU indicators among adults aged ≥18 years. IDU indicators included acute or chronic HCV infection (only among adults aged 18-35 years), arm cellulitis and abscess, OUD, and opioid-related overdose. We calculated rates per 10 000 AI/AN adults for each IDU indicator overall and stratified by sex, age group, and region and evaluated rate ratios and trends by using Poisson regression analysis. RESULTS: Rates of HCV infection among adults aged 18-35 increased 9.4% per year, and rates of OUD among all adults increased 13.3% per year from 2010 to 2014. The rate of HCV infection among young women was approximately 1.3 times that among young men. Rates of opioid-related overdose among adults aged <50 years were approximately 1.4 times the rates among adults aged ≥50 years. Among young adults with HCV infection, 25.6% had concurrent OUD. Among all adults with arm cellulitis and abscess, 5.6% had concurrent OUD. CONCLUSIONS: Rates of HCV infection and OUD increased significantly in the AI/AN population. Strengthened public health efforts could ensure that AI/AN communities can address increasing needs for culturally appropriate interventions, including comprehensive syringe services programs, medication-assisted treatment, and opioid-related overdose prevention and can meet the growing need for treatment of HCV infection.

Using an Established Outbreak Response Plan and Molecular Epidemiology Methods in an HIV Transmission Cluster Investigation, Tennessee, January-June 2017.

INTRODUCTION: In April 2017, the Tennessee Department of Health (TDH) was notified of an increase in the number of persons newly diagnosed with HIV in eastern Tennessee in the same month. Two were identified as persons with a history of injection drug use (IDU) and named each other as syringe-sharing partners, prompting an investigation into a possible HIV cluster among persons with a history of IDU. MATERIALS AND METHODS: TDH and public health staff members in eastern Tennessee collaborated to implement procedures outlined in TDH's HIV/hepatitis C virus (HCV) Outbreak Response Plan, including conducting enhanced interviewing and using a preestablished database for data collection and management. To complement contact tracing and enhanced interviewing, TDH partnered with the Centers for Disease Control and Prevention to conduct molecular HIV analyses. RESULTS: By June 27, 2017, the investigation had identified 31 persons newly diagnosed with HIV infection; 8 (26%) self-reported IDU, 4 of whom were also men who have sex with men (MSM). Of the remaining 23 persons newly diagnosed with HIV infection, 10 were MSM who did not report IDU, 9 reported high-risk heterosexual contact, and 4 had other or unknown risk factors. Molecular analysis of the 14 HIV-1 polymerase genes (including 7 of the 8 persons self-reporting IDU) revealed 3 distinct molecular clusters, one of which included 3 persons self-reporting IDU. PRACTICE IMPLICATIONS: This investigation highlights the importance of implementing an established Outbreak Response Plan and using HIV molecular analyses in the event of a transmission cluster or outbreak investigations. Future HIV outbreak surveillance will include using Global Hepatitis Outbreak Surveillance Technology to identify HCV gene sequences as a potential harbinger for HIV transmission networks.

Phylodynamic Analysis Complements Partner Services by Identifying Acute and Unreported HIV Transmission.

Tailoring public health responses to growing HIV transmission clusters depends on accurately mapping the risk network through which it spreads and identifying acute infections that represent the leading edge of cluster growth. HIV transmission links, especially those involving persons with acute HIV infection (AHI), can be difficult to uncover, or confirm during partner services investigations. We integrated molecular, epidemiologic, serologic and behavioral data to infer and evaluate transmission linkages between participants of a prospective study of AHI conducted in North Carolina, New York City and San Francisco from 2011-2013. Among the 547 participants with newly diagnosed HIV with polymerase sequences, 465 sex partners were reported, of whom only 35 (7.5%) had HIV sequences. Among these 35 contacts, 23 (65.7%) links were genetically supported and 12 (34.3%) were not. Only five links were reported between participants with AHI but none were genetically supported. In contrast, phylodynamic inference identified 102 unreported transmission links, including 12 between persons with AHI. Importantly, all putative transmission links between persons with AHI were found among large clusters with more than five members. Taken together, the presence of putative links between acute participants who did not name each other as contacts that are found only among large clusters underscores the potential for unobserved or undiagnosed intermediaries. Phylodynamics identified many more links than partner services alone and, if routinely and rapidly integrated, can illuminate transmission patterns not readily captured by partner services investigations.

Opioid Use Fueling HIV Transmission in an Urban Setting: An Outbreak of HIV Infection Among People Who Inject Drugs-Massachusetts, 2015-2018.

Objectives. To describe and control an outbreak of HIV infection among people who inject drugs (PWID).Methods. The investigation included people diagnosed with HIV infection during 2015 to 2018 linked to 2 cities in northeastern Massachusetts epidemiologically or through molecular analysis. Field activities included qualitative interviews regarding service availability and HIV risk behaviors.Results. We identified 129 people meeting the case definition; 116 (90%) reported injection drug use. Molecular surveillance added 36 cases to the outbreak not otherwise linked. The 2 largest molecular groups contained 56 and 23 cases. Most interviewed PWID were homeless. Control measures, including enhanced field epidemiology, syringe services programming, and community outreach, resulted in a significant decline in new HIV diagnoses.Conclusions. We illustrate difficulties with identification and characterization of an outbreak of HIV infection among a population of PWID and the value of an intensive response.Public Health Implications. Responding to and preventing outbreaks requires ongoing surveillance, with timely detection of increases in HIV diagnoses, community partnerships, and coordinated services, all critical to achieving the goal of the national Ending the HIV Epidemic initiative.

Changes in Reported Injection Behaviors Following the Public Health Response to an HIV Outbreak Among People Who Inject Drugs: Indiana, 2016.

A syringe services program (SSP) was established following the Indiana HIV outbreak among persons who inject drugs (PWID) in Scott County. Among Indiana-based PWID, we examined injection behaviors associated with HIV status, SSP use after its establishment, and changes in injection behaviors after the outbreak response. During 2016, we interviewed 200 PWID and assessed injection behaviors before the response by HIV status. We reported injection behaviors prior to the response and used Fisher's exact Chi square tests (P < 0.05) to assess differences by HIV status. Next, among persons who injected both before (July-December 2014) and after (past 30 days) the response, we (1) reported the proportion of persons who used the SSP to obtain sterile syringes, and assessed differences in SSP use by HIV status using Fisher's exact Chi square tests; and (2) compared distributive and receptive sharing of injection equipment and disposal of syringes before and after the outbreak response, and assessed statistical differences using McNemar's test. We also compared injection behaviors before and after the response by HIV status. Injecting extended release oxymorphone (Opana® ER); receptive sharing of syringes and cookers; and distributive sharing of cookers, filters, or water before the response were associated with HIV infection. SSP use was high (86%), particularly among HIV-positive compared with HIV-negative persons (98% vs. 84%). Injection equipment sharing decreased and safe disposal of used syringes increased after the response, especially among HIV-positive persons. Injection equipment sharing contributed to the outbreak. High SSP use following the response, particularly among HIV-positive persons, contributed to decreased high-risk injection practices.

Evaluation of a Rapid Syphilis Test in an Emergency Department Setting in Detroit, Michigan.

BACKGROUND: Syphilis transmission can be prevented by prompt diagnosis and treatment of primary and secondary infection. We evaluated the performance of a point-of-care rapid syphilis treponemal (RST) test in an emergency department (ED) setting. METHODS: Between June 2015 and April 2016, men aged 18 to 34 years seeking services in a Detroit ED, and with no history of syphilis, were screened for syphilis with the RST test, rapid plasma reagin (RPR) test, and Treponema pallidum particle agglutination assay (TP-PA). A positive reference standard was both a reactive RPR and a reactive TP-PA. We compared test results in self-reported men who have sex with men (MSM) to non-MSM. RESULTS: Among 965 participants, 10.9% of RST tests were reactive in MSM and only 1.5% in non-MSM (P < 0.001). Sensitivity of the RST test was 76.9% and specificity was 99.0% (positive predictive value, 50.0%) compared with the positive reference standard. Three discordant specimens found negative with the RST test but positive with the reference standard had an RPR titer of 1:1, compared with 10 specimens with concordant positive results that had a median RPR titer of 1:16. The RST sensitivity was 50.0% (positive predictive value, 68.4%) compared to the TP-PA test alone. Among men seeking care in an ED, the RST detected 76.9% of participants with a reactive RPR and TP-PA. CONCLUSIONS: The RST test detected all of the participants with an RPR titer ≥1:2 but less than 20% of participants with a positive TP-PA and negative RPR. The RST test was useful to detect a high proportion of participants with an active syphilis in an urban ED.

A Multiplex HIV Incidence Assay for Inferring Recent HIV-1 Transmission and Time of Infection.

BACKGROUND: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies. METHODS: Plasma samples (n = 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. In addition, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak. RESULTS: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, and 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, and 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (≤3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015. CONCLUSIONS: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions.

Performance evaluation of the Bio-Rad Geenius HIV 1/2 supplemental assay.

BACKGROUND: In the US, the HIV diagnostic algorithm for laboratory settings recommends the use of an HIV-1/HIV-2 differentiation supplemental assay after an initial reactive antigen/antibody (Ag/Ab) assay result. Since the discontinuation of the Multispot HIV-1/HIV-2 Rapid Test (MS), the Geenius HIV-1/2 Supplemental assay (Geenius) is the only FDA-approved supplemental differentiation test. OBJECTIVE: We compared the performance of Geenius to MS and Western Blot (WB). STUDY DESIGN: The relative seroconversion plasma reactivity of Geenius and MS was assessed using a 50% cumulative frequency analysis from 17 HIV-1 seroconverters. In addition, previously characterized plasma specimens, 186 HIV-1 positive, 100 HIV-2 positive, and 93 Ag/Ab-positive/HIV-1 RNA-negative, were tested with Geenius v1.1 software. McNemar's test was used for paired comparison analysis. A subset of 48 specimens were retested with the upgraded Geenius v1.3 software. RESULTS: In HIV-1 seroconverters, the relative seroconversion reactivity was 2.5 and 2 days before the first positive HIV-1 WB for Geenius and MS, respectively. In HIV-1 positive samples, Geenius performed similarly to HIV-1 WB (p=0.1687) and MS (p=0.8312). In HIV-2 positive samples, Geenius underperformed compared to HIV-2 WB (p=0.0005) and MS (p=0.0012). When using the upgraded software among the HIV-1 positive and Ag/Ab-reactive/HIV-1 RNA-negative samples, gp140 reactivity decreased without affecting characterization of HIV-2 samples. CONCLUSIONS: With HIV-1 samples, Geenius, WB and MS performance was similar as supplemental tests. The updated Geenius software reduced false gp140 reactivity, but had no impact on identifying true HIV-2 infections. Further evaluation will assess the impact of the Geenius software update on final diagnostic interpretations.

A Strategy for PrEP Clinicians to Manage Ambiguous HIV Test Results During Follow-up Visits.

Prompt determination of HIV infection status is critical during follow-up visits for patients taking pre-exposure prophylaxis (PrEP) medication. Those who are uninfected can then continue safely taking PrEP, and those few who have acquired HIV infection can initiate an effective treatment regimen. However, a few recent cases have been reported of ambiguous HIV test results using common testing algorithms in PrEP patients. We review published reports of such cases and testing options that can be used to clarify true HIV status in these situations. In addition, we review the benefits and risks of 3 antiretroviral management options in these patients: (1) continue PrEP while conducting additional HIV tests, (2) initiate antiretroviral therapy for presumptive HIV infection while conducting confirmatory tests, or (3) discontinue PrEP to reassess HIV status after a brief antiretroviral-free interval. A clinical consultation resource is also provided.

A large HCV transmission network enabled a fast-growing HIV outbreak in rural Indiana, 2015.

BACKGROUND: A high prevalence (92.3%) of hepatitis C virus (HCV) co-infection among HIV patients identified during a large HIV outbreak associated with injection of oxymorphone in Indiana prompted genetic analysis of HCV strains. METHODS: Molecular epidemiological analysis of HCV-positive samples included genotyping, sampling intra-host HVR1 variants by next-generation sequencing (NGS) and constructing transmission networks using Global Hepatitis Outbreak and Surveillance Technology (GHOST). FINDINGS: Results from the 492 samples indicate predominance of HCV genotypes 1a (72.2%) and 3a (20.4%), and existence of 2 major endemic NS5B clusters involving 49.8% of the sequenced strains. Among 76 HIV co-infected patients, 60.5% segregated into 2 endemic clusters. NGS analyses of 281 cases identified 826,917 unique HVR1 sequences and 51 cases of mixed subtype/genotype infections. GHOST mapped 23 transmission clusters. One large cluster (n = 130) included 50 cases infected with ≥2 subtypes/genotypes and 43 cases co-infected with HIV. Rapid strain replacement and superinfection with different strains were found among 7 of 12 cases who were followed up. INTERPRETATION: GHOST enabled mapping of HCV transmission networks among persons who inject drugs (PWID). Findings of numerous transmission clusters, mixed-genotype infections and rapid succession of infections with different HCV strains indicate a high rate of HCV spread. Co-localization of HIV co-infected patients in the major HCV clusters suggests that HIV dissemination was enabled by existing HCV transmission networks that likely perpetuated HCV in the community for years. Identification of transmission networks is an important step to guiding efficient public health interventions for preventing and interrupting HCV and HIV transmission among PWID. FUND: US Centers for Disease Control and Prevention, and US state and local public health departments.