Use of Next-Generation Sequencing in a State-Wide Strategy of HIV-1 Surveillance: Impact of the SARS-COV-2 Pandemic on HIV-1 Diagnosis and Transmission.

BACKGROUND: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed an unpreceded threat to the management of other pandemics such as human immunodeficiency virus-1 (HIV-1) in the United States. The full impact of the SARS-CoV-2 pandemic on the HIV-1 pandemic needs to be evaluated. METHODS: All individuals with newly reported HIV-1 diagnoses from NC State Laboratory of Public Health were enrolled in this prospective observational study, 2018-2021. We used a sequencing-based recency assay to identify recent HIV-1 infections and to determine the days postinfection (DPI) for each person at the time of diagnosis. RESULTS: Sequencing used diagnostic serum samples from 814 individuals with new HIV-1 diagnoses spanning this 4-year period. Characteristics of individuals diagnosed in 2020 differed from those in other years. People of color diagnosed in 2021 were on average 6 months delayed in their diagnosis compared to those diagnosed in 2020. There was a trend that genetic networks were more known for individuals diagnosed in 2021. We observed no major integrase resistance mutations over the course of the study. CONCLUSIONS: SARS-CoV-2 pandemic may contribute to the spread of HIV-1. Public health resources need to focus on restoring HIV-1 testing and interrupting active, ongoing, transmission.

Ten Years of Disseminated Gonococcal Infections in North Carolina: A Review of Cases From a Large Tertiary Care Hospital.

BACKGROUND: The detection and reporting of disseminated gonococcal infection (DGI) has been increasing across the United States. METHODS: We conducted a retrospective chart review of DGI case-patients diagnosed between 2010 and 2019 at a large tertiary care hospital in North Carolina. RESULTS: We identified 12 DGI case-patients (7 men and 5 women, aged 20 to 44 years), of whom 5 had Neisseria gonorrheae isolated from a sterile site (confirmed), 2 had N. gonorrheae detected at a nonsterile mucosal site and had clinical manifestations consistent with DGI (probable), and 5 did not have N. gonorrheae isolated from any site, but DGI was the most likely diagnosis (suspect). Among the 12 DGI case-patients, the most common manifestation was arthritis or tenosynovitis (n = 11); 1 patient had endocarditis. Half of the patients had significant underlying comorbidities or predisposing factors, including complement deficiency. Eleven of the 12 case-patients were hospitalized, and 4 required surgical intervention. CONCLUSIONS: This case series highlights the difficulty of making a definitive diagnosis of DGI, which could negatively affect reporting to public health authorities and hinder surveillance efforts to determine the true prevalence of DGI. A high index of suspicion is required, and a full diagnostic workup should be pursued in all cases of suspected DGI.

Measuring Success: Disease Intervention Specialists Performance Metrics and Outcome Assessments.

ABSTRACT: Disease intervention specialists (DIS) are the cornerstone of public health. However, the incremental gains of DIS-led interventions are difficult to detect at the population level. Health departments attempt to quantify the impact of key DIS activities through performance measures that assess how many and how quickly both patients are interviewed, and contacts are notified, tested, and treated. However, DIS work encompasses more than case finding and existing performance measures may not capture the full value DIS provide to health departments. In this article, we first describe how DIS investigations and contact tracing are conducted for sexually transmitted diseases and other communicable diseases to understand how the definition of effectiveness may vary by disease. Then, we examine the benefits and limitations of traditional performance measures using syphilis investigations as an example. Recognizing the limits of existing measures will improve our understanding of DIS impact and assist in the development of new measures of effectiveness that better represent the totality of DIS work.

Associations between Antenatal Syphilis Test Results and Adverse Pregnancy Outcomes in Western Kenya.

Maternal syphilis remains a major contributor to poor pregnancy outcomes. Syphilis point-of-care (POC) tests are now used for pregnancy screening; the effect of screening on outcomes is unclear. We enrolled women presenting to antenatal care (ANC) in a matched cohort study at a single site in Kenya tested by either a syphilis-only or an HIV/syphilis dual POC test. Syphilis POC-positive women (patients) were matched 1:2 with POC-negative women (control subjects) on gravidity, gestational age, and HIV status, and were monitored through delivery. Syphilis serum testing was performed every 8 weeks. Pregnancy outcomes were assessed up to 1 month after delivery and compared using prevalence ratios. A total of 151 women were enrolled (51 patients and 100 control subjects) at a mean of 22 weeks gestation; 24% were HIV positive and 40% were paucigravid. A positive Treponema pallidum hemagglutination test was more common among patients (64.7%) than control subjects (11.1%, P < 0.001). Only two women met the definition for incident syphilis. Pregnancy outcomes were available for 147 women. The prevalence of low birthweight (LBW) was greater among patients (15.2%) than control subjects (5.4%, P = 0.052). Of the 109 women with concordant syphilis POC and Treponema pallidum hemagglutination test results at ANC enrollment, LBW prevalence was significantly greater among test-positive (25%) than test-negative (4.9%) women (adjusted prevalence ratio, 5.84; 95% CI, 1.08-31.5). Despite treatment with penicillin, latent syphilis at ANC enrollment was associated with a more than 5-fold increased risk of LBW. Alternate implementation strategies for syphilis POC testing may be necessary to realize the potential of ANC syphilis screening to improve pregnancy outcomes.

Prenatal Syphilis Screening Among Medicaid Enrollees in 6 Southern States.

INTRODUCTION: The rates of syphilis among pregnant women and infants have increased in recent years, particularly in the U.S. South. Although state policies require prenatal syphilis testing, recent screening rates comparable across Southern states are not known. The purpose of this study is to measure syphilis screening among Medicaid enrollees with delivery in states in the U.S. South. METHODS: A total of 6 state-university research partnerships in the U.S. South developed a distributed research network to analyze Medicaid claims data using a common analytic approach for enrollees with delivery in fiscal years 2017-2018 and 2018-2019 (combined N=504,943). In 2020-2021, each state calculated the percentage of enrollees with delivery with a syphilis screen test during the first trimester, third trimester, and at any point during pregnancy. Percentages for those with first-trimester enrollment were compared with the percentages of those who enrolled in Medicaid later in pregnancy. RESULTS: Prenatal syphilis screening during pregnancy ranged from 56% to 91%. Screening was higher among those enrolled in Medicaid during the first trimester than in those enrolled later in pregnancy. CONCLUSIONS: Despite state laws requiring syphilis screening during pregnancy, screening was much lower than 100%, and states varied in syphilis screening rates among Medicaid enrollees. Findings indicate that access to Medicaid in the first trimester is associated with higher rates of syphilis screening and that efforts to improve access to screening in practice settings are needed.

Intersection of Syphilis and Human Immunodeficiency Virus (HIV) Networks to Identify Opportunities to Enhance HIV Prevention.

BACKGROUND: Human immunodeficiency virus (HIV) and syphilis infection continue at disproportionate rates among minority men who have sex with men (MSM) in the United States. The integration of HIV genetic clustering with partner services can provide important insight into local epidemic trends to guide interventions and control efforts. METHODS: We evaluated contact networks of index persons defined as minority men and transgender women diagnosed with early syphilis and/or HIV infection between 2018 and 2020 in 2 North Carolina regions. HIV clusters were constructed from pol sequences collected through statewide surveillance. A combined "HIV-risk" network, which included persons with any links (genetic or sexual contact) to HIV-positive persons, was evaluated by component size, demographic factors, and HIV viral suppression. RESULTS: In total, 1289 index persons were identified and 55% named 1153 contacts. Most index persons were Black (88%) and young (median age 30 years); 70% had early syphilis and 43% had prevalent HIV infection. Most people with HIV (65%) appeared in an HIV cluster. The combined HIV-risk network (1590 contact network and 1500 cluster members) included 287 distinct components; however, 1586 (51%) were in a single component. Fifty-five percent of network members with HIV had no evidence of viral suppression. Overall, fewer index persons needed to be interviewed to identify 1 HIV-positive member without viral suppression (1.3 vs 4.0 for contact tracing). CONCLUSIONS: Integration of HIV clusters and viral loads illuminate networks with high HIV prevalence, indicating recent and ongoing transmission. Interventions intensified toward these networks may efficiently reach persons for HIV prevention and care re-engagement.

Effectiveness of Syphilis Partner Notification After Adjusting for Treatment Dates, 7 Jurisdictions.

BACKGROUND: Disease intervention specialists (DIS) prevent syphilis by ensuring treatment for patients' sex partners through partner notification (PN). Different interpretations of how to measure partners treated due to DIS efforts complicates PN evaluation. We measured PN impact by counting partners treated for syphilis after DIS interviewed the patient. METHODS: We reviewed data from early syphilis cases reported during the 2015-2017 period in 7 jurisdictions. We compared infected partners brought to treatment using the following: (1) DIS-assigned disposition codes or (2) all infected partners treated 0 to 90 days after the patient's interview (adjusted treatment estimate). Stratified analyses assessed patient characteristics associated with the adjusted treatment estimate. RESULTS: Disease intervention specialists interviewed 23,613 patients who reported 20,890 partners with locating information. Many of the 3569 (17.1%) partners classified by DIS as brought to treatment were treated before the patient was interviewed. There were 2359 (11.3%) partners treated 0 to 90 days after the patient's interview. Treatment estimates were more consistent between programs when measured using our adjusted estimates (range, 6.1%-14.8% per patient interviewed) compared with DIS-assigned disposition (range, 6.1%-28.3%). Treatment for ≥1 partner occurred after 9.0% of interviews and was more likely if the patient was a woman (17.9%), younger than 25 years (12.6%), interviewed ≤7 days from diagnosis (13.9%), HIV negative (12.6%), or had no reported history of syphilis (9.8%). CONCLUSIONS: Counting infected partners treated 0 to 90 days after interview reduced variability in reporting and facilitates quality assurance. Identifying programs and DIS who are particularly good at finding and treating partners could improve program impact.

Beyond Disease Intervention: Exploring an Expanded Role for Partner Services in the MATRix-NC Demonstration Project.

BACKGROUND: Disease intervention specialists (DIS) provide partner services for sexually transmitted infections (STIs). We assessed an expansion of DIS services for clients with HIV and/or syphilis, and contacts within their social and sexual networks. METHODS: Black and Latinx cisgender men and transgender women who have sex with men diagnosed with HIV and/or syphilis in 4 urban North Carolina counties were referred to designated DIS, who were trained to recruit clients as "seeds" for chain-referral sampling of sociosexual network "peers." All received HIV/STI testing and care; referrals for preexposure prophylaxis (PrEP) and social, behavioral, and non-STI medical services were offered. Participants completed baseline, 1-month, and 3-month computerized surveys. RESULTS: Of 213 cases referred to DIS from May 2018 to February 2020, 42 seeds (25 with syphilis, 17 with HIV) and 50 peers participated. Median age was 27 years; 93% were Black and 86% were cisgender men. Most peers came from seeds' social networks: 66% were friends, 20% were relatives, and 38% were cisgender women. Incomes were low, 41% were uninsured, and 10% experienced recent homelessness. More seeds than peers had baseline PrEP awareness; attitudes were favorable, but utilization was poor. Thirty-seven participants were referred for PrEP 50 times; 17 (46%) accessed PrEP by month 3. Thirty-nine participants received 129 non-PrEP referrals, most commonly for housing assistance, primary care, Medicaid navigation, and food insecurity. CONCLUSIONS: Chain-referral sampling from partner services clients allowed DIS to access persons with significant medical and social service needs, demonstrating that DIS can support marginalized communities beyond STI intervention.

Automated Digital Notification of COVID-19 Diagnoses Through Text and Email Messaging - North Carolina, December 2020-January 2021.

During October 3, 2020-January 9, 2021, North Carolina experienced a 400% increase in daily reported COVID-19 cases (1). To handle the increased number of cases and rapidly notify persons receiving a positive SARS-CoV-2 test result (patients), North Carolina state and local health departments moved from telephone call notification only to telephone call plus automated text and email notification (digital notification) beginning on December 24, 2020. Overall, among 200,258 patients, 142,975 (71%) were notified by telephone call or digital notification within the actionable period (10 days from their diagnosis date)* during January 2021, including at least 112,543 (56%) notified within 24 hours of report to North Carolina state and local health departments, a significantly higher proportion than the 25,905 of 175,979 (15%) notified within 24 hours during the preceding month (p<0.001). Differences in text notification by age, race, and ethnicity were observed. Automated digital notification is a feasible, rapid and efficient method to support timely outreach to patients, provide guidance on how to isolate, access resources, inform close contacts, and increase the efficiency of case investigation staff members.

Enhancing Gonococcal Antimicrobial Resistance Surveillance in Cisgender Women, Strengthening the US Response to Resistant Gonorrhea, 2018 to 2019.

BACKGROUND: Cisgender women have been underrepresented in antibiotic-resistant gonorrhea (ARGC) surveillance systems. Three of 8 project sites (City of Milwaukee [MIL], Guilford County [GRB], Denver County [DEN]), funded under the Centers for Disease Control and Prevention's Strengthening the US Response to Resistant Gonorrhea (SURRG), focused efforts to better include cisgender women in ARGC surveillance. METHODS: MIL, GRB, and DEN partnered with diverse health care settings and developed gonorrhea culture criteria to facilitate urogenital specimen collection in cisgender women and men. Regional laboratories within the Antibiotic Resistance Laboratory Network performed agar dilution antibiotic susceptibility testing (AST) of gonococcal isolates. Data from 2018 and 2019 were analyzed. RESULTS: In SURRG, 90.5% (11,464 of 12,667) of the cisgender women from whom urogenital culture specimens were collected were from MIL, GRB, and DEN. Of women in SURRG whose gonococcal isolates underwent AST, 70% were from these 3 sites. In these 3 sites, a substantial proportion of cisgender women with positive urogenital cultures and AST were from health care settings other than sexually transmitted disease (STD) clinics (non-STD clinics; MIL, 56.0%; GRB, 80.4%; and DEN, 23.5%). Isolates with AST were obtained from 5.1%, 10.2%, and 2.4% of all diagnosed gonorrhea cases among cisgender women in MIL, GRB, and DEN, respectively, and were more often susceptible to all antibiotics than those from cisgender men from each of these sites. CONCLUSIONS: With focused efforts and partnerships with non-STD clinics, 3 SURRG sites were able to include robust ARGC surveillance from cisgender women. These findings may guide further efforts to improve gender equity in ARGC surveillance.

HIV-1 Transmission linkages among persons with incident infection to inform public health surveillance.

BACKGROUND: We evaluated features of HIV transmission networks involving persons diagnosed during incident HIV infection (IHI) to assess network-based opportunities to curtail onward transmission. METHODS: Transmission networks were constructed using partial pol sequences reported to North Carolina surveillance among persons with recent (2014-2018) and past (<2014) HIV diagnoses. IHI were defined as documented acute infections or seroconversion. Demographic and virologic features of HIV genetic clusters (<1.5% pairwise genetic distance) involving ≥ 1 IHI were assessed. Persons with viral genetic links and who had diagnoses >90 days prior to an IHI were further characterized. We assessed named partner outcomes among IHI index persons using contact tracing data. FINDINGS: Of 4,405 HIV diagnoses 2014-2018 with sequences, there were 323 (7%) IHI index persons; most were male (88%), Black (65%), young (68% <30 years), and reported sex with men (MSM) risk (79%). Index persons were more likely to be cluster members compared to non-index persons diagnosed during the same period (72% vs. 49%). In total, 162 clusters were identified involving 233 IHI, 577 recent diagnoses, and 163 past diagnoses. Most IHI cases (53%) had viral linkages to ≥1 previously diagnosed person without evidence of HIV viral suppression in the year prior to the diagnosis of the IHI index. In contact tracing, only 53% IHI cases named an HIV-positive contact, resulting in 0.5 previously diagnosed persons detected per IHI investigated. When combined with viral analyses, the detection rate of viremic previously diagnosed persons increased to 1.3. INTERPRETATION: Integrating public health with molecular epidemiology, revealed that more than half of IHI have viral links to persons with previously diagnosed unsuppressed HIV infection which was largely unrecognized by traditional contact tracing. Enhanced partner services to support engagement and retention in HIV care and improved case finding supported by rapid phylogenetic analysis are tools to substantially reduce onward HIV transmission.

Near Real-Time Identification of Recent Human Immunodeficiency Virus Transmissions, Transmitted Drug Resistance Mutations, and Transmission Networks by Multiplexed Primer ID-Next-Generation Sequencing in North Carolina.

BACKGROUND: The identification of recent human immunodeficiency virus (HIV) 1 infections among people with new HIV diagnoses is important to both tailoring and assessing the impact of HIV-1 prevention strategies. METHODS: We developed a multiplexed Primer ID-next-generation sequencing approach to identify recent infections by measuring the intrahost viral diversity over multiple regions of the HIV-1 genome, in addition to detecting drug resistance mutations (DRMs) and phylogenetically linked clusters. We summarize the field implementation of this all-in-one platform among persons with newly diagnosed HIV-1 by the North Carolina State Laboratory of Public Health in 2018. RESULTS: Overall, recent infection was identified in 94 (35%) of 268 patients with new HIV diagnoses. People <30 years old, and people who inject drugs were more likely to have diagnoses of recent infection. The reverse-transcriptase region K103N was the most commonly detected DRM (prevalence, approximately 15%). We found a total of 28 clusters, and persons with recent infection were more likely to be cluster members than were those with chronic infections (P = .03). CONCLUSIONS: We demonstrate the rapid identification of recent infection and pretreatment DRMs coupled with cluster analysis that will allow prioritization of linkage to care, treatment, and prevention interventions to those at highest risk of onward transmission.

Unnamed Partners From Syphilis Partner Services Interviews, 7 Jurisdictions.

BACKGROUND: Reducing transmission depends on the percentage of infected partners treated; if many are missed, impact on transmission will be low. Traditional partner services metrics evaluate the number of partners found and treated. We estimated the proportion of partners of syphilis patients not locatable for intervention. METHODS: We reviewed records of early syphilis cases (primary, secondary, early latent) reported in 2015 to 2017 in 7 jurisdictions (Florida, Louisiana, Michigan, North Carolina, Virginia, New York City, and San Francisco). Among interviewed syphilis patients, we determined the proportion who reported named partners (with locating information), reported unnamed partners (no locating information), and did not report partners. For patients with no reported partners, we estimated their range of unreported partners to be between one and the average number of partners for patients who reported partners. RESULTS: Among 29,719 syphilis patients, 23,613 (80%) were interviewed and 18,581 (63%) reported 84,224 sex partners (average, 4.5; 20,853 [25%] named and 63,371 [75%] unnamed). An estimated 11,138 to 54,521 partners were unreported. Thus, 74,509 to 117,892 (of 95,362-138,745) partners were not reached by partner services (78%-85%). Among interviewed patients, 71% reported ≥1 unnamed partner or reported no partners; this proportion was higher for men who reported sex with men (75%) compared with men who reported sex with women only (65%) and women (44%). CONCLUSIONS: Approximately 80% of sex partners were either unnamed or unreported. Partner services may be less successful at interrupting transmission in networks for men who reported sex with men where a higher proportion of partners are unnamed or unreported.

HIV Outbreak Control With Effective Access to Care and Harm Reduction in North Carolina, 2017-2018.

Objectives. To assess and control a potential outbreak of HIV among people who inject drugs in Western North Carolina.Methods. Disease intervention specialists offered testing for hepatitis B and hepatitis C, harm reduction materials, and linkage to care to 7 linked people recently diagnosed with HIV who also injected drugs. Contacts were offered the same services and HIV testing. HIV genotype analysis was used to characterize HIV spread. We assessed testing and care outcomes by using state surveillance information.Results. Disease intervention specialists contacted 6 of 7 linked group members and received information on 177 contacts; among 96 prioritized contacts, 42 of 96 (44%) were exposed to or diagnosed with hepatitis C, 4 of 96 (4%) had hepatitis B, and 14 of 96 (15%) had HIV (2 newly diagnosed during the investigation). HIV genotype analysis suggested recent transmission to linked group members and 1 contact. Eleven of 14 with HIV were virally suppressed following the outbreak response.Conclusions. North Carolina identified and rapidly responded to an HIV outbreak among people reporting injecting drugs. Effective HIV care, the availability of syringe exchange services, and the rapid response likely contributed to controlling this outbreak.

Performance of the Syphilis Health Check in Clinic and Laboratory-Based Settings.

BACKGROUND: In this study, we evaluate the performance of the Syphilis Health Check (SHC) in clinical and laboratory settings using fingerstick whole blood and serum. METHODS: Fingerstick whole blood and serum specimens from adult patients (n = 562) without prior syphilis history presenting at 2 county health department STD clinics in North Carolina were tested. Fingerstick specimens were tested with the SHC in clinic, and serum specimens were tested at the North Carolina State Laboratory of Public Health with: (1) qualitative rapid plasma reagin, (2) treponemal EIA, and (3) SHC. Sensitivity and specificity were calculated with 95% confidence intervals. RESULTS: The fingerstick whole blood had a sensitivity of 100% (7 of 7) and specificity of 95.7% (531 of 555), compared with consensus reference testing (CRT) (rapid plasma reagin and EIA reactive), but a sensitivity of 50% (8 of 16), and specificity of 95.9% (523 of 546), when compared with the treponemal EIA. Both laboratory-based SHC on serum and whole-blood SHC performed similarly, compared with CRT, and the treponemal EIA alone. Twenty-four specimens SHC reactive on whole blood were nonreactive by CRT. In 8 of these 24 cases, STD clinic staff reported difficulty reading the test line for the SHC. Of the fingerstick whole-blood SHC reactive specimens, only 14 of 31 were also serum SHC reactive. CONCLUSIONS: The SHC on whole blood appears to be sensitive at detecting patients likely to have syphilis and could be an option for testing among high-risk populations. However, given challenges in interpreting SHC test results, adequate training of persons performing testing and ongoing quality assurance measures are key.

Ocular Syphilis and Human Immunodeficiency Virus Coinfection Among Syphilis Patients in North Carolina, 2014-2016.

BACKGROUND: Ocular syphilis (OS) has been associated with human immunodeficiency virus (HIV) coinfection previously. We compared demographic and clinical characteristics of syphilis patients with and without HIV to identify risk factors for developing OS. METHODS: We reviewed all syphilis cases (early and late) reported to the North Carolina Division of Public Health during 2014 to 2016 and categorized HIV status (positive, negative, unknown) and OS status based on report of ocular symptoms with no other defined etiology. We estimated prevalence ratios (PR) and 95% confidence intervals (CI) for OS by HIV status. Among syphilis patients with HIV, we compared viral loads and CD4 cell counts by OS status. We compared symptom resolution by HIV status for a subset of OS patients. RESULTS: Among 7123 confirmed syphilis cases, 2846 (39.9%) were living with HIV, 109 (1.5%) had OS, and 59 (0.8%) had both. Ocular syphilis was more prevalent in syphilis patients with HIV compared to HIV-negative/unknown-status patients (PR, 1.8; 95% CI, 1.2-2.6). Compared with other patients with HIV, the prevalence of OS was higher in patients with viral loads greater than 200 copies/mL (1.7; 1.0-2.8) and in patients with a CD4 count of 200 cells/mL or less (PR, 2.3; 95% CI, 1.3-4.2). Among 11 patients with severe OS, 9 (81.8%) were HIV-positive. Among 39 interviewed OS patients, OS symptom resolution was similar for HIV-positive (70.0%) and HIV-negative/unknown-status (68.4%) patients. CONCLUSIONS: Syphilis patients with HIV were nearly twice as likely to report OS symptoms as were patients without documented HIV. Human immunodeficiency virus-related immunodeficiency possibly increases the risk of OS development in co-infected patients.