A public health approach to monitoring HIV with resistance to HIV pre-exposure prophylaxis.

BACKGROUND: The risk of HIV pre-exposure prophylaxis (PrEP) failure with sufficient medication adherence is extremely low but has occurred due to transmission of a viral strain with mutations conferring resistance to PrEP components tenofovir (TDF) and emtricitabine (FTC). The extent to which such strains are circulating in the population is unknown. METHODS: We used HIV surveillance data to describe primary and overall TDF/FTC resistance and concurrent viremia among people living with HIV (PLWH). HIV genotypes conducted for clinical purposes are reported as part of HIV surveillance. We examined the prevalence of HIV strains with mutations conferring intermediate to high level resistance to TDF/FTC, defining primary resistance (predominantly K65R and M184I/V mutations) among sequences reported within 3 months of HIV diagnosis and total resistance for sequences reported at any time. We examined trends in primary resistance during 2010-2019 and total resistance among all PLWH in 2019. We also monitored resistance with viremia (≥1,000 copies/mL) at the end of 2019 among PLWH. RESULTS: Between 2010 and 2019, 2,172 King County residents were diagnosed with HIV; 1,557 (72%) had a genotypic resistance test within three months; three (0.2%) had primary TDF/FTC resistance with both K65R and M184I/V mutations. Adding isolated resistance for each drug resulted in 0.3% with primary TDF resistance and 0.8% with primary FTC resistance. Of 7,056 PLWH in 2019, 4,032 (57%) had genotype results, 241 (6%) had TDF/FTC resistance and 15 (0.4% of those with a genotype result) had viremia and TDF/FTC resistance. CONCLUSIONS: Primary resistance and viremia combined with TDF/FTC resistance are uncommon in King County. Monitoring trends in TDF/FTC resistance coupled with interventions to help ensure PLWH achieve and maintain viral suppression may help ensure that PrEP failure remains rare.

Direct and Indirect Effects of a Project ECHO Longitudinal Clinical Tele-Mentoring Program on Viral Suppression for Persons With HIV: A Population-Based Analysis.

BACKGROUND: Project Extension for Community Health Outcomes (ECHO) aims to connect community providers to academic specialists, deliver longitudinal clinical mentorship and case consultations, plus encourage dissemination of knowledge and resources. The impact on outcomes for persons with HIV (PWH) is uncertain. SETTING: PWH in Washington and Oregon outside of the Seattle and Portland metro areas, January 2011 to March 2018. METHODS: Using viral load (VL) surveillance data, we assessed difference in the percentage of PWH who were virally suppressed among PWH whose providers participated versus did not participate in Project ECHO. Analyses included multiple mixed-effects regression models, adjusting for time and for patient, provider, and clinic characteristics. RESULTS: Based on 65,623 VL results, Project ECHO participation was associated with an increase in the percentage of patients with VL suppression (13.7 percentage points greater; P < 0.0001), although the effect varied by estimated provider PWH patient volume. The difference was 14.7 percentage points ( P < 0.0001) among patients of providers who order <20 VL's/quarter and 2.3 and -0.6 percentage points among patients of providers who order 20-40 or >40 VL's/quarter, respectively ( P > 0.5). The magnitude of difference in VL suppression was associated with the number of sessions attended. Among patients of lower-volume providers who did not participate, VL suppression was 6.2 percentage points higher if providers worked in a clinic where another provider did participate ( P < 0.0001). CONCLUSION: Project ECHO is associated with improvement in VL suppression for PWH whose providers participate or work in the same clinic system as a provider who participates, primarily because of benefits for patients of lower-volume providers.

Community and Provider Perspectives on Molecular HIV Surveillance and Cluster Detection and Response for HIV Prevention: Qualitative Findings From King County, Washington.

ABSTRACT: Responding quickly to HIV outbreaks is one of four pillars of the U.S. Ending the HIV Epidemic (EHE) initiative. Inclusion of cluster detection and response in the fourth pillar of EHE has led to public discussion concerning bioethical implications of cluster detection and response and molecular HIV surveillance (MHS) among public health authorities, researchers, and community members. This study reports on findings from a qualitative analysis of interviews with community members and providers regarding their knowledge and perspectives of MHS. We identified five key themes: (a) context matters, (b) making sense of MHS, (c) messaging, equity, and resource prioritization, (d) operationalizing confidentiality, and (e) stigma, vulnerability, and power. Inclusion of community perspectives in generating innovative approaches that address bioethical concerns related to the use of MHS data is integral to ensure that widely accessible information about the use of these data is available to a diversity of community members and providers.

A Multifaceted Evaluation of a COVID-19 Contact Tracing Program in King County, Washington.

CONTEXT: Despite the massive scale of COVID-19 case investigation and contact tracing (CI/CT) programs operating worldwide, the evidence supporting the intervention's public health impact is limited. OBJECTIVE: To evaluate the Public Health-Seattle & King County (PHSKC) CI/CT program, including its reach, timeliness, effect on isolation and quarantine (I&Q) adherence, and potential to mitigate pandemic-related hardships. DESIGN: This program evaluation used descriptive statistics to analyze surveillance records, case and contact interviews, referral records, and survey data provided by a sample of cases who had recently ended isolation. SETTING: The PHSKC is one of the largest governmental local health departments in the United States. It serves more than 2.2 million people who reside in Seattle and 38 other municipalities. PARTICIPANTS: King County residents who were diagnosed with COVID-19 between July 2020 and June 2021. INTERVENTION: The PHSKC integrated COVID-19 CI/CT with prevention education and service provision. RESULTS: The PHSKC CI/CT team interviewed 42 900 cases (82% of cases eligible for CI/CT), a mean of 6.1 days after symptom onset and 3.4 days after SARS-CoV-2 testing. Cases disclosed the names and addresses of 10 817 unique worksites (mean = 0.8/interview) and 11 432 other recently visited locations (mean = 0.5/interview) and provided contact information for 62 987 household members (mean = 2.7/interview) and 14 398 nonhousehold contacts (mean = 0.3/interview). The CI/CT team helped arrange COVID-19 testing for 5650 contacts, facilitated grocery delivery for 7253 households, and referred 9127 households for financial assistance. End of I&Q Survey participants (n = 304, 54% of sampled) reported self-notifying an average of 4 nonhousehold contacts and 69% agreed that the information and referrals provided by the CI/CT team helped them stay in isolation. CONCLUSIONS: In the 12-month evaluation period, CI/CT reached 42 611 households and identified thousands of exposure venues. The timing of CI/CT relative to infectiousness and difficulty eliciting nonhousehold contacts may have attenuated the intervention's effect. Through promotion of I&Q guidance and services, CI/CT can help mitigate pandemic-related hardships.

Molecular Epidemiology of Individuals Experiencing Unstable Housing or Living Homeless at HIV Diagnosis: Analysis of HIV Surveillance Data in King County, Washington.

We examined patterns of genetic clustering among individuals diagnosed with HIV between 2010 and 2018 using data from King County, Washington's National HIV Surveillance System. Among 2,371 individuals newly diagnosed with HIV, 231 (10%) experienced unstable housing or were living homeless at the time of diagnosis. Among the 1,658 (70%) people with an available HIV-1 pol gene sequence, 1,071 (65%) were identified to be part of 296 genetic clusters. In our analysis, housing status was not associated with genetic clustering (OR 1.02; 95%CI:0.75,1.39). After adjusting for demographic and behavioral factors, people who were living homeless at HIV diagnosis had 35% lower odds of being identified as part of a genetic cluster (AOR 0.65; 95%CI:0.44,0.95) compared to people with stable housing. Our findings highlight that people experiencing unstable housing are disproportionately burdened by HIV, and that within this population in King County, being in a genetic cluster is predominantly associated with substance use.

Detection and Response to an HIV Cluster: People Living Homeless and Using Drugs in Seattle, Washington.

INTRODUCTION: The HIV epidemic in King County, Washington has traditionally been highly concentrated among men who have sex with men, and incidence has gradually declined over 2 decades. In 2018, King County experienced a geographically concentrated outbreak of HIV among heterosexual people who inject drugs. METHODS: Data sources to describe the 2018 outbreak and King County's response were partner services interview data, HIV case reports, syringe service program client surveys, hospital data, and data from a rapid needs assessment of homeless individuals and people who inject drugs. In 2020, the authors examined the impact of delays in molecular sequence analyses and cluster member size thresholds, for identifying genetically similar clusters, on the timing of outbreak identification. RESULTS: In 2018, the health department identified a North Seattle cluster, growing to 30 people with related HIV infections diagnosed in 2008-2019. In total, 70% of cluster members were female, 77% were people who inject drugs, 87% were homeless, and 27% reported exchanging sex. Intervention activities included a rapid needs assessment, 2,485 HIV screening tests in a jail and other outreach settings, provision of 87,488 clean syringes in the outbreak area, and public communications. A lower cluster size threshold and more rapid receipt and analyses of data would have identified this outbreak 4-16 months earlier. CONCLUSIONS: This outbreak shows the vulnerability of people who inject drugs to HIV infection, even in areas with robust syringe service programs and declining HIV epidemics. Although molecular HIV surveillance did not identify this outbreak, it may have done so with a lower threshold for defining clusters and more rapid receipt and analyses of HIV genetic sequences.

Combining traditional and molecular epidemiology methods to quantify local HIV transmission among foreign-born residents.

OBJECTIVES: We evaluated the ability for molecular epidemiology to augment traditional HIV surveillance beyond the detection of clusters for outbreak investigation. To do this, we address a question of interest to Public Health - Seattle and King County: what proportion of HIV diagnoses among people born outside of the United States are acquired locally? DESIGN: King County residents diagnosed with HIV, 2010-2018. METHODS: We linked HIV-1 pol gene sequences to demographic information obtained from the National HIV Surveillance System, Public Health - Seattle and King County case investigation and partner services interviews. We determined the likely location of HIV acquisition based on HIV testing, travel histories and cluster-based molecular analyses. RESULTS: Among 2409 people diagnosed with HIV, 798 (33%) were born outside of the United States. We inferred the location of acquisition for 77% of people born outside of the United States: 26% likely acquired HIV locally in King County (of whom 69% were MSM, 16% heterosexual), and 51% likely acquired HIV outside of King County (primarily outside of the United States). Of this 77% of people for whom we inferred the location of HIV acquisition, 45% were determined using traditional epidemiology methods and an additional 32% were inferred using molecular epidemiology methods. CONCLUSION: We found that the National HIV Surveillance System misclassified the majority of HIV-infected foreign-born residents as 'new' local infections, and that these cases contribute to an overestimate of local incidence. Our findings highlight how molecular epidemiology can augment traditional HIV surveillance activities and provide useful information to local health jurisdictions beyond molecular cluster detection.

Outbreak of Human Immunodeficiency Virus Infection Among Heterosexual Persons Who Are Living Homeless and Inject Drugs - Seattle, Washington, 2018.

Although diagnoses of human immunodeficiency virus (HIV) infection among persons who inject drugs in the United States are declining, an HIV outbreak among such persons in rural Indiana demonstrated that population's vulnerability to HIV infection (1). In August 2018, Public Health-Seattle and King County (PHSKC) identified a cluster of cases of HIV infection among persons living homeless, most of whom injected drugs. Investigation identified 14 related cases diagnosed from February to mid-November 2018 among women who inject drugs and men who have sex with women (MSW) who inject drugs and their sex partners. All 14 persons were living homeless in an approximately 3-square-mile area and were part of a cluster of 23 cases diagnosed since 2008. Twenty-seven cases of HIV infection were diagnosed among women and MSW who inject drugs in King County during January 1-November 15, 2018, a 286% increase over the seven cases diagnosed in 2017. PHSKC has alerted medical and social service providers and the public about the outbreak, expanded HIV testing among persons who inject drugs or who are living homeless, and is working to increase the availability of clinical and prevention services in the geographic area of the outbreak. This outbreak highlights the vulnerability of persons who inject drugs, particularly those who also are living homeless, to outbreaks of HIV infection, even in areas with high levels of viral suppression and large syringe services programs (SSPs).

Evaluating the Completeness of HIV Surveillance Using Capture-Recapture Models, Alameda County, California.

HIV prevalence in Alameda County (including Oakland) is among the highest in California, yet the case registry may under-appreciate the full burden of disease. Using lists from health care facilities serving socioeconomically diverse populations and the HIV surveillance list, we applied capture-recapture methods to evaluate the completeness of the surveillance system by estimating the number of diagnosed people living with HIV and seeking care in Alameda County in 2013. Of the 5376 unique individuals reported from the lists, 397 were missing from the surveillance list. Models projected the total population size to be 5720 (95% CI 5587-6190), estimating the surveillance system as 87% complete. Subgroup analyses identified groups facing a disproportionate burden of HIV as more likely to be detected by the surveillance list. The Alameda County HIV surveillance system reports a high proportion of persons diagnosed with HIV within the jurisdiction. Capture-recapture analysis can help track progress towards maximizing engagement in HIV care.

Variation in adherence to the treatment guidelines for Neisseria gonorrhoeae by clinical practice setting, California, 2009 to 2011.

BACKGROUND: Declining susceptibility of Neisseria gonorrhoeae to available antimicrobial agents has prompted repeated updates of the Centers for Disease Control and Prevention (CDC) treatment guidelines. The only regimen currently recommended as first-line treatment is dual therapy consisting of an intramuscular dose of ceftriaxone together with azithromycin or doxycycline. The objective of this analysis is to identify how adherence to the CDC guidelines varies by clinical practice setting. METHODS: A geographically representative random sample of N. gonorrhoeae cases reported from 2009 to 2011 was analyzed. Weighted generalized linear models were fit to calculate cumulative incidence ratios for receipt of non-recommended treatment regimen in relation to clinical practice setting, adjusted for age, race, and whether or not the participant was a man who has sex with men. RESULTS: Data from 3178 participants were available for analysis. Overall, 14.9% (weighted) of participants received non-recommended treatment. Among participants with gonorrhea identified by surveillance data as having received non-recommended treatment, the largest proportions were treated at private physicians' offices or health maintenance organizations (34.7% of participants receiving non-recommended treatment), family planning facilities (22.3%), and emergency departments/urgent care centers (12.8%). CONCLUSIONS: Barriers to adherence to the CDC treatment guidelines for gonorrhea seem to be experienced in a variety of clinical practice settings. Despite only moderate rates of nonadherence, interventions targeting private physicians/health maintenance organizations and family planning facilities may produce the largest absolute reductions in guideline-discordant treatment.