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We describe the first documented case of Jamestown Canyon virus (JCV) in North Carolina, which occurred in a liver transplant patient who presented acutely with headache, aphasia, and confusion. This is also the first report of recovery from JCV encephalitis following treatment with intravenous immune globulin. [ABSTRACT FROM AUTHOR]

Importance: Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection.Objective: To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing.Design, Setting, and Participants: Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection.Exposures: All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test.Main Outcomes and Measures: Number and proportion with acute HIV infections detected.Results: Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P < .001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%).Conclusions and Relevance: In a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention. [ABSTRACT FROM AUTHOR]

Objective: HIV transmission is influenced by status awareness and receipt of care and treatment. We analyzed these attributes of named partners of persons with acute HIV infection (index AHI cases) to characterize the transmission landscape in North Carolina (NC). Design: Secondary analysis of programmatic data. Methods: We used data from the NC Screening and Tracing of Active Transmission Program (2002–2013) to determine HIV status (uninfected, AHI, or chronic HIV infection [CHI]), diagnosis status (new or previously-diagnosed), and care and treatment status (not in care, in care and not on treatment, in care and on treatment) of index AHI cases' named partners. We developed an algorithm identifying the most likely transmission source among known HIV-infected partners to estimate the proportion of transmissions arising from contact with persons at different HIV continuum stages. We conducted a complementary analysis among a subset of index AHI cases and partners with phylogenetically-linked viruses. Results: Overall, 358 index AHI cases named 932 partners, of which 218 were found to be HIV-infected (162 (74.3%) previously-diagnosed, 11 (5.0%) new AHI, 45 (20.6%) new CHI). Most transmission events appeared attributable to previously-diagnosed partners (77.4%, 95% confidence interval 69.4–85.3%). Among these previously-diagnosed partners, 23.2% (14.0–32.3%) were reported as in care and on treatment near the index AHI case diagnosis date. In the subset study of 33 phylogenetically-linked cases and partners, 60.6% of partners were previously diagnosed (43.9–77.3%). Conclusions: A substantial proportion of HIV transmission in this setting appears attributable to contact with previously-diagnosed partners, reinforcing the need for improved engagement in care after diagnosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program., Methods: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo., Results: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability., Conclusion: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments., Competing Interests: Declaration of Conflicting InterestsCEG served in a consulting role for Gilead and received research support from Gilead. HS reports being a full-time employee of ViiV Healthcare. CJM has received grants, contracts and/or participated in clinical trials with Becton Dickinson, Biomedical Advanced Research and Development Authority/GlaxoSmithKline, Centers for Disease Control and Prevention, Cepheid, Hologic, Lupin, The National Association of County and City Health Officials, and the National Institutes of Health, and is on the advisory board for Talis Biomedical paid to her employer Wake Forest University School of Medicine. CLG has received research support from ViiV Healthcare, Moderna and Novavax. All other authors have no conflicts to disclose.

Social networks can be leveraged to identify undiagnosed HIV-infected individuals. The NC-LINK clinic-based testing initiative utilized these networks to achieve a 5% (95% CI 1.1-8.9%) positivity rate by providing free HIV testing to anyone who accompanied an HIV-infected patient to their clinic appointment. During 2013-2015, 120 individuals were tested at two clinics (N > 1000 patients each) in North Carolina, with 5 new and 6 total positive results. Of these, three linked to care within 30 days and all within 365 days. If expanded further, this initiative could significantly increase the number of HIV-infected individuals aware of their status.

Objective: To describe demographic and behavioral characteristics of persons with acute HIV infection (AHI) over time., Methods: We conducted a retrospective assessment of AHI identified through the Screening and Tracing Active Transmission (STAT) program from 2003 to 2012 in North Carolina (NC). AHI was identified using pooled nucleic acid amplification for antibody negative samples and individual HIV-1 RNA for antibody indeterminate samples. The STAT program provides rapid notification and evaluation. We compared STAT-collected demographic and risk characteristics with all persons requesting tests and all non-AHI diagnoses from the NC State Laboratory of Public Health., Results: The STAT Program identified 236 AHI cases representing 3.4% (95% confidence interval: 3.0% to 3.9%) of all HIV diagnoses. AHI cases were similar to those diagnosed during established HIV. On pretest risk-assessments, AHI cases were predominately black (69.1%), male (80.1%), young (46.8% < 25 years), and men who have sex with men (MSM) (51.7%). Per postdiagnosis interviews, the median age decreased from 35 (interquartile range 25-42) to 27 (interquartile range 22-37) years, and the proportion <25 years increased from 23.8% to 45.2% (trend P = 0.04) between 2003 and 2012. AHI men were more likely to report MSM risk post-diagnosis than on pretest risk-assessments (64%-82.9%; P < 0.0001). Post-diagnosis report of MSM risk in men with AHI increased from 71.4% to 96.2%., Conclusions: In NC, 3.4% of individuals diagnosed with HIV infection have AHI. AHI screening provides a real-time source of incidence trends, improves the diagnostic yield of HIV testing, and offers an opportunity to limit onward transmission.

Human immunodeficiency virus (HIV) prevention interventions, such as preexposure prophylaxis (PrEP), are often targeted to men who have sex with men (MSM) who self-report high-risk behaviors. Data from a prospective study evaluating methods to detect acute HIV infection among a primarily young (aged <25 years) and black or African American (African American) population from North Carolina were analyzed. In the study, participants were asked about risk behaviors during pretest counseling (at the time of testing) and then during a partner services interview (at HIV diagnosis). Participants whose disclosure of sexual risk behaviors during pretest counseling was different from their disclosure of sexual risk behaviors during their partner services interview were identified, and factors associated with these discordant responses were examined. Among 113 HIV-infected men, 26 (23.0%) did not disclose male sex partners at pretest counseling, but subsequently did disclose this information during their partner services interview. When compared with men who disclosed having male partners at pretest counseling, these 26 MSM who did not disclose male partners during pretest counseling were found to have a similar number of male partners during contact tracing, but were more likely to have a female partner (30.8% versus 6.9%). In addition, the proportions of MSM found to have at least one HIV-infected partner were similar for both groups (MSM who disclosed having male partners during pretest counseling and those who did not). To better customize HIV prevention interventions for MSM, HIV prevention programs might consider using novel strategies to accurately assess risk in this population.

Objectives: We evaluated emergency department (ED) provider adherence to guidelines for concurrent HIV-sexually transmitted disease (STD) testing within an expanded HIV testing program and assessed demographic and clinical factors associated with concurrent HIV-STD testing., Methods: We examined concurrent HIV-STD testing in a suburban academic ED with a targeted, expanded HIV testing program. Patients aged 18-64 years who were tested for syphilis, gonorrhea, or chlamydia in 2009 were evaluated for concurrent HIV testing. We analyzed demographic and clinical factors associated with concurrent HIV-STD testing using multivariate logistic regression with a robust variance estimator or, where applicable, exact logistic regression., Results: Only 28.3% of patients tested for syphilis, 3.8% tested for gonorrhea, and 3.8% tested for chlamydia were concurrently tested for HIV during an ED visit. Concurrent HIV-syphilis testing was more likely among younger patients aged 25-34 years (adjusted odds ratio [AOR] = 0.36, 95% confidence interval [CI] 0.78, 2.10) and patients with STD-related chief complaints at triage (AOR=11.47, 95% CI 5.49, 25.06). Concurrent HIV-gonorrhea/chlamydia testing was more likely among men (gonorrhea: AOR=3.98, 95% CI 2.25, 7.02; chlamydia: AOR=3.25, 95% CI 1.80, 5.86) and less likely among patients with STD-related chief complaints at triage (gonorrhea: AOR=0.31, 95% CI 0.13, 0.82; chlamydia: AOR=0.21, 95% CI 0.09, 0.50)., Conclusions: Concurrent HIV-STD testing in an academic ED remains low. Systematic interventions that remove the decision-making burden of ordering an HIV test from providers may increase HIV testing in this high-risk population of suspected STD patients.

In 1998 a collaboration between Duke University and the University of North Carolina, Chapel Hill (UNC) was founded to enhance identification of persons with acute HIV-1 infection (AHI). The Duke-UNC AHI Research Consortium Cohort consists of patients ≥18 years old with a positive nucleic acid amplification test (NAAT) and either a negative enzyme immunoassay (EIA) test or a positive EIA with a negative/indeterminate Western blot. Patients were referred to the cohort from acute care settings and state-funded HIV testing sites that use NAAT testing on pooled HIV-1 antibody-negative samples. Between 1998 and 2010, 155 patients with AHI were enrolled: 81 (52%) African-Americans, 63 (41%) white, non-Hispanics, 137 (88%) males, 108 (70%) men who have sex with men (MSM), and 18 (12%) females. The median age was 27 years (IQR 22-38). Most (n=138/155) reported symptoms with a median duration of 17.5 days. The median nadir CD4 count was 408 cells/mm(3) (IQR 289-563); the median observed peak HIV-1 level was 726,859 copies/ml (IQR 167,585-3,565,728). The emergency department was the most frequent site of initial presentation (n=55/152; 3 missing data). AHI diagnosis was made at time of first contact in 62/137 (45%; 18 missing data) patients. This prospectively enrolled cohort is the largest group of patients with AHI reported from the Southeastern United States. The demographics reflect the epidemic of this geographic area with a high proportion of African-Americans, including young black MSM. Highlighting the challenges of diagnosing AHI, less than half of the patients were diagnosed at the first healthcare visit. Women made up a small proportion despite increasing numbers in our clinics.

In this study we characterized factors associated with the late initiation of HIV care in the southeastern United States. At initiation of care, antiretroviral therapy was indicated for 75% of patients, 50% had a CD4 cell count of less than 200 cells/mul, and 27% presented with an AIDS-defining illness. Male sex was an independent predictor in multivariable analysis. These results indicate an urgent need to increase HIV testing for earlier diagnosis in the southeastern USA.