Electronic Messaging for Gonorrhea and Chlamydia Test Result Notification, Improving Treatment and Patient Satisfaction.

BACKGROUND: Approximately 20% of chlamydia (CT) and gonorrhea (GC) cases in Louisiana are diagnosed at Parish Health Units. Patient notification of CT and GC test results involves nurses' phone calls and letters to positive patients, which is time-consuming and inefficient. METHODS: In December 2018, electronic results notification was implemented in Caddo Parish Health Unit using Chexout software to notify enrolled patients via text or email when test results are ready to view in a patient portal. We compared the timeliness of GC/CT results notification and treatment pre-Chexout (December 2017 to November 2018) and post-Chexout (December 2018 to November 2019) implementation. A random sample of patients was interviewed to assess acceptability. RESULTS: During December 2018 to November 2019, 5432 patients were tested for CT/GC, 3924 (72%) enrolled in Chexout, and notifications were sent to 3884 (99%). Among CT-positives, 472 of 568 (83%) viewed results in the portal compared with 2451 of 3356 (73%) CT-negatives. Among GC-positives, 300 of 353 (85%) viewed results compared with 2657 of 3571 (74%) GC-negatives. Treatment success for CT improved from 493 of 670 (74%) to 506 of 568 (89%), and for GC, from 332 of 409 (81%) to 325 of 353 (92%). Mean time to treatment decreased for CT (13.4-10.7 days) and GC (11.3-9.2 days). Enrolled patients found Chexout notification satisfactory in 168 of 169 (99%) and easy to use in 130 of 141 (92%). Reasons for declining electronic notification included lack of personal cell phone for 55 of 86 (64%) and confidentiality concerns for 42 of 86 (49%). CONCLUSIONS: Electronic messaging decreased time to notification and increased treatment success. Nurses spent less time notifying patients leaving more time for patient care.

Neighborhood Poverty and Control of HIV, Hypertension, and Diabetes in the Women's Interagency HIV Study.

Neighborhoods with high poverty rates have limited resources to support residents' health. Using census data, we calculated the proportion of each Women's Interagency HIV Study participant's census tract (neighborhood) living below the poverty line. We assessed associations between neighborhood poverty and (1) unsuppressed viral load [VL] in HIV-seropositive women, (2) uncontrolled blood pressure among HIV-seropositive and HIV-seronegative hypertensive women, and (3) uncontrolled diabetes among HIV-seropositive and HIV-seronegative diabetic women using modified Poisson regression models. Neighborhood poverty was associated with unsuppressed VL in HIV-seropositive women (> 40% versus ≤ 20% poverty adjusted prevalence ratio (PR), 1.42; 95% confidence interval (CI) 1.04-1.92). In HIV-seronegative diabetic women, moderate neighborhood poverty was associated with uncontrolled diabetes (20-40% versus ≤ 20% poverty adjusted PR, 1.75; 95% CI 1.02-2.98). Neighborhood poverty was associated with neither uncontrolled diabetes among HIV-seropositive diabetic women, nor uncontrolled hypertension in hypertensive women, regardless of HIV status. Women living in areas with concentrated poverty may need additional resources to control health conditions effectively.

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.

Repeat Human Immunodeficiency Virus Testing by Transmission Risk Group and Rurality of Residence in North Carolina.

BACKGROUND: Understanding of repeat human immunodeficiency virus (HIV) testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden. METHODS: We used HIV surveillance data from publicly funded HIV testing sites in North Carolina to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study. Linear binomial regression models were used to estimate adjusted, 1-year cumulative incidences and cumulative incidence differences comparing RHT within transmission risk populations by level of rurality. RESULTS: In our total study population of 600,613 persons, 19,275 (3.2%) and 9567 (1.6%) self-identified as men who have sex with men (MSM) and persons who inject drugs (PWID), respectively. A small minority, 13,723 (2.3%) resided in rural ZIP codes. Men who have sex with men were most likely to repeat test (unadjusted, 1-year cumulative incidence after an initial negative test, 16.4%) compared with PWID (13.2%) and persons who did not identify as either MSM or PWID (13.6%). The greatest effect of rurality was within PWID; the adjusted, 1-year cumulative incidence of RHT was 6.4 (95% confidence interval, 1.4-11.4) percentage points higher among metropolitan versus rural PWID. CONCLUSIONS: One-year cumulative incidence of RHT was low among all clients of publicly funded HIV testing sites in North Carolina, including MSM and PWID for whom annual testing is recommended. Our findings suggest a need for public health efforts to increase access to and support for RHT, particularly among rural PWID.

The Number of Interviews Needed to Yield New Syphilis and Human Immunodeficiency Virus Cases Among Partners of People Diagnosed With Syphilis, North Carolina, 2015.

Compare syphilis investigation yield among patient groups using number needed to interview. GOAL: To increase investigation efficiency. STUDY DESIGN: Retrospective review of North Carolina 2015 syphilis investigations, using the number of cases needed to interview (NNTI) and the total number of cases and contacts needed to interview (TNTI) to compare yield of new syphilis and human immunodeficiency virus diagnoses between patient groups. RESULTS: We reviewed 1646 early syphilis cases and 2181 contacts; these yielded 241 new syphilis cases (NNTI, 6.9; TNTI, 16.4) and 38 new human immunodeficiency virus cases (NNTI, 43). Interviews of women (prevalence difference [PD] = 6%, 95% confidence interval [CI], 12-16), patients <30 years old (PD = 5%, 95% CI, 1-8), and patients with titer >1:16 (PD = 5%, 95% CI, 1-9) yielded more new syphilis cases in our adjusted model; no other patient factors increased investigation yield. CONCLUSIONS: The NNTI and TNTI are useful measures of efficiency. Prioritizing early syphilis investigation by gender, rapid plasmin reagin titer, and age provides small increases in efficiency; no other factors increased efficiency.

Distance to testing sites and its association with timing of HIV diagnosis.

Early HIV diagnosis enables prompt treatment initiation, thereby contributing to decreased morbidity, mortality, and transmission. We aimed to describe the association between distance from residence to testing sites and HIV disease stage at diagnosis. Using HIV surveillance data, we identified all new HIV diagnoses made at publicly funded testing sites in central North Carolina during 2005-2013. Early-stage HIV was defined as acute HIV (antibody-negative test with a positive HIV RNA) or recent HIV (normalized optical density <0.8 on the BED assay for non-AIDS cases); remaining diagnoses were considered post-early-stage HIV. Street distance between residence at diagnosis and (1) the closest testing site and (2) the diagnosis site was dichotomized at 5 miles. We fit log-binomial models using generalized estimating equations to estimate prevalence ratios (PR) and robust 95% confidence intervals (CI) for post-early-stage diagnoses by distance. Models were adjusted for race/ethnicity and testing period. Most of the 3028 new diagnoses were black (N = 2144; 70.8%), men who have sex with men (N = 1685; 55.7%), and post-early-stage HIV diagnoses (N = 2010; 66.4%). Overall, 1145 (37.8%) cases traveled <5 miles for a diagnosis. Among cases traveling ≥5 miles for a diagnosis, 1273 (67.6%) lived <5 miles from a different site. Residing ≥5 miles from a testing site was not associated with post-early-stage HIV (adjusted PR, 95% CI: 0.98, 0.92-1.04), but traveling ≥5 miles for a diagnosis was associated with higher post-early HIV prevalence (1.07, 1.02-1.13). Most of the elevated prevalence observed in cases traveling ≥5 miles for a diagnosis occurred among those living <5 miles from a different site (1.09, 1.03-1.16). Modest increases in post-early-stage HIV diagnosis were apparent among persons living near a site, but choosing to travel longer distances to test. Understanding reasons for increased travel distances could improve accessibility and acceptability of HIV services and increase early diagnosis rates.

Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies.

The quantitative viral outgrowth assay (QVOA) provides a precise minimal estimate of the reservoir of resting CD4(+) T-cell infection (resting cell infection [RCI]). However, the variability of RCI over time during antiretroviral therapy (ART), relevant to assess potential effects of latency-reversing agents or other interventions, has not been fully described. We performed QVOA on resting CD4(+) T cells obtained via leukapheresis from 37 human immunodeficiency virus (HIV)-infected patients receiving stable suppressive ART for a period of 6 years. Patients who started ART during acute (n = 17) or chronic (n = 20) HIV infection were studied once HIV RNA levels were <50 copies/mL for ≥ 6 months. Using random effects analysis of 160 RCI measurements, we found that RCI declined significantly over time (P < .001), with an estimated mean half-life of 3.6 years (95% confidence interval, 2.3-8.1 years), remarkably consistent with findings of prior studies. There was no evidence of more rapid decay in acute versus chronic HIV infection (P = .99) for patients suppressed ≥ 6 months. RCI was reliably estimated with longitudinal measurements generally showing < 2-fold variation from the previous measure. When QVOA is performed in this format, RCI decreases of >6-fold were rare. We suggest that a 6-fold decline is a relevant threshold to reliably identify effects of antilatency interventions on RCI.

Incident sexually transmitted infection as a biomarker for high-risk sexual behavior after diagnosis of acute HIV.

BACKGROUND: Sexually transmitted infection (STI) diagnosis after diagnosis of acute HIV infection (AHI) indicates ongoing high-risk sexual behavior and possible risk of HIV transmission. We assessed predictors of STI acquisition and the effect of time since care entry on STI incidence in patients with AHI in care and receiving consistent risk-reduction messaging. METHODS: Data on incident gonorrhea, chlamydia, trichomoniasis, primary/secondary syphilis, demographic, and clinical risk factors were abstracted from medical charts for patients diagnosed as having AHI and engaged in care. Poisson regression models using generalized estimating equations were fit to estimate incidence rates (IRs), IR ratios, and robust 95% confidence intervals. RESULTS: Among 185 patients with AHI, 26 (14%) were diagnosed as having at least 1 incident STI over 709.4 person-years; 46 STIs were diagnosed during follow-up (IR, 6.8/100 person-years). The median time from HIV care entry to first STI diagnosis was 609 days (range, 168-1681 days). Men who have sex with men (P = 0.03), a shorter time between presentation to medical care and AHI diagnosis (P = 0.06), and STI diagnosis before AHI diagnosis (P = 0.0003) were predictors of incident STI. Sexually transmitted infection IR greater than 1 year after entering care was double that of patients in care 1 year or less (IR ratio, 2.0; 95% confidence interval, 0.8-4.9). HIV viral load was above the limits of detection within 1 month of 11 STI diagnoses in 6 patients (23.1%) (median, 15,898 copies/mL; range, 244-152,000 copies/mL). CONCLUSIONS: Despite regular HIV care, STI incidence was high among this primarily young, men who have sex with men AHI cohort. Early antiretroviral initiation may decrease HIV transmission given ongoing risk behaviors despite risk-reduction messaging.

Immunogenicity of AGS-004 Dendritic Cell Therapy in Patients Treated During Acute HIV Infection.

AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4+ T-cell infection (RCI) was measured by quantitative viral outgrowth assay. Participants demonstrating increased immune response postvaccination were eligible for analytic treatment interruption (ATI). AGS-004 induced a positive immune response defined as ≥2-fold increase from baseline in the number of multifunctional HIV-1 specific CD28+/CD45RA- CD8+ effector/memory cytoxic T-lymphocytes (CTLs) in all six participants. All participants underwent ATI with rebound viremia at a median of 29 days. Immune correlates between time to viral rebound and the induction of effector CTLs were determined. Baseline RCI was low in most participants (0.043-0.767 IUPM). One participant had a >2-fold decrease (0.179-0.067 infectious units per million [IUPM]) in RCI at week 10. One participant with the lowest RCI had the longest ATI. AGS-004 dendritic cell administration increased multifunctional HIV-specific CD28+/CD45RA- CD8+ memory T cell responses in all participants, but did not permit sustained ART interruption. However, greater expansion of CD28-/CCR7-/CD45RA- CD8+ effector T cell responses correlated with a longer time to viral rebound. AGS-004 may be a useful tool to augment immune responses in the setting of latency reversal and eradication strategies.

Changing Attitudes About Concurrency Among Young African Americans: Results of a Radio Campaign.

We created and evaluated an 8-month campaign of provocative radio ads to change attitudes about concurrent (overlapping) sexual partnerships among young African Americans. We created a concurrency attitude scale and compared its score distributions in independent samples of African Americans, ages 18-34 years, interviewed by telephone before (n = 678) and after (n = 479) the campaign. Pre- and post-campaign samples reflected similar response rates (pre: 32.6%; post: 31.8%) and distributions of personal characteristics. Reported exposure to concurrency messages was greater after the campaign (pre: 6.3%, post: 30.9%), and mean scores indicated less acceptance of concurrency (pre: 3.40 [95% CI 3.23, 3.57]; post: 2.62 [2.46, 2.78]). Score differences were not a function of differences in composition of the samples (adjusted means: pre: 3.37 [3.21, 3.53]; post: 2.62 [2.47, 2.76]). Findings demonstrate that a carefully targeted, intensive mass media campaign can change attitudes about concurrency, which should facilitate behavior change.

Measuring Concurrency Attitudes: Development and Validation of a Vignette-Based Scale.

BACKGROUND: Concurrent sexual partnerships (partnerships that overlap in time) may contribute to higher rates of HIV transmission in African Americans. Attitudes toward a behavior constitute an important component of most models of health-related behavior and behavioral change. We have developed a scale, employing realistic vignettes that appear to reliably measure attitudes about concurrency in young African American adults. METHODS: Vignette-based items to assess attitudes about concurrency were developed following focus groups and cognitive testing of items adapted from existing scales assessing psychosocial constructs surrounding related sexual behaviors. The new items were included in a telephone survey of African American adults (18-34 years old) in Eastern North Carolina immediately before and after a radio campaign designed to discourage concurrency. We performed an exploratory factor analysis on each sample (pre- and post-campaign) to cross-validate results. We retained factors with a primary loading of ≥0.50 and no secondary loading >0.30. Cronbach's coefficient alpha was used to evaluate internal reliability. Associations in the predicted direction between the mean responses to items on the final factor and known correlates of concurrency validated the scale. RESULTS: Factor analysis in a random pre-campaign subsample yielded a one-factor 6-item scale with acceptable internal consistency (Cronbach's α = 0.79). As expected, the attitude factor was positively associated with participation in concurrent partnerships, whether assessed by self-report (r = 0.298, p<0.0001) or deduced from dates of recent sexual partnerships (r = 0.298, p<0.0001). The factor was also positively associated with alcohol (r = 0.216, p<0.0001) and drug use (r = 0.225, p<0.0001) and negatively associated with increasing age (r = -0.088, p- = 0.02) and female gender (r = -0.232, p<0.0001). Factor analyses repeated in the second random pre-campaign subsample and post-campaign sample confirmed these results. CONCLUSION: A vignette-based scale may be an effective measure of key attitudes related to concurrency and potentially a useful tool to evaluate interventions addressing this network pattern.

Ten Years of Screening and Testing for Acute HIV Infection in North Carolina.

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.

Fixed-dose combination emtricitabine/tenofovir/efavirenz initiated during acute HIV infection; 96-week efficacy and durability.

BACKGROUND: Updated guidelines recommend immediate antiretroviral treatment (ART) during acute HIV infection (AHI), but efficacy data on regimens during AHI are limited. METHODS: We provide final data on a prospective, single-arm 96-week open-label study of once-daily emtricitabine/tenofovir/efavirenz initiated during AHI. The primary endpoint was the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression, retention, and CD8 cell activation through week 96 in relation to baseline characteristics. RESULTS: Between January 2005 and December 2011, 92 AHI participants enrolled. Most participants (78%) were men who have sex with men (MSM), and 42% were young MSM (18-25 years of age). Two participants withdrew leaving 90 patients for analysis. Eighty-one (90%) remained on therapy and achieved viral suppression to less than 200 copies/ml by week 24, and 71 (79%) to less than 50 copies/ml at week 48. The median time from ART initiation to suppression less than 200 copies/ml was 65 days (range 7-523) and to less than 50 copies/ml was 105 days (range 14-523). The frequency of immune activation declined from a median of 67% to 16% through week 96. Retention on study was maintained in 92% of participants at week 48 and in 83% through week 96. Among 75 participants retained through week 96, 92% were suppressed to less than 50 copies/ml. Among 39 young MSM, 79% completed a week 96 visit and 67% were suppressed at week 96. CONCLUSION: ART during AHI resulted in rapid and sustained viral suppression with high rates of retention in care and on ART in this cohort including a large proportion of young MSM.

Ongoing HIV Transmission and the HIV Care Continuum in North Carolina.

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.

Acute HIV-1 infection in the Southeastern United States: a cohort study.

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.