Factors Associated With Delays in Presentation and Treatment of Gonorrhea, Massachusetts 2015-2019.

BACKGROUND: Rates of gonorrhea are increasing across the United States. Understanding and addressing contributing factors associated with longer time to diagnosis and treatment may shorten the duration of infectiousness, which in turn may limit transmission. METHODS: We used Massachusetts data from the US Centers for Disease Control and Prevention Sexually Transmitted Disease Surveillance Network collected between July 2015 and September 2019, along with routinely reported surveillance data, to assess time from gonorrhea symptom onset to presentation to care, and time from presentation to care to receipt of treatment. Factors associated with longer time to presentation (TTP) and time to treatment (TTT) were assessed using Cox proportional hazard models with a constant time variable. RESULTS: Among symptomatic patients (n = 672), 31% did not receive medical care within 7 days of symptom onset. Longer TTP was associated with younger age, female gender, reporting cost as a barrier to care, and provider report of proctitis. Among patients with symptoms and/or known contact to gonorrhea (n = 827), 42% did not receive presumptive treatment. Longer TTT was associated with female gender, non-Hispanic other race/ethnicity, and clinics with less gonorrhea treatment experience. Among asymptomatic patients without known exposure to STI (n = 235), 26% did not receive treatment within 7 days. Longer TTT was associated with sexually transmitted disease clinic/family planning/reproductive health clinics and a test turnaround time of ≥3 days. CONCLUSIONS: Delays in presentation to care and receipt of treatment for gonorrhea are common. Factors associated with longer TTP and TTT highlight multiple opportunities for reducing the infectious period of patients with gonorrhea.

Predictors of HIV Care Outcomes among Recently Out-of-Care Individuals in The Massachusetts Cooperative Re-engagement Controlled Trial Cohort.

A cohort of individuals in care for HIV infection who were identified as being recently out-of-care (OOC) was recruited for a trial using a data-to-care approach and an intervention to facilitate re-engagement and retention in care. This allowed for analysis of demographic and clinical characteristics correlated with recently being OOC, re-engagement, and successful retention in care and viral suppression. Recently OOC persons with HIV infection (PWH) were identified for enrollment in the Cooperative Re-engagement Controlled Trial (CoRECT). CoRECT employed a data-to-care strategy, using both clinical and surveillance data, and an active public health re-engagement intervention. We estimated relative risks (RRs), unadjusted and with multivariate log binomial regression models, to analyze associations between sociodemographic and clinical predictors of being OOC, re-engagement, retention in care, and viral suppression. Of the 630 OOC PWH enrolled in CoRECT, most were male (72.7%) and over 30 years old (91.3%). Almost 40.0% were Black non-Hispanic, 29.7% were non-US born, and 41.6% were men who have sex with men (MSM). Possible predictors of re-engagement, retention in care, and viral suppression included younger age, Hispanic race/ethnicity, birth in a US dependency, AIDS status, and HIV exposure mode. Viral suppression status within 1-year pre-enrollment was significantly associated with all outcomes: re-engagement (aRR 1.28), retention (aRR 1.72), viral suppression (aRR 1.81), and durable viral suppression (aRR 3.30). Findings elucidate factors associated with care engagement and continuity for recently OOC PWH which can be used to inform targeted re-engagement activities for priority populations and guide future data-to-care interventions.

Gaps in HIV Preexposure Prophylaxis Continuum of Care Following State Partner Services for Massachusetts Primary and Secondary Syphilis Cases, 2017 to 2018.

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) reduces HIV acquisition. We used a PrEP continuum of care to measure impact of field epidemiologist-facilitated referrals for PrEP-naive infectious syphilis cases across multiple clinical and pharmacy sites of care. METHODS: Retrospective analysis of 2017 to 2018 primary and secondary syphilis cases, medical charts, and pharmacy data to identify PrEP education, referral offer, referral acceptance, first visit, prescription pickup (PrEP initiation) and 2 to 3 months (PrEP persistence). The HIV seroconversion was determined using database match at syphilis diagnosis date and at 12 months. χ 2 or Fisher's exact tests were used to compare demographic characteristics associated with steps with lower progression rates. RESULTS: Of 1077 syphilis cases, partner services engaged 662 of 787 (84%) HIV-negative cases; 490 were PrEP-naive, 266 received education, 166 were offered referral, 67 accepted referral, 30 attended an initial appointment, and 22 were prescribed PrEP. Of 16 with pharmacy data, 14 obtained medication, and 8 persisted on PrEP at 2 to 3 months. Continuum progression was lowest from (1) PrEP-naïve to receiving PrEP education, (2) offered referral to referral acceptance, and (3) referral acceptance to initial PrEP appointment. Men with male partners were more likely to receive PrEP education or accept a referral. Higher social vulnerability was associated with increased PrEP referral acceptance. CONCLUSIONS: Few individuals accepted PrEP referrals and persisted on PrEP. Field and clinic data capture were inconsistent, possibly underestimating referral volume and impact of field engagement. Efforts aimed at increasing referral acceptance and clinic attendance may improve PrEP uptake especially among women and heterosexual men with syphilis.

Human Immunodeficiency Virus (HIV) Outbreak Investigation Among Persons Who Inject Drugs in Massachusetts Enhanced by HIV Sequence Data.

BACKGROUND: The Massachusetts Department of Public Health and the Centers for Disease Control and Prevention collaborated to characterize a human immunodeficiency virus (HIV) outbreak in northeastern Massachusetts and prevent further transmission. We determined the contributions of HIV sequence data to defining the outbreak. METHODS: Human immunodeficiency virus surveillance and partner services data were analyzed to understand social and molecular links within the outbreak. Cases were defined as HIV infections diagnosed during 2015-2018 among people who inject drugs with connections to northeastern Massachusetts or HIV infections among other persons named as partners of a case or whose HIV polymerase sequence linked to another case, regardless of diagnosis date or geography. RESULTS: Of 184 cases, 65 (35%) were first identified as part of the outbreak through molecular analysis. Twenty-nine cases outside of northeastern Massachusetts were molecularly linked to the outbreak. Large molecular clusters (75, 28, and 11 persons) were identified. Among 161 named partners, 106 had HIV; of those, 40 (38%) diagnoses occurred through partner services. CONCLUSIONS: Human immunodeficiency virus sequence data increased the case count by 55% and expanded the geographic scope of the outbreak. Human immunodeficiency virus sequence and partner services data each identified cases that the other method would not have, maximizing prevention and care opportunities for HIV-infected persons and their partners.

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.

Characteristics of Cases With Repeated Sexually Transmitted Infections, Massachusetts, 2014-2016.

Background: Persons with prior sexually transmitted infections (STIs) are at high risk for reinfection. No recent studies have examined frequency with which persons are diagnosed and reported with multiple bacterial STIs over time. Methods: We conducted a retrospective, of confirmed syphilis, gonorrhea, and chlamydial infections reported to Massachusetts state surveillance system within a 2-year period, 28 July 2014-27 July 2016. Results: Among Massachusetts population aged 13-65 years (4847510), 49142 (1.0%) were reported with ≥1 STIs; 6999 (14.2% of those with ≥1 STI) had ≥2 STIs, accounting for 27.7% of STIs. Of cases with ≥5 or more STIs (high-volume repeaters), 118 (74%) were men and 42 (26%) were women. Men spanned the age spectrum and were predominantly non-Hispanic white; 87% reported same-sex contacts. Women were younger, predominantly nonwhite, and without known same-sex contacts. Women were reinfected with gonorrhea and chlamydia or chlamydia alone; none had syphilis or human immunodeficiency virus (HIV) infection. All men with syphilis also had gonorrhea and/or chlamydia; 35% were diagnosed with HIV before, during, or within 10 months after study period. The majority (56%) of high-volume repeaters were seen at more than 1 care site/system. Conclusions: In Massachusetts, a large proportion of bacterial STIs are reported from a small subpopulation, many of whom have repeated infections and are likely to have higher impact on STI and HIV rates. Public health can play a crucial role in reaching high-volume repeaters whose STI histories may be hidden from clinicians due to fragmented care.

Does Nonmetropolitan Residence Impact Timely Chlamydia Treatment in Massachusetts?

A mean of 4.5 days until treatment was documented in a subset of reported laboratory-confirmed Massachusetts chlamydia cases selected for active case report form completion. Treatment delay was associated with longer test result turnaround time, and absence of symptoms or contact to sexually transmitted disease. Nonmetropolitan versus metropolitan residence did not appear to impact treatment time.

Using the exploration, preparation, implementation, sustainment (EPIS) framework to assess the cooperative re-engagement controlled trial (CoRECT).

Background: "Data to Care" (D2C) is a strategy which relies on a combination of public health surveillance data supplemented by clinic data to support continuity of HIV care. The Cooperative Re-Engagement Controlled Trial (CoRECT) was a CDC-sponsored randomized controlled trial of a D2C model, which provided an opportunity to examine the process of implementing an intervention for people with HIV (PWH) who are out-of-care across three public health department jurisdictions. Using the EPIS (Exploration, Preparation, Implementation, Sustainment) framework, we aimed to retrospectively describe the implementation process for each site to provide insights and guidance to inform future D2C activities implemented by public health agencies and their clinical and community partners. Methods: After completion of CoRECT, the three (Connecticut, Massachusetts, Philadelphia) trial sites reviewed study protocols and held iterative discussions to describe and compare their processes regarding case identification, interactions with partnering clinics and patients, and sustainability. The EPIS framework provided a structure for comparing key organizational and operational practices and was applied to the entire implementation process. Results: The trial sites varied in their implementation processes and the specific elements of the intervention. Factors including prior D2C experience, data management and analytic infrastructure, staff capacity, and relationships with clinic partners informed intervention development and implementation. Additionally, this review identified key lessons learned including to: (1) explore new supplemental sources for public health surveillance data; (2) work with stakeholders representing core functions/components in the early stages of the intervention design process; (3) build flexibility into all components of the follow-up activities; and (4) integrate data sharing, project management, and follow-up activities within existing DPH organizational structure. Conclusion: The CoRECT study provides a general blueprint and lessons learned for implementing a D2C intervention for re-engagement in HIV care. Interventions should be tailored to local operational and structural factors, and responsive to evolving clinical and public health practices.

Chlamydia Treatment Practices and Time to Treatment in Massachusetts: Directly Observed Therapy Versus Pharmacy Prescriptions.

BACKGROUND: Directly observed therapy (DOT) is recommended for the treatment of chlamydia, however pharmacy prescriptions are frequently used. Adherence to DOT and the association between treatment method and time to treatment is unknown. METHODS: We conducted a retrospective review of a randomized 2% of laboratory-confirmed chlamydia infections reported to the Massachusetts Department of Public Health from January 1, 2019 to May 31, 2019. Clinicians and pharmacies were contacted to ascertain treatment methods and timing. We assessed frequency of DOT and pharmacy prescriptions in the treatment of chlamydia infection in Massachusetts. We used log rank test to compare time to treatment initiation for patients receiving DOT versus pharmacy prescriptions. Data were stratified according to whether treatment was empiric or laboratory-driven. KEY RESULTS: We ascertained full outcomes for 199 patients. Eighty patients received DOT and 119 patients received pharmacy prescriptions. DOT was more common among those receiving empiric treatment and pharmacy prescriptions were more common among those receiving laboratory-driven treatment. The median time to treatment was 1.5 days for patients treated with DOT and 3 days for those treated with pharmacy prescriptions. For both groups, the median time to treatment for empiric therapy was 0 days and for laboratory-driven therapy was 4 days. The differences in time to treatment were not statistically significant. CONCLUSIONS: Pharmacy prescriptions are frequently used for the treatment of chlamydia in Massachusetts. We did not observe a significant difference in the time to treatment between DOT and pharmacy prescriptions.

The Partnerships for Care Project in Massachusetts: Developing Partnerships and Data Systems to Increase Linkage and Engagement in Care for Individuals Living With HIV.

BACKGROUND: Before implementation of the Massachusetts Partnerships for Care (MA P4C) project, Massachusetts did not routinely provide HIV partner services to newly diagnosed individuals. Identification of individuals disengaged from HIV care and assistance for re-engagement relied on community- and clinic-based HIV medical case management services. Processes to identify individuals out of HIV care used either surveillance or clinic data, but did not combine both. METHODS: The Massachusetts Department of Public Health collaborated with 6 community health centers to implement HIV partner services and out-of-care re-engagement services. Implementation of these services required development of both health department and community health center capacity. Capacity development strategies included the following: development and implementation of operational protocols, establishment of communication strategies and processes, training and education for health department and health center staff, and enhancement of disease surveillance systems. RESULTS: Development of operational protocols supported implementation of public health services and collaboration with health centers. Health department-facilitated meetings, training, and technical assistance enhanced communication with health centers and promoted buy-in for collaboration. A strategy for combining clinic and surveillance data to identify individuals out of HIV care was implemented. Surveillance data system enhancements improved efficiency of out-of-care identification, assignment of cases for public health follow-up, and provided quality improvement tools. CONCLUSIONS: Collaboration between health departments and community health centers to identify and support patient engagement in HIV medical care is feasible and supports improved continuity of care. Use of surveillance and clinic data to identify out-of-care patients promotes efficiency in Data to Care activities.

Using HIV Surveillance and Clinic Data to Optimize Data to Care Efforts in Community Health Centers in Massachusetts: The Massachusetts Partnerships for Care Project.

BACKGROUND: We describe Data to Care processes of the Massachusetts Partnerships for Care (MA P4C) project and identify factors associated with engagement, retention, and viral suppression outcomes. METHODS: The Massachusetts Department of Public Health and participating community health centers generated lists of patients not in care based on a temporal gap in laboratory results, missed clinic visits, and provider concern regarding engagement. The Massachusetts Department of Public Health and community health centers reviewed the lists monthly and identified out-of-care patients in need of linkage or re-engagement. RESULTS: Between October 2015 and June 2017, of 1418 patients potentially out of care, 83 (5.9%) were confirmed to be out of care. Forty-four of those out of care (53%) received services or were re-engaged in care within 90 days, 45 (54%) were retained in care, and 40 (48%) were virally suppressed. The odds of being re-engaged or retained were lower for patients who were 6 months out-of-care (vs. those newly diagnosed). Patients with an AIDS-defining condition had increased odds of retention and viral suppression. The odds of viral suppression were reduced for patients who reported exposure categories other than men who have sex with men and were younger (30-49 years vs. ≥50 years). CONCLUSIONS: Although rates of re-engagement, retention, and viral suppression were low, the MA P4C Data to Care procedures provided a means for accurate ascertainment of out-of-care status. Future Data to Care programs should investigate the factors that contribute to disengagement from care.

HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL response.

Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection.

Reconstitution of virus-specific CD4 proliferative responses in pediatric HIV-1 infection.

Gag-specific CD4 proliferative responses correlate inversely with HIV-1 RNA levels in infected adults, and robust responses are characteristic of long-term nonprogressive infection. However, strong responses are seldom detected in adult subjects with progressive infection and are not generally reconstituted on highly active antiretroviral therapy (HAART). To date, the role of HIV-1-specific Th responses in children has not been thoroughly examined. We characterized Gag-specific CD4 responses among 35 perinatally infected subjects, including 2 children who spontaneously control viremia without antiretroviral therapy, 21 children with viral loads (VL) of <400 on HAART, and 12 viremic children. Gag-specific Th activity was assessed by lymphoproliferative assay, and responses were mapped using overlapping Gag peptides in an IFN-gamma ELISPOT. Robust proliferative responses were detected in the children exhibiting spontaneous control of viremia, and mapping of targeted Gag regions in one such subject identified multiple epitopes. Among children >or=5 years old, 14 of 17 subjects with VL of <400 on HAART demonstrated a significant p24 proliferative response (median p24 stimulation index, 20), in contrast with only 1 of 9 viremic children (median p24 stimulation index, 2.0; p = 0.0008). However, no subject younger than 5 years of age possessed a significant response, even when viremia was fully suppressed. When compared with adults with VL of <400 on HAART, Th responses among children with VL of <400 were both more frequent (p = 0.009) and of greater magnitude (p = 0.002). These data suggest that children may have a greater intrinsic capacity to reconstitute HIV-1-specific immunity than adults, and may be excellent candidates for immune-based therapies.