High-Risk Injection-Related Practices Associated with anti-HCV Positivity among Young Adults Seeking Services in Three Small Cities in Wisconsin.

BACKGROUND: Hepatitis C virus (HCV) infection has been increasing among people who inject drugs (PWID), younger than 30 years, and living in rural or suburban areas. We examined injection-related behaviors of young PWID to determine factors associated with HCV infection. METHODS: From September 2013-May 2015, respondent-driven and snowball sampling were used in 3 suburban areas of Wisconsin to recruit PWID 18-29 years who reported injection drug use in the previous 12 months. Participants were tested for HCV antibody (anti-HCV) and reported injection-related behaviors/practices via self-administered computer-based survey. We calculated anti-HCV prevalence and assessed associated factors using multivariable logistic regression. RESULTS: Forty-two percent (117/280) of participants were male, 83% (231/280) were white, and median age was 23 years. Overall HCV prevalence was 33%, but HCV prevalence among males was 39%. Adjusting for age, sex, race/ethnicity, education, relationship status, insurance status and income, anti-HCV positivity was associated with higher injection frequency (> 100 times in the past six months) (aOR = 3.07; 95% Confidence Interval (95% CI): 1.72-5.45), ever shared syringes (aOR = 5.15; 95% CI: 2.52-10.51), past week/last use receptive rinse water sharing (aOR = 1.88; 95% CI: 1.06-3.33), past week/last use receptive filter sharing (aOR = 3.25; 95% CI: 1.61-6.54), reusing syringes (aOR = 1.91, 95% CI: 1.08-3.37), history of overdose (aOR = 8.82; 95% CI: 2.26-3.95), and having ever injected another PWID (aOR = 8.82; 95%CI 3.94-19.76). DISCUSSION: Anti-HCV positivity is associated with high-risk injection practices. Young PWID would benefit from access to evidence-based interventions that reduce their risk of infection, link those infected to HCV treatment, and provide education to reduce further transmission.

Sharing the cure: Building primary care and public health infrastructure to improve the hepatitis C care continuum in Maryland.

In 2014, trained healthcare provider capacity was insufficient to deliver care to an estimated 70 000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14-9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3237 HCV antibody-positive patients of which 2624 (81%) were RNA+. Of those HCV RNA+, 1739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (27%) completed treatment and 543 (21%) achieved cure. Among 1739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody-positive people increased from 40% (baseline) to 95% among STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland were a major barrier to treatment.

Geographic Disparities in Access to Syringe Services Programs Among Young Persons With Hepatitis C Virus Infection in the United States.

Using commercial laboratory data, we found 80% of 29382 young persons currently infected with hepatitis C virus lived >10 miles from a syringe services program. The median distance was 37 miles, with greater distances in rural areas and Southern and Midwestern states. Strategies to improve access to preventive services are warranted.

State HCV Incidence and Policies Related to HCV Preventive and Treatment Services for Persons Who Inject Drugs - United States, 2015-2016.

Hepatitis C is associated with more deaths in the United States than 60 other infectious diseases reported to CDC combined. Despite curative hepatitis C virus (HCV) therapies and known preventive measures to interrupt transmission, new HCV infections have increased in recent years (1,2). Injection drug use is the primary risk factor for new HCV infections (2). One potential strategy to decrease the prevalence of HCV is to create and strengthen public health laws and policies aimed specifically at reducing transmission risks among persons who inject drugs. To evaluate factors affecting access to HCV preventive and treatment services, CDC assessed state laws governing access to safe injection equipment and Medicaid policies related to sobriety requirements for approval of HCV treatment for persons who inject drugs. Acute HCV incidence rates were obtained from CDC's National Notifiable Disease Surveillance System (NNDSS). States were categorized based on analysis of laws related to access to clean needles and syringes and Medicaid HCV treatment policies associated with sobriety requirements. In 2015, HCV incidence remained high in the United States, with rates in 17 states exceeding the national average. Three states were determined to have state laws and Medicaid policies capable of comprehensively preventing and treating HCV among persons who inject drugs. Opportunities exist for states to adopt laws and policies that could help increase access to HCV preventive and treatment services reducing the number of persons at risk for HCV transmission and disease.

The Burden of Hepatitis C Infection-Related Liver Fibrosis in the United States.

BACKGROUND: Knowledge of the estimated proportion of hepatitis C virus (HCV)-infected persons with advanced fibrosis or cirrhosis is critical to estimating healthcare needs. METHODS: We analyzed HCV-related testing conducted by Quest Diagnostics from January 2010 through December 2013. Tests included hepatitis C antibody, HCV RNA, HCV genotype (nucleic acid tests [NAT]), liver function tests, and platelet counts; patient age was also determined. Aspartate aminotransferase (AST)-to-platelet ratio (APRI) was calculated as = 100*(aspartate aminotransferase [AST]/upper limit of AST)/platelet. Fibrosis-4 (FIB-4) was calculated as (age × AST)/(platelet ×√ alanine aminotransferase [ALT]). Persons were "currently infected" if they had ≥1 positive HCV NAT; "in care" if a positive RNA test was followed <6 months by ≥1 additional NAT(s), or ALT, AST, and platelets <90 days, or any test ordered by an infectious diseases or gastroenterology specialist; and "evaluated for treatment" if they had a genotype test. RESULTS: Approximately 10 million HCV test results were analyzed, representing 5.6 million unique patients. Of the 2.6 million patients with data to estimate liver disease, 5% were currently infected. Among those currently infected, APRI and FIB-4 scores indicated that 23% overall-and 27% among the cohort born during 1945-1965-had advanced fibrosis or cirrhosis at first diagnosis. A total of 54% of infected were in care and 51% of infected with advanced fibrosis or cirrhosis were evaluated for treatment. CONCLUSIONS: Testing from a large US commercial laboratory indicates that about 1 in 4 HCV-infected persons have levels of liver disease put them at highest risk for complications and could benefit from immediate antiviral therapy.

Increased Hepatitis C Virus (HCV) Detection in Women of Childbearing Age and Potential Risk for Vertical Transmission - United States and Kentucky, 2011-2014.

Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality (1). Transmission of HCV is primarily via parenteral blood exposure, and HCV can be transmitted vertically from mother to child. Vertical transmission occurs in 5.8% (95% confidence interval = 4.2%-7.8%) of infants born to women who are infected only with HCV and in up to twice as many infants born to women who are also infected with human immunodeficiency virus (HIV) (2) or who have high HCV viral loads (3,4); there is currently no recommended intervention to prevent transmission of infection from mother to child (3). Increased reported incidence of HCV infection among persons aged ≤30 years (5,6) with similar increases among women and men in this age group (6), raises concern about increases in the number of pregnant women with HCV infection, and in the number of infants who could be exposed to HCV at birth. Data from one large commercial laboratory and birth certificate data were used to investigate trends in HCV detection among women of childbearing age,* HCV testing among children aged ≤2 years, and the proportions of infants born to HCV-infected women nationally and in Kentucky, the state with the highest incidence of acute HCV infection during 2011-2014 (6). During 2011-2014, commercial laboratory data indicated that national rates of HCV detection (antibody or RNA positivity(†)) among women of childbearing age increased 22%, and HCV testing (antibody or RNA) among children aged ≤2 years increased 14%; birth certificate data indicated that the proportion of infants born to HCV-infected mothers increased 68%, from 0.19% to 0.32%. During the same time in Kentucky, the HCV detection rate among women of childbearing age increased >200%, HCV testing among children aged ≤2 years increased 151%, and the proportion of infants born to HCV-infected women increased 124%, from 0.71% to 1.59%. Increases in the rate of HCV detection among women of childbearing age suggest a potential risk for vertical transmission of HCV. These findings highlight the importance of following current CDC recommendations to identify, counsel, and test persons at risk for HCV infection (1,7), including pregnant women, as well as consider developing public health policies for routine HCV testing of pregnant women, and expanding current policies for testing and monitoring children born to HCV-infected women. Expansion of HCV reporting and surveillance requirements will enhance case identification and prevention strategies.

Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques.

During HIV/SIV infection, mucosal immune system dysfunction and systemic immune activation are associated with progression to AIDS; however, it is unclear to what extent pre-existing gastrointestinal damage relates to disease progression postinfection. Pigtail macaques (PTM) are an excellent model in which to assess mucosal dysfunction in relation to HIV/SIV pathogenesis, as the majority of these animals have high levels of gastrointestinal damage, immune activation, and microbial translocation prior to infection, and rapidly progress to AIDS upon SIV infection. In this study, we characterized the mucosal immune environment prior to and throughout SIV infection in 13 uninfected PTM and 9 SIV-infected PTM, of which 3 were slow progressors. This small subset of slow progressors had limited innate immune activation in mucosal tissues in the periphery, which was associated with a more intact colonic epithelial barrier. Furthermore, we found that preinfection levels of microbial translocation, as measured by LPS-binding protein, in PTM correlated with the rate of progression to AIDS. These data suggest that pre-existing levels of microbial translocation and gastrointestinal tract dysfunction may influence the rate of HIV disease progression.

Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques.

Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4(+) T cell depletion, as CD4(+) T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination.

HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.

A Population-Based Intervention to Improve Care Cascades of Patients With Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct-acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population-based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV-related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response. Conclusion: A combination of EHR-based health care system interventions, active linkage to care, and clinician training contributed to a tripling in the number of patients screened and a more than 10-fold increase of those treated. The interventions are scalable and foundational to the goal of HCV elimination.

Hepatitis C Virus in Women of Childbearing Age, Pregnant Women, and Children.

INTRODUCTION: Perinatal transmission is an increasingly important mode of hepatitis C virus transmission. The authors characterized U.S. births among hepatitis C virus-infected women and evaluated trends in hepatitis C virus testing and positivity in women of childbearing age, pregnant women, and children aged less than 5years. METHODS: In 2017, National Center for Health Statistics birth certificate data (48 states and District of Columbia) were analyzed to assess the number of hepatitis C virus-infected women delivering live births in 2015, and commercial laboratory data were analyzed to assess hepatitis C virus testing and positivity among women of childbearing age, pregnant women, and children aged <5years from 2011 to 2016. RESULTS: In 2015, a total of 0.38% (n=14,417) of live births were delivered by hepatitis C virus-infected women. Births delivered by hepatitis C virus-infected women, compared with births overall, occurred more often in women who were aged 20-29years (60.7% vs 50.9%); white, non-Hispanic (80.2% vs 52.8%); covered by Medicaid or other government insurance (79.2% vs 43.9%); and had rural residence (26.0% vs 14.0%). From 2011 to 2016 laboratory data, among women of childbearing age, hepatitis C virus testing increased by 39%, from 6.1% to 8.4%, and positivity increased by 36%, from 4.4% to 6.0%. Among pregnant women, hepatitis C virus testing increased by 135%, from 5.7% to 13.4%, and positivity increased by 39%, from 2.6% to 3.6%. Among children, hepatitis C virus testing increased by 25%, from 0.47% to 0.59%, and positivity increased by 13%, from 3.6% to 4.0%. CONCLUSIONS: The potential for perinatal hepatitis C virus transmission exists. Expanded hepatitis C virus testing guidelines may address the burden of disease in this population.

Transitioning couple's voluntary HIV counseling and testing (CVCT) from stand-alone weekend services into routine antenatal and VCT services in government clinics in Zambia's two largest cities.

INTRODUCTION: Most HIV infections in Africa are acquired by married/cohabiting adults and WHO recommends couple's voluntary HIV counseling and testing (CVCT) for prevention. The handover from NGO-sponsored weekend CVCT to government-sponsored services in routine weekday antenatal care (ANC) and individual voluntary testing and counseling (VCT) services in Zambia's two largest cities from 2009-2015 is described. METHODS: Government clinic counselors were trained to provide CVCT, and along with community health workers they promoted CVCT services in their clinic and surrounding areas. When client volume exceeded the capacity of on-duty staff in ANC and VCT, non-governmental organization (NGO) subsidies were offered for overtime pay. RESULTS: Implementation of routine CVCT services varied greatly by clinic and city. The 12 highest volume clinics were examined further, while 13 clinics had CVCT numbers that were too low to warrant further investigation. In Lusaka, the proportion of pregnant women whose partners were tested rose from 2.6% in 2009 to a peak of 26.2% in 2012 and 24.8% in 2015. Corresponding reports in Ndola were 2.0% in 2009, 17.0% in 2012 and 14.5% in 2015. Obstacles to CVCT included: limited space and staffing, competing priorities, record keeping not adapted for couples, and few resources for promotion and increasing male involvement. Conflicting training models for 'partner testing' with men and women separately vs. CVCT with joint post-test counseling led to confusion in reporting to district health authorities. DISCUSSION: A focused and sustained effort will be required to reach a meaningful number of couples with CVCT to prevent heterosexual and perinatal HIV transmission. Establishing targets and timelines, funding for dedicated and appropriately trained staff, adoption of standardized data recording instruments with couple-level indicators, and expansion of community and clinic-based promotions using proven models are recommended.

Acceptability of Couples' Voluntary HIV Testing Among HIV-infected Patients in Care and Their HIV-negative Partners in the United States.

INTRODUCTION: Couples' voluntary HIV counseling and testing (CHTC) is an HIV risk reduction strategy not widely available in the US. METHODS: We assessed willingness to participate in CHTC among US HIV-infected clinic patients via tablet-based survey and among HIV-negative persons with HIV-infected partners in care via mixed-method phone interviews. RESULTS: Most of the N=64 HIV-infected partners surveyed were men (89%), on antiretroviral treatment (ART) (92%), and many self-identified homosexual (62%). We observed high levels of willingness to participate in CHTC (64%) among HIV-infected partners. Reasons for not wanting to participate included perceived lack of need (26%), desire to self-disclose their status (26%), and fear of being asked sensitive questions with their partner present (17%). HIV-infected partners were interested in discussing ART (48%), other sexually transmitted infections (STIs) (44%), and relationship agreements like monogamy (31%) during CHTC sessions. All N=15 HIV-negative partners interviewed were men, most identified as homosexual (73%), and about half (54%) reported consistent condom use with HIV-infected partners. We observed high levels of willingness to participate in CHTC (87%) among HIV-negative partners, who were also interested in discussing ART (47%), other STIs (47%), mental health services (40%), and relationship agreements (33%). Most negative partners (93%) indicated that they believed their HIV-infected partner was virally suppressed, but in the event that they were not, many (73%) were willing to take pre-exposure prophylaxis (PrEP). CONCLUSION: These results indicate that CHTC for serodiscordant couples is acceptable and should emphasize aspects most pertinent to these couples, such as discussion of ART/PrEP, STIs, and relationship agreements.

Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques.

HIV infection results in gastrointestinal (GI) tract damage, microbial translocation, and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, to enhance GI tract physiology, we treated SIV-infected pigtail macaques with ARVs, probiotics, and prebiotics or with ARVs alone. This synbiotic treatment resulted in increased frequency and functionality of GI tract APCs, enhanced reconstitution and functionality of CD4+ T cells, and reduced fibrosis of lymphoid follicles in the colon. Thus, ARV synbiotic supplementation in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis.