Alice Asher

Comparison of Hepatitis C Virus RNA and antibody detection in dried blood spots and plasma specimens.

BACKGROUND Current diagnostic tests for Hepatitis C Virus (HCV) involve phlebotomy and serologic testing for HCV antibodies (anti-HCV) and RNA, which are not always feasible. Dried blood spots (DBS) present a minimally invasive sampling method and are suitable for sample collection, storage and testing. OBJECTIVES To assess the utility of DBS in HCV detection, we evaluated the sensitivity and specificity of DBS for anti-HCV and HCV RNA detection compared to plasma specimens. STUDY DESIGN This cross-sectional validation study was conducted in the context of an existing prospective study of HCV in young injection drug users. Blood samples were collected by venipuncture into serum separator tubes (SST) and via finger stick onto Whatman 903(®) protein-saver cards. Plasma samples and eluates from the DBS were tested for anti-HCV using either a third generation enzyme-linked or chemiluminescent immunoassay (IA), and HCV RNA using discriminatory HCV transcription-mediated amplification assay (dHCV TMA). DBS results were compared to their corresponding plasma sample results. RESULTS 148 participants were tested for anti-HCV and 132 participants were tested for HCV RNA. For anti-HCV, the sensitivity of DBS was 70%, specificity was 100%, positive predictive value (PPV) was 100%, negative predictive value (NPV) was 76% and Kappa was 0.69. For HCV RNA, the sensitivity of DBS was 90%, specificity was 100%, PPV was 100%, NPV was 94% and Kappa was 0.92. CONCLUSIONS DBS are sensitive and very specific in detecting anti-HCV and HCV RNA, demonstrate good correlation with plasma results, and have potential to facilitate diagnosis of HCV infection.

Clinicians' Views of Hepatitis C Virus Treatment Candidacy With Direct-Acting Antiviral Regimens for People Who Inject Drugs

ABSTRACT Background: Direct-acting antivirals (DAAs) are curative in most persons with chronic hepatitis C virus (HCV) infection. However, high cost and concerns about adherence and reinfection may present continued barriers to treatment, particularly for people who inject drugs (PWID). Objective: To understand changes in assessments of treatment candidacy, given advances in treatment. Methods: Clinicians attending the Liver Meeting® in 2014 who reported prescribing HCV treatment in the past three years were invited to complete a survey regarding HCV treatment decisions. Participants assessed their likelihood to treat HCV in PWID in association with time of abstinence from injection drug use and what impacts their decision to provide treatment using interferon and DAAs. Results: 108 clinicians completed the survey; 10% were willing to treat an active PWID (last injection within 30 days) using interferon-containing regimens, and 15% with all-oral regimens. For each increasing time interval of injection abstinence, there was an increase in the odds of a clinician reporting willingness to treat with DAAs (Odds Ratio (OR) 2.57, 95% CI 2.18, 3.03) and with interferon-based treatment (OR 2.22 (95% CI 1.90, 2.61), Reinfection and medication cost were cited as most important concerns when determining candidacy. Conclusions: A cure is now the norm in HCV treatment, and there is an increasing need to address the barriers to treating PWID, the population with the highest burden of infection. Understanding treatment candidacy assessments is essential to improving uptake. This study provides insight into how clinicians view treatment candidacy in this era of DAAs and can help identify supportive treatment environments and concurrent programs.

The impact of social context on self-management in women living with HIV

HIV self-management is central to the health of people living with HIV and is comprised of the daily tasks individuals employ to manage their illness. Women living with HIV are confronted with social context vulnerabilities that impede their ability to conduct HIV self-management behaviors, including demanding social roles, poverty, homelessness, decreased social capital, and limited access to health care. We examined the relationship between these vulnerabilities and HIV self-management in a cross-sectional secondary analysis of 260 women living with HIV from two U.S. sites. All social context variables were assessed using validated self-report scales. HIV Self-Management was assessed using the HIV Self-Management Scale that measures daily health practices, HIV social support, and the chronic nature of HIV. Data were analyzed using appropriate descriptive statistics and multivariable regression. Mean age was 46 years and 65% of participants were African-American. Results indicated that social context variables, particularly social capital, significantly predicted all domains of HIV self-management including daily health practices (F = 5.40, adjusted R(2) = 0.27, p < 0.01), HIV social support (F = 4.50, adjusted R(2) = 0.22, p < 0.01), and accepting the chronic nature of HIV (F = 5.57, adjusted R(2) = 0.27, p < 0.01). We found evidence to support the influence of the traditional social roles of mother and employee on the daily health practices and the chronic nature of HIV domains of HIV self-management. Our data support the idea that womens social context influences their HIV self-management behavior. While social context has been previously identified as important, our data provide new evidence on which aspects of social context might be important targets of self-management interventions for women living with HIV. Working to improve social capital and to incorporate social roles into the daily health practices of women living with HIV may improve the health of this population.

people who inject drugs HIV risk and HIV testing uptake in sub-Saharan Africa.

&NA; Dramatic rises in injection drug use (IDU) in sub‐Saharan Africa account for increasingly more infections in a region already overwhelmed by the HIV epidemic. There is no known estimate of the number of people who inject drugs (PWID) in the region, or the associated HIV prevalence in PWID. We reviewed literature with the goal of describing high‐risk practices and exposures in PWID in sub‐Saharan Africa, as well as current HIV prevention activities aimed at drug use. The literature search looked for articles related to HIV risk, injection drug users, stigma, and HIV testing in sub‐Saharan Africa. This review found evidence demonstrating high rates of HIV in IDU populations in sub‐Saharan Africa, high‐risk behaviors of the populations, lack of knowledge regarding HIV, and low HIV testing uptake. There is an urgent need for action to address IDU in order to maintain recent decreases in the spread of HIV in sub‐Saharan Africa.

Frequent Longitudinal Sampling of Hepatitis C Virus Infection in Injection Drug Users Reveals Intermittently Detectable Viremia and Reinfection

BACKGROUND Detection of hepatitis C virus (HCV) reinfection and intercalation (ie, intermittent recurrent bouts of viremia with homologous virus interspersed with aviremic periods) requires extensive and frequent evaluation and viral sequencing. METHODS HCV infection outcomes were studied prospectively in active injection drug users with recurrent HCV RNA-positive tests after serial negative results. HCV viremia and viral sequences (Core/E1) were assessed from monthly blood samples. RESULTS Viral clearance, reinfection, and intercalating infection were all detected. Among 44 participants with apparently resolved HCV (26 incident HCV clearers and 18 enrolled with already resolved infection), 36 (82%) remained persistently HCV RNA negative, but 8 demonstrated intermittent recurrent viremia. Four of these (50%) had confirmed reinfection with a heterologous virus; 3 demonstrated viral intercalation, and 1 was not classifiable as either. Estimated incidence of first reinfection was 5.4 per 100 person-years (95% confidence interval, 2.0-14.5). Six (75%) participants, including 3 of 4 with reinfection, demonstrated sustained viral clearance for a median of 26 months since last HCV RNA test. CONCLUSIONS These results show that frequent monitoring and viral sequencing are required to correctly assess HCV outcomes and estimate incidence of reinfection (which was previously overestimated). Sustained clearance may take many months and occur after episodes of reinfection and viral intercalation. Three of 4 subjects who had confirmed reinfection showed evidence of long-term clearance. Viral intercalation occurs with significant frequency. Further studies of these events, especially immunological, are needed to inform HCV clinical care and vaccine development.

Measuring HIV Self-Management in Women Living with HIV/AIDS: A Psychometric Evaluation Study of the HIV Self-Management Scale

Objective:To develop and validate the HIV Self-management Scale for women, a new measure of HIV self-management, defined as the day-to-day decisions that individuals make to manage their illness. Methods:The development and validation of the scale was undertaken in 3 phases: focus groups, expert review, and psychometric evaluation. Focus groups identified items describing the process and context of self-management in women living with HIV/AIDS (WLHA). Items were refined using expert review and were then administered to WLHA in 2 sites in the United States (n = 260). Validity of the scale was assessed through factor analyses, model fit statistics, reliability testing, and convergent and discriminate validity. Results:The final scale consists of 3 domains with 20 items describing the construct of HIV self-management. Daily self-management health practices, social support and HIV self-management, and chronicity of HIV self-management comprise the 3 domains. These domains explained 48.6% of the total variance in the scale. The item mean scores ranged from 1.7 to 2.8, and each domain demonstrated acceptable reliability (0.72–0.86) and stability (0.61–0.85). Conclusions:Self-management is critical for WLHA, who constitute over 50% of people living with HIV/AIDS (PLWHA) and have poorer health outcomes than their male counterparts. Methods to assess the self-management behavior of WLHA are needed to enhance their health and wellbeing. Presently, no scales exist to measure HIV self-management. Our new 20-item HIV Self-management Scale is a valid and reliable measure of HIV self-management in this population. Differences in aspects of self-management may be related to social roles and community resources, and interventions targeting these factors may decrease morbidity in WLHA.

Human leukocyte antigen B*57 does not fully explain hepatitis C clearance in HIV controllers.

Objective:HIV controllers demonstrate high rates of spontaneous clearance of hepatitis C virus (HCV) infection. The objective of this study was to evaluate the role of human leukocyte antigen (HLA) B*57 and other genetic polymorphisms on HCV clearance in HIV controllers. Design:This is a prospective cohort study. Methods:Patients in the Study of the Consequences of Protease Inhibitor Era (SCOPE) were tested for anti-HCV using enzyme immunoassay (EIA3) and HCV RNA using discriminatory HCV transcription-mediated amplification assay (Norvatis). We compared the proportion of HIV controllers and noncontrollers demonstrating HCV clearance and fitted multivariable Poisson regression models with robust standard errors to estimate adjusted prevalence ratios (APRs) and assessed genetic and immunologic predictors of HCV clearance. Results:Of 279 HIV/HCV seropositive individuals, 48 were HIV controllers. HIV controllers compared to HIV noncontrollers, were significantly more likely to have HLA B*57 (33 vs. 10%, P < 0.01). In multivariate analyses, adjusting for HLAB57, IL28B genotype, age, sex and race/ethnicity, HCV clearance was significantly more likely in HIV controllers than HIV noncontrollers [APR 1.78; 95% confidence interval (CI) 1.06–3.0; P = 0.03]. HLA B*57 did not explain the increased proportion of HCV clearance in HIV controllers, but IL28B CC genotype was independently associated with spontaneous HCV clearance (APR 2.76; 95% CI 1.85–4.11; P < 0.001). Conclusion:Although enriched in HIV controllers, HLA B*57 does not explain the increased HCV clearance. Further identification of host immunologic or genetic factors that contribute to control of HIV and HCV may support the development of novel treatments for and effective vaccines against both viruses.

Appreciating Reasons for Nonadherence in Women

Women aged 15–24 years have an HIV infection rate twice that of men the same age. In this study we examined reasons why HIV-infected women taking antiretroviral therapy (ART) report missing HIV medications. Women (N = 206) on ART were 2.2 times more likely to endorse reasons pertaining to forgetfulness versus reasons pertaining to problems taking pills (OR = 2.2, 95% CI = 1.63, 2.94, p <.001). There was a difference between the adherent and nonadherent groups in types of reasons overall (p <.001, 95% CI = –3.82, –2.03). Using a patient-centered approach to understand type of nonadherence (intentional vs. unintentional) may support development of novel interventions.

Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.

&NA; Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely‐infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infections short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care.

A closer look at hepatitis C clearance in HIV controllers: a response.

Seaberg and Thio [1] refer to evidence that suggests that route of infection may play a role in hepatitis C virus (HCV) spontaneous clearance. We did not examine the role of the route of infection on HCV clearance in HIV controllers in our study. HCV clearance differs by HIV status, but little prospective data are available to assess clearance by transmission route. One retrospective analysis showed that presumed sexually acquired HCV had higher rates of spontaneous clearance than parenterally acquired HCV [2]. Other studies have not shown this [3,4]. In prospective studies of HCV monoinfected patients, there is no evidence that clearance differs by transmission route [5,6]. Less examined is how genetic variations and mode of transmission impact divergent HCV outcomes. Seaberg et al. [7] found a higher magnitude of association between IL28B CC and HCV clearance in men MSM with reported injected drug use (IDU) than in those without, but this analysis includes MSM with and without HIV. We examined these factors in HIV controllers, the study population examined in our study ‘Human Leukocyte Antigen (HLA) B*57 Does Not Fully Explain Hepatitis C Clearance in HIV Controllers’ [8]. People with the IL28B CC (vs. CT or TT) allele are significantly more likely to spontaneously clear HCV infection [9,10]. In our study, the presumed mode of HCV acquisition did not modify the association between IL28B genotype and HCV clearance: there was no difference in the effect of IL28B CC (vs. CT/TT) on HCV clearance between those with a history of IDU [prevalence ratio 2.98; 95% confidence interval (CI) 1.57–5.64] and those without reported IDU history (prevalence ratio 2.51; 95% CI 1.52–4.16; test for heterogeneity P=0.93). Unlike the study by Seaberg et al. [7], we found no evidence that the impact of IL28B CC (vs. CT/TT) on HCV clearance was modified by IDU history among MSM (prevalence ratio in non-IDU MSM 2.13; 95% CI 1.25–3.65; prevalence ratio in IDU and MSM 1.57; 95% CI 0.36–6.86). HLA B*57 has been shown to be highly enriched in people who innately control their HIV infection [11,12], prompting questions about whether this may hold true for other viral infections, including HCV. We found no evidence that HLA B*57 is associated with clearance in HIV-infected patients (adjusted prevalence ratio 1.36; 95% CI 0.71−2.60, P = 0.35) [8]. Although power was limited, we also found no evidence for a protective role of HLA B*57 in any subgroup of interest. For example, patients with HLA B*57 had similar prevalence of HCV clearance to those without HLA B*57 among both HIV controllers (31 vs. 34%, P = 0.83) and noncontrollers (29 vs. 27%, P = 0.79). HLA B*57 does not explain the increase in HCV clearance in controllers in our cohort. We also found no association between HLA B*57 and HCV clearance in those with and without an IDU history (prevalence ratio 1.18; 95% CI 0.56−2.51 vs. prevalence ratio 1.19; 95% CI 0.62−2.28) and in MSM vs. non-MSM exposure groups (prevalence ratio 0.98; 95% CI 0.49−1.99 vs. prevalence ratio 1.36; 95% CI 0.68−2.70). The table presenting the multivariate analysis in the original article was mis-printed and omitted the significance of IL28B CC on clearance. An erratum will correct this. Seaberg and Thio [1] state that we did not discuss the finding that HIV controllers were more likely to clear HCV when negative for HLA B*57. The original publication states that HLA B*57 cannot explain the increased prevalence of HCV clearance in HIV controllers in our cohort. We agree with our colleagues that this is perhaps the most important novel finding from our study. It suggests that other unmeasured factors associated with HIV control must also contribute to HCV clearance in this setting. Future host genetic studies of HIV/HCV-coinfected controllers and noncontrollers may help shed light on these factors, potentially identifying novel genetic factors that contribute to the clearance and/or control of multiple viral pathogens. Nevertheless, as pointed out, HLA B*57 has been associated with HCV clearance in other studies [13,14]. Our study does not discount those studies, as a larger sample size might have revealed a more significant effect of HLA B*57. However, our study does suggest that there are factors other than HLA B*57 that contribute to HCV clearance in HIV controllers. The evidence of differential outcome of HCV in association with route of exposure is inconclusive; further research is necessary to improve our understanding of this potential effect and putative mechanisms involved. We agree that further research is needed to understand why HIV controllers are more likely to clear HCV, as this cannot be entirely explained by enrichment for HLA B*57.