H. Nina Kim

Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons

Summary: Protective response rates to hepatitis B (HB) vaccination have been reported as low as 18-62% in HIV-infected persons. The relative importance of various predictors for this poor response has not been fully characterized. In this retrospective cohort study, we examined the relationship between clinical characteristics and vaccine non-response (HB surface antibody <10 IU/L) among patients attending an urban HIV clinic. Among the 97 patients who met the inclusion criteria, 43 (44%) developed a protective antibody response. In multivariate analyses, age >40 years (odds ratio [OR] 3.03 [95% confidence interval [CI], 1.14-8.06]; P = 0.026) and alcohol abuse (OR 4.92 [95% CI, 1.72-20.89]; P = 0.007) were independent predictors of failure to develop vaccine response. In addition, CD4 nadir <200 (OR 7.24 [95% CI, 1.91-27.41]; P = 0.004), rather than CD4 current to vaccination, remained a strong independent risk factor. Patients with HIV viral suppression on highly active antiretroviral therapy had a significantly lower rate of vaccine failure (OR 0.31 [95% CI, 0.11-0.91]; P = 0.033), after adjusting for these other covariates. Our findings underscore the importance of confirming seroconversion after HB vaccination in HIV-infected patients and initiating vaccination early in the course of HIV infection.

Prevalence, clinical and virologic outcomes of hepatitis B virus co-infection in HIV-1 positive Kenyan women on antiretroviral therapy.

Background Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART. Methods In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression. Results In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4–4.5), 11 (6.9%; 95% CI 3.1–10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1–5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression. Conclusion The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population.

Offering an American Graduate Medical HIV Course to Health Care Workers in Resource-Limited Settings via the Internet

Background Western accredited medical universities can offer graduate-level academic courses to health care workers (HCWs) in resource-limited settings through the internet. It is not known whether HCWs are interested in these online courses, whether they can perform as well as matriculated students, or whether such courses are educationally or practically relevant. Methods and Findings In 2011, the University of Washington (UW) Schools of Medicine and Nursing offered the graduate course, “Clinical Management of HIV”, to HCWs that included a demographic survey, knowledge assessment, and course evaluation. UW faculty delivered HIV clinical topics through ten 2-hour weekly sessions from the perspectives of practicing HIV medicine in developed and developing settings. HCWs viewed lectures through Adobe Acrobat Connect Pro (Adobe Systems, San Jose, CA), and completed online homework on HIV Web Study (http://depts.washington.edu/hivaids/) and online quizzes. HCWs, who met the same passing requirements as UW students by attending 80% lectures, completing ≥90% homework, and achieving a cumulative ≥70% grade on quizzes, were awarded a certificate. 369 HCWs at 33 sites in 21 countries joined the course in 2011, a >15-fold increase since the course was first offered in 2007. The majority of HCWs came from Africa (72%), and most were physicians (41%), nurses (22%), or midlevel practitioners (20%). 298 HCWs (81%) passed all requirements and earned a certificate. In a paired analysis of pre- and post-course HIV knowledge assessments, 56% of HCWs improved their post-course score (p<0.0001) with 27% improving by at least 30%. In the course evaluation, most HCWs rated the course as excellent (53%) or very good (39%). Conclusions This online HIV course demonstrated that opening a Western graduate medical and nursing curriculum to HCWs in resource-limited settings is feasible, popular, and valuable, and may address logistic and economic barriers to the provision of high quality education in these settings.

Hepatocellular carcinoma among US and non-US-born patients with chronic hepatitis B: Risk factors and age at diagnosis

Background Risk factors for hepatocellular carcinoma (HCC) have not been well characterized among African immigrants with chronic hepatitis B virus (HBV) infection. We conducted a case-control study to identify demographic and clinical factors associated with HCC among a diverse cohort of patients with chronic HBV infection seen in a large academic health setting. Methods We identified a total of 278 patients with HCC and chronic HBV seen at two medical centers in a 14-year span from January 2002 to December 2015. These cases were age- and sex-matched in a 1:3 ratio with 823 non-cancer control subjects with chronic HBV. Conditional logistic regression was used to estimate the odds of HCC by race, with black race stratified by African-born status, after adjusting for diabetes, HIV or HCV coinfection, alcohol misuse and cirrhosis. Results Of the 278 HCC cases, 67% were 60 years of age or older, 78% were male, 87% had cirrhosis and 72% were Asian. HIV infection was present in 6% of cases. Only 7% (19 of 278) of HCC cases were black, of whom 14 were African immigrants. The median age at HCC diagnosis was 44 years in Africans. Notably, nearly all (93%) of the African-born patients with HCC were diagnosed at an age younger than 60 years compared with 52% of Asian cases (P<0.001). The main factors independently associated with greater odds of HCC overall were Asian race (adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 1.9–5.5) and cirrhosis (aOR 19.7, 95% CI 12.2–31.8). Conclusion African immigrants accounted for a small proportion of HBV-associated HCC cases overall compared with Asians but appeared to have greater likelihood of early-onset HCC. Optimal strategies for HCC prevention in these key subroups with chronic HBV warrant further study.

Risk Factors for Indeterminate Outcome on Interferon Gamma Release Assay in Non-US-Born Persons Screened for Latent Tuberculosis Infection

Abstract Background Non-US-born individuals account for the majority of active tuberculosis (TB) in the United States. Interferon gamma release assay (IGRA) is the preferred diagnostic test for latent TB but can produce an indeterminate result. We investigated the prevalence and predictors of an indeterminate IGRA (IND-IGRA) in a diverse cohort of non-US-born individuals and evaluated outcomes after IND-IGRA. Methods We identified patient age ≥18 years who had an outpatient IGRA between 2010 and 2017 in our health system and whose primary language was not English. We used univariate and multivariable logistic regression to examine the association of IND-IGRA with a variety of clinical factors. Results Of 3128 outpatients with ≥1 IGRA done, 33% were Asian, 30% Hispanic, and 29% black; 44% were men, and the median age was 50 years. An initial IND-IGRA occurred in 118 (3.8%; 95% confidence interval [CI], 3.1%–4.5%); notably, Asian race (55%) and rheumatologic conditions (25%) were prevalent in this group. In multivariable analysis, Asian race was independently associated with IND-IGRA (adjusted odds ratio [aOR], 2.9; 95% CI, 1.9–4.3), in addition to the presence of anemia and hypoalbuminemia (aOR for interaction, 4.3; 95% CI, 1.3–14.3). Only 55% of patients with an initial IND-IGRA underwent repeat testing; of those who did, 66% had a determinate result. Conclusions Asian race and anemia/hypoalbuminemia were independent risk factors for an indeterminate IGRA outcome in foreign-born patients screened in the United States. Our study underscores the importance of following through on indeterminate results in these key subgroups.

Washington state satellite HIV clinic program: a model for delivering highly effective decentralized care in under-resourced communities*

ABSTRACT To improve access to high-quality HIV care in underserved regions of Western Washington (WA) State, we collaborated with the WA State Department of Health (DOH) and community partners to launch four satellite HIV clinics. Here, we describe this innovative clinical care model, present an estimate of costs, and evaluate patient care outcomes, including virologic suppression rates. To accomplish this, we assessed virologic suppression rates 12 months before and 12 months after the satellite clinics opened, comparing people living with HIV (PLWH) who enrolled in the satellite clinics versus all PLWH in the same regions who did not. We also determined virologic suppression rates in 2015 comparing satellite clinic versus non-satellite clinic patients and compared care quality indicators between the satellite clinics and the parent academic clinic. Results demonstrate that the change in virologic suppression rate 12 months before to 12 months after the satellite clinics opened was higher for patients who enrolled in the satellite clinics compared to all those in the same region who did not (18% versus 6%, p < 0.001). Virologic suppression in 2015 was significantly higher for satellite clinic than non-satellite clinic patients at three of four sites. Care quality indicators were met at a high level at the satellite clinics, comparable to the parent academic clinic. Overall, through community partnerships and WA DOH support, the satellite clinic program increased access to best practice HIV care and improved virologic suppression rates in difficult-to-reach areas. This model could be expanded to other regions with inadequate access to HIV practitioners, though financial support is necessary.