Social Vulnerability among Foreign-Born Pregnant Women and Maternal Virologic Control of HIV.

OBJECTIVE: The aim of this study was to assess whether social vulnerability among foreign-born pregnant women living with HIV is associated with maternal viremia during pregnancy. STUDY DESIGN: This retrospective cohort study included all foreign-born pregnant women living with HIV who received prenatal care in a multidisciplinary prenatal clinic between 2009 and 2018. A licensed clinical social worker evaluated all women and kept detailed clinical records on immigration status and social support. Social vulnerability was defined as both living in the United States for less than 5 years and reporting no family or friends for support. The primary outcome was evidence of viral non-suppression after achievement of initial suppression. Secondary outcomes were the proportion of women who required > 12 weeks after starting antiretroviral therapy to achieve viral suppression, median time to first viral suppression (in weeks) after initiation of antiretroviral therapy, and the proportion who missed ≥ 5 doses of antiretroviral therapy. Bivariable analyses were performed. RESULTS: A total of 111 foreign-born women were eligible for analysis, of whom 25 (23%) were classified as socially vulnerable. Social and clinical characteristics of women diverged by social vulnerability categorization but no differences reached statistical significance. On bivariable analysis, socially-vulnerable women were at increased risk for needing > 12 weeks to achieve viral suppression (relative risk: 1.78, 95% confidence interval: 1.18-2.67), though there was no association with missing ≥ 5 doses of antiretroviral therapy or median time to viral suppression after initiation of antiretroviral therapy. CONCLUSION: Among foreign-born, pregnant women living with HIV, markers of virologic control during pregnancy were noted to be worse among socially-vulnerable women. Insofar as maternal viremia is the predominant driver of perinatal transmission, closer clinical surveillance and support may be indicated in this population. KEY POINTS: · 23% of foreign-born pregnant women living with HIV were identified as socially vulnerable.. · Socially-vulnerable women were at higher risk for re-emergent viremia (24 vs. 7%, RR 3.44).. · Socially-vulnerable women were at higher risk for needing >12 weeks to become aviremic (64 vs. 36%, RR: 1.7)..

Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta.

BACKGROUND & AIMS: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection. METHODS: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up. RESULTS: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p <0.001). HDV viral load at baseline was significantly lower in responders than in non-responders. CONCLUSION: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients. LAY SUMMARY: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.

Prevalence of Viremic Hepatitis C Virus Infection by Age, Race/Ethnicity, and Birthplace and Disease Awareness Among Viremic Persons in the United States, 1999-2016.

BACKGROUND: Athough curative therapy is now available for hepatitis C virus (HCV) infection in the United States, it is not clear whether all affected persons have been diagnosed and/or linked to care. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (1999-2016) and included 46 465 nonincarcerated and noninstitutionalized participants. RESULTS: Viremic HCV prevalence decreased from 1.32% in 1999-2004 to 0.80% in 2011-2016, although most of the decrease occurred in US-born whites and blacks but not the foreign-born or those born after 1985. In 2011-2016, approximately 1.90 million US adults remained viremic with HCV, and 0.33 million were at higher risk for advanced fibrosis, but only 49.8% were aware of their HCV infection, with higher disease awareness in those with health insurance coverage and US-born persons. CONCLUSIONS: The prevalence of viremic HCV has decreased in recent years among US born whites and blacks but not in other race/ethnicities and foreign-born persons and birth cohort born after 1985. Less than half of the viremic population was aware of having HCV infection. Improved HCV screening and linkage to care are needed, especially for the uninsured, foreign-born, birth cohort after 1985 and certain ethnic minorities.

RICH2 is implicated in viraemic control of HIV-1 in black South African individuals.

An intronic single nucleotide polymorphism (SNP) in RICH2 (rs2072255; 255i), in complete linkage disequilibrium (LD) with an exonic SNP (rs2072254; 254e), has been identified in a genome wide association study to be associated with progression to AIDS in Caucasian individuals. RICH2 links tetherin to the cortical actin network and the RICH2/tetherin interaction has been shown to be important for the downstream activation of NF-κß and the consequential promotion of proinflammatory responses. We investigated the role of these two SNPs in natural control of HIV-1 in black South Africans including healthy controls (HCs; N=102) and antiretroviral-naive HIV-1-infected controllers (HICs; N=52) and progressors (N=74). HICs were stratified as elite controllers (ECs; N=11), viraemic controllers (VCs; N=30), high viral load (VL) long term non-progressors (HVL LTNPs; N=11) and also according to VL<400RNA copies/ml (HICs VL<400; N=20) and VL>400RNA copies/ml (HICs VL>400; N=32). Results showed that in contrast to Caucasians who had very strong LD between these SNPs (r2=0.97), black populations exhibited low LD (r2=0.11-0.27), however a 254e minor allele was always present with a 255i minor allele but not vice versa. The SNPs did not show significant over- or underrepresentation in any particular group, however the combination of 254e major allele homozygosity and 255i heterozygosity (254eAA/255iGA) was underrepresented in HICs (OR=3.26; P=0.04) and VCs (OR=7.77; P=0.02) compared to HCs, and in HICs VL>400 compared to both HCs (P=0.002) and progressors (P=0.02). A lower CD4+ T-cell count was associated with 254eAA/255iGA and 255i (GA+AA) in the total HIV-1-infected group (P=0.043) and progressors (P=0.017), respectively. In silico analysis predicted loss of an exonic splice enhancer site with the 254e-G allele. We postulate that altered splicing of RICH2 will affect levels of RICH2 expression and consequently NF-κß activation. These findings point to a role for RICH2 and tetherin in viraemic natural control of HIV-1.

African American Race Is a Newly Identified Risk Factor for Postengraftment Blood Stream Infections in Pediatric Allogeneic Blood and Marrow Transplantation.

Blood stream infections (BSI) are a major source of morbidity and mortality both in allogeneic blood and marrow transplant (BMT) recipients. Various risk factors for BSI in BMT have been identified. The impact of race and cytomegalovirus (CMV) viremia, a common complication after engraftment, however, has not been rigorously assessed. This is important because both CMV infection and ganciclovir, the mainstay of pre-emptive therapy, have myelosuppressive and immunosuppressive effects. We conducted a retrospective analysis to test the hypothesis that race and CMV viremia predispose allogeneic BMT patients to postengraftment BSI. We analyzed 278 allogeneic BMT performed at Children's Healthcare of Atlanta between January 1, 2005 and December 31, 2014 that met eligibility criteria. We performed a multivariate analysis to estimate the effect of CMV viremia on risk for BSI in the postengraftment period (days +30 to 100). Risk for BSI was associated with CMV viremia (hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.51 to 7.36; P = .003); grade III and IV acute graft-versus-host disease (HR, 3.28; 95% CI, 1.55 to 6.92; P = .002), and African American race (HR, 2.22; 95% CI, 1.09 to 4.51; P = .027). The results of our study highlight the importance of a novel risk factor for postengraftment BSI, not previously considered-African American race.

Hepatitis B, C, and D and HIV infections among immigrants from Equatorial Guinea living in Spain.

A total of 1,220 subjects from Equatorial Guinea living in Spain (median age = 41 years; 453 male and 767 female) was examined for antibodies to human immunodeficiency virus (HIV) and Hepatitis B (HBV), C (HCV), and D (HDV) viruses. Extracted RNA and DNA from the positive samples were used to quantify viral load. The prevalence of HIV antibodies, HCV RNA, and HBV surface antigen (HBsAg) was 10.8% (N = 132), 11.6% (N = 141), and 7.9% (N = 96), respectively. The most prevalent HIV variant was CRF02_AG (38.5%; N = 40). HCV genotype 4 (60%; N = 36) and HBV genotype A3 (32%; N = 8) were the hepatitis variants most frequently found. Superinfection with HDV was seen in 20.9% (N = 24) of HBsAg carriers. A control group of 276 immigrants from other sub-Saharan countries showed similar rates of HIV and HBsAg, although no HCV cases were found. Immigrants constitute a major source of HIV and hepatitis viruses in Spain; therefore, it is important that control measures are intensified.

HCV RNA levels in a multiethnic cohort of injection drug users: human genetic, viral and demographic associations.

UNLABELLED: In patients with chronic hepatitis C, the hepatitis C virus (HCV) RNA level is an important predictor of treatment response. To explore the relationship of HCV RNA with viral and demographic factors, as well as IL28B genotype, we examined viral levels in an ethnically diverse group of injection drug users (IDUs). Between 1998 and 2000, the Urban Health Study (UHS) recruited IDUs from street settings in San Francisco Bay area neighborhoods. Participants who were positive by HCV enzyme immunoassay were tested for HCV viremia by a branched-chain DNA assay. HCV genotype was determined by sequencing the HCV nonstructural 5B protein region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1,701 participants with HCV viremia, median age was 46 years and median duration of injection drug use was 26 years; 56.0% were African American and 34.0% were of European ancestry (non-Hispanic). Human immunodeficiency virus type 1 (HIV-1) prevalence was 13.9%. The overall median HCV RNA level was 6.45 log(10) copies/mL. In unadjusted analyses, higher levels were found with older age, male gender, African-American ancestry, hepatitis B virus infection, HIV-1 infection, and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotypes 3 or 4. In an adjusted analysis, age, gender, racial ancestry, HIV-1 infection, HCV genotype, and IL28B rs12979860 genotype were all independently associated with HCV RNA. CONCLUSION: The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors.

African americans are less likely to have clearance of hepatitis C virus infection: the findings from recent U.S. population data.

BACKGROUND: Hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States. African Americans are known to have a higher prevalence of HCV and lower response to anti-HCV therapy. GOAL: The aim of this study is to assess the differences in the prevalence of chronic HCV infection in according to patients' ethnic background. STUDY: We used the recent National Health and Nutrition Examination Survey with extensive clinical and laboratory data. Active HCV infection was defined as having HCV-positive antibody with detectable HCV RNA by polymerase chain reaction. HCV clearance was defined as HCV-positive antibody with negative HCV RNA. Clinico-demographic data were compared between anti-HCV positive individuals with or without HCV clearance. The stratum-specific χ test for independence was used. Logistic regression was used to identify independent predictors of HCV clearance. P-values ≤0.05 were considered statistically significant. All analyses were run using SAS 9.1 and SUDAAN 10.0. RESULTS: The cohort included 14,750 adults (age 47.6 ± 0.75 y, 64% white, 21% African American, 10% Hispanics, and 63% male). Of these, 1.32 ± 0.11% were anti-HCV positive with 75.94 ± 4.72% having active HCV viremia. The only parameter significantly different between those who did or did not clear HCV was the proportion of African Americans: 8.0 ± 3.7% versus 24.9 ± 5.0%, P=0.0163. Indeed, the rate of HCV clearance was lowest among African Americans (9.3 ± 3.5%) as compared with both whites (27.2 ± 6.5%) and Hispanics 31.2 ± 9.1% (P<0.05). In multivariate analysis, the only independent predictor of active HCV infection was African American race: odds ratio (95% confidence interval)=3.80 (1.31-11.06), P=0.0151. CONCLUSIONS: African Americans not only have lower response to anti-HCV therapy but also are less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV.

Ethnic differences in viral dominance patterns in patients with hepatitis B virus and hepatitis C virus dual infection.

UNLABELLED: Studies of hepatitis B virus (HBV)/hepatitis C virus (HCV) dual infection are limited. Most are small, conducted outside the United States, and compare dual infection with HCV monoinfection. The goal of this study was to characterize HBV/HCV dual infection in a large multiethnic, matched, case-control study of dual-infected and HBV-monoinfected patients at two United States centers. Using an International Classification of Disease Version 9 electronic query and chart review, we identified 115 HBV/HCV dual-infected patients with serial HBV DNA, HCV RNA, and alanine aminotransferase (ALT) levels. As a control, 115 HBV-monoinfected patients were chosen randomly and matched with cases by age ±10 years, sex, Asian versus non-Asian ethnicity, and study site. Both groups had similar sex, ethnic, and age distributions (68% male, 83% Asian, age 52 ± 14 years). The median follow-up times were 33 and 38 months for the dual-infected and monoinfected groups, respectively. More monoinfected patients received HBV antiviral therapy than dual-infected patients (43% versus 24%; P = 0.002). No significant difference was detected between the proportion of monoinfected versus dual-infected patients with ALT above 40 U/L at presentation or during follow-up. Dual infection patients exhibited very little HBV/HCV codominance at baseline and throughout follow-up: patients had either HBV viremia with low or absent HCV RNA or detectable HCV RNA with low or absent HBV DNA. Asian ethnicity was predictive of HBV dominance after adjusting for sex, age, and baseline ALT elevation (odds ratio 7.35; P = 0.01). CONCLUSION: HBV/HCV dual-infected and HBV-monoinfected patients had similar clinical characteristics. Asian ethnicity is a major independent predictor of HBV-dominant disease, and HCV dominance with undetectable HBV DNA is more common in non-Asian individuals. Larger studies are needed to further characterize the natural history of HBV/HCV dual infection in Asian and non-Asian individuals.

Importance of patient, provider, and facility predictors of hepatitis C virus treatment in veterans: a national study.

OBJECTIVES: Several patient characteristics are known to impact hepatitis C virus (HCV) antiviral treatment rates. However, it is unclear whether, and to what extent, health-care providers or facility characteristics impact HCV treatment rates. METHODS: Using national data obtained from the Department of Veterans Affairs (VA) HCV Clinical Case Registry, we conducted a retrospective cohort study of patients with active HCV viremia, who were diagnosed between 2003 and 2004. We evaluated patient-, provider-, and facility-level predictors of receipt of HCV treatment with hierarchical logistic regression. RESULTS: The overall HCV treatment rate in 29,695 patients was 14.2%. The strongest independent predictor for receipt of treatment was consultation with an HCV specialist (odds ratio=9.34; 8.03-10.87). Patients were less likely to receive HCV treatment if they were Black, older, male, current users of alcohol or drugs, had HCV genotype 1 or 4, had higher creatinine levels, or had severe anxiety/post-traumatic stress disorder or depression. Patients with high hemoglobin levels, cirrhosis, and persistently high liver enzyme levels were more likely to receive treatment. Patient, provider, and facility factors explained 15, 4, and 4%, respectively, of the variation in treatment rates. CONCLUSIONS: Treatment rates for HCV are low in the VA. In addition to several important patient-level characteristics, a specialist consultant has a vital role in determining whether a patient should receive HCV treatment. These findings support the development of patient-level interventions targeted at identifying and managing comorbidities and contraindications and fostering greater involvement of specialists in the care of HCV.

Influence of alcohol use, race, and viral coinfections on spontaneous HCV clearance in a US veteran population.

Hepatitis C virus (HCV) is spontaneously cleared in 15% to 45% of individuals during primary infection. To define the role of alcohol, race, and HBV or HIV coinfections in natural HCV clearance, we examined these parameters in 203 spontaneously HCV-recovered subjects (HCV Ab(+)/RNA(-) subjects without prior antiviral therapy) and 293 chronically HCV-infected patients (HCV Ab(+)/RNA(+)). Subjects were identified from 1,454 HCV antibody-seropositive US veterans tested for HCV RNA between January 2000 and July 2002 at the Philadelphia Veterans Affairs Medical Center. In univariate analysis, alcohol use disorder (odds ratio [OR] 0.52; 95% CI, 0.31-0.85; P =.006) and black race (OR 0.65; 95% CI, 0.44-0.96; P =.024) were both associated with decreased likelihood of spontaneous HCV clearance. In multivariate analyses adjusting for race, HIV infection, age, and alcohol use disorder, alcohol remained strongly associated with reduced HCV clearance (OR 0.49; 95% CI, 0.30-0.81; P =.005). In contrast, the association between black race and viral clearance was no longer statistically significant (adjusted OR 0.72; 95% CI, 0.48-1.09; P =.125). HIV coinfection was negatively associated with HCV clearance (OR 0.37; 95% CI, 0.16-0.83; P =.016), while HBV coinfection was positively associated with HCV clearance (unadjusted OR 5.0; 95% CI, 1.26-28.6; P =.008). In conclusion, the likelihood of spontaneous clearance of HCV may be influenced by alcohol and viral coinfections.

Ethnicity and discordance in plasma HIV-1 RNA viral load and CD4+ lymphocyte count in a cohort of HIV-1-infected individuals.

BACKGROUND: Guidelines for commencing therapy for HIV infection have been based upon HIV-1 RNA and CD4 lymphocyte thresholds. The influence of confounding factors such as gender, ethnicity and co-infections is unproven. OBJECTIVES: To analyse ethnic discordance in plasma HIV-1 viral load (VL) and CD4+ count and its potential clinical significance in Black and Caucasian groups. STUDY DESIGN: Retrospective, cross-sectional, observational study of 537 antiretroviral nai;ve HIV-1-positive individuals attending two East London clinics. Baseline data were obtained from individuals who registered at the clinic from November 1996 to August 1999. An analysis was performed comparing ethnic differences in plasma HIV-1 VL, CD4+ count, CD8+ count, co-infections, CDC disease category, AIDS-defining illnesses and mode of transmission. RESULTS: Plasma HIV-1 VL was significantly lower in Blacks (4.5 copies/ml versus 4.7 copies/ml; P<0.05) despite lower baseline CD4+ counts and similar rates of disease progression to Caucasian groups. This association remained for patients with less advanced disease after stratification for CD4+ count (CD4+ 200-500, VL 4.5 copies/ml versus 4.7 copies/ml, P<0.01; CD4+ >500, VL 3.4 copies/ml versus 4.3 copies/ml, P<0.001) and disease category (non-AIDS, 4.4 copies/ml versus 4.7 copies/ml; P<0.005). On multivariate analysis, the association persisted following adjustment for gender, age, co-infections, CD4+ count and mode of transmission. CONCLUSIONS: These results suggest that plasma HIV-1 VL is discordantly low in Black compared with Caucasian groups stratified for CD4+ count, in this cohort of antiretroviral nai;ve HIV-1-positive individuals living in London. Although there are a number of possible explanations for this finding, it has considerable clinical relevance for the management of Black HIV-1-infected patients within UK, with significant implications for the decision about when to commence antiretroviral or immune-based therapies.

Human T-cell leukaemia/lymphoma virus risk may be enhanced in some selected donor populations.

BACKGROUND AND OBJECTIVES: Certain patient ethnic groups may require blood components from donors under-represented in the UK donor population. Selective recruitment of Afro-Caribbean donors is therefore necessary but was considered to pose an increased risk of human T-cell leukaemia/lymphoma virus (HTLV) infection. To assess this a seroprevalence study of HTLV was undertaken in Afro-Caribbean and Caucasian donors. MATERIALS AND METHODS: Sera from 1100 Afro-Caribbean and 1100 Caucasian donors were tested for antibody to HTLV. Reactive samples were confirmed for specificity using an algorithm comprising two additional assays and polymerase chain reaction (PCR) where possible. RESULTS: Six Afro-Caribbean donors (0.55%) were considered to be infected with HTLV I. CONCLUSION: Donor selection in this case caused a significantly elevated prevalence of HTLV infection and serves as a warning of the need for care in the design of policies for selective donor recruitment.

Pattern of HIV viraemia and CD4 levels in relation to pregnancy in HIV-1 infected women.

The objective was to study HIV-1 viraemia and CD4 levels during and 6 months after pregnancy. HIV cultures on peripheral blood mononuclear cells (PBMC) and plasma from 225 samples were performed in 90 HIV-1 infected women with 59 continued and 35 terminated pregnancies. P-24 antigen and HIV-DNA were also studied. 34 women originated from European, 44 from African and 10 from other countries while 2 were of unknown origin. HIV was detected in 30% of the plasma cultures from the first trimester and in approximately 50% thereafter. Repeated plasma isolations did not give an indication of HIV activation, nor did the cross-sectional time-to-culture positivity in plasma and in PBMC, PBMC isolation frequencies, HIV-DNA and CD4 levels. The plasma viraemia frequencies were generally higher and the CD4 levels lower in the African women than in the European ones. Six months after delivery there was a significant decrease in the CD4 cell counts compared to delivery, but not when compared to the values during the first or second trimesters. The results showed that HIV activity during pregnancy was relatively stable, followed by indications of resumed activity during the first 6 months after delivery.