Showing papers by "Eric C. Seaberg published in 2014"

Association of the IFNL4-ΔG Allele With Impaired Spontaneous Clearance of Hepatitis C Virus.

Abstract: Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti–hepatitis C virus (HCV)–positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10−5) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P = .86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10−14) for IFNL4-TT/TT and 1.44 (P = .03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.

Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts

Abstract: Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment. A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled. Baseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia. In these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.

Differences in hepatitis C virus prevalence and clearance by mode of acquisition among men who have sex with men.

Abstract: The hepatitis C virus (HCV) is most effectively transmitted via parenteral exposures including injection drug use (IDU) and blood transfusions (1). Although heterosexual transmission of HCV is uncommon (2), sexual transmission has been recognized among men who have sex with men (MSM) (3). During the past decade, increasing HCV infection rates among human immunodeficiency virus (HIV)-infected MSM have been reported around the world (4-7). Host characteristics that have been linked to HCV infection among MSM include HIV infection (8;9), lower CD4+ cell count (10), unsafe sex practices including unprotected anal intercourse and fisting (4;11-13), the presence of certain sexually transmitted infections including syphilis (2;14), and recreational drug use (8). However, it is unknown whether each of these characteristics might differentially affect the risk of HCV acquisition via sexual versus parenteral exposures. It is also unclear whether spontaneous HCV clearance differs by mode of acquisition. Overall, spontaneous clearance occurs in about 25% of people (15;16), but individual reports have ranged from 11% to 49% (17-21) demonstrating substantial heterogeneity for successful immune responses to acute HCV infection. Lower spontaneous clearance has been associated with IDU (18;22), Black race (17), male gender (16), HIV-infection (23), and age>40 years (24). Two characteristics linked to higher HCV clearance are infection with the hepatitis B virus (HBV)(18;22;25;26) and homozygosity for the C allele of the single nucleotide polymorphism (SNP) rs12979860 (24) which is also referred to as ‘IL28B’ and is located within intron 1 of the interferon lambda 4 (IFNL4) gene (27). Because the majority of previously published HCV studies have included predominantly IDU study populations, generalizations to MSM who do not use injection drugs may be problematic. The objective of this study was to determine whether the factors associated with HCV prevalence and spontaneous clearance among MSM differ by mode of acquisition. We examined these outcomes in a large cohort of MSM that included both injection drug users (IDUs) and non-IDUs as well as HIV-infected and HIV-uninfected men.

Variants in HAVCR1 gene region contribute to hepatitis C persistence in African-Americans

Abstract: To confirm previously identified polymorphisms in HAVCR1 that were associated with persistent hepatitis C virus (HCV) infection in individuals of African and of European descent, we studied 165 subjects of African descent and 635 subjects of European descent. Because the association was only confirmed in subjects of African descent (rs6880859; odds ratio, 2.42; P = .01), we then used 379 subjects of African descent (142 with spontaneous HCV clearance) to fine-map HAVCR1. rs111511318 was strongly associated with HCV persistence after adjusting for IL28B and HLA (adjusted P = 8.8 × 10−4), as was one 81-kb haplotype (adjusted P = .0006). The HAVCR1 genomic region is an independent genetic determinant of HCV persistence in individuals of African descent.

Reply to Bradshaw and Danta

Abstract: To the Editor—We read with interest the comments by Bradshaw and Danta on our article [1] and would like to address several points. Comparing our study to the UK study is problematic because the UK study described a group of men who have sex with men (MSM) during the early and current highly active antiretroviral therapy (HAART) eras (1998–2008) [2]. In contrast, 83% of participants in our study were enrolled during the pre-HAART era. Because sexual practices in the MSM community changed rapidly as effective anti–human immunodeficiency virus (HIV) therapies evolved, a comparison between our study and the UK study may be confounded by changes in sexual behaviors in the gay community between 1984 and 2011. The authors also state that “rates of URAI [unprotected receptive anal sex] declined in later recruits” and speculate that this decline could be attributed to underreporting. In fact, we did not discuss trends in URAI rates. Rather, we reported in our Table 1 [1] the proportions of men who reported a history of URAI with multiple partners prior to enrollment into the Multicenter AIDS Cohort Study (MACS)—essentially a baseline assessment. However, to address the point raised, we examined the reported rates of URAI and found that those rates for later recruits were comparable to those reported by earlier recruits during follow-up in 2001. Thus, we did not find evidence to support the hypothesis that a greater degree of underreporting of URAI in later recruits occurred. Bradshaw and Danta also note that, in the HIV-infected men recruited from 2001–2003, the hepatitis C virus (HCV) incident rate (IR) declined between 2000–2004 and 2005–2011. However, this was not a statistically significant decline; the 95% confidence intervals (CIs) around the IRs are large and overlap (IR, 6.74 [95% CI, 2.71–10.89] vs 5.16 [95% CI, 2.57–9.23]). Nevertheless, we acknowledge that our finding that HCV incidence did not increase among MSM during this time period is in stark contrast to the 18-fold increase reported in the Swiss HIV Cohort Study (SHCS) [3]. Interestingly, the increase among MSM in the SHCS occurred exclusively between 2008 and 2011. As the SHCS has ongoing enrollment, we will see if the observed HCV increase occurred among a unique group of recent enrollees, and whether this increase continued. The authors note that the association of syphilis and incident HCV is lost in the non–injection drug use (IDU), non–blood transfusion group in our study, and they assert that this observation is in contrast to associations reported in other studies of HIV-infected MSM. Because >50% of our non-IDU, non–blood transfusion study group was HIV negative, the most appropriate group for comparison in our study is all HIV-infected men among whom, as shown in our Table 5 [1], syphilis was independently associated with incident HCV (relative risk, 2.75 [95% CI, 1.76–4.29]). This argues against the authors’ assertion that the MACS is “a relatively unusual MSM cohort.” Last, the authors are concerned that HCV antibody–negative recruits who did not have follow-up HCV testing might have been at higher risk for HCV than those with follow-up HCV testing. The proportion of men who reported having had URAI with ≥2 partners prior to enrollment among those included in our study was not different compared to those who did not have follow-up HCV testing (36% vs 34%; P = .39). Because this important marker of sexual exposure was similar among the MSM included in and excluded from our study, we do not believe that the exclusion of these men is likely to have affected the results of our study.