HOST GENETIC INFLUENCE ON HIV AND HCV INFECTIONS

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 EIA were tested for HCV viremia by a bDNA assay. HCV genotype was determined by sequencing the HCV NS5B region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1701 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). HIV-1 prevalence was 13.9%. The overall median HCV RNA level was 6.45 log10 copies/ml. In unadjusted analyses, higher levels were found with older age, male gender, African American ancestry, HBV infection, HIV-1 infection and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotype 3 or genotype 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. The level of HCV viremia is influenced by a large number of demographic, viral and human genetic factors. HIV The clinical course of HIV-1 infection is highly variable among individuals, at least in part as a result of genetic polymorphisms in the host. Toll-like receptors (TLR) play a crucial role in the host’s innate immunity and may influence HIV-1 disease progression. The transcription factor IRF-5 is an important player in the TLR-MyD88 signaling cascade. We investigated the impact of two SNPs in TLR9 gene, rs352139 and rs352140, and two SNPs in IRF5 gene, rs10954213 and rs11770589, on CD4 count, HIV viral load, and clinical progression in a cohort of HIV-infected patients. Two SNPs in TLR9 and IRF5 are in linkage disequilibrium and rs352140GA TLR9 was associated with the rapid progressors phenotype: for rs352140 GG+GA versus AA, P = 0.025, OR= 0.5479, confidence interval (CI) 0.31-0.97. No other association was found between TLR9 and IRF5 SNPs and viral load, CD4 count or other clinical data. Rapid progression of HIV-1 infection was associated with TLR9 polymorphisms. Because of its potential implications for intervention strategies and vaccine developments, additional epidemiological and experimental studies are needed to confirm this association.