Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men

Abstract

ObjectiveAn epidemic of acute hepatitis C virus (HCV) infection in HIV-positive men-who-have-sex-with-men (MSM) is emerging in Europe, Australia and the USA. The aim of this study was to characterise the natural history of primary HCV in this setting and to assess host and viral factors which predict spontaneous clearance.MethodsThis prospective longitudinal cohort study was carried out in 112 HIV-positive patients who were followed in a single centre (the St Mary's Acute HCV Cohort). Plasma and peripheral blood mononuclear cells (PBMCs) were obtained at monthly intervals for 3 months and at 3-monthly intervals thereafter for a median of 45 months (IQR=29–69 months). The primary end point was spontaneous clearance of HCV. Cox regression was used to assess the impact of clinical and virological variables on outcome, including liver function, CD4 count, rate of HCV RNA decline, T cell response and clonal sequence evolution within the HCV E2 envelope gene.Results15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. The latter group included a significant proportion of ‘fluctuating’ progressors (37.5%), in whom a fall followed by a rise (>1 log10) in viraemia was observed. This was associated with superinfection with new HCV strains and partially effective T cell responses. Spontaneous clearance was strongly associated with a 2.2 log10 viral load drop within 100 days of infection (HR=1.78; p<0.0001), elevated bilirubin (≥40 μmol/l; HR=5.04; p=0.006), elevated alanine aminotransferase (ALT; ≥1000 IU/ml; HR=2.62; p=0.048) and baseline CD4 count ≥650×106/l (HR=2.66; p=0.045), and only occurred in patients with genotype 1 infection. Evolution to spontaneous clearance occurred in patients with low viral diversity in the presence of an early multispecific T cell response.ConclusionsSpontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.

HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe

“…We found a spontaneous HCV clearance rate of 15.6% at the first reinfection episode consistent with findings from others in HIV-HCVcoinfected populations (26). However, at second reinfection the spontaneous clearance rate showed a non-significant increase to 28.6%.…”

“…Factors such as female sex (37), coinfection with hepatitis B virus, a favorable IL28B genotype (38), and a higher CD4 cell count have been associated with clearance in clinical cohorts, as well as higher ALT levels, higher bilirubin levels, a faster decline in HCV viral load (26), and a less diverse viral quasispecies (39). Likewise, in this study, ALT levels above 1000 IU/mL were associated with spontaneous clearance as it has been described by other groups (26). These observations potentially Our study lacks detailed behavioral information, notably on injection drug use in this population, which hampers conclusions on prevention efforts.…”

Hepatitis B virus and hepatitis C virus infection among HIV-1-infected injection drug users in Dali, China: prevalence and infection status in a cross-sectional study

“…In previous reports, it was observed that the spontaneous HCV clearance during acute infection in HIVpositive men who have sex with men (MSM) could be predicted by high baseline CD4 ? T cell count (C650 cells/ ll) [32], and if the virus persisted, the CD4 ? T cell responses in the acute phase generally failed to be sustained at high levels [4].…”

Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection—the InC3Study

“…Potential interactions between study site-categorized as the Baltimore Before and After Acute Study of Hepatitis (BBAASH; the study contributing largest number of reinfection events) versus other sites-and hypothesized predictors were evaluated. Hypothesized predictors were determined a priori on the basis of established predictors of primary clearance, including age [21], sex [1,15,22,23], IFNL4 genotype (SNP rs12979860; CC vs CT/TT) [24][25][26], the combined effect of sex and IFNL4 genotype (female rs12979860 CC vs others) [15,23], HCV genotype during reinfection (genotype 1 vs non-genotype 1) [15,27], and reinfection with the same versus a different HCV genotype from that in the primary infection. It was hypothesized that participants reinfected with the same HCV genotype would have a greater propensity toward reclearance [28,29].…”