 |
|
|
| |
High HCV Load Doubles the Death Risk in People Coinfected With HIV
|
| |
| |
16th Conference on Retroviruses and Opportunistic Infections,
February 8-11, 2009, Montreal
Mark Mascolini
HIV-infected EuroSIDA cohort members with high HCV RNA ran a significantly greater risk of death from any cause and liver-related death than people with a lower HCV load, according to results of a 1952-person analysis [1] That finding differs from results in people infected with HCV but not HIV, in whom HCV load does not predict death. The study also determined people with HCV genotype 3 have a significantly lower death risk than people with genotype 1.
Earlier work by Jurgen Rockstroh and EuroSIDA colleagues found that HCV serostatus did not influence virologic or CD4 response to potent antiretroviral therapy [2]. This and previous studies relied on anti-HCV antibody positivity to identify coinfected people. The new study set out to determine the influence of HCV RNA load and HCV genotype on HCV and HIV progression in coinfected EuroSIDA cohort members.
The investigators determined HCV RNA level and HCV genotype in all anti-HCV antibody-positive samples from cohort members. Then they compared all-cause and liver-related death rates in people in three HCV load clusters. The analysis involved 1952 antibody-positive people: 415 (21%) had HCV RNA below 615 IU/mL and were rated aviremic; 716 people (37%) made up the low viral load group with an HCV RNA reading above 615 but below 500,000 IU/mL; and 821 people (42%) in the high viral load group had an HCV RNA quotient above 500,000 IU/mL.
To determine the impact of HCV load on mortality, Rockstroh and coworkers built a multivariate model that considered gender, HIV transmission group, region of Europe, HBV coinfection, race, prior AIDS, age, CD4 count at genotyping, date recruited, type of antiretroviral therapy, and date of HCV genotyping.
Seventy-eight aviremic people died of any cause for an incidence of 3.12 per 100 person-years, compared with 96 people with a low viral load for an incidence of 1.74 per 100 person-years, and 158 people with a high viral load for an incidence of 4.17 per 100 person-years. All-cause mortality did not differ significantly between the aviremic and low viral load groups. But compared with the low viral load group, people with a high HCV load had a 1.94 times higher risk of death (95% confidence interval [CI] 1.48 to 2.58, P < 0.0001).
There were 17 liver-related deaths in the aviremic group for an incidence of 0.68 per 100 person-years, 32 in the low viral load group for an incidence of 0.58, and 49 in the high viral load group for an incidence of 1.29. Again the death risk did not differ significantly between the first two groups. But people with a high HCV load had a 1.77 times higher risk of death than people with a low HCV load (95% CI 1.11 to 2.82, P = 0.016). HCV load had no major impact on response to antiretroviral therapy.
Of the 1537 people genotyped, 800 (52%) had genotype 1, 218 (14%) genotype 2, 466 (30%) genotype 3, and 53 (3%) genotype 4. Rockstroh observed that the low genotype 4 prevalence weakened statistical calculations for that genotype. Risk of death from any cause was significantly lower with genotype 3 than genotype 1 (P = 0.031), with a trend toward a lower death risk with genotype 2 (P = 0.070). Genotype did not significantly influence liver-related death risk.
Compared with genotype 1, response to antiretroviral therapy was significantly worse with the other three genotypes, but this difference reached statistical significance only for genotype 4 when response was measured as an HIV load below 500 copies (P = 0.011) or a 50% gain in CD4 cells (P = 0.010).
Rockstroh noted that the correlation between high HCV load and mortality is not seen in HCV-infected people without HIV. He speculated that faster progression in people coinfected with HIV enabled the EuroSIDA team to reach this conclusion, while longer follow-up may be needed with monoinfected people. Rockstroh added that excluding patients treated for HCV infection did not change the results. He agreed that the analysis is limited by the inability to control for alcoholism, a trait not recorded by EuroSIDA clinicians.
References
1. Rockstroh J, Peters L, Soriano V, et al. High hepatitis C viremia is associated with an increased risk of mortality in HIV/HCV-co-infected individuals. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 101.
2. Rockstroh JK, Mocroft A, Soriano V, et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis. 2005;192:992-1002.
|
| |
|
|
|
|
|
