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and Hepatitis.com Coverage of the
17th Conference on Retroviruses and
Opportunistic Infections (CROI 2010)
February 16 - 19, San Franciso, California
Sustained Response to Interferon Reduces both Liver-related and AIDS-related Disease and Death in HIV/HCV Coinfected Patients
Prior studies in both HIV negative and HIV/HCV coinfected populations have shown that interferon-based therapy reduces the likelihood of liver disease progression and liver-related death. This is seen most often in people who achieve sustained response, but some studies have found that even people who are not "cured" can still benefit from treatment.
While the detrimental effect of HIV infection and immune suppression on hepatitis C progression is well recognized, the effect of HCV on HIV disease is more controversial, as research has produced conflicting data.
Juan Berenguer from Hospital Universitario Gregorio Maranon in Madrid and colleagues designed a study to assess whether sustained response to treatment would affect HIV disease progression and mortality not related to liver disease.
The analysis included 1428 HIV/HCV coinfected participants enrolled in the multicenter Spanish GESIDA 3603 Study Cohort who started treatment with interferon-based therapy between January 2000 and July 2007.
As is typical of coinfected patients in Spain, about 75% were men, the median age was 42 years, and 81% had a history of injection drug use. More than 80% were on combination antiretroviral therapy (ART) and 62% had suppressed HIV viral load. The median current CD4 cell count was 528 cells/mm3, but the median CD4 nadir (lowest-ever level) was 216 cells/mm3 and 22% had a prior AIDS diagnosis.
With regard to hepatitis C status, 60% had hard-to-treat HCV genotypes 1 or 4, a majority (65%) had high HCV viral load (>500,000 IU/mL), and 30% had advanced liver fibrosis (stage F3 or greater) -- all factors that predict poor treatment response -- but very few (5%) were very heavy drinkers (> 50 g/day).
Most patients received the current standard-of-care therapy consisting of pegylated interferon alfa-2a (Pegasys) (48%) or pegylated interferon alfa-2b (PegIntron) (38%) plus ribavirin; however, 14% used the older conventional form of interferon.
defined as continued undetectable HCV viral load 24 weeks after completion
of treatment. The non-SVR group included patients who never responded,
those who responded only partially, and those who had undetectable HCV
RNA at the end of treatment but then relapsed.
The researchers concluded that these results suggest that "achievement of an SVR after interferon-ribavirin therapy in HIV/HCV [coinfected] patients reduces not only liver-related complications and mortality, but also HIV progression and mortality not related to liver disease."
"These findings may be associated with a poorer immune response (that does not seem to depend on control of HIV) and/or complications of HCV viremia in patients that did not achieve an SVR," they suggested.
During his presentation, Berenguer briefly showed data from another study indicating that HIV/HCV coinfected people have elevated levels of biomarkers of endothelial dysfunction, but these improved among patients who achieved SVR.
At a press conference following his session, Berenguer was asked whether hepatitis C treatment that does not result in SVR might still have beneficial effects. He said this does appear to be the case, compared with remaining untreated. While these data are not yet fully analyzed, there were "some hints" that coinfected individuals who achieved an end-of-treatment response but relapsed also had improved clinical outcomes.
Hosp Univ Gregorio Marañon, Madrid, Spain; Hosp Univ Bellvitge, Spain; Hosp Clin Valencia, Spain; Hosp Clin San Carlos, Spain; Hosp de Mostoles, Spain; Hosp Santa Creu y Sant Pau, Spain; Hosp 12 de Octubre, Madrid, Spain; Fndn SEIMC-GESIDA, Spain; Hosp Univ La Paz, Madrid, Spain.