HIV Positive People with Hepatitis C Virus Coinfection Are More Likely to Develop AIDS-defining Illnesses

HIV-HCV coinfected patients are more likely than HIV positive people without hepatitis C to develop opportunistic bacterial and fungal infections and other AIDS-defining illnesses, according to an Italian study published in the August 15, 2009 issue of Clinical Infectious Diseases.

By Liz Highleyman

A considerable body of evidence indicates that HIV-HCV coinfection is associated with more rapid progression of liver disease compared with HCV monoinfection, but research looking at the effect of hepatitis C on HIV disease outcomes is less clear, with several studies showing little or no effect. Few studies have examined the risk of specific opportunistic illnesses (OIs) in patients with and without hepatitis C.

Investigators with the ICONA study evaluated the correlation between occurrence of various AIDS-defining illnesses and chronic hepatitis C infection or HCV-related liver cirrhosis.

The analysis included more than 5000 HIV positive participants in this large Italian cohort (most on combination antiretroviral therapy), stratified into 2 groups: approximately half HIV-HCV coinfected (mostly untreated for hepatitis C), and the rest without HCV and with persistently normal aminotransferase (ALT and AST) levels. Patients with HCV coinfection were further stratified according to whether they had \liver cirrhosis.

The researchers calculated incidences of new AIDS-defining illnesses as the number of events per 1000 person-years (PY) of follow-up. They looked at the malignancy non-Hodgkin's lymphoma (NHL), illnesses with a viral cause (e.g., Kaposi's sarcoma), bacterial infections, fungal (mycotic) infections including Pneumocystis pneumonia, protozoa infections (e.g., toxoplasmosis), and HIV-related illnesses (e.g, wasting syndrome).

Results

	A total of 496 AIDS-defining illnesses were observed among 5397 patients, representing 25,105 PY of follow-up.
	HIV-HCV coinfection was associated with more than double the risk of developing an AIDS-defining illness (adjusted relative rate [RR] 2.61).
	The illnesses with the greatest increase in risk were:
	Fungal diseases: adjusted ARR 3.87. Bacterial infections: adjusted RR 3.15; HIV-related diseases: adjusted RR 2.68;
	However, there was no observed increase in the risk of NHL (adjusted RR 0.88), in conflict with some past studies.
	There was likewise no strong association between HCV coinfection and viral infections or toxoplasmosis.
	Patients with cirrhosis had significantly higher rates of fungal infections, bacterial infections, toxoplasmosis, and HIV-related AIDS-defining illnesses than HIV monoinfected patients, with a greater increase in risk than HCV positive patients without cirrhosis.
	Current and nadir (lowest-ever) CD4 count < 200 cells/mm3 and higher viral load were significant risk factor for most AIDS-defining illnesses studied.

"HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis," the study authors concluded. "Clinicians should take into account these data when making decisions on initiation of antiretroviral therapy for HCV-coinfected individuals."

In their discussion, the researchers said that the increased risk of AIDS-defining illness associated with hepatitis C did not differ, overall, between patients currently receiving antiretroviral therapy compared and those who had never been treated or were undergoing a treatment interruption -- a finding that is difficult to explain in light of recent research showing benefits of early and continuous HIV treatment.

In an accompanying editorial, Lionel Piroth from Centre Hospitalier Universitaire in Dijon, France, noted that before HAART became available, HIV-related morbidity and mortality were "so high that they largely overshadowed the potential clinical consequences of coinfection with hepatitis C virus." In the HAART era, in contrast, "the dramatic decrease in AIDS illnesses and mortality brought to light the clinical consequences of chronic HCV infection in HIV-infected patients."

The ICONA analysis, he added, "highlights and strengthens the need for careful follow-up of HCV-HIV coinfected patients, including preventive measures (screening, prophylaxis, and vaccination for preventable diseases), effective management of associated comorbidities (particularly addictions), and early and effective therapies against HIV and HCV."

Clinic of Infectious and Tropical Diseases, San Paolo Hospital, University of and Istituto Ricerca Clinica Carattere Scientifico San Raffaele Hospital, Milan, Italy; Istituto Nazionale Malattie Infettive Lazzaro Spallanzani and Clinic of Infectious Diseases, Cattolica University, Rome, Italy; Clinic of Infectious Diseases, Modena University, Modena, Italy; Santissima Annunziata Hospital, Bagno a Ripoli, Florence, Italy; Hospital of Rimini, Rimini, Italy; Hospital of Reggio Emilia, Reggio Emilia, Italy; Hospital of Vicenza, Vicenza, Italy; Riuniti Hospital, Bergamo, Italy; Institute of Infectious Diseases, University of Brescia, Italy; Royal Free and University College Medical School, London, UK.

8/7/09

References

A d'Arminio Monforte, A Cozzi-Lepri, A Castagna, and others (Icona Foundation Study Group). Risk of developing specific AIDS-defining illnesses in patients coinfected with HIV and hepatitis C virus with or without liver cirrhosis. Clinical Infectious Diseases 49(4): 612-622. August 15, 2009. (Abstract).

L Piroth. Coinfection with hepatitis C virus and HIV: more than double trouble (Editorial). Clinical Infectious Diseases 49(4): 623-625. August 15, 2009.