Pegylated interferon can cause serious eye problems in HIV/HCV coinfected patients, says study

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Treatment with pegylated interferon alpha-2b (PegIntron) and ribavirin can cause serious eye problems in individuals coinfected with HIV and hepatitis C virus according to an article published in the September 3rd edition of AIDS.The US investigators recommend that patients coinfected with HIV and hepatitis C and treated with pegylated interferon and ribarvirin receive regular ophthalmic monitoring.

Optic neuropathy, including retinal haemorrhage, cotton wool spots and decreased colour vision have been reported in individuals receiving interferon therapy who are monoinfected with hepatitis B or hepatitis C. However, these are the first cases to be reported of serious eye problems developing in HIV and hepatitis C coinfected patients receiving therapy with pegylated interferon.

A total of 23 patients were included in the investigators’ analysis. All had received at least twelve weeks of pegylated interferon alpha-2b and ribavirin in an open-label, prospective trial at a National Institutes of Health facility.

Glossary

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

pathology

The study of disease, focusing on causes, development and progression.

interferon alfa

A natural protein produced by the human body in response to infection. Manufactured interferon alfa is a treatment against hepatitis B, hepatitis C, genital warts and some cancers. See also ‘pegylated interferon’ – this is the form of the most commonly used drug.

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

Eye examinations included visual acuity, visual field testing, and a colour vision examination. In addition, indirect ophthalmoscopy were performed at baseline, then at least every three months or when the need was suggested by symptoms.

At baseline the patients had a median CD4 cell count of 553 cells/mm3, a median HIV viral load of below 50 copies/ml and a median hepatitis C viral load of over 1,000,000 copies/ml.

Eight individuals (35% of the study population) developed ophthalmologic pathology during hepatitis C treatment, including six patients who developed cotton wool spots, indicative of retinal haemorrhage. These were detected at the week twelve ophthalmoscopy, and "waxed and waned while [hepatitis C] therapy was continued." In addition, two patients developed cataracts. Hepatitis C treatment was continued in these individuals and the cataracts remained stable both during and after therapy.

Decreases in red-green colour vision were detected in two patients. One patient discontinued hepatitis C treatment and within ten weeks of its cessation this individual’s colour vision had returned to normal. Colour vision returned to normal in the other patient at week 23 of hepatitis C treatment without any cessation of therapy.

“The rapid development of serious ocular pathology in our coinfected patients demonstrates a concerning phenomenon associated with peglyated interferon and ribavirin therapy for hepatitis C virus” write the investigators. They add “both cotton wool spots and cataracts developed in several patients soon after beginning therapy. These lesions occurred in patients with high CD4 cell counts and in patients with and without comorbidities such as diabetes and hypertension.”

The investigators cannot say which factors led to the development of these serious eye problems in their patients, and note that there were no differences in the CD4 cell count, HIV viral load, or hepatitis C viral load between the patients who did and did not develop ophthalmologic pathologies. They note that a much larger cohort of patients would be needed to determine if any of these factors were significant. They also speculate that pegylated interferon could induce an immune response leading to retinal ganglion cell toxicities in susceptible individuals.

The investigators conclude, “routine ophthalmologic monitoring in persons receiving pegylated interferon and ribavirin may be warranted in order to optimize the benefit from current anti-hepatitis C virus therapy.”

References

Farel C et al. Serious ophthalmic pathology compromising vision in HCV/HIV coinfected patients treated with peginterferon alpha-2b and ribavirin. AIDS 18: 1805-1809, 2004.