Ribavirin Does Not Appear to Increase Risk of HIV NRTI Resistance Mutations in HIV-HCV Coinfected Patients

By Liz Highleyman

It is well known that using nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as monotherapy or dual therapy rapidly leads to development of resistance and consequent treatment failure in HIV patients.

Ribavirin, used with pegylated interferon as standard therapy for chronic hepatitis C virus (HCV) infection, is structurally similar to NRTIs used for HIV treatment. In fact, the drug was once studied as an anti-HIV candidate, but without success.

Because many people are coinfected with both HIV and HCV, some experts have expressed concern that exposure to ribavirin might cause HIV to develop resistance mutations that confer cross-resistance to NRTIs. This would primarily be an issue for people not receiving effective combination antiretroviral therapy.

Rolando Barrios from the British Columbia Centre for Excellence in HIV/ AIDS and colleagues designed a retrospective study to determine whether exposure to ribavirin in HIV-HCV coinfected patient without full HIV suppression causes the emergence of HIV mutations that allow for NRTI cross-resistance.

The study included 21 adult HIV-HCV coinfected patients seen at 2 specialty clinics in Vancouver, Canada and Seville, Spain. All participants had detectable HIV viral load before and during ribavirin exposure and were not taking ART while using ribavirin.

Genotypic testing was performed on blood samples from patients with HIV viral loads > 200 copies/mL taken periodically starting from baseline prior to ribavirin exposure until the end of ribavirin treatment. Baseline HIV reverse transcriptase gene mutations from codons 1-400 were compared to mutations observed during the period of ribavirin exposure. New mutations that appeared during ribavirin therapy and remained present until end of treatment were classified as "persisting" changes.

Results

	15 cases of new, persisting mutations were detected in 10 patients.
	The observed mutations were 35wt/I, 86wt/D, 106wt/I, 122wt/Q, 123wt/E, 165wt/I, 178wt/L, 189wt/I, 211wt/K, 21wt/D, 277wt/K, 324wt/E, 344wt/D, and 360wt/T.
	No specific pattern was observed in the emergence of the reported mutations reported.
	None of these mutations are known to be associated with NRTI resistance.

Based on these findings, the researchers said that the observed mutations probably represent "background noise," and concluded that "it is safe to continue treating HIV-HCV coinfected patients with ribavirin as part of combined therapy for HCV infection without simultaneous use of ART."

7/28/09

BC Centre for Excellence in HIV/ AIDS, Vancouver, Canada; University of British Columbia, Vancouver, Canada; Hospital Universitario Virgen del Rosio, Instituto de Biomedicina, Laboratorio de Inmunovirologia, Sevilla, Spain; St Paul's Hospital, Infectious Diseases, Vancouver, Canada.

Reference
RA Barrios, M Genebat, PR Harrigan, and others. HIV-HCV co-infection: risk of development of cross-resistance to nucleosides after exposure to ribavirin. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract WePeB208.