Should we spare the nukes? NRTI HIV drugs may impair success of hepatitis C treatment

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Patients with HIV who start pegylated interferon and ribavirin treatment have considerably lower success rates if they are also taking nucleoside reverse transcriptase inhibitor (NRTI) drugs for HIV, two European studies have found.

One study from Germany found that people taking NRTIs were much less likely to achieve a Sustained Viral Response (SVR) from hepatitis C treatment than people taking NRTI-sparing regimens or no HIV treatment. (An SVR is an undetectable viral load six months after the end of hepatitis C treatment, generally seen as equivalent to a cure.) Another study from four countries found evidence that the drugs AZT and abacavir might be especially implicated.

The first study was a prospective cohort study of people both with and without HIV taking hepatitis C treatment from ten clinics in five German cities. This was a partially randomised study: patients needing HIV treatment were randomised to NRTI-containing and NRTI-sparing regimens (44 and 19 patients respectively). Their treatment success rates were then compared with 41 HIV-positive patients taking no HIV treatment and 48 HIV-negative patients.

Glossary

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

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. 

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

Interestingly, in this study, comparable SVR rates were achieved in patients with and without HIV, with rates of 55% in both groups. Neither was there a statistically significant difference in SVR rates between HIV-positive patients taking and not taking antiretrovirals (ARVs) (52% and 59% SVR rates respectively).

However there was a statistically significant difference observed between patients taking ARVs according to regimen: 74% of the patients in the NRTI-sparing group achieved an SVR compared with 43% in the NRTI-taking group (p=0.031).

There was no difference in adverse events observed according to NRTI status, and all groups had similar rates of adverse events, though patients taking ARVs had more laboratory abnormalities (29% in NRTI-sparing regimens and 21% in NRTI-based ones) than HIV patients not taking ARVs (15%) or HIV negative (6%).

The researchers concluded that “certain antiretroviral regimens may impact on SVR by other means than advanced toxicity and further studies are needed to investigate this matter.”

In the second study some of the same researchers from Germany teamed up with clinics in Barcelona and London (Chelsea and Westminster Hospital) and performed a retrospective study on 90 HIV positive patients who had taken pegylated interferon and ribavirin for hepatitis C. Seventy-one of the 90 patients (79%) were on ARVs.

In this group 52% achieved an SVR. The one factor that influenced SVR rates other than hepatitis C genotype was choice of ARVs: 77% of patients taking NRTI-sparing regimens had an SVR compared with 42% taking NRTIs.

The drugs abacavir and AZT appeared to have a particularly negative impact on SVR rates. Twenty-eight per cent of patients taking abacavir achieved an SVR and 29% of patients taking AZT. AZT is already known to be problematic because both ribavirin and AZT can cause anaemia, but although lab figures were not collected in this study, there was no relationship between ribavirin dose and SVR rate.

References

Vogel M et al. Safety of nucleoside containing HAART during interferon/ribavirin combination therapy for chronic HCV infection. Fifth Workshop on HIV & Hepatitis Co-infection, Lisbon. Abstract P_15. 2009.

Vogel M et al. ART components and their influence on treatment rates after pegylated interferon and ribavirin combination therapy in HIV-positive individuals with chronic HCV infection. Fifth Workshop on HIV & Hepatitis Co-infection, Lisbon. Abstract P_06. 2009.