Care of Patients With Hepatitis C and HIV Co-Infection

Vincent Soriano; Massimo Puoti; Mark Sulkowski; Stefan Mauss; Patrice Cacoub; Antonietta Cargnel; Douglas Dieterich; Angelos Hatzakis; Jurgen Rockstroh

Disclosures

AIDS. 2004;18(1) 

In This Article

Monitoring the Response to Anti-Hepatitis C Virus Therapy in HIV-Positive Patients

Background

Almost all patients who will clear HCV with anti-HCV treatment show an early virological response after beginning therapy.[3,64] Therefore, an early assessment of serum or plasma HCV-RNA titres after starting treatment may permit the identification of those who would benefit from prolonging therapy and those who would not. In HIV-negative patients, those who show a decline in HCV-RNA levels greater than 2 logs or undetectable levels at 12 weeks of therapy are those who will eventually reach a sustained response.[64] In contrast, almost none of those who show HCV-RNA declines of less than 2 logs at 12 weeks achieve that goal. Therefore, anti-HCV therapy may be discontinued at 12 weeks considering these virological criteria in early non-responders.[3] This principle to guide HCV therapy might spare side-effects and costs in individuals with no chance of cure. In HIV-HCV-co-infected patients these considerations should be regarded as even more crucial, because interactions between antiretroviral drugs and anti-HCV therapy are frequent, and issues related to poor compliance in individuals under polymedications are of much relevance.

Kinetic studies suggest that HCV clearance after beginning therapy with IFN may be delayed in the setting of HIV infection[65] (see Fig. 1a). Therefore, concern exists about the reliability of the principle of a 2-log reduction in HCV-RNA at 12 weeks: it might not work in HCV-HIV-co-infected patients. However, preliminary data suggest that despite a slower decay in HCV-RNA noticed in HIV-co-infected patients after beginning anti-HCV therapy, all patients who will reach a sustained response show a decline greater than 2 logs at 12 weeks on therapy.[66] Therefore, the principles guiding anti-HCV therapy in HIV-negative individuals may also apply to HIV-co-infected patients (see Fig. 2). However, patients with high HCV loads may show an early good virological response, but may not reach undetectable viraemia at week 24, but will clear HCV much later.[67] This subgroup of patients represents less than 3% of HCV-monoinfected individuals, but may be larger among HIV-co-infected patients, in whom higher baseline HCV-RNA titres are frequent and slower HCV-RNA decays on treatment have been described.[33]

Hepatitis C virus dynamics under interferon therapy. Influence of HIV infection. (a) Early phase; (b) late phase.

Hepatitis C virus treatment algorithm. aIn patients with high baseline hepatitis C virus (HCV) loads, treatment might be prolonged beyond 24 weeks despite the recognition of detectable viraemia at that moment, if a reduction greater than 2 logs was observed at week 12 of therapy. bIn the light of higher relapse rates in the setting of HCV-HIV co-infection, patients showing good virological responses at early timepoints and having good tolerance to anti-HCV therapy might consider prolonging therapy beyond 6 months (HCV genotypes 2-3) or 12 months (HCV genotypes 1-4). Peg-IFN, pegylated interferon; RBV, ribavirin.

There is a second phase of clearance of HCV-RNA in individuals on prolonged anti-HCV therapy, which accounts for the steady destruction of infected cells (hepatocytes).[68,69] A slower decay in the setting of HIV infection (see Fig. 1b) could explain why the early discontinuation of therapy might result in higher relapse rates in virological responders. Recent data support this notion, and make it necessary to reconsider how long anti-HCV therapy should be extended in HIV-HCV-positive early virological responders.[57,66] This observation seems to apply particularly to HCV genotype 3, because relapses are uncommon in HIV-negative individuals infected with this genotype, whereas it occurs in up to a third of HIV-HCV-co-infected patients who receive anti-HCV therapy for only 6 months, following what is recommended in HIV-negative individuals.[3] Further studies examining extended periods of anti-HCV therapy (i.e. 12 months in HCV genotypes 2 and 3, and up to 18 months in HCV genotypes 1 and 4) should be conducted in early virological responders to examine whether this strategy may reduce their chance of relapse.

Recent reports have shown that HCV-monoinfected patients who do not clear HCV-RNA on anti-HCV treatment, might benefit from long-term therapy with IFN alone.[70,71,72] Maintenance therapy with IFN may provide histological improvement and even reduce the risk of hepatocellular carcinoma, and is currently being investigated as an alternative approach in large trials in HCV-monoinfected patients (HALT-C and EPIC). Whether this strategy may be considered in some HIV-HCV-co-infected individuals with advanced fibrosis who did not respond virologically to anti-HCV therapy should be investigated further. The use of lower doses of peg-IFN (half those recommended as first line) may improve tolerance and facilitate long-term administration of the drug.

Panel Recommendation

Early virological response to anti-HCV therapy predicts the chance of sustained response in HIV-co-infected patients as it does in HCV-monoinfected individuals. Moreover, the use of an early timepoint for treatment decision-making seems to be equally appropriate in co-infected patients. Only patients showing a decline in serum HCV-RNA levels greater than 2 logs at 12 weeks on therapy will have chance of reaching a sustained response. Therefore, treatment might be discontinued in the rest. This is of particular relevance, given the concern about the risk of toxicity derived from interactions between anti-HCV therapy and antiretroviral drugs. SCORE: C.II

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