Treatment of HBV or HCV in triple-infected individuals not seen to cause rebound of untreated virus

A small retrospective study has found that, in people coinfected with HIV, hepatitis B and hepatitis C, treatment of either viral hepatitis infection does not seem to result in reactivation of the other. The findings were published in the April 15^th edition of the Journal of Infectious Diseases.

Between 3 - 5% of people with HIV are also infected with both hepatitis B virus (HBV) and hepatitis C (HCV). A “reciprocal inhibition” is usually seen with dual HBV/HCV infection; i.e., one or the other of the viruses tends to predominate, and active viral replication of both HBV and HCV is rarely seen simultaneously. This has led to concerns that HBV- or HCV-suppressive treatment could lead to reactivation of the other virus.

However, a retrospective Spanish study of triply-infected individuals did not find evidence of such outcomes. The study looked at 21 patients from an HIV clinic in Madrid, all of whom were antibody-positive for HIV, HBV and HCV. The group median age was 39, all were white, 19 were male, 19 were former injection drug users, and median CD4 counts were 427 cells/mm³. None had undergone HIV or HCV treatment before the year 2000. People were considered viremic for HBV if they had detectable HBV DNA, and viremic for HCV if they had detectable HBV RNA.

Of the 21, four also had antibodies to hepatitis D virus (HDV). Hepatitis D is known to suppress other hepatitis viruses, and in fact none of the HDV-positive people were viremic for HBV. Low-level HCV viremia was seen in one (who had a CD4 cell count of 96 cells/mm³).

Of the remaining 17, nine were viremic for HBV only (i.e., had measurable blood plasma HBV DNA), five were viremic for HCV (plasma HCV RNA), two had both, and one had no detectable HBV or HCV in the blood plasma.

Results: HCV-viremic only

All five of the patients with detectable HCV RNA only were treated with pegylated interferon-alpha and weight-dosed ribavirin. Treatment success was mixed – the two with HCV genotype 1 relapsed after treatment, while the three with genotype 3 had sustained HCV virologic response. However, even though none of the five received tenofovir or 3TC during the study period, none became HBV-viremic either during or after HCV treatment (although such rebounds have been reported in other reports). The researchers believe this observation “warrants further study and monitoring for longer periods.”

Results: HBV-viremic only

All nine of the patients with detectable HBV DNA only, plus the three who were HDV-antibody positive but not HCV viremic, received HIV antiretroviral therapy that included tenofovir and/or 3TC (both of which are active against HBV). The level of HBV viremia dropped to undetectable levels in all but one of these patients within one year (half were undetectable by week 24). More rapid decreases were seen with tenofovir than with 3TC.

No rebounds in HCV viremia were seen in any of these dozen patients, even after a year of follow-up. The researchers suggest “that HCV had already been eradicated in these subjects, either spontaneously or as a result of continued HBV interference.”

Results: dual viremia

The two patients who were viremic for both HBV and HCV received HCV treatment as well as antiretrovirals including tenofovir and/or 3TC. After one year, both viruses were undetectable in blood serum; unfortunately, HCV viremia rebounded in both after the completion of twelve months interferon-based therapy.

The researchers conclude “the reciprocal inhibitory interaction between HBV and HCV also occurs in HIV-infected patients, at least in those without severe immunosuppression. A careful virologic assessment is warranted… to ascertain which virus is replicating and which is suppressed, so that that appropriate therapeutic decision can be made.” Regarding the consequences of treating HBV and HCV, “our findings suggest that complete suppression of the dominant virus … is generally not followed by a rebound of the other virus.”