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a substantial proportion of HIV-infected patients are chronically infected with hepatitis C virus (HCV), hepatitis B virus (HBV), or both. How best to treat these patients is still under investigation and was the focus of several presentations at the 14th Retrovirus Conference.
As previously reported, entecavir’s package insert was changed this year, based on findings that the drug may have modest anti-HIV activity not noted in previous trials (ACC Mar 5 2007). Now, for the first time, investigators have described the data that led to this change [Abstract 136LB]. Three patients at a single institution had at least a 1-log drop in HIV RNA while receiving entecavir for concurrent HBV infection. In one prospectively followed patient, the M184V mutation was not seen in any clones at the start of entecavir treatment, but it was observed in 61% of clones at 4 months and in 98% at 6 months. The patient had previously received a 3TC-containing antiretroviral regimen, which might have influenced these findings. In an in vitro single-cell assay using an HIV pseudovirus and CD4 lymphoblasts, entecavir inhibited HIV at the subnanomolar level. Even more disturbing was that the M184V mutation, which renders 3TC and FTC ineffective, was induced in HIV exposed to entecavir.
Although these findings conflict with those of previous studies, the discrepancy could be explained by the new sensitive assay used. Alternatively, the conditions produced through use of a pseudovirus and transformed CD4 cells might be different from those encountered in patients. Although this reasoning still does not explain the viral-load drop observed in some patients, those patients could have been taking additional antiviral medications without the knowledge of their treating physicians. Given that entecavir is currently the drug of choice for coinfected patients who do not yet require anti-HIV therapy, these findings must be reevaluated in additional studies. Furthermore, to avoid similar late surprises with other drugs, we should encourage or even force the pharmaceutical industry to include HIV-infected patients earlier in trials of treatments and vaccines for syndemic conditions (tuberculosis, sexually transmitted infections, hepatitis).
In other hepatitis-related studies at the conference, a double dose of HBV vaccine given monthly for 3 months was shown to induce a response in 51% to 87% of HIV-infected patients whose first vaccine series had failed [Abstracts 883 and 884]. A three-dose vaccine for hepatitis A virus was associated with significantly higher response rates in HIV-infected patients than was a two-dose vaccine (71% vs. 58%) [Abstract 885]. Finally, in HCV-coinfected patients, antiretroviral regimens including 3TC with either d4T or tenofovir were associated with higher rates of sustained response to interferon and ribavirin [Abstract 898], whereas regimens containing abacavir were associated with much worse response rates, probably because of a ribavirin interaction [Abstract 897].