Treatment of hepatitis B with lamivudine and tenofovir in HIV/HBV‐coinfected patients: factors associated with response

Abstract

As therapy for human immunodeficiency virus (HIV) infection evolves, optimizing hepatitis B virus (HBV) treatment and identifying factors that impact its response in the HIV/HBV-coinfected population is critical. We identified retrospectively 45 HBV/HIV-coinfected patients with detectable HBV DNA by the Bayer VERSANT HBV 3.0 bDNA assay (limit of quantification 2000 copies/mL) at baseline and/or year 1 of therapy. Patients were divided into three groups based on the active HBV agent in their antiretroviral regimen: group 1 (n = 15) received lamivudine; group 2 (n = 10), lamivudine plus tenofovir and group 3 (n = 20), lamivudine followed by lamivudine plus tenofovir. HBV genotypes and resistance profiles were determined by the Bayer Trugene HBV 1.0 assay. More patients in group 2 achieved HBV DNA suppression below 2000 copies/mL (80%), loss of HBe antigen (HBeAg) (40%) and loss of HBeAg and gain of anti-HBe (20%) than did patients in group 1 or 3. More patients with HBV genotype A, achieved HBV DNA suppression <2000 copies/mL than did patients with non-A genotypes [74% (26/35) vs 20% (2/10)], respectively (P = 0.003). Risk for virological nonresponse was significant in those with non-A genotypes [odds ratio (OR) 11.1; 95% CI: 2.0-50], previous HIV therapy (OR 6.5; 95% CI: 1.2-35) and <90% compliance (OR 3.7; 95% CI: 0.99-14.3). Simultaneous therapy with lamivudine/tenofovir suppresses HBV DNA more effectively than lamivudine or tenofovir added to lamivudine. More patients infected with HBV genotype A responded than the non-A patients, regardless of therapeutic regimen, compliance or prior HIV therapy.

Tenofovir and its potential in the treatment of hepatitis B virus

“…Also Jain et al demonstrate that infection with genotypes G, A/G, F and D is signifi cantly associated with non-response. 1,32,33 In contrast, Lacombe et al concluded in their study that baseline HBV genomics such as genotype did not infl uence HBV decay; similar results had been reported previously with LAM and ADV. 14,34,35 Stephan et al showed that patients with high-replicative virus may benefit from TDF therapy with a reduction in replicative status while subjects with low-level HBV replication who become undetectable HBV DNA and HBsAg carriers remain DNA negative.…”

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…Resistance is rare and combination with 3TC or FTC has been demonstrated to be effective at suppressing HBV DNA and may induce HBeAg seroconversion. Combining 3TC/FTC with tenofovir may reduce the risk of breakthrough [137].…”

“…If renal toxicity precludes the use of tenofovir, entecavir is an option that can be used along with a fully active antiretroviral regimen [137].…”

“…3TC/FTC-resistant strains will normally respond to tenofovir [118][119][120][121][122][123][134][135][136][137] Tenofovir is effective at suppressing HBV DNA and may induce HBeAg seroconversion although, as for other antivirals in coinfection, this may be less likely than in an HIV-negative person [127,[134][135][136]. Resistance is rare and combination with 3TC or FTC has been demonstrated to be effective at suppressing HBV DNA and may induce HBeAg seroconversion.…”

Current and future antiviral drug therapies of hepatitis B chronic infection

“…It has been shown to have an additive suppression effect on viral replication when administered in combination with lamivudine, entecavir or telbivudine [47,48] .…”