Tenofovir showed long-term antiviral activity against hepatitis B virus (HBV) lasting 5 to 8 years, with minimal evidence of kidney toxicity, and HBsAg levels declined steadily over time, according to 2 posters presented this week at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) in San Francisco.
Tenofovir (Viread, also in the Truvada and Atripla coformulations) is active against both HIV and HBV, and treatment guidelines recommend that it be included in antiretroviral therapy (ART) regimens for HIV/HBV coinfected patients. U.S. and European guidelines also recommend that HIV/HBV coinfected people consider earlier ART initiation. HBV Viral Load Decline In the first study, Olivier Lada and colleagues conducted a retrospective analysis of the long-term efficacy and renal (kidney) safety of tenofovir-containing therapy among 166 HIV/HBV coinfected patients followed at Bichat Claude Bernard Hospital in Paris between 2003 and 2008. Nearly 90% were men and the median age was about 42 years.
Within this cohort, 141 (86%) had been treated with tenofovir; 15 had started treatment with tenofovir plus lamivudine (3TC; Epivir) or emtricitabine (Emtriva) -- both of which are also dually active against HIV and HBV -- while 46 added tenofovir to existing lamivudine therapy. The median duration of tenofovir use was 46 months years (range 25 to 72 months).
The researchers identified 61 coinfected patients who had detectable HBV DNA at baseline (> 2.3 log IU/mL), 57 with undetectable HBV viral load, and 23 with unavailable data. Results
Patients treated with tenofovir-containing regimens had a median CD4 T-cell count of 309 cells/mm3 at baseline, rising to 502 cells/mm3 at the last follow-up visit.
66% had HIV RNA < 50 copies at baseline, compared with 100% at the last visit.
HBV DNA levels fell from a median of 5.9 log IU/mL at baseline to < 1.3 log at the last visit.
All tenofovir-treated patients had undetectable HBV viral load at the end of follow-up.
No HBV virological breakthrough was observed during a median of about 5 years on tenofovir.
22% experienced hepatitis B "e" antigen (HBeAg) and 4% had hepatitis B surface antigen (HBsAg) loss.
3 people had elevated ALT at baseline, but none did so at the last visit.
No patients showed clinically relevant changes in kidney function.
The median creatinine level -- an indicator of potential kidney impairment -- was about the same at baseline and at the last visit (79 vs 80 mcmol/L).
Estimated glomerular filtration rate (GFR) by the MDRD method was 103.5, in the normal range for the study population's age.
Based on these findings, the researchers concluded, "[Tenofovir] associated with lamivudine or emtricitabine showed significant and sustained antiviral activity against HBV in HIV-coinfected patients."
"A good renal safety profile of [tenofovir] was observed after a median follow-up of 5 years of therapy," they continued, but recommended that patients with pre-existing renal insufficiency should nevertheless be carefully monitored. HBsAg Changes In the second study, Roeland Zoutendijk from Erasmus Medical Center in Rotterdam and colleagues looked at HBsAg changes during long-term tenofovir treatment, with the aim of learning more about HBV clearance.
This multicenter analysis included 104 HIV/HBV coinfected patients treated with ART regimens containing tenofovir. Again, most (about 90%) were men, the age range was similar, and about 60% were white; about two-thirds were HBeAg positive at baseline.
The investigators measured HBsAg levels at baseline, month 6, and then annually; the median duration of follow-up was 56 months (range 8-97 months). HBsAg clearance is generally considered a cure, though "occult: or hidden HBV may remain. Results
At baseline, HBsAg was significantly higher among HBeAg positive patients compared with HBeAg negative people (4.6 vs 2.8 log IU/mL).
5 HBeAg positive people (8%) and 3 HBeAg negative people (also 8%) achieved HBsAg loss.
HBsAg levels declined steadily among HBeAg positive people, but the decrease was smaller among HBeAg negative patients.
In HBeAg positive patients, immune reconstitution -- as indicated by higher CD4 cell counts at months 6 and 12 -- was correlated with HBsAg decline.
HBeAg positive patients with month 6 HBsAg levels <100 IU/mL had about a 70% probability of HBsAg loss, compared with none of the participants with HBsAg >100 IU/mL.
Extrapolating these numbers, the researchers estimated that the estimated median time to HBsAg loss would be about 18 years for HBeAg positive people and 41 years for HBeAg negative patients.
"HBsAg levels declined steadily, particularly in HBeAg positive patients, during [tenofovir treatment] up to 8 years in HIV/HBV coinfected patients," the investigators concluded. "On-treatment correlation between CD4 count and HBsAg decline indicates a possible role of immune reconstitution in HBsAg loss," they suggested. Investigator affiliations: Abstract 1428: Hepatologie, Hopital Beaujon and INSERM U773 CRB3, Clichy, France; Service des Maladies Infectieuses et Tropicales, AP-HP Hôpital Bichat Claude Bernard, Paris, France; Laboratoire de Virologie, Service de Microbiologie, AP-HP Hôpital Bichat Claude Bernard, Paris, France; Service de pharmacie, AP-HP Hôpital Bichat Claude Bernard, Paris, France. Abstract 1378: Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands; Medical Microbiology and Karl Landsteiner Laboratory, Academic Medical Center, Amsterdam, Netherlands; Internal Medicine-Infectious Diseases, Erasmus MC, Rotterdam, Netherlands; Internal Medicine, Slotervaart Hospital, Amsterdam, Netherlands; Infectious Diseases, Leids University Medical Center, Leiden, Netherlands; Internal Medicine, Rijnstate Hospital, Arnhem, Netherlands; Virology, Erasmus MC, Rotterdam, Netherlands.
11/8/11 References
O Lada, A Gervais, M Branger, et al. Long-Term Efficacy and Safety of Tenofovir for Treatment of HIV/HBV-Coinfected Patients. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 1428.
R Zoutendijk, HL Zaaijer, T de Vries-Sluijs, et al. Tenofovir treatment for up to eight years results in pronounced HBsAg decline in HBeAg-positive HIV/HBV co-infected patients. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 1378.
It is good to know that: 3 HBeAg negative people (also 8%) achieved HBsAg loss
However, I remember that there was a 4 year tenofovir efficacy study (102 hbeag - and 103 hbeag +) by Gilead show that there was 0% hbeag - patients achieve loss of hbsag. Please reference the following:
No, I find it difficult to generalize about HBV - there are too many variables: individual factors, viral factors, and mutations. As I stated, the results related to HIV/HBV co-infected patients. However, I wanted to show the kinetics of HBsAg levels during treatment, generally.
