Telbivudine exerts no antiviral activity against HIV-1 in vitro and in humans.
BACKGROUND
HIV-HBV-coinfected individuals who need to be treated only for their HBV infection have limited therapeutic options, since most approved anti-HBV agents have a risk of selecting for drug-resistant HIV mutants. In vivo data are inconclusive as to whether telbivudine (LdT) may exert antiviral effects against HIV. Thus, we investigated in further detail the antiviral activity and the biochemical properties of LdT against HIV-1.


METHODS
To investigate the activity of LdT against HIV-1 in humans we analysed viral dynamics and genotypic and phenotypic resistance development in two HIV-HBV-coinfected individuals with no prior antiviral exposure. To investigate the activity of LdT against HIV-1 in vitro, LdT susceptibility for HIV-1 wild-type strains as well as drug-resistant strains was determined. Furthermore, we studied whether the 5'-triphosphate form of LdT (LdT-TP) can act as a substrate for wild-type HIV-1 RT.


RESULTS
In the two patients studied, LdT treatment did not result in a significant decline of HIV-1 RNA load nor in selection of genotypic or phenotypic resistance in HIV-1 RT. In vitro virological analyses demonstrated that LdT had no activity (50% effective concentration >100 μM) against wild type HIV and drug-resistant variants. Biochemical analyses demonstrated that LdT-TP is not incorporated by wild-type HIV-1 RT.


CONCLUSIONS
Based on the in vivo and in vitro evidence obtained in this study, we conclude that LdT has no anti-HIV-1 activity and is currently the only selective anti-HBV agent among the five FDA-approved nucleoside/nucleotide analogues for treatment of HBV infections in HIV-infected individuals.
Department of Medical Microbiology, Virology, University Medical Center Utrecht, Utrecht, The Netherlands. N.M.vanMaarseveen-2@umcutrecht.nl
Noortje M
NM
van Maarseveen
Annemarie Mj
AM
Wensing
Dorien
D
de Jong
Greg L
GL
Beilhartz
Aleksandr
A
Obikhod
Sijia
S
Tao
Marieke
M
Pingen
Joop E
JE
Arends
Andy Im
AI
Hoepelman
Raymond F
RF
Schinazi
Matthias
M
Götte
Monique
M
Nijhuis
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002460:Cell Line; D060085:Coinfection; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005838:Genotype; D057809:HEK293 Cells; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D010641:Phenotype; D011744:Pyrimidinones / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D009705:Nucleosides; D011744:Pyrimidinones; D012367:RNA, Viral; D000077712:Telbivudine; D013936:Thymidine