Antiretroviral Efficacy and Virological Profile of a Zidovudine/Lamivudine/Tenofovir Disoproxil Fumarate Combination Therapy in Antiretroviral-Naive Patients
Free accessAnnouncementFirst published online August, 2006
Antiretroviral Efficacy and Virological Profile of a Zidovudine/Lamivudine/Tenofovir Disoproxil Fumarate Combination Therapy in Antiretroviral-Naive Patients
To study the antiviral efficacy and the mutations selected by a triple therapy with zidovudine (AZT), lamivudine (3TC) and tenofovir disoproxil fumarate (TDF).
Methods
Antiretroviral-naive patients received 300 mg AZT/150 mg 3TC twice a day plus 300 mg TDF once a day in an open pilot study. Follow-up was assessed at baseline therapy (M0) and at months 1, 3, 6, 9 and 12. Reverse transcriptase (RT) genotypic resistance analysis and in selected cases, a recombinant drug susceptibility and replication capacity assay were performed from plasma RNA at baseline and in case of virological failure (VF); that is, rebound of viral load >50 copies/ml on therapy.
Results
Twenty-four patients were included. At baseline, the median CD4+ T-cell count was 443 cells/μl and the median plasma viral load (VL) was 4.38 log10 copies/ml. RT resistance mutations were observed at M0 in 4 patients. At M12, the proportion of patients with a VL <50 copies/ml reached 88% using an on-treatment analysis and 67% with an intent-to-treat analysis. The median increase in CD4+ T cells at M12 was 94 cells/μl. Four patients had a VF on therapy: two with wild-type viruses, one with selection of M184V and thymidine analogue mutations (TAMs) on a background of TAMs, and one with selection of K65R and M184V, with a replication capacity at 2.4%.
Conclusion
The virological response in our study demonstrates the antiviral efficacy of the AZT/3TC/TDF combination therapy, which needs further evaluation. The moderate frequency of selection of K65R could be due to the presence of AZT in the regimen.
References
1.
KhanlouH., YehV., GuyerB., FarthingC.Early virologic failure in a pilot study evaluating the efficacy of therapy containing once-daily abacavir, lamivudine, and tenofovir DF in treatment-naive HIV-infected patients.AIDS Patient Care STDS2005; 19: 135–140.
2.
GallantJ.E., RodriguezA.E., WeinbergW.G.Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects.J Infect Dis2005; 192: 1921–1930.
3.
LandmanR., DescampsD., PeytavinG.Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study.HIV Clin Trials2005; 6: 291–301.
4.
JemsekJ., HutchersonP., HarperE.Poor virologic responses and early emergence of resistance in treatment naive, HIV-infected patients receiving a once daily triple nucleoside regimen of didanosine, lamivudine, and tenofovir DF.11th Conference on Retroviruses and Opportunistic Infections. 8–11 February 2004, San Francisco, CA, USA. Abstract 51.
5.
SchooleyR.T., RuaneP., MyersR.A.Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study.AIDS2002; 16: 1257–1263.
6.
MargotN.A., IsaacsonE., McGowanI., ChengA., MillerM.D.Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses.J Acquir Immune Defic Syndr2003; 33: 15–21.
7.
MillerM.D., MargotN., LuB., ZhongL., ChenS.S., ChengA., WulfsohnM.Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients.J Infect Dis2004; 189: 837–846.
8.
MasquelierB., TamaletC., MontesB.Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.Antivir Ther2004; 9: 315–323.
9.
BoucherS., Recordon-PinsonP., RagnaudJ., DuponM., FleuryH., MasquelierB.K65R prevalence and genotypic patterns in patients failing tenofovir DF-containing regimens.2nd European HIV Drug Resistance Workshop: From Basic Science to Clinical Implications. 11–13 March 2004, Rome, Italy. Abstract 51:P4.9.
10.
ParikhU., KoontzD., Sluis-CremerN.K65R: a multi-nucleoside resistance mutation of increasing prevalence exhibits bi-directional phenotypic antagonism with TAM.11th Conference on Retroviruses and Opportunistic Infections. 8–11 February 2004, San Francisco, California. Abstract 54.
11.
WhiteK., MargotN., ChenJ.M.The HIV-1 K65R RT mutant utilizes a combination of decreased incorporation and decreased excision to evade NRTI.11th Conference on Retroviruses and Opportunistic Infections. 8–11 February 2004, San Francisco, California. Abstract 55.
12.
DeeksS.G., WrinT., LieglerT.Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia.N Eng J Med2001; 344: 472–480.
13.
PetropoulosC.J., ParkinN.T., LimoliK.L.A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1.Antimicrob Agents Chemother2000; 44: 920–928.
14.
ViolinM., Cozzi-LepriA., VellecaR.Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy.AIDS2004; 18: 227–235.
15.
KaleebuP., and the DART Trial Team. 48 week virological response to a triple nucleoside/nucleotide analogue regimen in adults with HIV infection in Africa within the DART trial.3rd International AIDS Society Conference on Pathogenesis and Treatment. 24–27 July 2005, Rio de Janeiro, Brasil,. Abstract LB0203.
