6th IAS Conference On HIV Pathogenesis, Treatment and Prevention


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WEPDB0103 - Poster Discussion Session

Virological efficacy of the four tenofovir-containing WHO-recommended regimens for initial antiretroviral therapy

Presented by Michele Tang (United States).

M. Tang1, P. Kanki2, R. Shafer1

1Stanford University School of Medicine, Infectious Diseases, Stanford, United States, 2Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, United States

Background: The 2010 WHO Antiretroviral (ARV) Treatment Guidelines have added four new ARV regimens for first-line therapy: tenofovir (TDF) plus lamivudine (3TC) plus nevirapine (NVP), TDF plus emtricitabine (FTC) plus NVP, TDF plus 3TC plus efavirenz (EFV), and TDF plus FTC plus EFV. It is not known, however, whether each of these new regimens are equally efficacious or even as efficacious as the older non-TDF-containing dual NRTI / NNRTI regimens.
Methods: We systematically reviewed published studies and abstracts of the virological efficacy of the four TDF-containing regimens for initial ARV therapy.
Results: Thirty prospective and retrospective studies assessed the efficacy of one or more of the four TDF-containing regimens: TDF/3TC/NVP (3 studies), TDF/FTC/NVP (9 studies), TDF/3TC/EFV (7 studies), and TDF/FTC/EFV (13 studies). Two of the studies included more than one TDF-containing regimen of interest. In most studies, TDF/FTC/NVP, TDF/3TC/EFV, and TDF/FTC/EFV were equivalent or superior to their respective comparator arms. In contrast, TDF/3TC/NVP was inferior to AZT/3TC/NVP in two of three studies: in one of these two studies and in a third open-label study, high rates of virological failure and drug resistance led to premature study discontinuation. Virological failure and the multi-nucleoside resistance mutation K65R occurred commonly among those receiving TDF/3TC/NVP, occasionally among those receiving TDF/3TC/EFV or TDF/FTC/NVP, and rarely among those receiving TDF/FTC/EFV.
Conclusion: TDF/3TC/NVP is the least well-studied and appears to be the least efficacious of the four WHO-recommended TDF-containing regimens. The apparent inferiority of TDF/3TC/NVP compared with AZT/3TC/NVP despite the greater antiviral activity of TDF compared with AZT underscores that ARV regimens are more than the sum of their parts. Further study of the TDF/3TC/NVP regimen is urgently required before this regimen is widely deployed for initial ARV therapy.

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