1. Home>
2. Specialties>
3. HIV/AIDS Clinical Care>
4. Summary and Comment

Resistance Development with Tenofovir/FTC vs. AZT/3TC

In a comparative clinical trial, patients receiving tenofovir/FTC were less likely to develop resistance mutations during virologic failure than were those receiving AZT/3TC.

Tenofovir/FTC has become the preferred dual-NRTI combination for initial antiretroviral therapy (ART), based in part on the results of Study 934, which demonstrated the virologic and tolerability advantages of tenofovir/FTC over AZT/3TC (JW AIDS Clin Care Feb 1 2006). Now, in a continued analysis of that study, researchers have investigated the effects of baseline NRTI and NNRTI resistance on treatment response and the patterns of resistance that emerged during treatment failure.

Study 934 was an open-label trial (sponsored by the maker of tenofovir/FTC) in which 509 treatment-naive patients were randomized to receive tenofovir/FTC or AZT/3TC, each together with efavirenz. Participants with virologic failure (19 in the tenofovir/FTC arm and 31 in the AZT/3TC arm) were evaluated for genotypic resistance. The most commonly seen mutations in both treatment arms were K103N and other NNRTI resistance mutations. Both the M184V mutation and multiclass resistance were less prevalent with tenofovir/FTC than with AZT/3TC. Levels of adherence, as measured by pill counts, were similar between treatment arms.

Although resistance testing was performed on baseline samples, results were not available before treatment initiation. Twenty-two patients were found to have a baseline primary NNRTI mutation, most commonly K103N; investigators were promptly notified, at which time 20 patients were discontinued from study medications, including nine individuals who had already experienced virologic failure. Seven of these nine patients developed additional mutations conferring resistance against NRTIs. Only two participants with baseline K103N mutations had durable virologic suppression on an efavirenz-containing regimen through 144 weeks of follow-up. NRTI resistance mutations were rarely seen at baseline, and even when detected, they were not associated with an increased risk of virologic failure.

Comment: These results provide evidence of an additional benefit of tenofovir/FTC over AZT/3TC, namely the lower risk of drug resistance in treatment failure. The superiority of tenofovir/FTC could not be explained by better adherence to the simpler regimen; instead, it may involve pharmacokinetics, because both tenofovir and FTC have longer intracellular half-lives than AZT and 3TC. Individuals with baseline NNRTI resistance not only had a high rate of treatment failure but also accumulated NRTI resistance mutations along the way. These findings reinforce the importance of genotypic drug resistance testing prior to ART initiation.

— Jonathan Z. Li, MD, and Paul E. Sax, MD

Dr. Li is a Fellow in the Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

Published in Journal Watch HIV/AIDS Clinical Care October 19, 2009

Citation(s):

Margot NA et al. Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naïve subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. J Acquir Immune Defic Syndr 2009 Oct 1; 52:209.

• Medline abstract (Free)

Reader Remarks:

Read all Reader Remarks on this article

• tenofovir resistance
  saka venkat satyaprasad, 21 Oct 2009 1:43 AM EST
  The study for deteection of resistance to AZT VS TENOFOVIR is interesting. AZT the most widely used drug is subject... [more]