Early Virologic Nonresponse to Tenofovir, Abacavir, and Lamivudine in HIV-Infected Antiretroviral-Naive Subjects

Gallant, Joel E.; Rodriguez, Allan E.; Weinberg, Winkler G.; Young, Benjamin; Berger, Daniel S.; Lim, Michael L.; Liao, Qiming; Ross, Lisa; Johnson, Judy; Shaefer, Mark S.
December 2005
Journal of Infectious Diseases;12/1/2005, Vol. 192 Issue 11, p1921
Academic Journal
Background. Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. Methods. This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log10 copies/mL decrease in HIV- 1 RNA level by week 8, (2) an HIV-1 RNA rebound of ⩾1.0 log10 copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions. Results. We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log10 copies/mL and 251 cells/mm³, respectively; 194 subjects with HIV-1 RNA data from ⩾8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P < .001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL. Conclusion. The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.


Related Articles

  • Integrase variability and susceptibility to HIV integrase inhibitors: impact of subtypes, antiretroviral experience and duration of HIV infection. Garrido, Carolina; Geretti, Anna Maria; Zahonero, Natalia; Booth, Clare; Strang, Angela; Soriano, Vincent; De Mendoza, Carmen // Journal of Antimicrobial Chemotherapy (JAC);Feb2010, Vol. 65 Issue 2, p320 

    Background: Little is known about the extent and predictors of polymorphisms potentially influencing the susceptibility to HIV integrase inhibitors (INIs).

  • The financial and service implications of splitting fixed-dose antiretroviral drugs – a case study. Taylor, R; Carlin, E; Sadique, Z; Ahmed, I; Adams, EJ // International Journal of STD & AIDS;Feb2015, Vol. 26 Issue 2, p75 

    In 2010/2011, regional commissioners withdrew payment for the fixed-dose combination Combivir, forcing a switch to component drugs. This was deemed clinically acceptable and annual savings of £44 k expected. We estimated the true costs of switching and examined patient outcomes....

  • Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection. Ananworanich, Jintanat; Schuetz, Alexandra; Vandergeeten, Claire; Sereti, Irini; De Souza, Mark; Rerknimitr, Rungsun; Dewar, Robin; Marovich, Mary; Van Griensven, Frits; Sekaly, Rafick; Pinyakorn, Suteeraporn; Phanuphak, Nittaya; Trichavaroj, Rapee; Rutvisuttinunt, Wiriya; Chomchey, Nitiya; Paris, Robert; Peel, Sheila; Valcour, Victor; Maldarelli, Frank; Chomont, Nicolas // PLoS ONE;Mar2012, Vol. 7 Issue 3, p1 

    Background: Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy. Methods and Findings:...

  • Predictors of Virologic Failure and Resistance in HIV-Infected Patients Treated with Nevirapine-or Efavirenz-Based Antiretroviral Therapy. Parienti, Jean-Jacques; Massari, Véronique; Descamps, Diane; Vabret, Astrid; Bouvet, Elisabeth; Larouzé, Bernard; Verdon, Renaud // Clinical Infectious Diseases;5/1/2004, Vol. 38 Issue 9, p1311 

    Resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) increases with the wider use of this class of antiretroviral therapy. The association between adherence and resistance to NNRTI-based regimens is poorly understood. Predictors of virologic failure and resistance according to a...

  • Pharmacogenomics -- Implications in the Development of HIV-Associated Brain Disease. Nolting, Thorsten; Arendt, Gabriele // Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry;Jun2009, Vol. 8 Issue 2, p164 

    Pharmacogenomics is a relatively new field in HIV-research, especially when neurological issues are concerned. Influence of polymorphisms in CYP3A4, CYP2B6, CYP2D6, ABCB1, ABCG2, ABCC4, SLC22, SLC28, SLC29 and MMP9-genes on pharmacokinetic data is discussed in the article. Due to the lack of...

  • Significantly Improved HIV Inhibitor Efficacy Prediction Employing Proteochemometric Models Generated From Antivirogram Data. van Westen, Gerard J. P.; Hendriks, Alwin; Wegner, Jörg K.; IJzerman, Adriaan P.; van Vlijmen, Herman W. T.; Bender, Andreas // PLoS Computational Biology;Feb2013, Vol. 9 Issue 2, Special section p1 

    Infection with HIV cannot currently be cured; however it can be controlled by combination treatment with multiple anti- retroviral drugs. Given different viral genotypes for virtually each individual patient, the question now arises which drug combination to use to achieve effective treatment....

  • Phosphodiesterase 8a Supports HIV-1 Replication in Macrophages at the Level of Reverse Transcription. Booiman, Thijs; Cobos Jiménez, Viviana; van Dort, Karel A.; van 't Wout, Angélique B.; Kootstra, Neeltje A. // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    Background: HIV-1 infected macrophages play a key role in HIV-1 infection. Even during anti-retroviral treatment, macrophages keep producing virus due to suboptimal tissue penetration and reduced efficacy of antiretrovirals. It is therefore of major importance to understand which host factors...

  • Clinical utility and consumer considerations for the use of once-daily nevirapine extended release for HIV infection treatment. Pefura Yone, Eric W.; Kengne, André P. // HIV/AIDS - Research & Palliative Care;2012, Vol. 4, p181 

    An extended-release formulation of nevirapine (NVP-XR) has been developed with the aim of simplifying antiretroviral treatment regimens and improving patients' adherence with a single daily intake. The VERxVE and TRANxITION clinical trials have demonstrated the noninferiority of NVP-XR compared...

  • CONTROLLED AND SUSTAINED RELEASE APPROACHES IN DEVELOPING SUITABLE DOSAGE FORMS FOR THE ANTIRETROVIRAL DRUG LAMIVUDINE. Vamshi Alla, Krishna; Praveen Kumar, Gannu; Cheruku, Vishvasa; Jannu, Anand; Kumari Bairi, Chaitanya // International Journal of Pharmaceutical Sciences Review & Resear;May/Jun2011, Vol. 8 Issue 1, p21 

    Lamivudine is a Nucleoside Reverse Transcriptase Inhibitor (NRTI), licensed for the treatment of HIV, and chronic Hepatitis B. The pharmacokinetic data of Lamivudine shows that, frequent administration for a prolonged period of time (lifelong in AIDS and for one year in hepatitis patients) is...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics