[21] RATE OF VIROLOGICAL FAILURE AND RESISTANCE MUTATIONS IN ANTIRETROVIRAL-EXPERIENCED PATIENTS SHIFT TO A QD SIMPLIFICATION REGIMEN WITH DIDANOSINE, TENOFOVIR AND EFAVIRENZ (EFADITE TRIAL)

14th International HIV Drug Resistance Workshop

7-11 June 2005, Québec City, Canada

RATE OF VIROLOGICAL FAILURE AND RESISTANCE MUTATIONS IN ANTIRETROVIRAL-EXPERIENCED PATIENTS SHIFT TO A QD SIMPLIFICATION REGIMEN WITH DIDANOSINE, TENOFOVIR AND EFAVIRENZ (EFADITE TRIAL)

Antivir Ther. 10, Suppl 1:S23 (abstract no. 21)

L Valer¹, A Barrios¹, P Domingo², P Labarga³, E Negredo⁴, J Vilaró-Rodríguez², V Estrada⁵, V Asensi⁶, D Morales⁷, J Gálvez⁷, J Santos⁸, J-A Terrón⁹, E Casas¹⁰, M Riera¹¹, A Vergara¹², E Pérez Guzmán¹³, MJ Galindo¹⁴, I Maida¹, L Martín-Carbonero¹, P Barreiro¹, T García-Benayas¹, M Núñez¹, F Blanco¹, J González-Lahoz¹, B Clotet² and V Soriano¹
¹ Hospital Carlos III, Madrid, Spain ² Hospital de Sant Pau, Barcelona, Spain ³ Hospital de San Millán, Logroño, Spain ⁴ Hospital Germans Trias i Pujol, Barcelona, Spain ⁵ Hospital Clínico San Carlos, Madrid, Spain ⁶ Hospital Central de Asturias, Oviedo, Spain ⁷ Hospital Virgen Macarena, Sevilla, Spain ⁸ Hospital Virgen de la Victoria, Málaga ⁹ Hospital de Jerez, Cádiz, Spain ¹⁰ Hospital Príncipe de Asturias, Alcalá, Spain ¹¹ Hospital Son Dureta, Mallorca, Spain ¹² Hospital de Puerto Real, Cádiz, Spain ¹³ Hospital Puerta del Mar, Cádiz, Spain ¹⁴ Hospital Clínico, Valencia, Spain

BACKGROUND: The use of antiretroviral regimens based on ddI-TDF has attracted much attention due to the pharmacokinetic interaction of this combination. Moreover, high rates of virological failure have been reported using ddI-TDF in drug-naïve individuals.

METHODS: The EFADITE trial was a prospective, multicentre, open label, comparative study in which HIV+ patients on HAART and with plasma HIV-RNA <50 cop/ml for >6 months were switched to TDF (300 mg) + ddI (250 or 400 mg) + EFV (600 mg) (QD arm) or remained on the same treatment regimen (control arm). Patients who subsequently developed grade 4 toxicities or repeatedly plasma HIV-RNA values >1000 cop/ml dropped out their assigned treatment arm.

RESULTS: A total of 390 patients were included in the trial (309 in the QD arm and 81 in the control arm). Baseline characteristics were well balanced between groups (median CD4 count: 558 and 581 cells/ml, respectively). Overall, 39% had received high and 61% low ddI doses. At 12 months, plasma HIV-RNA <400 cop/ml were attained in 95% QD patients and 92% controls using an on-treatment analysis (P=NS). These figures were 69% vs 75%, respectively, in the intent-to-treat analysis (P=NS).

The median CD4 count change at 12 months was -25 and +46 cells/ml, respectively (P=0.007). Limiting this analysis to subjects who attained HIV-RNA <400 copies/ml, CD4 changes were -24 and +42 cells/ml, respectively (P=0.009). Moreover, CD4 declines in the QD arm were significantly higher at 12 months in patients taking high vs low ddI doses (-65 and -13 cells/ml, respectively).

Treatment discontinuation occurred in 68 QD cases (22%) and 16 controls (20%), being drop-outs due to virological failure recognised in 15 QD (4.8%) and two controls (2.5%) (P=NS). Genotypic testing in patients who failed in the QD arm showed that most of them showed drug resistance for NNRTI: K103N (13), G190A/S (four), V108I (three), and Y181C (three). For NRTI the most prevalent changes were: K65R (seven), M184V (three) and L74V (one). Of note, three TAMs were present in four (27%) patients.

CONCLUSIONS: In patients on HAART with complete virus suppression, simplification to a QD regimen with ddI-TDF-EFV provides virological responses at 12 months similar to those seen in patients who do not change therapy. While improvements in lipid abnormalities and treatment adherence might favour this simplification regimen, concerns on CD4 declines (particularly with high ddI doses) may discourage its use. While most patients failing virologically develop drug resistance to EFV, mutation K65R was the most frequent change for NRTI.

PRESENTING AUTHOR: L Valer

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2005-06-07
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