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The Safety and Efficacy of Tenofovir DF (TDF) in Combination with Lamivudine (3TC) and Efavirenz (EFV) in Antiretroviral-naive Patients Through Seven Years
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Reported by Jules Levin
CROI Feb 8-12 2009 Montreal, Canada
JVR Madruga1, I Cassetti,2 A Etzel,3 J Suleiman,4 Y Zhou,5
AK Cheng,5 and J Enejosa5 for the 903E Study Team
1Centro de Referencia e Treinamento DST/AIDS, Sao Paulo, Brazil; 2Fundacion Centro Estudios Infectologicos,
Buenos Aires, Argentina; 3Hospital Guilherme Alvaro, Santos, Brazil; 4Brasilmed Assistencia Medica e Pesquisas,
Sao Paulo, Brazil; 5Gilead Sciences, Inc., Foster City, CA, USA
Study 903 is a Phase III trial with an ongoing 336-week open-label extension phase and a completed 144-week randomized, double-blind phase designed to evaluate TDF compared to stavudine (d4T) in combination with 3TC and EFV in antiretroviral-naive patients
METHODS
Study 903 inclusion/exclusion criteria:
-- HIV-infected patients naive to antiretroviral treatment, 18-65 years of age, with plasma HIV RNA > 5,000 copies/mL (c/mL)
-- No significant laboratory or clinical abnormalities
-- No CD4+ cell count criteria
Patients in select sites (Argentina, Brazil, and Dominican Republic) rolled-over into a 7-year (336-week) open-label extension phase (903E)
Data obtained from patients originally randomized to TDF and participating in 903E were analyzed
Patient Disposition Through 7 Years
86 patients enrolled in Study 903 open-label extension phase and continued treatment with TDF
15 patients discontinued from the study prior to Year 7 (Week 336)
-- 1 patient discontinued due to adverse event (asymptomatic increase in serum amylase/lipase)
-- 4 patients had virologic failure
-- 2 patients discontinued due to pregnancy
-- 8 patients either withdrew consent, were non-compliant or lost to follow-up
No patient developed Fanconi syndrome
No patient discontinued due to renal abnormalities
Resistance
4 patients discontinued due to virologic failure
-- 2 Wild type genotypes
-- 1 T69N, M184V, K103N at Week 240
-- 1 M184M/V, K103K/N, V108V/I, P225P/H, T69A/T, K219K/R, K70K/E/G/R at Week 336
-- No K65R
Bone Factures Through 7 Years
Through 7 years, 5 patients experienced bone fractures; all were trauma related and none were considered related to TDF
AUTHOR CONCLUSIONS
Through 7 years of therapy in antiretroviral naive patients, TDF+3TC+EFV demonstrated the following:
• Sustained, durable antiretroviral efficacy
• Continued CD4 cell count increases
• No discontinuations due to renal adverse events
• No evidence of clinically relevant bone effects
• Significant increases in limb fat from Years 2 through 7
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