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The Safety And Efficacy of Tenofovir DF (TDF) in Combination with Lamivudine (3TC) and Efavirenz (EFV) Through 5 Years in Antiretroviral-naive Patients
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Reported by Jules Levin
8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006, Glasgow, UK
I Cassetti,1 JVR Madruga,2 JMAH Suleiman,3 L Zhong,4 J Enejosa,4
and AK Cheng4 for the 903E Study Team
1Fundacion Centro Estudios Infectologicos, Buenos Aires, Argentina;
2Centro de Referencia e Treinamento DST/AIDS, Sao Paulo, Brazil;
3Brasilmed Assistencia Medica e Pesquisas, Sao Paulo, Brazil; 4Gilead Sciences, Inc., Foster City, CA, USA
Study 903 is a Phase III trial with an ongoing 192-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.
The Authors concluded:
Through 5 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 lipoatrophy
- No evidence of clinically relevant bone effects
Brief Summary:
--83% (n=86, M=F) had <50 copies/ml at 5 yrs.
--limb fat was in normal range: 8.0 kg at year 2, 8.2 kg at year 5. There was no baseline limb fat measure.
--Bone Mineral Density: there was an initial decline in year 1 on therapy that remained stable in years 2 through 5.
--mean CD4 increase was 421 through 5 years.
--2 patients discontinued due to virologic failure: 1 with wild-type genotype; 1 with M184V, K103N, T69N; there was no K65R.
--Renal parameters: there were 2 grade 1 creatinine cases (>1.5-2.0); no grade 2, 3, or 4. Estimated GFR by Cockroft-Gault, no significant change from 116 mL/min at baseline to 122 at 5 yrs; MDRD, nonsignificant change, 112 at baseline, 117 at 5 yrs.
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 192-week (4-year) open-label extension phase (903E)
- Data obtained from patients originally randomized to TDF and participating in 903E were analyzed
Patient Disposition Through 5 Years
- 86 patients enrolled in Study 903 open-label extension phase and continued treatment with TDF
- 9 patients discontinued from the study prior to Year 5 (Week 240)
- 1 patient discontinued due to adverse event (asymptomatic increase in serum amylase/lipase)
- 2 patients had virologic failure
- 2 patients discontinued due to pregnancy
- 4 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
- 2 patients discontinued due to virologic failure
- 1 Wild type genotype at Week 228
- 1 T69N, M184V, K103N at Week 240
- No K65R
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