AEGiS-15IAC: Long-term safety and efficacy of tenofovir DF (TDF) versus stavudine (d4T) in combination with lamivudine (3TC) and efavirenz (EFV) in antiretroviral-naïve women: 144-week results.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Long-term safety and efficacy of tenofovir DF (TDF) versus stavudine (d4T) in combination with lamivudine (3TC) and efavirenz (EFV) in antiretroviral-naïve women: 144-week results.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrB1083)

A De Ruiter¹, A L Pozniak², S Staszewski³, J E Gallant⁴, K Yale⁵, B Lu⁵, J Enejosa⁵, A K Cheng⁵
¹St. Thomas' Hospital, London, United Kingdom; ²Chelsea and Westminster Hosp., London, United Kingdom; ³University Hospital, J.W. Goethe-Universitat, Frankfurt, Germany; ⁴Johns Hopkins Univ. School of Medicine, Baltimore, MD, United States; ⁵Gilead Sciences, Foster City, CA, United States

BACKGROUND: The paucity of long-term data on the efficacy and safety of highly active antiretroviral therapy in females has hampered management of HIV-1 infected women. Study 903 was a Phase III, 144-week, randomized, double-blind, active-controlled trial designed to evaluate the efficacy and safety of TDF compared to d4T; 26% of the study participants were women.

METHODS: Patients with HIV-1 RNA >5,000 copies/mL and any CD4+ cell count were randomized to receive either TDF or d4T plus 3TC and EFV. Baseline HIV-related characteristics were similar: mean HIV-1 RNA 4.75 log₁₀ c/mL, mean CD4 count 291 cells/mm³, 16% AIDS.

RESULTS: The study enrolled 155 women; 7/79 in the TDF arm vs. 12/76 in the d4T arm discontinued study medication due to adverse events, and 4 in each arm discontinued due to pregnancy. The frequencies of treatment-emergent Grade 3/4 adverse events and laboratory toxicities were similar in both arms.

Week 144 Results	TDF+3TC+EFV	d4T+3TC+EFV	Stratum-Weighted Difference (95%CI)/p-value
HIV-1 RNA <400 c/mL ITT M=F	70%	67%	4 (-10,19)
HIV-1 RNA <50 c/mL ITT M=F	67%	65%	6 (-9,20)
Mean CD4 Cell Count Change from Baseline (cells/mm³)	314	320	-10 (-77,57)
Mean Change from Baseline in Fasting Total Cholesterol (mg/dL)	23	53	p<0.001
Fasting Triglycerides (mg/dL)	-4	58	p<0.001
Fasting LDL Cholesterol (mg/dL)	4	30	p<0.001
Fasting HDL Cholesterol (mg/dL)	11	8	p=0.2
Mean Total Limb Fat (kg) (TDF:n=32, d4T:n=31)	11	6	p<0.001

CONCLUSIONS: TDF- and d4T-based therapy demonstrated sustained efficacy in ART-naïve women through 144 weeks. Women in TDF arm had smaller changes in fasting total cholesterol, LDL and triglycerides. Significantly less limb fat was seen in the d4T arm at week 144.

Keywords: AEGIS, Stavudine, Lamivudine, Oxazines, Adenine, Organophosphorus Compounds, CD4 Lymphocyte Count, Anti-HIV Agents, HIV-1, HIV Infections, Antiretroviral Therapy, Highly Active, HIV Protease Inhibitors, Acquired Immunodeficiency Syndrome, HIV, Safety, efavirenz, tenofovir, Humans, Female, Pregnancy

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MoOrB1083