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Elvucitabine Versus 3TC in
First-Line Regimens for 96 Weeks - see slides from poster below
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Elvucitabine, a cytosine nucleoside analog, proved virologically equivalent to lamivudine (3TC) when combined with efavirenz and tenofovir as a first-line regimen taken for 96 weeks [1]. However, because of the small size of this phase 2 trial and the high dropout rate, elvucitabine lagged 3TC in a noncompleter-equals-failure virologic analysis, so further study will be needed to get a better fix on where elvucitabine may fit in treatment planning.
Elvucitabine has a half-life of about 100 hours and an in vitro 50% effective concentration of 1.1 ng/mL, suggesting 3 to 4 times greater antiviral activity than 3TC, according to Edwin DeJesus and collaborators. This double-blind trial at 16 US sites and three in India recruited 77 antiretroviral-naive people and randomized them take 10 mg of elvucitabine once daily or standard-dose 3TC plus efavirenz and tenofovir. All study participants had a CD4 count between 200 and 500, so the trial did not include people with relatively advanced HIV infection.
The primary endpoint, proportion of people with a viral load under 50 copies, came at the end of the 12-week blinded phase. An 84-week open-label extension led to the secondary endpoint--proportion of people with fewer than 50 copies at week 96.
Of the 39 people randomized to elvucitabine, 30 (77%) completed week 12 and 21 (54%) completed week 96. Thirty-five of 38 people (92%) randomized to 3TC completed 12 weeks, and 27 (71%) completed 96. Adverse events accounted for 3 dropouts in the elvucitabine group and 1 in the 3TC group. Only one of the three adverse events with elvucitabine--neutropenia—was judged related to study drugs. Loss to follow-up explained 5 dropouts in the elvucitabine arm and 2 in the 3TC arm. One person taking elvucitabine died, a suicide judged unrelated to study drugs.
In a 96-week noncompleter-equals-failure analysis, 68% taking 3TC (25 of 37) and 54% taking elvucitabine (20 of 37) had a viral load below 50 copies (95% confidence interval [CI] -36 to 9), a difference reflecting the higher proportion of noncompleters in the elvucitabine group. In a 96-week as-treated analysis, sub-50 rates were 95% with elvucitabine (20 of 21) and 93% with 3TC (25 of 27) (95% CI -11 to 16).
Defining virologic failure as a viral load above 400 copies through 12 weeks of treatment or less than a 100-fold (2-log) change in viral load, the investigators counted 2 virologic failures with elvucitabine and 1 with lamivudine in the first 12 study weeks. The K103N efavirenz mutation, but no nucleoside-related mutations, emerged during one of these two elvucitabine failures. The other failure was not genotyped. K103N, M184V, and P225H emerged in the one 3TC failure.
Defining virologic failure at a confirmed viral load above 50 in weeks 24 to 48, the researchers counted 1 failure with elvucitabine and none with 3TC. In weeks 48 to 96, there were 2 failures with elvucitabine and 6 with 3TC. So, all told, there were 5 virologic failures with elvucitabine and 7 with 3TC.
CD4 percent gains through week 96 averaged 11.2% with elvucitabine and 11.6% with 3TC. The investigators did not report pretreatment CD4 counts or absolute CD4 gains.
There were 13 serious adverse events with elvucitabine and 12 with 3TC reported by 11 people taking elvucitabine and 5 taking 3TC. The researchers attributed none of these problems to study drugs. Among drug-related side effects, headache (14% versus 1%) and diarrhea (14% versus 5%) were more common with 3TC, nausea (15% versus 11%) and dizziness (13% versus 5%) with elvucitabine.
Reference
1. DeJesus E, Saple D, Morales-Ramirez J, et al. Elvucitabine vs lamivudine with tenofovir and efavirenz in ART-naive HIV-1-infected patients: 96-week final results. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 511. http://www.retroconference.org/2010/PDFs/511.pdf.
Elvucitabine vs Lamivudine with Tenofovir and Efavirenz in Antiretroviral-Treatment-Naïve HIV-1 Infected Patients: 96 Week Final Results
E. DEJESUS1, D. SAPLE2, J. MORALES-RAMIREZ3, N. KUMARASAMY4, T. JEFFERSON5, N. BELLOS6, B.H. WADE7, H. ROBISON8, E. OLEK8
1Orlando Immunology Ctr., Orlando, FL, 2Dr. Saple’s Clinic, Mumbai, India, 3Clinical Res. Puerto Rico, San Juan, Puerto Rico, 4YRGCare VHS, Chennai, India, 5Hlth. for Life Clinic, Little Rock, AR, 6Private Practice, Dallas, TX, 7Ctr. for the Prevention and Treatment of Infections, Pensacola, FL, 8Achillion Pharmaceuticals, Inc., New Haven, CT
AUTHORS CONCLUDED
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