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Response in Etravirine Expanded Access With Diverse Background Regimens
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XVII International AIDS Conference
August 3-8, 2008
Mexico City
Mark Mascolini
About two thirds of US enrollees in the etravirine expanded-access program reached a viral load below 75 copies within 24 weeks of starting this new nonnucleoside [1]. Most people also started the integrase inhibitor raltegravir, the protease inhibitors (PIs) darunavir/ritonavir, or both when they began etravirine (TMC125). Only 2% of enrollees had to stop their regimen within 24 weeks because of side effects.
The expanded-access program accepted people who had tried drugs in the first three antiretroviral classes or who had taken nucleosides and PIs and had evidence of resistance to nonnucleosides. Everyone had used as least two PI-based regimens and had uncontrolled viremia on their current regimen. The program allowed use of raltegravir, the CCR5 antagonist maraviroc, the fusion inhibitor enfuvirtide, any licensed nucleoside, and six ritonavir-boosted PIs: atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, or saquinavir.
Among program participants who reached week 24, (1) 486 (41%) added both darunavir/ritonavir and raltegravir to etravirine (and other background drugs), (2) 338 (28%) added darunavir without raltegravir, (3) 234 (19%) added raltegravir without darunavir, and (4) 140 (12%) added neither darunavir nor raltegravir. About 15% overall used enfuvirtide as part of their salvage regimen. The investigators did not report proportions using maraviroc.
Median pre-etravirine viral loads in those four groups ranged from 4.0 to 4.4 log copies (or about 10,000 to 25,000 copies), and these medians did not differ substantially between groups. Median baseline CD4 counts were 115 for group 1, 184 for group 2, 143 for group 3, 217 for group 4, and 152 overall.
The response analysis included 1620 people, 1198 of whom reached 24 weeks of follow-up. Thirty-one people (2%) quit the program because of side effects. Although 195 enrollees (12%) had a serious side effect, clinicians attributed only 27 of these (2%) to one of the salvage drugs. The serious side effect rate was marginally higher among people who took both raltegravir and darunavir/ritonavir with etravirine (14%) than in those who took one of the other defined regimens, as were serious side effects possibly related to therapy (3%). On the other hand, discontinuations because of side effects proved most common in the subgroup that took neither raltegravir nor darunavir (4%). The meaning of these small differences in side effect rates--if they have a meaning--cannot be determined in a nonrandomized study like this.
About two thirds of enrollees in each of the four subgroups defined above had a 24-week viral load below 75 copies, and about 80% had fewer than 400 copies:
1. 66% below 75 copies, 84% below 400 copies
2. 62% below 75 copies, 79% below 400 copies
3. 65% below 75 copies, 83% below 400 copies
4. 66% below 75 copies, 86% below 400 copies
Overall: 65% below 75 copies, 83% below 400 copies
The similar response rates with all four background regimens suggest treating clinicians did a good job of picking new or old antiretrovirals to give with etravirine. But from this type of analysis, it is impossible to tell, for example, whether people who started both raltegravir and darunavir needed both drugs in the salvage regimen or whether some clinicians erred on the side of caution.
Median CD4 count rose by 88 among people who completed 24 weeks of treatment and did not vary substantially from one defined background regimen to another.
Reference
1. Towner W, Haigney Z, Sension MG, et al. Efficacy, safety and tolerability of etravirine with and without darunavir and/or raltegravir in treatment-experienced patients: preliminary analysis of TMC125-C214 early access program in the US. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract TUPE0066.
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