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Darunavir vs Lopinavir at 96 Weeks in People With Naïve Advanced HIV - ARTEMIS Study
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HIV DART 2008, December 9-12, 2008, Rio Grande, Puerto Rico
Mark Mascolini
Antiretroviral-naive people starting treatment with once-daily darunavir/ritonavir had a significantly better 96-week virologic response than those starting once- or twice-daily lopinavir/ritonavir in the ARTEMIS trial [1]. Response differences between darunavir and lopinavir were more marked among people who began treatment with a viral load above 100,000 copies or a CD4 count under 200. The findings extend recently published 48-week results [2].
ARTEMIS randomized 689 previously untreated people to 800/100 mg of darunavir/ritonavir once daily or to a lopinavir/ritonavir dose of 800/200 mg daily. In the 346-person lopinavir group, 77% took 400/100 mg twice daily, 15% took 800/200 mg once daily, and 8% started with twice-daily dosing and moved to a once-a-day regimen. Most lopinavir patients, 83%, started with the old capsules and switched to tablets, 15% stayed with capsules, and 2% took only tablets. Everyone took fixed-dose tenofovir/emtricitabine with their protease inhibitors (PIs).
Median pretreatment viral load stood at 70,800 copies in the darunavir group and 62,100 copies in the lopinavir group. Respective median baseline CD4 counts 228 and 218. Just over 40% in each treatment arm began ARTEMIS with fewer than 200 CD4s, and just over one third in each arm began with more than 100,000 copies of HIV RNA.
By week 96, the darunavir group lost 59 people (17%) and the lopinavir group 81 (23%). While 13 people (4%) dropped out of the darunavir arm because of adverse events, 32 (9%) quit the lopinavir arm for that reason. Dropouts due to virologic failure numbered 3 (1%) with darunavir and 8 (2%) with lopinavir.
At week 96 a time-to-loss-of-virologic response (TLOVR) analysis figured that 79% in the darunavir group and 71% in the lopinavir group had a viral load below 50 copies, a significant difference (P = 0.012). The 96-week response difference was more marked among people starting therapy with more than 100,000 copies--76% with darunavir and 63% with lopinavir (P = 0.023). Among people starting treatment with fewer than 100,000 copies, 81% taking darunavir and 75% taking lopinavir had a week-96 load below 50 copies, but that difference lacked statistical significance (P = 0.174). Defining virologic failure as a confirmed viral load above 50 copies, the ARTEMIS team counted 40 (12%) in the darunavir arm and 59 (17%) in the lopinavir arm by week 96.
Among study participants starting their PIs with fewer than 200 CD4 cells, 79% taking darunavir versus 65% taking lopinavir had a viral load under 50 copies at 96 weeks (P = 0.009). The 96-week virologic response difference between darunavir and lopinavir was negligible among people beginning treatment with more than 200 CD4s.
Comparing all 343 people randomized to darunavir with 258 people who took lopinavir/ritonavir twice daily, a TLOVR analysis figured that 79% taking darunavir and 72% taking lopinavir had a week-96 viral load under 50 copies, a significant difference (P = 0.038).
Grade 2 to 4 treatment-related diarrhea affected 11% taking lopinavir versus 4% taking darunavir. Grade 2 to 4 rashes were rare but more common with darunavir (3%) than lopinavir (1%); no one taking darunavir had a new grade 2 to 4 rash after week 48. Triglycerides rose less with darunavir/ritonavir (average 0.1 mmol/L) than with lopinavir/ritonavir (0.6 mmol/L). While 4% randomized to darunavir had grade 2 to 4 triglyceride jumps, 13% randomized to lopinavir did.
Other studies that enrolled previously untreated people have yielded diverging results on the virologic response to lopinavir/ritonavir in people beginning those PIs with a viral load above or below 100,000 copies. A 664-person comparison of once- versus twice-daily lopinavir/ritonavir tablets, study M05-730, found that pretreatment load had no impact on virologic response at 48 weeks [3]. Comparing lopinavir/ritonavir taken twice daily, once daily self-administered, or once daily under direct observation, the 402-person ACTG 5073 trial found that people beginning lopinavir/ritonavir with a load topping 100,000 copies were less likely to have a sustained virologic response through 48 weeks if they self-administered their PIs once daily instead of twice daily [4].
References
1. Jayaweera D, Ortiz R, Mills A, et al. ARTEMIS: efficacy and safety of darunavir/ritonavir 800/100 mg once-daily vs lopinavir/ritonavir in treatment-naive, HIV-1-infected patients at 96 weeks. HIV DART, December 9-12, 2008, Rio Grande, Puerto Rico. Abstract 51.
2. Ortiz R, DeJesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naïve HIV-1-infected patients at week 48. AIDS. 2008;22:1389-1397.
3. Gathe J, da Silva BA, Loutfy M, et al. Study M05-730 primary efficacy results at week 48: phase 3, randomized, open-label study of lopinavir/ritonavir tablets once daily versus twice daily, co-administered with tenofovir DT + emtricitabine in antiretroviral-naive HIV-1 infected subjects. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 775 (http://www.retroconference.org/2008/PDFs/775.pdf).
4. Mildvan D, Tierney C, Gross R, et al. Randomized comparison in treatment-naive patients of once-daily vs twice-daily lopinavir/ritonavir-based ART and comparison of once-daily self-administered vs directly observed therapy. 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007. Los Angeles. Abstract 138 (http://www.retroconference.org/2007/Abstracts/28619.htm).
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