| Abstract | BACKGROUND: The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. METHODS: Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response -12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov, number NCT00110877. FINDINGS: Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2-16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. INTERPRETATION: In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population. |
| Authors | José Valdez Madruga, Daniel Berger, Marilyn McMurchie, Fredy Suter, Denes Banhegyi, Kiat Ruxrungtham, Dorece Norris, Eric Lefebvre, Marie-Pierre de Béthune, Frank Tomaka, Martine De Pauw, Tony Vangeneugden, Sabrina Spinosa-Guzman, TITAN study group
(Affiliation: Centro de Referência e Treinamento DST/AIDS, Mariana-São Paulo, Brazil. valdezmr at uol.com.br)
|
| Journal | Lancet
(Lancet)
Vol. 370
Issue 9581
Pg. 49-58
(Jul 7 2007)
ISSN: 1474-547X England |
| PMID | 17617272
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- HIV Protease Inhibitors
- Pyrimidinones
- RNA, Viral
- Ritonavir
- Sulfonamides
- darunavir
- lopinavir
|
| Topics |
- Adult
- Antiretroviral Therapy, Highly Active
- Female
- HIV Infections
(drug therapy)
- HIV Protease Inhibitors
(adverse effects, therapeutic use)
- HIV-1
(drug effects)
- Humans
- Male
- Middle Aged
- Pyrimidinones
(adverse effects, therapeutic use)
- RNA, Viral
(blood)
- Ritonavir
(adverse effects, therapeutic use)
- Sulfonamides
(adverse effects, therapeutic use)
|
