A randomized comparison of second-line lopinavir/ritonavir monotherapy versus tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI regimens: the HIV STAR study

作者：Bunupuradah Torsak; Chetchotisakd Ploenchan; Ananworanich Jintanat; Munsakul Warangkana; Jirajariyavej Supunnee; Kantipong Pacharee; Prasithsirikul Wisit; Sungkanuparph Somnuek; Bowonwatanuwong Chureeratana; Klinbuayaem Virat; Kerr Stephen J; Sophonphan Jiratchaya; Bhakeecheep Sorakij; Hirschel Bernard; Ruxrungtham Kiat^*

来源：Antiviral Therapy, 2012, 17(7): 1351-1361.

DOI：10.3851/IMP2443

Background: Data informing the use of boosted protease inhibitor (PI) monotherapy as second-line treatment are limited. There are also no randomized trials addressing treatment options after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimens. %26lt;br%26gt;Methods: HIV-infected subjects %26gt;= 18 years, with HIV RNA %26gt;= 1,000 copies/ml while using NNRTI plus 2 NRTIs, and naive to PIs were randomized to lopinavir/ritonavir (LPV/r) 400/100 mg twice daily monotherapy (mono-LPV/r) or tenofovir disoproxil fumarate (TDF) once daily plus lamivudine (3TC) twice daily plus LPV/r 400/100 mg twice daily (TDF/3TC/LPV/r) at nine sites in Thailand. The primary outcome was time-weighted area under curve (TWAUC) change in HIV RNA over 48 weeks. The a priori hypothesis was that the mono-LPV/r arm would be considered non-inferior if the upper 95% confidence limit in TWAUC mean difference was %26lt;= 0.5 log 10 copies/ml. %26lt;br%26gt;Results: The intention-to-treat (ITT) population comprised 195 patients (mono-LPV/r n=98 and TDF/3TC/LPV/r n=97): male 58%, baseline mean (sd) age of 38 (7) years, CD4(+) T-cell count of 204 (135) cells/mm(3) and HIV RNA of 4.1 (0.6) log(10) copies/ml. The majority had HIV-1 recombinant CRF01_AE infection, and thymidine analogue mutation (TAM)-2 was 3x more common than TAM-1. At 48 weeks, the difference in TWAUC HIV RNA between arms was 0.15 (95% CI -0.04, 0.33) log(10) copies/ml, consistent with our definition of non-inferiority. However, the proportion with HIV RNA%26lt;50 copies/ml was significantly lower in the mono-LPV/r arm: 61% versus 83% (ITT, P%26lt;0.01). Baseline HIV RNA %26gt;= 5 log(10) copies/ml (P%26lt;0.001) and mono-LPV/r use (P=0.003) were predictors of virological failure. Baseline genotypic sensitivity scores %26gt;= 2 and TAM-2 were associated with better virological control in subjects treated with the TDF-containing regimen. %26lt;br%26gt;Conclusions: In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA%26lt;50 copies/ml compared to the TDF/3TC/LPV/r treatment. Thus, mono-LPV/r should not be recommended as a second-line option.

• 出版日期2012