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


METHODS
HIV-infected subjects ≥18 years, with HIV RNA≥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 ≤0.5 log(10) copies/ml.


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 3× 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<50 copies/ml was significantly lower in the mono-LPV/r arm: 61% versus 83% (ITT, P<0.01). Baseline HIV RNA≥5 log(10) copies/ml (P<0.001) and mono-LPV/r use (P=0.003) were predictors of virological failure. Baseline genotypic sensitivity scores ≥2 and TAM-2 were associated with better virological control in subjects treated with the TDF-containing regimen.


CONCLUSIONS
In PI-naive patients failing NNRTI-based first-line HAART, mono-LPV/r had a significantly lower proportion of patients with HIV RNA<50 copies/ml compared to the TDF/3TC/LPV/r treatment. Thus, mono-LPV/r should not be recommended as a second-line option.
HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Torsak
T
Bunupuradah
Ploenchan
P
Chetchotisakd
Jintanat
J
Ananworanich
Warangkana
W
Munsakul
Supunnee
S
Jirajariyavej
Pacharee
P
Kantipong
Wisit
W
Prasithsirikul
Somnuek
S
Sungkanuparph
Chureeratana
C
Bowonwatanuwong
Virat
V
Klinbuayaem
Stephen J
SJ
Kerr
Jiratchaya
J
Sophonphan
Sorakij
S
Bhakeecheep
Bernard
B
Hirschel
Kiat
K
Ruxrungtham
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D005260:Female; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D000068698:Tenofovir
D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D061466:Lopinavir; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir