A
Two-year Trial of Lopinavir/Ritonavir Monotherapy after Induction Treatment Compared
to Efavirenz-based HAART Lopinavir/ritonavir
(Kaletra) may be effective as monotherapy in selected patients, according
to the results of a study presented by Dr. William Cameron at the 16th
International IADS Conference in Toronto this week. This may be due to the
drug's potency and high genetic barrier to resistance. In
the current study (M03-613), conducted at medical centers in the US, Canada and
Spain, researchers enrolled 155 treatment-naive HIV patients. Participants were
then randomized 2:1 to LPV/r + zidovudine
(ZDV; Retrovir) + lamivudine
(3TC; Epivir) induction (n=104) for at least 24 weeks followed by maintenance
LPV/r monotherapy after 3 consecutive monthly viral loads (VL) <50 copies/mL,
or to EFV+ZDV+3TC (n=51). The
primary endpoint was the proportion achieving and maintaining VL <50 copies/mL
through 96 weeks. Results 
Baseline characteristics were similar between arms.
92 (88%) of 104 LPV/r subjects started monotherapy. 79 LPV/r (69/92 on monotherapy)
and 34 EFV-treated subjects completed the study.
Drug-related discontinuations occurred in 3% of LPV/r-treated and 2% of EFV-treated
subjects.
In the primary analysis, 50% of LPV/r-treated and 61% of EFV treated subjects
achieved and maintained VL <50 copies/mL through 96 weeks (intent-to-treat,
previous failure=failure, p=0.23).
By Kaplan-Meier analysis, the proportions maintaining VL <50, and <500 copies/mL
through 72 weeks on LPV/r after deintensification were 62% and 84% respectively.
Corresponding
Kaplan-Meier estimates for EFV subjects after 3 consecutive VL <50 copies/mL
were 91% <50 (p=0.002 vs. LPV/r monotherapy) and 95% <500 copies/mL (p=0.10
vs. LPV/r monotherapy).
LPV/r monotherapy subjects with VL rebound to 50-500 copies/mL generally demonstrated
viral re-suppression to <50 copies/mL while continuing LPV/r monotherapy (11/12)
or with resumption of NRTIs (2/4).
New PI resistance mutations were detected in 2/15 (13%) LPV/r-treated subjects,
while NNRTI resistance mutations were detected in 1/5 (20%) EFV-treated subjects
(p>0.9).
In
conclusion, the authors write, "After successful induction treatment with
LPV/r+ZDV+3TC, LPV/r monotherapy continuously maintained VL suppression in a majority
of subjects." "LPV/r
monotherapy had more intermittent VL increases between 50 and 500 copies/mL versus
EFV+ZDV+3TC, but most subjects returned to <50 copies/mL. LPV/r monotherapy
may be effective in selected patients." University
of Ottawa at the Ottawa Hospital, Ottawa, Canada, Abbott Laboratories, Abbott
Park, United States, Hospital La Paz, Madrid, Spain, Body Positive Inc., Phoenix,
United States, Southwest Infectious Disease Associates, Dallas, United States,
McGill University Health Center, Montreal, Canada. Reference
W Cameron, B da Silva, J Arribas, and others. A two-year randomized
controlled clinical trial in antiretroviral-naive subjects using lopinavir/ritonavir
(LPV/r) monotherapy after initial induction treatment compared to an efavirenz
(EFV) 3-drug regimen (Study M03-613). 16th International AIDS Conference. August
13-18, 2006. Toronto, Canada. Abstract THLB0201.
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