The use of the HIV protease inhibitor (PI) lopinavir/ritonavir (LPV/r; Kaletra) monotherapy is experimental and data on its use as single-agent therapy in antiretroviral-naïve patients are scarce.

IMANI-2 is an ongoing prospective, single-arm, open-label, 96-week pilot trial testing LPV/r single-agent therapy as a treatment for chronic HIV-1 infection. Dr. Joseph Gathe, Jr. of Abbott Laboratories (USA) presented 48-week efficacy results of the IMANI trial at the 4^th IAS conference in Sydney (July 22-25, 2007).

Patient Population

Antiretroviral-naïve subjects with any viral load (VL) and CD4 and without baseline resistance to LPV/r were eligible.

Endpoints

Endpoints were proportion <400 copies/mL at weeks 24 and 48 and proportion <75 copies/mL at week 48.

Suboptimal response was defined as <1 log VL decrease by week 4, or VL >400 copies/mL at week 16, or a VL rebound after nadir <400 copies/mL. Subjects suppressed at week 40 were considered week 48 responders (LOCF [last observation carried forward]).

Suboptimal responders were intensified to either addition of tenofovir/emtricitabine or LPV/r dose increase to 600/150 bid. Data are presented as medians (range).

Results

–       39 subjects were enrolled. Median baseline VL was 4.5 log copies/mL (3.6 – 5.7). Median baseline CD4 was 258 cells/mm3 (12-1165).

–       At week 24, 92% (36/39) of subjects were VL < 400 copies/mL ITT Missing=Failure (M=F).

–       At week 48, 87% (26/30) were VL < 75 copies/mL ITT M=F.

–       32/39 (82%) were < 75 copies/mL at week 48 ITT=LOCF and 33/39 were < 400 copies/mL (85%) ITT=LOCF.

–       Median time to <400 copies/mL was 4 weeks (4-16), and to < 75copies/mL was 8 weeks (4-44).

–       CD4 through weeke48 increased median 258 cells/mm3 (64-802).

–       6 had confirmed rebound. Despite counseling, 5/6 rebounds had poor adherence.

–       5/6 were subsequently intensified - 3/5 to LPV/r 600/150 BID, 2/5 added tenofovir/emtricitabine. 4/5 re-suppressed by week 48. Genotypic changes in protease occurred in 3/6 suboptimal responders.

In conclusion, the study authors write, “Lopinavir/ritonavir single-agent therapy demonstrated sustained virologic response through week 48 with 82 % < 75 copies/mL.”

“When rebound occurred, it was associated with non-adherence. The majority of rebounding patients re-suppressed upon intensification.”

Finally, they conclude, “Lopinavir/ritonavir single-agent therapy appears to be effective in some patients and should be evaluated further.”

Therapeutic Concepts, Houston, United States, University of Houston, Houston, United States, Donald R. Watkins Foundation, Houston, United States, Abbott Laboratories, Houston, United States, Abbott Laboratories, Abbott Park, United States.

Presented by Joseph C. Gathe, Jr., Therapeutic Concepts, Houston, TX, United States.

07/24/07

Reference
J C Gathe Jr, R F Yeh, C Mayberry, and others. Single-agent therapy with lopinavir/ritonavir suppresses plasma HIV-1 viral replication in HIV-1 naïve subjects: IMANI-2 48-week results. 4^th IAS. July 22-25, 2007. Sydney, AU. Abstract (poster) WePeB034.

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