IDWeek 2012: Simplified Protease Inhibitor Monotherapy Fails to Maintain HIV Suppression

A simplified regimen of lopinavir/ritonavir (Kaletra) monotherapy did not keep HIV viral load fully suppressed after patients switched from a standard 3-drug antiretroviral regimen, researchers reported at the IDWeek 2012 conference last week in San Diego.

IDWeek is a new joint meeting of the Infectious Diseases Society of America (IDSA), the HIV Medicine Association (HIVMA), the Society for Health and Epidemiology of America, and the Pediatric Infectious Diseases Society.

Reducing the number of drugs in an antiretroviral therapy (ART) regimen can improve convenience, reduce side effects, and lower cost, all of which can help people stay on treatment and achieve good adherence. One simplification approach is switching to protease inhibitor maintenance monotherapy after achieving undetectable viral load on a standard ART regimen.

Harold Katner from Mercer University School of Medicine and fellow MONDAKAL (MONo Daily KALetra) investigators conducted a prospective, open-label, single-arm pilot study to evaluate the durability of viral suppression among 13 people with stable undetectable viral load.

At study entry participants had HIV RNA < 75 copies/mL and no more than 2 "blips" (transient low-level viral loads) during at least 48 weeks on a first-line regimen containing lopinavir/ritonavir plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); 10 people were on tenofovir/emtricitabine (the drugs in Truvada) while 3 were on zidovudine/lamivudine (Combivir).

Participants were to stop taking their NRTIs and continue on 800/200 mg once-daily lopinavir/ritonavir for 48 weeks. Those who started on 400/100 mg twice-daily lopinavir/ritonavir first spent 4 weeks on the higher dose plus NRTIs to determine tolerability. Out of the original group, 2 people were excluded from further analysis due to detectable viral load at screening and 1 did not tolerate the higher lopinavir/ritonavir dose.

Among the remaining 10 participants, 7 were men, 3 were women, 8 were black, 2 were white, and the average age was 42 years. They had been on ART for 252 weeks on average. The current mean CD4 T-cell count was 338 cells/mm³, but the mean nadir (lowest-ever) count was 67 cells/mm³, indicating that many started treatment with advanced disease.

Results

• 1 of the 10 remaining participants completed the entire 48 weeks of lopinavir/ritonavirmonotherapy.
• 1 person withdrew at 22 weeks after having 2 detectable viral load measurements 5 weeks apart (both < 400 copies/mL).
• 8 people discontinued monotherapy prior to 48 weeks (4 after 36 weeks, 2 after 24 weeks, and 2 after 12 weeks).
• 4 of these 8 participants experienced virological failure, defined as HIV RNA > 400 copies/mL on 2 consecutive tests(1 person at week 36 and 3 at week 12).
• 2 of these 4 reported poor adherence to monotherapy.
• 1 person who experienced treatment failure had NRTI and protease inhibitor resistance mutations.
• No participants experienced severe adverse events during the study.
• Based on the protocol, the study was halted ahead of schedule and all 5 remaining participants were put back on a 3-drug regimen.

"Simplifying subjects to once daily dosing of lopinavir/ritonavir failed to maintain viral suppression in a sufficient number of subjects to continue this study," the researchers summarized.

"Possible reasons for virologic failure include adherence, low CD4 nadir, and the possibility of pre-existing [resistance] mutations," they concluded. "The results of our pilot study do not support a role for lopinavir/ritonavir[once-daily] as monotherapy in patients de-escalated from a lopinavir/ritonavirbased triple therapy regimen."

10/26/12

Reference

H Katner, R Kumar, C Nylund, et al. Lopinavir/Ritonavir Once Daily Monotherapy Pilot Study: The MONDAKAL Study. IDWeek. San Diego. October 17-21, 2012. Abstract 1353.