SAN DIEGO, CA—A pilot study presented at IDWeek 2012 to assess durability of HIV-1 virologic suppression in subjects who switched from a lopinavir/ritonavir-based triple highly active antiretroviral therapy (HAART) regimen dosed once or twice a day to lopinavir/ritonavir monotherapy dosed daily failed to maintain viral suppression in a sufficient number of subjects to continue the study, investigators reported.
Previously, lopinavir/ritonavir as a component of HAART has demonstrated durable antiretroviral activity in both twice and once daily dosing regimens and has exhibited a high barrier to resistance, noted Harold P. Katner, MD, from Mercer University School of Medicine, Macon, GA, and colleagues.
The primary end point of the MONo-DAily-KALetra (MONDAKAL) observation cohort study was proportion of subjects with sustained virologic suppression (HIV-1 RNA PCR <75 copies/mL) through week 48 following de-escalation to daily lopinavir/ritonavir monotherapy. The subjects underwent frequent clinical, virologic, and immunologic monitoring.
Virologic failure was defined as sustained virologic rebound in subjects with detectable plasma HIV-1 RNA levels >400 copies/mL on two consecutive samples, drawn 2 weeks apart. For subjects with virologic failure, HIV-1 genotyping was used to guide the choice of a subsequent HAART regimen. The study was designed to be terminated when four subjects reached the definition for virologic failure.
A total of 13 subjects initiated the lopinavir/ritonavir-based HAART regimen and maintained HIV-1 viral loads <75 copies/mL for at least 48 weeks prior to enrolling in the study; 3 failed screening, 2 due to viral loads being elevated and 1 due to inability to tolerate lopinavir/ritonavir daily dosing. Of the 10 subjects, 8 were African American (2 females and 6 males) and 2 were Caucasian (1 male and 1 female). Mean age of the subjects was 42.1 years (range, 27–53 years) and mean duration on therapy prior to de-escalation (baseline) was 252 weeks (range, 105–413 weeks). Mean CD4 count at baseline was 338 cells/m3 (range, 120–512 cells/m3).
One subject completed 48 weeks of once daily lopinavir/ritonavir monotherapy on study and one subject withdrew from the study at 22 weeks after experiencing 2 detectable viral loads 5 weeks apart (both <400 copies/mL). Four subjects experienced virologic failure, 1 at Week 36 and 3 at Week 12, two “admitted non-adherence to lopinavir/ritonavir monotherapy,” they reported. The study was terminated.
One of the four subjects with virologic failure developed multiple nucleoside and protease inhibitor mutations. No severe adverse events were reported by any of the study subjects.