Once-daily
Lopinavir/ritonavir Works as Well as Twice-daily dosing in treatment-experienced
Patients
 | Treatment-experienced
patients who took lopinavir/ritonavir (Kaletra) once-daily as part of a combination
antiretroviral regimen were as likely to achieve virological suppression and CD4
cell gains as those who took the drug twice-daily, but less frequent dosing was
associated with better adherence, according to a presentation at the 5th International
AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention last week
in Cape Town, South Africa. |
By
Liz Highleyman Prior
research has shown that antiretroviral
therapy (ART) containing once-daily lopinavir/ritonavir
works as well as twice-daily dosing in treatment-naive HIV patients, and it has
been approved for this indication since 2005. Sharlaa Badal-Faesen and an international
team of colleagues aimed to determine whether this also holds true for treatment-experienced
individuals. Study
M06-802 included 599 participants who were currently on ART but had a viral load
above 1000 copies/mL. Though treatment-experienced, they had not previously used
lopinavir/ritonavir; about half had used 1 other protease
inhibitor (PI), however, and many had used 2 or more. A
majority of participants (66%) were men and the mean age was about 40 years; about
half were white, one-third were black and one-third were Latino/Hispanic (the
latter overlapped with the other groups). The median HIV viral load at baseline
was about 4000 copies/mL and the median CD4 cell count was 254 cells/mm3. Resistance
tests revealed a mean 1.2 major PI resistance mutations. Participants
were randomly assigned (1:1) to switch to either a once-daily dose of 800 mg lopinavir
plus 200 mg ritonavir or else twice-daily doses of 400 mg lopinavir plus100 mg
ritonavir. In addition, all received 2 nucleoside/nucleotide
reverse transcriptase inhibitors (NRTIs), selected according to treatment
history and resistance profile. Patients received lopinavir/ritonavir in bottles
with electronic caps to monitor adherence.
Results  | At
week 48, using an intent-to-treat TLOVR (time to loss of virological response)
analysis, 55.3% of patients taking once-daily lopinavir/ritonavir achieved HIV
RNA below 50 copies/ml, compared with 51.8% of those taking twice-daily lopinavir/ritonavir.
| | This
was not a significant difference, indicating that once-daily dosing was non-inferior
to twice-daily administration. | | Response
rates were similar with once-daily and twice-daily dosing in patients with 0 to
2 major lopinavir resistance mutations. | | However
the response rate was 2-fold higher with twice-daily dosing among individuals
with 3 or more such mutations (30.8% vs 57.1%). | | CD4
cell increases were 135 cells/mm3 in the once-daily group and 122 cells/mm3 in
the twice-daily group, again not a significant difference. | | 5%
of patients in the once-daily arm and 7% in the twice-daily group withdrew due
to adverse events. | | About
25% of patients in both the once-daily and twice-daily groups experienced side
effects, most commonly diarrhea (14% vs 11%) and nausea (3% vs 7%). | | Similar
proportions of patients in both arms had elevated cholesterol (about 7%) and triglyceride
(about 5%) levels. | | Emergence
of new PI resistance mutations was uncommon in both groups among participants
with inadequate virological suppression. | | Once-daily
administration was associated with significantly better adherence than twice-daily
dosing. |
"Through
48 weeks, lopinavir/ritonavir dosed [once-daily] or [twice-daily] had similar
efficacy in treated-experienced subjects," the investigators concluded. "Through
24 weeks, [once-daily] dosing of lopinavir/ritonavir resulted in higher treatment
compliance than [twice-daily dosing]," they added. Both regimens were "[g]enerally
well tolerated with few study drug-related discontinuations." Projeto
Praça Onze, UFRJ, Rio de Janeiro, Brazil; University of Witwatersrand,
Clinical HIV Research Unit, Houghton, Johannesburg, South Africa; Hospital Civil
de Guadalajara, Guadalajara, Mexico; Therapeutic Concepts, Houston, TX; Muñiz
Hospital, HIV Outpatient Care Unit, Buenos Aires City, Argentina; Abbott Laboratories,
Abbott Park, IL. 7/31/09 Reference
R
Zajdenverg, S. Badal-Faesen, J Andrade-Villanueva, and others. Lopinavir/ritonavir
tablets administered once- or twice-daily with NRTIs in antiretroviral-experienced
HIV-1 infected subjects: results of a 48-week randomized trial (Study M06-802).
5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and
Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract TuAb104.
(Abstract).
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