Lopinavir/Ritonavir as Monotherapy for Maintenance of HIV Viral
Suppression: 48-Week Results
This randomized, controlled, open-label, multicenter,
pilot clinical trial evaluated maintenance with lopinavir/ritonavir
(Kaletra) monotherapy versus continuing lopinavir/ritonavir
and 2 nucleosides
in HIV patients with suppressed HIV replication.
Twenty-four week preliminary results of this pilot study
were first presented at the 15th International AIDS
Conference in Bangkok,
Thailand.
Adult patients were eligible if they had no history of
virologic
failure while receiving a protease
inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir
(400/100 mg b.i.d.) for >1 month and had maintained serum HIV
RNA <50 copies/mL for >6 months prior to enrollment.
The primary outcome measures for efficacy were the proportion
of patients with <500 copies/mL of HIV RNA of plasma at 48
weeks.
Secondary efficacy outcomes included the proportion of
patients with <50 copies/mL of HIV RNA at week 48, time to
loss of virologic suppression through week 48, development of
HIV
resistance, and changes in the CD4
cell count.
To assess safety, the frequency and severity of treatment-related adverse
events, the incidence of laboratory abnormalities,
and changes from baseline in clinical and laboratory values were
compared between the 2 treatment groups.
Results
- Forty-two
patients were randomly assigned 1:1 to continue or stop the
nucleosides.
- At
baseline there were no significant differences between groups
in median CD4 cells/[mu]L (baseline or nadir), pre-HAART (highly
active antiretroviral therapy) HIV log10 viremia, or time
with HIV RNA <50 copies/mL prior to enrollment.
- After
48 weeks of follow-up, percentage of patients remaining at
<50 HIV RNA copies/mL (intention to treat, M = F) was 81%
for the monotherapy group (95% CI: 64% to 98%) vs. 95% for
the triple-therapy group (95% CI: 86% to 100%); P = 0.34.
- Patients
in whom monotherapy failed had significantly worse adherence
than patients who remained virally suppressed on monotherapy.
- Monotherapy
failures did not show primary resistance mutations in the
protease gene and were successfully re-induced with pre-randomization
nucleosides.
- Mean
change in CD4 cells/microliter: +70 (monotherapy) and +8 (triple)
(P = 0.27). Mean serum fasting lipids remained stable in both
groups.
- No
serious adverse events were observed.
Conclusion
Based on these results, the authors conclude, “Most of
the patients maintained with lopinavir/ritonavir monotherapy remain
with undetectable viral load
after 48 weeks.”
“Failures of lopinavir/ritonavir monotherapy were not
associated with the development of primary resistance mutations
in the protease gene and could be successfully re-induced adding
back prior nucleosides.”
Discussion
The study authors emphasize, “Our pilot clinical trial
provides preliminary evidence suggesting that lopinavir/r alone
could maintain HIV-1 viral suppression in a large proportion of
HIV-1-infected patients. In our study, 81% of patients randomly
allocated to maintenance with lopinavir/r monotherapy had plasma
HIV RNA levels <50 copies/mL after 72 weeks by intention to
treat.”
The authors also note that unlike with the use 3-drug
regimens, patients who experience treatment failure with lopinavir/ritonavir
monotherapy can be safely re-induced with prior nucleosides.
“Our results serve as proof of concept that it is possible
to use a [ritonavir]
boosted protease inhibitor alone as maintenance
of viral
suppression,” write the authors, and further, “Given
these results and the obvious benefits of single-drug treatment
of HIV infection, we believe that an adequately powered trial
of lopinavir/r monotherapy is warranted. Such a trial is currently
recruiting patients in 30 centers in Spain.”
10/28/05
Reference
J
R Arribas and others. Lopinavir/Ritonavir as Single-Drug Therapy
for Maintenance of HIV-1 Viral Suppression: 48-Week Results of
a Randomized, Controlled, Open-Label, Proof-of-Concept Pilot Clinical
Trial (OK Study). Journal of Acquired Immune Deficiency Syndromes.
40(3):280-287. November 1, 2005.
