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Efficacy and Tolerability of a NRTI-sparing
Combination of Lopinavir/Ritonavir and Efavirenz
The
US
Department of Health and Human Services (DHHS) HIV treatment guidelines
and other international guidelines recommend 2 first-line regimens
consisting of a backbone of 2 nucleoside
reverse transcriptase inhibitors (NRTIs), with 1
of them being lamivudine
(Epivir) or emtricitabine
(Emtriva), and lopinavir/ritonavir
(Kaletra) or efavirenz (Sustiva).
Lopinavir/ritonavir is considered the
preferred protease
inhibitor (PI) because of its high antiviral potency
and durability as well as acceptable patient tolerance, and efavirenz
is the preferred non
nucleoside
reverse transcriptase inhibitor (NNRTI).
Although the advantages associated
with all classes of antiviral drugs are numerous, several disadvantages
do exist. PIs are associated with an increased risk of lipodystrophy,
hyperlipidemia,
and insulin
resistance. The principal limitation of NNRTIs is
the high risk of cross-class
resistance that occurs in the setting of suboptimal
adherence or potency
Therefore, an innovative approach would
be to construct and evaluate an NRTI-free antiretroviral regimen
as part of a broader therapeutic strategy. Researchers designed
an open-label proof-of-concept study to assess the immunologic and
virologic efficacy and tolerability of an NRTI-free combination
of efavirenz and lopinavir/ritonavir in NNRTI-naive HIV-1-infected
adults for 48 weeks.
In this pilot open-label study, 65
antiretroviral-naive and 21 experienced but nonnucleoside reverse
transcriptase inhibitor-naive HIV-1-infected adults were given a
combination of lopinavir/ritonavir (533.3/133.3 mg twice daily)
and efavirenz (600 mg once daily) for 48 weeks.
Results
· At baseline, the mean
viral load was 4.84 log10 copies/mL and the mean CD4
count was 311 cells/mm3.
· At week 24, the proportions
of patients with a viral load <400 copies/mL were 78% and 93%
using an intent-to-treat and on-treatment analysis, respectively.
· At week 48, proportions
were 73% and 97%, respectively.
· Treatment
discontinuation occurred in 21 patients during the
48-week period, with 33% of those attributable to drug-related adverse effects.
· A viral load >400
copies/mL at week 24 or 48 was associated with non adherence in
3 patients and virologic failure in 1 patient.
· After an increase
during the first 8 weeks, fasting lipid levels remained stable up
to 48 weeks.
Conclusions
In conclusion, the authors write, “This
pilot study has proven that an NRTI-sparing regimen combining a
potent boosted PI, lopinavir/ritonavir, and a potent NNRTI, efavirenz,
is associated with a high rate of virologic success for up to 48
weeks as well as a sustained
immunologic response.”
“Most discontinuations were not related
to adverse event emergence or virologic failure
and could have been related to the pill burden of the formulations
used in this study. The availability of a more convenient formulation
of efavirenz should lessen the risk of dropouts unrelated to tolerability
problems. In addition, the relative lack of drug resistance
or virologic failure among subjects who remained on the medication
holds promise for this regimen.”
“Larger randomized and controlled trials
are needed to assess the immunologic and virologic response further,
to evaluate the safety of a PI-NNRTI combination compared with standard
NRTI-inclusive regimens, and to determine the best components, in
terms of efficacy and safety as well as convenience, within the
NNRTI and the boosted-PI
drug classes.”
06/29/05
Reference
C Allavena and others (the Bitherapy
Kaletra-Sustiva Study Group). Efficacy and Tolerability of a Nucleoside
Reverse Transcriptase Inhibitor-Sparing Combination of Lopinavir/Ritonavir
and Efavirenz in HIV-1-Infected Patients.
Journal of Acquired Immune Deficiency Syndromes 39(3):300-306,
July 1, 2005.
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