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HIV and AIDS
An Overview of the ArTEN Trial
a report by
Vicente Soriano
1
and Lothar de Rossi
2
1. Assistant Director, Department of Infectious Diseases, Hospital Carlos III;
2. Section Leader, Department of Clinical Research Virology, Boehringer Ingelheim Pharma GmbH & Co KG
The Atazanavir, Ritonavir, Tenofovir, Emtricitabine and Nevirapine ATZ is the first once-daily PI,
11
and it has shown efficacy both
(ArTEN) trial was designed as an open-label, prospective, randomised, unboosted and in combination with ritonavir as part of highly active
comparative phase IIIb clinical trial. Its primary purpose is to determine antiretroviral therapy (HAART).
12,13
One of the distinct properties of
the comparative efficacy and safety of nevirapine (NVP) and ritonavir- ATZ is its favourable effect on dyslipidaemia and its apparent lack
boosted atazanavir (ATZ/r), both on a Truvada
®
tenofovir/emtricitabine of negative effects on glucose metabolism.
14,15
However, ATZ/r has
(TDF/FTC) backbone, in antiretroviral-naïve HIV-1-infected individuals. shown a less favourable lipid profile compared with unboosted ATZ.
16
The trial will also allow a prospective examination of the efficacy and
safety of NVP in a patient population using the CD4 T-cell count TDF/FTC has become the most frequently used backbone for non-
thresholds as described on the label, which indicates that NVP should nucleoside reverse transcriptase inhibitors (NNRTIs) and PI-based
not be initiated in adult females with CD4
+
T-cell counts greater than HAART in HIV-1-infected treatment naïve patients.
17
To date, there are
250 cells/mm
3
or in adult males with CD4
+
T-cell counts greater only limited clinical data available on the efficacy, safety and metabolic
than 400 cells/mm
3
, unless the benefits outweigh the risks. effects of the combination of NVP and TDF/FTC. Two studies based on
small patient samples, which were prematurely halted, suggested that
Study Drugs regimens consisting of TDF/FTC and NVP could be associated with a
The use of NVP-based regimens in routine clinical settings has been risk of early virological failure in antiretroviral-naïve HIV-1-infected
established as safe and effective when treating HIV-1-infected patients.
18,19
These reports are not in accordance with larger studies
individuals.
1–4
A Randomized Comparative Trial of First-line Antiretroviral that have indicated that this regimen results in effective viral
Therapy with Regimens Containing Either Nevirapine Alone, Efavirenz suppression. Moreover, there is no evidence of any significant
Alone or Both Drugs Combined, Together with Stavudine and pharmacokinetic interaction between TDF and NVP that would
Lamivudine (2NN) study, which compared the efficacy and safety of NVP compromise the virological efficacy of a regimen composed of TDF/FTC
once or twice daily with efavirenz (all regimens on a backbone of and NVP.
20–24
stavudine and lamivudine), showed no significant differences in
treatment failure between these regimens.
4
The trial also showed that Study Rationale and Questions Addressed
NVP once daily had similar antiviral efficacy to NVP twice daily, and Currently, ATZ/r in combination with TDF/FTC is one of the most
therefore might be appropriated for treatment simplification.
4–6
Data frequently recommended PI-based regimens for the treatment of
collected retrospectively from the 2NN study for a further three years antiretroviral-naïve patients.
16
As for NVP, ATZ/r has a favourable
showed no significant difference between the treatment arms through impact on lipids compared with other PIs. However, there are only
week 144.
7
NVP has consistently been shown to have a favourable lipid limited data on the comparable efficacy and safety of ATZ/r and
and metabolic profile in comparison with both efavirenz and protease NNRTIs such as NVP. Therefore, ATZ/r was used as the comparator in
inhibitors (PI).
8–10
the ArTEN study.
In comparison with NNRTIs, such as NVP, the efficacy results obtained
Vincent Soriano is Assistant Director of the Department of
Infectious Diseases at the Hospital Carlos III in Madrid. He is
with PIs have been affected by a poorer tolerability profile and thus
Chair of the HIV–Hepatitis International Panel, which worse adherence to treatment.
25
Recently, ATZ has been marketed as a
periodically releases guidelines on how to manage HIV
PI with certain characteristics that are similar to those of the NVP, such
patients co-infected with hepatitis B and C. Dr Soriano is
involved in the National AIDS Programme in Spain and is the
as being generally well tolerated, associated with potentially favourable
editor of Manual del SIDA, an HIV/AIDS reference book for
lipid profiles, a convenient dosing schedule and a low pill burden.
Spanish-speaking countries.
Therefore, it is sensible to consider the intrinsic virological efficacy of
E:
vsoriano@dragonet.es
ATZ and NVP and the reduced impact of confounding factors, such as
reduced adherence to treatment and impaired tolerability.
Lothar de Rossi is Section Leader in the Department of
Clinical Research Virology at Boehringer Ingelheim Pharma
GmbH & Co KG in Biberach. He is the international head Several studies have suggested that in antiretroviral-naïve patients
responsible for planning and conducting the phase IIIb
PI-based regimens might be associated with a better immune recovery
ArTEN (Atazanavir, Ritonavir, Tenofovir, Emtricitabine and
Nevirapine Trial) study. Dr de Rossi is also a Reader in
than NNRTI-based regimens.
26–28
Inhibition of peripheral CD4
+
Anaesthesiology and Intensive Care Medicine at the
T-lymphocyte apoptosis and a greater degree of suppression of HIV
University Hospital Aachen.
replication with PIs have been reported to account for this further immune
benefit beyond viral suppression. However, this observation has not been
42 © TOUCH BRIEFINGS 2008
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