Early
HAART regimens characteristically
involved complicated combinations of drugs, which often were taken as varying
numbers of pills and as multiple doses each day. With the recent availability
of once-daily drugs, simpler regimens have becoming increasingly popular because
of increased convenience.
To
help physicians and their patients make informed decisions about updating treatment
regimens, a review described in a recent issue of Drugs compared newer
once-daily administration regimens against older twice-daily administration regimens
in terms of efficacy, durability, potential for adverse effects, and patient adherence.
More than 10
antiretroviral agents or drug combinations are now approved for once-daily administration
in some countries: abacavir (Ziagen),
didanosine (ddI; Videx), emtricitabine
(Emtriva), lamivudine (3TC;
Epivir), tenofovir (Viread),
efavirenz (Sustiva), atazanavir
(Reyataz), ritonavir-boosted
atazanavir, boosted fosamprenavir (Lexiva),
and co-formulated lopinavir/ritonavir (Kaletra).
In addition,
some drugs have been co-formulated for once-daily administration: abacavir/lamivudine
(Epzicom), tenofovir/emtricitabine
(Truvada), and tenofovir/emtricitabine/efavirenz
(Atripla).
Clinical
trials have validated the efficacy of HAART combination regimens for once-daily
or twice-daily administration in patients who were treatment-naive or who required
salvage therapy.
On
the basis of efficacy measures reflecting reduced viral load (percentage of patients
with HIV RNA levels <400 or <50 copies/mL), once-daily regimens were consistently
found to be at least as effective as twice-daily regimens, and sometimes more
effective.
Most
of the regimens studied for efficacy consisted of a combination of two nucleoside/nucleotide
reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse transcriptase
inhibitor (NNRTI). Efavirenz was the most commonly used NNRTI, and it was typically
used in combination with either lamivudine or emtricitabine plus either didanosine,
abacavir, or tenofovir.
In
regimens that replaced efavirenz with a once-daily protease inhibitor, those that
included atazanavir or lopinavir/ritonavir has similar efficacy as either once-daily
or twice-daily regimens.
In
terms of adherence to specific regimens, reviewed studies demonstrated that once-daily
HAART regimens were at least non-inferior, and were often superior, to twice-daily
regimens, with no significant decrease in efficacy.
In
conclusion, according the review author Jean-Michel Molina, once-daily HAART regimens
have been validated in clinical trials as safe, effective, and well tolerated.
Such combinations are likely to improve patient adherence because they are simpler
and more convenient than earlier therapeutic regimens.
Department
of Infectious Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital
Saint-Louis, Université Paris Diderot, Paris 7, France.
4/25/08
Reference
JM Molina.
Efficacy and Safety of Once-daily Regimens in the Treatment of HIV Infection.
Drugs 68(5): 567-78. 2008.
Related
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Care STDs. February 1, 2008. [Epub ahead of print].
J
Eron Jr, P Yeni, J Gathe Jr, and others (KLEAN study team. The KLEAN study of
fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine,
for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority
trial. Lancet 368 (9534): 476-482. August 5, 2006.
S
Moreno, B Hernandez and F Dronda. Didanosine enteric-coated capsule: current role
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