Retrovirus Conference Update
by Patrick G. Clay, PharmD
The 9th Retroviruses
Conference held in Seattle provided useful information about
drug interactions and pharmacokinetics. At this meeting as
well as upcoming ones, it is imperative to learn more information
about how the various medications interact and what levels
are obtained.
An assessment of how increasing
the dose of ritonavir (Norvir) changes the body’s level of
GlaxoSmithKline’s pipeline protease inhibitor 908, was presented.
Non-HIV infected persons were given 908 with ritonavir and
efavirenz (Sustiva). The dose of 908 and efavirenz remained
the same (700 mg and 600 mg, respectively). The dose of ritonavir
was 100 mg for one group and 200 mg for the other. The researchers
found no significant increase in the plasma concentrations
of 908 when a higher dose of ritonavir was given. This is
important as this is helping to decide how much ritonavir
is going to be given in clinical trials and, likely, the expanded
access program with the new protease inhibitor.
Examining how delavirdine
(Rescriptor) is affected by amprenavir (Agenerase) was reported.
There are those who believe that delavirdine, given its potent
liver metabolism inhibitory properties, could be used in the
place of ritonavir in boosting levels of other agents. Eighteen
non-HIV infected persons were given delavirdine or amprenavir
for 10 days, had levels checked and then given the other drug
for another 10 days and had levels checked again. It was found
that the delavirdine levels were significantly dropped. The
levels of amprenavir, however, were increased “favorably.”
The investigators may be planning on examining this further
to find out what may be the optimal combination of medications.
Critical to preventing transmission
of HIV from mother to infant is the assurance that adequate
levels of drugs are maintained in both mother and infant.
Two posters examined the levels of medications in these populations.
One study looked to see the levels of nelfinavir (Viracept)
in women before, during and after labor as well as in their
infants. The study had 23 HIV-1 infected women. The authors
report good levels in the women, but that in 28% of infants,
levels were less than desirable. Both groups tolerated the
medications well. The adjacent poster was evaluating ritonavir
in women and children. The ritonavir was given before, during
and after labor as well. The infants received one dose of
ritonavir between 8–12 days after birth. The investigators
reported that the dose used for the infants did not produce
adequate blood levels. More studies are clearly needed to
ensure that adequate dosing of these agents are achieved in
this population of highly preventable transmission.
Abbott presented information
about using their new protease inhibitor, lopinavir/ritonavir
(Kaletra), once daily versus the approved twice daily dosing
schedule. Thirty-eight HIV positive persons were given either
four capsules twice a day or eight capsules once daily. Three
weeks later, the blood concentrations were assessed. These
same concentrations were checked again over the next 48 weeks.
They found much greater variance in the amount of drug in
the plasma at the end of the dosing times in the once daily
compared to the twice daily regimen. They also stated the
amount of drug needed for good outcomes was achieved. The
researchers compared the percent of patients with viral loads
less than 50 copies/mL at week 48 and found no difference
between the two arms. This data raises a number of questions
about targeting once daily regimens as the ultimate goal of
pharmaceutical company development. Many studies have found
that, from an adherence standpoint, once daily offers no improvement
compared to twice daily. Yet, this type of regimen may allow
for dosing in special populations (e.g., incarcerated, marginally
housed) persons with new evidence that the amount of drug
being given a person is not being compromised.
Lastly, a session at the
conference, appropriately entitled, “Controversies in HIV
Therapy” given by David Back, PhD, provided insight into the
direction being taken by investigators utilizing Therapeutic
Drug Monitoring (TDM). Dr. Back discussed at length the studies
completed to date, both those showing evidence to support
as well as refute the need to conduct TDM in clinical practice,
which measures drug levels in individuals. His points included
the need to conduct TDM to be incorporated into practice as
a complementary and not stand alone nor replacement tool for
others. This was driven home by the review of data in which
using the inhibitory quotient (IQ) versus resistance assays
or TDM alone proved more predictive of outcomes. He then went
on to point out that IQ itself is still a research tool and
controversies still surround it.
The abstracts I have chosen
to summarize here represent only a snapshot of what was presented
at CROI and a miniscule amount of what is available in the
literature. TDM continues to be evaluated as a component of
clinical practice, but from the data presented in this conference
and others, it is not quite ready for “prime time.”
Patrick G. Clay, PharmD
is an Assistant Professor of Pharmacy Practice at the University
of Missouri-Kansas City School of Pharmacy. He is also the
HIV Clinical Specialist at the KC Free Health Clinic, 3515
Broadway, Kansas City, MO 64111. Clay can be reached by phone:
(816) 777-2721; fax: (816) 753-0804; or email: claypg@umkc.edu.
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