C H A P T E R 1 0
Antiviral agents
137
treat HIV infections. These are drugs that compete with
the naturally occurring nucleosides within a human cell
that the virus would need to develop. The nucleoside
reverse transcriptase inhibitors include the following
agents: abacavir (
Ziagen
), didanosine (
Videx
), emtrici
tabine (
Emtriva
), lamivudine (
Combivir, 3TC, Zeffix
),
stavudine (
Zerit
), tenofovir (
Viread
) and zidovudine
(
Retrovir
).
Therapeutic actions and indications
Nucleoside reverse transcriptase inhibitors compete
with the naturally occurring nucleosides within the cell
that the virus would use to build the DNA chain. These
nucleosides, however, lack a substance needed to extend
the DNA chain. As a result, the DNA chain cannot
lengthen and cannot insert itself into the host DNA. Thus
the virus cannot reproduce. They are used as part of com-
bination therapy for the treatment of HIV infection. See
Table 10.3 for usual indications for each of these agents.
Pharmacokinetics
Abacavir is an oral drug that is rapidly absorbed from
the GI tract. It is metabolised in the liver and excreted in
faeces and urine with a half-life of 1 to 2 hours.
Didanosine is rapidly destroyed in an acid environ-
ment and therefore must be taken in a buffered form.
It reaches peak levels in 15 to 75 minutes. Didanosine
undergoes intracellular metabolism with a half-life of
8 to 24 hours. It is excreted in the urine.
Emtricitabine has the advantage of being a one-
capsule-a-day therapy. Emtricitabine has a rapid onset
and peaks in 1 to 2 hours. It has a half-life of 10 hours,
and after being metabolised in the liver is excreted in
the urine and faeces. Dose needs to be reduced in indi-
viduals with renal impairment. It has been associated
with severe and even fatal hepatomegaly with steatosis,
a fatty degeneration of the liver.
Lamivudine is rapidly absorbed from the GI tract
and is excreted primarily unchanged in the urine. It
peaks within 4 hours and has a half-life of 5 to 7 hours.
Because excretion depends on renal function, dose
reduction is recommended in the presence of renal
impairment. The drug is available as an oral solution,
Epivir-HBV
;
it is also recommended for the treatment of
chronic hepatitis B.
Stavudine is rapidly absorbed from the GI tract,
reaching peak levels in 1 hour. Most of the drug is
excreted unchanged in the urine, making it important
to reduce dose and monitor people carefully in the
presence of renal dysfunction. It can be used for adults
and children and is only available in an extended-release
form, allowing for once-a-day dosing.
Tenofovir is a newer drug that affects the virus at a
slightly different point in replication—a nucleotide that
becomes a nucleoside. It is used only in combination with
other antiretroviral agents. It is rapidly absorbed from
the GI tract, reaching peak levels in 45 to 75 minutes. Its
metabolism is not known, but it is excreted in the urine.
Zidovudine was one of the first drugs found to be
effective in the treatment of AIDS. It is rapidly absorbed
from the GI tract, with peak levels occurring within
30 to 75 minutes. Zidovudine is metabolised in the liver
and excreted in the urine, with a half-life of 1 hour.
Contraindications and cautions
Of the nucleosides, zidovudine is the only agent that has
been proven to be safe when used during pregnancy.
Of the other agents, there have been no adequate studies
in pregnancy, so use should be limited to situations in
which the benefits clearly outweigh any risks. Women
TABLE 10.3
DRUGS IN FOCUS Agents for HIV and AIDS continued
Drug name
Dosage/route
Usual indications
Protease inhibitors (continued)
tipranavir (Aptivus)
Adults: 500 mg PO b.d. with ritonavir 200 mg
PO b.d.
Paediatric >2 years: 375 mg/m
2
b.d. with
ritonavir 150 mg/m
2
b.d.
Treatment of adults and children with HIV
in combination with ritonavir
Fusion inhibitor
enfuvirtide (Fuzeon)
Adult: 90 mg PO b.d. by SC injection
Paediatric 6–16 years: 2 mg/kg b.d. by SC
injection
Part of combination therapy in treatment
of people with HIV with evidence of HIV
replication despite antiretroviral therapy
CCR5 coreceptor antagonist
maraviroc (Celsentri)
Adult: 150 mg PO b.d.
Part of combination therapy for treatment
of HIV-1 infections
Integrase inhibitor
raltegravir (Isentress)
Adult: 400 mg PO b.d.
Part of combination therapy for treatment
of HIV-1 infections
