The protease inhibitors include atazanavir p. 423 , darunavir
p. 423 , fosamprenavir p. 425 (a pro-drug of amprenavir),
lopinavir (available as lopinavir with ritonavir), ritonavir
p.^426 , and tipranavir p.^426. Ritonavir in low doses boosts
the activity of atazanavir, darunavir, fosamprenavir,
lopinavir (available as lopinavir with ritonavir), and
tipranavir increasing the persistence of plasma
concentrations of these drugs; at such a low dose, ritonavir
has no intrinsic antiviral activity. The protease inhibitors are
metabolised by cytochrome P 450 enzyme systems and
therefore have a significant potential for drug interactions.
Protease inhibitors are associated with lipodystrophy and
metabolic effects.
The non-nucleoside reverse transcriptase inhibitors
efavirenz, etravirine p. 413 , nevirapine and rilpivirine p. 415
are active against the subtype HIV- 1 but not HIV- 2 ,a
subtype that is rare in the UK. These drugs may interact with
a number of drugs metabolised in the liver. Nevirapine is
associated with a high incidence of rash (including Stevens-
Johnson syndrome) and rarely fatal hepatitis. Rash is also
associated with efavirenz and etravirine but it is usually
milder. Psychiatric or CNS disturbances are common with
efavirenz. CNS disturbances are often self-limiting and can
be reduced by taking the dose at bedtime (especially in the
first 2 – 4 weeks of treatment). Efavirenz has also been
associated with an increased plasma cholesterol
concentration. Etravirine is used in regimens containing a
boosted protease inhibitor for HIV infection resistant to
other non-nucleoside reverse transcriptase inhibitors and
protease inhibitors.
Enfuvirtide below, which inhibits the fusion of HIV to the
host cell, is licensed for managing infection that has failed to
respond to a regimen of other antiretroviral drugs.
Enfuvirtide should be combined with other potentially active
antiretroviral drugs; it is given by subcutaneous injection.
Maraviroc p. 427 is an antagonist of the CCR 5 chemokine
receptor. It is used in patients exclusively infected with
CCR 5 – tropic HIV.
Dolutegravir p. 411 and raltegravir p. 411 are inhibitors of
HIV integrase. They are used for the treatment of HIV
infection when non-nucleoside reverse transcriptase
inhibitors or protease inhibitors cannot be used because of
intolerance, drug interactions, or resistance.Immune reconstitution syndrome
Improvement in immune function as a result of
antiretroviral treatment may provoke a marked
inflammatory reaction against residual opportunistic
organisms; these reactions may occur within thefirst few
weeks or months of initiating treatment. Autoimmune
disorders (such as Graves’disease) have also been reported
many months after initiation of treatment.Osteonecrosis
Osteonecrosis has been reported in children with advanced
HIV disease or following long-term exposure to combination
antiretroviral therapy.HIV infection in neonates
In order to prevent transmission of infection, neonates born
to HIV-positive mothers should be given post-exposure
prophylaxis as soon as possible after birth, but starting no
later than 72 hours after birth. Zidovudine p. 422 alone
should be given to neonates whose mothers had a viral load
less than 50 HIV RNA copies/mL between 36 weeks’
gestation and delivery, or whose mothers underwent
caesarean section while taking zidovudine monotherapy.
Combination antiretroviral therapy should be given to
neonates whose mothers had a viral load over 50 HIV RNA
copies/mL at delivery or whose mothers are found to be HIV
positive after delivery. Prophylaxis is continued for 4 weeks.ANTIVIRALS›HIV-FUSION INHIBITORS
Enfuvirtide
lDRUG ACTIONEnfuvirtide inhibits the fusion of HIV to the
host cell.lINDICATIONS AND DOSE
HIV infection in combination with other antiretroviral
drugs for resistant infection or for patients intolerant to
other antiretroviral regimens
▶BY SUBCUTANEOUS INJECTION
▶Child 6–15 years: 2 mg/kg twice daily (max. per dose
90 mg)
▶Child 16–17 years: 90 mg twice dailylSIDE-EFFECTS
▶Common or very commonAnxiety.appetite decreased.
asthenia.concentration impaired.conjunctivitis.diabetes
mellitus.gastrooesophageal reflux disease.haematuria.
hypertriglyceridaemia.increased risk of infection.
influenza like illness.irritability.lymphadenopathy.
myalgia.nasal congestion.nephrolithiasis.nightmare.
numbness.pancreatitis.peripheral neuropathy.skin
papilloma.skin reactions.tremor.vertigo.weight
decreased
▶Frequency not knownDiarrhoea.hypersensitivity.
immune reconstitution inflammatory syndrome.nausea.
osteonecrosis
SIDE-EFFECTS, FURTHER INFORMATION
HypersensitivityHypersensitivity reactions including
rash, fever, nausea, vomiting, chills, rigors, low blood
pressure, respiratory distress, glomerulonephritis, and
raised liver enzymes reported; discontinue immediately if
any signs or symptoms of systemic hypersensitivity
develop and do not rechallenge.
OsteonecrosisOsteonecrosis has been reported in
patients with advanced HIV disease or following long-term
exposure to combination antiretroviral therapy.
lPREGNANCYManufacturer advises use only if potential
benefit outweighs risk.
lHEPATIC IMPAIRMENTManufacturer advises caution—no
information available; chronic hepatitis B or C (possibly
greater risk of hepatic side-effects).
lDIRECTIONS FOR ADMINISTRATIONForsubcutaneous
injection, reconstitute with 1. 1 mL Water for Injections and
allow to stand (for up to 45 minutes) to dissolve; donot
shake or invert vial.
lPATIENT AND CARER ADVICE
Hypersensitivity reactionsPatients or carers should be told
how to recognise signs of hypersensitivity, and advised to
discontinue treatment and seek immediate medical
attention if symptoms develop.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Powder and solvent for solution for injection
ELECTROLYTES:May contain Sodium
▶Fuzeon(Roche Products Ltd)
Enfuvirtide 108 mgFuzeon 108 mg powder and solvent for solution
for injection vials| 60 vialP£ 1 , 081. 57410 Viral infection BNFC 2018 – 2019
Infection5