▶ Common or very common Diarrhoea . nausea . vomiting
l CONCEPTION AND CONTRACEPTION The effect on human
fertility is not known—impairment of fertility has been
l PREGNANCY Manufacturer advises avoid—toxicity in
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
moderate impairment in those with co-existing moderate
or severe renal impairment, and in severe impairment (risk
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (March
2019) that letermovir (Prevymis ®) is accepted for use
within NHS Scotland for the prophylaxis of
cytomegalovirus (CMV) reactivation and disease in adult
CMV-seropositive recipients [R+] of an allogeneic
haematopoietic stem cell transplant. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Prevymis (Merck Sharp & Dohme Ltd) A
Letermovir 240 mg Prevymis 240mg tablets | 28 tablet P £3,723.16
There is no cure for infection caused by the human
immunodeficiency virus (HIV) but a number of drugs slow or
halt disease progression. Drugs for HIV infection
(antiretrovirals) may be associated with serious side-effects.
Although antiretrovirals increase life expectancy
considerably and decrease the risk of complications
associated with premature ageing, mortality and morbidity
remain slightly higher than in uninfected individuals.
Treatment should be undertaken only by those experienced
Treatment aims to prevent the mortality and morbidity
associated with chronic HIV infection whilst minimising
drug toxicity. Although it should be started before the
immune system is irreversibly damaged, the need for early
drug treatment should be balanced against the risk of
toxicity. Commitment to treatment and strict adherence
over many years are required; the regimen chosen should
take into account convenience and patient tolerance. The
development of drug resistance is reduced by using a
combination of drugs; such combinations should have
synergistic or additive activity while ensuring that their
toxicity is not additive. It is recommended that viral
sensitivity to antiretroviral drugs is established before
starting treatment or before switching drugs if the infection
Treatment also reduces the risk of HIV transmission to
sexual partners, but the risk is not eliminated completely;
this risk and strategies to reduce HIV transmission should be
discussed with patients and their sexual partners.
The optimum time for initiating antiretroviral treatment
depends primarily on the CD4 cell count. The timing and
choice of treatment should also take account of clinical
symptoms, comorbidities, and the possible effect of
antiretroviral drugs on factors such as the risk of
cardiovascular events. Treatment includes a combination of
drugs known as ‘highly active antiretroviral therapy’.
Treatment of HIV-1 infection is initiated with 2 nucleoside
reverse transcriptase inhibitors and either a non-nucleoside
reverse transcriptase inhibitor, or a boosted protease
inhibitor, or an integrase inhibitor; the regimens of choice
contain tenofovir disoproxil p. 654 and emtricitabine p. 651
with either efavirenz p. 644 or ritonavir-boosted atazanavir
p. 656, or ritonavir-boosted darunavir p. 657, or raltegravir
p. 643. Alternative regimens contain abacavir p. 647 and
lamivudine p. 653 with either lopinavir with ritonavir p. 659,
or ritonavir-boosted fosamprenavir p. 658, or nevirapine
p. 645, or rilpivirine p. 646. Patients who require treatment
for both HIV and chronic hepatitis B should be treated with
antivirals active against both diseases.
HIV infection, switching therapy
Deterioration of the condition (including clinical and
virological changes) may require a change in therapy. The
choice of an alternative regimen depends on factors such as
the response to previous treatment, tolerance and the
possibility of cross-resistance.
Treatment of HIV infection in pregnancy aims to reduce the
risk of toxicity to the fetus (although information on the
teratogenic potential of most antiretroviral drugs is limited),
to minimise the viral load and disease progression in the
mother, and to prevent transmission of infection to the
neonate. All treatment options require careful
assessment by a specialist. Combination antiretroviral
therapy maximises the chance of preventing transmission
and represents optimal therapy for the mother. However, it
may be associated with a greater risk of preterm delivery.
Pregnancies in HIV-positive women and babies born to them
should be reported prospectively to the National Study of
HIV in Pregnancy and Childhood at www.ucl.ac.uk/nshpc/and
to the Antiretroviral Pregnancy Registry at www.apregistry.com.
HIV infection and breast-feeding
Breast-feeding by HIV-positive mothers may cause HIV
infection in the infant and should be avoided.
HIV infection, pre-exposure prophylaxis
The risk of acquiring HIV is increased in:
. men or transgender individuals who have unprotected anal
. sexual partners of people who are HIV-positive with a
. HIV-negative heterosexual individuals who have
unprotected intercourse with a HIV-positive person, and
are likely to repeat this with the same person or another
Emtricitabine with tenofovir disoproxil p. 652 may be
appropriate for pre-exposure prophylaxis to reduce the risk
of sexually acquired HIV-1 infection in combination with
safer sex practices in adults at high risk; recommendations
developed by the British Association for Sexual Health and
HIV are available at: www.bashh.org.
HIV infection, post-exposure prophylaxis
Prophylaxis with antiretroviral drugs [unlicensed indication]
may be appropriate following exposure to HIV-contaminated
material. Immediate expert advice should be sought in such
cases; national guidelines on post-exposure prophylaxis for
healthcare workers have been developed (by the Chief
Medical Officer’s Expert Advisory Group on AIDS),www.gov.
uk/dh and local ones may also be available. Antiretrovirals for
prophylaxis are chosen on the basis of efficacy and potential
for toxicity. Prompt prophylaxis with antiretroviral drugs
[unlicensed indication] is also appropriate following
potential sexual exposure to HIV; recommendations have
been developed by the British Association for Sexual Health
Zidovudine p. 655, a nucleoside reverse transcriptase
inhibitor (or ‘nucleoside analogue’), was the first anti-HIV
drug to be introduced. Other nucleoside reverse
transcriptase inhibitors include abacavir, didanosine p. 648,
emtricitabine, lamivudine, stavudine p. 654, and tenofovir
The protease inhibitors include atazanavir, darunavir,
fosamprenavir (a pro-drug of amprenavir), lopinavir
(available as lopinavir with ritonavir), ritonavir, saquinavir
p. 660, and tipranavir p. 660. Ritonavir in low doses boosts
the activity of atazanavir, darunavir, fosamprenavir,
lopinavir (available as lopinavir with ritonavir), saquinavir,
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 P450 enzyme systems and
therefore have a significant potential for drug interactions.
Protease inhibitors are associated with lipodystrophy and
The non-nucleoside reverse transcriptase inhibitors
efavirenz, etravirine p. 645, nevirapine, and rilpivirine are
used in the treatment of HIV-1 infection, but not against the
subtype HIV-2, a subtype that is rare in the UK. Nevirapine 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
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
Maraviroc p. 660 is an antagonist of the CCR5 chemokine
receptor. It is licensed for patients exclusively infected with
Dolutegravir p. 642, elvitegravir p. 643 and raltegravir
p. 643 are inhibitors of HIV integrase. They are licensed for
the treatment of HIV infection in combination with other
Cobicistat p. 661 is a pharmacokinetic enhancer that
boosts the concentrations of other antiretrovirals, but it has
no antiretroviral activity itself.
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 the first few
weeks or months of initiating treatment. Autoimmune
disorders (such as Graves’ disease) have also been reported
many months after initiation of treatment.
Osteonecrosis has been reported in patients with advanced
HIV disease or following long-term exposure to combination
HIV disease in children has a different natural progression to
adults. Children infected with HIV should be managed within
a formal paediatric HIV clinical network by specialists with
access to guidelines and information on antiretroviral drugs
ANTIVIRALS › HIV-FUSION INHIBITORS
l DRUG ACTION Enfuvirtide inhibits the fusion of HIV to the
HIV infection in combination with other antiretroviral
drugs for resistant infection or for patients intolerant to
papilloma . skin reactions .tremor. vertigo . weight
SIDE-EFFECTS, FURTHER INFORMATION Hypersensitivity
Hypersensitivity 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
Osteonecrosis Osteonecrosis has been reported in
patients with advanced HIV disease or following long-term
exposure to combination antiretroviral therapy.
l PREGNANCY Manufacturer advises use only if potential
l HEPATIC IMPAIRMENT Manufacturer advises caution— no
information available; chronic hepatitis B or C (possibly
greater risk of hepatic side-effects).
l DIRECTIONS FOR ADMINISTRATION For subcutaneous
injection, reconstitute with 1.1 mL Water for Injections and
allow to stand (for up to 45 minutes) to dissolve; do not
Hypersensitivity reactions Patients or carers should be told
how to recognise signs of hypersensitivity, and advised to
discontinue treatment and seek immediate medical
attention if symptoms develop.
l MEDICINAL 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
Enfuvirtide 108 mg Fuzeon 108mg powder and solvent for solution
for injection vials | 60 vial P £1,081.57
ANTIVIRALS › HIV-INTEGRASE INHIBITORS
l DRUG ACTION Dolutegravir is an inhibitor of HIV
HIV infection without resistance to other inhibitors of HIV
integrase, in combination with other antiretroviral drugs
HIV infection in patients where resistance to other
inhibitors of HIV integrase suspected, in combination
with other antiretroviral drugs
▶ Adult: 50 mg twice daily, dose to be taken with food
HIV infection in combination with other antiretroviral
drugs (with concomitant carbamazepine, efavirenz,
etravirine (without boosted protease inhibitors, but see
also Interactions), fosphenytoin, phenobarbital,
phenytoin, primidone, nevirapine, oxcarbazepine, St
John’s wort, rifampicin, or tipranavir)
▶ Adult: 50 mg twice daily, avoid concomitant use with
these drugs if resistance to other inhibitors of HIV
MHRA/CHM ADVICE: DOLUTEGRAVIR (TIVICAY ®, TRIUMEQ ®,
JULUCA ®): SIGNAL OF INCREASED RISK OF NEURAL TUBE
DEFECTS; DO NOT PRESCRIBE TO WOMEN SEEKING TO BECOME
PREGNANT; EXCLUDE PREGNANCY BEFORE INITIATION AND
ADVISE USE OF EFFECTIVE CONTRACEPTION (JUNE 2018)
New safety recommendations have been issued while an
EU review evaluates cases of neural tube defects in
babies born to mothers who became pregnant while
taking dolutegravir. The MHRA advises:
. dolutegravir should not be prescribed to women who
are trying to become pregnant;
. pregnancy should be excluded in women of
childbearing potential with pregnancy testing before
. women of childbearing potential should be advised to
use effective contraception throughout treatment with
. if pregnancy is confirmed in the first trimester while a
woman is taking dolutegravir, switch to an alternative
treatment unless there is no suitable alternative;
. women taking dolutegravir for HIV should be advised
not to stop taking their medicine without first
l INTERACTIONS → Appendix 1: dolutegravir
SIDE-EFFECTS, FURTHER INFORMATION Hypersensitivity
Hypersensitivity reactions (including severe rash, or rash
accompanied by fever, malaise, arthralgia, myalgia,
blistering, oral lesions, conjunctivitis, angioedema,
eosinophilia, or raised liver enzymes) reported
uncommonly. Discontinue immediately if any sign or
symptoms of hypersensitivity reactions develop.
Osteonecrosis Osteonecrosis has been reported in
patients with advanced HIV disease or following long-term
exposure to combination antiretroviral therapy.
l PREGNANCY Manufacturer advises avoid, see Important
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment—no information available.
l PATIENT AND CARER ADVICE Patients or carers should be
given advice on how to administer dolutegravir tablets.
Missed doses If a dose is more than 20 hours late on the
once daily regimen (or more than 8 hours late on the twice
daily regimen), the missed dose should not be taken and
the next dose should be taken at the normal time.
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (May 2014)
that dolutegravir (Tivicay ®) is accepted for use within NHS
adults. This advice is contingent upon the continuing
availability of the patient access scheme in NHS Scotland
or a list price that is equivalent or lower.
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised
(October 2017) that dolutegravir (Tivicay ®) is
recommended as an option for use within NHS Wales in
combination with other anti-retroviral medicinal products
for the treatment of HIV infected adults. This
recommendation applies only in circumstances where the
approved Wales Patient Access Scheme (WPAS) is utilised
or where the list/contract price is equivalent or lower than
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Tivicay (ViiV Healthcare UK Ltd) A
Dolutegravir (as Dolutegravir sodium) 10 mg Tivicay 10mg tablets
| 30 tablet P £99.75 DT = £99.75
Dolutegravir (as Dolutegravir sodium) 25 mg Tivicay 25mg tablets
| 30 tablet P £249.38 DT = £249.38
Dolutegravir (as Dolutegravir sodium) 50 mg Tivicay 50mg tablets
| 30 tablet P £498.75 DT = £498.75
Combinations available: Abacavir with dolutegravir and
Dolutegravir with rilpivirine 28-Sep-2018
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, dolutegravir above, rilpivirine p. 646.
HIV-1 infection (initiated by a specialist)
DOSE EQUIVALENCE AND CONVERSION
▶ Dose expressed as x/y mg dolutegravir/rilpivirine.
l INTERACTIONS → Appendix 1: dolutegravir.rilpivirine
Missed doses If a dose is more than 12 hours late, the
missed dose should not be taken and the next dose should
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of dizziness
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (September
2018) that dolutegravir with rilpivirine film-coated tablet
(Juluca ®) is accepted for use within NHS Scotland for the
(HIV-1 RNA <50 copies/mL) on a stable antiretroviral
regimen for at least six months with no history of
virological failure and no known or suspected resistance to
any non-nucleoside reverse transcriptase inhibitor
(NNRTI) or integrase inhibitor. This advice is contingent
upon the continuing availability of the patient access
scheme in NHS Scotland or a list price that is equivalent or
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised
(December 2018) that dolutegravir with rilpivirine
(Juluca ®) is recommended as an option for use within NHS
Wales for the treatment of human immunodeficiency virus
type 1 (HIV-1) infection in adults who are virologically
suppressed (HIV-1 RNA < 50 copies/ml) on a stable
antiretroviral regimen for at least six months with no
history of virological failure and no known or suspected
resistance to any nonnucleoside reverse transcriptase
inhibitor or integrase inhibitor. This recommendation
applies only in circumstances where the approved Wales
Patient Access Scheme (WPAS) is utilised or where the
list/contract price is equivalent or lower than the WPAS
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Juluca (ViiV Healthcare UK Ltd) A
Rilpivirine (as Rilpivirine hydrochloride) 25 mg, Dolutegravir (as
Dolutegravir sodium) 50 mg Juluca 50mg/25mg tablets | 30 tablet P £699.02
l DRUG ACTION Elvitegravir is an inhibitor of HIV integrase,
which is an enzyme required for viral replication.
HIV infection without resistance to other inhibitors of HIV
integrase, in combination with low-dose ritonavir and
▶ Adult: 85 mg once daily, take at the same time as a
once daily ritonavir-boosted regimen or with the first
dose of a twice daily ritonavir-boosted regimen
HIV infection without resistance to other inhibitors of HIV
integrase, in combination with low-dose ritonavir and
▶ Adult: 150 mg once daily, take with the first dose of a
twice daily ritonavir-boosted regimen
l CAUTIONS Elderly—limited information available
l INTERACTIONS → Appendix 1: elvitegravir
▶ Common or very common Diarrhoea . fatigue . headache . nausea .rash . vomiting
suicidal ideation (in patients with history of depression or
psychiatric illness).taste altered
▶ Frequency not known Hyperglycaemia . osteonecrosis . weight increased
SIDE-EFFECTS, FURTHER INFORMATION For further
information regarding osteonecrosis see HIV infection
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of child-bearing potential should use effective
contraception during treatment (if using a hormonal
contraceptive, it must contain norgestimate as the
progestogen and at least 30 micrograms ethinylestradiol).
l PREGNANCY Manufacturer advises avoid unless
essential—limited data available.
Missed doses Manufacturer advises if a dose is more than
18 hours late, the missed dose should not be taken and the
next dose should be taken at the normal time. If vomiting
occurs within 1 hour of taking a dose, a replacement dose
l MEDICINAL FORMS No licensed medicines listed.
Combinations available: Elvitegravir with cobicistat,
emtricitabine and tenofovir alafenamide, p. 649 . Elvitegravir
with cobicistat, emtricitabine and tenofovir disoproxil, p. 650
l DRUG ACTION Raltegravir is an inhibitor of HIV integrase.
HIV-1 infection (initiated by a specialist)
▶ Adult: 400 mg twice daily, alternatively 1200 mg once
daily, once daily dosing for use in patients who are
treatment naive or virologically suppressed on an
initial regimen of 400 mg twice daily—use 600 mg
l CONTRA-INDICATIONS Pre-term neonates—no information
l CAUTIONS Psychiatric illness (may exacerbate underlying
illness including depression).risk factors for myopathy . risk factors for rhabdomyolysis
l INTERACTIONS → Appendix 1: raltegravir
reactions . sleep disorders . vertigo . vomiting
impairment. sensation abnormal . severe cutaneous
adverse reactions (SCARs). skin papilloma . submandibular
mass . suicidal tendencies . sweat changes .taste altered .
tendinitis .thrombocytopenia .tinnitus .tremor. visual
▶ Frequency not known Osteonecrosis
SIDE-EFFECTS, FURTHER INFORMATION Rash occurs
commonly. Discontinue if severe rash or rash accompanied
by fever, malaise, arthralgia, myalgia, blistering, mouth
ulceration, conjunctivitis, angioedema, hepatitis, or
For further information regarding lipodystrophy and
osteonecrosis see HIV infection p. 640
l PREGNANCY Manufacturer advises avoid—toxicity in
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment—no information available. Use with
caution in patients with chronic hepatitis B or C (at greater
risk of hepatic side-effects).
l PRESCRIBING AND DISPENSING INFORMATION Dispense
raltegravir chewable tablets in original container (contains
l NATIONAL FUNDING/ACCESS DECISIONS
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