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The predictive value of total lymphocyte count (TLC) for mortality is not reliable, especially for young-er

infants, and it is therefore not recommended to use TLC to guide decisions on starting ART.

etermination of viral load (e.g. using plasma !"#-$ R%A levels) is not considered a prere&uisite

to starting ART. 'ecause of the cost and compleity of viral load testing, currently, !* does not

re-&uire its routine use to assist +ith decisions on +hen to start therapy, to determine adherence,

or to recognie treatment failure in resource-limited settings. "t is hoped, ho+ever, that

increasingly feasi-ble and affordable methods of determining viral load +ill become available.

Table Recommendations for initiating ART in !"#-infected infants and children

according to clinical stage and immunological mar/ers

Clinical stage "mmunological

012 months Treat all

3tage 2a

Treat allb

412 months

3tage 5a

Treat all

3tage 1

Treat if C2 belo+ age-ad6usted

threshold

3tage $ on7t treat if no C2 available

1 3tabilie any opportunistic infection (*") before initiating ART.

2 'aseline C2 is useful for monitoring ART even if it is not re&uired to initiate ART.

5.6 Criteria for starting ART in infants and children less than $8 months +ith apresumptive diagnosis of severe !"# disease

here access to virological testing is not yet available, !* has developed criteria for ma/ing apresumptive diagnosis of severe !"# disease in children less than $8 months of age, in order to

allo+ initiation of potentially life-saving ART. Any presenting acute illnesses should be managed

first fol-lo+ed by prompt initiation of antiretroviral therapy.

"n infants and children +ho have been started on ART on the basis of a presumptive diagnosis of

severe !"# disease, treatment should be closely monitored and confirmation of !"# infection

should be obtained as soon as possible using age-appropriate testing methods. Additionally, !"#

serologi-cal testing should be performed at $8 months of age to confirm definitive !"# infection

status in the child. ecisions on further treatment should be ad6usted at that time in accordance

+ith the results. ART should be stopped in infants and children only +here !"# infection can beconfidently ruled out and +hen such children are no longer eposed to !"# (i.e. through

breastfeeding from an !"#-infect-ed mother).

The initiation of ART on the basis of a presumptive diagnosis of severe !"# disease is not recom-

mended for use by providers +ho are not appropriately trained in !"# care or the administration of

ART. 9resumptive diagnosis of severe !"# disease should not be used in children aged $8

months and older as antibody testing establishes their !"# infection status.

Table 8 lists the criteria for a presumptive clinical diagnosis.

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1:

A%T"R;TR*#"RAL T!;RA9< =*R !"# "%=;CT"*% "% "%=A%T3 A% C!"LR;%

T*AR3 >%"#;R3AL ACC;33

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Table 8 Criteria for presumptive diagnosis of severe !"# disease in infants and

children 0$8 months of age +here viral testing is not available

A presumptive diagnosis of severe !"# disease should be made if

$. The child is confirmed asbeing

1

a.

The infant is symptomatic +ith t+o or more of thefollo+ing

!"# antibody-positive ? oral thrush

? severe pneumonia

A% ? severe sepsis

*R1b. A diagnosis of any A"3-indicator condition(s) a can bemade

*ther findings that support the diagnosis of severe !"# disease in an !"#-seropositive infant include

@ Recent !"#-related maternal death or advanced !"# disease

@ Child7s C2B 01

Confirm the diagnosis of !"# infection as soon as possible.

1 A"3-indicator conditions include some but not all !"# paediatric clinical stage 2 conditions such as 9neumocystis pneumo-nia, cryptococcal meningitis, severe +asting or severe malnutrition, Daposi sarcoma, etrapulmonary T'.

As per the "EC" definition

*ral thrush Creamy +hite-to-yello+ soft small pla&ues on red or normally coloured mucosa +hich can often be scraped off

(pseudomembranous), or red patches on the tongue, palate or lining of mouth, usually painful or tender.

3evere pneumonia Cough or difficult breathing in a child +ith chest indra+ing, stridor or any of the "EC" general danger

signsF i.e. lethargic or unconscious, not able to drin/ or breastfeed, vomiting, and presence or history of convulsions during

current illnessF responding to antibiotics.

3evere sepsis =ever or lo+ body temperature in a young infant +ith any severe sign, e.g. fast breathing, chest indra+ing,

bulging fontanelle, lethargy, reduced movement, not feeding or suc/ing breast mil/, convulsions.

"t is unclear ho+ often C2 is lo+ered in the above conditions in !"#-uninfected children.

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WHAT TO START RECOMMENDED FIRST-LINE ARV

REGIMENS FOR INFANTS AND CHILDREN

:.$ Recommendations

:.$.$ "nfants

1. =or infants not eposed to AR#s, start ART +ith nevirapine (%#9) B 1 nucleoside reversetran-scriptase inhibitors (%RT"s).

(Strong recommendation, moderate quality of evidence)

2. =or infants eposed to maternal or infant %#9 or other %%RT"s used for maternal treatment or9ETCT, start ART +ith lopinavirGritonavir (L9#Gr) B 1 %RT"s.


3. =or infants +hose eposure to AR#s is un/no+n, start ART +ith %#9 B 1 %RT"s.(Conditional recommendation, low quality of evidence)

:.$.1 Children

2. =or children bet+een $1 and 12 months of age eposed to maternal or infant %#9 or other

%%RT"s used for maternal treatment or 9ETCT, start ART +ith lopinavirGritonavir (L9#Gr) B 1

%RT"s

(Conditional recommendation, low quality of evidence)

5. =or children bet+een $1 and 12 months of age, not eposed to %%RT"s, start ART +ith %#9 B1 %RT"s.


6. =or children more than 12 months and less than 5 years of age, start ART +ith %#9 B 1 %RT"s.(Strong recommendation, moderate quality of evidence)

7. =or children 5 years of age and above, start ART +ith an %#9 or efaviren (;=#)-containingregi-men B 1 %RT"s.


8. =or infants and children, the nucleoside bac/bone for an ART regimen should be one of thefol-lo+ing, in preferential order

1 Lamivudine (5TC) B idovudine (AHT)

2 5TC B abacavir (A'C)

3 5TC B stavudine (d2T)(Conditional recommendation, low quality of evidence)

:.$.5 "nfants and children +ith specific conditions

9. =or children 45 years of age +ith T', the preferred regimen is ;=# B 1 %RT"s.(Conditional recommendation, very low quality of evidence)

10. =or infants and children less than 5 years of age +ith T', the preferred regimens are%#9 B 1 %RT"s or a triple nucleoside regimen.

(Conditional recommendation, very low quality of evidence)

11. =or a child or adolescent +ith severe anaemia (0.I gGdl) or severe neutropenia (0IcellsGmm

5), the preferred regimen is %#9 B 1 %RT"s (avoid AHT).

(Conditional recommendation, very low quality of evidence)

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A%T"R;TR*#"RAL T!;RA9< =*R !"# "%=;CT"*% "% "%=A%T3 A% C!"LR;%T*AR3 >%"#;R3AL ACC;33

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12. =or adolescents 4$1 years of age +ith hepatitis ', the preferred regimen is tenofovirdisoproil fumarate (T=) B emtricitabine (=TC) or 5TC B %%RT".(Conditional recommendation, very low quality of evidence)

:.1 Antiretroviral treatment using a public health approach

Countries are encouraged to use a public health approach to support and facilitate +ider access to ART

J:K. Among the /ey tenets of this approach are standardiation and simplification of ART regimens.

Therefore, it is suggested that countries select a limited number of first-line regimens and suitable

second-line regimens, recogniing that children +ho cannot tolerate or +ho fail the first-line and sec-

ond-line regimens may re&uire input from more eperienced physicians. The use of three AR# medica-

tions is the current standard treatment for !"# infection, in order to achieve the best possible suppres-

sion of viral replication and to arrest the progression of !"# disease. "t is important to maimie the

durability and efficacy of any first-line regimen by incorporating approaches to support adherence.

'o $ 3tandard regimen for first-line ART

1 %RT"s B $ %%RT"

%RT"G%%RT"-based regimens are efficacious and generally less epensive. "n addition, generic

for-mulations may be available, and a cold chain is not re&uired.

Table ;amples of %RT"s and %%RT"s

%RT"s include

Thymidine analogue Cytidine analogue Muanosine analogue

idovudine (AHT) lamivudine (5TC) abacavir (A'C)

stavudine (d2T)

%%RT"s includeefaviren (;=#)

nevirapine (%#9)

hen appropriate AR# regimens are being selected for the national formulary, the follo+ing pro-

gramme-level factors should be ta/en into consideration

1 ability to treat all ages

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2 suitability of drug formulation, particularly for dosing in infants, young children

3 ease of dispensing for pharmacists and caregivers

4 licensing approval by national drug regulatory authorities for the product and therecommended dose

5 toicity profile

6 laboratory monitoring re&uirement

1

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1 potential for maintenance of future treatment options2 possibility of infant eposure to maternal ART or preventive AR# regimens, +hich could

result in drug resistance

3 issues of adherence

4 prevalent coeisting conditions (e.g. coinfections, malnutrition, malaria, T', hepatitis ' and hepatitisC)

5 availability and cost-effectiveness

6 capacity of drug procurement and supply systems.

The choice of an appropriate AR# regimen may be further influenced by

1 access to a limited number of AR#s in forms suitable for the treatment of infants andyoung chil-dren (see special considerations belo+)F

2 limited health service infrastructures (including human resources)F

3 the presence of varied !"# types (e.g. !"#-1).

6.3 Considerations for drug formulations and doses for infants and

children

Nuality-assurediAR# drugs in fied-dose combinations (=Cs)

iior blister co-pac/s

iii+ere previously

used for adults and older children but have recently become available for use by young children. *nce-

daily dosing has become available for some adult AR# combinations and further simplifies drug regi-

mens. The advantages of =Cs and once-daily dosing include improved adherence +hich, in turn, limits

the emergence of drug resistance. =Cs also simplify AR# storage and distribution logistics.

!* strongly encourages the continued development of ne+

formulations specifically for infants and children.

3yrups, solutions and sprin/les may remain necessary for treating infants and very young children +ho

cannot s+allo+ tablets or capsules, but they have shortcomings including limited availability, high cost,

storage difficulties, reduced shelf-life, sometines high alcohol content and poor palatabil-ity. As children

become older, it is preferable to give solid formulations. 3ee the report of the !* 9aediatric

Antiretroviral or/ing Mroup on AR# formulations for children at httpGG+++.+ho.intGhivG

pubGpaediatricGantiretroviralGenGinde.html) J22K. =or most AR#s, capsules and tablets are available in

sufficiently lo+ doses to enable accurate dosing for children. 3ome drugs, ho+ever, do not have solid

formulations in doses appropriate for paediatric use. The pharmaco/inetic profile of some but not all

crushed tablets or sprin/led capsule contents have been evaluated.

>sing tablets that must be cut can result in underdosing or overdosing, particularly if the tablets are

unscored, and this may increase the ris/ of resistance or toicity. 3ome solid formulations do not

(1)"n the contet of this document, &uality-assured medicines assembled in =Cs include individual products deemed to meet

international standards of &uality, safety and efficacy. =or !*7s +or/ on the pre&ualification of AR#s, see httpGG

+++.+ho.intGhivGamdsGenG

(2)=Cs include t+o or more active pharmacological products in the same pill, capsule, granules, tablet or oral li&uid.
http://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.htmlhttp://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.htmlhttp://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.htmlhttp://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.htmlhttp://www.who.int/hiv/amds/en/http://www.who.int/hiv/amds/en/http://www.who.int/hiv/amds/en/http://www.who.int/hiv/amds/en/http://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.htmlhttp://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.htmlhttp://www.who.int/hiv/amds/en/http://www.who.int/hiv/amds/en/http://www.who.int/hiv/amds/en/http://www.who.int/hiv/pub/paediatric/antiretroviral/en/index.html

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(3)A blister co-pac/ is a plastic or aluminium blister containing t+o or more pills, capsules or tablets.

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5C



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have even distribution of drug throughout the tablet. !o+ever, +hile suboptimal, cutting adult-

dose solid formulation AR#s may be considered +hen no alternatives are available. hen cutting

un-scored tablets, the use of tablet cutters is preferred. >nscored tablets should not be cut to

fractions belo+ one half. 9harmaco/inetic studies have confirmed that for younger children the

use of single-drug li&uid formulations is better than splitting adult =Cs J2IK.

osing in children is usually based on either +eight or body surface area J2:K. As these change +ith

gro+th, drug doses must be ad6usted in order to avoid the ris/ of underdosing. 3tandardiation is

important and it is recommended that health-care +or/ers be provided +ith tables of simplified drug

doses for administration. 3uch tables may vary +ith the local availability of AR# drugs and formula-

tions. !* has developed prototype +eight-band based dosing tables, as +ell as tools to assist

countries +ith the standardiation and calculation of drug doses iv(seeAnne ;). A range of fied-dose

formulations for children are available including d2TG5TCG%#9, AHTG5TCG%#9 and A'CG5TC.

:.2 Choice of a first-line regimen

3tudies of many different potent AR# regimens in children have demonstrated that similar improve-

ments to those obtained in adults are seen in morbidity, mortality and surrogate mar/ers J58, 2-I1K.

:.2.$ "nfants and children 012 months

The recommended first-line regimen for infants and children 012 months +ith no prior eposure tomaternal or infant %%RT"s, or +hose eposure to maternal or infant AR#s is un/no+n, is to start

standard %#9-containing triple therapy.

'o 1 9referred regimen for %#9-naive infants or children 012

months +ith no /no+n prior eposure to %#9

%#9 B 5TC B AHT

T+o %RT"s are combined +ith %#9 as the %%RT" ('o 1). Reverse transcriptase inhibitor drugspre-vent !"# replication by inhibition of the action of reverse transcriptase, the enyme that !"#

uses to ma/e a %A copy of its R%A. ;=# is not currently recommended for use in children less

than 5 years of age due to lac/ of information on appropriate dosing.

ata from a recent meta-analysis and from observational studies confirm that !"#-infected infants e-

posed to %%RT"s through infant prophylais or maternal treatment or prophylais have demonstrable

viral resistance JI5, I2K. An observational study JI5K and a recent RCT JIIK demonstrate that response

to %#9-containing first-line treatment regimens may be compromised in infants and older children +ho

ac&uire !"# despite intrapartum or peripartum eposure to %#9. Therefore, for !"#-infected infants and

children under 12 months of age +ith a history of eposure to %#9 or other %%RT"s used for maternal

(4)A generic ecel-based spreadsheet tool to assist in the development of dosing tables is available on the !* +ebsite athttpGG+++.+ho.intGhivGpaediatricGgenerictoolGenG

5$
http://www.who.int/hiv/paediatric/generictool/en/http://www.who.int/hiv/paediatric/generictool/en/http://www.who.int/hiv/paediatric/generictool/en/http://www.who.int/hiv/paediatric/generictool/en/

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treatment or 9ETCT, a 9"-based triple ART regimen is recommended. here 9"s are not available, af-

fordable or feasible, %#9-based therapy is recommended JI:K (see Anne O, =igure I).

'o 5 9referred initial regimen for %%RT"-eposed infants or children 012 months

L9#Gr B 5TC B AHT

hile the guidelines panel felt the evidence and ris/ @ benefit analysis +arranted the above

recom-mendation to be strong, they also recognied that in many resource-limited settings, L9#Gr

is not available, affordable or, due to cold chain re&uirements, not feasible for use. "t is also

ac/no+ledged that the use of L9#Gr in a first-line regimen may compromise the potential to

construct a potent sec-ond-line regimen.

:.2.1 Children P12 months

The recommended first-line regimen for !"#-infected children P12 months of age, is t+o %RT"s

plus one %%RT" ('o $). There are t+o eceptions the use of ;=# should be avoided in

adolescent girls (due to the teratogenic potential of ;=# in the first trimester of pregnancy) and in

children less than 5 years of age (due to lac/ of appropriate dosing information in this age group).

(3ee Table $for a summary of recommended first-line ART regimens for infants and children.)

The use of a triple %RT" regimen (i.e. JAHT or d2TK B 5TC B A'C) can be considered as an option for initial

therapy in special circumstances (see 'o 2). *f concern is the some+hat lo+er virological po-tency of this

regimen compared +ith a t+o-class triple-drug combination in adult studies JI-:K. Cur-rently, a triple %RT"

regimen is only recommended in children less than three years of age +ho are receiv-ing treatment for T', a

situation +here %#9 may not be an optimal choice because of drug interactions +ith rifampicin (see Chapter

$5). This regimen could be considered for adolescents +ho may become pregnant, or adolescents +ith

anticipated or documented poor adherence (see Chapter $I).

'o 2 Recommended alternative AR# regimen for infants and children to

simplify management of toicity, comorbidity and drug @ drug interaction

AHT or d2TaB 5TC

bB A'C

1 AHT should not be given in combination +ith d2T.

2 =TC can be used instead of 5TC in children more than 5 months of age.

:.I Choice of %RT"s

%RT" drugs recommended for children are described belo+.

Lamivudine (3TC) is a potent %RT" +ith an ecellent record of efficacy, safety and tolerability in

!"#-infected children, and is a core component of the dual %RT" bac/bone of triple therapy. "t is

usually given t+ice daily in children and has been incorporated into a number of =Cs. *nce-

daily dosing is possible in older children.

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Emtricitabine (FTC) is a ne+er %RT" that has recently been included in !*7s recommended

first-line regimens for adults as an option and is also available for use in childrenF it can be given

once daily. =TC is structurally related to 5TC and shares its resistance profile J:$K. here

available, it can be used in children more than three months of age as an alternative to 5TC J:1K.

Stavudine (dT) initially is better tolerated than AHT and does not re&uire haemoglobin or

laboratory monitoring. !o+ever, among the %RT"s, d2T has been most often associated +ith

lipoatrophy and lactic acidosis J:5K. "n addition, peripheral neuropathy, elevated hepatic

transaminases and pancre-atitis have been observed.

!idovudine ("!T) is generally +ell tolerated in children but has been associated +ith metabolic complica-tions,

although to a lesser etent than d2T. "nitial drug-related side-effects are more fre&uent +ith AHT and the drugcan cause severe anaemia and neutropeniaF haematological monitoring is advised J:2K. This is particularly

important in areas +here malaria is endemic or +here malnutrition is common and anaemia is highly prevalent

in young children. Large volumes of AHT li&uid formulation are often poorly tolerated, and =Cs containing

AHT are no+ available for children. "n the event of intolerance, A'C or d2T can be substituted for AHT, ecept

in cases of suspected lactic acidosis, +here A'C is preferred.

"bacavir ("#C) is an alternative %RT" in first-line therapy. ata from clinical trials indicate a similar

safety profile in children to that in adults, +ith very little haematological toicity J:IK. !o+ever, t+o large

clinical trials found an association bet+een A'C and myocardial infarction in adults J::, :K but a meta-

analysis from I2 clinical trials of A'C and another more recent clinical trial did not find this predisposi-tion to cardiovascular diseases J:8, :K. Therefore, %RT" combinations containing A'C provide a good

%RT" bac/bone for use +ith %%RT"s or as part of a triple nucleoside regimen. *f all the %RT" drugs,

A'C has the least effect on mitochondrial %A JK and +ould be the preferred substitute for d2T or

AHT in children developing lactic acidosis. !o+ever, in studies in ;urope and the >nited 3tates, A'C is

associated +ith a potentially fatal hypersensitivity reaction in about 5 of children J$K. The fre&uency

of A'C hypersensitivity in other regions is not /no+n. "n infants and children suspected of having a

hypersensitivity reaction, A'C should be stopped and never restarted (see Anne =). Children starting

A'C andGor their caregivers should be advised about the ris/ of hypersensitivity and the need to con-

sult their care provider immediately if signs or symptoms of hypersensitivity occur.

Tenofovir (T$F) is included as an option for first-line regimens in adults. "n adults, T= is generally +ell

tolerated J1K although there are numerous reports of renal insufficiency J5-IK. 'ecause of limited

paediatric safety data (especially the potential for effects on bone mineraliation), the use of T= in

younger children is not yet recommended. A study in $: !"#-infected children (age range :.2 @ $.

years) comparing T= and d2T after $1 months of treatment reported that T= did not impair bone

mineral accrual and resulted in a good immunological response to ART J:K. !o+ever, a study using

T= as part of salvage therapy in children (age range 8.5 @ $:.1 years) demonstrated a : decrease in

bone density in 5 of children after 28 +ee/s of T= JK. 3ubse&uent research has sho+n similar

results J8K, suggesting that T= may be of limited use in prepubertal children. Additional clinical trials in

ART-naive children as young as 1 years are ongoing.

$idanosine (dd%) is an adenosine nucleoside analogue %RT". "ts use is usually reserved for

second-line regimens (see Chapter $1).

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:.I.$ Choosing bet+een %RT"s for first-line

The decision to use d2T, AHT or A'C in the first-line regimen needs to be made at the country

level on the basis of local considerations, but it is recommended that at least t+o of these %RT"s

be avail-able to allo+ the substitution of one drug for the other should there be toicity.

=e+er laboratory monitoring re&uirements may be a good reason to favour d2T over AHT as the

chosen %RT" component, in particular, during the rapid scale-up of programmes. !o+ever, there

is a long term ris/ of toicity, particularly lipoatrophy in children treated +ith d2T-containing

regimens. The use of d2T is being reduced in adults because d2T toicity is fre&uently

irreversible. 2T toicity relates to the intracellular accumulation of the drug and its metabolites,

and the subse&uent poison-ing of mitochondrial function. This eplains +hy d2T toicity developsgradually, over a longer time frame than toicity to other AR#s. "n children, ho+ever, d2T

clearance is enhanced and intracellular levels are typically lo+er than in adults. Children can and

do develop d2T toicity but it is reported less often than in adults J:2, -8$K.

>nli/e d2T, AHT toicity is increased in children compared +ith adults, +ith a high proportion

devel-oping anaemia over the first fe+ months of therapy. !o+ever, in the long term, AHT is much

better tolerated than d2T and is preferred over d2T despite the problem of anaemia and the

relatively higher cost.

These guidelines introduce A'C as a preferred %RT" for first-line therapy. The choice of first-line

%RT"s impacts second-line ART. 'oth AHT and d2T are thymidine analogues +ith very similar

resis-tance profiles. =ailure of AHT or d2T therapy results in the accumulation of thymidine

analogue muta-tions (TAEs). The longer a child stays on a failing d2T- or AHT-based regimen, the

more TAEs ac-cumulate. Eultiple TAEs reduce susceptibility to A'C, and thus may impact the

success of future second-line therapy. 'y contrast, resistance to A'C does not result in resistance

to thymidine ana-logues and one important advantage of A'C as a first-line drug is that both AHT

and d2T +ill remain active in second-line.

There are limited options for paediatric treatment but all of these first-line choices are no+

available as generic, child-friendly =Cs. These guidelines recommend a preferential order of

%RT"s to be used in first-line regimens, +ith AHT preferred over A'C, and A'C preferred over

d2T. This recom-mendation see/s to balance toicity, cost and practicality. %ational programmes

should ta/e into account the comparative short and long-term toicities, as +ell as the relative

ris/s and benefits to determine the optimal choice of %RT" for use in first-line therapy. 'ecause of

proven antagonism, d2T and AHT should never be used together J81, 85K.

:.: Choice of %%RT"s

%%RT"-based regimens are no+ the most +idely prescribed combinations for initial therapy. They are

potent, i.e. they rapidly reduce viral load, but are inactive +ith respect to !"#-1 and group * of !"#-$. "naddition, a single mutation can induce cross-class resistance to the currently available %%RT"s. The

%%RT"s ;=# and %#9 have both demonstrated clinical efficacy +hen administered in appropri-ate

combination regimens in children. !o+ever, differences in toicity profile, the potential for interac-

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tion +ith other treatments, a lac/ of dosing information for ;=# in young children and cost are

factors that need to be ta/en into consideration +hen choosing an %%RT" J82-$K.

Efaviren& (EF') is not currently recommended for use in children less than three years of age because

there is no established dosing. ;=# is primarily associated +ith toicities related to the central ner-vous

system (C%3), teratogenicity and rash. Rash is more fre&uent in children than in adults, is gen-erally

mild, and usually does not re&uire discontinuation of therapy. The C%3 symptoms typically abate after

$ @ $2 days in the ma6ority of patientsF observational studies have revealed transient C%3 disturbance

in 1: @ 5: of children receiving ;=# JI1, $K. ;=# should be avoided in children +ith a history of

severe psychiatric illness, +here there is a potential for pregnancy (unless effective contra-ception can

be assured) and during the first trimester of pregnancy. "n these situations, %#9 may be the better

choice (seebelo+). ;=# is preferred as the %%RT" of choice in children more than three years of age

+ith T'G!"# coinfection J1K (see Chapter $5).

eviraine ('*) should be given only in combination +ith other AR#s, ecept +hen used for pro-

phylais to reduce the ris/ of perinatal !"# transmission. %#9 has a higher incidence of rash than other

AR#s. %#9-related rash may be severe and life-threatening, including 3tevens @ Oohnson syn-drome

and, as noted belo+, %#9 is associated +ith a rare but potentially life-threatening ris/ of hepatotoicity.

"n these situations, %#9 should be permanently discontinued and not restarted (see Chapter and

Anne =). This ma/es the drug less suitable for treating children +ho are on other hepatotoic

medications, or drugs that can cause rash. There are limited data on the use of %#9 in children

coinfected +ith !"# and hepatitis '. %#9 is currently the only %%RT" that can be used in infants. "n

addition, %#9 is a component of all the three-drug =Cs currently available.

%#9 may be the preferred choice in adolescent girls +hen there is potential for pregnancy or

during the first trimester of pregnancy +hen ;=# should be avoided because of its potential

teratogenic ef-fect. hile there have been reports of possible %#9-associated hepatotoicity or

serious rash, a re-vie+ of %#9 safety in pregnant +omen +ith C2 bet+een 1I-5I cellsGmm5

has not confirmed an increased ris/ of any serious adverse events, leading to the conclusion that

the benefits of using %#9 in pregnancy out+eigh the ris/s J1$K. Careful monitoring is none-the-

less +arranted for initiation of ART in adolescent, !"#-infected pregnant girls.

Limited data indicate that both ;=# and %#9 may interact +ith estrogen-based contraceptive pills.

'ecause eposure to ;=# should be avoided in the first trimester of pregnancy, it is recommended that

seually active adolescent girls receiving ;=# consistently use barrier methods to prevent preg-nancy in

addition to or instead of oral contraceptives. 3tudies are in progress to evaluate interactions bet+een

in6ectable depot medroyprogesterone acetate (E9A) and selected 9"s and %%RT"s. e-spite initial

pharmaco/inetic studies suggesting some compromise of contraceptive efficacy, a large clinical study

evaluated potential interactions bet+een E9A and selected 9" and %%RT" drugs, and did not find

significant clinical interactions J5-:K.

Etravirine (ET') is a ne+ %%RT" that maintains activity against !"# +ith some %%RT" resistancemuta-tions "t is +ell tolerated in adults. A paediatric 1I mg tablet is in clinical trials.

Anne ; provides more detailed information on dosing, preparations, storage and special instruc-

tions on the administration of the above-listed drugs.

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