HIV TREATMENT

OVERVIEW
The causative agent of AIDS (acquired immunodeficiency syndrome) is the

human immunodeficiency virus. The most common is HIV-1, which occurs

worldwide. HIV-2 is found mainly in West Africa and is associated with a
slower progression to AIDS than HIV-1.

Chronic HIV infection is characterised by gradual depletion of CD4+ T

lymphocytes resulting in progressive immunodeficiency. This may become
clinically apparent when symptoms such as fatigue, weight loss, recurrent

fever, diarrhoea, or thrush occur.

OVERVIEW CONTD
Since the availability of highly active antiretroviral
therapy (HAART), the incidence of AIDS-defining
illnesses has markedly declined.

HIV TREATMENT IN INFANTS

Considering Factors

Diagnosis
When to initiate therapy
Therapeutic Options
Special needs
Treatment Failure
Monitoring

Diagnosis
According to WHO 2010/2011 Antiretroviral Treatment Guidelines in Infants: All infants should have their HIV exposure status established. (at or birth,
ALWAYS 6weeks of age)
Virological testing should be conducted at 4-6wks of age for infants known
to be exposed to HIV.
HIV-exposed infants either who have not had a virological test or have had
an earlier negative virological test, are recommended to have HIV
serological testing at around nine months of age (or at the time of the last
immunization visit).
Those who have reactive serological assays at nine months should have a
virological test to identify infected infants who need ART.

Diagnosis

Initiation of Antiretroviral Therapy

The age of the child must be considered when interpreting the risk of
disease progression based on CD4 percentage or count and plasma HIV
RNA level (AII). For any given CD4 percentage or count, younger children,
especially those in the first year of life, face higher risk of progression than
do older children.
In children younger than 5 years of age, CD4 percentage is preferred for
monitoring immune status because of age-related changes in absolute
CD4 count in this age group (AII).
CD4 percentage or count should be measured at the time of diagnosis of
HIV infection and at least every 3-4 months thereafter (AIII).
Plasma HIV RNA should be measured to assess viral load at the time of
diagnosis of HIV infection and at least every 3-4 months thereafter (AIII).
More frequent CD4 cell and plasma HIV RNA monitoring should be
considered in children with suspected clinical, immunologic, or virologic
deterioration or to confirm an abnormal value.

Clinical criteria to start ART

Clinical staging should be used once HIV infection has been confirmed.

Starting the therapy

Special considerations
For children diagnosed with TB and HIV
(WHO ART GUIDELINES 2011)
Any child with active TB disease should begin TB treatment immediately,
and start ART as soon as tolerated in the first 8 weeks of TB therapy,
irrespective of CD4 count and clinical stage

TREATMENT REGIME
Preferred regimen for children <3 years of age 2
NRTIs + NVP or a triple nucleoside regimen
Preferred regimen for children >3 years of age 2
NRTIs + EFV
Preferred regimen for children <2 years of age who
have been exposed to NVP is a triple NRTI regimen.

Special considerations
Infants already on ART who develop TB
Anti-TB therapy should be started immediately upon TB
diagnosis.
Adjustment ART as needed to decrease the potential for
toxicities and drug interactions
If on 2 NRTIs + NVP, substitute EFV for NVP if child
is >3 years
If on 2 NRTIs + NVP and under 3 years ensure
NVP is at high dose (200mg/m2)
If on LPV/r, consider adding RTV to a 1:1 ratio of
LPV:RTV to achieve the full therapeutic dose of
RTV

Monitoring
Within 1-2weeks of starting a new antiretroviral (ARV) regimen, children
should be evaluated:
Side effects
Patient/caretaker Adherence
Efficacy

Treatment Failure
Virologic failure incomplete response to therapy
Immunologic failure failure to improve CD4 count
Clinical failure occurrence of new opportunistic infections

HIV TREATMENT IN CHILDREN

ANTIRETROVIRAL THERAPY IN
CHILDREN
Initiate ART for all HIV-infected children between 12 and
24 months of age irrespective of CD4 count or WHO
clinical stage.
Initiate ART for any child less than 18 months of age who
has been given a presumptive clinical diagnosis of HIV
infection.

ANTIRETROVIRAL THERAPY IN
CHILDREN
Initiate ART for all HIV-infected children between 24 and 59 months of age
with
CD4 count of 750 cells/mm3
Or %CD4+ 25

whichever is lower, irrespective of WHO clinical stage.

ANTIRETROVIRAL THERAPY IN
CHILDREN
Initiate ART for all HIV-infected children more than 5 years of age with
CD4 count of 350 cells/mm3 (as in adults), irrespective of WHO
clinical stage.
Initiate ART for all HIV-infected children with WHO clinical stages 3 and 4,
irrespective of CD4 count.

ANTIRETROVIRAL THERAPY IN
CHILDREN
Which antiretroviral (ARV) drugs should be used?
Two nucleoside reverse transcriptase inhibitors (NRTIs)
combined with either one non-nucleoside reverse transcriptase
inhibitor (NNRTI) or a protease inhibitor (PI). (FDA, 2009) (WHO 2010)

RECOMMENDED FIRST-LINE ART

REGIMENS FOR CHILDREN
Children between 12 and 24 months of age exposed to:
Maternal or infant NVP
Other NNRTIs used for maternal treatment or PMTCT

Treatment should contain PIs, start ART with lopinavir/ritonavir (LPV/r) + 2

NRTIs.

RECOMMENDED FIRST-LINE ART

REGIMENS FOR CHILDREN

Children between 12 and 24 months of age not:

Exposed to NNRTIs

Start ART with NVP + 2 NRTIs.

RECOMMENDED FIRST-LINE ART

REGIMENS FOR CHILDREN
Children more than 24 months and less than 3 years of age start ART with
NVP + 2 NRTIs.

For children 3 years of age and older, start ART with NVP or efavirenz
(EFV)-containing regimen + 2 NRTIs

RECOMMENDED SECOND-LINE
REGIMENS
After failure on a first-line NNRTI-based regimen, a boosted PI plus 2 NRTIs
are recommended for second-line ART

ANTIRETROVIRAL THERAPY IN
CHILDREN
LPV/r is the preferred boosted PI for a second-line ART regimen after
failure on a first-line NNRTI based regimen.
After failure on a first-line regimen of AZT or d4T + 3TC, ABC + 3TC is the
preferred NRTI backbone option for second-line ART; ABC + ddI is an
alternative.

ANTIRETROVIRAL THERAPY IN
CHILDREN CONTD
After failure on a first-line regimen of ABC + 3TC, AZT + 3TC is the
preferred NRTI backbone option for second-line ART; AZT + ddI is an
alternative.
Children with nucleoside backbone for an ART regimen should be one of
the following, in preferential order:
Lamivudine (3TC) + zidovudine (AZT) or 3TC + abacavir (ABC) or 3TC
+ stavudine (d4T)

NRTI
Abacavir
>3mo; 8mg/kg/day; max 600mg/day
Combivir (lamivudine/Zidovudine)/150/300
>30kg; 1 tab po bid
Emtricitabine
<3mo; 3mg/kg po qd
3mo 17; 6mg/kg
Lamivudine
3mo 16yr; 8mg/kg po divided bid

NRTI
Stavudine
<30kg, < 14days; 0.5mg/kg po q12h
< 30kg, > 14days; 1mg/kg po q12h
30-50kg; 30mg po q12h
>60kg; 40mg/kg po q12h
Zidovudine
>4wk, 4-8kg; 24mg/kg/day
>4wk, 9-29kg; 18mg/kg/day
>4wk, >30kg; 600mg/kg/day

NNRTI
NEVIRAPINE
>2wk; 150mg/m^2 po bid
Efavirenz
>3yr, 10-15kg; 200mg po qhs
>3yr, 15-20kg; 250mg po qhs

PI
Ritonavir
400mg/m^2 po bid, start 250mg/m^2 po then increase by dose of
50mg bid q2-3weeks. Max 600mg po bid
Lopinavir/ritonavir
2wk 6mo; 16mg/4mg/kg po bid
6mo- 18 yr; 12mg/3mg/kg po bid
Darunavir
3-17yr, 10-14kg; 20mg /kg po bid
3-17yr, 15-29kg; 375mg /kg po bid
3-17yr, >40kg; 600mg /kg po bid

HIV TREATMENT IN PREGNANT

WOMEN

Antepartum Care
All pregnant women who are HIV positive should have there CD4 count
done.
If the CD4 count is less than 350 cells/ul or 250 cells/mm3 then triple
therapy should be started as soon as possible.

Antepartum Care
For those with CD4 count above 350cells/ul or 250 cells/mm3 then
treatment may start at 14 weeks of pregnancy or as soon as possible if the
woman presents late in her pregnancy.

Antepartum Care
Generally nucleoside reverse transcriptase inhibitors (NRTIs) are
recommended for use as part of combination regimens, usually two NRTIs
with either a Non-nucleoside reverse transcriptase inhibitor (NNRTI) or
one or more protease inhibitors (PIs).

Antepartum Care
HIV-Infected Pregnant Women Who Have Never Received Antiretroviral
Drugs
Starting ARV therapy after the first trimester can be considered if the
patient has a high CD4 count and a low HIV RNA levels.

Antepartum Care
Efavirenz and other teratogenic drugs should not be used in the first
trimester as well as any other drugs that would have an adverse effect
during the pregnancy.

Antepartum Care
NRTIs which pass the placenta well should be included in the mothers
regimen. These include zidovudine, lamivudine, emtricitabine and
abacavir.
Nevirapine should not be used if
the CD4 count is greater than 250 cells/mm3 or 350cells/ul as this can
result in hepatotoxicity in the patient.

Antepartum Care
After delivery the patient should be evaluated to see if treatment should
continue.
If the CD4 count is equal to or below 350 cells/ul then ARV therapy should
continue. If it is above then antiretroviral should be discontinued and
follow ups should take place.

Antepartum Care
HIV-Infected Pregnant Women Who Are Currently Receiving
Antiretroviral Therapy
For these patients their ARV therapy should not be stopped during the
first trimester of pregnancy.

Antepartum Care
Once the therapy is effective in suppressing the patients viral levels and
the drug is well tolerated then the patient should remain on their
treatment.

Antepartum Care
HIV-infected Pregnant Women Who Are ARV Experienced but Not
Currently Receiving ARV Drugs
A full patient drug history should be taken, to determine which drug is
suitable.

Antepartum Care
A three combination ARV therapy is usually started in these patients.

Local Guideline Drug Combination

CD4 Count

Regimen

Dosages

350 cells/ul

Zidovudine +
Lamivudine +
Nevirapine

AZT 300mg + 3TC

150mg , one tablet
every twelve hours
and NVP 200mg
every twelve hours.

350 cell/ul

Zidovudine+
Lamivudine +
Lopinavir and
Ritonavir

AZT 300mg + 3TC

150mg, one tablet
every twelve hours
and LPV 200mg + r
50mg two tablets
twice daily

Antepartum Care
According to Aids Info treatment guidelines preferred NRTIs are
lamivudine and zidovudine, alternatives are abacavir and emtricitabine.
Preferred NNRTI is nevirapine
Preferred PI Lopinavir +Ritonavir, alternatives are saquinavir and indinavir.

Antepartum Care
All ARVs should be continued during labour and delivery for all pregnant
HIV mothers.

Antiretroviral-naive HIV-Infected
Infants 12 Months or Younger
Antiretroviral therapy is started in infants as soon as they are born
regardless of clinical, immunologic, or virologic symptoms.

According to the National Guidelines for the Prevention of Mother to child

transmission of HIV 2011, the HIV Exposed Infant (HEI) should be treated
with single dose Nevirapine 2mg/kg immediately at birth or within
24hours, and then Zidovudine 4mg/kg every 12 hours for 6 weeks and for
premature babies, Nevirapine 2m/kg single dose at birth or with 24 hours
for infants less than 34 weeks, Zidovudine 2mg/kg every 12hrs should be
administered for 2 weeks, and then 3mg/kg every 12 hours for four
weeks.

WHY NEVIRAPINE IS GIVEN

AS A STAT DOSE
Nevirapine is a (NNRTI) which is an immediate release
dosage form.
HIV virus easily develops resistance to Nevirapine based
on the structure of the drug, and this is why only a STAT
dose given to infants, to prevent and reduce the risk of
resistance.
Therefore, STAT doses of Nevirapine is given as it has a
fast acting and is highly absorbed (>90%).

INTERACTIONS OF NEVIRAPINE
Nevirapine is an inducer of cytochrome P450 isoenzymes

CYP3A4 and CYP2B6.

It reduces the levels of several co-administered drugs

including the antiretrovirals efavirenz, indinavir, lopinavir,

nelfinavir and saquinavir, as well as clarithromycin,

ketoconazole, forms of hormonal contraception, and
methadone.

ADVERSE EFFECTS OF NEVIRAPINE

Nausea,

Stomach pain
Vomiting and
Tiredness.

However, with regards to allergic reactions, the infant may

experience:
Chest tightness

Rashes

Swelling of the face lips and tongue.

ZIDOVUDINE
Zidovudine is given as a maintenance therapy for exposed
infants. Zidovudine is given for six weeks after the STAT dose
of Nevirapine, and this is done to ensure that the risk of

vertical transmission is reduced.

Additional antiretroviral drugs may be needed in some highrisk newborns such as preterm infants, such as Zidolam
(Zidovudine and Lamivudine) and Zidovudine and Nevirapine.

ADVERSE EFFECTS OF ZIDOVUDINE

Infants may experience headaches, stomach pains, anemia,
skeletal weakness, vomiting, constipation, mouth ulcers,
and skin and nail pigmentation.

DRUG TOXICITY IN INFANTS

During administration of the antiretroviral (ARV), if a child
presents with a severe or life-threatening toxicity, the
complete drug regimen should be stopped immediately.

Once the symptoms of toxicity have resolved, antiretroviral

therapy (ART) should be resumed with a replacement drug
for the offending agent.

PREVENTION OF MOTHER TO CHILD

TRANSMISSION
Elective cesarean section
Early antiretroviral therapy as early as fourteen weeks of
pregnancy

Refraining from breast feeding the infant

REFERENCES

Aboulker JP, Babiker A, Chaix ML, et al. Highly active antiretroviral therapy started in infants

under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance
outcome. AIDS. 2004;18(2):237-245.

Kline MW, Dunkle LM, Church JA, et al. A phase I/II evaluation of stavudine (d4T) in children

with human immunodeficiency virus infection. Pediatrics. 1995;96(2 Pt 1 (Aug)):247-252.

Kline MW, Fletcher CV, Federici ME, et al. Combination therapy with stavudine and didanosine in
children with advanced human immunodeficiency virus infection: pharmacokinetic properties,
safety, and immunologic and virologic effects. Pediatrics. 1996;97(6 Pt 1):886-890.

REFERENCES

Lacy, C., Armstrong, L., Goldman, M., & Lance, L. (2009). Drug Information Handbook with International

Trade Names Index. Ohio, United States of America: Lexi-Comp Inc.

AIDSInfo (2011). Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Management
of Medication Toxicity or Intolerance. Received on September 27, 2012 From:
http://aidsinfo.nih.gov/guidelines/html/2/pediatric-arv-guidelines/89/management-of-medication-toxicityor-intolerance

AIDSInfo (2012). Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women
for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.
Retrieved on September 24, 2012
From:http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf