HIV 1 and HIV 2 belong to Genus – Lentivirus
Family – Retroviridae
HIV 1 contains 2 copies of SS-RNA
At both ends of the genome there are identical
regions called long terminal repeats
It contains regulation and expression genes for
The remainder of the genome includes 3 major
1. GAG region : encodes viral core proteins
2. POL region :encodes viral enzymes ( reverse
transcriptase(p51), protease (p10),integrase
3. ENV region : encodes the viral envelope
proteins (gp120, gp41)
Gp120 glycoprotein carries binding site for
CD4 molecule which is the most common
host cell surface receptor ofT lymphoctes
HIV 2 has a similar life cycle to HIV 1
It is known to cause infection in several
HIV 2 differs from HIV 1 in accesory genes
Primary route of infection in the pediatric population
is vertical transmission accounting for almost all new
Vertical transmission can occur
Through breast fedding
• 30-40% of the infected newborns are infected in utero
• Intrauterine infection has been suggested by
identification of HIV by culture or PCR in fetal tissue
as early as 10 weeks
• Children infected in the intrauterine period have
positive viral culture or PCR in the 1 st wk of life
60-70% acquire infection in the intrapartum
The mechanism of transmission is exposure to
infected cervicovaginal secretions and blood in
the birth canal
Breast feeding is responsible for 40% of
perinatal transmission in resource limited
The risk of transmission through breast feeding
in chronically infected women is appx 9to 16%
but 29-53% in women who acquire HIV
Several risk factors influence the rate of
Preterm delivery (<34 weeks gestation )
A low maternal antenatalCD4 count
Use of recreational drugs during pregnancy
> 4 hr duration of Ruptured membranes
Birthweight < 2500gm
doubles the transmission rate
Elective ceaserean section decreases the
transmission rate by 87% if used in
conjunction with zidovudine in infant and
In USA it is recommended to consider
Cesearean section if the viral load is > 1,000
copies / ml
Transfusion of infected blood or blood
products has been accounted for 3-6 % of all
Sexual contact is a major route of
transmission in adolescent population
accountig for most of the cases
HIV classification is used to categorise the
stage of pediatric disease by 2 parameters :
clinical classification and immunological
Normal CD4 count/% in children are:
A. <12 months: >1500 cells/mm3 ( >= 25%)
B.1-5 years: >1000 cells/mm3 (>= 25%)
C. > 6 years: >500 cells/mm3
Maternal antibody persists for as long as 18
Breast feeding poses an ongoing risk for
HIV infection can only be excluded after breast-
feeding is stopped for > 6 weeks.
In India, antibody tests and ELISA can be used
for infants > 18 months as per adults; and for
infants < 18 months, DNA PCR will be done
using dried blood spots (DBS).
There are two ways to exclude HIV infection in infants and
1. A child has negative virologic test result and > 6 weeks after
complete cessation of breastfeeding.
HIV- DNA PCR can be done ideally at age 6–8 weeks to exclude
HIV infection acquired during delivery.The infection can only be
ruled out by DNA PCR test done at more than 6 weeks after
2.A child has negative HIV antibody test resultat ≥ 18 months of age
if not breast-feeding and more than 6 weeks after complete
A child who has negative HIV antibody test result at the age of ≥ 9
months and at least 6 weeks after complete cessation of
breastfeeding is HIV-uninfected. Confirm by repeat HIV antibody
testing at 18 months.
A report of “HIV Positive” is given when 2
PCR tests are positive; and a report of “HIV
negative” is given when 2 PCR tests are
For symptomatic children: the sample should
be reactive with two different kits.
For asymptomatic children : the sample
should be reactive with three different kits
The blood sample collected at one time is
tested with the 1st kit, and if reactive,
retested sequentially with the 2nd and 3rd
kits depending on the clinical status of the
If the child is < 18 months and has symptoms and
signs that are suggestive of HIV infection and
there is no virologic testing available, it is
possible to make a presumptive diagnosis by
addressing the following issues:
Is there evidence of HIV exposure mother or
baby’s serology is HIV positive?
Is there evidence of immuno-suppression
(low CD4 count/%) and symptoms or illness
consistent with HIV infection?
Does the child meet the clinical criteria for
presumptive diagnosis of severe HIV infection?
1. I nitiate ART for all HIV-infected infants diagnosed in the firsst year of
life, irrespective of CD4 count orWHO clinical stage.
1. InitiateART for all HIV-infected children between 12 and 24 months of age
irrespective of CD4 count orWHO clinical stage
2. InitiateART 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 ofWHO clinical stage.
3. InitiateART for all HIV-infected children more than 5 years of age with a
CD4 count of ≤350 cells/mm3 (as in adults), irrespective ofWHO
4. InitiateART for all HIV-infected children with WHO clinical stages 3 and
4, irrespective of CD4 count.
5. InitiateART for any child less than 18 months of age who has been given
a presumptive clinical diagnosis of HIV infection.
To prevent drug resistance
To act at different points of the life cycle and
to achieve maximal suppression of the viral
NRTI: inhibit viral DNA synthesis
Thymidine analogs (Stavudine and
Zidovudine ): inhibit atively proliferating virus
NonThymidine (Didanosine , lamivudine)
Act on resting virus
NNRTI attach to the reverse transcriptase:
inhibit its activity
PI : prevent viral proteins to form an
Thus the combination therapy includes a
a thymidine analog + a non thymidine analog to
inhibit active and resting cells and a PI or
NNRTI to produce prolong viral suppresion
The use of threeARV medications is the
current standard treatment for HIV infection,
in order to achieve the best possible
suppression of viral replication and to arrest
the progression of HIV disease
Standard regimen for 1 st lineArt therapy is 2
NRTI + 1NNRTI
1. For infants not exposed to ARVs, start ART with
nevirapine (NVP) + 2 nucleoside reverse
transcriptase inhibitors (NRTIs).
2. For infants exposed to maternal or infant NVP
or other NNRTIs used for maternal treatment or
PMTCT, start ART with lopinavir/ritonavir
(LPV/r) + 2 NRTIs.
3. For infants whose exposure to ARVs is
unknown, start ART with NVP + 2 NRTIs.
1. For children between 12 and 24 months of age exposed to
maternal or infant NVP or other NNRTIs used for maternal
treatment or PMTCT, start ART with lopinavir/ritonavir (LPV/r) + 2
2. For children between 12 and 24 months of age not exposed to
NNRTIs, startART with NVP + 2 NRTIs.
3. For children more than 24 months and less than 3 years of age
startART with NVP + 2 NRTIs.
4. For children 3 years of age and older, start ART with NVP or
efavirenz (EFV)-containing regimen + 2 NRTIs.
5. For infants and children, the 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)
Infants and children with special conditions
1. For children more than 3 years of age with
tuberculosis (TB), the preferred regimen is EFV
+ 2 NRTIs.
2. For infants and children less than 3 years of age with
TB, the preferred regimens are NVP + 2 NRTIs or a
triple nucleoside regimen.
3. For a child or adolescent with severe anaemia
(<7.5 g/dl) or severe neutropenia (<0.5/mm3), the
preferred regimen is NVP + 2 NRTIs (avoid AZT).
4. For adolescents more than 12 years of age with
hepatitis B, the preferred regimen is tenofovir (TDF)
+ emtricitabine (FTC) or 3TC + NNRTI
EFV is not currently recommended for children
<3 years of age or < 10kg
Should be avoided in post-pubertal adolescent
girls who are either in 1st trimester of
pregnancy or are sexually active and not
receiving adequate contraception.
EFV is used to substitute NPV when anti-
tuberculous treatment has to be provided
concomitantly. However, after 2 weeks of
completion of ATT, EFV should be switched back
1. CD4 should be measured at the time of diagnosis of HIV
infection, and every 6 months thereafter. Monitor with
increasing frequency as CD4 count approaches threshold
for starting ART.
2. CD4 should be measured prior to initiatingART.
3. CD4 should be measured every 6 months after initiating
4. Measure CD4 if new clinical staging events develop,
including growth faltering and neurodevelopmental delay.
5. Where capacity for CD4 measurement is limited, target
the use of CD4 monitoring to assess the significance of
Viral Load Monitoring
1.VL determination is desirable, but not essential, prior to
2.VL should be assessed to confirm clinical or immunological
failure where possible, prior to switching treatment
regimen. viral load should be used whenever possible to
confirm suspected clinical or immunological failure.
3.Where available, viral load should be assessed at six
4. Failure to suppress the viral load to below 5 000 copies/ml
in an adherent child at this time warrants switching to a
Routine clinical and laboratory monitoring
1. Baseline haemoglobin level (and white cell count, if
available) should be assessed at initiation of ART.
2. For infants and children, measure haemoglobin at week 8
after initiation of AZT-containing regimens, or more
frequently if symptoms indicate.
3. Growth, development and nutrition should be monitored
4. Laboratory monitoring for toxicity should be symptom
The inability to perform laboratory monitoring, notably for
CD4 or viral load, should not prevent children from
Once an infant or child is on ART, the
frequency of clinical monitoring will depend
on their response to ART. At a minimum,
after starting ART, follow-up visits should
• for infants, at weeks 2, 4, 8, and then every 4
weeks for the first year
• for children, at weeks 2, 4, 8, 12, and then
every 2 to 3 months once the child has
stabilized on therapy.
Key signs of an infant’s and child’s response to
• improvement in growth in infants and children
who have been failing to grow
• improvement in neurological symptoms and
development in children with encephalopathy or
those who have demonstrated delay in the
achievement of developmental milestones
• decreased frequency of infections (bacterial
infections, oral thrush and/or other OIs).
The most common toxicities include the following:
Haematological: drug-induced bone-marrow suppression, most
commonly seen with AZT (anaemia, neutropenia and, more
Mitochondrial dysfunction: primarily seen with the NRTI drugs
and include lactic acidosis, hepatic toxicity, pancreatitis and
peripheral neuropathy.The NRTIs differ in their ability to affect
mitochon-drial function: d4T and ddI are worse than AZT; 3TC and
ABC have the least toxicity of all.
Lipodystrophy and other metabolic abnormalities: primarily seen
with d4T and the PI class, and to a lesser degree with other NRTI
drugs.Abnormalities include fat maldistribution and body habitus
changes, hyperlipidaemia, hyperglycaemia, insulin resistance,
diabetes mellitus, osteopaenia, osteo-porosis and osteonecrosis.
Allergic reactions: including skin rashes and
hypersensitivity reactions.These are more
common with the NNRTI drugs, but also
seen with certain NRTI drugs, such as ABC.
Because of the risk of potentially life-
threatening hepatotoxicity associated with
NVP, hepatic dysfunction of any etiology in a
child on NVP requires careful consideration of
whether NVP should be discontinued
For HIV-infected pregnant women, the
initiation of ART for their own health is
recommended for all women who have CD4
cell counts of ≤350 cells/mm3, irrespective of
WHO clinical staging, and for all women in
WHO clinical stage 3 or 4, irrespective of the
CD4 cell count.
SuspectTB if the child has:
1.Contact with adult who has pulmonaryTB
2. Fever and/or cough for more than 3 weeks
3.With or without weight loss or poor/no
4. Pneumonia not responding to antibiotics
5. Recent glandular enlargement
PulmonaryTB: May be non-specific symptoms such as fever,
weight loss, failure to thrive and cough. Features of presentation
in HIV infected children are similar to those among non-HIV
Young children present with localized pulmonary infiltrates with
hilar adenopathy. 25% of children may have more than 1 lobe
involved. Middle lobe collapse and consolidation may result due
to endobronchial tuberculosis.
Older children and adolescents may present with cavitatory
ExtrapulmonaryTB: Common sites involved are lymph nodes,
DisseminatedTB, CNSTB, BoneTB andTB of the serosal
Mantoux test / MT (Tuberculin test):- Can be done from
3 months onwards using 5TU PPD injected intradermally.
Induration more than 5 mm is considered positive in
HIV infected children.
Gastric lavage/ sputum examination: Three
consecutive morning gastric aspirates have a better
yield than a single sample. Better diagnostic yield is
seen on culture.
Other fluids and tissues for culture: Bronchoalveolar
lavage (BAL), lung biopsy, lymph node biopsy, serosal
fluids and CSF. Specimens should be cultured for 2-6
weeks by radiometric culture methods (Bactec) or culture
on L-J medium for 8 weeks.
Localized pulmonary infiltrates with hilar adenopathy
Middle lobe collapse and consolidation
In older children – cavitatory tuberculosis.
PCR assays are not useful as primary diagnostic tool
because a negative PCR does not rule outTB and a
positive result does not absolutely confirm
M.tuberculosis infection. Also false positive rates are
high with sensitivity ranging from 45-83%. Serological
tests forTB are not very specific.
Isoniazid preventive therapy.
1. All HIV-infected infants and children exposed toTB through
household contacts, but with no evidence of active disease,
should begin isoniazid preventive therapy (IPT).
2.Children living with HIV (>12 months of age and including those
previously treated forTB), who are not likely to have activeTB
and are not known to be exposed toTB, should receive 6 months
of IPT as part of a comprehensive package of HIV care.
3. Infants living with HIV, who are unlikely to have activeTB and are
not known to be exposed, should not receive IPT
4. The recommended dose of isoniazid (INH) for preventive therapy in
HIV coinfection is 10 mg/kg daily for 6 months (maximum
Infants and children diagnosed withTB and HIV
1. Any child with activeTB disease should beginTB treatment
immediately, and start ART as soon as tolerated in the first 8 weeks of
TB therapy, irrespective of the CD4 count and clinical stage.
2. The preferred first-lineARV regimen for infants and children less than 3
years of age who are taking a rifampicin-containing regimen forTB is 2
NRTIs + NVP or a triple NRTI regimen.
3. The preferred first-lineARV regimen for children more than 3 years of
age who are taking a rifampicin-containing regimen forTB is 2 NRTIs
4. The preferred first-lineARV regimen for infants and children less than 2
years of age who have been exposed to NVP and are taking a rifampicin-
containing regimen forTB is a triple NRTI regimen.
HIV-infected infants and children who developTB on ART
1. For all HIV-infected children, anti-TB therapy should be
started immediately upon the diagnosis ofTB; ART should
2. Make adjustments to ART regimens as needed to
decrease the potential for toxicities and drug interactions:
• If on a regimen of 2 NRTIs + NVP, substitute EFV for NVP
if the child is 3 years or more in age
• If on a regimen of 2 NRTIs + NVP and substitution with
EFV is not possible, ensure NVP is dosed at the maximum
dose of 200 mg/m2 per dose twice daily
• If on a regimen of LPV/r, consider adding RTV in a 1:1 ratio
of LPV: RTV to achieve a full therapeutic dose of LPV.
All HIV-exposed infants and children should
benefit from co-trimoxazole preventive
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