7. “Human Immunodeficiency Virus”
•H = Infects only Human beings
•I = Immunodeficiency virus weakens the immune
system and increases the risk of infection
•V = Virus that attacks the body
8. • H.I.V (Human Immunodeficiency Virus) is a unique type of virus (a
retrovirus) that invades the T- helper cells (CD4 cells) in the body of
the host (defense mechanism of a person).
12. • India has estimated 145,000 children <15 years of age who are infected
by HIV/AIDS, and about 22,000 new infections occur every year.
Children account for 7% of all the new HIV infections.
13.
14. Human immuno-defiency virus:
• Retrovirus
• 2 types - HIV1 and HIV2 with similar epidemiological
and pathological characteristics
• Virus size ~ 100 nm
• Genetic polymorphism
• Not resistant in the external environment
• HIV is made up of Genetic material, Chemicals and a coating
• Genetic material – RNA
• Chemicals – enzymes, which help the virus enter and use other cells to make
copies of itself.
• lipid-containing Outer coverings, which mounted surface antigens gp41, gp120;
26. Acute Seroconversion Phase or Primary HIV-1 infection
• occurs in approximately 60-90% of patients.
• difficult to identify. – COMMON COLD LIKE SYMPTOMS.
• glandular fever type illness may be encountered 2 to 6 weeks after
exposure.
• acute meningitis, myelopathy and neuropathy.
27. Asymptomatic HIV infection
• Most HIV-infected patients in the early stages are asymptomatic.
• With the progressive fall of CD4+ T-lymphocyte count characteristic of
the disease, various symptoms and signs will become apparent.
• This phase may vary from 2 to 7 years before the appearance of
constitutional symptoms which may herald the onset of AIDS.
28. Persistent Generalised Lymphadenopathy
(PGL)
• As the CD4+ T-lymphocytes progressively decline, symptoms may
appear.
• The commonest symptoms and signs encountered in the early stages
are:
1. Malaise
2. Lethargy
3. Loss of appetite
4. Loss of weight
5. Diarrhoea
6. Intermittent fever
29. Over time, the patient may develop progressive weight loss of more the 10%
the ideal body weight, prolonged fevers of more than 3 months, persistent
generalised Iymphadenopathy of more than two groups of Iymph nodes. The
appearance of multi-dermatomal herpes zoster, oral candidiasis and oral hairy
leukoplakia may herald the progression to AIDS.
31. The useful markers commonly used in
predicting progression to AIDS are:
• Absolute platelet counts
• Total Lymphocyte count
• CD4+ T-lymphocyte count (cells/uL)
• CD4+/CD8+ Ratio
• p24 antigen
• beta 2-microglobulins
• Serum Neopterin
• PCR-RNA-HIV
32. Acquired Immunodeficiency Syndrome (AIDS)
• NOT all HIV -infected individuals will progress to AIDS.
• The time from seroconversion to the development of AIDS may vary
from 2 to 15 years.
• Rapid progressors - individuals who harbour HIV that induces
syncytium formation.
• slow progressors - non-syncytium inducing variants of HIV.
33. “Acquired Immune Deficiency Syndrome”
•A = Acquired, not inherited
•I = Weakens the Immune system
•D = Creates a Deficiency of CD4+ cells in the immune
system
•S = Syndrome, or a group of illnesses taking place at
the same time
34. • AIDS: Acquired immunodeficiency syndrome is a disease of the
human immune system caused by infection with human
immunodeficiency virus.
In children it is acquired perinatally or by vertical –maternal-
infant trasmission.
35. • CHILDREN
• Growth failure, fever , diarrhea, secondary infections
• Mild symptoms for many years
• Recurrent ear infections with sinusitis,parotitis, chronic otitis media
• Lymphadenopathy persists
• OLDER CHILDREN
• Growth failure, delayed puberty, cognitive dysfunction
• Systemic manifestation- common
36. CLINICAL CATEGORIES
• CATEGORY N- not symptomatic
No signs / symptoms or 1 condition from category A
• CATEGORY A- mildly symptomatic
2 or more of conditions
lymphadenopathy
Hepatomegaly
Spleenomegaly
Dermatitis
Parotitis
Recurrent/persistent URTI/sinusitis/otitis media
37. • CATEGORY B-moderately
symptomatic
other than those listed in A or C
Anaemia( Hb<8g/dl, >30
neutropenia(WBC <1000/microl) days
,thrombocytopenia(1 lakh)
Bacterial meningitis,
pneumonia/sepsis
Candidiasis, oropharyngeal(>2mo)
Cardiomyopathy
CMV before 1mo of age
Diarrhea
Hepatitis
HSV stomatitis(>2 episodes in 1yr)
HSV
bronchitis,pneumonitis/esophagitis(<
1 mo)
HZ
Leiomyosarcoma
Lymphoid interstitial pneumonia or
primary lymphoid hyperplasia
complex
Nephropathy
Nocardiosis
Persistent fever(>1 mo)
Toxoplasmosis( before 1 mo)
Varicella, disseminated( complicated
chickenpox)
38. CATEGORY C- severely symptomatic
Serious bacterial infections
Candidiasis(oesophageal/pulmonary)
Coccidiomycois, disseminated
Cryptosporidiosis or isosporiasis with
diarrhea > 1mo
CMV after 1mo
Encephalopathy
HSV infection causing mucocutaneous
ulcer
Histoplasmosis, disseminated
Kaposi sarcoma
Lymphoma(primary) in brain
Lymphoma,burkitt/large cell
Mycobacterium tuberculosis, disse
Pneumocystis jirovecii
Progressive multifocal
leukoencephalopathy
Salmonella(non typhoid) septicemia
Toxoplasmosis after 1mo
Wasting syndrome
39. Pediatric HIV classification system 1994
Immunological
Categories
CD4 +
Lymphocyte
count
Clinical categories
No sign /
symptom
(N)
Mild sign/
symptom
(A)
Moderate sign/
symptom
(B)
Severe sign/
symptom
(C)
No evidence of
suppression
Normal >25% N1 A1 B1 C1
Evidence of
moderate
suppression
Moderate
reduction (15-
24%)
N2 A2 B2 C2
Severe
suppression
Severe
reduction
(<15%)
N3 A3 B3 C3
41. Respiratory conditions in children with HIV
infection:
• Pneumonia and chronic lung diseases contribute to the increased
morbidity and mortality of HIV-infected children.
• The different pulmonary conditions are difficult to differentiate from
each other but are common in immune suppressed children.
• The most common respiratory conditions include
42. Bacterial pneumonia
• • History of fever, cough and fast breathing (tachypnoea) - With or
without signs of severe pneumonia (chest indrawing, cyanosis and
lethargy).
• • On auscultation of the chest one hears unilateral or bilateral
crepitations (crackles), decreased breath sounds or bronchial
breathing
• • When pulse oximetry is available it may demonstrate hypoxia (02
saturation less than 95%).
43. Diagnosis
• • Diagnosis of pneumonia is mainly made by medical history and
physical examination. Other laboratory investigations may be of
assistance:
• • Complete blood counts; raised white blood cells (WBC) with a
neutrophilia suggest bacterial pneumonia
44. Lymphocytic Interstitial Pneumonitis
• Lymphocytic Interstitial Pneumonitis (LIP) usually occurs in children more
than one year of age and is often mistaken for pulmonary TB.
• Diagnosis is usually by exclusion. The following are common clinical
symptoms.
• Clinical signs and symptoms
• Chronic cough
• Cyanosis
• Digital/finger clubbing
• Difficulty in breathing
• Associated with parotitis, generalised lymphadenopathy and hepatosplenomegaly
• Poor response to TB therapy
45. • Radiological picture (Chest X-ray)
• • Diffuse bilateral reticulonodular infiltrates may appear similar to
miliary TB
• • May develop consolidation, cystic lesions; bilateral hilar or
mediastinal lymph node enlargement
46. Tuberculosis in children
• HIV-infected children should be evaluated for TB disease at the time
of their HIV diagnosis and any time they present with symptoms
suggestive of TB or have a history of a new contact to an adult with
TB.
47. CENTRAL NERVOUS SYSTEM
• 50-90% in perinatally infected
• Subtle developmental delay to progressive encephalopathy
• Cerebral atrophy in 85% with neurological symptoms
• Focal neurological signs and seizures are unusual
• CNS lymphoma- focal neurologic signs,headache seizures
• CNS toxoplasmosis is rare
• CMV and JC virus( progressive multifocal leukoencephalopathy)
48. CVS
• Dilated cardiomyopathy and left ventricular hypertrophy
• Resting sinus tachycardia- 64%
• Marked sinus arrhythmias-17%
• Gallop rhythm,tachypnea and hepatospleenomegaly- best indicators
of congestive heart failure
49. GASTROINTESTINAL AND HEPATOBILIARY
TRACT
• MAC and protozoal infection
• AIDS enteropathy- malabsorption with partial villous atrophy
• Disaccharide intolerance
• Chronic/recurrent diarrhea,malabsorption, abdominal pain,
dysphagia,FTT
• pancreatitis
52. • HEMATOLOGIC AND MALIGNANT DISEASES
• Anaemia- 20-70%( s.c recombinant erythropoietin)
• Leukopenia-30% (GCSF)
• Thrombocytopenia-10-20% ( IVIG or anti D, steroids)
• Def of clotting factors -2,7,10
• Malignancies- 2%
• NHL, primary CNS lymphoma and leiomyosarcoma
• Kaposis sarcoma
53. Diarrhea
• Diarrhea is one of the most common causes of under-5 mortality.
• Diarrheal illness is more frequent in HIV-infected children, tends to be
more severe and prolonged, and is often associated with other
comorbid conditions, including severe acute malnutrition and
pneumonia.
54. Clinical features:
• Increased frequency, volume of liquid stools
• Acute watery diarrhea – non-bloody diarrhea lasting <14 days
• Dysentery – diarrhea with visible blood mixed in stools
• Persistent diarrhea – diarrhea lasting more than 14 days
56. Management:
• Management of diarrhea in HIV-exposed and HIV-infected children should
generally be the same as for HIV-uninfected children
• Low-osmolarity ORS is preferable to standard ORS for treatment of
dehydration (intravenous electrolyte solution in cases of severe dehydration) in
HIV-infected and -exposed infants and children with diarrhoea.
• Elemental zinc supplementation is recommended for 10–14 days.
• Emphasize continued or increased feeding during and after the diarrheal
episode
• Ciprofloxacin 15mg/kg BD for 3 days - bloody diarrhoea.
• Daily micronutrients are recommended for 2 weeks
Persistent diarrhea not responding to standard treatments is a WHO Clinical
Stage III condition, and an indication for ART in children
57. kaposi sarcoma (KS):
• Though not as common as in adults, children do get Kaposi sarcoma.
• However, children are also likely to present with enlargement of
lymph nodes and may have enlarged lymph nodes as their only
presenting symptom of Kaposi sarcoma.
• • Management •
• Children with severe KS should be referred to specialty centers for
chemotherapy
• • ART should also be given as treatment for KS
58. Varicella-zoster virus:
• Prophylaxis Immunosuppressed HIV-infected children who are
susceptible to varicella-zoster virus.
• Should avoid exposure to people with chicken pox or shingles.
• For the prophylaxis of chicken pox, HIV-infected patients susceptible
to VZV should be administered varicella-zoster immunoglobulin (VZIg)
as soon as possible, ideally within 96 hours after any close contact
with chicken pox or shingles.
59. Malnutrition:
• Childhood acute malnutrition is high among HIV-infected children.
• Severe wasting is a common clinical presentation of HIV infection in
children.
• HIV-infected children with severe malnutrition have a higher risk of
mortality than uninfected children due to the frequency and severity
of OIs including TB.
• Children with an unknown HIV status, who present with severe
malnutrition should be tested for HIV and considered for ART.
60. Clinical presentation of severe malnutrition
• Severe malnutrition is characterized by the presence of any of the
following:
• weight/height z score < -3, a MUAC of < 11.5cm in children of 6-59
months of age
• visible wasting in infants of < 6 months of age
• bilateral pitting oedema.
61. • IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME
• Increased inflammatory response from recovered immune system to
subclinical opportunistic infections
• In progressive disease and severe CD4 depletion
• NSAIDS OR corticosteroids
• May take weeks to months to subside
63. • HIV is present in saliva, however it is not considered a risk factor for
transmission.
• It contains low levels of HIV that can be detected, and the endogenous
antiviral factors present in saliva.
Oral pathophysiology of HIV infection
• Oral lesions may be present at all stages of HIV infection.
• As the immunodeficient state gradually impairs humoral and cell-mediated
immunity it allows other diseases to affect the patient.
64. • Oral conditions associated with HIV infection are divided into
five major groups:
-Microbiological infections (fungal, bacterial, viral)
-Oral neoplasias
-Neurological conditions
-Lesions of uncertain aetiology
-Oral conditions associated with HIV treatment.
• Other co-infections and conditions associated with HIV infection,
which are significant to dentists are:
-Syphilis
-Tuberculosis
-Persistent generalised lymphadenopathy
-Gastro-oesophageal reflux disease (GORD).
65. Dry lips:
• Associated with HIV-treatment.
• The cracking and crusting of the lips
can be extremely uncomfortable and
unaesthetic.
• Protective creams designed for use
on the dry lips.
Other conditions associated with HIV treatment include:
• Xerostomia
• Oral ulceration
• Hyperpigmentation
66. HIV and tooth decay
• Dental caries is common in people with HIV infection,due to
Xerostomia which occurs due to the HIV infection or its treatment.
67. Microbiological infections
Fungal Infections
• Mycoses or fungal infections are often the first and most prevalent
conditions affecting the oral mucosal surfaces of patients with HIV
infection.
• The main fungal pathogen involved in oral disease is Candida albicans.
• Lesions occurring by candida albicans,
-Pseudomembranous candidiasis
-Erythematous candidiasis
-Chronic hyperplastic candidiasis
68. Oral candidiasis:
• Oral candidiasis or thrush is a very common presentation of HIV in
children, and persistent or recurrent outside of the neonatal period is
a WHO Clinical Stage III condition and an indication for ART in
children.
• Management
• Nystatin suspension
• Infants –100,000 units every 6 hours
• Children – 400,000 – 600,000 units every 6 hours
• Clotrimazole oral drops
• Miconazole oral gel
69. Esophageal candidiasis:
• Clinical features
• Usually associated with extensive oral thrush
• Infants and young children - Refusal to feed and crying during feeds
• Older children – pain with swallowing
• Vomiting
• Management
• Fluconazole 3-6 mg/kg once daily
• If the child is not responding to oral formulation-IV fluconazole (3-
6mg/kg once daily) can be prescribed
70. Pseudomembranous candidiasis
• Description: creamy white or yellow plaques which, when scraped, reveal an
erythematous or bleeding mucosal surface.
• Location: may be found on any of the
intra-oral surfaces.
• Symptoms: none or mild-to-moderate
pain or burning.
• Duration: usually intermittent, however may be chronic.
• Diagnosis: clinical, with a swab for microscopy and culture
when the diagnosis is uncertain.
71. Bacterial Infections
• There is a wide range of bacterial pathogens that cause oral disease in patients
with HIV infection.
• Common bacterial infection occurs in HIV are,
-Necrotising ulcerative gingivitis
-Necrotising ulcerative periodontitis
-Necrotising ulcerative stomatitis
72. Necrotising ulcerative gingivitis
• It presents with pain, ulceration and gingival bleeding.
• The lesion does not involve the alveolar bone.
• Description: the characteristic lesion is a punched out, ulcerated and
erythematous interdental papilla covered by a greyish necrotic slough.
• Location: gingival tissues particularly
the interdental papillae.
• Symptoms: moderate-to-severe pain,
bleeding.Systemic features such as
fever, malaise and lymphadenopathy.
• Duration: sudden onset and rapidly deteriorating
• Diagnosis: clinical.
73. Necrotising ulcerative periodontitis
• The lesion involves the alveolar bone.
• Description: There may be exposed bone
gingival recession and tooth mobility.
• Location: the interdental papilla extending
into deeper periodontal tissues.
• Symptoms: moderate-to-severe pain, bleeding.Systemic features
such as fever, malaise and lymphadenopathy may be present.
• Duration: sudden onset and rapidly worsening
• Diagnosis: clinical
74. Viral Infections
Herpes simplex virus (HSV)
• Description: Small, round vesicles that rupture, leaving shallow ulcers which can
coalesce.
• Location : Hard palate, gingiva and
dorsum of the tongue
• symptoms: Mild-to-severe pain.
Fever, lymphadenopathy and
other symptoms may occur.
• Duration: rapid onset with a duration of 7–14 days.
• Diagnosis: swab for PCR analysis.
75. Epstein-Barr virus (EBV)
• EBV has been linked to oral ulceration in patients with advanced HIV
infection.
• The chief manifestation of EBV in people with HIV infection is
Oral hairy leukoplakia.
76. Oral neoplasias
• Two common malignancies associated with HIV infection that are -- --Kaposi’s
sarcoma
-non-Hodgkin’s lymphoma (NHL).
Kaposi’s sarcoma(KS)
• KS starts red macule which enlarges to form a red-blue plaque and these
plaques may grow into lobulated nodules that may ulcerate sometimes cause
pain.
• Description: Pigmented lesions ranges from flat macules to ulcerated nodular
masses. The lesions can be red, purple, blue or brown in colour.
• Location: Hard palate,gingiva and
buccal mucosa.
• Symptoms: lesions are usually painless
• Duration: chronic
• Diagnosis: clinical followed by biopsy.
77. Non-Hodgkin’s lymphoma (NHL)
• HIV infection is association with EBV can induce NHL.
• Description: Diffuse, rapidly proliferating, slightly purplish mass
• Location: In the palatal-retromolar complex.
• Symptoms: Generalised symptoms fever, night sweats and weight loss.
• Duration: chronic.
• Diagnosis: clinical followed by biopsy.
78.
79. DIAGNOSIS
• All infants of HIV infected mothers- antibody positive at birth
- upto 12-15 months
• Without any exposure- lose maternal antibody between 6 and 12
months- serovertors
• <18 mon- HIV culture,HIV DNA PCR, P24 antigen
• >18mon- IgG antibody to HIV- by EIA and confirmatory western blot
80.
81. • PCR
• Highly sensitive and specific
• 2 types-1. qualitative
-2. quantitative
• Sensitivity is increased to 95% at 4 weeks
99% at 6 months
• Positive at birth- infected in utero
• Negative at birth and positive later- intrapartum or post partum
• Non breast fed infants- at 4-6 weeks
• Breast fed- 1-2 months after cessation of breast feeding
82. • HIV Culture- done from peripheral blood mononuclear cells
-equally sensitive as DNA PCR- complex and expensive
(+ve) results in 1-2 weeks
negative results- no growth for 30 days
• Sensitivity 50% at birth
90% at 3 months
• p24 antigen test- reduces detection period to 2 weeks
-cheaper highly specific, easy to perform
- less sensitive
-false negativity is high in younger children
83. TEST COMMENT
HIV DNA PCR
Preferred test to diagnose HIV-1 subtype B infection in
infants and children(<18yrs), highly sensitive and
specific by 2wks, on blood mononuclear cells
FALSE NEGATIVE-non B subtype HIV-1
HIV CULTURE
Expensive, not easily available, requires upto 4wks to
do test, not recommended
HIV RNA PCR
Less sensitive than DNA PCR- negative result cannot
exvlude HIV
Preferred test for non B subtype HIV -1
84. • DIAGNOSIS > 18 YEARS
• ELISA- reliable
- sensitivity >99.5% and specificity 99%
• Positive ELISA- confirmed by western blot
85.
86.
87. Monitoring HIV disease progression
• Immunological changes- decrease in CD4 count
- transient increase in CD8 and Total lymphocytes
- inversion of CD4/CD8 ratio
• Plasma HIV VL, CD4 count and CD4 %- clinical course and response to
therapy
88. • CD4 COUNT ESTIMATION
• To monitor clinical progression and need for initiation of therapy
• >5 years- absolute CD4 counts
• <5 years- CD4 %
• HIV AND VIRAL LOAD
• Perinatally infected- progress more rapidly to disease
• No rapid fall in viremia like adults
• Reaches adult set point by 5 years of age
• Risk of death is 2.1 times more if RNA> 1lakh copies/ml
89. HIV associated
immunodeficiency < 11mon( %CD4+) 12-35 mon
(%CD4+)
35- 59
mon(%CD4+)
>5 yrs( CD4+)
None/ not
significant >35 >30 >25 >500
mild 30-35 25-30 20-25 350-499
advanced 25-29 20-24 15-19 200-349
severe <25 <20 <15 <200 or <15%
WHO IMMUNOLOGICAL CLASSIFICATION
90.
91. Criteria for presumptive diagnosis of severe HIV disease in infants and children <18 months of age where viral
testing is not available
96. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
1st class available
Inhibit reverse transcriptase
Active against HIV 1 and 2
Act by competing with normal nucleoside triphosphates
ZIDOVUDINE (AZT/ZDV)
LAMIVUDINE (3TC)
STAVUDINE (d4T)
DIDANOSINE ( ddI)
ABACAVIR (ABC)
ZALCITABINE (ddC)
EMTRICITABINE( FTC)
TENOFOVIR ( TDF)- nucleotide
reverse
97. Risks of adverse side effects.
• NRTIs The NRTIs can interfere with mitochondrial DNA synthesis and
lead to high levels of lactate and lactic acidosis, liver steatosis,
peripheral neuropathy, myopathy andlipoatrophy.
• Current first line NRTIs such as lamivudine/emtrictabine, tenofovir,
and abacavir are less likely to cause mitochondrial dysfunction.
99. • NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
• 2nd class
• Inhibit HIV-1 RT by binding to hydrophobic pocket
• Rapidly reduces viral load
• Drug resistance, cross resistance
NEVIRAPINE (NVP)
EFAVIRENZ (EFV)
ETRAVIRINE- second generation NNRTI
active against HIV-1 isolates resistant to other NNRTIs
100. Risks of adverse side effects.
• NNRTIs NNRTIs are generally safe and well tolerated.
• The main reason for discontinuation of efavirenz is neuro-psychiatric
effects including suicidal ideation.
• Nevirapine can cause severe hepatotoxicity, especially in women with
high CD4 counts.
102. Risks of adverse side effects.
• Integrase inhibitors Integrase inhibitors (INSTIs) are among the best
tolerated of the antiretrovirals with excellent short and medium term
outcomes.
• Given their relatively new development there is less long term safety
data.
• They are associated with an increase in creatinine kinase levels and
rarely myopathy.
104. PROTEASE INHIBITORS
Inhibit protease enzyme by binding to active site- preventing cleavage of precursor
polyproteins
Highly potent
Active against HIV 1 and 2
High genetic barrier to resistance
NELFINAVIR ( NFV)
RITONAVIR ( RTV)
LOPINAVIR/ RITONAVIR ( LPVr)
AMPRENAVIR
INDINAVIR ( IPV)
SAQUINAVIR ( SQV)
ATAZANAVIR
DARUNAVIR
TIPRANAVIR
105. Risks of adverse side effects.
• Protease inhibitors Protease inhibitors (PIs) are often given with
ritonavir, a strong inhibitor of cytochrome P450 enzymes, leading to
numerous drug-drug interactions.
• They are also associated with lipo-dystrophy, elevated triglycerides
and elevated risk of heart attack.
106. • BOOSTED PI’S
• Low dose RTV- inhibitor of cyt P450 3A4 isoenzyme- inhibits
metabolism of other PI’s
• Pharmakokinetic booster
• Coformulated LPVr in children > 6 wks of age
• Low dose RTV- > 6 years of age
107. New classes
• ENTRY INHIBITORS ( ENFUVURTIDE)
• Inhibit viral binding/ fusion to host target cells
• T20- ENFUVIRTIDE
• S.C twice daily dose-- > 6yrs
• 36 a.a polypeptide binds to gp41 glycoprotein- prevents fusion
• Salvage regimen- in multi ART regimen failure
108. • CCR5 CORECEPTOR ANTAGONIST ( MARAVIROC)
• Blocks CCR5 coreceptor on CD4 cell surface
• First ARV drug- does not target virus itself
• As combination in multidrug resistant HIV 1
• Should check for CCR5 tropism
110. NRTI NNRTI PI
ZDV 360 mg/m2
To max 600 mg
NVP 300-400 mg/m2
Max 400 mg
NFV 110-150 mg/kg
Max 2500 mg
3TC 8 mg/kg
Max 300 mg
EFV 15 mg/kg
Max 600 mg
LPVr 460/115/m2
Max 800/200
mg
ABV 16 mg/kg
Max 600 mg
RTV 700 mg/m2
Max 1200 mg
ddI 180 mg/m2
Max 400 mg
d4T 2 mg/kg
Max 80 mg
RECOMMENDED DOSAGES
111. FOOD INTERACTIONS
didanosine Fasting increases
absorption
Given at fasting or 2hrs
after meal
saquinavir High fat meal increases
absorption
With high fat meal
Ritonavir
Atazanavir
Tipranavir
Lopinavir
darunavir
Meals increases
absorption
With meals
indinavir Fasting increases
absorption
In fasting state
etavirine Meals increase absorption Given after meal
112. Trends in HIV therapy
• middle 1990s- monotherapy- immunological benefit with treatment
• 1996/97 (dual NRTIs)- combination therapy- better immunological,
clinical and viral outcomes
• Currently- highly active combination therapy- atleast 3 drugs
- enhanced survival, reduction in OIs and other
complications, improved growth and quality of life
113. TREATMENT
• Earlier safer and simpler antiretroviral therapy can push HIV epidemic
into irreversible decline
• WHEN TO START
• Initiation of ART in all children <5yrs of age
• Increased immunological criteria of CD4 counts to <500 cells/mm3
in children >5yrs
114. New recommendations( WHO 2013)
• ART should be initiated in all children infected with HIV below 5 years
of age regardless of WHO clinical stage or CD4 count
infants diagnosed in the first year of life(strong recommendation, moderate
quality evidence)
children 1-5years( conditional recommendation,very low quality evidence)
• ART should be initiated in all HIV infected children 5 years of age and
older with CD4<500 cells/mm3 regardless of clinical stage
CD4< 350 cells/mm3(strong recommendation, moderate quality evidence)
CD4 between 350 and 500 cells/mm3(conditional recommendation,very low
quality evidence)
115. • ART should be initiated in all children infected with HIV with severe or
advanced symptomatic disease( stage 3 or 4) regardless of age and
CD4 count. (strong recommendation, moderate quality evidence)
• ART should be initiated in any child younger than 18 mon of age who
has been given a presumptive clinical diagnosis of HIV infection(strong
recommendation, low quality evidence)
116. • Initiating ART at CD4>350 cells/mm3– reduces risk of progression to
AIDS, TB and increases immune recovery compared to treatment at
<350 cells
117. • WHAT TREATMENT REGIMEN TO START WITH
• Simplified, less toxic, easy to administer “fixed drug combination”
• First line ART for children <3yrs of age
a LPV/r based regimen should be used as first line ART for all children infected
with HIV <3yrs of age regardless of NNRTI exposure. If LPV/r is not feasible
treatment should be initiated with NVP based regimen
Where VL monitoring is available LPV/r can be substituted with NNRTI after
virological suppression is sustained
When children get TB while on ART with NVP or LPV/r---ABC+3TC+AZT
For <3years the NRTI backbone should be ABC+3TC or AZT+3TC
118. Children 3y to 10 yrs and
adolescents <35 kg
Adolescents (10-19 yrs)
>35 kg
preferred ABC+ 3TC + EFV TDF + 3TC(OR FTC)+ EFV
alternatives
ABC+ 3 TC+ NVP
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC ( OR FTC) + EFV
TDF + 3TC (OR FTC) + NVP
AZT + 3TC + EFV
AZT+ 3TC+ NVP
TDF+ 3 TC(OR FTC) + NVP
SPECIAL CIRCUMSTANCES
D4t +3TC +EFV
D4t + 3TC + NVP
ABC + 3TC + EFV
ABC + 3 TC + NVP
119. TREATMENT ASSESSMENT AND LABORATORY MONITORING
• Before ART is initiated thorough clinical and basic lab assessment
should be undertaken
• Adherence , toxicities and treatment failures
• Childs nutritional status, growth and development, comorbidities and
immunization status
• Each follow up- educate on nutrition, hygiene, adverse drug reactions
120. • CLINICAL FAILURE
• Occurrence of new/ recurrent clinical event indicating advanced or
severe immunodeficiency(WHO clinical stage 3 or 4 with exception of
TB) after 6 mon of effective treatment
• IMMUNOLOGICAL FAILURE
• In <5yrs-Persistently low CD4 levels below 200 cells/mm3 or < 10%
• In > 5yrs, including adolescents- CD4 falling below baseline or
persistently < 100 cells/mm3( in absence of recent infection)
121. • The CD4 count has to be checked baseline and at 12 monthly intervals
before initiation of ART
• While on ART- CD4 monitored once in every 6 months
• VIROLOGICAL FAILURE
• Persistently detectable viral load exceeding >1,000 copies/ml in 2
consecutive measurements within 3 month interval after atleast 6
months of ART
122. • SECOND LINE ART FOR CHILDREN( INCL. ADOLESCENTS)
• After failure of first line NNRTI regimen, a boosted PI plus 2 NRTIs are
recommended- LPV/r is boosted PI
• After failure of first line LPV/r regimen, children < 3yrs- should remain
on 1st regimen
• After failure of 1st line LPV/r based regimen, >3yrs children- 2nd line-
NNRTI + 2 NRTIs ( EFV is preferred NNRTI)
• After failure of first line regimen ABC or TDF + 3TC, preferred NRTI
backbone option is AZT + 3TC
• After failure of AZT or d4T + 3TC, preferred NRTI backbone option is
ABC or TDF + 3TC
123. • 3rd LINE ART FOR CHILDREN
• Newer drugs such as etravirine( ETV), DRV and Raltegravir(RAL)
• Choice of PI is DRV/r after treatment failure with LPV/r or ATV/r
• Children with failing 2nd line with no new options should continue on
tolerated regimen
124. Drugs which should not be used together
• Zidovudine + stavudine : pharmacological antagonism
• Atazanavir + indinavir : additive unconjugated hyperbilirubinemia
• Didanosine/ stavudine + zalcitabine : additive peripheral neuropathy
• Lamivudine + zalcitabine : in vitro antagonism
125. SUPPORTIVE CARE
• Quality of life and survival of HIV infected children
• Multidisciplinary approach
• Nutritional status- dental evaluation and oral hygiene
• ARV related central lipoaccumulation
• Development evaluated- physical occupational or speech therapy
126. Care of HIV infected children
• All children should be assessed for symptoms related to HIV as well as the need
for treatment and prophylaxis for opportunistic infections and other HIV related
conditions.
• • Baseline laboratory tests should be performed to establish viral and
immunological status whenever possible.
• • A complete medical and immunization history should be obtained, with
particular emphasis on the suspected mode of HIV transmission, history of ARV
exposure (pre-, intra-, postpartum, and during breastfeeding) and timing of HIV
diagnosis. HIV-infected children should receive routine paediatric care and be
monitored for their HIV disease progression. Children should be seen monthly.
• • At each visit, a complete physical examination should be done paying particular
attention to signs commonly associated with HIV infection (e.g. adenopathy,
hepatomegaly and splenomegaly).
127. • Visits should also focus on assesment and management of intercurrent
illness as well as assessment for development of new WHO stage 3 or 4
clinical conditions, which may indicate treatment failure
• • Nutrition, growthand neuro development assessment should be done
and charted at all stages of development right through adolescence.
• • Doses of prophylactic or treatment medications should be adjusted on
the basis of growth and compliance and tolerability should be assessed at
every visit.
• • Medication plans (OI prophylaxis and ARV therapy) need to be discussed
intensively with parents or guardians. It is advisable that one single person
in the household is identified as the consistent care provider responsible
for dispensing treatment to the child.
128. • HIV related care needs of parents or guardians themselves need to be
discussed and appropriate referrals made accordingly.
• • Children exposed to ARVs should be closely monitored at every visit
for signs of toxicity (i.e. clinical or laboratory indications) and adverse
events should be properly documented and reported to the Ministry
of Health and Social Welfare.
• • Counselling and psychosocial support should include the children
and be provided in an age appropriate fashion
129. Management of infants born to HIV positive
women
• The HIV-exposure status of all infants attending RCH services should
routinely be established and documented. The counseling of parents
on the care of infants born to HIV positive mothers is an essential
component of the management of HIV exposed children.
Management strategies include:
• • HIV diagnostic testing for the child • Scheduled clinic visits for care
• • Chemoprophylaxis with cotrimoxazole, a fixed dose combination of
trimethoprim/sulfamethoxazole (TMP/SMX) even if HIV status is
unconfirmed
130. • IMMUNISATION
• Standard pediatric immunization
• Live oral polio vaccine – not given
• BCG should be avoided
• Varicella and MMR- can be given in not severely
immunocompromised children
131.
132. • PROPHYLACTIC REGIMENS
• All infants between 4-6 weeks and 1yr of age proven to be HIV
infected- pneumocystis jirovecii prophylaxis(regardless of CD4)
• When child > 1year- according to CD4 count
• 150mg/m2/day of trimethoprim component of TMP/SMZ
• 1-2 daily doses, 3 days per week
133. AGE/ HIV INFECTION STATUS PCP PROPHYLAXIS CD4 MONITORING
Birth to 4-6 weeks, HIV exposed no prophylaxis none
Hiv infection reasonably
excluded
no prophylaxis none
4-6 weeks to 4 months,HIV
exposed
prophylaxis 3 mo
6 wk- 1yr, HIV infected/
indeterminate
prophylaxis 6,9 and 12 mo
1-5 yr, HIV infected prophylaxis if CD4
<500cells/micl or <15%
every 3-4 mo
>6 yr, HIV infected Prophylaxis if CD4 <200
cells/micl or <15%
every 3-4 mo
134. • Prophylaxis against MAC- azithromycin (20mg/kg) once a week PO
or clarithromycin( 7.5 mg/kg BD PO)
• Primary prophylaxis can be discontinued if immune reconstitution has
been sustained with HAART
• All HIV infected should have tuberculin skin testing for TB atleast once
per year
• IFN-gamma release assays are more specific
135. PROGNOSIS
• Improved understanding and availability of more effective ARV drugs
improved prognosis
• Mortality in perinatally infected children declined >90%
• Mean age at death increased from 9 to >18 years
• Best prognostic indicators- sustained suppression of plasma viral load
- restoration of normal CD4 count
• In resource limited countries- clinical staging system to predict
prognosis
136. • Opportunistic infections, encephalopathy or wasting syndrome- worst
prognosis- 75% die below 3 yrs
• Lymphadenopathy, splenomegaly, hepatomegaly and LIP- better
prognosis
137. PREVENTION
• Landmark pediatric clinical trails protocol- ZDV prophylaxis to
pregnant women as early as 4 wks of gestation, during labor and
delivery and to newborn for 1st 6 weeks- reduced transmission by
75%
• Maternal HAART – decreases transmission to <2%
• Elective LSCS and maternal zidovudine- reduces transmission by 87%
• Single dose NVP- once to mother in labour and to infant in 48-72 hrs-
reduces by 50%
138. • Who do not meet indications for therapy- ZDV from 14 wks+/- SD
NVP during labor and oral ZDV+ 3TC during labor and 1 wk
postpartum
infants ZDV/NVP for 6 weeks
BREAST FEEDING
• WHO recommended exclusive breast feeding for atleast 6 mon
• Treat mothers with triple ART and infants with daily nevirapine ( upto
6wks) –reduces risk to 2%
• Others with high CD4- discontinue ART 1 wk after delivery and treat
infant with daily nevirapine
139. WHO recommendations for PPTCT
• Option A
• For pregnant women
antepartum daily AZT
single dose NVP at onset of labor
AZT+3TC during labor or delivery
Twice daily AZT+ 3TC for & days
postpartum
• Option B
• For pregnant women
triple ARV from 14 wks of gestation
until 1week after stopping breast
feeding
recommended regimens include
AZT+3TC+LPV/r
AZT+ 3TC+ ABC
AZT+3TC+EFV
TDF+3TC+ EFV
140. • For infants
• If breast feeding single dose NVP
at birth upto cessation of Breast
feed (1 week)
• If not breast feeding, single dose
NVP at birth and upto 4-6 weeks
of age
• Daily administration of AZT or
NVP from birth until 4-6 weeks
of age
141. Prevention of Parent-To-Child Transmission Program in India
• Over the past few years, India has witnessed a significant scaling up of
prevention of parent-to-child transmission (PPTCT) program and
antiretroviral therapy (ART) services for pregnant and breastfeeding
women and their children.
• Under the National AIDS Control Programme (NACP), various HIV-
related services are provided through public and private health providers.
• The NACP is implemented by the National AIDS Control Organization
(NACO) of the Government of India, in partnership with other partner
agencies
142. POST EXPOSURE PROPHYLAXIS
CHILDREN >6 MONTHS
AND < 13 YEARS
>10KG
Zidovudine 9mg/kg b.d upto 300mg + lamivudine
4mg/kg b.d upto 150 mg PO + lopinavir/ ritonavir (
lopinavir 10 mg/kg/ ritonavir 2.5mg/kg upto 400/100
mg
ADOLESCENTS > 13 YRS Above regimen or
ZDV 300 mg Po b.d + 3TC 150 mg PO b.d + TDF 300mg
PO O.D
Or
ZDV 300 mg po B.D +FTC200 mg PO OD + TDF 300mg PO
OD
143. COUNSELLING
• Voluntary counselling and testing(VCT)- preventing HIV transmission
from mother to child during childbirth
• Support for treatment of OIs
• Management of HIV TB coinfection
• Referrals to medical centres- for ART
• It is non-coercive,confidential and cost effective-
information,education and communication
• In 2006-07- VCT and PPTCT were merged to form ICTC( integrated
counselling and testing centres)
145. • The fact that so many Indians remain unaware of their HIV status and
so few individuals with HIV are virally suppressed is unacceptable.
• The oral health care team should be vigilant in recognizing oral
manifestations that may be related to HIV infection.
146. • Over the past 34 years, significant advances have been made in HIV
testing and treatment.
• Whereas in 1986 only one U.S. Food and Drug Administration-
approved ARV was available, now there are 37, including combination
medications.
• While in 1986 there was one class of drugs, today there are seven,
with two more in clinical trials.
• These drug classes target the many opportunities HIV has to invade a
cell, reproduce, depart the cell, and go on to infect other cells
147. COLLABORATION IS KEY
• There are many opportunities for dental, medical, and support teams
to collaborate to ensure patients with HIV are linked to medical and
dental care, retained in care, and adhere to their prescribed
treatment regimens. This is where the intersection of oral-systemic
associations is important
148. • As long as dental professionals follow recommended infection
prevention protocols to prevent pathogenic exposure, there are no
safety concerns regarding the use of hand-pieces and ultrasonic
scalers, and these devices should be used when indicated.
HIV is a blood-borne, not an airborne, disease.
149.
150. Restorative Considerations
• The combination of periodontal disease, reduced salivary flow,
exposure to gastric fluids and poor oral hygiene increases the
likelihood of root caries. When these conditions are present, they
must be addressed (along with their cause) and, whenever possible,
treated or eliminated before further restorative treatment is initiated.
151. Prosthetic Considerations
• Prosthetic treatment for the HIV population is similar to prosthetic
treatment for the elderly population—both groups may be prone to
candidiasis, xerostomia and wasting syndrome.
• An acrylic partial denture can be replaced by using thermoplastic
materials which can prove a good option for a patient with a
questionable dental prognosis.
152. General Prevention Recommendations
• The dental clinician must stress good oral hygiene and home care
procedures (brushing, flossing, mouth rinses). On a case-by-case
basis, the dentist should establish a plan for periodic office visits for
oral examinations and periodontal supportive therapy. These
procedures constitute fundamental standards of care and facilitate
the early diagnosis of oral disease
153. Reduced Salivary Flow (Xerostomia)
• When reduced salivary flow is diagnosed in the HIV infected patient, a
treatment program consisting of replacement or stimulation of saliva
should be instituted. Secretory stimulants (Pilocarpine, Salagen®,
Bethanecol®), as well as saliva substitutes (e.g Oral balance®,
Xerolube®, Salivart®, Unimist®), will provide lubrication of the oral
tissues, ease patient discomfort and enhance local defensive barriers.
154. Caries
• Reduced salivary secretion and function and poor diet (especially a
carbohydraterich diet frequently associated with recreational drug
use) can predispose patients to rampant dental caries.
155. PERIODONTAL CONSIDERATIONS
• HIV-gingivitis was renamed linear gingival erythema (LGE) and HIV-
periodontitis was renamed necrotizing ulcerative periodontitis (NUP).
In addition, necrotizing ulcerative gingivitis (NUG), also known as
ANUG, was also shown to be associated with HIV infection in some
patients.
156. linear gingival erythema (LGE)
• Treatment of LGE is directed at preventing this lesion from
progressing to the
• more severe NUP. The treatment protocol includes instruction in
improved oral hygiene and thorough root planing and scaling.
Patients are typically placed on chlorhexidine rinses twice a day
indefinitely, and are recalled every three months.
157. Necrotizing Ulcerative Gingivitis (NUG) and
Necrotizing Ulcerative Periodontitis (NUP)
• At the first visit, the priority is to alleviate the patient's symptoms.
• Thorough mechanical debridement, removal of calculus, bacteria, and
necrotic tissue should be accomplished as soon as possible.
• The use of 10% povidone-iodine is suggested during the irrigation and
debridement procedure to help control patient discomfort and bleeding.
• Povidone-iodine has antimicrobial activity against certain oral bacteria and
fungi, improves early periodontal wound healing, and provides some
topical anesthesia.
• Patients should then be instructed in oral hygiene procedures, with
emphasis on diligent compliance.
158. Extractions
• For all patients, regardless of HIV status, the use of aseptic and
atraumatic surgical techniques is essential to minimize the
introduction of pathogens into a surgical wound and to reduce
postoperative complications.
• Preoperative scaling of the teeth to be extracted may also help reduce
the rate of postoperative infections, and should be considered in
tandem with educating and motivating patients to improve their oral
hygiene.
159. ENDODONTIC CONSIDERATIONS
• In cases of acute pulpitis, endodontic treatment must be performed
immediately to eliminate the risk of periapical infection and other
complications.
• This is especially important when surgical treatment cannot be
performed because of systemic limitations (e.g., coagulation
concerns)
160. Orthodontic considerations
• Late-stage AIDS, like certain leukemias, uncontrolled diabetes or any
other debilitating systemic disease, is a primary contraindication for
extensive orthodontic treatment.
• For minor tooth movement, the health of patients with HIV/AIDS
should be carefully evaluated, as these patients may have labile
health even when they appear to be in good physical condition.
161. The Pediatric Dentist as Part of the Overall
Care Team
• Preventive services for children should include:
• Dental education and counseling as part of prenatal and perinatal care.
• Preventive dental education and counseling of adult caregivers responsible
for health care of the child with HIV.
• Preventive dental counseling of medical and nursing colleagues.
• Frequent periodic oral health examinations (1-3 months).
• Placement of pit and fissure sealants, when appropriate.
• Appropriate use of systemic or topical fluorides.
• Appropriate use of antimicrobials for plaque-associated diseases
162. Pain management strategies
• Pain management in HIV-infected children should combine pharmacological and non-
pharmacological therapies.
• The latter include:
• • relaxation techniques and behaviour modification;
• • environmental management: play, music, scheduled medical and nursing
interventions, and structured time for sleep and rest;
• • gentle handling and supportive positioning;
• • nutritional support, adequate hydration and electrolyte replacement;
• • optimized tissue perfusion and oxygenation; • transcutaneous electrical nerve
stimulation (TENS), gentle massage, whirlpool baths and physical therapy; and
• • electrical or needle stimulation of acupuncture meridians by HIV-knowledgeable
practitioners.
163. Infection Control
Hand Hygiene
• The purpose of hand hygiene is to reduce the quantity of micro
organisms of hands.
Protective Equipment
• Protective equipment would include gloves, masks, protective eye-wear
and protective clothing.
• It protects from the splashing or spraying of blood, saliva or other body
fluids.
Gloves
• Double-gloving may be utilized for some specific procedures and in the
infected patient’s treatment.
Masks ,Eye wear, Protective Clothing
• They are weared to protect from splashes, sprays or spatter of blood,
saliva, other body fluids, or contaminated water.
164. INOCULATION ACCIDENTS SHARPS INJURIES
PROCEDURE:
• 1. Cuts and puncture wounds should be washed out at once with soap and water.
• 2. Inform immediate superior and
• a) Complete an Inoculation Accident Surveillance form IAS-1 b) Inform the consultant
(office hours).
• c) Enter information in Inoculation/Sharp Accident record book (to be kept at
ward/clinic/unit).
• 3. It is essential to: a) identify "sharp" and the patient contact
• b) obtain 5 ml blood sample from the staff member and the patient (if known) involved.
• 4. Immediately attend Staff Health Clinic between 08.00 and 16.00 hours on weekdays,
or outside these hours attend Accident & Emergency for:
• a) wound dressing b) antitetanus, if necessary
• c) collect 5 ml blood specimen (in plain tube) for HIV and Hepatitis B testing.
• If this not possible, contact the Medical Staff in the Medical Department.
165. • 5. Surveillance Form (IAS-1), blood specimens from the staff involved and
the source patient (if known) should be delivered to The Department of
Medical Microbiology immediately together with request forms (pink
virology form) duly completed with full details and marked "Urgent
Innoculation accident". Use labels stating "Danger of Infection" or
Biohazard Tapes.
• 6. Refer to Guidelines for Health Care Workers if the patient is a known HIV
carrier.
• 7. The results of the blood test will be available within 48 hours. If further
treatment is recommended this will be arranged through Staff Health
Clinic.
• It is your responsibility to ensure that you get the necessary follow-up
treatment.
166. • Where should you get yourself tested?
• • ICTC centre (Integrated Counseling & Testing Centre) – District
Hospitals – Medical colleges
• • Free HIV testing • Confidential counseling • Referral to nearest ART
(Anti Retroviral Therapy) centre ,DOTS,PPTCT, STD.
167. Ethical Considerations
A Common Form of Human Rights Violation is a Dentist
refusing to take on a new patient due to their HIV status.
• Courts have recognized that privacy concerns are of paramount importance for
people with HIV.
• HIV status of a patient should be protected and not revealed without the
patient’s written informed consent.
• The form must be signed and dated and a witness signature may be prudent.
169. • National AIDS Control Organisation is a division of the Ministry of
Health and Family Welfare that provides leadership to HIV/AIDS
control programme in India through 35 HIV/AIDS Prevention and
Control Societies.
• In 1986, following the detection of the first AIDS case in the country,
the National AIDS Committee was constituted in the Ministry of
Health and Family Welfare.
170.
171. Challenges in the Control of Pediatric Hiv
Infection:
• Lack of awareness about prevention of parent-to-child transmission
services
• Utilization of antiretroviral therapy services
• Maternal antiretroviral therapy/antiretroviral adherence
• Antiretroviral therapy adherence among children
172. Societal level
• Maternal nondisclosure of HIV status
• Disclosure of HIV diagnosis to children
• Delayed infant diagnosis
• Delayed entry into HIV care
• Lack of intranatal testing for HIV infection
• High unmet need for contraception
173. What’s New in the Pediatric Guidelines (Last
updated November 15, 2017; last reviewed
November 15, 2017)
• Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV Infection
• The Panel recommends that the selection of a newborn ARV regimen should be determined
based on maternal and infant factors that influence risk of HIV transmission. The uses of ARV
regimens in newborns include:
• • ARV prophylaxis – the administration of one or more ARVs to a newborn without confirmed HIV
infection to reduce the risk of HIV acquisition
• • Empiric HIV therapy – the administration of a three-drug combination ARV regimen to
newborns at highest risk of HIV acquisition. Empiric HIV therapy is intended to be early treatment
for a newborn who is later confirmed to be HIV-infected but also serves as prophylaxis against HIV
acquisition for those newborns who are exposed to HIV in utero, during the birthing process or
during breastfeeding and who do not become infected with HIV
• • HIV therapy – the administration of three-drug combination ARVs at treatment dosages (ART) to
newborns with confirmed HIV infection (see Diagnosis of HIV Infection).
• • The Panel recommends combination ARV prophylaxis or empiric HIV therapy for newborns at
higher risk of HIV acquisition and HIV therapy for newborns with confirmed HIV infection.
174. Future Recommendations:
Promoting antiretroviral therapy adherence in mothers and children
• Parental and caregiver counseling
• Exploring options for providing child-friendly formulations
• Promote counseling, emotional support, and skill building for coping
mechanisms for mothers living with HIV/AIDS
• HIV disclosure should be done as a planned intervention and not as
an abrupt process. A timely, sensitive, and well-managed disclosure is
shown to significantly improve ART adherence and reduce
psychological stress in the parents and children
175. • Involving community level workers: The “Asha-Life intervention” has
shown a significant effect in improving ART adherence and decreasing
barriers among rural women living with AIDS in India
• In this program, the “Accredited Health Social Activist” worker
provides basic education and counseling, promotes healthy lifestyle
choices, and links women living with AIDS to community resources to
match health needs.
176. Improved case detection:
• Scaling up of infant diagnostic services and strengthening programs to
retain HIV-exposed children in care and ensure timely testing for HIV
infection
• Exploring feasibility for virological testing at birth: About 30%–40% of HIV-
infected infants can be identified by 48 h of age.
• Factors such as the institutional delivery rate, time taken to deliver the test
report, and dosing data need to be taken into account
• Ensure continued follow-up of exposed babies for their full participation in
postnatal care
• Promote intranatal testing for HIV for patients with no prior record of HIV
testing
• Promote antenatal HIV testing
177. Strengthening of health systems:
• Strengthen mechanisms for integrating PPTCT across private sector by means of
promoting public–private partnership.
• Ensure retention of HIV-infected women in the health-care system smooth
transmission from PPTCT program to long-term HIV care
• Integrating HIV-screening program at primary health: An initiation to provide
facility-based integrated counseling and testing centers at all round-the-clock
primary health centers resulted in an additional 27% of HIV-infected women
getting detected.
• This involves capacity building and sensitization of community level workers on
HIV prevention
178. CONCLUSION
• ART now freely available for children- HIV children live longer and into
adolescence
• Thus newer issues in management of HIV arise- toxicities, resistance issues and
psychosocial aspects of adolescents
• Promising results in area of PPTCT- era of preventing disease is not far
179. Future prospects
HIV Vaccine-
Several vaccine are under study keeping in mind the objective for the control of AIDS.
1. Preventive vaccine
2. Therapeutic vaccine
3. Perinatal vaccine
Type of vaccines-
1. Whole virus vaccine –live attenuated & inactivated
2. Subunit virus vaccine-envelop protein & core protein
3. Live virus vector of HIV gene with vaccinia virus recombinants & adeno virus recombinants
4. Anti idiotype HIV vaccine.
some of these vaccine have completed phase I (safety) phase II (immunogenicity)
human trail but phase III (efficacy) among HIV infected are being under trial.
180. Gene therapy
• This therapy required the introduction of anti HIV gene into the cells
to prevent or inhibit HIV 1 viral gene expression of function &
consequently to limit HIV replication & AIDS pathogenesis.
• Gene also down regulate HIV in contrast to conventional drug
thearpy.
181. Goal for future
• To improve treatment with effective chemotherapeutics or
antiretroviral agents or drug combinations.
• Implement steps to prevent perinatal transmission with maternal
screening.
• Prevention of adolescents HIV infection with sex education, safe sex
with use of condom, campaign against drugs & health education are
some of the ways to curb transmission of HIV .
182.
183.
184.
185. "Berlin patient“
• So far only one adult (the so-called "Berlin patient") has been potentially
cured and has been off of treatment since 2006 with no detectable virus.
• This was achieved through two bone marrow transplants that replaced his
immune system with a donor's that did not have the CCR5 cell surface
receptor, which is needed for some variants of HIV to enter a cell.
• It has inspired research into other methods to try to block CCR5 expression
through gene therapy.
• A zinc finger nuclease has been used in a Phase I trial of 12 humans and led
to an increase in CD4 count and decrease in their viral load while off
antiretroviral treatment.
186. • After the "Berlin patient", two extra patients (who suffered from both
HIV and cancer) had no traceable HIV virus after successful stem cell
transplantations, as announced on 17 July 2016 by virologist
Annemarie Wensing of the University Medical Center Utrecht, during
a speech entitled "Allogeneic Stem Cell Transplantation in HIV-1
Infected Individuals; the EpiStem Consortium", presented during the
2016 Towards an HIV Cure Symposium in Durban, South Africa.
187. The principles of good oral health care are the same for people with HIV
as they are for all dental patients.
188. REFERENCES
• NELSONS TEXTBOOK
• O.P GHAI TEXTBOOK OF PEDIATRICS
• IAP TEXTBOOK OF PEDIATRIC INFECTIOUS DISEASES
• MANAGEMENT OF PEDIATRIC HIV- DR IRAH SHAH
• NACO GUDELINES 2015 FOR ARV
• INDIAN JOURNAL OF PEDIATRICS- TREATING PEDIATRIC HIV
Editor's Notes
AIDS was first reported in the United States in 1981 and has since become a major worldwide epidemic
The names HIV and AIDS be confusing because both terms describe the same disease.
AIDS is the most advanced stage of infection caused by HIV. But most people who are HIV positive do not have AIDS.
An HIV-positive person is said to have AIDS when his or her immune system becomes so weak it can't fight off certain kinds of infections and cancers, such as PCP (a type of pneumonia) or KS (Kaposi sarcoma, a type of cancer that affects the skin and internal organs), wasting syndrome (involuntary weight loss), memory impairment, or tuberculosis.
Globally- 3.3 million children with HIV with 3,30,000 new HIV infections in 2011
2,30,000- AIDS deaths in 2011
17.3 million AIDS orphans
1.45 lakh children with HIV
1lakh- registered in ART centres
34,000 children- free ART
Perinatal transmission- 5.74%
1.Adsorption: HIV glycoprotein (gp120) + host cell’s CD4 receptor,
2. Breaking in to the target cell
3. undressing (,,striptise’’)
4. virus-RNS sinthesis to DNS (reverse transcription),
5. Entering into nucleus
6. integration into cell’s genome 7.b dormant HIV pro-virus formation
7.a -b HIV proteins un RNS copies synthesis, fitting,
8. HIV particles gemmation
9. liberation
10. maturation
• HIV enters T lymphocyte or other ,,target” cell
• HIV uses cell’s own DNA and enzymes to copy its RNA
• Enzymes divide RNA to make new HIV
• Reproduct a new HIV then emerges out of the T lymphocyte
Lower segment ceaserian section
The majority of children with HIV acquire the infection from their mothers during pregnancy, labour and delivery or after birth during breastfeeding.
Exposure to HIV continues as long as a child of an HIV-infected mother is breastfed.
HIV infected infants may not have any signs or symptoms of infection soon after birth but usually develop features of infection in the early infancy period, although these features may overlap with those of other common childhood diseases.
The HIV infection progresses more rapidly in children than in adults.
The human immunodeficiency virus, upon entry into the human body seeks out the CD4+ receptors on T-helper Iymphocytes and other cells with CD4+ molecule.
The virus then enters into the cell and incorporates itself into the cellular genome eventually causing cell death.
With the decline in CD4+ Tlymphocytes, the body's defence mechanism will be compromised. This will allow opportunistic organisms to cause life-threatening infections. Atypical tumours may also develop. HIV infection is a chronic infection which causes the immune system to fail. The period from the onset of the infection to the development of AIDS-defining illnesses varies from 7 - 11 years. During this period the HIV-infected individual is asymptomatic; however he is infectious and can transmit the virus to others.
This seroconversion phase occurs in approximately 60-90% of patients; however this phase may be difficult to identify because most of our patients may not remember the flu-like illness, or may attribute it to the ordinary common cold. This glandular fever type illness may be encountered 2 to 6 weeks after exposure. The symptoms and signs are indistinguishable from that of a flu-like illness. However this mononucleosis-like illness differs from the common cold in that the symptoms are more prolonged and may last 2-4 weeks. Sometimes neurological manifestations may occur during this phase.
An acute encephalitis-like illness with reversible encephalopathy (disorientation, impairment of consciousness and cognitive functions etc) has been described during seroconversion, as has acute meningitis, myelopathy and neuropathy.
Recovery is complete and the patient will feel well. Occasionally the acute seroconversion illness may be completely asymptomatic.
The rapid progressors are those individuals who harbour HIV that induces syncytium formation and cause clumping of cells AND the slow progressors are those with non-syncytium inducing variants of HIV.
Infants born to HIV-infected women have passively transferred antibodies that can persist until 9 to 18 months of age. The positive rapid antibody tests may only indicate the presence of passively transferred maternal HIV antibodies. Therefore, virologic tests or DNA PCR, are required in order to confirm HIV infection in children <18 months of age.
A single positive PCR test means the infant is presumably infected and should be initiated on ART. At initiation, a second PCR should be taken to confirm the infection. NB: The second test should not delay ART initiation.
For a child that was never breastfed: A single negative PCR test after the age of 4 weeks excludes HIV infection.
For a child that has completely stopped breastfeeding for more than 6 weeks prior to virologic (DNA PCR) testing, a negative PCR test excludes HIV infection.
If the child is being breastfed, a negative virologic test does not exclude infection. On-going exposure to HIV through breastfeeding continues to put the child at risk of infection. Confirmatory testing should be done 6 weeks after complete cessation of breastfeeding as described above to determine final infection status.
•Entry inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several targets.
• Maraviroc and enfuvirtide are the two currently available agents in this class. •Maraviroc works by targeting CCR5, a co-receptor located on human helper T-cells. •Enfuvirtide is a peptide drug that must be injected and acts by interacting with the Nterminal heptad repeat of gp41 of HIV to form an inactive hetero six-helix bundle, therefore preventing infection of host cells.
are nucleoside and nucleotide analogues which inhibit reverse transcription. •HIV is an RNA virus and hence unable to become integrated into the DNA in the nucleus of the human cell; it must be "reverse" transcribed into DNA. •Since the conversion of RNA to DNA is not done in the mammalian cell it is performed by a viral protein which makes it a selective target for inhibition. • NRTIs are chain terminators such that once incorporated, work by preventing other nucleosides from also being incorporated into the DNA chain because of the absence of a 3' OH group. • Both act as competitive substrate inhibitors. •Examples of currently used NRTIs include zidovudine, abacavir, lamivudine,emtricitabine, and tenofovir
Non-Nucleoside reverse transcriptase inhibitors (NNRTI) inhibit reverse transcriptase by binding to an allosteric site of the enzyme; NNRTIs act as noncompetitive inhibitors of reverse transcriptase. • NNRTIs affect the handling of substrate (nucleotides) by reverse transcriptase by binding near the active site. •NNRTIs can be further classified into 1st generation and 2nd generation NNRTIs.
• 1st generation NNRTIs include nevirapine and efavirenz. • 2nd generation NNRTIs are etravirine and rilpivirine.
•HIV-2 is naturally resistant to NNRTIs
Integrase inhibitors inhibit the viral enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. •There are several integrase inhibitors currently under clinical trial, and raltegravir became the first to receive FDA approval in October 2007. • Raltegravir has two metal binding groups that compete for substrate with two Mg2+ ions at the metal binding site of integrase. •As of early 2014, two other clinically approved integrase inhibitors are elvitegravir and dolutegravir.
Protease inhibitors block the viral protease enzyme necessary to produce mature virions upon budding from the host membrane. Particularly, these drugs prevent the cleavage of gag and gag/pol precursor proteins. Virus particles produced in the presence of protease inhibitors are defective and mostly non-infectious.
•Examples of HIV protease inhibitor lopinavir, indinavir, nelfinavir, amprenavir and ritonavir. •Darunavir and atazanavir are currently recommended as first line therapy choices. •Maturation inhibitors have a similar effect by binding to gag, but development of two experimental drugs in this class, bevirimat and vivecon, was halted in 2010. •Resistance to some protease inhibitors is high. •Second generation drugs have been developed that are effective against otherwise resistant HIV variants.