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HIVHIV
Dr. Manish Bhagat,
Assist. Prof.
Dept of Pediatrics, KJSH, Sion,
Mumbai
Topic outlineTopic outline
I. Introduction
II. Etiology
III. Pathogenesis
I. Hiv life-cycle
II. Transmission
IV. Diagnosis
I. Clinical staging
II. Testing algorithm
V. Criteria for starting ART
VI. Recommended first-line ART regimens
VII. Clinical and laboratory monitoring
VIII. PMTCT programme
IntroductionIntroduction
HIV Burden
 Worldwide
 33.3 million people are living with HIV
 2.5 million children are living with HIV
 There were 370000 new infections and 260000
AIDS-related deaths in 2009
 In India
 Adult HIV prevalence is 0.31%
 Children (<15 years) account for 3.5% of all
infections.
EtiologyEtiology
Family --- human retroviruses
(Retroviridae)
Subfamily---lentiviruses
Types -- HIV -1 and HIV-2
Major Groups-- M , N, O, P
O and N are very Rare
90% of HIV-1 infection
belongs to Group M
Subtypes--
A, B, C, D, F, G, H, J
and K
C being the prominent subtype
in India
 CXCR4 (Fusin)
• Expressed on T-cells
• HIV gp120 interacts with both CD4 &
CXCR4
• Effect conformational changes in
gp120/gp41
complex that allow membrane fusion
 CCR5
• Expressed on macrophages
• Individuals with certain mutations in CCR5 are
resistant to HIV infection
HIV life cycleHIV life cycle
TransmissionTransmission
 Vertical transmission
 95% of cases in children
 30-40% of infected newborns are infected in utero
 Intrapartum=60-70%
 Without intervention, the risk of transmission =25% to 45%
 breast-feeding= 5-20% risk of post partum transmission
 Blood borne infections=3-6%
 Sexual transmission uncommon but sexual abuse can lead
to tranmission
Diagnosis of HIV Infection in Infants andDiagnosis of HIV Infection in Infants and
ChildrenChildren
 WHO clinical classification of established HIV infection
 CLINICAL STAGE 1 Asymptomatic
Persistent generalizedlymphadenopathy
 CLINICAL STAGE 2 Unexplained persistent hepatosplenomegaly
Papular pruritic eruptions
HIV associated symptoms WHO clinical stage
Asymptomatic 1
Mild symptoms 2
Advanced symptoms 3
Severe symptoms 4
• Papular pruritic vesicular lesions
• Extensive wart virus
• Extensive molluscum contagiosum
• Fungal nail infections, Fungal paronychia
• Recurrent oral ulceration
• Unexplained persistent parotid enlargement
• Lineal gingival erythema
• Herpes zoster
• Recurrent upper respiratory tract infection
 CLINICAL STAGE 3 Unexplained moderate malnutrition
Unexplained persistent diarrhea
Unexplained persistent fever
Oral candidiasis (after the first 6–8 week)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis
Lymph node tuberculosis
Pulmonary tuberculosis
Severe recurrent bacterial pneumonia
Symptomatic lymphocytic interstitial
Pneumonia
Chronic HIV-associated lung disease
Unexplained anaemia (<8 g/dl),neutropaenia
(<0.5 × 109
per litre) and or chronic
thrombocytopaenia (<50 × 109
per litre)
CLINICAL STAGE 4
Unexplained severe wasting, stunting or Severe malnutrition not adequately
responding to standard therapy
Pneumocystis pneumonia
Chronic herpes simplex infection;
Extrapulmonary or disseminated tuberculosis
Kaposi sarcoma
Cytomegalovirus retinitis
Central nervous system toxoplasmosis
Extrapulmonary cryptococcosis (including meningitis)
HIV encephalopathy
Disseminated mycosis (coccidiomycosis,histoplasmosis or penicilliosis)
Disseminated mycobacteriosis,
Chronic cryptosporidiosis
Chronic isospora
Cerebral or B-cell non- Hodgkin lymphoma
Progressive multifocal leukoencephalopathy
Symptomatic HIV associated nephropathy or cardiomyopathy
Presumptive diagnosis among infants &Presumptive diagnosis among infants &
children under 18 months should be made ifchildren under 18 months should be made if
1. The infant is confirmed as being HIV antibody positive and
2. a) Diagnosis of any AIDS indicator condition can be made or
b)The infant symptomatic with two or more of the following:
Oral thrush
Severe pneumonia
Severe sepsis
Other factors that support the diagnosis of severe HIV disease in an
HIV seropositive infant include
1. Recent HIV related maternal death or advanced HIV disease in the
mother
2. CD4<20%
AIDS-indicator conditions include some but not all HIV paediatric clinical stage 4
conditions such as Pneumocystis pneumonia, cryptococcal meningitis, severe
wasting or severe malnutrition, Kaposi sarcoma, extrapulmonary TB.
When to start antiretroviral therapy inWhen to start antiretroviral therapy in
infants and childreninfants and children
Age <24 months >2=<5 yrs >5yrs
CD4% All ≤25 NA
Absolute CD4 All ≤750 ≤350
Clinical stage immunological
<24 months Treat all
>24 months Stage 4 Treat all
Stage 3 Treat all
Stage 2 Treat if CD4 below age
adjusted threshholdsStage 1
Antiretroviral TherapyAntiretroviral Therapy
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
Drugs in this class include zidovudine (AZT), lamivudine (3TC), abacavir
(ABC), stavudine (D4T), didanosine, emtricitabine, and tenofovir.
Non-nucleoside Reverse Transcriptase Inhibitors
nevirapine (NVP) and efavirenz (EFV).
Protease Inhibitors
Lopinavir/Ritonavir, nelfinavir, ritonavir, saquinavir and indinavir.
Fusion inhibitors
Enfuvirtide binds to gp41 and interferes with its ability to approximate the
two membranes.
Integrase Inhibitors and Co-receptor (CCR5 and CXCR4) inhibitors
Raltegravir, Elvitegravir, Globoidnan A (experimental), Maraviroc and
vicriviroc etc.
Recommended first-line ART regimens forRecommended first-line ART regimens for
infants and childreninfants and children
The nucleoside backbone for an ART regimen
in preferential order should be:
I. Lamivudine (3TC) + zidovudine (AZT) or
II. 3TC + abacavir (ABC) or
III. 3TC + stavudine (d4T)
Criteria for initiation of ART Ist line ART
1 Infants & children <24 months not exposed
to ARVs
NVP + 2NRTIs
2 Infants & children <24 months exposed to
maternal or infant NVP or other NNRT
lopinavir /ritonavir
(LPV/r) + 2 NRTIs.
3 Infants & children <24 months whose
exposure to ARVs is unknown
NVP + 2 NRTIs
4 children >24 months = < 3 years NVP + 2 NRTIs
5 children ≥3 years of age NVP or EFV + 2 NRTIs
Infants and children with specificInfants and children with specific
conditionsconditions
Specific conditions Preferred
regimen
1 children more than 3 years of age
with TB
EFV+ 2 NRTIs
2 Severe anaemia (<7.5 g/dl) or
severe neutropenia (<0.5/mm3)
NVP + 2 NRTIs
(avoid AZT)
3 Adolescents >12 years of age
with hepatitis B
Tenofovir (TDF) +
Emtricitabine
(FTC) or 3TC +
NNRTI
Clinical andClinical and laboratorylaboratory monitoringmonitoring
• CD4 should be measured
1. at the time of diagnosis of HIV infection, and
every 6 months thereafter
2. prior to initiating ART
3. every 6 months after initiating ART
Viral load monitoring
1. Desirable, but not essential, prior to initiating
ART.
2. Viral Load should be assessed to confirm
clinical or immunological failure where possible,
prior to switching a treatment regimen.
Routine clinical and laboratoryRoutine clinical and laboratory
monitoringmonitoring
◦ Baseline Hb level & WBCs - at initiation of ART
◦ Hb at week 8 after initiation of AZT-containing
regimens, or more frequently if symptoms indicate.
◦ Growth, development and nutrition should be
monitored monthly.
◦ Laboratory monitoring for toxicity should be symptom
directed.
PMTCT continues….
Thank you

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Hiv

  • 1. HIVHIV Dr. Manish Bhagat, Assist. Prof. Dept of Pediatrics, KJSH, Sion, Mumbai
  • 2. Topic outlineTopic outline I. Introduction II. Etiology III. Pathogenesis I. Hiv life-cycle II. Transmission IV. Diagnosis I. Clinical staging II. Testing algorithm V. Criteria for starting ART VI. Recommended first-line ART regimens VII. Clinical and laboratory monitoring VIII. PMTCT programme
  • 3. IntroductionIntroduction HIV Burden  Worldwide  33.3 million people are living with HIV  2.5 million children are living with HIV  There were 370000 new infections and 260000 AIDS-related deaths in 2009  In India  Adult HIV prevalence is 0.31%  Children (<15 years) account for 3.5% of all infections.
  • 4. EtiologyEtiology Family --- human retroviruses (Retroviridae) Subfamily---lentiviruses Types -- HIV -1 and HIV-2 Major Groups-- M , N, O, P O and N are very Rare 90% of HIV-1 infection belongs to Group M Subtypes-- A, B, C, D, F, G, H, J and K C being the prominent subtype in India
  • 5.  CXCR4 (Fusin) • Expressed on T-cells • HIV gp120 interacts with both CD4 & CXCR4 • Effect conformational changes in gp120/gp41 complex that allow membrane fusion  CCR5 • Expressed on macrophages • Individuals with certain mutations in CCR5 are resistant to HIV infection
  • 6. HIV life cycleHIV life cycle
  • 7. TransmissionTransmission  Vertical transmission  95% of cases in children  30-40% of infected newborns are infected in utero  Intrapartum=60-70%  Without intervention, the risk of transmission =25% to 45%  breast-feeding= 5-20% risk of post partum transmission  Blood borne infections=3-6%  Sexual transmission uncommon but sexual abuse can lead to tranmission
  • 8. Diagnosis of HIV Infection in Infants andDiagnosis of HIV Infection in Infants and ChildrenChildren  WHO clinical classification of established HIV infection  CLINICAL STAGE 1 Asymptomatic Persistent generalizedlymphadenopathy  CLINICAL STAGE 2 Unexplained persistent hepatosplenomegaly Papular pruritic eruptions HIV associated symptoms WHO clinical stage Asymptomatic 1 Mild symptoms 2 Advanced symptoms 3 Severe symptoms 4
  • 9. • Papular pruritic vesicular lesions • Extensive wart virus • Extensive molluscum contagiosum • Fungal nail infections, Fungal paronychia • Recurrent oral ulceration • Unexplained persistent parotid enlargement • Lineal gingival erythema • Herpes zoster • Recurrent upper respiratory tract infection
  • 10.  CLINICAL STAGE 3 Unexplained moderate malnutrition Unexplained persistent diarrhea Unexplained persistent fever Oral candidiasis (after the first 6–8 week) Oral hairy leukoplakia Acute necrotizing ulcerative gingivitis Lymph node tuberculosis Pulmonary tuberculosis Severe recurrent bacterial pneumonia Symptomatic lymphocytic interstitial Pneumonia Chronic HIV-associated lung disease Unexplained anaemia (<8 g/dl),neutropaenia (<0.5 × 109 per litre) and or chronic thrombocytopaenia (<50 × 109 per litre)
  • 11. CLINICAL STAGE 4 Unexplained severe wasting, stunting or Severe malnutrition not adequately responding to standard therapy Pneumocystis pneumonia Chronic herpes simplex infection; Extrapulmonary or disseminated tuberculosis Kaposi sarcoma Cytomegalovirus retinitis Central nervous system toxoplasmosis Extrapulmonary cryptococcosis (including meningitis) HIV encephalopathy Disseminated mycosis (coccidiomycosis,histoplasmosis or penicilliosis) Disseminated mycobacteriosis, Chronic cryptosporidiosis Chronic isospora Cerebral or B-cell non- Hodgkin lymphoma Progressive multifocal leukoencephalopathy Symptomatic HIV associated nephropathy or cardiomyopathy
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  • 14. Presumptive diagnosis among infants &Presumptive diagnosis among infants & children under 18 months should be made ifchildren under 18 months should be made if 1. The infant is confirmed as being HIV antibody positive and 2. a) Diagnosis of any AIDS indicator condition can be made or b)The infant symptomatic with two or more of the following: Oral thrush Severe pneumonia Severe sepsis Other factors that support the diagnosis of severe HIV disease in an HIV seropositive infant include 1. Recent HIV related maternal death or advanced HIV disease in the mother 2. CD4<20% AIDS-indicator conditions include some but not all HIV paediatric clinical stage 4 conditions such as Pneumocystis pneumonia, cryptococcal meningitis, severe wasting or severe malnutrition, Kaposi sarcoma, extrapulmonary TB.
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  • 16. When to start antiretroviral therapy inWhen to start antiretroviral therapy in infants and childreninfants and children Age <24 months >2=<5 yrs >5yrs CD4% All ≤25 NA Absolute CD4 All ≤750 ≤350 Clinical stage immunological <24 months Treat all >24 months Stage 4 Treat all Stage 3 Treat all Stage 2 Treat if CD4 below age adjusted threshholdsStage 1
  • 17. Antiretroviral TherapyAntiretroviral Therapy Nucleoside/Nucleotide Reverse Transcriptase Inhibitors Drugs in this class include zidovudine (AZT), lamivudine (3TC), abacavir (ABC), stavudine (D4T), didanosine, emtricitabine, and tenofovir. Non-nucleoside Reverse Transcriptase Inhibitors nevirapine (NVP) and efavirenz (EFV). Protease Inhibitors Lopinavir/Ritonavir, nelfinavir, ritonavir, saquinavir and indinavir. Fusion inhibitors Enfuvirtide binds to gp41 and interferes with its ability to approximate the two membranes. Integrase Inhibitors and Co-receptor (CCR5 and CXCR4) inhibitors Raltegravir, Elvitegravir, Globoidnan A (experimental), Maraviroc and vicriviroc etc.
  • 18. Recommended first-line ART regimens forRecommended first-line ART regimens for infants and childreninfants and children The nucleoside backbone for an ART regimen in preferential order should be: I. Lamivudine (3TC) + zidovudine (AZT) or II. 3TC + abacavir (ABC) or III. 3TC + stavudine (d4T) Criteria for initiation of ART Ist line ART 1 Infants & children <24 months not exposed to ARVs NVP + 2NRTIs 2 Infants & children <24 months exposed to maternal or infant NVP or other NNRT lopinavir /ritonavir (LPV/r) + 2 NRTIs. 3 Infants & children <24 months whose exposure to ARVs is unknown NVP + 2 NRTIs 4 children >24 months = < 3 years NVP + 2 NRTIs 5 children ≥3 years of age NVP or EFV + 2 NRTIs
  • 19. Infants and children with specificInfants and children with specific conditionsconditions Specific conditions Preferred regimen 1 children more than 3 years of age with TB EFV+ 2 NRTIs 2 Severe anaemia (<7.5 g/dl) or severe neutropenia (<0.5/mm3) NVP + 2 NRTIs (avoid AZT) 3 Adolescents >12 years of age with hepatitis B Tenofovir (TDF) + Emtricitabine (FTC) or 3TC + NNRTI
  • 20. Clinical andClinical and laboratorylaboratory monitoringmonitoring • CD4 should be measured 1. at the time of diagnosis of HIV infection, and every 6 months thereafter 2. prior to initiating ART 3. every 6 months after initiating ART Viral load monitoring 1. Desirable, but not essential, prior to initiating ART. 2. Viral Load should be assessed to confirm clinical or immunological failure where possible, prior to switching a treatment regimen.
  • 21. Routine clinical and laboratoryRoutine clinical and laboratory monitoringmonitoring ◦ Baseline Hb level & WBCs - at initiation of ART ◦ Hb at week 8 after initiation of AZT-containing regimens, or more frequently if symptoms indicate. ◦ Growth, development and nutrition should be monitored monthly. ◦ Laboratory monitoring for toxicity should be symptom directed.
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