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Hiv

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Manish Bhagat
Manish Bhagat

This document discusses HIV in children, including: 1. HIV has infected over 33 million people worldwide, including 2.5 million children. In India, prevalence is 0.31% with children accounting for 3.5% of infections. 2. HIV is transmitted vertically in 95% of pediatric cases, including in utero, during birth, and through breastfeeding. Other transmission methods are rare in children. 3. Diagnosis involves clinical staging based on symptoms and lab tests including CD4 counts. Treatment involves antiretroviral therapy regimens depending on age and exposure history. 4. Clinical and lab monitoring of HIV-infected children on treatment includes regular CD4 and viral load testing to monitor response

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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 68 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
Hiv
Hiv
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.
Hiv
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.
Hiv
PMTCT continues.
Hiv
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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 68 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
  • 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.
  • 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.