PAEDIATRIC HIV INFECTION. Dr Ashendri Pillay Paediatric Infectious Diseases Specialist

Transcription

1 PAEDIATRIC HIV INFECTION Dr Ashendri Pillay Paediatric Infectious Diseases Specialist

2 Paediatric HIV Infection Epidemiology Immuno-pathogenesis Antiretroviral therapy Transmission Diagnostics Clinical manifestations Universal Test & Treat PMTCT Vaccine Development

3 P D r A s h e n d r i

4 Immunopathogenesis

5 reverse transcriptase inhibitors DS dna COMPLEX integrase inhibitors protease inhibitors chemokine receptor inhibitors fusion inhibitors HIV entry inhibitors

6 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Zidovudine (ZDV, AZT) Didanosine (ddi) Stavudine (d4t) Lamivudine (3TC) Abacavir (ABC) Tenofovir (TDF)

7 Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Nevirapine (NVP) Efavirenz (EFV) (>3years/ 13 kg) Etravirine Rilpilvarine

8 Protease Inhibitors (PIs): Lopinavir/rtv (LPV/r) Ritonavir (full dose) Atazanavir/rtv (ATZ/r) Daurinavir/rtv (DRV/r)

9 Children Are Not Little Adults What s Different? Transmission Presentation of HIV Progression Diagnostic Issues Drug Distribution Dosing Occurrence of toxicities Adherence and Psychosocial Issues Physical, Emotional and social needs Dependence / Vulnerability

10 Transmission >90% occurs vertically breast feeding In utero Intra partum Risk has declined from 30-45% to as low as 1% with ART

11 Transmission Sexual abuse by an HIV infected adult Unprotected sexual intercourse in adolescents Use of contaminated blood & blood products Drug abuse Scarification by traditional healers, body piercings

12 Diagnosis

13 Clinical Manifestations of In-utero Infection

14 Systemic Manifestations Malnutrition & Growth Failure

15 Skin

16 Haematological Multi-factorial causes of anaemia Direct effect of HIV on marrow Iron Deficiency Antiretroviral therapy Recurrent Infections Parvovirus induced red cell aplasia CMV infections

17 Central Nervous System HIV encephalopathy Seizures CNS infections Malignancy

18 Respiratory

19 Gastrointestinal System Acute infective diarrhoea Persistent diarrhoea with failure to thrive Malabsorption Opportunistic intestinal infections Microbiome

20 Cardiovascular System HIV associated cardiomyopathy Pericardial Effusion Conduction abnormalities Pulmonary hypertension

21 Renal HIVAN Glomerulonephritis Nephrotic Syndrome

22 Musculoskeletal Low bone mineral density is commonly observed among children infected with HIV compared with their uninfected peers, with rates ranging from 7% to 32% Associated risk factors include time on ART, treatment with tenofovir and protease inhibitors, advanced HIV disease, and delayed puberty. Initial studies have not found a higher rate of fractures but the longterm effects as these children age into adulthood are unknown

23 Universal Test & Treat

24 Benefits of early initiation of ART Controls viral replication while genetic quasispecies are relatively homogeneous and before significant viral mutations occur Could control development of heterogeneous viral strains/mutations Potentially leads to less drug resistance Could lower viral setpoint fewer viral strains Slows immune system destruction preserving immune function and preventing clinical progression

25 Plasma HIV RNA levels in Adults Plasma HIV RNA levels in Infants Viral load no.copies/ml (log) years Months/Years Viral load no. of copies/ml years Months/Years

26

27

28

29 First Line Therapy < 3 years (<10kg) > 3 years > 10kg

30 Changing ARV Therapy Failure based on virologic, immunologic, or clinical parameters Toxicity or intolerance on the current therapy

31 Clinical Failure

32 Immunological Failure A persistent decline of 5 percentiles or more in CD4% (15% to 10%) A rapid decrease in absolute CD4 count (>30% decline in <6 months)

33 Virological Failure Persistent detectable viral load > 1000 copies/ml after 6 months on HAART

34 Adherence Issues in Children Availability of drugs in palatable, liquid or mixable formulations Difficulty of giving drugs that have food restrictions, because of children s (particularly infant) eating schedules Children s dependence on caregivers for administration

35 Failure of 1 st line therapy Patients on NNRTI based regimen can be changed to 2 nd line therapy Zidovudine, Lamivudine, Lopinavir/Ritonavir Patients on a PI based regimen, due to high genetic barrier of resistance of PIs, concern is development of class resistance to NRTIs, NNRTIs These patients should be referred for HIV resistance testing Third line therapy

36 PMTCT

37 Newly Diagnosed HIV Positive: Unbooked women & previously HIV negative In-labour management: Stat sd NVP Stat sdtruvada (FTC/TDF) 3 hourly AZT Baby: Birth PCR 12 weeks NVP Repeat PCR at 18 weeks FDC dispensed before discharge to start the following day 37

38 Dried Blood Spot (DBS)

39 Birth PCR WHO? ALL HIV EXPOSED NEONATES 39

40 Infant Prophylaxis Choice of infant prophylaxis regimen depends on risk profile of mother Prophylaxis to be started immediately or soon after birth Counsel re adherence to maternal ART and infant prophylaxis

41 Most Infants

42 Infants who need additional prophylaxis 12 weeks NVP 6 weeks NVP plus AZT Infants born to mothers who have not been on ART for long enough to be virally suppressed by the time the infant is 6 weeks old: < 4 weeks on ART Diagnosed in labour/delivery Diagnosed during breastfeeding and still breastfeeding Infants born to mothers who have been on ART for > 3 months and still have a viral load >1000 copies/ml. These women may have poor adherence These women may have ART resistance 42

43 Mother diagnosed HIV+ve after delivery If the mother is breastfeeding: Initiate infant onto NVP plus AZT immediately. Initiate mother on FDC immediately Review infant PCR result within 7 days. If the infant s HIV PCR is negative: Stop AZT. Continue infant NVP for a total of 12 weeks.

44 Mothers Failing 2 nd /3 rd Line If mother has VL> 1000 copies/ml and is on SECOND or THIRD LINE therapy: This baby should preferably not be BREASTFED Prescribe infant formula (medically indicated) Need to ensure facilities have stock If formula not available: Careful counselling of mother Intensive adherence support Exclusive breastfeeding These mother-baby pairs should be referred/ telephonically discussed 44

45 PMTCT Testing Schedule

46 Vaccine Development HIV infection does not induce broadly neutralising antibodies Goals for HIV vaccine induction of neutralising antibodies Hypervariability of HIV

47