Dr Steve WelchBirmingham Heartlands Hospital

3rd Annual Conference of the Children’s HIV Association‘Young People and HIV: Back to the Future’

Friday 15 May, The Bridgewater Hall, Manchester

Other opportunistic infections

Steve WelchHeartlands Hospital, Birmingham

3rd Annual CHIVA ConferenceManchester, 15th May 2009

Other opportunistic infections

• Cases

• When to start ART in OI?

• Effect of OI on HIV – CMV

• Areas not covered - guidance

Case

• 15 yo

• Recurrent pneumonia and then PcP

• Started kivexa, efavirenz

• Good VL, CD4 response

• VL undetectable for more than 1 year

• CD4 400

http://www.heartofengland.nhs.uk/

1st cxr 5/11/08

Why?

• Not adherent to medication?

• On wrong medication?

• Should still be on septrin?

• Has developed resistance to penicillin?

• Susceptible because of rheumatic fever?

• That’s what happens

• Blame National Express

Effect of HAART on bacterial infections in children with HIV

0

2

4

6

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Pneumonia Bacteraemia

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/ 1

00 c

hil

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ears

HIV pre-HAART

HIV on HAART

Effect of HAART on bacterial infections in children with HIV

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2

4

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Pneumonia Bacteraemia

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00 c

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HIV pre-HAART

HIV on HAART

HIV uninfected

Effect of HAART on bacterial infections in children with HIV

1

10

100

1000

10000

100000

Pneumonia Bacteraemia

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HIV pre-HAART

HIV on HAART

HIV uninfected

Prevention of bacterial disease

• HAART

• Antibiotic prophylaxis

• Immunisation

• Immunoglobulins

Why?

• Not adherent to medication?

• On wrong medication?

• Should still be on septrin?

• Has developed resistance to penicillin?

• Susceptible because of rheumatic fever?

• That’s what happens

• Blame National Express

• 15yr old Zimbabwean girl

• In UK 2005

• Unusual rash 2yrs• Nodular, pruritic• Biopsy : nodular prurigo• Hiv 1positive (mar 2006)

• Further work up– Low CD4 4%(19)– Lymphadenopathy– Viral load : 276000c/ml

• Drug • Kivexa/efavirenz/septrin (April 2006)• Kaletra /lamivudine/abacavir(Nov 2006)• Lamivudine (dec 2006)• Kaletra/Truvada (from January 2007)

• Adherence issues• Poor drug compliance / DNA• PEG inserted Oct 2007• Poor response to treatment/ viral resistance• Counselling

0.00E+00

1.00E+05

2.00E+05

3.00E+05

4.00E+05

5.00E+05

6.00E+05

04/04/06 04/04/07 04/04/08

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ad

0

20

40

60

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100

120

140

cd4 vl

CD4

Should she be on MAI prophylaxis?

MAI prophylaxis

• Evidence that it works:

• 90-95% reduction in incidence in adults by prophylaxis or HAART

MAI prophylaxis

• Recommended by US guidelines

• What are suitable agents?

• In what circumstances?

MAI prophylaxis

• What are suitable agents?– Azithromycin– Clarithromycin– Rifabutin– Rifampicin– Clofazamine

MAI prophylaxis

• In what circumstances?

• CD4 < 50

• At new diagnosis

• After starting treatment until immune reconstitution

• If not on treatment

• If not adherent to treatment

Case

• 13 yo from Zambia• Weight loss, chronic cough• Bronchiectasis• Hi influenzae, pneumococcus• VL 10 million• CD4 2 (<1%)• HLA B*5701 negative• No significant resistance mutations• Now has secondary fevers• ALT 250

When should he start HAART?

• Now

• When fever abates and LFT’s back down

• When fever abates

• When LFT’s back down

• When completely stable

• Should have started before having RT and HLA result back

CROI 2008 Abstract142Immediate vs Deferred ART in the Setting of Acute AIDS-related Opportunistic

Infection: Final Results of a Randomized Strategy Trial, ACTG A5164Andrew Zolopa*1, J Andersen2, L Komarow2, A Sanchez3, C Suckow4, I Sanne5, E

Hogg6, W Powderly7, and ACTG A5164 Study Team

• 282 patients randomised to immediate (<14 days) or deferred (>4 weeks) ART• PcP 63%• Cryptococcal meningitis 13%• Pneumonia 10%

• No progression and VL<50 48 v 45%

• BUT 14 v 24% progression to AIDS or death, faster time to undetectable VL and VD4 >50, >100

CROI 2009: 36cLBEarly vs Delayed ART in the Treatment of Cryptococcal Meningitis in Africa

Azure Makadzange*1,2, C Ndhlovu2, K Takarinda2, M Reid2, M Kurangwa2,Vhikwasha2,

and J Hakim2 • 54 patients randomised to early (<72 hours) v late (10 weeks) ART in

cryptococcal meningitis:

• Mortality 82% v 37%

Case

• 7 yo from Zimbabwe

• VL 2 million

• CD4 10 (1%)

• Presents with allergic reaction to septrin

• Ongoing fevers and symptoms

34

35

36

37

38

39

40

41

What is the likely diagnosis?

• Septrin allergy• Bacterial infection• Common respiratory virus• TB• Atypical Mycobacteria• PcP• Candida• Cryptococcus• Other

What are alternatives to septrin?

What are alternatives to septrin?

• Dapsone

• Atovaquone

• Pentamidine

• Fansidar (Pyrimethamine-sulfadoxine)

• 4-month old girl

• Birthweight 4.1 kg (75th centile)

• Now 5.2 kg (2nd centile)

• Respiratory distress, diagnosed PcP

• Good response to ART. CD4 2300 (35%)

• When can she stop septrin?

AIDS 2005

Stopping PcP prophylaxis

• Cd4>15%, 200 for 6 months

• Cd4> 15%, 500 below age 5

• Not in first 12-18 months of life?

What not covered?

• Immunisation

• Guideline

• Other OIs - cryptosporidia

• Varicella