Dr Steve Welch Birmingham Heartlands Hospital 3rd Annual Conference of the Children’s HIV Association ‘Young People and HIV: Back to the Future’ Dr Steve Welch Birmingham Heartlands Hospital Friday 15 May, The Bridgewater Hall, Manchester

Other opportunistic infections Steve Welch Heartlands Hospital, Birmingham 3rd Annual CHIVA Conference Manchester, 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

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

Effect of HAART on bacterial infections in children with HIV

Effect of HAART on bacterial infections in children with HIV

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 Further work up Nodular, pruritic Biopsy : nodular prurigo Hiv 1positive (mar 2006) Further work up Low CD4 4%(19) Lymphadenopathy Viral load : 276000c/ml

Drug Adherence issues 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

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 Abstract142 Immediate vs Deferred ART in the Setting of Acute AIDS-related Opportunistic Infection: Final Results of a Randomized Strategy Trial, ACTG A5164 Andrew 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: 36cLB Early 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

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