HIV in 2009 Susan Hopkins Consultant in Infectious Diseases & Microbiology Royal Free Hampstead NHS Trust What we will cover Not Opportunistic Infections Important adverse events Important points to consider in A&E CCR5 antagonists Maraviroc Integrase inhibitors Elvitegravir Raltegrevir Protease inhibitors Atazanivir Darunivir Fosamprenavir Indinavir Ritonavir Lopinivir Nelfinavir Saquinivir Tipranavir Fusion inhibitors Enfurvitide (T20) Reverse transcriptase inhibitors Abacavir Didanosine Emtricitabine Lamividine Stavudine Tenofovir Zidovidine Delaviridine Efaverinz Etravirine Nevirapine Case 1. 35 year old gay white man HIV positive CD4=180 Recently started antiretrovirals Kivexa (abacavir/lamivudine) Efavirenz 4/7 progressive fever, rash, abdominal pain Bloods: Bili 44 AST 350 ALT 424 Hb 10.9 WCC 2.5 Plts 140 De Clercq Nature Reviews 2007 What is the most likely diagnosis 1. Acute Hepatitis B 2. Cytomegalovirus infection 3. Parvovirus infection 4. Drug reaction 5. Syphilis drug reaction which drug? HIV drugs frequently cause drug reactions 1
HIV drugs frequently cause drug reactions drug reaction which drug? abacavir hypersensitivity syndrome predicted by HLA B570*1 (Caucsians) can be fatal can be quickly fatal on rechallenge efavirenz rash and liver toxicity well recognised Efavirenz Monotherapy = NNRTI CLASS RESISTANCE Mutations can be found in minor variants in ~70% Efavirenz Monotherapy = NNRTI CLASS RESISTANCE Mutations can be found in minor variants in ~70% Call HIV doctor In large centre 24/7; In DGH first thing in the morning Consider other drugs Prevents resistance developing during washout Case 2 46 yo male ex-ivdu, still smokes marijuana HIV+ HCV+ 14 years Kivexa (Abacavir/ Lamividine), Kaletra (Lopinivir/r), Methadone VL<50 CD4>300 Presents to A&E with painful left leg and intermittent chest pain at rest 2
What is your most likely diagnosis? 1. 2. 3. 4. 5. Cardiac Risk Factors DVT & PE Mycotic aneursym in L groin with emboli Peripheral vascular disease & IHD Infective Endocarditis with embolisation to L leg Nothing just wants opiates Cardiovascular disease increasing Protease inhibitors more associated with CVS events Increased CVS risk with time on HAART RR 1 9 (1 5 2 5) ddi RR 1 5 (1 1-2.0) HIV Antiretrovirals Hyperlipidaemia -> Treatment So he needs secondary prevention. Which drug is contraindicated? 1. 2. 3. 4. 5. - related to lipids, glucose, and other factors Abc Male >40 years Family History Smoker Perindopril Simvastatin Atenolol Aspirin Clopidrogel Sabin et al, for D:A:D, Lancet 2008 Cooper Aids 2008 Cytochrome p450 Chemically oxidise or reduce drugs 4 major families, 6 sub-families e.g 3A4, 2D6 Inhibition: Competitive (rev) or Mechanism (irrev) Induction: Increased synthesis of enzyme Enzyme inhibition 1st dose Enzyme induction 2-7d All protease inhibitors = 3A4 Ritonavir most potent PIs: Ritonavir, Nelfinavir NNRTIs 3
Inform HIV team & pharmacist too BHIVA Mortality audit 2004-5 Bacterial sepsis PCP TB Other OI Lymphoma KS Dementia Other malignancy Multiorgan end-stage HIV CVD Renal Other disease probably related to HIV Chronic liver disease due to co-infection/alcohol Suicide Accident/injury Overdose Other, not related to HIV Not known Renal disease & HIV ARF in 20% HIV hospitalised patients (cf 3-5%) Ambulatory care: Incidence 5.9 per 1000 person-yrs Causes Azotemia/ ATN HIVAN- classically FSGS Interstitial nephritis secondary to drugs used to treat OI ARV Drugs Tenofovir: ARF, Fanconi Syndrome, Nephrogenic DI Indinavir: crystalluria, renal calculi Risk factors Male, Hepatitis C, IVDU, Antivirals HIV, AIDS defining illnesses Top bars: reclassified during audit Bottom bars: as initially reported 0% 2% 4% 6% 8% 10% 12% 14% Percentage of patients 4
Case 3. 24 yo man attends A&E on Friday night Says that a condom burst during sex in a darkroom in London the previous night Otherwise well No medical problems Last STI screen & HIV test 6 months ago What do you advise? 1. Hepatitis B vaccination 2. HIV test 3. Post exposure prophylaxis 4. Attend GU OPD Monday morning 5. Go to his GP 6. Tell him he s wasting your time HIGH MEDIUM LOW Did sexual exposure occur <72 hours ago? Assess risk that source is HIV+ Y Known HIV+ MSM (London/ Manchester) Hetero (SSA) IVDU MSM Hetero (Asia, E Europe etc) Other hetero/ivdu Low Medium High Low No PEPSE Assess risk of exposure Repeated exposure additive risk HIGH MEDIUM LOW Medium N Rape Receptive anal intercourse Sharing injecting equipment Blood transfusion Receptive vaginal NSI Other sex Mucus membrane exposure High Review by trained individual Starter pack Refer to HIV service Do baseline bloods Check/give Hep B immunisation NO PEP Fisher et al Int J STD & AIDS 2006 Summary Points 1. HIV drugs have frequent serious adverse events 2. with HIV specialist before you stop HIV drugs 3. Many HIV drugs are enzyme inducers and enzyme inhibitors 4. Before prescribing new drugs click on www.hivdruginteractions.co.uk 5. HIV patients increasingly present with non-hiv related diseases 6. HIV and ARV independent risk factors for cardiovascular disease 7. Renal disease x 3 in HIV+ compared to age matched controls 8. Patients presenting post sexual exposure need PEP assessment 5