1. HIV and Related GI Disorders By Matt Johnson Gastro SpR

2. HIV Lentivirus group of the Retrovirus family 2 main types –HIV 1 –HIV 2(confined to W. Africa) HIV attaches to CD4 molecules on CD4 cells (eg. Tcells) and then invades the cell. It uses reverse transcriptase to transcribe RNA to DNA, which is later incorporated into the host genome and thence replicated.

3. HIV Symptoms CDC Gp1 - Self limiting non-specific illness at 4-8/52 CDC Gp2 - Asymptomatic infection for 10 years CDC Gp3 - Persistent generalised lymphadenopathy (>1cm in >2 places for >3/12) CDC Gp4 -Symptomatic HIV infections

4. HIV Symptoms Symptomatic HIV Infection a) Constitutional Symptoms (lethargy, sweats, weight loss) b) Haematology (pancytopenia) c) GI - HIV Enteropathy (N+V+D+Anorexia+Weight loss) d) Neuro (S+M+Auto/polyneuropathy) e) Dermatology (hairy oral leukoplakia)

5. HIV Ix and Mx HIV RNA titre is the best predictor of progression to AIDS and the best marker (after 3/12) of therapeutic effect British HIV Assoc guidelines When to treat –a) Symptomatic –b) HIV-1 RNA >10,000 / ml –c) CD-4 count < 500 * 10 6 / L

6. HIV Treatments Nucleoside Analogue Reverse Transciptase Inhibitors (NRTI’s) –Zidovudine (AZT= thymidine analogue DNA terminator, like ddI and ddC) –Lamivudine Non - NRTI’s –Nevirapine HIV Protease Enzyme Inhibitors –Indinavir or Saquinovir

7. Treatment Regimes and Aims <50,000 RNA= Triple Therapy AZT + Lamivudine + Nevirapine >50,000 RNA = Quadruple Therapy AZT + Lamivudine + Indinavir + Saquinavir HAART = Highly Active Antiretroviral Therapy AIM Improve and extend life Decrease viral load to < 500 copies / ml after 6/12

8. HIV Trials Concorde AZT given to asymptomatic patients with CD4 counts > 500 improved the count but with no survival benefit Delta 1 AZT + ddI > AZT + ddC > AZT Delta 2 If the patient has been on AZT for 3/12 there is added benefit from starting ddI but not ddC Prolongs life and delays progression

9. HIV Trials ACTG Decreased vertical transmission with AZT + ddI > AZT + ddC > AZT ACTG 320 Triple therapy with protease inhibitors > Dual therapy Stopped early as the addition of indinavir decreased infection rate and mortalitiy by > 50%

10. Prophylaxis UK Department of Health –AZT + Lamivudine + Indinavir –Given preferably 72hr –Continued for 4/52 –Reduces risk by 80%

11. GI Complications of HIV Oropharyngeal Oesophageal Constipation Diarrhoea Liver Abdominal Pain Rectal Bleeding

12. Oropharyngeal Oral Hairy Leukoplakia Oral Candida HSV type1 Gonorrhoea Syphilis Kaposi Sarcoma

13. Oesophageal Candidiasis CMV

14. Constipation Chlamydia (Rectal Strictures) Lymphogranuloma Venereum

15. Diarrhoea Moderate –HIV Enteropathy, –Gonorrhoea –Mycobacterium spp –Giardia. Lamblia –Salmonella spp –Campylobacter spp

16. Diarrhoea Severe / Malabsorption –Cryptosporidium spp –CMV –I. Belli –Enterocytozoon bieneusi –Cyclospora spp

17. Diarrhoea Bloody –HSV –Campylobacter spp –Chlamydia trachomatis –CMV –E. histolytica –Shigella spp

18. Liver Hepatitis A, Hepatitis B, Hepatitis B+D, Hepatitis C Sclerosing Cholangitis (microsporidia) Drugs

19. Abdominal Pain Intestinal lymphoma Kaposi Sarcoma Mycobacterium CMV (gallbladder)

20. Rectal Bleeding Syphilis Lymphogranuloma venereum Kaposi Sarcoma Anorectal Carcinoma Thrombocytopenia (drug induced)

21. Parasites Protozoa Giardia. Lamblia = Tinidazole 2g stat E. histolytica =Metronidazole 800mg tds 5/7 Cryptosporidium =None Nematodes A. Lumbricoides = Mebendazole 100mg bd3/7 Cestodes Taenia spp =Niclosamide 2g stat Lymphogranuloma Venereum S. Japonicum = Praziquantel 25mg/kg tds 2/7

22. Oesophageal Candidiasis Most common opportunistic infection Nearly always C.albicans Retrosternal chest pain and dysphagia OGD with brushings or biopsies Differential (HSV,MAI, Neoplasia, ulcerating hairy leukoplakia) Oral = Fluconazole 50mg 7/7 (or 14/7) Oesoph/systemic = Ketocon 200mg od 14/7

23. CMV Encephalitis, Chorioretinitis, Pneumonitis, Oesophagitis –Severe odynophagia 2 0 to serpigenious ulcers Colitis –10% of AIDS patients –profuse bloody diarrhoea, LIF pain, weight loss –fever, sb ulcers, toxic megacolon, SSC,hepatitis Ix = RigidSig + Bx (owls eye cyto inclusion bodies) Rx = Ganciclovir or Foscarnet

24. HSV Kaposi Sarcoma = HSV type 8 –multifocal prolif of vascular endo (15%of gays) –haemorrhage, perforation, bile obstruction –localised/cutaneous = XRT –disseminated/visceral = Vincristine + aIFN Oesophagitis with severe dyspagia –OGD + Bx = multiple deep ulcers Proctocolitis ( cellular inclusion bodies on rectal Bx) Acyclovir IV (5-10mg/kg tds) PO (200mg 5*/d 5/7)

25. Cryptosporidiosis Enterocyte infection causes villous fusion and increased secretions N + V + watery D + Anorexia Commonly affects the biliary tree = SSC Ix = acid fast staining cysts + oocytes Rx = No satisfactory treatment Spiramycin1g tds 3/52 (not available in UK)

26. Chlamydia Proctitis –similar to Crohns –Rectal Bx = Chlamydial inclusion bodies –Micro-immunoflurescent antibody tests Treatment –Tetracycline 500mg qds

27. Mycobacterium MAI = M. avium intracellulare fever, night sweats, periumbilical pain, diarrhoea Mx = symptom relief, but eradication is difficult Occurs when CD4 < 200 Rx = Rifabutin Prophlactic Rifabutin when CD4 < 100 M.tuberculosis = terminal ilietis lifelong isoniazid, treatment is non-curative

28. Microsporidiasis Diarrhoea Rx = Albendazole

29. Lymphoma Non Hodgkins Lymphoma (Bcell) fever + night sweats oesophagus - dysphagia and chest pain gastric - haematemesis bowel - obstruction, perforation, bleeding intussusception, altered bowel habits Ix = Endoscopy and fine needle biopsy Rx = CHOP + ABVD