The Prevention and Treatment of Opportunistic Infections in HIV infected

The Prevention and Treatment of Opportunistic Infections in HIV infected Adults Halima Dawood Prevention and Treatment of Opportunistic Infections in HIV infected Adults • Guidelines based on national department of health guidelines • Alternate regimen(s) discussed, but not exhaustive • More complex problems should be discussed or referred Prevention and Treatment of Opportunistic Infections in HIV infected Adults Best method to prevent opportunistic infections in HIV-infected individuals is to use HAART Leads to partial immune reconstitution Separate guidelines for the management of sexually transmitted diseases,tuberculosis Primary and secondary prevention should be emphasised at all opportunities during treatment of HIV infected persons Natural History of Untreated HIV Infection 1200 1100 1000 900 Infection + Acute HIV syndrome Wide dissemination of virus Seeding of lymphoid organs Clinical latency 107 106 HIV/RNA (c/mL) CD4 Cell Count (cells/mm3) 800 700 600 500 400 300 103 200 100 0 0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 105 Opportunistic Diseases Death 104 AIDS Weeks Constitutional Symptoms 102 11 Years Fauci et al 1996 WHO Classification • Stage 1:acute retroviral syndrome, asymptomatic,persistent generalised LAD • Stage 2:symptoms but ambulatory, mild HIV related diseases e.g. LOW,mucocutaneous lesions • Stage 3:bedridden <50% of daytime, HIV related conditions eg.chronic diarrhea,oral candida • Stage 4:bedridden > 50% of time in prior month, AIDS eg.PCP,CNS toxoplasmosis,lymphoma Principles of management of HIV/AIDS • Monitor the immune system • Clinical surveillance and diagnosis of opportunistic infections or HIV associated conditions • Prophylaxis and treatment of serious opportunistic infections • Early medical intervention for complications • Promoting safer sexual practices • Palliative and terminal care for severe/advanced disease Management according to WHO stage of disease First Visit(post VCT) • Clinical: history of current and previous illness,full physical examination,determine clinical stage • Lab:document HIV result,FBC, LFT,U&E,CD4,RPR,PAP smear,Anti-HBc • Prophylaxis: Cotrimoxazole for stage 3,4, refer for nutritional support prn. First Visit/Review • Review:in one week • RPR positive: Penicillin 2.4 million units IM wk X 3 • PAP smear abnormal:refer • Hepatitis B vaccine if anti-HBc negative • Repeat visits dependent on stage WHO STAGE 1 • Clinical: asymptomatic,review systems and physical examination • Lab: PAP smear annually • Prophylaxis: reinforce healthy lifestyle,multivitamins prn,,Influenza vaccine 0.5ml IM before flu season • Review: 6 monthly WHO STAGE 2 Clinical: minor weight loss,skin rash,URTI. review systems + examination concentrating on mucocutaneous system Lab: PAP smear annually Prophylaxis: reinforce healthy lifestyle multivitamins 1 tab daily prn flu vaccine Review: 3-6 monthly WHO STAGE 3 Clinical:patient may stay in bed as unwell: weight loss,candida,diarrhea,fever , TB,pneumonia review of systems and examination LAB: annual PAP smear Prophylaxis:lifestyle,cotrimoxazole,multivit,flu vac, Review: 3 monthly/as clinically indicated Refer: social support grant,if required WHO STAGE 4 • Clinical : sick patient,bedridden > 50% of day,opportunistic infections,may require referral for investigation and treatment • Lab : annual PAP smear • Prophylaxis: lifestyle,multivit, cotrimoxazole,?flu vac • Review: 3 monthly/as clinically indicated • Refer: social support grant, ARV rollout Opportunistic infections and HIV/AIDS • Opportunistic infections major cause of death • result of re-activation of previous infections, as the immune system is weakened • Most patients are diagnosed with HIV infection as result of opportunistic infection • Opportunistic infections accelerate HIV infection Opportunistic infections and HIV/AIDS • Opportunistic infections can be prevented • Many can be treated successfully • Identification, prevention and treatment of opportunistic diseases can significantly decrease patient morbidity and mortality Natural History of HIV Infection 500 vaginal candidiasis skin disease fatigue bacterial pneumonia herpes zoster oral hairy leukoplakia, thrush, fever, diarrhea, weight loss 200 Kaposi’s sarcoma, non-Hodgkin’s lymphoma Pneumocystis carinii pneumonia 100 50 Toxoplasmosis, esophageal candidiasis, cryptococcosis, CMV, MAC, CNS lymphoma Time CD4 Count Opportunistic infections at stages of HIV disease • Opportunistic Infections occur at different levels of immunosuppression, CD4 count : • < 500-350 cells/mm³ – skin conditions, bacterial infections • < 350 cells/mm³ – candidiasis, KS, TB Opportunistic infections at stages of HIV disease • < 200 cells/mm³ – pneumocystis pneumonia – HSV • < 100 cells/mm³ – oesophageal candidiasis, cryptoccoccal meningitis, toxoplasmosis, CMV, MAI Opportunistic Diseases • Respiratory infections • Pneumocystis carinii pneumonia(PCP) • Bacterial pneumonia and sinusitis • Tuberculosis • Oral and gastrointestinal infections • Skin conditions • Neurologic infections and complications • HIV dementia • Toxoplasmosis • Cryptococcal meningitis Strategies to decrease opportunistic infections • Prophylaxis – Primary: co-trimoxazole, INH – Secondary: co-trimoxazole, fluconazole, CMV, +/HSV • Treatment – early diagnosis and proper therapy • Vaccinations – Pneumovax, Influenza, Hepatitis B/A • Decrease exposure to pathogens – TB control programme, avoidance of exposure to toxoplasma, enteric pathogens Skin Conditions • Seborrhea • Molluscum contagiosum • Folliculitis(S.Aureus,eosinophillic inflammation,P.ovale) • Herpes infections • Kaposi’s sarcoma Skin Conditions-Treatment • Seborrhea -steroid cream +/- topical azole, amines • Molluscum contagiosum-topical tincture of iodine or 1% phenol , if severe refer • Folliculitis- depends on cause - S.Aureus: topical cleansing,consider flucloxicillain - fungal: azole cream - eosinophillic inflammation: topical steroid cream, antihistamines Skin Conditions-Treatment • Herpes infections- Herpes simplex acyclovir /valaciclovir/famciclovir -Varicella zoster(shingles):acyclovir/valaciclovir/ famciclovir • Kaposi’s sarcoma – ARV,intralesional vinblastine,cryotherapy,excision, chemotherapy Oral and Oesophageal Diseases • Candidiasis-oral and oesophageal • Herpes simplex-oral and oesophageal • Cytomegalovirus-oesophageal • Apthous Ulcers • Kaposi’s Sarcoma Oral and Oesophageal Diseases • Candidiasis - oral: Nystatin 1-2ml 4 times/day - oesophageal: fluconazole 200mg daily, ketoconazole,itraconazole, - secondary prophylaxis not recommended • Herpes simplex-Acyclovir 800 mg tid,valaciclovir, famciclovir for 7 days. - secondary prophylaxis not recommended Oral and Oesophageal Diseases • Cytomegalovirus-ganciclovir iv the orally for lifelong • Apthous ulcers-topical steroids(Kenalog) or steroid inhaler or tetracycline 250mg dissolved in water as mouthwash qid. severe : oral prednisine • Kaposi’s Sarcoma HAART/Chemotherapy/DXT Chronic or recurrent diarrhoea • Challenge to manage • Infective diarrhea : manage as HIV uninfected • Non-infective diarrhea: - attention to hydration,diet(low fat,no milk) - Loperamide or codeine : NOT in infective diarrhea Pneumocystis carinii(jiroveci) Pneumonia (PCP) • PCP is an AIDS-defining diagnosis and the major cause of death in pts with AIDS • The risk of PCP occurs when CD4 cell < 200/mm3; • Rate in patients with prior PCP is 6070%/yr PCP Prophylaxis • rate of PCP with primary or secondary prophylaxis 0-4%/yr • indications for prophylaxis: symptomatic HIV disease ( WHO clinical stage 3,4 AIDS, thrush, unexplained fever >2 weeks, weight loss) • prior PCP, PCP Prophylaxis • CD4 <200mm³, • Total lymphocyte count < 1.25 X 10 9/l (when CD4 count unavailable – may miss 25% of patients with CD4 < 200) • Prophylaxis: TMP-SMX DS 1 double or 2 single strength po daily , TMP-SMX also confers cross protection vs. toxoplasmosis and common bacterial respiratory infections Cotrimoxazole intolerance Common in late disease Maculopapular rash Most respond to antihistamine Caution in systemic symptoms or mucosal involvement • Desensitisation/rechallenge safe if no mucosal involvement or systemic symptoms • • • • Desensitisation regimen • • • • • • • Cotrimoxazole syrup (250mg/5ml) Day 1: 1.25ml daily Day 2: 1.25 ml bd Day 3: 1.25 ml tds Day 4: 2.5ml bd Day 5:2.5ml tds Day 6: one tablet Alternate to cotrimoxazole • dapsone 100mg daily • As effective as cotrimoxazole for PCP • Does not prevent other opportunistic infection: toxoplasmosis,isosporiasis,bacterial infections PCP Treatment Acute PCP: Cotrimoxazole: 3-4 tabs qid po, Or 20/100 mg/kg/day in 4 doses IV – total duration of treatment -21 days • Hypoxia -prednisone, 40 mg/bd; taper dose • Alternative:dapsone 100mg daily plus trimethoprim 300mg tds or Clindamycin 450mg tds + primaquine 15 mg daily • Follow respiratory rate and oxygenation • Secondary prophylaxis mandatory Community Acquired Pneumonia • Pnuemonia -abrupt presentation with fever, purulent sputum, pleuritic chest pain. • Exclude TB/PCP • Hospitalize severe infections • May need empiric Rx whilst awaiting results Community Acquired Pneumonia • Ampicillin/amoxicillin/amoxicillinclavulinic acid, • erythromycin (penicillin allergy,atypical pneumonia ), • cephalosporins, • Aminoglycosides (gram neg) • quinolones Neurologic Conditions • Peripheral neuropathy • Myopathy • HIV Dementia • Toxoplasma encephalitis • Cryptococcal meningitis Neurologic Conditions • Peripheral neuropathy - related to HIV or drugs eg. INH,ddI,d4T Treatment - NSAIDs eg. ibuprofen AND - -amitriptylline at night (incremental dose) - Alternative: carbamazepine Neurologic Conditions • Myopathy: - proximal muscle weakness,increased CPK - AZT related or HIV related - Recommend drug holiday • HIV Dementia - neurocognitive tests Treatment:HAART Toxoplasmosis • CNS mass lesion :75% of cases occur with CD4 < 50 mm3 • Most disease is due to reactivation, • serum Toxoplasma IgG is positive >90%; 2 year risk among AIDS pts with + IgG Toxo is 26% Toxoplasmosis • empiric course of Rx, if no response in 1014 day refer • Rx: cotrimoxazole 4 tabs bd for 4 weeks, then 2 tabs bd for 12 week or • Clindamycin 600mg qid +Pyrimethamine 50mg daily for 6 weeks( add folinic acid 10 mg/day to treat bone marrow suppression. Toxoplasmosis Prophylaxis • All HIV+ patients should be tested for IgG antibody to Toxoplasmosis gondii. Advise patients not to eat raw or undercooked meat (esp. pork, lamb, venision) cook to 150°F or until no longer pink (>165°F). Wash hands after contact with raw meat, soil, vegetables, changing cat litter. CD4 < 100/mm³:Cotrimoxazole 2 tabs daily • • • Cryptococcal meningitis • Headache,Fever,Malaise • Vomiting,nausea:40% • Meningism,photophobia:uncommon • Altered mental status ,Seizures • Focal signs:cryptococoma at site of dense neurologic conduction eg.internal capsule Cryptococcal meningitis • Diagnosis: Focal neurological signs or obtundation: CNS imaging before LP • Opening pressure >250 mm : drain CSF until < 200mm or 50% of opening pressure • May need daily LP until stable • india ink, cryptococcal antigen, culture Cryptococcal meningitis Treatment: • Amphotericin B 0.7 mg/kg daily : 7-14 days • Then fluconazole 400mg daily : 8-10 wks • Fluconazole 100-200mg daily for life or until CD4 > 100-200 cell/mm³ for 6 months • No role for primary prophylaxis Tuberculosis • TB is the leading cause of death world wide among persons infected with HIV. • Risk of active TB among co-infected 5-16 / 100 p/ yr. • Clinical presentation less typical at low CD4 cell counts Cytomegalovirus (CMV) • Causes: retinitis, esophagitis, colitis, enetritis, radiculitis, encephalitis and hepatitis. Prior to HAART CMV retinitis occurred in 15-25% of AIDS patients. Most cases occur when CD4s <50 cells/mm³ in CMV sero-positive patients. • • Cytomegalovirus Treatment • IV ganciclovir 15mg/kg Q8h X2 wks then 5 mg/kg/day 5 days /week or 1g tds po,lifelong • Refer opthalmologist : intra-ocular ganciclovir Opportunistic Tumours • most frequent opportunistic tumour, Kaposi's sarcoma(KS), is observed in 20% of patients with AIDS. • KS associated with a human herpes virus 8 (HHV-8) • Treatment: HAART, chemotherapy/DXT • Lymphomas are also frequently seen in AIDS patients. • Refer to haematology:chemotherapy Decline in Incidence of OIs Attributed2000;342:1416-1429. (Based on CDC data.) to HAART Kovacs JA, et al. N Engl J Med. 350 Any Opportunistic Infection HAART 300 Incidence per 1000 Patient-Years 250 200 150 100 1992 1993 1994 Year 1995 1996 1997 Initiation and Discontinuation of Primary Prophylaxis of OIs in HIV-Infected Patients Adapted from Kovacs JA, et al. N Engl J Med. 2000;342:1416-1429 Primary Prophylaxis Pathogen Pneumocystis carinii Start Restart CD4 cell count <200 cells/µL or oropharyngeal oropharyngeal candidiasis candidiasis Follow P carinii <100 cells/µL and pneumonia IgG antibodies to guidelines Toxoplasma activity Stop CD4 cell count ≥200 cells/µL for 3–6 months Toxoplasma gondii Follow P carinii pneumonia guidelines Immune-reconstitution syndrome • Restoration of immune competence on HAART may result in flare of underlying opportunistic disease • Described with: – – – – – PCP MAI CMV Hepatitis C Fungal disease Vaccination • • • • • • • Live vaccines should avoided Yellow fever may be safe: CD4>200 CD4 < 200/mm3: ag response poor and short-lived Transient increase in viral load may occur Influenza vaccine: annually Pneumoccoccal vaccine: further studies Hepatitis B vaccine