The prevention and treatment of opportunistic infections in HIV-infected adults

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[Find the meaning and references behind the names: Robin, Francois, Dave, Martin, Mark, Steve, Gary]

CLINICAL GUIDELINE THE PREVENTION AND TREATMENT OF OPPORTUNISTIC INFECTIONS IN HIV-INFECTED ADULTS HIV Clinicians Society of Southern Africa Corresponding author: G Mauriens, Infectious Diseases Unil, Department of Medicine, University of Cape Town A number of lengthy and comprehensive articles and guidelines exist with regard to the treatment and prevention of opportunistic infections, but this guideline is designed to be easy and simple for a practitioner to use. It is presented in a simplified format. The guideline is supported by evidence-based studies and adapted to be appropriate to the local situation. It should be noted that only the drugs that are licensed in South Africa have been recommended and in addition, at all times, the most cost-effective regimen(s) have been endorsed. Alternative regimen(s) have been listed where appropriate, but these are not exhaustive. A practitioner dealing with a more complex problem may find it necessary to consult with a colleague or refer to more comprehensive material. The best method of preventing opportunistic infections in HIV-infected individuals is to use highly active antiretroviral therapy, which leads to partial immune reconstitution. However, even if antiretroviral therapy is available a substantial proportion of patients will either present with severe immune suppression or remain severely immune-suppressed despite antiretroviral therapy. Many opportunistic infections can be prevented in these patients by using primary prophylaxis (see below) or vaccination (see below). Relapses are common after initial treatment of many opportunistic infections and maintenance therapy (also known as secondary prophylaxis - see Table I) is necessary while patients remain immunesuppressed. The following delegates attended the opportunistic infections guideline workshop of the SA HIV Clinicians Society, held in Cape Town on 9 March: Dr Mark Cotton, Professor Gary Maartens, Dr Steve Andrews, Dr Steve Miller, Dr Dave Spencer, Dr Des Martin, Dr Francois Venter, and Pofessor Robin Wood. PRIMARY PROPHYLAXIS Tuberculosis preventive therapy was covered in the February 2001 issue of the SA Journal of HIV Medicine. INDICATIONS FOR CO-TRIMOXAZOLE PROPHYLAXIS WHO clinical stage CD4 count <200 3 or 4 Total lymphocyte count < 1.25 x 10%/1 (should only be used when CD4 count unavailable - may miss 25% of patients CD4 <200). DOSE OF CO-TRIMOXAZOLE PROPHYLAXIS All the following regimens are equally efficacious against Pneumocystis carinii pneumonia (PCP): 960 mg daily 960 mg three days/week 480 mg daily. All dosages are acceptable, but lower dose regimens are better tolerated. There is scanty evidence for lower dose regimens against toxoplasmosis and strongest evidence for higher-dose regimens. CO-TRIMOXAZOLE INTOLERANCE Co-trimoxazole intolerance is common in late disease and usually presents as a maculopapular rash. Many intolerant patients may continue to receive co-trimoxazole with the addition of an antihistamine unless there are systemic symptoms or mucosal involvement. If co-trimoxazole therapy is discontinued, desensitisation or rechallenge appear to be safe unless there are systemic symptoms or mucosal involvement. Because co-trimoxazole reduces the incidence of many opportunistic infections, rechallenge or desensitisation should be considered. Studies have demonstrated that desensitisation and rechallenge appear safe. Both rechallenge and desensitisation should be done under antihistamine cover starting the day before. Rechallenge should be done with co-trimoxazole 480 mg and the patient observed for several hours. Several desensitisation regimens exist; one of the simplest uses coTHE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE MARCII 2002 17

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TABLE I. TREATMENT AND SECONDARY PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS IN ADULTS Standard adult doses have been given. Every effort has been made to check doses, but readers should check other sources. Usual duration of therapy has been given, but longer courses may be needed in individual cases. Infection Herpes simplex Treatment options Valaciclovir 500 mg bid Acyclovir 400 mg tid Duration 7 days Secondary prophylaxis' Not usually recommended (acyclovir 400 mg bid) Famciclovir 125 mg bid Tuberculosis Candida oesophagitis Standard short-course therapy Fluconazole 100 mg daily Itraconazole 200 mg daily Pneumocystis carinii pneumonia² Toxoplasmosis Cytomegalovirus Ketoconazole 400 mg daily Co-trimoxazole 3-4 tabs qid Dapsone 100 mg daily plus trimethoprim 300 mg tid Clindamycin 450 mg tid plus primaquine 15 mg daily Co-trimoxazole 4 tabs bid Then 2 tabs bid Clindamycin 600 mg qid plus pyrimethamine 50 mg daily Ganciclovir 5 mg/kg bid IV then 6 months 14-28 days Not recommended Not recommended 14-21 days Co-trimoxazole 2 tabs daily Dapsone 100 mg daily 4 weeks 12 weeks 6 weeks Cotrimoxazole 2 tabs daily Ganciclovir 5 mg/kg/day IV 14 days Lifelong N/A 5 days/week or 1 g tid PO Atypical mycobacteriosis Clarithromycin 500 mg bid plus ethambutol 800 mg daily Lifelong N/A Salmonella bacteraemia Isosporiasis Ciprofloxacin 500 mg bid Co-trimoxazole² 4 tablets bid Pyrimethamine 25 mg daily 6 weeks Not recommended 4 weeks Co-trimoxazole³ 2 tabs daily Pyrimethamine 75 mg daily Cryptosporidiosis Bacterial pneumonia None available (antimotility drugs) N/A N/A Cefuroxime 750 mg - 1.5 g tid IV³ Cefamandole 1-2 g qid IV³ 5 - 10 days Not recommended Cryptococcal meningitis Herpes zoster (shingles) Microsporidiosis Ceftriaxone 1-2 g daily IV Cefotaxime 1-2 g bid IV* Co-amoxiclav 1.2 g tid V Moxifloxacin 400 mg daily Gatifloxacin 400 mg daily Amphotericin B 0.7 mg/kg³ IV daily then fluconazole 400 mg daily Acyclovir 800 mg 5 times/day Valaciclovir 1 g tid Famciclovir 250 mg tid 7 - 14 days 8-10 weeks 7 days Fluconazole 100-200 mg daily* Not recommended Albendazole 400 mg bid' 21 days Not recommended 1. Prophylaxis or lifelong therapy can be discontinued if the CD4 count increases to > 200 on antiretroviral therapy. 2. Adjunctive corticosteroids are indicated in hypoxic patients (oral prednisone 40 mg bid followed by taper after 5 - 10 days). 3. Single-strength (480 mg) tablets. 4. Folinic acid (not folic acid) should be used to treat or prevent bone marrow suppression. 5. Therapy should be completed with oral antibiotics (amoxicillin, co-amoxiclav, moxifloxacin or gatifloxacin are recommended). These antibiotics are recommended in the South African Thoracic Society guidelines on community-acquired pneumonia (in press). 6. A test dose of 1 mg should be given over 30 minutes. If this is tolerated then half the daily dose can be infused over 4 hours with the full dose given the next day. Many experts omit the test dose. 7. Only certain species (notably Encephalitozoon intestinalis) respond well to albendazole. THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE MARCH 2002 19

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trimoxazole syrup (240 mg/5 ml): 1.25 ml daily Day 1 Day 2 1.25 ml bid Day 3 1.25 ml tid Day 4 2.5 ml bid Day 5 2.5 ml tid Day 6 One tablet (480 mg) daily (Leoung GS, Stanford JF, Giordano MF, et al. Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus infected patients with previous adverse reaction to TMP-SMZ J Infect Dis 2001; 184-992 997) THE ALTERNATIVE TO CO-TRIMOXAZOLE If co-trimoxazole cannot be tolerated, dapsone 100 mg daily should be substituted. Dapsone is as effective as cotrimoxazole for prophylaxis against PCP but does not prevent other opportunistic infections, e.g. toxoplasmosis, isosporiasis and bacterial infections. VACCINATION Aerosolised pentamidine is not cost effective in the local setting. Live vaccines should generally be avoided in adults. Yellow fever vaccine may be safe if the CD4+ count is > 200. When the CD4+ count is < 200 antigenic responses tend to be poor and short-lived for all types of vaccinations. A transient increase in viral load, experienced following vaccination, can be discounted. Influenza vaccination should be administered annually. The present 23 polyvalent pneumococcal vaccine should be avoided as there is strong evidence that it is harmful. Further trials on other pneumococcal vaccines are awaited. Hepatitis B vaccine should be administered to hepatitis B surface antigen-negative patients. 20 MARCH 2002 An 1 ONE of ind greatest to earth threats SF NA Face THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE