THE SOU lrifRN A~RICAN JOURNAL O~ HIV MEDICINE ------------ MARCH 2002 CLINICAL GUIDELINE HIV Clinicians Society of Southern Africa Corresponding author: G Maartells, ["tedious Diseases Unit, Department of Medicine, University of Cape Town 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. DOSE OF CO-TRIMOXAZOLE PROPHYlAXIS INDICATIONS FOR CO-TRIMOXAZOLE PROPHYlAXIS PRIMARY PROPHYlAXIS 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 co- CO-TRIMOXAZOLE INTOLERANCE Tuberculosis preventive therapy was covered in the Februory 2001 issue of the SA Journal of HIV Medicine. All the following regimens are equally efficacious against Pneumocystis carinii pneumonia (PCP): • 960 mg daily • 960 mg three days/week • 480 mg daily. • WHO clinical stage 3 or 4 • CD4 count < 200 • Total Iymphocyte count < 1.25 x 10'/1 (should only be used when CD4 count unavailable - may miss 25% of patients C04 < 200). THE PREVENTION AND TREATMENT OF OPPORTUNISTIC INFECTIONS IN HIV-INFECTED ADULTS 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 l) is necessary while patients remain immune- suppressed. The following delegates attended the opportunistic infections guideline workshop of the SA HIV Clinicians Society, held in Cape Town on 9 March: Or Mark Cotton, Professor Gary Maartens, Or Steve Andrews, Or Steve Miller, Or Dave Spencer, Or Des Martin, Or Francois Venter, and Pofessor Robin Wood. 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 regiments) have been endorsed. Alternative regiments) 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. TABLE I. TREATMENT AND SECONDARY PROPHYlAXlS OF OPPORTUNISTIC INFEcnONS 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 Treatment options Duration Se<:ond,ry prophylaxis' Herpes simplex Valacidovir 500 mg bid 7 days Not usually recommended Acyclovir 400 mg tid (acyclovir 400 mg bid) Famcidovir 125 mg bid Tuberculosis Standard short-eourse therapy 6 months Not recommended Candida oesophagitis Ruconazole 100 mg daily 14 - 28 days Not recommended Itraconazole 200 mg daily Ketoconazole 400 mg daily Pneumocystis codnii Co-trimoxazoleJ 3-4 tabs qid 14-21 days pneumonia1 Dapsone 100 mg daily plus Co-trimoxazole' 2 tabs daily trimethoprim 300 mg tid Dapsone 100 mg daily Clindamycin 450 mg tid plus primaquine 15 mg daily Toxoplasmosis Co-trimoxazoleJ 4 tabs bid 4 weeks Cotrimoxazole' 2 tabs daily Then 2 tabs bid 12 weeks C1indamycin 600 mg qid plus 6 weeks pyrimethamine' 50 mg daily Cytomegalovirus Gancielovir 5 mglkg bid IV then 14 days N/A Ganciciovir 5 mglkg/day IV Ufelong! 5 days/week or 19tidPO Atypical mycobacteriosis Clarithromycin 500 mg bid plus Ufelong' N/A ethambutol 800 mg daily Salmonella bacteraemia Ciprofloxacin 500 mg bid 6 weeks Not recommended lsosporiasis Co-trimoxazole' 4 table" bid 4 weeks Co-trimoxazole' 2 tabs Pyrimethamine' 25 mg daily daily Pyrimethamine' 75 mg daily Cryptosporidiosis None available (anti motility drugs) N/A N/A Bacterial pneumonia Cefuroxime 750 mg - 1.5 g tid IV' 5 - 10 days Not recommended Ceramandole 1 - 2 9 qid IV' Ceftriaxone 1 - 2 9 daily IV' Cefotaxime 1 - 2 9 bid IV' Co-amoxielav 1.2 9 tid IV' Moxifloxacin 400 mg daily Gatifloxacin 400 mg daily Cryptococcal meningitis Amphotericin B 0.7 mg(kg'lV daily 7-14days Auconazole 100 - 200 mg then fluconazole 400 mg daily 8 - 10 weeks daily' Herpes zoster [shingles! Acyclovir 800 mg 5 times/day 7 days Not recommended Valacielovir 1 9 tid Famciclovir 250 mg tid Microsporidiosis A1bendazole 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 patien" [oral prednisone 40 mg bid followed by taper after 5 - 10 days). 3. Single-strength (480 mg) table". 4. Folinic acid (nor. 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 pressl. 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 MEOICINE ----------- MARCH 2002 MARCH 2002 ------------- 'Ht SOUTHH1N MRICAN JOURNAL O~ HV MtD CINt trimoxazole syrup [240 mg/5 ml): Day 1 1.25 ml daily 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 llnurg GS. StQnford Jf. e'ora;;no Mf,~;: a. Trirrethoprim-sJ.TGrretnoxaro e (TMP-SMl) dost~ arion 'versus d" 'et{ retn" en;e ~r PreurrOCYSLS ca{l"!ii pneJMO" a propn, axis in nlJp';4J'1 immuncxf(:""ciercy ... ·rus in=~:M paL~IS w'rn pre-w OUS al:herse reac:.on to TMp·SMl. J In=ect Dis 2001; 184: 992-997L THE ALTERNATIVE TO CO-TRIMOXAZOLE If co-trimoxazole cannot be tolerated, dapsone 100 mg daily should be substituted. Dapsone is as effec ive as co- trimoxazole 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 C04+ 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.