TREATMENT AND PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS IN HIV (Except Mycobacterium tuberculosis)

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TREATMENT AND PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS IN HIV (Except Mycobacterium tuberculosis) All doses stated should be reviewed f each individual patient and adjusted if they have renal liver

1 TREATMENT AND PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS IN HIV (Except Mycobacterium tuberculosis) All doses stated should be reviewed f each individual patient and adjusted if they have renal liver impairment. Any potential interactions with HIV medicines can be checked at druginteractions.g Primary care may be requested to prescribe medicines f prophylaxis maintenance. Unless otherwise requested in hospital discharge clinic letters moniting is undertaken by secondary care. Infections covered by this guidance: Pneumocystis Pneumonia (PCP) Cryptococcal Meningitis Pulmonary Cryptococcosis Cerebral Toxoplasmosis CMV retinitis CMV colitis Oral Candidiasis Oesophageal Candidiasis Mycobacterium Avium Complex (MAC) Cryptospidosis Microspidosis Genital Herpes Genital Warts Syphilis Other STIs F guidance on samples to be taken f each infection refer to the lab handbook (available on ICE requesting system) discuss with Microbiology.

2 INFECTION TREATMENT SEVERITY 1 ST LINE 2 ND LINE FURTHER INFORMATION PROPHYLAXIS LICENCE/ AVAILABILITY PNEUMOCYSTIS PNEUMONIA (PCP) (Pneumocystis jiroveci) Mild to Moderate PaO 2 >9.3kpa on room air Co trimoxazole al 1920mg TDS 90mg/kg/day in 3 divided doses (rounded to nearest 480mg) Duration: 21 days Option1: Clindamycin al mg every 6 8 hours * Primaquine al 15 30mg OD Option2: Dapsone 100mg al daily Trimethoprim al 20mg/kg/day in 3 divided doses rounded to nearest 50mg Option3: Atovaquone al 750mg BD, with food (preferably high fat) Duration: 21 days Check G6PD pri to prescribing dapsone primaquine but do not delay treatment. If significant haemolysis while on other treatment then check G6PD. Atovaquone has po bioavailability. Presence of food (particularly high fat) increases the absption 2 3 fold. Essential after first infection. Co trimoxazole 480mg OD Dapsone 100mg OD Atovaquone 750mg BD Primary prophylaxis: F all patients with CD4 count 200 CD4% <14. Treat as per secondary prophylaxis above. Discontinue prophylaxis when CD4 count >200 F >3months. * Primaquine is not licensed in the UK but can be prescribed on a named patient basis contact pharmacist to der. Atovaquone is only available as a liquid. Clindamycin and trimethoprim are not licensed f treatment of PCP. Atovaquone and dapsone are not licensed f prophylaxis of PCP. Severe PaO 2 9.3kpa on room air Co trimoxazole IV infusion 120mg/kg/day in 3 4 divided doses f 21 days steroids (see further infmation box) Switch to al co trimoxazole at same dose when appropriate during course. Option1: Clindamycin IV infusion mg 6 8 hourly * Primaquine al 15 30mg OD Option2: Pentamidine isetionate IV infusion 4mg/kg OD in 250ml 5% glucose Caution: hypotension, hypoglycaemia Duration: 21 days Check G6PD pri to prescribing dapsone primaquine but do not delay treatment. If significant haemolysis while on other treatment then check G6PD. If O 2 saturations <92% PaO2 9.3kpa on room air start steroids at the same time as treatment ( within 72 hours). Prednisolone al 40mg bd f 5 days, 40mg od f 5 days then 20mg daily f 11 days then stop. If IV required use methylprednisolone at 75% of al prednisolone dose. Pneumothax is a common complication of severe disease and carries a po prognosis. CXR required if deteriation and/ chest pain. Essential after first infection. Co trimoxazole 480mg OD Dapsone 100mg OD Atovaquone 750mg BD Primary prophylaxis: F all patients with CD4 count 200 CD4% <14. Treat as per secondary prophylaxis above. Discontinue prophylaxis when CD4 count >200 F >3months. * Primaquine is not licensed in the UK but can be prescribed on a named patient basis contact pharmacist to der. Atovaquone and dapsone are not licensed f prophylaxis of PCP. Atovaquone is only available as a liquid.

4 INFECTION CRYPTOCOCCAL MENINGITIS (Cryptococcus neofmans) PULMONARY CRYPTOCOCCOSIS (Cryptococcus neofmans) TREATMENT 1 ST LINE 2 ND LINE Induction therapy: Liposomal Amphoteracin B IV infusion (Ambisome) 1mg/kg/day increasing to 4mg/kg/day *Flucytosine PO/IV infusion 100mg/kg/day in 4 divided doses Duration: 14 days consider extending duration until negative CSF culture on repeat LP f patients with po prognosis at baseline a po initial clinical response to induction therapy. Then step down to: Fluconazole PO 400mg OD f 8 weeks F patients who cannot tolerate are unresponsive to amphoteracin consider using: Induction therapy: Fluconazole PO/IV infusion 400mg OD *Flucytosine PO/IV infusion mg/kg/day in 4 divided doses Duration: 14 days until negative CSP culture on repeat LP Then step down to: Fluconazole PO 400mg OD f 8 weeks Other options f step down: Ambisome IV infusion 4mg/kg/weekly Itraconazole PO 200mg OD FURTHER INFORMATION PROPHYLAXIS LICENCE / AVAILABILITY A test dose of Ambisome should be given at start of course 1mg over 10 mins then patient observed foe 30 mins f signs of allergic reaction. CSF manometry should be perfmed on all patients at baseline if any signs of neurological deteriation occur. Serial lumbar punctures neurosurgical procedures are indicated f individuals with an opening pressure >250mmH 2 O. Cticosteroids and acetazolamide have not been shown to be of any benefit. 1 st line combination therapy has me rapid CSF sterilisation and decreased incidence of relapse compared to amphoteracin alone. Monit U&Es, Mg, LFTs, FBC daily. Monit flucytosine trough levels pre 5 th dose. Aim f 35 50mg/L and definitely not >80mg/L. F azole anti fungals consider interactions with other medicines. As per cryptococcal meningitis As per cryptococcal meningitis If CSF exam is negative and there is no other evidence of dissemination and radiological infiltrates are focal and there is no hypoxia Fluconazole PO 400mg OD f 10 weeks then 200mg OD thereafter is an alternative strategy. Primary prophylaxis: not indicated Fluconazole PO 200mg OD Other options f prophylaxis: Ambisome 4mg/kg/weekly Or Itraconazole PO 200mg OD Discontinue prophylaxis when CD4 count is >100 f at least 3 months and viral load undetectable. As per cryptococcal meningitis * Oral flucytosine is not licensed in the UK but can be prescribed on a named patient basis contact pharmacist to der. Licensed dose of flucytosine IV is 200mg/kg/day but a lower dose is sufficient in this situation as it is synergistic when coadministered. IV Flucytosine is available in NW night emergency drug cupboard.

5 INFECTION CEREBRAL TOXOPLASMOSIS (Toxoplasma gondii) TREATMENT 1 ST LINE 2 ND LINE Sulfadiazine PO 1 2g QDS 15mg/kg Pyrimethamine PO 200mg once off then 50mg (<60kg) 75mg ( 60kg) OD Folinic Acid PO 15mg OD Duration: minimum 6 weeks Then step down to: Maintenance Therapy: Sulfadiazine PO 500mg QDS 1gBD Pyrimethamine PO 25mg OD Folinic Acid PO 15mg OD (additional PCP prophylaxis not required) Maintenance therapy can be discontinued when CD4 >200 f 6 months and VL undetectable. Clindamycin PO/IV infusion 600mg QDS Pyrimethamine PO 200mg once off then 50mg (<60kg) 75mg ( 60kg) OD Folinic Acid PO 15mg OD Duration: minimum 6 weeks Then step down to: Maintenance Therapy: Clindamycin PO 300mg QDS 600mg TDS Pyrimethamine PO 25mg OD Folinic Acid PO 15mg OD (additional PCP prophylaxis is required) Maintenance therapy can be discontinued when CD4 >200 f 6 months and VL undetectable. FURTHER INFORMATION PROPHYLAXIS LICENCE / AVAILABILITY If need IV therapy use 2 nd line option. IV sulfadiazine is no longer available. With sulfadiazine a fluid output of >1200ml/day should be maintained to prevent crystalluria. If this does occur stop treatment and alkalise urine using bicarbonate. Lack of response to 2 weeks of treatment, clinical deteriation of features that are not typical should lead to consideration of a brain biopsy. Sulfadiazine and clindamycin have good bioavailability so the al route is preferred. Cticosteroids are only indicated in patients with signs and symptoms of raised ICP when dexamethasoone 4mg QDS gradually reducing should be used. Primary prophylaxis: all patients with CD4 <200 and positive toxoplasma serology. Co trimoxazole PO 480mg OD (also covers PCP) Dapsone PO 50mg OD (also covers PCP) Pyrimethamine PO 50mg weekly Folinic acid PO 15mg OD Primary prophylaxis can be discontinued when CD4 count >200 f 3months and VL undetectable. See maintenance therapy IV sulfadiazine no longer available. Alternative name f folinic acid is calcium folinate. Oral sulfadiazine is available in the NW night emergency drug cupboard.

6 INFECTION CMV RETINITIS (Cytomegalovirus) INDUCTION Option 1: Valganciclovir PO 900mg bd f 21 days Option 2: Ganciclovir IV infusion 5mg/kg bd f days Option 3: Foscarnet IV infusion 90mg/kg bd f days Option 4: Cidofovir IV infusion 5mg/kg weekly f 2 weeks TREATMENT MAINTENANCE Option1: Valganciclovir PO 900mg OD Option 2: Ganciclovir IV infusion 5mg/kg od 6mg/kg/day f 5 days a week Option 3: Foscarnet IV infusion 90mg/kg od 120mg/kg/day f 5 days a week Option 4: Cidofovir IV infusion 5mg/kg given ftnightly Maintenance therapy can be stopped when CD4>100 f >3 6 months and VL undetectable. FURTHER INFORMATION PROPHYLAXIS LICENCE / AVAILABILITY Monit FBC, U&Es, LFTs f all anti CMV medications. Valganciclovir should be taken with food. Valganciclovir/ganciclovir are considered potential teratogens and carcinogens in humans. Avoid direct contact of broken crushed tablets, infusion powder solution with skin mucous membranes. If such contact occurs, wash thoughly with soap and water rinse eyes thoughly with sterile water, plain water if sterile water is unavailable. Foscarnet should be administered via a central line must be diluted in pharmacy aseptic department to be given peripherally. Slower infusion rates may reduce rates of electrolyte disturbances. Patients should be encouraged to maintain a high level of hygiene to avoid genital ulceration. Cidofovir requires to be administered with IV hydration and probenecid tablets. See SmPC f details. Primary prophylaxis: not indicated See maintenance therapy Ganciclovir infusions should ideally be made in pharmacy aseptic department. Foscarnet and Cidofovir are not routinely kept as stock and will require to be dered in. CMV COLITIS Option 1: Ganciclovir IV infusion 5mg/kg bd f days Option 2: Foscarnet IV infusion 90mg/kg bd f days Not routinely recommended unless patient relapses after induction therapy ceases. See above f infmation on ganciclovr and foscarnet. Valganciclovir may be considered as a treatment option if symptoms do not interfere with absption. See maintenance therapy Foscarnet and valganciclovir are not licensed f this indication.

7 INFECTION ORAL CANDIDIASIS OESOPHAGEAL CANDIDIASIS TREATMENT 1 ST LINE 2 ND LINE Fluconazole PO mg OD f 7 14 days In severe disease: up to 200mg OD Fluconazole PO mg OD f days In severe disease: up to 400mg OD 200mg BD Itraconazole liquid PO 100mg BD (10 20ml) f 7 14 days Itraconazole liquid PO mg BD (10 20ml) f up to 14 days Non responders to resistant Candida: Viconazole, posaconazole anidulafungin FURTHER INFORMATION PROPHYLAXIS LICENCE / AVAILABILITY F all azole antifungals check f interactions with other medications. Itraconazole liquid has increased al bioavailability and it may also have some local effect. The liquid should be taken 1 hour befe food on an empty stomach. F all azole antifungals check f interactions with other medications. Itraconazole liquid has increased al bioavailability and it may also have some local effect so is the preferred fmulation. The liquid should be taken 1 hour befe food on an empty stomach. The dose should be swished around the mouth and swallowed without rinsing. Primary prophylaxis: not recommended promotes resistance. not recommended promotes resistance. Primary prophylaxis: not recommended promotes resistance. not recommended promotes resistance. CSM warning: itraconazole is contra indicated in patients with evidence of histy of congestive heart failure Patients should have a full ophthalmological examination pri to starting ethambutol. MYCOBACTERIUM AVIUM COMPLEX (MAC) Clarithromycin PO 500mg BD Ethambutol PO 15mg/kg (rounded to nearest 100mg) / Rifabutin PO 300mg OD (see further infmation) Treatment can be stopped when CD4 >100 f 2 results at least 3 months apart, clinical response to MAC treatment f at least 3 months and undetectable VL. F treatment failure: 3 drug combination to include at least 2 drugs not previously used. Options include: Rifabutin if not used 1 st line Ethambutol can be continued as it facilitates the penetration of other agents in mycobacteria Ciprofloxacin PO mg BD Amikacin IV 7.5mg/kg BD 15mg/kg OD (maximum 1.5g/day) f 10 days maximum. Linezolid, Cycloserine, Prothionamide Rifabutin should be added if CD4<25 markedly symptomatic DMAC features and/ labaty parameters if effective HAART regime cannot be given. Rifabutin dose requires adjustment f HAART interactions. Amikacin serum level moniting is required. If treatment is to exceed 10 days an audiogram should be perfmed and repeated during therapy. Therapy should be stopped if tinnitus subjective hearing loss develops. Primary prophylaxis: Consider if CD4 <50 Azithromycin PO 1250mg weekly Follow food /antacid administration instructions f fmulation dispensed. Prophylaxis can be stopped if VL undetectable and CD4 >50 f at least 3 months. Unlicensed indication f clarithromycin, ciprofloxacin, amikacin, linezolid, azithromycin. Rifabutin, Cycloserine and prothionamide are not routinely kept as stock and will require to be dered in.

8 INFECTION CRYPTOSPORIDOSIS (Cryptospidium parvum) TREATMENT 1 st LINE 2 nd LINE Initiate optimise HAART Symptomatic treatment of diarrhoea Adequate hydration MICROSPORIDOSIS Initiate optimise HAART Symptomatic treatment of diarrhoea Adequate hydration GENITAL HERPES Treat as per TSRH guidelines GENITAL WARTS Treat as per TSRH guidelines SYPHILIS Treat as per TSRH guidelines OTHER STIs Treat as per non HIV patients See Tayside Area Fmulary Section 5, Genitourinary section. Consider Nitazoxinide PO 500mg 1g BD f 3 days up to 12 weeks Consider Albendazole PO 400mg BD f days FURTHER INFORMATION PROPHYLAXIS LICENCE / AVAILABILITY Nitazoxanide efficacy is limited in severely immunocompromised patients. Albendazole has po al bioavailability so should be taken with fatty food to maximise absption. Check f drug interactions. Primary prophylaxis: not indicated Primary prophylaxis: not indicated Nitazoxinide is not licensed in the UK. Available on a named patient basis. Contact Pharmacist to der. Albendazole is not licensed in the UK. Available on a named patient basis. Contact Pharmacist to der. Adapted from BHIVA 2011 Treatment of OI Guidelines/Electronic Medicines Compendium Prepared by: K Hill, HIV/Antimicrobial Pharmacist Reviewed by: HIV MDT May 2012 Approved by: AMG June 2012 Review: June 2014

9 TSRH PROTOCOL MANAGEMENT OF STIS IN HIV POSITIVE PATIENTS The treatment of the majity of sexually transmitted infections is the same as in the uninfected population. Please refer to current NHS Tayside GUM protocols. The exceptions include genital herpes, syphilis and genital warts. Genital Herpes 1 Symptoms Primary genital herpes in those who are immunocompromised may last longer and be me severe than in HIV negative patients. Symptoms generally include: Painful ulceration (which may be anywhere in the anogenital region) Dysuria Tender inguinal lymphadenopathy Increased urethral vaginal discharge It can be associated with systemic complications including pneumonia and fulminant hepatitis. Investigations A HSV PCR swab should be taken from the base of an ulcer. Consider VZV (shingles) as part of the differential diagnosis and request VZV PCR if clinically indicated. The sample and virology fm should be labelled with a red dot and the fm marked as a high-risk patient. Treatment of primary herpes Treatment should be initiated promptly with Aciclovir 400mg x 5/day f 7-10 days. If the patient is not able to tolerate al therapy an inpatient admission should be sought and treatment commenced with acyclovir 5-10mg/kg body weight every 8 hours. Recurrent Herpes Patients with HIV are likely to have me frequent recurrences especially if they have significant immunosuppression (CD4<200). It is imptant to establish those with immunosuppression on antiretroviral therapy, as this should improve the frequency of their outbreaks. Episodic therapy f recurrences Treatment may be provided in the fm of Aciclovir 200mg x5/day f 5-10 days. If this were too high a pill burden f some patients an alternative would be Valaciclovir 1g BD x 5-10 days. Suppressive therapy f frequent recurrences Suppressive therapy is usually reserved f those patients who have greater than six outbreaks of genital herpes per year. Treatment is in the fm of Aciclovir 400mg BD, which is usually provided f one year. The first one-month of a prescription is provided from the hospital and the following 11 months should be accessed from their GP. A letter should be sent to the GP with the patient s consent. Treatment would be stopped at that time and the patient should expect

10 to have an initial rebound attack. The frequency of recurrences would be assessed following this. If the frequency of outbreaks is still high beyond this point, treatment can be resumed with a trial of stopping again after 12 months. If a patient were on antiretroviral therapy it would be imptant to ensure that viral suppression is achieved and maintained. Drug resistant herpes If a patient continues to have outbreaks whilst on recommended antiviral therapy the possibility of a drug resistant virus must be considered. A diagnosis is made by isolating HSV from genital lesions whilst the patient is taking suppressive treatment. A trial of systemic therapy should be considered with either: Foscarnet 40 mg/kg I.V. every 8 12 hours Cidofovir 5 mg/kg body weight. IV infusion over 1 hour diluted with Nmal Saline once per week f 2 consecutive weeks. Administered with al Probenecid. Genital Warts 1 Human papilloma virus infection is me commonly associated with anogenital warts and either CIN AIN in those who are immunocompromised. CIN Women are recommended to undergo annual cervical screening. Patients who receive a rept of mild dyskaryosis should be referred to colposcopy. Please refer to the HIV smear protocol. AIN Men especially MSM who have anogenital warts should have proctoscopy perfmed. The presence of any atypical lesions should ensure a prompt referral f biopsy of the affected area. MSM should be offered an anal examination annually. Anogenital warts Warts can be me problematic in those living with HIV infection especially in those with low CD4 counts. First line therapy should be with Imiquimod 5% Cream (Aldara) in those who are immunocompromised. Instructions of use should be provided and suppted with a drug infmation leaflet. Imiquimod cream can be used f up to 16 weeks. If there were po treatment response it would be imptant to establish the patient on antiretroviral therapy, as a rise in their CD4 count may be helpful in eradicating persistent HPV infection.

11 Syphilis 2 Screening Syphilis serological screening should be perfmed 3 monthly in the HIV positive population. In those who decline serology are at low risk of acquiring syphilis this should be documented clearly in their case notes along with a risk assessment and readdressed again at their next appointment. Infection Symptoms, signs and investigations are as per the uninfected population. Patients with HIV may have me extensive genital ulceration and a higher incidence of neurological complications. All HIV positive patients with a rash should have syphilis serology undertaken. If there are any neurological symptoms signs the patient should have a CT scan of brain perfmed followed by a lumbar puncture. A positive CSF VDRL in the absence of contamination with blood is diagnostic of neurosyphilis. A negative CSF TPPA excludes infection. Please follow the guidance in the standard GUM Syphilis protocol. Treatment HIV positive patients should receive the same treatment as per the uninfected population and is dependant upon the stage of disease. Early syphilis Benzathine Penicillin 2.4 mega units I.M. as a single dose It is imptant to ensure close follow up and serological testing at the recommended intervals. Late latent/cardiovascular Gummatous syphilis Benzathine Penicillin 2.4 mega units I.M. on day 1, day 8 and day 15 Neurosyphilis Procaine penicillin G 2.4 mega units I.M. once daily x 17 days plus al probenecid 500mg qds x 17 days. Treatment with al therapies is not recommended.

12 Lymphogranuloma Venereum In HIV-infected MSM presenting with symptoms of proctitis, a high index of suspicion f LGV should be held. Swabs should be undertaken at proctoscopy and include microscopy, GC culture, GC/CT NAAT and if there is any ulceration then swabs f both HSV and syphilis PCR should be taken. The NAAT fm should be labelled proctitis in HIV MSM. Please send f LGV serovars. Inguinal lymph nodes can be aspirated and aspirate sent f Chlamydia PCR and LGV serovars. Empiric treatment should be commenced with doxycycline 100mg bd f 7 days. If there is significant ulceration then HSV treatment should be added as above. The patient should be followed up with results at 7 days and if the rectal Chlamydia is positive then doxycycline should be continued f up to three weeks until LGV has been excluded. All patients diagnosed with LGV should have syphilis serology and hepatitis C serology undertaken. Public health interventions All HIV infected patients diagnosed with an acute STI should be seen by a sexual health adviser f partner notification f both the acute STI and f HIV. They should receive in depth counselling regarding safer sex advice to protect their own health and to reduce the risk of onward transmission of HIV. They should be made aware of the legal issues relating to sexual transmission of HIV and made aware of the availability of PEPSE. Histy should also include interventions around substance misuse and domestic violence. Condoms should be made available to all HIV-infected individuals and should be offered at every clinic visit. References: 1) British HIV Association, BASHH and FSRH guidelines f the management of the sexual and reproductive health of people living with HIV, HIV Medicine (2008) 9: ) UK National guidelines on the management of Syphilis; International Journal of STD and AIDS 2008; 19: Reviewed by Dr S Allstaff, January 2012

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