Starting ARVs in the setting of Opportunistic Infections 2 Learning Objectives At the end of this presentation, the participant should be able to: • Cite 3 opportunistic infections where ARV therapy is part of the treatment • Cite 5 opportunistic infections where ARV initiation may lead to IRS • Give the appropriate management for a newly diagnosed PLWHA on TB therapy who has a CD4 count < 200. • Give the dose of EFV that should be used when treating TB in Vietnam. • Cite the recommendation of the MOH of the use of NVP with a RIF containing TB therapy • Cite the best time and clinical conditions that a patient with a treated OI can be started on ARV therapy 3 Outline of Presentation • Introduction • In which OIs can you start ARVs right away and in which can you not? Tuberculosis – What therapy can we start? • Tuberculosis – When can we start therapy? • Tuberculosis – Four treatment scenarios. • Cryptococcus – When can we start therapy? • Side Effects of ARV and OI medications Starting ARVs in the setting of an active Opportunistic Infection Introduction 5 Introduction • The decision to start ARVs is a balance between – wanting the immune system to recover in order to fight infection vs. – the risk of drug interactions and side effects – the risk of immune reconstitution syndrome 6 Introduction • Little data exists on the best time to start ARVs when the patient is being treated for an OI. Clinical judgment must be used. • Prior starting ARV therapy the patient should be responding to OI therapy, with no fever and no active side effects (rash). • It is important to know the drug interactions of all medications before they are prescribed (look it up!) 7 Guiding principles • Always treat the acute OI first • Begin ARVs when the patient is clinically stable • Be vigilant for drug interactions and overlapping toxicities • Beware of Immune reconstitution syndrome Do not be afraid to treat! Starting ARVs in the setting of an active Opportunistic Infection In which OIs can you start ARVs right away and in which can you not? 9 Starting ARVs in the setting of an active Opportunistic Infection Some OIs include ARVs as critical components of treatment. In these OIs, ARV therapy should not be delayed. • Cryptosporidiosis • Microsporidiosis • Kaposi Sarcoma • Progressive Multifocal Lymphadenopathy (PML) 10 Starting ARVs in the setting of an active Opportunistic Infection In other OIs, ARV therapy can exacerbate the condition with IRS. In these infections ARV therapy should be delayed: • Tuberculosis • Penicilliosis • Toxoplasmosis • Cryptococcosis • Pneumocystis Carinii Pneumonia [...]... et al AIDS 24 2001 Starting ARVs in the setting of an active Opportunistic Infection Tuberculosis Four Treatment Scenarios ARV therapy in co-infected patients: Scenario 1 If patient has: 1 2 3 Pulmonary TB only No other signs of clinical stage III or IV Not yet on ARVs Then: Treat TB first and start ARVs after TB therapy is completed if CD4 < 350 26 Anti-retroviral therapy in co-infected patients:... 200 Start TB treatment then start ARVs as soon as TB treatment is tolerated (2 weeks-2 months) Guidelines for Diagnosis and Treatment of HIV/AIDS, Ministry of Health, Vietnam March, 2005 30 Starting ARVs in the setting of an active Opportunistic Infection Cryptococcal Meningitis When should we start therapy? Case Study • 30 year old man presented to the hospital because of 4 days of fever, severe headache,.. .Starting ARVs in the setting of an active Opportunistic Infection Tuberculosis What therapy should we start? Review of Drug Metabolism Rifampicin Induces Cytochrome P450 Activiy Ritonavir Inhibits Cytochrome P450 Activity 12 Rifampin and ARV blood levels SQV Rifampin IDV NFV LPV NVP EFV       84% 89% 82% 75% 37% 25% Finch et al Arch Intern Med 2002;162:985-92 13 Rifampin and ARV •... start NVP containing ARV Weerawat M et al CID 2006;43:253-5 Guidelines for Diagnosis and Treatment of HIV/AIDS, Ministry of Health, Vietnam March, 2005 16 Starting ARVs in the setting of an active Opportunistic Infection Tuberculosis When should we start therapy? Antiretroviral Therapy and TB You have just started your HIV patient on TB therapy Her CD4 count is less than 250 When do you start ARVs? 1 2... of Dr A.L Pozniak 19 Antiretroviral Therapy and TB Immediate vs Delayed ARV Arguments for initiating potent HIV therapy at the onset of TB: 1.TB is associated with increased HIV replication and and HIV disease progression 2.Potent antiretroviral therapy can reduce HIV RNA levels and slow HIV disease progression 3.HIV therapy reduces risk of developing other opportunistic infections Slide courtesy of. .. taking NVP + Rifampin, 82% of these patients had good virological suppression • As per MOH guidelines, substitute EFV for NVP if the patient will start of RIF and if it is available • But, if EFV not available, do not need to stop NVP containing ARV therapy in the event one needs to start a RIF based TB therapy • And, if EFV is not available, do not need to wait until after the induction period of. .. Secondary Prophylaxis • Remember that after 8-10 weeks of “consolidation” treatment with fluconazole 400 mg daily, the dose can be reduced to 200 mg daily for secondary prophylaxis (“maintenance phase”) – This should continue until his immune system is improving (CD4 > 200) on ARVs for 36 months 35 Starting ARVs in the setting of an active Opportunistic Infection Medication Side Effects ... Signs of clinical stage III or IV disease 3 Not yet on ARVs Then: 1 Start TB treatment 2 Start ARVs after initiation phase of TB treatment (earlier if patient is severely ill) 27 Anti-retroviral therapy in co-infected patients: Scenario 3 • Patient has extrapulmonary (disseminated) TB • Not yet on ARVs Then: • Start ARV as soon as patient tolerates TB meds (between 2 weeks and 2 months) regardless of. .. 28 Anti-retroviral therapy in co-infected patients: Scenario 4 • If patient is already receiving ARVs Then • Continue ARV • Begin TB therapy (evaluate for potential drug interactions and additive toxicities) 29 If CD4 counts are available CD4 > 350 Treat TB first unless other WHO stage III or IV signs are present CD4 200-350 Start TB treatment first Start ARVs after initiation phase of TB treatment CD4... Pozniak 20 Study on Initiating ARV Therapy in PLWHA with TB Prospective study looking at British patients being treated for TB and who were newly diagnosed with HIV • 188 patients with a mean CD4 count of 70 cells/mm3 started ARVs • Outcomes measured: – – AIDS defining illnesses (ADI) Mortality Dean et al AIDS 2002:16(1):75-83 Dean et al AIDS 21 2001 Study on Initiating ARV Therapy in PLWHA with TB Results: . Lymphadenopathy (PML) 10 Starting ARVs in the setting of an active Opportunistic Infection In other OIs, ARV therapy can exacerbate the condition with IRS. In these infections ARV therapy should be. Starting ARVs in the setting of Opportunistic Infections 2 Learning Objectives At the end of this presentation, the participant should be able to: • Cite 3 opportunistic infections. which can you not? 9 Starting ARVs in the setting of an active Opportunistic Infection Some OIs include ARVs as critical components of treatment. In these OIs, ARV therapy should not be delayed. • Cryptosporidiosis