IRIS? IRIS? No thank you, I prefer RosesNo thank you, I prefer Roses
Allison AgwuAllison Agwu
LEAH Adolescent Grand RoundsLEAH Adolescent Grand Rounds
Advanced HIV ManagementAdvanced HIV Management
October 9, 2009October 9, 2009
Clinical CaseClinical Case
18* year old AA male with a history of AIDS18* year old AA male with a history of AIDS Prior history of candida esophagitisPrior history of candida esophagitis Two week history of acute onset fevers,Two week history of acute onset fevers, headaches and headaches and
anorexiaanorexia Associated weight lossAssociated weight loss Started on HAART one month priorStarted on HAART one month prior Nadir CD4 count 5 cells/Nadir CD4 count 5 cells/µLµL, Viral load >750,000 copies/ml, Viral load >750,000 copies/ml
*case slightly altered from original*case slightly altered from original
HistoryHistory
Medications: Efavirenz (Sustiva), Didanosine (Videx), Medications: Efavirenz (Sustiva), Didanosine (Videx), Stavudine (Zerit) , Paxil, Iron, Bactrim, PrilosecStavudine (Zerit) , Paxil, Iron, Bactrim, Prilosec
Physical ExaminationPhysical Examination Temp 103Temp 103°F°F, PR 120bpm, RR 22 cpm, BP 106/90 mmHg, PR 120bpm, RR 22 cpm, BP 106/90 mmHg Cachectic, acutely ill looking maleCachectic, acutely ill looking male Tender hepatomegaly with liver edge palpable 4cm below Tender hepatomegaly with liver edge palpable 4cm below
the right costal marginthe right costal margin
Work-upWork-up
CBC-WBC 6.6, CBC-WBC 6.6, HCT 24.0HCT 24.0, Platelet count 149, Platelet count 149 BMP- BMP- Na 128Na 128 otherwise WNLotherwise WNL Ca 8.2, Alb 2.6, Ca 8.2, Alb 2.6, ALT 136, AST 222, Alk phos 360ALT 136, AST 222, Alk phos 360 Lumbar puncture- negativeLumbar puncture- negative Cultures of blood (including AFB), stool, urine - negativeCultures of blood (including AFB), stool, urine - negative Imaging - Hepatomegaly, contracted gallbladder, no Imaging - Hepatomegaly, contracted gallbladder, no
biliary tract dilatation or obstructionbiliary tract dilatation or obstruction
PathologyPathology
Liver biopsy- Granulomas and multiple AFB Liver biopsy- Granulomas and multiple AFB consistent with mycobacteria infectionconsistent with mycobacteria infection
What is Responsible for Patient’s What is Responsible for Patient’s Clinical Presentation ?Clinical Presentation ?
Severe immune deficiency secondary to HIV ?Severe immune deficiency secondary to HIV ? Severe inflammatory reaction after immune reconstitution ?Severe inflammatory reaction after immune reconstitution ? Drug Toxicity ?Drug Toxicity ?
HIV and the Immune Reconstitution HIV and the Immune Reconstitution Inflammatory Syndrome (IRIS)Inflammatory Syndrome (IRIS)
A Challenge to the Recovering Immune System?A Challenge to the Recovering Immune System?
ObjectivesObjectives
Briefly review our current understanding of the effects of Briefly review our current understanding of the effects of HIV infection on the immune systemHIV infection on the immune system
Review proposed mechanisms of Immune reconstitution by Review proposed mechanisms of Immune reconstitution by Highly Active Antiretroviral Therapy (HAART)Highly Active Antiretroviral Therapy (HAART)
Discuss the epidemiology, pathogenesis, common Discuss the epidemiology, pathogenesis, common presentations and management of IRISpresentations and management of IRIS
Identify gaps in current IRIS knowledge baseIdentify gaps in current IRIS knowledge base Take home points!!!Take home points!!!
ABP Adolescent Medicine Content SpecificationsABP Adolescent Medicine Content Specifications
Identify the major opportunistic infections most commonly Identify the major opportunistic infections most commonly encountered in immunocompromised hosts with acquired encountered in immunocompromised hosts with acquired immunodeficiency syndrome (AIDS)immunodeficiency syndrome (AIDS)
Understand the importance of close monitoring of Understand the importance of close monitoring of adolescents infected with human immunodeficiency virus adolescents infected with human immunodeficiency virus (HIV) to determine the co-occurrence of opportunistic (HIV) to determine the co-occurrence of opportunistic infectionsinfections
Virologic and Immunologic Dynamics of Virologic and Immunologic Dynamics of HIV InfectionHIV Infection
Fauci AS et al. Ann Intern Med 1996
CD4 level and Risk of CD4 level and Risk of Opportunistic Infections (OIs)Opportunistic Infections (OIs)
HAART: Current DrugsHAART: Current Drugs
Fusion InhibitorFusion Inhibitor
Enfuvirtide/T-20 Enfuvirtide/T-20 (Fuzeon, SQ inj)(Fuzeon, SQ inj)
Integrase InhibitorsIntegrase Inhibitors
Raltegravir (Isentress)Raltegravir (Isentress)
CCR5 InhibitorsCCR5 Inhibitors
Maraviroc (Selzentry)Maraviroc (Selzentry)
VicrivirocVicriviroc
NNRTIsNNRTIsEfavirenz (Sustiva,)Efavirenz (Sustiva,)Nevirapine (Viramune)Nevirapine (Viramune)Delavirdine (Rescriptor)Delavirdine (Rescriptor)Etravirine (Intelence)Etravirine (Intelence)
Protease InhibitorsProtease InhibitorsRitonavir (Norvir)Ritonavir (Norvir)Saquinavir-HGC Saquinavir-HGC
(Invirase)(Invirase)Indinavir (Crixivan)Indinavir (Crixivan)Nelfinavir (Viracept)Nelfinavir (Viracept)Fosamprenavir (Lexiva)Fosamprenavir (Lexiva)Lopinavir/r (Kaletra)Lopinavir/r (Kaletra)Atazanavir (Reyataz)Atazanavir (Reyataz)Tipranavir (Aptivus)Tipranavir (Aptivus)Darunavir (Prezista)Darunavir (Prezista)
NRTIsNRTIsZidovudine/AZT Zidovudine/AZT
(Retrovir,(Retrovir,Stavudine/d4T (Zerit,Stavudine/d4T (Zerit,Didanosine/ddI Didanosine/ddI
(Videx-EC)(Videx-EC)Lamivudine/3TC (Epivir,)Lamivudine/3TC (Epivir,)Abacavir/ABC (Ziagen)Abacavir/ABC (Ziagen)Zalcitabine/ddC (Hivid)Zalcitabine/ddC (Hivid)Tenofovir/TDF (Viread)Tenofovir/TDF (Viread)Emtricitabine (Emtriva)Emtricitabine (Emtriva)AZT/3TC (Combivir)AZT/3TC (Combivir)AZT/3TC/abacavir AZT/3TC/abacavir
(Trizivir)(Trizivir)ABC/3TC (Epzicom)ABC/3TC (Epzicom)TDF/FTC (Truvada)TDF/FTC (Truvada)TDF/FTC/EFV (Atripla)TDF/FTC/EFV (Atripla)
Virologic Response to HAARTVirologic Response to HAART
CD4 RecoveryCD4 Recovery
Battegay et al. Lancet Inf Dis 2006
Immune Recovery following HAARTImmune Recovery following HAART
First Phase (3-6 months)First Phase (3-6 months)REDISTRIBUTIONREDISTRIBUTION Release of activated memory CD4 cells trapped in lymphoid Release of activated memory CD4 cells trapped in lymphoid
tissues and reduction in apoptotic cell deathtissues and reduction in apoptotic cell death Second phase (6 months- 4years)Second phase (6 months- 4years)
RECONSTITUTIONRECONSTITUTION Naive CD4 cells and memory CD4 contribute to reconstitutionNaive CD4 cells and memory CD4 contribute to reconstitution
Immune Reconstitution Inflammatory SyndromeImmune Reconstitution Inflammatory Syndrome
A pathologic inflammatory immune recognition of antigens A pathologic inflammatory immune recognition of antigens associated with a known or unknown replicating infection associated with a known or unknown replicating infection or persistent non-replicating antigens from a previous or persistent non-replicating antigens from a previous infectioninfection
Results in spectrum of presentations ranging from clinical Results in spectrum of presentations ranging from clinical worsening of a treated opportunistic infection (OI), atypical worsening of a treated opportunistic infection (OI), atypical presentation of an unrecognized OI or autoimmune presentation of an unrecognized OI or autoimmune disorders such as Graves’ diseasedisorders such as Graves’ disease
Occurs in subset of HIV-infected patients on HAARTOccurs in subset of HIV-infected patients on HAART
Categories of IRISCategories of IRIS
Related to underlying opportunistic infectionRelated to underlying opportunistic infection Inflammatory “unmasking” of a previously untreated Inflammatory “unmasking” of a previously untreated
infectioninfection Paradoxical clinical deterioration of an infective process Paradoxical clinical deterioration of an infective process
for which patient is on appropriate treatmentfor which patient is on appropriate treatment Autoimmune e.g Graves DiseaseAutoimmune e.g Graves Disease Malignancies e.g worsening of Kaposi’s sarcomaMalignancies e.g worsening of Kaposi’s sarcoma
Historical View of Non-HIV IRISHistorical View of Non-HIV IRIS
Paradoxical responses well described among non-HIV Paradoxical responses well described among non-HIV infected patients treated for infected patients treated for Mycobacterium tuberculosisMycobacterium tuberculosis (MTB)(MTB)
Thought to be linked to reversal of immunosuppression Thought to be linked to reversal of immunosuppression induced by MTB infectioninduced by MTB infection
Inflammatory reactions during treatment routine in patients Inflammatory reactions during treatment routine in patients with with Mycobacterium lepraeMycobacterium leprae
Recovery of immune cells following bone marrow Recovery of immune cells following bone marrow transplantation or chemotherapytransplantation or chemotherapy
Infections associated with HIV IRISInfections associated with HIV IRIS MycobacteriaMycobacteria
Mycobacterium tuberculosisMycobacterium tuberculosis Mycobacterium aviumMycobacterium avium complex complex M. lepraeM. leprae
CytomegalovirusCytomegalovirus Herpes VirusesHerpes Viruses
Herpes zoster virusHerpes zoster virus Herpes simplex virusHerpes simplex virus Human Herpes virus-8 associated Human Herpes virus-8 associated
Kaposi’s SarcomaKaposi’s Sarcoma Cryptococcus neoformansCryptococcus neoformans BacteriaBacteria
B. HenselaeB. Henselae
Pneumocystis jiroveciiPneumocystis jirovecii pneumonia pneumonia Histoplasma capsulatumHistoplasma capsulatum DermatophytosisDermatophytosis ToxoplasmosisToxoplasmosis Hepatitis B virusHepatitis B virus Hepatitis C virusHepatitis C virus JC virus-PMLJC virus-PML Parvovirus B19Parvovirus B19 Molluscum contagiosumMolluscum contagiosum Strongyloides stercoralisStrongyloides stercoralis & other & other
parasitic infectionsparasitic infections
Most Commonly Seen EntitiesMost Commonly Seen Entities
In a case series and literature review of 182 episodes In a case series and literature review of 182 episodes of IRIS, the most frequently reported associated of IRIS, the most frequently reported associated infections were:infections were: localized herpes zoster (22 percent)localized herpes zoster (22 percent) M. tuberculosis M. tuberculosis (20 percent)(20 percent) M. aviumM. avium complex (17 percent) complex (17 percent) CMV (12 percent)CMV (12 percent) Cryptococcus (6.5 percent)Cryptococcus (6.5 percent)
Shelburne, SA etal. Medicine (Baltimore) 2002; 81:213. Shelburne, SA etal. Medicine (Baltimore) 2002; 81:213.
Non-infectious HIV IRIS EtiologiesNon-infectious HIV IRIS Etiologies
Graves DiseaseGraves Disease Systemic lupus erythematosus (SLE)Systemic lupus erythematosus (SLE) Rheumatoid arthritisRheumatoid arthritis SarcoidosisSarcoidosis Guillain-Barre syndromeGuillain-Barre syndrome AIDS related lymphomaAIDS related lymphoma
Difficulties with Definition of HIV IRISDifficulties with Definition of HIV IRIS
Wide variety of underlying OIsWide variety of underlying OIs Need to incorporate both unmasking of clinically silent Need to incorporate both unmasking of clinically silent
infections and worsening of previously diagnosed OIsinfections and worsening of previously diagnosed OIs Difficulty in establishing that patient’s clinical presentation Difficulty in establishing that patient’s clinical presentation
is not due to a new microbial process or drug toxicityis not due to a new microbial process or drug toxicity
Proposed Diagnostic Criteria for HIV IRISProposed Diagnostic Criteria for HIV IRIS
HIV positiveHIV positive Receiving HAARTReceiving HAART
Decrease in HIV-1 RNA level from baselineDecrease in HIV-1 RNA level from baseline Increase in CD4+ cells from baselineIncrease in CD4+ cells from baseline
Clinical symptoms consistent with inflammatory Clinical symptoms consistent with inflammatory processprocess
Clinical course not consistent with:Clinical course not consistent with: Expected course of previously diagnosed OIExpected course of previously diagnosed OI Expected course of newly diagnosed OIExpected course of newly diagnosed OI Drug toxicityDrug toxicity
Shelburne et al. Medicine 2002
EpidemiologyEpidemiology
Develops in 15-25% of patients receiving HAARTDevelops in 15-25% of patients receiving HAART Up to 45% incidence rate in patients with known Up to 45% incidence rate in patients with known
opportunistic infectionsopportunistic infections Most cases develop within the first 3 months of treatment Most cases develop within the first 3 months of treatment
(median 6-8 weeks)(median 6-8 weeks) Reports of patients presenting up to 2 years after initiation of Reports of patients presenting up to 2 years after initiation of
treatmenttreatment
Why Do These Why Do These Inflammatory Reactions Occur?Inflammatory Reactions Occur?
PathogenesisPathogenesis
Not well understoodNot well understood May vary from one infection to the otherMay vary from one infection to the other The trigger for this paradoxical reaction is The trigger for this paradoxical reaction is probablyprobably an an
excessive enhancement of immune response to excessive enhancement of immune response to disease-specific antigens leading to an overproduction of disease-specific antigens leading to an overproduction of inflammatory mediators. inflammatory mediators.
Host genetic susceptibility –carriage of specific HLA allelesHost genetic susceptibility –carriage of specific HLA alleles
HIV IRIS SymptomsHIV IRIS Symptoms
Depends on prevailing opportunistic infections in the Depends on prevailing opportunistic infections in the environmentenvironment
Corresponds to patients’ specific underlying Corresponds to patients’ specific underlying condition and locationcondition and location M. tuberculosis, M. tuberculosis, zoster, zoster, M. aviumM. avium complex, CMV, complex, CMV,
Cryptococcus Cryptococcus
Shelburne et al. Medicine 2002
Paradoxical HIV Tuberculosis IRISParadoxical HIV Tuberculosis IRIS
Recurrent, worsening or new clinical or radiologic Recurrent, worsening or new clinical or radiologic manifestations of TBmanifestations of TB
Return of symptoms, fever, enlargement of nodes, Return of symptoms, fever, enlargement of nodes, worsening radiographic pulmonary infiltratesworsening radiographic pulmonary infiltrates
CNS involvement with tuberculomata or tuberculous CNS involvement with tuberculomata or tuberculous meningitismeningitis
Paradoxical TB IRIS LymphadenitisParadoxical TB IRIS Lymphadenitis
Dhasmana et al. Drugs 2008
Paradoxical TB IRISParadoxical TB IRIS
Dhasmana et al. Drugs 2008
At HAART Initiation 10 Days into TB IRIS
Non-Tuberculous MycobacteriaNon-Tuberculous Mycobacteria
Usual presentation is pulmonary disease or bacteremic Usual presentation is pulmonary disease or bacteremic wasting illness associated with fever, gastrointestinal wasting illness associated with fever, gastrointestinal disease and anemiadisease and anemia
MAC IRIS presents with more focal inflammatory diseaseMAC IRIS presents with more focal inflammatory disease Peripheral lymphadenitis with or without abscess formation, Peripheral lymphadenitis with or without abscess formation,
intraabdominal disease and involvement of joint, skin, soft intraabdominal disease and involvement of joint, skin, soft tissues and spinetissues and spine
MAC IRISMAC IRIS
Abdominal lymphadenopathy with evidence of psoas abscess
CMV IRIS-Immune Recovery UveitisCMV IRIS-Immune Recovery Uveitis
Patients present with visual impairment and floatersPatients present with visual impairment and floaters Occurs in patients with prior CMV infectionOccurs in patients with prior CMV infection Distinct from necrotizing retinitis with minimal intraocular Distinct from necrotizing retinitis with minimal intraocular
inflammation of classic CMV retinitisinflammation of classic CMV retinitis High intensity of inflammatory response inducing High intensity of inflammatory response inducing
proliferative vitroretinopathy and posterior subcapsular proliferative vitroretinopathy and posterior subcapsular cataractscataracts
Diagnosis requires a high level of suspicionDiagnosis requires a high level of suspicion
CMV RetinitisCMV Retinitis
CMV RetinitisNormal Retina
Paradoxical Cryptococcal IRISParadoxical Cryptococcal IRIS
Presents with recurrent meningitis symptomsPresents with recurrent meningitis symptoms CSF shows inflammation with marked leukocytosis but CSF shows inflammation with marked leukocytosis but
fungal cultures typically negativefungal cultures typically negative Neuroimaging shows significant inflammationNeuroimaging shows significant inflammation Other findings include cryptococcomas, cerebellitis, Other findings include cryptococcomas, cerebellitis,
lymphadenitis, mediastinitis, cavitating pneumonia and skin lymphadenitis, mediastinitis, cavitating pneumonia and skin lesionslesions
Patients typically have raised intracranial pressure requiring Patients typically have raised intracranial pressure requiring serial lumbar punctures.serial lumbar punctures.
Mortality up to 66%Mortality up to 66%
Neuroimaging in Cryptococcal IRISNeuroimaging in Cryptococcal IRIS
Zoster HIV IRISZoster HIV IRIS
Dermatomal varicella zoster comprises 9-40% of IRIS cases Dermatomal varicella zoster comprises 9-40% of IRIS cases in large observational IRIS cohortsin large observational IRIS cohorts
Patients present with typical or atypical dermatomal Patients present with typical or atypical dermatomal involvement without dissemination or systemic symptomsinvolvement without dissemination or systemic symptoms
Complications such as encephalitis, myelitis, cranial and Complications such as encephalitis, myelitis, cranial and peripheral nerve palsies possible but rare.peripheral nerve palsies possible but rare.
Risk Factors for HIV IRIS?Risk Factors for HIV IRIS?
Design: Retrospective cohort identified through a city-wide Design: Retrospective cohort identified through a city-wide prospective surveillance programprospective surveillance program
Method: Retrospective chart review of 180 HIV infected Method: Retrospective chart review of 180 HIV infected patients on HAART coinfected with patients on HAART coinfected with Mycobacterium Mycobacterium TuberculosisTuberculosis, , Mycobacterium avium complexMycobacterium avium complex or or Cryptococcus neoformansCryptococcus neoformans between 1997-2000 between 1997-2000
AIDS 2005, 19:399-406
Shelburne et al. AIDS 2005
CD4 and Viral Load Response CD4 and Viral Load Response as IRIS Risk Factorsas IRIS Risk Factors
Shelburne et al. AIDS 2005
Determinants of IRISDeterminants of IRIS
1) extent of CD4+ T-cell 1) extent of CD4+ T-cell immune suppression prior to immune suppression prior to the initiation of HAART the initiation of HAART (rapidity of increase)(rapidity of increase)
2) degree of viral 2) degree of viral suppression and immune suppression and immune recovery following the recovery following the initiation of HAART initiation of HAART
3) Prior opportunistic 3) Prior opportunistic infections (known or infections (known or unknown)unknown)
Design: Case-control studyDesign: Case-control study Methods: Patients from Johns Hopkins HIV Clinic who had Methods: Patients from Johns Hopkins HIV Clinic who had
IRIS were identified and matched with 4 controls without IRIS were identified and matched with 4 controls without IRIS who initiated HAART within 6 months of the caseIRIS who initiated HAART within 6 months of the case
Journal of Acquired Immune Deficiency Syndrome Dec 2007
Manabe et al. J Acquir Immune Defic Syndr 2007
*BPI- boosted protease inhibitor
Risk Factors for IRISRisk Factors for IRIS
An active or subclinical OIAn active or subclinical OI A nadir CD4 cell count below 100 cells/µl (or 50 cells/µl A nadir CD4 cell count below 100 cells/µl (or 50 cells/µl
as reported in other studies)as reported in other studies) Robust immunologic response to HAARTRobust immunologic response to HAART The initiation of HAART within the first 4–8 weeks of The initiation of HAART within the first 4–8 weeks of
starting therapy for an OIstarting therapy for an OI Being ART naïve at the time of OI diagnosisBeing ART naïve at the time of OI diagnosis
DiagnosisDiagnosis
Clinical- History! History! History!Clinical- History! History! History! Investigations to exclude alternative explanations for Investigations to exclude alternative explanations for
clinical deteriorationclinical deterioration Failure of antimicrobial therapyFailure of antimicrobial therapy Suboptimal drug concentrations due to non-adherence or Suboptimal drug concentrations due to non-adherence or
malabsorptionmalabsorption Adverse drug reactionAdverse drug reaction Alternative infection or malignancyAlternative infection or malignancy
TreatmentTreatment
No randomized control trials available so largely based on No randomized control trials available so largely based on anecdotal reportsanecdotal reports
Treatment for the underlying pathogen should generally be Treatment for the underlying pathogen should generally be started or continued in patients who develop IRIS. started or continued in patients who develop IRIS. For most patients with untreated HIV and known OIs with effective For most patients with untreated HIV and known OIs with effective
antimicrobial therapies, reasonable to delay HAART for 1-2 months antimicrobial therapies, reasonable to delay HAART for 1-2 months while treating the OIs in an attempt to decrease the likelihood of IRIS. while treating the OIs in an attempt to decrease the likelihood of IRIS.
Continue HAART in the majority of cases. However, if Continue HAART in the majority of cases. However, if the manifestations of IRIS are considered to be life or the manifestations of IRIS are considered to be life or organ-threatening, discontinuation of HAART is organ-threatening, discontinuation of HAART is sometimes necessary.sometimes necessary.
Corticosteroids or NSAIDS may help decrease the Corticosteroids or NSAIDS may help decrease the inflammatory response in some patients with IRIS.inflammatory response in some patients with IRIS.
PrognosisPrognosis
Usually self-limited, especially if the preexisting infection is Usually self-limited, especially if the preexisting infection is effectively treated. effectively treated.
Retrospective review Retrospective review IRIS patients had 1.34 more hospital admissions and 2.52 more IRIS patients had 1.34 more hospital admissions and 2.52 more
invasive procedures after 12 monthsinvasive procedures after 12 months Patients with IRIS had greater likelihood of successful immune Patients with IRIS had greater likelihood of successful immune
reconstitution (RR 2.24; P= 0.003) and increased rate of viral reconstitution (RR 2.24; P= 0.003) and increased rate of viral suppression (RR 3.32; P,< 0.001) after 24 monthssuppression (RR 3.32; P,< 0.001) after 24 months
No significant difference in mortality 24months after No significant difference in mortality 24months after starting HAARTstarting HAART
•Shelburne et al AIDS 2005
Unanswered QuestionsUnanswered Questions
Disease specific guidelines?Disease specific guidelines? True pathophysiology of IRIS ?True pathophysiology of IRIS ? Genetic markers to help predict patients who will develop Genetic markers to help predict patients who will develop
HIV-IRIS?HIV-IRIS? Predictors of HIV IRIS?Predictors of HIV IRIS? Optimal treatment for HIV IRIS?Optimal treatment for HIV IRIS? Optimal timing to start HAART in patients with Optimal timing to start HAART in patients with
opportunistic infections?opportunistic infections? Impact of IRIS on successful HAART implementation in Impact of IRIS on successful HAART implementation in
developing countries?developing countries?
Back to the PatientBack to the Patient
Received clarithromycin, ethambutol and rifabutin for MAI Received clarithromycin, ethambutol and rifabutin for MAI treatmenttreatment
Went on to develop CMV retinitis and dermatomal zoster Went on to develop CMV retinitis and dermatomal zoster thought related to IRISthought related to IRIS
Currently on HAART with CD4 count of 419 and an Currently on HAART with CD4 count of 419 and an undetectable viral loadundetectable viral load
Patient doing very wellPatient doing very well
Take Home PointsTake Home Points
History! History! History!History! History! History! Specific symptoms and time courseSpecific symptoms and time course History of OI’s including recently diagnosed OI’sHistory of OI’s including recently diagnosed OI’s Treatment of OI’s including initiation, medication adherence, therapy duration Treatment of OI’s including initiation, medication adherence, therapy duration
and clinical responseand clinical response ART initiation: date, regimen, adherenceART initiation: date, regimen, adherence Nadir CD4 count and viral loadNadir CD4 count and viral load Current CD4 count and HIV viral loadCurrent CD4 count and HIV viral load Medications especially new medicationsMedications especially new medications
HIV IRIS is a diagnosis of exclusionHIV IRIS is a diagnosis of exclusion Be suspicious!Be suspicious!
http://www.tac.org.za/community/files/Avelile%20before%20and%20after%20ART.jpg
AcknowledgementsAcknowledgements
Dr Seun Falade-NwuliaDr Seun Falade-Nwulia
ReferencesReferences
Hung YF, Ross FC Luis PV . AIDS Science and Society 4Hung YF, Ross FC Luis PV . AIDS Science and Society 4thth Edition Edition Shelburne SA et al. Immune reconstitution Syndrome. Emergence of a Unique Shelburne SA et al. Immune reconstitution Syndrome. Emergence of a Unique
Syndrome During Highly Active Antiretroviral Therapy. Medicine 2002:81. Syndrome During Highly Active Antiretroviral Therapy. Medicine 2002:81. 213-27213-27
Shelburne SA, Richard JH. The Immune Reconstitution Inflammatory Shelburne SA, Richard JH. The Immune Reconstitution Inflammatory Syndrome. AIDS Rev 2003;5:67-79Syndrome. AIDS Rev 2003;5:67-79
Dhasmana DJ et al. Immune Reconstitution Inflammatory Syndrome in HIV-Dhasmana DJ et al. Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients Receiving Antiviral therapy. Pathogenesis, Clinical Infected Patients Receiving Antiviral therapy. Pathogenesis, Clinical Manifestations and Management. Drugs 2008:68(2) 191-208Manifestations and Management. Drugs 2008:68(2) 191-208
Shelburne SA et al. Incidence and risk factors for immune reconstitution Shelburne SA et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005;19:399-4062005;19:399-406
Shelburne SA et al Immune reconstitution inflammatory syndrome: more Shelburne SA et al Immune reconstitution inflammatory syndrome: more answers, more questions. Journal of Antimicrobial therapy (2006) 57: 167-answers, more questions. Journal of Antimicrobial therapy (2006) 57: 167-170170
Manabe YC et al. Immune Reconstitution Inflammatory Syndrome. Risk Manabe YC et al. Immune Reconstitution Inflammatory Syndrome. Risk facors and Treatment Implications. J Acquir Immune Defic Syndr facors and Treatment Implications. J Acquir Immune Defic Syndr 2007:46(4)456-462 2007:46(4)456-462
ReferencesReferences
Murdoch D et al. Immune reconstitution inflammatory syndrome (IRIS): Murdoch D et al. Immune reconstitution inflammatory syndrome (IRIS): review of commom infectious manifestations and treatment options. AIDS review of commom infectious manifestations and treatment options. AIDS Research and Therapy 2007 4:9Research and Therapy 2007 4:9
Boer M et al. Immune restoration disease in HIV-Infected individuals Boer M et al. Immune restoration disease in HIV-Infected individuals receiving highly active antiretroviral therapy: clinical and immunologic receiving highly active antiretroviral therapy: clinical and immunologic characteristics. Netherlands Journal of Medicine 2003;61(12)408-412characteristics. Netherlands Journal of Medicine 2003;61(12)408-412
French et al. Immune restoration disease after the treatment of French et al. Immune restoration disease after the treatment of immunodeficient HIV infected patients with highly active antiretroviral immunodeficient HIV infected patients with highly active antiretroviral therapy. HIV Medicine 2000;1107-115therapy. HIV Medicine 2000;1107-115
Jevtovic et al. The prevalence and risk of immune restoration disease in Jevtovic et al. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV HIV-infected patients treated with highly active antiretroviral therapy. HIV Medicine 2005;6:140-143Medicine 2005;6:140-143
Murdoch D et al. Incidence and risk factors for the immune reconstitution Murdoch D et al. Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective inflammatory syndrome in HIV patients in South Africa: a prospective study. AIDS 2008 22:601- 610study. AIDS 2008 22:601- 610
““Atazana….who?” Atazana….who?” A Discussion of Antiretrovirals for the A Discussion of Antiretrovirals for the
Management of HIV InfectionManagement of HIV Infection
Allison Agwu, M.D. Allison Agwu, M.D. Alice Jenh, PharmDAlice Jenh, PharmD
Adolescent Grand RoundsAdolescent Grand RoundsJune 26, 2009June 26, 2009
ObjectivesObjectives
To review important considerations, To review important considerations, contraindications and precautions in contraindications and precautions in selecting/reviewing an antiretroviral selecting/reviewing an antiretroviral regimen (first-line and subsequent). regimen (first-line and subsequent).
To recognize appropriate and inappropriate To recognize appropriate and inappropriate regimens and relevant medication regimens and relevant medication interactions interactions and adverse effects. and adverse effects.
ABP Adolescent Medicine Content OutlineABP Adolescent Medicine Content Outline
Primary Provider & HIV-Infected PatientsPrimary Provider & HIV-Infected Patients
Make no assumptions about medications (names, doses)Make no assumptions about medications (names, doses) Be able to recognize an appropriate/inappropriate regimenBe able to recognize an appropriate/inappropriate regimen Be cognizant of potential for drug-drug interactions (need for dose Be cognizant of potential for drug-drug interactions (need for dose
adjustments)adjustments) Be aware of contraindications/precautions when initiating other Be aware of contraindications/precautions when initiating other
medications!!!medications!!! Suspect and recognize adverse affects of therapy and medicationsSuspect and recognize adverse affects of therapy and medications Maintain open communication with HIV provider & ID serviceMaintain open communication with HIV provider & ID service Utilize pharmacy review and assistanceUtilize pharmacy review and assistance
Potential Drug InteractionsPotential Drug Interactions
CHECK EVERYTHING!!!CHECK EVERYTHING!!! PIs- cytochrome P450 inhibitors/inducers can have major PIs- cytochrome P450 inhibitors/inducers can have major
interactions with:interactions with: anticonvulsants, azoles; OCPs; rifampin, rifabutin; lipid-lowering anticonvulsants, azoles; OCPs; rifampin, rifabutin; lipid-lowering
agents (simvastatin/atorvastatin- contra-indicated); H2 blockers agents (simvastatin/atorvastatin- contra-indicated); H2 blockers (ATV!!!); CCBs, anticoagulants, anti-depressants, methadone, (ATV!!!); CCBs, anticoagulants, anti-depressants, methadone, anti-histamines, inhaled steroids; macrolides anti-histamines, inhaled steroids; macrolides
NNRTIs-lipid-lowering agents (reduces), OCPs, NNRTIs-lipid-lowering agents (reduces), OCPs, anticoagulants, methadoneanticoagulants, methadone
NRTIs- metforminNRTIs- metformin
Recognize adverse effects of ARVsRecognize adverse effects of ARVs
Lactic acidosis (NRTIs)Lactic acidosis (NRTIs) Pancreatitis (NRTIs, primarily DDI)Pancreatitis (NRTIs, primarily DDI) ABC - hypersensitivity (HLA B*5701), myocardial riskABC - hypersensitivity (HLA B*5701), myocardial risk Renal calculi (IDV)Renal calculi (IDV) Peripheral neuropathy (NRTIs)Peripheral neuropathy (NRTIs) Teratogenecity (EFV)Teratogenecity (EFV) Tenofovir (bone loss, renal dysfunction)Tenofovir (bone loss, renal dysfunction) Metabolic syndrome (PIs)Metabolic syndrome (PIs) Lipodystrophy (NRTIs, PIs)Lipodystrophy (NRTIs, PIs)
HIV ResourcesHIV Resources
Utilize resources Utilize resources HIV specialists HIV specialists IPC teamIPC team ID consultation service ID consultation service ALICE JENH, PHARMD (PAGERBOX-ABLE)ALICE JENH, PHARMD (PAGERBOX-ABLE)
THANK YOU!!!THANK YOU!!!
Other topics that you want to hear about?Other topics that you want to hear about?