chemical pathology ii hiv aids

8/6/2019 Chemical Pathology II HIV AIDS

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MANAGEMENT OF HIVMANAGEMENT OF HIV

INFECTED PATIENTSINFECTED PATIENTS&&

METABOLICMETABOLIC

COMPLICATIONS OFCOMPLICATIONS OF

HAARTHAART

A SEMINAR PRESENTATION BYA SEMINAR PRESENTATION BY

GROUP 3GROUP 3

Coordinator - Dr. S.A Adebisi


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INTRODUCTIONINTRODUCTION

Human Immunodeficiency Virus (HIV)Human Immunodeficiency Virus (HIV)infection is a chronic non curable butinfection is a chronic non curable butcontrollable condition.controllable condition.

The clinical manifestation of HIV infectionThe clinical manifestation of HIV infectionis a syndrome called Acquired Immuneis a syndrome called Acquired Immune

Deficiency Syndrome (AIDS)Deficiency Syndrome (AIDS)


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Management of HIV infectionManagement of HIV infection

involves the following steps:involves the following steps: Proper History takingProper History taking

Past medical history eg history of bloodPast medical history eg history of bloodtransfusiontransfusion

Social history eg multiple sexual partnersSocial history eg multiple sexual partners Family historyFamily history

Proper physical examinationProper physical examination Appropriate investigation eg lentiviral screeningAppropriate investigation eg lentiviral screening

testtest Treatment using both pharmacologic and nonTreatment using both pharmacologic and non--

pharmacologic approachpharmacologic approach


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AIMS OF MANAGEMENTAIMS OF MANAGEMENT

To alleviate the symptoms of AIDS in order toTo alleviate the symptoms of AIDS in order tomaintain proper physical and mental healthmaintain proper physical and mental health

To avoid transmission of the virusTo avoid transmission of the virus To provide appropriate palliative support as neededTo provide appropriate palliative support as needed To provide psychological support for patients asTo provide psychological support for patients as

well as their family and friendswell as their family and friends To achieve all these aims, a multidisciplinary teamTo achieve all these aims, a multidisciplinary team

approach is needed and patient confidentiality mustapproach is needed and patient confidentiality must

be strictly observed.be strictly observed.


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CURRENT TREATMENTCURRENT TREATMENT

GUIDELINESGUIDELINES Non Pharmacologic approachNon Pharmacologic approach

-- Strict confidentialityStrict confidentiality

-- Psychological support for patient as well asPsychological support for patient as well asfamily members, friends and care giversfamily members, friends and care givers-- Dietary advice and assessmentDietary advice and assessment-- Clear advice on reducing the risk of HIVClear advice on reducing the risk of HIV

transmissiontransmission Pharmacologic approachPharmacologic approach

--Use of Antiretroviral drugsUse of Antiretroviral drugs


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CLASSIFICATION OFCLASSIFICATION OF

ANTIRETROVIRAL DRUGSANTIRETROVIRAL DRUGS Reverse transcriptase inhibitorsReverse transcriptase inhibitors

Nucleoside analogues (NRTIs) eg Zidovudine,Nucleoside analogues (NRTIs) eg Zidovudine,Didanosine, LamivudineDidanosine, Lamivudine

Nucleotide analogues (NtRTIs) eg TenofovirNucleotide analogues (NtRTIs) eg Tenofovir Non nucleoside drugs eg Nevirapine, EfavirenzNon nucleoside drugs eg Nevirapine, Efavirenz

Protease inhibitors eg Nelfinavir, Amprenavir,Protease inhibitors eg Nelfinavir, Amprenavir,IndinavirIndinavir

Fusion inhibitors eg EnfurvitideFusion inhibitors eg Enfurvitide Integrase inhibitorsIntegrase inhibitors Entry inhibitorsEntry inhibitors


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None of these drugsNone of these drugs isis used alone in theused alone in thechemotherapy of HIV because of the highchemotherapy of HIV because of the highrisk of development of resistance thus arisk of development of resistance thus acombination therapy is employed in thecombination therapy is employed in theform of HAART (Highly Activeform of HAART (Highly Active

Antiretroviral Therapy) whichAntiretroviral Therapy) which is theis thecurrent WHO approved drug combinationcurrent WHO approved drug combinationregimenregimen


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Starting TherapyStarting Therapy


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INDICATIONS FOR THERAPYINDICATIONS FOR THERAPY1. Clinically advanced HIV disease1. Clinically advanced HIV disease

yy WHO Stage I or II HIV Disease with CD 4 Cell count


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Adherence

Access to medication

Life situation

Disease stage

Challenges to Successful HIV TherapyChallenges to Successful HIV Therapyand Considerations When Initiating Therapyand Considerations When Initiating Therapy

Replication rate - Viral load

Mutation rate resistance

Latent reservoirs of HIV

Virus Drug

Patient

Clinician

PotencyPotency PharmacokineticsPharmacokinetics

(dosage schedule)(dosage schedule)

TolerabilityTolerability

ToxicityToxicity

ConvenienceConvenience

ResistanceResistance

Clinician experience

Communication skills


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CHOICE OF DRUGS AND DRUGCHOICE OF DRUGS AND DRUG

COMBINATIONSCOMBINATIONSThe drug regimen used for starting therapyThe drug regimen used for starting therapy

must be formulated to suit each patientsmust be formulated to suit each patients

needsneedsTreatment is initiated with three drugsTreatment is initiated with three drugs

Two NRTIs, which form the backbone ofTwo NRTIs, which form the backbone of

the regimenthe regimen A boosted protease inhibitor or anA boosted protease inhibitor or an

NNRTINNRTI


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Basis of drug selectionBasis of drug selection

1.1. EffectivenessEffectiveness

2.2. Adherence issues eg Efavirenz is suitable for once dailyAdherence issues eg Efavirenz is suitable for once dailydosingdosing

3.3. Side effect profile and potential drug reactionsSide effect profile and potential drug reactions

4.4. Drug interactions e.g. Zidovudine blocks intracellularDrug interactions e.g. Zidovudine blocks intracellularphosphorylation of Stavudinephosphorylation of Stavudine

5.5. Resistance and cross resistance pattern of drugsResistance and cross resistance pattern of drugs

6.6. Psychologic state of the patient eg Drug of choice forPsychologic state of the patient eg Drug of choice fornaive patients include Abacavir, Didanosine, Lamivudine,naive patients include Abacavir, Didanosine, Lamivudine,Tenofovir and Zidovudine. Stavudine is notTenofovir and Zidovudine. Stavudine is notrecommended for such patients.recommended for such patients.


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Drug CombinationsDrug Combinations

The preferred initial regimens areThe preferred initial regimens are

1.1. Zidovudine + Lamivudine + EfavirenzZidovudine + Lamivudine + Efavirenz

2.2. Tenofovir + Emtricitabine + EfavirenzTenofovir + Emtricitabine + Efavirenz

3.3. Zidovudine + Lamivudine + LopinavirZidovudine + Lamivudine + Lopinavirboosted with Ritonavirboosted with Ritonavir

4.4. Tenofovir + Emtricitabine + LopinazirTenofovir + Emtricitabine + Lopinazirboosted with Ritonavirboosted with Ritonavir


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MONITORING THERAPYMONITORING THERAPY

After initiation of TherapyAfter initiation of Therapy-- Viral load measured 4Viral load measured 4--8 wks to assess efficacy8 wks to assess efficacy

. In nave patients viral load of < 50. In nave patients viral load of < 50 copies per mls shouldcopies per mls shouldbe achievedbe achieved within 3within 3--6 months of therapy6 months of therapy

. In heavily pre. In heavily pre--treated patients viral load of 1000 copies per mlstreated patients viral load of 1000 copies per mlsshould beshould be achieved within 3achieved within 3--6 months of therapy6 months of therapy

-- Regular clinical assessment should includeRegular clinical assessment should include-- clinical history and examinationclinical history and examination-- WeightWeight-- HIV Viral loadHIV Viral load-- CD 4 countCD 4 count-- FBCFBC

-- Liver and renal function tests.Liver and renal function tests.-- Fasting lipid profileFasting lipid profile-- Blood GlucoseBlood Glucose

Viral load and CD 4 count to be measured at 12 wks or 3 monthlyViral load and CD 4 count to be measured at 12 wks or 3 monthlyintervalsintervals


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Drug InteractionsDrug Interactions

Both protease inhibitors and NNRTIs areBoth protease inhibitors and NNRTIs aremetabolized through the cytochrome P450metabolized through the cytochrome P450

dependent pathway and some are able todependent pathway and some are able toinhibit and induce hepatic cytochromeinhibit and induce hepatic cytochrome

P450 enzyme system thus theyre capableP450 enzyme system thus theyre capable

of influencing both their own and otherof influencing both their own and otherdrug metabolic rates.drug metabolic rates.


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Drug Interactions may result in theDrug Interactions may result in the

followingfollowing1.1. Sub therapeutic or toxic drug levelsSub therapeutic or toxic drug levels

2.2. Risk of treatment failuresRisk of treatment failures

3.3. Development of viral resistanceDevelopment of viral resistance


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Circumstances that warrantCircumstances that warrant

stoppage of antiretroviral therapystoppage of antiretroviral therapy Cumulative toxicityCumulative toxicity Potential drug interaction with modificationPotential drug interaction with modification

needed to deal with another pressing problem.needed to deal with another pressing problem.E.g. treatment of Tuberculosis with antimicrobialE.g. treatment of Tuberculosis with antimicrobialagentsagents

Patients poor adherence which increases the riskPatients poor adherence which increases the riskof viral resistanceof viral resistance

Virologically failing therapy and multidrugVirologically failing therapy and multidrugresistant viral strainsresistant viral strains

Poor quality of life of patient despite treatmentPoor quality of life of patient despite treatment


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Limitations to HAART TherapyLimitations to HAART Therapy

1.1.Inability of the current drugs to clear HIV fromInability of the current drugs to clear HIV fromcertain intracellular poolscertain intracellular pools

2.2.The occurrence of serious side effectsThe occurrence of serious side effects3.3.Failure of strict drug adherenceFailure of strict drug adherence4.4.Complex drug interactionsComplex drug interactions5.5.The on going emergence of multiThe on going emergence of multi--drug resistantdrug resistant

viral strainsviral strains In case of resistance to HAART,In case of resistance to HAART,

-- MegaMega--HAART or Salvage therapyHAART or Salvage therapy-- one or two ARV that induce HIV mutationsone or two ARV that induce HIV mutations


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Main Reasons for Discontinuation ofMain Reasons for Discontinuation of

HAARTHAART

Other

8%

Toxicity

58%

Virological

Failure

14%

Nonadherence

20%

d Arminio Monforte et al. AIDS 2000;14:499-507d Arminio Monforte et al. AIDS 2000;14:499-507


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METABOLICMETABOLIC

COMPLICATIONSCOMPLICATIONSOFOF

HAARTHAART(Highly Active Antiretroviral Therapy)(Highly Active Antiretroviral Therapy)


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METABOLIC COMPLICATIONSMETABOLIC COMPLICATIONS

LipodystrophyLipodystrophy

Insulin resistanceInsulin resistance

Frank DiabetesFrank DiabetesMellitusMellitus

DyslipidaemiaDyslipidaemia

HyperbilirubinaemiaHyperbilirubinaemia

Bone DisordersBone Disorders

Lactic acidaemia &Lactic acidaemia &

acidosisacidosis PancreatitisPancreatitis

JaundiceJaundice


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LIPODYSTROPHYLIPODYSTROPHY

LipoatrophyLipoatrophy-- Peripheral and subcutaneous fat lossPeripheral and subcutaneous fat loss

-- Pathogenesis not clearly understood but some factorsPathogenesis not clearly understood but some factorshave been implicatedhave been implicated

-- Management involves change of drug regimen amongManagement involves change of drug regimen amongother practicesother practices

LipohypertrophyLipohypertrophy-- Dorsocervical fat accumulation patients may present asDorsocervical fat accumulation patients may present ashaving cushignoid syndromehaving cushignoid syndrome


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LipoatrophyLipoatrophy

Facial lipoatrophy characterised bysunken cheeks and hollow temples due to

buccal and subcutaneous fat loss


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LipohypertrophyLipohypertrophy

Fat redistribution in an HIV infected patient


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Metabolic SyndromeMetabolic Syndrome

Insulin Resistance & Frank type IIInsulin Resistance & Frank type IIdiabetesdiabetes

HyperinsulinaemiaHyperinsulinaemia

Impaired glucose intoleranceImpaired glucose intolerance

HypertriglyceridaemiaHypertriglyceridaemia


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Other lipid abnormalities andOther lipid abnormalities and

dyslipidaemiadyslipidaemia Increased high density lipoprotein (HDL)Increased high density lipoprotein (HDL)

Increased total cholesterolIncreased total cholesterol

HypertriglyceridaemiaHypertriglyceridaemia


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Managing dyslipidaemia in HIV-infected patients


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Bone disordersBone disorders

OsteopeniaOsteopenia

OsteoporosisOsteoporosis

As a result of high bone turnover withAs a result of high bone turnover withincreased levels of bone formation andincreased levels of bone formation andresorptionresorption


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Lactic acidosis and acidaemiaLactic acidosis and acidaemia

Characterised byCharacterised by Asymptomatic elevation of blood lactate levelsAsymptomatic elevation of blood lactate levels Acidemia is characterised by lactate levels > 2.5 mmol/LAcidemia is characterised by lactate levels > 2.5 mmol/L

Acidosis is characterised by an increase in venous lactateAcidosis is characterised by an increase in venous lactateconc. > 2.0mmol/L and pH levels < 7.30.conc. > 2.0mmol/L and pH levels < 7.30.Clinical features include constitutional symptoms such asClinical features include constitutional symptoms such asfatigue, malaise and weight loss. Multiorgan failure suchfatigue, malaise and weight loss. Multiorgan failure such

as dysarrthmias, respiratory failure, coma and evenas dysarrthmias, respiratory failure, coma and evendeath could occur.death could occur.


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ConclusionConclusion

The treatment of HIV infection has been complicated byThe treatment of HIV infection has been complicated byshortshort--term toxicities and longterm toxicities and long--term complications. Theterm complications. Thelatter were initially referred to as the components of thelatter were initially referred to as the components of the

"lipodystrophy syndrome." These complications are more"lipodystrophy syndrome." These complications are moreaccurately referred to as the morphologic and metabolicaccurately referred to as the morphologic and metaboliccomplications of HIV disease and ART. Although thesecomplications of HIV disease and ART. Although thesecomplications have been well described andcomplications have been well described andcharacterized, the mechanisms underlying theircharacterized, the mechanisms underlying their

occurrence remain elusive.occurrence remain elusive.These metabolic complications are life threatening andThese metabolic complications are life threatening andshould be taking into consideration in HIVshould be taking into consideration in HIV--infectedinfectedpatients and those patients on the HAART therapy.patients and those patients on the HAART therapy.


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chemical pathology ii hiv aids

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