PHARMACOTHERAPY OF HIV-AIDS and HAART induced ADRs

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PHARMACOTHERAPY OF HIV/AIDS AND COMMON HAART INDUCED ADVERSE DRUG REACTIONS IN ADULTS: 

PHARMACOTHERAPY OF HIV/AIDS AND COMMON HAART INDUCED ADVERSE DRUG REACTIONS IN ADULTS BY: MINYAHIL ALEBACHEW Clinical Pharmacy, PG Yr-II Jimma University, Ethiopia JAN. 2012

Outline: 

Outline

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Introduction

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Potent combinations of antiretroviral drugs (HAART) dramatically altered the natural progression significantly improved the quality of life a pronounced decline AIDS-related opportunistic infections and deaths shifted the outlook of HIV infection from a fatal a manageable disease

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HAART Advances continue new antiretroviral agents in new therapeutic drug classes, and novel, potent combinations of antiretrovirals clinicians working in the area of HIV remain cautious 25% of patients will fail therapy in the first year approximately 25% will have to change regimens within the first year owing to drug-related adverse events development of resistance patient compliance

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Epidemiology

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HIV infection/AIDS is a global pandemic . At the end of 2009 , an estimated 33.3 million PLWHA according to UNAIDS. More than 95% of people living with HIV/AIDS reside in low- and middle-income countries; 50% are female , and 2.5 million are children <15 years .

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dramatic decline (# of AIDS-related opportunistic infections and deaths) industrialized countries HIV remains a leading cause of death throughout many regions of the world Access to newer, more potent antiretroviral regimens and monitoring techniques are often limited economics and politics

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the availability of antiretroviral therapy has resulted in an 80% decline in AIDS death rates between 1990 and 2003. A significant proportion of people ( 25% ) are unaware that they are HIV-positive Racial and ethnic minorities continue to be disproportionately affected by HIV

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Transmission through sexual intercourse remains a predominant route of infection, unsafe sex between men ~ 44% of cases, heterosexual intercourse ~34% of cases The proportion of women newly diagnosed has increased dramatically (from 15% in 1995 to 27% in 2004). patients >50 years of age represent a rapidly expanding group new infections and On HAART (extending life expectency )

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Pathophysiology

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The HIV attacks and binds to specific cells of the immune system, including monocytes , macrophages , & T-cell lymphocytes CD4 receptors ( for binding ) coreceptor proteins (CCR-5, CXCR-4)( for fusion ) conformational changes to key HIV proteins (gp41 & gp120) HIV fuses releases its contents

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13

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HIV life cycle and antiretroviral drug targets

Natural Hx of Untreated HIV infection: 

Natural Hx of Untreated HIV infection

Viral-host Dynamics : 

Viral-host Dynamics About 10 billion virions are produced daily Average life-span of an HIV virion in plasma is ~6 hours Average life-span of an HIV-infected CD4 lymphocytes is ~1.6 days HIV can lie dormant within a cell for many years, especially in resting (memory) CD4 cells, unlike other retroviruses 17

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Diagnosis

Testing: 

Testing ELISA is the gold Standard (99.5% sensitive) Western blot for confirmatory Positive rapid HIV test results need to be confirmed with standard testing modalities 20% of ELISA are indeterminate , due to: Early HIV Late stage with waning immunity Cross-reactive antibodies

The testing algorithm: 

The testing algorithm The testing algorithm for ELISA and rapid HIV testing Two concordant parallel rapid HIV tests , or Two concordant parallel ELISA tests Any specimen that is reactive on parallel ELISA testing or parallel rapid testing is considered HIV antibody positive, and is diagnostic for HIV infection for anyone over 18 months of age.

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Clinical Pictures

Primary HIV infection S/S: 

Primary HIV infection S/S Fever-96% Adenopathy-74% Pharyngitis-70% Rash-70% Myalgias-54% Diarrhea-32% Headache-32% N&V-27% Hepatospleenomegaly-14% Weight loss-13% Thrush-12% Neurologic symptoms-12%

WHO Staging of HIV/AIDS: 

WHO Staging of HIV/AIDS Primary HIV Infection Stage I – asymptomatic Stage II - mild disease Stage III - moderate disease Stage IV - advanced immunocompromised

WHO Clinical Stage I: 

WHO Clinical Stage I Asymptomatic or Persistent generalized lymphadenopathy ( PGL ) Performance scale 1 : able to carry on normal activity

WHO Clinical Stage II: 

WHO Clinical Stage II Moderate unexplained weight loss ( <10% body weight) Recurrent URTIs Herpes zoster Angular cheilitis Recurrent oral ulcerations Papular pruritic eruptions Seborrheic dermatitis Fungal fingernail infections And/or perfom. scale 2 ( Normal activity with effort, but unable to do active work)

WHO Stage III: 

WHO Stage III Severe weight loss ( >10% body weight) Unexplained chronic diarrhea(>1mo) Unexplained persistent feve r (intermittent/constant for >1mo ) Oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis ( TB ) diagnosed in last two years

WHO Stage III (2): 

WHO Stage III (2) Severe presumed bacterial infections (e.g. pneumonia, empyema , pyomyositis , bone or joint infection, meningitis, bacteraemia ) Acute necrotizing ulcerative stomatitis , gingivitis or periodontitis Unexplained anemia (<8 g/dl) Neutropenia (<500/mm3) Thrombocytopenia (<50 000/ mm3) for more than one month

WHO Stage IV: 

28 WHO Stage IV HIV wasting syndrome Pneumocystis pneumonia Recurrent severe or radiological bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration) Esophageal candidiasis Extrapulmonary TB Kaposi’s sarcoma Central nervous system (CNS) toxoplasmosis HIV encephalopathy

WHO Stage IV (2): 

29 WHO Stage IV (2) Extrapulmonary cryptococcosis including meningitis Disseminated non-tuberculous mycobacteria infection Progressive multifocal leukoencephalopathy ( PML ) Candida of trachea, bronchi or lungs Cryptosporidiosis Isosporiasis Visceral herpes simplex infection

WHO Stage IV (3): 

30 WHO Stage IV (3) Cytomegalovirus ( CMV ) infection (retinitis or of an organ other than liver, spleen or lymph nodes) Any disseminated mycosis (e.g. histoplasmosis , coccidiomycosis , penicilliosis ) Recurrent non- typhoidal salmonella septicaemia Lymphoma (cerebral or B cell non-Hodgkin) Invasive cervical carcinoma Visceral leishmaniasis

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Treatment

Goals of ARV Therapy: 

Goals of ARV Therapy To restore immunologic function and quality of life, and to increase life expectancy by decreasing morbidity and mortality due to HIV infection. For HAART initiation in patients of all ages, initial treatment success or failure is determined by the viral load 6 months after HAART initiation:

The virologic goal of HAART initiation: 

The virologic goal of HAART initiation to achieve viral load < 400 copies/ mL by no later than 6 months after starting HAART . For the vast majority of adult patients initiated on HAART, the viral load obtained at 3 months post-initiation will be < 400 copies/ mL. For the adult patient whose viral load at 3 months is not < 400 copies/ mL treatment failure? Nonadherence ?

virologic failure for both adult/adolescent and pediatric patients: 

virologic failure for both adult/adolescent and pediatric patients occurred whenever one of the following two situations arises: Viral load is not < 400 copies/mL by 6 months after HAART initiation, or After initially being suppressed to < 400 copies/mL, viral load becomes detectable (i.e., > 400 copies/mL) at some later time in the future.

Currently Available Antiretroviral Drugs: 

Currently Available Antiretroviral Drugs Twenty-three antiretroviral agents are now approved for use in the United States with more in development. (2009) Antiretroviral drugs fall into five classes : nucleoside/nucleotide reverse transcriptase inhibitors ( NRTIs ), non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), protease inhibitors ( PIs) , entry inhibitors , and integrase inhibitors .

Antiretroviral Agents: 

36 Antiretroviral Agents Protease Inhibitors (PI) Lopinavir/ritonavir (Kaletra) Atazanavir Indinavir (IDV) Ritonavir (RTV) Nelfinavir (NFV) Saquinavir (SQV) Darunavir Fosamprenavir Non-nucleoside reverse transcriptase inhibitors (NNRTI) Efavirenz Nevirapine Etravirine (2008) Delaverdine Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) Zidovudine (ZDV,AZT) Didanosine (ddI) Tenofovir (TDF) Emtricitabine (FTC) Lamivudine (3TC) Abacavir (ABC)

Entry Inhibitors: 

Entry Inhibitors prevent entry of HIV into the target cell through a variety of mechanisms. Enfuvirtide , a fusion inhibitor, interferes with the process of viral binding (fusion) to the cell membrane by binding to proteins on the surface of the cell, which then prevents the virus from binding to the target cell. Maraviroc prevents entry by blocking CCR5 , a co-receptor on the cell, necessary for viral attachment. As some viral strains may use an alternate co-receptor CXCR4 for entry, a tropism assay is necessary to confirm that the patient’s virus only uses CCR5 for entry.

Integrase Inhibitors: 

Integrase Inhibitors block viral replication by preventing the incorporation of viral DNA into the host genome by inhibiting the HIV integrase enzyme. E.g. Raltegravir & Elvitegravir

Combination Formulations of Antiretroviral Drugs: 

Combination Formulations of Antiretroviral Drugs Name Combination Combivir Zidovudine + lamivudine Epzicom Zidovudine + abacavir Trizivir (combivir +ABC) Zidovudine + lamivudine + abacavir Truvada Tenofovir + emtricitabine Atripla (Truvada +EFV) Tenofovir + emtricitabine + efavirenz Triomune a Stavudine + lamivudine + nevirapine

Criteria for ART Initiation in specific populations: 

Criteria for ART Initiation in specific populations

When to start antiretroviral therapy: 

When to start antiretroviral therapy

When to start antiretroviral therapy…: 

When to start antiretroviral therapy…

What antiretroviral therapy to start: 

What antiretroviral therapy to start

What antiretroviral therapy to start…: 

What antiretroviral therapy to start…

Preferred first-line ART in treatment-naive adults and adolescents: 

Preferred first-line ART in treatment-naive adults and adolescents

Recommended second-line antiretroviral therapy: 

Recommended second-line antiretroviral therapy

Dose and Toxicity of common ARV drugs: 

Dose and Toxicity of common ARV drugs Drug Dose in combination Toxicity AZT 200 mg q8h or 300 mg bid Anemia, granulocytopenia , myopathy, lactic acidosis, hepatomegaly with steatosis, nail pigmentation, lipid abnormalities, lipoatrophy, hyperglycemia ddl Buffered tabs (on empty stomach) 60 kg: 200 mg bid <60 kg: 125 mg bid Enteric coated: 60 kg: 400 mg qd < 60 kg: 250 mg qd Pancreatitis, peripheral neuropathy, abnormalities on liver function tests, lactic acidosis, hepatomegaly with steatosis , optic neuritis, nausea, hyperglycemias, peripheral neuropathy

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Drug Dose in combination Toxicity ddC 0.75 mg tid Peripheral neuropathy , pancreatitis , lactic acidosis, hepatomegaly with steatosis , oral ulcers d4T 60 kg: 40 mg bid <60 kg: 30 mg bid Peripheral neuropathy, pancreatitis , lactic acidosis, hepatomegaly with steatosis , ascending neuromuscular weakness, lipodystrophy , lipid abnormalities, hyperglycemia 3TC 150 mg bid 300 mg qd Flare of hepatitis in HBV- coinfected patients who discontinue drug FTC 200 mg qd Hepatotoxicity in HBV- coinfected patients who discontinue drug, skin discoloration

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Drug Dose in combination Toxicity ABC 300 mg bid Hypersensitivity reaction In HLA-B5701+ individuals (can be fatal); fever, rash, nausea, vomiting, malaise or fatigue, and loss of appetite TDF 300 mg qd Renal osteomalacia , flare of hepatitis in HBV- coinfected patients who discontinue drug DLV 400 mg tid Skin rash, abnormalities in liver function tests NVP 200 mg/d x 14 days then 200 mg bid or 400 mg extended release qd Skin rash, hepatotoxicity

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Drug Dose in combination Toxicity EFV 600 mg qhs Rash, dysphoria, elevated liver function tests, drowsiness, abnormal dreams, depression, lipid abnormalities, potentially teratogenic Ritonavir 600 mg bid Nausea, abdominal pain, hyperglycemia, fat redistribution, lipid abnormalities, may alter levels of many other drugs, including saquinavir, paresthesias, hepatitis Lopinavir/ritonavir (Kaletra) 400 mg qd or 300 mg qd + ritonavir 100 mg qd when given with efavirenz Hyperbilirubinemia , PR prolongation, nausea, vomiting, hyperglycemia, fat maldistribution , rash transaminase elevations

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Drug Dose in combination Toxicity Atazanavir 400 mg qd or 300 mg qd + ritonavir 100 mg qd when given with efavirenz Hyperbilirubinemia, PR prolongation, nausea, vomiting, hyperglycemia, fat maldistribution, rash transaminase elevations Enfuvirtide 90 mg SC bid Local injection reactions, hypersensitivity reactions, increased rate of bacterial pneumonia Maraviroc 150–600 mg bid depending on concomitant medications Hepatotoxicity, nasopharyngitis , fever, cough, rash, abdominal pain, dizziness, musculoskeletal symptoms

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Drug Dose in combination Toxicity Raltegravir 400 mg bid Nausea, headache, diarrhea, CPK elevation, muscle weakness and rhabdomyolysis

Dosing of Antiretroviral Agents in Hepatic Failure: 

Dosing of Antiretroviral Agents in Hepatic Failure

Dosing of Antiretroviral Agents in Renal Failure: 

Dosing of Antiretroviral Agents in Renal Failure

Types of Treatment Failure:: 

Types of Treatment Failure: Virologic Failure : if viral load is not <400 copies/mL after 3mo Immunologic Failure : The CD4 cell count persistently falls below the baseline CD4 cell count The CD4 cell count fails to increase by more than 25-50 cells/μL after one year of treatment There is a > 50% decline in CD4 cell count from its highest level on HAART Clinical Failure : when the patient has a new AIDS-defining illness —i.e., a new WHO stage 3 or 4 condition--after initiation of HAART, excluding IRIS

When to switch ART ....: 

When to switch ART .... 1. When there is treatment failure. use viral load (VL) to confirm (followQ6mo) A persistent VL of >5000 copies/ml confirms treatment failure When VL is not available, use immunological criteria to confirm clinical failure 2. When there is severe toxicity from ARV drugs

Clinical Indications to Change ART Due to Toxicity: 

57 Clinical Indications to Change ART Due to Toxicity Symptom Clinical Indication Nausea Severe discomfort or minimal intake for > 3 days Vomiting Severe vomiting of all foods/fluids in 24 hrs, orthostatic hypotension or need of IV fluids Diarrhea Bloody diarrhea, orthostatic hypotension or need of IV fluids Fever Unexplained fever of > 39.6 C Headache Severe or requires narcotics Allergic Reaction Generalized urticaria, angioedema or anaphylaxis Peripheral Neuropathy Severe discomfort, objective weakness, loss of 2-3 previously present reflexes or sensory dermatomes Fatigue Normal activity reduced > 50%

Lab Indications to Change ART Due to Toxicity: 

58 Lab Indications to Change ART Due to Toxicity Parameter Grade 3 Toxicity Normal Reference Values Hematology Hemoglobin (Hgb) < 7.0 g/dL M: 13.8 – 17.2 g/dL F: 12 – 15.6 g/dL *ANC < 750/mm 3 1500 to 7000/mm 3 Platelet count < 49 x 10 3 /µL 130-400 x 10 3 /µL Chemistries Total Bilirubin > 3-7.5 x ULN*= 3.9-9.75mg/dL ≤ 1.3 mg/dL SCr > 1.7-2.0 (adult) ≤ 1.2 mg/dL LFTs AST / ALT 5-10 x ULN* = 210-420 U/L, 240-480 U/L ≤ 42 U/L , ≤ 48U/L Pancreatic Enzymes Amylase, Lipase > 2-3 x ULN* 23-85 U/L, 0-160 U/L Lipids Triglyceride (TG) 8.49- 13.56 mmol/L < 200 mg/dL Cholesterol 1.6-2.0 X ULN < 200 mg/ dL * ULN = Upper Limit of Normal *ANC= Absolute neutrophil count

Toxicity: Changing One Drug: 

59 Toxicity: Changing One Drug Regimen: d4T/3TC/NVP d4T-related neuropathy or pancreatitis: Switch d4T to ZDV NVP-related rash or hepatotoxicity: Switch NVP to EFZ (except pregnancy) Switch NVP to PI’s (in cases of pregnancy or severe adverse effect) Regimen: d4T/3TC/EFV EFZ-related persistent CNS toxicity: Switch EFZ to NVP Regimen: ZDV/3TC/EFV ZDV-related anemia or neutropenia: Switch ZDV to d4T/TDF

Co-morbidities: 

60 Co-morbidities A change in clinical status of patients may mandate change in ART Pregnancy: If on EFV based regimen – change EFV to NVP (1 st timester ) Occurrence of active TB: If on NVP based regimen – change to EFV (with adjusted dose), to LPV/r, or ATV/r

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HAART induced ADRs

ADVERSE DRUG REACTIONS: 

ADVERSE DRUG REACTIONS Anti-retroviral can lead to short-term toxicities or long-term side effects. Short-term toxicities : Organ: Liver, kidney, bone marrow Cutaneous Reactions: SJ syndrome, hypersensitivity

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Long term side effects : Morphologic complications Lipoaccumulation / lipohypertrophy , visceral adiposity Breast enlargement Dorso -ventral fat pad Lipomas Cosmetic disfigurement Metabolic Abnormalities Dyslipidimias Abnormalities of glucose metabolism Insulin resistance Lactic acidosis Hepatosteatosis Osteonecrosis , osteopenia , osteoporosis Increasing bleeding in hemophiliacs

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64 All NRTIs ** Lactic acidosis/fatty liver* Lipoatrophy (loss of subcutaneous fat) Anemia Zidovudine (AZT, ZDV) Pancreatitis* didanosine (ddI) Neuropathy didanosine (ddI) zalcitabine (ddC) stavudine (d4T) *Potentially life-threatening **d4T > ddI, AZT > ABC, TDF, 3TC Serious Adverse Effects of NRTIs

Serious Adverse Effects of NNRTIs: 

65 Serious Adverse Effects of NNRTIs All NNRTIs Hepatitis* Skin rash CNS symptoms efavirenz Stevens-Johnson syndrome* nevirapine *Potentially life-threatening

Serious Adverse Effects of PIs: 

66 Serious Adverse Effects of PIs All PIs Insulin resistance  hyperglycemia and diabetes Elevated serum lipids Abnormal fat accumulation Liver toxicity* *Potentially life-threatening

LIPODYSTROPHY SYNDROME: 

LIPODYSTROPHY SYNDROME Main clinical features are peripheral fat loss, central fat accumulation , gyneacomastia , buffalo hump and other peripheral lipomatosis . Incidence : 20-80% of pts in ARV drugs ARV agents: Fat acc. 1°ly associated wz PI use , Lipoatrophy is more closely wz NRTIs d4T or d4T/ ddl

Lipodystrophy Syndrome: NRTIs versus PIs : 

NRTIs d4T>ZDV Lactic acid SC fat wasting TG Buffalo hump Intra-abdominal fat Cholesterol TG Insulin resistance PIs Lipodystrophy Syndrome: NRTIs versus PIs John M, et al. Antiviral Ther . 2001;6:9-20.

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Presumed Mechanism of toxicity: inhibition of DNA polymerase gamma resulting in depletion of mitochondrial DNA Evaluation: Patient perception P/E & serial photography Waist hip ratio (>0.85 for F, >0.95 for M) DEXA (dual energy x-ray absorptionmetry ) Ultrasound, Ct, MRI

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Rx Low fat diet and aerobic exercise Testosterone replacement therapy (in hypogonadal men) or anabolic steroids (eugonadal men) Growth hormone ( 6mg/kg) may reduce fat accumulation Metformin (500mg bid) improves insulin sensitivity, results in weight loss and decreased intra- abdominal fat Restorative surgery Regimen change : PIs to NNRTIs or ABC

Lipodystrophy Illustrations: 

Lipodystrophy Illustrations “Buffalo hump” “Crix belly” “Facial wasting” http://www.hivandhepatitis.com/recent/lipo/fataccumulation/1.html#buf

Lactic Acidosis/Hepatic Steatosis: 

Lactic Acidosis/Hepatic Steatosis Hyperlactemia is defined as venous lactate >2mmol/L Mortality rate : up to 55% Presumed Mechanism of toxicity: inhibition of DNA polymerase gamma resulting in depletion of mitochondrial DNA

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Dx Clinical: vague and asymptomatic wz N & V myalgia, abd. Pain & distention, diarrhea wt loss Lab. Elevated venous lactic acid Surrogate markers include elevated creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), amylase or aspartate aminotransferase (AST), increase anion gap (Na +(Cl+Co2)>16), CT, US, biopsy showing liver steatosis

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Rx Lactic acid <5mmol/L may not require Rx in the absence of Sxs ( Sxic pts La is usually> 5mmol/L) Therapeutic switch : D4T, ddl , or AZT to ABC,3TC or TDF may be reasonable Supportive measures : hydration, mitochondrial ventilation and dialysis Anecdotal case reports show possible benefit of thiamine , L- carnitine , vit -C and antioxidants Riboflavin 50mg/kg - most extensive & favourable

Insulin Resistance: 

Insulin Resistance Incidence : 30-90% pts on PIs and overt DM occurs in 1-11% wz a mean of 7% in 5yr Screening : RBG , FBG and HgA1c after 2-3 mo of the start of PI base regimen Risk: Risk of atherosclerosis

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Rx STD RX of type II DM and exercise The two major classes of agents are insulin secretagogues (sulunylureas ) and insulin sensitizing agents ( metformin and thiazolidinediones / glitazones) Metformin and glitazones have the potential advantage of improving insulin resistance and decreasing visceral fat accumulation (N.B: The FDA issued a "black box" warning for rosiglitazone in 2007, and in 2010 "risk evaluation and mitigation strategy" for severe DM cases only) Therapeutic switch to non PI base ARV agents

Hyperlipidemia: 

Hyperlipidemia All PIs appears to have this effect with the possible exception of atazanavir ; however the most profound changes are seen wz ritonavir and are dose dependant. Changes usually observed within 2 to 3 month of initiating PI based regimen

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Risk: The possible risk of atherogenesis is compounded by insulin resistance DX & Rx: LDL and TG--PI based HAART esp.wz retonavir TC and HDL—EFV & NVP Rx is based of the NCEP guidelines

Rx of hyperlipidemia: 

Rx of hyperlipidemia Lipid problem Preferred alternative comment Isolated high LDL Statin niacin Start low dose and titrate upward, watch for myopathy with PIs High cholesterol and TG Statin or fibrate Start one and add other Combination may increase risk of myopathy Isolated high TG fibrate statin Combination may increase risk of myopathy

Hepatotoxicity: 

Hepatotoxicity NRTIs can cause hepatic steatosis , generally after more than 6 months of therapy, probably via mitochondrial toxicity .(D4T!) NNRTIs can cause hepatitis in the first 2-3 months of therapy, sometimes as a part of hypersensitivity reaction.(NVP>EFV, DLV)- fluminant hepatic necrosis (NVP) PIs can also cause hepatitis by an unknown mechanism , particularly in patients co-infected with hepatitis B or C , raised hepatic aminotransferase concentrations and alcoholism (RTV-the most common, among PIs)

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Of the current available ARV drugs, the most hepatotoxic appears to be NVP followed by full dose RTV Monitoring of transaminase level is recommended for all pts receiving PIs Dose reduction should be considered for AZT, PIs and all NNRTIs pts wz overt liver failure

HYPERSENSITIVITY: 

HYPERSENSITIVITY is about 100 times more common In HIV Pts than in general population. Erythematous maculopapular , pruritic and confluent rash with or without fever . Rash is most prominent on body and arms and begins after 1-2 weeks of therapy .

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Constitutional features are often prominent and can precede rash (with abacavir ) or occur without rash. SJ syndrome or Toxic Epidermal Necrolysis ( TEN ) develops in less than 0.3% of patients. All NNRTI ( Nevirapine,Delavirdine,Efavirenz , Etravirine ), NRTI ( Abacavir ) and PI ( Amprenavir ) are common ARV that cause hypersensitivity

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About 50% of ARV hypersensitivity resolves spontaneously despite continuation of therapy. Therapy should be stopped if there is mucosal involvement, blistering, exfoliation, clinically significant hepatic dysfunction (e.g. tender hepatomegaly, aminotransferase concentrations greater than five times baseline ), fever (> 39°C or intolerable prutiritus).

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Glucocorticosteroids are ineffective for the prevention of nevirapine hypersensitivity . Rechallenge is possible for mild to moderate NNRTI hypersensitivity but not for abacavir, since several deaths have been attributed to abacavir rechallenges

Steven Johnson Syndrome or Toxic Epidermal Necrolysis : 

Steven Johnson Syndrome or Toxic Epidermal Necrolysis http://www.fromthewilderness.com/images/stevenJohnsonSyndrome2.jpg

GASTROINTESTINAL EFFECTS: 

GASTROINTESTINAL EFFECTS All ARV can cause transient N,V & D early in therapy. Among NRTI nausea is more common with Zidovudine and Didanosine Indinavir is also associated with esophageal reflux (about 3%) but should not be given with antacid because salts in the antacids can bind to Indinavir and prevent its absorption. H2 blockers and proton pump inhibitors are acceptable options.

Enhanced bleeding in pts with hemophillia: 

Enhanced bleeding in pts with hemophillia Has been attributed to PIs but supporting data are sparse

Osteopenia: 

Osteopenia Osteopenia ( wz potential for osteoporosis) or osteonecrosis ( wz pt for avascular necrosis) have been observed in pts on HAART esp. on TDF , but the casual R/S has not been established. Theses processes may also be caused by long standing HIV infection rather than HAART.

Recommended Schedule for Monitoring Patients on HAART: 

Recommended Schedule for Monitoring Patients on HAART Clinical evaluation include inquiry into possible ARV side effects Include assessment of adherence (>90%), initiation of any interventions and life style modification at least every- 3-month basis (1 st 2years) After 2yr, if stable,Q6mo

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Laboratory monitoring of patients on HAART: CD4 cell count/%: 3 and 6 months post-initiation, then every 6 months (all ages) Viral load: 3 and 6 months post-initiation, then as follows: (Every 6 months for adults) FBC: AZT-based HAART : at 4 and 12 weeks post-initiation , then annually only, and as clinically indicated If not on AZT-based HAART : annually only , and as clinically indicated

Laboratory monitoring of patients on HAART:: 

Laboratory monitoring of patients on HAART: AST/ALT : NVP-based HAART : 2, 4, and 12 weeks post-initiation, thereafter only as clinically indicated EFV-based HAART : 4 and 12 weeks post-initiation, thereafter only as clinically indicated PI-based HAART : only as clinically indicated

Laboratory monitoring of patients on HAART:: 

Laboratory monitoring of patients on HAART: Glucose and total cholesterol/triglycerides annually only if on PI-based HAART Creatinine and creatinine clearance ( CCreat ): 3 and 6 months post-initiation and then, if stable, every 6 months ( TDF only ) Chemistry : after baseline, only as indicated RPR ( rapid plasma reagin ) or VDRL test : after baseline, only as indicated

Adult 1st Line Regimen: TDF + FTC (or 3TC) + NVP or EFV: 

Adult 1st Line Regimen: TDF + FTC (or 3TC) + NVP or EFV

Adult 2ndLine Regimen: AZT + 3TC + LPV/r : 

Adult 2ndLine Regimen: AZT + 3TC + LPV/r

Summary: 

Summary Talk with patients to stress adherence to therapy Review all medications with patients Function in an interdisciplinary environment

References: 

References David K McCulloch, M. (2011). Overview of medical care in adults with diabetes mellitus. UPTODATE DESKTOP M. David M Nathan. 19.1. Joseph T. DiPiro , P., FCCP; Executive Dean and Professor, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina and Medical University of South Carolina, Charleston, South Carolina (2008). Pharmacotherapy A Pathophysiologic Approach, McGraw-Hill. John G. Bartlett(2003). Medical Management of HIV infection. Johns Hopkins University . Mary Anne Kodda kible , Applied therapeutics ; the clinical use of drugs (2009). 9 th edition

References: 

References John G. Bartlett(2003). Medical Management of HIV infection. Johns Hopkins University . Harrison. Harrison's Principles of Internal Medicine. 18 ed. al Le, editor2010.

Questions?: 

Questions?

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