Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Long Term Side Effects of ARVs HAIVN Harvard Medical School AIDS Initiative in Vietnam 1 Learning Objectives By the end of this session, participants should be able to: Describe the symptoms and explain how to diagnose and manage the following side effects: • • • • • • Lipodystrophy syndrome Peripheral neuropathy Diabetes Dyslipidemia Gynecomastia Bone disorders 2 Lipodystrophy 3 Overview of Lipodystrophy (1) Lipodystrophy is a syndrome of body shape abnormalities characterized by: • central fat accumulation • peripheral fat loss Some patients have only fat loss, others have fat gain, and others have a mixed picture of both There can also be associated disorders in glucose and lipid metabolism 4 Overview of Lipodystrophy (2) Lipoatrophy: Loss of subcutaneous body fat: • Extremities • Face • Buttocks Lipohypertrophy: Increased fat accumulation in the center of the body: • Abdomen • Breasts • Dorso-cervix 5 Prevalence of Lipodystrophy 6 6 Lipodystrophy: Prevalence in Asian Cohorts Cambodian cohort: • D4T-associated lipodystrophy in 20% of patients after 24 months of follow-up Singapore cohort: • Lipoatrophy 46% • Fat accumulation 32% • Mixed 8% Sources: Ferradini AIDS 2007; Nicholas CID 2002 7 Lipoatrophy: Risk Factors Risk factors for lipoatrophy include: NRTIs D4T is strongest risk factor AZT to a lesser extent 3TC, TDF, ABC much less common Other non-drug factors Older age Lower body weight AIDS diagnosis Lower pretreatment CD4 cell count 8 Lipohypertrophy: Risk Factors Risk factors for lipohypertrophy include: Older age Female sex Amount of body fat Longer duration of ART Exposure to protease inhibitors 9 Manifestations of Lipoatrophy Face Extremities: Prominent vein Buttocks 10 Manifestations of Lipohypertrophy Dorsocervical Area Breasts Abdomen 11 Treatment of Lipodystrophy Lipoatrophy: Change d4T to AZT, ABC or TDF Cosmetic surgery or injections Lipohypertrophy: Change PI’s to NNRTI Exercise Liposuction 12 Metabolic Disorders Insulin resistance and diabetes Dyslipidemia Lactic acidosis/hyperlactatemia Cardiovascular risk 13 Insulin Resistance and Diabetes (1) Incidence of 3-5 % among ARV patients • After months or years Risk factors • Use of PI-containing ARV regimen • Previous hyperglycemia • Family history of diabetes Laboratory diagnosis: the same as for non-HIV patients 14 Insulin Resistance and Diabetes (2) Screening: • Fasting glucose before starting ARV, then every 6-12 months Treatment: • Treat diabetes as in non-HIV patients • Consider switch PI to another PI (such as ATV if available) or NNRTI (if not already resistant to 1st line ARV) 15 Dyslipidemia 16 Dyslipidemia – Terms Parameter Total Cholesterol Low Density Lipoprotein High Density Lipoprotein Triglycerides Acronym Comment TC Total cholesterol found in the serum LDL LDL: increased risk for cardiovascular disease HDL •HDL levels (>1.6mmol/l): protective of cardiovascular disease •HDL levels (< 1.03mmol/l): risks for cardiovascular disease TG levels: associated with cardiovascular disease, 17 pancreatitis 17 ART – Induced Lipid Abnormalities 18 18 Dyslipidemia - ARV Specific Effects Drug PIs (except Atazanavir) Ritonavir D4T EFV or NVP Effect LDL, TC & TG HDL TG, LDL and TC TG, occasional LDL and TC TG, especially EFV HDL 19 PI – Induced Lipid Effects 20 20 Dyslipidemia: Screening Dyslipidemia occurs is up to 75% of patients on PIs Screening should be performed for all patients on ART and especially for those on PIs: • Baseline fasting lipid level • Yearly lipid screening 21 Management of Dyslipidemia Screen for other cardiovascular risk factors to assess likelihood of future cardiovascular events Encourage positive behavior change Consider lipid lowering drugs Consider changing PI to another agent that does not cause lipid elevations (NNRTI or ATV) 22 Drug Management of Dyslipidemia (1) HMG-coA reductase inhibitors “Statins” Start for elevated TC and/or LDL Very effective at LDL ( 20-60%) Beware of drug interactions • Atorvastatin & Pravastatin: safe to use with PI • Lovastatin & Simvastatin: levels when used with PI Do Not Use 23 Drug Management of Dyslipidemia (2) Fibrates (Fenofibrate, Gemfibrozil ) Indication usually if TG > 500 mg/dL Best for isolated TG: • TG 30-50% • LDL 10-20%; HDL 5-15 % No significant drug interactions with ARV Less expensive than statins 24 Cardiovascular Risk 25 What are the Traditional Cardiac Risk Factors? Male gender Older age Hypertension Diabetes mellitus Tobacco use Hyperlipidemia Family history of premature coronary artery disease (CAD) Personal history of CAD 26 HIV and ARVs As Risk Factors for Cardiovascular Disease Use of ART has been associated with an increased risk of cardiovascular events: • May be seen from a few months to years after the start of ARV • Can occur in patients without any other cardiac risk factor PIs have highest risk Presence of the lipodystrophy syndrome has been shown to add further risk of cardiovascular events in some studies 27 Management of Cardiovascular Complications of ARV Early diagnosis and treatment of traditional cardiac risk factors Behavioral changes • Diet • Regular physical exercise • Smoking cessation Diminish further risks from ARV by: • Use NNRTI instead of PI • Use NRTIs, but avoid d4T 28 Peripheral Neuropathy 29 Peripheral Neuropathy NRTIs and other drugs may cause peripheral neuropathy: • D4T and DDI have the highest risk • Increased risk when D4T combined with DDI or Ribavirin 30 Risk Factors The risk of NRTI-induced neuropathy is higher in the following circumstances: • • • • • • • Preexisting neuropathy Concurrent diabetes Lower pretreatment CD4+ cell count Higher viral load Alcoholism Poor nutrition Older age 31 Symptoms Onset after many weeks or months “Stocking and glove” distribution: starts at fingertips/toes and spreads inward Symptoms: numbness, tingling, pain Progressive and irreversible if left untreated 32 Treatment Eliminate other causes or contributing factors: • Stop alcohol use • Screen for and treat other diseases: diabetes, thyroid dysfunction, syphilis • Stop use of other neurotoxic agents (INH) Switch from D4T to AZT, ABC or TDF Neuropathic pain can be treated with Amitriptyline 33 Lactic Acidosis 34 Lactic Acidosis Incidence 0.5% - 1.5% per year Risk of lactic acidosis: • D4T+DDI > D4T > DDI > AZT • Very Low risk: 3TC, TDF, ABC Symptoms: can develop slowly • Mild: fatigue, body aches, nausea, vomiting, diarrhea, weight loss • Severe: wasting, dyspnea, abdominal pain, coma 35 Lactic Acidosis: Diagnosis Elevated lactic acid levels Normal Mild elevation Moderate elevation Severe elevation < 2 mmol/L 2 – 5 mmol/L 5-10 mmol/L > 10 mmol/L If lactic acid testing is not available: • Increased anion gap [Na-(Cl+HCO3)] > 16 • LFT, CPK, LDH, pH, HCO3 36 Lactic Acidosis: Treatment No or mild symptoms Lactic acid level ≤10 Change NRTI: d4T AZT ddI ABC or TDF Severe symptoms Lactic acid level >10 Hospitalize Provide supportive care Stop all ARVs When stable, restart ARV: •use ABC or TDF plus 3TC •or use NRTI-sparing regimens 37 37 Bone Disorders 38 Osteonecrosis (1) Ischemic death of the cellular components of the bone, normally at the epiphyseal or subarticular regions 85% of cases are at one or both femoral heads but, may affect any bone 39 Symptoms and Diagnosis Presentation often insidious onset with subtle symptoms The most common presenting symptom is pain • Groin pain is most common location • Pain on movement or weight bearing Diagnosis is made clinically in a symptomatic patient with typically radiologic findings 40 Risk Factors Diabetes Prior history of prolonged steroid use Older age Excessive use of alcohol Hyperlipidemia HIV infection Use of protease inhibitors Glesby M, Clin Inf Dis.2003;37:S91-S95 41 Treatment Eliminate contributing factors: alcohol, steroids Treat the pain with NSAIDS and/or opiate drugs Severe pain in the hip may be an indication for hip replacement surgery 42 Gynecomastia 43 Gynecomastia (1) Enlargement of one or both breasts as a result of increased glandular tissue Most common with EFV, D4T is less common 44 44 Gynecomastia (2) Symptoms: may be painful Differential diagnosis • Other medications (INH, ketoconazole, cimetidine, metronidazole) • Pseudo-gynecomastia (fatty deposit such as in lipodystrophy) • Hypogonadism (testicular tumors) • Breast cancer 45 Treatment of EFV-Induced Gynecomastia NSAIDS for pain Treatment options: Continue EFV: Complete regression after 2 months when no change in treatment was done (One author noted) Stop EFV: Complete regression seen after 5 months when EFV changed to NVP (in a cohort of patients 46 46 in Haiti) Key Points Patients on ARVs may develop one or more long term side effects Screening and early recognition of these potential side effects is important Cardiovascular disease is an increasingly recognized complication of long-term HIV infection and ARV use 47 Thank you Questions? 48