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Case Presentation Managing treatment side effects in the correctional environment. Stephen Tabet, MD, MPH University of Washington Division of Infectious Diseases Harborview Medical Center Northwest AETC. Background.
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Case PresentationManaging treatment side effects in the correctional environment Stephen Tabet, MD, MPH University of Washington Division of Infectious Diseases Harborview Medical Center Northwest AETC
Background • 48-year-old Caucasian female presents to the prison infimary with yeast vaginitis. A review of her chart reveals this is her fourth episode since her initial incacercation 2 months ago. She had previously been treated with topical miconazole vaginal suppositories. • On examination, she has erythematous vaginal mucosa with few areas of abrasion; no ulcerations. • What would you do next? • At this point, would you do a vaginal yeast culture and do resistance testing?
Background • The patient is treated with oral fluconazole 150 mg/day for 3 days. HIV testing is done. • One week later, the patient presents asymptomatic with minimal vaginal erythema. She is positive for HIV antibodies. • Among other labs, CD4 count and viral load are done. CD4 T-cell count is 32 and HIV bDNA is >500,000 • She is given tmp/smx for PCP prophylaxis and azithromycin for MAC prophylaxis
Next Step? • The patient is expected to be incarcerated another 16 months. • Is offering antiretroviral therapy appropriate or should it be addressed when she is released?
Initial Regimen • An initial regimen of d4T (30 mg) BID (weight adjusted), 3TC (150 mg) BID, and SQV (400 mg) / RTV (400 mg) BID is initiated • One month later - HIV bDNA: 60,575 • 3 months later - HIV RNA: undetectable (<50 copies); CD4 count: 219 • She has no recurrence of yeast vaginitis
Lipid Profile • Six months after starting HAART, a routine lipid and glucose profile reveals the following: • Fasting total cholesterol 295 mg/dl • HDL 52 mg/dl • LDL 193 mg/dl • Triglycerides 352 mg/dl • Fasting glucose 83 mg/dl • (HIV RNA remains undetectable and CD4+ T-cells increase further to 280.)
> 1 Physical Features Peripheral Wasting Characteristic Fat > 1 Metabolic Features Elevated Blood Lipids(cholesterol and/or triglycerides) Elevated C-peptides Elevated blood glucose Proposed Definition of PI-Associated Lipodystrophy (Carr et al. Lancet. 1999;353:2093-98)
Risk Factors for Lipodystrophy • Age > 40 • HIV-infected > 7 years • AIDS > 2 years • Hemophiliac • Nadir CD4 count < 100 • Time since CD4 nadir ≥ 3 years (Lichtenstein et al. 13th ICOA, 2000)
Patient’s Lifestyle • The patient reports eating a regular prison diet consisting of 3800 calories/day. She is placed on a “low-cholesterol diet”. • She doesn’t have hypertension or diabetes mellitus
Discussion What Would You Do Next? • Treat her with a ‘statin’ - HMG-CoA reductase inhibitor • Change her regimen to a PI-sparing one • Take her off her medications until her lipids normalize and then restart a different regimen • Treat her with gemfibrozil
RTV/SQV, and HMG-CoA Reductase Inhibitors • Pharmacokinetics of Pravastatin, Atorvastatin, and Simvastatin studied in 41 subjects receiving RTV/SQV (400/400 mg) BID • Pravastatin concentrations declined by 50% with RTV/SQV • Atorvastatin concentrations increased by 4.5-fold with RTV/SQV • Simvastatin concentrations increased by 31.6-fold with RTV/SQV • Pravastatin may not need dose reduction with RTV/SQV, but Atorvastatin and Simvastatin should be reduced or avoided for patients taking RTV/SQV (Fichtenbaum, 7th CROI, 2000)
The Patient is Prescribed Pravastatin • The patient is continued on her current antiretroviral regimen • She is started on Pravastatin (40 mg) QD • 3 months later her total cholesterol, LDL, HDL, and triglycerides have normalized
Patient Presents Visceral Fat Accumulation • One year after starting HAART, the patient reports weight gain in her abdomen and breasts and weight loss in her buttocks, thighs and legs at her follow-up visit for treatment of hypercholesterolemia • The patient’s weight is stable at 119 lbs; her face is normal in appearance with no wasting • Her abdomen is protuberant • Her breasts are symmetrically enlarged (since last examination 7 months prior) with no palpable masses • Her thighs and legs are thin but not overtly atrophied
CT Scan of Patient’s Visceral Fat Accumulation* Subcutaneous FatAccumulation† Visceral FatAccumulation‡ *L4/L5 slice†Black represents subcutaneous fat.‡Black represents visceral fat.
Gender Differences: Lipodystrophy and Metabolic Differences • Women: Greater prevalence of visceral and truncal fat accumulation, insulin resistance and lactic acidosis • Men: Greater prevalence of peripheral fat wasting and hyperlipidemia (Mulligan. 7th CROI, 2000)
Discussion What would you do? • Switch her to a PI-sparing regimen (Studies indicate that switching to PI sparing regimens rarely resolves lipodystrophy) • Bonnet et al. 7th CROI, 2000 • Collier et al. 8th CROI, 2001 • Bernasconi 13th Intl AIDS Conference, 2000
The Patient is Continued on Current HAART • The patient is written for a daily exercise regimen • She is motivated to continue antiretrovirals
Insulin Resistance • A random blood glucose sample is drawn • The patient has a fasting glucose of 187 with a normal hemoglobin A1c
Discussion • What should you do?
Metformin Therapy and Insulin Resistance • 26 HIV-infected, nondiabetic patients presented fat redistribution and abnormal oral glucose tolerance test (OGTT) results, and they were randomly assigned to receive Metformin (500 mg) BID (n = 14) or identical placebo (n = 12) for 3 months • Main Outcome Measures: Insulin area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at baseline vs a 3-month follow-up (Hadigan et al. JAMA. 2000;284:472-477)
Metformin Therapy andInsulin Resistance • Results: Patients treated with Metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT and at 3 months • The study suggests that a relatively low dosage of Metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy (Hadigan et al. JAMA. 2000;284:472-477)
Patient is Started on Metformin • The patient is started on Metformin (500 mg) BID • She is cautioned about the potential for lactic acidemia
Managing Dyslipidemia in HIV: Conclusions • Dyslipidemia is influenced by HAART and host factors • Disease progression is involved in the development of dyslipidemia • Treatment changes should not be made without careful consideration of virologic and immunologic outcomes • Symptoms management and lifestyle changes should be the focus of patients with dyslipidemia