HIV와 HAART 요법과 관련된 대사합병증: 개요및임상증례보고 최은주

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HIV와 HAART 요법과 관련된 대사합병증: 개요 및 임상증례보고

최은주

*·Kathleen K. Graham

1조선대학교 약학대학 & 임상약학대학원,²Children's Diagnostic & Treatment Center, FL, USA (2012년 8월 24일 접수·2012년 9월 14일 수정·2012년 9월 17일 승인)

Metabolic Complications Associated with HIV and Highly Active Antiretroviral Therapy : Overview & A Clinical Case Report

Eun Joo Choi

* and Kathleen K. Graham

1College of Pharmacy & Graduate School of Clinical Pharmacy, Chosun University, Gwangju 501-759, Korea

2Children’s Diagnostic & Treatment Center, Ft. Lauderdale, FL, USA (Received August 24, 2012·Revised September 14, 2012·Accepted September 17, 2012)

현재 HIV(human immunodeficiency virus) 감염에 대하여 보다 많은 효과적인 약물치료법이 가능하다. Highly active antiretroviral therapy (HAART) 로 언급되는 이 치료법은 항 HIV치료제의 다양한 병용법으로 구성된다. 그러나, 최근에 이렇게 치료된 환자들에게 중요한 독성들(toxicities)로서 빈번하게 상당한 지질이상과 혈중당의 항상성 조절장애와 연관 된 몸의 지방 분포 비정상으로서 나타나는, 광범위한 대사성 합병증(metabolic complications)이 출현해왔다. 이러한 합 병증의 관리는 표준적인 치료 중재(interventions)와 연관하여 지질과 당 대사와 관련된 항 HIV치료제의 특성 있는 효 과를 이해하면서, 항 HIV 약물들을 조절하는 것을 포함한다. 본 증례는 항HIV 약물요법과정에서 나타난 상당한 지질 이상, 매우 높은 LDL 수치와 높은 TG수치에 따르는 후속 약물요법을 보여주며, 개별화된 항 HIV 약물요법을 수행 하면서, 대사성 합병증에 관련된 수치의 검사와 주기적인 약물치료과정의 모니터링을 권하여 HIV에 감염된 환자들의 효과적인 치료를 향상시키기 위한 것이다.

□ Key words - HIV, Metabolic complications, dyslipidemia, HAART

INTRODUCTION

Antiretroviral therapy (ART) for the treatments of human immunodeficiency virus (HIV) infection has pro- moted consistently since the appearance of effective combination therapy in 1995.

The extensive applica- tion of combination ART has led to a remarkable and continuous reduction in the morbidity and mortality in HIV-infected patients and has converted a HIV-infected condition into a chronic state.

The therapies, known as highly active antiretroviral therapy (HAART), consist of diverse combinations of anti-HIV drugs from differ- ent drug groups.

The worldwide use of HAART has

led to frequent occurrence related to metabolic abnor- malities.

Metabolic complications such as frequently profound dyslipidemia and glucose homeostasis dysreg- ulation have appeared as significant toxicities in HIV- treated patients.

Especially, the long-term implications of altered lipids in HIV-infected persons is still under study, but it is potential that cardiovascular health will be imperiled, with the possibility for increased cardiac mortality.

Dyslipidemia has commomly been related to the use of Protease Inhibitor (PI)-based regimens in HAART, and ritonavir-containing regimens have spe- cially been associated with enhanced incidence of dys- lipidemia.

Prevention and management of Metabolic complications have issued as major challenges to health- care professionals for the care of HIV-infected per- sons.

Potential contributing factors are associated with host characteristics, HIV viral parameters and spe- cific effects of anti-HIV drugs on adipose-tissue biology

Correspondence to : Eun Joo Choi

College of Pharmacy & Graduate School of Pharmacy, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759, Korea

Tel: +82-62-230-6382, Fax: +82-62-222-5414 E-mail: [email protected]

Table 1. ANTIRETROVIRALS (ARVs) Generic Name,

Abbreviation (Trade Name)

Adult Dosing Food Effect Adverse Events NOTE

Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Lactic acidosis/hepatic steatosis; pancreatitis (severe mitochondrial toxicities);

hepatotoxicity, body fat redistribution Abacavir,

ABC (Ziagen)

300 mg BID; or 600 mg QD

No restrictions

Hypersensitivity reaction, (If R, do not rechallenge), N, V, HA, Fatigue, mal- aise, or loss of appetite, respiratory symptoms such as sore throat, cough, shortness of breath

DI : Minimal

Didanosine, ddI

(Videx EC)

≥ 60 kg : 400 mg QD

< 6 0 kg: 250 mg QD

Empty stomach

Pancreatitis, peripheral neuropathy: N/

D,

Lactic acidosis w/ hepatic steatosis (rare but fatal)

TDF increases ddI AUC: reduce ddI dose to 250 mg QD with TDF (≥ 60 kg), IF < 60 kg with TDF, 200 mg QD.

Dosage ADJ in renal insufficiency Emtricitabine,

FTC (Emtriva)

200 mg QD, or 240 mg(24 mL) QD

No restrictions

Minimal toxicity, Lactic acidosis w/

hepatic steatosis, hyperpigmentation of palms and soles

DI: Minimal

Dosage ADJ in renal insufficiency Lamivudine,

3TC (Epivir)

150 mg BID or 300 mg QD

No restrictions

Minimal toxicity, Lactic acidosis with hepatic steatosis

(rare but fatal), HA, dry mouth

DI: Minimal

Dosage ADJ in renal insufficiency Stavudine, d4T

(Zerit) ≥ 60 kg : 40 mg BID

< 60 kg : 30 mg BID No restrictions Peripheral neuropathy, Lipodystrophy, Pancreatitis, Lactic acidosis, D

DI: Minimal

Dosage ADJ in renal insufficiency

Tenofovir,

TDF (Viread) 300 mg QD No restrictions Asthenia, HA, D, N, V, & flatulence, Acute renal insufficiency

· Dosage ADJ in renal insuffi- ciency

· Increases ddI AUC: reduce ddI dose to 250 mg QD if given with TDF,

· Decreases Cmin of ATV: Boost ATV 300 mg with RTV 100 mg QD if given with TDF

Zidovudine, AZT, ZDV (Retrovir)

300 mg BID or

200 mg TID No restrictions

Bone marrow suppression, Anemia;

neutropenia GI intolerance, HA

DI: Minimal, but Avoid use with other bone marrow toxic medica- tions, Dosage ADJ in renal insuffi- ciency

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Rash including Steven’s Johnson Syndrome (SJS)/Toxic epidermal necrosis;

hepatotoxicity Delavirdine, DLV (Rescriptor)

400 mg TID No restrictions R, Increased transaminase levels, HA, Fatigue; N/D

Substrate and Inhibitor of liver enzymes

Efavirenz, EFV (Sustiva)

600 mg QD

Empty stom- ach , at or before bedtime

R, CNS symptioms( dizziness, somno- lence, insomnia, abnormal dreams), Ter- atogenic

Inducer, Inhibitor, and Substrate of liver enzymes

Etravirine, ETV (Intelence)

200 mg BID With food N, R

· ETV is a substrate(3A4, 2C9, 2C19), Inducer (3A4) & Inhibi- tor (2C19) of liver enzymes

· Do not co-administer with TPV/

r, f-APV/r, ATV/r, non-RTV- boosted PIs, and other NNRTIs Nevirapine,

NVP (Viramune)

200 mg QD for 14 days;

then, 200 mg by mouth BID

No restrictions R, Symptomatic hepatitis including fatal hepatic necrosis

Substrate and Inducer of liver enzymes

Fusion Inhibitor Enfuvirtide, T- 20

(Fuzeon)

90 mg(1 mL) SC, BID Not applicable Local Injection site reactions, Increased bacterial pneumonia

DI: Minimal, Storage : Room Temperature, Reconstituted solu- tion should be stored under refrig- eration and used within 24 hrs.

*N/V/D = nausea/vomiting/diarrhea; GI = gastrointestinal; HA = headache; R = rash; QD = once daily; BID = twice daily; TID = three times daily;

ADJ = adjustment; DI = Drug Interactions

- Adapted and summarized from reference 1 and 16.

Table 1. ANTIRETROVIRALS (ARVs) (continued) Generic Name,

Abbreviation (Trade Name)

Adult Dosing Food Effect Adverse Events NOTE

CCR5 Antagonists

Maraviroc, MVC (Selzentry)

150 mg BID - MVC + strong CYP3A inhibitor:

300 mg BID- MVC + NRTIs, T20, TPV/RTV, NVP & other drugs that are not strong CYP3A inhibi- tors:

600 mg BID - MVC + CYP3A inducers W/O CYP3A inhibitor

No restrictions

Abdominal pain, cough, dizziness, musculoskeletal symptoms, R, pyr- exia, upper respiratory tract Infec- tion, hepatotoxicitiy, orthostatic hypotension sleep disturbances

· Substrate of liver enzymes.

· CYP3A inhibitors (except TPV/r) and DLV increase MVC.

· CYP3A inducers decrease MVC.

Integrase Inhibitors Raltegravir, RAL

(Isentress) 400 mg BID No restrictions N, HA, D, pyrexia, CPK elevation · Metabolism: UGT1A1- mediated

Glucuronidation Protease Inhibitors(PIs): Metabolic abnormalities including dyslipidemia, hyperglycemia, insulin resistance, and lipodystrophy (Ataza- navir is less likely to cause dyslipidemia) Osteonecrosis and hepatotoxicity, increased the risk of bleeding in hemophiliacs, or significant interactions with other drugs.

Atazanavir, ATV (Reyataz)

400 mg QD

* If taken w/ EFV or TDF:

300 mg QD + RTV 100 mg QD

With food Avoid taking

with antacids.,

Hyperbilirubinemia, Prolonged PR interval, hyperglycimia, Nephroli- thiasis

Substrate and Inhibitor of liver enzymes.

Boost with RTV when given with TDF.

Dosage adjustment in hepatic insufficiency recommanded Darunavir, DRV

(Prezista)

(DRV 600 mg + RTV

100 mg) BID With food R, D, N, HA, Hyperlipidemia,Tran- saminase elevation

Substrate and Inhibitor of liver enzymes (CYP450 3A4)

Fosamprenavir, FPV

(Lexiva)

ARV naïve pt:

-FPV 1400 mg BID or -(FPV1400 mg QD + RTV 200 mg) QD or

- (FPV 700 mg + RTV 100 mg) BID

-(FPV 1400 mg + RTV 100 mg) QD

PI-experienced pts (QD not recommended):

(FPV 700 mg + RTV 100 mg) BID

Coadministration w/ EFV (FPV boosted only):

(FPV 700 mg + RTV 100 mg) BID or (FPV 1,400 mg + RTV 300 mg) QD

No restrictions

R, D, N, V, HA, Hyperglycemia, Hyperlipidemia

Transaminase elevation, oral paresthesias

Substrate and inhibitor of liver enzymes;

Consider DI

Dosage adjustment in hepatic insufficiency recommanded

N/V/D = nausea/vomiting/diarrhea; GI = gastrointestinal; HA = headache; R = rash; QD = once daily; BID = twice daily; TID = three times daily;

ADJ = adjustment; DI = Drug Interaction ***COMBINATION DRUGs: 1. Zidovudine / Lamivudine, AZT + 3TC (Combivir)-One BID 2.

Lamivudine / Abacavir, 3TC + ABC (Epzicom)-One QD 3. Zidovudine, Lamivudine, Abacavir, AZT + 3TC + ABC (Trizivir)-One BID 4.

Tenofovir, Emtricitabine, TDF + FTC (Truvada)-One QD 5. Efavirenz / emtricitabine / tenofovir, EFV + FTC + TDF (Atripla)-One QD - Adapted and summarized from reference 1 and 16.

Table 1. ANTIRETROVIRALS (ARVs) (continued) Generic Name,

Abbreviation (Trade Name)

Adult Dosing Food Effect Adverse Events NOTE

(continued) Protease Inhibitors(PIs): Metabolic abnormalities including dyslipidemia, hyperglycemia, insulin resistance, and lipodystro- phy (Atazanavir is less likely to cause dyslipidemia) Osteonecrosis and hepatotoxicity, increased the risk of bleeding in hemophiliacs, or significant interactions with other drugs.

Indinavir, IDV (Crixivan)

800 mg q8h (800 mg + RTV 100- 200 mg) BID

Unboosted IDV Levels decrease by 77% ,

Take 1 hour before or 2 hours after meals RTV-boosted IDV:

No restrictions

Nephrolithiasis, GI intoler- ance, N, Hyperbilirubine- mia, Hyperlipidemia, HA, R, metalic taste,

Hemolytic anemia, Fat maldistribution

Inhibitor of liver enzymes(CYP450 3A4) Dosage adjustment in hepatic insufficiency recommanded

Lopinavir / ritonavir, LPV/r

(Kaletra)

Two tablets or 5 mL BID or

ARV Naïve pts : four tablets or 10 mL QD With EFV or NVP:

For treatment-experi- enced pts:

3 tablets BID or 6.7 mL oral solution BID

Oral tablet- No restriction /

Oral Solution- With Food

GI intolerance, N/ V/ D, Hyperlipidemia, Transam- inase elevation, Fat mald- istribution

Substrate and Inhibitor of liver enzymes(CYP450 3A4);

Nelfinavir, NFV (Viracept)

1250 mg BID or

750 mg TID With food

N/ V/ D, Hyperlipidemia, Hyperglycemia,

Transaminase elevation, Fat maldistribution

Substrate and Inhibitor of liver enzymes(CYP450 3A4);

Ritonavir, RTV (Norvir)

*600 mg every 12 hours

(when ritonavir is used as sole PI)

As pharmacokinetic booster for other PIs – 100 mg~400 mg / day in 1-2 divided doses

With food

GI intolerance, N/ V/ D, Paresthesias, Hyperlipi- demia, Hepatitis, Taste perversion

Significant drug interac- tions due to potent inhibi- tion of liver

enzymes(Potent CYP450 3A4)

Saquinavir, SQV (Invirase)

(SQV1000 mg + RTV 100 mg) BID

Take within 2 hours of a meal when taken with RTV

GI intolerance, N, D, HA, Hyperlipidemia, Transam- inase elevation, Fat mald- istribution

Substrate and Inhibitor of liver enzymes(CYP-3A4)

Tipranavir, TPV (Aptivus)

(TPV500 mg + RTV

200 mg) BID No data available

Hepatotoxicity, R, Hyper- lipidemia, Fat maldistribu- tion

Rare cases of fatal and non-fatal intracranial hem- orrhages, N/ V/ D.

TPV - Cytochrome P450 (3A4 inducer and sub- strate)

Net effect when combined with RTV - CYP 3A4 inhibitor and CYP 2D6 inhibitor

Unboosted tipranavir is not recommended

ADJ = adjustment; DI = Drug Interaction ***COMBINATION DRUGs: 1. Zidovudine / Lamivudine, AZT + 3TC (Combivir)-One BID 2.

Lamivudine / Abacavir, 3TC + ABC (Epzicom)-One QD 3. Zidovudine, Lamivudine, Abacavir, AZT + 3TC + ABC (Trizivir)-One BID 4.

Tenofovir, Emtricitabine, TDF + FTC (Truvada)-One QD 5. Efavirenz / emtricitabine / tenofovir, EFV + FTC + TDF (Atripla)-One QD - Adapted and summarized from reference 1 and 16.

and metabolism.

Management of the metabolic compli- cations include manipulation of the anti-HIV drugs with a knowledge of their specific effects on lipid and glucose metabolism, related to established therapeutic interven- tions (Table 1).

Additionally, lifestyle interventions as smoking cessation, a healthy diet and excercise play a pivotal role in reducing dyslipidemia in HIV-infected persons.

This article is to report an unusual case that very high level of low-density lipoprotein (LDL) and high level of triglyceride (TG) were measured in the process of anti-HIV pharmacotherapy, suggesting regu- lar monitoring of labs for the optimal individualized treatment in HIV-infected persons to prevent and man- age metabolic complications.

CASE REPORT

The patient, ES was a 35-year-old Caucasian female (Height: 5’8”(172.7 cm), Weight: 200 lbs(91 kg)) who pre- sented to HIV Clinic. She reported that she didn’t want to take her HIV medications due to severe nausea &

vomiting and also stopped these meds 3 days ago. In addition, she reported that she thought her HIV meds made her sick. She mentioned that she took her HIV medications(meds) on empty stomach and with no breakfast every morning until 3 days ago. Her current

antiretrovirals (ARVs) were needed to change because of her severe nausea & vomiting. The patient had been HIV positive since 1999. She was on ARVs. She visited the HIV meds on Mar.4, 2008 due to diarrhea for a cou- ple of days. She took Immodium, and continued with her current meds. Her lab was ordered. Her return to clinic was scheduled to Mar 21, 2008. Previously, she had severe diarrhea on viracept and rash on viramune on 2000.

Her recent antiretroviral therapy (ART) which was PI-based is truvada 1 tablet once daily, kaletra 2 tab- lets twice a day.

Her previous and current medica- tion lists shows Table 2.

Table 2. Patient's Medication List

Previous Meds :

03/04/08 Immodium 2 mg, 1 capsule BID PRN for diarrhea

02/04/08 Flagyl 500 mg 1 tab po twice daily for seven days.

01/04/08 FeSO

1 tab po 3 times a day Truvada 1 tab po daily

Kaletra 400/100 mg 2 tab po daily (D/C Viracept due to diarrhea) Procrit 40,000 units/ml Inject 1 ml (one ml)

-Once weekly dispense,1 month supply(*4)

10/10/07 Truvada 1 tab once daily Viracept 625 mg, 2 tabs twice daily

Previous ARVs :

Emtricitabine(FTC), Tenofovir(TDF), Nelfi- navir(NFV)

Current Meds: Truvada 1 daily, Kaletra 2 tablets twice a day Vit B12, Iron pill

Meds: medications, BID: two times a day, PRN: as needed, PO: per oral

Table 3. The patient's lab data after HIV clinic visit

CBC 03/04/08 01/05/08 10/05/07

WBC (4.5-10.5 thou/cmm) 6.4 4.8 4.1

RBC (3.8-5.3 ml/cmm) 3.77 3.65 2.81

Hgb (12-16 g/dL) 9.9 9.7 9.7

Hct (33-43%) 30.5 29.4 26.6

RDW 20.9 17.4 16.7

MCH (27-34 pg) 26.2 26.4 31.8

MCHC (32-36 g/dl) 32.8 32 33.5

Plt (140-400 thou/cmm) 434 316 257

CHEMISTRY

BUN (6-21 mg/dl) 5

SCr (0.6-1.2 mg/dL) 0.9 0.9

Na+ (136-145 mmol/l) 139 138

K+ (3.5-5.1 mmol/l) 3.9 3.2

Cl- (98-108 mmol/L) 100 103

Ca(8.5-10.6) mmol/L 8.4 8.2

Gluc (70-110 mg/dl) 64 68

Albumin (3.9-5.0 g/dl) 4.2 4.0

AST (SGOT) (5-40 U/L) 24 22

ALT (SGPT) (7-56 U/L) 15 24

Other labs

Total Cholesterol mg/ml 172

Triglyceride mg/dl 239

LDL mg/dl 902

Serum Iron (35-155) 22

Iron Saturated (15-55) 5

Vit B12 (211-911) 217 171

Folate (> 5.4 ) 3.8 5.8

Ferritin, Serum (10-291) 6

Lipase (0-59) U/L 48

Bilirubin, Total 0.1

CD4 % (30.8-58.5) 30.6 28.9 31

CD4 Cell/mm

490 318 453

VL cell/ml (390-1480) 48 < 48 < 400

Her family history was hypertension, diabetes, myo- cardiac infarction (MI) and cancer. She has no known drug allergy. Her husband died of acquired immune defi- ciency syndrome (AIDS) prior to transmitting it to her.

She lived in an assisted living facility. She is not drug abuser. She smokes tobacco one pack per day. On March 13, 2008, her pulse was 106, respiratory rate was 20, body temperature was 98.9 F (37.2

C) and blood pressure (BP) was 105/75 mmHg. On Jan 5, 2008, her lab data were red blood count (RBC) 3.65, hemoglobin (Hgb) 9.7, hematocrit (Hct) 29.4, triglyceride (TG) 239, serum iron 22, iron saturated 5, CD4% 30.6, CD4 cell/mm

490, viral load (VL) 48. She had no hepatitis B and C. On Mar 5, 2008, her lab data were red blood count (RBC) 3.77, hemoglobin (Hgb) 9.9, hematocrit (Hct) 30.5, low-density lipoprotein (LDL) 902, folate 3.8 and serum HCG < 2. Her stool culture was negative (Table 3). She was not really symptomatic with her anemia unlike her lab data, specifi- cally no fatigue, lethargy or problem of natures. She is HIV positive. Her CD4 count (cell/mm

) increased from

318 to 490, her viral load is still undetectable (< 50) based on her lab data. Her lab data shows Table 3. She is sched- uled to return to clinic (RTC) in 10 days for follow-up with HLAB*5701 test result and starting her new regimen including abacarvir and atazanavir based on guideline (preferred option).

DISCUSSION

This is the rare, unusual case of very highly elevated low-density lipoprotein (LDL) and elevated triglyceride (TG) level in the process of HIV pharmacotherapy. This case suggests that healthcare professionals need to moni- tor regularly patients’ labs in the middle of HIV-infected persons’ pharmacotherapy with ARVs for the optimal individualized treatment as well as prevention and man- agement of metabolic complications, while considering adverse reaction profile of each ARV. Higher LDL levels increase the risk of cardiovascular disease, and reduc- tion thereof reduces this risk.

Table 4. Therapeutic & Toxic effects with monitoring parameters for each drug lists

Drug's Name Therapeutic(+) Toxic (-)

EPZICOM (Abacarvir + lamivudine)

(+) No food restrictions QD dosing available, Preferred option by guidelines

(-) Hypersensitivity reaction and Dosage adjustment in patients(pts) with renal insufficiency

* Monitor BUN, Scr

* Not for patients with CrCl < 50 mL/min Abacarvir (+) No need for dosage adjustment in

patient with renal or hepatic Insufficiency, No food restriction

* Abacarvir for patients(pts) who test negative for

HLAB*5701 (inform pts of hypersensitivity reaction such as Fever, Rash, Malaise and Nausea which usually appear within the first 6 weeks of treatement, IF pts get the symptom, Just Discontinue and let Doctor know.

Test & Monitor HLAB*5701

* Do not rechallence.

Lamivudine (+) minimal drug interaction No food restriction

(-) lactic acidosis with hepatic steatosis, dry mouth, Headache Monitor BUN, Scr

* Dosage adjustment in renal Insufficiency

* Never can be used as monotherapy because resistance devel- ops rapidly

REYATAZE (Atazanavir)

(+) Less cause dyslipidemia Take with food

(-) Indirect hyperbilirubinemia, Prolonged PR interval, Neph- rolithiasis

*Avoid taking with antacids. *Should not be taken with PPIs / Should be dose adjustment needed if taken with H2 blockers.

No dosage adjustment for patients with renal dysfunction not requiring hemodialysis

* Monitor : LFTs * Dosage adjustment for patients with hepatic impairment (Child-Pugh Score (7-9) 300 mg QD, (> 9) Not recommended )

Adapted and summarized from reference 1,16, 23-25

There are several aspects we need to consider for her HIV pharmacotherapy. The patient had severe nausea and vomiting and stopped her HIV meds. She also took her HIV meds on empty stomach with no breakfast daily.

Her current ARV regimen is needed to change new regi- men to improve her compliance and continuously increase CD4 cell (> 350) as well as to suppress HIV virus and pre- vent resistance related to her ART. She needs to be Informed of new drug information, which includes reviewed adverse drug reactions (ADRs) of new regimen and importance of adherence to prevent resistance of her ART.

In addition, she needs to be educated regarding how to take her ARV correctly to get optimal therapy outcome.

In case of her dyslipidemia, etiology of problem & risk factors were PI-based HAART, obesity, smoking, diet, high LDL, high TG and family history of MI.

Her Current ART, PI based regimen-Truvada 1 tablet once daily, Kaletra 2 tablets twice a day-was known to cause dyslipidemia in patients over time leading to elevated TG and LDL levels.

However, currently patient doesn’t have any therapy to control dyslipidemia. Studies have shown that a diet, exercise and maintaining normal body weight tend to reduce dyslipidaemia; if not effec- tive, consider a change of ART and then consider lipid- lowering medication in high-risk patients.

Co- administration of statins and ARVs should be carried out possible drug-drug interactions.

Simvastatin is contraindicated in patients receiving ritonavir-boosted PI- based ARV like Kaletra.

Statins are recommended as first-line therapy to reduce elevated LDL-cholesterol lev- els.

In her case, LDL is the primary target of therapy which remains above goal (LDL-902), so that current patient's PI-based regimen is needed to change new regi- men, Atazanavir (ATV) based regimen, which is less cause dyslipidemia.

Furthermore, the patient requires intervention to reduce future events such as cardiac and cerebrovascular and possible mortality in this high risk patient using lipid lowering agent to control abnormal lipid panels.

Primary goal for treatment of dyslipi- demia problem is LDL < 130 based on ATP III Guide- lines (NCEP III), then TG < 150, to prevent coronary

heart disease (CHD) event and to Improve the quality of life.

Therefore, for her dyslipidemia, she needs to start HMG Co-A reductase inhibitors such as pravasta- tin, atorvastatin and rosuvastatin.

According to the recent study which compared the effectiveness and toxicity of statins among HIV-infected patients in clinical care, it suggests that atorvastatin and rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients with dyslipidemia, due to greater declines in total cholesterol, LDL-C, and non-HDL-C, with similar lower toxicity rates.

Drug treatment for her problem is also recom- mended by Reyataz 200 mg, 2 capsules and Epzicom 1 tablet daily with food based on HIV guideline instead of Kaletra and Truvada.

She needs to hold her new regimen during 10 days until checking HLA-5701B test result before taking Epzicom.

In addition, she needs to be educated to take her meds with food instead of tak- ing them on empty stomach to optimize her therapy.

Monitoring & further tests of her pharmacotherapy need efficacy based on lab test as following fasting lipid panel (initially, 3-6 months after initiating, yearly) and monitor- ing labs such as LFTs (initially, 6-8 wks after initiating, twice a year), and creatinine kinase (CK) if suspect rhab- domyolysis with symptoms like muscle pain or weak- ness.

Therapeutic & Toxic effects for each drug with Monitoring parameters listed in Table 4.

There are further tests as following, recheck viral load (VL) and CD4 counts (2-8 wks after initiating new ther- apy), monitor every 3-4 month while on therapy, and resistance test if incomplete virologic response or viro- logic rebound with compliance on HAART (VL > 400 after 24 weeks, VL > 50 after 48 weeks, CD4 increase of

< 25-50 in 1

year or CD4 decrease below baseline on therapy).

Her Body Mass Index (BMI) is 30.43 (wt (kg) / ht

(m)). According to the WHO, any BMI more than 30 kg/

m

is considered obese. Her weight actually increased 6

pounds compared to last visit on Mar. 13, 2008. Etiology

and Risk Factors of her anemia includes weight gain, PI-

based HAART (High LDL, High TG), lifestyle, Diet and

lack of physical activity.

According to European AIDS

Clinical Society (EACS) guidelines, a healthy diet, exer-

cise and maintaining normal body weight tend to reduce dyslipidemia; if not effective, a change of ART should be considered, followed by use of lipid-lowering medi- cation in high-risk patients.

Therefore, the evaluation for her therapy needs related adverse drug reac- tions(ADRs) of meds and diet & lifestyle. The goal for treatment of problem is to manage weight gain up to nor- mal level to avoid further metabolic complication by appropriate medication selection, lifestyle medication &

diet including check-up BMI more frequently (every 4 weeks-quaterly).

The patient was not really symptomatic with her anemia unlike her lab data, specifically no fatigue, lethargy or problem of natures. Etiology and Risk Factors of her ane- mia include chronic HIV/AIDS, iron deficiency, impaired bone marrow function, inadequate dietary intake, inade- quate GI absorption.

Based on her labs, she had hypo- chromic/microcytic anemia. The lab testing raises concerns about iron deficiency states. However, she is relatively asymptomatic (No fatigue, lethargic). Actually, she takes her iron sulfate tab twice daily. she needs continuous therapy for her anemia based on her lab data and need to monitor closely her platelet level & recheck serum eryth- ropoietin level for further evaluation.

She is recom- mended to take continuously Ferrous Sulfate 325 mg orally three times daily on an empty stomach and vit B12 pills to correct her deficiency states as well as to avoid transfusion, not recommended erythropoetin stimulating agent at this time because she is asymptomatic and has a high serum erythropoietin level and platelet level.

She needs re-evaluation after further recent labs results such as serum iron, Iron saturated, serum ferritin, intrinsic fac- tor antibodies, serum erythropoetinetc level.

There are monitoring & further tests such as RBC indices, reticulocytes, and iron studies monthly until stable.

Etiology and risk factors for her smoking for several years include inappropiate method to stop smoking results in failure to smoking cessation, one of current CHD risk factors.

After evaluation, she may need to start nico- tine replace therapy (NRT) for reducing physical with- drawal. There are drugs that may have a decreased effect due to induction of CYP1A2 with smokers, caffeine, flu-

voxamine, olanzapine, tacrine and theophylline.

In clinical setting, there is a limitation of evidence from randomized controlled trials on how to most effec- tively manage metabolic complication in HIV-infected persons.

Therefore, management is currently based on HIV guidelines which are being regularly updated by clinical research findings.

When using pharmacologi- cal interventions to prevent and manage metabolic com- plication(s), the efficacy of ART should be clarified by considering the potential of drug-drug interactions and compromised adherence.

This is the unusual case of very highly elevated low-density lipoprotein (LDL) and elevated triglyceride (TG) level in the process of HIV pharmacotherapy. This case suggests that HIV-infected persons’ pharmacotherapy is needed to monitor regularly patients’ labs in the middle of treatment process with ARVs not only for prevention and management of meta- bolic complications but also for the optimal individual- ized treatment, considering adverse reaction profile of each ARV.

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