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Report for Advanced Clinical Pharmacy Class

Millet Villarosa

on 9 October 2012

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Transcript of HIV/AIDS

Human Immunodeficiency Virus The human immunodeficiency virus (HIV) is a retrovirus that infects cells of the immune system, destroying or impairing their function. As the infection progresses, the immune system becomes weaker, and the person becomes more susceptible to infections. The most advanced stage of HIV infection is acquired immunodeficiency syndrome (AIDS).
It can take 10-15 years for an HIV-infected person to develop AIDS. ETIOLOGY •More than 34 million people now live with HIV/AIDS.
•3.4 million of them are under the age of 15.
•In 2010, an estimated 2.7 million people were newly infected with HIV.
•390,000 were under the age of 15.
•Every day more than 7,000 people contract HIV—nearly 300 every hour.
•In 2010, 1.8 million people died from AIDS.
•250,000 of them were under the age of 15.
•Since the beginning of the epidemic, more than 60 million people have
contracted HIV and nearly 30 million have died of HIV-related causes. Worldwide Status Status: Philippines In July 2012, there were 278 new HIV Ab Sero-positive individuals confirmed by the STD/AIDS Cooperative Central Laboratory (SACCL) and reported to the HIV and AIDS Registry. This was 36% higher compared to the same period last year (n=204 in 2011). - Philippine National AIDS Council -fever, sore throat, fatigue, weight loss and myalgia
-morbillform or macupapular rash usually involving the trunk
-diarrhea, nausea, vomiting
-lymphadenopathy, night sweats
-aseptic meningitis (fever,headache,photophobia, stiff neck) Symptoms HIV-1
HIV-2 Types Stages if HIV 2.The stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) lasts an average of eight to 10 years. 3.The stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed, is called the acquired immunodeficiency syndrome (AIDS). ELISA
Western Blot
Viral Load Laboratory Tests and Procedure WESTERN BLOT TEST -more difficult than the ELISA to perform
-done to confirm the results of two positive ELISA tests. -finds either the RNA of the HIV virus or the HIV DNA in white blood cells infected with the virus
-requires technical skill and expensive equipment.
-genetic material may be found even if other tests are negative for the virus. --determine if an HIV infection is present when antibody test results were uncertain
-screen blood or organs for HIV before donation. POLYMERASE CHAIN REACTION -quantifies viremia
-measures viral RNA
-viral load used as prognostic factor in disease progression and effects of treatment VIRAL LOAD Goals
Prevention TREATMENT -maximum suppression of HIV Replication
-increase in CD4 Lymphocytes
-improved quality of life
-decreased morbidity and mortality Goals NRTIs
Protease Inhibitors
Entry Inhibitors
Integrase Inhibitor Antiretrovirals 2.Stavudine (d4T)
-Reduce mitochondrial DNA synthesis
-Peripheral neuropathy, lipoatrophy, hyperlipidemia

3.Didanosine (ddl)
-Acid-labile, taken in fasting state
-Pancreatitis, monitor serum amylase
-Dose-limiting toxicity = peripheral neuropathy 4.Tenofovir (TDF)
-First approved nucleotide analogue
-Long half-life, allows once-daily dosing
-Gastrointestinal complaints
-Increases ddl concentrations
-Decrease concentrations of Atazanavir, must be boosted with Ritonavir

5.Lamivudine (3TC)
-Approved in combination with AZT
-Terminates synthesis of proviral DNA
-Inhibits reverse transcriptase of both HIV and HBV
-Does not affect mitochondrial DNA synthesis 6.Emtricitabine (FTC)
-As effective as Lamivudine
-Does not affect CYP450 isozymes
-Headache,diarrhea, nausea, rash
-Hyperpigmentation of soles and palms
-Associated with lactic acidosis, fatty liver, hepatomegaly
-Withdrawal in HBV-infected patients may worsen hepatitis

7.Zalcitabine (ddC)
-Removed from the market

8.Abacavir (ABC)
-GI disturbance, headache, dizziness
-Hypersensitivity reaction – drug fever, rash,malaise,repiratory distress 1.Nevirapine (NVP)
-Potential severe hepatotoxicity (CD4+ Tcells W= 250/mm3,M= 400/mm3)
-Inducer of CYP34A
-Increase metabolism of protease inhibitors
-Rash,fever,headache, elevated serum transaminase,fatal hepatotoxicity
-SJS, toxic epidermal necrolysis (14-day titration period at half the dose is mandatory)

2.Delavirdine (DLV)
-Inhibitor of CYP450 and protease inhibitors
-Fluoxetine and Ketoconazole increase plasma levels
-Phenytoin, Phenobarbital,Carbamazepine decrease plasma levels
-Rash NNRTIs 3.Efavirenz (EFV)
-Increase CD4+ T cell counts and decrease viral load (with NRTIs)
-Once-daily dosing
-Potent inducer of CYP450 enzyme
-Dizziness, headache, vivid dreams, loss of concentration
-Rash most common side effect
-Should be avoided in pregnant women 1.Ritonavir (RTV)
-Pharmacokinetic enhancer or booster of other protease inhibitor
-Potent inhibitor of CYP3A at low doses
-Self-inducer of its own metabolism
-Nausea,vomiting,diarrhea,circumoral parethesias

2.Saquinavir (SQV)
-Given with Ritonavir
-Headache,fatigue,diarrhea, other GI disturbances
-Increased level of hepatic amonitransferases in patients with viral hepatitis B or C

3.Indinavir (IDV)
-Least protein bound and has the shortest half-life among protease inhibitors
-Ritonavir permits absorption when taken with meals
-Nephrolithiasis, hyperbilirubinemia, kidney stone formation, fat redistribution Protease Inhibitors 4.Nelfinavir (NFV)
-Only protease inhibitor that cannot be boosted by Ritonavir (extensively metabolized by CYP3A
-Diarrhea can be controlled by loperamide

5.Fosamprenavir (fAPV)
-Prodrug metabolized to amprenavir
-Preferred protease inhibitor with Ritonavir in DHHS treatment guidelines

6.Lopinavir (LPVr)
-GI adverse effect and hypertriglyceridemia
-Oral solution contains alcohol (unpleasant reaction with disulfiram and metronidazole) 7.Atazanavir (ATV)
-Structurally unrelated to other HIV protease inhibitors
-Preferres once-daily dosing with Ritonavir
-Competitive inhibitor of glucoronyl transferase
-Benign hyperbilirubinemia, jaundice
-Prolong PR interval and slows heart rate
-Decreased risk of hyperlipidemia
-Contraindicated with PPIs, 12hrs apart H2 antagonists and antacids

8.Tipranavir (TPV)
-Resistant to other protease inhibitors
-CYP450 inducer
-Black box warnings for severe and fatal hepatitis and fatal and nonfatal intracranial hemorrhages
-Useful in salvage regimens in patients with multidrug resistance

9.Darunavir (DRV)
-Decreased risk of hyperlipidemia
-Useful in salvage regimens in patients with multidrug resistance 1.Enfuvirtide
-Fusion inhibitor
-Binds to gp41 to prevent conformational change of viral transmembrane and entry to the host cell
-Peptide, SC administration
-Pain, erythema, induration, nodules
-Needs reconstitution, expensive

-Second entry inhibitor
-Blocks CCR5 coreceptor that works together with gp41 Entry Inhibitors 1.Raltegavir (RAL)
-Specifically inhibits the final step in integration of stand transfer of viral DNA to the host cell DNA
-No drug interaction with CYP450 inducers, inhibitors and substrates
-For treatment-experienced patients with evidence of viral replication despite ongoing antiretroviral drug therapy. Integrase Inhibitors REGIMEN Preferred Regimens: Regimens with optimal and durable efficacy, favorable tolerability and toxicity profile and ease of use)

NNRTI-based Regimen:
PI-based Regimen (Alphabetical order):
-DRV/r (once daily) + TDF/FTC
INSTI-based Regimen:
Preferred regimen for pregnant women:
-LPV/r (twice daily) + ZDV/3TC

-EFV should not be used during the first trimester of pregnancy or in women of child-bearing potential who are trying to conceive or not using effective or consistent contraception
-TDF should be used in patients with renal insufficiency
- ATV/r should not be used in patients who require >20mg Omeprazole equivalent per day. Alternative Regimens: Regimens that are effective and tolerable but have potential disadvantages compared with preferred regimen. Alternative ragimen can be the preferred regimen for some patients.

NNRTI-based Regimen:
PI-based Regimen (Alphabetical order):
-ATV/r + ABC/3TC

-DRV/r + ABC/3TC

-FPV/r (once or twice daily) + ABC/3TC or TDF/FTC

-LPV/r (once or twice daily) + ABC/3TC or TDF/FTC

INSTI-based Regimen:
- RAL + ABC/3TC REGIMEN Comments:
-Use RPV with caution in patients with pretreatment HIV RNA >100,000

-Use of PPIs with RPV is contraindicated.

-ABC should not be used in patients who test positive for HLAB*5701.

-Use ABC with caution in patients with known high risk of CVD or with pretreatment HIV RNA >100,000 copies/mL. (See text.)

-Once-daily LPV/r is not recommended for use in pregnant women. Acceptable Regimens: Regimens that may be selected to some patients but are less satisfactory than preferred or alternative regimens and Regimens that may be acceptable but more definitive data are needed.
NNRTI-Based Regimen:




PI-Based Regimen:
-ATV + (ABC or ZDV)/3TC

-ATV/r + ZDV/3TC

-DRV/r + ZDV/3TC

-FPV/r + ZDV/3TC

-LPV/r + ZDV/3TC
INSTI-Based Regimen:

CCR5 Antagonist-Based Regimen:

-NVP should not be used in patients with moderate to severe hepatic impairment.

-NVP should not be used in women with pre-ART CD4 count >250cells/mm3 or in men with pre-ART CD4 count >400 cells/mm3.

-Use NVP and ABC together with caution because both can cause HSRs within the first few weeks after
initiation of therapy.

-ZDV can cause bone marrow suppression, lipoatrophy, and rarely lactic acidosis with hepatic steatosis.

-LPV/r (twice daily) + ZDV/3TC is the preferred regimen for use in pregnant women.

-ATV/r is generally preferred over unboosted ATV. Unboosted ATV
may be used when RTV boosting is not possible.

-Perform tropism testing before initiation of therapy with MVC.MVC may be considered in patients who have only CCR5-tropic virus. REGIMEN Regimens that may be acceptable but should be used with caution: Regimens that have demonstrated virologic efficacy in some studies but are associated with concerns about safety, resistance, or efficacy.

PI-Based Regimen:
-SQV/r + (ABC or ZDV)/3TC

-SQV/r was associated with PR and QT prolongation in a healthy volunteer study.

-Baseline ECG is recommended before initiation of SQV/r.

-SQV/r is not recommended in patients with any of the
1. pretreatment QT interval >450 msec
2. refractory hypokalemia or hypomagnesemia
3. concomitant therapy with other drugs that prolong QT
4. complete AV block without implanted pacemaker
5. risk of complete AV block •Know your HIV status
•Abstain from sexual activity or be in a long-term mutually monogamous relationship with an uninfected partner.
•Correct and consistent condom use.
•Get tested and treated for STDs and insist that your partners do too.
•Male circumcision has also been shown to reduce the risk of HIV transmission
•Do not inject drugs. If you inject drugs, you should get counseling and treatment to stop or reduce your drug use. If you cannot stop injecting drugs, use clean needles and works when injecting.
•Participate in risk reduction programs. PREVENTION
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