Card Set Information
Chapter on HIV drugs
Human Immunodeficiency Virus
: Lacks ability to self-replicate~ Obligate intracellular parasite
RNA is genetic material rather than DNA
Reverse transcriptase is enzyme needed to transcribe RNA to DNA
Two types ( First described in 1981 )
HIV-1 Found world-wide
HIV-2 Found mainly in west Africa (increased population mobility will cause HIV-2 to travel globally too.)
Be aware that there are different genotypes/phenotypes. Will become important to identify which group the individual belongs to.)
What are CRFs?
Circulating Recombinate Forms: Different genotypes/phenotypes may combine (ie A and C) to form a new form that is both A and C.
Target CD4 T Helper Cells (Helper T lymphocytes)
Immune system undergoes progressive decline
Person becomes more susceptible to opportunistic infections
HIV Clinical Course
Triphasic (three phases of treatment)
~ Massive replication of virus
Experience flu-like acute retroviral syndrome
~ Prolonged clinical latency
~ CD4 T cells drops below critical level (<350mm/cm
At this point you should be treating to increase CD4 T cell count. Will help to prevent HIV from becoming AIDS.
HIV damages many cell types including
Nervous system, ie peripheral neuropathies like numbness, tingling, feeling like walking on cotton balls, "sleeping" limbs.
Tests for HIV
Viral Load (Plasma HIV-RNA)
: Antibody tests like...
Enzyme Immunoassy (EIA)- 2 weeks for results
Rapid HIV antibody test- 10 to 20 minutes
Western Blot Test- confirms Rapid HIV in 2 weeks.
CD4 T Cell Count
HIV Drug Resistance
Two types of Assays available
Genotypic and Phenotypic
31 drugs on the market for HIV
Only 6 have been approved since 2004
3 years ago---7 drugs in stage 3
none have made it to market
Only 2 remain in the final stage
What are the 4 Major Classes of HIV Drugs?
HIV Fusion Inhibitors
: Prevent HIV from entering cells
Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors (NRTI”S)
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI’S)
Nucleotide reverse transcriptase inhibitors
: Most effective drug available. Its the first one used.
Usually multi-drug therapy to prevent virus from becoming immune to the one drug your taking.
Who is at highest risk for contracting HIV in US
Homosexual black males.
Enfuvirtide (T-20 )
Blocks entry of HIV into CD4 T cells
Requires 2 x day Sub –q injections
Cost $20,000 a year
Must be taken with other drugs
Will develop resistance if taken alone
Drug company is recommending
both phenotype and genotype resistance testing
Adverse reactions to Enfuvirtide (T-20)
Skin reactions at injection sites
Itching, redaness, swelling, hardened skin, lumps
Pain and numbness in legs and feet
Loss of sleep
: Eleveted eosinophils (T-cells which respond to foreign proteins) counts. Becomes harder to diagnose cause of histamine responses. Allergies will become worse.
Reduces viral load
Increases CD4 T Cell counts
Delays onset of disease symptoms
Reduces symptom severity
1st drug administered in new HIV pts.
: Inhibits HIV replication; Blocks viral DNA synthesis by inhibiting reverse transcriptase--becomes incorporated into growing viral DNA strand
Penetrates CNS well--assists in relieving cognitive symptoms and periferal neuropathies.
Should be combined with at least one other agent
Adverse Effects of NRTI's
*** Anemia and Neutropenia ***
Especially seen with multiple drug therapy and advanced disease
May require repeated blood transfusions
Epoetin--Stimulates increased production of RBCs
Sargramostim--Stimulated increased production of WBCs
Determine hematologic status before treatment then q (every) 2 wks for first 8 wks ….then q 4 wks
Lactic Acidosis (pts with HepB and HepC)
With severe hepatomegaly and hepatic stenosis. Dosing then becomes an issue.
Will tire more easily and rapid respirations
: 1st line of defense against foreign agents.
Patient Education with NRTIs
Take exactly as ordered -- around the clock
Does not cure disease and does not reduce the risk of transmission. Will only decrease amount of virus and increase CD4 T cells.
Notify Health Care Provider of S&S (signs and symptoms) because will become open to all of the fungal infxns of infection
Avoid OTC medications because this Rx will interact with just about everything, especially St. Johns Wart as well as other herbs. Will increase risk and severity of SEs.
Importance of regular follow-up exams and blood counts
Nonnucleotide Reverse Transcriptase Inhibitors (NNRTIs)
Binds directly to HIV reverse transcriptase and disrupts active center of enzyme
Only for HIV- 1
Resistance develops rapidly if drug is used alone
Nonnucleotide Reverse Transcriptase Inhibitors (NNRTIs)Nevirapine (Viramune)
Rash ~ All over body, may advance to Epidermal Necrolysis (aka Stephen Johnson's syndrome)
Especially during the 1st month of therapy
(is now contraindicated)
Monitor liver enzyme levels ~ AST and ALT
Especially during 1st 6 months of therapy
Those with Hepatitis B or C
Nonnucleotide Reverse Transcriptase Inhibitors (NNRTIs)Nevirapine (Viramune)
Same as AZT
Women of childbearing age should use an additional , nonhormonal BC Measure other than BC Pills
Does not protect you from multiple strains of HIV.
Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)
Works exactly the same as NNRTI
Only one on market,
Most effective antiretroviral drugs available
When used with other drugs …
Viral levels are reduced to levels not detected by current assays
All inhibit Cytochrome P450…dosing is a challenge
Never use alone
Binds to the active site of HIV protease preventing the enzyme from cleaving HIV polyprotein. Therefore,
the structural proteins and enzymes of HIV are unable to function and the virus remains immature and noninfectious.
Hyperglycemia. Essentially puts pt into a diabetic state.
Monitor blood glucose levels
prior to and during therapy
Assess for signs of Hyperglycemia like:
~ Increased thirst. Body's effort to dilute excess sugar in the body.
Unexplained weight loss
~ Increased urination
Fatigue due to lack of glucose.
Dry, itchy skin
Managed with Insulin and oral hypoglycemics
Fat Redistribution to
Between the shoulder blades
Fat is lost from the arms, legs, face and buttocks
Skinny arms/legs, "buffalo" hump.
(Muscle mass and strength is not affected.)
Elevated levels of cholesterol and triglycerides. Related to fat redistribution.
Can lead to cardiovascular disease.
Can occur regardless of fat redistribution
May lead to CV disease, pancreatitis
Monitor lipid levels prior to and during treatment
Avoid treatment with lovastatin andsimvastatin
Inhibition of P450--Toxic levels
Increased bleeding in Hemophiliacs
Usually seen in 1st month of treatment, usually in joints and soft tissue
May need to increase coagulation factors
Reduced Bone Mineral Density
Studies found 10-21 % taking Protease Inhibitors developed osteoporesis
Elevation of Serum Transaminase
Indicates Liver Injury
Monitor Liver enzymes prior to and during treatment
Especially in those with Hepatitis and cirrhosis
Too many to identify.
Related to P450 effects
May cause severe adverse rxn
NO OTC meds should be taken
What is the Protease Inhibitor synergistic Rx
Is not used for its antiviral proberties
Used to “Boost” other HIV meds
Inhibits the catalytic activity of HIV-1 which is required for viral replication
Nephrotoxicity. Increased levels of creatine kinase. Be sure to check creatinine clearance.
Atripla (multi – class)
Efavirenz ( NNRTI )
Emtricitabine ( NRTI )
Tenofovir disoproxil fumarate ( NRTI )
Side effects of multidrugs are multiplied x4!
General Drug Interactions of all HIV/AIDS drugs
St John’s Wort -- Reduce levels of NNRTI’s and PI’s related to accelerated induction of P450
Garlic supplements can decrease levels of PI’s…. Up to 50%, so Dietary garlic should be kept to minimum