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Human Immunodeficiency Virus
- A retrovirus: 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)
- Initial Phase ~ Massive replication of virus
- Experience flu-like acute retroviral syndrome
- Middle Phase ~ Prolonged clinical latency
- Late Phase ~ CD4 T cells drops below critical level (<350mm/cm3) 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 (Entry 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
- Protease Inhibitors: Most effective drug available. Its the first one used.
- Integrase Inhibitors
- 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
- Peripheral neuropathy
- Pain and numbness in legs and feet
- Loss of sleep
- Eosinophilia: 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.
- Action: 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
- Neutrophils: 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
- D/C med (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 like condomns.
- Does not protect you from multiple strains of HIV.
Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)
- Works exactly the same as NNRTI
- Only one on market, Tenofovir (Viread)
- 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:
- Polydipsia ~ Increased thirst. Body's effort to dilute excess sugar in the body.
- Polyphagia ~ hunger
- Unexplained weight loss
- Polyuria ~ Increased urination
- Fatigue due to lack of glucose.
- Dry, itchy skin
- Managed with Insulin and oral hypoglycemics
- Fat Redistribution to:
- Between the shoulder bladesFat 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
- Ritonavir (Norvir)
- 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
- Side Effects
- Diarrhea, Nausea
- Nephrotoxicity. Increased levels of creatine kinase. Be sure to check creatinine clearance.
- Atripla (multi – class)
- Efavirenz ( NNRTI )
- Emtricitabine ( NRTI )
- Tenofovir disoproxil fumarate ( NRTI )
- Emtricitabine (NRTI)
- Tenofovir (PI)
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