Pharmville

• 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.)

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

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
• Immune
• Nervous system, ie peripheral neuropathies like numbness, tingling, feeling like walking on cotton balls, "sleeping" limbs.

• 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

• 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
• (NtRTI’S)
• 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.

Homosexual black males.

• 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

• Skin reactions at injection sites
• Redness
• Itching, redaness, swelling, hardened skin, lumps
• Peripheral neuropathy
• HA
• Pain and numbness in legs and feet
• Dizziness
• 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

• *** 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.

• 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

• Binds directly to HIV reverse transcriptase and disrupts active center of enzyme
• Only for HIV- 1
• Resistance develops rapidly if drug is used alone

• 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)
• Hepatoxicity
• Monitor liver enzyme levels ~ AST and ALT
• Especially during 1st 6 months of therapy
• Those with Hepatitis B or C

• Same as AZT
• Plus
• 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.

• 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:
• Abdomen
• Breasts
• 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.)

• Hyperlipidemia
• 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

• Ritonavir (Norvir)
• Is not used for its antiviral proberties
• Used to “Boost” other HIV meds

• Action
• 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 )

• Truvada
• Emtricitabine (NRTI)
• Tenofovir (PI)

Side effects of multidrugs are multiplied x4!

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