HIV and AIDS. Shan Nanji

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1 HIV and AIDS Shan Nanji

2 HIV 2 Description: Enveloped Positive Sense

3 HIV 3 Structural Genes: Cleavage of gp160 leads to formation of ENV: Gp120: attachment to host CD4 T Cell Gp41: GAG (p24) Capsid protein POL Reverse transcriptase Integrase

4 HIV Presentation: Initial infection = often asymptomatic May also present with mononucleosis-like symptoms Later presentation Night sweats Weight loss Thrush Recurrent infections CD4 Count: Indicates the Viral Load: May indicate the of disease advancement 4

5 HIV Diagnosis: ELISA test Highly sensitive ( ) Moderately specific Western blot Low sensitivity Highly specific ( ) 5

6 HIV 6 Diagnosis: ELISA test Used to detect the presence of either a specific antibody or antigen Direct and Indirect Direct: uses a test antigen-detect specific antibody Indirect: uses a test antibody-detect specific antigen Intense color change indicates

7 HIV Diagnosis: Western blot Sample protein is separated via gel electrophoresis Labeled antibody binds relevant Confirmatory 7

8 HIV Prophylaxtic Treatments: CD4 < 200 cells/mm3 TMP-SMX for CD4 < 100 cells/mm3 TMP-SMX for Pneumocystis and toxoplasmosis CD4 < 50 cells/mm3 Azithromycin for 8

9 9 Trimethoprim - TMP MOA: Bacteriostatic Inhibits Bacterial Clinical Use: As a Combination TMP-SMX UTI Shigella Salmonella Pneumocystis jirovecii Pneumonia

10 10 Trimethoprim - TMP S/E: MegaloblasticAnemia Leukopenia Granulocytopenia Possible use of to Alleviate

11 Sulfonamides - Sulfamethoxazole(SMX), Sulfisoxazole, Sulfadiazine MOA: Bacteriostatic Inhibit Through PABA Antimetabolites 11 Clinical Use: Gram () Gram (-) Nocardia Chlamydia Simple UTI

12 Sulfonamides - Sulfamethoxazole(SMX), Sulfisoxazole, Sulfadiazine S/E: Hypersensitivity Reactions Nephrotoxicity Photosensitivity Kernicterus Infants Hemolysis If Deficient 12 Resistance: Altered Enzyme Decreased Uptake Increased PABA Synthesis

13 13 Macrolides mac-ro-slides MOA: Bacteriostatic Block Inhibit Protein Synthesis RESISTANCE: Methylation of the rrna Binding Site At the of the 50s Subunit

14 Macrolides mac-ro-slides 14 Clinical Use: Atypical Pneumonias Mycoplasma Chlamydia Legionella URI STDs Gram Cocci Streptococcal Infections In Patients Allergic To Also Neisseria

15 15 Macrolides mac-ro-slides S/E: Prolonged QT Interval (Erythromycin) GI Discomfort Acute Cholestatic Hepatitis Eosinophilia Skin Rashes Increases Serum Concentration of: Theophyllines

16 HAART 16 (Highly Active AntiRetroviral Therapy) Initally treat: Symptomatic patients Pts. with AIDS-defining illnesses Patients with a CD4 count < 350/mm 3 Pregnant Patients Patients with specific HIV-related conditions Consists of: 2 nucleoside/nucleotide reverse transcriptase inhibitors ( ) plus either 1 non-nucleoside RTI ( ) or 1 protease inhibitor

17 AIDS - NRTI 17 MOA : Comp/Rev. Inhibit nucleotide binding to reverse transcriptase Needs to be active. S/E : Bone Marrow Suppression (reversed with G-CSF and EPO) Peripheral Neuropathy Lactic Acidosis (nucleosides) Rash (non-nucleosides) Megaloblastic Anemia (ZDV)

18 AIDS - NRTI 18 Abacavir Tenofovir Does NOT need to be phosphorylated ZalcitaBINE EmtricitaBINE LamivuDINE ZidovuDINE Used for general prophylaxis and during pregnancy to reduce transmission risk. Decreases vertical transmission. Blasts your StavuDINE DidanoSINE Painful neuropathy and pancreatitis

19 Protease Inhibitors -navir 19 MOA: Inhibit -> prevents maturation S/E: Hyperglycemia GI Intolerance Lipodystrophy

20 Protease Inhibitors 20 LopiNAVIR AtzaNAVIR FosampreNAVIR SaquiNAVIR IdiNAVIR Can cause in the urine RitoNAVIR Liver disease

21 NNRTI 21 MOA: Bind to Reverse Transcriptase at a Different Site Need Thymidine Kinase to be Activated. S/E : Bone Marrow Suppression (reversed with G-CSF and EPO) Peripheral Neuropathy Lactic Acidosis (nucleosides) Rash (non-nucleosides) Megaloblastic Anemia (ZDV)

22 NNRTI 22 NeVIRapine EfaVIRenz DelaVIRdine

23 Integrase Inhibitor 23 RalTEGRAvir MOA: Inhibits HIV Genome Integration into Host Cell Chromosome by Reversibly Inhibiting S/E: Hypercholesterolemia

24 Fusion Inhibitors 24 EnFUvirtide MOA: Binds Inhibits viral entry S/E: Skin reaction at injection sites

25 Fusion Inhibitors 25 Maraviroc MOA: Binds on surface of T cells Inhibits cell interaction with gp120

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