CDC Stage of HIV Disease
-Stage I: Acute HIV infection
-Stage II: Asymptomatic HIV
-Stage III: Early Symptomatic HIV
-Stage IV: Late Symptomatic HIV
= A Constitutional Disease
= B Neurological Disease
= C Secondary Infections
-C1 AIDS defining
-C2 Other infections
= D Secondary Cancers
= E Other Conditions
Clinical Staging of Oral Manifestations of HIV
Adults and Adolescents (>15yo)
Angular Chellitis, Recurrent oral ulcerations
Angular Chellitis, Linear gingival erythema, extensive warts, Recurrent oral ulcerations, Parotid enlarge
Persistent oral candidiasis, Oral hairy leukoplakia, Acute necrotizing ulcerative stomatitis, gingivitis, periodontitis
Persistent oral candidiasis (after 8wks), Oral hairy leukoplakia, Acute necrotizing ulcerative gingivitis or periodontitis.
Chronic (>1mo) orolabial HSV, Kaposi's sarcoma,
Chronic (>1mo) orolabial HSV, Karpo's Sarcoma, Non-Hodgkin's lymphoma
HIV-related Oral Lesions:
- Fungal, Viral, Bacteria
- Kaposi's Sarcoma, Non-Hodgkin's Lymphoma
- Aphthous-like Ulcers, Lichenoid or drug reactions, Salivary Gland Disease
-Herpes Simplex Infection
-Necrotizing ulcerative gingivitis/ periodontitis
-Necrotizing Stomamtitis (NS)
There are many different causes of oral ulceration in patients with HIV infection = Herpes simplex infection, Varicella zoster infection. Accurate diagnosis and appropriate management of oral ulceration in patients with HIV infection generally result in complete healing of the ulceration.
Aphthous Lesions Clinical Types
Triamcinolone: 40 mg /ml (0.5 ml-1.0 ml injected bid)
Prednisone: 0.5-1.0 mg/kg qd x 7-10d, then taper
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Thalidomide: 200 mg PO qd
Nucleoside OR Nucleotide Reverse Transcriptase Inhibitors (Nukes)
Non-nucleoside Reverse Transcriptase Inhibitors (non-nukes)
Chemokine Receptor Antagonists
Current Antiretroviral Targets
Reverse Transcriptase Inhibitors:
Nucleoside Analogues Zidovudine (AZT, ZDV) Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Lamivudine (3TC) Abacavir (ABC) Emtricitabine (FTC)
Non-nucleoside analogues: Nevirapine (NVP) delavirdine (DLV) Efavirenz (EFV) etravirine (ETV) rilpivirine (RPV)
Reverse Transcriptase Inhibitors:
NRTIs Mechanism of Action:
Nucleoside Analogs (like AZT):
Analog of thymidine, cytosine or guanine
Triphosphorylated inside lymphocytes to active compound.
Incorporate into growing HIV viral DNA strand by reverse transcriptase.
does NOT need to be tri-phosphorylated only di-phosphorylated to activate compound.
After incorporation of NRTIs, viral DNA synthesis will be terminated.
Non-nucleoside Reverse Transcriptase Inhibitors:
Agents directly bind to reverse transcriptase to inhibit transcription.
NNRTIs do not require phosphorylation to be active.
Protease Inhibitors (PIs) MOA:
Protease enzyme cleaves HIV precursor proteins into active proteins that are needed to assemble a new, mature HIV virus.
PIs bind to protease preventing the cleavage and inhibiting the assembly of new HIV viruses.
Chemokine Receptor Antagonists:
CCR5 or CXCR4 receptors on cell surface
Virus will bind to one of the 2 receptors (some pt virus will bind to either receptors)
Marviroc blocks viral entry at CCR5
Dosed 300mg BID= 150mg BID with P450 inhibitors. = 600mg BID with P450 inducers
Dosed = 400mg BID (1tab BID)
No induction or inhibition on CYP450 enzymes or Pgp
Metabolized by UGT1A1 (glucuronidation) = Only affected by drugs that inhibit or induce UGTs (ie. rifampin)