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Microbiology ` microbiology—aNtimicrobials Microbiology ` microbiology—aNtimicrobials SEcTioN ii 203

HIV therapy Antiretroviral therapy (ART): often initiated at the time of HIV diagnosis.
Strongest indication for use with patients presenting with AIDS-defining illness, low CD4+ cell
3
counts (< 500 cells/mm ), or high viral load. Regimen consists of 3 drugs to prevent resistance:
2 NRTIs and preferably an integrase inhibitor.
All ARTs are active against HIV-1 and HIV-2 with the exception of NNRTIs and enfuvirtide.

DrUg mecHaNism toXicity
NRTIs
Abacavir (ABC) Competitively inhibit nucleotide binding to Bone marrow suppression (can be reversed
Didanosine (ddI) reverse transcriptase and terminate the DNA with granulocyte colony-stimulating factor
Emtricitabine (FTC) chain (lack a 3′ OH group). Tenofovir is a [G-CSF] and erythropoietin), peripheral
Lamivudine (3TC) nucleoTide; the others are nucleosides. All neuropathy, lactic acidosis (nucleosides),
Stavudine (d4T) need to be phosphorylated to be active. anemia (ZDV), pancreatitis (didanosine).
Tenofovir (TDF) ZDV can be used for general prophylaxis and Abacavir contraindicated if patient has
Zidovudine (ZDV, during pregnancy to  risk of fetal transmission. HLA-B*5701 mutation due to  risk of
formerly AZT) Have you dined (vudine) with my nuclear hypersensitivity.
(nucleosides) family?

NNRTIs
Delavirdine Bind to reverse transcriptase at site different Rash and hepatotoxicity are common to all
Efavirenz from NRTIs. Do not require phosphorylation NNRTIs. Vivid dreams and CNS symptoms
Nevirapine to be active or compete with nucleotides. are common with efavirenz.
Integrase inhibitors
Bictegravir Inhibits HIV genome integration into host cell  creatine kinase.
Dolutegravir chromosome by reversibly inhibiting HIV
Elvitegravir integrase.
Raltegravir
Protease inhibitors
Atazanavir Assembly of virions depends on HIV-1 protease Hyperglycemia, GI intolerance (nausea,
Darunavir (pol gene), which cleaves the polypeptide diarrhea), lipodystrophy (Cushing-like
Fosamprenavir products of HIV mRNA into their functional syndrome).
Indinavir parts. Thus, protease inhibitors prevent Nephropathy, hematuria, thrombocytopenia
Lopinavir maturation of new viruses. (indinavir).
Ritonavir Ritonavir can “boost” other drug concentrations Rifampin (potent CYP/UGT inducer) reduces
Saquinavir by inhibiting cytochrome P-450. protease inhibitor concentrations; use rifabutin
Navir (never) tease a protease. instead.
Entry inhibitors
Enfuvirtide Binds gp41, inhibiting viral entry. Skin reaction at injection sites.
Enfuvirtide inhibits fusion.
Maraviroc Binds CCR-5 on surface of T cells/monocytes, Maraviroc inhibits docking.
inhibiting interaction with gp120.

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