infectious diseases
Antiretroviral Treatment of HIV Infection
Classes of antiretrovirals
Multiple classes of antiretrovirals are used in ART. Two classes inhibit HIV entry, and the others inhibit one of the 3 HIV enzymes needed to replicate inside human cells; 3 classes inhibit reverse transcriptase by blocking its RNA-dependent and DNA-dependent DNA polymerase activity. Nucleoside reverse transcriptase inhibitors (NRTIs)are phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and terminate synthesis of DNA chains. Nucleotide reverse transcriptase inhibitors (nRTIs)competitively inhibit the HIV reverse transcriptase enzyme, as do NRTIs, but do not require initial phosphorylation. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)bind directly to the reverse transcriptase enzyme. Protease inhibitors (PIs)inhibit the viral protease enzyme that is crucial to maturation of immature HIV virions after they bud from host cells. Entry inhibitors (EIs),sometimes called fusion inhibitors, interfere with the binding of HIV to CD4+ receptors and chemokine co-receptors; this binding is required for HIV to enter cells. For example, CCR-5 inhibitors block the CCR-5 receptor. Post-attachment inhibitorsbind to the CD4 receptor and prevent HIV (that also binds to the CD4 receptor) from entering the cell. Integrase inhibitorsprevent HIV DNA from being integrated into human DNA. Attachment inhibitorsbind directly to the viral envelope glycoprotein 120 (gp120), close to the CD4+ binding site, which prohibits the conformational change necessary for initial interaction between the virus and the surface receptors on CD4 cells, thereby preventing attachment and subsequent entry into host T cells and other immune cells. 