Because disease-related complications can occur in untreated patients with high CD4 counts, less toxic drugs have been developed and antiretroviral therapy (ART) is now recommended for all patients. The benefits of ART outweigh the risks in each patient group, and careful studies have been conducted on this issue.
ART aims to
- Reducing plasma HIV RNA levels to an undetermined value (i.e., < 20-50 copies/mL)
- Restoring CD4 cell counts to normal levels (immune reconstitution or restoration)
ART is usually effective if patients take their medications > 95% of the time.
If treatment is unsuccessful, drug susceptibility (resistance) assays are performed to all available drugs. Genotype assays are also helpful in diagnosis.
Many patients living with HIV infection are treated with a combination regimen that involves taking multiple pills. With the availability of new HIV combination drugs, many patients could benefit from simplifying their ART regimen, guided by DNA Archive Genotype Testing.
Antiretroviral drug classes
Many classes of antiretroviral drugs are used as part of ART. 2 classes inhibit HIV entry, others inhibit one of the three HIV enzymes required for replication within the human cell; all 3 classes inhibit reverse transcriptase, blocking its RNA-dependent and DNA-dependent DNA polymerase activity.
Classes of antiretroviral drugs
Many classes of antiretroviral drugs are used as part of ART. 2 classes inhibit HIV entry, others inhibit one of the three HIV enzymes required for replication within the human cell; all 3 classes inhibit reverse transcriptase, blocking its RNA-dependent and DNA-dependent DNA polymerase activity.
- Nucleoside reverse transcriptase inhibitors are phosphorylated active metabolites that compete to penetrate viral DNA. They inhibit the HIV reverse transcriptase enzyme on the principles of competition and stop the synthesis of DNA strands.
- Nucleotide reverse transcriptase inhibitors inhibit the HIV reverse transcriptase enzyme on the principles of competition, just like nucleoside reverse transcriptase inhibitors, but do not require initial phosphorylation.
- Non-nucleoside reverse transcriptase inhibitors bind directly to the reverse transcriptase enzyme.
- Protease inhibitors inhibit the viral protease enzyme, which is critical for the maturation of immature HIV virions after they bud off from host cells.
- Entry inhibitors, sometimes called fusion inhibitors, interfere with the attachment of HIV to CD4+ and parallel chemokine receptors; this attachment is required for HIV to enter cells. For example, CCR-5 inhibitors block the CCR-5 receptor.
- Post-joining inhibitors bind to the cell’s CD4 receptor and prevent HIV (which also binds to the CD4 receptor) from entering the cell.
- Integrase inhibitors prevent HIV DNA from being integrated into human DNA.
- The attachment inhibitors bind directly to viral envelope glycoprotein 120 (gp120) near the CD4+ binding site, which prevents the conformational changes necessary for the initial interaction between the virus and surface receptors on CD4 cells, thereby preventing attachment and subsequent entry of the virus into host T cells and other immune cells.