How Does Antiretroviral Therapy for HIV Work?

Antiretroviral therapy for HIV targets the AIDS-causing virus at different points in its replication cycle with a combination of different medications.

Antiretroviral therapy (ART) refers to combination drug therapy used to treat human immunodeficiency virus (HIV). Antiretroviral drug therapy frequently combines three or more drugs from more than one class (combination therapy) to help prevent drug resistance.

Antiretroviral therapy does not cure HIV, but it helps patients live longer and also reduces the risk of transmitting the virus to others. People who are diagnosed with HIV should start taking HIV medications right away.

Antiretroviral therapy medication prevents the human immunodeficiency virus from multiplying, which reduces the viral load in the body. Having less HIV in the body allows the immune system to recover and produce more infection-fighting CD4 cells. Because the amount of HIV in the body is reduced, this also helps reduce the risk of HIV transmission. 

There are several steps in the life cycle of HIV that form the basis for antiretroviral therapy.

Entry 

HIV circulates in the bloodstream and binds to receptors on the surface of the CD4 immune cells, which leads to membrane fusion and internalization of the viral genetic material and enzymes necessary for replication of the virus. 

Entry inhibitors include:

• CCR5 antagonist — maraviroc (Selzentry, Celsentri)
• Fusion inhibitor — enfuvirtide (T-20, Fuzeon)

Reverse transcription

HIV uses reverse transcriptase to convert its genetic material (RNA) into DNA, which results viral DNA migrating into the nucleus of the cell. 

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) include:

• Tenofovir disoproxil fumarate (Viread) and tenofovir alafenamide (Vemlidy)
• Emtricitabine (Emtriva) and lamivudine (Epivir)
• Abacavir sulfate (Ziagen)
• Zidovudine (AZT, Retrovir)
• Didanosine (Videx, Videx EC)
• Stavudine (Zerit)
• Lamivudine (Epivir)
• Combivir (combination of zidovudine and lamivudine)
• Trizivir (combination of zidovudine, lamivudine and abacavir)
• Truvada (combination of emtricitabine and tenofovir)
• Epzicom (combination of abacavir and lamivudine)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) include: 

• Efavirenz (Sustiva, Stocrin, part of Atripla)
• Nevirapine (Viramune)
• Rilpivirine (Edurant, part of Complera or Epivlera)
• Etravirine (Intelence)
• Doravirine (Pifeltro)
• Delavirdine (Rescriptor)

Integration

The virus uses the enzyme integrase to integrate (insert) its viral DNA into the DNA of the host CD4 cell. Once viral DNA is integrated into the cell's DNA, the cell is infected for life. 

Integrase strand inhibitors include:

• Raltegravir (Isentress)
• Elvitegravir (part of Stribild)
• Dolutegravir (Tivicay)

Replication (transcription and translation) 

HIV replicates in activated cells. There are no antiretroviral agents that inhibit this step of the replication cycle.

Assembly

The new materials come together and assemble into an immature, noninfectious HIV particle or bud. There are no antiretroviral agents that inhibit this step of the replication cycle. 

Budding and maturation

The virus bud is released from the host CD4 cell. The new HIV virus matures. 

Protease inhibitors include:

• Saquinavir (Invirase)
• Indinavir (Crixivan)
• Ritonavir (Norvir)
• Nelfinavir (Viracept)
• Amprenavir (Agenerase)
• Lopinavir/ritonavir (Kaletra, Aluvia)
• Atazanavir (Reyataz)
• Fosamprenavir (Lexiva, Telzir)
• Tipranavir (Aptivus)
• Darunavir (Prezista)