Types of Antiretroviral Drugs for HIV

Potent combination antiretroviral therapy has dramatically changed the prognosis for patients with HIV infection, allowing the infection to be effectively managed with medication. The 6 type of antiretroviral drugs are :

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

The reverse transcriptase enzyme wa an attractive initial therapeutic target after the discovery of AIDS was a retrovirus. There are 8  US Food and Drug Adiministration (FDA)-approved NRTIs : Zidovudine, Didanosine, Stavudine, Lamivudine, Abacavir, Tenofovir, and Emtricitabine.

Zidovudine became the first FDA-approved anti-HIV drug in March 1986. Originally known as azidothymidine, it was initially synthesized in 1964 as a possible treatment for cancer, cut was found to lack activity. Zidovudine is currently indicated for treatment of HIV infection in combination with other antiretroviral agents and prevention of mother-to-child transmission of HIV. The coformulation of lamivudine/zidovudine remains an NRTI choice for alternative first-line therapy regimens in both US Department of Health and Human Services and the International AIDS Society-USA panel guidelines and is an important part of antiretroviral therapy to prevent mother-to-child transmission.

Protease Inhibitors (PIs)

First generation PIs had inconvenient dosing schedules, high pill burdens, and frequent gastrointestinal and metabolic adverse effects, they were life-saving agents for many patients when combined with NRTIs. But newer PIs have the advantage of improved tolerance, a more favorable dosing schedule, and increased activity against PI-resistant strains of HIV.Currently available PIs are Saquinavir, Ritonavir, Nidinavir, Nelfinavir, Lopinavir/ritonavir, Atazanavir, Fosamprenavir, Tipranavir, Darunavir.

Non Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Rashes is a class-wide adverse effect with use of currently approved NNRTIs. These range in severity from mild to life threatening. Currently approved NNRTIs are Nevirapine, Delavirdine, Efavirenz, and Etravirine. Nevirapine can cause potentially fatal skin reactions that may be part of a hypersensitivity reaction, and that occur most frequently during the first 6 weeks of therapy. Nevirapine should be immediately and permanently discontinued in any patient who develops severe skin rash, skin rash associated with increases transaminases, or hypersensitivity reaction. Delavirdine also causes rashes. Etravirine is generally well tolerated with lower rates of in clinical trials when compared with other NNRTIs, although cases of Steven-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported in post-marketing surveillance. Rilpivirine has lower incidence of having adverse effects such as rash compared to efavirenz.

Fusion Inhibitors

Fusion inhibitors are a class of antiretroviral agents  that act by blocking the fusion of the HIV and host cell membranes. There is currently only 1 FDA-approved fusion inhibitor : Enfuvirtide.

Entry Inhibitors

Entry inhibitors block the binding og gp120 to the chemokine receptor, CCR5. The only FDA-approved entry inhibitor is Maraviroc, an approved CCR5 antagonist. Maraviroc in combination with other antiretroviral agents is indicated for adult patients with only CCR5-tropic HIV-1.

Integrase Inhibitors

Integrase inhibitors act to inhibit strand transfer, a process catalyzed by the integrase enzyme. There is currently 1 integrase inhibitor approved by the FDA: Raltegravir. Raltegravir is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adult patient.

Maturation Inhibitors

Maturation inhibitors block a final step in the production of infectious HIV virions. The investigational agent bevirimat is the first maturation inhibitor that has reached later-stage clinical trials, and phase II studies are ongoing.

The availability of multiple agents from above classes of antiretrovirals has made virulogic suppression possible for nearly all adherent patients.