Delavirdine is a nonnucleoside reverse transcriptase inhibitor (NNRTI). Delavirdine binds directly to reverse transcriptase (RT) and blocks RNA-dependent and DNA-dependent DNA polymerase activities. Delavirdine does not compete with template:primer or deoxynucleoside triphosphates. HIV-2 RT and human cellular DNA polymerases alfa, gamma, or delta are not inhibited by delavirdine. In addition, HIV-1 group O, a group of highly divergent strains that are uncommon in North America, may not be inhibited by delavirdine. Delavirdine is marketed under the trade name Rescriptor, indicated for the treatment of HIV-1 infection in combination with at least 2 other active antiretroviral agents when therapy is warranted. .

Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. Stavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Stavudine is used for the treatment of human immunovirus (HIV) infections. Stavudine is sold under the brand name Zerit among others.

The nucleoside analog 2',3'-dideoxycytidine (ddCyd), also known as Zalcitabine is a nucleoside analog reverse transcriptase inhibitor (NRTI) sold under the trade name Hivid. HIVID is indicated in combination with antiretroviral agents for the treatment of HIV infection. It is used as part of a combination regimen with antiretroviral agents. But it was discontinued by Roche Pharmaceuticals on December 31, 2006 due to the availability of newer HIV medicines. Within cells, zalcitabine is converted to the active metabolite, dideoxycytidine 5'-triphosphate (ddCTP), by the sequential action of cellular enzymes. Dideoxycytidine 5'-triphosphate inhibits the activity of the HIV-reverse transcriptase both by competing for utilization of the natural substrate, deoxycytidine 5'-triphosphate (dCTP), and by its incorporation into viral DNA. The lack of a 3'- OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation and, therefore, the viral DNA growth is terminated. The active metabolite, ddCTP, is also an inhibitor of cellular DNA polymerasebeta and mitochondrial DNA polymerase-gamma and has been reported to be incorporated into the DNA of cells in culture.

Didanosine was developed by Bristol-Myers Squibb in collaboration with the NIH for the treatment of HIV-1 infections. Upon administration the drug is metabolized to the active metabolite which inhibits HIV-1 reverse transcriptase both by competing with deoxyadenosine 5'-triphosphate and by its incorporation into viral DNA. Didanosine was approved by FDA under the name Videx (among the other names).

Oxothiazolidinecarboxylic Acid (L-2-oxothiazolidine-4-carboxylic acid, OTC) was currently undergoing evaluation in a Phase II clinical trial. It is suggested that an ideal drug may be an antisense oligonucleotide that blocks the expression of glycolate oxidase, a key enzyme in hepatic oxalate synthesis.

Baicalin is a flavonoid compound with anti-inflammatory and anti-oxidant activity extracted from Scutellarua rivularis. Limited distribution data suggest that baicalin reached several sites such as the brain, eye lens, thymus, etc. Metabolism data suggest the rapid conversion of baicalin to baicalein. Baicalin has the potential to be used in novel anti-cancer therapeutic formulations for treatment of ovarian cancer and other cancers. Baicalin markedly inhibits replication of human immunodeficiency virus type 1 (HIV-1) in a concentration-dependent manner in normal peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA) in vitro. The preventive medication of baicalin shows a protective effect on C57 BL mouse with Parkinson's disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).

Atevirdine (U-87201E) is a nonnucleoside inhibitor of HIV-1 reverse transcriptase, that has been studied for the treatment of HIV infection. Atevirdine mesylate is the first-generation member of the bisheteroarylpiperazine class of nonnucleoside inhibitors, which inhibits reverse transcriptase noncompetitively by binding near the catalytic site. The safety, tolerability, and antiviral activity of atevirdine were studied in phase I/II clinical trial. Rash was the most common adverse event, with a grade 3 or 4 rash. No significant change from baseline in HIV-1 plasma RNA mean copy number was detected.

Dapivirine, an anti-retroviral (ARV)-based microbicide, is a substituted diaminopyrimidine (DAPY) derivative and a potent non-nucleoside reverse-transcriptase inhibitor (NNRTI) with antiviral activity against HIV-1. Dapivirine showed high activity against wild-type and mutant HIV in in virto HIV models inhibiting a broad panel of HIV-1 isolates from different classes, including a wide range of NNRTI-resistant isolates. Developed by Janssen Sciences (formerly Tibotec Pharmaceuticals), dapivirine was initially tested as an oral treatment for HIV in a number of Phase I/II clinical trials. In 2014 the International Partnership for Microbicides (IPM) began its work on the monthly dapivirine ring. Phase I/II clinical trials in Africa, Europe and the United States proved that dapivirine is safe and well-tolerated. Phase III long-term safety and efficacy studies of the monthly dapivirine ring as part of IPM's Dapivirine Ring Licensure Program confirmed that the monthly dapivirine ring can safely help prevent HIV infection in women. In 2016 the ASPIRE Study reported a 27 percent reduction in HIV-1 acquisition with a trend toward greater protection in women over age 21 and no significant protection for women under age 21.

Sennoside A, derived from the traditional chinese medicine plant Rheum L., has being shown to be a dual HIV-1 inhibitor effective on HIV-1 replication. Sennoside A is a kind of irritant laxative. It is also used for colonoscopy preparation. It mildly inhibits bovine serum monoamine oxidase with IC50 of 17uM.

Emtricitabine was discovered by Emory researchers Dr. Dennis C. Liotta, Dr. Raymond F. Schinazi and Dr. Woo-Baeg Choi and licensed to Triangle Pharmaceuticals by Emory University in 1996. Triangle was acquired by Gilead in 2003. Emtricitabine, marketed by Gilead as Emtriva, was first approved by the U.S. Food and Drug Administration in July 2003 for the treatment of HIV infection in combination with other antiretroviral agents. Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination.