Amprenavir is an inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles. Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). Fosamprenavir (GW433908, Lexiva, Telzir) is an oral prodrug of amprenavir, with a reduced daily pill burden. The use of protease inhibitors has also been associated with dyslipidemia and an increased risk of cardiovascular disease. Amprenavir activates Pregnane X receptor to mediate dyslipidemia.

Abacavir is a nucleoside reverse transcriptase inhibitor used for treatment of HIV infection (either alone or in combination with other antiviral drugs). It was shown that abacavir exerts its antiviral activity through its active metabolite, carbovir triphosphate. Carbovir triphosphate is a guanine analogue and a potent and selective inhibitor of viral reverse transcriptases. Upon administration, abacavir is first converted to abacavir monophosphate by ADK, then the monophosphate is deaminated to carbovir monophosphate, which is then anabolized by cellular kinases to carbovir diphosphate and then finally to carbovir triphosphate. Abacavir causes hypersensitivity reaction in patients with HLA-B*57:01 allele.

Abacavir is a nucleoside reverse transcriptase inhibitor used for treatment of HIV infection (either alone or in combination with other antiviral drugs). It was shown that abacavir exerts its antiviral activity through its active metabolite, carbovir triphosphate. Carbovir triphosphate is a guanine analogue and a potent and selective inhibitor of viral reverse transcriptases. Upon administration, abacavir is first converted to abacavir monophosphate by ADK, then the monophosphate is deaminated to carbovir monophosphate, which is then anabolized by cellular kinases to carbovir diphosphate and then finally to carbovir triphosphate. Abacavir causes hypersensitivity reaction in patients with HLA-B*57:01 allele.

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles. Nelfinavir is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. Nelfinavir is marketed under the brand name Viracept.

Foscarnet is an antiviral agent. Foscarnet shows activity against human herpesviruses and HIV. Foscarnet is used for treating eye problems caused by CMV in people with AIDS. It is also used to treat a type of HSV that cannot be treated by another medicine in people with a weak immune system. FOSCAVIR is the brand name for foscarnet sodium. FOSCAVIR is an organic analogue of inorganic pyrophosphate that inhibits replication of herpesviruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). FOSCAVIR exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virusspecific DNA polymerases at concentrations that do not affect cellular DNA polymerases. FOSCAVIR does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to FOSCAVIR.

Apricitabine (ATC) is an investigational drug that was being studied for the treatment of HIV infection. Apricitabine belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block an HIV reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. In vitro studies have shown that apricitabine appears to work on certain HIV strains against which other FDA-approved NRTIs, such as lamivudine (brand name: Epivir), may no longer work. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. The study of apricitabine as an HIV medicine was discontinued in 2016. The company developing the drug decided to stop their clinical trials due to a lack of funding and a lack of interest in apricitabine’s early access program.

Fozivudine tidoxil is a thioether lipid–Zidovudine (ZDV) conjugate. After intake it is split intracellularly into the lipid moiety and ZDV-monophosphate, which is subsequently phosphorylated to the active metabolite ZDV-triphosphate. The rationale behind the development of fozivudine (FZD) was to take advantage of the high cleavage activity in mononuclear cells and other organs resulting in increased amounts of intracellular ZDV available for phosphorylation to the active metabolite, and a very low activity in red blood and stem cells, which should result in reduced haematologic toxicity. It is member of the family of nucleoside reverse transcriptase (RT) inhibitors. Fozivudine tidoxil has been in Phase II clinical trials for the treatment of HIV infection. There were three adverse events possibly related to fozivudine: urine abnormality, gastrointestinal pain and abnormal dreams.

Bevirimat (3-O-(3',3'-dimethylsuccinyl) betulinic acid or MPC-4326 or PA-457) potently inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate that the compound acts by disrupting a late step in Gag processing involving conversion of the capsid precursor (p25) to mature capsid protein (p24). Bevirimat inhibits replication of both wild-type and drug-resistant HIV-1 isolates in vitro, achieving similar 50% inhibitory concentration values with both categories. Serial drug passage studies have identified six single amino acid substitutions that independently confer bevirimat resistance. These resistance mutations occur at or near the CA-SP1 cleavage site, which is not a known target for resistance to other antiretroviral drugs. Bevirimat has been in phase 2 trial for the treatment of HIV infections. Bevirimat has demonstrated a consistent pharmacokinetic profile in healthy volunteers and HIV-infected patients. The demonstration of an antiviral effect following a single oral dose of bevirimat validates maturation inhibition as a potential target for antiretroviral therapeutics in humans.

Droxinavir is hydroxyethylurea human immunodeficiency virus type 1 (HIV-1) protease inhibitor. Position 88 of HIV-1 protease gene plays a key role in the interaction between droxinavir and the protease molecule. A mutation in this position, located outside the active site, confers resistance to the hydroxyethylurea inhibitor droxinavir. The V82A and N88S substitutions conferred droxinavir resistance on HIV-1 recombinant variants. Positions 82 and 88 are reported to be variable in natural populations isolated from patients who have not been treated with protease inhibitors. Droxinavir had been in preclinical phase for the treatment of HIV-1 infection. However, this study was discontinued.

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. vicriviroc binds specifically to the CCR5 receptor and prevents infection of target cells by CCR5-tropic HIV-1 isolates. In antiviral assays, vicriviroc showed potent, broad-spectrum activity against genetically diverse and drug-resistant HIV-1 isolates and was consistently more active than SCH-C in inhibiting viral replication. This compound demonstrated synergistic anti-HIV activity in combination with drugs from all other classes of approved antiretrovirals. Competition binding assays revealed that vicriviroc binds with higher affinity to CCR5 than SCH-C. Functional assays, including inhibition of calcium flux, guanosine 5'-[35S]triphosphate exchange, and chemotaxis, confirmed that vicriviroc acts as a receptor antagonist by inhibiting signaling of CCR5 by chemokines. Finally, vicriviroc demonstrated diminished affinity for the human ether a-go-go related gene transcript ion channel compared to SCH-C, suggesting a reduced potential for cardiac effects. Vicriviroc represented a promising new candidate for the treatment of HIV-1 infection. Vicriviroc for HIV treatment was previously in Phase III studies but has since been discontinued.