Darunavir
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Systematic (IUPAC) name |
[(1R,5S,6R)-2,8-dioxabicyclo[3.3.0]oct-6-yl] N-[(2S,3R)-4- [(4-aminophenyl)sulfonyl- (2-methylpropyl)amino]-3-hydroxy-1-phenyl- butan-2-yl] carbamate
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Clinical data |
Trade names |
Prezista |
AHFS/Drugs.com |
monograph |
MedlinePlus |
a607042 |
Pregnancy
category |
- AU: B2
- US: C (Risk not ruled out)
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Legal status |
- AU: Prescription Only (S4)
- CA: ℞-only
- UK: Prescription-only (POM)
- US: ℞-only
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Routes of
administration |
oral |
Pharmacokinetic data |
Bioavailability |
37% (without ritonavir), 82% (with ritonavir) |
Protein binding |
95% |
Metabolism |
hepatic (CYP3A4) |
Biological half-life |
15 hours |
Excretion |
Faeces (80%), urine (14%) |
Identifiers |
CAS Registry Number |
206361-99-1 Y |
ATC code |
J05AE10 |
PubChem |
CID: 213039 |
DrugBank |
DB01264 Y |
ChemSpider |
184733 Y |
UNII |
YO603Y8113 Y |
KEGG |
D03656 Y |
ChEBI |
CHEBI:367163 Y |
ChEMBL |
CHEMBL1323 N |
NIAID ChemDB |
073035 |
Chemical data |
Formula |
C27H37N3O7S |
Molecular mass |
547.665 g/mol |
SMILES
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O=S(=O)(c1ccc(N)cc1)N(CC(C)C)C[C@@H](O)[C@@H](NC(=O)O[C@H]2CO[C@H]3OCC[C@@H]23)Cc4ccccc4
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InChI
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InChI=1S/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1 Y
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Key:CJBJHOAVZSMMDJ-HEXNFIEUSA-N Y
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N (what is this?) (verify) |
Darunavir (brand name Prezista, formerly known as TMC114) is a protease inhibitor drug used to treat HIV infection. Prezista is an OARAC recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents.[1] Developed by pharmaceutical company Tibotec, darunavir is named after Arun K. Ghosh, the chemistry professor who discovered the molecule at the University of Illinois at Chicago.[2] It was approved by the Food and Drug Administration (FDA) on June 23, 2006.[3]
Darunavir is a second-generation protease inhibitor (PIs), designed specifically to overcome problems with the older agents in this class, such as indinavir. Early PIs often have severe side effects and drug toxicities, require a high therapeutic dose, are costly to manufacture, and show a disturbing susceptibility to drug resistant mutations. Such mutations can develop in as little as a year of use, and effectively render the drugs useless.
Darunavir was designed to form robust interactions with the protease enzyme from many strains of HIV, including strains from treatment-experienced patients with multiple resistance mutations to PIs.[4][5]
Darunavir received much attention at the time of its release, as it represents an important treatment option for patients with drug-resistant HIV. Patient advocacy groups pressured developer Tibotec not to follow the previous trend of releasing new drugs at prices higher than existing drugs in the same class. Darunavir was priced to match other common PIs already in use, such as the fixed-dose combination drug lopinavir/ritonavir.
Contents
- 1 HIV therapy and drug resistance
- 2 Development of protease inhibitors
- 3 Benefits
- 4 Darunavir in the catalytic site
- 5 Efficacy
- 5.1 ARTEMIS trial
- 5.2 TITAN trial
- 5.3 POWER 1 and POWER 2 trials
- 6 Pharmacoeconomic considerations
- 7 Safety
- 8 See also
- 9 References
- 10 Other References
- 11 External links
HIV therapy and drug resistance
In 2005, the death toll for HIV/AIDS peaked at 2.3 million. However, it has since steadily declined with the development and availability of antiretroviral therapies and fewer newly infected patients.[6] Currently, six major classes of HIV drugs aim to inhibit different stages of the HIV lifecycle. New developments with protease inhibitors (PIs), the most effective class of anti-HIV drugs, have dramatically improved conditions for patients diagnosed with the disease.[7]
HIV-protease
Figure 1. Three different views of PR interacting with PI darunavir - chain A colored pink with flap in coral and chain B colored teal with the flap sky blue Darunavir, the ligand colored sea-foam green, is held within a tunnel formed by the flap. The three views, front (a), back (b), and bottom (c), demonstrate how the ligand is enclosed and held stable by the flaps in the tunnel (PDB 4dqb).
HIV- 1 protease (PR) is a symmetrical homodimer with two identical 99-amino-acid subunits.[8] The two chains of this homodimer form a tunnel with a “flap” from each protein chain helping to secure the polyprotein in place.[9] The active site of this tunnel is also where many inhibitory drugs, like darunavir, interact (Figure 1).
PIs target HIV-1 protease, a protein that performs an essential function in the lifecycle of HIV by breaking up the viral polypeptide into components that can be used to form mature virus particles.[8] The proteins necessary for the production of mature HIV virus are translated onto a long polypeptide strand. This strand needs to be broken down into the smaller protein structures that contribute to a mature HIV particle and PR performs this function.[10]
The PIs act as noncovalent inhibitors of HIV protease and compete with the natural substrate to occupy the active site. When a protease inhibitor binds, the HIV lifecycle is halted as the protein components for new viral particles are unable to be produced.[9]
Development of protease inhibitors
Figure 2. Hydrogen bonds between darunavir and HIV-1 protease: The bonds with the red residues indicate hydrogen bonds that are also present between the PI saquinavir and HIV-1 protease. The hydrogen bonds with the blue residue are unique to darunavir.
The development of first-generation clinical inhibitors was founded on creating more protease-ligand interactions through hydrogen bonding and hydrophobic interactions.[7] The first HIV protease inhibitor approved by the FDA was saquinavir, which was designed to target wild-type HIV-1 protease.[11] However, this inhibitor is no longer effective due to resistance-causing mutations on the HIV-1 protease structure. The HIV genome has high plasticity, so has been able to become resistant to multiple HIV-1 protease inhibitors.[12] Since saquinavir, the FDA has approved several PIs, including darunavir.[13] Darunavir was granted approval by the FDA on June 23, 2006, and is one of the most recently developed protease inhibitors approved for treatment of HIV.[13]
Benefits
Darunavir is a nonpeptidic inhibitor of PR that lodges itself in the active site of PR through a number of hydrogen bonds.[7] It was developed to increase interactions with HIV-1 protease and to be more resistant against HIV-1 protease mutations. With a Kd value of 4.5 x 10−12 M, darunavir has a much stronger interaction with PR and its dissociation constant is 1/100 to 1/1000 of other protease inhibitors.[6] This strong interaction comes from increased hydrogen bonds between darunavir and the backbone of the PR active site (Figure 2). Darunavir’s structure allows it to create more hydrogen bonds with the PR active site than most PIs that have been developed and approved by the FDA.[14] Furthermore, the backbone of HIV-1 protease maintains its spatial conformation in the presence of mutations.[15] Because darunavir interacts with this stable portion of the protease, the PR-PI interaction is less likely to be disrupted by a mutation.[14]
Figure 3. Ribbon structure of PR with darunavir in active site: Structures colored as in Fig. 1. with certain residues partaking in hydrogen bonding further highlighted. The catalytic aspartates, 25 and 25’, are in orange and the other interacting residues in green. Right image is a magnified view of the image on the left (PDB 4qdb).
Darunavir in the catalytic site
The chemical activity of the HIV-1 protease depends on two residues in the active site, Asp25 and Asp25’, one from each copy of the homodimer.[10] Darunavir interacts with these catalytic aspartates and the backbone of the active site through hydrogen bonds, specifically binding to residues Asp25, Asp25’, Asp 29, Asp 30, Asp 30’, and Gly 27 (Figure 3). This interaction prevents viral replication, as it competitively inhibits the viral polypeptides from gaining access to the active site and strongly binds to the enzymatic portions of this protein.[7]
Efficacy
Prezista is an OARAC (DHHS) recommended treatment option for treatment-naïve and treatment-experienced adults and adolescents.[1] It showed comparable efficacy to lopinavir/ritonavir at 96 weeks with a once-daily dosing in treatment-naïve patients.[16] It was approved by the FDA for treatment-naive patients on October 21, 2008.[17]
Darunavir showed superiority to lopinavir/ritonavir and other protease inhibitors in the POWER trials. POWER 1 and POWER 2 were designed for treatment-experienced patients, together with supportive data from the POWER 3 analysis.[18] The patients eligible for these studies had experience with at least one protease inhibitor, one non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors , and had one or more primary protease inhibitor mutations.
Darunavir also showed superior results to lopinavir in the TITAN trials (preplanned, secondary endpoint, week 48), which was designed for patients with less advanced HIV disease compared to the POWER trials.[19]
ARTEMIS trial
ARTEMIS includes 689 treatment-naive participants with a baseline viral load of at least 5000 copies/ml who were randomly assigned to receive 800/100 mg once-daily darunavir/ritonavir or 800/200 mg lopinavir/ritonavir given once- or twice-daily. At 96 weeks, darunavir/ritonavir remained not inferior to lopinavir/ritonavir.
- In an intent-to-treat analysis, significantly more patients in the darunavir/ritonavir arm achieved HIV RNA below 50 copies/ml compared with the lopinavir/ritonavir arm (79% vs. 71%; p = 0.012).
- Response rates in the darunavir/ritonavir arm were statistically superior to those in the lopinavir/ritonavir arm for patients with high baseline viral load and low baseline CD4 count.
- Among patients with baseline viral load below 100,000 copies/ml, 76% of patients in the darunavir/ritonavir arm and 63% in the lopinavir/ritonavir arm achieved HIV RNA below 50 copies/ml (p = 0.023).
- Once-daily darunavir/ritonavir was generally safe and well tolerated.
- Fewer patients in the darunavir/ritonavir arm discontinued treatment due to adverse events (4% vs. 9%).
- Patients taking darunavir/ritonavir were less likely to have moderate to severe (grade 2–4) treatment-related diarrhea (4% vs. 11%; p < 0.001).
- Grade 2-4 treatment-related rash occurred infrequently in both arms (3% with darunavir/ritonavir vs. 1% with lopinavir/ritonavir; p = 0.273).
- Patients taking darunavir/ritonavir had smaller average increases in triglycerides (0.1 vs. 0.8 mmol/l, or 12% vs. 50%) and total cholesterol (0.6 vs. 0.9 mmol/l, or 15% vs. 23%) (both p < 0.0001).
TITAN trial
Analysis of 595 treatment-experienced patients being lopinavir/ritonavir-naïve, HIV-1 infected adults with a viral load of greater than 1000 HIV-1 RNA copies/ml. Pre-planned secondary endpoint findings include:
- About 71% of patients in the darunavir/ritonavir arm reached an undetectable viral load (less than 50 copies/ml) vs. 60% of patients in the lopinavir/ritonavir arm, a statistically significant difference (p = 0.005)
- About 77% of patients in the darunavir/ritonavir arm achieved at least a one-log10 reduction in HIV RNA vs. 69% in the lopinavir/ritonavir arm, a statistically significant difference (p = 0.028)
- The median increase from baseline in CD4 cell count was similar between the darunavir/ritonavir and lopinavir/ritonavir arms (88 cells per cubic millimeter vs. 81 cells per cubic millimeter)
Development of resistance also was studied. Findings include:
- About 10% of patients in the darunavir/ritonavir arm experienced virological failure vs. 22% of patients in the lopinavir/ritonavir arm.
- Among patients experiencing virologic failure who had baseline and endpoint genotype data, 21% of patients in the darunavir/ritonavir arm developed primary PI resistance mutations vs. 36% of patients in the lopinavir/ritonavir arm, and 14% of patients in the darunavir/ritonavir arm developed primary NRTI resistance mutations vs. 27% of patients in the lopinavir/ritonavir arm
POWER 1 and POWER 2 trials
A pooled analysis of results from POWER 1 and POWER 2 demonstrated, after 24 weeks:
- Significantly more treatment-experienced patients achieved a reduction in viral load at the 24-week primary endpoint with darunavir, compared with the investigator-selected PI (70% vs. 21%, respectively).
- Almost four times as many treatment-experienced patients (45%) have achieved an undetectable viral load with the darunavir-containing regimen, compared with the investigator-selected PI arm (12%).
- In treatment-experienced patients, the darunavir containing regimen increased CD4 cell counts five times more than the investigator-selected PI arm (92 cells/mm3 vs. 17 cells/mm3, respectively).[20]
The efficacy results of POWER 1 and POWER 2 are confirmed by data from a large, nonrandomized, open-label analysis known as POWER 3. After 24 weeks:
- About 65% of patients achieved a reduction in viral load of one log10 or more, versus baseline.
- About 40% of patients reached undetectable virus levels (less than 50 HIV RNA copies/mL).[21]
Pharmacoeconomic considerations
In the US and UK, healthcare costs were estimated to be lower with boosted darunavir than with investigator-selected control protease inhibitors in treatment-experienced patients.[22]
Safety
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As with other antiretrovirals, darunavir does not cure HIV infection or AIDS, and does not prevent passing HIV to others.
In studies, darunavir was generally well tolerated. Mild to moderate rash was seen in 7% of patients. Some patients developed severe rash. In clinical studies, 0.3% of patients discontinued due to rash. The most common moderate to severe side effects associated with darunavir include diarrhea (2.3%), headache (3.8%), abdominal pain (2.3%), constipation (2.3%), and vomiting (1.5%). Four percent of patients discontinued treatment due to adverse events. People who are allergic to darunavir or any of its ingredients, or ritonavir (Norvir) should not take darunavir.
Relevant drug-drug interactions with other medications commonly used in HIV patient populations were few, such as other antiretroviral medications, proton pump inhibitors, and H2 receptor antagonists. St. John's wort may reduce its effectiveness by interaction with CYP3A. Patients should talk to their healthcare providers about all the medicines they are taking or plan to take, including prescription and nonprescription medicines, vitamins, and herbal supplements.
Before taking darunavir, patients should tell their healthcare providers if they have any medical conditions, including diabetes, liver problems, hemophilia, or allergy to sulfa medicines, and should tell their doctors if they are pregnant or planning to become pregnant, or are nursing. Darunavir should be used with caution in patients with hepatic impairment.
High blood sugar, diabetes or worsening of diabetes, muscle pain, tenderness or weakness, and increased bleeding in people with hemophilia have been reported in patients taking protease inhibitor medicines like darunavir. Changes in body fat have been seen in some patients taking anti-HIV medicines, including loss of fat from legs, arms and face, increased fat in the abdomen and other internal organs, breast enlargement, and fatty lumps on the back of the neck. The cause and long-term health effects of these conditions are not known at this time.
Clinical laboratory safety observed in the darunavir group was comparable to the control group.[23]
See also
References
- ^ a b Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, November 3, 2008, Developed by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC). full guidelines.
- ^ Ghosh Group, Purdue University
- ^ Rodger D MacArthura, Darunavir: promising initial results, doi:10.1016/S0140-6736(07)60499-1
- ^ Ghosh AK, Dawson ZL, Mitsuya H (2007). "Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV". Bioorg. Med. Chem. 15 (24): 7576–80. doi:10.1016/j.bmc.2007.09.010. PMC 2112938. PMID 17900913. Retrieved 2007-12-22.
- ^ Darunavir–ritonavir more effective than Lopinavir–ritonavir in HIV infected, treatment-experienced patients, The Lancet, 2007, 370, article URL
- ^ a b King, N. M., Prabu-Jeyabalan, M. et al. "Structural and Thermodynamic Basis for the Binding of TMC114, a Next-Generation Human Immunodeficiency Virus Type 1 Protease Inhibitor" Journal of Virology. 2004, vol. 78 no. 21
- ^ a b c d Leonis, G., Czyznikowska, Z. et al. "Computational Studies of Darunavir into HIV-1 Protease and DMPC Bilayer: Necessary Conditions for Effective Binding and the Role of the Flaps" J. Chem. Inf. Model. 2012, 52, 1542-1558.
- ^ a b Mittal, S., Bandaranayake, R. M. et al "Structural and Thermodynamic Basis of Amprenavir/Darunavir and Atazanavir Resistance in HIV-1 Protease with Mutations at Residue 50" J. Virology. 2013, 87, 4176-4184.
- ^ a b Goodsell, D. "HIV-1 Protease" Protein Data Bank. June 2000 Molecule of the Month.
- ^ a b Li, D., Zhang, Y. et al. "Investigation on the mechanism for the binding and drug resistance of wild type and mutations of G86 residue in HIV-1 protease complexed with Darunavir by molecular dynamic simulation and free energy calculation" J. Molecular Modeling, 2014, 20:2122.
- ^ Liu, F., Kovalevsky, A.Y. "Effect of Flap Mutations on Structure of HIV-1 Protease and Inhibition by Saquinavir and Darunavir" J. Mol. Biol. 2008; 381(1): 102-115.
- ^ Eron, J. "HIV-1 Protease Inhibitors" Oxford Journal of Clinical Infectious Diseases. 2000, vol. 30, Issue Supplement 2, 160-170.
- ^ a b "HIV/AIDS Historical Time Line 2000-2010" FDA. 2011.
- ^ a b Lefebvre, E., Schiffer, C. A. "Resilience to Resistance of HIV-1 Protease Inhibitors: Profile of Darunavir" AIDS Rev. 2008; 10(3): 131-142
- ^ Lascar, R. M., Benn, P. "Role of darunavir in the management of HIV infection" HIV AIDS (Auckl). 2009; 1:31-39.
- ^ hivandhepatitis.com, Efficacy and Safety of Boosted Darunavir (Prezista) Are Superior to Lopinavir/ritonavir (Kaletra) at 96 Weeks: ARTEMIS Trial, 2008-10-28, URL.
- ^ hivandhepatitis.com, Darunavir (Prezista) Receives Full Traditional Approval, Dose Set for Treatment-naive Patients, Caution Urged for Pregnant Women, 2008-10-24, URL.
- ^ Bonaventura Clotet, Nicholas Bellos, Jean-Michel Molina, David Cooper, Jean-Christophe Goffard, Adriano Lazzarin, Andrej Wöhrmann, Christine Katlama, Timothy Wilkin, Richard Haubrich, et al., Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials, The Lancet, Volume 369, Issue 9568, 7–13 April 2007, Pages 1169–78.
- ^ José Valdez Madruga, Daniel Berger, Marilyn McMurchie, Fredy Suter, Denes Banhegyi, Kiat Ruxrungtham, Dorece Norris, Eric Lefebvre, Marie-Pierre de Béthune, Frank Tomaka, et al., Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial, Pages 49-58. doi:10.1016/S0140-6736(07)61049-6
- ^ Johnson & Johnson Press Release, 2006; Lazzarin, 2005
- ^ Molina, 2005
- ^ McKeage K, Perry CM, Keam SJ.[1]. Drugs 2009;69(4):477-503. doi:10.2165/00003495-200969040-00007.
- ^ (Product Monograph, Darunavir)
Other References
- Lazzarin A, Queiroz-Telles F, Frank I, Rockstroh J, Walmsley S, De Paepe E, Vangeneugden T, Spinosa-Guzman S and Lefebvre E Lazzarin A, et al. XVI IAC 2006.
- Johnson & Johnson FDA Approval Press Release, June 23, 2006, http://www.jnj.com/news/jnj_news/20060623_191250.htm;jsessionid=NT1BC4RC4RHKYCQPCAOWU3YKB2IIWTT
- Molina JM, Cohen C, Katlama C et al. TMC114/r in treatment-experienced HIV patients in power 3: 24-week efficacy and safety analysis. Poster abstract TUPE0060.
- Janssen-Ortho, Darunavir Mongraph information. Updated 2006. http://www.janssen-ortho.com/JOI/pdf_files/Darunavir_E.pdf
- TMC114, Tibotec, http://www.tibotec.com/bgdisplay.jhtml?itemname=HIV_tmc114
- Ghosh, A. K., et al. Bioorg. Med. Chem. Lett. 1998, 8, 687-90;
- Mitsuya, H. Ghosh, A. K., et al. J. Virology 2002, 76, 1349;
- Ghosh, A. K. Duzguiness, N., et al. Antiviral Res. 2002, 54, 29;
- Koh, Y., Ghosh, A. K., Mitsuya, H., et al. Antimicrobial Agents and Chemotherapy, 2003, 47, 3123
- Ghosh, A. K., Mitsuya, H., et al. ChemMedChem 2006, 1, 937
- A. K. Ghosh, B. D. Chapsal, I. T. Weber, H. Mitsuya. Acc. Chem. Res. 2007, ASAP.
- A. K. Ghosh, Z. L. Dawson, H. Mitsuya. Bioorg. Med. Chem. 2007, 15, 7576.
External links
- Darunavir FAQ at AIDSmeds.com
- Drug information in PDF
- Arun Ghosh group
- Tibotec
Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)
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Entry/fusion inhibitors
(Discovery and development) |
- gp41 (Enfuvirtide (ENF, T-20))
- CCR5 (Maraviroc (MVC)
- Vicriviroc†, Cenicriviroc†, PRO 140†)
- CD4 (Ibalizumab†)
- gp120 (Fostemsavir†)
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Reverse-transcriptase
inhibitors (RTIs) |
Nucleoside and
nucleotide (NRTI) |
- Nucleoside analogues/NRTIs: Abacavir (ABC)°#
- Emtricitabine (FTC)°#
- Lamivudine (3TC)°#
- Didanosine (ddI)#
- Zidovudine (AZT, ZDV)#
- Apricitabine†
- Stampidine†
- Elvucitabine†
- Racivir†
- Amdoxovir†
- Stavudine (d4T)#
- Zalcitabine (ddC)◊
- Festinavir†
- Nucleotide analogues/NtRTIs: Tenofovir disoproxil fumarate (TDF)°#
- Tenofovir alafenamide fumarate (TAF)†
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|
Non-nucleoside (NNRTI)
(Discovery and development) |
- (1st generation) Efavirenz (EFV)°#
- Nevirapine (NVP)#
- Delavirdine (DLV)◊
(2nd generation) diarylpyrimidines (Etravirine (ETR)
- Rilpivirine (RPV)°)
- Doravirine
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|
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Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI)) |
- Raltegravir (RAL)°
- Elvitegravir (EVG)°
- Dolutegravir (DTG)°
- Globoidnan A (experimental)
- MK-2048†
- BI 224436†
- Cabotegravir†
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Maturation inhibitors |
|
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Protease Inhibitors (PI)
(Discovery and development) |
1st generation |
- Fosamprenavir (FPV)
- Lopinavir (LPV)°#
- Nelfinavir (NFV)#
- Ritonavir (RTV)#
- Saquinavir (SQV)#
- Amprenavir (APV)◊
- Indinavir (IDV)◊#
- Telinavir
- Droxinavir
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2nd generation |
- Atazanavir (ATV)°
- Darunavir (DRV)°
- Tipranavir (TPV)
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Combined formulations |
- Abacavir/lamivudine°
- Abacavir/dolutegravir/lamivudine°
- Abacavir/lamivudine/zidovudine
- Atazanavir/cobicistat
- Darunavir/cobicistat
- Efavirenz/emtricitabine/tenofovir°
- Elvitegravir/cobicistat/emtricitabine/tenofovir°
- Emtricitabine/rilpivirine/tenofovir°
- Lamivudine/raltegravir
- Lamivudine/zidovudine
- Lopinavir/ritonavir°
- Tenofovir/emtricitabine°
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Pharmacokinetic boosters |
- Ritonavir (r)
- Cobicistat (c)
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Experimental agents |
Uncoating inhibitors |
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Transcription inhibitors |
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Translation inhibitors |
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Other |
- Abzyme
- Calanolide A
- Ceragenin
- Cyanovirin-N
- Diarylpyrimidines
- Epigallocatechin gallate (EGCG)
- Foscarnet
- Fosdevirine†
- Griffithsin
- Hydroxycarbamide
- Miltefosine
- Portmanteau inhibitors
- Scytovirin
- Seliciclib†
- Synergistic enhancers
- Tre recombinase
- Zinc finger protein transcription factor
- KP-1461†
- BIT225†
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Failed agents |
- Aplaviroc
- Atevirdine
- Brecanavir
- Capravirine
- Dexelvucitabine
- Emivirine
- Lersivirine
- Lodenosine
- Loviride
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
°DHHS recommended initial regimen options. ◊Formerly or rarely used agent.
Index of viral disease
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Description |
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Disease |
- Systemic
- Cutaneous
- Zoster
- Human papillomavirus
- Zoonotic
- Symptoms and signs
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Treatment |
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