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Human Immunodeficiency Virus

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HIV Human immunodeficiency virus HIV (Human immunodeficiency virus) is a lentivirus (a subgroup of retrovirus) that causes the acquired immunodeficiency syndrome (AIDS), a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. HIV infects vital cells in the human immune system such as helper T cells (specifically CD4 + T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4 + T cells through a number of mechanisms, including apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4 + T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4 + T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections. www.MedChemExpress.com 1 HIV Inhibitors & Modulators (Z)-9-Propenyladenine (±)-BI-D ((Z)-Mutagenic Impurity of Tenofovir Disoproxil) Cat. No.: HY-100079A Cat. No.: HY-18601 Bioactivity: (Z)-9-Propenyladenine is a mutagenic impurity in tenofovir Bioactivity: (±)-BI-D is a potent ALLINI(An allosteric IN inhibitor) that disoproxil fumarate. Tenofovir is an antiretroviral drug known binds integrase at the LEDGF/p75 binding site. as nucleotide analogue reverse transcriptase ( NtART) inhibitor, which blocks reverse transcriptase, a crucial virus enzyme in HIV-1 and HBV. Purity: 98.0% Purity: 96.90% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg 5 mg, 10 mg, 50 mg, 100 mg 2',3'-Dideoxyadenosine 3'-Azido-3'-deoxy-5-methylcytidine Cat. No.: HY-W013441 Cat. No.: HY-111640 Bioactivity: 2',3'-Dideoxyadenosine is an inhibitor of HIV replication [1]. Bioactivity: 3'-Azido-3'-deoxy-5-methylcytidine (CS-92) is a potent xenotropic murine leukemia-related retrovirus ( XMRV) Antiretroviral activity [1]. Antiviral efficacy [1]. inhibitor with a CC50 of 43.5 μM in MCF-7 cells. 3'-Azido-3'-deoxy-5-methylcytidine also inhibits HIV-1 reve… Purity: >98% Purity: 99.39% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mg Size: 10mM x 1mL in DMSO, 10 mg, 50 mg 3-Deazaadenosine 3-Deazaadenosine hydrochloride Cat. No.: HY-W013332 Cat. No.: HY-W013332A Bioactivity: 3-Deazaadenosine is an inhibitor of S-adenosylhomocysteine Bioactivity: 3-Deazaadenosine (hydrochloride) is an inhibitor of S-adenosylhomocysteine hydrolase, with a K of 3.9 µM; hydrolase, with a Ki of 3.9 µM; 3-Deazaadenosine has i anti-inflammatory, anti-proliferative and anti- HIV activity. 3-Deazaadenosine has anti-inflammatory, anti-proliferative and anti- HIV activity. Purity: 99.0% Purity: 98.06% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg Size: 10mM x 1mL in DMSO, 1 mg, 5 mg, 10 mg 9-Propenyladenine (Mutagenic Impurity of Tenofovir Abacavir Disoproxil; Tenofovir Impurity 2) Cat. No.: HY-100079 Cat. No.: HY-17423 Bioactivity: 9-Propenyladenine is a mutagenic impurity in tenofovir Bioactivity: Abacavir is a potent nucleoside analog reverse-transcriptase disoproxil fumarate. Tenofovir is an antiretroviral drug known inhibitor (NRTI). as nucleotide analogue reverse transcriptase inhibitors, which block reverse transcriptase, a crucial virus enzyme in HIV-1 and HBV. Purity: 96.81% Purity: 98.17% Clinical Data: No Development Reported Clinical Data: Launched Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg 10 mg, 50 mg, 100 mg, 200 mg ABX464 AMD 3465 Cat. No.: HY-100870 (GENZ-644494) Cat. No.: HY-15971A Bioactivity: ABX464 is a potent anti-HIV agent. ABX464 inhibits HIV-1 Bioactivity: AMD 3465 is a potent antagonist of CXCR4, inhibits binding of replication in stimulated peripheral blood mononuclear cells AF647 12G5 mAb and CXCL12 to CXCR4, with IC50s of 0.75 nM (PBMCs) with an IC ranging between 0.1 μM and 0.5 μM. 50 and 18 nM in SupT1 cells; AMD 3465 also potently inhibits the replication of X4 HIV strains ( IC50: 1-10 nM), but has… Purity: 99.81% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 5 mg, 10 mg, 50 mg, 100 mg 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg 2 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] AMD 3465 hexahydrobromide Amprenavir (GENZ-644494 hexahydrobromide) Cat. No.: HY-15971 (VX-478) Cat. No.: HY-17430 Bioactivity: AMD 3465 hexahydrobromide is a potent antagonist of CXCR4, Bioactivity: Amprenavir (VX-478) is a HIV protease inhibitor(Ki=0.6 nM) inhibits binding of 12G5 mAb and CXCL12 AF647 to CXCR4, with used to treat HIV infection. IC50s of 0.75 nM and 18 nM in SupT1 cells; AMD 3465 also potently inhibits the replication of X4 HIV strains ( IC50 Purity: 98.79% Purity: 99.61% Clinical Data: No Development Reported Clinical Data: Phase 4 Size: 10mM x 1mL in Water, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg, 100 mg 5 mg, 25 mg, 50 mg Aplaviroc Atazanavir (AK 602; GSK 873140; GW 873140) Cat. No.: HY-17450 (BMS-232632) Cat. No.: HY-17367 Bioactivity: Aplaviroc, a SDP derivative, is a CCR5 antagonist, with IC50s Bioactivity: Atazanavir(BMS-232632) is an highly potent HIV-1 protease inhibitor. of 0.1-0.4 nM for HIV-1 Ba-L, HIV-1 JRFL and HIV-1 MOKW. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: Launched Size: 250 mg, 500 mg Size: 10 mg, 50 mg, 100 mg Atazanavir sulfate beta-L-D4A (BMS-232632 sulfate) Cat. No.: HY-17367A (2'3'-didehydro-2'3'-dideoxyadenosine) Cat. No.: HY-100260 Bioactivity: Atazanavir sulfate is a sulfate salt form of atazanavir that Bioactivity: NSC 108602 is a nucleoside HIV-1 reverse transcriptase is an highly potent HIV-1 protease inhibitor. Target: HIV-1 inhibitor. protease inhibitor Atazanavir sulfate is a sulfate salt form of atazanavir that is an highly potent HIV-1 protease inhibitor. It has a pharmacokinetic profile that supports… Purity: 99.64% Purity: >98% Clinical Data: Launched Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 1 mg, 5 mg, 10 mg 10 mg, 50 mg, 100 mg Betulinic acid Bevirimat (Lupatic acid; Betulic acid) Cat. No.: HY-10529 (PA-457; MPC-4326; YK FH312) Cat. No.: HY-N0842 Bioactivity: Betulinic acid is a natural pentacyclic triterpenoid, acts as Bioactivity: Bevirimat (PA-457; MPC-4326; YK FH312) is an anti-HIV drug a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 derived from a betulinic acid-like compound; is believed to μM, and possesses anti-HIV, anti-malarial, anti-inflammatory inhibit HIV by a novel mechanism, so-called maturation and anti-tumor properties. inhibition. Purity: 98.18% Purity: 98.0% Clinical Data: Phase 2 Clinical Data: Phase 2 Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 100 mg, 200 mg, 500 mg 5 mg, 10 mg BI 224436 Bictegravir Cat. No.: HY-18595 (GS-9883) Cat. No.: HY-17605 Bioactivity: BI 224436 is a novel HIV-1 noncatalytic site integrase Bioactivity: Bictegravir is a novel, potent inhibitor of HIV-1 integrase with inhibitor with EC50 values of less than 15 nM against an IC50 of 7.5 nM. different HIV-1 laboratory strains. Purity: 98.17% Purity: 98.27% Clinical Data: Phase 1 Clinical Data: Launched Size: 5 mg, 10 mg, 50 mg, 100 mg Size: 10mM x 1mL in DMSO, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg www.MedChemExpress.com 3 BMS-378806 BMS-707035 (BMS-806) Cat. No.: HY-14134 Cat. No.: HY-13269 Bioactivity: BMS-378806 is a potent HIV-1 attachment inhibitor that Bioactivity: BMS-707035 is an HIV-1 integrase (IN) inhibitor with an IC50 interferes with CD4-gp120 interactions. BMS-378806 selectively value of 15 nM. inhibits the binding of HIV-1 gp120 to the CD4 receptor with EC50 of 0.85-26.5 nM in virus. Purity: 98.89% Purity: 99.95% Clinical Data: No Development Reported Clinical Data: Phase 2 Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg, 100 mg 5 mg, 10 mg, 50 mg, 100 mg CA inhibitor 1 Cabotegravir Cat. No.: HY-124594 (GSK-1265744; S/GSK1265744) Cat. No.: HY-15592 Bioactivity: CA inhibitor 1 is a potent HIV capsid inhibitor for HIV Bioactivity: Cabotegravir is a potent HIV integrase inhibitor as an oral inhibition [1]. lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection. Cabotegravir is an inhibitor of OAT1 (IC50 0.81 μM) and OAT3 (IC50 0.41 μM). Purity: >98% Purity: 99.85% Clinical Data: No Development Reported Clinical Data: Phase 3 Size: 500 mg, 100 mg, 250 mg Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg, 100 mg CCR5 antagonist 1 CDK9-IN-1 Cat. No.: HY-100261 Cat. No.: HY-13231 Bioactivity: CCR5 antagonist 1 is a CCR5 antagonist which can inhibit HIV Bioactivity: CDK9-IN-1 is a novel, selective CDK9 inhibitor for the replication extracted from WO 2004054974 A2. treatment of HIV infection, with an IC50 of 39 nM for CDK9/CycT1, extracted from reference, compound 87. Purity: >98% Purity: 95.48% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg, 100 mg Celgosivir hydrochloride (MBI 3253 (hydrochloride); MDL 28574 Cenicriviroc (hydrochloride); MX3253 (hydrochloride)) Cat.
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  • Tim Horn Deputy Executive Director, HIV & HCV Programs Treatment

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    Tim Horn Deputy Executive Director, HIV & HCV Programs Treatment Action Group NASTAD Prevention and Care Technical Assistance Meeting Washington, DC July 19, 2017 ▪ Pipeline is robust! ▪ Several drugs, coformulations, and biologics in late-stage development and Phase I trials ▪ Trends are clear ▪ Maximizing safety and efficacy of three-drug regimens ▪ Validating two-drug regimens as durable maintenance therapy and, potentially, for PLWHIV starting treatment for the first time ▪ Advancing long-acting and extended release products ▪ Development new drugs and biologics for multi-drug/class-resistant HIV ▪ Cost considerations in high- and middle-income countries Compound Class/Type Company Status DRUGS Isentress HD INSTI Merck FDA Approved 5/30/17 Bictegravir plus TAF/FTC INSTI plus NtRTI & NRTI Gilead Phase III; mid-2018 approval Doravirine (plus TDF/3TC) NNRTI (plus NtRTI & NRTI) Merck Phase III; mid-2018 approval Darunavir plus cobicistat, PI plus PK booster, NtRTI & Janssen Phase III; mid-2018 approval TAF & FTC NRTI Dolutegravir plus rilpivirine INSTI plus NNRTI ViiV/Jansse Phase III; early 2018 approval n Dolutegravir plus lamivudine INSTI plus NRTI ViiV Phase III; late 2018 approval BIOLOGICS Ibalizumab Entry Inhibitor TaiMed Phase III; late 2017 or early Biologics 2018 Compound Class/Type Company Status DRUGS LA Cabotegravir + INSTI + NNRTI ViiV/ Phase III LA Rilpivirine Janssen Albuvirtide Fusion Inhibitor Frontier Phase III; China is primary Biologics launch target Fostemsavir CD4 attachment inhibitor ViiV Phase III Elsulfavirine
  • Lamivudine in Combination with Zidovudine, Stavudine, Or Didanosine in Patients with HIV-1 Infection

    Lamivudine in Combination with Zidovudine, Stavudine, Or Didanosine in Patients with HIV-1 Infection

    Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial Daniel R. Kuritzkes*, Ian Marschner†, Victoria A. Johnson‡, Roland Bassett†, Joseph J. Eron§, Margaret A. FischlII, Robert L. Murphy¶, Kenneth Fife**, Janine Maenza††, Mary E. Rosandich*, Dawn Bell‡‡, Ken Wood§§, Jean-Pierre Sommadossi‡, Carla PettinelliII II and the National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators Objective: To study the antiviral activity of lamivudine (3TC) plus zidovudine (ZDV), didanosine (ddI), or stavudine (d4T). Design: Randomized, placebo-controlled, partially double-blinded multicenter study. Setting: Adult AIDS Clinical Trials Units. Patients: Treatment-naive HIV-infected adults with 200–600 × 106 CD4 T lymphocytes/l. Interventions: Patients were openly randomized to a d4T or a ddI limb, then randomized in a blinded manner to receive: d4T (80 mg/day), d4T plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos; or ddI (400 mg/day), ddI plus 3TC (300 mg/day), or ZDV (600 mg/day) plus 3TC, with matching placebos. After 24 weeks 3TC was added for patients assigned to the monotherapy arms. Main outcome measure: The reduction in plasma HIV-1 RNA level at weeks 24 and 48. From the *University of Colorado Health Sciences Center and Veterans Affairs Medical Center, Denver, Colorado, the †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, the