Retrovirology

Mozambique has severe resource constraints, yet with international partnerships, the nation has placed over 145,000 HIV- infected persons on antiretroviral therapies (ART) through May 2009. HIV clinical services are provided at .215 clinical venues in all 11 of Mozambique’s provinces. Friends in Global Health (FGH), affiliated with Vanderbilt University in...

Zidovudine and lamivudine (ZDV and 3TC) are long-standing nucleoside analog-reverse transcriptase inhibitors (NRTIs) with extensive clinical experience in a wide spectrum of patients from in utero through childhood and adult ages. The safety profiles of both drugs are well-known and side effects for ZDV most commonly include nausea/vomiting, fatigue, anemia/neutopenia,...

Darunavir is a next-generation protease inhibitor that demonstrates potent in vitro activity against wild type strains of HIV type-1, as well as against numerous strains resistant to available protease inhibitors. Numerous trials conducted in naïve and in the treatment-experienced HIV-infected individuals have significantly demonstrated greater virological suppression when darunavir was...

Darunavir is an oral peptidomimetic HIV-1 protease inhibitor with antiretroviral activity against wild type HIV strains and HIV strains with protease inhibitor mutations. Ritonavir-boosted darunavir is rapidly absorbed and it has a higher bioavailability than unboosted darunavir. In HIV infected adults, the pharmacokinetic profile of darunavir showed that the drug...

In these studies, we tested the effectiveness of combinatorial gene delivery to CCR5-expressing cell lines and primary cells to enhance resistance to HIV-1 infection. The transgenes used were chosen both to decrease membrane CCR5 and to inhibit HIV-1 replication, and were delivered using Tag-deleted SV40-derived vectors. rSV40s are very effective...

Sustained inhibition of HIV-1, the goal of antiretroviral therapy, is often impeded by the emergence of viral drug resistance. For patients infected with HIV-1 resistant to conventional drugs from the viral reverse transcriptase and protease inhibitor classes, the recently approved entry and integration inhibitors effectively suppress HIV-1 and offer additional...

Reverse transcriptase (RT) is a viral enzyme crucial for HIV-1 replication. Currently, 12 drugs are targeted against the RT. The low fidelity of the RT-mediated transcription leads to the quick accumulation of drug-resistance mutations. The sequence-resistance relationship remains only partially understood. Using publicly available data collected from over 15 years...

Reverse transcriptase (RT) is a viral enzyme crucial for HIV-1 replication. Currently, 12 drugs are targeted against the RT. The low fidelity of the RT-mediated transcription leads to the quick accumulation of drug-resistance mutations. The sequence-resistance relationship remains only partially understood. Using publicly available data collected from over 15 years...

Didanosine (ddI) has been used to treat HIV infection, in combination with other anti-retroviral drugs, for over 15 years. However, the use of the original formulation of ddI was limited by serious gastro-intestinal adverse effects, which were mainly attributable to the buffer used to protect ddI from the effect of...

Raltegravir is the first antiretroviral drug in the class of integrase inhibitors approved for the treatment of human immunodeficiency virus type 1 (HIV-1) in combination with other antiretroviral agents in treatment-experienced adults with evidence of ongoing viral replication and resistance to multiple antiretroviral drugs. Since raltegravir has a different mechanism...

Tipranavir (TPV) is a selective nonpeptidic HIV-1 protease inhibitor (PI) which is used in the treatment of treatment-experienced adults with HIV-1 infection. Tipranavir is administered orally twice daily in combination with low-dose ritonavir. The durable efficacy of tipranavir, in combination with low-dose ritonavir (tipranavir/ritonavir 500 mg/200 mg twice daily), has...

Matthias Leyh1, Sven Zipperich2, Ralf Winzer3, Philipp Drechsel1, Johannes Bogner4, Andreas Trein5, Lothar Schneider6, Hartwig Klinker1 and Peter Langmann71Department of Internal Medicine II, Division of Infectious Diseases, University of Wuerzburg, 97070 Wuerzburg, Germany. 2Department of Internal Medicine II, Zentralklinikum, 98527 Suhl, Germany. 3Department of Internal Medicine, Outpatient Clinic for Infectious...

Giuseppe Lapadula, Alessandro Soria and Andrea GoriClinic of Infectious Diseases, “San Gerardo” Hospital, Monza, Italy.AbstractEtravirine (ETR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) designed for binding to HIV reverse transcriptase in spite of most of the mutations which normally confer resistance to the other drugs of the same class....

Clotilde Allavena1, Stéphanie Trancart2,3 and Lise Cuzin21Infectious Diseases Unit, Hotel Dieu University Hospital, Nantes, France. 2Infectious Diseases Unit, Purpan Hospital, Toulouse, France. 3Laboratory of Clinical Toxicology and Pharmacology, Toulouse, France.AbstractAtazanavir is the first azapeptide protease inhibitor. As a consequence of metabolism by the Cytochrome P450 system and excretion by drug-transporters...

Marianne HarrisAIDS Research Program, St. Paul’s Hospital, Vancouver, BC, Canada.AbstractRaltegravir is the first integrase strand transfer inhibitor to be approved for the treatment of HIV infection. Administered orally in doses of 400 mg twice daily, it is well-tolerated and has minimal drug-drug interactions with coad- ministered antiretrovirals and other agents....

Sam Khalouei1 and Xuhua Xia2,31Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada. 2Department of Biology and Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada. 3Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.AbstractThe human immunodeficiency virus type 1 (HIV-1)...

Élcio Leal1, Leonardo O. Martins2, L. Mario Janini1 and Ricardo S. Diaz1 1Federal University of São Paulo, São Paulo, Brazil. 2Graduate School of Agriculture and Life Sciences, University of Tokyo. Abstract Analysis of the near full-length genomes revealed that the subtype F appeared in Brazilian HIV-1 epidemics...

Krishan K. Pandey and Duane P. Grandgenett Institute for Molecular Virology, Saint Louis University Health Sciences Center, Saint Louis, MO 63104. U.S.A. Abstract Human immunodeficiency virus type-1 integrase (IN) is a new and novel target for inhibitors. Strand transfer inhibitors effectively prevent concerted integration of viral DNA...

Krishna K. Ratnam, Cijiang John He and Paul Klotman Department of Medicine, Mount Sinai School of Medicine, New York, New York, U.S.A. Abstract HIV-associated nephropathy (HIVAN) is the leading cause of end-stage renal disease in patients with HIV-1 infection. While HIVAN involves all portions of the kidney,...

Luis Isamu Barros Kanzaki1 and Jorge Casseb2 1Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasilia, Darcy Ribeiro University Campus, Brasilia, D.F. Brazil, CEP 70.910-900. 2Institute of Tropical Medicine at Sao Paulo University Av. Enéas de Carvalho Aguiar, 500/prédio IMT II/3º andar. São Paulo, SP. Brazil, CEP...

James P. Keblesh, Benjamin C. Reiner, Jianuo Liu and Huangui Xiong Neurophysiology laboratory, the Center for Neurovirology and Neurodegenerative Disorders, and Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, U.S.A. Abstract HIV-1-associated dementia (HAD) describes the cognitive impairments and behavioral...

William A. Cafruny1, Richard G. Duman1, Raymond R. Rowland2, Eric A. Nelson3, and Grace H. Wong4 1Sanford School of Medicine, University of South Dakota, 414 E. Clark St., Vermillion, S.D. 57069. 2Department of Diagnostic Medicine and Pathobiology, L-229 Mosier Hall, College of Veterinary Medicine, Kansas State University, Manhattan, KS...

Howard A. Ross1, David C. Nickle2, Yi Liu2, Laura Heath2, Mark A. Jensen2, Allen G. Rodrigo1 and James I. Mullins2 1Bioinformatics Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand; 2Department of Microbiology, University of Washington, Seattle, Washington 98195-8070, USA Abstract: We characterized the variation in the reconstructed ancestor...