RECENT TRANSLATIONAL RESEARCH IN HIV/AIDS Edited by Yi-Wei Tang Recent Translational Research in HIV/AIDS Edited by Yi-Wei Tang Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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ISBN 978-953-307-719-2 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Pathogenesis and Epidemiology 1 Chapter 1 HIV-1 Glycoprotein Immunogenicity 3 Fahd Benjelloun, Christian Genin and Stephane Paul Chapter 2 Characterisation, Evaluation and Clinical Significance of Latent HIV-1 Reservoirs and Therapeutic Strategies for HIV Eradication 43 James Williams, Sarah Fidler and John Frater Chapter 3 The Changing Trends of HIV Subtypes and Its Implication on Mother-to-Child Transmission 71 Michael Kiptoo Part 2 Pharmacology and Host Interaction 87 Chapter 4 Transport Mechanisms of Nucleosides and Nucleoside Analogues ReverseTranscriptase Inhibitors in the Brain 89 Zoran B. Redzic and Sonja Misirlic Dencic Chapter 5 Interaction of Traditional Remedies Against HIV, Nutrients and ARVs 111 Eugenia Barros Part 3 Opportunistic Microbial Infections 127 Chapter 6 Syphilis in Men Infected with the Human Immunodeficiency Virus 129 Francisco Rodríguez-Gómez, Hortencia Cachay, David Chinchón, Enrique Jorquera and Emilio Pujol Chapter 7 Rifamycin Use in HIV-Infected Patients with Tuberculosis 145 Aline Bergesch Barth, Eric Free Egelund and Charles Arthur Peloquin VI Contents Chapter 8 Reversal Reaction as a Manifestation of Immune Reconstitution Inflammatory Syndrome 161 Vinicius Menezes, Anna Maria Sales, José Augusto Nery, Ximena Illarramendi, Alice Miranda, Maria Clara Galhardo and Euzenir Sarno Part 4 Laboratory Diagnosis 177 Chapter 9 The HIV Seronegative Window Period: Diagnostic Challenges and Solutions 179 Tamar Jehuda-Cohen Chapter 10 Pearls and Pitfalls of HIV-1 Serologic Laboratory Testing 203 Jiasheng Shao , Yunzhi Zhang, Yi-Wei Tang and Hongzhou Lu Chapter 11 Surgical Pathology in HIV Infection in the Era of Antiretroviral Therapy 213 Mónica Belinda Romero-Guadarrama Part 5 Antiretroviral Therapy 235 Chapter 12 Simplification of Antiretroviral Therapy (ART) 237 Maria Paloma Geijo Martinez Chapter 13 Highly Active Antiretroviral Therapy (HAART) and Metabolic Complications 253 Beth S. Zha, Elaine J. Studer, Weibin Zha, Philip B. Hylemon, William Pandak and Huiping Zhou Chapter 14 Future Perspectives in NNRTI-Based Therapy: Bases for Understanding Their Toxicity 275 Ana Blas-García, Nadezda Apostolova and Juan V. Esplugues Chapter 15 Antiretroviral Therapy and HIV-Associated Neurocognitive Disorders 295 Cagla Akay and Kelly L. Jordan-Sciutto Part 6 Special Clinical Cares 323 Chapter 16 Special Considerations in the Management of HIV Infection in Pregnancy 325 Chi Dola, Sean Kim and Juliet Tran Chapter 17 HIV-1 Treatment-Experienced Patients: Treatment Options and Management 343 Gail Reid and Richard M. Novak Contents VII Chapter 18 InforMatrix Nucleoside/Nucleotide Reverse Transcriptase Inhibitors “Backbones” 361 Gerrit Schreij and Rob Janknegt Part 7 New Therapy Strategies 385 Chapter 19 Crippling of HIV at Multiple Stages with Recombinant Adeno-Associated Viral Mediated RNA Interference 387 Ramesh B. Batchu, Oksana V. Gruzdyn, Aamer M. Qazi, Assaad Y. Semaan, Shelly M. Seward, Christopher P. Steffes, David L. Bouwman, Donald W. Weaver and Scott A. Gruber Chapter 20 Cell-Delivered Gene Therapy for HIV 405 Scott Ledger, Borislav Savkovic, Michelle Millington, Helen Impey, Maureen Boyd, John M. Murray and Geoff Symonds Chapter 21 Gene Therapy for HIV-1 Infection 431 Lisa Egerer, Dorothee von Laer and Janine Kimpel Chapter 22 HIV-Screening Strategies for the Discovery of Novel HIV-Inhibitors 457 María José Abad, Luis Miguel Bedoya and Paulina Bermejo Part 8 Vaccine Development 469 Chapter 23 HIV Vaccine 471 Alexandre de Almeida, Telma Miyuki Oshiro, Alessandra Pontillo and Alberto José da Silva Duarte Chapter 24 Towards a Functional Cure for HIV Infection: The Potential Contribution of Therapeutic Vaccination 493 Maja A. Sommerfelt Part 9 Beyond Conventional 511 Chapter 25 Micronutrient Synergy in the Control of HIV Infection and AIDS 513 Raxit J. Jariwalla, Aleksandra Niedzwiecki and Matthias Rath Chapter 26 Substance Abuse Treatment Utilizing Medication Assisted Treatment as HIV Prevention 527 Thomas F Kresina, Robert Lubran and Laura W. Cheever Chapter 27 The Pertinence of Applying Qualitative Investigation Strategies in the Design and Evaluation of HIV Prevention Policies 549 Carmen Rodríguez, Teresa Blasco, Antonio Vargas and Agustín Benito Preface A translational research serves a bench-to-bedside 'translation' of basic scientific research to practicable diagnostic procedure and therapies with meaningful improvements in physical, mental, or social health outcomes. To improve human health, scientific discoveries must be translated into practical applications. Such discoveries typically begin at “the bench” with basic research in which scientists study disease at a molecular or cellular level and then progress to the clinical level, or the patient's “bedside.” Basic scientists provide clinicians with new tools for use in patients and for assessment of their impact, and clinical researchers make novel observations about the nature and progression of the disease that often stimulate basic investigations. Translational research is a way of thinking about and conducting a much broader scientific research, which is practiced in the natural, biological, behavioural, and social sciences. HIV/AIDS is a perfect area to conduct translational researches. This InTech book, entitled “Recent Translational Research in HIV/AIDS”, includes 27 chapters covering HIV/AIDS translational researches on pathogenesis, diagnosis, treatment and prevention, and also those beyond conventional fields. These chapters, which are divided into nine sections, provide excellent examples of translational research for HIV/AIDS. These are by no means inclusive, but they do offer a good foundation for the development of clinical patient care. The first section on Pathogenesis and epidemiology comprises three chapters. Benjelloun and colleagues from the University of Saint-Etienne, France, provided an excellent review on HIV-1 glycoprotein immunogenicity. Williams and colleagues from the University of Oxford and other institutes in Oxford, UK, described characterisation, evaluation and clinical significance of latent HIV-1 reservoir and therapeutic strategies for HIV eradication. Kiptoo from Kenya Medical Research Institute overviewed changing trends of HIV subtypes and its implication on mother-to-child transmission. In the Pharmacology and host interaction section (Chapters 4-5), Redzic and Misirlic Dencic from Kuwait University, Kuwait, and Belgrade University, Serbia, provided a comprehensive review on transport mechanisms of nucleosides and nucleoside analogues reverse transcriptase inhibitors in the brain. Eugenia Barros from CSIR X Preface Biosciences, Pretoria, South Africa provided a comprehensive review on interaction of traditional remedies against HIV, nutrients and ARVs. In the next section on Opportunistic microbial infections (Chapters 6-8), Rodriguez- Gomez and colleagues from two hospitals in Spain covered current status of syphilis in men infected with HIV-1. Cases are presented with a focus on diagnosis and treatment. Barth and colleagues from the University of Florida, USA, focused their chapter on rifamycin used in HIV-infected patients with tuberculosis. Interactions between rifamycin and antiretroviral drugs were illustrated in details. Menezes and colleagues from Oswaldo Cruz Foundation, Brazil explored reversal reaction as a manifestation of immune reconstitution inflammatory syndrome focusing on leprosy and other mycobacterial infections. Diagnosis plays a bridge role in the translational researches. Chapters 9-11 are included in the section on Laboratory diagnosis. Jehuda-Cohen from Technion Israel Institute of Technology, Haifa, Israel, provided a comprehensive review on the HIV seronegative window period in relation to diagnostic challenges and solutions. My long-term collaborator Lu from Shanghai Public Health Clinical Center of Fudan University, China, used clinical case-based approach to summarize potential pitfalls of currently used HIV serology testing. Patient care providers should keep in mind that serology false negative results can happen in the clinical setting. Romero-Guadarrama from National Autonomous University of Mexico, Mexico provided unique comments on surgical pathology in HIV infection in the era of antiretroviral therapy. Antiretroviral therapy (ART) is the center of the HIV-1 infection treatment thereby playing a critical role in the HIV translational researches. In Chapter 12, Martinez and Imbroda from Cuenca, Spain, provided a comprehensive review on simplification of ART in order to improve the quality of life, facilitate adherence and prevent or reverse some adverse effects. Zha and colleagues from Virginia Commonwealth University and VA Medical Center in Richmond, USA (Chapter 13), described the relationship between highly active antiretroviral therapy (HAART) and metabolic complications. Blas-Garcia and colleagues from the University of Valencia, Spain, provided future perspectives in NNRTI-based therapy in relation to their toxicity (Chapter 14). In Chapter 15, Akay et al from the University of Pennsylvania, Philadelphia, USA, provided a thorough review on ART and HIV-associated neurocognitive disorders. Special clinical cares section includes Chapters 16-18. Dola et al from Tulane University, New Orleans, USA, described special considerations in the management of HIV infection in pregnancy. Reid and Novak from the University of Illinois in Chicago, USA, described treatment options and management in HIV-1 treatment-experienced patients. An InforMatrix interactive matrix model was described in details by Schreij and Janknegt from the Netherlands. Chapters 19-22 form the New therapy strategies section. Batchu and colleagues from Wayne State University and VA Medical Center in Detroit, USA, introduced crippling [...]... binding site is composed of relatively conserved regions located between the two domains of gp120, and the β inter-domains sheet The contact areas are discontinuous in the native three-dimensional structure of protein The CD4 binding domain is located in the D1 domain of the CDR2 loop (Complementarity Determining Region 2), on the opposite side of HLA type II binding domain (Fleury et al., 1991) In. .. studies have shown that the V1/V2 domain of the HIV-1 gp120 envelope protein is involved in viral tropism during infection V1V2 region interfere by masking conserved neutralizing epitopes, in the conformational changes occurring after co-receptor binding As V1/V2 domain is highly glycosylated, numerous studies have determined the influence of carbohydrates on neutralizing antibodies production As an example,... in orange (Walker and Burton, 2010) 3.1.1 Receptor-binding sites Binding of gp120 to CD4 results in gp120 conformational changes that expose the binding site for a secondary co-receptor, which is either of the chemokine receptors CCR5 or CXCR4 (Sterjovski et al., 2011) Crystallographic and biochemical studies of gp120 have provided valuable insights into mechanisms involved in CD4-binding and CD4-induced... the interaction with gp41 and V1-V2 loops Oligomeric gp120 protein can adopt a conformation called 'closed' as in primary isolates resulting in masking the receptor binding site of CD4 in V1 and V2 regions while gp120 of TCLA viruses preferentially adopt an 'open' shape thereby reducing its affinity for this receptor Finally the interaction with CD4 gives rise to an open structure enabling the link... packed in the capsid Viral enzymes: reverse transcriptase (RT), integrase (IN) , protease (Pr) and structural proteins; capsid (CA), nucleocapsid (NC), matrix (MA) and p6 are inside the particle together with the viral regulatory protein Vpr and the cellular protein cyclophilin (Phogat et al., 2007) 4 Recent Translational Research in HIV/AIDS primates (Simian Immunodeficiency Virus, SIV), feline and ovine... resulting in the cytopathic membrane fusion of several adjacent cells leading to the formation of a 'giant cell' multinucleate) at a T cell line (MT-2) It is now accepted that viruses using the CXCR4 coreceptor to enter target cells induce the formation of syncytia (SI virus like 'Syncytium Inducing virus') in contrast to viruses using exclusively CCR5 (NSI viruses for 'No Syncytium Inducing virus') 8 Recent. .. Kettering Cancer Center in the New York City I am looking forward to applying strategies and techniques described in this XI XII Preface book to conduct translational researches in diagnostic microbiology field in immunocomprised hosts, including patients receiving chemotherapy and stem cell transplantation Yi-Wei Tang, MD, PhD, F(AAM), FIDSA Chief of Clinical Microbiology Service Memorial Sloan Kettering... CD4 binding site represents the encounter of three separate regions via their surface-exposed residues These regions are distributed over 6 segments of gp120 These regions include the α-helices of the inner domain, the CD4-binding loop of outer domain, and the β20–β21 ribbon, that incorporate the gp120 bridging sheet, which is a structural element of gp120 formed after CD4 binding that is involved in. .. Spain explored new HIV-screening strategies for the discovery of novel HIV-inhibitors An effective HIV vaccine is badly needed to help halt the inexorable spread of HIV/AIDS Translational- research programs need to be expanded to connect basic science with existing vaccine-development tools, including hypothesis-driven clinical trials to assess novel immunogen designs There are only two chapters in. .. called evolving glycanshield model by which, through the continuous repositioning of its N-glycosylations positons, HIV is able to escape from a specific neutralizing Ab response Thus, the developed resistance is not a comprehensive one but, instead, a specific adaptation to the particular Ab response in each infected individual (Wei et al., 2003) In addition to being involved in blocking neutralizing Ab . sciences. HIV/AIDS is a perfect area to conduct translational researches. This InTech book, entitled Recent Translational Research in HIV/AIDS , includes 27 chapters covering HIV/AIDS translational. RECENT TRANSLATIONAL RESEARCH IN HIV/AIDS Edited by Yi-Wei Tang Recent Translational Research in HIV/AIDS Edited by Yi-Wei Tang Published by InTech Janeza. protein Vpr and the cellular protein cyclophilin (Phogat et al., 2007). Recent Translational Research in HIV/AIDS 4 primates (Simian Immunodeficiency Virus, SIV), feline and ovine. Infection