CURRENT PERSPECTIVES IN HIV INFECTION pdf

CURRENT PERSPECTIVES IN HIV INFECTION Edited by Shailendra K Saxena Current Perspectives in HIV Infection http://dx.doi.org/10.5772/46042 Edited by Shailendra K Saxena Contributors Wan Majdiah Wan Mohamad, Rehana Basri, Osaro Erhabor, TEDDY ADIAS, Cagla Akay, Jennifer King, Brigid Jensen, Patrick Gannon, Claudia Colomba, Raffaella Rubino, Robert Muga, Arantza Sanvisens, Ferran Bolao, Daniel Fuster, Santiago Pérez-Hoyos, Jordi Tor, Marta Torrens, Gabriel Vallecillo, Inmaculada Rivas, José Miguel Azevedo-Pereira, Bakari Adamu Girei, Sani-Bello Fatima, Jose Castro, Maria Alcaide, Paula Freitas, Doris Wilflingseder, Wilfried Posch, Enrique Valdes, Joseph Ongrádi, Balázs Stercz, Károly Nagy, Mauro Pistello, Abdulkarim Alhetheel, Mahmoud Aly, Marko Kryworuchko, Gbemisola Agbelusi, Chi Dola, Amanda Johnson, Olivia Chang, Maga Martinez, Peter J Jay Chipimo, Nitya Nathwani, Shailendra K Saxena Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are 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instructions, methods or ideas contained in the book Publishing Process Manager Iva Simcic Technical Editor InTech DTP team Cover InTech Design team First published April, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Current Perspectives in HIV Infection, Edited by Shailendra K Saxena p cm ISBN 978-953-51-1057-6 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Section HIV and Altered Immune Responses Chapter Immune Responses and Cell Signaling During Chronic HIV Infection Abdulkarim Alhetheel, Mahmoud Aly and Marko Kryworuchko Chapter Role of Dendritic Cell Subsets on HIV-Specific Immunity 31 Wilfried Posch, Cornelia Lass-Flörl and Doris Wilflingseder Chapter Hematopoietic Stem Cell Transplantation in HIV Infected Patients 57 Nitya Nathwani Section HIV Screening Chapter Screening for HIV Infection in Pregnancy 77 Chi Dola, Maga Martinez, Olivia Chang and Amanda Johnson Chapter Human Immunodeficiency Virus Testing Algorithm in Resource Limiting Settings 95 Teddy Charles Adias and Osaro Erhabor Section HIV and NeuroAIDS Chapter NeuroAIDS: Mechanisms, Causes, Prevalence, Diagnostics and Social Issues 109 Shailendra K Saxena, Sneham Tiwari and Madhavan P.N Nair 75 107 VI Contents Chapter Human Immunodeficiency Virus Infection and Co-Morbid Mental Distress 125 Peter J Chipimo and Knut Fylkesnes Chapter Neurological Manifestations of HIV-1 Infection and Markers for HIV Progression 137 Rehana Basri and Wan Mohamad Wan Majdiah Chapter Persistence of HIV-Associated Neurocognitive Disorders in the Era of Antiretroviral Therapy 161 Jennifer M King, Brigid K Jensen, Patrick J Gannon and Cagla Akay Section Manifestations of HIV Infection 207 Chapter 10 Oral Manifestations of HIV 209 G.A Agbelusi, O.M Eweka, K.A Ùmeizudike and M Okoh Chapter 11 Endocrine Manifestations of HIV Infection 243 Bakari Adamu Girei and Sani-Bello Fatima Chapter 12 Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance Syndrome 261 Paula Freitas, Davide Carvalho, Selma Souto, António Sarmento and José Ls Medina Chapter 13 HIV/AIDS: Vertical Transmission 301 Enrique Valdés Rubio Chapter 14 Reproductive Health Challenges of Living with HIV-Infection in Sub Saharan Africa 325 O Erhabor, T.C Adias and C.I Akani Section Prevention and Treatment of HIV Infection 349 Chapter 15 The Downside of an Effective cART: The Immune Restoration Disease 351 Claudia Colomba and Raffaella Rubino Chapter 16 HIV Infection and Viral Hepatitis in Drug Abusers 367 Arantza Sanvisens, Ferran Bolao, Gabriel Vallecillo, Marta Torrens, Daniel Fuster, Santiago Pérez-Hoyos, Jordi Tor, Inmaculada Rivas and Robert Muga Contents Chapter 17 Section Prevention of Sexually Transmitted HIV Infection 385 Jose G Castro and Maria L Alcaide Recent Advances 409 Chapter 18 HIV-2 Interaction with Target Cell Receptors, or Why HIV-2 is Less Pathogenic than HIV-1 411 José Miguel Azevedo-Pereira Chapter 19 Interaction of FIV with Heterologous Microbes in the Feline AIDS Model 447 Joseph Ongrádi, Stercz Balázs, Kövesdi Valéria, Nagy Károly and Pistello Mauro VII Preface During the past three decades, the world scientific community has witnessed major achieve‐ ments understanding the pathogenesis of Human immunodeficiency virus (HIV) which leads to a deadly catastrophic disease acquired immune deficiency syndrome (AIDS) As per recent UNAIDS reports currently ~34 million adults and children are estimated to be living with HIV Ever since the discovery of HIV, it has been an ultimate challenge to the health and scientific authorities There is a constant research being done by scientists worldwide to find ways to combat with HIV HIV has occupied place as a topmost health and social disas‐ ter It is affecting several developing economies Thus it becomes an urgency to find ways of management against HIV infection To device a way, basic and thorough knowledge about HIV, stands as a priority We need to understand viral morphology, functions, and mecha‐ nisms of viral replication, budding, cell signaling, pathogenesis, interaction with host fac‐ tors, and various other important aspects However many aspects of HIV infection are still poorly understood HIV-1, a retrovirus, attacks the T-lymphocytes of the hosts, and causes several multifaceted altered immune responses and finally leads to fatality HIV-1 displays extraordinary genetic variation, leading to the classification of the viral strains into phylogenetically distinct groups and subtypes Amongst the various subtype/clade (A to K) of HIV-1, subtype C is linked to ~48% of the infections globally and is associated with rapidly growing epidemics in Sub-Saharan Africa and parts of Asia, including India and China In addition to genetic and demographic factors, biological properties unique to the subtype of HIV may also play a role in their exponential proliferation HIV is capable of being latent and hidden in various reservoirs in the body where drug tar‐ geting becomes impossible HIV can enter brain and attack neuronal cells and deregulate there functioning which leads to neuropathogenesis Hence drug targeting to viral reser‐ voirs like brain stands as a big issue Drugs capable of travelling across the Blood Brain Bar‐ rier (BBB) are an urgent need Along with these genes specific targeting drugs are also important These drugs can focus on one particular gene or a part of gene that is motif, which is conserved and is most stable This stable part can be very well targeted by the de‐ signed drugs Henceforth, keeping in mind all the issues, this book gives a comprehensive overview of HIV and AIDS including NeuroAIDS The book is divided into several parts which cover various topics deeply, explaining HIV and related pathology, immunity and immunopathol‐ ogy, altered immune responses, screening, diagnosis, manifestations, prevention, treatment, epidemiology and etiology to current clinical recommendations in management of HIV/ X Preface AIDS including NeuroAIDS, It also highlights the ongoing issues, recent advances and fu‐ ture directions in diagnostic approaches and therapeutic strategies The authors and editors of the book hope that this work might increase the interest in this field of research and that the readers will find it useful for their investigations, management and clinical usage Also I would like to thank Council of Scientific and Industrial Research (CSIR-CCMB), Director CCMB Dr CM Rao, colleagues, family, and parents who gave me a lot of encouragement and support during the work on this book Shailendra K Saxena, PhD, DCAP, FAEB, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India 456 Current Perspectives in HIV Infection (17.1%), cats cohabiting with rats (19.6%), and cats feeding on homemade food and raw milk (27.2%) were positive for this protozoon In addition, 4.2% of cats were positive for Leishma‐ nia spp [30] In several countries, parasitic infections, especially intestinal parasites, of cats are more frequent than infections with FIV or FeLV In Italy, comparison of FIV, FeLV and TG IgG seropositivity resulted in the same ratio: 6.6%, 3.8% and 30.5%, respectively [11] Ep‐ idemiological studies in Portugal found 24.2% TG seropositivity, 31% carrier state of intesti‐ nal parasites (Toxocara cati, Isospora felis, Ankylostoma stenocephala, Toxascaris leonina) as compared to FIV and FeLV infection (10.2% and 7.1%, respectively) in the same stray cat population [28] In a confined region of Canada, 29.8% of cats had TG antibodies, 1.3% ex‐ creted oocysts in their feces, while FIV and FeLV seropositivity was significantly lower (5.2% and 3.1%, respectively [33] In Thailand, although the ratio between retroviral and parasitic infections were different (FIV, FeLV, heartworm (Dirofilaria immitis) and TG IgG (20.1%, 24.5%, 4.6% and 10.1%, respectively) from the other data mentioned above, of the 348 cats sampled for all four pathogens, 3.1%, 2.8% and 0.28% were positive for TG antibod‐ ies and FIV antibodies, FeLV antigen or D immitis antigen, respectively Of the 35 TG sero‐ positive cats, 42.9% were coinfected with at least one of the other three pathogens [18] Feral cats from Cairo, Egypt exhibited an extremely high ratio of TG infestation as compared to FIV, FeLV of heartworm seroprevalence: 95.5%, 33.9%, 4.6% and 3.4%, respectively It is of interest that 57.4% of TG positive cats had very high antibody titre (>1:640) [31] Oocyst shedding was found to be accompanied by high level antibodies: cats shedding TG had high antibody level (>1:256) In the same cat cohort, Toxocara cati eggs were identified in 37%, Cys‐ toisospora felis oocysts in 14%, Taenia sp segments in 15% of animals Most of the fecal sam‐ ples showed evidence of at least one intestinal parasite, while many samples contained evidence of multiple intestinal parasites High prevalence of antibodies reflects latent infec‐ tions However, it must be emphasized that cats with latent infection can pose a considera‐ ble zoonotic risk with respect to the shedding of intestinal parasites in their feces Stress conditions induce shedding Intercurrent retroviral infections (FIV or FeLV or both) with consequent declination in systemic and mucosal immunity are regarded as important stress factors [33] Result of the multivariate logistic regression analysis of another recent survey on simultaneous virus and parasite seropositivity (FIV, FeLV and TG was 19.2%, 14.2% and 32.1%, respectively) in Iran showed that retroviral-associated immunosuppression is a risk factor for activation of toxoplasmosis in cats [21] Beside toxoplasmosis, Leishmania infec‐ tion is frequent in many countries Cellular immunity of normal cats effectively controls Leishmania infantum (syn L chagasi) However, feline immunosuppressive diseases such as FIV and FeLV infection impair the normal response to infection and expose cats to reactiva‐ tion or new infections by other pathogens, among them Leishmania Although no statistical evidence of association between TG and Leishmania was found, but in cats coinfected with FIV, a strong statistical association for the triple coinfection was found [16] One can con‐ clude from these epidemiological surveys, that parasites cause not only opportunistic infec‐ tions in retrovirus infected cats, but activation of their latent infection by retroviruses suggests existence of a closer relationship between phylogenetically distant two groups of foreign agents at molecular or immunological level Interaction of FIV with Heterologous Microbes in the Feline AIDS Model http://dx.doi.org/10.5772/52767 Following infection of FIV carrier cats with a secondary pathogen, cytokine dysregulation is more pronounced TG increases both IFN-γ and IL-10, but fails to increase IL-2, IL-12, while TG infected FIV negative cats show an increase in IFN-γ, IL-2 and IL-12 [72] A similar dys‐ regulation has been reported in cats challenged with LM [73] The increase in IL-10 to IL-12 ratio predicts the loss of cellular immunity in FIV infected cats [72,74] These in vivo studies are in good correlation with in vitro experiments Latent infection in HIV or FIV infected lymphocytes and macrophages can be reactivated and virus production can be increased by chemical immune activators such as phorbol myristate acetate [75], concanavalin A [5], granulocyte macrophage-colony stimulating factor [76] Both HIV and FIV induce apoptosis not only in the infected cells, but in the vicinity of infected cells as well Programmed cell death of infected cells is mediated mainly by TNF-α released from infected cells [77] Cyto‐ kine dysregulation affects not only the FIV carrier animal, but damages the fetus by causing a pro-inflammatory placental microenvironment at early pregnancy: increased expression of IL-6, IL-12, decreased expression of IL-1β, SDF-1α Similarly to AIDS patients, IL-6 expres‐ sion correlated with FIV load [78] The exact role of cytokines and chemokines in the process of simultaneous infections waits for clarification Diagnosis, treatment and prevention of simultaneous infections Preventing exposure of healthy cats to FIV or FeLV infected cats by tests and removal or iso‐ lation is an important measure, and is not alternative to vaccination The most common method for diagnosis of FIV infection is screening for antibodies (typically against p24 and p15) using an ELISA Several commercial kits are available worldwide Confirmatory testing for cats with positive results is strongly recommended, Western-blot and immunofluores‐ cent antibody assays (IFA) are used Infection from queens can be transmitted to kittens, testing for newly acquired cats and kittens is strongly recommended Vaccinated cats also produce antibodies that cannot be distinguished, by any commercially available antibody test [79], from antibodies due to natural infection, and queens might transmit these antibod‐ ies to the litter via colostrum FIV vaccine induces fewer antibodies for non-structural pro‐ teins compared to natural infection There are tests to discriminate this pattern, but these are unsuitable for routine use Polymerase chain reaction (PCR) has promoted by some com‐ mercial laboratories as a method to determine a cat’s true infection status The test detects FIV RNA or proviral DNA A real-time PCR assay for FIV quantification of proviral DNA in PBMC has high sensitivity and specificity This and reverse transcriptase (RT)-PCR are methods to quantitate viral load and dissemination in the body after activation of latent FIV infection Due to genetically heterologous nature of FIV, tests with concurrent determination of subtype differentiation are recommended Serological diagnosis of FeLV relies on detec‐ tion of the core antigen p27 in PBMC using an ELISA IFA test is also used but discordant results might occur PCR is offered by a number of commercial laboratories, it can be per‐ formed on blood, saliva, bone marrow and tissues Kittens can be tested for FeLV at any age, as passively acquired maternal antibody does not interfere with testing for viral antigen 457 458 Current Perspectives in HIV Infection Compliance of cat owners with FIV and FeLV testing is low, in spite of using combined test kits, and professional recommendations by veterinarians (Table 1) At risk of infection cats access to outdoors known exposure to retrovirus infected cats multicat environment bite wounds oral disease Sick cats Cats entering new homes, shelters Newly acquired cats and kittens about to be vaccinated for FIV or FeLV Cats used for blood or tissue donation Table Major recommendations for FIV and FeLV testing of cats The owner must also consider the cost of immunisation, fecal parasite testing, de-worming, or blood screening to reveal and eliminate concomitant infections [17] Further commercially available kits for serological screening, and/or antigen detection including FHV-1 and the most pathogens are widely available for domestic and large cats These kits used separately depending on the clinical course of the animal can be combined in definitively Well estab‐ lished, cheap but somewhat laborious and time consuming classical methods have been used for direct detection of common bacteria, fungi and parasites (cultivation, biochemistry, microscopy, etc.) For feline pathogens causing infection in humans, the same methods and kits can be used as in human medicine With technological advances quantitative real-time or RT-PCR assays have been used subsequently their products are sequenced to determine species or variants Load of viruses in body fluids can be determined by quantitative molec‐ ular methods [5,7,24,36] Simultaneous detection of nucleic acids of coinfecting microbes would be ideal by using multiple PCR [20, 29] Development of easily available panels is a financial interest of biotechnology companies Gene arrays capable of detecting even hun‐ dreds of microbes at nucleic acid level could also be marketed in near future Aims of detecting simultaneous infection in cats and large felids are very variable As retro‐ viral infection might represent a considerable risk factor to several bacterial, fungal and par‐ asitic opportunistic infections and activating potential of their latency, demonstration of retroviruses ought to be followed by screening for other pathogens [21] Vice versa, cats liv‐ Interaction of FIV with Heterologous Microbes in the Feline AIDS Model http://dx.doi.org/10.5772/52767 ing in endemic areas of certain parasites are significantly more likely to be co-infected with FIV and/or FeLV, which may present confounding clinical signs and therefore cats in such areas should be always carefully screened for coinfections [16] Occasionally, knowing the cat’s geographical location can be helpful, while the nature of the clinical presentation might be less informative [23] Informations concerning risk assessment of viral pathogens to other animal populations are currently an important issue [28] Screening for multiple infections is appropriate prior to relocation of cats and other felids to prevent introduction of pathogens in host colonies (households, catteries, zoos, national parks, etc.) [29] As with HIV, careful consideration should also be given to systematic testing and treatment of individuals in high-risk populations, and this may prove to be a potential strategy to prevent FIV transmis‐ sion [67] Preventive measures are important, because transmission of pathogens in cluster conditions may occur between asymptomatic cats and immunocompromised animals [25,32] Furthermore, certain FIV or FeLV strains are able to emerge in new host species Do‐ mestic cat strains of viruses can cross species barriers with potentially devastating conse‐ quences to fragile populations of large felids [12] As seen with feline haemoplasma, it could infect even the immunocompromised human cat owner [69] so; cat owners ought to be pro‐ tected from common zoonotic infections While testing and identification of infected cats is necessary for prevention and transmis‐ sion, vaccination is also an important tool Various independent bodies, including the Inter‐ national Vaccination Guidelines Group (IVGG), the European Advisory Board on Cat Diseases (ABCD), the World Small Animal Veterinary Association (WSAVA), or the Ameri‐ can Association of Feline Practitioners (AAFP) have developed and regularly issues recom‐ mendations for vaccination protocols for cats and kittens The guidelines encompass the types of antigens used, the types of vaccines available, the frequency of vaccination and the anatomical site used for administration These guidelines differ from each other and also from the manufacturer’s datasheets or recommendations of national authorities General as‐ pects and details of vaccination of cats are far beyond the scope of recent review; in this re‐ gard see a recent publication by Dean et al 2012 Core vaccines are defined as those vaccines which all cats, regardless of circumstances, should receive to protect animals from severe, life threatening diseases which have global distribution Only to emphasize those in context with microbes with transactivating and opportunistic potential, FHV-1 vaccination of kittens seems to be important Vaccination against FCV, FPV also belongs to core vaccines These vaccinations are recommended to start as early as vaccination with FeLV, applying revacci‐ nations up to 16-20 weeks of age Most practices routinely give the commonly used antigens annually, although with the exception of the FHV, the FCV and FIV vaccination is recom‐ mended every years [80] Non-core vaccines are those that are required by only those ani‐ mals whose geographic location, local environment or lifestyle place them at risk of contracting specific infections This moment, both FIV and FeLV vaccines are regarded as non-core FIV vaccine development was initiated as a model for HIV vaccination Vaccina‐ tion against HIV started with experiments to trigger a specific, potent and long-lasting im‐ munity in a surrogate animal model Later, several novel approaches were tested in the feline model Although the quest for a truly effective AIDS vaccine is years away [81], vacci‐ nation against FIV became available [82] This vaccine (Fel-O-Vax FIV®) is marketed in many 459 460 Current Perspectives in HIV Infection countries, but it might not protect cats against all field strains of subtypes A or B Lifespan of infected cats appears similar to that of uninfected cats, but exposure to other infectious dis‐ eases drastically reduces survival of FIV positive animals [17] Historically, FeLV vaccina‐ tion has been used for decades, well before FIV vaccination The combined use of testing and vaccination programs is assumed to have decreased the prevalence of FeLV over the last 20 years [17,19] Administering the first vaccine to kittens is at 8-10 weeks of age, with regular revaccinations usually every year Several practitioners stopped revaccinating in‐ door and older cats, once they reached a certain age (≥ years) assuming that they would not have close contact with a persistently infected cat, or elder cats are less easily infected with FeLV than younger animals As persistently infected cats have been diagnosed at all ages, due to the decreased susceptibility to FeLV infection, vaccinating at 2-3 years intervals rather than annually seems to be acceptable For free-roaming cats, annual FeLV vaccination is recommended To increase revaccination interval assuming the presence of high level an‐ tibodies is not feasible because quantitative assays to measure serum FeLV antibodies are commercially available in few countries [80] A marked difference in vaccination efficacy ex‐ ists, and suggests that only inactivated whole virus or canarypox-vectored recombinant vac‐ cines should be used Cats with access to outdoors should be vaccinated, but should have at least one negative FeLV ELISA test before vaccination Several studies showed that the mean survival time of FeLV positive cats are significantly shorter than that of FeLV-negative cats including vaccinated ones (references in 17) Aspecific measures to prevent FIV and FeLV transmission were set according to the biological characteristics of these viruses Al‐ though retroviruses become inactivated within a few hours on dry surfaces, they may re‐ main viable in dried biological deposits for more than a week Both viruses are inactivated by common detergents and hospital disinfectants Spreading via body fluids is best prevent‐ ed by single set of instruments in clinical practice To prevent infections by other microbes, including those with transactivation or opportunistic potential, hospitalised cats should not be allowed to have direct contact with one another It is important not to keep retrovirusinfected cats in contagious disease ward as they are potentially immunosuppressed and car‐ ry or acquire other pathogens [17] A recent survey in the UK showed that several veterinarians are not aware of the guidelines, or they not adhere to them Similarly to guidelines in human healthcare, other barriers included lack of agreement or lack of ability to follow guidelines, lack of motivation to follow them, and lack to perceive benefits to pa‐ tients The frequency, combination and selection of antigens routinely given to cats by veter‐ inarians remain unknown, as are the anatomical sites to inject cats Therefore, the impact of the published guidelines on practitioners working also remains unknown [80] Further work is required to elicit why following guidelines may reduce occurrence and severity of both opportunistic infections and halt onset and slow progression of FAIDS by eliminating infec‐ tion by other microbes The FIV/cat model has provided a unique opportunity to test novel therapeutic interven‐ tions aimed at eradicating latent virus, but the use of antiretroviral drugs in FIV infected cats and other felids has not gained grounds in the routine veterinary practice [7,8] Several conventional microbial coinfections are treated with routine medication Interaction of FIV with Heterologous Microbes in the Feline AIDS Model http://dx.doi.org/10.5772/52767 Conclusions Descriptive epidemiological surveys on the simultaneous infection by feline retroviruses, namely FIV and/or FeLV, and heterologous microbes clearly show that progression of FAIDS is facilitated by certain viruses, bacteria and other parasites that also induce oppor‐ tunistic infections in a vicious circle Scarce experimental data suggest that FIV transactivat‐ ing potential of heterologous microbes might increase FIV load, facilitate FAIDS course, and help induce malignancies resulting in considerably impaired quality of life and shorter life span of afflicted domestic cats Simultaneous cross-species transmission of infection by par‐ ticular FIV and FeLV strains in endangered big cats may also occur Emerging infections by FIV transactivating and opportunistic feline microbes in immunocompromised humans have already been described Additive or synergistic impairing effects on the native immune reactions, activation of negatively affecting Treg cells, depression of cytotoxic T cell activi‐ ties, and abnormal cytokine pattern exerted by heterologous microbes demonstrate striking similarities between AIDS and FAIDS Regular vaccination against transactivating microbes (e.g FeLV, FHV-1) and transactivated microbe (FIV) starting at early age prevents and dis‐ rupts deleterious microbial interactions These result in a complete halt or a significant slow‐ down of acquired immunodeficiency states Experience verified in the feline model enables us to continue studying microbial interactions at molecular, cellular, immunological or clini‐ cal levels Further experiments are warranted to better delineate the role of putative cofac‐ tors in FIV infection Further studies should examine concurrent infections as contributing factors in the development and progression of neoplasia in FIV-positive cats Determination of viral cooperative mechanisms that promote cancer during co-infection would be highly relevant to both FIV- and HIV-related diseases Author details Joseph Ongrádi1*, Stercz Balázs1, Kövesdi Valéria1, Nagy Károly1 and Pistello Mauro2 *Address all correspondence to: ongjos@hotmail.com Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary Retrovirus Centre, University of Pisa, Pisa, Italy References [1] Folkl A, Wen X, Kuczynski E, Clark ME, Bienzle D Feline programmed death and its ligand: characterization and changes with feline immunodeficiency virus infection The Veterinary Immunology and Immunopathology 2010;134(1-2) 107-114 461 462 Current Perspectives in HIV Infection [2] Simões RD, Howard KE, Dean GA In Vivo assessment of natural killer cell responses during chronic 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(SAM domain and HD domain-containing protein 1) to be responsible for inhibiting HIV- 1 replication in DC and other cells of the mye‐ loid lineage by degrading or preventing accumulation of HIV- 1