Evaluation of: Watts JM, Dang KK, Gorelick RJ: Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460(6), 711–716 (2009). The ssRNA, comprising the HIV genome, present as a doublet in HIV-1, has the ability of all RNA molecules to fold using Watson–Crick and noncanonical base pairing to form helices and loops, which are themselves functional as protein- and RNA-binding sites that regulate many stages of the viral lifecycle. This article explores the ability of a single technique (SHAPE) to map these structures in full length HIV RNA and attempts to suggest functions associated with these structures. The demonstration of a novel rapid technique that can generate extensive base by base data is an important achievement and it is useful to see this technique being publicized. This well-presented article is an attractive showpiece for the capabilities of SHAPE. However, some of the data are ambiguous and some are subject to alternative interpretations. SHAPE is a useful additional rapid...
{"title":"Secondary structure of the HIV‑1 genome","authors":"J. D. Stephenson, A. Lever","doi":"10.2217/HIV.09.44","DOIUrl":"https://doi.org/10.2217/HIV.09.44","url":null,"abstract":"Evaluation of: Watts JM, Dang KK, Gorelick RJ: Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460(6), 711–716 (2009). The ssRNA, comprising the HIV genome, present as a doublet in HIV-1, has the ability of all RNA molecules to fold using Watson–Crick and noncanonical base pairing to form helices and loops, which are themselves functional as protein- and RNA-binding sites that regulate many stages of the viral lifecycle. This article explores the ability of a single technique (SHAPE) to map these structures in full length HIV RNA and attempts to suggest functions associated with these structures. The demonstration of a novel rapid technique that can generate extensive base by base data is an important achievement and it is useful to see this technique being publicized. This well-presented article is an attractive showpiece for the capabilities of SHAPE. However, some of the data are ambiguous and some are subject to alternative interpretations. SHAPE is a useful additional rapid...","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"11 1","pages":"557-563"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81653456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In most parts of the world, first-line antiretroviral therapy typically contains a non-nucleoside reverse-transcriptase inhibitor (NNRTI). This class of drugs includes efavirenz, nevirapine and new generation agents including etravirine (ETR). NNRTI-containing regimens are widely preferred as first-line therapy in treatment guidelines. There is the potential for significant drug interactions when NNRTIs are coadministered with other drugs, for example those used in the treatment of TB and other antiretroviral therapy drugs, such as protease inhibitors. Pharmacokinetic profiles of these NNRTIs, together with immunological and virological factors, would influence the choice of agents used in the various regimens for the treatment of HIV infection. Despite being disparate agents with different chemical structures, NNRTIs share similar modes of action on HIV reverse-transcriptase. They are principally metabolized by the various cytochrome P450 isoforms, including CYP3A4 and CYP2B6. They themselves may be indu...
{"title":"Pharmacokinetics of HIV non-nucleoside reverse-transcriptase inhibitors.","authors":"M. Danjuma","doi":"10.2217/HIV.09.42","DOIUrl":"https://doi.org/10.2217/HIV.09.42","url":null,"abstract":"In most parts of the world, first-line antiretroviral therapy typically contains a non-nucleoside reverse-transcriptase inhibitor (NNRTI). This class of drugs includes efavirenz, nevirapine and new generation agents including etravirine (ETR). NNRTI-containing regimens are widely preferred as first-line therapy in treatment guidelines. There is the potential for significant drug interactions when NNRTIs are coadministered with other drugs, for example those used in the treatment of TB and other antiretroviral therapy drugs, such as protease inhibitors. Pharmacokinetic profiles of these NNRTIs, together with immunological and virological factors, would influence the choice of agents used in the various regimens for the treatment of HIV infection. Despite being disparate agents with different chemical structures, NNRTIs share similar modes of action on HIV reverse-transcriptase. They are principally metabolized by the various cytochrome P450 isoforms, including CYP3A4 and CYP2B6. They themselves may be indu...","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"159 1","pages":"625-632"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86455906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Treatment of HIV-1 infection with combined antiretroviral therapy substantially improves survival and quality of life, but is associated with metabolic disturbances such as insulin resistance, dyslipidemia and body fat partitioning disorders. These metabolic complications in the setting of suppression of viral replication are associated with increased observed risk for Type 2 diabetes mellitus. Disorders of glucose metabolism present additional challenges in the management of HIV infection, including the long-term complications of hyperglycemia, such as nephropathy, neuropathy and retinopathy, and magnified cardiovascular risk. This article considers how HIV infection and its treatment increases susceptibility to disorders of glucose metabolism. Diagnostic criteria, historical and clinical antecedents that assist the clinician in detection of diabetes susceptibility and treatment objectives are discussed.
{"title":"How sweet it is? Susceptibility to diabetes mellitus in HIV-1 treatment","authors":"K. Samaras","doi":"10.2217/HIV.09.46","DOIUrl":"https://doi.org/10.2217/HIV.09.46","url":null,"abstract":"Treatment of HIV-1 infection with combined antiretroviral therapy substantially improves survival and quality of life, but is associated with metabolic disturbances such as insulin resistance, dyslipidemia and body fat partitioning disorders. These metabolic complications in the setting of suppression of viral replication are associated with increased observed risk for Type 2 diabetes mellitus. Disorders of glucose metabolism present additional challenges in the management of HIV infection, including the long-term complications of hyperglycemia, such as nephropathy, neuropathy and retinopathy, and magnified cardiovascular risk. This article considers how HIV infection and its treatment increases susceptibility to disorders of glucose metabolism. Diagnostic criteria, historical and clinical antecedents that assist the clinician in detection of diabetes susceptibility and treatment objectives are discussed.","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"17 1","pages":"613-624"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85450807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In 2007, 2.5 million people have been newly infected with HIV and 2.1 million people died from AIDS, worldwide. HAART has turned AIDS into a manageable disease. However, numerous questions remain unanswered, such as the when to initiate HAART and what are the most effective doses of antiretroviral drugs. HIV reservoirs and how they could be attacked by therapeutic strategies is another issue. The 5th International AIDS Society (IAS) Conference in Cape Town, South Africa, focused on these subjects as well as on the hotly discussed funding budget. As has been indicated in the Sydney Declaration 2 years ago, 10% of the funding budget must be spent on clearly defined fields of HIV research. The following article presents highlights of the IAS Conference 2009.
{"title":"HIV infection: just an infectious disease?","authors":"C. Armbruster","doi":"10.2217/HIV.09.47","DOIUrl":"https://doi.org/10.2217/HIV.09.47","url":null,"abstract":"In 2007, 2.5 million people have been newly infected with HIV and 2.1 million people died from AIDS, worldwide. HAART has turned AIDS into a manageable disease. However, numerous questions remain unanswered, such as the when to initiate HAART and what are the most effective doses of antiretroviral drugs. HIV reservoirs and how they could be attacked by therapeutic strategies is another issue. The 5th International AIDS Society (IAS) Conference in Cape Town, South Africa, focused on these subjects as well as on the hotly discussed funding budget. As has been indicated in the Sydney Declaration 2 years ago, 10% of the funding budget must be spent on clearly defined fields of HIV research. The following article presents highlights of the IAS Conference 2009.","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"69 1","pages":"553-555"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87635175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In many HIV prevalent countries in sub-Saha¬ran Africa death among HIV-infected moth¬ers and their children is a major obstacle to achieving the millennium development goals (MDGs) for maternal and child mortality. In South Africa HIV/AIDS is the leading cause of maternal and child mortality and with HIV incidence estimated at 5% (per year) in 2006 life expectancy has decreased by more than 20 years since 1994. From 1990 onwards infant mortality has increased and maternal mortality has remained unchanged so with¬out drastic action it is unlikely South Africa will achieve the two-thirds reduction in infant mortality or three-quarters reduction in mater¬nal mortality required to reach MDGs 3 and 4 by 2015. As we make our way through the third decade of the AIDS epidemic we now have affordable antiretroviral combinations capable of adding years to the lives of people living with HIV. In many cases these are the productive years of teachers nurses and doctors in high prevalence countries. We need to adapt to the realities of the diverse mosaic of countries and delivery systems. The laboratory monitoring regarded as the standard of care in Europe and North America is unfeasible in large parts of Africa that lack the human resources and laboratory capacities to implement it. However life-saving therapies can still be provided through evidence-based clinical protocols that balance technical quality with an availability of resources. Although the economic recovery is expected to be slow global economic conditions have improved quicker than expected mainly due to public intervention. While many countries may be questioning whether they can maintain the measures needed to support people living with HIV and AIDS the world cannot afford to have a shortfall in antiretroviral treatment programs which are so essential to the lives of millions of people around the world. (excerpt)
{"title":"Impact of the global economic crisis on antiretroviral treatment programs","authors":"C. Ávila-Figueroa, P. Delay","doi":"10.2217/HIV.09.45","DOIUrl":"https://doi.org/10.2217/HIV.09.45","url":null,"abstract":"In many HIV prevalent countries in sub-Saha¬ran Africa death among HIV-infected moth¬ers and their children is a major obstacle to achieving the millennium development goals (MDGs) for maternal and child mortality. In South Africa HIV/AIDS is the leading cause of maternal and child mortality and with HIV incidence estimated at 5% (per year) in 2006 life expectancy has decreased by more than 20 years since 1994. From 1990 onwards infant mortality has increased and maternal mortality has remained unchanged so with¬out drastic action it is unlikely South Africa will achieve the two-thirds reduction in infant mortality or three-quarters reduction in mater¬nal mortality required to reach MDGs 3 and 4 by 2015. As we make our way through the third decade of the AIDS epidemic we now have affordable antiretroviral combinations capable of adding years to the lives of people living with HIV. In many cases these are the productive years of teachers nurses and doctors in high prevalence countries. We need to adapt to the realities of the diverse mosaic of countries and delivery systems. The laboratory monitoring regarded as the standard of care in Europe and North America is unfeasible in large parts of Africa that lack the human resources and laboratory capacities to implement it. However life-saving therapies can still be provided through evidence-based clinical protocols that balance technical quality with an availability of resources. Although the economic recovery is expected to be slow global economic conditions have improved quicker than expected mainly due to public intervention. While many countries may be questioning whether they can maintain the measures needed to support people living with HIV and AIDS the world cannot afford to have a shortfall in antiretroviral treatment programs which are so essential to the lives of millions of people around the world. (excerpt)","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"14 1","pages":"545-548"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88480574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The failure of HIV vaccine concepts based upon either simple antibody or T-cell immunity means that newer concepts in immunity to HIV require urgent investigation. Antibody-dependent cellular cytotoxicity (ADCC) responses, utilizing the arms of humoral and innate immunity, have been studied for many years, but their role in controlling or preventing HIV-1 remains controversial. Newer technologies can now be applied to study and map ADCC responses. This permits experiments to purify and isolate HIV-specific ADCC antibodies and directly assess their role in preventing simian–HIV infections in macaques. Analogous to complexities in the quality and specificity of T-cell and neutralizing antibody immunity to HIV, it is likely that some ADCC antibodies will be more efficient than others in controlling HIV infection and limiting viral escape. Rationally defining broadly reactive ADCC antibodies with potent in vivo activity should allow the selection of the most appropriate ADCC-inducing vaccine antigens. This pa...
{"title":"Designing immunity to HIV: manipulating antibody-dependent cellular cytotoxicity antibodies","authors":"Gamze Isitman, M. Navis, S. Kent, I. Stratov","doi":"10.2217/HIV.09.37","DOIUrl":"https://doi.org/10.2217/HIV.09.37","url":null,"abstract":"The failure of HIV vaccine concepts based upon either simple antibody or T-cell immunity means that newer concepts in immunity to HIV require urgent investigation. Antibody-dependent cellular cytotoxicity (ADCC) responses, utilizing the arms of humoral and innate immunity, have been studied for many years, but their role in controlling or preventing HIV-1 remains controversial. Newer technologies can now be applied to study and map ADCC responses. This permits experiments to purify and isolate HIV-specific ADCC antibodies and directly assess their role in preventing simian–HIV infections in macaques. Analogous to complexities in the quality and specificity of T-cell and neutralizing antibody immunity to HIV, it is likely that some ADCC antibodies will be more efficient than others in controlling HIV infection and limiting viral escape. Rationally defining broadly reactive ADCC antibodies with potent in vivo activity should allow the selection of the most appropriate ADCC-inducing vaccine antigens. This pa...","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"67 1","pages":"633-640"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81394428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaccination has been shown to be one of the most powerful tools to decrease morbidity and mortality caused by an array of infectious diseases. The risk and complications of some vaccine-preventable diseases is higher in HIV-infected individuals, underscoring the importance of vaccination in these patients. However, the immune response upon vaccination is generally impaired and shorter lasting in HIV-infected individuals, especially in those with low CD4+ T-lymphocyte counts and detectable HIV RNA, as compared with healthy controls. Even in patients responding to antiretroviral treatment, an impaired immune response may persist despite normalization of the CD4+-cell count. Caution with live-attenuated vaccines is warranted in HIV-infected individuals with low CD4 T-lymphocyte counts. Decisions regarding administering a live-attenuated vaccine should be made after weighing the risks and benefits on an individual basis. In this article the immunology of vaccination in HIV-infected individuals, as well as the...
{"title":"Vaccination of HIV-infected adults.","authors":"Lbs Gelinck, FP Kroon","doi":"10.2217/HIV.09.39","DOIUrl":"https://doi.org/10.2217/HIV.09.39","url":null,"abstract":"Vaccination has been shown to be one of the most powerful tools to decrease morbidity and mortality caused by an array of infectious diseases. The risk and complications of some vaccine-preventable diseases is higher in HIV-infected individuals, underscoring the importance of vaccination in these patients. However, the immune response upon vaccination is generally impaired and shorter lasting in HIV-infected individuals, especially in those with low CD4+ T-lymphocyte counts and detectable HIV RNA, as compared with healthy controls. Even in patients responding to antiretroviral treatment, an impaired immune response may persist despite normalization of the CD4+-cell count. Caution with live-attenuated vaccines is warranted in HIV-infected individuals with low CD4 T-lymphocyte counts. Decisions regarding administering a live-attenuated vaccine should be made after weighing the risks and benefits on an individual basis. In this article the immunology of vaccination in HIV-infected individuals, as well as the...","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"10 1","pages":"565-572"},"PeriodicalIF":0.0,"publicationDate":"2009-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73062193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management of late presentation in HIV: what the data tell us","authors":"P. Mallon, W. Powderly","doi":"10.2217/HIV.09.32","DOIUrl":"https://doi.org/10.2217/HIV.09.32","url":null,"abstract":"","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"55 1","pages":"423-426"},"PeriodicalIF":0.0,"publicationDate":"2009-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74578234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth A. Miller, N. Bhardwaj, Meagan P. O’Brien
Dendritic cells (DCs) are antigen-presenting cells that serve as critical links between innate and adaptive immunity. Recent advances have revealed that DC interactions with HIV are pleiotropic. As direct antimicrobial effector cells, DCs may play a role in whether HIV infection is established upon mucosal exposure. As potent antigen-presenting cells, DCs probably modulate control of chronic HIV disease through the priming of adaptive immune responses. By contrast, DCs may contribute to HIV pathogenesis through the enhancement of T-cell infection, production of inflammatory cytokines that lead to chronic immune activation (and a proapoptotic state) and the formation of suppressive T-regulatory cells. In this article, recent progress in the field of HIV–DC interactions, including mucosal infection and HIV transmission to T cells, DC infection and activation, DC number and function in acute and chronic HIV infection, and DC immunoregulatory effects are discussed.
{"title":"Dendritic cell function in HIV infection","authors":"Elizabeth A. Miller, N. Bhardwaj, Meagan P. O’Brien","doi":"10.2217/HIV.09.34","DOIUrl":"https://doi.org/10.2217/HIV.09.34","url":null,"abstract":"Dendritic cells (DCs) are antigen-presenting cells that serve as critical links between innate and adaptive immunity. Recent advances have revealed that DC interactions with HIV are pleiotropic. As direct antimicrobial effector cells, DCs may play a role in whether HIV infection is established upon mucosal exposure. As potent antigen-presenting cells, DCs probably modulate control of chronic HIV disease through the priming of adaptive immune responses. By contrast, DCs may contribute to HIV pathogenesis through the enhancement of T-cell infection, production of inflammatory cytokines that lead to chronic immune activation (and a proapoptotic state) and the formation of suppressive T-regulatory cells. In this article, recent progress in the field of HIV–DC interactions, including mucosal infection and HIV transmission to T cells, DC infection and activation, DC number and function in acute and chronic HIV infection, and DC immunoregulatory effects are discussed.","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"35 1","pages":"527-537"},"PeriodicalIF":0.0,"publicationDate":"2009-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87243621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"5th European Conference on Clinical and Social Research on AIDS and Drugs","authors":"V. Lukashov, S. Čaplinskas","doi":"10.2217/HIV.09.31","DOIUrl":"https://doi.org/10.2217/HIV.09.31","url":null,"abstract":"","PeriodicalId":88510,"journal":{"name":"HIV therapy","volume":"12 1","pages":"431-433"},"PeriodicalIF":0.0,"publicationDate":"2009-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75359038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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