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Sample records for hiv therapeutic possibilities

  1. Novel therapeutic strategies targeting HIV integrase

    PubMed Central

    2012-01-01

    Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds. PMID:22498430

  2. Therapeutic PossibilitiesTherapeutic Possibilities of Stem Cell Researchof Stem Cell Research

    E-print Network

    Brutlag, Doug

    Therapeutic PossibilitiesTherapeutic Possibilities of Stem Cell Researchof Stem Cell Research.stemcellresearchfoundationstemcellresearchfoundation..org/WhatsNew/EmbryonicStemCellsorg/WhatsNew/EmbryonicStemCells..htmhtm #12;http://www.stemcellresearchfoundation.org/WhatsNew/PSA_2.htmhttp://www.stemcellresearchfoundation.org/WhatsNew/PSA_2.htm #12;Olfactory Bulb Stem Cells

  3. Developments in HIV-1 immunotherapy and therapeutic vaccination

    PubMed Central

    Tanner, Helen; Dalgleish, Angus

    2014-01-01

    Since the human immunodeficiency virus (HIV-1) pandemic began, few prophylactic vaccines have reached phase III trials. Only one has shown partial efficacy in preventing HIV-1 infection. The introduction of antiretroviral therapy (ART) has had considerable success in controlling infection and reducing transmission but in so doing has changed the nature of HIV-1 infection for those with access to ART. Access, compliance, and toxicity alongside the emergence of serious non-AIDS morbidity and the sometimes poor immune reconstitution in ART-treated patients have emphasized the need for additional therapies. Such therapy is intended to contribute to control of HIV-1 infection, permit structured treatment interruptions, or even establish a functional cure of permanently suppressed and controlled infection. Both immunotherapy and therapeutic vaccination have the potential to reach these goals. In this review, the latest developments in immunotherapy and therapeutic vaccination are discussed. PMID:24991420

  4. The structural biology of HIV-1: mechanistic and therapeutic insights

    PubMed Central

    Engelman, Alan; Cherepanov, Peter

    2013-01-01

    Three-dimensional molecular structures can provide detailed information on biological mechanisms and, in cases where molecular function impacts on human health, significantly aid in the development of therapeutic interventions. Over the past 23 years, key components of the lentivirus HIV-1, including its envelope glycoproteins and capsid, and the replication enzymes reverse transcriptase, integrase and protease, have accordingly been scrutinized to near atomic scale resolution. Structural analyses of the interactions between viral and host cell components have moreover yielded key insights into the mechanisms of virus entry, chromosomal integration, transcription and egress from cells. Here, we review recent advances in HIV-1 structural biology, focusing on the impact these results have had on our understanding of virus replication and the development of new therapeutics. PMID:22421880

  5. Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges

    PubMed Central

    Nissapatorn, Veeranoot; Sawangjaroen, Nongyao

    2011-01-01

    After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leismaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection. PMID:22310820

  6. Affect regulation and HIV risk among youth in therapeutic schools.

    PubMed

    Brown, Larry K; Houck, Christopher; Lescano, Celia; Donenberg, Geri; Tolou-Shams, Marina; Mello, Justin

    2012-11-01

    The acquisition of affect regulation skills is often impaired or delayed in youth with mental health problems but the relationship between affect dysregulation and risk behaviors has not been well studied. Baseline data from adolescents (N = 417; ages 13-19) recruited from therapeutic school settings examined the relationship between affect dysregulation, substance use, self-cutting, and sexual risk behavior. Analyses of covariance demonstrated that adolescents who did not use condoms at last sex, ever self-cut, attempted suicide, used alcohol and other drugs and reported less condom use self-efficacy when emotionally aroused were significantly more likely (p < .01) to report greater difficulty with affect regulation than peers who did not exhibit these behaviors. General patterns of difficulty with affect regulation may be linked to HIV risk behavior, including condom use at last sex. HIV prevention strategies for youth in mental health treatment should target affect regulation in relation to multiple risk behaviors. PMID:22669595

  7. Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China

    PubMed Central

    Dong, Yuan; Shen, Xiaoxing; Guo, Ruizhang; Liu, Baochi; Zhu, Lingyan; Wang, Jing; Zhang, Linxia; Sun, Jun; Zhang, Xiaoyan; Xu, Jianqing

    2014-01-01

    Background More and more HIV therapeutic vaccines will enter clinical trials; however, little is known about the willingness to participate (WTP) in HIV therapeutic vaccine trials among HIV-positive individuals. Objective To investigate the WTP in HIV therapeutic vaccine trials among Chinese HIV-infected patients. Methods We conducted a cross-sectional survey on HIV-positive inpatients and outpatients at Shanghai Public Health Center. A total of 447 participants were recruited into this study. Following an introduction with general information on HIV therapeutic vaccine and its potential effectiveness and side effects, each participant completed a questionnaire in a self-administered form. The questionnaires covered demographics, high-risk behaviors, clinical characteristics and willingness to participate in HIV therapeutic vaccine trial. Results The overall willingness to participate in HIV therapeutic vaccine trials was 91.5%. Interestingly, multivariate logistic regression analyses demonstrated that the willingness was higher for those sexually infected by HIV (odds ratio [OR]: 4.36; 95% confidence interval [CI]: 1.53–12.41), diagnosed as HIV-1 infection for greater than 5 years (OR: 7.12, 95% CI: 1.83–27.76), and with the presence of infectious complications (OR: 2.75; 95% CI: 1.02–7.45). The primary reason for participation was to delay or reduce antiretroviral treatment (ART) and to avoid ART side effects (76.6%), and then followed by delaying disease progression (74.9%), increasing immune response to suppress opportunistic infections (57.7%) and preventing the development of drug resistance (37.1%). Reasons for unwillingness to participate mainly included concern for safety (37.0%), lack of knowledge on therapeutic vaccine (33.3%), and satisfaction with ART effectiveness (22.2%). Conclusions The WTP in HIV therapeutic vaccine trials was high among HIV-infected Chinese patients. HIV+ subjects who acquired infection through sexual contact and who were diagnosed for more than 5 years may represent a good candidate population for enrollment in therapeutic vaccine trials. PMID:25372044

  8. Toward a cure for HIV-Seeking effective therapeutic vaccine strategies.

    PubMed

    Autran, Brigitte

    2015-12-01

    This review article focuses on the rationale and evaluation of therapeutic vaccines against HIV. This strategy has been developed in order to restore or restimulate HIV-specific immunity in patients treated with antiretroviral therapies. Despite the lack of good candidate vaccines against HIV, two objectives have been targeted during the past 15 years. Therapeutic immunization was first proposed to help control virus relapses during treatment interruptions. More recently, the concept of therapeutic immunization has been boosted by efforts to reach HIV remission or cure, in combination to HIV reactivating agents, to help purge HIV reservoirs in a "shock and kill" strategy. This review analyses the rationales for these strategies and the results of the most widely therapeutic vaccines designed to generate T-cell immunity, i.e. recombinant viral vectors and dendritic cell-based strategies, while extremely few strategies targeted HIV-specific Abs. Only marginal control of HIV was obtained with cellular-based strategies, suggesting that approaches targeting or using broadly neutralizing Abs, should be of benefit for future efforts of therapeutic immunization against HIV in the quest toward a cure for HIV. PMID:26542079

  9. Activation of latent HIV-1 expression by protein kinase C agonists. A novel therapeutic approach to eradicate HIV-1 reservoirs.

    PubMed

    Sánchez-Duffhues, Gonzalo; Vo, Minh Q; Pérez, Moisés; Calzado, Marco A; Moreno, Santiago; Appendino, Giovanni; Muñoz, Eduardo

    2011-03-01

    The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication in patients treated with highly active antiretroviral therapy. The molecular mechanisms by which integrated HIV-1 is repressed during latency have been partially identified in different models of HIV-1 latency, and the involvement of multiple processes has been demonstrated. Therefore, several molecular targets amenable to pharmacological manipulation have emerged to antagonize HIV-1 latency in the viral reservoirs. In this context, it has been suggested that successful depletion of such latent reservoirs will require a combination of therapeutic agents that can specifically and efficiently act on cells harbouring latent HIV-1 provirus. HIV-1 reactivation therapy is a potential therapeutic option to purge the viral reservoirs. The goal of this therapy is to enhance the transcriptional activity of the latent HIV-1 without inducing the polyclonal activation of non-infected cells. In this sense natural or semisynthetic protein kinase C agonists lacking tumour-promoter activities clearly fulfil this criterion, thereby opening new research avenues to purge HIV-1 reservoirs. In this review article, we have succinctly summarized the known effects of "natural products", focusing on phorboids like prostratin and ingenols, macrolides like bryostatin 1, and macrocyclic polyesters like ingols and jatrophanes. A comprehensive view on the molecular mechanisms underlying the principle of HIV-1 reactivation from latency is provided, discussing the combination of "natural products" with other experimental or conventional therapeutics. PMID:20955147

  10. HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible contributions to drug

    E-print Network

    Batzoglou, Serafim

    HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible immunodeficiency virus (HIV-1) is a critical drug target against which many therapeutically useful inhibitors have water) of both a wild-type and the drug-resistant V82F/I84V mutant of HIV-1 protease. The V82F/I84V

  11. High-Throughput Humanized Mouse Models for Evaluation of HIV-1 Therapeutics and Pathogenesis.

    PubMed

    Thomas, Tynisha; Seay, Kieran; Zheng, Jian Hua; Zhang, Cong; Ochsenbauer, Christina; Kappes, John C; Goldstein, Harris

    2016-01-01

    Mice cannot be used as a model to evaluate HIV-1 therapeutics because they do not become infected by HIV-1 due to structural differences between several human and mouse proteins required for HIV-1 replication. This has limited their use for in vivo assessment of anti-HIV-1 therapeutics and the mechanism by which cofactors, such as illicit drug use accelerate HIV-1 replication and disease course in substance abusers. Here, we describe the development and application of two in vivo humanized mouse models that are highly sensitive and useful models for the in vivo evaluation of candidate anti-HIV therapeutics. The first model, hu-spl-PBMC-NSG mice, uses NOD-SCID IL2r?(-/-) (NSG) mice intrasplenically injected with human peripheral blood mononuclear cells (PBMC) which develop productive splenic HIV-1 infection after intrasplenic inoculation with a replication-competent HIV-1 expressing Renilla reniformis luciferase (HIV-LucR) and enables investigators to use bioluminescence to visualize and quantitate the temporal effects of therapeutics on HIV-1 infection. The second model, hCD4/R5/cT1 mice, consists of transgenic mice carrying human CD4, CCR5 and cyclin T1 genes, which enables murine CD4-expressing cells to support HIV-1 entry, Tat-mediated LTR transcription and consequently develop productive infection. The hCD4/R5/cT1 mice develop disseminated infection of tissues including the spleen, small intestine, lymph nodes and lungs after intravenous injection with HIV-1-LucR. Because these mice can be infected with HIV-LucR expressing transmitted/founder and clade A/E and C Envs, these mouse models can also be used to evaluate the in vivo efficacy of broadly neutralizing antibodies and antibodies induced by candidate HIV-1 vaccines. Furthermore, because hCD4/R5/cT1 mice can be infected by vaginal inoculation with replication-competent HIV-1 expressing NanoLuc (HIV-nLucR)-, this mouse model can be used to evaluate the mechanisms by which substance abuse and other factors enhance mucosal transmission of HIV-1. PMID:26714715

  12. Affect management for HIV prevention with adolescents in therapeutic schools: the immediate impact of project balance.

    PubMed

    Brown, Larry K; Houck, Christopher; Donenberg, Geri; Emerson, Erin; Donahue, Kelly; Misbin, Jesse

    2013-10-01

    Adolescents in therapeutic schools are at greater risk for HIV and other STIs than their peers due to earlier higher rates of sexual risk and difficulty managing strong emotions. HIV prevention programs that incorporate techniques for affect management (AM) during sexual situations may be beneficial. This paper determined the immediate impact of such an intervention, AM, compared to a standard, skills-based HIV prevention intervention and a general health promotion intervention (HP) for 377 youth, ages 13-19, in therapeutic schools in two cities. 1 month after the intervention, analyses that adjusted for the baseline scores found adolescents in AM were more likely to report condom use at last sex than those in HP (0.89 vs. 0.67, p = 0.02) and that their HIV knowledge was significantly greater. These data suggest that AM techniques might improve the impact of standard skills-based prevention programs for adolescents in therapeutic schools. PMID:23975475

  13. Affect Management for HIV Prevention with Adolescents in Therapeutic Schools: The immediate impact of Project Balance

    PubMed Central

    Brown, Larry K.; Houck, Christopher; Donenberg, Geri; Emerson, Erin; Donahue, Kelly; Misbin, Jesse

    2013-01-01

    Adolescents in therapeutic schools are at greater risk for HIV and other STIs than their peers due to earlier higher rates of sexual risk and difficulty managing strong emotions. HIV prevention programs that incorporate techniques for affect management during sexual situations may be beneficial. This paper determined the immediate impact of such an intervention, Affect Management (AM), compared to a standard, skills-based HIV prevention intervention (SB) and a general health promotion intervention (HP) for 377 youth, ages 13 to 19, in therapeutic schools in two cities. One month after the intervention, analyses that adjusted for the baseline scores found adolescents in AM were more likely to report condom use at last sex than those in HP (.89 vs. .67, p=.02) and that their HIV knowledge was significantly greater. These data suggest that affect management techniques might improve the impact of standard skills-based prevention programs for adolescents in therapeutic schools. PMID:23975475

  14. HIV-Associated Neurocognitive Disorder: Pathogenesis and Therapeutic Opportunities

    PubMed Central

    Lindl, Kathryn A.; Marks, David R.; Kolson, Dennis L.

    2010-01-01

    Human immunodeficiency virus type 1 (HIV) infection presently affects more that 40 million people worldwide, and is associated with central nervous system (CNS) disruption in at least 30% of infected individuals. The use of highly active antiretroviral therapy has lessened the incidence, but not the prevalence of mild impairment of higher cognitive and cortical functions (HIV-associated neurocognitive disorders) as well as substantially reduced a more severe form dementia (HIV-associated dementia). Furthermore, improving neurological outcomes will require novel, adjunctive therapies that are targeted towards mechanisms of HIV-induced neurodegeneration. Identifying such molecular and pharmacological targets requires an understanding of the events preceding irreversible neuronal damage in the CNS, such as actions of neurotoxins (HIV proteins and cellular factors), disruption of ion channel properties, synaptic damage, and loss of adult neurogenesis. By considering the specific mechanisms and consequences of HIV neuropathogenesis, unified approaches for neuroprotection will likely emerge using a tailored, combined, and non-invasive approach. PMID:20396973

  15. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions

    PubMed Central

    Graziani, Gina M; Angel, Jonathan B

    2015-01-01

    Introduction The development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART), would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates. Discussion This review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI) as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy. Conclusions Given the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of an ATI is not ideal. PMID:26561337

  16. A Therapeutic Dendritic Cell-Based Vaccine for HIV-1 Infection

    PubMed Central

    Climent, Núria; Assoumou, Lambert; Gil, Cristina; González, Nuria; Alcamí, José; León, Agathe; Romeu, Joan; Dalmau, Judith; Martínez-Picado, Javier; Lifson, Jeff; Autran, Brigitte; Costagliola, Dominique; Clotet, Bonaventura; Gatell, Josep M; Plana, Montserrat; Gallart, Teresa

    2011-01-01

    A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects. Clinical trial.gov NCT00402142 PMID:21233310

  17. Host Factors and HIV-1 Replication: Clinical Evidence and Potential Therapeutic Approaches

    PubMed Central

    Santa-Marta, Mariana; de Brito, Paula Matos; Godinho-Santos, Ana; Goncalves, Joao

    2013-01-01

    HIV and human defense mechanisms have co-evolved to counteract each other. In the process of infection, HIV takes advantage of cellular machinery and blocks the action of the host restriction factors (RF). A small subset of HIV+ individuals control HIV infection and progression to AIDS in the absence of treatment. These individuals known as long-term non-progressors (LNTPs) exhibit genetic and immunological characteristics that confer upon them an efficient resistance to infection and/or disease progression. The identification of some of these host factors led to the development of therapeutic approaches that attempted to mimic the natural control of HIV infection. Some of these approaches are currently being tested in clinical trials. While there are many genes which carry mutations and polymorphisms associated with non-progression, this review will be specifically focused on HIV host RF including both the main chemokine receptors and chemokines as well as intracellular RF including, APOBEC, TRIM, tetherin, and SAMHD1. The understanding of molecular profiles and mechanisms present in LTNPs should provide new insights to control HIV infection and contribute to the development of novel therapies against AIDS. PMID:24167505

  18. HBV and HIV co-infection: Impact on liver pathobiology and therapeutic approaches

    PubMed Central

    Parvez, Mohammad Khalid

    2015-01-01

    The consequences of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection on progression of severe liver diseases is a serious public health issue, worldwide. In the co-infection cases, about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals, liver-related mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIV-induced liver diseases includes hepatitis, steatohepatitis, endothelialitis, necrosis, granulomatosis, cirrhosis and carcinoma. Moreover, HIV co-infection significantly alters the natural history of hepatitis B, and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology, only a few data is available on interactions between HBV and HIV proteins. Thus, the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms, and to design effective therapeutic strategies. PMID:25625003

  19. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

    PubMed Central

    Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2015-01-01

    Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID:26136672

  20. [Chronic depressive syndrome--characteristics and therapeutic possibilities].

    PubMed

    Umann, E; Kulawik, H; Rindtorff, A

    1990-11-01

    The files of 322 patients with depressive syndromes in the period 1978-1987, covering 413 in-patient treatments, revealed therapeutic factors whose tendency is to lengthen the period of hospitalisation. There is no indication of therapeutic factors with a tendency to reduce the length of time spent in hospital. Lithium treatment was again shown to increase the hospital stay (chronicity of the overall disorder), others being (treatment with/Netofenazat), electric shock treatment during the initial disorder, and optimum simultaneous treatment with thymoleptics. PMID:2093197

  1. Exploring the potential of monoclonal antibody therapeutics for HIV-1 eradication.

    PubMed

    Euler, Zelda; Alter, Galit

    2015-01-01

    The HIV field has seen an increased interest in novel cure strategies. In particular, new latency reversal agents are in development to reverse latency to flush the virus out of its hiding place. Combining these efforts with immunotherapeutic approaches may not only drive the virus out of latency, but allow for the rapid elimination of these infected cells in a "shock and kill" approach. Beyond cell-based approaches, growing interest lies in the potential use of functionally enhanced "killer" monoclonal therapeutics to purge the reservoir. Here we discuss prospects for a monoclonal therapeutic-based "shock and kill" strategy that may lead to the permanent elimination of replication-competent virus, making a functional cure a reality for all patients afflicted with HIV worldwide. PMID:25385703

  2. HIV-infected People in Sudan Moving Toward Chronic Poverty: Possible Interventions.

    PubMed

    Ismail, Salwa Muddthir; Eisa, Ammar Abobakre; Ibrahim, Faisal

    2016-01-01

    We sought to identify the socioeconomic impact on people living with HIV (PLWH) in Sudan. Focus group discussions were used to collect data and identify the most outstanding domains of HIV impact on PLWH and the survival mechanisms that may be common to a group of diverse HIV-infected persons (n = 30). The findings indicated that the most striking financial and social impacts were due to stigma associated with HIV in the conservative Sudanese society, which led to loss of work with all its consequences (e.g., children's education and health care expenses were affected). The socioeconomic impacts of HIV on infected populations are discussed, and suggestions for possible interventions to mitigate harmful impacts and stigma within the society, the workplace, and health care settings are highlighted. We concluded that HIV has intensified the existing problems of infected people, contributing to their vulnerability to poverty. PMID:26190419

  3. Targeting nicotine addiction: the possibility of a therapeutic vaccine.

    PubMed

    Escobar-Chávez, José Juan; Domínguez-Delgado, Clara Luisa; Rodríguez-Cruz, Isabel Marlen

    2011-01-01

    Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA) for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results show that the efficiency of the vaccines is directly related to the antibody levels, a fact which will help to optimize the vaccine effect. The vaccines are expected to appear on the market between 2011 and 2012. PMID:21607018

  4. Inhibition of the HIV Rev transactivator : a new target for therapeutic intervention.

    PubMed

    Heguy, A

    1997-01-01

    The viral transactivator Rev is essential for HIV replication, since it allows the nuclear export of unspliced and partially spliced viral mRNAs that encode the structural proteins. Rev is an RNA binding protein that interacts with a highly structured RNA element, the RRE, found within the envelope sequences. This viral protein also interacts with cellular proteins, termed nucleoporins, and acts as an adaptor between the viral mRNAs and the cellular nuclear export machinery. Both interactions are specific, and required for Rev function. Because of its crucial role in the HIV replication cycle, and its novel mechanism of action, Rev represents an ideal target for therapeutic intervention. This review describes the efforts towards Rev inhibition. Gene therapy approaches, including the expression of trans-dominant mutants and RNA decoys, as well as antisense therapies and small molecule inhibitors of Rev-RRE binding or Rev interaction with the cellular machinery will be discussed PMID:9206979

  5. Demographical, Viro-Immunological, Clinical and Therapeutical Characteristics of HIV-Infected Patients in an “Epidemiologically Unexplored” Region of Italy (Calabria Region): the CalabrHIV Cohort

    PubMed Central

    Postorino, Maria Concetta; Luciani, Filippo; Mangano, Carmelo; Carpentieri, Maria Stella; Scerbo, Paolo; Priamo, Armando; Berardelli, Giuseppina; Marino, Roberto; Vallone, Alfredo; Serrao, Nicola; Pisani, Vincenzo; Costa, Chiara; Terremoto, Albano; Foti, Giuseppe; Cosco, Lucio; Calderazzo, Massimo; Corigliano, Domenico; Scordo, Preziosa; Strazzulla, Alessio; Torti, Carlo

    2015-01-01

    Background and Objectives HIV epidemics may differ among epidemiological contexts. We aimed at constructing an HIV clinical cohort whose main epidemiological, clinical and therapeutical characteristics are described (the CalabrHIV cohort, Calabria Region, Southern Italy). Methods The CalabrHIV Cohort includes all HIV patients on active follow-up in all infectious disease centers in the Calabria Region as at October 2014. All information was recorded in a common electronic database. Not-infectious co-morbidities (such as cardiovascular diseases, bone fractures, diabetes, renal failure and hypertension) were also studied. Results 548 patients (68% males; 59% aged <50 years) were included in the CalabrHIV cohort. Major risk factors were: sexual transmission (49%) and intravenous drug use (34%). 39% patients had HCV and/or HBV co-infection. Amongst 404 patients who had a complete clinical history, 34% were AIDS presenters and 49.3% had CD4 count ?350/mm3 at HIV diagnosis. 83% patients on HAART had undetectable HIV-RNA. Hypertension was the most frequent co-morbidity (21.5%). Multimorbidity was more frequent in >50 years old patients than in <50 years old ones (30% vs. 6%; p<0.0001). Co-morbidity was more frequent in HCV and/or HBV co-infected than in HIV mono-infected patients (46.6% vs. 31.7%: p=0.0006). Conclusion This cohort presentation study sheds light, for the first time, on HIV patients’ characteristics in the Calabria Region. We showed that HIV-infected patients with chronic hepatitis were affected by concomitant not-infectious co-morbidities more than the HIV mono-infected individuals. New HCV treatments are therefore to be implemented in the co-infected population. PMID:26543523

  6. Dose–response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies

    PubMed Central

    Webb, Nicholas E.; Montefiori, David C.; Lee, Benhur

    2015-01-01

    A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose–response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120–gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations. PMID:26416571

  7. Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots

    PubMed Central

    van Kampen, Jeroen J. A.; Reedijk, Mariska L.; Scheuer, Rachel D.; Dekker, Lennard J. M.; Burger, David M.; Hartwig, Nico G.; Osterhaus, Albert D. M. E.; Luider, Theo M.; Gruters, Rob A.

    2010-01-01

    Kaletra® (Abott Laboratories) is a co-formulated medication used in the treatment of HIV-1-infected children, and it contains the two antiretroviral protease inhibitor drugs lopinavir and ritonavir. We validated two new ultrafast and high-throughput mass spectrometric assays to be used for therapeutic drug monitoring of lopinavir and ritonavir concentrations in whole blood and in plasma from HIV-1-infected children. Whole blood was blotted onto dried blood spot (DBS) collecting cards, and plasma was collected simultaneously. DBS collecting cards were extracted by an acetonitrile/water mixture while plasma samples were deproteinized with acetone. Drug concentrations were determined by matrix-assisted laser desorption/ionization-triple quadrupole tandem mass spectrometry (MALDI-QqQ-MS/MS). The application of DBS made it possible to measure lopinavir and ritonavir in whole blood in therapeutically relevant concentrations. The MALDI-QqQ-MS/MS plasma assay was successfully cross-validated with a commonly used high-performance liquid chromatography (HPLC)–ultraviolet (UV) assay for the therapeutic drug monitoring (TDM) of HIV-1-infected patients, and it showed comparable performance characteristics. Observed DBS concentrations showed as well, a good correlation between plasma concentrations obtained by MALDI-QqQ-MS/MS and those obtained by the HPLC-UV assay. Application of DBS for TDM proved to be a good alternative to the normally used plasma screening. Moreover, collection of DBS requires small amounts of whole blood which can be easily performed especially in (very) young children where collection of large whole blood amounts is often not possible. DBS is perfectly suited for TDM of HIV-1-infected children; but nevertheless, DBS can also easily be applied for TDM of patients in areas with limited or no laboratory facilities. PMID:20632164

  8. Short Communication: Exploring Antibody Potential as Prophylactic/Therapeutic Strategies for Prevention of Early Mucosal HIV-1 Infection.

    PubMed

    Su, Bin; Peressin, Maryse; Ducloy, Camille; Penichon, Julien; Mayr, Luzia M; Laumond, Géraldine; Schmidt, Sylvie; Decoville, Thomas; Moog, Christiane

    2015-11-01

    Mucosal tissues are the predominant sites for genital HIV-1 transmission. We investigated the mechanisms by which broadly neutralizing antibodies (bNAbs) inhibit HIV-1 replication in a coculture model including primary mucosal dendritic cells (DCs), such as Langerhans cells, interstitial dendritic cells, and CD4(+) T lymphocytes. We show that bNAbs efficiently prevent HIV-1 infection by inhibiting HIV-1 transmission to CD4(+) T lymphocytes. This inhibition of cell-to-cell transmission was observed with equal potency as the inhibition of cell-free infection of primary CD4(+) T lymphocytes. In addition, a decrease in HIV-1 replication in DCs and the induction of DC maturation were detected. This additional inhibition was Fc mediated as it was blocked by the use of specific anti-Fc?R monoclonal Abs. The DC maturation by bNAbs during HIV transmission may contribute to mucosal protection. Therefore, multiple antibody-mediated inhibitory functions should be combined for the improvement of future preventive/therapeutic strategies to cure HIV. PMID:26252799

  9. Safety and immunogenicity of an adjuvanted protein therapeutic HIV-1 vaccine in subjects with HIV-1 infection: a randomised placebo-controlled study.

    PubMed

    Harrer, Thomas; Plettenberg, Andreas; Arastéh, Keikawus; Van Lunzen, Jan; Fätkenheuer, Gerd; Jaeger, Hans; Janssens, Michel; Burny, Wivine; Collard, Alix; Roman, François; Loeliger, Alfred; Koutsoukos, Marguerite; Bourguignon, Patricia; Lavreys, Ludo; Voss, Gerald

    2014-05-01

    The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4(+) T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4(+) and CD8(+) T-cell responses, absolute CD4(+) T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4(+) T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (p<0.05). Vaccine-induced HIV-1-specific CD4(+) T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8(+) T-cells or change in CD8(+) T-cell activation marker expression profile was detected. Absolute CD4(+) T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4(+) T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4(+) T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection. PMID:24144472

  10. The Therapeutic Potential of Adenosine Triphosphate as an Immune Modulator in the Treatment of HIV/AIDS: A Combination Approach with HAART

    PubMed Central

    Wagner, Marc C.E.

    2011-01-01

    Extracellular adenosine triphosphate (eATP) is a potent molecule that has the capacity to modulate various aspects of cell functions including gene expression. This element of modulation is essential to the role of ATP as a therapeutic agent. The hypothesis presented is that ATP can have an important impact on the treatment of HIV infection. This is supported in part by published research, although a much greater role for ATP is suggested than prior authors ever thought possible. ATP has the ability to enhance the immune system and could thus improve the host’s own defense mechanisms to eradicate the virus-infected cells and restore normal immune function. This could provide effective therapy when used in conjunction with highly active antiretroviral therapies (HAART) to eliminate the latently infected cells. The key lies in applying ATP through the methodology described. This article presents a strategy for using ATP therapeutically along with background evidence to substantiate the importance of using ATP in the treatment of HIV infection. PMID:21675943

  11. Cross-Learning: The Possibilities of a Learning Dialogue between the HIV and AIDS and Disability Movements

    ERIC Educational Resources Information Center

    Rule, Peter

    2011-01-01

    Sub-Saharan Africa is the region of the world most affected by HIV & AIDS, accounting for two-thirds of the global burden of the pandemic. People with disabilities are regarded as a high-risk group for HIV but have been largely neglected in programmes of education, treatment and support. This paper examines the possibilities for a learning…

  12. HIV-1 infection and alcohol abuse: Neurocognitive impairment, mechanisms of neurodegeneration and therapeutic interventions

    PubMed Central

    Persidsky, Yuri; Ho, Wenzhe; Ramirez, Servio H.; Potula, Raghava; Abood, Mary E.; Unterwald, Ellen; Tuma, Ronald

    2011-01-01

    Clinical studies indicate that alcohol dependence has an additive effect on cognitive deficits associated with HIV-1 infection. Findings in humans and animal models suggest that alcohol, similar to HIV-1, induces inflammatory processes in the brain leading to neurodegeneration. The causes of HIV-1-associated neurotoxicity are comparable to those mediating alcohol-induced neuronal injury. This review aims to present the mechanisms of the combined effects of HIV-1 and alcohol abuse in the brain and to discuss neuroprotective therapies. Oxidative stress, overproduction of pro-inflammatory factors, impairment of blood brain barrier and glutamate associated neurotoxicity appear to play important roles in alcohol driven neurodegeneration. Diminution of neuroinflammation constitutes a logical approach for prevention of HIV-1 and alcohol mediated neurodegeneration. Agonists of cannabinoid receptor 2 (CB2) possess potent anti-inflammatory and neuroprotective properties. We address multifaceted beneficial effects of CB2 activation in the setting of HIV-1 brain infection and alcohol abuse. PMID:21397004

  13. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    SciTech Connect

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  14. Aging and HIV/AIDS: pathogenetic role of therapeutic side effects.

    PubMed

    Torres, Rebecca A; Lewis, William

    2014-02-01

    The intersection of aging and HIV/AIDS is a looming 'epidemic within an epidemic.' This paper reviews how HIV/AIDS and its therapy cause premature aging or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA). Survival with HIV/AIDS has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly active antiretroviral therapy). Because NRTIs and PIs together prevent or attenuate HIV-1 replication, and prolong life, the population of aging patients with HIV/AIDS increases accordingly. However, illnesses frequently associated with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS patients. Theories that help to explain biological aging include oxidative stress (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome telomere shortening with associated cellular senescence, and accumulation of lamin A precursors (a nuclear envelop protein). Each of these has the potential to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both. Antiretroviral therapy has been shown to enhance events seen in biological aging. Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative stress, and mitochondrial DNA defects that resemble features of both HANA and aging. More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as they cause prelamin A accumulation. Overall, toxic side effects of HAART may both resemble and promote events of aging and are worthy of mechanistic studies. PMID:24336070

  15. Aging and HIV/AIDS: pathogenetic role of therapeutic side effects

    PubMed Central

    Torres, Rebecca A; Lewis, William

    2014-01-01

    The intersection of aging and HIV/AIDS is a looming ‘epidemic within an epidemic.’ This paper reviews how HIV/AIDS and its therapy cause premature aging or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA). Survival with HIV/AIDS has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly active anti-retroviral therapy). Because NRTIs and PIs together prevent or attenuate HIV-1 replication, and prolong life, the population of aging patients with HIV/AIDS increases accordingly. However, illnesses frequently associated with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS patients. Theories that help to explain biological aging include oxidative stress (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome telomere shortening with associated cellular senescence, and accumulation of lamin A precursors (a nuclear envelop protein). Each of these has the potential to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both. Antiretroviral therapy has been shown to enhance events seen in biological aging. Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative stress, and mitochondrial DNA defects that resemble features of both HANA and aging. More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as they cause prelamin A accumulation. Overall, toxic side effects of HAART may both resemble and promote events of aging and are worthy of mechanistic studies. PMID:24336070

  16. Cytotoxic and Cytolytic Cnidarian Venoms. A Review on Health Implications and Possible Therapeutic Applications

    PubMed Central

    Mariottini, Gian Luigi; Pane, Luigi

    2013-01-01

    The toxicity of Cnidaria is a subject of concern for its influence on human activities and public health. During the last decades, the mechanisms of cell injury caused by cnidarian venoms have been studied utilizing extracts from several Cnidaria that have been tested in order to evaluate some fundamental parameters, such as the activity on cell survival, functioning and metabolism, and to improve the knowledge about the mechanisms of action of these compounds. In agreement with the modern tendency aimed to avoid the utilization of living animals in the experiments and to substitute them with in vitro systems, established cell lines or primary cultures have been employed to test cnidarian extracts or derivatives. Several cnidarian venoms have been found to have cytotoxic properties and have been also shown to cause hemolytic effects. Some studied substances have been shown to affect tumour cells and microorganisms, so making cnidarian extracts particularly interesting for their possible therapeutic employment. The review aims to emphasize the up-to-date knowledge about this subject taking in consideration the importance of such venoms in human pathology, the health implications and the possible therapeutic application of these natural compounds. PMID:24379089

  17. The Effect of Therapeutic HIV Vaccination With ALVAC-HIV With or Without Remune on the Size of the Viral Reservoir (A CTN 173 Substudy)

    PubMed Central

    Routy, Jean-Pierre; Graziani, Gina M.; Tremblay, Cécile L.

    2015-01-01

    Objectives: To assess whether therapeutic vaccination with ALVAC-HIV ± Remune affects viral reservoir size in antiretroviral therapy–treated individuals. Methods: Participants in CTN 173, a multicentre, randomized, 3-arm, placebo-controlled, double-blind study, were vaccinated with ALVAC-HIV ± Remune (groups 1 and 2, respectively) or with placebos (group 3) over 20 weeks and assessed for changes in the size of their viral reservoirs from weeks 0 to 24. Results: Sixteen participants completed the viral reservoir substudy. The median sizes (interquartile range) of the viral reservoir at baseline (week 0) were 0.07 (0.03–0.37), 0.04 (0.02–0.33), and 0.13 (0.06–0.99) infectious units per million peripheral blood mononuclear cells for groups 1, 2, and 3, respectively; these baseline viral reservoir sizes were not significantly different (P = 0.37). By week 24, the median sizes of the viral reservoirs were 0.04 (0.01–2.16), 0.04 (0.01–0.34), and 0.12 (0.01–0.44) infectious units per million peripheral blood mononuclear cells for groups 1, 2, and 3 respectively; these week 24 viral reservoir sizes were not significantly different (P = 0.91). Furthermore, there were no statistically significant differences between baseline and week 24 reservoir sizes for any of the 3 groups (P = 0.88, P = 1.00, and P = 0.44, respectively). Conclusions: Despite evidence that ALVAC-HIV ± Remune was associated with a trend toward a delay in viral rebound and a smaller decrease in CD4 T-cell counts following antiretroviral therapy interruption, ALVAC-HIV ± Remune did not influence the size of the viral reservoir. PMID:26375464

  18. Is gene therapy a good therapeutic approach for HIV-positive patients?

    PubMed Central

    Marathe, Jai G; Wooley, Dawn P

    2007-01-01

    Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and the application of these treatments in current and ongoing clinical trials. PMID:17300725

  19. Therapeutic strategies underpinning the development of novel techniques for the treatment of HIV infection

    PubMed Central

    Tan, Jian J.; Cong, Xiao J.; Hu, Li M.; Wang, Cun X.; Jia, Lee; Liang, Xing-Jie

    2010-01-01

    The HIV replication cycle offers multiple targets for chemotherapeutic intervention, including the viral exterior envelope glycoprotein, gp120; viral co-receptors CXCR4 and CCR5; transmembrane glycoprotein, gp41; integrase; reverse transcriptase; protease and so on. Most currently used anti-HIV drugs are reverse transcriptase inhibitors or protease inhibitors. The expanding application of simulation to drug design combined with experimental techniques have developed a large amount of novel inhibitors that interact specifically with targets besides transcriptase and protease. This review presents details of the anti-HIV inhibitors discovered with computer-aided approaches and provides an overview of the recent five-year achievements in the treatment of HIV infection and the application of computational methods to current drug design. PMID:20096804

  20. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys

    E-print Network

    Barouch, Dan H.

    Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to ...

  1. Mitochondrial abnormalities in Alzheimer’s disease: Possible targets for therapeutic intervention

    PubMed Central

    Silva, Diana F.; Selfridge, J. Eva; Lu, Jianghua; Lezi, E; Cardoso, Sandra M.; Swerdlow, Russell H.

    2013-01-01

    Mitochondria from persons with Alzheimer’s disease (AD) differ from those of age-matched, control subjects. Differences in mitochondrial morphology and function are well-documented, and are not brain-limited. Some of these differences are present during all stages of AD, and are even seen in individuals who are without AD symptoms and signs but who have an increased risk of developing AD. This chapter considers the status of mitochondria in AD subjects, the potential basis for AD subject mitochondrial perturbations, and the implications of these perturbations. Data from multiple lines of investigation, including epidemiologic, biochemical, molecular, and cytoplasmic hybrid studies are reviewed. The possibility that mitochondria could potentially constitute a reasonable AD therapeutic target is discussed, as are several potential mitochondrial medicine treatment strategies. PMID:22840745

  2. A decade of follow-up and therapeutic drug monitoring in HIV-2 immunocompromised patients at St Camille and General Lamizana Military Medical Centers, Burkina Faso, West Africa.

    PubMed

    Sanou, M; Soubeiga, S T; Bationo, F; Compaore, T R; Zohoncon, T M; Diatto, G N; Ouedraogo, P; Pietra, V; Nagalo, B M; Bisseye, C; Traore, R Ouedraogo; Simpore, J

    2014-12-01

    Although, HIV-2 is generally less pathogenic than HIV-1 and its progression towards AIDS occurs less frequently. HIV-2 remains an important cause of disease in West Africa. This study aimed to evaluate HIV-1 and HIV-2 prevalence among pregnant women and to describe the demographic and clinical profile of patients with HIV-2 infection from 2003-2013 at St Camille and General Lamizana Military Medical Centers. A retrospective investigation was conducted using 12,287 medical records from patients screened for HIV. To respond to the lack of data available regarding HIV-2 treatment and also to address the approach to clinical, biological as well as therapeutic monitoring, 62 HIV-2 infected patients' medical records were studied. Seroprevalence of 10.6 and 0.14% were obtained, respectively for HIV-1 and HIV-2 among 12,287 women screened during the study period. From the sixty two (62) HIV-2 patients, the average age was 49.2 years (sex ratio was 0.65). The weight loss and diarrhea were the major clinical manifestations observed, respectively 54.8 and 25.8%. Fungi and herpes zoster (shingles) infections were reported as major opportunistic infections. Also, nearly half of the patients had more than 60 kg, less than 2% were in WHO stage IV and about 2/3 had a CD4 count bellow 250 cells mm(-3). AZT-3TC-IDV/LPV/R was the most prescribed combination. The gain in weight gain the Body Mass Index (BMI) improvement and the non-significant increase of the rate of CD4 between 1st (M1) and 24th month (M24) were observed after treatment with antiviral. PMID:26027168

  3. Human Immunodeficiency Virus-1 (HIV-1)-Mediated Apoptosis: New Therapeutic Targets

    PubMed Central

    Mbita, Zukile; Hull, Rodney; Dlamini, Zodwa

    2014-01-01

    HIV has posed a significant challenge due to the ability of the virus to both impair and evade the host’s immune system. One of the most important mechanisms it has employed to do so is the modulation of the host’s native apoptotic pathways and mechanisms. Viral proteins alter normal apoptotic signaling resulting in increased viral load and the formation of viral reservoirs which ultimately increase infectivity. Both the host’s pro- and anti-apoptotic responses are regulated by the interactions of viral proteins with cell surface receptors or apoptotic pathway components. This dynamic has led to the development of therapies aimed at altering the ability of the virus to modulate apoptotic pathways. These therapies are aimed at preventing or inhibiting viral infection, or treating viral associated pathologies. These drugs target both the viral proteins and the apoptotic pathways of the host. This review will examine the cell types targeted by HIV, the surface receptors exploited by the virus and the mechanisms whereby HIV encoded proteins influence the apoptotic pathways. The viral manipulation of the hosts’ cell type to evade the immune system, establish viral reservoirs and enhance viral proliferation will be reviewed. The pathologies associated with the ability of HIV to alter apoptotic signaling and the drugs and therapies currently under development that target the ability of apoptotic signaling within HIV infection will also be discussed. PMID:25196285

  4. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    PubMed Central

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  5. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma.

    PubMed

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I-II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%-0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  6. Possible HIV transmission modes among at-risk groups at an early epidemic stage in the Philippines.

    PubMed

    Telan, Elizabeth Freda O; Samonte, Genesis May J; Palaypayon, Noel; Abellanosa-Tac-An, Ilya P; Leaño, Prisca Susan A; Tsuneki, Akeno; Kageyama, Seiji

    2013-12-01

    A concentrated human immunodeficiency virus (HIV) epidemic might have started in the Philippines. A subsequent characterization of viruses was carried out to estimate HIV transmission modes. Most HIV strains from injecting drug users belonged to subtype-B. CRF-01 was a major subtype harbored by three other at-risk populations: male visa applicants who had sex with men, "men who have sex with men," and visa applicants. An HIV phylogeny suggested that two strain groups of injecting drug users and others circulated separately. In contrast, there was substantial genetic overlap between two strain groups from "men who have sex with men" and visa applicants. Mean nucleotide distance within strains was shorter among subtype-B strains harbored by the injecting drug users (0.010) than among CRF-01 strains of the other three populations: male visa applicants who had sex with men (0.034), "men who have sex with men" (0.023), and visa applicants (0.032). Closely related strains of hepatitis C virus were derived from not only HIV-positive but also -negative individuals. These results suggest that there is potential for transmission from visa applicants to "men who have sex with men," and that once HIV occurs in injecting drug users, it spreads rapidly among them. Close contacts of hepatitis C virus carriers composed of HIV-negative and -positive individuals indicated ongoing HIV spread via blood and possible intervention points. Large-scale analysis is needed to provide more precise information on the transmission directions and to help curb the growth of this HIV epidemic in the Philippines. PMID:23959846

  7. Performance of Clinical Criteria for Screening of Possible Antiretroviral Related Mitochondrial Toxicity in HIV-Infected Children in Accra.

    PubMed

    Langs-Barlow, Allison; Renner, Lorna; Katz, Karol; Northrup, Veronika; Paintsil, Elijah

    2013-01-01

    Mitochondrial damage is implicated in highly active antiretroviral therapy (HAART) toxicity. HIV infection also causes mitochondrial toxicity (MT). Differentiating between the two is critical for HIV management. Our objective was to test the utility of the Mitochondrial Disease Criteria (MDC) and the Enquête Périnatale Française (EPF) to screen for possible HAART related MT in HIV-infected children in Ghana. The EPF and MDC are compilations of clinical symptoms, or criteria, of MT: a (+) score indicates possible MT. We applied these criteria retrospectively to 403 charts of HIV-infected children. Of those studied, 331/403 received HAART. Comparing HAART exposed and HAART naïve children, the difference in EPF score, but not MDC, approached significance (P = 0.1). Young age at HIV diagnosis or at HAART initiation was associated with (+) EPF (P ? 0.01). Adherence to HAART trended toward an association with (+) EPF (P = 0.09). Exposure to nevirapine, abacavir, or didanosine increased risk of (+) EPF (OR = 3.55 (CI = 1.99-6.33), 4.76 (2.39-9.43), 4.93 (1.29-18.87)). Neither EPF nor MDC identified a significant difference between HAART exposed or naïve children regarding possible MT. However, as indicators of HAART exposure are associated with (+) EPF, it may be a candidate for prospective study of possible HAART related MT in resource-poor settings. PMID:23533730

  8. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

    PubMed

    Pertwee, Roger G

    2012-12-01

    Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; ?(9)-tetrahydrocannabinol (?(9)-THC)) and Sativex (?(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive 'multi-targeting'. PMID:23108552

  9. Nanoparticle-conjugated animal venom-toxins and their possible therapeutic potential

    PubMed Central

    Biswas, Archita; Gomes, Aparna; Sengupta, Jayeeta; Datta, Poulami; Singha, Santiswarup; Dasgupta, Anjan Kr; Gomes, Antony

    2012-01-01

    Nano-medical approaches to develop drugs have attracted much attention in different arenas to design nanoparticle conjugates for better efficacy of the potential bio-molecules. A group of promising candidates of this category would be venom-toxins of animal origin of potential medicinal value. Traditional systems of medicine as well as folklores mention the use of venom-toxins for the treatment of various diseases. Research has led to scientific validation of medicinal applications of venoms-toxins and many active constituents derived from venoms-toxins are already in clinical use or under clinical trial. Nanomedicine is an emerging field of medicine where nanotechnology is used to develop molecules of nano-scale dimension, so that these molecules can be taken up by the cells more easily and have better efficacy, as compared to large molecules that may tend to get eliminated. This review will focus on some of the potential venoms and toxins along with nanoparticle conjugated venom-toxins of snakes, amphibians, scorpions and bees, etc., for possible therapeutic clues against emerging diseases. PMID:23236583

  10. [Post-therapeutic lymphedema of the arm--possibilities and limits of diagnosis and therapy].

    PubMed

    Döller, W

    1999-01-01

    The post-therapeutical secondary arm lymphedema is the most frequent complication after a curatively treated cancer of mamma. For the diagnosis and therapy the knowledge of physiology and pathophysiology of lymphedema and of specific anatomy are necessary. The diagnosis facilities are essentially limited to a basic diagnosis (anamnesis, inspection, palpation, sonography, functional-diagnosis). Specific apparative diagnostics like lab, sonography, CT, MRI and PTE have to be applied especially at an early stage of the secondary arm lymphedema for the differential diagnosis between the secondary malign and secondary benign arm lymphedema. Specific apparative examinations like lymphscintigraphy and lymphography are limited and solely indicated for special questions. As a therapy possibility of the secondary arm-lymph edema, a conservative therapy, that is, the complex two-stage-decongestive physiotherapy (CDP) is recommended as first choice. Surgical therapies such as autologous lympho-lymphostatic anastomoses and lymphovenous anastomoses are only recommended in selected individual cases. The secondary malignant arm lymphedema must be primarily treated oncologically; lymphological therapy measures have to be postponed. Diagnosis and therapy are limited through lymphological incompetence and insufficient patient compliance. In this respect the provision of financial resources through National Health policy ist regarded as utterly important. PMID:10378339

  11. Possible Therapeutic Effect of Stem Cell in Atherosclerosis in Albino Rats. A Histological and Immunohistochemical Study

    PubMed Central

    Abdel-Kawi, Samraa H; Hashem, Khalid S

    2015-01-01

    Background Atherosclerosis is the leading cause of death worldwide. there are no effective approaches to regressing atherosclerosis due to not fully understood mechanisms. Recently, stem cell-based therapies have held promises to various diseases, including vascular diseases. Aim The present study aimed at investigating the possible effect of cord blood mesenchymal stem cell (MSC) therapy on atherosclerosis. Material and Methods Eighty adult male albino rats were divided into control group (I), atherogenic group (II): subjected to high cholesterol fed diet (200~300 mg/kg body weight) for 12 weeks and 1.8 million units of vitamin D / kg of diet for 6 weeks. Stem cell therapy group (III): injected with stem cells in the tail vein following confirmation of atherosclerosis. Histological, Immunohistochemical and morphometric studies were performed were conducted. Results Atherogenic group (II) showed increased aortic thickness, intimal proliferation, smooth muscle proliferation and migration. Increased area % of collagen fibers, iNOS and vimentin immunoreactions were recorded and proved morphometrically. All findings regressed on stem cell therapy. Conclusion A definite therapeutic effect of mesenchymal stem cells was found on atherosclerosis. PMID:26634068

  12. Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation

    PubMed Central

    Agarwal, Akansha; Fanelli, Giorgia; Letizia, Marilena; Tung, Sim Lai; Boardman, Dominic; Lechler, Robert; Lombardi, Giovanna; Smyth, Lesley A.

    2014-01-01

    Exosomes are extracellular vesicles released by many cells of the body. These small vesicles play an important part in intercellular communication both in the local environment and systemically, facilitating in the transfer of proteins, cytokines as well as miRNA between cells. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has paved the way for these structures to be considered as potential immunotherapeutic reagents. Indeed, clinical trials using DC derived exosomes to facilitate immune responses to specific cancer antigens are now underway. Exosomes can also have a negative effect on the immune response and exosomes isolated from regulatory T cells (Tregs) and other subsets of T cells have been shown to have immune suppressive capacities. Here, we review what is currently known about Treg derived exosomes and their contribution to immune regulation, as well as highlighting their possible therapeutic potential for preventing graft rejection, and use as diagnostic tools to assess transplant outcome. PMID:25414702

  13. HIV/AIDS Clinical Trials

    MedlinePLUS

    ... APIs Widgets Order Publications Skip Nav HIV/AIDS Clinical Trials Home > Clinical Trials Español Text Size Use ... Vaccine Research HIV Preventive Vaccines HIV Therapeutic Vaccines Clinical Trial News Wednesday, December 23, 2015 HIV Antibody ...

  14. A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART

    PubMed Central

    Gómez, Carmen Elena; Perdiguero, Beatriz; García-Arriaza, Juan; Cepeda, Victoria; Sánchez-Sorzano, Carlos Óscar; Mothe, Beatriz; Jiménez, José Luis; Muñoz-Fernández, María Ángeles; Gatell, Jose M.; López Bernaldo de Quirós, Juan Carlos; Brander, Christian; García, Felipe; Esteban, Mariano

    2015-01-01

    Trial Design Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. Methods The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. Results MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses. Conclusion MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity. Trial Registration ClinicalTrials.gov NCT01571466 PMID:26544853

  15. Two cases of possible transmitted drug-resistant HIV: likely HIV superinfection and unmasking of pre-existing resistance

    PubMed Central

    Lee, John; Thomson, Emma; Tarrant, Nick; Hale, Antony; Lacey, Charles J

    2016-01-01

    In the UK, patients undergo HIV viral load and genotype testing before they are prescribed antiretroviral therapy. The genotype test guides clinicians in prescribing antiretroviral therapy with maximum efficacy against the patient’s specific viral strain. HIV viral load escape under antiretroviral drug therapy, to which the virus was thought to be genotypically susceptible, is commonly observed in patients with poor adherence. We observed early viral escapes in two-newly diagnosed patients, during antiretroviral treatment, with different sequences compared to their original viral resistance test and who reported excellent adherence to and tolerance of their therapy. HIV superinfection with a new viral strain was identified in a patient with multiple risk factors and co-infections with sexually transmitted infections. The second patient was a case of the emergence of primary resistant virus under drug pressure. Both suppressed their virus promptly after treatment switch. PMID:25663247

  16. Two cases of possible transmitted drug-resistant HIV: likely HIV superinfection and unmasking of pre-existing resistance.

    PubMed

    Martin, Fabiola; Lee, John; Thomson, Emma; Tarrant, Nick; Hale, Antony; Lacey, Charles J

    2016-01-01

    In the UK, patients undergo HIV viral load and genotype testing before they are prescribed antiretroviral therapy. The genotype test guides clinicians in prescribing antiretroviral therapy with maximum efficacy against the patient's specific viral strain. HIV viral load escape under antiretroviral drug therapy, to which the virus was thought to be genotypically susceptible, is commonly observed in patients with poor adherence. We observed early viral escapes in two-newly diagnosed patients, during antiretroviral treatment, with different sequences compared to their original viral resistance test and who reported excellent adherence to and tolerance of their therapy. HIV superinfection with a new viral strain was identified in a patient with multiple risk factors and co-infections with sexually transmitted infections. The second patient was a case of the emergence of primary resistant virus under drug pressure. Both suppressed their virus promptly after treatment switch. PMID:25663247

  17. Successful therapeutic splenectomy in an HIV patient with relapsing visceral leishmaniasis.

    PubMed

    Alon, D; Chowers, M

    2012-04-01

    A 43-year-old HIV-positive Ethiopian immigrant presented with persistent diarrhoea, hepatosplenomegaly and pancytopaenia. Visceral leishmaniasis was diagnosed by multiple gastrointestinal tract biopsies. Blood polymerase chain reaction (PCR) was positive for Leishmania donovani. Despite highly active antiretroviral therapy (HAART) and multiple courses of antileishmanial treatments, including liposomal amphotericin and sodium stibogluconate, the patient had multiple relapses. CD4 counts remained at 40-60 cells/µL although viral loads were undetectable. Splenectomy resulted in resolution of the patient's pancytopaenia and in rising CD4 levels, which enabled a long-lasting remission. PMID:22581957

  18. Exploring the Possibilities and Limitations of Service-Learning: A Critical Analysis of College Student Narratives about HIV/AIDS

    ERIC Educational Resources Information Center

    Jones, Susan Robb; LePeau, Lucy A.; Robbins, Claire K.

    2013-01-01

    This article reports the results of a study that explored the possibilities and limitations of service-learning by deconstructing the narratives about HIV/AIDS that emerged from five college students who participated in an alternative spring break program. Employing a critical (Rhoads, 1997) and anti-foundational (Butin, 2010) approach to inquiry,…

  19. Glucagon-like Peptide-1 (GLP-1) Analogs: Recent Advances, New Possibilities, and Therapeutic Implications

    PubMed Central

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin that plays important physiological roles in glucose homeostasis. Produced from intestine upon food intake, it stimulates insulin secretion and keeps pancreatic ?-cells healthy and proliferating. Because of these beneficial effects, it has attracted a great deal of attention in the past decade, and an entirely new line of diabetic therapeutics has emerged based on the peptide. In addition to the therapeutic applications, GLP-1 analogs have demonstrated a potential in molecular imaging of pancreatic ?-cells; this may be useful in early detection of the disease and evaluation of therapeutic interventions, including islet transplantation. In this Perspective, we focus on GLP-1 analogs for their studies on improvement of biological activities, enhancement of metabolic stability, investigation of receptor interaction, and visualization of the pancreatic islets. PMID:25349901

  20. JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14+CD16+ monocytes in HIV-infected individuals.

    PubMed

    Williams, Dionna W; Anastos, Kathryn; Morgello, Susan; Berman, Joan W

    2015-02-01

    Monocyte transmigration across the BBB is a critical step in the development of cognitive deficits termed HAND that affect 40-70% of HIV-infected individuals, even with successful antiretroviral therapy. The monocyte subsets that enter the CNS during HIV infection are not fully characterized. We examined PBMC from HIV-positive individuals from 2 distinct cohorts and enumerated monocyte populations, characterized their transmigration properties across an in vitro human BBB model, and identified surface proteins critical for the entry of these cells into the CNS. We demonstrated that the frequency of peripheral blood CD14(+)CD16(+) and CD14(low)CD16(+) monocytes was increased in HIV-seropositive compared with -seronegative individuals, despite virologic control. We showed that CD14(+)CD16(+) monocytes selectively transmigrated across our BBB model as a result of their increased JAM-A and ALCAM expression. Antibody blocking of these proteins inhibited diapedesis of CD14(+)CD16(+) monocytes but not of T cells from the same HIV-infected people across the BBB. Our data indicate that JAM-A and ALCAM are therapeutic targets to decrease the entry of CD14(+)CD16(+) monocytes into the CNS of HIV-seropositive individuals, contributing to the eradication of neuroinflammation, HAND, and CNS viral reservoirs. PMID:25420915

  1. Modelling the long-term impacts on affected children of adult HIV: benefits, challenges and a possible approach.

    PubMed

    Desmond, Christopher; Bruce, Faikah; Tomlinson, M; Marlow, Marguerite B; Aber, J Lawrence; Ouifki, Rachid; Welte, Alex

    2014-07-01

    We outline the benefits, challenges and possible approaches to developing mathematical models that could be used to estimate the magnitude of negative consequences of adult HIV infection for children. Adult HIV infection can lead to numerous negative consequences for dependent children, including depression, anxiety, withdrawal from school and early sexual debut, among others. For advocacy and planning purposes, it is important to highlight and consider as many of these as possible. A focus solely on orphan numbers, which is the typical summary measure for children affected by HIV and AIDS, can be misleading. The complexity of child development that is characterized by the interaction of a multitude of proximal and distal factors, coupled with a significant lack of data on child development in the context of adult HIV infection make the development of models a challenging task. Although it may not be possible in the first attempt to develop a population-based model capable of examining family dynamics, the negative consequences together with the impact of interventions, steps in that direction can be taken. We propose approaches and assumptions that we believe will allow the development of a useful first set of models. We conclude with a brief discussion of the type of data that, if collected, would facilitate refinement and development of these models. PMID:24991900

  2. A Future of Possibilities: Educating Children Living in HIV Impacted Households

    ERIC Educational Resources Information Center

    Kagotho, Njeri

    2012-01-01

    Close to one and a half million Kenyans reportedly live with HIV/AIDS. Using qualitative in-depth interviews this study explores the ways in which parents living with HIV/AIDS navigate their social and economic environment to provide educational opportunities for their children. Barriers identified include the economic costs of a free primary…

  3. Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy.

    PubMed

    Miller, Elizabeth; Spadaccia, Meredith; Sabado, Rachel; Chertova, Elena; Bess, Julian; Trubey, Charles Mac; Holman, Rose Marie; Salazar, Andres; Lifson, Jeffrey; Bhardwaj, Nina

    2015-01-01

    Therapeutic interventions for HIV-1 that successfully augment adaptive immunity to promote killing of infected cells may be a requisite component of strategies to reduce latent cellular reservoirs. Adoptive immunotherapies utilizing autologous monocyte-derived dendritic cells (DCs) that have been activated and antigen loaded ex vivo may serve to circumvent defects in DC function that are present during HIV infection in order to enhance adaptive immune responses. Here we detail the clinical preparation of DCs loaded with autologous aldrithiol-2 (AT-2)-inactivated HIV that have been potently activated with the viral mimic, Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC). HIV is first propagated from CD4+ T cells from HIV-infected donors and then rendered non-replicative by chemical inactivation with aldrithiol-2 (AT-2), purified, and quantified. Viral inactivation is confirmed through measurement of Tat-regulated ?-galactosidase reporter gene expression following infection of TZM-bl cells. In-process testing for sterility, mycoplasma, LPS, adventitious agents, and removal of AT-2 is performed on viral preparations. Autologous DCs are generated and pulsed with autologous AT-2-inactivated virus and simultaneously stimulated with Poly-ICLC to constitute the final DC vaccine product. Phenotypic identity, maturation, and induction of HIV-specific adaptive immune responses are confirmed via flow cytometric analysis of DCs and cocultured autologous CD4+ and CD8+ T cells. Lot release criteria for the DC vaccine have been defined in accordance with Good Manufacturing Practice (GMP) guidelines. The demonstrated feasibility of this approach has resulted in approval by the FDA for investigational use in antiretroviral (ART) suppressed individuals. We discuss how this optimized DC formulation may enhance the quality of anti-HIV adaptive responses beyond what has been previously observed during DC immunotherapy trials for HIV infection. PMID:25444812

  4. Pediatric Sarcomas: Translating Molecular Pathogenesis of Disease to Novel Therapeutic Possibilities

    PubMed Central

    Anderson, Jennifer L.; Denny, Christopher T.; Tap, William D.; Federman, Noah

    2014-01-01

    Pediatric sarcomas represent a diverse group of rare bone and soft tissue malignancies. Though the molecular mechanisms that propel the development of these cancers are not well understood, identification of tumor-specific translocations in many sarcomas has provided significant insight into their tumorigenesis. Each fusion protein resulting from these chromosomal translocations is thought to act as a driving force in the tumor, either as an aberrant transcription factor, constitutively active growth factor, or ligand-independent receptor tyrosine kinase. Identification of transcriptional targets or signaling pathways modulated by these oncogenic fusions has led to the discovery of potential therapeutic targets. Some of these targets have shown considerable promise in pre-clinical models and are currently being tested in clinical trials. This review summarizes the molecular pathology of a subset of pediatric sarcomas with tumor-associated translocations and how increased understanding at the molecular level is being translated to novel therapeutic advances. PMID:22546864

  5. The nitric oxide pathway and possible therapeutic options in pre-eclampsia

    PubMed Central

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-01-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide–soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3?,5?-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

  6. The nitric oxide pathway and possible therapeutic options in pre-eclampsia.

    PubMed

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-08-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

  7. Why are some HIV/AIDS patients reluctant to receive antiviral therapy as soon as possible in China?

    PubMed

    Sun, Yang; Lu, Hongzhou

    2014-06-01

    In more than 20 years of medical practice, a surprising phenomenon has often occurred: some patients with acquired immunodeficiency syndrome (AIDS) decide not to go to the hospital and they do not let others know that they are suffering from the disease unless they believe that they are dieing. Zhang Shan (a pseudonym) is one such patient with human immunodeficiency virus (HIV)/AIDS who was reluctant to receive antiviral therapy as soon as possible, and this paper shares Zhang's story as he related it. Clearly, there are numerous views as to why patients in China behave as Zhang did. Presented here are several reasons, including society, history, morality and ideology, family, and education. Although all of these reasons do play a role, the patient's mindset and behavior is the most significant reason for a patient's reluctance to seek treatment or disclose his/her status. If the individual patient's mindset and behavior are not dealt with effectively, then HIV/AIDS can continue to spread and threaten additional lives and even the fabric of society. This paper analyzes the reasons why patients are hesitant to receive antiviral therapy, but this paper also suggests steps healthcare personnel can take to encourage patients to seek treatment. Such steps can save the lives of current patients with HIV/AIDS. In addition, sound public health measures and a rational approach to treatment are important to helping potential patients with HIV/AIDS. PMID:25030855

  8. Bullous Lesions After Use of a Commercial Therapeutic Hypothermia Temperature Management System: A Possible Burn Injury?

    PubMed Central

    Wells, James M.; Rizk, Dana V.

    2013-01-01

    Therapeutic hypothermia (TH) is a novel technique for improving the likelihood of survival with good neurologic outcome after cardiopulmonary arrest. While commercial temperature management systems (TMS) are intended to facilitate cooling of the body during TH, their operation also involves body exposure to heat. We describe the case of a 72-year-old female postarrest patient who underwent TH using a commercial water-circulating TMS and concurrent continuous renal replacement therapy. The patient developed bullous lesions on the thigh and torso suspected to constitute a scald burn injury from the TMS. Clinicians must be aware of this important adverse event when providing TH, especially in the setting of concurrent hemodialysis therapy. PMID:24066269

  9. The possible therapeutic benefits of utilizing motion gaming systems on pediatric patients presenting autism.

    PubMed

    Crowder, Stephen A; Merritte, Kristin

    2013-09-01

    Autism is a pervasive developmental disorder that affects a growing number of children in the United States each year. It is characterized by substantive differences in brain structure and function that lead to long-term cognitive and social deficits. These differences, combined with the increasing prevalence of autism in children, warrant the need for development of innovative, cost-effective and widely available alternative and complementary therapies. Motion gaming has the potential to be highly efficacious as a therapeutic technique to aid in developing memory, facial recognition, motor skills and social integration in the pediatric autistic population. This paper outlines the major deficits in the brains of individuals with autism and describes how the use of motion gaming could capitalize on the individual strengths of each patient, leading to improvements in a variety of deficits. PMID:24027887

  10. Melatonin and Its Agonist Ramelteon in Alzheimer's Disease: Possible Therapeutic Value

    PubMed Central

    Srinivasan, Venkatramanujam; Kaur, Charanjit; Pandi-Perumal, Seithikurippu; Brown, Gregory M.; Cardinali, Daniel P.

    2011-01-01

    Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by the progressive loss of cognitive function, loss of memory and insomnia, and abnormal behavioral signs and symptoms. Among the various theories that have been put forth to explain the pathophysiology of AD, the oxidative stress induced by amyloid ?-protein (A?) deposition has received great attention. Studies undertaken on postmortem brain samples of AD patients have consistently shown extensive lipid, protein, and DNA oxidation. Presence of abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation all have been demonstrated in neural tissues of AD patients. Moreover, AD patients exhibit severe sleep/wake disturbances and insomnia and these are associated with more rapid cognitive decline and memory impairment. On this basis, the successful management of AD patients requires an ideal drug that besides antagonizing A?-induced neurotoxicity could also correct the disturbed sleep-wake rhythm and improve sleep quality. Melatonin is an effective chronobiotic agent and has significant neuroprotective properties preventing A?-induced neurotoxic effects in a number of animal experimental models. Since melatonin levels in AD patients are greatly reduced, melatonin replacement has the potential value to be used as a therapeutic agent for treating AD, particularly at the early phases of the disease and especially in those in whom the relevant melatonin receptors are intact. As sleep deprivation has been shown to produce oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, and altered proteosomal processing with abnormal activation of enzymes, treatment of sleep disturbances may be a priority for arresting the progression of AD. In this context the newly introduced melatonin agonist ramelteon can be of much therapeutic value because of its highly selective action on melatonin MT1/MT2 receptors in promoting sleep. PMID:21197086

  11. Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions

    PubMed Central

    Hassan, Waseem; Silva, Carlos Eduardo Barroso; Mohammadzai, Imdad Ullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J.

    2014-01-01

    Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related disorders. Furthermore, the manifestation of anxiety in numerous psychiatric disorders, such as generalized anxiety disorder, depressive disorder, panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress disorder, highlights the importance of studying the underlying biology of these disorders to gain a better understanding of the disease and to identify common biomarkers for these disorders. Most recently, the expression of glutathione reductase 1 and glyoxalase 1, which are genes involved in antioxidative metabolism, were reported to be correlated with anxiety-related phenotypes. This review focuses on direct and indirect evidence of the potential involvement of oxidative stress in the genesis of anxiety and discusses different opinions that exist in this field. Antioxidant therapeutic strategies are also discussed, highlighting the importance of oxidative stress in the etiology, incidence, progression, and prevention of psychiatric disorders. PMID:24669207

  12. [Sense of humour in schizophrenia--ability of humour reception and possibilities of its application in therapeutic interventions].

    PubMed

    Parnowska, Dorota; Braniecka, Anna; Radomska, Anna

    2013-01-01

    The existing research on sense of humour in schizophrenia is focused on two main areas, mainly, assessment of patients' abilities to understand and appreciate humour and denoting the possibilities of its application in therapeutic programs concentrating on the improvement of patients' functionality and preventing illness relapses. The vast majority of the conclusions from the above mentioned research corroborate the opinion on the usefulness of developing and reinforcing sense of humour in schizophrenia, emphasizing its beneficial effect on the patients' quality of life, above all, in terms of reducing aggression, anxiety and depression as well as improving general life satisfaction and social functioning. At the same time numerous research indicate low reception of humour in schizophrenia which can negatively influence its effective usage in therapeutic interventions. Further constraint with regard to the therapy can constitute an intensified fear for being laughed at, which has been confirmed in numerous empirical reports. Therefore, it seems that addressing humorous therapeutic interventions to the above mentioned group of patients requires especially careful planning taking into consideration its cognitive and affective limitations in the perception of humour and intensified fear for being laughed at. PMID:25011239

  13. Modified therapeutic community aftercare for clients triply diagnosed with HIV/AIDS and co-occurring mental and substance use disorders.

    PubMed

    Sacks, Stanley; McKendrick, Karen; Vazan, Peter; Sacks, Joann Y; Cleland, Charles M

    2011-12-01

    This clinical trial evaluated a modified therapeutic community aftercare (MTC-A) program for a population triply diagnosed with HIV/AIDS, a substance use disorder, and a mental disorder. After six months of MTC residential treatment (MTC-R), subjects were randomly assigned to MTC-A (n=42) or to standard aftercare (C; n=34). Follow-up interviews at six and 12 months assessed eight outcome domains and adherence to prescribed HIV medication. A propensity model was used to re-balance the retrieved sample. At the six-month follow-up, High stratum MTC-A clients (those with greater psychological functioning and stable physical health at baseline) had greater improvement overall and for substance use and mental health than C clients in the same stratum. In contrast, C clients in the Low/Medium stratum (those with poorer psychological functioning and improved physical health) had more favorable outcomes overall and for substance use than their MTC-A counterparts; however, this stratum was not re-balanced effectively. Differences in HIV medication adherence were not detected. Clients with greater psychological functioning and stable health at treatment entry benefit more from the MTC-A program. In view of the potentially progressive nature of HIV, measuring physical and mental health during treatment and controlling for changes could be important in future research. PMID:21711215

  14. Ready to Use Therapeutic Foods (RUTF) improves undernutrition among ART-treated, HIV-positive children in Dar es Salaam, Tanzania

    PubMed Central

    2012-01-01

    Background HIV/AIDS is associated with an increased burden of undernutrition among children even under antiretroviral therapy (ART). To treat undernutrition, WHO endorsed the use of Ready to Use Therapeutic Foods (RUTF) that can reduce case fatality and undernutrition among ART-naïve HIV-positive children. However, its effects are not studied among ART-treated, HIV-positive children. Therefore, we examined the association between RUTF use with underweight, wasting, and stunting statuses among ART-treated HIV-positive children in Dar es Salaam, Tanzania. Methods This cross-sectional study was conducted from September-October 2010. The target population was 219 ART-treated, HIV-positive children and the same number of their caregivers. We used questionnaires to measure socio-economic factors, food security, RUTF-use, and ART-duration. Our outcome variables were underweight, wasting, and stunting statuses. Results Of 219 ART-treated, HIV-positive children, 140 (63.9%) had received RUTF intervention prior to the interview. The percentages of underweight and wasting among non-RUTF-receivers were 12.4% and 16.5%; whereas those of RUTF-receivers were 3.0% (P?=?0.006) and 2.8% (P?=?0.001), respectively. RUTF-receivers were less likely to have underweight (Adjusted Odd Ratio (AOR) =0.19, CI: 0.04, 0.78), and wasting (AOR?=?0.24, CI: 0.07, 0.81), compared to non RUTF-receivers. Among RUTF receivers, children treated for at least four months (n?=?84) were less likely to have underweight (P?=?0.049), wasting (P?=?0.049) and stunting (P?HIV-positive children under ART, the provision of RUTF for at least four months was associated with low proportions of undernutrition status. RUTF has a potential to improve undernutrition among HIV-positive children under ART in the clinical settings in Dar es Salaam, Tanzania. PMID:22931107

  15. VS411 Reduced Immune Activation and HIV-1 RNA Levels in 28 Days: Randomized Proof-of-Concept Study for AntiViral-HyperActivation Limiting Therapeutics

    PubMed Central

    Lori, Franco; De Forni, Davide; Katabira, Elly; Baev, Denis; Maserati, Renato; Calarota, Sandra A.; Cahn, Pedro; Testori, Marco; Rakhmanova, Aza; Stevens, Michael R.

    2012-01-01

    Background A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4+ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects. Methods Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests. Results VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4+ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: ?1.47 log10 copies/mL; CD4+ T cell count: +135 cells/mm3) and fewest adverse events. Conclusions VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system activation associated with HIV-1 disease. Rapid reductions in markers of immune system hyperactivation and cellular proliferation were obtained despite the fact that VS411 did not attain maximal suppression of HIV RNA, suggesting this effect was due to the HALT component. Trial Registration ITEudraCT 2007-002460-98 PMID:23094055

  16. Fabry disease: case report with emphasis on enzyme replacement therapy and possible future therapeutic options.

    PubMed

    Möhrenschlager, Matthias; Pontz, Bertram F; Lanzl, Ines; Podskarbi, Theodor; Henkel, Verena; Ring, Johannes

    2007-07-01

    A 38-year-old male Caucasian with Fabry disease presented with angiokeratomas and tortuous conjunctival and retinal vessels. Additionally, the patient showed characteristic skin lesions of psoriasis and seborrheic dermatitis. His past medical history revealed anhidrosis, acral paresthesias, myocardial infarction, phlebothrombosis, hypertension, antithrombin III deficiency, factor V Leiden disease, chronic obstructive lung disease, tinnitus, diarrhea, recurrent abdominal pain, headache, and depressive mood. He was treated with intravenous substitution of the deficient enzyme alpha-galactosidase A. Possible future options in treatment of Fabry disease are discussed. PMID:17610610

  17. The current status and challenges in the development of fusion inhibitors as therapeutics for HIV-1 infection.

    PubMed

    Tan, Jian Jun; Ma, Xue Ting; Liu, Chang; Zhang, Xiao Yi; Wang, Cun Xin

    2013-01-01

    HIV-1 membrane fusion as a part of the process of viral entry in the target cells is facilitated by gp41 and gp120, which are encoded by Env gene of HIV-1. Based on the structure and the mechanism researches, new treatment options targeting HIV-1 entry process have been proposed. Enfuvirtide, which mimics amino acid sequences of viral envelope glycoprotein gp41, is the first HIV-1 fusion inhibitor approved by FDA. Although it fulfills vital functions by binding to gp41 and abolishing the membrane fusion reaction when used in combination, it could induce drug resistant virus variants. Currently, a number of design and modification schemes have been presented, a large number of prospective fusion peptides have emerged. For these fusion inhibitors, multiple mutations in gp41 have been associated with the loss of susceptibility to agents. This review reported the current developments and innovative designs of HIV-1 membrane fusion inhibitors. PMID:23092283

  18. Postprandial Reactive Hypoglycaemia: Varying Presentation Patterns on Extended Glucose Tolerance Tests and Possible Therapeutic Approaches

    PubMed Central

    Stuart, Kevin; Field, Annmarie; Raju, Jessie; Ramachandran, Sudarshan

    2013-01-01

    Reactive hypoglycemia is a state characterised by sympathetic or neuroglycopenic symptoms associated with hypoglycaemia in the postprandial state resulting in considerable distress to the patient. It is our practice to carry out either extended glucose tolerance tests (eGTTs) or mixed meal tests in these patients. We describe two patients who experienced hypoglycaemic symptoms early and late during eGTT. The patient who experienced symptoms early, in contrast to the patient who presented with late symptoms, did not possess any characteristics of the metabolic syndrome. Based on clinical symptoms, glucose, insulin, and free fatty acid (FFA) levels, we speculate on possible mechanisms that may have accounted for each of their presentation patterns. We then discuss low glycaemic index diet which will be the mainstay of management. PMID:23424590

  19. A multi-scale mathematical modeling framework to investigate anti-viral therapeutic opportunities in targeting HIV-1 accessory proteins.

    PubMed

    Suryawanshi, Gajendra W; Hoffmann, Alexander

    2015-12-01

    Human immunodeficiency virus-1 (HIV-1) employs accessory proteins to evade innate immune responses by neutralizing the anti-viral activity of host restriction factors. Apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, A3G) and bone marrow stromal cell antigen 2 (BST2) are host resistance factors that potentially inhibit HIV-1 infection. BST2 reduces viral production by tethering budding HIV-1 particles to virus producing cells, while A3G inhibits the reverse transcription (RT) process and induces viral genome hypermutation through cytidine deamination, generating fewer replication competent progeny virus. Two HIV-1 proteins counter these cellular restriction factors: Vpu, which reduces surface BST2, and Vif, which degrades cellular A3G. The contest between these host and viral proteins influences whether HIV-1 infection is established and progresses towards AIDS. In this work, we present an age-structured multi-scale viral dynamics model of in vivo HIV-1 infection. We integrated the intracellular dynamics of anti-viral activity of the host factors and their neutralization by HIV-1 accessory proteins into the virus/cell population dynamics model. We calculate the basic reproductive ratio (Ro) as a function of host-viral protein interaction coefficients, and numerically simulated the multi-scale model to understand HIV-1 dynamics following host factor-induced perturbations. We found that reducing the influence of Vpu triggers a drop in Ro, revealing the impact of BST2 on viral infection control. Reducing Vif?s effect reveals the restrictive efficacy of A3G in blocking RT and in inducing lethal hypermutations, however, neither of these factors alone is sufficient to fully restrict HIV-1 infection. Interestingly, our model further predicts that BST2 and A3G function synergistically, and delineates their relative contribution in limiting HIV-1 infection and disease progression. We provide a robust modeling framework for devising novel combination therapies that target HIV-1 accessory proteins and boost antiviral activity of host factors. PMID:26385832

  20. Stability and in vitro release profile of enalapril maleate from different commercially available tablets: possible therapeutic implications.

    PubMed

    Lima, Dione Marçal; dos Santos, Leandro Dias; Lima, Eliana Martins

    2008-08-01

    Stability of enalapril maleate formulations can be affected when the product is exposed to higher temperature and humidity, with the formation of two main degradation products: enalaprilat and a diketopiperazine derivative. In this work, stability and drug release profiles of 20 mg enalapril maleate tablets (reference, generic and similar products) were evaluated. After 180 days of the accelerated stability testing, most products did not exhibit the specified amount of drug. Additionally, drug release profiles were markedly different from that of the reference product, mainly due to drug degradation. Changes in drug concentration and drug release profile of enalapril formulations are strong indicators of a compromised bioavailability, with possible interferences on the therapeutic response for this drug. PMID:18472382

  1. Therapeutic DNA Vaccination of Vertically HIV-Infected Children: Report of the First Pediatric Randomised Trial (PEDVAC)

    PubMed Central

    Palma, Paolo; Romiti, Maria Luisa; Montesano, Carla; Santilli, Veronica; Mora, Nadia; Aquilani, Angela; Dispinseri, Stefania; Tchidjou, Hyppolite K.; Montano, Marco; Eriksson, Lars E.; Baldassari, Stefania; Bernardi, Stefania; Scarlatti, Gabriella

    2013-01-01

    Subjects Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3. Intervention Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p?=?0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p?=?0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration clinicaltrialsregister.eu _2007-002359-18IT PMID:24312194

  2. Rebuilding Synaptic Architecture in HIV-1 Associated Neurocognitive Disease (HAND) – A Therapeutic Strategy Based on Modulation of Mixed Lineage Kinase

    PubMed Central

    Gelbard, Harris A.; Dewhurst, Stephen; Maggirwar, Sanjay B.; Kiebala, Michelle; Polesskaya, Oksana; Gendelman, Howard E.

    2010-01-01

    Work from our laboratories has validated mixed lineage kinase type 3 (MLK3) as an enzyme pathologically activated in the central nervous system (CNS) by HIV-1 neurotoxins. In this review, we discuss MLK3 activation in the context of the neuropathogenesis of HIV-1 associated neurocognitive deficits (HAND). We use findings from the literature to substantiate the neuropathologic relevance of MLK3 to neurodegenerative disease, with an emphasis on Parkinson’s disease (PD) that shares a number of important phenotypic and neuropathologic characteristics with HAND. We discuss signal transduction pathways downstream from MLK3 activation, with an emphasis on their involvement in microglia and neurons in preclinical models of HAND. Finally, we make a case for pharmacologic intervention targeted at inhibition of MLK3 as a strategy to reverse HAND in light of the fact that combination antiretroviral therapy, despite successfully managing systemic infection of HIV-1, has been largely unsuccessful in eradicating HAND. PMID:20880503

  3. Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

    PubMed Central

    Marech, Ilaria; Gadaleta, Cosmo Damiano; Ranieri, Girolamo

    2014-01-01

    Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC. PMID:25056544

  4. Demonstration of HIV-1 infected cells in human placenta by in situ hybridisation and immunostaining.

    PubMed Central

    Backé, E; Jiménez, E; Unger, M; Schäfer, A; Jauniaux, E; Vogel, M

    1992-01-01

    AIMS: To show the presence of HIV infected cells in the placentas and membranes exposed to HIV during pregnancy, and to trace the possible transmission routes from mother to fetus. METHODS: Twenty three therapeutic abortions and 11 term placentas were investigated for the presence of HIV antigen by immunostaining with HIV core protein specific antibodies and HIV nucleic acids by in situ hydridisation (ISH) with a 35S-labelled HIV specific RNA probe. RESULTS: HIV antigen as well as HIV RNA positive cells were rarely found in placental tissue and membranes. In therapeutic abortions HIV antigen was shown in 10 out of 23 placentas, HIV RNA in two. HIV antigen was detected in five out of 11 term placentas and HIV RNA in two. Infected cell types comprised syncytiotrophoblasts, Hofbauer cells, amnionic epithelium, chorionic macrophages as well as maternal lymphocytes in the intervillous space and decidua. CONCLUSION: These data suggest that the transmission routes are: (1) a haematogenous route from the maternal intervillous space to villous stromal cells; (2) from chorion laeve to amnionic fluid and vice versa. Two additional transmission routes are partly suggested by the data: (1) in early gestation by direct extension from basal decidua to budding trophoblastic cells; (2) from the capsular decidua to chorion laeve and chorionic plate, entering the fetal circulation via the small veins. Images PMID:1430256

  5. HIV and the Gut Microbiota, Partners in Crime: Breaking the Vicious Cycle to Unearth New Therapeutic Targets

    PubMed Central

    Jenabian, Mohammad-Ali

    2015-01-01

    The gut microbiota plays a key role in health and immune system education and surveillance. The delicate balance between microbial growth and containment is controlled by the immune system. However, this balance is disrupted in cases of chronic viral infections such as HIV. This virus is capable of drastically altering the immune system and gastrointestinal environment leading to significant changes to the gut microbiota and mucosal permeability resulting in microbial translocation from the gut into the peripheral blood. The changes made locally in the gut have far-reaching consequences on the other organs of the body starting in the liver, where microbes and their products are normally filtered out, and extending to the blood and even brain. Microbial translocation and their downstream effects such as increased indolamine 2,3-dioxygenase (IDO) enzyme expression and activity create a self-sustaining feedback loop which enhances HIV disease progression and constitute a vicious cycle of inflammation and immune activation combining viral and bacterial factors. Understanding this self-perpetuating cycle could be a key element in developing new therapies aimed at the gut microbiota and its fallout after infection. PMID:25759844

  6. Which Antibody Functions are Important for an HIV Vaccine?

    PubMed Central

    Su, Bin; Moog, Christiane

    2014-01-01

    HIV antibody (Ab) functions capable of preventing mucosal cell-free or cell-to-cell HIV transmission are critical for the development of effective prophylactic and therapeutic vaccines. In addition to CD4+ T cells, other potential HIV-target cell types including antigen-presenting cells (APCs) (dendritic cells, macrophages) residing at mucosal sites are infected. Moreover, the interactions between APCs and HIV lead to HIV cell-to-cell transmission. Recently discovered broadly neutralizing antibodies (NAbs) are able to neutralize a broad spectrum of HIV strains, inhibit cell-to-cell transfer, and efficiently protect from infection in the experimentally challenged macaque model. However, the 31% protection observed in the RV144 vaccine trial in the absence of detectable NAbs in blood samples pointed to the possible role of additional Ab inhibitory functions. Increasing evidence suggests that IgG Fc? receptor (Fc?R)-mediated inhibition of Abs present at the mucosal site may play a role in protection against HIV mucosal transmission. Moreover, mucosal IgA Abs may be determinant in protection against HIV sexual transmission. Therefore, defining Ab inhibitory functions that could lead to protection is critical for further HIV vaccine design. Here, we review different inhibitory properties of HIV-specific Abs and discuss their potential role in protection against HIV sexual transmission. PMID:24995008

  7. Lessons Learned from HIV Vaccine Clinical Efficacy Trials

    PubMed Central

    Day, Tracey A.; Kublin, James G.

    2014-01-01

    The past few years have witnessed many promising advances in HIV prevention strategies involving pre-exposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end. PMID:24033299

  8. Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model HIV/AIDS

    PubMed Central

    De Forni, D; Stevens, MR; Lori, F

    2010-01-01

    BACKGROUND AND PURPOSE Antiviral hyper-activation-limiting therapeutic agents (AV-HALTs) are a novel experimental drug class designed to both decrease viral replication and down-regulate excessive immune system activation for the treatment of chronic infections, including human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. VS411, a first-in-class AV-HALT, is a single-dosage form combining didanosine (ddI, 400 mg), an antiviral (AV), and hydroxyurea (HU, 600 mg), a cytostatic agent, designed to provide a slow release of ddI to reduce its maximal plasma concentration (Cmax) to potentially reduce toxicity while maintaining total daily exposure (AUC) and the AV activity. EXPERIMENTAL APPROACH This was a pilot phase I, open-label, randomized, single-dose, four-way crossover trial to investigate the fasted and non-fasted residual variance of AUC, Cmax and the oral bioavailability of ddI and HU, co-formulated as VS411, and administered as two different fixed-dose combination formulations compared to commercially available ddI (Videx EC) and HU (Hydrea) when given simultaneously. KEY RESULTS Formulation VS411-2 had a favourable safety profile, displayed a clear trend for lower ddI Cmax (P = 0.0603) compared to Videx EC, and the 90% confidence intervals around the least square means ratio of Cmax did not include 100%. ddI AUC? was not significantly decreased compared to Videx EC. HU pharmacokinetic parameters were essentially identical to Hydrea, although there was a decrease in HU exposure under fed versus fasted conditions. CONCLUSIONS AND IMPLICATIONS A phase IIa trial utilizing VS411-2 formulation has been fielded to identify the optimal doses of HU plus ddI as an AV-HALT for the treatment of HIV disease. PMID:20860662

  9. Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen--ANRS 111 trial

    PubMed Central

    Duval, Xavier; Mentré, France; Rey, Elisabeth; Auleley, Solange; Peytavin, Gilles; Biour, Michel; Métro, Annie; Goujard, Cecile; Taburet, Anne-Marie; Lascoux, Cecile; Panhard, Xaviere; Tréluyer, Jean-Marc; Salmon-Céron, Dominique

    2009-01-01

    Due to high inter-patient variability, and efficacy-concentration and toxicity-concentration relationships, optimization of HIV-protease inhibitor doses based on plasma concentrations could be beneficial. During a 48-week open prospective non-randomized interventional study of 115 protease inhibitor-naïve patients initiating an indinavir/ritonavir or lopinavir/ritonavir or nelfinavir containing therapy, protease inhibitor dose was modified when plasma trough concentrations (Ctrough) at week 2, 8, 16 and 24 were outside predefined optimal concentration ranges. Failure of the strategy was defined as the proportions of patients with HIV-RNA above 200 copies/ml from week 24 to 48 and/or experiencing grade 2, 3 or 4 PI-related adverse events during the study; proportion of patients with last Ctrough measurement outside the concentration range was determined at each visit. Virological failure and/or occurrence of adverse event were observed in 37/94 assessable patients (39% CI95%: 29.4–50.0). In the on-treatment analysis, failure of the strategy was noted in 16% of indinavir/r or lopinavir/r treated patients (8/51; CI95% 7.0–28.6; virological failure: 2; adverse event: 6) but in 44% of nelfinavir-treated patients (11/25; CI95%: 24.4–65.1; virological failure: 10; adverse event: 1); Ctrough concentrations outside the range were less frequent at the last measurement than at W2 (41% versus 66%; p < 0.05) with proportions of 35% for indinavir/r or lopinavir/r treated patients, but 57% for nelfinavir treated patients. The proposed strategy of therapeutic drug monitoring may be beneficial to indinavir/r and lopinavir/r-treated patients, but for nelfinavir failed to move concentrations into the predefined range and to produce the expected virological success. PMID:19709326

  10. Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen--ANRS 111 trial.

    PubMed

    Duval, Xavier; Mentré, France; Rey, Elisabeth; Auleley, Solange; Peytavin, Gilles; Biour, Michel; Métro, Annie; Goujard, Cecile; Taburet, Anne-Marie; Lascoux, Cecile; Panhard, Xaviere; Tréluyer, Jean-Marc; Salmon-Céron, Dominique

    2009-08-01

    As a result of high inter-patient variability, and efficacy-concentration and toxicity-concentration relationships, optimization of HIV-protease inhibitor (PI) doses based on plasma concentrations could be beneficial. During a 48-week open prospective non-randomized interventional study of 115 protease inhibitor-naïve patients initiating an indinavir/ritonavir- or lopinavir/ritonavir-, or nelfinavir-containing therapy, protease inhibitor dose was modified when plasma trough concentrations (C(trough)) at weeks 2, 8, 16 and 24 were outside predefined optimal concentration ranges. Failure of the strategy was defined as the proportions of patients with HIV-RNA above 200 copies/mL from weeks 24 to 48 and/or experiencing grades 2, 3 or 4 PI-related adverse events during the study; proportion of patients with last C(trough) measurement outside the concentration range was determined at each visit. Virological failure and/or occurrence of adverse event were observed in 37/94 assessable patients (39%; 95% CI: 29.4-50.0). In the on-treatment analysis, failure of the strategy was noted in 16% of indinavir/r- or lopinavir/r-treated patients (8/51; 95% CI: 7.0-28.6; virological failure: 2; adverse event: 6) but in 44% of nelfinavir-treated patients (11/25; 95% CI: 24.4-65.1; virological failure: 10; adverse event: 1); C(trough) concentrations outside the range were less frequent at the last measurement than at W2 (41% vs. 66%; P < 0.05), with proportions of 35% for indinavir/r- or lopinavir/r-treated patients, but 57% for nelfinavir-treated patients. The proposed strategy of therapeutic drug monitoring may be beneficial to indinavir/r- and lopinavir/r-treated patients, but failed to move concentrations into the predefined range and to produce the expected virological success for nelfinavir-treated patients. PMID:19709326

  11. An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections.

    PubMed

    Zapotoczna, Marta; McCarthy, Hannah; Rudkin, Justine K; O'Gara, James P; O'Neill, Eoghan

    2015-12-15

    High-level resistance to antimicrobial drugs is a major factor in the pathogenesis of chronic Staphylococcus aureus biofilm-associated, medical device-related infections. Antimicrobial susceptibility analysis revealed that biofilms grown for ?24 hours on biomaterials conditioned with human plasma under venous shear in iron-free cell culture medium were significantly more susceptible to antistaphylococcal antibiotics. Biofilms formed under these physiologically relevant conditions were regulated by SaeRS and dependent on coagulase-catalyzed conversion of fibrinogen into fibrin. In contrast, SarA-regulated biofilms formed on uncoated polystyrene in nutrient-rich bacteriological medium were mediated by the previously characterized biofilm factors poly-N-acetyl glucosamine, fibronectin-binding proteins, or autolytic activity and were antibiotic resistant. Coagulase-mediated biofilms exhibited increased antimicrobial resistance over time (>48 hours) but were always susceptible to dispersal by the fibrinolytic enzymes plasmin or nattokinase. Biofilms recovered from infected central venous catheters in a rat model of device-related infection were dispersed by nattokinase, supporting the important role of the biofilm phenotype and identifying a potentially new therapeutic approach with antimicrobials and fibrinolytic drugs, particularly during the early stages of device-related infection. PMID:26044292

  12. S100A12 and the S100/Calgranulins: Emerging Biomarkers for Atherosclerosis and Possibly Therapeutic Targets.

    PubMed

    Oesterle, Adam; Hofmann Bowman, Marion A

    2015-12-01

    Atherosclerosis is mediated by local and systematic inflammation. The multiligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell-targeted expression of S100A12 demonstrate increased coronary and aortic calcification, as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis-susceptible apolipoprotein E null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 apolipoprotein E null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis, and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis. PMID:26515415

  13. Changes in key constituents of clonally propagated Artemisia annua L. during preparation of compressed leaf tablets for possible therapeutic use

    PubMed Central

    Weathers, Pamela J.; Towler, Melissa J.

    2014-01-01

    Artemisia annua L., long used as a tea infusion in traditional Chinese medicine, produces artemisinin. Although artemisinin is currently used as artemisinin-based combination therapy (ACT) against malaria, oral consumption of dried leaves from the plant showed efficacy and will be less costly than ACT. Many compounds in the plant have some antimalarial activity. Unknown, however, is how these plant components change as leaves are processed into tablets for oral consumption. Here we compared extracts from fresh and dried leaf biomass with compressed leaf tablets of A. annua. Using GC-MS, nineteen endogenous compounds, including artemisinin and several of its pathway metabolites, nine flavonoids, three monoterpenes, a coumarin, and two phenolic acids, were identified and quantified from solvent extracts to determine how levels of these compounds changed during processing. Results showed that compared to dried leaves, artemisinin, arteannuin B, artemisinic acid, chlorogenic acid, scopoletin, chrysoplenetin, and quercetin increased or remained stable with powdering and compression into tablets. Dihydroartemisinic acid, monoterpenes, and chrysoplenol-D decreased with tablet formation. Five target compounds were not detectable in any of the extracts of this cultivar. In contrast to the individually measured aglycone flavonoids, using the AlCl3 method, total flavonoids increased nearly fivefold during the tablet formation. To our knowledge this is the first study documenting changes that occurred in processing dried leaves of A. annua into tablets. These results will improve our understanding of the potential use of not only this medicinal herb, but also others to afford better quality control of intact plant material for therapeutic use. PMID:25228784

  14. Phosphodiesterase-4 modulation as a potential therapeutic for cognitive loss in pathological and non-pathological aging: possibilities and pitfalls.

    PubMed

    Hansen, Rolf T; Zhang, Han-Ting

    2015-01-01

    Phosphodiesterases (PDEs) are a super family of 11 enzyme families responsible for the hydrolysis of the intracellular secondary messengers cyclic AMP (cAMP) and cyclic GMP (cGMP). PDE4, in particular, is highly expressed in brain regions involved with regulation of memory, anxiety, and depression, including the hippocampus, amygdala, and nucleus accumbens. Senescence has been shown to result in extreme dysregulation of the cAMP pathway in various brain regions. Thus, as a critical controller of intracellular cAMP levels, PDE4 may be a potential target for the treatment of senescence-related cognitive disorders, which could be pathological and/or non-pathological in origin. While there is great potential in the development of novel PDE4 inhibitors for treatment of senescent-cognition impairment, there are also currently many pitfalls that need to be overcome. PDE4 has four subfamilies (PDE4A, B, C, and D) that are differentially expressed throughout the brain and body, as well as at least 25 splice variants derived from alternative splicing and multiple promoter sites. PDE4 subtypes have been shown to have differential effects on behavior, and cAMP itself has also been shown to play a contrasting role in behavior in different brain regions. This review will focus on what is currently understood about PDE4 in aging, the potential for PDE4 modulation as a cognitive therapy, and current pitfalls and limitations that need to be overcome in the PDE4 field. Overall, furthering our understanding of this incredibly complex pathway may one day assist with the development of novel therapeutics for both pathological and non-pathological cognitive disorders associated with senescence. PMID:25159075

  15. Successful treatment of aplastic anaemia associated with HIV infection with eltrombopag: implications for a possible immunomodulatory role.

    PubMed

    Bart-Smith, Emily E; Kordasti, Shahram; Kulasekararaj, Austin G; Richardson, Daniel; Mufti, Ghulam J; Marsh, Judith C W

    2014-11-28

    We report the first successful treatment with the thrombopoietin receptor mimetic eltrombopag in a patient with severe aplastic anaemia (SAA) associated with HIV infection, thereby avoiding the use of standard immunosuppressive agents for treatment of SAA. Eltrombopag induced a trilineage haematological response. We also show that eltrombopag had an immunomodulatory role with a decrease in proinflammatory T helpers (Th1 and Th17 cells) with increased T-regulatory cell/T-helper ratio, thus contributing to recovery of haemopoiesis. PMID:25333665

  16. Schizotypy and leadership: a contrasting model for deficit symptoms, and a possible therapeutic role for sex hormones.

    PubMed

    Alias, A G

    2000-04-01

    Associational loosening, slow and faulty information processing, poor gating of irrelevant stimuli, poor ability to shift attention, poor working memory, passivity, ambivalence, anhedonia, and impaired motor coordination are cardinal features of schizophrenia but, unlike delusions and hallucinations, they are related more to negative/deficit symptoms. As summarized by Bass, numerous studies have correlated leadership with 'ambition, initiative and persistence' (opposite of passivity), 'speed and accuracy of thought', 'finality of decision,' or decisiveness (the opposite of ambivalence), 'mood control, optimism and sense of humor' (opposite of anhedonia), etc. Andreasen et al postulate that a disruption in the circuitry among nodes located in the prefrontal regions, the thalamic nuclei, and the cerebellum produces 'cognitive dysmetria', meaning difficulty in prioritizing, coordinating, and responding to information, and that it can account for the broad diversity of symptoms of schizophrenia. A relationship between cognitive processes and cerebellar and basal ganglia functions, and a role of neocerebellum in rapidly shifting attention, have been demonstrated. The cognitive styles, including a proficiency to quickly shift attention, of several famous leaders are used as examples of this contrasting model. Julius Caesar and Napoleon, for instance, could dictate to up to six secretaries simultaneously, using their exceptional working memories, and proficiency in quickly and effortlessly shifting attention while flawlessly gating irrelevant external and internal stimuli. It is suggested that specific brain imaging studies could illustrate this contrast. Gray et al noted positive correlations between 'dominance', an important leadership trait, and serum levels of dehydroepiandrosterone (DHEA) and testosterone (T), but not of more potent dihydrotestosterone (DHT), in over 1700 older men. Though not scientifically rigorous, the author noted positive correlations (P = 0.0162) between the self-rated ratings of voice depth (promoted by T) and of leadership, but none between those of body hair (DHT dependent) and of leadership in 47 male US National Academy of Sciences members. And 43 male US Senators had deeper voices than 36 male House members (P<0.01) who, in turn, had deeper voices than either of two groups (numbers 102 and 72) of male scientists (P<0.01). Therapeutically, before chlorpromazine, DHEA had been used in young schizophrenics with modest success in improving deficit symptoms. DHEA, or other sex hormones, or some of their natural and synthetic derivatives may prove to be valuable to treat deficit symptoms of schizophrenia in both sexes. PMID:10859637

  17. HIV Prevention

    MedlinePLUS

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  18. Increasing Obesity in Treated Female HIV Patients from Sub-Saharan Africa: Potential Causes and Possible Targets for Intervention

    PubMed Central

    McCormick, Claire L.; Francis, Arianne M.; Iliffe, Kim; Webb, Helen; Douch, Catherine J.; Pakianathan, Mark; Macallan, Derek C.

    2014-01-01

    Objectives: To investigate changing nutritional demographics of treated HIV-1-infected patients and explore causes of obesity, particularly in women of African origin. Methods: We prospectively reviewed nutritional demographics of clinic attenders at an urban European HIV clinic during four one-month periods at three-yearly intervals (2001, 2004, 2007, and 2010) and in two consecutive whole-year reviews (2010–2011 and 2011–2012). Risk-factors for obesity were assessed by multiple linear regression. A sub-study of 50 HIV-positive African female patients investigated body-size/shape perception using numerical, verbal, and pictorial cues. Results: We found a dramatic rise in the prevalence of obesity (BMI?>?30?kg/m2), from 8.5 (2001) to 28% (2011–2012) for all clinic attenders, of whom 86% were on antiretroviral treatment. Women of African origin were most affected, 49% being obese, with a further 32% overweight (BMI 25–30?kg/m2) in 2012. Clinical factors strongly associated with obesity included female gender, black African ethnicity, non-smoking, age, and CD4 count (all P?

  19. Intranasal Administration of a Therapeutic HIV Vaccine (Vacc-4x) Induces Dose-Dependent Systemic and Mucosal Immune Responses in a Randomized Controlled Trial

    PubMed Central

    Brekke, Kristin; Lind, Andreas; Holm-Hansen, Carol; Haugen, Inger Lise; Sørensen, Birger; Sommerfelt, Maja; Kvale, Dag

    2014-01-01

    Background Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant. Methods Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-?. Results Vacc-4x proliferative T cell responses increased only among the vaccinated (p?0.031). The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p?=?0.037) and developed larger DTH (p?=?0.005) than the adjuvant group. Rectal (distal) Vacc-4x IgA and IgG antibodies also increased (p?=?0.043) in this group. In contrast, the high dose generated higher nasal (local) Vacc-4x IgA (p?=?0.028) and serum IgG (p?=?0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r?=??0.82, p<0.001) and high regulation (r?=?0.61, p?=?0.010) at baseline. Conclusion Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation. Trial Registration ClinicalTrials.gov NCT01473810 PMID:25398137

  20. Potentiation of cytotoxicity of paclitaxel in combination with Cl-IB-MECA in human C32 metastatic melanoma cells: A new possible therapeutic strategy for melanoma.

    PubMed

    Soares, Ana S; Costa, Vera M; Diniz, Carmen; Fresco, Paula

    2013-10-01

    Metastatic melanoma monotherapies with drugs such as dacarbazine, cisplatin or paclitaxel (PXT) are associated with significant toxicity and low efficacy rates. These facts reinforce the need for development of novel agents or combinatory strategies. Cl-IB-MECA is a small molecule, orally bioavailable, well tolerated and currently under clinical trials as an anticancer agent. Our aim was to investigate a possible combinatory therapeutic strategy using PXT and Cl-IB-MECA on human C32 melanoma cells and its underlying mechanisms. Cytotoxicity was evaluated using MTT reduction, lactate dehydrogenase leakage and neutral red uptake assays, for different concentrations and combinations of both agents, at 24 and 48 h. Apoptosis was also assessed using fluorescence microscopy and through the evaluation of caspases 8, 9, and 3 activities. We demonstrated, for the first time, that combination of PXT and Cl-IB-MECA significantly increases cytotoxicity for clinically relevant concentrations. This combination seems to act synergistically in disrupting membrane integrity, but also causing lysosomal and mitochondrial dysfunction. When using the lowest PTX concentration (10 ng/mL), co-incubation with CI-IB-MECA (micromolar concentrations) potentiated overall cytotoxic effects and morphological signs of apoptosis. All combinations studied enhanced caspase 8, 9, and 3 activities, suggesting the involvement of both intrinsic and extrinsic apoptotic pathways. The possibility that cytotoxicity elicited by Cl-IB-MECA, alone or in combination with PXT, involves adenosine receptor activation was discarded and results confirmed that oxidative stress is only involved in cytotoxicity after treatment with PXT, alone. Being melanoma a very apoptosis-resistance cancer, this combination seems to hold promise as a new therapeutic strategy for melanoma. PMID:24035253

  1. Damaging the Integrated HIV Proviral DNA with TALENs

    PubMed Central

    Strong, Christy L.; Guerra, Horacio P.; Mathew, Kiran R.; Roy, Nervik; Simpson, Lacy R.; Schiller, Martin R.

    2015-01-01

    HIV-1 integrates its proviral DNA genome into the host genome, presenting barriers for virus eradication. Several new gene-editing technologies have emerged that could potentially be used to damage integrated proviral DNA. In this study, we use transcription activator-like effector nucleases (TALENs) to target a highly conserved sequence in the transactivation response element (TAR) of the HIV-1 proviral DNA. We demonstrated that TALENs cleave a DNA template with the HIV-1 proviral target site in vitro. A GFP reporter, under control of HIV-1 TAR, was efficiently inactivated by mutations introduced by transfection of TALEN plasmids. When infected cells containing the full-length integrated HIV-1 proviral DNA were transfected with TALENs, the TAR region accumulated indels. When one of these mutants was tested, the mutated HIV-1 proviral DNA was incapable of producing detectable Gag expression. TALEN variants engineered for degenerate recognition of select nucleotide positions also cleaved proviral DNA in vitro and the full-length integrated proviral DNA genome in living cells. These results suggest a possible design strategy for the therapeutic considerations of incomplete target sequence conservation and acquired resistance mutations. We have established a new strategy for damaging integrated HIV proviral DNA that may have future potential for HIV-1 proviral DNA eradication. PMID:25946221

  2. Therapeutic effects of minocycline on mild-to-moderate depression in HIV patients: a double-blind, placebo-controlled, randomized trial.

    PubMed

    Emadi-Kouchak, Hamid; Mohammadinejad, Payam; Asadollahi-Amin, Ali; Rasoulinejad, Mehrnaz; Zeinoddini, Atefeh; Yalda, Alireza; Akhondzadeh, Shahin

    2016-01-01

    Patients with the HIV infection are at high risk for developing depression. The aim of this study was to investigate the safety and efficacy of antidepressant effects of minocycline on HIV patients with depression. Forty-six HIV patients, with mild-to-moderate depression and a Hamilton Depression Rating Scale (HDRS) up to 18, participated in a parallel, randomized, double-blind, placebo-controlled trial and underwent 6 weeks of treatment with either minocycline (100?mg twice daily) or placebo in the same manner. Patients were assessed using HDRS at baseline and at weeks 3 and 6. The primary outcome measure was to evaluate the efficacy of minocycline in improving depressive symptoms. General linear model repeated measures showed significant effect for time×treatment interaction on the HDRS score during the trial course [F(2,?88)=7.50, P=0.001]. There was no significant difference between the two groups regarding adverse events. No serious adverse event was reported. The administration of 100?mg minocycline twice daily seems to be safe and effective in improving depressive symptoms in HIV/AIDS patients with mild-to-moderate depression. PMID:26465919

  3. HIV-1 Proteins, Tat and gp120, Target the Developing Dopamine System

    PubMed Central

    Fitting, Sylvia; Booze, Rosemarie M.; Mactutus, Charles F.

    2015-01-01

    In 2014, 3.2 million children (< 15 years of age) were estimated to be living with HIV and AIDS worldwide, with the 240,000 newly infected children in the past year, i.e., another child infected approximately every two minutes [1]. The primary mode of HIV infection is through mother-to-child transmission (MTCT), occurring either in utero, intrapartum, or during breastfeeding. The effects of HIV-1 on the central nervous system (CNS) are putatively accepted to be mediated, in part, via viral proteins, such as Tat and gp120. The current review focuses on the targets of HIV-1 proteins during the development of the dopamine (DA) system, which appears to be specifically susceptible in HIV-1-infected children. Collectively, the data suggest that the DA system is a clinically relevant target in chronic HIV-1 infection, is one of the major targets in pediatric HIV-1 CNS infection, and may be specifically susceptible during development. The present review discusses the development of the DA system, follows the possible targets of the HIV-1 proteins during the development of the DA system, and suggests potential therapeutic approaches. By coupling our growing understanding of the development of the CNS with the pronounced age-related differences in disease progression, new light may be shed on the neurological and neurocognitive deficits that follow HIV-1 infection. PMID:25613135

  4. A Randomized Clinical Trial Evaluating Therapeutic Drug Monitoring (TDM) for Protease Inhibitor–Based Regimens in Antiretroviral-Experienced HIV-Infected Individuals: Week 48 Results of the A5146 Study

    PubMed Central

    Albrecht, Mary; Mukherjee, A. Lisa; Tierney, Camlin; Morse, Gene D.; Dykes, Carrie; Klingman, Karin L.; Demeter, Lisa M.

    2012-01-01

    Background We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI-experienced patients with treatment failure. Secondary analyses through 48 weeks are presented. Methods Eligible HIV-infected subjects with a screening viral load of ?1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2. Subjects with an NIQ ?1 were randomized at week 4 to a standard-of-care (SOC) arm or TDM arm featuring PI dose escalation. Results One hundred and eighty-three subjects were randomized. There was no significant treatment difference in change from randomization to week 48 in HIV-1 RNA [P = .13, median (25th, 75th percentile log10 copies/mL change): ?0.03 (?0.74, 0.62) with TDM and 0.11 (?2.3, 0.82) with SOC]. In subgroup analysis, patients with ?0.69 active PIs benefited from TDM compared to those with <0.69 active PIs (P = .05). Conclusions While the TDM strategy of PI dose escalation did not improve virologic response at week 48 overall, in subgroup analysis, TDM favorably impacted virologic outcome in subjects taking PI-based regimens with moderate antiviral activity. PMID:22044856

  5. Potential anti-HIV agents from marine resources: an overview.

    PubMed

    Vo, Thanh-Sang; Kim, Se-Kwon

    2010-01-01

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great deal of interest has been expressed regarding marine-derived anti-HIV agents such as phlorotannins, sulfated chitooligosaccharides, sulfated polysaccharides, lectins and bioactive peptides. This contribution presents an overview of anti-HIV therapeutics derived from marine resources and their potential application in HIV therapy. PMID:21339954

  6. Potential Anti-HIV Agents from Marine Resources: An Overview

    PubMed Central

    Vo, Thanh-Sang; Kim, Se-Kwon

    2010-01-01

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great deal of interest has been expressed regarding marine-derived anti-HIV agents such as phlorotannins, sulfated chitooligosaccharides, sulfated polysaccharides, lectins and bioactive peptides. This contribution presents an overview of anti-HIV therapeutics derived from marine resources and their potential application in HIV therapy. PMID:21339954

  7. HIV Symptoms

    MedlinePLUS

    ... Submit Home > HIV/AIDS > What is HIV/AIDS? HIV/AIDS This information in Spanish ( en español ) HIV symptoms Photo courtesy of AIDS.gov Facing AIDS ... and brain Return to top More information on HIV symptoms Explore other publications and websites Basic Information ...

  8. Emerging Principles for the Therapeutic Exploitation of

    E-print Network

    Emerging Principles for the Therapeutic Exploitation of Glycosylation Martin Dalziel, Max Crispin-inflammatories. The development of therapeutic glycopro- teins has been greatly stimulated by the advances in recombinant cellular humoral and cellular immunity. Additionally, the HIV glycan shield is proving to be an effective target

  9. Stages of HIV Infection

    MedlinePLUS

    ... HIV Infection Translate Text Size Print Stages of HIV Infection How Does HIV Progress In Your Body? Without treatment, HIV advances ... are the three stages of HIV infection: Acute HIV Infection Stage Within 2-4 weeks after HIV ...

  10. Addressing Ebola-related Stigma: Lessons Learned from HIV/AIDS

    PubMed Central

    Davtyan, Mariam; Brown, Brandon; Folayan, Morenike Oluwatoyin

    2014-01-01

    Background HIV/AIDS and Ebola Virus Disease (EVD) are contemporary epidemics associated with significant social stigma in which communities affected suffer from social rejection, violence, and diminished quality of life. Objective To compare and contrast stigma related to HIV/AIDS and EVD, and strategically think how lessons learned from HIV stigma can be applied to the current EVD epidemic. Methods To identify relevant articles about HIV/AIDS and EVD-related stigma, we conducted an extensive literature review using multiple search engines. PubMed was used to search for relevant peer-reviewed journal articles and Google for online sources. We also consulted the websites of the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and the National Institutes of Health to retrieve up-to-date information about EVD and HIV/AIDS. Results Many stigmatizing attitudes and behaviors directed towards those with EVD are strikingly similar to those with HIV/AIDS but there are significant differences worthy of discussion. Both diseases are life-threatening and there is no medical cure. Additionally misinformation about affected groups and modes of transmission runs rampant. Unlike in persons with EVD, historically criminalized and marginalized populations carry a disproportionately higher risk for HIV infection. Moreover, mortality due to EVD occurs within a shorter time span as compared to HIV/AIDS. Conclusions Stigma disrupts quality of life, whether it is associated with HIV infection or EVD. When addressing EVD, we must think beyond the immediate clinical therapeutic response, to possible HIV implications of serum treatment. There are emerging social concerns of stigma associated with EVD infection and double stigma associated with EVD and HIV infection. Drawing upon lessons learned from HIV, we must work to empower and mobilize prominent members of the community, those who recovered from the disease, and organizations working at the grassroots level to disseminate clear and accurate information about EVD transmission and prevention while promoting stigma reduction in the process. In the long run, education, prevention, and a therapeutic vaccine will be the optimal solutions for reducing the stigma associated with both EVD and HIV. PMID:25382685

  11. Immunotherapy with an HIV-DNA Vaccine in Children and Adults

    PubMed Central

    Palma, Paolo; Gudmundsdotter, Lindvi; Finocchi, Andrea; Eriksson, Lars E.; Mora, Nadia; Santilli, Veronica; Aquilani, Angela; Manno, Emma C.; Zangari, Paola; Romiti, Maria Luisa; Montesano, Carla; Grifoni, Alba; Brave, Andreas; Ljungberg, Karl; Blomberg, Pontus; Bernardi, Stefania; Sandström, Eric; Hejdeman, Bo; Rossi, Paolo; Wahren, Britta

    2014-01-01

    Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals’ immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children’s and adults’ responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4–16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected. PMID:26344746

  12. Universal Tre (uTre) recombinase specifically targets the majority of HIV-1 isolates.

    PubMed

    Karpinski, Janet; Chemnitz, Jan; Hauber, Ilona; Abi-Ghanem, Josephine; Paszkowski-Rogacz, Maciej; Surendranath, Vineeth; Chakrabort, Debojyoti; Hackmann, Karl; Schröck, Evelin; Pisabarro, María Teresa; Hauber, Joachim; Buchholz, Frank

    2014-01-01

    Current drugs against HIV can suppress the progression to AIDS but cannot clear the patient from the virus. Because of potential side effects of these drugs and the possible development of drug resistance, finding a cure for HIV infection remains a high priority of HIV/AIDS research. We recently generated a recombinase (termed Tre) tailored to efficiently eradicate the provirus from the host genome of HIV-1 infected cells by specifically targeting a sequence that is present in the long terminal repeats (LTRs) of the viral DNA [1]. In vivo analyses in HIV-infected humanized mice demonstrated highly significant antiviral effects of Tre recombinase [2]. However, the fact that Tre recognizes a particular HIV-1 subtype A strain may limit its broad therapeutic application. To advance our Tre-based strategy towards a universally efficient cure, we have engineered a new, universal recombinase (uTre) applicable to the majority of HIV-1 infections by the various virus strains and subtypes. We employed the search tool SeLOX [3] in order to find a well-conserved HIV-1 proviral sequence that could serve as target site for a universal Tre from sequences compiled in the Los Alamos HIV Sequence Database. We selected a candidate (termed loxLTRu) with a mean conservation rate of 94% throughout the major HIV-1 subtype groups A, B and C. We applied loxLTRu as substrate in our established substrate-linked protein evolution (SLiPE) process [4] and evolved the uTre recombinase in 142 evolution cycles. Highly specific enzymatic activity on loxLTRu is demonstrated for uTre in both Escherichia coli and human cells. Naturally occurring viral variants with single mutations within the loxLTRu sequence are also shown to be efficiently targeted by uTre, further increasing the range of applicability of the recombinase. Potential off-target sites in the human genome are not recombined by uTre. Furthermore, uTre expression in primary human T cells shows no obvious Tre-related cytopathic or genotoxic effects. Finally, uTre expressing mice show no undesired phenotypes during their normal lifespan. We have developed a broad-range HIV-1 LTR specific recombinase that has the potential to be effective against the vast majority of HIV-1 strains and to cure HIV-1 infected cells from the infection. These results strongly encouraged us in our confidence that a Tre recombinase-mediated HIV eradication strategy may become a valuable component of a future therapy for HIV-infected patients. PMID:25397454

  13. HIV-1 Entry Inhibitor

    Cancer.gov

    Soluble forms (sCD4) of human CD4, the HIV-1 primary receptor, are potent HIV-1 entry inhibitors. Both four-domain (D1-4) and two-domain (D1D2) sCD4 and their fusion proteins have been tested as candidate therapeutics in animal models and in human clinical trials and were well tolerated by patients with no significant clinical or immunologic toxicities and exhibited significant inhibitory activities. However, their activities were transient and the virus rapidly rebound.

  14. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K. (Idaho Falls, ID)

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  15. Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

    PubMed

    Bianchi, Enrica; Taurone, Samanta; Bardella, Lia; Signore, Alberto; Pompili, Elena; Sessa, Vincenzo; Chiappetta, Caterina; Fumagalli, Lorenzo; Di Gioia, Cira; Pastore, Francesco S; Scarpa, Susanna; Artico, Marco

    2015-10-01

    Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-?1, interleukin (IL)-1? and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-?1, IL-1? and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-?1, IL-1? and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD). PMID:26201022

  16. YC-1 reduces placental sFlt-1 and soluble endoglin production and decreases endothelial dysfunction: A possible therapeutic for preeclampsia.

    PubMed

    Brownfoot, Fiona C; Tong, Stephen; Hannan, Natalie J; Hastie, Roxanne; Cannon, Ping; Tuohey, Laura; Kaitu'u-Lino, Tu'uhevaha J

    2015-09-15

    Preeclampsia is a serious complication of pregnancy with no medical treatment. It is caused by intermittent placental hypoxia and release of sFlt-1 and soluble endoglin, leading to wide spread maternal endothelial dysfunction and multisystem organ injury. YC-1 is a guanylyl cyclase activator and HIF1? inhibitor developed for use in hypertension and atherosclerosis. We examined whether YC-1 reduces sFlt-1 and sENG secretion and reverses endothelial dysfunction in primary human tissues. YC-1 significantly reduced sFlt-1 and sENG secretion from human umbilical vein endothelial cells, purified primary trophoblast cells and placental explants taken from patients with preterm preeclampsia. This was concordant with reduced HIF1? expression. YC-1 also reversed TNF? induced endothelial dysfunction, including reduced vascular cell adhesion molecule 1 expression and monocyte adhesion to primary endothelial cells. We conclude YC-1 decreases placental production of sFlt-1 and sENG and decreases endothelial dysfunction. It is a novel therapeutic candidate for preeclampsia. PMID:26159901

  17. Allicin as a possible adjunctive therapeutic drug for stage II oral submucous fibrosis: a preliminary clinical trial in a Chinese cohort.

    PubMed

    Jiang, X; Zhang, Y; Li, F; Zhu, Y; Chen, Y; Yang, S; Sun, G

    2015-12-01

    The objective of this study was to investigate the efficacy and safety of allicin in the treatment of stage II oral submucous fibrosis (OSF) in a Chinese patient cohort. A randomized clinical trial was performed. Triamcinolone acetonide (TA) or allicin was injected intralesionally weekly for 16 weeks. Improvements in mouth opening, burning sensation, and oral health-related quality of life were evaluated. Forty-eight subjects completed the study without obvious adverse reactions. At 40 weeks, the net gain in mouth opening was 2.27±0.84mm in the TA group and 5.16±1.04mm in the allicin group. Burning sensation improved by 2.79±0.87 in the TA group and by 4.33±1.04 in the allicin group. The OHIP-14 score improved by 4.67±2.94 in the TA group and by 12.58±9.82 in the allicin group. Allicin intralesional injections improved mouth opening, burning sensation, and oral health-related quality of life in these stage II OSF patients. Allicin appears to be a potential adjunctive therapeutic drug. PMID:26165773

  18. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    PubMed Central

    Reddy, Pichili Vijaya Bhaskar; Pilakka-Kanthikeel, Sudheesh; Saxena, Shailendra K.; Saiyed, Zainulabedin; Nair, Madhavan P. N.

    2012-01-01

    HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB). Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population. PMID:22666564

  19. Retinal pigment epithelial cells secrete neurotrophic factors and synthesize dopamine: possible contribution to therapeutic effects of RPE cell transplantation in Parkinson's disease

    PubMed Central

    Ming, Ming; Li, Xuping; Fan, Xiaolan; Yang, Dehua; Li, Liang; Chen, Sheng; Gu, Qing; Le, Weidong

    2009-01-01

    Background New strategies for the treatment of Parkinson's disease (PD) are shifted from dopamine (DA) replacement to regeneration or restoration of the nigro-striatal system. A cell therapy using human retinal pigment epithelial (RPE) cells as substitution for degenerated dopaminergic (DAergic) neurons has been developed and showed promising prospect in clinical treatment of PD, but the exact mechanism underlying this therapy is not fully elucidated. In the present study, we investigated whether the beneficial effects of this therapy are related to the trophic properties of RPE cells and their ability to synthesize DA. Methods We evaluated the protective effects of conditioned medium (CM) from cultured RPE cells on the DAergic cells against 6-hydroxydopamine (6-OHDA)- and rotenone-induced neurotoxicity and determined the levels of glial cell derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) released by RPE cells. We also measured the DA synthesis and release. Finally we transplanted microcarriers-RPE cells into 6-OHDA lesioned rats and observed the improvement in apomorphine-induced rotations (AIR). Results We report here: (1) CM from RPE cells can secret trophic factors GDNF and BDNF, and protect DAergic neurons against the 6-OHDA- and rotenone-induced cell injury; (2) cultured RPE cells express L-dopa decarboxylase (DDC) and synthesize DA; (3) RPE cells attached to microcarriers can survive in the host striatum and improve the AIR in 6-OHDA-lesioned animal model of PD; (4) GDNF and BDNF levels are found significantly higher in the RPE cell-grafted tissues. Conclusion These findings indicate the RPE cells have the ability to secret GDNF and BDNF, and synthesize DA, which probably contribute to the therapeutic effects of RPE cell transplantation in PD. PMID:19558709

  20. HIV among Women

    MedlinePLUS

    ... you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | Subscribe ... Get Email Updates on HIV Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV ...

  1. HIV Transmission

    MedlinePLUS

    ... HIV-negative partner. HIV is not spread through saliva. Learn more about how to protect yourself and ... not spread by Mosquitoes, ticks, or other insects. Saliva, tears, or sweat that is not mixed with ...

  2. HIV/AIDS and Pregnancy

    MedlinePLUS

    If you have HIV/AIDS and find out you are pregnant or think you may be pregnant, you should let your health care provider know as soon as possible. Some HIV/AIDS medicines may harm your baby. Your health care ...

  3. [A possible therapeutic improvement of the antibacterial effect by monitoring the production of leukocyte free oxygen radicals during antibiotic treatment of infertile patients with chronic bacterial prostatitis].

    PubMed

    Vicari, E; Sidoti, G; Mongioì, A

    1996-04-01

    In the male chronic accessory gland bacterial infections (AGBI), antibiotic treatment (AT) efficacy usually evaluates the antimicrobial outcome through one or more spermiocolture (SC) become negative. Recently, bacterial olipeptide fMPL has been used to detect a specific Radical Oxygen Species production by leukocytes (L-RLO), even when they are present at low concentrations in sperm fractions specimens. In the male AGBI could be present endogenous fMLP at sufficient levels to produce L chemiotaxis in the semen, and secondly active their specific L-RLO production, till when bacteriospermia remained positive. In the Percoll 50% (Pc50%) fraction, at higher L concentrations, from 22 infertile patients affected by chronic bacterial prostatitis (BP) and enrolled to a randomly AT treatment with a Quinolone (n = 12) or a Macrolide (n = 10), through two secondary milestones (possible elevated basal L-RLO in the pre-treatment, T0; significant changes in the basal and fMLP-stimulated L-RLO production within each treatment group and between groups), we would verify if a normalized L-RLO production could be taken as break-point for the AT withdrawal before checking SC for control. Indeed, in T0 all patients had positive SC and exhibited both basal and fMLP-stimulated L-RLO levels higher than those observed in 2 control groups (group cA = 10 fertile men, without chronic BP; group cB = 10 patients affected by chronic abacterial prostatitis (AP). On the 3rd AT cycle for 14 days, together in 20/22 AT-treated patients, basal and fMLP-stimulated L-RLO levels become low or normal, as well as their SCs become negative (CFU/ml = 0), whilst in a third control group (group cC) of 10 not-AT-treated BP patients, through matched-follow-up observations, these L-RLO values were always elevated and their SC remained positive (CFU/ml > or = 10(5)). In chronic BP patients, AT seems to demonstrate both antimicrobial effectiveness and reduction of L-RLO production with values similar to those of control group cA. The monitored L-RLO values during AT could be useful in order to ottimize antimicrobial effect: this tool being able to previse SC outcome, could be assumed to define clearly AT break-point and/or cycle numbers. PMID:8713566

  4. Apolipoprotein L1 (APOL1) Variants (Vs) a possible link between Heroin-associated Nephropathy (HAN) and HIV-associated Nephropathy (HIVAN)

    PubMed Central

    Lan, Xiqian; Rao, T. K. S.; Chander, Praveen N.; Skorecki, Karl; Singhal, Pravin C.

    2015-01-01

    In 1970s, Heroin-associated Nephropathy (HAN), one form of focal and segmental glomerulosclerosis (FSGS), was a predominant cause of End-stage Kidney Disease (ESKD) in African-Americans (AAs). In 1980s, with the surge of Acquired Immune Deficiency Syndrome (AIDS) in AAs, HAN more or less disappeared, and the incidence of Human Immunodeficiency Virus associated Nephropathy (HIVAN) markedly increased. Recent studies in AAs have identified APOL1 variants (Vs) as a major risk factor for the development and progression of non-diabetic kidney diseases including idiopathic FSGS and hypertension-attributed nephrosclerosis. These observations have also offered partial insights into the mechanisms of development, and higher rate of occurrence of both HAN and HIVAN in AAs. AAs with APOL1Vs develop idiopathic FSGS at four-fold higher rate compared to European Americans (EAs). Similarly, HIV infected AAs with APOL1Vs (if not on antiviral therapy), risk a 50% (10-fold greater) chance of developing HIVAN. It has been suggested that APOL1Vs expression may render podocytes more vulnerable to various types of injury: bacterial, viral, and others. However, in addition to genetic variants, additional factors such as persistence of a second hit may determine the nature and severity of glomerular disease. In patients with HAN, heroin or contaminants may have been the offending second insult(s) which caused renal disease in susceptible AA patients. In the 80's, since heroin-induced second hit was neither consistent nor sustained (depending on drug availability in the street), the disease was masked or replaced HIV infected patients (especially in untreated subjects), by an overwhelming second hit by the virus which was both intense as well as persistent. It appears that APOL1Vs may be one of the links between the disappearance of HAN and emergence of HIVAN in AA patients. PMID:26106375

  5. HIV and Atherosclerosis

    MedlinePLUS

    ... Pressure High Blood Pressure Tools & Resources Stroke More HIV and Atherosclerosis Updated:Jan 22,2014 Featured Video ... improve your cholesterol ratios, with or without HIV. HIV and Your Heart • Home • About HIVHIV and ...

  6. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  7. Dendritic cell based vaccines for HIV infection

    PubMed Central

    García, Felipe; Plana, Montserrat; Climent, Nuria; León, Agathe; Gatell, Jose M; Gallart, Teresa

    2013-01-01

    Dendritic cells have a central role in HIV infection. On one hand, they are essential to induce strong HIV-specific CD4+ helper T-cell responses that are crucial to achieve a sustained and effective HIV-specific CD8+ cytotoxic T-lymphocyte able to control HIV replication. On the other hand, DCs contribute to virus dissemination and HIV itself could avoid a correct antigen presentation. As the efficacy of immune therapy and therapeutic vaccines against HIV infection has been modest in the best of cases, it has been hypothesized that ex vivo generated DC therapeutic vaccines aimed to induce effective specific HIV immune responses might overcome some of these problems. In fact, DC-based vaccine clinical trials have yielded the best results in this field. However, despite these encouraging results, functional cure has not been reached with this strategy in any patient. In this Commentary, we discuss new approaches to improve the efficacy and feasibility of this type of therapeutic vaccine. PMID:23912672

  8. The role of non-nucleoside reverse transcriptase inhibitors in children with HIV-1 infection.

    PubMed

    Maddocks, S; Dwyer, D

    2001-01-01

    Over 1.4 million of the worlds' children are infected with HIV-1, mostly acquired in the perinatal period. Antiviral therapeutic options for children with HIV-1 infection have lagged behind those for infected adults. However, we now know that prevention of perinatal HIV-1 transmission to children is possible and that combination therapy for the management of infected children is efficacious. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are developing a more prominent role in combination therapy regimens, particularly as alternatives to protease inhibitors. They also have a role in preventing perinatal transmission, where it has been shown that only 2 doses of the NNRTI nevirapine can significantly reduce mother-to-child transmission of HIV-1. This has major therapeutic implications, particularly in areas where combination therapy is not readily available. Palatable paediatric formulations of NNRTIs are available or are being developed. Whilst pharmacokinetic data regarding the use of antiretrovirals in children remain scarce, published clinical trials have demonstrated the efficacy of NNRTIs when used as part of combination regimens in the management of HIV-1 infected children. The toxicity profile of NNRTIs is relatively favourable; however, severe skin rash, hepatotoxicity and central nervous system adverse effects with various NNRTIs can lead to treatment cessation. The development of class resistance with single step mutations in the reverse transcriptase gene remains a major therapeutic problem with this class of antiretrovirals. Novel NNRTIs under development are of interest either because of improved pharmacodynamics, reduced toxicity profiles or because of action against NNRTI-mutation containing resistant virus. There are no data available yet on the use of these drugs in the paediatric population. PMID:11688599

  9. Get Tested for HIV

    MedlinePLUS

    ... Submit Home > HIV/AIDS > Get tested for HIV HIV/AIDS This information in Spanish ( en español ) Get tested for HIV When should I get tested for HIV? Types ... to top More information on Get tested for HIV Explore other publications and websites HIV Anonymous Testing, ...

  10. Evaluation of cystatin C activities against HIV

    PubMed Central

    Vernekar, Vandana; Velhal, Shilpa; Bandivdekar, Atmaram

    2015-01-01

    Background & objectives: Several host defense proteins known to possess antimicrobial activities are present on mucosal surfaces and are consequently found in body fluids of vertebrates. Naturally occurring protease inhibitors like cystatins, especially cystatin C (cys C), are abundantly present in human seminal plasma. Although its antiviral activity against herpes simplex virus (HSV) has been demonstrated, the role of this protein against HIV is not well studied. Therefore, the aim of the present study was to evaluate the anti-HIV activities of cys C, which is present innately in the male reproductive tract. Methods: Protein-protein interaction of cys C with various HIV proteins was studied using a commercially available HIV blot and specific interaction with HIV protease was studied by dot-blot technique using commercially available cys C. To purify biologically active cys C from human seminal plasma to be used for subsequent experiments, gel-permeation chromatography followed by affinity chromatography was used. The HIV infectivity inhibition activity of the purified cystatin C was tested in TZM-bl cells. To study its activity on HIV protease, time-course enzyme kinetics studies were performed using spectrometric assay. Results: Cystatin C reacted with some HIV proteins including HIV protease. Biologically active cys C was purified using gel permeation chromatography followed by affinity chromatography. When tested in TZM-bl cells, purified cystatin C demonstrated HIV-infectivity inhibitory activity (IC50: 0.28 ?M). Enzyme kinetic studies demonstrated that it abrogated the action of HIV protease on its substrate. Interpretation & conclusions: The present data demonstrate that cystatin C possesses anti-HIV activities. Molecular models need to be designed with this protein which would assist towards prevention/therapeutics against HIV. PMID:26112843

  11. HIV-1 Coreceptor Usage Assessment by Ultra-Deep Pyrosequencing and Response to Maraviroc

    PubMed Central

    Rodriguez, Christophe; Soulié, Cathia; Marcelin, Anne-Geneviève; Calvez, Vincent; Descamps, Diane; Charpentier, Charlotte; Flandre, Philippe; Recordon-Pinson, Patricia; Bellecave, Pantxika; Pawlotsky, Jean-Michel

    2015-01-01

    Background Maraviroc is an HIV entry inhibitor that alters the conformation of CCR5 and is poorly efficient in patients infected by viruses that use CXCR4 as an entry coreceptor. The goal of this study was to assess the capacity of ultra-deep pyrosequencing (UDPS) and different data analysis approaches to characterize HIV tropism at baseline and predict the therapeutic outcome on maraviroc treatment. Methods 113 patients with detectable HIV-1 RNA on HAART were treated with maraviroc. The virological response was assessed at months 1, 3 and 6. The sequence of the HIV V3 loop was determined at baseline and prediction of maraviroc response by different software and interpretation algorithms was analyzed. Results UDPS followed by analysis with the Pyrotrop software or geno2pheno algorithm provided better prediction of the response to maraviroc than Sanger sequencing. We also found that the H34Y/S substitution in the V3 loop was the strongest individual predictor of maraviroc response, stronger than substitutions at positions 11 or 25 classically used in interpretation algorithms. Conclusions UDPS is a powerful tool that can be used with confidence to predict maraviroc response in HIV-1-infected patients. Improvement of the predictive value of interpretation algorithms is possible and our results suggest that adding the H34S/Y substitution would substantially improve the performance of the 11/25/charge rule. PMID:26068869

  12. The HIV entry inhibitors revisited.

    PubMed

    Leonard, J Thomas; Roy, Kunal

    2006-01-01

    The new generation of antiviral drugs intended to counter HIV-1 entry into susceptible cells is emerging swiftly. The antiviral agents that inhibit HIV entry to the target cells (denoted as HIV entry inhibitors) are already in different phases of clinical trials. Operating early in the viral life cycle, they prevent viral entry, and have a novel, highly specific mechanism of action with a low toxicity profile. Entry inhibitors have different toxicity and resistance profiles than the existing reverse transcriptase and protease inhibitors. Some of these compounds demonstrated in vitro synergism with other classes of antivirals, thus offering the rationale for their combination in therapies for HIV-infected individuals. It is worth focusing on recent developments in HIV entry inhibitors, as most of the current drug regimens suffer from the events of developing resistance against existing combination therapies. Recent advances in the understanding of the cellular and molecular mechanisms of HIV-1 entry provide the basis for novel therapeutic strategies that prevent viral penetration of the target cell-membrane, while reducing detrimental virus and treatment effects on cells and prolonging virion exposure to immune defenses. A number of potential sites for therapeutic intervention become accessible during the narrow window between virus attachment and the subsequent fusion of viral envelope with the cell membrane. The HIV-1 coreceptors are particularly attractive from the perspective of identifying new antiviral compounds, since they are seven-transmembrane motif G protein-coupled receptors (GPCRs), a family of proteins that is a well-validated target for drug development. Among the many chemokine receptors that can mediate HIV-1 entry in vitro, only CCR5 and CXCR4 are of frontline pharmacological importance. In particular, CCR5 is essential for viral transmission and replication during the early and clinically latent phase of disease. Several small-molecule antagonists of CCR5 and CXCR4 that block chemokine binding and HIV-1 entry have been identified in recent years. Considerable advances have been made in the last years in the design of derivatives acting as inhibitors of HIV entry. The molecular mechanism involved in viral entry, the structural and functional aspects of entry inhibitors are reviewed here. We have also summarized the recent insights into how small-molecule antagonists interact with CCR5 and CXCR4, focusing on drug development programs that are well documented in the scientific literature. An overview of the entry inhibitors that are in preclinical or early clinical development, and the Quantitative Structure-Activity Relationships (QSAR) studies reported for the coreceptor antagonists are also be presented. PMID:16611075

  13. Hepatitis B and HIV

    MedlinePLUS

    ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latino AIDS ... of Opportunistic Infections in HIV-Infected Adults and Adolescents , HRSA’s Clinical Guide for HIV/AIDS Care , and ...

  14. Testing for HIV

    MedlinePLUS

    ... Vaccines, Blood & Biologics Safety & Availability (Biologics) HIV Home Test Kits Testing for HIV Share Tweet Linkedin Pin it ... for HIV? A complete list of the HIV test kits approved in the U.S. is available on our ...

  15. HIV and Your Heart

    MedlinePLUS

    ... Pressure High Blood Pressure Tools & Resources Stroke More HIV and Your Heart Banner 1 - HIV and Your ... Commercial support for this program was provided by HIV Wellness Checklist People living with HIV have even ...

  16. HIV Medication Adherence

    MedlinePLUS

    HIV Treatment HIV Medication Adherence (Last updated 4/29/2015; last reviewed 4/29/2015) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  17. HIV and Cardiovascular Disease

    MedlinePLUS

    ... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

  18. Basic HIV/AIDS Statistics

    MedlinePLUS

    ... you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | Subscribe ... Get Email Updates on HIV Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV/ ...

  19. HIV and Ribozymes.

    PubMed

    Scarborough, Robert J; Gatignol, Anne

    2015-01-01

    Ribozymes are structured RNA molecules that act as catalysts in different biological reactions. From simple genome cleaving activities in satellite RNAs to more complex functions in cellular protein synthesis and gene regulation, ribozymes play important roles in all forms of life. Several naturally existing ribozymes have been modified for use as therapeutics in different conditions, with HIV-1 infection being one of the most studied. This chapter summarizes data from different preclinical and clinical studies conducted to evaluate the potential of ribozymes to be used in HIV-1 therapies. The different ribozyme motifs that have been modified, as well as their target sites and expression strategies, are described. RNA conjugations used to enhance the antiviral effect of ribozymes are also presented and the results from clinical trials conducted to date are summarized. Studies on anti-HIV-1 ribozymes have provided valuable information on the optimal expression strategies and clinical protocols for RNA gene therapy and remain competitive candidates for future therapy. PMID:25757617

  20. Newer Gene Editing Technologies toward HIV Gene Therapy

    PubMed Central

    Manjunath, N.; Yi, Guohua; Dang, Ying; Shankar, Premlata

    2013-01-01

    Despite the great success of highly active antiretroviral therapy (HAART) in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy. PMID:24284874

  1. Predictors of HIV serostatus disclosure to partners among HIV-positive pregnant women in Morogoro, Tanzania

    PubMed Central

    2013-01-01

    Background Prevention of mother to child transmission of HIV (PMTCT) has been scaled, to more than 90% of health facilities in Tanzania. Disclosure of HIV results to partners and their participation is encouraged in the program. This study aimed to determine the prevalence, patterns and predictors of HIV sero-status disclosure to partners among HIV positive pregnant women in Morogoro municipality, Tanzania. Methods A cross sectional study was conducted in March to May 2010 among HIV-positive pregnant women who were attending for routine antenatal care in primary health care facilities of the municipality and had been tested for HIV at least one month prior to the study. Questionnaires were used to collect information on possible predictors of HIV disclosure to partners. Results A total of 250 HIV-positive pregnant women were enrolled. Forty one percent (102) had disclosed their HIV sero-status to their partners. HIV-disclosure to partners was more likely among pregnant women who were?HIV status before the current pregnancy [AOR?=?3.7; 95% CI: 1.7–8.3], and discussed with their partner before testing [AOR?=?6.9; 95% CI: 2.4–20.1]. Dependency on the partner for food/rent/school fees, led to lower odds of disclosure to partners [AOR?=?0.4; 95% CI: 0.1–0.7]. Nine out of ten women reported to have been counseled on importance of disclosure and partner participation. Conclusions Six in ten HIV positive pregnant women in this setting had not disclosed their results of the HIV test to their partners. Empowering pregnant women to have an individualized HIV-disclosure plan, strengthening of the HIV provider initiated counseling and testing and addressing economic development, may be some of the strategies in improving HIV disclosure and partner involvement in this setting. PMID:23641927

  2. HIV / AIDS

    MedlinePLUS

    ... Marketing Share this: Main Content Area Understanding HIV/AIDS AIDS was first reported in the United States in ... and has since become a major worldwide epidemic. AIDS is caused by the human immunodeficiency virus, or ...

  3. Relative resistance of HIV-1 founder viruses to control by interferon-alpha

    PubMed Central

    2013-01-01

    Background Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFN?2 (22 U/ml) was lower than that for IFN? (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFN?2 and IFN?, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFN? than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions The establishment of systemic HIV-1 infection by relatively IFN?-resistant founder viruses lends strong support to the hypothesis that IFN? plays an important role in the control of HIV-1 replication during the earliest stages of infection, prior to systemic viral spread. These findings suggest that it may be possible to harness the antiviral activity of type 1 IFNs in prophylactic and potentially also therapeutic strategies to combat HIV-1 infection. PMID:24299076

  4. [HIV infection: relevant pediatric aspects].

    PubMed

    Rudin, C

    1998-01-01

    After 15 years of intense AIDS research several fascinating new findings have recently produced real hope for people infected with HIV and new optimism among scientists. A second group of powerful antiretroviral drugs (proteinase inhibitors) has been introduced. These drugs can virtually stop viral replication when used in combination with other drugs (nucleoside or non-nucleoside reverse transcriptase inhibitors), which also almost totally eliminates the emergence of HIV-resistance. New moleculargenetic methods (plasma HIV-RNA assays) made a new marker to quantify and survey therapeutic effects and to accurately predict individual progression of HIV infection available. These new instruments also provided us with a more realistic imagination about pathogenesis and viral dynamics in HIV infection. In neonates prophylactic antiretroviral treatment of pregnant women already prevents two thirds of vertically acquired infections, and the vertical transmission rate may well continue to decline with new prophylactic regimens and/or other interventions (e.g. cesarean section). Given these splendid innovations, a huge impact on prognosis can well be anticipated in the near future. PMID:9492620

  5. Nanotechnology: a magic bullet for HIV AIDS treatment.

    PubMed

    Kumar, Lalit; Verma, Shivani; Prasad, Deo Nandan; Bhardwaj, Ankur; Vaidya, Bhuvaneshwar; Jain, Amit Kumar

    2015-04-01

    Human immunode?ciency virus (HIV) infection has become devastating in last a few years. Nearly 7400 new infection cases are coming every day. Highly active antiretroviral therapy (HAART), which involves combination of at least three antiretroviral (ARV) drugs, has been used to extend the life span of the HIV-infected patients. HAART has played an important role to reduce mortality rate in the developed countries but in the developing countries condition is still worst with millions of people being infected by this disease. For the improvement of the situation, nanotechnology-based drug system has been explored for the HIV therapeutics. Nanosystems used for HIV therapeutics offer some unique advantage like enhancement of bioavailability, water solubility, stability, and targeting ability of ARV drugs. Main nanotechnology-based systems explored for HIV therapeutics are liposomes, nanoparticles, niosomes, polymeric micelles, and dendrimers. Present manuscript reviews conventional method of HIV therapeutics and recent advances in the field of nanotechnology-based systems for treatment of HIV-AIDS. PMID:24564348

  6. Hormonal contraception and HIV disease progression.

    PubMed

    Stringer, Elizabeth; Antonsen, Erik

    2008-10-01

    The majority of the 15.4 million human immunodeficiency virus (HIV)-infected women worldwide are of child-bearing age and need access to contraception. Hormonal methods of contraception are safe, acceptable, and effective in preventing unwanted pregnancies. Many published studies have examined the impact of hormonal contraception on HIV disease acquisition and transmissibility. Far fewer have investigated the relationship between hormonal contraception and HIV disease progression. This review examines available data on this relationship from clinical, animal, and immunological studies. Several clinical studies suggest an overall effect but are not definitive, and the mechanisms behind HIV disease progression are unclear. Animal and immunological data suggest that immunomodulation by hormonal contraceptive methods may affect the immune response to HIV infection. Additional work is needed in this area to elucidate the possible relationship between hormonal methods for birth control and progression to acquired immunodeficiency syndrome in HIV-infected women. PMID:18715161

  7. HIV-1 capsid: the multifaceted key player in HIV-1 infection.

    PubMed

    Campbell, Edward M; Hope, Thomas J

    2015-08-01

    In a mature, infectious HIV-1 virion, the viral genome is housed within a conical capsid core made from the viral capsid (CA) protein. The CA protein and the structure into which it assembles facilitate virtually every step of infection through a series of interactions with multiple host cell factors. This Review describes our understanding of the interactions between the viral capsid core and several cellular factors that enable efficient HIV-1 genome replication, timely core disassembly, nuclear import and the integration of the viral genome into the genome of the target cell. We then discuss how elucidating these interactions can reveal new targets for therapeutic interactions against HIV-1. PMID:26179359

  8. Short communication: high cellular iron levels are associated with increased HIV infection and replication.

    PubMed

    Chang, Hsiang-Chun; Bayeva, Marina; Taiwo, Babafemi; Palella, Frank J; Hope, Thomas J; Ardehali, Hossein

    2015-03-01

    HIV is a pandemic disease, and many cellular and systemic factors are known to alter its infectivity and replication. Earlier studies had suggested that anemia is common in HIV-infected patients; however, higher iron was also observed in AIDS patients prior to the introduction of antiretroviral therapy (ART). Therefore, the relationship between iron and viral infection is not well delineated. To address this issue, we altered the levels of cellular iron in primary CD4(+) T cells and showed that higher iron is associated with increased HIV infection and replication. In addition, HIV infection alone leads to increased cellular iron, and several ART drugs increase cellular iron independent of HIV infection. Finally, HIV infection is associated with increased serum iron in HIV-positive patients regardless of treatment with ART. These results establish a relationship between iron and HIV infection and suggest that iron homeostasis may be a viable therapeutic target for HIV. PMID:25291189

  9. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  10. Targeting TNF-Alpha in HIV-1 Infection.

    PubMed

    Kumar, Amit; Coquard, Laurie; Herbein, Georges

    2016-01-01

    Highly active antiretroviral therapy (HAART) has dramatically extended the lifespan and quality of life of individuals infected with human immunodeficiency virus type 1 (HIV-1). HAART comprises of a cocktail of various pharmacological inhibitors which interfere with almost every stages of HIV-1 life cycle. However, constant application of drugs often results in the evolution of hostpathogen relationship resulting in the emergence of drug resistant viral strains. Drug resistant HIV-1 is a potent threat for the humankind. Therefore, there is a constant need to search for novel therapeutic molecules. HIV-1 infection results in the depletion of CD4+/CD8+T cells and alters the cytokine network in the infected individuals. Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, plays a critical role in HIV-1 pathogenesis. HIV-1 utilizes the TNF-alpha signaling pathway for expanding its reservoir. Several HIV-1 proteins mimic and regulate the TNF-alpha signaling pathway. TNF-alpha inhibitors have been used in several inflammatory pathologies with success to some extent. In the present mini review we will discuss the role of TNF-alpha in HIV-1 pathogenesis. Furthermore we will evaluate the TNF-alpha inhibitors as an additional therapeutic option for HIV-1 infection. PMID:26073859

  11. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection

    PubMed Central

    Jin, Qingwen; Chen, Hong; Wang, Xingxia; Zhao, Liandong; Xu, Qingchen; Wang, Huijuan; Li, Guanyu; Yang, Xiaofan; Ma, Hongming; Wu, Haoquan; Ji, Xiaohui

    2015-01-01

    Background Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed. Methods We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects. Results Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5. Conclusions Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents. PMID:26154172

  12. Therapeutic Drug Monitoring

    MedlinePLUS

    ... limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page helpful? ... Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement of ...

  13. Preventive hiv vaccine acceptability and behavioral risk compensation among a random sample of high-risk adults in los angeles (La voices): Research briefs

    E-print Network

    2009-01-01

    active government policies to subsidize HIV vaccine costsHIV/AIDS Preventive Vac- cines Based on Possible PoliciesHIV Vaccine: Why We Need to Do Better. Reliable Estimates Would Help in Achieving Sveral Policy

  14. Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells.

    PubMed

    Sahu, Gautam K; Sango, Kaori; Selliah, Nithianandan; Ma, Qiangzhong; Skowron, Gail; Junghans, Richard P

    2013-11-01

    The current antiretroviral therapy (ART) can effectively reduce plasma HIV loads to undetectable levels, but cannot eliminate latently infected resting memory CD4 T cells that persist for the lifetime of infected patients. Therefore, designing new therapeutic approaches to eliminate these latently infected cells or the cells that produce HIV upon reactivation from latency is a priority in the ART era in order to progress to a cure of HIV. Here, we show that "designer" T cells expressing chimeric antigen receptor (CAR), CD4-CD28-CD3?, can target and kill HIV Env-expressing cells. Further, they secrete effector cytokines upon contact with HIV Env+ target cells that can reactivate latent HIV in a cell line model, thereby exposing those cells to recognition and killing by anti-HIV CAR+ T cells. Taken to the limit, this process could form the basis for an eventual functional or sterilizing cure for HIV in patients. PMID:24074590

  15. HIV Life Cycle

    MedlinePLUS

    HIV Overview The HIV Life Cycle (Last updated 9/22/2015; last reviewed 9/22/2015) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

  16. Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes.

    PubMed

    Heesters, Balthasar A; Lindqvist, Madelene; Vagefi, Parsia A; Scully, Eileen P; Schildberg, Frank A; Altfeld, Marcus; Walker, Bruce D; Kaufmann, Daniel E; Carroll, Michael C

    2015-12-01

    Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans. PMID:26623655

  17. Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes

    PubMed Central

    Heesters, Balthasar A.; Lindqvist, Madelene; Vagefi, Parsia A.; Scully, Eileen P.; Schildberg, Frank A.; Altfeld, Marcus; Walker, Bruce D.; Kaufmann, Daniel E.; Carroll, Michael C.

    2015-01-01

    Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans. PMID:26623655

  18. Purinergic Receptors: Key Mediators of HIV-1 Infection and Inflammation

    PubMed Central

    Swartz, Talia H.; Dubyak, George R.; Chen, Benjamin K.

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) causes a chronic infection that afflicts more than 30?million individuals worldwide. While the infection can be suppressed with potent antiretroviral therapies, individuals infected with HIV-1 have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV-1 pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here, we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets. PMID:26635799

  19. HIV-related neuropathy: current perspectives

    PubMed Central

    Schütz, Sonja G; Robinson-Papp, Jessica

    2013-01-01

    Distal symmetric polyneuropathy (DSP) related to human immunodeficiency virus (HIV) is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient’s daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. PMID:24049460

  20. HIV/AIDS

    MedlinePLUS

    HIV stands for human immunodeficiency virus. It kills or damages the body's immune system cells. AIDS stands for acquired immunodeficiency syndrome. It is the most advanced stage of infection with HIV. HIV most ...

  1. Travelers' Health: HIV Infection

    MedlinePLUS

    ... AGENT HIV, a single-stranded, positive-sense, enveloped RNA virus in the genus Lentivirus. TRANSMISSION HIV can ... be diagnosed is approximately 9 days, when HIV RNA becomes detectable in blood; however, tests needed to ...

  2. Women and HIV

    MedlinePLUS

    ... Many women think AIDS is a disease of gay men. But women get HIV from heterosexual sex ... Sheets 111. Optimizing the HIV Care Environment 115. Adolescents and the HIV Care Continuum 114. Increasing retention ...

  3. Children and HIV

    MedlinePLUS

    ... Children Translate Text Size Print Children Children and HIV Most HIV-positive children under the age of ... Frequently Asked Questions How long do children with HIV typically live? Because effective treatments are relatively new ...

  4. HIV Antibody Test

    MedlinePLUS

    ... limited. Home Visit Global Sites Search Help? HIV Antibody Share this page: Was this page helpful? Also ... Screen; HIV Serology Formal name: Human Immunodeficiency Virus Antibody Test Related tests: p24 Antigen ; HIV Antigen/Antibody ...

  5. Preventing HIV with Medicine

    MedlinePLUS

    ... information in Spanish ( en español ) Preventing HIV with medicine Get medicine right after you are exposed to ... to top More information on Preventing HIV with medicine Explore other publications and websites National HIV and ...

  6. How HIV Causes AIDS

    MedlinePLUS

    ... Share this: Main Content Area How HIV Causes AIDS HIV destroys CD4 positive (CD4+) T cells, which ... and disease, ultimately resulting in the development of AIDS. Most people who are infected with HIV can ...

  7. HIV and AIDS

    MedlinePLUS

    ... How the Body Works Main Page HIV and AIDS KidsHealth > Kids > Health Problems > Infections > HIV and AIDS ... serious infection. Continue How Many People Have HIV/AIDS? Since the discovery of the virus almost 30 ...

  8. HIV/AIDS Basics

    MedlinePLUS

    ... Enter ZIP code or city Follow Act Against AIDS Act Against AIDS @talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV/ ...

  9. HIV-AIDS Connection

    MedlinePLUS

    ... Marketing Share this: Main Content Area The HIV-AIDS Connection AIDS was first recognized in 1981 and ... is there overwhelming scientific consensus that HIV causes AIDS? Before HIV infection became widespread in the human ...

  10. HIV transmission risk behavior among HIV-positive patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa.

    PubMed

    Shuper, Paul A; Kiene, Susan M; Mahlase, Gethwana; MacDonald, Susan; Christie, Sarah; Cornman, Deborah H; Fisher, William A; Greener, Ross; Lalloo, Umesh G; Pillay, Sandy; van Loggerenberg, Francois; Fisher, Jeffrey D

    2014-08-01

    The aim of this investigation was to identify factors associated with HIV transmission risk behavior among HIV-positive women and men receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. Across 16 clinics, 1,890 HIV+ patients on ART completed a risk-focused audio computer-assisted self-interview upon enrolling in a prevention-with-positives intervention trial. Results demonstrated that 62 % of HIV-positive patients' recent unprotected sexual acts involved HIV-negative or HIV status unknown partners. For HIV-positive women, multivariable correlates of unprotected sex with HIV-negative or HIV status unknown partners were indicative of poor HIV prevention-related information and of sexual partnership-associated behavioral skills barriers. For HIV-positive men, multivariable correlates represented motivational barriers, characterized by negative condom attitudes and the experience of depressive symptomatology, as well as possible underlying information deficits. Findings suggest that interventions addressing gender-specific and culturally-relevant information, motivation, and behavioral skills barriers could help reduce HIV transmission risk behavior among HIV-positive South Africans. PMID:24158486

  11. Comparison of the sensitivities of primary isolates of HIV type 2 and HIV type 1 to antiviral drugs and drug combinations.

    PubMed

    Cox, S W; Apéria, K; Albert, J; Wahren, B

    1994-12-01

    The sensitivity of primary isolates of HIV-2 to the antiretroviral drugs 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI), and 3'-fluoro-3'-deoxythymidine (FLT) was measured in vitro in PBMCs and compared to that of primary isolates of HIV-1. HIV-2 isolates showed a similar sensitivity to the drugs compared to HIV-1 isolates. Both the relative and the absolute potencies of the three drugs were similar for inhibition of HIV-1 or HIV-2 replication. The effect of combinations of the antiviral drugs was also studied. The combinations of AZT plus FLT, AZT plus ddI, and FLT plus ddI showed synergistic inhibition of three primary HIV-2 isolates, similar to that previously shown for primary HIV-1 isolates. These results indicate that primary isolates of HIV-2 from untreated persons show a level of sensitivity to antiviral nucleoside analogs similar to that shown by HIV-1 isolates, and are also synergistically inhibited by drug combinations shown to be synergistic against HIV-1. Therapeutic regimes with nucleoside analogs used clinically against HIV-1 infection may therefore also be similarly useful against infection with HIV-2. PMID:7888232

  12. HIV persistence in the setting of antiretroviral therapy: when, where and how does HIV hide?

    PubMed Central

    Kulpa, Deanna A.; Chomont, Nicolas

    2015-01-01

    Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals. However, the possible long-term toxicity associated with antiretroviral therapy (ART), stigma and cost, all contribute to the necessity of finding a cure for HIV infection. In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person. These persistently infected cells, usually referred as the ‘reservoirs for HIV infection’, are the main barriers to a cure. The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV. In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist? PMID:26448966

  13. Therapeutics Based On The Induced Internalization Of Surface Receptors

    Cancer.gov

    The National Cancer Institute, Laboratory of Cellular Oncology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics for diseases or conditions associated with target receptors, such as cancer, angiogenesis, or HIV infections.

  14. A review of nanotechnological approaches for the prophylaxis of HIV/AIDS

    PubMed Central

    Date, Abhijit A.; Destache, Christopher J.

    2013-01-01

    Successful treatment and control of HIV/AIDS is one of the biggest challenges of 21st century. More than 33 million individuals are infected with HIV worldwide and more than 2 million new cases of HIV infection have been reported. The situation demands development of effective prevention strategies to control the pandemic of AIDS. Due to lack of availability of an effective HIV vaccine, antiretroviral drugs and nucleic acid therapeutics like siRNA have been explored for HIV prophylaxis. Clinical trials shave shown that antiretroviral drugs, tenofovir and emtricitabine can offer some degree of HIV prevention. However, complete prevention of HIV infection has not been achieved yet. Nanotechnology has brought a paradigm shift in the diagnosis, treatment and prevention of many diseases. The current review discusses potential of various nanocarriers such as dendrimers, polymeric nanoparticles, liposomes, lipid nanocarriers, drug nanocrystals, inorganic nanocarriers and nanofibers in improving efficacy of various modalities available for HIV prophylaxis. PMID:23726227

  15. Curcumin and its analogues: a potential natural compound against HIV infection and AIDS.

    PubMed

    Prasad, Sahdeo; Tyagi, Amit K

    2015-11-01

    No safe and effective cure currently exists for human immunodeficiency virus (HIV). However, antiretroviral therapy can prolong the lives of HIV patients and lowers the secondary infections. Natural compounds, which are considered to be pleiotropic molecules, could be useful against HIV. Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), can be used for the treatment of several diseases including HIV-AIDS because of its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial nature. In this review we have summarized that how curcumin and its analogues inhibit the infection and replication of viral genes and prevent multiplicity of HIV. They are inhibitors of HIV protease and integrase. Curcumin also inhibits Tat transactivation of the HIV1-LTR genome, inflammatory molecules (interleukins, TNF-?, NF-?B, COX-2) and HIV associated various kinases including tyrosine kinase, PAK1, MAPK, PKC, cdk and others. In addition, curcumin enhances the effect of conventional therapeutic drugs and minimizes their side effects. PMID:26404185

  16. A novel small-molecule inhibitor of HIV-1 entry

    PubMed Central

    Heredia, Alonso; Latinovic, Olga S; Barbault, Florent; de Leeuw, Erik PH

    2015-01-01

    Background Antiretroviral therapy has transformed HIV-1 infection into a managed condition with near-normal life expectancy. However, a significant number of patients remain with limited therapeutic options due to HIV-1 resistance, side effects, or drug costs. Further, it is likely that current drugs will not retain efficacy, due to risks of side effects and transmitted resistance. Results We describe compound 5660386 (3-ethyl-2-[3-(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)-1-propen-1-yl]-1,3-benzothiazol-3-ium) as a novel inhibitor of HIV-1 entry. Compound 5660386 inhibits HIV-1 entry in cell lines and primary cells, binds to HIV-1 envelope protein, and inhibits the interaction of GP120 to CD4. Further, compound 5660386 showed a unique and broad-range activity against primary HIV-1 isolates from different subtypes and geographical areas. Conclusion Development of small-molecule entry inhibitors of HIV-1 such as 5660386 may lead to novel classes of anti-HIV-1 therapeutics. These inhibitors may be particularly effective against viruses resistant to current antiretroviral drugs and could have potential applications in both treatment and prevention. PMID:26491257

  17. Hydroxyurea for HIV infection.

    PubMed

    Zachary, K C; Davis, B

    1998-04-01

    Hydroxyurea, an inhibitor of DNA synthesis, is used to treat HIV infection. By inhibiting ribonucleotide reductase, hydroxyurea depletes the pool of deoxynucleoside triphosphates, particularly dATP, available for DNA synthesis. Hydroxyurea may be a candidate for use with nucleoside analogs, particularly ddI. Hydroxyurea's use in treating HIV infection with and without ddI, with ddI and without d4T, and with ddI plus a protease inhibitor are discussed. Studies using hydroxyurea with ddI and d4T have shown clinical promise and could be a viable antiretroviral strategy in some patients, especially in countries with limited resources. A regimen containing hydroxyurea, ddI, and a protease inhibitor could be used in aggressive initial or salvage antiretroviral therapy. It is also possible that during acute HIV infection, hydroxyurea's cytostatic properties could contribute to the ultimate preservation of normal immunologic function. Hydroxyurea's dosage level is still uncertain; 500 mg twice daily has been used most often. PMID:11365149

  18. HIV-Induced Epigenetic Alterations in Host Cells.

    PubMed

    Abdel-Hameed, Enass A; Ji, Hong; Shata, Mohamed Tarek

    2016-01-01

    Human immunodeficiency virus (HIV), a member of the Retroviridae family, is a positive-sense, enveloped RNA virus. HIV, the causative agent of acquired immunodeficiency syndrome (AIDS) has two major types, HIV-1 and HIV-2 In HIV-infected cells the single stranded viral RNA genome is reverse transcribed and the double-stranded viral DNA integrates into the cellular DNA, forming a provirus. The proviral HIV genome is controlled by the host epigenetic regulatory machinery. Cellular epigenetic regulators control HIV latency and reactivation by affecting the chromatin state in the vicinity of the viral promoter located to the 5' long terminal repeat (LTR) sequence. In turn, distinct HIV proteins affect the epigenotype and gene expression pattern of the host cells. HIV-1 infection of CD4(+) T cells in vitro upregulated DNMT activity and induced hypermethylation of distinct cellular promoters. In contrast, in the colon mucosa and peripheral blood mononuclear cells from HIV-infected patients demethylation of the FOXP3 promoter was observed, possibly due to the downregulation of DNA methyltransferase 1. For a curative therapy of HIV infected individuals and AIDS patients, a combination of antiretroviral drugs with epigenetic modifying compounds have been suggested for the reactivation of latent HIV-1 genomes. These epigenetic drugs include histone deacetylase inhibitors (HDACI), histone methyltransferase inhibitors (HMTI), histone demethylase inhibitors, and DNA methyltransferase inhibitors (DNMTI). PMID:26659262

  19. Characterizing HIV epidemiology in stable couples in Cambodia, the Dominican Republic, Haiti, and India.

    PubMed

    Chemaitelly, H; Abu-Raddad, L J

    2016-01-01

    Using a set of statistical methods and HIV mathematical models applied on nationally representative Demographic and Health Survey data, we characterized HIV serodiscordancy patterns and HIV transmission dynamics in stable couples (SCs) in four countries: Cambodia, the Dominican Republic, Haiti, and India. The majority of SCs affected by HIV were serodiscordant, and about a third of HIV-infected persons had uninfected partners. Overall, nearly two-thirds of HIV infections occurred in individuals in SCs, but only about half of these infections were due to transmissions within serodiscordant couples. The majority of HIV incidence in the population occurred through extra-partner encounters in SCs. There is similarity in HIV epidemiology in SCs between these countries and countries in sub-Saharan Africa, despite the difference in scale of epidemics. It appears that HIV epidemiology in SCs may share similar patterns globally, possibly because it is a natural 'spillover' effect of HIV dynamics in high-risk populations. PMID:25916602

  20. Autophagy in Mycobacterium tuberculosis and HIV infections

    PubMed Central

    Espert, Lucile; Beaumelle, Bruno; Vergne, Isabelle

    2015-01-01

    Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (M.tb) are among the most lethal human pathogens worldwide, each being responsible for around 1.5 million deaths annually. Moreover, synergy between acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) has turned HIV/M.tb co-infection into a major public health threat in developing countries. In the past decade, autophagy, a lysosomal catabolic process, has emerged as a major host immune defense mechanism against infectious agents like M.tb and HIV. Nevertheless, in some instances, autophagy machinery appears to be instrumental for HIV infection. Finally, there is mounting evidence that both pathogens deploy various countermeasures to thwart autophagy. This mini-review proposes an overview of the roles and regulations of autophagy in HIV and M.tb infections with an emphasis on microbial factors. We also discuss the role of autophagy manipulation in the context of HIV/M.tb co-infection. In future, a comprehensive understanding of autophagy interaction with these pathogens will be critical for development of autophagy-based prophylactic and therapeutic interventions for AIDS and TB. PMID:26082897

  1. Exosomes: Implications in HIV-1 Pathogenesis

    PubMed Central

    Madison, Marisa N.; Okeoma, Chioma M.

    2015-01-01

    Exosomes are membranous nanovesicles of endocytic origin that carry host and pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by most cell types into the extracellular milieu and are subsequently internalized by recipient cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. The role of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1 [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes from various sources play important but different roles in the pathogenesis of HIV-1. From these reports, it appears that the source of exosomes is the defining factor for the exosomal effect on HIV-1. In this review, we will describe how HIV-1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV-1 factors. Finally, we will discuss potentially emerging therapeutic options based on exosomal cargos that may have promise in preventing HIV-1 transmission. PMID:26205405

  2. HIV Structural Database

    National Institute of Standards and Technology Data Gateway

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  3. Oligonucleotide conjugates for therapeutic applications

    PubMed Central

    Winkler, Johannes

    2013-01-01

    Insufficient pharmacokinetic properties and poor cellular uptake are the main hurdles for successful therapeutic development of oligonucleotide agents. The covalent attachment of various ligands designed to influence the biodistribution and cellular uptake or for targeting specific tissues is an attractive possibility to advance therapeutic applications and to expand development options. In contrast to advanced formulations, which often consist of multiple reagents and are sensitive to a variety of preparation conditions, oligonucleotide conjugates are defined molecules, enabling structure-based analytics and quality control techniques. This review gives an overview of current developments of oligonucleotide conjugates for therapeutic applications. Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small molecules, including cholesterol, tocopherol and folic acid. Important linkage types and conjugation methods are summarized. The distinct ligands directly influence biochemical parameters, uptake machanisms and pharmacokinetic properties. PMID:23883124

  4. Continuous Antigenic Stimulation of DO11.10 TCR Transgenic Mice in the Presence or Absence of IL-1?: Possible Implications for Mechanisms of T Cell Depletion in HIV Disease.

    PubMed

    Ladell, Kristin; Hazenberg, Mette D; Fitch, Mark; Emson, Claire; McEvoy-Hein Asgarian, Bridget K; Mold, Jeff E; Miller, Corey; Busch, Robert; Price, David A; Hellerstein, Marc K; McCune, Joseph M

    2015-11-01

    Untreated HIV disease is associated with chronic immune activation and CD4(+) T cell depletion. A variety of mechanisms have been invoked to account for CD4(+) T cell depletion in this setting, but the quantitative contributions of these proposed mechanisms over time remain unclear. We turned to the DO11.10 TCR transgenic mouse model, where OVA is recognized in the context of H-2(d), to explore the impact of chronic antigenic stimulation on CD4(+) T cell dynamics. To model dichotomous states of persistent Ag exposure in the presence or absence of proinflammatory stimulation, we administered OVA peptide to these mice on a continuous basis with or without the prototypic proinflammatory cytokine, IL-1?. In both cases, circulating Ag-specific CD4(+) T cells were depleted. However, in the absence of IL-1?, there was limited proliferation and effector/memory conversion of Ag-specific T cells, depletion of peripheral CD4(+) T cells in hematolymphoid organs, and systemic induction of regulatory Foxp3(+)CD4(+) T cells, as often observed in late-stage HIV disease. By contrast, when OVA peptide was administered in the presence of IL-1?, effector/memory phenotype T cells expanded and the typical symptoms of heightened immune activation were observed. Acknowledging the imperfect and incomplete relationship between Ag-stimulated DO11.10 TCR transgenic mice and HIV-infected humans, our data suggest that CD4(+) T cell depletion in the setting of HIV disease may reflect, at least in part, chronic Ag exposure in the absence of proinflammatory signals and/or appropriate APC functions. PMID:26416271

  5. Influence of HIV and HCV on T cell antigen presentation and challenges in the development of vaccines

    PubMed Central

    John, Mina; Gaudieri, Silvana

    2014-01-01

    Some of the central challenges for developing effective vaccines against HIV and hepatitis C virus (HCV) are similar. Both infections are caused by small, highly mutable, rapidly replicating RNA viruses with the ability to establish long-term chronic pathogenic infection in human hosts. HIV has caused 60 million infections globally and HCV 180 million and both viruses may co-exist among certain populations by virtue of common blood-borne, sexual, or vertical transmission. Persistence of both pathogens is achieved by evasion of intrinsic, innate, and adaptive immune defenses but with some distinct mechanisms reflecting their differences in evolutionary history, replication characteristics, cell tropism, and visibility to mucosal versus systemic and hepatic immune responses. A potent and durable antibody and T cell response is a likely requirement of future HIV and HCV vaccines. Perhaps the single biggest difference between the two vaccine design challenges is that in HCV, a natural model of protective immunity can be found in those who resolve acute infection spontaneously. Such spontaneous resolvers exhibit durable and functional CD4+ and CD8+ T cell responses (Diepolder et al., 1995; Cooper et al., 1999; Thimme et al., 2001; Grakoui et al., 2003; Lauer et al., 2004; Schulze Zur Wiesch et al., 2012). However, frequent re-infection suggests partial or lack of protective immunity against heterologous HCV strains, possibly indicative of the degree of genetic diversity of circulating HCV genotypes and subtypes. There is no natural model of protective immunity in HIV, however, studies of “elite controllers,” or individuals who have durably suppressed levels of plasma HIV RNA without antiretroviral therapy, has provided the strongest evidence for CD8+ T cell responses in controlling viremia and limiting reservoir burden in established infection. Here we compare and contrast the specific mechanisms of immune evasion used by HIV and HCV, which subvert adaptive human leukocyte antigen (HLA)-restricted T cell immunity in natural infection, and the challenges these pose for designing effective preventative or therapeutic vaccines. PMID:25352836

  6. In Vitro Selection of Highly Darunavir-Resistant and Replication-Competent HIV-1 Variants by Using a Mixture of Clinical HIV-1 Isolates Resistant to Multiple Conventional Protease Inhibitors? †

    PubMed Central

    Koh, Yasuhiro; Amano, Masayuki; Towata, Tomomi; Danish, Matthew; Leshchenko-Yashchuk, Sofiya; Das, Debananda; Nakayama, Maki; Tojo, Yasushi; Ghosh, Arun K.; Mitsuya, Hiroaki

    2010-01-01

    We attempted to select HIV-1 variants resistant to darunavir (DRV), which potently inhibits the enzymatic activity and dimerization of protease and has a high genetic barrier to HIV-1 development of resistance to DRV. We conducted selection using a mixture of 8 highly multi-protease inhibitor (PI)-resistant, DRV-susceptible clinical HIV-1 variants (HIV-1MIX) containing 9 to 14 PI resistance-associated amino acid substitutions in protease. HIV-1MIX became highly resistant to DRV, with a 50% effective concentration (EC50) ?333-fold greater than that against HIV-1NL4-3. HIV-1MIX at passage 51 (HIV-1MIXP51) replicated well in the presence of 5 ?M DRV and contained 14 mutations. HIV-1MIXP51 was highly resistant to amprenavir, indinavir, nelfinavir, ritonavir, lopinavir, and atazanavir and moderately resistant to saquinavir and tipranavir. HIV-1MIXP51 had a resemblance with HIV-1C of the HIV-1MIX population, and selection using HIV-1C was also performed; however, its DRV resistance acquisition was substantially delayed. The H219Q and I223V substitutions in Gag, lacking in HIV-1CP51, likely contributed to conferring a replication advantage on HIV-1MIXP51 by reducing intravirion cyclophilin A content. HIV-1MIXP51 apparently acquired the substitutions from another HIV-1 strain(s) of HIV-1MIX through possible homologous recombination. The present data suggest that the use of multiple drug-resistant HIV-1 isolates is of utility in selecting drug-resistant variants and that DRV would not easily permit HIV-1 to develop significant resistance; however, HIV-1 can develop high levels of DRV resistance when a variety of PI-resistant HIV-1 strains are generated, as seen in patients experiencing sequential PI failure, and ensuing homologous recombination takes place. HIV-1MIXP51 should be useful in elucidating the mechanisms of HIV-1 resistance to DRV and related agents. PMID:20810732

  7. Regulatory T Cells Expanded from Hiv-1-Infected Individuals Maintain Phenotype, Tcr Repertoire and Suppressive Capacity

    E-print Network

    Angin, Mathieu

    While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis ...

  8. The role of enacted stigma in parental HIV disclosure among HIV-infected parents in China

    PubMed Central

    Qiao, Shan; Li, Xiaoming; Zhou, Yuejiao; Shen, Zhiyong; Tang, Zhenzhu; Stanton, Bonita

    2015-01-01

    Existing studies have delineated that HIV-infected parents face numerous challenges in disclosing their HIV infection to the children (“parental HIV disclosure”), and practices of parental HIV disclosure vary with individual characteristics, family contexts, and social environment. Using cross-sectional data from 1254 HIV-infected parents who had children aged 5–16 years in southwest China, the current study examined the association of parental HIV disclosure with mental health and medication adherence among parents and explored the possible effect of enacted stigma on such association. Multivariate analysis of variance revealed that parents who had experienced disclosure to children reported higher level enacted stigma, worse mental health conditions, and poorer medication adherence. Enacted stigma partially mediated the associations between disclosure and both mental health and medication adherence after controlling basic background characteristics. Our findings highlight the importance of providing appropriate disclosure-related training and counseling service among HIV-infected parents. In a social setting where HIV-related stigma is still persistent, disclosure intervention should address and reduce stigma and discrimination in the practice of parental HIV disclosure. PMID:26616123

  9. The role of enacted stigma in parental HIV disclosure among HIV-infected parents in China.

    PubMed

    Qiao, Shan; Li, Xiaoming; Zhou, Yuejiao; Shen, Zhiyong; Tang, Zhenzhu; Stanton, Bonita

    2015-12-01

    Existing studies have delineated that HIV-infected parents face numerous challenges in disclosing their HIV infection to the children ("parental HIV disclosure"), and practices of parental HIV disclosure vary with individual characteristics, family contexts, and social environment. Using cross-sectional data from 1254 HIV-infected parents who had children aged 5-16 years in southwest China, the current study examined the association of parental HIV disclosure with mental health and medication adherence among parents and explored the possible effect of enacted stigma on such association. Multivariate analysis of variance revealed that parents who had experienced disclosure to children reported higher level enacted stigma, worse mental health conditions, and poorer medication adherence. Enacted stigma partially mediated the associations between disclosure and both mental health and medication adherence after controlling basic background characteristics. Our findings highlight the importance of providing appropriate disclosure-related training and counseling service among HIV-infected parents. In a social setting where HIV-related stigma is still persistent, disclosure intervention should address and reduce stigma and discrimination in the practice of parental HIV disclosure. PMID:26616123

  10. Novel two-round phenotypic assay for protease inhibitor susceptibility testing of recombinant and primary HIV-1 isolates.

    PubMed

    Puertas, Maria C; Buzón, Maria J; Ballestero, Mònica; Van Den Eede, Peter; Clotet, Bonaventura; Prado, Julia G; Martinez-Picado, Javier

    2012-12-01

    Antiretroviral drug susceptibility tests facilitate therapeutic management of HIV-1-infected patients. Although genotyping systems are affordable, inaccuracy in the interpretation of complex mutational patterns may limit their usefulness. Currently available HIV-1 phenotypic assays are based on the generation of recombinant viruses in which the specific viral gene of interest, derived from a patient plasma sample, is cloned into a susceptible genetic viral backbone prior to in vitro drug susceptibility evaluation. Nevertheless, in the case of protease inhibitors, not only are mutations in the HIV-1 protease-coding region involved in resistance, but the role of Gag in drug susceptibility has also recently been reported. In order to avoid the inherent limitations resulting from partial cloning of the viral genome, we designed and evaluated a new experimental strategy to test the in vitro susceptibility of primary viral isolates to protease inhibitors. Our protocol, which is based on a two-round infection protocol using the reporter TZM-bl cell line, showed a good correlation with genotypic resistance prediction and with the Antivirogram phenotypic assay, in both protease-recombinant viruses and primary viral isolates. The protocol is suitable for any HIV-1 subtype and enables rapid in-house measurement of protease inhibitor susceptibility, thus making it possible to evaluate the concomitant effects of both patient-derived gag and protease-coding regions. PMID:23015664

  11. Core chemotype diversification in the HIV-1 entry inhibitor class using field-based bioisosteric replacement.

    PubMed

    Tuyishime, Marina; Lawrence, Rae; Cocklin, Simon

    2016-01-01

    Demand remains for new inhibitors of HIV-1 replication and the inhibition of HIV-1 entry is an extremely attractive therapeutic approach. Using field-based bioisosteric replacements, we have further extended the chemotypes available for development in the HIV-1 entry inhibitor class. Moreover, using field-based disparity analysis of the compounds, 3D structure-activity relationships were derived that will be useful in the further development of these inhibitors towards clinical utility. PMID:26531151

  12. CD4 mimetics sensitize HIV-1-infected cells to ADCC

    PubMed Central

    Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S.; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B.; Park, Jongwoo; Jones, David M.; Courter, Joel R.; Melillo, Bruno N.; Kaufmann, Daniel E.; Hahn, Beatrice H.; Permar, Sallie R.; Haynes, Barton F.; Madani, Navid; Sodroski, Joseph G.; Finzi, Andrés

    2015-01-01

    HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection. PMID:25941367

  13. New drug regimens for HIV in pregnancy and a national strategic plan to manage HIV: A South African perspective.

    PubMed

    Ngene, Nnabuike C; Moodley, Jagidesa

    2015-10-01

    In South Africa, new drug regimens (WHO treatment Option B) used to manage HIV infection in pregnancy and the national strategic plan on HIV have resulted in improved health outcomes. Among these outcomes are reductions in the following: mother-to-child transmission (MTCT) of HIV to 2.4%; maternal deaths attributable to HIV; and adverse reactions due to antiretroviral therapy (ART). The present article describes these new drug regimens and the national strategic HIV management plan, as well as their challenges and the implications of improved health outcomes. Such outcomes imply that further decreases in MTCT of HIV, and HIV attributable maternal deaths are possible if potential challenges are addressed and treatment option B+ offered. A confidential enquiry into each case of MTCT is advocated to reduce vertical transmission rates to zero levels. PMID:26433498

  14. Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes

    PubMed Central

    Matoso, Paula; Foxall, Russell B.; Tendeiro, Rita; Pires, Ana R.; Carvalho, Tânia; Pinheiro, Ana I.; Soares, Rui S.

    2014-01-01

    ABSTRACT A unique HIV-host equilibrium exists in untreated HIV-2-infected individuals. This equilibrium is characterized by low to undetectable levels of viremia throughout the disease course, despite the establishment of disseminated HIV-2 reservoirs at levels comparable to those observed in untreated HIV-1 infection. Although the clinical spectrum is similar in the two infections, HIV-2 infection is associated with a much lower rate of CD4 T-cell decline and has a limited impact on the mortality of infected adults. Here we investigated HIV-2 infection of the human thymus, the primary organ for T-cell production. Human thymic tissue and suspensions of total or purified CD4 single-positive thymocytes were infected with HIV-2 or HIV-1 primary isolates using either CCR5 or CXCR4 coreceptors. We found that HIV-2 infected both thymic organ cultures and thymocyte suspensions, as attested to by the total HIV DNA and cell-associated viral mRNA levels. Nevertheless, thymocytes featured reduced levels of intracellular Gag viral protein, irrespective of HIV-2 coreceptor tropism and cell differentiation stage, in agreement with the low viral load in culture supernatants. Our data show that HIV-2 is able to infect the human thymus, but the HIV-2 replication cycle in thymocytes is impaired, providing a new model to identify therapeutic targets for viral replication control. IMPORTANCE HIV-1 infects the thymus, leading to a decrease in CD4 T-cell production that contributes to the characteristic CD4 T-cell loss. HIV-2 infection is associated with a very low rate of progression to AIDS and is therefore considered a unique naturally occurring model of attenuated HIV disease. HIV-2-infected individuals feature low to undetectable plasma viral loads, in spite of the numbers of circulating infected T cells being similar to those found in patients infected with HIV-1. We assessed, for the first time, the direct impact of HIV-2 infection on the human thymus. We show that HIV-2 is able to infect the thymus but that the HIV-2 replication cycle in thymocytes is impaired. We propose that this system will be important to devise immunotherapies that target viral production, aiding the design of future therapeutic strategies for HIV control. PMID:25473058

  15. [Epidemiology of HIV infection].

    PubMed

    Blanche, S

    1988-01-01

    Maternal-fetal HIV transmission has become almost the only mode of infection for children in countries that screen their blood supplies. In many African countries with only partial screening of the blood supply, transfusions and the use of poorly sterilized syringes and other medical materials remain major sources of infection. The epidemiology of HIV infection among women and hence among children has progressively changed since the onset of the epidemic in Western countries. The rapid increase in the proportion of seropositive women corresponds to the massive infestation of intravenous drug addicts during 1984-85. Intravenous drug users now account for 18% of adult AIDS cases in Europe, with enormous disparities between countries from 1% in the United Kingdom to 62% in Italy. 60-70% of intravenous drug users in France are likely to be seropositive for HIV, including 30-40,000 women. In May 1988, a multicenter prospective study of infants of seropositive mothers demonstrated that intravenous drug use was the principal mode of transmission for women in France, accounting for 59% of cases. The true importance of heterosexual transmission in France is still difficult to assess. Until now, the vast majority of seropositive women have been infected by men in high-risk groups. The situation is very different in Africa, where HIV 1 seroprevalence reaches 7-8% in some urban areas. Transmission is almost exclusively heterosexual. In rural areas, seroprevalence rates are lower and apparently more stable over time. Data for large parts of Africa are still fragmentary. The rate of HIV transmission from mothers to their children is not well defined. It is estimated at 30-40% according to preliminary data from the multicenter French study. No significant differences have been noted according to the mode of contamination of the mother, but it is not clear that results can be extrapolated to Africa or other geographic zones. Contamination of 1 child by another has never been proven, and nothing should prevent seropositive children from leading as normal a family and social life as possible. PMID:3187865

  16. DEFINING HOPE AMONG HIV-Positive AFRICAN AMERICAN FEMALES.

    PubMed

    Kennedy, Toshua W

    2015-01-01

    Human immunodeficiency virus (HIV) affects heterosexual African American females (AAFs) with morbidity and mortality rates higher than females of any other race, accounting for thefourth largest number of HIV infections in the United States. Defining hope is importantfor understanding and therapeutic use of the concept in AAFs with HITA literature review exploring uses for this concept among HIV-positive AAFs, and a dimensional analysis, revealed positive and negative influences for hope. Tuthful and positive messages need to be developed for this population. PMID:26211301

  17. RNA interference approaches for treatment of HIV-1 infection.

    PubMed

    Bobbin, Maggie L; Burnett, John C; Rossi, John J

    2015-01-01

    HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery. PMID:26019725

  18. HIV Medicines and Side Effects

    MedlinePLUS

    ... depend on a person’s individual needs. Can HIV medicines cause side effects? HIV medicines help people with ... are common short-term side effects from HIV medicines? When starting an HIV medicine for the first ...

  19. Side Effects of HIV Medicines: HIV and Osteoporosis

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Osteoporosis (Last updated 7/31/2015; last reviewed 12/9/2014) Key Points Osteoporosis is a disease that ... HIV include HIV infection itself and some HIV medicines (for example, tenofovir [brand name: Viread]). Also, HIV ...

  20. HIV-1 subtypes and recombinants in Northern Tanzania: distribution of viral quasispecies.

    PubMed

    Kiwelu, Ireen E; Novitsky, Vladimir; Margolin, Lauren; Baca, Jeannie; Manongi, Rachel; Sam, Noel; Shao, John; McLane, Mary F; Kapiga, Saidi H; Essex, M

    2012-01-01

    This study analyzed the distribution and prevalence of HIV-1 subtypes, multiplicity of HIV-1 infection, and frequency of inter-subtype recombination among HIV-1-infected female bar and hotel workers in Moshi, Kilimanjaro Region, Tanzania, from 2004 to 2007. The HIV-1 viral sequences spanning the V1-C5 region of HIV-1 env gp120 were analyzed from 50 subjects by single genome amplification and sequencing (SGA/S) technique. A total of 1740 sequences were amplified and sequenced from the HIV-1 proviral DNA template. The median env sequences analyzed per subject per two time points was 38 (IQR 28-50) over one year of HIV infection. In a subset of 14 subjects, a total of 239 sequences were obtained from HIV-1 RNA template at the baseline visit. The most prevalent HIV-1 subtypes were A1 (56%) and C (30%), while HIV-1 subtype D and inter-subtype recombinant viruses were found in 6% and 8% of subjects respectively. Transmission of multiple HIV-1 variants was evident in 27% of the subjects infected with pure HIV-1 subtypes A1, C, or D. The HIV-1 inter-subtype recombinants were found in 8% including HIV-1 C/A, D/A, and complex mosaic recombinants. Multiple viral variants were found in two subjects infected with inter-subtype recombinants. One subject harbored quasispecies of both pure HIV-1 A1 and C/A recombinant. The other subject was infected with two complex mosaic inter-subtype recombinant variants belonging to subtype D. HIV-1 multiple infections and ongoing recombination contribute significantly to the genetic diversity of circulating HIV-1 in Tanzania and have important implications for vaccine design and the development of therapeutic strategies. PMID:23118882

  1. HIV infection en route to endogenization: two cases

    PubMed Central

    Colson, P; Ravaux, I; Tamalet, C; Glazunova, O; Baptiste, E; Chabriere, E; Wiedemann, A; Lacabaratz, C; Chefrour, M; Picard, C; Stein, A; Levy, Y; Raoult, D

    2014-01-01

    The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3–100% per gene) and 24% overall (0–50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication. PMID:25366539

  2. HIV among Gay and Bisexual Men

    MedlinePLUS

    ... you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | Subscribe ... Get Email Updates on HIV Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV ...

  3. Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells

    PubMed Central

    Grillberger, Leopold; Kreil, Thomas R; Nasr, Sonia; Reiter, Manfred

    2009-01-01

    Mammalian cells are the expression system of choice for therapeutic proteins, especially those requiring complex post-translational modifications. Traditionally, these cells are grown in medium supplemented with serum and other animal-or human-derived components to support viability and productivity. Such proteins are also typically added as excipients and stabilizers in the final drug formulation. However, the transmission of hepatitis B in the 1970s and of hepatitis C and HIV in the 1980s through plasma-derived factor VIII concentrates had catastrophic consequences for hemophilia patients. Thus, due to regulatory concerns about the inherent potential for transmission of infectious agents as well as the heterogeneity and lack of reliability of the serum supply, a trend has emerged to eliminate the use of plasma-derived additives in the production and formulation of recombinant protein therapeutics. This practice began with products used in the treatment of hemophilia and is progressively expanding throughout the entire industry. The plasma-free method of producing recombinant therapeutics is accomplished by the use of both cell culture media and final product formulations that do not contain animal-or human-derived additives. A number of recombinant therapeutic proteins for the treatment of several different diseases have been produced by plasma-free processes, with the objective of improving safety by eliminating blood-borne pathogens or by reducing immunogenicity. This review describes the factors that drove the development of plasma-free protein therapeutics and provides examples of advances in manufacturing that have made possible the removal of human and animal-derived products from all steps of recombinant protein production. PMID:19226552

  4. Anti-HIV-1 activities of extracts from the medicinal plant Rhus chinensis.

    PubMed

    Wang, Rui-Rui; Gu, Qiong; Yang, Liu-Meng; Chen, Ji-Jun; Li, Shun-Ying; Zheng, Yong-Tang

    2006-04-21

    Rhus chinensis, a species used in folk medicine by Chinese native people, the anti-HIV-1 activities of the petroleum ether, ethyl acetate, butanol and aqueous extract of Rhus chinensis, named as RC-1, RC-2, RC-3 and RC-4, respectively, was evaluated. The petroleum ether extract RC-1 can inhibit the syncytium formation and HIV-1 p24 antigen at non-cytotoxic concentrations, the 50% effective concentration (EC50) were 0.71 and 0.93 microg/ml, respectively. The therapeutic index (TI) was about 100. RC-1 had no activity on inhibiting HIV-1 recombinant RT and HIV-1 entry into host cells. Results showed that RC-1 was effective against HIV-1 and Rhus chinensis would be a useful medicinal plant for the chemotherapy of HIV-1 infection. RC-1 might inhibit the post steps or target the new sites of HIV-1 replication. PMID:16368204

  5. Canadian consensus statement on HIV and its transmission in the context of criminal law

    PubMed Central

    Loutfy, Mona; Tyndall, Mark; Baril, Jean-Guy; Montaner, Julio SG; Kaul, Rupert; Hankins, Catherine

    2014-01-01

    INTRODUCTION: A poor appreciation of the science related to HIV contributes to an overly broad use of the criminal law against individuals living with HIV in cases of HIV nondisclosure. METHOD: To promote an evidence-informed application of the law in Canada, a team of six Canadian medical experts on HIV and transmission led the development of a consensus statement on HIV sexual transmission, HIV transmission associated with biting and spitting, and the natural history of HIV infection. The statement is based on a literature review of the most recent and relevant scientific evidence (current as of December 2013) regarding HIV and its transmission. It has been endorsed by >70 additional Canadian HIV experts and the Association of Medical Microbiology and Infectious Disease Canada. RESULTS: Scientific and medical evidence clearly indicate that HIV is difficult to transmit during sex. For the purpose of informing the justice system, the per-act possibility of HIV transmission through sex, biting or spitting is described along a continuum from low possibility, to negligible possibility, to no possibility of transmission. This possibility takes into account the impact of factors such as the type of sexual acts, condom use, antiretroviral therapy and viral load. Dramatic advances in HIV therapy have transformed HIV infection into a chronic manageable condition. DISCUSSION: HIV physicians and scientists have a professional and ethical responsibility to assist those in the criminal justice system to understand and interpret the science regarding HIV. This is critical to prevent miscarriage of justice and to remove unnecessary barriers to evidence-based HIV prevention strategies. PMID:25285108

  6. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

    PubMed Central

    Arcinue, Cheryl A.; Bartsch, Dirk-Uwe; El-Emam, Sharif Y.; Ma, Feiyan; Doede, Aubrey; Sharpsten, Lucie; Gomez, Maria Laura; Freeman, William R.

    2015-01-01

    Purpose To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Methods Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Results Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Conclusion Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis. PMID:26244973

  7. An In-Silico Analysis of the SMART Study of HIV Infection

    E-print Network

    Duffy, Ken

    An In-Silico Analysis of the SMART Study of HIV Infection Jorge Ferreira and Rick Middleton T cells with Human Immunodeficiency Virus (HIV) mutations. We study how the dynamics are affected to identify possible causes of its failure. We mathematically describe the HIV infection and perform numerical

  8. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    SciTech Connect

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-10-25

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics.

  9. HIV-1 Prevention for HIV-1 Serodiscordant Couples

    PubMed Central

    Curran, Kathryn; Baeten, Jared M.; Coates, Thomas J.; Kurth, Ann; Mugo, Nelly R.

    2013-01-01

    A substantial proportion of HIV-1-infected individuals in sub-Saharan Africa are in stable relationships with HIV-1-uninfected partners, and HIV-1 serodiscordant couples thus represent an important target population for HIV-1 prevention. Couple-based HIV-1 testing and counseling facilitates identification of HIV-1 serodiscordant couples, counseling about risk reduction, and referrals to HIV-1 treatment, reproductive health services, and support services. Maximizing HIV-1 prevention for HIV-1 serodiscordant couples requires a combination of strategies, including counseling about condoms, sexual risk, fertility, contraception, and the clinical and prevention benefits of antiretroviral therapy (ART) for the HIV-1-infected partner; provision of clinical care and ART for the HIV-1-infected partner; antenatal care and services to prevent mother to child transmission for HIV-1- infected pregnant women; male circumcision for HIV-1-uninfected men; and, pending guidelines and demonstration projects, oral pre-exposure prophylaxis (PrEP) for HIV-1-uninfected partners. PMID:22415473

  10. [Health security--GMOs in therapeutics].

    TOXLINE Toxicology Bibliographic Information

    Trouvin JH

    2003-03-01

    The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

  11. Therapeutic use exemption.

    PubMed

    Dvorak, J; Kirkendall, D; Vouillamoz, M

    2006-07-01

    Football players who have either physical symptoms or disease after injury may need to be treated with specific medicines that are on the list of prohibited substances. Therapeutic use exemption may be granted to such players, in accordance with strictly defined criteria-these are presented in this article. Procedures of how to request for an abbreviated or a standard therapeutic use exemption are explained, and data on therapeutic use exemptions (UEFA and FIFA, 2004 and 2005) are also presented. PMID:16799102

  12. HIV Treatment: The Basics

    MedlinePLUS

    ... of HIV transmission. When is it time to start treatment with HIV medicines? When to start ART depends on a person’s individual needs. Factors that influence the decision to start ART include: The overall health of the person ...

  13. Treatment of HIV Infection

    MedlinePLUS

    ... Marketing Share this: Main Content Area Treatment of HIV Infection Photo of a variety of different drug ... drugs in order to maintain their health quality. HIV/AIDS Treatment Research NIAID is focused on finding ...

  14. HIV and AIDS

    MedlinePLUS

    ... High School How Can I Stop Cutting? Scoliosis HIV and AIDS KidsHealth > Teens > Sexual Health > STDs & Other ... can begin treatment if necessary. Continue How Does HIV Affect the Body? A healthy body has CD4 ...

  15. HIV and Pulmonary Hypertension

    MedlinePLUS

    HIV Pulmonary & PH Hypertension Did you know that if you are HIV-positive, you are at risk for pulmonary hypertension? www.PHAssociation.org About Pulmonary Hypertension PULMONARY HYPERTENSION, OR PH, is complex and often misunderstood. PH means high ...

  16. HIV/AIDS

    MedlinePLUS

    ... immunodeficiency virus (HIV) is the virus that causes AIDS. When a person becomes infected with HIV, the ... cancers. When that happens, the illness is called AIDS. Once a person has the virus, it stays ...

  17. HIV/AIDS

    MedlinePLUS

    ... Fact sheets Features Commentaries 2014 Multimedia Contacts HIV/AIDS Fact sheet N°360 Updated November 2015 Key ... 2015, new HIV infections have fallen by 35%, AIDS-related deaths have fallen by 24% with some ...

  18. Children and HIV

    MedlinePLUS

    ... available. Children have a very high rate of metabolism. This gradually slows as they mature. The liver ... Newest Fact Sheets 111. Optimizing the HIV Care Environment 115. Adolescents and the HIV Care Continuum 114. ...

  19. Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles

    SciTech Connect

    Peretti, Silvia; Schiavoni, Ilaria; Pugliese, Katherina; Federico, Maurizio . E-mail: federico@iss.it

    2006-02-05

    We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies.

  20. Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT.

    PubMed Central

    Rubbert, A; Bock, E; Schwab, J; Marienhagen, J; Nüsslein, H; Wolf, F; Kalden, J R

    1994-01-01

    Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P = 0.002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences. Images Fig. 1 Fig. 2 Fig. 3 PMID:7994900

  1. Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura.

    PubMed

    Cines, Douglas B; McKenzie, Steven E; Siegel, Don L

    2003-12-01

    Idiopathic thrombocytopenic purpura (ITP) is a common immune disorder caused by platelet-reactive autoantibodies. Antibody-coated platelets are cleared more rapidly from the circulation, often in the spleen, than they can be replaced by compensatory stimulation of platelet production in the bone marrow. In some patients, platelet production is depressed as well. ITP in adults does not generally remit spontaneously, and most patients require treatment to prevent bleeding at one time or another. Therapy with corticosteroids, danazol, intravenous immune globulin, anti-D antibody, and several other agents inhibits clearance of the antibody-coated platelets but is rarely curative. Most patients will sustain a hemostatic response after splenectomy, although relapses may occur at any time. Patients may be more responsive to these same modalities after splenectomy, but treatment with an immunosuppressant that inhibits T- and B-cell function and cooperation, including azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, or anti-CD20, may be required. Antiviral therapy is useful in patients with HIV or hepatitis C infection, but no consensus has been reached as to the efficacy of antibiotics to eradicate Helicobacter pylori. Promising results have been seen in several patients treated with a modified thrombopoietin. It may be possible to design therapeutics that exploit the apparent restricted immunoglobulin gene usage by antiplatelet antibodies, perhaps in the form of engineered anti-idiotypic antibodies or other compounds that specifically target autoantibody-producing B cells. Rationale therapy awaits a more thorough understanding of autoantibody production. PMID:14668641

  2. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  3. Inhaled corticosteroids in persons with HIV infection: not that harmless.

    PubMed

    Spruyt, S; Vlieghe, E; Bomans, P; Moerman, F; Colebunders, R; Van den Ende, J

    2012-01-01

    There is a growing group of HIV-seropositive patients at risk for chronic lung disease due to their life style and age. The interaction between certain antiretroviral drugs and corticosteroid inhalation therapy is potentially dangerous but often unrecognised. We present three cases from our HIV-clinic of whom two developed full blown Cushing's syndrome over a short period of time and one presented with asymptomatic hypocortisolaemia due to serious drug interactions between HIV-drugs and inhaled corticosteroids. General practitioners, HIV and chest physicians should all be aware of this potentially life-threatening interaction and the combination of those products should be avoided where possible. PMID:22712167

  4. Oral candidosis in HIV-infected patients.

    PubMed

    Egusa, Hiroshi; Soysa, Niroshani S; Ellepola, Arjuna N; Yatani, Hirofumi; Samaranayake, Lakshman P

    2008-11-01

    Oral candidosis (syn. Oral candidiasis; OC), is a collective term given to a group of oral mucosal disorders caused by the fugal pathogen belonging to the genus Candida. The association of OC with the human immunodeficiency virus (HIV) infection has been known since the advent of the acquired immune deficiency syndrome (AIDS) pandemic. OC is one of the earliest manifestations of HIV disease in high risk individuals not undergoing chemotherapy and is also a strong predictor of the subsequent risk of AIDS-related illness or death. With the advances in HIV therapy, such as highly active anti-retroviral therapy (HAART), the prevalence and presenting features of OC have changed in HIV-infected individuals, especially those in industrialized countries. The presence of OC in "controlled" HIV-positive individuals may be indicative of a patient nonadherence to therapy or possible failure. The factors contributing to the genesis of OC and its progression in these individuals are poorly understood, but may include an interrelationship between HIV and Candida and/or a dysfunction in the local immunity, superimposed on weakened cell-mediated immunity and depletion of CD4 T cells. The dramatic increase in publications on this topic matches the increased importance and awareness of this opportunistic infection in HIV-infected individuals. In this review we first address the epidemiologic and clinical features of OC in HIV-infected persons, followed by the current understanding of the pathogenesis of OC in the context of HIV infection with a concluding section on the current management concepts of OC. PMID:18991614

  5. HIV-Positive Athletes. When Medicine Meets the Law.

    ERIC Educational Resources Information Center

    Mitten, Matthew, J.

    1994-01-01

    Though the risk of HIV transmission in sports is slight, physicians who treat active patients can encounter weighty legal issues. Mandatory testing, exclusion of HIV-positive athletes, and breaching of patient confidentiality can lead to lawsuits. Knowing the possible consequences can help physicians in setting effective, legal prevention…

  6. Silence, Sexuality and HIV/AIDS in South African Schools

    ERIC Educational Resources Information Center

    Morrell, Robert

    2003-01-01

    In South Africa where there is a very high HIV infection rate among teenagers and young adults, it is surprising to find that students and teachers are very unwilling to talk about the possibility of being or becoming HIV positive. While AIDS messages dominate public discourse, there is a silence in schools about the personal in relation to AIDS.…

  7. Women and HIV

    MedlinePLUS

    ... HIV who take HIV medicines during pregnancy. To Learn More AIDS.gov National Library of Medicine- AIDS/HIV More in For Women Medication Safety for Women ¡Nunca Más! Novelas An Invitation to Collaborate Free Publications English Publications Spanish Publications Publications in Other Languages Take ...

  8. HIV and Immunizations

    MedlinePLUS

    HIV Treatment HIV and Immunizations (Last updated 4/29/2015; last reviewed 4/29/2015) Key Points Vaccines are products that protect people from diseases ... taking HIV medicines before getting immunizations. What are vaccines? Vaccines are products that protect people from diseases ...

  9. HIV-Associated Cancers

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > HIV-Associated Cancers HIV-Associated Cancers [1] The Office of Cancer Genomics (OCG)Opens in a New Tab [2], along with the Office of HIV and AIDS Malignancies (OHAM)Opens in a New

  10. HIV-Associated Cancers

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > HIV-Associated Cancers HIV-Associated Cancers [1] The Office of Cancer Genomics (OCG)Opens in a New Tab [2], along with the Office of HIV and AIDS Malignancies (OHAM)Opens in a New

  11. Novel Approaches to Targeting Visceral and Hepatic Adiposities in HIV-Associated Lipodystrophy.

    PubMed

    Tien, Phyllis C

    2015-12-01

    Visceral and hepatic adiposities have been associated with both cardiovascular and liver disease and are of concern in HIV-infected persons in the modern era of combination antiretroviral therapy (ART). The development of therapeutic targets to reduce visceral and hepatic adiposities in HIV-infected persons has been slow, because of early reports that attributed the excess adiposity to specific antiretroviral drugs. Visceral adiposity was initially thought to occur as part of a protease inhibitor-induced "HIV-associated lipodystrophy syndrome." Subsequent studies show that visceral adiposity is likely a result of effective ART, recovery of health, and the normal aging process. Visceral adiposity is an established risk factor for hepatic adiposity. Identifying drug targets for non-alcoholic fatty liver disease is under active investigation. The present review summarizes the recent literature on the pathogenesis of visceral and hepatic adiposities in HIV-infected persons, current therapeutic strategies, and novel interventions in HIV-infected and uninfected persons. PMID:26493063

  12. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  13. Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women

    PubMed Central

    Shen, Ruizhong; Achenbach, Jenna; Shen, Yue; Palaia, Jana; Rahkola, Jeremy T.; Nick, Heidi J.; Smythies, Lesley E.; McConnell, Michelle; Fowler, Mary G.; Smith, Phillip D.; Janoff, Edward N.

    2015-01-01

    Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT). Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs) and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process. PMID:26680219

  14. Therapeutic Recreation Practicum Manual.

    ERIC Educational Resources Information Center

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  15. Trends in Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Smith, Ralph W.

    1995-01-01

    Discusses the implications of the rapid, dramatic changes taking place in therapeutic recreation for individuals with physical disabilities. The article notes the impact of changes in managed care, examines programming trends in therapeutic recreation (adventure/outdoor education, competitive sports, handcycling, health enhancement activities, and…

  16. Visceral Leishmaniasis and HIV Coinfection in the Mediterranean Region

    PubMed Central

    Monge-Maillo, Begoña; Norman, Francesca F.; Cruz, Israel; Alvar, Jorge; López-Vélez, Rogelio

    2014-01-01

    Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%–6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region. PMID:25144380

  17. HIV-negative Men-who-Have-Sex-with-Men who Bareback are Concerned about HIV Infection: Implications for HIV Risk Reduction Interventions

    PubMed Central

    Balán, Iván C.; Carballo-Diéguez, Alex; Ventuneac, Ana; Remien, Robert H.; Dolezal, Curtis; Ford, Jordan

    2012-01-01

    The emergence of barebacking (intentional unprotected anal intercourse in situations where there is risk of HIV infection) among men who have sex with men (MSM) has been partially attributed to a decrease in HIV-related concerns due to improved anti-retroviral treatment. It is important to understand the level of concern these men have regarding HIV infection because it can affect their interest in risk reduction behaviors as well as their possible engagement in risk reduction interventions. As part of a study on MSM who use the Internet to seek sexual partners, 89 ethnic and racially diverse men who reported never having an HIV-positive test result completed an in-depth qualitative interview and a computer-based quantitative assessment. Of the 82 men who were asked about concerns of HIV infection during the qualitative interviews, 30 expressed “significant concern” about acquiring HIV, while 42 expressed “moderate concern,” and 10 expressed “minimal concern. Themes that emerged across the different levels of concern were their perceptions of the severity of HIV infection, having friends who are HIV positive, and their own vulnerability to HIV infection. However, these themes differed depending on the level of concern. Among the most frequently mentioned approaches to decrease risk of HIV infection, participants mentioned avoiding HIV-positive sex partners, limiting the number of partners with whom they barebacked, and not allowing partners to ejaculate inside their rectum. Findings suggest that many MSM who bareback would be amenable to HIV prevention efforts that do not depend solely on condom use. PMID:22218787

  18. Recent Advances in Humanized Mice: Accelerating the Development of an HIV Vaccine

    PubMed Central

    Tager, Andrew M.; Pensiero, Michael; Allen, Todd M.

    2013-01-01

    Recent advances in the development of humanized mice hold great promise to advance our understanding of protective immunity to human immunodeficiency virus (HIV) infection and to aid in the design of an effective HIV vaccine. This supplement of the Journal of Infectious Diseases summarizes work in the humanized mouse model presented at an HIV Humanized Mouse workshop in Boston, Massachusetts, in November 2012, including recent advances in the development of humanized mice, the trafficking of human immune cells following mucosal HIV transmission, the role of immune activation and Toll-like receptor agonists in the control of HIV, the induction and efficacy of HIV-specific cellular and humoral immune responses, and the preclinical modeling of novel anti-HIV therapeutics. Many gaps remain in our understanding of how to design an effective HIV vaccine and novel therapeutics to eliminate the viral reservoir. Promising early results from studies in humanized mice suggest great potential and enthusiasm for this model to accelerate these critical areas of HIV research. PMID:24151317

  19. Virologic and immunologic outcome of HAART in Human Immunodeficiency Virus (HIV)-1 infected patients with and without tuberculosis (TB) and latent TB infection (LTBI) in Addis Ababa, Ethiopia

    PubMed Central

    2013-01-01

    Background HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB. Methods A total of 232 adults, including 59 HIV patients with clinical TB (HIV?+?TB+), 125 HIV patients without clinical TB (HIV?+?TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV?+?patients (28 TB?+?and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-? responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation. Results The majority of HIV?+?TB- (70%, 81%, 84%) as well as HIV?+?TB?+?patients (60%, 77%, 80%) had virologic success (HIV RNA?HIV?+?TB?+?(from 110.3 to 289.9 cells/?l), HIV?+?TB- patients (197.8 to 332.3 cells/?l), HIV?+?TST- (199 to 347 cells/?l) and HIV?+?TST?+?individuals (195 to 319 cells/?l). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-? response at baseline was significantly lower in HIV?+?TB?+?(3.6 pg/ml) compared to HIV-TB?+?patients (34.4 pg/ml) and HIV?+?TST?+?(46.3 pg/ml) individuals; and in HIV-TB?+?patients compared to HIV-TST?+?individuals (491.2 pg/ml). By M18 on HAART, the IFN-? response remained impaired in HIV?+?TB?+?patients (18.1 pg/ml) while it normalized in HIV?+?TST?+?individuals (from 46.3 to 414.2 pg/ml). Conclusions Our data show that clinical and latent TB infections do not influence virologic and immunologic outcomes of ART in HIV patients. Despite this, HAART was unable to restore optimal TB responsiveness as measured by Mtb specific IFN-? response in HIV/TB patients. Improvement of Mtb-specific immune restoration should be the focus of future therapeutic strategies. PMID:23842109

  20. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    PubMed Central

    Meng, Jingjing; Sindberg, Gregory M.; Roy, Sabita

    2015-01-01

    Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV) infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population. PMID:26167159

  1. Sociocultural and epidemiological aspects of HIV/AIDS in Mozambique

    PubMed Central

    2010-01-01

    Background A legacy of colonial rule coupled with a devastating 16-year civil war through 1992 left Mozambique economically impoverished just as the human immunodeficiency virus (HIV) epidemic swept over southern Africa in the late 1980s. The crumbling Mozambican health care system was wholly inadequate to support the need for new chronic disease services for people with the acquired immunodeficiency syndrome (AIDS). Methods To review the unique challenges faced by Mozambique as they have attempted to stem the HIV epidemic, we undertook a systematic literature review through multiple search engines (PubMed, Google Scholar™, SSRN, AnthropologyPlus, AnthroSource) using Mozambique as a required keyword. We searched for any articles that included the required keyword as well as the terms 'HIV' and/or 'AIDS', 'prevalence', 'behaviors', 'knowledge', 'attitudes', 'perceptions', 'prevention', 'gender', drugs, alcohol, and/or 'health care infrastructure'. Results UNAIDS 2008 prevalence estimates ranked Mozambique as the 8th most HIV-afflicted nation globally. In 2007, measured HIV prevalence in 36 antenatal clinic sites ranged from 3% to 35%; the national estimate of was 16%. Evidence suggests that the Mozambican HIV epidemic is characterized by a preponderance of heterosexual infections, among the world's most severe health worker shortages, relatively poor knowledge of HIV/AIDS in the general population, and lagging access to HIV preventive and therapeutic services compared to counterpart nations in southern Africa. Poor education systems, high levels of poverty and gender inequality further exacerbate HIV incidence. Conclusions Recommendations to reduce HIV incidence and AIDS mortality rates in Mozambique include: health system strengthening, rural outreach to increase testing and linkage to care, education about risk reduction and drug adherence, and partnerships with traditional healers and midwives to effect a lessening of stigma. PMID:20529358

  2. Types of HIV/AIDS Antiretroviral Drugs

    MedlinePLUS

    ... reverse transcriptase (RT) from converting single-stranded HIV RNA into double-stranded HIV DNA?a process called ... RT, interfering with its ability to convert HIV RNA into HIV DNA Integrase Inhibitors block the HIV ...

  3. How Do You Get HIV or AIDS?

    MedlinePLUS

    ... Translate Text Size Print How Do You Get HIV or AIDS? How Is HIV Spread? HIV is spread from an infected person ... to find a testing site near you. Ways HIV Is Transmitted In the United States, HIV is ...

  4. Salk's HIV immunogen: an immune-based therapy in human trials since 1988.

    PubMed

    Jonas Salk, the developer of the first polio vaccine, has created a therapeutic vaccine for HIV which helps the immune system fight disease progression. Salk uses inactivated HIV-1 virus combined with Incomplete Freund's Adjuvant (IFA) in the vaccine preparation. The resulting HIV-1 immunogen was first studied in 1987, and since then, 235 seropositive individuals have received inoculations without serious adverse effects. Data from the first 25 subjects indicate that immunization with the HIV-1 immunogen results in improvement of cell-mediated response against the virus, a slower increase in the amount of virus present, and a reduced rate of clinical progression. Subsequent studies also show that higher doses of immunogen may produce stronger cell-mediated responses and high HIV-DTH (delayed-type hypersensitivity responsiveness immunogen) is associated with better outcome. Additional trials of HIV-1 immunogen are awaiting Food and Drug Administration approval. PMID:11362152

  5. Technologies of the HIV/AIDS corpse.

    PubMed

    Troyer, John Erik

    2010-04-01

    In the early 1980s, unprecedented numbers of gay men and intravenous drug users began dying of what would later become known as HIV/AIDS. What the HIV/AIDS corpse posed was a direct challenge to the institutional controls developed by funeral directors to normalize and transform the dead body. How the funeral service industry reacted and changed in response to the emergence of the HIV/AIDS corpse offers an opportunity to re-examine the productive potential of the dead human body. My article examines the epidemic's production of what I call the HIV/AIDS corpse, and the institutional affects those corpses had on the US funeral service industry. The theoretical concept I use to analyze the productive qualities of the HIV/AIDS corpse is the technologies of the corpse. These technologies are the machines, laws, and institutions that control the corpse by classifying, organizing, and physically transforming it. What emerges from the institutional challenges posed by the HIV/AIDS corpse is a specific kind of dead body that offers political possibilities for both the concept of a queer body and the broader subject of human death. PMID:20455141

  6. HIV status, gender, and marriage dynamics among adults in Rural Malawi

    PubMed Central

    Anglewicz, Philip; Reniers, Georges

    2014-01-01

    Marriage and partnerships bring about non-negligible health risks in populations with generalized HIV epidemics, and concerns about the possible transmission of HIV thus often factor in the decision-making about partnership formation and dissolution. The awareness of and responses to HIV risk stemming from regular sexual partners have been well documented in African populations, but few studies have estimated the effects of observed HIV status on marriage decisions and outcomes. We study marriage dissolution and remarriage using longitudinal data with repeated HIV and marital status measurements from rural Malawi. Results indicate that HIV positive individuals face greater risks of union dissolution (both via widowhood and divorce) and lower remarriage rates. Modeling studies suggest that the exclusion of HIV positives from the marriage or partnerships market will decelerate the propagation of HIV. PMID:25469927

  7. Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS

    PubMed Central

    Dahal, Santosh; Chitti, Sai V. P.; Nair, Madhavan P. N.; Saxena, Shailendra K.

    2015-01-01

    Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-?B that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection in cocaine using HIV infected population. PMID:26441868

  8. HIV-1 latency in actively dividing human T cell lines

    PubMed Central

    Jeeninga, Rienk E; Westerhout, Ellen M; van Gerven, Marja L; Berkhout, Ben

    2008-01-01

    Background Eradication of HIV-1 from an infected individual cannot be achieved by current drug regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy and are able to replenish systemic infection upon interruption of the treatment. Therapeutic targeting of viral latency will require a better understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 in resting memory CD4 T cells, the most prominent reservoir of transcriptional silent provirus. However, the molecular mechanisms that permit long-term transcriptional control of proviral gene expression in these cells are still not well understood. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication. Results We set out to develop a new in vitro HIV-1 latency model system using the doxycycline (dox)-inducible HIV-rtTA variant. Stable cell clones were generated with a silent HIV-1 provirus, which can subsequently be activated by dox-addition. Surprisingly, only a minority of the cells was able to induce viral gene expression and a spreading infection, eventhough these experiments were performed with the actively dividing SupT1 T cell line. These latent proviruses are responsive to TNF? treatment and alteration of the DNA methylation status with 5-Azacytidine or genistein, but not responsive to the regular T cell activators PMA and IL2. Follow-up experiments in several T cell lines and with wild-type HIV-1 support these findings. Conclusion We describe the development of a new in vitro model for HIV-1 latency and discuss the advantages of this system. The data suggest that HIV-1 proviral latency is not restricted to resting T cells, but rather an intrinsic property of the virus. PMID:18439275

  9. CXCR4-tropic HIV-1 suppresses replication of CCR5-tropic HIV-1 in human lymphoid tissue by selective induction of CC-chemokines.

    PubMed

    Ito, Yoshinori; Grivel, Jean-Charles; Chen, Silvia; Kiselyeva, Yana; Reichelderfer, Patricia; Margolis, Leonid

    2004-02-01

    In infected individuals, human immunodeficiency virus type 1 (HIV-1) exist as a "swarm" of quasi species compartmentalized in tissues where individual viral variants may interact locally. We have used human lymphoid tissue, where the critical events of HIV disease occur, to study local interactions in model HIV-1 binary swarms ex vivo. We infected tissue blocks with binary mixtures consisting either of CCR5-dependent and CXCR4-dependent variants or of 2 dual-tropic HIV-1 variants, of which one is skewed to utilization of CXCR4 and the other of CCR5. HIV-1 variants that use CXCR4 suppress replication of CCR5-dependent HIV-1 variants, whereas CCR5-dependent HIV-1 variants do not affect replication of CXCR4-dependent HIV-1. CC-chemokines that inhibit replication of CCR5-dependent HIV-1 variants were up-regulated by CXCR4-dependent HIV-1, thus possibly contributing to this suppression. Tissue-specific chemokine/cytokine network modulations triggered by individual HIV-1 variants may be an important mechanism of local interactions among HIV-1 quasi species in infected tissue. PMID:14745709

  10. [Therapeutic approach to bilateral hepatoblastoma].

    PubMed

    Babut, J M; Le Gall, E; Bourdelat, D; Jouan, H; Gruel, Y

    1983-01-01

    The treatment of a case of bilateral hepatoblastoma by continuous infusion of adriamycin in the hepatic artery accompanied by ligature of the right hepatic artery enabled the authors to carry out six weeks later an extensive right lobe hepatectomy. Unfortunately the patient died seven weeks after the partial hepatectomy from complication of surgery. Thus it was possible to demonstrate the effectiveness of the intra arterial chemotherapy. No residual tumor could be found at autopsy. As in the case with the adult, arterial ligature combined with carefully targeted chemotherapy would seem to be potentially important therapeutic option in the treatment of malignant liver tumors in children. PMID:6303615

  11. Towards Combination HIV Prevention for Injection Drug Users: Addressing Addictophobia, Apathy and Inattention

    PubMed Central

    Strathdee, Steffanie A.; Shoptaw, Steven; Dyer, Typhanye Penniman; Quan, Vu Minh; Aramrattana, Apinun

    2013-01-01

    Purpose of the review Recent breakthroughs in HIV-prevention science led us to evaluate the current state of combination HIV-prevention for injection drug users (IDUs). We review the recent literature focusing on possible reasons why coverage of prevention interventions for HIV, HCV and tuberculosis among IDUs remains dismal. We make recommendations for future HIV research and policy. Recent findings IDUs disproportionately under-utilize VCT, primary care and ART, especially in countries that have the largest burden of HIV among IDUs. IDUs present later in the course of HIV infection and experience greater morbidity and mortality. Why are IDUs under-represented in HIV-prevention research, access to treatment for both HIV and addiction, and access to HIV combination prevention? Possible explanations include addictophobia, apathy, and inattention, which we describe in the context of recent literature and events. Summary This commentary discusses the current state of HIV-prevention interventions for IDUs including, VCT, NSP, OST, ART and PrEP, and discusses ways to work towards true combination HIV-prevention for IDU populations. Communities need to overcome tacit assumptions that IDUs can navigate through systems that are maintained as separate silos, and take a rights-based approach to HIV-prevention to ensure that IDUs have equitable access to life-saving prevention and treatments. PMID:22498479

  12. HIV-1 Induced Nuclear Factor I-B (NF-IB) Expression Negatively Regulates HIV-1 Replication through Interaction with the Long Terminal Repeat Region

    PubMed Central

    Vemula, Sai Vikram; Veerasamy, Ravichandran; Ragupathy, Viswanath; Biswas, Santanu; Devadas, Krishnakumar; Hewlett, Indira

    2015-01-01

    Background: Retroviruses rely on host factors for cell entry, replication, transcription, and other major steps during their life cycle. Human Immunodeficiency Virus-1 (HIV-1) is well known for utilizing a plethora of strategies to evade the host immune response, including the establishment of latent infection within a subpopulation of susceptible cells. HIV-1 also manipulates cellular factors in latently infected cells and persists for long periods of time, despite the presence of successful highly active antiretroviral therapy (HAART). Results: In this study we demonstrate that Nuclear Factor-IB (NF-IB) is induced during HIV-1 infection and its expression negatively impacts viral replication. During HIV-1 infection in peripheral blood mononuclear cells (PBMCs), and the T cell line, Jurkat or during induction of virus replication in latently infected cells, ACH2 and J1.1, we observed a time-dependent alteration in NF-IB expression pattern that correlated with HIV-1 viral expression. Using the Chip assay, we observed an association of NF-IB with the long terminal repeat region of HIV-1 (LTR) (-386 to -453 nt), and this association negatively correlated with HIV-1 transcription. Furthermore, knock-down of NF-IB levels in J1.1 cells resulted in an increase of HIV-1 levels. Knock-down of NF-IB levels in J-Lat-Tat-GFP (A1), (a Jurkat cell GFP reporter model for latent HIV-1 infection) resulted in an increase in GFP levels, indicating a potential negative regulatory role of NF-IB in HIV-1 replication. Conclusion: Overall, our results suggest that NF-IB may play a role in intrinsic antiretroviral defenses against HIV-1. These observations may offer new insights into the correlation of the latently infected host cell types and HIV-1, and help to define new therapeutic approaches for triggering the switch from latency to active replication thereby eliminating HIV-1 latent infection. PMID:25664610

  13. Therapeutics for Bowel Disorders

    Cancer.gov

    The National Cancer Institute''s Laboratory of Metabolism is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics that ameliorate bowel disorders.

  14. Modeling HIV-associated neurocognitive disorders in mice: new approaches in the changing face of HIV neuropathogenesis

    PubMed Central

    Jaeger, Laura B.; Nath, Avindra

    2012-01-01

    It is well established that infection with the human immunodeficiency virus (HIV) leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART), the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals surviving for decades with a high quality of life. Despite these advances, many HIV-infected individuals develop some degree of neurodegeneration and cognitive impairment. The underlying pathophysiological mechanisms are not well understood, and there are no effective treatments. Thus, there is an unmet need for animal models that enable the study of HIV-associated neurocognitive disorders (HAND) and the testing of new therapeutic approaches to combat them. Here, we review the pros and cons of existing mouse models of HIV infection for addressing these aims and propose a detailed strategy for developing a new mouse model of HIV infection. PMID:22563057

  15. Antiviral agents and HIV prevention: controversies, conflicts, and consensus

    PubMed Central

    Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.

    2013-01-01

    Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation. PMID:22507927

  16. HIV/AIDS in Women

    MedlinePLUS

    HIV, the human immunodeficiency virus, kills or damages cells of the body's immune system. The most advanced stage of infection with HIV is AIDS, which stands for acquired immunodeficiency syndrome. HIV often ...

  17. Legal Disclosure of HIV Status

    MedlinePLUS

    ... Legal Disclosure Translate Text Size Print Legal Disclosure HIV Disclosure Policies and Procedures If your HIV test ... aids.gov • locator.aids.gov • facing.aids.gov • HIV/AIDS Service Locator Locator Widgets • Instructions • API Find ...

  18. HIV, AIDS, and the Future

    MedlinePLUS

    ... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 Table ... and your loved ones from HIV/AIDS. The AIDS Memorial Quilt In 1987, a total of 1, ...

  19. Medicare and HIV/AIDS

    MedlinePLUS

    HIV/AIDS POLICY FACT SHEET Medicare and HIV/AIDS February 2009 Medicare, the federal health insurance program for people ... beneficiaries. 2 Figure 1: Federal Funding for HIV/AIDS Care by Program, FY 2008 4,5,6 ...

  20. HIV/AIDS and Alcohol

    MedlinePLUS

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). Each year in the United States, between 55, ...

  1. HIV / AIDS: An Unequal Burden

    MedlinePLUS

    ... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 Table ... Victoria Cargill talks to students about HIV and AIDS at the opening of a National Library of ...

  2. Therapeutic development in psoriasis.

    PubMed

    Sobell, Jeffrey M; Leonardi, Craig L

    2014-06-01

    Advances in molecular biology have provided the basis for development of new therapeutic approaches to psoriasis. New, more effective therapies target specific molecules in the inflammatory cascade involved in the pathogenesis of psoriasis.The biologic era of psoriasis therapy began with inhibitors of T-cell activation, tumor necrosis factor-?, and interleukin (IL)-12/23. Continued investigation has led to therapies and therapeutic candidates that target IL-17, IL-23, phosphodiesterase-4, and isomers of Janus kinase. PMID:25268599

  3. Bioengineering Beige Adipose Tissue Therapeutics

    PubMed Central

    Tharp, Kevin M.; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and their potential for the metabolic therapies. PMID:26539163

  4. Recent advances in HIV-associated cardiovascular diseases in Africa.

    PubMed

    Syed, Faisal F; Sani, Mahmoud Umar

    2013-08-01

    The last decade has witnessed major advances in our understanding of the epidemiology and pathophysiology of HIV-related cardiovascular disease in sub-Saharan Africa. In this review, we summarise these and discuss clinically relevant advances in diagnosis and treatment. In the Heart of Soweto Study, 10% of patients with newly diagnosed cardiovascular disease were HIV positive, and the most common HIV-related presentations were cardiomyopathy (38%), pericardial disease (13%) and pulmonary arterial hypertension (8%). HIV-related cardiomyopathy is more common with increased immunosuppression and HIV viraemia. With adequate antiretroviral therapy, the prevalence is low. Contributing factors such as malnutrition and genetic predisposition are under investigation. In other settings, pericardial disease is the most common presentation of HIV-related cardiovascular disease (over 40%), and over 90% of pericardial effusions are due to Mycobacterium tuberculosis (TB) pericarditis. HIV-associated TB pericarditis is associated with a greater prevalence of myopericarditis, a lower rate of progression to constriction, and markedly increased mortality. The role of steroids is currently under investigation in the form of a randomised controlled trial. HIV-associated pulmonary hypertension is significantly more common in sub-Saharan Africa than in developed countries, possibly as a result of interactions between HIV and other infectious agents, with very limited treatment options. It has recently been recognised that patients with HIV are at increased risk of sudden death. Infection with HIV is independently associated with QT prolongation, which is more marked with hepatitis C co-infection and associated with a 4.5-fold higher than expected rate of sudden death. The contribution of coronary disease to the overall burden of HIV-associated cardiovascular disease is still low in sub-Saharan Africa. PMID:23680889

  5. [Therapeutic equivalence of the new oral anticoagulants].

    PubMed

    Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L

    2015-10-01

    In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics. PMID:26146035

  6. Analysis of HIV-1 sequences before and after co-infecting syphilis.

    PubMed

    Koga, Ichiro; Odawara, Takashi; Matsuda, Masakazu; Sugiura, Wataru; Goto, Mieko; Nakamura, Tetsuya; Iwamoto, Aikichi

    2006-01-01

    Increasing syphilis incidence among men who have sex with men (MSM) has been reported. The index case was a human immunodeficiency virus type 1 (HIV-1)-positive MSM who presented coincidentally with the secondary syphilis and a rebound of plasma viral load after complete suppression of HIV-1 (below 50 copies/ml) for 13 months with potent antiretroviral therapy (PART), suggesting a possibility of HIV-1 superinfection. We analyzed HIV-1 sequences before and after syphilis in four HIV-1-positive patients including the index case to explore drug resistance mutations (DRMs) and a possibility of HIV-1 superinfection. There were patients who obtained DRMs around syphilis infection but no evidence of HIV-1 superinfection was obtained. Our results underline the importance of strict adherence to PART. PMID:17113333

  7. HIV-1 transcription and latency: an update

    PubMed Central

    2013-01-01

    Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound of viremia. Reactivation of latently infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to eradication. In this review, we will discuss the latest reports on the molecular mechanisms that may regulate HIV-1 latency at the transcriptional level, including transcriptional interference, the role of cellular factors, chromatin organization and epigenetic modifications, the viral Tat trans-activator and its cellular cofactors. Since latency mechanisms may also operate at the post-transcriptional level, we will consider inhibition of nuclear RNA export and inhibition of translation by microRNAs as potential barriers to HIV-1 gene expression. Finally, we will review the therapeutic approaches and clinical studies aimed at achieving either a sterilizing cure or a functional cure of HIV-1 infection, with a special emphasis on the most recent pharmacological strategies to reactivate the latent viruses and decrease the pool of viral reservoirs. PMID:23803414

  8. Barriers and Facilitators of HIV Disclosure: Perspectives from HIV-Infected Men Who Have Sex with Men

    PubMed Central

    Driskell, Jeffrey R.; Salomon, Elizabeth; Mayer, Kenneth; Capistrant, Benjamin; Safren, Steven

    2013-01-01

    HIV disclosure among sexually active HIV-infected men who have sex with men (MSM) is a complex phenomenon. To better understand factors that impact the decision-making process regarding HIV disclosure among HIV-infected MSM, the present study analyzed content from previously conducted counseling sessions where HIV disclosure was selected as the primary focus of the session. The counselor/participant dialogue was audio-recorded, transcribed, and analyzed qualitatively using content analysis. Factors identified as barriers that deter HIV-infected MSM from disclosing include rejection, issues of confidentiality, possible missed sexual opportunities, partner’s HIV status, deferred responsibility, sexual partner type, and public sex environments. Participants identified ethical obligation, the potential for a dating relationship, timing of disclosure, and bidirectional communication as facilitators of disclosure. Findings can be used for policy development as well as to guide social workers and other healthcare providers’ assessment and development of clinical interventions addressing sexual health among HIV-infected MSM as it relates to HIV disclosure. PMID:23671405

  9. HIV/AIDS Treatment Overview of HIV

    E-print Network

    Brutlag, Doug

    Treatment Different drugs attack the replication at different steps HIV is adaptable so a "cocktail interleukin-2 valproic acid toxicity or efficacy problems Phorbol-13-myrisitate-12-acetate (PMA), tumor

  10. Insulin resistance in brain and possible therapeutic approaches.

    PubMed

    Cetinkalp, Sevki; Simsir, Ilgin Y; Ertek, Sibel

    2014-01-01

    Although the brain has long been considered an insulin-independent organ, recent research has shown that insulin has significant effects on the brain, where it plays a role in maintaining glucose and energy homeostasis. To avoid peripheral insulin resistance, the brain may act via hypoinsulinemic responses, maintaining glucose metabolism and insulin sensitivity within its own confines; however, brain insulin resistance may develop due to environmental factors. Insulin has two important functions in the brain: controlling food intake and regulating cognitive functions, particularly memory. Notably, defects in insulin signaling in the brain may contribute to neurodegenerative disorders. Insulin resistance may damage the cognitive system and lead to dementia states. Furthermore, inflammatory processes in the hypothalamus, where insulin receptors are expressed at high density, impair local signaling systems and cause glucose and energy metabolism disorders. Excessive caloric intake and high-fat diets initiate insulin and leptin resistance by inducing mitochondrial dysfunction and endoplasmic reticulum stress in the hypothalamus. This may lead to obesity and diabetes mellitus (DM). Exercise can enhance brain and hypothalamic insulin sensitivity, but it is the option least preferred and/or continuously practiced by the general population. Pharmacological treatments that increase brain and hypothalamic insulin sensitivity may provide new insights into the prevention of dementia disorders, obesity, and type 2 DM in the future. PMID:23627981

  11. [Therapeutic possibilities in lens opacity after silicon oil tamponade].

    PubMed

    Grewing, R; Mester, U

    1992-01-01

    The most important complication of intraocular silicone oil is cataract formation. This leads not only to deterioration of the patients vision, but also to impairment of fundus visualisation. Preventing cataract formation by removing the silicone oil in the first postoperative weeks is hampered by an increased risk of redetachment. Furthermore, even with silicone oil vitreoretinal complications occur in up to 37%. Therefore if cataract surgery becomes necessary, it should be performed maintaining the silicone oil tamponade. The most suitable technique under this condition is phacoemulsification, avoiding damage to the posterior capsule and zonules. Due to this consideration we performed phacoemulsification with in the bag implantation of intraocular lenses in 13 eyes after silicone oil procedure. In no case intra- or postoperatively silicone oil was visible in the anterior chamber. Visual acuity improved in about 50% of the eyes despite of capsular fibrosis being present in all cases. Postoperatively YAG-lasercapsulotomy led to functional improvement in only one out of three eyes. PMID:1583838

  12. Analysis Using TCGA Data Identifies New Therapeutic Possibility

    Cancer.gov

    Research conducted by Wei Zhang, Ph.D. and his colleagues describing a method to prevent the spread of ovarian cancer in both in-vitro and in-vivo models was published in the Feb. 11, 2013 issue of Cancer Cell. Ovarian cancer develops in the tissues of one or both ovaries, which are situated in the abdominal cavity and buffered by peritoneal fluid.

  13. [Neuropharmacology of smoking: basic research opens new therapeutic possibilities].

    PubMed

    Svensson, T H; Grenhoff, J

    1991-05-29

    Cigarette smoking and other forms of tobacco usage may be described as pharmacological nicotine-dependence. In the article are reviewed recent findings regarding nicotine dependence and its neuropharmacological basis. Nicotine acts via nicotinic receptors, and its dependence-promoting properties appear to be chiefly mediated by stimulation of noradrenaline and dopamine neurons in the brain, which may help to explain the excessive tobacco consumption associated with certain psychiatric disorders. Pharmacological treatment with nicotine substitution has been shown to improve prognosis significantly in smoking cessation programmes. New forms of non-addictive treatment are suggested by recent neuropharmacological findings. PMID:2051876

  14. ACTG 5197: A Placebo Controlled Trial of Immunization of HIV-1 Infected Persons with a Replication Deficient Ad5 Vaccine Expressing the HIV-1 Core Protein

    PubMed Central

    Schooley, Robert T.; Spritzler, John; Wang, Hongying; Lederman, Michael M.; Havlir, Diane; Kuritzkes, Daniel R.; Pollard, Richard; Battaglia, Cathy; Robertson, Michael; Mehrotra, Devan; Casimiro, Danilo; Cox, Kara; Schock, Barbara

    2010-01-01

    Background HIV-1 specific cellular immunity contributes to control of HIV-1 replication. HIV-1 infected volunteers on antiretroviral therapy received a replication defective Ad5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study. Methods HIV-1-infected vaccine or placebo recipients underwent a 16-wk analytical treatment interruption (ATI). The log10 HIV-1 RNA at the ATI set point and time averaged area under the curve (TA-AUC) served as co-primary endpoints. Immune responses were measured by intracellular cytokine staining and CFSE dye dilution. Results Vaccine benefit trends were seen for both primary endpoints, but did not reach a pre-specified p ? 0.025 level of significance. The estimated shift in TA-AUC and set point were 0.24 (unadjusted p=0.04) and 0.26 (unadjusted p=0.07) log10 copies lower in the vaccine than in the placebo arm. HIV-1 gag-specific CD4+ interferon-? producing cells were an immunologic correlate of viral control. Conclusion The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the pre-specified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated. PMID:20662716

  15. Effect of histone deacetylase inhibitors on HIV production in latently infected, resting CD4(+) T cells from infected individuals receiving effective antiretroviral therapy.

    PubMed

    Blazkova, Jana; Chun, Tae-Wook; Belay, Bietel W; Murray, Danielle; Justement, J Shawn; Funk, Emily K; Nelson, Amy; Hallahan, Claire W; Moir, Susan; Wender, Paul A; Fauci, Anthony S

    2012-09-01

    Persistence of the latent viral reservoir has been recognized as a major obstacle to eradicating human immunodeficiency virus (HIV) in infected individuals receiving antiretroviral therapy. It has been suggested that histone deacetylase inhibitors (HDACis) may purge HIV in the latent viral reservoir. However, the effect of HDACis on the degree and extent of HIV expression in the latent viral reservoir has not been fully delineated. Here we demonstrate that HDACis do not induce HIV production in the latent viral reservoir of aviremic individuals. Therefore, alternative therapeutic strategies may be necessary to eliminate HIV in the latent viral reservoir. PMID:22732922

  16. Cavitation effects of therapeutic ultrasound

    NASA Astrophysics Data System (ADS)

    Bader, Kenneth; Gipson, Karen

    2005-04-01

    In order to model possible effects of cavitation on bone structure, the formation of cavitation along an acoustically reflective PVC surface was studied. The bubbles were generated by a commerical therapeutic transducer (1 MHz), for both water and agar gel mediums. Bubble formation and activity were monitored using light scattering techniques: a HeNe laser was directed through the medium, and the transmitted light was detected using an optical power meter. The data show a decline in cavitation activity further from the surface and offer suggestive evidence of a boundary layer. Temporal saturation is also evident in both mediums, though an anomalous increase in transmitted light for the agar medium suggests the possibility of pressure variations due to microstreaming. Analysis of the microstreaming pattern was subsequently performed at lower frequencies in order to allow visualization with a standard laboratory microscope.

  17. The Oral Mucosa Immune Environment and Oral Transmission of HIV/SIV

    PubMed Central

    Wood, Lianna F.; Chahroudi, Ann; Chen, Hui-Ling; Jaspan, Heather B.; Sodora, Donald L.

    2013-01-01

    Summary The global spread of human immunodeficiency virus (HIV) is dependent on the ability of this virus to efficiently cross from one host to the next by traversing a mucosal membrane. Unraveling how mucosal exposure of HIV results in systemic infection is critical for the development of effective therapeutic strategies. This review focuses on understanding the immune events associated with the oral route of transmission (via breastfeeding or sexual oral intercourse), which occurs across the oral and/or gastrointestinal mucosa. Studies in both humans and simian immunodeficiency virus (SIV) monkey models have identified viral changes and immune events associated with oral HIV/SIV exposure. This review covers our current knowledge of HIV oral transmission in both infants and adults, the use of SIV models in understanding early immune events, oral immune factors that modulate HIV/SIV susceptibility (including mucosal inflammation), and interventions that may impact oral HIV transmission rates. Understanding the factors that influence oral HIV transmission will provide the foundation for developing immune therapeutic and vaccine strategies that can protect both infants and adults from oral HIV transmission. PMID:23772613

  18. Heme Oxygenase-1 Dysregulation in the Brain: Implications for HIV-Associated Neurocognitive Disorders

    PubMed Central

    Ambegaokar, Surendra S; Kolson, Dennis L

    2014-01-01

    Heme oxygenase-1 (HO-1) is a highly inducible and ubiquitous cellular enzyme that subserves cytoprotective responses to toxic insults, including inflammation and oxidative stress. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, HO-1 expression is increased, presumably reflecting an endogenous neuroprotective response against ongoing cellular injury. In contrast, we have found that in human immunodeficiency virus (HIV) infection of the brain, which is also associated with inflammation, oxidative stress and neurodegeneration, HO-1 expression is decreased, likely reflecting a unique role for HO-1 deficiency in neurodegeneration pathways activated by HIV infection. We have also shown that HO-1 expression is significantly suppressed by HIV replication in cultured macrophages which represent the primary cellular reservoir for HIV in the brain. HO-1 deficiency is associated with release of neurotoxic levels of glutamate from both HIV-infected and immune-activated macrophages; this glutamate-mediated neurotoxicity is suppressed by pharmacological induction of HO-1 expression in the macrophages. Thus, HO-1 induction could be a therapeutic strategy for neuroprotection against HIV infection and other neuroinflammatory brain diseases. Here, we review various stimuli and signaling pathways regulating HO-1 expression in macrophages, which could promote neuronal survival through HO-1-modulation of endogenous antioxidant and immune modulatory pathways, thus limiting the oxidative stress that can promote HIV disease progression in the CNS. The use of pharmacological inducers of endogenous HO-1 expression as potential adjunctive neuroprotective therapeutics in HIV infection is also discussed. PMID:24862327

  19. Classifying HIV-1 Circulating Recombinant Forms A. Steven Eliuk1, B. Keith Ruiter2, and C. Pierre Boulanger1

    E-print Network

    Alberta, University of

    Classifying HIV-1 Circulating Recombinant Forms A. Steven Eliuk1, B. Keith Ruiter2, and C. Pierre-of-the-art functions in HIV-1 subtyping, such as those found in Wu et al. and NCBI. The paper identi- fies deficiencies for a multitude of real-world possibilities. Keywords: Recombination, HIV-1 subtyping, statistical classifi

  20. Bone Marrow Gene Therapy for HIV/AIDS

    PubMed Central

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-01-01

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. PMID:26193303

  1. Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection

    PubMed Central

    Hanauske-Abel, Hartmut M.; Saxena, Deepti; Palumbo, Paul E.; Hanauske, Axel-Rainer; Luchessi, Augusto D.; Cambiaghi, Tavane D.; Hoque, Mainul; Spino, Michael; Gandolfi, Darlene D'Alliessi; Heller, Debra S.; Singh, Sukhwinder; Park, Myung Hee; Cracchiolo, Bernadette M.; Tricta, Fernando; Connelly, John; Popowicz, Anthony M.; Cone, Richard A.; Holland, Bart; Pe’ery, Tsafi; Mathews, Michael B.

    2013-01-01

    HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal antivirals that eliminate viral infection by destroying infected cells. A drug-based drug discovery program, based on these compounds, is warranted to determine the potential of such agents in clinical trials of HIV-infected patients. PMID:24086341

  2. Cytoplasmic HIV-RNA in monocytes determines microglial activation and neuronal cell death in HIV-associated neurodegeneration.

    PubMed

    Faissner, Simon; Ambrosius, Björn; Schanzmann, Kirsten; Grewe, Bastian; Potthoff, Anja; Münch, Jan; Sure, Ulrich; Gramberg, Thomas; Wittmann, Sabine; Brockmeyer, Norbert; Uberla, Klaus; Gold, Ralf; Grunwald, Thomas; Chan, Andrew

    2014-11-01

    Despite highly active antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) are still highly prevalent. Direct neurotoxicity of microglia activated by HIV-infected monocytes independent from viral replication may account for this observation. To investigate underlying molecular and viral determinants, human monocytoid cells (U937) transduced with HIV-particles were co-cultured with primary human microglia or astrocytes. Using genetically-engineered HIV-particles key steps of infection were examined. Levels of pro-inflammatory/neurotoxic cytokines were investigated in co-culture supernatants by flow cytometry. Neurotoxicity mediated by the supernatants was analysed using primary cortical rat neurons. To corroborate our findings, cytokine profiles in cerebrospinal fluid (CSF) of neuropsychologically asymptomatic HIV positive (HIV(+)) patients (n=45) were correlated with neurofilament H (NfH) as surrogate of neuronal/axonal degeneration. In contrast to direct exposure of HIV to microglia, only the presence of HIV-transduced monocytoid cells strongly activated human microglia as evidenced by enhanced secretion of CXCL10, CCL5, CCL2, and IL-6 (1.3-7.1-fold; p<0.01) leading to two-fold increased neurotoxicity (p<0.001). In direct comparison, astrocyte activation by HIV-transduced monocytoid cells was limited. Using different mutant HIV-particles we show that the presence of cytoplasmic HIV-RNA in monocytoid cells is the viral determinant for this unique microglial activation pattern and subsequent neuronal cell death; reverse transcription and expression of viral genes were not essential. In CSF of presymptomatic HIV(+) patients, CXCL10, CCL5 and IL-6 were correlated with NfH as surrogate marker of neurodegeneration as well as CSF-pleocytosis. In conclusion, cytosolic viral RNA in monocytes is mandatory for subsequent microglial activation and neurotoxicity; activated astrocytes may augment neuroinflammation. In addition, neuroinflammation and neurodegeneration occur even in preclinical HIV(+) patients and are associated with cytokines regulated in vitro. Our data may aid in the development of biomarkers and glia-directed therapeutic approaches of HAND. PMID:25150097

  3. [The Médicins sans Frontières HIV/AIDS programme in Ukraine].

    PubMed

    van den Berk, G E L; Telnov, A; Venis, S F; Mills, C F; O'Brien, D P

    2007-12-01

    In 1999, Médicins sans Frontières started an HIV/AIDS programme in Ukraine, a country with an estimated 410,000 people with HIV (1.4% prevalence), including 53,000 in urgent need of antiretroviral therapy. Between 1999 and 2004, a comprehensive HIV/AIDS programme was implemented in close collaboration with the Ministry of Health in AIDS centres in Odessa, Mikolaev and Simferopol. Initial activities included prevention and treatment advocacy campaigns, which were later followed by prevention of mother-to-child transmission, treatment of opportunistic infections, antiretroviral therapy for infants and adults and palliative care. This programme has served as a model and has led to meaningful improvements in HIV/AIDS care in Ukraine. It demonstrates that adequate care for patients with HIV or AIDS is possible in countries like Ukraine. PMID:18179088

  4. Possible sensations

    E-print Network

    Shin, Yae Jin

    2013-01-01

    This thesis explores the sensory human experience through the study of facial expression and non-verbal vocal articulation in hopes of better understanding the range of modes of communications possible both interpersonally ...

  5. Side Effects of HIV Medicines: HIV and Hepatotoxicity

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Hepatotoxicity (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Hepatotoxicity means damage to the ... the liver can be life-threatening. What HIV medicines can cause hepatotoxicity? HIV medicines in the following ...

  6. Side Effects of HIV Medicines: HIV and Hyperlipidemia

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Hyperlipidemia (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Hyperlipidemia refers to high levels ... pancreas). HIV infection and treatment with some HIV medicines can increase the risk of hyperlipidemia. Other risk ...

  7. Side Effects of HIV Medicines: HIV and Lactic Acidosis

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Lactic Acidosis (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Lactic acidosis is a ... rare but serious side effect of some HIV medicines. All HIV medicines in the nucleoside reverse transcriptase ...

  8. Gene therapy: beating HIV at its own game.

    PubMed

    Servilio, J

    1995-01-01

    Gene therapy difficulties and promising approaches are discussed. Virus replication inhibitors, including ribozymes, RNA decoys, and transdominant mutant proteins, have made the greatest progress. Gene immunotherapy and the problems it presents are discussed. A sidebar defines the following HIV-related drug classifications: opportunistic infection drugs, nucleoside analogues, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and therapeutic vaccines. Concluding comments briefly highlight open trials of new types of anti-HIV therapies that have been approved by the Recombinant Advisory Committee. PMID:11363145

  9. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  10. Safe Thinking and Affect Regulation (STAR): Human Immunodeficiency Virus Prevention in Alternative/Therapeutic Schools

    ERIC Educational Resources Information Center

    Brown, Larry K.; Nugent, Nicole R.; Houck, Christopher D.; Lescano, Celia M.; Whiteley, Laura B.; Barker, David; Viau, Lisa; Zlotnick, Caron

    2011-01-01

    Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as…

  11. Negotiating Risk: Knowledge and Use of HIV Prevention by Persons With Serious Mental Illness Living in Supportive Housing

    PubMed Central

    Kloos, Bret; Gross, Steven M.; Meese, Katharine J.; Meade, Christina S.; Doughty, Jhan D.; Hawkins, Dietra D.; Zimmerman, Susan O.; Snow, David L.; Sikkema, Kathleen J.

    2008-01-01

    As a population, persons with serious mental illness (SMI) have an elevated risk for HIV infection. However, relatively little is known about how the risk of HIV has affected their lives, how persons with SMI evaluate their HIV risk, and what preventive measures they undertake. Furthermore, relatively little is known about community-based HIV prevention for persons with SMI as most interventions have been restricted to clinical settings. This report presents findings on the HIV-related experiences of persons with SMI living in supportive housing programs, one possible setting for implementing community-based HIV prevention with this population. The qualitative investigation interviewed 41 men and women living in five supportive housing programs. In-depth, qualitative interviews elicited discussion of research participants’ (a) experiences with HIV, (b) knowledge about HIV and HIV prevention, (c) assessments of their own risk, (d) descriptions of how they apply their prevention knowledge, and (e) reports of barriers for HIV prevention. Research participants describe social networks that have substantial contact with persons affected by HIV. However, contrary to some expectations of persons with SMI, research participants report using HIV prevention knowledge in negotiating their risk of contracting HIV. The implications of these findings are discussed in terms of their relevance for implementing community-based HIV prevention for persons with SMI. PMID:16389505

  12. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo

    PubMed Central

    Søgaard, Ole S.; Graversen, Mette E.; Leth, Steffen; Olesen, Rikke; Brinkmann, Christel R.; Nissen, Sara K.; Kjaer, Anne Sofie; Schleimann, Mariane H.; Denton, Paul W.; Hey-Cunningham, William J.; Koelsch, Kersten K.; Pantaleo, Giuseppe; Krogsgaard, Kim; Sommerfelt, Maja; Fromentin, Remi; Chomont, Nicolas; Rasmussen, Thomas A.; Østergaard, Lars; Tolstrup, Martin

    2015-01-01

    Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. Trial Registration clinicaltrials.gov NTC02092116 PMID:26379282

  13. Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America

    PubMed Central

    Lipshultz, Steven E; Miller, Tracie L; Wilkinson, James D; Scott, Gwendolyn B; Somarriba, Gabriel; Cochran, Thomas R; Fisher, Stacy D

    2013-01-01

    Introduction Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late-stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi-agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis. Discussion Before highly active antiretroviral therapy (HAART), the two-to-five-year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long-term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV-infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late-stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV-infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV-uninfected and HIV-infected children with HIV-infected mothers. In non-HIV-infected infants born to HIV-infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life. Conclusions Routine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV-infected adults and children as cardiovascular illness has become a part of care for long-term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted. PMID:23782480

  14. HIV/AIDS Report to Council 2012 RESPONSES TO HIV & AIDS AT

    E-print Network

    Tadross, Mark

    HIV/AIDS Report to Council 2012 RESPONSES TO HIV & AIDS AT UCT Prepared by The HIV......................................................................................................................... 4 GLOBAL, NATIONAL AND INSTITUTIONAL HIV PREVALENCE...................................................... 27 APPENDIX B: HIV & AIDS CURRICULUM DEVELOPMENT

  15. Individualised cancer therapeutics: dream or reality? Therapeutics construction.

    PubMed

    Shen, Yuqiao; Senzer, Neil; Nemunaitis, John

    2005-11-01

    The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi. PMID:16255647

  16. Antiviral Stratagems Against HIV-1 Using RNA Interference (RNAi) Technology

    PubMed Central

    Vlachakis, Dimitrios; Tsiliki, Georgia; Pavlopoulou, Athanasia; Roubelakis, Maria G.; Champeris Tsaniras, Spyridon; Kossida, Sophia

    2013-01-01

    The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude antiretroviral agents by mutating may be its most invincible weapon. Viruses, including HIV, in order to adapt and survive in their environment evolve at extremely fast rates. Given that conventional approaches which have been applied against HIV have failed, novel and more promising approaches must be employed. Recent studies advocate RNA interference (RNAi) as a promising therapeutic tool against HIV. In this regard, targeting multiple HIV sites in the context of a combinatorial RNAi-based approach may efficiently stop viral propagation at an early stage. Moreover, large high-throughput RNAi screens are widely used in the fields of drug development and reverse genetics. Computer-based algorithms, bioinformatics, and biostatistical approaches have been employed in traditional medicinal chemistry discovery protocols for low molecular weight compounds. However, the diversity and complexity of RNAi screens cannot be efficiently addressed by these outdated approaches. Herein, a series of novel workflows for both wet- and dry-lab strategies are presented in an effort to provide an updated review of state-of-the-art RNAi technologies, which may enable adequate progress in the fight against the HIV-1 virus. PMID:23761954

  17. Recent developments of peptidomimetic HIV-1 protease inhibitors.

    PubMed

    Qiu, X; Liu, Z-P

    2011-01-01

    HIV protease plays a crucial role in the viral life cycle by processing the viral Gag and Gag-Pol polyproteins into structural and functional proteins essential for viral maturation. Inhibition of HIV-1 protease leads to the production of noninfectious virus particles and hence is an important therapeutic target for antiviral therapy in AIDS patients. Among many strategies to combat this disease, highly active antiretroviral therapy (HAART) with HIV protease inhibitors (PIs) in combination with reverse transcriptase inhibitors and fusion inhibitor continues to be the first line treatment for control of HIV infection. However, the rapid emergence of drug-resistant HIV-1 strains and the appearance of cross-resistance are severely limiting the long-term treatment options. Thus, numerous efforts have been made in the design and synthesis of novel protease inhibitors with broad-spectrum activity against multidrug-resistant HIV-1 variants by medicinal chemists. This review will focus on the substrate-based drug design of novel peptidomimetic PIs in recent years since 2006. PMID:21864279

  18. Autophagy induction by histone deacetylase inhibitors inhibits HIV type 1.

    PubMed

    Campbell, Grant R; Bruckman, Rachel S; Chu, Yen-Lin; Spector, Stephen A

    2015-02-20

    Histone deacetylase inhibitors (HDACi) are being evaluated in a "shock-and-kill" therapeutic approach to reverse human immunodeficiency virus type-1 (HIV) latency from CD4(+) T cells. Using this approach, HDACi have induced HIV RNA synthesis in latently infected cells from some patients. The hope is that the increase in viral production will lead to killing of the infected cell either by the virus itself or by the patient's immune system, a "sterilizing cure." Although administered within the context of combination antiretroviral therapy, the infection of bystander cells remains a concern. In this study, we investigated the effect of HDACi (belinostat, givinostat, panobinostat, romidepsin, and vorinostat) on the productive infection of macrophages. We demonstrate that the HDACi tested do not alter the initial susceptibility of macrophages to HIV infection. However, we demonstrate that HDACi decrease HIV release from macrophages in a dose-dependent manner (belinostat < givinostat < vorinostat < panobinostat < romidepsin) via degradation of intracellular HIV through the canonical autophagy pathway. This mechanism involves unc-51-like autophagy-activating kinase 1 (ULK1) and the inhibition of the mammalian target of rapamycin and requires the formation of autophagosomes and their maturation into autolysosomes in the absence of increased cell death. These data provide further evidence in support of a role for autophagy in the control of HIV infection and suggest that careful consideration of off-target effects will be essential if HDACi are to be a component of a multipronged approach to eliminate latently infected cells. PMID:25540204

  19. Potent Inhibition of HIV-1 Replication by a Tat Mutant

    PubMed Central

    Major, Lee; Suhrbier, Andreas; Harrich, David

    2009-01-01

    Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection. PMID:19901984

  20. HIV and malnutrition: effects on immune system.

    PubMed

    Duggal, Shalini; Chugh, Tulsi Das; Duggal, Ashish Kumar

    2012-01-01

    HIV or human immunodeficiency virus infection has assumed worldwide proportions and importance in just a span of 25 years. Continuous research is being done in many parts of the world regarding its treatment and vaccine development, and a lot of money has flown into this. However, fully understanding the mechanisms of immune depletion has still not been possible. The focus has also been on improving the quality of life of people living with HIV/AIDS through education, counselling, and nutritional support. Malnutrition further reduces the capacity of the body to fight this infection by compromising various immune parameters. Knowledge of essential components of nutrition and incorporating them in the management goes a long way in improving quality of life and better survival in HIV-infected patients. PMID:22242039

  1. Psychoneuroimmunology and HIV-1.

    ERIC Educational Resources Information Center

    Antoni, Michael H.; And Others

    1990-01-01

    Presents evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high risk human immunodeficiency virus-Type 1 (HIV-1) seronegative and very early stage seropositive homosexual men. HIV-1 infection is cast as chronic disease for which early…

  2. Positive: HIV Affirmative Counseling.

    ERIC Educational Resources Information Center

    Kain, Craig D.

    At the end of the 1980s, counselors largely lacked an integrated approach to counseling people living with HIV disease. This book describes the experience of counseling this group of persons. The major premise here is that counselors who counsel HIV-positive clients must come to understand and affirm their clients' experiences. The text defines a…

  3. HIV and Communication

    ERIC Educational Resources Information Center

    McNeilly, L.G.

    2005-01-01

    The human immunodeficiency virus (HIV) continues to plague many countries across the globe, including the United States, Africa, China and India. Children and adults have been infected with HIV, and both populations can present with communication disorders that coexist with the presence of the virus. The purpose of this paper is to present an…

  4. HIV at School.

    ERIC Educational Resources Information Center

    Miller, Liz; Becker-Dunn, Eileen

    1993-01-01

    School boards are increasingly responsible for the needs of children who live in families with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS). Boards must provide the climate and the policies that will enable open, factual, and sensitive discussion of the issues surrounding AIDS and HIV. Sidebars summarize some…

  5. Living with HIV/AIDS

    MedlinePLUS

    Infection with HIV is serious. But the outlook for people with HIV/AIDS is improving. If you are infected with HIV, there are many things you can do to ... health care provider who knows how to treat HIV. You may want to join a support group. ...

  6. Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

    PubMed

    Mutchler, Matt G; McDavitt, Bryce; Ghani, Mansur A; Nogg, Kelsey; Winder, Terrell J A; Soto, Juliana K

    2015-09-01

    Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options. PMID:26121564

  7. Evaluating the CDC program for HIV counseling and testing.

    PubMed Central

    Rugg, D L; MacGowan, R J; Stark, K A; Swanson, N M

    1991-01-01

    The Centers for Disease Control is conducting two investigations of the outcomes of HIV counselling and testing services offered persons at high risk for infection with the human immunodeficiency virus (HIV). One investigation is a trial conducted at sexually transmitted disease clinics where an enhanced version of HIV counseling and testing is compared with a standard version. The other investigation is a longitudinal study of the effects of HIV counseling and testing in drug treatment programs that use methadone therapy. In the evaluation, comparisons are being made of different ways of offering HIV counseling and testing and of the effectiveness of the program among persons who know their HIV serostatus and those who do not. The outcome variables include self-reported sexual and drug-using behaviors, together with corroborating laboratory tests, drug treatment compliance, mental health effects, and services utilization. Methodological, practical, and sociopolitical challenges were encountered in the evaluations. Possible solutions to the problems are described. The authors conclude that the designs of the evaluations were appropriate, but that considerable resources are required to carry them out. In settings with low levels of resources, thorough evaluation of the process and an assessment of the immediate outcomes may be the most appropriate evaluation strategy. As HIV counseling and testing are of fundamental importance to national and international HIV prevention efforts, their evaluation is a critical issue. PMID:1659720

  8. GYNECOLOGIC ISSUES IN THE HIV-INFECTED WOMAN

    PubMed Central

    Cejtin, Helen E.

    2008-01-01

    With the advent of highly active antiretroviral therapy (HAART), women living with HIV can now enjoy longer lifespans in relative good health as well as the prospect of bearing children with an overwhelmingly low risk of vertical transmission. Thus, increasingly, seropositive women are now facing issues around longevity as well as those associated with fertility. The clinician caring for the HIV-infected woman must be alert to the gynecologic issues that are prevalent in this population. Among those faced by the gynecologist are menstrual abnormalities, lower genital tract neoplasia, sexually transmitted infections, the need for gynecologic surgery, and menopausal issues including osteopenia/osteoporosis. Contraception in HIV seropositive women presents unique management issues, because of the necessity for a dual role of prevention of both pregnancy and HIV transmission, the possible effect of birth control on HIV infection, and the interaction between birth control and HIV therapies. With ever increasing frequency, the gynecologist will be presented with the seropositive woman or couple who wishes to conceive. The purpose of this chapter is to review the current knowledge on the relationship between HIV infection and menstrual abnormalities, genital neoplasias, contraceptive options, surgical complications, and menopause with its associated disorders. Special considerations in the seropositive woman contemplating pregnancy will also be discussed. The treatment of pelvic infections is discussed elsewhere in this volume, and only changes in standard therapy because of concurrent HIV-infection will be discussed here. PMID:18954760

  9. HIV, Alcohol Dependence and the Criminal Justice System: A Review and Call for Evidence-Based Treatment

    PubMed Central

    Springer, Sandra A.; Azar, Marwan M.; Altice, Frederick L.

    2011-01-01

    People with both HIV and alcohol use disorders are disproportionately concentrated within the U.S. criminal justice system; approximately one-quarter of all people with HIV cycle through the system each year. HIV-infected prisoners with alcohol problems face many obstacles as they transition back to the community. Specifically, although they have impressive HIV treatment outcomes during the period of incarceration while they are free from alcohol, upon release, however, they face inordinate challenges including relapse to alcohol use resulting in significant morbidity and mortality. Randomized controlled trials affirm the role of pharmacotherapy using naltrexone (NTX) as the therapeutic option conferring the best treatment outcome for alcohol use disorders within the community. Absent from these trials were inclusion of prisoners or HIV-infected individuals. Relapse to alcohol use among HIV-infected prisoners is associated with reduced retention in care, poor adherence to antiretroviral therapy with consequential poor HIV treatment outcomes and higher levels of HIV risk behaviors. Untreated alcohol dependence, particularly for released HIV-infected prisoners, has both negative consequences for the individual and society and requires a concentrated effort and rethinking of our existing approaches for this vulnerable population. The specific aim of this manuscript is to review the existing literature regarding the relationship of HIV and treatment for alcohol use disorders in criminal justice populations in an effort to determine “best practices” that might effectively result in improved treatment of HIV and alcohol disorders for released prisoners. PMID:21171933

  10. Developing Therapeutic Listening

    ERIC Educational Resources Information Center

    Lee, Billy; Prior, Seamus

    2013-01-01

    We present an experience-near account of the development of therapeutic listening in first year counselling students. A phenomenological approach was employed to articulate the trainees' lived experiences of their learning. Six students who had just completed a one-year postgraduate certificate in counselling skills were interviewed and the…

  11. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  12. THERAPEUTIC DRUG DISCOVERY

    E-print Network

    Mootha, Vamsi K.

    that drugs that boost OXPHOS capacity in muscle might improve diabetes. Accordingly, it has long been knownTHERAPEUTIC STRATEGIES DRUG DISCOVERY TODAY Estrogen-related receptor a (ERRa): A novel target in type 2 diabetes Christoph Handschin1,*, Vamsi K. Mootha2 1 Dana-Farber Cancer Institute and Department

  13. Stem cell therapeutic possibilities: future therapeutic options for male-factor and female-factor infertility?

    PubMed

    Easley, Charles A; Simerly, Calvin R; Schatten, Gerald

    2013-07-01

    Recent advances in assisted reproduction treatment have enabled some couples with severe infertility issues to conceive, but the methods are not successful in all cases. Notwithstanding the significant financial burden of assisted reproduction treatment, the emotional scars from an inability to conceive a child enacts a greater toll on affected couples. While methods have circumvented some root causes for male and female infertility, often the underlying causes cannot be treated, thus true cures for restoring a patient's fertility are limited. Furthermore, the procedures are only available if the affected patients are able to produce gametes. Patients rendered sterile by medical interventions, exposure to toxicants or genetic causes are unable to utilize assisted reproduction to conceive a child - and often resort to donors, where permitted. Stem cells represent a future potential avenue for allowing these sterile patients to produce offspring. Advances in stem cell biology indicate that stem cell replacement therapies or in-vitro differentiation may be on the horizon to treat and could cure male and female infertility, although significant challenges need to be met before this technology can reach clinical practice. This article discusses these advances and describes the impact that these advances may have on treating infertility. PMID:23664220

  14. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung

    PubMed Central

    Zhang, Xuefeng; Jiang, Susan; Yu, Jinlong; Kuzontkoski, Paula M; Groopman, Jerome E

    2015-01-01

    Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure increased fibronectin (FN) expression, decreased Robo4 expression, and enhanced the permeability of L-LEC monolayers. Moreover, incubating L-LECs with both cocaine and HIV-1 gp120 exacerbated hyperpermeability, significantly enhanced apoptosis, and further impaired in vitro wound healing as compared with cocaine alone. Our studies also suggested that the sigma-1 receptor (Sigma-1R) and the dopamine-4 receptor (D4R) are involved in cocaine-induced pathology in L-LECs. Seeking clinical correlation, we found that FN levels in sera and lung tissue of HIV+ donors were significantly elevated as compared to HIV? donors. Our in vitro data demonstrate that cocaine and HIV-1 gp120 induce dysfunction and damage of lung lymphatics, and suggest that cocaine use may exacerbate pulmonary edema and fibrosis associated with HIV infection. Continued exploration of the interplay between cocaine and HIV should assist the design of therapeutics to ameliorate HIV-induced pulmonary disorders within the drug using population. PMID:26311830

  15. The kidney as a reservoir for HIV-1 after renal transplantation.

    PubMed

    Canaud, Guillaume; Dejucq-Rainsford, Nathalie; Avettand-Fenoël, Véronique; Viard, Jean-Paul; Anglicheau, Dany; Bienaimé, Frank; Muorah, Mordi; Galmiche, Louise; Gribouval, Olivier; Noël, Laure-Helene; Satie, Anne-Pascale; Martinez, Frank; Sberro-Soussan, Rebecca; Scemla, Anne; Gubler, Marie-Claire; Friedlander, Gérard; Antignac, Corinne; Timsit, Marc-Olivier; Onetti Muda, Andrea; Terzi, Fabiola; Rouzioux, Christine; Legendre, Christophe

    2014-02-01

    Since the recent publication of data showing favorable outcomes for patients with HIV-1 and ESRD, kidney transplantation has become a therapeutic option in this population. However, reports have documented unexplained reduced allograft survival in these patients. We hypothesized that the unrecognized infection of the transplanted kidney by HIV-1 can compromise long-term allograft function. Using electron microscopy and molecular biology, we examined protocol renal transplant biopsies from 19 recipients with HIV-1 who did not have detectable levels of plasma HIV-1 RNA at transplantation. We found that HIV-1 infected the kidney allograft in 68% of these patients. Notably, HIV-1 infection was detected in either podocytes predominately (38% of recipients) or tubular cells only (62% of recipients). Podocyte infection associated with podocyte apoptosis and loss of differentiation markers as well as a faster decline in allograft function compared with tubular cell infection. In allografts with tubular cell infection, epithelial cells of the proximal convoluted tubules frequently contained abnormal mitochondria, and both patients who developed features of subclinical acute cellular rejection had allografts with tubular cell infection. Finally, we provide a novel noninvasive test for determining HIV-1 infection of the kidney allograft by measuring HIV-1 DNA and RNA levels in patients' urine. In conclusion, HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, and this infection might influence graft outcome. PMID:24309185

  16. HIV/AIDS in Ethiopia: where is the epidemic heading?

    PubMed Central

    Hladik, W; Shabbir, I; Jelaludin, A; Woldu, A; Tsehaynesh, M; Tadesse, W

    2006-01-01

    Objectives A possible decline in prevalence of HIV in some sub?Saharan African countries has been reported recently. The present study aimed to evaluate the prevalence and incidence of HIV and behavioural data to investigate trends in HIV/AIDS in Ethiopia. Methods A review was conducted of published reports and literature, raw and modelled (using Epidemic Projection Package and Spectrum software) surveillance data and estimates from antenatal clinics (ANCs) and data from voluntary counselling and testing centres. Observations were restricted to the adult population. Results Between 2001 and 2003, more ANC sites showed a decline than a rise in HIV prevalence, but most lacked statistical significance. Modelled data suggested a rise in prevalence of HIV in rural areas (2003: 2.6%) and in all Ethiopia (2003: 4.4%), but a stable or declining prevalence in Addis Ababa (2003: 14.6%) and other urban areas (2003: 11.8%). Modelled HIV incidence, inferred from prevalence changes, showed a slowly rising trend in Addis Ababa (2003: 2.0%), other urban areas (2003: 1.7%), and rural Ethiopia (2003: 0.46%). The total burden of HIV/AIDS is expected also to rise substantially due to population growth. In Addis Ababa, crude data on HIV prevalence from ANCs too suggested a falling trend. Voluntary counselling and testing data from 2002 to 2004 supported this trend but indicated a mixed trend pattern for high risk behaviour. No other serial behavioural trend data were available. Conclusions Lack of quality data on behavioural trends impedes the interpretation of prevalence and incidence data in Ethiopia. Modelled data suggest an expanding HIV epidemic in rural and all Ethiopia, but a possible decline in some urban areas. Crude site prevalence values may be more sensitive to acute changes, possibly indicating a slowing/reversal of the epidemic's expansion. PMID:16581757

  17. Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells.

    PubMed

    Sloan, Derek D; Lam, Chia-Ying Kao; Irrinki, Alivelu; Liu, Liqin; Tsai, Angela; Pace, Craig S; Kaur, Jasmine; Murry, Jeffrey P; Balakrishnan, Mini; Moore, Paul A; Johnson, Syd; Nordstrom, Jeffrey L; Cihlar, Tomas; Koenig, Scott

    2015-11-01

    HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy (cART). Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that exist despite effective cART. The HIV envelope protein (Env) is emerging as a highly specific viral target for therapeutic elimination of the persistent HIV-infected reservoirs via antibody-mediated cell killing. Dual-Affinity Re-Targeting (DART) molecules exhibit a distinct mechanism of action via binding the cell surface target antigen and simultaneously engaging CD3 on cytotoxic T lymphocytes (CTLs). We designed and evaluated Env-specific DARTs (HIVxCD3 DARTs) derived from known antibodies recognizing diverse Env epitopes with or without broadly neutralizing activity. HIVxCD3 DARTs derived from PGT121, PGT145, A32, and 7B2, but not VRC01 or 10E8 antibodies, mediated potent CTL-dependent killing of quiescent primary CD4 T cells infected with diverse HIV isolates. Similar killing activity was also observed with DARTs structurally modified for in vivo half-life extension. In an ex vivo model using cells isolated from HIV-infected participants on cART, combinations of the most potent HIVxCD3 DARTs reduced HIV expression both in quiescent and activated peripheral blood mononuclear cell cultures isolated from HIV-infected participants on suppressive cART. Importantly, HIVxCD3 DARTs did not induce cell-to-cell virus spread in resting or activated CD4 T cell cultures. Collectively, these results provide support for further development of HIVxCD3 DARTs as a promising therapeutic strategy for targeting HIV reservoirs. PMID:26539983

  18. Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells

    PubMed Central

    Sloan, Derek D.; Lam, Chia-Ying Kao; Irrinki, Alivelu; Liu, Liqin; Tsai, Angela; Pace, Craig S.; Kaur, Jasmine; Murry, Jeffrey P.; Balakrishnan, Mini; Moore, Paul A.; Johnson, Syd; Nordstrom, Jeffrey L.; Cihlar, Tomas; Koenig, Scott

    2015-01-01

    HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy (cART). Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that exist despite effective cART. The HIV envelope protein (Env) is emerging as a highly specific viral target for therapeutic elimination of the persistent HIV-infected reservoirs via antibody-mediated cell killing. Dual-Affinity Re-Targeting (DART) molecules exhibit a distinct mechanism of action via binding the cell surface target antigen and simultaneously engaging CD3 on cytotoxic T lymphocytes (CTLs). We designed and evaluated Env-specific DARTs (HIVxCD3 DARTs) derived from known antibodies recognizing diverse Env epitopes with or without broadly neutralizing activity. HIVxCD3 DARTs derived from PGT121, PGT145, A32, and 7B2, but not VRC01 or 10E8 antibodies, mediated potent CTL-dependent killing of quiescent primary CD4 T cells infected with diverse HIV isolates. Similar killing activity was also observed with DARTs structurally modified for in vivo half-life extension. In an ex vivo model using cells isolated from HIV-infected participants on cART, combinations of the most potent HIVxCD3 DARTs reduced HIV expression both in quiescent and activated peripheral blood mononuclear cell cultures isolated from HIV-infected participants on suppressive cART. Importantly, HIVxCD3 DARTs did not induce cell-to-cell virus spread in resting or activated CD4 T cell cultures. Collectively, these results provide support for further development of HIVxCD3 DARTs as a promising therapeutic strategy for targeting HIV reservoirs. PMID:26539983

  19. Ethical and regulatory issues surrounding African traditional medicine in the context of HIV/AIDS.

    PubMed

    Nyika, Aceme

    2007-04-01

    It has been estimated that more than 80% of people in Africa use traditional medicine (TM). With the HIV/AIDS epidemic claiming many lives in Africa, the majority of people affected rely on TM mainly because it is relatively affordable and available to the poor populations who cannot afford orthodox medicine. Whereas orthodox medicine is practiced under stringent regulations and ethical guidelines emanating from The Nuremburg Code, African TM seems to be exempt from such scrutiny. Although recently there have been calls for TM to be incorporated into the health care system, less emphasis has been placed on ethical and regulatory issues. In this paper, an overview of the use of African TM in general, and for HIV/AIDS in particular, is given, followed by a look at: (i) the relative laxity in the application of ethical standards and regulatory requirements with regards to TM; (ii) the importance of research on TM in order to improve and demystify its therapeutic qualities; (iii) the need to tailor-make intellectual property laws to protect traditional knowledge and biodiversity. A framework of partnerships involving traditional healers' associations, scientists, policy makers, patients, community leaders, members of the communities, and funding organizations is suggested as a possible method to tackle these issues. It is hoped that this paper will stimulate objective and constructive debate that could enhance the protection of patients' welfare. PMID:17355329

  20. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

    NASA Astrophysics Data System (ADS)

    Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

    2014-01-01

    The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1?, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

  1. Executive summary of the consensus statement on assistance to women with HIV infection in the health care sector. National AIDS Plan (PNS) and AIDS Study Group (GeSIDA).

    PubMed

    2014-02-01

    The aim of this paper was to develop a consensus on clinical recommendations for health care assistance for women with HIV infection. To this end, a panel of experts, appointed by the Secretariat of the National AIDS Plan and GeSIDA was assembled, that included internal medicine physicians with expertise in the field of HIV infection, gynecologists, pediatricians and psychologists, with two members of the panel acting as coordinators. Scientific information was reviewed in publications and conference reports up to October 2012. In keeping with the criteria of the Infectious Disease Society of America, two levels of evidence were applied to support the proposed recommendations: the strength of the recommendation according to expert opinion (A, B, C) and the level of empirical evidence (I, II, III), already used in previous documents from SPNS/GESIDA. Multiple recommendations are provided for the clinical management of women with HIV infection, considering both the diagnostic and possible therapeutic strategies. This document presents recommendations for the treatment of women with HIV infection. This must be multidisciplinary, taking into account the differences that can be found in the diagnosis, development of disease and treatment between men and women. PMID:23931832

  2. Cryptic Leishmania infantum infection in Italian HIV infected patients

    PubMed Central

    2009-01-01

    Background Visceral leishmaniasis (VL) is a protozoan diseases caused in Europe by Leishmania (L.) infantum. Asymptomatic Leishmania infection is more frequent than clinically apparent disease. Among HIV infected patients the risk of clinical VL is increased due to immunosuppression, which can reactivate a latent infection. The aims of our study were to assess the prevalence of asymptomatic L. infantum infection in HIV infected patients and to study a possible correlation between Leishmania parasitemia and HIV infection markers. Methods One hundred and forty-five HIV infected patients were screened for the presence of anti-Leishmania antibodies and L. infantum DNA in peripheral blood. Statistical analysis was carried out by using a univariate regression analysis. Results Antibodies to L. infantum were detected in 1.4% of patients. L. infantum DNA was detected in 16.5% of patients. Significant association for PCR-Leishmania levels with plasma viral load was documented (p = 0.0001). Conclusion In our area a considerable proportion of HIV infected patients are asymptomatic carriers of L. infantum infection. A relationship between high HIV viral load and high parasitemic burden, possibly related to a higher risk of developing symptomatic disease, is suggested. PCR could be used for periodic screening of HIV patients to individuate those with higher risk of reactivation of L. infantum infection. PMID:20003257

  3. Gut Microbiota in HIV Infection: Implication for Disease Progression and Management

    PubMed Central

    Nwosu, Felix Chinweije; Avershina, Ekaterina; Wilson, Robert; Rudi, Knut

    2014-01-01

    Survival rates among HIV patients have significantly improved since the introduction of antiretroviral therapy (ART) in HIV management. However, persistent disease progression and clinical complications in virally suppressed individuals point to additional contributing factors other than HIV replication; microbial translocation is one such factor. The role of underlying commensal microbes and microbial products that traverse the intestinal lumen into systemic circulation in the absence of overt bacteraemia is under current investigation. This review focuses on current knowledge of the complex microbial communities and microbial markers involved in the disruption of mucosal immune T-cells in the promotion of inflammatory processes in HIV infections. Unanswered questions and aims for future studies are addressed. We provide perspective for discussing potential future therapeutic strategies focused on modulating the gut microbiota to abate HIV disease progression. PMID:25024700

  4. Recent development of new substituted indole and azaindole derivatives as anti-HIV agents.

    PubMed

    Ölgen, Süreyya

    2013-10-01

    Human immunodeficiency virus-1 (HIV-1) infections cause global health problems. Indole derivatives have been considered as one of the promising HIV inhibitors. Recent inventions have focused on substituted indole and azaindole derivatives that possess unique antiviral activities against HIV-1. In this review, the evaluation of recent advances in substituted indole and azaindole derivatives for the treatment or prevention of HIV-1 and acquired immune deficiency syndrome (AIDS) has been focused. In this respect, compounds having drug and bio-active properties, including their synthesis and pharmacologic properties have been reported. In addition, anti-HIV properties of compounds, the structural features of inhibitors, the current progress in terms of therapeutic interventions and the leading groups in the field are discussed. Moreover, clinical and ADME (Absorption, Distribution, Metabolism, Elimination) properties of some clinically important compounds such as BMS-378806, L-737126 and IDX899 are reported. PMID:23895189

  5. Developing neuroprotective strategies for treatment of HIV-associated neurocognitive dysfunction

    PubMed Central

    Rumbaugh, Jeffrey A; Steiner, Joseph; Sacktor, Ned; Nath, Avindra

    2009-01-01

    Important advances have been made in recent years in identifying the molecular mechanisms of HIV neuropathogenesis. Defining the pathways leading to HIV dementia has created an opportunity to therapeutically target many steps in the pathogenic process. HIV itself rarely infects neurons, but significant neuronal damage is caused both by viral proteins and by inflammatory mediators produced by the host in response to infection. Highly active antiretroviral therapy (HAART) does not target these mediators of neuronal damage, and the prevalence of HIV-associated neurocognitive dysfunction has actually been rising in the post-HAART era. This review will briefly summarize our current understanding of the mechanisms of HIV-induced neurological disease, and emphasize translation of this basic research into potential clinical applications. PMID:19774095

  6. HIV treatment for prevention.

    PubMed

    Ambrosioni, Juan; Calmy, Alexandra; Hirschel, Bernard

    2011-01-01

    "No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions) is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear.Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission.More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated waves of testing would precisely measure the incidence of HIV infection. Such trials face formidable logistical, practical and ethical obstacles. However, without definitive data, the intuitive appeal of "test-and-treat" is unlikely to translate into action on a global scale. In the meantime, based on the available evidence, we must strive to provide treatment to all those in medical need under the current medical guidelines. This will lead to a decrease in HIV transmission while "test-and-treat" is fully explored in prospective clinical trials. PMID:21612619

  7. The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

    PubMed Central

    Mediouni, Sonia; Garibaldi Marcondes, Maria Cecilia; Miller, Courtney; McLaughlin, Jay P.; Valente, Susana T.

    2015-01-01

    Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV-associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood–brain barrier into the CNS, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments. PMID:26557111

  8. Emergence of Individual HIV-Specific CD8 T Cell Responses during Primary HIV-1 Infection Can Determine Long-Term Disease Outcome

    PubMed Central

    Lu, Richard; Beckwith, Noor; Milazzo, Mark; Liu, Michelle; Routy, Jean-Pierre; Little, Susan; Jessen, Heiko; Kelleher, Anthony D.; Hecht, Frederick; Sekaly, Rafick-Pierre; Alter, Galit; Heckerman, David; Carrington, Mary; Rosenberg, Eric S.; Altfeld, Marcus

    2014-01-01

    ABSTRACT Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral set point have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1. A total of 620 individuals with primary HIV-1 infection were screened by gamma interferon (IFN-?) enzyme-linked immunospot (ELISPOT) assay for HLA class I-restricted, epitope-specific CD8 T cell responses using optimally defined epitopes approximately 2 months after initial presentation. The cohort was predominantly male (97%) and Caucasian (83%) (Fiebig stages II/III [n = 157], IV [n = 64], V [n = 286], and VI [n = 88] and Fiebig stage not determined [n = 25]). Longitudinal viral loads, CD4 count, and time to ART were collected for all patients. We observed strong associations between viral load at baseline (initial viremia) and the established early viral set points (P < 0.0001). Both were significantly associated with HLA class I genotypes (P = 0.0009). While neither the breadth nor the magnitude of HIV-specific CD8 T cell responses showed an influence on the early viral set point, a broader HIV-specific CD8 T cell response targeting epitopes within HIV-1 Gag during primary HIV-1 infection was associated with slower disease progression. Moreover, the induction of certain HIV-specific CD8 T cell responses—but not others—significantly influenced the time to ART initiation. Individual epitope-specific CD8 T cell responses contribute significantly to HIV-1 disease control, demonstrating that the specificity of the initial HIV-specific CD8 T cell response rather than the restricting HLA class I molecule alone is a critical determinant of antiviral function. IMPORTANCE Understanding which factors are involved in the control of HIV-1 infection is critical for the design of therapeutic strategies for patients living with HIV/AIDS. Here, using a cohort of over 600 individuals with acute and early HIV-1 infection, we assessed in unprecedented detail the individual contribution of epitope-specific CD8 T cell responses directed against HIV-1 to control of viremia and their impact on the overall course of disease progression. PMID:25165102

  9. Challenges for HIV vaccine dissemination and clinical trial recruitment: if we build it, will they come?

    PubMed

    Newman, Peter A; Duan, Naihua; Rudy, Ellen T; Anton, Peter A

    2004-12-01

    HIV vaccine availability does not guarantee uptake. Given suboptimal uptake of highly efficacious and already accessible vaccines in the United States, low vaccine coverage in the developing world, and the expectation that initial HIV vaccines will be only partially efficacious, the public health community will face formidable challenges in disseminating U.S. Food and Drug Administration (FDA)-approved HIV vaccines. HIV/AIDS stigma, fear of vaccine- induced HIV infection, social side effects of testing HIV-positive, and mistrust of government and research present additional obstacles to HIV vaccine dissemination. Increased risk behaviors because of HIV vaccine availability can undermine the effectiveness of partially efficacious vaccines in reducing HIV incidence. HIV vaccine efficacy trials also face significant challenges in recruitment of sufficient volunteers and possible increases in risk behaviors due to trial participation. Planning and designing interventions to facilitate successful recruitment for large-scale phase 3 efficacy trials is a vital step towards U.S. FDA-approved HIV vaccines. Rather than despair in the face of momentous HIV vaccine dissemination challenges, or presume unrealistically that vaccine uptake will ensue automatically and that risk behavior increases will not occur, let us deem the estimated 10-year window to an approved HIV vaccine as an opportunity to investigate and confront these challenges. A consumer research agenda founded on social marketing principles is needed to facilitate the design of empirically-based interventions tailored to the unique needs and preferences of specific segments of consumers. Social marketing interventions may increase future HIV vaccine uptake and clinical trial participation, and mitigate increases in HIV risk behaviors. PMID:15659880

  10. Interactions between HIV-1 and the Cell-Autonomous Innate Immune System

    PubMed Central

    Towers, Greg J.; Noursadeghi, Mahdad

    2014-01-01

    HIV-1 was recognized as the cause of AIDS in humans in 1984. Despite 30 years of intensive research, we are still unraveling the molecular details of the host-pathogen interactions that enable this virus to escape immune clearance and cause immunodeficiency. Here we explore a series of recent studies that consider how HIV-1 interacts with the cell-autonomous innate immune system as it navigates its way in and out of host cells. We discuss how these studies improve our knowledge of HIV-1 and host biology as well as increase our understanding of transmission, persistence, and immunodeficiency and the potential for therapeutic or prophylactic interventions. PMID:25011104

  11. TARGETING POLYMER THERAPEUTICS TO BONE

    PubMed Central

    Low, Stewart; Kope?ek, Jind?ich

    2012-01-01

    An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

  12. HIV/AIDS and the Flu

    MedlinePLUS

    ... Submit What's this? Submit Button Past Newsletters HIV/AIDS and the Flu Questions & Answers Language: English Españ ... people with HIV/AIDS. Should people with HIV/AIDS receive the inactivated influenza vaccine? People with HIV/ ...

  13. HIV and AIDS: Medicines to Help You

    MedlinePLUS

    ... by Audience For Women Free Publications HIV and AIDS--Medicines to Help You Share Tweet Linkedin Pin ... HIV treatment. HIV is the virus that causes AIDS. HIV stands for H uman I mmunodeficiency V ...

  14. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    PubMed

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection. PMID:26315816

  15. Strategies for therapeutic hypometabothermia.

    PubMed

    Liu, Shimin; Chen, Jiang-Fan

    2012-01-01

    Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. These problems are commonly seen in hypothermia and barbiturate coma. The main innovative concept of this review is to propose thermogenically optimal and synergistic reduction of core temperature and metabolic rate in therapeutic hypometabothermia using novel and clinically practical approaches. When metabolism and body temperature are reduced in a systematically synergistic manner, the outcome will be maximal protection and safe recovery, which happen in natural process, such as in hibernation, daily torpor and estivation. PMID:24179563

  16. Therapeutic antibodies against cancer

    PubMed Central

    Adler, Mark J.; Dimitrov, Dimiter S.

    2012-01-01

    Antibody-based therapeutics against cancer are highly successful in clinic and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States (one, mylotarg, was withdrawn from market in 2010). Three of the mAbs (bevacizumab, rituximab, trastuzumab) are in the top six selling protein therapeutics with sales in 2010 of more than $5 bln each. Hundreds of mAbs including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs and mAbs with optimized pharmacokinetics are in clinical trials. However, challenges remain and it appears that deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems and individual variations. PMID:22520975

  17. [Therapeutic adherence in elderly].

    PubMed

    Petermans, J; Suarez, A Samalea; Van Hees, T

    2010-01-01

    Therapeutic adherence can be defined as the degree of concordance between the behaviour of a person in relation with drugs prescription and medical recommendations. It represents the ability of people to follow a treatment. Bad adherence is frequent in geriatric patients. The behaviour of the patient is important but the role of the prescriptor and distributor of the drugs should also be emphasized. A bad adherence is responsible for iatrogenic consequences, which has a great impact on the functionality of the old person, but also on the cost and organization of care. Therapeutic education, a standardised method to help the patient take care of his own treatment, must be developed. The aims and means should be clearly efined. The patient himself must be involved and human or material sources of help must be sought. PMID:20684404

  18. Multistage vector (MSV) therapeutics.

    PubMed

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  19. New levodopa therapeutic strategies.

    PubMed

    LeWitt, Peter A

    2016-01-01

    During its almost half-century of use for treating Parkinson's disease, levodopa therapy has permitted most patients to reverse much of this disorder's symptomatology. However, the full range of its therapeutic properties is not completely understood, as levodopa is showing itself to be more than just a metabolic intermediate for dopamine synthesis. Improving the constancy of drug delivery is the next frontier for enhancing therapeutic options with levodopa. Because conventional immediate-release carbidopa-levodopa tablets yield such variable pharmacokinetic profiles (as do other marketed products attempting to extend levodopa effect), improved formulations are greatly needed by patients experiencing motor fluctuations. Products under development or recently released in the U.S. include intestinal infusion, sustained-release microtablets, gastric-retentive formulations, a levodopa pro-drug, and methods for delivery of the drug by inhalation or subcutaneous infusion. PMID:26459662

  20. Women and HIV

    PubMed Central

    Gatali, Marene; Archibald, Chris

    2004-01-01

    Health Issue The epidemic of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in developed countries has changed from the early epidemic that affected primarily men who have sex with men, to one that increasingly affects other groups such as injecting drug users (IDU) and heterosexuals. As a result, the number and percentage of women with HIV and AIDS is increasing. Key Findings The number of women in Canada living with HIV, including those with AIDS, has increased over time. An estimated 6,800 women were living with HIV at the end of 1999, an increase of 48.0 % from the 1996 estimate of 4,600. On an annual basis, women account for a growing proportion of positive HIV test reports among adults in Canada. This proportion increased from 10.7% in the period 1985–95 to 25% in 2001. Heterosexual contact is the main risk factor for HIV infection in women, accounting for 63% of newly diagnosed cases of HIV infection in adult Canadian women in 2001; the majority of the remainder is due to IDU. Key Data Gaps and Recommendations Research is needed to address specific information gaps regarding risk behaviours, testing patterns and HIV incidence and prevalence in women. This research needs to include the broader contextual factors that influence women's lives and their risk of HIV infection. Programmes and prevention efforts must be gender and age-specific and should target not only individual behaviours, but also the social and cultural context in which these behaviours occur. PMID:15345090

  1. Antibody B cell responses in HIV-1 infection.

    PubMed

    Mouquet, Hugo

    2014-11-01

    In rare cases, B cells can supply HIV-1-infected individuals with unconventional antibodies equipped to neutralize the wide diversity of viral variants. Innovations in single-cell cloning, high-throughput sequencing, and structural biology methods have enabled the capture and thorough characterization of these exceptionally potent broadly neutralizing antibodies (bNAbs). Here, I review the recent findings in humoral responses to HIV-1, focusing on the interplay between naturally occurring bNAbs and the virus both at systemic and mucosal levels. In this context, I discuss how an improved understanding of bNAb generation may provide invaluable insight into the fundamental mechanisms governing adaptive B cell responses to viruses, and how this knowledge is currently contributing to the development of vaccine and therapeutic strategies against HIV-1. PMID:25240985

  2. HIV-1 Neuroimmunity in the Era of Antiretroviral Therapy

    PubMed Central

    Kraft-Terry, Stephanie D.; Stothert, Andrew R.; Buch, Shilpa; Gendelman, Howard E.

    2010-01-01

    Human immunodeficiency virus type one (HIV-1) associated neurocognitive disorders (HAND) can affect < 50% of infected people during the disease course. While antiretroviral therapies have substantively increased the quality of life and reduced HIV-1 associated dementia, less severe minor cognitive and motor deficits continue. Trafficking of HIV-1 into the central nervous system (CNS), peripheral immune activation, dysregulated glial immunity, and diminished homeostatic responses are the disease-linked pathobiologic events. Monocyte-macrophage passage into the CNS remains an underlying force for disease severity. Monocyte phenotypic may change at an early stage of cell maturation and immune activation of hematopoietic stem cells. Activated monocytes are pulled into the brain in response to chemokines made as a result of glial inflammatory processes, which in turn cause secondary functional deficits in neurons. Current therapeutic approaches are focused on adjunctive and brain-penetrating antiretroviral therapies. These may attenuate virus-associated neuroinflammatory activities thereby decreasing the severity and frequency of HAND. PMID:20044002

  3. Peptide substrates and inhibitors of the HIV-1 protease.

    PubMed

    Moore, M L; Bryan, W M; Fakhoury, S A; Magaard, V W; Huffman, W F; Dayton, B D; Meek, T D; Hyland, L; Dreyer, G B; Metcalf, B W

    1989-03-15

    Oligopeptides containing the consensus retroviral protease cleavage sequence Ser/Thr-X-Y-Tyr/Phe-Pro are substrates for purified recombinant HIV-1 protease with Km's in the millimolar range. The minimum sequence containing the consensus pentapeptide which serves as a good substrate is a heptapeptide spanning the P4-P3' residues. Substitution of reduced Phe-Pro or Tyr-Pro dipeptide isosteres or the statine analog 3-hydroxy-4-amino-5-phenylpentanoic acid for the scissile dipeptide afforded inhibitors of HIV-1 protease with Ki values in the micromolar range, three orders of magnitude better in affinity than the corresponding substrates. Inhibitors of HIV-1 protease may provide a novel and potentially useful therapeutic approach to the treatment of acquired immune deficiency syndrome (AIDS). PMID:2649094

  4. Drugs of abuse and HIV infection/replication: implications for mother-fetus transmission

    PubMed Central

    Wang, Xu; Ho, Wen-Zhe

    2011-01-01

    Human immunodeficiency virus (HIV) infection and progression of acquired immunodeficiency syndrome (AIDS) can be modulated by a number of cofactors, including drugs of abuse. Opioids, cocaine, cannabinoids, methamphetamine (METH), alcohol, and other substances of abuse have been implicated as risk factors for HIV infection, as they all have the potential to compromise host immunity and facilitate viral replication. Although epidemiologic evidence regarding the impact of drugs of abuse on HIV disease progression is mixed, in vitro studies as well as studies using in vivo animal models have indicated that drugs of abuse have the ability to enhance HIV infection/replication. Drugs of abuse may also be a risk factor for perinatal transmission of HIV. Because high levels of viral load in maternal blood are associated with increased risk of HIV vertical transmission, it is likely that drugs of abuse play an important role in promoting mother-fetus transmission. Furthermore, because the neonatal immune system differs qualitatively from the adult system, it is possible that maternal exposure to drugs of abuse would exacerbate neonatal immunity defects, facilitating HIV infection of neonate immune cells and promoting HIV vertical transmission. The availability and use of antiretroviral therapy for women infected with HIV increase, there is an increasing interest in determining the impact of drug abuse on efficacy of AIDS Clinical Trials Group (ACTG) -standardized treatment regimens for woman infected with HIV in the context of HIV vertical transmission. PMID:21056582

  5. High HIV prevalence among children presenting for general consultation in rural Cameroon.

    PubMed

    Zoufaly, A; Hammerl, R; Sunjoh, F; Jochum, J; Nassimi, N; Awasom, C; Tayong, G; Sauter, F; Schmiedel, S; van Lunzen, J; Burchard, G; Feldt, T

    2014-09-01

    Data on the HIV-prevalence children presenting to health care facilities in sub-Saharan Africa are scant in general, and the debate about opportunities for paediatric HIV screening is ongoing. Nine hundred and eighty-one children with unknown HIV-status presenting to a large general paediatric outpatient department in rural Cameroon were tested using the Determine HIV-1/2 rapid test (Abbott), and positive results were confirmed with the Hexagon HIV rapid test (Human Diagnostics). In children younger than 18 months, HIV infection was confirmed by PCR testing. Median age was 1.3 years and 52.8% were of male gender. In 514 children below 18 months of age, 16 (3.1%) tested positive. Of those, HIV-1 PCR was available for 11 children, of whom 6 had a positive PCR result. HIV prevalence was highest in the age group 5-9 years, being 8.8%. Malnutrition (33.3 vs 5.2%, p?HIV infection. Our study results indicate that HIV testing should be offered to all children at possible entry points to medical care, irrespective of symptoms, in order to reduce HIV-associated mortality through timely initiation of antiretroviral therapy. PMID:24469969

  6. Proteases as therapeutics

    PubMed Central

    Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

    2015-01-01

    Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

  7. HIV infection is associated with attenuated frontostriatal intrinsic connectivity

    PubMed Central

    Ipser, Jonathan C.; Brown, Gregory G.; Bischoff-Grethe, Amanda; Connolly, Colm G.; Ellis, Ronald J.; Heaton, Robert K.; Grant, Igor

    2015-01-01

    Objective HIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the impact of HIV infection on functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Method Fifteen HIV-positive and 15 demographically matched control participants underwent 6 minutes of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). Results HIV – associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (< 50 years, N = 9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was associated with reduced frontostriatal connectivity. Conclusions In conclusion, our data indicate that a diagnosis of HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies. PMID:25824201

  8. The influence of delivery vectors on HIV vaccine efficacy

    PubMed Central

    Ondondo, Beatrice O.

    2014-01-01

    Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy. PMID:25202303

  9. Therapeutic potential of cannabinoids in CNS disease.

    PubMed

    Croxford, J Ludovic

    2003-01-01

    The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders. PMID:12617697

  10. Leveraging HIV Treatment to End AIDS, Stop New HIV Infections, and Avoid the Cost of Inaction

    PubMed Central

    Sidibé, Michel; Zuniga, José M.; Montaner, Julio

    2014-01-01

    We have the tools at our disposal to significantly bend AIDS-related morbidity and mortality curves and reduce human immunodeficiency virus (HIV) incidence. It is thus essential to redouble our efforts to reach the goal of placing 15 million people on life-saving and -enhancing antiretroviral therapy (ART) by 2015. In reaching this milestone, we can write a new chapter in the history of global health, demonstrating that a robust, multidimensional response can succeed against a complex pandemic that presents as many social and political challenges as it does medical ones. This milestone is also critical to advance our ultimate goal of ending AIDS by maximizing the therapeutic and preventive effects of ART, which translates into a world in which AIDS-related deaths and new HIV infections are exceedingly rare. PMID:24926030

  11. Inhibition of HIV-1 gp41 expression with hammerhead ribozymes.

    PubMed

    Fedoruk-Wyszomirska, Agnieszka; Szyma?ski, Maciej; G?odowicz, Pawe?; Gabryelska, Marta; Wyszko, Eliza; Estrin, William J; Barciszewski, Jan

    2015-10-01

    Despite great progress in the treatment of AIDS, HIV-1 remains one of the major concerns as a human pathogen. One of the therapeutic strategies against viral infections is the application of catalytic ribonucleic acids (ribozymes) that can significantly reduce expression of a target gene by site-specific hydrolysis of its mRNA. In the present paper, we report a study on the activity of several variants of hammerhead ribozymes targeting a conserved region within mRNA encoding HIV-1 envelope glycoprotein gp41. On the basis of the data from in vitro assays and gene silencing in the cultured cells, we propose a new hammerhead ribozyme targeting the gp41-encoding sequence that can be potentially used as a therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic activity of the ribozyme in the intracellular environment cannot be inferred solely from the results of in vitro experiments. PMID:26209679

  12. HIV transmission biology: translation for HIV prevention.

    PubMed

    Ronen, Keshet; Sharma, Amit; Overbaugh, Julie

    2015-11-01

    Rigorous testing of new HIV-prevention strategies is a time-consuming and expensive undertaking. Thus, making well informed decisions on which candidate-prevention approaches are most likely to provide the most benefit is critical to appropriately prioritizing clinical testing. In the case of biological interventions, the decision to test a given prevention approach in human trials rests largely on evidence of protection in preclinical studies. The ability of preclinical studies to predict efficacy in humans may depend on how well the model recapitulates key biological features of HIV transmission relevant to the question at hand. Here, we review our current understanding of the biology of HIV transmission based on data from animal models, cell culture, and viral sequence analysis from human infection. We summarize studies of the bottleneck in viral transmission; the characteristics of transmitted viruses; the establishment of infection; and the contribution of cell-free and cell-associated virus. We seek to highlight the implications of HIV-transmission biology for development of prevention interventions, and to discuss the limitations of existing preclinical models. PMID:26418086

  13. Challenges in HIV Vaccine Research for Treatment and Prevention

    PubMed Central

    Ensoli, Barbara; Cafaro, Aurelio; Monini, Paolo; Marcotullio, Simone; Ensoli, Fabrizio

    2014-01-01

    Many attempts have been made or are ongoing for HIV prevention and HIV cure. Many successes are in the list, particularly for HIV drugs, recently proposed also for prevention. However, no eradication of infection has been achieved so far with any drug. Further, a residual immune dysregulation associated to chronic immune activation and incomplete restoration of B and T cell subsets, together with HIV DNA persistence in reservoirs, are still unmet needs of the highly active antiretroviral therapy, causing novel “non-AIDS related” diseases that account for a higher risk of death even in virologically suppressed patients. These “ART unmet needs” represent a problem, which is expected to increase by ART roll out. Further, in countries such as South Africa, where six millions of individuals are infected, ART appears unable to contain the epidemics. Regretfully, all the attempts at developing a preventative vaccine have been largely disappointing. However, recent therapeutic immunization strategies have opened new avenues for HIV treatment, which might be exploitable also for preventative vaccine approaches. For example, immunization strategies aimed at targeting key viral products responsible of virus transmission, activation, and maintenance of virus reservoirs may intensify drug efficacy and lead to a functional cure providing new perspectives also for prevention and future virus eradication strategies. However, this approach imposes new challenges to the scientific community, vaccine developers, and regulatory bodies, such as the identification of novel immunological and virological biomarkers to assess efficacy end-points, taking advantage from the natural history of infection and exploiting lessons from former trials. This review will focus first on recent advancement of therapeutic strategies, then on the progresses made in preventative approaches, discussing concepts, and problems for the way ahead for the development of vaccines for HIV treatment and prevention. PMID:25250026

  14. Intravenous immunoglobulin treatment in a HIV-1 positive patient with Guillain-Barré syndrome.

    PubMed

    Rosca, Elena Cecilia; Rosca, Ovidiu; Simu, Mihaela

    2015-12-01

    We report the case of an HIV-1 positive patient with primary demyelinating neuropathy (Guillain-Barré syndrome); after intravenous immunoglobulin treatment (IVIG), he presented with an increase in CD4 and CD8 cell counts and a decrease in plasma viral load. Currently, there is little reported research regarding IVIG treatment in adults with HIV-1. The present report brings further evidence regarding the possible benefit of IVIG in HIV-1 infected patients, providing a novel perspective on treatment. PMID:26428850

  15. HIV prevalence and risk behaviours among injecting drug users in six indonesian cities implications for future HIV prevention programs

    PubMed Central

    2012-01-01

    Background The HIV prevalence among injecting drug users (IDUs) in Indonesia reached 50% in 2005. While drug use remains illegal in Indonesia, a needle and syringe program (NSP) was implemented in 2006. Methods In 2007, an integrated behavioural and biological surveillance survey was conducted among IDUs in six cities. IDUs were selected via time-location sampling and respondent-driven sampling. A questionnaire was administered face-to-face. IDUs from four cities were tested for HIV, syphilis, gonorrhoea and chlamydia. Factors associated with HIV were assessed using generalized estimating equations. Risk for sexual transmission of HIV was assessed among HIV-positive IDUs. Results Among 1,404 IDUs, 70% were daily injectors and 31% reported sharing needles in the past week. Most (76%) IDUs received injecting equipment from NSP in the prior week; 26% always carried a needle and those who didn’t, feared police arrest. STI prevalence was low (8%). HIV prevalence was 52%; 27% among IDUs injecting less than 1 year, 35% among those injecting for 1–3 years compared to 61% in long term injectors (p?HIV-positive status was associated with duration of injecting, ever been imprisoned and injecting in public parks. Among HIV-infected IDUs, consistent condom use last week with steady, casual and commercial sex partners was reported by 13%, 24% and 32%, respectively. Conclusions Although NSP uptake has possibly reduced HIV transmission among injectors with shorter injection history, the prevalence of HIV among IDUs in Indonesia remains unacceptably high. Condom use is insufficient, which advocates for strengthening prevention of sexual transmission alongside harm reduction programs. PMID:22943438

  16. Visceral Leishmaniasis and HIV Coinfection in Latin America

    PubMed Central

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-01-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population. PMID:25233461

  17. METABOLIC SYNDROME IN RELATION TO CARDIORESPIRATORY FITNESS, ACTIVE AND SEDENTARY BEHAVIOR IN HIV+ HISPANICS WITH AND WITHOUT LIPODYSTROPHY

    PubMed Central

    Ramírez-Marrero, Farah A.; Santana-Bagur, Jorge L.; Joyner, Michael J.; Rodríguez-Zayas, Jorge; Frontera, Walter

    2015-01-01

    Hispanics in Puerto Rico (PR) have a high prevalence of metabolic syndrome (met-syn), partially explained by low physical activity (PA) and possibly low cardiorespiratory fitness (VO2peak). Met-syn is also associated with lipodystrophy in HIV infected (HIV+) adults taking antiretroviral therapies. However, associations between met-syn, VO2peak, PA, sedentary behavior and lipodystrophy among HIV+ Hispanics have not been adequately reported. Objective We tested the following hypotheses: 1) HIV+ Hispanics with lipodystrophy (HIV-Lipo) would have a higher prevalence of met-syn, lower VO2peak and PA, and higher sedentary behavior compared with those without lipodystrophy (HIV-no-Lipo) and without HIV infection (Non-HIV); and 2) met-syn would be inversely associated with VO2peak and PA, and directly associated with sedentary behavior. METHODS Ninety Hispanic adults (32 HIV-Lipo, 28 HIV-no-Lipo, 30 Non-HIV) completed measurements of VO2peak, anthropometry, PA and sedentary behavior with accelerometry, blood pressure, fasting glucose, insulin, and lipids. ANOVA and chi-square tests were used to detect differences between groups, and regression analyses to test associations between variables. RESULTS More HIV-Lipo (69%) had met-syn compared with HIV-no-Lipo (39%) and Non-HIV (37%) (P=0.002). Sedentary behavior and PA were not different, but VO2peak differed between all groups: lowest in HIV-Lipo and highest in non-HIV. PA and sedentary behavior were not associated with met-syn, but PA was directly associated with VO peak (R2=0.26, p<0.01). Also, a lower odds ratio for met-syn was observed with higher VO2peak (0.87; 95% CI: 0.83-0.95). CONCLUSION Met-syn is related to lipodystrophy in HIV+ Hispanics in PR, and high VO2peak may protect against met-syn in this population. PMID:25563033

  18. HIV and Pregnancy

    MedlinePLUS

    ... week of pregnancy until the end of pregnancy. Human Immunodeficiency Virus (HIV): A virus that attacks certain cells of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS). Immune System: ...

  19. HIV Viral Load

    MedlinePLUS

    ... begin treatment Guide recommendations for therapy Monitor the effectiveness of therapy and help detect drug resistance Predict ... effective. A decreasing viral load indicates improvement, treatment effectiveness, and suppression of the HIV infection. ^ Back to ...

  20. Hepatitis C and HIV

    MedlinePLUS

    ... Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the ... related pages, Hepatitis A and Hepatitis B . Hepatitis C AND HIV About 25% of people living with ...

  1. HIV/AIDS Medicines

    MedlinePLUS

    ... few years. But today, there are many effective medicines to fight the infection, and people with HIV ... healthier lives. There are five major types of medicines: Reverse transcriptase (RT) inhibitors - interfere with a critical ...

  2. Recreational Drugs and HIV

    MedlinePLUS

    ... use may decrease ARV effectiveness by diminishing adherence. Crystal meth, methamphetamine, Crank, Glass, Tina, others A recent study found that gay men who use crystal meth have five times the risk of HIV ...

  3. Older People and HIV

    MedlinePLUS

    ... worse for older people. This can result in hiding their infection from family and friends. IS HIV ... to be diagnosed and treated correctly. FOR MORE INFORMATION See the website of the National Center for ...

  4. Reduce HIV Risk

    MedlinePLUS

    ... incidence could be reduced if people changed their sexual behaviors. Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Spring 2008 ...

  5. Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

    PubMed Central

    Carryl, Heather; Swang, Melanie; Lawrence, Jerome; Curtis, Kimberly; Kamboj, Herman; Van Rompay, Koen K. A.; De Paris, Kristina; Burke, Mark W.

    2015-01-01

    Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1, neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems. PMID:26034832

  6. Attitudes of women and men living with HIV and their healthcare providers towards pregnancy and abortion by HIV-positive women in Nigeria and Zambia.

    PubMed

    Moore, Ann M; Bankole, Akinrinola; Awolude, Olutoin; Audam, Suzette; Oladokun, Adesina; Adewole, Isaac

    2015-01-01

    Fertility decisions among people living with HIV/AIDS (PLWHA) are complicated by disease progression, the health of their existing children and possible antiretroviral therapy (ART) use, among other factors. Using a sample of HIV-positive women (n = 353) and men (n = 299) from Nigeria and Zambia and their healthcare providers (n = 179), we examined attitudes towards childbearing and abortion by HIV-positive women. To measure childbearing and abortion attitudes, we used individual indicators and a composite measure (an index). Support for an HIV-positive woman to have a child was greatest if she was nulliparous or if her desire to have a child was not conditioned on parity and lowest if she already had an HIV-positive child. Such support was found to be lower among HIV-positive women than among HIV-positive men, both of which were lower than reported support from their healthcare providers. There was wider variation in support for abortion depending on the measure than there was for support for childbearing. Half of all respondents indicated no or low support for abortion on the index measure while between 2 and 4 in 10 respondents were supportive of HIV-positive women being able to terminate a pregnancy. The overall low levels of support for abortion indicate that most respondents did not see HIV as a medical condition which justifies abortion. Respondents in Nigeria and those who live in urban areas were more likely to support HIV-positive women's childbearing. About a fifth of HIV-positive respondents reported being counselled to end childbearing after their diagnosis. In summary, respondents from both Nigeria and Zambia demonstrate tempered support of (continued) childbearing among HIV-positive women while anti-abortion attitudes remain strong. Access to ART did not impart a strong effect on these attitudes. Therefore, pronatalist attitudes remain in place in the face of HIV infection. PMID:25920981

  7. 'Every disease has its cure': faith and HIV therapies in Islamic northern Nigeria.

    PubMed

    Tocco, Jack Ume

    2010-12-01

    Northern Nigeria has one of the highest levels of HIV prevalence among societies that are predominantly Muslim. In the last decade the region has experienced marked expansion of religiously-oriented healing practices following the formal adoption of Islamic sharia law. Since 2005, international funding has also made antiretroviral therapy (ART) more widely available throughout Nigeria. This study uses ethnographic data collected in Kano, northern Nigeria's largest city, to examine Muslims' perspectives on HIV treatment in the context of popular health beliefs and expanding therapeutic options. The research found that passages from classical Islamic texts are regularly cited by both HIV/AIDS practitioners and patients, especially when talking about the supposition that Allah sends a cure to humankind for every disease. Some religious scholar-practitioners (malamai) working in the Islamic traditions of prophetic medicine insist that HIV can be completely cured given sufficient faith in the supernatural power of the Quran; others claim that the natural ingredients prescribed in Islamic texts can cure HIV. Such assertions contradict the mainstream biomedical position that, with the proper therapeutic regimen, infection with HIV can be managed as a chronic illness, although not cured. Thus, these assertions constitute a challenge to the increasing therapeutic hegemony of antiretroviralbased care in Nigeria. Without falsifying the proposition that a divine cure for HIV exists, many Muslim patients on ART, and the predominantly Muslim biomedical staff who treat them, express scepticism about whether the cure has yet to be revealed to humans. These findings suggest that despite recent efforts in Nigeria to assert a unified Islamic perspective on HIV and AIDS, substantive disagreements persist over the causes, treatments and curability of the disease. The healing systems in which practitioners and patients operate influence how they interpret Islamic texts concerning the divinely ordained relationships between Allah, humans, diseases and cures. PMID:25875887

  8. Cystic Fibrosis Therapeutics

    PubMed Central

    Ramsey, Bonnie W.

    2013-01-01

    A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco. PMID:23276843

  9. Computerized and traditional stroop task dysfunction in HIV-1 infection.

    PubMed

    Hinkin, C H; Castellon, S A; Hardy, D J; Granholm, E; Siegle, G

    1999-04-01

    Controlled processing, response inhibition, and set adoption were examined in 51 HIV-1 infected participants and 21 uninfected controls who were administered a vocal reaction time (RT) version of the Stroop task (Stroop-RT; J. R. Stroop, 1935) as well as the traditional 100 item paper-and-pencil version. Response set expectancies on the Stroop-RT were manipulated by presenting 50% of trials in homogenous blocks and randomly varying the stimulus type during the remaining trials. As hypothesized, HIV seropositive (HIV+) participants were significantly slower than HIV seronegative controls on both versions of the Stroop. Significant interference effects were apparent on the paper-and-pencil version of the Stroop, but were not as prominent on the Stroop-RT. The HIV+ participants did profit from the blocking manipulation on the Stroop-RT, suggesting that set adoption is retained in HIV infection. These data suggest that HIV infection may result in deficient response inhibition, possibly secondary to frontostriatal dysfunction and dopaminergic alterations. PMID:10353380

  10. Therapeutic approaches to cellulite.

    PubMed

    Green, Jeremy B; Cohen, Joel L; Kaufman, Joely; Metelitsa, Andrei I; Kaminer, Michael S

    2015-09-01

    Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution. PMID:26566570

  11. Systemic Effects of Inflammation on Health during Chronic HIV Infection

    PubMed Central

    Deeks, Steven G.; Tracy, Russell; Douek, Daniel C.

    2014-01-01

    Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications, but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affect health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging. PMID:24138880

  12. HIV-1 functional cure: will the dream come true?

    PubMed

    Liu, Chao; Ma, Xiancai; Liu, Bingfeng; Chen, Cancan; Zhang, Hui

    2015-01-01

    The reservoir of human immunodeficiency virus type 1 (HIV-1), a long-lived pool of latently infected cells harboring replication-competent viruses, is the major obstacle to curing acquired immune deficiency syndrome (AIDS). Although the combination antiretroviral therapy (cART) can successfully suppress HIV-1 viremia and significantly delay the progression of the disease, it cannot eliminate the viral reservoir and the patient must continue to take anti-viral medicines for life. Currently, the appearance of the 'Berlin patient', the 'Boston patients', and the 'Mississippi baby' have inspired many therapeutic strategies for HIV-1 aimed at curing efforts. However, the specific eradication of viral latency and the recovery and optimization of the HIV-1-specific immune surveillance are major challenges to achieving such a cure. Here, we summarize recent studies addressing the mechanisms underlying the viral latency and define two categories of viral reservoir: 'shallow' and 'deep'. We also present the current strategies and recent advances in the development of a functional cure for HIV-1, focusing on full/partial replacement of the immune system, 'shock and kill', and 'permanent silencing' approaches. PMID:26588898

  13. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

    PubMed Central

    Maganga, Emmanuel; Smart, Luke R.; Kalluvya, Samuel; Kataraihya, Johannes B.; Saleh, Ahmed M.; Obeid, Lama; Downs, Jennifer A.; Fitzgerald, Daniel W.; Peck, Robert N.

    2015-01-01

    Introduction Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ? 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution. PMID:26287742

  14. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    PubMed Central

    Sehl, Mary; Sinsheimer, Janet S.; Hultin, Patricia M.; Hultin, Lance E.; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D.

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x10-200 and 0.47, p<1x10-200. Weighted gene correlation network analysis (WGCNA) identified 17 co-methylation modules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: ?age= 0.007088, p=2.08 x 10-9; ?HIV= 0.099574, p=0.0011; Data set 2: ?age= 0.008762, p=1.27x 10-5; ?HIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to age-associated patterns and suggest that general aging and HIV-1 related aging work through some common cellular and molecular mechanisms. These results are an important first step for finding potential therapeutic targets and novel clinical approaches to mitigate the detrimental effects of both HIV-1-infection and aging. PMID:25807146

  15. Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.

    PubMed Central

    Prince, A M; Horowitz, B; Baker, L; Shulman, R W; Ralph, H; Valinsky, J; Cundell, A; Brotman, B; Boehle, W; Rey, F

    1988-01-01

    To assess the possible efficacy of passive immunization against human immunodeficiency virus (HIV) an immune globulin was prepared from plasma of HIV-seropositive donors selected to be among those having the top 12.5% of virus-neutralizing antibody titers. The immune globulin was treated with pepsin to render it intravenously tolerable. The preparation, which we termed HIVIG, neutralized 100 tissue culture 50% infective doses (TCID50) of HIV at an average dilution of 1:1000 in neutralization tests in vitro. During preparation HIVIG was subjected to virus inactivation and removal procedures that in theory resulted in a reduction in HIV infectivity by a factor of 10(25). At a dose of 9-10 ml/kg of body weight both the virus-inactivated source plasma and the final immunoglobulin preparation were noninfective and without adverse effect in two chimpanzees. Two chimpanzees inoculated intravenously with HIVIG at 1 ml/kg and two inoculated with 10 ml/kg were challenged intravenously 1 day later with 400 TCID50 of the same strain of HIV (HTLV-IIIb) used in neutralization assays in vitro. All animals became infected. Incubation periods to virus isolation (by cocultivation with human mononuclear cells) in HIVIG recipients did not differ significantly from the incubation period seen in a control animal that received a normal anti-HIV-free immunoglobulin. These findings may have implications for understanding the failure of experimental vaccines to protect against HIV challenge in chimpanzee experiments. Images PMID:3413127

  16. Bryostatin-1 synergizes with histone deacetylase inhibitors to reactivate HIV-1 from latency.

    PubMed

    Pérez, Moisés; de Vinuesa, Amaya García; Sanchez-Duffhues, Gonzalo; Marquez, Nieves; Bellido, M Luz; Muñoz-Fernandez, M Angeles; Moreno, Santiago; Castor, Trevor P; Calzado, Marco A; Muñoz, Eduardo

    2010-09-01

    The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication on patients treated with HAART. It has been suggested that successful depletion of such latent reservoirs will require a combination of therapeutic agents that can specifically and efficiently act on cells harboring latent HIV-1 provirus. Using Jurkat-LAT-GFP cells, a tractable model of HIV-1 latency, we have found that bryostatin -1 reactivates HIV-1 through a classical PKC-dependent pathway. Bryostatin-1 also activates MAPKs and NF-?B pathways and synergizes with HDAC inhibitors to reactivate HIV-1 from latency. Bryostatin-1 downregulates the expression of the HIV-1 co-receptors CD4 and CXCR4 and prevented de novo HIV-1 infection in susceptible cells. We applied proteomic methods to investigate major changes in protein expression in Jurkat-LAT-GFP under latency and reactivation conditions. We identified up-regulation of proteins that may be involved in the innate anti-HIV-1 response (NKEF-A and MHD2) and in different cell functions (i.e. cofilin-1 and transgelin-2) of the host cells. PKC agonists may represent a valuable pharmacological approach to purge latent HIV from cellular reservoirs and at the moment, the only clinically available PKC agonist is bryostatin-1. This drug has been tested in numerous clinical trials and its pharmacokinetics and toxicity in humans is well known. Moreover, bryostatin-1 potently synergizes with other HDAC inhibitors commonly used in the medical practice such as valproic acid. Therefore, bryostatin-1, alone or in combination with HDAC inhibitors, could be used in HAART treated patients to validate the hypothesis that reactivating HIV-1 from latency could purge HIV-1 reservoirs. PMID:20636281

  17. Identification of dual-tropic HIV-1 using evolved neural networks.

    PubMed

    Fogel, Gary B; Lamers, Susanna L; Liu, Enoch S; Salemi, Marco; McGrath, Michael S

    2015-11-01

    Blocking the binding of the envelope HIV-1 protein to immune cells is a popular concept for development of anti-HIV therapeutics. R5 HIV-1 binds CCR5, X4 HIV-1 binds CXCR4, and dual-tropic HIV-1 can bind either coreceptor for cellular entry. R5 viruses are associated with early infection and over time can evolve to X4 viruses that are associated with immune failure. Dual-tropic HIV-1 is less studied; however, it represents functional antigenic intermediates during the transition of R5 to X4 viruses. Viral tropism is linked partly to the HIV-1 envelope V3 domain, where the amino acid sequence helps dictate the receptor a particular virus will target; however, using V3 sequence information to identify dual-tropic HIV-1 isolates has remained difficult. Our goal in this study was to elucidate features of dual-tropic HIV-1 isolates that assist in the biological understanding of dual-tropism and develop an approach for their detection. Over 1559 HIV-1 subtype B sequences with known tropisms were analyzed. Each sequence was represented by 73 structural, biochemical and regional features. These features were provided to an evolved neural network classifier and evaluated using balanced and unbalanced data sets. The study resolved R5X4 viruses from R5 with an accuracy of 81.8% and from X4 with an accuracy of 78.8%. The approach also identified a set of V3 features (hydrophobicity, structural and polarity) that are associated with tropism transitions. The ability to distinguish R5X4 isolates will improve computational tropism decisions for R5 vs. X4 and assist in HIV-1 research and drug development efforts. PMID:26419858

  18. HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

    PubMed Central

    Borgmann, Kathleen; Ghorpade, Anuja

    2015-01-01

    As a popular psychostimulant, methamphetamine (METH) use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10 and 15% of human immunodeficiency virus-1 (HIV-1) patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND) through direct and indirect mechanisms. Repetitive METH use impedes adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression toward AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte numbers and activity, cytokine signaling, phagocytic function and infiltration through the blood brain barrier. Further, METH triggers the dopamine reward pathway and leads to impaired neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation, which modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress, and excitotoxicity. Pathologically, reactive gliosis is a hallmark of both HIV-1- and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus, this review highlights alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, with special emphasis on HAND-associated neuroinflammation. Importantly, this review carefully evaluates interventions targeting astrocytes in HAND and METH as potential novel therapeutic approaches. This comprehensive overview indicates, without a doubt, that during HIV-1 infection and METH abuse, a complex dialog between all neural cells is orchestrated through astrocyte regulated neuroinflammation. PMID:26579077

  19. Person-centered Therapeutics

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many challenges. The Temperament and Character Inventory (TCI) provides an effective way to describe personality thoroughly and to predict both the positive and negative aspects of health. Strengths and weaknesses in TCI personality traits allow strong predictions of individual differences of all aspects of well-being. Diverse therapeutic techniques, such as diet, exercise, mood self-regulation, meditation, or acts of kindness, influence health and personality development in ways that are largely indistinguishable from one another or from effective allopathic treatments. Hence the development of well-being appears to be the result of activating a synergistic set of mechanisms of well-being, which are expressed as fuller functioning, plasticity, and virtue in adapting to life’s challenges PMID:26052429

  20. Nitrones as Therapeutics

    PubMed Central

    Floyd, Robert A.; Kopke, Richard D.; Choi, Chul-Hee; Foster, Steven B.; Doblas, Sabrina; Towner, Rheal A.

    2008-01-01

    Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones including PBN (?-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes can not readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our observations and others where the use of selected nitrones as novel therapeutics have been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases. PMID:18793715

  1. Side Effects of HIV Medicines: HIV and Lipodystrophy

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Lipodystrophy (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Lipodystrophy refers to the changes ... loss on the face and leg . Which HIV medicines are linked to lipodystrophy? Although more research is ...

  2. Side Effects of HIV Medicines: HIV and Rash

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Rash (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points A rash is an irritated ... health care provider tells you to. What HIV medicines can cause a hypersensitivity reaction? Nevirapine (brand name: ...

  3. Side Effects of HIV Medicines: HIV and Diabetes

    MedlinePLUS

    Side Effects of HIV Medicines HIV and Diabetes (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Diabetes is a disease in ... are also infected with hepatitis C. What HIV medicines increase the risk of type 2 diabetes? Some ...

  4. What Is HIV/AIDS?

    MedlinePLUS

    ... Video Games Video Sharing Sites Webcasts/ Webinars Widgets Wikis Follow Us on New Media Virtual Office Hours ... HIV currently exists, but with proper treatment and medical care, HIV can be controlled. The medicine used ...

  5. A case of HIV ulcer

    PubMed Central

    2015-01-01

    HIV-associated ulcers must be distinguished from idiopathic anal fissures in HIV-positive patients and from other sexually transmitted diseases that cause anogenital ulcers as the treatments differ. PMID:26266040

  6. Depression and HIV/AIDS

    MedlinePLUS

    ... For More Information on HIV/AIDS Citations Reprints Depression and HIV/AIDS Order a free hardcopy En ... difficult, so proper treatment is important. What is depression? Major depressive disorder, or depression, is a serious ...

  7. HIV/AIDS and Vaccines

    MedlinePLUS

    ... is also engaged in HIV vaccine research and led a large collaboration of clinical scientists also funded ... the risk of becoming HIV infected. This has led to a better understanding of the type of ...

  8. Women and HIV/AIDS

    MedlinePLUS

    ... About Us Contact Us Text size | Print | HIV/AIDS This information in Spanish ( en español ) The human ... HIV, is a sexually transmitted infection and causes acquired immunodeficiency syndrome, or AIDS. Today, about one in four Americans ...

  9. Research Report: HIV/AIDS

    MedlinePLUS

    ... Home » HIV/AIDS » Letter from the Director HIV/AIDS Email Facebook Twitter Letter from the Director Human ... the virus that causes acquired immune deficiency syndrome (AIDS) — has been with us for three decades now. ...

  10. Modeling the implementation of universal coverage for HIV treatment as prevention and its impact on the HIV epidemic

    PubMed Central

    Ying, Roger; Barnabas, Ruanne V.; Williams, Brian G.

    2015-01-01

    The Joint United Nations Programme on HIV/AIDS (UNAIDS) recently updated its global targets for antiretroviral therapy (ART) coverage for HIV-positive persons under which 90% of HIV-positive people are tested, 90% of those are on ART, and 90% of those achieve viral suppression. Treatment policy is moving toward treating all HIV-infected persons regardless of CD4 cell count—otherwise known as treatment as prevention—in order to realize the full therapeutic and preventive benefits of ART. Mathematical models have played an important role in guiding the development of these policies by projecting long-term health impacts and cost-effectiveness. To guide future policy, new mathematical models must consider the barriers patients face in receiving and taking ART. Here, we describe the HIV care cascade and ART delivery supply chain to examine how mathematical modeling can provide insight into cost-effective strategies for scaling-up ART coverage in sub-Saharan Africa and help achieve universal ART coverage. PMID:25249293

  11. Glu659Leu substitution of recombinant HIV fusion inhibitor C52L induces soluble expression in Escherichia coli with equivalent anti-HIV potency.

    PubMed

    Shang, Shufeng; Tan, Suiyi; Li, Kangbai; Wu, Jun; Lin, Huina; Liu, Shuwen; Deng, Yiqun

    2011-07-01

    The C-peptides used to prevent HIV infection, such as T20 and C34, are chemically synthesized, making them costly drugs. The sensitivity of peptides to protease also restricts their clinical application. We showed previously that C52L, a recombinant peptide produced in bacteria, is a potent anti-HIV C-peptide, although most of the peptide accumulates in inclusion bodies. Here we applied leucine and glutamine scanning mutagenesis to the heptad-repeat of C52L to produce an optimized variant of C52L that is potent and soluble when expressed in bacteria. We present that the substitution of Asn656 and Glu659 with leucine (peptide L14 and L15, respectively) can increase the helical content of this peptide. These substitutions also result in soluble expression. We measured the inhibitory activities of these mutant peptides against laboratory-adapted HIV-1 strains and found that L15 and its parental peptide C52L have equivalent anti-HIV activities. Moreover, L15 was found to be more stable to proteinase K digestion than C52L. Thus, we show that the L15 peptide can be expressed in a soluble state and exhibits potent anti-HIV activity. This peptide may be further developed as an anti-HIV therapeutic and/or microbicide for the prevention of HIV sexual transmission. PMID:21478177

  12. Bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride blocks the CD4 cell receptor for HIV.

    PubMed

    Neurath, A R; Jiang, S; Strick, N; Lin, K; Li, Y Y; Debnath, A K

    1996-02-01

    Sexual transmission is the most frequent (86%) route of adult HIV-1 transmission worldwide. In the absence of a prophylactic anti-HIV vaccine, other methods of preventing infection should be implemented. Virucidal spermicides have been considered for this purpose, but their application is contraindicated by adverse effects. Anti-HIV drugs or virus-neutralizing monoclonal antibodies are expensive, suggesting that their wide use in topical chemoprophylaxis is unlikely. This emphasizes the importance of developing other methods for preventing HIV transmission. The target cells for sexual and mucosal HIV transmission include T lymphocytes, monocytes/macrophages and dendritic cells. Therefore, compounds blocking HIV-CD4 binding are expected to inhibit virus transmission. In exploring the possibility that chemical modification of food proteins might lead to compounds with anti-HIV-1 activity, we found that bovine beta-lactoglobulin (beta-LG) modified by 3-hydroxyphthalic anhydride (3HP-beta-LG) (1) blocked at nanomolar concentrations the binding to CD4 of human (HIV) and simian (SIV) immunodeficiency virus surface glycoproteins and monoclonal antibodies specific for the HIV binding site on CD4 and (2) inhibited infection by HIV-1, including primary virus isolates, by HIV-2 and by SIV. The inexpensive and widely available source (whey) for production of 3HP-beta-LG suggests its potential application (nonparenteral) for diminishing the frequency of HIV transmission. PMID:8574970

  13. Renal transplantation in human immunodeficiency virus (HIV)-positive children.

    PubMed

    McCulloch, Mignon I; Kala, Udai K

    2015-04-01

    Renal transplantation is being performed in adult human immunodeficiency virus (HIV)-positive patients and increasingly in paediatric patients as well. A multidisciplinary team involving an infectious disease professional is required to assist with HIV viral-load monitoring and in choosing the most appropriate highly active antiretroviral therapy (HAART). Drug interactions complicate immunosuppressant therapy and require careful management. The acute rejection rates appear to be similar in adults to those in noninfective transplant recipients. Induction with basiliximab and calcineurin-based immunosuppression appears to be safe and effective in these recipients. Prophylaxis is advised for a variety of infections and may need life-long administration, especially in children. Organ shortage remains a significant problem, and kidneys from deceased HIV-positive donors have been used successfully in a small study population. Overall, with careful planning and close follow-up, successful renal transplantation for paediatric HIV-infected recipients is possible. PMID:24691821

  14. RNA viruses at the forefront of human infections - HIV, hepatitis C, and now Ebola.

    PubMed

    Soriano, Vicente; Peña, José M

    2014-01-01

    AIDS emerged in 1981, breaking a period of proud medical progresses in controlling infectious diseases with antimicrobials and vaccines. In an unprecedented way, HIV has attracted much attention for three decades, driving the discovery of new extraordinary molecular diagnostic tools and antiviral drugs. As a result, advances in antiretroviral therapy have made it possible to change HIV infection into a chronic illness. However, the prospects for HIV eradication in the short term are not envisioned for the more than 35 million people worldwide estimated to be living with HIV. PMID:25373350

  15. Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity

    PubMed Central

    Williams, James P; Southern, Paul; Lissina, Anya; Christian, Helen C; Sewell, Andrew K; Phillips, Rodney; Pankhurst, Quentin; Frater, John

    2013-01-01

    The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. PMID:23901272

  16. Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity.

    PubMed

    Williams, James P; Southern, Paul; Lissina, Anya; Christian, Helen C; Sewell, Andrew K; Phillips, Rodney; Pankhurst, Quentin; Frater, John

    2013-01-01

    The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. PMID:23901272

  17. Novel HIV-1 MiRNAs Stimulate TNF? Release in Human Macrophages via TLR8 Signaling Pathway

    PubMed Central

    Bernard, Mark A.; Zhao, Hui; Yue, Simon C.; Anandaiah, Asha; Koziel, Henry; Tachado, Souvenir D.

    2014-01-01

    Purpose To determine whether HIV-1 produces microRNAs and elucidate whether these miRNAs can induce inflammatory response in macrophages (independent of the conventional miRNA function in RNA interference) leading to chronic immune activation. Methods Using sensitive quantitative Real Time RT-PCR and sequencing, we detected novel HIV-derived miRNAs in the sera of HIV+ persons, and associated with exosomes. Release of TNF? by macrophages challenged with HIV miRNAs was measured by ELISA. Results HIV infection of primary alveolar macrophages produced elevated levels of viral microRNAs vmiR88, vmiR99 and vmiR-TAR in cell extracts and in exosome preparations from conditioned medium. Furthermore, these miRNAs were also detected in exosome fraction of sera from HIV-infected persons. Importantly, vmiR88 and vmiR99 (but not vmiR-TAR) stimulated human macrophage TNF? release, which is dependent on macrophage TLR8 expression. These data support a potential role for HIV-derived vmiRNAs released from infected macrophages as contributing to chronic immune activation in HIV-infected persons, and may represent a novel therapeutic target to limit AIDS pathogenesis. Conclusion Novel HIV vmiR88 and vmiR99 are present in the systemic circulation of HIV+ persons and could exhibit biological function (independent of gene silencing) as ligands for TLR8 signaling that promote macrophage TNF? release, and may contribute to chronic immune activation. Targeting novel HIV-derived miRNAs may represent a therapeutic strategy to limit chronic immune activation and AIDS progression. PMID:25191859

  18. HIV and Men Who Have Sex with Men: Where Is the Canadian Epidemic Headed?

    ERIC Educational Resources Information Center

    Siushansian, Jennifer A.; Nguyen, Mai; Archibald, Chris P.

    2000-01-01

    Canada's recent increase in HIV infections among men who have sex with men (MSM) is substantiated by data on ongoing sexual risk behavior and increases in sexually transmitted diseases among MSM. This situation is discussed in the international context, noting an upswing in HIV-associated risk behaviors among MSM worldwide and possible

  19. Testing the Sexually Abused Child for the HIV Antibody: Issues for the Social Worker.

    ERIC Educational Resources Information Center

    Gellert, George A.; And Others

    1993-01-01

    Discusses identifying children infected with human immunodeficiency virus (HIV) through sexual abuse. Reviews testing guidelines. Sees social workers contributing to test decision making when perinatal HIV transmissions is possibility, when assailant may be tested, and when parents/legal guardians insist on testing child. Discusses family…

  20. Modelling the impact of chlamydia screening on the transmission of HIV among men who have sex with men

    PubMed Central

    2013-01-01

    Background Recent studies have found high prevalences of asymptomatic rectal chlamydia among HIV-infected men who have sex with men (MSM). Chlamydia could increase the infectivity of HIV and the susceptibility to HIV infection. We investigate the role of chlamydia in the spread of HIV among MSM and the possible impact of routine chlamydia screening among HIV-infected MSM at HIV treatment centres on the incidence of chlamydia and HIV in the overall MSM population. Methods A mathematical model was developed to describe the transmission of HIV and chlamydia among MSM. Parameters relating to sexual behaviour were estimated from data from the Amsterdam Cohort Study among MSM. Uncertainty analysis was carried out for model parameters without confident estimates. The effects of different screening strategies for chlamydia were investigated. Results Among all new HIV infections in MSM, 15% can be attributed to chlamydia infection. Introduction of routine chlamydia screening every six months among HIV-infected MSM during regular HIV consultations can reduce the incidence of both infections among MSM: after 10 years, the relative percentage reduction in chlamydia incidence would be 15% and in HIV incidence 4%, compared to the current situation. Chlamydia screening is more effective in reducing HIV incidence with more frequent screening and with higher participation of the most risky MSM in the screening program. Conclusions Chlamydia infection could contribute to the transmission of HIV among MSM. Preventive measures reducing chlamydia prevalence, such as routine chlamydia screening of HIV-infected MSM, can result in a decline in the incidence of chlamydia and HIV. PMID:24047261

  1. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    PubMed Central

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2015-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  2. Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides.

    PubMed

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R; Kluge, Silvia F; Müller, Janis A; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C; Kirchhoff, Frank; Münch, Jan

    2014-11-12

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. We report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was maraviroc. This HIV entry inhibitor targets the host cell CCR5 co-receptor and was highly active against both untreated and semen-exposed HIV. These data help to explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  3. Measuring the Potential Impact of Combination HIV Prevention in Sub-Saharan Africa

    PubMed Central

    Khademi, Amin; Anand, Sunanth; Potts, David

    2015-01-01

    Abstract A public health approach to combination HIV prevention is advocated to contain the epidemic in sub-Saharan Africa. We explore the implications of universal access to treatment along with HIV education scale-up in the region. We develop an HIV transmission model to investigate the impacts of universal access to treatment, as well as an analytical framework to estimate the effects of HIV education scale-up on the epidemic. We calibrate the model with data from South Africa and simulate the impacts of universal access to treatment along with HIV education scale-up on prevalence, incidence, and HIV-related deaths over a course of 15 years. Our results show that the impact of combined interventions is significantly larger than the summation of individual intervention impacts (super-additive property). The combined strategy of universal access to treatment and HIV education scale-up decreases the incidence rate by 74% over the course of 15 years, whereas universal access to treatment and HIV education scale up will separately decrease that by 43% and 8%, respectively. Combination HIV prevention could be notably effective in transforming HIV epidemic to a low-level endemicity. Our results suggest that in designing effective combination prevention in sub-Saharan Africa, priorities should be given to achieving universal access to treatment as quickly as possible and improving compliance to condom use. PMID:26376383

  4. In vitro activity of readily available household materials against HIV-1: is bleach enough?

    PubMed

    Flynn, N; Jain, S; Keddie, E M; Carlson, J R; Jennings, M B; Haverkos, H W; Nassar, N; Anderson, R; Cohen, S; Goldberg, D

    1994-07-01

    This report describes experiments assessing the effectiveness against HIV of potential disinfecting agents that are commonly available to IDU when they are sharing syringes. We exposed cell-free HIV, HIV-infected cells, and HIV-infected blood containing known quantities of HIV to household cleaning agents, alcohols, peroxide, and highly acidic materials for 1 min, in order to examine the effects of these materials on the infectivity of the HIV. Undiluted liquid laundry bleach and dilute liquid dish detergent reduced the number of culturable HIV to an undetectable level under the experimental conditions used. Diluted bleach was not completely effective. Other potential disinfecting agents, including ethanol, isopropyl alcohol, and hydrogen peroxide, were unable to disinfect high numbers of HIV-infected cells or infected blood. Liquid dish detergent warrants further study as a possible acceptable alternative to bleach. Our data provide support for recommendations to IDU that they disinfect shared syringes every time between users with full-strength liquid laundry bleach to reduce their risk of acquiring or transmitting HIV. When bleach is not available, liquid dish detergent or other available disinfecting agents such as rubbing alcohol, hydrogen peroxide, or high alcohol content beverages are more effective than water at disinfecting HIV, recognizing that these materials are less effective than bleach. Although these materials are effective, they should not be viewed as a substitute for decreased sharing of injection equipment by IDU, or increased availability of sterile needles and syringes. PMID:8207658

  5. Prevalence of Pulmonary Tuberculosis Among HIV Positive Patients Attending Antiretroviral Therapy Clinic

    PubMed Central

    Giri, Purushottam A; Deshpande, Jayant D; Phalke, Deepak B

    2013-01-01

    Background: Tuberculosis (TB) is the most common serious opportunistic infection in HIV positive patients and is the manifestation of AIDS in more than 50% of cases in developing countries. TB can occur at any time during the course of HIV infection. Aim: To describe the socio-demographic profile and prevalence of pulmonary tuberculosis (HIV/TB co-infection) among HIV positive patients been attended at the antiretroviral therapy clinic (ART) clinic at tertiary care teaching hospital of western Maharashtra, India. Materials and Methods: A cross-sectional study was carried out at the ART clinic of Pravara Rural Hospital, Loni, from June 2011 to May 2012. A total of 1012 HIV positive patients, who attended ART clinic, receiving ART treatment during the study period, were included in the analysis. The statistical analysis was performed using SPSS software (Version 17.0). Results: This study showed 1012/172 (17%) prevalence of pulmonary tuberculosis among HIV positive patients, of which 87 (50.58%) were males and 85 (48.42%) were females. Low CD4 count (< 50/?l) had statistically significant association with HIV/TB co-infection as compared to HIV infection only (P < 0.0001). Conclusion: The study showed that 17% of HIV infected persons had tuberculosis co-infection. More strategic preventive measures that enhance body immunity among HIV patients are highly needed as early as possible before they develop active tuberculosis. PMID:23923111

  6. Reproductive desires of men and women living with HIV: implications for family planning counselling.

    PubMed

    van Zyl, Cornelia; Visser, Maretha J

    2015-09-01

    The reproductive desires of people living with HIV/AIDS (PLHIV) of low socioeconomic standing attending public health facilities in South Africa were studied. HIV-positive men, pregnant and non-pregnant women were recruited from two clinics at a large public hospital in Tshwane, South Africa. Individual interviews were used to explore the reproductive desires of HIV-positive participants. HIV counsellors' perceptions of their clients' reproductive desires were explored during focus group discussions. Parenthood proved to be an important factor to all participants in continuation of the family and establishing their gender identities, despite the possible risk of HIV transmission and community stigmatization. Different cultural procreation rules for men and women and stigmatizing attitudes towards PLHIV affected their reproductive decision making. Women had the dilemma of choosing which community expectations they wanted to fulfil. Community stigmatization towards PLHIV was visible in the negative attitudes of some HIV counsellors regarding HIV and procreation. Because the reproductive desires of PLHIV are currently not given high priority in HIV prevention and family planning in the public health sector in South Africa, the prevention of HIV transmission may be jeopardized. These results necessitate the integration of HIV and sexual and reproductive health counselling on a primary health care level. PMID:26208447

  7. HIV among African American Youth

    MedlinePLUS

    ... the word(s) Clear All Simple Search HIV among African American youth Corporate Authors: National Center for HIV/AIDS, ... Syndrome/Ethnology/Statistics/United States Adolescent Adolescent Behavior African Americans/Statistics/United States HIV Infections/Ethnology/Statistics/United ...

  8. Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection

    PubMed Central

    Hochman, Sarah E.; Madaline, Theresa F.; Wassmer, Samuel C.; Mbale, Emmie; Choi, Namjong; Seydel, Karl B.; Whitten, Richard O.; Varughese, Julie; Grau, Georges E. R.; Kamiza, Steve; Molyneux, Malcolm E.; Taylor, Terrie E.; Lee, Sunhee; Milner, Danny A.

    2015-01-01

    ABSTRACT? Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV+) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV+ and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV+ children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV+ children exacerbates the pathological features associated with CM. Importance? There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing coma and death are uncertain. Sub-Saharan Africa has a high HIV prevalence, with 3 million HIV-infected (HIV+) children, but the effects of HIV on CM pathogenesis and mortality are unknown. In a study of pediatric CM in Malawi, HIV prevalence was high and CM-attributed mortality was higher in HIV+ than in HIV-uninfected children. Brain pathology in children with fatal CM was notable not only for sequestered malaria parasites but also for intravascular accumulations of monocytes and platelets that were more severe in HIV+ children. Our findings raise the possibility that HIV+ children at risk for malaria may benefit from targeted malaria prophylaxis and that adjunctive treatments targeting inflammation and/or coagulation may improve CM outcomes. PMID:26396242

  9. Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection.

    PubMed

    Hochman, Sarah E; Madaline, Theresa F; Wassmer, Samuel C; Mbale, Emmie; Choi, Namjong; Seydel, Karl B; Whitten, Richard O; Varughese, Julie; Grau, Georges E R; Kamiza, Steve; Molyneux, Malcolm E; Taylor, Terrie E; Lee, Sunhee; Milner, Danny A; Kim, Kami

    2015-01-01

    Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV(+)) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV(+) and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV(+) children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV(+) children exacerbates the pathological features associated with CM. IMPORTANCE?: There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing coma and death are uncertain. Sub-Saharan Africa has a high HIV prevalence, with 3 million HIV-infected (HIV(+)) children, but the effects of HIV on CM pathogenesis and mortality are unknown. In a study of pediatric CM in Malawi, HIV prevalence was high and CM-attributed mortality was higher in HIV(+) than in HIV-uninfected children. Brain pathology in children with fatal CM was notable not only for sequestered malaria parasites but also for intravascular accumulations of monocytes and platelets that were more severe in HIV(+) children. Our findings raise the possibility that HIV(+) children at risk for malaria may benefit from targeted malaria prophylaxis and that adjunctive treatments targeting inflammation and/or coagulation may improve CM outcomes. PMID:26396242

  10. Antibody Engineering and Therapeutics

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  11. Microfabricated therapeutic actuators

    SciTech Connect

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  12. Antimicrobial peptides: therapeutic potentials.

    PubMed

    Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

    2014-12-01

    The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations. PMID:25371141

  13. Outpatient therapeutic nuclear oncology.

    PubMed

    Turner, J Harvey

    2012-05-01

    In the beginning, nuclear medicine was radionuclide therapy, which has evolved into molecular tumour-targeted control of metastatic cancer. Safe, efficacious, clinical practice of therapeutic nuclear oncology may now be based upon accurate personalised dosimetry by quantitative gamma SPECT/CT imaging to prescribe tumoricidal activities without critical organ toxicity. Preferred therapy radionuclides possess gamma emission of modest energy and abundance to enable quantitative SPECT/CT imaging for calculation of the beta therapy dosimetry, without radiation exposure risk to hospital personnel, carers, family or members of the public. The safety of outpatient radiopharmaceutical therapy of cancer with Iodine-131, Samarium-153, Holmium-166, Rhenium-186, Rhenium-188, Lutetium-177 and Indium-111 is reviewed. Measured activity release rates and radiation exposure to carers and the public are all within recommendations and guidelines of international regulatory agencies and, when permitted by local regulatory authorities allow cost-effective, safe, outpatient radionuclide therapy of cancer without isolation in hospital. PMID:22222779

  14. [Therapeutic education didactic techniques].

    PubMed

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective. PMID:23157069

  15. Mitochondrial Energetics and Therapeutics

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei; Procaccio, Vincent

    2011-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics. PMID:20078222

  16. Microfabricated therapeutic actuators

    DOEpatents

    Lee, A.P.; Northrup, M.A.; Ciarlo, D.R.; Krulevitch, P.A.; Benett, W.J.

    1999-06-15

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use. 8 figs.

  17. Therapeutic applications of melatonin

    PubMed Central

    2013-01-01

    Melatonin is a methoxyindole synthesized within the pineal gland. The hormone is secreted during the night and appears to play multiple roles within the human organism. The hormone contributes to the regulation of biological rhythms, may induce sleep, has strong antioxidant action and appears to contribute to the protection of the organism from carcinogenesis and neurodegenerative disorders. At a therapeutic level as well as in prevention, melatonin is used for the management of sleep disorders and jet lag, for the resynchronization of circadian rhythms in situations such as blindness and shift work, for its preventive action in the development of cancer, as additive therapy in cancer and as therapy for preventing the progression of Alzheimer’s disease and other neurodegenerative disorders. PMID:23515203

  18. Controlling HIV-1: Non-Coding RNA Gene Therapy Approaches to a Functional Cure

    PubMed Central

    Ahlenstiel, Chantelle L.; Suzuki, Kazuo; Marks, Katherine; Symonds, Geoff P.; Kelleher, Anthony D.

    2015-01-01

    The current treatment strategy for HIV-1 involves prolonged and intensive combined antiretroviral therapy (cART), which successfully suppresses plasma viremia. It has transformed HIV-1 infection into a chronic disease. However, despite the success of cART, a latent form of HIV-1 infection persists as integrated provirus in resting memory CD4+ T cells. Virus can reactivate from this reservoir upon cessation of treatment, and hence HIV requires lifelong therapy. The reservoir represents a major barrier to eradication. Understanding molecular mechanisms regulating HIV-1 transcription and latency are crucial to develop alternate treatment strategies, which impact upon the reservoir and provide a path toward a “functional cure” in which there is no detectable viremia in the absence of cART. Numerous reports have suggested ncRNAs are involved in regulating viral transcription and latency. This review will discuss the latest developments in ncRNAs, specifically short interfering (si)RNA and short hairpin (sh)RNA, targeting molecular mechanisms of HIV-1 transcription, which may represent potential future therapeutics. It will also briefly address animal models for testing potential therapeutics and current gene therapy clinical trials. PMID:26441979

  19. HIV sequence compendium 2002

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Freed, Eric; Hahn, Beatrice; Marx, Preston; McCutchan, Francine; Mellors, John; Wolinsky, Steven; Korber, Bette

    2002-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Traditionally, we present the sequence data themselves in the form of alignments: Section II, an alignment of a selection of HIV-1/SIVcpz full-length genomes (a lot of LAI-like sequences, for example, have been omitted because they are so similar that they bias the alignment); Section III, a combined HIV-1/HIV-2/SIV whole genome alignment; Sections IV–VI, amino acid alignments for HIV-1/SIV-cpz, HIV-2/SIV, and SIVagm. The HIV-2/SIV and SIVagm amino acid alignments are separate because the genetic distances between these groups are so great that presenting them in one alignment would make it very elongated because of the large number of gaps that have to be inserted. As always, tables with extensive background information gathered from the literature accompany the whole genome alignments. The collection of whole-gene sequences in the database is now large enough that we have abundant representation of most subtypes. For many subtypes, and especially for subtype B, a large number of sequences that span entire genes were not included in the printed alignments to conserve space. A more complete version of all alignments is available on our website, http://hiv-web.lanl.gov/content/hiv-db/ALIGN_CURRENT/ALIGN-INDEX.html. Importantly, all these alignments have been edited to include only one sequence per person, based on phylogenetic trees that were created for all of them, as well as on the literature. Because of the number of sequences available, we have decided to use a different selection principle this year, based on the epidemiological importance of the subtypes. Subtypes A–D and CRFs 01 and 02 are by far the most widespread variants, and for these (when available) we have included 8–10 representatives in the alignments. The other subtypes and CRFs are of lesser importance, and of these 4–5 each, or as many as are available, were included. In the alignments we have also included the ‘Circulating Recombinant Forms’, mosaic genomes that have epidemiological significance. See the 1999 review of nomenclature (http://hiv-web.lanl.gov/content/hiv-db/REVIEWS/nomenclature/Nomen.html) for more on CRFs, and see for an overview of the patterns of known CRFs. Amino acid alignment chapters begin with an annotation table that includes sequence names, accession numbers, genomic region represented, author, and references. We have made an effort to bring the HIV-2/SIV and SIVagm alignments up-to-date as well.

  20. Where are the young men in HIV prevention efforts? Comments on HIV prevention programs and research from young men who sex with men in Los Angeles county.

    PubMed

    Holloway, Ian W; Cederbaum, Julie A; Ajayi, Antonette; Shoptaw, Steven

    2012-12-01

    Despite increasing rates of HIV infection among young men who have sex with men (YMSM), only a minority participate in formal HIV prevention efforts. Semi-structured mixed-methods interviews were conducted with a diverse sample of YMSM (N = 100, M(age) = 25.0 years) in Los Angeles, California, to identify facilitators and barriers to participation in HIV prevention programs. Summative content analyses were used to evaluate transcribed field notes from these interviews. Results showed that 28.0 % of all participants had previously attended an HIV prevention program, and that 21.3 % of those who were also asked if they had ever participated in any research pertaining to HIV prevention had done so. A significantly higher percentage of those who had participated in HIV prevention programs had been tested for HIV in the past 6 months compared to those who had not (p < .05). The most frequently mentioned barriers to participation in such a program were being too busy to attend (12.0 %), not perceiving themselves to be at risk for HIV infection (14.0 %), and believing that they already knew everything they needed to know about HIV transmission (23.0 %). YMSM suggested that future interventions should use technology (e.g., the Internet, mobile devices), engage their social networks, and highlight HIV prevention as a means for community connection. Collectively, these results provide some explanations for why YMSM account for a minority of HIV prevention program participants and offer possible directions for future HIV prevention efforts that target YMSM. PMID:23132515

  1. HIV Sequence Compendium 2015

    SciTech Connect

    Foley, Brian Thomas; Leitner, Thomas Kenneth; Apetrei, Cristian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette Tina Marie

    2015-10-05

    This compendium is an annual printed summary of the data contained in the HIV sequence database. We try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2015. Hence, though it is published in 2015 and called the 2015 Compendium, its contents correspond to the 2014 curated alignments on our website. The number of sequences in the HIV database is still increasing. In total, at the end of 2014, there were 624,121 sequences in the HIV Sequence Database, an increase of 7% since the previous year. This is the first year that the number of new sequences added to the database has decreased compared to the previous year. The number of near complete genomes (>7000 nucleotides) increased to 5834 by end of 2014. However, as in previous years, the compendium alignments contain only a fraction of these. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/ content/sequence/NEWALIGN/align.html As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  2. Microbicides for HIV prevention

    PubMed Central

    Ramjee, Gita

    2011-01-01

    Although the HIV incidence rate has slowed in some countries, HIV remains a serious health challenge, particularly in the developing world. The epidemic is increasingly feminised, with young women at high risk of acquiring the virus. There is thus a clear requirement for acceptable woman-initiated methods of HIV prevention. Foremost among these are vaginally-applied substances known as microbicides; early research into potential microbicides focussed on non-HIV-specific compounds such as surfactants and polyanionic entry inhibitors. However, proof of the microbicide concept as a viable prevention strategy was not provided until the CAPRISA 004 trial of a microbicide containing the HIV-specific antiretroviral tenofovir was completed in mid-2010. Confirmation of the proof of concept provided by CAPRISA 004 by at least two major trials will hopefully lead to licensure of the product by 2018. Parallel studies are planned to ascertain the feasibility of implementation of these products in the public sector with subsequent research focussed on appropriate and acceptable methods of delivery of the active ingredient, and to increase adherence through other delivery systems such as vaginal rings. PMID:22310825

  3. [Infectious complications in patients after cardiac arrest undergoing therapeutic hypothermia].

    PubMed

    Sýkora, R

    2011-05-01

    Therapeutic hypothermia is currently recommended neuroprotective therapeutic measure for comatose patients after cardiac arrest. Hypothermia has been proven not only to affect the neurological outcomes but also the survival of patients after cardiac arrest. This communication summarizes the issue of early infectious complications in patients after cardiac arrest undergoing therapeutic hypothermia. Diagnosis of infectious events is complicated in patients after cardiac arrest not only by the physiological effects of therapeutic hypothermia but also by the consequences of reperfusion injury and development of postresuscitation disease associated with systemic inflammatory response syndrome. Furthermore, there are discussed limited diagnostic options of infectious complications. The significance of the usual symptoms of infections is reduced, as well as the value of laboratory markers such as procalcitonin and C-reactive protein. Finally, the possibility of antibiotic treatment and eventual antibiotic prophylaxis during therapeutic hypothermia in patients after cardiac arrest outside hospitals is mentioned. PMID:21695930

  4. Therapeutic cloning: The ethical limits

    SciTech Connect

    Whittaker, Peter A. . E-mail: p.whittaker@lancaster.ac.uk

    2005-09-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated.

  5. Phenyl-1-Pyridin-2yl-Ethanone-Based Iron Chelators Increase I?B-? Expression, Modulate CDK2 and CDK9 Activities, and Inhibit HIV-1 Transcription

    PubMed Central

    Kumari, Namita; Iordanskiy, Sergey; Kovalskyy, Dmytro; Breuer, Denitra; Niu, Xiaomei; Lin, Xionghao; Xu, Min; Gavrilenko, Konstantin; Kashanchi, Fatah; Dhawan, Subhash

    2014-01-01

    HIV-1 transcription is activated by the Tat protein, which recruits CDK9/cyclin T1 to the HIV-1 promoter. CDK9 is phosphorylated by CDK2, which facilitates formation of the high-molecular-weight positive transcription elongation factor b (P-TEFb) complex. We previously showed that chelation of intracellular iron inhibits CDK2 and CDK9 activities and suppresses HIV-1 transcription, but the mechanism of the inhibition was not understood. In the present study, we tested a set of novel iron chelators for the ability to inhibit HIV-1 transcription and elucidated their mechanism of action. Novel phenyl-1-pyridin-2yl-ethanone (PPY)-based iron chelators were synthesized and examined for their effects on cellular iron, HIV-1 inhibition, and cytotoxicity. Activities of CDK2 and CDK9, expression of CDK9-dependent and CDK2-inhibitory mRNAs, NF-?B expression, and HIV-1- and NF-?B-dependent transcription were determined. PPY-based iron chelators significantly inhibited HIV-1, with minimal cytotoxicity, in cultured and primary cells chronically or acutely infected with HIV-1 subtype B, but they had less of an effect on HIV-1 subtype C. Iron chelators upregulated the expression of I?B-?, with increased accumulation of cytoplasmic NF-?B. The iron chelators inhibited CDK2 activity and reduced the amount of CDK9/cyclin T1 in the large P-TEFb complex. Iron chelators reduced HIV-1 Gag and Env mRNA synthesis but had no effect on HIV-1 reverse transcription. In addition, iron chelators moderately inhibited basal HIV-1 transcription, equally affecting HIV-1 and Sp1- or NF-?B-driven transcription. By virtue of their involvement in targeting several key steps in HIV-1 transcription, these novel iron chelators have the potential for the development of new therapeutics for the treatment of HIV-1 infection. PMID:25155598

  6. RNAi-Mediated CCR5 Knockdown Provides HIV-1 Resistance to Memory T Cells in Humanized BLT Mice

    PubMed Central

    Shimizu, Saki; Ringpis, Gene-Errol; Marsden, Matthew D; Cortado, Ruth V; Wilhalme, Holly M; Elashoff, David; Zack, Jerome A; Chen, Irvin S Y; An, Dong Sung

    2015-01-01

    Transplantation of hematopoietic stem/progenitor cells (HSPC) modified with a lentiviral vector bearing a potent nontoxic short hairpin RNA (sh1005) directed to the HIV coreceptor CCR5 is capable of continuously producing CCR5 downregulated CD4+ T lymphocytes. Here, we characterized HIV-1 resistance of the sh1005-modified CD4+ T lymphocytes in vivo in humanized bone marrow/liver/thymus (hu BLT) mice. The sh1005-modified CD4+ T lymphocytes were positively selected in CCR5-tropic HIV-1–challenged mice. The sh1005-modified memory CD4+ T lymphocytes (the primary target of CCR5-tropic HIV-1) expressing sh1005 were maintained in lymphoid tissues in CCR5-tropic HIV-1–challenged mice. Frequencies of HIV-1 p24 expressing cells were significantly reduced in the sh1005-modified splenocytes by ex vivo cell stimulation confirming that CCR5 downregulated sh1005 modified cells are protected from viral infection. These results demonstrate that stable CCR5 downregulation through genetic modification of human HSPC by lentivirally delivered sh1005 is highly effective in providing HIV-1 resistance. Our results provide in vivo evidence in a relevant small animal model that sh1005 is a potent early-step anti-HIV reagent that has potential as a novel anti-HIV-1 HSPC gene therapeutic reagent for human applications. PMID:25689223

  7. Centralized HIV Program Oversight.

    PubMed

    Pacha, Laura A; Hakre, Shilpa; Myles, Otha; Sanders-Buell, Eric E; Scoville, Stephanie L; Kijak, Gustavo H; Price, Michael W; Mody, Rupal M; Liu, Ying; Miller, Shana L; Pham, Phuc T; Michael, Nelson L; Kim, Jerome H; Peel, Sheila A; Tovanabutra, Sodsai; Jagodzinski, Linda L; Cersovsky, Steven B; Scott, Paul T

    2015-11-01

    Centralized HIV program oversight and repeal of the Department of Defense policy "Don't Ask Don't Tell" permitted characterization of HIV transmission among soldiers assigned to a large US Army base continental United States from 2012 to 2013. An investigation of a greater than expected number of new HIV infections among soldiers was initiated to characterize transmission and identify opportunities to disrupt transmission and deliver services.All soldiers who were assigned to the base at the time of their first positive HIV test and who had their first positive HIV test in 2012 or in the first 6 months of 2013 and who had a clinical genotype available for analysis were eligible for inclusion in the investigation.All patients (n?=?19) were men; most were black (52%) and less than 30 years old (64%). Fifteen of the 19 patients participated in in-depth interviews. Eighty percent were men who have sex with men who reported multiple sex partners having met through social and electronic networks. All were subtype B infections. Significant knowledge gaps and barriers to accessing testing and care in the military healthcare system were identified. Most (58%) belonged to transmission networks involving other soldiers.This investigation represents an important step forward in on-going efforts to develop a comprehensive understanding of transmission networks in the Army that can inform delivery of best practices combination prevention services. The Army is developing plans to directly engage individuals in key affected populations most at risk for HIV infection to identify and address unmet needs and expand delivery and uptake of prevention services. Further investigation is underway and will determine whether these findings are generalizable to the Army. PMID:26579822

  8. Therapeutic interventions in acute stroke.

    PubMed Central

    Lees, K R

    1992-01-01

    1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; intravenous glycerol is unproven. 3. Haemodilution to reduce whole blood viscosity and improve perfusion is ineffective. Thrombolytic drugs have not been adequately tested but several randomised multicentre trials are now commencing. Early treatment and CT scanning are essential. 4. Anticoagulants and antiplatelet drugs may have wide applicability but have not been tested in the acute phase of stroke. A multi-centre trial will address this issue. 5. Neuronal cytoprotection offers exciting prospects for acute stroke treatment. Antagonists of glutamate at the NMDA receptor, calcium and sodium channel blocking agents and free radical scavenging drugs have potent effects experimentally. Several agents are now reaching clinical trials. The calcium antagonist nimodipine has been disappointing in large scale trials but some studies were flawed by late treatment. 6. Successful treatment of acute stroke is likely to combine several approaches. 7. Therapeutic trials in stroke must include CT scanning, early treatment and a multicentre approach to achieve large numbers of patients. PMID:1493080

  9. Therapeutic potential of cannabinoid medicines.

    PubMed

    Robson, P J

    2014-01-01

    Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines. The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology. In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders. PMID:24006213

  10. Thymoquinone and its therapeutic potentials.

    PubMed

    Darakhshan, Sara; Bidmeshki Pour, Ali; Hosseinzadeh Colagar, Abasalt; Sisakhtnezhad, Sajjad

    2015-01-01

    Herbal medicine has attracted great attention in the recent years and is increasingly used as alternatives to chemical drugs. Several lines of evidence support the positive impact of medicinal plants in the prevention and cure of a wide range of diseases. Thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa seeds and most properties of N sativa are mainly attributed to TQ. A number of pharmacological actions of TQ have been investigated including anti-oxidant, anti-inflammatory, immunomodulatory, anti-histaminic, anti-microbial and anti-tumor effects. It has also gastroprotective, hepatoprotective, nephroprotective and neuroprotective activities. In addition, positive effects of TQ in cardiovascular disorders, diabetes, reproductive disorders and respiratory ailments, as well as in the treatment of bone complications as well as fibrosis have been shown. In addition, a large body of data shows that TQ has very low adverse effects and no serious toxicity. More recently, a great deal of attention has been given to this dietary phytochemical with an increasing interest to investigate it in pre-clinical and clinical researches for assessing its health benefits. Here we report on and analyze numerous properties of the active ingredient of N. sativa seeds, TQ, in the context of its therapeutic potentials for a wide range of illnesses. We also summarize the drug's possible mechanisms of action. The evidence reported sugests that TQ should be developed as a novel drug in clinical trials. PMID:25829334

  11. Cardiovascular Disease and HIV Infection

    PubMed Central

    Triant, Virginia A.

    2014-01-01

    The emergence of chronic disease complications in controlled HIV disease has changed the landscape of HIV clinical care. HIV infection confers an increased cardiovascular disease risk which is thought to be due to a complex interplay of mechanistic factors. While traditional cardiovascular risk factors likely play a role, recent evidence suggests that HIV-associated inflammation and immune activation are important mediators of cardiovascular risk. It is unclear whether established preventative interventions for the general population are applicable to HIV-infected patients, and the need to translate mechanistic knowledge into HIV-specific clinical interventions represents an important priority. Developing strategies to prevent cardiovascular disease in HIV-infected individuals calls for a multidisciplinary approach and represents an opportunity to exert a major public health impact in an at-risk population. PMID:23793823

  12. Advancing Biosocial Pedagogy for HIV Education

    ERIC Educational Resources Information Center

    Davis, Mark David McGregor

    2011-01-01

    This article develops the concept of biosocial pedagogy in HIV education for this era of expanding biomedical forms of HIV control. With reference to critical pedagogy and teaching and learning materials addressing HIV treatment and prevention, I explain how HIV education can problematize its own role in HIV control. I also discuss how educational…

  13. Stapled HIV-1 Peptides Recapitulate Antigenic Structures and Engage Broadly Neutralizing Antibodies

    PubMed Central

    Bird, Gregory H.; Irimia, Adriana; Ofek, Gilad; Kwong, Peter D.; Wilson, Ian A.; Walensky, Loren D.

    2014-01-01

    Hydrocarbon stapling can restore bioactive, ?-helical structure to natural peptides, yielding research tools and prototype therapeutics to dissect and target protein interactions. Here, we explore the capacity of peptide stapling to generate high fidelity, protease-resistant mimics of antigenic structures for vaccine development. HIV-1 has been refractory to vaccine technologies thus far, although select human antibodies can broadly neutralize HIV-1 by targeting sequences of the gp41 juxtamembrane fusion apparatus. To develop candidate HIV-1 immunogens, we generated and characterized stabilized ?-helices of the membrane proximal external region (SAH-MPER) of gp41. SAH-MPER peptides were remarkably protease-resistant and bound to the broadly neutralizing 4E10 and 10E8 antibodies with high affinity, recapitulating the structure of the MPER epitope when differentially engaged by the two anti-HIV Fabs. Thus, stapled peptides may provide a new opportunity to develop chemically-stabilized antigens for vaccination. PMID:25420104

  14. Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor

    PubMed Central

    Schimer, Ji?í; Pávová, Marcela; Anders, Maria; Pachl, Petr; Šácha, Pavel; Cígler, Petr; Weber, Jan; Majer, Pavel; ?ezá?ová, Pavlína; Kräusslich, Hans-Georg; Müller, Barbara; Konvalinka, Jan

    2015-01-01

    HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time. PMID:25751579

  15. A paradoxical decline: intracranial lesions in two HIV-positive patients recovering from cryptococcal meningitis.

    PubMed

    Pettersen, Kenneth D; Pappas, Peter G; Chin-Hong, Peter; Baxi, Sanjiv M

    2015-01-01

    Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is an increasingly important manifestation among patients with HIV/AIDS, especially as the use of antiretroviral therapy (ART) is expanding worldwide. Cryptococcus and associated C-IRIS are common causes of meningitis. While intracranial lesions are common in HIV/AIDS, they are rarely due to cryptococcosis or C-IRIS. We describe two cases of paradoxical C-IRIS associated with the development of intracranial cryptococcomas in HIV/AIDS. Both patients had an initial episode of cryptococcal meningitis treated with antifungal therapy. At the time, they had initiated or modified ART with subsequent evidence of immune reconstitution. Two months later, they developed aseptic meningitis with intracranial lesions. After exhaustive work ups, both patients were diagnosed with paradoxical C-IRIS and biopsy confirmed intracranial cryptococcomas. We review the important clinical, diagnostic and therapeutic features of cryptococcomas associated with C-IRIS in HIV/AIDS. PMID:26475880

  16. N-Linked glycoengineering for human therapeutic proteins in bacteria.

    PubMed

    Pandhal, Jagroop; Wright, Phillip C

    2010-09-01

    Approx. 70% of human therapeutic proteins are N-linked glycoproteins, and therefore host cells for production must contain the relevant protein modification machinery. The discovery and characterisation of the N-linked glycosylation pathway in the pathogenic bacterium Campylobacter jejuni, and subsequently its functional transfer to Escherichia coli, presents the opportunity of using prokaryotes as cell factories for therapeutic protein production. Not only could bacteria reduce costs and increase yields, but the improved feasibility to genetically control microorganisms means new and improved pharmacokinetics of therapeutics is an exciting possibility. This is a relatively new concept, and progress in bacterial N-glycosylation characterisation is reviewed and metabolic engineering targets revealed. PMID:20449632

  17. Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women

    PubMed Central

    Money, Deborah M.; Wagner, Emily C.; Maan, Evelyn J.; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E.; Forbes, John C.; Burdge, David R.; Albert, Arianne Y. K.; Lohn, Zoe; Côté, Hélène C. F.

    2015-01-01

    Introduction Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. Methods This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30–40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Results Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p?0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). Conclusions In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety and efficacy of cART regimens during pregnancy. PMID:26247211

  18. Diagnostic and therapeutic pitfalls in benign vocal fold diseases

    PubMed Central

    Bohlender, Jörg

    2013-01-01

    More than half of patients presenting with hoarseness show benign vocal fold changes. The clinician should be familiar with the anatomy, physiology and functional aspects of voice disorders and also the modern diagnostic and therapeutic possibilities in order to ensure an optimal and patient specific management. This review article focuses on the diagnostic and therapeutic limitations and difficulties of treatment of benign vocal fold tumors, the management and prevention of scarred vocal folds and the issue of unilateral vocal fold paresis. PMID:24403969

  19. Diagnostic and therapeutic pitfalls in benign vocal fold diseases.

    PubMed

    Bohlender, Jörg

    2013-01-01

    More than half of patients presenting with hoarseness show benign vocal fold changes. The clinician should be familiar with the anatomy, physiology and functional aspects of voice disorders and also the modern diagnostic and therapeutic possibilities in order to ensure an optimal and patient specific management. This review article focuses on the diagnostic and therapeutic limitations and difficulties of treatment of benign vocal fold tumors, the management and prevention of scarred vocal folds and the issue of unilateral vocal fold paresis. PMID:24403969

  20. Leech therapeutic applications.

    PubMed

    Abdualkader, A M; Ghawi, A M; Alaama, M; Awang, M; Merzouk, A

    2013-03-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20(th) century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  1. Therapeutic apheresis in Taiwan.

    PubMed

    Yeh, J H; Chiu, H C

    2001-12-01

    From July 1, 1999, to June 30, 2000, the Formosan Blood Purification Society conducted a survey on the current status of therapeutic apheresis (TA) treatments in Taiwan. There were 13 centers with a total of 437 patients, 498 courses, and 2,086 procedures. The most common indication was for neurological disorders (58.4%), which included mainly myasthenia gravis (34.9%) and Guillain-Barré syndrome (18.2%). The other indications were hematological disorders (19.3%), hepatic-pancreatic disorders (12.3%), and rheumatic disorders (7.1%). Seventy-one percent of TA treatments were reported to be effective. Plasma exchange (PE) performed by either centrifugation or the filtration method constituted 55.4% of TA treatments, the double-filtration (DF) method constituted 39.3% of treatments, and cytapheresis constituted 5.3% of treatments. The most common machines used for TA were the Plasauto iQ, the KM 8800, the Hemonetics series, and the Fenwal CS-3000. The overall frequency of complications was 42.2% per course and 12.9% per procedure. Among them, fever, urticaria, and hypotension were the major complications. As compared with the trends of TA treatment in the world, PE still represents the major TA treatment in Taiwan, which should be replaced by DF or more selective adsorptive methods to reduce the PE-related adverse effects. PMID:11800091

  2. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ?-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization. PMID:25051278

  3. Leech Therapeutic Applications

    PubMed Central

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  4. Mustard Gas Inhalation Injury: Therapeutic Strategy.

    PubMed

    Keyser, Brian M; Andres, Devon K; Holmes, Wesley W; Paradiso, Danielle; Appell, Ashley; Letukas, Valerie A; Benton, Betty; Clark, Offie E; Gao, Xiugong; Ray, Prabhati; Anderson, Dana R; Ray, Radharaman

    2014-05-01

    Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies using the other drugs, that is, anti-inflammatory, antioxidant, and protease inhibitor compounds. PMID:24801489

  5. Women's HIV Disclosure to Family and Friends

    PubMed Central

    Craft, Shonda M.; Reed, Sandra J.

    2012-01-01

    Abstract Previous researchers have documented rates of HIV disclosure to family at discrete time periods, yet none have taken a dynamic approach to this phenomenon. The purpose of this study is to take the next step and provide a retrospective comparison of rates of women's HIV disclosure to family and friends over a 15-year time span. Of particular interest are the possible influences of social network and relationship characteristics on the time-to-disclosure of serostatus. Time-to-disclosure was analyzed from data provided by 125 HIV-positive women. Participants were primarily married or dating (42%), unemployed (79.2%), African American (68%) women with a high school diploma or less (54.4%). Length of time since diagnosis ranged from 1 month to over 19 years (M=7.1 years). Results pointed to statistically significant differences in time-to-disclosure between family, friends, and sexual partners. Additionally, females and persons with whom the participant had more frequent contact were more likely to be disclosed to, regardless of the type of relationship. The results of this study underscore possible challenges with existing studies which have employed point prevalence designs, and point to new methods which could be helpful in family research. PMID:22313348

  6. DCTD — Developmental Therapeutics Program (DTP)

    Cancer.gov

    In 2009, NCI consolidated its anticancer drug discovery and development resources in support of a robust, balanced, goal-driven therapeutics pipeline--the NCI Experimental Therapeutics (NExT) Program. For more information about this new initiative, including how to submit an application, please visit the NExT website.

  7. Language Patterns and Therapeutic Change.

    ERIC Educational Resources Information Center

    Phoenix, Valdemar G.; Lindeman, Mary L.

    Noting that the mental health practitioner needs highly developed linguistic and communicative skills in order to precipitate therapeutic changes, this paper discusses the nature of the contexts of therapeutic interaction. It examines verb tense as a linguistic context marker and shows how various schools of therapy can use it. In addition, it…

  8. Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

    SciTech Connect

    Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie . E-mail: v.bosch@dkfz.de

    2007-05-10

    Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767{sup stop}, which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752{sup N750K}) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752{sup N750K} exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses.

  9. HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study

    PubMed Central

    Gold, Julian; Goldacre, Raph; Maruszak, Hubert; Giovannoni, Gavin; Yeates, David; Goldacre, Michael

    2015-01-01

    Objectives Even though multiple sclerosis (MS) and HIV infection are well-documented conditions in clinical medicine, there is only a single case report of a patient with MS and HIV treated with HIV antiretroviral therapies. In this report, the patient's MS symptoms resolved completely after starting combination antiretroviral therapy and remain subsided for more than 12?years. Authors hypothesised that because the pathogenesis of MS has been linked to human endogenous retroviruses, antiretroviral therapy for HIV may be coincidentally treating or preventing progression of MS. This led researchers from Denmark to conduct an epidemiological study on the incidence of MS in a newly diagnosed HIV population (5018 HIV cases compared with 50?149 controls followed for 31?875 and 393?871 person-years, respectively). The incidence rate ratio for an HIV patient acquiring MS was low at 0.3 (95% CI 0.04 to 2.20) but did not reach statistical significance possibly due to the relatively small numbers in both groups. Our study was designed to further investigate the possible association between HIV and MS. Methods We conducted a comparative cohort study accessing one of the world’s largest linked medical data sets with a cohort of 21?207 HIV-positive patients and 5?298?496 controls stratified by age, sex, year of first hospital admission, region of residence and socioeconomic status and ‘followed up’ by record linkage. Results Overall, the rate ratio of developing MS in people with HIV, relative to those without HIV, was 0.38 (95% CI 0.15 to 0.79). Conclusions HIV infection is associated with a significantly decreased risk of developing MS. Mechanisms of this observed possibly protective association may include immunosuppression induced by chronic HIV infection and antiretroviral medications. PMID:25091370

  10. Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis

    PubMed Central

    Rao, P. S. S.; Kumar, Santosh

    2015-01-01

    High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and disease progression. While the effect of smoking on the occurrence of lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of cytochrome P450 (CYP) in smoking/nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette smoke, mediated HIV pathogenesis. More specifically, we will discuss the role of CYP1A1 and CYP1B1, which are the major PAH-activating CYP enzymes. Our results have shown that treatment with cigarette smoke condensate (CSC) increases viral replication in HIV-infected macrophages. CSC contains PAH, which are known to be activated by CYP1A1 and CYP1B1 into procarcinogens/toxic metabolites. The expression of these CYPs is regulated by aryl hydrocarbon receptors (AHR), the cellular target of PAH, and an important player in various diseases including cancer. We propose that PAH/AHR-mediated CYP pathway is a novel target to develop new interventions for HIV positive smokers. PMID:26082767

  11. Ethical issues related to HIV/AIDS: case reports.

    PubMed

    Meel, B L

    2005-06-01

    The continents of Africa and Asia have the highest number of HIV infected persons in the world. Worldwide there are 42 million and 29.7 million (70%) are in sub Saharan Africa [United Nations AIDS (UNAIDS). Available from: www.unaids.org]. The stigma and discrimination attached to HIV/AIDS are hampering control of the disease. Family life has greatly been disrupted by the pandemic. AIDS causes illness, disability and death as well as severe economic and emotional disruptions to the families. The epidemic is well established in South Africa. The mortality will be doubled over the next five years. A broad range of coercive measures has been considered to be applied internationally in the interest of controlling the spread of HIV. Responsibility of the employers to their HIV/AIDS employees at workplace, choice of termination of pregnancy when a woman is HIV positive, attitude of health care provider to their HIV infected patients, informed consent for taking blood to protect from transmission of infection in a case of accidental prick, and forced resignation from employment, are discussed in this manuscript. The ethical problems are highlighted, and possible solutions recommended. PMID:15914310

  12. The Transmission Dynamics of Human Immunodeficiency Virus (HIV)

    NASA Astrophysics Data System (ADS)

    May, R. M.; Anderson, R. M.

    1988-10-01

    The paper first reviews data on HIV infections and AIDS disease among homosexual men, heterosexuals, intravenous (IV) drug abusers and children born to infected mothers, in both developed and developing countries. We survey such information as is currently available about the distribution of incubation times that elapse between HIV infection and the appearance of AIDS, about the fraction of those infected with HIV who eventually go on to develop AIDS, about time-dependent patterns of infectiousness and about distributions of rates of acquiring new sexual or needle-sharing partners. With this information, models for the transmission dynamics of HIV are developed, beginning with deliberately oversimplified models and progressing - on the basis of the understanding thus gained - to more complex ones. Where possible, estimates of the model's parameters are derived from the epidemiological data, and predictions are compared with observed trends. We also combine these epidemiological models with demographic considerations to assess the effects that heterosexually-transmitted HIV/AIDS may eventually have on rates of population growth, on age profiles and on associated economic and social indicators, in African and other countries. The degree to which sexual or other habits must change to bring the `basic reproductive rate', R_0, of HIV infections below unity is discussed. We conclude by outlining some research needs, both in the refinement and development of models and in the collection of epidemiological data.

  13. Local biologies and HIV/AIDS in highlands Papua, Indonesia.

    PubMed

    Butt, Leslie

    2013-03-01

    The province of Papua, Indonesia has one of the fastest growing rates of HIV infection in Asia. Within volatile political conditions, HIV has reached generalized epidemic status for indigenous Papuans. This article explores the merits of using the concept of local biologies as an analytic tool to assess the range of factors which affect a local pattern of untreated HIV and rapid onset of AIDS. A research team conducted 32 in-depth interviews with HIV-positive indigenous persons and 15 interviews with health care workers in urban and peri-urban sites in the central highlands region. The results show fear of gossip and stigmatization, regional political conditions and gaps in care interweave to create local biological conditions of evasion of care and rapid onset of AIDS. The normative emphasis in contemporary scholarship on stigma as shaping subjective responses to HIV needs to be complemented by a full assessment of the physiological impact of health services, and the ways political conditions trickle down and mediate local biological patterns. The concept of local biologies is highly effective for explaining the full scope of possible factors affecting the intersection of social and physical realms for HIV-positive persons. PMID:23242628

  14. Role of MicroRNA Modulation in the Interferon-?/Ribavirin Suppression of HIV-1 In Vivo

    PubMed Central

    Abdel-Mohsen, Mohamed; Deng, Xutao; Danesh, Ali; Liegler, Teri; Jacobs, Evan S.; Rauch, Andri; Ledergerber, Bruno; Norris, Philip J.; Günthard, Huldrych F.; Wong, Joseph K.; Pillai, Satish K.

    2014-01-01

    Background Interferon-? (IFN-?) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN-? may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN-?-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-? treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. Methods Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-?/ribavirin therapy (IFN-?/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. Results miR-422a was the only miRNA significantly modulated by IFN-?/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo. Conclusions The specific reduction of miR-422a is associated with exogenous IFN-? treatment, and likely contributes to the IFN-? suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo. PMID:25275557

  15. Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

    PubMed

    Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B

    2015-11-01

    Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy. PMID:26469251

  16. Pro-inflammatory cytokines and HIV-1 synergistically enhance CXCL10 expression in human astrocytes

    PubMed Central

    Williams, Rachel; Dhillon, Navneet K.; Hegde, Sonia T.; Yao, Honghong; Peng, Fuwang; Callen, Shannon; Chebloune, Yahia; Davis, Randall L.; Buch, Shilpa J.

    2009-01-01

    HIV encephalitis (HIVE), the pathologic correlate of HIV-associated dementia (HAD) is characterized by astrogliosis, cytokine/chemokine dysregulation and neuronal degeneration. Increasing evidence suggests that inflammation is actively involved in the pathogenesis of HAD. In fact, the severity of HAD/HIVE correlates more closely with the presence of activated glial cells than with the presence and amount of HIV-infected cells in the brain. Astrocytes, the most numerous cell type within the brain, provide an important reservoir for the generation of inflammatory mediators, including interferon-? inducible peptide-10 (CXCL10), a neurotoxin and a chemoattractant, implicated in the pathophysiology of HAD. Additionally, the pro-inflammatory cytokines, IFN-? and TNF-?, are also markedly increased in CNS tissues during HIV-1 infection. In the present study we hypothesized that the interplay of host cytokines and HIV-1 could lead to enhanced expression of the toxic chemokine, CXCL10. Our findings demonstrate a synergistic induction of CXCL10 mRNA and protein in human astrocytes exposed to HIV-1 and the pro-inflammatory cytokines. Signaling molecules, including JAK, STATs, MAPK (via activation of Erk1/2, AKT, and p38), and NF-?B were identified as instrumental in the synergistic induction of CXCL10. Understanding the mechanisms involved in HIV-1 and cytokine mediated up-regulation of CXCL10 could aid in the development of therapeutic modalities for HAD. PMID:18985732

  17. Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells

    PubMed Central

    Wei, Min; Zhao, Xia; Liu, Mi; Huang, Zhi; Xiao, Yong; Niu, Meijuan; Shao, Yiming; Kleiman, Lawrence

    2015-01-01

    Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new host protein, coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles. Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8 and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV-1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The interaction between exogenously expressed CCDC8 and Gag on the plasma membrane changes the assembly of Gag, and redirects it into intracellular sites, or causes Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1) and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination and degradation. This pathway presents potential therapeutic strategies against HIV infection. PMID:26423533

  18. Therapeutic cloning: promises and issues

    PubMed Central

    Kfoury, Charlotte

    2007-01-01

    Advances in biotechnology necessitate both an understanding of scientific principles and ethical implications to be clinically applicable in medicine. In this regard, therapeutic cloning offers significant potential in regenerative medicine by circumventing immunorejection, and in the cure of genetic disorders when used in conjunction with gene therapy. Therapeutic cloning in the context of cell replacement therapy holds a huge potential for de novo organogenesis and the permanent treatment of Parkinson’s disease, Duchenne muscular dystrophy, and diabetes mellitus as shown by in vivo studies. Scientific roadblocks impeding advancement in therapeutic cloning are tumorigenicity, epigenetic reprogramming, mitochondrial heteroplasmy, interspecies pathogen transfer, low oocyte availability. Therapeutic cloning is also often tied to ethical considerations concerning the source, destruction and moral status of IVF embryos based on the argument of potential. Legislative and funding issues are also addressed. Future considerations would include a distinction between therapeutic and reproductive cloning in legislative formulations. PMID:18523539

  19. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  20. Exploring the social meaning of curing HIV: a qualitative study of people who inject drugs in Guangzhou, China.

    PubMed

    Chu, Carissa E; Wu, Feng; He, Xi; Ma, Qingyan; Cheng, Yu; Cai, Weiping; Volberding, Paul; Tucker, Joseph D

    2015-01-01

    Our objective was to explore the social meaning of HIV and perceptions of an HIV cure among people who inject drugs (PWID) in Guangzhou, China, which speaks to ethical and resource challenges to development in this field. We conducted a qualitative research study using in-depth interviews. We analyzed interview transcripts from 29 PWID, eight physicians, and three social workers from an outpatient HIV clinic and two methadone maintenance treatment centers. The social meaning of HIV infection and perceptions of an HIV cure reflected patients' relationships with society, health systems, and physicians. First, HIV infection decreased perceived social worth and disrupted peer relationships. The possibility of being cured renewed patient hope for regaining physical well-being and achieving social mobility. However, the existence of a cure may not alter the HIV-related stigma due to its association with stigmatized behaviors and marginalized groups. Second, although stigma was a significant barrier to engagement in health care, hope for a cure may outweigh fears of stigma and enhance linkage to HIV testing and treatment as well as methadone services. A cure may exacerbate perceived health disparities if inaccessible to key affected populations such as PWID. The social implications of an HIV cure among this key affected population may inform the design and implementation of cure clinical trials. Careful management of patient expectations, focusing research on key affected populations, expanding HIV testing and treatment systems, improving access to harm reduction programs, and ensuring post-trial access are important considerations for HIV cure research. PMID:25427547

  1. Measuring Glutathione Redox Potential of HIV-1-infected Macrophages*

    PubMed Central

    Bhaskar, Ashima; Munshi, MohamedHusen; Khan, Sohrab Zafar; Fatima, Sadaf; Arya, Rahul; Jameel, Shahid; Singh, Amit

    2015-01-01

    Redox signaling plays a crucial role in the pathogenesis of human immunodeficiency virus type-1 (HIV-1). The majority of HIV redox research relies on measuring redox stress using invasive technologies, which are unreliable and do not provide information about the contributions of subcellular compartments. A major technological leap emerges from the development of genetically encoded redox-sensitive green fluorescent proteins (roGFPs), which provide sensitive and compartment-specific insights into redox homeostasis. Here, we exploited a roGFP-based specific bioprobe of glutathione redox potential (EGSH; Grx1-roGFP2) and measured subcellular changes in EGSH during various phases of HIV-1 infection using U1 monocytic cells (latently infected U937 cells with HIV-1). We show that although U937 and U1 cells demonstrate significantly reduced cytosolic and mitochondrial EGSH (approximately ?310 mV), active viral replication induces substantial oxidative stress (EGSH more than ?240 mV). Furthermore, exposure to a physiologically relevant oxidant, hydrogen peroxide (H2O2), induces significant deviations in subcellular EGSH between U937 and U1, which distinctly modulates susceptibility to apoptosis. Using Grx1-roGFP2, we demonstrate that a marginal increase of about ?25 mV in EGSH is sufficient to switch HIV-1 from latency to reactivation, raising the possibility of purging HIV-1 by redox modulators without triggering detrimental changes in cellular physiology. Importantly, we show that bioactive lipids synthesized by clinical drug-resistant isolates of Mycobacterium tuberculosis reactivate HIV-1 through modulation of intracellular EGSH. Finally, the expression analysis of U1 and patient peripheral blood mononuclear cells demonstrated a major recalibration of cellular redox homeostatic pathways during persistence and active replication of HIV. PMID:25406321

  2. DCTD — Developmental Therapeutics Program (DTP)

    Cancer.gov

    In 1994, DTP launched its website, making its drug discovery and development services and the results from the human tumor cell line assay publicly accessible to researchers worldwide. At first, the site offered in vitro human cell line data for a few thousand compounds and in vitro anti-HIV screening data for roughly 42,000 compounds.

  3. DCTD — Developmental Therapeutics Program (DTP)

    Cancer.gov

    In 1994, DTP launched its Website, making its drug discovery and development services and the results from the human tumor cell line assay publicly accessible to researchers worldwide. At first, the site offered in vitro human cell line data for a few thousand compounds and in vitro anti-HIV screening data for roughly 42,000 compounds.

  4. HIV Aspartyl Peptidase Inhibitors Interfere with Cellular Proliferation, Ultrastructure and Macrophage Infection of Leishmania amazonensis

    PubMed Central

    Santos, Lívia O.; Marinho, Fernanda A.; Altoé, Ellen F.; Vitório, Bianca S.; Alves, Carlos R.; Britto, Constança; Motta, Maria Cristina M.; Branquinha, Marta H.; Santos, André L. S.; d'Avila-Levy, Claudia M.

    2009-01-01

    Background Leishmania is the etiologic agent of leishmanisais, a protozoan disease whose pathogenic events are not well understood. Current therapy is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the increase in the number of cases of Leishmania-HIV coinfection, due to the overlap between the AIDS epidemic and leishmaniasis. Methodology/Principal Findings In the present report, we have investigated the effect of HIV aspartyl peptidase inhibitors (PIs) on the Leishmania amazonensis proliferation, ultrastructure, interaction with macrophage cells and expression of classical peptidases which are directly involved in the Leishmania pathogenesis. All the HIV PIs impaired parasite growth in a dose-dependent fashion, especially nelfinavir and lopinavir. HIV PIs treatment caused profound changes in the leishmania ultrastructure as shown by transmission electron microscopy, including cytoplasm shrinking, increase in the number of lipid inclusions and some cells presenting the nucleus closely wrapped by endoplasmic reticulum resembling an autophagic process, as well as chromatin condensation which is suggestive of apoptotic death. The hydrolysis of HIV peptidase substrate by L. amazonensis extract was inhibited by pepstatin and HIV PIs, suggesting that an aspartyl peptidase may be the intracellular target of the inhibitors. The treatment with HIV PIs of either the promastigote forms preceding the interaction with macrophage cells or the amastigote forms inside macrophages drastically reduced the association indexes. Despite all these beneficial effects, the HIV PIs induced an increase in the expression of cysteine peptidase b (cpb) and the metallopeptidase gp63, two well-known virulence factors expressed by Leishmania spp. Conclusions/Significance In the face of leishmaniasis/HIV overlap, it is critical to further comprehend the sophisticated interplays among Leishmania, HIV and macrophages. In addition, there are many unresolved questions related to the management of Leishmania-HIV-coinfected patients. For instance, the efficacy of therapy aimed at controlling each pathogen in coinfected individuals remains largely undefined. The results presented herein add new in vitro insight into the wide spectrum efficacy of HIV PIs and suggest that additional studies about the synergistic effects of classical antileishmanial compounds and HIV PIs in macrophages coinfected with Leishmania and HIV-1 should be performed. PMID:19325703

  5. HIV Excess Cancers JNCI

    Cancer.gov

    In 2010, an estimated 7,760 new cancers were diagnosed among the nearly 900,000 Americans known to be living with HIV infection. According to the first comprehensive study in the United States, approximately half of these cancers were in excess of what wo

  6. The Science of HIV.

    ERIC Educational Resources Information Center

    DiSpezio, Michael

    This book is the first curriculum developed to bring cutting edge research on the HIV virus into science classrooms. The book and video are coordinated to provide a range of learning opportunities--labs, activities, readings, model design, guided discussions and, in the video, a way to see research in action. Both the book and video emphasize the…

  7. Migrants and HIV / AIDS.

    PubMed

    Duckett, M

    2000-06-01

    This paper outlines some of the imperatives that should drive attention to the rights of legal and illegal migrants to health, particularly in relation to HIV/AIDS. It is noted that migrants can be especially vulnerable to HIV/AIDS/sexually transmitted diseases (STDs), but they are often excluded or simply missed in many prevention and care programs. In terms of the effects of globalization, it would seem that governments are required to ensure that this state of affairs does not continue. Evidence indicates that human rights and other ethical violations are occurring and need to be urgently addressed at local, national and international levels. In view of such, it is recommended that HIV/AIDS/STD prevention and care programs for migrant populations should be developed with and guided by migrant communities, and involving substantial community mobilization. Although some progress in preventing the spread of HIV to and from migrants have been documented, and projects addressing their needs have been made accessible, the challenge of dealing more comprehensively the complex issues involved still remains. PMID:12179440

  8. Integrating School-Based and Therapeutic Conflict Management Models at School.

    ERIC Educational Resources Information Center

    D'Oosterlinck, Franky; Broekaert, Eric

    2003-01-01

    Explores the possibility of integrating school-based and therapeutic conflict management models, comparing two management models: a school-based conflict management program, "Teaching Students To Be Peacemakers"; and a therapeutic conflict management program, "Life Space Crisis Intervention." The paper concludes that integration might be possible

  9. Sexual mixing patterns among social networks of HIV-positive and HIV-negative Beijing men who have sex with men: a multilevel comparison using roundtable network mapping.

    PubMed

    Ruan, Yuhua; Pan, Stephen W; Chamot, Eric; Qian, Han-Zhu; Li, Dongliang; Li, Qing-Chun; Liang, Hong-Yuan; Spittal, Patricia; Shao, Yiming; Kristensen, Sibylle

    2011-08-01

    Men who have sex with men (MSM) are of immediate concern in China's HIV epidemic. In 2008, approximately 2.5-6.5% of China's eight million MSM were HIV positive, while MSM represented 11% of all new HIV cases. Two factors that will in-part determine HIV-transmission dynamics among MSM, are sexual mixing patterns and the social networks which shape them. Sexual mixing patterns and social networks of Chinese MSM, however, remain poorly understood with little refined data available. One reason is that stigma discourages disclosure of names and identifiers to researchers. Using an alternative network-mapping approach, matched case-control design, and snowball sampling, this pilot study sought to compare characteristics of social networks of HIV-positive and HIV-negative Beijing MSM at the individual, dyad, and network levels. First, HIV-negative MSM controls were matched to HIV-positive MSM cases based on age, education, residency, and ethnicity. Then, each case or control and their MSM social network convened at a specific time and location with study investigators. Venues included health clinics, karaoke clubs, brothels, and community centers. Then, using arbitrarily assigned numbers in lieu of actual names, all participants simultaneously completed self-administered surveys regarding their sexual relationships with other participants of the same social network. These new findings indicate that cross-generational sex (anal or oral sex between men with ?10 years age difference) was more prevalent among social networks of HIV-positive MSM, and was due to older age structure of the social network, rather than behavioral differences in sex-partner selection. Members of social networks of HIV-positive MSM were also less likely to have ever disclosed their MSM identity to non-MSM. Future studies should partner with MSM advocacy groups to explore behavioral and structural interventions as possible means of reducing the cross-generational sex and sexual identity-development issues elevating HIV risk for young Chinese MSM. PMID:21400315

  10. Black Americans and HIV/AIDS

    MedlinePLUS

    ... Americans and HIV/AIDS Black Americans and HIV/AIDS Apr 25, 2014 Black Americans have been disproportionately ... and 30% of whites. 16 Concern About HIV/AIDS A recent survey found that Black Americans express ...

  11. 9G4+ Antibodies Isolated from HIV-Infected Patients Neutralize HIV-1 and Have Distinct Autoreactivity Profiles

    PubMed Central

    Alcéna, Danielle C.; Kobie, James J.; Kaminski, Denise A.; Rosenberg, Alexander F.; Mattiacio, Jonelle L.; Brewer, Matthew; Dewhurst, Stephen; Dykes, Carrie; Jin, Xia; Keefer, Michael C.; Sanz, Ignacio

    2013-01-01

    Potent HIV-1 specific broadly neutralizing antibodies (BNA) are uncommon in HIV infected individuals, and have proven hard to elicit by vaccination. Several, isolated monoclonal BNA are polyreactive and also recognize self-antigens, suggesting a breach of immune tolerance in persons living with HIV (PLWH). Persons with systemic lupus erythematosus (SLE) often have elevated levels of autoreactive antibodies encoded by the VH4-34 heavy chain immunoglobulin gene whose protein product can be detected by the 9G4 rat monoclonal antibody. We have recently found that levels of these “9G4+” antibodies are also elevated in PLWH. However, the putative autoreactive nature of these antibodies and the relationship of such reactivities with HIV neutralization have not been investigated. We therefore examined the autoreactivity and HIV neutralization potential of 9G4+ antibodies from PLWH. Results show that 9G4+ antibodies from PLWH bound to recombinant HIV-1 envelope (Env) and neutralized viral infectivity in vitro, whereas 9G4+ antibodies from persons with SLE did not bind to Env and failed to neutralize viral infectivity. In addition, while 9G4+ antibodies from PLWH retained the canonical anti-i reactivity that mediates B cell binding, they did not display other autoreactivities common to SLE 9G4+ antibodies, such as binding to cardiolipin and DNA and had much lower reactivity with apoptotic cells. Taken together, these data indicate that the autoreactivity of 9G4+ antibodies from PLWH is distinct from that of SLE patients, and therefore, their expansion is not due to a general breakdown of B cell tolerance but is instead determined in a more disease-specific manner by self-antigens that become immunogenic in the context of, and possibly due to HIV infection. Further studies of 9G4+ B cells may shed light on the regulation of B cell tolerance and interface between the generation of specific autoreactivities and the induction of antiviral immunity in persons living with HIV. PMID:24386452

  12. HIV Testing and Diagnosis Rates in Kiev, Ukraine: April 2013 - March 2014

    PubMed Central

    Simmons, Ruth; Malyuta, Ruslan; Medoeva, Antonia; Kruglov, Yuri; Yurchenko, Alexander; Copas, Andrew; Porter, Kholoud

    2015-01-01

    Objective Data from Ukraine on risk factors for HIV acquisition are limited. We describe the characteristics of individuals testing for HIV in the main testing centres of the Ukrainian capital Kiev, including HIV risk factors, testing rates, and positivity rates. Methods As part of a larger study to estimate HIV incidence within Kiev City, we included questions on possible risk factors for HIV acquisition and testing history to existing systems in 4 infectious disease clinics. Data were provided by the person requesting an HIV test using a handheld electronic tablet. All persons (?16yrs) presenting for an HIV test April 2013–March 2014 were included. Rates per 100,000 were calculated using region-specific denominators for Kiev. Results During the study period 6370 individuals tested for HIV, equivalent to a testing rate of 293.2 per 100,000. Of these, 467 (7.8%) were HIV-positive, with the highest proportion positive among 31–35 year olds (11.2%), males (9.4%), people who inject drugs (PWID) (17.9%) and men who have sex with men (MSM) (24.1%). Using published population size estimates of MSM, diagnosis rates for MSM ranged from 490.6to 1548.3/100,000. A higher proportion of heterosexual women compared to heterosexual men reported contact with PWID, (16% vs. 4.7%) suggesting a bridging in risk between PWID and their sexual partners. Conclusion Collection of HIV risk factor information in Kiev, essential for the purposes of developing effective HIV prevention and response tools, is feasible. The high percentage of MSM among those testing positive for HIV, may indicate a significant level of undisclosed sex between men in national figures. PMID:26322977

  13. HIV Sequence Compendium 2010

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Leitner, Thomas; Apetrei, Christian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette

    2010-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2010. Hence, though it is called the 2010 Compendium, its contents correspond to the 2009 curated alignments on our website. The number of sequences in the HIV database is still increasing exponentially. In total, at the time of printing, there were 339,306 sequences in the HIV Sequence Database, an increase of 45% since last year. The number of near complete genomes (>7000 nucleotides) increased to 2576 by end of 2009, reflecting a smaller increase than in previous years. However, as in previous years, the compendium alignments contain only a small fraction of these. Included in the alignments are a small number of sequences representing each of the subtypes and the more prevalent circulating recombinant forms (CRFs) such as 01 and 02, as well as a few outgroup sequences (group O and N and SIV-CPZ). Of the rarer CRFs we included one representative each. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html. Reprints are available from our website in the form of both HTML and PDF files. As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  14. Novel Approaches to Inhibiting HIV-1 Replication

    PubMed Central

    Adamson, Catherine S.; Freed, Eric O.

    2009-01-01

    Considerable success has been achieved in the treatment of HIV-1 infection, and more than two-dozen antiretroviral drugs are available targeting several distinct steps in the viral replication cycle. However, resistance to these compounds emerges readily, even in the context of combination therapy. Drug toxicity, adverse drug-drug interactions, and accompanying poor patient adherence can also lead to treatment failure. These considerations make continued development of novel antiretroviral therapeutics necessary. In this article, we highlight a number of steps in the HIV-1 replication cycle that represent promising targets for drug discovery. These include lipid raft microdomains, the RNase H activity of the viral enzyme reverse transcriptase, uncoating of the viral core, host cell machinery involved in the integration of the viral DNA into host cell chromatin, virus assembly, maturation, and budding, and the functions of several viral accessory proteins. We discuss the relevant molecular and cell biology, and describe progress to date in developing inhibitors against these novel targets. PMID:19782103

  15. Patient and Provider Perspectives on HIV and HIV-Related Stigma in Dutch Health Care Settings

    PubMed Central

    Sicking, Lenneke; Brands, Ronald; Baas, Ineke; Roberts, Hilde; van Brakel, Wim H.; Lechner, Lilian; Kok, Gerjo; Bos, Arjan E. R.

    2014-01-01

    Abstract Ensuring that people living with HIV (PLWH) feel accepted in health care settings is imperative. This mixed methods study explored the perspectives of PLWH and health professionals on their interactions. A total of 262 predominantly gay men of Dutch origin participated in a survey study of possible negative interactions with health professionals, and semi-structured interviews were subsequently conducted with 22 PLWH and 14 health professionals. Again, most PLWH were gay men of Dutch origin. All health professionals were Dutch. PLWH reported negative experiences with health professionals including awkward interactions, irrelevant questions, rude treatment, blame, pity, excessive or differential precautions, care refusal, unnecessary referrals, delayed treatment, poor support, and confidentiality breaches. They also reported positive experiences including equal treatment, being valued as a partner in one's health, social support provision, and confidentiality assurances. Health professionals reported having little experience with PLWH and only basic knowledge of HIV. They contended that PLWH are treated equally and that HIV is no longer stigmatized, but also reported fear of occupational infection, resulting in differential precautions. Additionally, they conveyed labeling PLWH's files to warn others, and curiosity regarding how patients acquired HIV. The findings suggest that there is a gap in perception between PLWH and health professionals regarding the extent to which negative interactions occur, and that these interactions should be improved. Implications for stigma reduction and care optimization are discussed. PMID:25459231

  16. The impact of criminalization of HIV non-disclosure on the healthcare engagement of women living with HIV in Canada: a comprehensive review of the evidence

    PubMed Central

    Patterson, Sophie E; Milloy, M-J; Ogilvie, Gina; Greene, Saara; Nicholson, Valerie; Vonn, Micheal; Hogg, Robert; Kaida, Angela

    2015-01-01

    Introduction In 2012, the Supreme Court of Canada ruled that people living with HIV (PLWH) must disclose their HIV status to sexual partners prior to sexual activity that poses a “realistic possibility” of HIV transmission for consent to sex to be valid. The Supreme Court deemed that the duty to disclose could be averted if a person living with HIV both uses a condom and has a low plasma HIV-1 RNA viral load during vaginal sex. This is one of the strictest legal standards criminalizing HIV non-disclosure worldwide and has resulted in a high rate of prosecutions of PLWH in Canada. Public health advocates argue that the overly broad use of the criminal law against PLWH undermines efforts to engage individuals in healthcare and complicates gendered barriers to linkage and retention in care experienced by women living with HIV (WLWH). Methods We conducted a comprehensive review of peer-reviewed and non-peer-reviewed evidence published between 1998 and 2015 evaluating the impact of the criminalization of HIV non-disclosure on healthcare engagement of WLWH in Canada across key stages of the cascade of HIV care, specifically: HIV testing and diagnosis, linkage and retention in care, and adherence to antiretroviral therapy. Where available, evidence pertaining specifically to women was examined. Where these data were lacking, evidence relating to all PLWH in Canada or other international jurisdictions were included. Results and discussion Evidence suggests that criminalization of HIV non-disclosure may create barriers to engagement and retention within the cascade of HIV care for PLWH in Canada, discouraging access to HIV testing for some people due to fears of legal implications following a positive diagnosis, and compromising linkage and retention in healthcare through concerns of exposure of confidential medical information. There is a lack of published empirical evidence focused specifically on women, which is a concern given the growing population of WLWH in Canada, among whom marginalized and vulnerable women are overrepresented. Conclusions The threat of HIV non-disclosure prosecution combined with a heightened perception of surveillance may alter the environment within which women engage with healthcare services. Fully exploring the extent to which HIV criminalization represents a barrier to the healthcare engagement of WLWH is a public health priority. PMID:26701080

  17. Mitochondrial toxicity and HIV therapy

    PubMed Central

    White, A.

    2001-01-01

    Nucleoside reverse transcriptase inhibitors (NRTIs) remain the cornerstone of highly active antiretroviral therapy (HAART) combination regimens. However, it has been known for some time that these agents have the potential to cause varied side effects, many of which are thought to be due to their effects on mitochondria. Mitochondria, the key energy generating organelles in the cell, are unique in having their own DNA, a double stranded circular genome of about 16 000 bases. There is a separate enzyme present inside the cell that replicates mitochondrial DNA, polymerase gamma. NRTIs can affect the function of this enzyme and this may lead to depletion of mitochondrial DNA or qualitative changes. The study of inherited mitochondrial diseases has led to further understanding of the consequences of mutations or depletion in mitochondrial DNA. Key among these is the realisation that there may be substantial heteroplasmy among mitochondria within a given cell, and among cells in a particular tissue. The unpredictable nature of mitochondrial segregation during cellular replication makes it difficult to predict the likelihood of dysfunction in a given tissue. In addition, there is a threshold effect for the expression of mitochondrial dysfunction, both at the mitochondrial and cellular level. Various clinical and in vitro studies have suggested that NRTIs are associated with mitochondrial dysfunction in different tissues, although the weight of evidence is limited in many cases. The heterogeneity in the tissues affected by the different drugs raises interesting questions, and possible explanations include differential distribution or activation of these agents. This article reviews the major recognised toxicities associated with NRTI therapy and evidence for mitochondrial dysfunction in these complications. Data were identified through searching of online databases including Medline and Current Contents for relevant articles, along with abstracts and posters from recent conferences in the HIV and mitochondrial fields. Key Words: mitochondrial toxicity; HIV therapy PMID:11402222

  18. Pharmacology and therapeutics of bronchodilators.

    PubMed

    Cazzola, Mario; Page, Clive P; Calzetta, Luigino; Matera, M Gabriella

    2012-07-01

    Bronchodilators are central in the treatment of of airways disorders. They are the mainstay of the current management of chronic obstructive pulmonary disease (COPD) and are critical in the symptomatic management of asthma, although controversies around the use of these drugs remain. Bronchodilators work through their direct relaxation effect on airway smooth muscle cells. at present, three major classes of bronchodilators, ?(2)-adrenoceptor (AR) agonists, muscarinic receptor antagonists, and xanthines are available and can be used individually or in combination. The use of the inhaled route is currently preferred to minimize systemic effects. Fast- and short-acting agents are best used for rescue of symptoms, whereas long-acting agents are best used for maintenance therapy. It has proven difficult to discover novel classes of bronchodilator drugs, although potential new targets are emerging. Consequently, the logical approach has been to improve the existing bronchodilators, although several novel broncholytic classes are under development. An important step in simplifying asthma and COPD management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence. Several once-daily ?(2)-AR agonists or ultra-long-acting ?(2)-AR-agonists (LABAs), such as indacaterol, olodaterol, and vilanterol, are already in the market or under development for the treatment of COPD and asthma, but current recommendations suggest the use of LABAs only in combination with an inhaled corticosteroid. In addition, some new potentially long-acting antimuscarinic agents, such as glycopyrronium bromide (NVA-237), aclidinium bromide, and umeclidinium bromide (GSK573719), are under development, as well as combinations of several classes of long-acting bronchodilator drugs, in an attempt to simplify treatment regimens as much as possible. This review will describe the pharmacology and therapeutics of old, new, and emerging classes of bronchodilator. PMID:22611179

  19. Kinetic model of HIV infection

    SciTech Connect

    Zhdanov, V. P.

    2007-10-15

    Recent experiments clarifying the details of exhaustion of CD8 T cells specific to various strains of human immunodeficiency virus (HIV) are indicative of slow irreversible (on a one-year time scale) deterioration of the immune system. The conventional models of HIV kinetics do not take this effect into account. Removing this shortcoming, we show the likely influence of such changes on the escape of HIV from control of the immune system.

  20. Prion degradation pathways: Potential for therapeutic intervention

    PubMed Central

    Goold, Rob; McKinnon, Chris; Tabrizi, Sarah J.

    2015-01-01

    Prion diseases are fatal neurodegenerative disorders. Pathology is closely linked to the misfolding of native cellular PrPC into the disease-associated form PrPSc that accumulates in the brain as disease progresses. Although treatments have yet to be developed, strategies aimed at stimulating the degradation of PrPSc have shown efficacy in experimental models of prion disease. Here, we describe the cellular pathways that mediate PrPSc degradation and review possible targets for therapeutic intervention. This article is part of a Special Issue entitled ‘Neuronal Protein’. PMID:25584786

  1. Development of Therapeutic Splice-Switching Oligonucleotides

    PubMed Central

    Kryczka, Adrianna; Liu, Yuqi; Badi, Yusef E.; Wong, Jessie J.; Owen, James S.; Khoo, Bernard

    2014-01-01

    Abstract Synthetic splice-switching oligonucleotides (SSOs) target nuclear pre-mRNA molecules to change exon splicing and generate an alternative protein isoform. Clinical trials with two competitive SSO drugs are underway to treat Duchenne muscular dystrophy (DMD). Beyond DMD, many additional therapeutic applications are possible, with some in phase 1 clinical trials or advanced preclinical evaluation. Here, we present an overview of the central factors involved in developing therapeutic SSOs for the treatment of diseases. The selection of susceptible pre-mRNA target sequences, as well as the design and chemical modification of SSOs to increase SSO stability and effectiveness, are key initial considerations. Identification of effective SSO target sequences is still largely empirical and published guidelines are not a universal guarantee for success. Specifically, exon-targeted SSOs, which are successful in modifying dystrophin splicing, can be ineffective for splice-switching in other contexts. Chemical modifications, importantly, are associated with certain characteristic toxicities, which need to be addressed as target diseases require chronic treatment with SSOs. Moreover, SSO delivery in adequate quantities to the nucleus of target cells without toxicity can prove difficult. Last, the means by which these SSOs are administered needs to be acceptable to the patient. Engineering an efficient therapeutic SSO, therefore, necessarily entails a compromise between desirable qualities and effectiveness. Here, we describe how the application of optimal solutions may differ from case to case. PMID:24826963

  2. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs

    PubMed Central

    Zhang, Yonggang; Yin, Chaoran; Zhang, Ting; Li, Fang; Yang, Wensheng; Kaminski, Rafal; Fagan, Philip Regis; Putatunda, Raj; Young, Won-Bin; Khalili, Kamel; Hu, Wenhui

    2015-01-01

    Current antiretroviral therapy does not eliminate the integrated and transcriptionally silent HIV-1 provirus in latently infected cells. Recently, a “shock and kill” strategy has been extensively explored to eradicate the HIV-1 latent reservoirs for a permanent cure of AIDS. The therapeutic efficacy of currently used agents remains disappointing because of low efficiency, non-specificity and cellular toxicity. Here we present a novel catalytically-deficient Cas9-synergistic activation mediator (dCas9-SAM) technology to selectively, potently and persistently reactivate the HIV-1 latent reservoirs. By screening 16 MS2-mediated single guide RNAs, we identified long terminal repeat (LTR)-L and O that surround the enhancer region (-165/-145 for L and -92/-112 for O) and induce robust reactivation of HIV-1 provirus in HIV-1 latent TZM-bI epithelial, Jurkat T lymphocytic and CHME5 microglial cells. This compulsory reactivation induced cellular suicide via toxic buildup of viral proteins within HIV-1 latent Jurkat T and CHME5 microglial cells. These results suggest that this highly effective and target-specific dCas9-SAM system can serve as a novel HIV-latency-reversing therapeutic tool for the permanent elimination of HIV-1 latent reservoirs. PMID:26538064

  3. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs.

    PubMed

    Zhang, Yonggang; Yin, Chaoran; Zhang, Ting; Li, Fang; Yang, Wensheng; Kaminski, Rafal; Fagan, Philip Regis; Putatunda, Raj; Young, Won-Bin; Khalili, Kamel; Hu, Wenhui

    2015-01-01

    Current antiretroviral therapy does not eliminate the integrated and transcriptionally silent HIV-1 provirus in latently infected cells. Recently, a "shock and kill" strategy has been extensively explored to eradicate the HIV-1 latent reservoirs for a permanent cure of AIDS. The therapeutic efficacy of currently used agents remains disappointing because of low efficiency, non-specificity and cellular toxicity. Here we present a novel catalytically-deficient Cas9-synergistic activation mediator (dCas9-SAM) technology to selectively, potently and persistently reactivate the HIV-1 latent reservoirs. By screening 16 MS2-mediated single guide RNAs, we identified long terminal repeat (LTR)-L and O that surround the enhancer region (-165/-145 for L and -92/-112 for O) and induce robust reactivation of HIV-1 provirus in HIV-1 latent TZM-bI epithelial, Jurkat T lymphocytic and CHME5 microglial cells. This compulsory reactivation induced cellular suicide via toxic buildup of viral proteins within HIV-1 latent Jurkat T and CHME5 microglial cells. These results suggest that this highly effective and target-specific dCas9-SAM system can serve as a novel HIV-latency-reversing therapeutic tool for the permanent elimination of HIV-1 latent reservoirs. PMID:26538064

  4. Immune reconstitution inflammatory syndrome in HIV-infected patients

    PubMed Central

    Walker, Naomi F; Scriven, James; Meintjes, Graeme; Wilkinson, Robert J

    2015-01-01

    Access to antiretroviral therapy (ART) is improving worldwide. Immune reconstitution inflammatory syndrome (IRIS) is a common complication of ART initiation. In this review, we provide an overview of clinical and epidemiological features of HIV-associated IRIS, current understanding of pathophysiological mechanisms, available therapy, and preventive strategies. The spectrum of HIV-associated IRIS is described, with a particular focus on three important pathogen-associated forms: tuberculosis-associated IRIS, cryptococcal IRIS, and Kaposi’s sarcoma IRIS. While the clinical features and epidemiology are well described, there are major gaps in our understanding of pathophysiology and as a result therapeutic and preventative strategies are suboptimal. Timing of ART initiation is critical to reduce IRIS-associated morbidity. Improved understanding of the pathophysiology of IRIS will hopefully enable improved diagnostic modalities and better targeted treatments to be developed. PMID:25709503

  5. Sulfonation pathway inhibitors block reactivation of latent HIV-1.

    PubMed

    Murry, Jeffrey P; Godoy, Joseph; Mukim, Amey; Swann, Justine; Bruce, James W; Ahlquist, Paul; Bosque, Alberto; Planelles, Vicente; Spina, Celsa A; Young, John A T

    2014-12-01

    Long-lived pools of latently infected cells are a significant barrier to the development of a cure for HIV-1 infection. A better understanding of the mechanisms of reactivation from latency is needed to facilitate the development of novel therapies that address this problem. Here we show that chemical inhibitors of the sulfonation pathway prevent virus reactivation, both in latently infected J-Lat and U1 cell lines and in a primary human CD4+ T cell model of latency. In each of these models, sulfonation inhibitors decreased transcription initiation from the HIV-1 promoter. These inhibitors block transcription initiation at a step that lies downstream of nucleosome remodeling and affects RNA polymerase II recruitment to the viral promoter. These results suggest that the sulfonation pathway acts by a novel mechanism to regulate efficient virus transcription initiation during reactivation from latency, and further that augmentation of this pathway could be therapeutically useful. PMID:25310595

  6. Novel mouse models for understanding HIV-1 pathogenesis.

    PubMed

    Joseph, Aviva; Sango, Kaori; Goldstein, Harris

    2009-01-01

    Small animal models in which in vivo HIV-1 infection, pathogenesis, and immune responses can be studied would permit both basic research on the biology of the disease, as well as a system to rapidly screen developmental therapeutics and/or vaccines. To date, the most widely-used models have been the severe combined immunodeficient (SCID)-hu (also known as the thy/liv SCID-hu) and the huPBL-SCID mouse models. Recently three new models have emerged, i.e., the intrasplenic huPBL/SPL-SCID model, the NOD/SCID/IL2Rgamma(null) mouse model, and the Rag2(-/-)gamma(c) (-/-) mouse model. Details on the construction, maintenance and HIV-1 infection of these models are discussed. PMID:19020834

  7. Broad-Spectrum Antiviral Therapeutics

    E-print Network

    Rider, Todd H.

    Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded ...

  8. How to Use Equipment Therapeutically.

    ERIC Educational Resources Information Center

    Bowne, Douglas

    1986-01-01

    Shares therapeutic and economic practices surrounding equipment used in New York's Higher Horizons adventure program of therapy for troubled youth. Encourages educators, therapists, and administrators to explore relationship between equipment selection, program goals, and clients. (NEC)

  9. DCTD — Developmental Therapeutics Program (DTP)

    Cancer.gov

    Skip to Content Click here to view the Site Map Home | Sitemap | Contact DCTD Search this site Developmental Therapeutics Program (DTP) Introduction Major Ongoing Initiatives Current Funding Opportunities Tools and Resources Scientific Advances DCTD

  10. Therapeutic Hypothermia: The Safar Vision

    PubMed Central

    Drabek, Tomas; Tisherman, Samuel A.

    2009-01-01

    Abstract At the 2nd International Brain Hypothermia conference, in Miami, the late Dr. Peter Safar was honored for his many contributions to the field of therapeutic hypothermia. Therapeutic hypothermia played a central role in his overall vision for optimized resuscitation and neurointensive care, across a large number of potential insults. The successful use of therapeutic hypothermia in comatose patients after cardiac arrest, for example, was already included in the historic first “ABCs” of resuscitation, published by Safar in 1964. This review addresses key historical events in the development and implementation of therapeutic hypothermia across a number of central nervous system insults. A discussion of future potential uses of this therapy in a variety of applications as part of the Safar vision is also presented. PMID:19271966

  11. Glycosylation of recombinant antibody therapeutics.

    PubMed

    Jefferis, Royston

    2005-01-01

    The adaptive immune system has the capacity to produce antibodies with a virtually infinite repertoire of specificities. Recombinant antibodies specific for human targets are established in the clinic as therapeutics and represent a major new class of drug. Therapeutic efficacy depends on the formation of complexes with target molecules and subsequent activation of downstream biologic effector mechanisms that result in elimination of the target. The activation of effector mechanisms is dependent on structural characteristics of the antibody molecule that result from posttranslational modifications, in particular, glycosylation. The production of therapeutic antibody with a consistent human glycoform profile has been and remains a considerable challenge to the biopharmaceutical industry. Recent research has shown that individual glycoforms of antibody may provide optimal efficacy for selected outcomes. Thus a further challenge will be the production of a second generation of antibody therapeutics customized for their clinical indication. PMID:15903235

  12. Cardiovascular applications of therapeutic ultrasound.

    PubMed

    Nazer, Babak; Gerstenfeld, Edward P; Hata, Akiko; Crum, Lawrence A; Matula, Thomas J

    2014-04-01

    Ultrasound (US) has gained widespread use in diagnostic cardiovascular applications. At amplitudes and frequencies typical of diagnostic use, its biomechanical effects on tissue are largely negligible. However, these parameters can be altered to harness US's thermal and non-thermal effects for therapeutic indications. High-intensity focused ultrasound (HIFU) and extracorporeal shock wave therapy (ECWT) are two therapeutic US modalities which have been investigated for treating cardiac arrhythmias and ischemic heart disease, respectively. Here, we review the biomechanical effects of HIFU and ECWT, their potential therapeutic mechanisms, and pre-clinical and clinical studies demonstrating their efficacy and safety limitations. Furthermore, we discuss other potential clinical applications of therapeutic US and areas in which future research is needed. PMID:24297498

  13. Deworming helminth co-infected individuals for delaying HIV disease progression

    PubMed Central

    Walson, Judd L; Herrin, Bradley R; John-Stewart, Grace

    2009-01-01

    Background The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings where other infectious diseases, such as helminth infections, also are highly prevalent. There are biologically plausible reasons for possible effects of helminth infection in HIV-1-infected individuals, and findings from multiple studies suggest that helminth infection may adversely affect HIV-1 progression. Since initial publication of this review (Walson 2007), additional data from randomized controlled trials (RCTs) has become available. We sought to evaluate all currently available evidence to determine if treatment of helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression. Objectives To determine if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression. Search strategy In this 2008 update, we searched online for published and unpublished studies in The Cochrane Library, MEDLINE, EMBASE, CENTRAL, and AIDSEARCH. We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted authors of included studies. Selection criteria We searched for RCTs and quasi-RCTs that compared HIV-1 progression as measured by changes in CD4 count, viral load, or clinical disease progression in HIV-1 infected individuals receiving anti-helminthic therapy. Data collection and analysis Data regarding changes in CD4 count, HIV-1 RNA levels, and/or clinical staging after treatment of helminth co-infection were extracted from identified studies. Main results Of 7,019 abstracts identified (6,384 from original searches plus 635 from updated searches), 17 abstracts were identified as meeting criteria for potential inclusion (15 from previous review plus an additional two RCTs). After restricting inclusion to RCTs, a total of three studies were eligible for inclusion in this updated review. All three trials showed individual beneficial effects of helminth eradication on markers of HIV-1 disease progression (HIV-1 RNA and/or CD4 counts). When data from these trials were pooled, the analysis demonstrated significant benefit of deworming on both plasma HIV-1 RNA and CD4 counts. Authors’ conclusions To date, three RCTs have evaluated the effects of deworming on markers of HIV-1 disease progression in helminth and HIV-1 co-infected individuals. All trials demonstrate benefit in attenuating or reducing plasma viral load and/or increasing CD4 counts. When taken together, there is evidence of benefit for deworming HIV-1 co-infected adults. Given that these studies evaluated different helminth species and different interventions, further trials are warranted to evaluate species-specific effects and to document long-term clinical outcomes following deworming. PMID:19588389

  14. Therapeutic Vaccines for Chronic Infections

    NASA Astrophysics Data System (ADS)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  15. DCTD — Developmental Therapeutics Program (DTP)

    Cancer.gov

    To address the mechanistic gap that occurs because of difficulties in determining the effect of a therapeutic intervention on its putative site of action in patients, in 2005, the DTP Toxicology and Pharmacology Branch was expanded to include NCTVL. This laboratory will elucidate novel methodologies in target tissues specifically applicable to human cancer clinical trials. These methodologies will demonstrate the therapeutic effects of small molecule anticancer agents on specific cellular pathways of interest.

  16. Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly

    PubMed Central

    Khamaikawin, Wannisa; Saoin, Somphot; Nangola, Sawitree; Chupradit, Koollawat; Sakkhachornphop, Supachai; Hadpech, Sudarat; Onlamoon, Nattawat; Ansari, Aftab A; Byrareddy, Siddappa N; Boulanger, Pierre; Hong, Saw-See; Torbett, Bruce E; Tayapiwatana, Chatchai

    2015-01-01

    Designed molecular scaffolds have been proposed as alternative therapeutic agents against HIV-1. The ankyrin repeat protein (AnkGAG1D4) and the zinc finger protein (2LTRZFP) have recently been characterized as intracellular antivirals, but these molecules, used individually, do not completely block HIV-1 replication and propagation. The capsid-binder AnkGAG1D4, which inhibits HIV-1 assembly, does not prevent the genome integration of newly incoming viruses. 2LTRZFP, designed to target the 2-LTR-circle junction of HIV-1 cDNA and block HIV-1 integration, would have no antiviral effect on HIV-1-infected cells. However, simultaneous expression of these two molecules should combine the advantage of preventive and curative treatments. To test this hypothesis, the genes encoding the N-myristoylated Myr(+)AnkGAG1D4 protein and the 2LTRZFP were introduced into human T-cells, using a third-generation lentiviral vector. SupT1 cells stably expressing 2LTRZFP alone or with Myr(+)AnkGAG1D4 showed a complete resistance to HIV-1 in viral challenge. Administration of the Myr(+)AnkGAG1D4 vector to HIV-1-preinfected SupT1 cells resulted in a significant antiviral effect. Resistance to viral infection was also observed in primary human CD4+ T-cells stably expressing Myr(+)AnkGAG1D4, and challenged with HIV-1, SIVmac, or SHIV. Our data suggest that our two anti-HIV-1 molecular scaffold prototypes are promising antiviral agents for anti-HIV-1 gene therapy. PMID:26305555

  17. HIV Protease Inhibitors Disrupt Lipid Metabolism by Activating Endoplasmic Reticulum Stress and Inhibiting Autophagy Activity in Adipocytes

    PubMed Central

    Zha, Beth S.; Wan, Xiaoshan; Zhang, Xiaoxuan; Zha, Weibin; Zhou, Jun; Wabitsch, Martin; Wang, Guangji; Lyall, Vijay; Hylemon, Phillip B.; Zhou, Huiping

    2013-01-01

    Background HIV protease inhibitors (PI) are core components of Highly Active Antiretroviral Therapy (HAART), the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER) stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome. Methodology and Principal Findings Cultured and primary mouse adipocytes and human adipocytes were used to examine the effect of frequently used HIV PIs in the clinic, lopinavir/ritonavir, on adipocyte differentiation and further identify the underlying molecular mechanism of HIV PI-induced dysregulation of lipid metabolism in adipocytes. The results indicated that lopinavir alone or in combination with ritonavir, significantly activated the ER stress response, inhibited cell differentiation, and induced cell apoptosis in adipocytes. In addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy activity. We also identified through the use of primary adipocytes of CHOP?/? mice that CHOP, the major transcriptional factor of the ER stress signaling pathway, is involved in lopinavir/ritonavir-induced inhibition of cell differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress appears to be associated with inhibition of autophagy activity in adipocytes. Conclusion and Significance Activation of ER stress and impairment of autophagy activity are involved in HIV PI-induced dysregulation of lipid metabolism in adipocytes. The key components of ER stress and autophagy signaling pathways are potential therapeutic targets for HIV PI-induced metabolic side effects in HIV patients. PMID:23533630

  18. The HIV Epidemic: High-Income Countries.

    PubMed

    Vermund, Sten H; Leigh-Brown, Andrew J

    2012-05-01

    The HIV epidemic in higher-income nations is driven by receptive anal intercourse, injection drug use through needle/syringe sharing, and, less efficiently, vaginal intercourse. Alcohol and noninjecting drug use increase sexual HIV vulnerability. Appropriate diagnostic screening has nearly eliminated blood/blood product-related transmissions and, with antiretroviral therapy, has reduced mother-to-child transmission radically. Affected subgroups have changed over time (e.g., increasing numbers of Black and minority ethnic men who have sex with men). Molecular phylogenetic approaches have established historical links between HIV strains from central Africa to those in the United States and thence to Europe. However, Europe did not just receive virus from the United States, as it was also imported from Africa directly. Initial introductions led to epidemics in different risk groups in Western Europe distinguished by viral clades/sequences, and likewise, more recent explosive epidemics linked to injection drug use in Eastern Europe are associated with specific strains. Recent developments in phylodynamic approaches have made it possible to obtain estimates of sequence evolution rates and network parameters for epidemics. PMID:22553497

  19. The HIV Epidemic: High-Income Countries

    PubMed Central

    Vermund, Sten H.; Leigh-Brown, Andrew J.

    2012-01-01

    The HIV epidemic in higher-income nations is driven by receptive anal intercourse, injection drug use through needle/syringe sharing, and, less efficiently, vaginal intercourse. Alcohol and noninjecting drug use increase sexual HIV vulnerability. Appropriate diagnostic screening has nearly eliminated blood/blood product-related transmissions and, with antiretroviral therapy, has reduced mother-to-child transmission radically. Affected subgroups have changed over time (e.g., increasing numbers of Black and minority ethnic men who have sex with men). Molecular phylogenetic approaches have established historical links between HIV strains from central Africa to those in the United States and thence to Europe. However, Europe did not just receive virus from the United States, as it was also imported from Africa directly. Initial introductions led to epidemics in different risk groups in Western Europe distinguished by viral clades/sequences, and likewise, more recent explosive epidemics linked to injection drug use in Eastern Europe are associated with specific strains. Recent developments in phylodynamic approaches have made it possible to obtain estimates of sequence evolution rates and network parameters for epidemics. PMID:22553497

  20. [Mutative processes of structural skills in therapeutic-pedagogic contexts].

    PubMed

    Traxl, Bernd

    2011-01-01

    Therapeutic-pedagogic processes are above all orientated on cognitive, perceptive, mnestic or motoric deficits, particularly with children and adolescents. Thereby psychodynamic dimensions and structural skills are neglected. I want to focus on this underrepresented domain and place it in the centre of the therapeutic-pedagogic interest. The OPD-2 is currently the most sophisticated raster of psychic structure and so I use it for my theoretic frame of reference. The specific criteria are described to work out the concrete support in the context of therapeutic-pedagogic. On the basis of a short case study, I illustrate the developmental and modification possibilities to corroborate my belief, that therapeutic-pedagogic relations advance mutative process in the range of structural skills. PMID:21425636