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Sample records for hiv therapeutic possibilities

  1. Fragment Screening and HIV Therapeutics

    PubMed Central

    Bauman, Joseph D.; Patel, Disha; Arnold, Eddy

    2013-01-01

    Fragment screening has proven to be a powerful alternative to traditional methods for drug discovery. Biophysical methods, such as X-ray crystallography, NMR spectroscopy, and surface plasmon resonance, are used to screen a diverse library of small molecule compounds. Although compounds identified via this approach have relatively weak affinity, they provide a good platform for lead development and are highly efficient binders with respect to their size. Fragment screening has been utilized for a wide-range of targets, including HIV-1 proteins. Here, we review the fragment screening studies targeting HIV-1 proteins using X-ray crystallography or surface plasmon resonance. These studies have successfully detected binding of novel fragments to either previously established or new sites on HIV-1 protease and reverse transcriptase. In addition, fragment screening against HIV-1 reverse transcriptase has been used as a tool to better understand the complex nature of ligand binding to a flexible target. PMID:21972022

  2. [Therapeutic possibilities after traumatic experiences].

    PubMed

    Kapfhammer, Hans-Peter

    2008-12-01

    Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) are frequent, but not obligatory psychological sequelae following trauma. A major subgroup of patients face a chronic course of illness associated with an increased psychiatric comorbidity and significant impairments in psychosocial adaptation. The typical psychopathological symptoms of ASD and PTSD are best described within a multifactorial model integrating both neurobiological and psychosocial influences. The complex etiopathogenesis of acute and posttraumatic stress disorder favours multimodal approaches in the treatment. Differential psychotherapeutic and pharmacological strategies are available. In a critical survey on empirical studies, psychological debriefing cannot be considered as a positive approach to be recommended as general preventive measure during the immediate posttraumatic phase. Positive effects of cognitive-behavioral interventions can be established for ASD. Psychodynamic psychotherapy, cognitive-behavioral therapy and EMDR show promising results in the treatment of PTSD. Major clinical restrictions of patient sampling within special research facilities, however, do not allow an unconditional generalization of these data to psychiatric routine care. In an empirical analysis the SSRIs are the most and best studied medications for ASD and PTSD. In comparison to tricyclic antidepressants SSRIs demonstrate a broader spectrum of therapeutic effects and are better tolerated. The substance classes of SSNRI, DAS, SARI and NaSSA are to be considered as drugs of second choice. They promise a therapeutic efficacy equivalent to the SSRIs, being investigated so far only in open studies. MAO-inhibitors may dispose of a positive therapeutic potential, their profile of side effects must be respected, however. Mood stabilizers and atypical neuroleptics may be used first and foremost in add-on strategies. Benzodiazepines should be used only with increased caution for a short time in states of

  3. [Dental caries--therapeutic possibilities].

    PubMed

    Perić, Tamara; Marković, Dejan; Zivković, Slavoljub

    2008-01-01

    Contemporary tendencies in dentistry are based on the concept of maximal protection of healthy tooth tissues. Caries removal has been done traditionally with mechanical rotary instruments that are fast and precise. However, conventional cavity preparation has potential adverse effects to the pulp due to heat, pressure and vibrations. Moreover, drilling often causes pain and requires local anaesthesia, and these procedures are frequently perceived as unpleasant. Etiology, development and prevention of dental caries are better understood today and new restorative materials that bond micromechanically and/or chemically to dental tissues have been introduced. Thus, development of a new, less destructive caries removal technique is allowed. In the last decades, many alternative methods have been introduced in an attempt to replace rotary instruments. These are claimed to be efficient and selective for diseased tissues and to offer comfortable treatment to the patients. New methods include air abrasion, air polishing, ultrasonic, polymer burs, enzymes, systems for chemo-mechanical caries removal, and lasers. The aim of this paper was to discuss various caries removal techniques and possibilities of their use in clinical practice. Based on the literature review it can be concluded that none of the new caries removal methods can completely replace conventional rotary instruments.

  4. Approaches to preventative and therapeutic HIV vaccines.

    PubMed

    Gray, Glenda E; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

    2016-04-01

    Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Non-efficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials.

  5. [Splenic abscess: etiology, diagnosis and possible therapeutics].

    PubMed

    Burnier, C; Ribordy-Baudat, V; Lamy, O

    2007-10-31

    We report the case of a 28-year-old intravenous drug abuser under quadritherapy for stage C3 AIDS and with past history of infectious endocarditis. He was admitted with a diminished general condition, weight loss, progressive unbearable abdominal pain and vomiting, without fever. An inflammatory syndrome is noted and imaging reveals a voluminous splenic abscess. Conservative treatment is initiated with repetitive drainages and intravenous antibiotics. Aetiologies, diagnosis and possible therapeutics of splenic abscesses are discussed. PMID:18018950

  6. Fighting HIV/AIDS: is success possible?

    PubMed Central

    Okware, S.; Opio, A.; Musinguzi, J.; Waibale, P.

    2001-01-01

    The fight against HIV/AIDS poses enormous challenges worldwide, generating fears that success may be too difficult or even impossible to attain. Uganda has demonstrated that an early, consistent and multisectoral control strategy can reduce both the prevalence and the incidence of HIV infection. From only two AIDS cases in 1982, the epidemic in Uganda grew to a cumulative 2 million HIV infections by the end of 2000. The AIDS Control Programme established in 1987 in the Ministry of Health mounted a national response that expanded over time to reach other relevant sectors under the coordinating role of the Uganda AIDS Commission. The national response was to bring in new policies, expanded partnerships, increased institutional capacity for care and research, public health education for behaviour change, strengthened sexually transmitted disease (STD) management, improved blood transfusion services, care and support services for persons with HIV/AIDS, and a surveillance system to monitor the epidemic. After a decade of fighting on these fronts, Uganda became, in October 1996, the first African nation to report declining trends in HIV infection. Further decline in prevalence has since been noted. The Medical Research Council (UK) and the Uganda Virus Research Institute have demonstrated declining HIV incidence rates in the general population in the Kyamulibwa in Masaka Districts. Repeat knowledge, attitudes, behaviour and practice studies have shown positive changes in the priority prevention indicators. The data suggest that a comprehensive national response supported by strong political commitment may be responsible for the observed decline. Other countries in sub-Saharan Africa can achieve similar results by these means. Since success is possible, anything less is unacceptable. PMID:11799443

  7. Sunitinib Possible Sex-Divergent Therapeutic Outcomes.

    PubMed

    Segarra, Ignacio; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L

    2016-10-01

    Sunitinib is a tyrosine kinase inhibitor used for the treatment of renal cell carcinoma and metastatic brain tumors. Preclinical pharmacokinetic studies have shown higher sunitinib hepatic and brain exposure in female mice and higher sunitinib kidney concentrations in male mice. We explored whether sex-divergent tissue pharmacokinetics may anticipate sex-divergent therapeutic and toxicology responses in male and female patients. The review of the available scientific literature identified case reports, case series reports, clinical trials, and other studies associating sex with sunitinib outcomes. The results suggest male patients may respond better to renal cell carcinoma treatment and female patients may have better brain tumor treatment outcomes but a higher incidence of adverse events. Although more high-quality evidence is needed, these results, as anticipated by the preclinical data, may indicate possible sunitinib sex-divergent therapeutic outcomes in patients. In addition, we propose the systematic analysis of sex-based outcomes in clinical trial reports and their inclusion and review in the ethics committees and review boards to prevent, amongst others, patient burden in upcoming clinical trials. PMID:27318944

  8. HIV therapeutic vaccines: moving towards a functional cure.

    PubMed

    Mylvaganam, Geetha H; Silvestri, Guido; Amara, Rama Rao

    2015-08-01

    Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV 'residual disease' that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vaccines (i.e., active immunization strategies using HIV-derived immunogens) as well as the use of checkpoint blockers such as anti-PD-1 antibodies. These approaches appear promising as key components of complex therapeutic strategies aimed at curing HIV infection.

  9. Which therapeutic strategy will achieve a cure for HIV-1?

    PubMed

    Cillo, Anthony R; Mellors, John W

    2016-06-01

    Strategies to achieve a cure for HIV-1 infection can be broadly classified into three categories: eradication cure (elimination of all viral reservoirs), functional cure (immune control without reservoir eradication), or a hybrid cure (reservoir reduction with improved immune control). The many HIV-1 cure strategies being investigated include modification of host cells to resist HIV-1, engineered T cells to eliminate HIV-infected cells, broadly HIV-1 neutralizing monoclonal antibodies, and therapeutic vaccination, but the 'kick and kill' strategy to expose latent HIV-1 with latency reversing agents (LRAs) and kill the exposed cells through immune effector functions is currently the most actively pursued. It is unknown, however, whether LRAs can deplete viral reservoirs in vivo or whether current LRAs are sufficiently safe for clinical use.

  10. Gene therapy: a possible future standard for HIV care.

    PubMed

    Abou-El-Enein, Mohamed; Bauer, Gerhard; Reinke, Petra

    2015-07-01

    Despite undeniable accomplishments in developing cell and gene therapeutic strategies to combat HIV infection, key social, economic, and policy-related challenges still need to be overcome for any future commercialization efforts of these novel therapies to be successful. Here, we address these challenges and structure a framework for eradicating HIV/AIDS using gene therapy.

  11. [Sialendoscopy: diagnostic possibilities and therapeutic options].

    PubMed

    Boehm, A; Faure, F; Dietz, A

    2008-05-01

    With the improved availability of sialendoscopy (SE) during the last decade the therapeutical concept for sialoliths has remarkably changed. Due to the introduction of SE the diagnostic opportunities could be extended. Before introduction of SE, the diagnostic was focused only on the existence and size of sialoliths. Now, questions like consistence of sialoliths and their mobility in the duct system, stenoses with sialolithiasis-like symptoms as well as the evaluation of the remaining secretory capacity of the involved gland became relevant for the therapeutic decision. Furthermore there are an increasing number of therapeutic opportunities available. For some of these techniques long term experiences are missing so far. On the basis of the review of the current literature and a retrospective analysis of 256 own patients the different techniques and their indication are described. The combination of different therapeutical options of the SE and the still established extracorporal shockwave lithotripsy (ESWL) results in an important reduction of glandular resection in patients with sialolithiasis. Thus, the rate of glandular resection for the glandular submandibular can be decreased to 5 % and for the glandular parotis to 1 %. In summary, the most effective way is a stepwise approach based on the diagnostic tools of SE and including the laser-lithotripsy and ESWL in the treatment of sialolithiasis.

  12. Healing Classrooms: Therapeutic Possibilities in Academic Writing

    ERIC Educational Resources Information Center

    Batzer, Benjamin

    2016-01-01

    This article asks us to consider what the process of healing and composition pedagogy have to learn from each other. More specifically, it identifies how the therapeutic potential of writing, which has been largely neglected in the academy in recent years, can influence the ways we teach transferable writing skills. The article considers how…

  13. The next therapeutic challenge in HIV: polypharmacy.

    PubMed

    Edelman, E Jennifer; Gordon, Kirsha S; Glover, Janis; McNicholl, Ian R; Fiellin, David A; Justice, Amy C

    2013-08-01

    With the adoption of combination antiretroviral therapy (ART), most HIV-infected individuals in care are on five or more medications and at risk of harm from polypharmacy, a risk that likely increases with number of medications, age, and physiologic frailty. Established harms of polypharmacy include decreased medication adherence and increased serious adverse drug events, including organ system injury, hospitalization, geriatric syndromes (falls, fractures, and cognitive decline) and mortality. The literature on polypharmacy among those with HIV infection is limited, and the literature on polypharmacy among non-HIV patients requires adaptation to the special issues facing those on chronic ART. First, those aging with HIV infection often initiate ART in their 3rd or 4th decade of life and are expected to remain on ART for the rest of their lives. Second, those with HIV may be at higher risk for age-associated comorbid disease, further increasing their risk of polypharmacy. Third, those with HIV may have an enhanced susceptibility to harm from polypharmacy due to decreased organ system reserve, chronic inflammation, and ongoing immune dysfunction. Finally, because ART is life-extending, nonadherence to ART is particularly concerning. After reviewing the relevant literature, we propose an adapted framework with which to address polypharmacy among those on lifelong ART and suggest areas for future work. PMID:23740523

  14. [Is it possible to cure HIV infection?].

    PubMed

    Gutiérrez, Carolina; Madrid, Nadia P; Moreno, Santiago

    2015-09-01

    Antiretroviral therapy has significantly improved the life expectancy in HIV-infected people, but it cannot cure the disease by itself. Several barriers have been identified for the cure of HIV infection, including a reservoir of latently infected cells, persistent viral replication in tissues, and anatomical sanctuaries. The main strategy proposed for the cure of HIV consists on the administration of drugs that, through the reactivation of latent HIV, would eliminate the cell reservoir. Ongoing clinical trials have shown the proof of concept, but the efficacy of these drugs in decreasing the reservoir size has not been proved so far.

  15. [Is it possible to cure HIV infection?].

    PubMed

    Gutiérrez, Carolina; Madrid, Nadia P; Moreno, Santiago

    2015-09-01

    Antiretroviral therapy has significantly improved the life expectancy in HIV-infected people, but it cannot cure the disease by itself. Several barriers have been identified for the cure of HIV infection, including a reservoir of latently infected cells, persistent viral replication in tissues, and anatomical sanctuaries. The main strategy proposed for the cure of HIV consists on the administration of drugs that, through the reactivation of latent HIV, would eliminate the cell reservoir. Ongoing clinical trials have shown the proof of concept, but the efficacy of these drugs in decreasing the reservoir size has not been proved so far. PMID:26365737

  16. Nanotechnology as a New Therapeutic Approach to Prevent the HIV-Infection of Treg Cells

    PubMed Central

    Jaramillo-Ruiz, Didiana; De La Mata, Francisco Javier; Gómez, Rafael; Correa-Rocha, Rafael; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    Background HIV-1 has proved to infect regulatory T cells (Treg) modifying their phenotype and impairing their suppressive capacity. As Treg cells are a crucial component in the preservation of the immune homeostasis, we researched that the antiviral capacity of carboxilan dendrimers prevents the HIV-1 infection of Treg and their effects. The phenotype and suppressive capacity of Treg treated or non-treated with carbosilane dendrimers were studied by flow cytometry. Treated and non-treated Treg from healthy donors were infected with HIV-1NL4.3. The infection of Treg cells by HIV-1, and protective effect of two dendrimers were determined by measuring antigen p24gag in the supernatant of the culture and intracellular. Results The Treg cells were treated with cationic and anionic carbosilane dendrimers. The results showed that both dendrimers did not modify the phenotype and functionality of Treg cells compared with non- treated Treg cells. Anionic dendrimers showed high biocompatibility with normal activity of the Treg cells and in antiviral assays. These dendrimers were highly active against HIV-1 preventing the infection of Treg, and were able to protect the Treg from the Foxp3 downregulation induced by the HIV-1 infection. Conclusions This is the first work showing that the in vitro use of anionic dendrimers prevent the HIV-1 replication and the infection of expanded Treg cells in culture, which raises the possibility to use Treg cells therapeutically in HIV-1-infected subjects. PMID:26785250

  17. Community-based therapeutic care in HIV-affected populations.

    PubMed

    Sadler, Kate; Bahwere, Paluku; Guerrero, Saul; Collins, Steve

    2006-01-01

    Community-based therapeutic care (CTC) is a community-based model for delivering care to malnourished people. CTC aims to treat the majority of severely malnourished people at home, rather than in therapeutic feeding centres. This paper describes the potential of the CTC approach to provide effective care and support for people living with HIV and AIDS (PLWHA). CTC includes many of the components of a home-based care model for PLWHA. It provides outpatient treatment for common complications of HIV and AIDS, such as acute malnutrition and simple infections, and an energy-dense ready-to-use food that could be made with the appropriate balance of micronutrients for the HIV-infected patient. Through the de-centralisation of outpatient treatment sites, CTC improves accessibility by moving treatment closer to people's homes and helps to promote the sustainability of care by building on the capacity of existing health infrastructure and staff. The CTC model contains many features that are appropriate for the care and support of HIV-affected people and, in its present form, can provide effective physical care for many HIV-affected individuals. We are currently working to adapt the CTC model to make it more suitable for the support of PLWHA in the longer term. PMID:16216293

  18. Thalidomide and HIV: several possible uses.

    PubMed

    Smith, D

    1995-04-21

    Thalidomide is currently under investigation for its proposed value in treating a number of AIDS-related conditions. Banned in the 1960s because it was found to cause birth defects, thalidomide has been found to inhibit tumor necrosis factor (TNF), a cytokine associated with the development of aphthous ulcers, dementia, fevers, fatigue and wasting, as well as enhanced HIV replication. Development rights to use the drug are owned by Celgene, which calls the drug Synovir. Celgene is currently developing several new TNF inhibitors which are chemically analogous to thalidomide but which might be safer or more effective. Currently, at least 38 sites around the country are testing thalidomide for HIV-related ulcers, and six trial sites are testing for wasting syndrome. Thalidomide is in trials for the treatment of primary HIV infection at five sites. However, it is unclear whether thalidomide does more to curb HIV activity beyond inhibiting TNF. Thalidomide trials have been slow to recruit, therefore buyers clubs are working to make the drug available through their services.

  19. Therapeutic genes for anti-HIV/AIDS gene therapy.

    PubMed

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  20. Intracellular defenses against HIV, viral evasion and novel therapeutic approaches.

    PubMed

    Lever, Robert A; Lever, Andrew M L

    2011-06-01

    Human immunodeficiency virus (HIV), the causative agent of AIDS, is a retrovirus. It is estimated that, while in the cell, it interacts with almost 10% of cellular proteins. Several of these have evolved to protect the cell from infection with retroviruses and are known as "restriction factors". Restriction factors tell us much about how the virus functions and open up new paradigms for exploring novel antiviral therapeutics. This article gives an update on the three best studied restriction factors, their putative mechanisms of action and how the virus has overcome their effects, together with an indication of novel therapeutic approaches based on this knowledge.

  1. 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

  2. Fairy tales as a trance experience: possible therapeutic uses.

    PubMed

    Stevens-Guille, M E; Boersma, F J

    1992-04-01

    The psychological literature contains little documentation of the therapeutic use of fairy tales. We suggest that fairy tales are uniquely suitable for hypnotherapy and for helping clients reframe existential issues. We propose that the structure of fairy tales allows the meaning of the story to be applied personally and that they also stimulate unconscious search. We examine the way in which hypnosis is achieved when fairy tales are read to children, as well as possible therapeutic uses of this learning set in therapy with both children and adults. We conclude by suggesting that fairy tales need to be given serious consideration as an alternative therapeutic trance procedure.

  3. An HIV-1 transmission case possibly associated with manicure care.

    PubMed

    Matsuda, Elaine Monteiro; Coelho, Luana Portes Ozório; Pimentel, Victor Figueiredo; Onias, Humberto Barjud; Brigido, Luís Fernando de Macedo

    2014-11-01

    A recently diagnosed 22-year-old female with no history of transmission risk factors prompted a thorough investigation of possible alternative risk factors. As the patient had evidence of advanced disease and laboratory data compatible with long-standing infection, past events were reviewed. About 10 years ago the patient shared manicure utensils with an older cousin, later known to be HIV infected; this prompted the phylogenetic analysis of the HIV sequences of both patients. Phylogenetic analyses of partial HIV-1 polymerase and envelope sequences from both patients revealed highly related sequences, with an estimated common ancestor date (about 11 years ago) that coincided with the putative sharing of manicure instruments, during a time in which the cousin was not virally suppressed. Taken together, the information about the infection of this patient suggests the use of shared manicure instruments as an alternative route of fomite HIV-1 transmission.

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

    PubMed Central

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

    2012-01-01

    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 =418; 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

  5. Virus Maturation as a Novel HIV-1 Therapeutic Target

    PubMed Central

    Adamson, Catherine S.; Salzwedel, Karl; Freed, Eric O.

    2009-01-01

    Development of novel therapeutic targets against HIV-1 is a high research priority due to the serious clinical consequences associated with acquisition of resistance to current antiretroviral drugs. The HIV-1 structural protein Gag represents a potential novel therapeutic target as it plays a central role in virus particle production, yet is not targeted by any of the currently approved antiretroviral drugs. The Gag polyprotein precursor multimerizes to form immature particles that bud from the infected cell. Concomitant with virus release, the Gag precursor undergoes proteolytic processing by the viral protease to generate the mature Gag proteins, which include capsid (CA). Once liberated from the Gag polyprotein precursor, CA molecules interact to reassemble into a condensed conical core, which organizes the viral RNA genome and several viral proteins to facilitate virus replication in the next round of infection. Correct Gag proteolytic processing and core assembly are therefore essential for virus infectivity. In this review, we discuss novel strategies to inhibit maturation by targeting proteolytic cleavage sites in Gag or CA-CA interactions required for core formation. The identification and development of lead maturation inhibitors are highlighted. PMID:19534569

  6. 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

  7. 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.

  8. HIV Testing Among Teens Attending Therapeutic Schools: Having a Personal Source of Information About HIV/AIDS Matters!

    PubMed

    Swenson, Rebecca R; Houck, Christopher; Sarfati, David; Emerson, Erin; Donenberg, Geri; Brown, Larry K

    2015-06-01

    Being informed and using positive coping strategies are associated with engaging in health-promoting behaviors. We assessed whether the type of information source about HIV (personal or impersonal) and coping strategies (optimism, avoidance, or emotion-focused) are associated with HIV testing among adolescents attending therapeutic schools. Participants were 417 adolescents, ages 13-19, who attended one of 20 therapeutic day schools for emotionally/behaviorally disordered youth in two US cities (Providence, RI and Chicago, IL) and completed a baseline assessment for an HIV prevention study. Among adolescents in the study, 29% reported having been tested for HIV. Adolescents were more likely to have been tested if they were older, female, Hispanic, identified as non-heterosexual, came from lower SES households, and had recently had unprotected sex. Additionally, youth who endorsed greater use of optimistic thinking and emotion-focused coping, and who reported having been informed about HIV by more personal sources, were also more likely to have been tested for HIV. In a multivariate analysis, having had recent unprotected sex and having more personal sources of information about HIV/AIDS were independently associated with HIV testing. Study findings suggest that, controlling for sociodemographic background, sexual risk behavior, and coping strategy, HIV testing among adolescents with emotional and behavioral problems may be increased when adolescents learn about HIV/AIDS from personal sources such as their healthcare providers, family, and friends.

  9. HIV testing among teens attending therapeutic schools: Having a personal source of information about HIV/AIDS matters!

    PubMed Central

    Swenson, Rebecca R.; Houck, Christopher; Sarfati, David; Emerson, Erin; Donenberg, Geri; Brown, Larry K.

    2015-01-01

    Being informed and using positive coping strategies are associated with engaging in health-promoting behaviors. We assessed whether the type of information source about HIV (personal or impersonal) and coping strategies (optimism, avoidance, or emotion-focused) are associated with HIV testing among adolescents attending therapeutic schools. Participants were 417 adolescents, ages 13 to 19, who attended one of 20 therapeutic day schools for emotionally/behaviorally disordered youth in two U.S. cities (Providence, RI and Chicago, IL) and completed a baseline assessment for an HIV prevention study. Among adolescents in the study, 29% reported having been tested for HIV. Adolescents were more likely to have been tested if they were older, female, Hispanic, identified as non-heterosexual, came from lower SES households, and had recently had unprotected sex. Additionally, youth who endorsed greater use of optimistic thinking and emotion-focused coping, and who reported having been informed about HIV by more personal sources, were also more likely to have been tested for HIV. In a multivariate analysis, having had recent unprotected sex and having more personal sources of information about HIV/AIDS were independently associated with HIV testing. Study findings suggest that, controlling for sociodemographic background, sexual risk behavior, and coping strategy, HIV testing among adolescents with emotional and behavioral problems may be increased when adolescents learn about HIV/AIDS from personal sources such as their healthcare providers, family, and friends. PMID:25656380

  10. T cell tolerance in transplantation: possibilities for therapeutic intervention.

    PubMed

    Cobbold, Stephen P

    2002-10-01

    It is now possible to induce donor-specific transplantation tolerance in adult rodents using a number of therapeutic strategies. These include the use of non-depleting monoclonal antibodies against T cell co-receptor and costimulation molecules, and immunisation with tolerogenic antigen-presenting cells. It is a common finding to all of these models of peripheral tolerance, as well as to various mouse models of autoimmune disease, that regulatory CD4(+) T cells are the principle mediators. There are currently no specific markers for regulatory T cells and their activity has been associated with different T cell subsets defined by the expression of activation markers, such as CD25 and cytotoxic T lymphocyte antigen-4 (CTLA-4), or anti-inflammatory cytokines, such as IL-10 and TGF-beta. Differential gene expression analyses have been used to identify potential new markers for regulatory T cells and to find novel targets for therapeutic manipulation of the immune system. The challenge now is to understand the biological principles that allow such immune reprogramming so that they can be safely applied to clinical situations. PMID:12387682

  11. [Toxoplasmosis in pregnancy. Diagnosis and new therapeutic possibilities].

    PubMed

    Mirlesse, V; Jacquemard, F; Daffos, F

    1993-02-20

    Congenital toxoplasmosis results from contamination of the foetus by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close surveillance of mothers at risk. During the last few years, numerous advances have been made in the diagnosis and treatment of toxoplasmosis. Its diagnosis in the mother is now more reliable due to improvements in serological techniques, while in the foetus the use of foetal vascular techniques has made it possible to detect those who are infected. Owing to a new and effective therapeutic method certain foetuses can now be treated successfully in utero, so that induced abortion is reserved to cases with severe and early toxoplasmosis. The contribution of new molecular biology techniques to advances in this ever moving field is explained.

  12. Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future Directions.

    PubMed

    Polizzotto, Mark N; Chen, Grace; Tressler, Randall L; Godfrey, Catherine

    2015-09-01

    Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the plasma, latent replication-competent HIV persists indefinitely in long-lived cells. Cessation of ART results in rebound of HIV from these persistent reservoirs. While this was thought to be an insurmountable obstacle to viral eradication, recent cases suggest otherwise. To date one patient has been "cured" of HIV and several others have been able to interrupt ART without viral rebound for prolonged periods. These events have sparked renewed interest in developing strategies that will allow eradication of HIV in infected individuals. We review the current knowledge of HIV latency and the viral reservoir, describe the potential utility of emerging cancer therapeutics in HIV cure research with an emphasis on pathways implicated in reservoir persistence, and outline opportunities and challenges in the context of the current clinical trial and regulatory environment.

  13. HIV-1 gp120 as a therapeutic target: Navigating a moving labyrinth

    PubMed Central

    Acharya, Priyamvada; Lusvarghi, Sabrina; Bewley, Carole A.; Kwong, Peter D.

    2015-01-01

    Introduction The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120. Areas covered An overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability. Expert opinion The gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutralize diverse HIV-1 strains. Synergies between advances in understanding, needs for therapeutics against novel viral targets, and characteristics of breadth and potency for a number of gp120-targetting lead molecules bodes well for gp120 as a HIV-1 therapeutic target. PMID:25724219

  14. 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 IL2rγ(-/-) (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

  15. Diacylglycerol kinase as a possible therapeutic target for neuronal diseases.

    PubMed

    Shirai, Yasuhito; Saito, Naoaki

    2014-04-07

    Diacylglycerol kinase (DGK) is a lipid kinase converting diacylglycerol to phosphatidic acid, and regulates many enzymes including protein kinase C, phosphatidylinositol 4-phosphate 5-kinase, and mTOR. To date, ten mammalian DGK subtypes have been cloned and divided into five groups, and they show subtype-specific tissue distribution. Therefore, each DGK subtype is thought to be involved in respective cellular responses by regulating balance of the two lipid messengers, diacylglycerol and phosphatidic acid. Indeed, the recent researches using DGK knockout mice have clearly demonstrated the importance of DGK in the immune system and its pathophysiological roles in heart and insulin resistance in diabetes. Especially, most subtypes show high expression in brain with subtype specific regional distribution, suggesting that each subtype has important and unique functions in brain. Recently, neuronal functions of some DGK subtypes have accumulated. Here, we introduce DGKs with their structural motifs, summarize the enzymatic properties and neuronal functions, and discuss the possibility of DGKs as a therapeutic target of the neuronal diseases.

  16. 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

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

    PubMed

    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.

  18. Preparatory studies for possible HIV vaccine trials in northern Thailand.

    PubMed

    Nelson, K E; Beyrer, C; Natpratan, C; Eiumtrakul, S; Celentano, D D; Khamboonruang, C

    1994-01-01

    We studied several populations of human immunodeficiency virus (HIV)-seronegative individuals from northern Thailand who were believed to be at relatively high risk of HIV infection in order to assess their potential suitability for inclusion in a preventive HIV vaccine trial. Included were female commercial sex workers (CSWs), male sexually transmitted disease (STD) clinic patients, male conscripts into the Royal Thai Army (RTA), and men who were recently discharged from the army. We evaluated their HIV prevalence, their interest in study participation, their compliance with prospective follow-up, and their HIV incidence. Among 1068 female CSWs the baseline HIV prevalence was 38.3%; of 659 HIV seronegatives 395 (59.9%) agreed to enrollment in the study. Follow-up at 6-9 months was 73.2%; it was 58% in brothel-based CSWs and 85% in non-brothel-based CSWs. Overall HIV incidence in CSWs was 8.2 per 100 person-years; incidence was 29 per 100 person-years in brothel-based CSWs and 4 per 100 person-years in non-brothel-based CSWs. Among 1031 male STD clinic patients, baseline HIV prevalence was 15.9%, follow-up was successful in 98.1%, and HIV incidence was 4.0 per 100 person-years. Among four cohorts of RTA conscripts who entered the military in 1991 and 1993, baseline HIV prevalence has been about 12%, follow-up about 90%, and HIV incidence has varied from 1.2-3.2 per 100 person-years. Discharged RTA conscripts have had baseline HIV prevalence of about 13%, successful follow-up of 94%, and an HIV incidence of about 5 per 100 person-years.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. [Causes, mechanisms and possible therapeutic targets of gout].

    PubMed

    Manigold, Tobias

    2016-01-01

    Gout is the most frequent arthritis worldwide with increasing prevalence in industrialized countries and massive socioeconomic consequences. The knowledge regarding the pathomechanisms which lead to arthritis has substantially increased during the last decade. Consistently, new therapeutic approaches and substances appear at the horizon. This review covers aspects of clinical presentation, diagnosis and current treatment. The pathomechanisms leading to NLRP3 inflammasome activation and IL-1beta secretion are reviewed in detail. Finally, selected new therapeutic targets and substances are discussed.

  20. Therapeutic Immunization In HIV Infected Ugandans Receiving Stable Antiretroviral Treatment: A Phase I Safety Study4

    PubMed Central

    Kityo, Cissy; Bousheri, Stephanie; Akao, Juliette; Ssali, Francis; Byaruhanga, Rose; Ssewanyana, Isaac; Muloma, Prossy; Myalo, Sula; Magala, Rose; Lu, Yichen; Mugyenyi, Peter; Cao, Huyen

    2011-01-01

    Therapeutic immunizations in HIV infection may boost immunity during antiretroviral treatment. We report on the first therapeutic vaccine trial in Uganda, Africa. This open label Phase I trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic HIV-1 vaccine candidate. Thirty HIV positive volunteers receiving a stable regimen of antiretroviral therapy with CD4 counts > 400 were recruited for the safety evaluation of LFn-p24C, a detoxified anthrax-derived polypeptide fused to the subtype C HIV gag protein p24. The vaccine was well tolerated and HIV RNA levels remained undetectable following three immunizations. CD4 counts in vaccine recipients were significantly higher compared to the control individuals after 12 months. HIV-specific responses were associated with higher gain in CD4 counts following LFn-p24C immunizations. Volunteers were subsequently asked to undergo a 30-day period of observed treatment interruption. 8/24 (30%) individuals showed no evidence of viral rebound during treatment interruption. All demonstrated prompt suppression of viral load following resumption of ART. Our data demonstrates the safety of LFn-p24C and suggests that adjunct therapeutic immunization may benefit select individuals in further boosting an immune response. PMID:21211581

  1. [Bladder dysfunction and surgery in the small pelvis. Therapeutic possibilities].

    PubMed

    Schönberger, B

    2003-12-01

    The more extensive a surgical procedure in a small pelvis, the higher the risk for the lower urinary tract with its nerve supply and nerve plexus. This concerns mainly the sympathetic chains, the parasympathetic structures and, rarely, the visceral supply of the pelvic floor. Direct trauma to the bladder and its vascular supply as well as indirect injury by displacement of the bladder need to be seriously considered. Problems with micturition and impaired storage capacity of the bladder are the result. Complete urodynamic examination and follow-up can help in differentiating between temporary and persisting disturbances and in taking therapeutical decisions. The most evident postoperative complication is disturbed micturition, managed initially by suprapubic urinary diversion, followed as soon as possible by intermittent self-catheterisation. This is the only way to avoid overstretching of the bladder, recurring urinary tract infection and damage to the upper urinary tract. Restoration of spontaneous micturition can be supported by drug treatment with parasympatholytics and/or alpha-blockers if the measured bladder pressure and residual urine are within tolerable limits. For electrostimulation of micturition, intravesical therapy, although timeconsuming, is best suited because it can easily be done on an outpatient basis. More promising seems bilateral sacral neuromodulation, which, however, is a rather complicated and expensive procedure. Surgical procedures to reduce the voiding resistance of the bladder involve the risk of postoperative incontinence because the sphincter function in those patients is often disturbed too. Persisting problems with bladder storage capacity as a result of tumor surgery in the small pelvis are frequently secondary to retention of urine (overflow incontinence). In these cases, regular evacuation of the bladder by intermittent self-catheterisation can lead to social acceptance. Reduced bladder compliance and lowering of the urethral

  2. Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector.

    PubMed

    Burke, Bryan P; Levin, Bernard R; Zhang, Jane; Sahakyan, Anna; Boyer, Joshua; Carroll, Maria V; Colón, Joanna Camba; Keech, Naomi; Rezek, Valerie; Bristol, Gregory; Eggers, Erica; Cortado, Ruth; Boyd, Maureen P; Impey, Helen; Shimizu, Saki; Lowe, Emily L; Ringpis, Gene-Errol E; Kim, Sohn G; Vatakis, Dimitrios N; Breton, Louis R; Bartlett, Jeffrey S; Chen, Irvin S Y; Kitchen, Scott G; An, Dong Sung; Symonds, Geoff P

    2015-01-01

    We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC) either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection. PMID:25872029

  3. Advancements in nano-enabled therapeutics for neuroHIV management.

    PubMed

    Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

    2016-01-01

    This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood-brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management. PMID:27621624

  4. Advancements in nano-enabled therapeutics for neuroHIV management

    PubMed Central

    Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

    2016-01-01

    This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood–brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management.

  5. Advancements in nano-enabled therapeutics for neuroHIV management

    PubMed Central

    Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

    2016-01-01

    This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood–brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management. PMID:27621624

  6. Cell-penetrating peptides: Possible transduction mechanisms and therapeutic applications

    PubMed Central

    GUO, ZHENGRONG; PENG, HUANYAN; KANG, JIWEN; SUN, DIANXING

    2016-01-01

    Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse peptides with 5–30 amino acids. CPPs are divided into cationic, amphipathic and hydrophobic CPPs. They are able to carry small molecules, plasmid DNA, small interfering RNA, proteins, viruses, imaging agents and other various nanoparticles across the cellular membrane, resulting in internalization of the intact cargos. However, the mechanisms of CPP internalization remain to be elucidated. Recently, CPPs have received considerable attention due to their high transduction efficiency and low cytotoxicity. These peptides have a significant potential for diagnostic and therapeutic applications, such as delivery of fluorescent or radioactive compounds for imaging, delivery of peptides and proteins for therapeutic application, and delivery of molecules into induced pluripotent stem cells for directing differentiation. The present study reviews the classifications and transduction mechanisms of CPPs, as well as their potential applications. PMID:27123243

  7. Identification of Vimentin as a Potential Therapeutic Target against HIV Infection

    PubMed Central

    Fernández-Ortega, Celia; Ramírez, Anna; Casillas, Dionne; Paneque, Taimi; Ubieta, Raimundo; Dubed, Marta; Navea, Leonor; Castellanos-Serra, Lila; Duarte, Carlos; Falcon, Viviana; Reyes, Osvaldo; Garay, Hilda; Silva, Eladio; Noa, Enrique; Ramos, Yassel; Besada, Vladimir; Betancourt, Lázaro

    2016-01-01

    A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1. PMID:27314381

  8. [GnRH analogs in gynecology. Possibilities for therapeutic use].

    PubMed

    Niesert, S

    1990-09-10

    Gonadotropin releasing hormone (GnRH) agonists are synthetic peptide analogues of the natural gonadotropin releasing hormone with a stronger and more prolonged effect than the natural GnRH. Repeated administration of GnRH agonists induces pituitary desensitization followed by a decrease in gonadotropin secretion and estradiol synthesis. Thus reversible hypogonadotropic hypogonadism is produced. Consequently, estrogen-dependent diseases can be treated successfully with GnRH analogues. The therapeutic results obtained in patients with endometriosis, leiomyoma, pubertas praecox, and metastatic breast cancer are discussed. Furthermore the contraceptive properties of GnRH analogues, and combination treatment with HMG to induce ovulation is reviewed. PMID:2262188

  9. The iron-regulatory hormone hepcidin: a possible therapeutic target?

    PubMed

    Rochette, Luc; Gudjoncik, Aurélie; Guenancia, Charles; Zeller, Marianne; Cottin, Yves; Vergely, Catherine

    2015-02-01

    The maintenance of stable extracellular and intracellular iron concentrations requires the coordinated regulation of iron transport into plasma. Iron is a fundamental cofactor for several enzymes involved in oxidation-reduction reactions. The redox ability of iron can lead to the production of oxygen free radicals, which can damage various cellular components. Therefore, the appropriate regulation of systemic iron homeostasis is decisive in vital processes. Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. It is synthesized in hepatocytes and in other cells and released into the circulation. It inhibits the release of iron from enterocytes of the duodenum and from macrophages by binding to the iron exporter protein, ferroportin (FPN). FPN is a transmembrane protein responsible for iron export from cells into the plasma. Hepcidin is internalized with FPN and both are degraded in lysosomes. The hepcidin-FPN axis is the principal regulator of extracellular iron homeostasis in health and disease. Its manipulation via agonists and antagonists is an attractive and novel therapeutic strategy. Hepcidin agonists include compounds that mimic the activity of hepcidin and agents that increase the production of hepcidin by targeting hepcidin-regulatory molecules. The inhibition of hepcidin could be a potentially attractive therapeutic strategy in patients suffering from anaemia or chronic inflammation. In this review, we will summarize the role of hepcidin in iron homeostasis and its contribution to the pathophysiology of inflammation and iron disorders. We will examine emerging new strategies that modulate hepcidin metabolism.

  10. 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

  11. IBA analysis of a possible therapeutic ancient tooth inlay

    NASA Astrophysics Data System (ADS)

    Andrade, E.; Pineda, J. C.; Zavala, E. P.; Murillo, G.; Chavez, R.; Lazcurain, R.; Espinosa, Ma. L.; Villanueva, O.

    1998-03-01

    Five pre-Columbian human teeth from the same skeleton found during excavation in an ancient ceremonial center in Mexico, have been analyzed by two conventional Ion Beam Analysis (IBA) techniques: PIXE and 4He RBS. The anthropologists have estimated that the skeleton is about 2000 years old. X-ray radiography studies of one of these teeth have revealed that they contain an inlay in the tooth crown. The IBA methods have been used to study the inlay materials and also the tooth enamel. The IBA studies show that the tooth inlay materials have almost the same atomic composition as the tooth enamel. These results suggest that the tooth inlay were made for therapeutic purposes, using healthy tooth grains as inlay materials which were glued into the prepared teeth to fill it up.

  12. Possibilities of new therapeutic strategies in brain tumors.

    PubMed

    Bouffet, Eric; Tabori, Uri; Huang, Annie; Bartels, Ute

    2010-06-01

    Advances in the management of pediatric brain tumors have been less successful than in other areas of pediatric oncology. This gap in outcome is essentially related to specific aspects of these tumors in this age group such as the fact that the surrounding brain is still developing, vital structures limit aggressive attempts at removing infiltrating lesions, drug penetration into the central nervous system is often poor and short and long term toxicities of some treatments to the surrounding brain are significant. This review describes new therapeutic strategies and their impact in the pediatric neuro-oncology practice. Although the number of new active antineoplastic agents has been limited during the last decade, significant improvements in the chemotherapeutic management of pediatric brain tumors have been observed. These relate to the optimization of chemotherapy protocols, the development of new schedules of administration such as metronomic schedules, sequential high dose chemotherapy, concomitant administration of chemotherapy and radiation, or the introduction of intrathecal or intraventricular chemotherapy in specific protocols. Technological advances in radiotherapy allow delivering optimal doses to the target volume while decreasing the volume of normal surrounding tissue receiving radiation. As a consequence, conformal radiation therapy currently plays a major role in the management of several pediatric brain tumors, including in infants where radiation has been traditionally avoided. The role of molecularly targeted agents is still unclear and a number of phase I and II trials are ongoing to better define the future of these new therapies in pediatric brain tumors.

  13. Brain tumour stem cells: possibilities of new therapeutic strategies.

    PubMed

    Piccirillo, Sara G M; Vescovi, Angelo L

    2007-08-01

    Cancers are composed of heterogeneous cell populations, including highly proliferative immature precursors and differentiated cells, which may belong to different lineages. Recent advances in stem cell research have demonstrated the existence of tumour-initiating, cancer stem cells (CSCs) in non-solid and solid tumours. These cells are defined as CSCs because they show functional properties that resemble those of their normal counterpart to a significant extent. This concept applies to CSCs from brain tumours and, particularly, to glioblastoma stem-like cells, which self-renew under clonal conditions and differentiate into neuron- and glia-like cells, and into aberrant cells, with mixed neuronal/astroglia phenotypes. Notably, across serial transplantation into immunodeficient mice, glioblastoma stem-like cells are able to form secondary tumours which are a phenocopy of the human disease. A significant effort is underway to identify both CSC-specific markers and the molecular mechanism that underpin the tumorigenic potential of these cells, for this will have a critical impact on the understanding of the origin of malignant brain tumour and the discovery of new and more specific therapeutic approaches. Lately, the authors have shown that some of the bone morphogenetic proteins can reduce the tumorigenic ability of CSCs in GBMs. This suggests that mechanisms regulating the physiology of normal brain stem cells may be still in place in their cancerous siblings and that this may lead to the development of cures that selectively target the population CSCs found in the patients' tumour mass.

  14. Engaging therapeutic citizenship and clientship: Untangling the reasons for therapeutic pacifism among people living with HIV in urban Zambia.

    PubMed

    Patterson, Amy S

    2016-10-01

    This article explores the reasons for therapeutic pacifism among people living with HIV (PLHIVs) in urban Zambia. It contributes to a growing ethnography on global health, biosociality, and patient-provider dynamics. Therapeutic citizenship is a biopolitical citizenship that includes claims and ethical projects that emerge from techniques to control and manage bodies. In some contexts, therapeutic citizenship has included activism and claims-making against local, national, and international power brokers. This article investigates therapeutic citizenship in the specific context of impoverished urban Zambian compounds, sites of food insecurity, unemployment, and political exclusion, as well as targets for donor, NGO, and faith-based organisation projects and PLHIV support group proliferation. The article utilises data from participant observations at two Lusaka AIDS clinics, interviews, and focused discussions with support groups of PLHIVs. It argues that PLHIVs continuously negotiate subjectivities related to kinship, clientship, religious belief, and political citizenship in processes that complicate therapeutic citizenship. Rather than fostering participation in PLHIV support groups or challenging 'politics as usual' through activist claims-making to institutions of biopower, these processes lead to therapeutic pacifism.

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

    PubMed Central

    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

  16. Past experiences, current realities and future possibilities for HIV nursing education and care in Canada

    PubMed Central

    Mill, Judy; Caine, Vera; Arneson, Cheryl; Maina, Geoffrey; De Padua, Anthony; Dykeman, Margaret

    2016-01-01

    Nurses may have inadequate basic education and opportunities for continuing education in relation to HIV care. As well nurses may perpetuate and impose stigma. We developed, implemented and evaluated an educational intervention to reduce stigma and discrimination among nurses providing HIV care. The intervention used a mentorship model that brought experienced nurses in HIV care and people living with HIV together with nurses who wanted to learn more about HIV nursing care. We examined our findings in relation to past experiences, current realities and future possibilities for HIV nursing education and care in Canada. Our findings demonstrated that many nurses were interested in improving their HIV care, yet few opportunities existed for them to do so. We found that HIV nursing education and expertise were significantly different among participants and across clinical sites. This difference was visible in basic education, services offered for HIV and AIDS care, the collaborative and inter-professional nature of care, and opportunities for continuing education. Mentorship education is an effective strategy to not only address a critical void in knowledge, but also to promote a fundamental shift in attitudes. With the recent call by the World Health Organization to place nurses in key positions to provide HIV care, treatment and prevention, it is imperative to prepare nurses at both the undergraduate and graduate level, as well as those in practice, to fulfill this call. PMID:27152130

  17. 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

  18. Therapeutic possibilities of techniques of extracorporeal blood circulation in oncology.

    PubMed

    Ricci, Sante Basso

    2012-01-01

    Malignant tumors in an advanced phase of diffusion have a very poor prognosis. However, there are conditions in the body which may impede, even if only partially, further spread of the disease. In addition to currently available treatments, other favorable conditions can help to improve the prognosis, even if only relatively, such as the presence of inhibitors of metalloproteinases, antiangiogenic factors, the absence of particular proteins that favor tumor development, and the possibility of positively activating the immune system. The authors believe that in cases where such conditions are concurrent, the addition of a new favorable condition could be very useful. On the other hand, cases of total spontaneous regression of malignancies, even if in metastatic diffusion, are well known. It was recently emphasized that the spread of metastasis of renal cell carcinoma, arising in patients on hemodialysis for a long time, is considerably reduced at the post-mortem examination compared to patients with renal cell carcinoma and not on hemodialysis. This may suggest a positive effect exerted by the dialytic membrane on metastatic spread. The authors hypothesize that extracorporeal circulation of the blood, used mainly for cardiovascular interventions and hemodialysis, could be used by applying filters suitable for cancer treatments, similar to those used in hemodialysis, even if without accomplishing the hemodialytic function, provided there are no objections to their biocompatibility. In this case, the block of metastatic cells could lead to a relative increase in the cellular elements of the immune system (NK cells and T lymphocytes) compared to cancer cells, or rather to the relative reduction in the number of cancer cells compared to NK cells and T lymphocytes. Such a block would prevent any feedback reactions, so frequent and damaging to the prognosis when using overall medical stimulation for the immune system.

  19. 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.

  20. An HIV/AIDS Prophylactic vaccine is possible.

    PubMed

    Zhong, Qiu; Luftig, Ronald B

    2007-01-01

    One needs to think outside of the box, as one of us (Ronald B Luftig) learned from many years as a mathematician, and a biophysicist.In this short Review, the need to focus on producing high levels of neutralizing antibodies (NAbs) to incoming and conformationally altered virus after it has bound to CD4+ cells is essential.Increasing the number of gp120 molecules on the surface of L-2 particles, could allow for an enhanced number of NAbs.The attempt at increasing CD8+ T cell responses in recent vaccine trials has not worked perhaps because it may have allowed HIV to enter into remote sanctuaries. Our approach focuses on increasing NAbs, before high levels of CD8+ T cells are produced. PMID:18093321

  1. Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor.

    PubMed

    Prasad, J V; Boyer, F E; Domagala, J M; Ellsworth, E L; Gajda, C; Hamilton, H W; Hagen, S E; Markoski, L J; Steinbaugh, B A; Tait, B D; Humblet, C; Lunney, E A; Pavlovsky, A; Rubin, J R; Ferguson, D; Graham, N; Holler, T; Hupe, D; Nouhan, C; Tummino, P J; Urumov, A; Zeikus, E; Zeikus, G; Gracheck, S J; Erickson, J W

    1999-12-01

    With the insight generated by the availability of X-ray crystal structures of various 5,6-dihydropyran-2-ones bound to HIV PR, inhibitors possessing various alkyl groups at the 6-position of 5,6-dihydropyran-2-one ring were synthesized. The inhibitors possessing a 6-alkyl group exhibited superior antiviral activities when compared to 6-phenyl analogues. Antiviral efficacies were further improved upon introduction of a polar group (hydroxyl or amino) on the 4-position of the phenethyl moiety as well as the polar group (hydroxymethyl) on the 3-(tert-butyl-5-methyl-phenylthio) moiety. The polar substitution is also advantageous for decreasing toxicity, providing inhibitors with higher therapeutic indices. The best inhibitor among this series, (S)-6-[2-(4-aminophenyl)-ethyl]-(3-(2-tert-butyl-5-methyl-phenylsulfa nyl)-4-hydroxy-6-isopropyl-5,6-dihydro-pyran-2-one (34S), exhibited an EC50 of 200 nM with a therapeutic index of > 1000. More importantly, these non-peptidic inhibitors, 16S and 34S, appear to offer little cross-resistance to the currently marketed peptidomimetic PR inhibitors. The selected inhibitors tested in vitro against mutant HIV PR showed a very small increase in binding affinities relative to wild-type HIV PR. Cmax and absolute bioavailability of 34S were higher and half-life and time above EC95 were longer compared to 16S. Thus 34S, also known as PD 178390, which displays good antiviral efficacy, promising pharmacokinetic characteristics and favorable activity against mutant enzymes and CYP3A4, has been chosen for further preclinical evaluation.

  2. The therapeutic application of CRISPR/Cas9 technologies for HIV

    PubMed Central

    Saayman, Sheena; Ali, Stuart A.; Morris, Kevin V.; Weinberg, Marc S.

    2015-01-01

    Introduction The use of antiretroviral therapy (ART) has led to a significant decrease in morbidity and mortality in HIV-infected individuals. Nevertheless gene-based therapies represent a promising therapeutic paradigm for HIV-1, as they have the potential for sustained viral inhibition and reduced treatment interventions. One new method amendable to a gene-based therapy is the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 gene editing system. Areas covered CRISPR/Cas9 can be engineered to successfully modulate an array of disease-causing genetic elements. We discuss the diverse roles that CRISPR/Cas9 may play in targeting HIV and eradicating infection. The Cas9 nuclease coupled with one or more small guide RNAs (sgRNAs) can target the provirus to mediate excision of the integrated viral genome. Moreover, a modified nuclease deficient Cas9 fused to transcription activating domains may induce targeted activation of proviral gene expression allowing for the purging of the latent reservoirs. These technologies can also be exploited to target host dependency factors such as the co-receptor CCR5, thus preventing cellular entry of the virus. Expert opinion The diversity of the CRISPR/Cas9 technologies hold great promise for targeting different stages of the viral life cycle, and have the capacity for mediating an effective and sustained genetic therapy against HIV. PMID:25865334

  3. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

    PubMed Central

    2009-01-01

    The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway. PMID:19961595

  4. Update and New Directions in Therapeutics for Neurological Complications of HIV Infections.

    PubMed

    Ellis, Ronald; Letendre, Scott L

    2016-07-01

    The pace of therapeutic developments in HIV presents unique challenges to the neurologist caring for patients. Combination antiretroviral therapy (cART) is remarkably effective in suppressing viral replication, preventing, and often even reversing disease progression. Still, not every patient benefits from cART for a variety of reasons, ranging from the cost of therapy and the burden of lifelong daily treatment to side effects and inadequate access to medical care. Treatment failure inevitably leads to disease progression and opportunistic complications. Many of these complications, even those that are treatable, produce permanent neurological disability. With ART, immune recovery itself may paradoxically lead to severe neurological disease; strategies for managing so-called immune reconstitution inflammatory syndrome are beginning to show benefits. Effective cART may nevertheless leave in its wake persistent neurocognitive impairment. Treatments for persistent impairment despite virologic suppression and good immune recovery are being tested but are not yet proven. As we shall see, these treatments target several proposed mechanisms including cerebral small vessel disease, which is highly prevalent in HIV. Most recently, an ambitious initiative has been undertaken to develop interventions to eradicate HIV. This will require elimination of all infectious forms of viral nucleic acid throughout the body. The influence of these interventions on the brain remains to be characterized. Meanwhile, clinical investigators continue to develop antiretroviral treatments that optimize effectiveness, convenience, and tolerability, while minimizing long-term toxicities. PMID:27383150

  5. 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

  6. 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…

  7. Role of fever in infection: has induced fever any therapeutic potential in HIV infection?

    PubMed Central

    Morton, R S; Rashid, S

    1997-01-01

    Ancient societies had no rational understanding of fever. The Greeks were the first to recognise that it may be part of nature's method of effecting cure in some diseases. How best to assist nature went through many trials and errors. Appreciation of the prognostic value of fever and how it may be controlled was slow to appear. That there was a place in the therapeutic arsenal for induced fever came only with the 20th century. Finding a suitable, safe, and satisfactory means came slowly. The curative power of well controlled and reproducible levels of fever was proved by the arrest of one deadly and incurable complication of a sexually transmitted disease in the first half of this century. The purpose of this review is to promote discussion and, hopefully, well ordered laboratory and clinical trials aimed at learning whether or not induced fevers have a place in the care of patients with HIV/AIDS. Images PMID:9306904

  8. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    PubMed

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  9. [Pregnancy, children, clinical trials and HIV infection. Ethical limitations and therapeutical implications].

    PubMed

    Gouveia-Andrade, Luís

    2003-01-01

    In what concerns women and children infected with HIV, clinical investigation related ethical issues are both unavoidable and controversial. Different arguments are presented by different partners, and policies and laws are made in order to protect women and children, who, in spite of all that, keep suffering the effects of all this controversy, protection and legislation. Evidence based Medicine is responsible for new and demanding challenges and the same ethics that requires that new drugs are used only after unquestionable safety and efficacy are presented, tends to protect children, pregnant women and other vulnerable groups from being exposed to investigational drugs. This is why there are so few therapeutical options for HIV-infected children and pregnant women. So, ironically, in times of evidence based medicine, these two special populations are treated in an empirical way, because the same Medicine that wants to protect them, offers wide-open doors to the most terrible infections that mankind has ever faced. In this article, ethical dilemmas, philosophical principles, epidemiological context and different perspectives concerning this painful, yet extremely important, subject will be presented. The purposes will be to broaden horizons, to stimulate discussion and to provide some light into a subject still so restrict, still so unspoken, still so left in the shadows of something that we like to describe as modern medicine.

  10. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    PubMed

    Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo

    2011-11-01

    Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials. PMID:21792065

  11. Pharmacological properties and therapeutic possibilities for drugs acting upon endocannabinoid receptors.

    PubMed

    Fowler, Christopher J

    2005-12-01

    Clinical trial data are beginning to emerge with respect to the therapeutic efficacy of cannabis extracts for the treatment of chronic pain. Although there is some evidence of efficacy, a major issue concerns the narrow margin between doses producing therapeutic effects and those producing the "highs" associated with cannabis misuse. In addition, long-term use is associated with an increased risk of psychiatric illness. These negative aspects constrain the doses of cannabis extracts and psychoactive cannabinoids that can be given to patients, and raise the risk that properly conducted clinical trials with too low dosages will impact negatively on subsequent drug development in this field. However, recent research has opened up a number of avenues whereby compounds acting directly upon cannabinoid (CB) receptors may have therapeutic potential. In this review, two such areas are discussed, namely a) the possible use of peripherally acting CB agonists and CB2 receptor-selective agonists for the treatment of pain, and b) the possible utility of CB2 receptor agonists for the prevention of stress-induced exacerbations of skin disorders such as psoriasis. A second area of drug development at present is that of CB1 receptor antagonists/inverse agonists, spearheaded by rimonabant, for the treatment of obesity and as an aid for smoking cessation. An important aspect of these compounds is their efficacy and selectivity, and this is discussed in detail in the present review.

  12. The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization

    PubMed Central

    Frecska, Ede; Bokor, Petra; Winkelman, Michael

    2016-01-01

    Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor (Sig-1R) agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: (1) the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and (2) on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the Sig-1R which can explain its widespread therapeutic indications. PMID:26973523

  13. Human amniotic fluid: a source of stem cells for possible therapeutic use.

    PubMed

    Dziadosz, Margaret; Basch, Ross S; Young, Bruce K

    2016-03-01

    Stem cells are undifferentiated cells with the capacity for differentiation. Amniotic fluid cells have emerged only recently as a possible source of stem cells for clinical purposes. There are no ethical or sampling constraints for the use of amniocentesis as a standard clinical procedure for obtaining an abundant supply of amniotic fluid cells. Amniotic fluid cells of human origin proliferate rapidly and are multipotent with the potential for expansion in vitro to multiple cell lines. Tissue engineering technologies that use amniotic fluid cells are being explored. Amniotic fluid cells may be of clinical benefit for fetal therapies, degenerative disease, and regenerative medicine applications. We present a comprehensive review of the evolution of human amniotic fluid cells as a possible modality for therapeutic use.

  14. Electrochemical monitoring-on-chip (E-MoC) of HIV-infection in presence of cocaine and therapeutics.

    PubMed

    Kaushik, Ajeet; Vabbina, Phani Kiran; Atluri, Venkata; Shah, Pratikkumar; Vashist, Arti; Jayant, Rahul Dev; Yandart, Adriana; Nair, Madhavan

    2016-12-15

    Electrochemical monitoring-on-chip (E-MoC)-based approach for rapid assessment of human immunodeficiency virus (HIV)-infection in the presence of cocaine (Coc) and specific drugs namely i.e., tenofovir (Tef), rimcazole (RA) is demonstrated here, for the first time, using electrochemical impedance spectroscopy (EIS). An in-vitro primary human astrocytes (HA) model was developed using a cultureware chip (CC, used for E-MoC) for HIV-infection, Coc exposure and treatment with anti-HIV drug i.e., Tef, and Coc antagonist i.e., RA. The charge transfer resistance (Rct) value of each CC well varies with respect to infection and treatment demonstrated highly responsive sensitivity of developed chip. The results of E-MoC, a proof-of-the concept, suggested that HIV-infection progression due to Coc ingestion and therapeutic effects of highly specific drugs are measurable on the basis of cell electrophysiology. Though, this work needs various molecular biology-based optimizations to promote this technology as an analytical tool for the rapid assessment of HIV-infection in a patient to manage HIV diseases for timely diagnosis. The presented study is based on using CNS cells and efforts are being made to perform this method using peripheral cells such as monocytes derived dendritic cells.

  15. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

    PubMed

    French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

    2013-01-01

    The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  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. Talking about sex in Botswana: social desirability bias and possible implications for HIV-prevention research.

    PubMed

    Chillag, Kata; Guest, Greg; Bunce, Arwen; Johnson, Laura; Kilmarx, Peter H; Smith, Dawn K

    2006-09-01

    Evaluations of the safety, effectiveness, and feasibility of HIV prevention interventions rely on self-reported sexual behaviour data. The accuracy of such data has sometimes been questioned. The absence of a so-called objective measure of sexual behaviour complicates this. Social desirability bias (SDB) is a key factor affecting the accuracy of self-reports. Individual, semi-structured interviews focusing on possible causes of and solutions to SDB were conducted with 30 Batswana women such as those who might enrol in planned vaginal microbicide trials. Respondents pointed to shame and the fear of public talk about them as key factors contributing to inaccurate self-reports, and they stressed the importance of privacy and confidentiality. Interviewer characteristics such as age, gender and personality were often viewed as likely to affect their candour. Alternative interviewing techniques such as audio computer-assisted self-interviewing (ACASI) were appealing to some for the potential to reduce embarrassment; others were sceptical. The possible implications for HIV-prevention research are presented.

  18. Implication of Green Tea as a Possible Therapeutic Approach for Parkinson Disease.

    PubMed

    Jurado-Coronel, Juan C; Ávila-Rodriguez, Marco; Echeverria, Valentina; Hidalgo, Oscar Alejandro; Gonzalez, Janneth; Aliev, Gjumrakch; Barreto, George E

    2016-01-01

    Green tea is a beverage consumed around the world that is believed to have substantial health benefits such as reducing the risk of cancer, cardiovascular diseases, diabetes and neurodegeneration. This beverage is prepared from the leaves (steamed and dried) of the Camellia sinesis plant and contains strong antioxidant and neuroprotective phenolic compounds from which the most important is (-)-Epigallocatechin-3-gallate. Parkinson's disease (PD) is the second more common neurodegenerative disorders, after Alzheimer's disease and is characterized by degeneration of dopaminergic neurons in the pars compact of the substantia nigra of the basal ganglia. It has been shown in pre-clinical and clinical studies that green tea may be able to prevent PD, but its optimal dose or a possible mechanism explaining its health benefit in PD has not been properly established. In this review, we discuss the potential role of green tea's phenolic compounds and their therapeutic effectin modulating key signaling pathways in the PD brain. PMID:26831259

  19. [Non-epileptic sleep disorders (somnambulism) in epilepsy. Diagnostic and therapeutic possibilities].

    PubMed

    Kaschnitz, W; Scheer, P J; Kratky-Dunitz, M; Broussalis, T

    1991-11-01

    The case history of a 15 1/2-year-old boy is presented who suffers from screaming fits during the night and epilepsia. The problem has existed since he was eight. He lives alone with his mother in a "partner-like" relationship. The previous diagnosis, namely epilepsy, has masked any possible psychodynamic element. Our diagnostic instruments were: 1. Standardized diagnostics with DSM III-R; 2. psychoanalytically oriented psychodiagnostics; 3. long term EEG-video-monitoring, which eventually succeeded in differentiating his multiple symptoms. Using these methods we were able to differentiate a sleep disorder (somnambulism) from his grandmal epilepsy. We changed his anticonvulsive pharmacological therapy and introduced an individual psychotherapy ("Katathymes Bilderleben"). This kind of psychotherapy is applied for the first time as a therapy for somnambulism. By using this therapeutic concept we cured our patient from his symptoms. PMID:1775145

  20. The Role of Mediators in the Indirect Effects of Religiosity on Therapeutic Compliance in African Migrant HIV-Positive Patients.

    PubMed

    Mambet Doue, Constance; Roussiau, Nicolas

    2016-12-01

    This research investigates the indirect effects of religiosity (practice and belief) on therapeutic compliance in 81 HIV-positive patients who are migrants from sub-Saharan Africa (23 men and 58 women). Using analyses of mediation and standard multiple regression, including a resampling procedure by bootstrapping, the role of these mediators (magical-religious beliefs and nonuse of toxic substances) was tested. The results show that, through magical-religious beliefs, religiosity has a negative indirect effect, while with the nonuse of toxic substances, religious practice has a positive indirect effect. Beyond religiosity, the role of mediators is highlighted in the interaction with therapeutic compliance. PMID:26531838

  1. True User Involvement by People Living With HIV is Possible: Description of a User-driven HIV Clinic in Norway.

    PubMed

    Berg, Rigmor C; Gamst, Are; Said, Maryan; Aas, Kristin Bårdsen; Songe, Solveig Helene; Fangen, Kim; Rysstad, Ole

    2015-01-01

    The Greater Involvement of People Living with or Affected by HIV principle highlights the various contributions HIV-infected people can make in HIV program development and implementation. We present a unique example of how service users' involvement led to a complete organizational redesign of an outpatient HIV clinic in Southern Norway. We applied a user-driven, case study method, which showed that establishing a user board laid the foundation for the redesign process, as the board provided a clear infrastructure of user involvement and developed a set of user-defined targets for services. The main targets-optimal health, holistic care and treatment, and empowerment-were operationalized as a set of action points, such as establishing HIV nurse coordinators. While there is no single method for user involvement, we offer useful ideas that can help others develop an involvement project that is effective and sustainable.

  2. Systemic and Mucosal Differences in HIV Burden, Immune and Therapeutic Responses

    PubMed Central

    Wahl, Sharon M.; Redford, Maryann; Christensen, Shawna; Mack, Wendy; Cohn, Jon; Janoff, Edward N.; Mestecky, Jiri; Jenson, Hal B.; Navazesh, Mahvash; Cohen, Mardge; Reichelderfer, Patricia; Kovacs, Andrea

    2011-01-01

    Background Mucosal tissues represent major targets for HIV transmission, but differ in susceptibility and reservoir function by unknown mechanisms. Methods In a cross-sectional study, HIV RNA and infectious virus were compared between oral and genital compartments and blood in HIV-infected women, in association with clinical parameters, co-pathogens and putative innate and adaptive HIV inhibitors. Results HIV RNA was detectable in 24.5% of women from all 3 compartments, whereas 45% had RNA in only one or two sites. By comparison, infectious HIV, present in blood of the majority, was rare in mucosal sites. Innate mediators, SLPI and TSP, were highest in mucosae. Highly active antiretroviral therapy (HAART) was associated with an 80% decreased probability of shedding. Multivariate logistic regression models revealed that mucosal HIV RNA was associated with higher plasma RNA, infectious virus, and total mucosal IgA, but not IgG. There was a 37-fold increased probability of detecting RNA in both genital and oral specimens (P=0.008;P=0.02, respectively) among women in highest vs lowest IgA tertiles. Conclusions Mucosal sites exhibit distinct characteristics of infectious HIV, viral shedding and responses to therapy, dependent upon both systemic and local factors. Of the putative innate and adaptive mucosal defense factors examined, only IgA was associated with HIV RNA shedding. However, rather than being protective, there was a striking increase in probability of detectable HIV RNA shedding in women with highest total IgA. PMID:21239996

  3. 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

  4. Lower HIV prevalence among Asian/Pacific Islander men who have sex with men: a critical review for possible reasons.

    PubMed

    Wei, Chongyi; Raymond, H Fisher; Wong, Frank Y; Silvestre, Anthony J; Friedman, Mark S; Documét, Patricia; McFarland, Willi; Stall, Ron

    2011-04-01

    We conducted a critical literature review for possible reasons that may explain the lower HIV prevalence observed among API MSM compared to MSM of other races/ethnicities. Trends emerging from the literature suggest that traditional individual-level factors-unprotected anal intercourse, substance use, STD prevalence, rates and frequency of HIV testing, and utilization of HIV prevention services-do not appear to be related to the lower HIV prevalence among API MSM. Some evidence suggests that socio-cultural and structural factors might be the more critical forces in determining racial/ethnic disparities of HIV among MSM. For API MSM, these factors include structures of sexual networks, access to and reception of medical care and treatment among HIV-positive MSM, and influences of different levels and types of acculturation. Moreover, emerging risk reduction strategies, such as seroadaptive behaviors, could play a role. Future research should address these factors in intervention design. In addition, better theories of resilience and measurement of strengths and protective factors are needed to enhance the efficacy of HIV interventions.

  5. Developmental, Ethnic, and Social Influences on Participation in Sexual Possibility Situations for Youth with HIV-Positive and HIV-Negative Mothers

    ERIC Educational Resources Information Center

    Lewis, Linwood J.; Mellins, Claude A.; Brackis-Cott, Elizabeth

    2006-01-01

    This cross-sectional study examined the relationship among maternal HIV, pubertal development, gender, ethnicity, and spirituality and adolescent participation in sexual possibility situations (SPSs) and in sexual activity. SPSs are social encounters with cross-gender peers that afford the opportunity to engage in sexual activity. Heterosexual…

  6. 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.

  7. 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

  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; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(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. Monocyte/macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets?

    PubMed Central

    Gillette, Devyn D.; Tridandapani, Susheela; Butchar, Jonathan P.

    2014-01-01

    Francisella tularensis can bypass and suppress host immune responses, even to the point of manipulating immune cell phenotypes and intercellular inflammatory networks. Strengthening these responses such that immune cells more readily identify and destroy the bacteria is likely to become a viable (and perhaps necessary) strategy for combating infections with Francisella, especially given the likelihood of antibiotic resistance in the foreseeable future. Monocytes and macrophages offer a niche wherein Francisella can invade and replicate, resulting in substantially higher bacterial load that can overcome the host. As such, understanding their responses to Francisella may uncover potential avenues of therapy that could promote a lowering of bacterial burden and clearance of infection. These response pathways include Toll-like Receptor 2 (TLR2), the caspase-1 inflammasome, Interferons, NADPH oxidase, Phosphatidylinositide 3-kinase (PI3K), and the Ras pathway. In this review we summarize the literature pertaining to the roles of these pathways during Francisella infection, with an emphasis on monocyte/macrophage responses. The therapeutic targeting of one or more such pathways may ultimately become a valuable tool for the treatment of tularemia, and several possibilities are discussed. PMID:24600590

  10. 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

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

    PubMed Central

    Pertwee, Roger G.

    2012-01-01

    Human tissues express cannabinoid CB1 and CB2 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 CB1/CB2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ9-tetrahydrocannabinol (Δ9-THC)) and Sativex (Δ9-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 CB2 receptors, and/or (v) adjunctive ‘multi-targeting’. PMID:23108552

  12. Advances in biosensing strategies for HIV-1 detection, diagnosis, and therapeutic monitoring.

    PubMed

    Lifson, Mark A; Ozen, Mehmet Ozgun; Inci, Fatih; Wang, ShuQi; Inan, Hakan; Baday, Murat; Henrich, Timothy J; Demirci, Utkan

    2016-08-01

    HIV-1 is a major global epidemic that requires sophisticated clinical management. There have been remarkable efforts to develop new strategies for detecting and treating HIV-1, as it has been challenging to translate them into resource-limited settings. Significant research efforts have been recently devoted to developing point-of-care (POC) diagnostics that can monitor HIV-1 viral load with high sensitivity by leveraging micro- and nano-scale technologies. These POC devices can be applied to monitoring of antiretroviral therapy, during mother-to-child transmission, and identification of latent HIV-1 reservoirs. In this review, we discuss current challenges in HIV-1 diagnosis and therapy in resource-limited settings and present emerging technologies that aim to address these challenges using innovative solutions. PMID:27262924

  13. The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

    PubMed

    Kumarasamy, N

    2016-04-01

    Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.

  14. Zinc as a possible preventive and therapeutic agent in pancreatic, prostate, and breast cancer.

    PubMed

    Hoang, Ba X; Han, Bo; Shaw, David Graeme; Nimni, Marcel

    2016-09-01

    Zinc is a vital nutrient for human health. Over 300 biological functions in the human body rely on zinc. Even though zinc is incredibly important for our physiology and pathology, our current understanding of zinc, as it relates to tumor cell biology, leaves much to be desired. As with other natural, nonpatentable, and inexpensive agents, zinc remains a subject of explorative research for scientific interest rather than being promoted for practical use. To date, more than 5000 studies with the keywords 'zinc' and 'cancer' have been indexed in the Web of Knowledge portal. Although the numbers of papers have increased 2.5-fold during the last decade, these vast research data have not generated a single recommendation for the incorporation of zinc use in cancer prevention and treatment. In this review, we intend to analyze the current available research data and epidemiological and clinical evidence on the role of zinc in human cancer prevention and treatment. We focus on the cancers - prostate, breast, and pancreatic - for which the most basic and epidemiological studies with zinc have been carried out. The pancreas, and prostate and mammary glands are secretory tissues that have unusual zinc requirements; they tightly regulate zinc metabolism through integration of zinc import, sequestration, and export mechanisms. This suggests to us that zinc could play an important role in the physiology and pathology of these organs. The objective of this review was to stimulate more interest in the research field, focusing on the role of zinc as a possible preventive and therapeutic agent and the accelerated application of this inexpensive and easily accessible nutrient in clinical oncology. PMID:26317381

  15. 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,…

  16. 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

  17. Traditional healers and the "Fast-Track" HIV response: is success possible without them?

    PubMed

    Leclerc-Madlala, Suzanne; Green, Edward; Hallin, Mary

    2016-07-01

    The rapid scale-up of effective HIV prevention strategies is a central theme of the post-2015 health and development agenda. All major global HIV and AIDS funders have aligned their policies and plans to achieve sharp reductions in new HIV infections and reach epidemic control by 2030. In these "fast-track" plans, increased antiretroviral treatment coverage and the attainment of viral suppression are pivotal, and there is firm recognition of the need for countries to mobilise more domestic resources and build stronger community clinic systems. There is little in these bold plans, however, to suggest that the now 30-year-old call by the World Health Organization (WHO) and other organisations to establish systematic collaborations with the traditional health sector will finally be heeded. In the context of sub-Saharan Africa's HIV epidemic, a significant body of literature demonstrates the critical role that traditional healers can play in improving the success of health programmes, including those for HIV prevention. This paper provides a brief history of collaboration with traditional healers for HIV followed by a description of several successful collaborations and discussion of key elements for success. We argue that the traditional health sector is a major resource that has yet to be sufficiently mobilised against HIV. As we shift from a short-term HIV response to a longer-term and more sustainable response, there is an urgent need to accelerate efforts to leverage and partner with the hundreds of thousands of traditional health practitioners who are already providing health services in communities. Failure to better attune our work to the medical pluralism of communities affected by HIV will continue to hinder HIV programming success and help assure that ambitious post-2015 HIV prevention and control goals are not realised.

  18. Traditional healers and the "Fast-Track" HIV response: is success possible without them?

    PubMed

    Leclerc-Madlala, Suzanne; Green, Edward; Hallin, Mary

    2016-07-01

    The rapid scale-up of effective HIV prevention strategies is a central theme of the post-2015 health and development agenda. All major global HIV and AIDS funders have aligned their policies and plans to achieve sharp reductions in new HIV infections and reach epidemic control by 2030. In these "fast-track" plans, increased antiretroviral treatment coverage and the attainment of viral suppression are pivotal, and there is firm recognition of the need for countries to mobilise more domestic resources and build stronger community clinic systems. There is little in these bold plans, however, to suggest that the now 30-year-old call by the World Health Organization (WHO) and other organisations to establish systematic collaborations with the traditional health sector will finally be heeded. In the context of sub-Saharan Africa's HIV epidemic, a significant body of literature demonstrates the critical role that traditional healers can play in improving the success of health programmes, including those for HIV prevention. This paper provides a brief history of collaboration with traditional healers for HIV followed by a description of several successful collaborations and discussion of key elements for success. We argue that the traditional health sector is a major resource that has yet to be sufficiently mobilised against HIV. As we shift from a short-term HIV response to a longer-term and more sustainable response, there is an urgent need to accelerate efforts to leverage and partner with the hundreds of thousands of traditional health practitioners who are already providing health services in communities. Failure to better attune our work to the medical pluralism of communities affected by HIV will continue to hinder HIV programming success and help assure that ambitious post-2015 HIV prevention and control goals are not realised. PMID:27399048

  19. [Lymphedema secondary to breast cancer treatment: possibility of diagnostic and therapeutic prevention].

    PubMed

    Campisi, C; Boccardo, F; Zilli, A; Maccio, A; Napoli, F; Ferreira Azevedo, W; Fulcheri, E; Taddei, G

    2002-01-01

    We performed a prospective randomized study upon 50 patients who had undergone a breast cancer treatment, considering particularly the possibility of appearance of arm secondary lymphedema. The patients were divided in two groups of 25 patients each. In the 1st group, we performed only a clinical follow-up, whilst in the 2nd one, we used also lymphoscintigraphy. The aim of the study was to compare the incidence of arm secondary lymphedema in the two groups, and relate the data with those of the international literature, in order to identify diagnostic procedures indicative of the risk of development of lymphedema and find proper therapeutic preventive measures. It is certainty complex to foresee the appearance of arm lymphedema due to breast cancer treatment. No specific preventive therapeutic methods based upon particular diagnostic investigations were ever reported. Patients had undergone surgery and radiation for breast cancer in the period between April 1992 and June 1994, and controlled at over 5 years after operation. Upper limb lymphoscintigraphy was performed only in one of the two groups of 25 patients, before operation and, furthermore, after 1-3-6 months and 1-3 years from the treatment. Patients who presented lymphoscintigraphic alterations (dermal back flow, diffused or delayed transit of the tracer, etc.), before edema appeared clinically, underwent physical and rehabilitative therapy (bandages, manual lymphatic drainage, mechanical lymph drainage, elastic garments, etc.) and microsurgery (lymphatic-venous anastomoses at the arm), performed early (stages Ib and II) in patients not responsive to physical therapy. In the first group followed only clinically, secondary arm lymphedema occurred in 9 cases (36%), and appeared after a period variable from 1 week to 2 years (3-6 months averagely). In the second group, lymphoscintigraphy, performed preoperatively, permitted to find lymphatic impairment (absence of deltoid way, reduced axillary lymph nodal

  20. 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…

  1. The Framing and Fashioning of Therapeutic Citizenship Among People Living With HIV Taking Antiretroviral Therapy in Uganda

    PubMed Central

    Russell, Steve; Namukwaya, Stella; Zalwango, Flavia; Seeley, Janet

    2015-01-01

    In this article, we examine how people living with HIV (PLWH) were able to reconceptualize or “reframe” their understanding of HIV and enhance their capacity to self-manage the condition. Two in-depth interviews were held with 38 PLWH (20 women, 18 men) selected from three government and nongovernment antiretroviral therapy (ART) delivery sites in Wakiso District, and the narratives analyzed. ART providers played an important role in shaping participants’ HIV self-management processes. Health workers helped PLWH realize that they could control their condition, provided useful concepts and language for emotional coping, and gave advice about practical self-management tasks, although this could not always be put into practice. ART providers in this setting were spaces for the development of a collective identity and a particular form of therapeutic citizenship that encouraged self-management, including adherence to ART. Positive framing institutions are important for many PLWH in resource-limited settings and the success of ART programs. PMID:26246523

  2. Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine

    PubMed Central

    Theiler, James; Yoon, Hyejin; Yusim, Karina; Picker, Louis J.; Fruh, Klaus; Korber, Bette

    2016-01-01

    Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Epigraph vaccine antigens are functionally similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Epigraph furthermore has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraph was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html). PMID:27703185

  3. 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 β-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 β-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

  4. Evidence of clinically significant change: the therapeutic alliance and the possibilities of outcomes-informed care.

    PubMed

    Manning, Walter H

    2010-11-01

    This article addresses the issue of clinically significant (or meaningful) change resulting from treatment for stuttering. Research in both medical and behavioral fields indicates that clients often have their own unique perspective of meaningful clinical change and that this perspective is often different from that of the professional administering the treatment. Among the variables that the client brings to the treatment session are their progression through stages of therapeutic change and the ways in which they believe they are capable of coping with their problem. Research has shown that how an individual interprets the meaning his or her therapeutic experience is central to clinically significant change. Procedures for obtaining feedback from clients concerning clinically significant change and the quality of the therapeutic alliance are described. PMID:21080293

  5. 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

  6. [Chronic disorders after interventions in the anorectal area--therapeutic possibilities].

    PubMed

    Geile, D; Haseitl, M; Osterholzer, G

    2002-01-01

    Long lasting alterations of anal function and persistent pain in a few patients after ano-rectal operations are a great therapeutic problem. Sometimes more than 6 months after LAR there are complaints about incontinence, disturbance connected to a spastic evacuation--whereas pain is more often connected with the situation after Stapler hemorrhiodectomy or other anal interventions. The therapeutic management has to consider all etiological factors and consists mainly of conservative therapy, including regulation of stool volume, slow-down of colon transit, strengthening of anal and pelvic floor muscles, regulation of co-ordination and ability of relaxation and straining, therapy of pain and--last not least--psychological support.

  7. 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.

  8. Uptake of HIV testing and outcomes within a Community-based Therapeutic Care (CTC) programme to treat Severe Acute Malnutrition in Malawi: a descriptive study

    PubMed Central

    Bahwere, Paluku; Piwoz, Ellen; Joshua, Marthias C; Sadler, Kate; Grobler-Tanner, Caroline H; Guerrero, Saul; Collins, Steve

    2008-01-01

    Background In Malawi and other high HIV prevalence countries, studies suggest that more than 30% of all severely malnourished children admitted to inpatient nutrition rehabilitation units are HIV-infected. However, clinical algorithms designed to diagnose paediatric HIV are neither sensitive nor specific in severely malnourished children. The present study was conducted to assess : i) whether HIV testing can be integrated into Community-based Therapeutic Care (CTC); ii) to determine if CTC can improve the identification of HIV infected children; and iii) to assess the impact of CTC programmes on the rehabilitation of HIV-infected children with Severe Acute Malnutrition (SAM). Methods This community-based cohort study was conducted in Dowa District, Central Malawi, a rural area 50 km from the capital, Lilongwe. Caregivers and children admitted in the Dowa CTC programme were prospectively (Prospective Cohort = PC) and retrospectively (Retrospective Cohort = RC) admitted into the study and offered HIV testing and counseling. Basic medical care and community nutrition rehabilitation was provided for children with SAM. The outcomes of interest were uptake of HIV testing, and recovery, relapse, and growth rates of HIV-positive and uninfected children in the CTC programme. Student's t-test and analysis of variance were used to compare means and Kruskall Wallis tests were used to compare medians. Dichotomous variables were compared using Chi2 analyses and Fisher's exact test. Stepwise logistic regression with backward elimination was used to identify predictors of HIV infection (α = 0.05). Results 1273 and 735 children were enrolled in the RC and PC. For the RC, the average age (SD) at CTC admission was 30.0 (17.2) months. For the PC, the average age at admission was 26.5 (13.7) months. Overall uptake of HIV testing was 60.7% for parents and 94% for children. HIV prevalence in severely malnourished children was 3%, much lower than anticipated. 59% of HIV-positive and 83

  9. Towards novel therapeutics for HIV through fragment-based screening and drug design.

    PubMed

    Tiefendbrunn, Theresa; Stout, C David

    2014-01-01

    Fragment-based drug discovery has been applied with varying levels of success to a number of proteins involved in the HIV (Human Immunodeficiency Virus) life cycle. Fragment-based approaches have led to the discovery of novel binding sites within protease, reverse transcriptase, integrase, and gp41. Novel compounds that bind to known pockets within CCR5 have also been identified via fragment screening, and a fragment-based approach to target the TAR-Tat interaction was explored. In the context of HIV-1 reverse transcriptase (RT), fragment-based approaches have yielded fragment hits with mid-μM activity in an in vitro activity assay, as well as fragment hits that are active against drug-resistant variants of RT. Fragment-based drug discovery is a powerful method to elucidate novel binding sites within proteins, and the method has had significant success in the context of HIV proteins. PMID:25455312

  10. Activities of Venom Proteins and Peptides with Possible Therapeutic Applications from Bees and WASPS.

    PubMed

    Ye, Xiujuan; Guan, Suzhen; Liu, Jiwen; Ng, Charlene C W; Chan, Gabriel H H; Sze, Stephen C W; Zhang, Kalin Y; Naude, Ryno; Rolka, Krzysztof; Wong, Jack Ho; Ng, Tzi Bun

    2016-01-01

    The variety of proteins and peptides isolated from honey bee venom and wasp venom includes melittin, adiapin, apamine, bradykinin, cardiopep, mast cell degranulating peptide, mastoparan, phospholipase A2 and secapin. Some of the activities they demonstrate may find therapeutic applications. PMID:27323949

  11. HIV infection and AIDS: new biology, therapeutic advances, and clinical implications. Introduction.

    PubMed

    Miles, S A

    1997-01-01

    Recent advances in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and the important role that viral load plays in the initial selection of antiretroviral therapy significantly alters our management of this disease. Guidelines from the British HIV Association, International AIDS Society-USA, and United States Public Health Service panels regarding the selection of appropriate antiretroviral therapy, and from the Centers for Disease Control and Prevention on prophylaxis for opportunistic infections, have recently been published. Despite tremendous advances in treating the disease and its related complications, a comprehensive, long-term disease management plan that includes recognition of patient concerns about quality of life is lacking. New approaches to managing HIV disease must now include strategies that address patient concerns about fatigue, gastrointestinal distress, malnutrition, and weight loss. Patients must become more involved in decisions about selection of specific drugs and drug regimens and must be consulted about their expectations and needs. We have made significant strides in the treatment of HIV disease. We can readily reduce the viral burden to virtually undetectable levels, and we must continue to develop even more potent and tolerable treatment regimens. We can make patients live longer. Helping patients live better quality lives deserves further study. PMID:9389309

  12. Possible therapeutic effect of a Traditional Chinese Medicine, Sinisan, on chronic restraint stress related disorders.

    PubMed

    Wang, Yu-Tong; Tan, Qing-Rong; Sun, Li-Li; Cao, Jun; Dou, Ke-Feng; Xia, Bing; Wang, Wen

    2009-01-16

    According to Traditional Chinese Medicine (TCM), the liver is the origin or most associated with stress related disorders such as depression. Sinisan, a TCM prescription, has been used as a hepatic protectant. We examined whether Sinisan exerts therapeutic effects in an experimental animal model: the chronic restraint stress (CRS) model. Sinisan was administered in the animal's drinking water at a concentration of 100mg/kg for 21 days (7 days pre-CRS and 14 days during the CRS). Spatial learning and memory were measured 24h after the CRS procedures using the Morris Water Maze (MWM). Aggressive behavior and body weight were determined as well. The Sinisan treatment decreased aggressive behaviors and reversed CRS-induced impairment of spatial learning and memory as well as decreased rate of growth. In conclusion, our results suggest that Sinisan does exert measurable therapeutic effects in an experimental chronic stress model.

  13. Targeting specific HATs for neurodegenerative disease treatment: translating basic biology to therapeutic possibilities

    PubMed Central

    Pirooznia, Sheila K.; Elefant, Felice

    2013-01-01

    Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HAT) activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC) inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and HATs in

  14. How genetic errors in GPCRs affect their function: Possible therapeutic strategies

    PubMed Central

    Stoy, Henriette; Gurevich, Vsevolod V.

    2015-01-01

    Activating and inactivating mutations in numerous human G protein-coupled receptors (GPCRs) are associated with a wide range of disease phenotypes. Here we use several class A GPCRs with a particularly large set of identified disease-associated mutations, many of which were biochemically characterized, along with known GPCR structures and current models of GPCR activation, to understand the molecular mechanisms yielding pathological phenotypes. Based on this mechanistic understanding we also propose different therapeutic approaches, both conventional, using small molecule ligands, and novel, involving gene therapy. PMID:26229975

  15. [Oxidative stress after preterm birth: origins, biomarkers, and possible therapeutic approaches].

    PubMed

    Yzydorczyk, C; Mitanchez, D; Buffat, C; Ligi, I; Grandvuillemin, I; Boubred, F; Simeoni, U

    2015-10-01

    The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future.

  16. Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells.

    PubMed

    Garbossa, D; Boido, M; Fontanella, M; Fronda, C; Ducati, A; Vercelli, A

    2012-07-01

    Spinal cord injury (SCI) often results in significant dysfunction and disability. A series of treatments have been proposed to prevent and overcome the formation of the glial scar and inhibitory factors to axon regrowth. In the last decade, cell therapy has emerged as a new tool for several diseases of the nervous system. Stem cells act as minipumps providing trophic and immunomodulatory factors to enhance axonal growth, to modulate the environment, and to reduce neuroinflammation. This capability can be boosted by genetical manipulation to deliver trophic molecules. Different types of stem cells have been tested, according to their properties and the therapeutic aims. They differ from each other for origin, developmental stage, stage of differentiation, and fate lineage. Related to this, stem cells differentiating into neurons could be used for cell replacement, even though the feasibility that stem cells after transplantation in the adult lesioned spinal cord can differentiate into neurons, integrate within neural circuits, and emit axons reaching the muscle is quite remote. The timing of cell therapy has been variable, and may be summarized in the acute and chronic phases of disease, when stem cells interact with a completely different environment. Even though further experimental studies are needed to elucidate the mechanisms of action, the therapeutic, and the side effects of cell therapy, several clinical protocols have been tested or are under trial. Here, we report the state-of-the-art of cell therapy in SCI, in terms of feasibility, outcome, and side effects.

  17. The caspase pathway as a possible therapeutic target in experimental pemphigus.

    PubMed

    Pacheco-Tovar, Deyanira; López-Luna, Argelia; Herrera-Esparza, Rafael; Avalos-Díaz, Esperanza

    2011-01-01

    Apoptosis plays a role in pemphigus IgG-dependent acantholysis; theoretically, the blockade of the caspase pathway could prevent the blistering that is caused by pemphigus autoantibodies. Using this strategy, we attempted to block the pathogenic effect of pemphigus IgG in Balb/c mice by using the caspase inhibitor Ac-DEVD-CMK. This inhibitor was administrated before the injection of pemphigus IgG into neonatal mice. The main results of the present investigation are as follows: (1) pemphigus IgG induces intraepidermal blisters in Balb/c neonatal mice; (2) keratinocytes around the blister and acantholytic cells undergo apoptosis; (3) the caspases inhibitor Ac-DEVD-CMK prevents apoptosis; (4) the inhibition of the caspase pathway prevents blister formation. In conclusion, inhibition of the caspase pathway may be a promising therapeutic tool that can help in the treatment of pemphigus flare ups. PMID:21403857

  18. 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.

  19. 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

  20. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets?

    PubMed

    Rochette, Luc; Lorin, Julie; Zeller, Marianne; Guilland, Jean-Claude; Lorgis, Luc; Cottin, Yves; Vergely, Catherine

    2013-12-01

    Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over-production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed.

  1. Natural products as anti-glycation agents: possible therapeutic potential for diabetic complications.

    PubMed

    Elosta, Abdulhakim; Ghous, Tahseen; Ahmed, Nessar

    2012-03-01

    Diabetes mellitus is characterised by hyperglycaemia, lipidaemia and oxidative stress and predisposes affected individuals to long-term complications afflicting the eyes, skin, kidneys, nerves and blood vessels. Increased protein glycation and the subsequent build-up of tissue advanced glycation endproducts (AGEs) contribute towards the pathogenesis of diabetic complications. Protein glycation is accompanied by generation of free radicals through autoxidation of glucose and glycated proteins and via interaction of AGEs with their cell surface receptors (referred to as RAGE). Glycationderived free radicals can damage proteins, lipids and nucleic acids and contribute towards oxidative stress in diabetes. There is interest in compounds with anti-glycation activity as they may offer therapeutic potential in delaying or preventing the onset of diabetic complications. Although many different compounds are under study, only a few have successfully entered clinical trials but none have yet been approved for clinical use. Whilst the search for new synthetic inhibitors of glycation continues, little attention has been paid to anti-glycation compounds from natural sources. In the last few decades the traditional system of medicine has become a topic of global interest. Various studies have indicated that dietary supplementation with combined anti-glycation and antioxidant nutrients may be a safe and simple complement to traditional therapies targeting diabetic complications. Data for forty two plants/constituents studied for anti-glycation activity is presented in this review and some commonly used medicinal plants that possess anti-glycation activity are discussed in detail including their active ingredients, mechanism of action and therapeutic potential. PMID:22268395

  2. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets?

    PubMed

    Rochette, Luc; Lorin, Julie; Zeller, Marianne; Guilland, Jean-Claude; Lorgis, Luc; Cottin, Yves; Vergely, Catherine

    2013-12-01

    Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over-production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed. PMID:23859953

  3. Possible participation of tumoricidal macrophages in the therapeutic effect of bleomycin on a transplantable rat fibrosarcoma.

    PubMed

    Morikawa, K; Hosokawa, M; Hamada, J; Xu, Z Y; Kobayashi, H

    1986-02-01

    When bleomycin (BLM) (5 mg/kg/day) was administered i.p. to WKA rats for 5 days from the eighth day after KMT-17 implantation, the therapeutic effects of BLM were demonstrated by complete tumor regression in 50% of the cases and prolongation of the mean survival time of the remainder [survival days, 44.3 +/- 13.6 (SD)]. The combined administration of an antimacrophage agent, carrageenan, with BLM significantly inhibited the therapeutic effects of BLM (cure rate, 33%; survival days, 29.8 +/- 5.8). By means of a Winn assay, the tumor neutralizing activity of both spleen cells and peritoneal cells (PC) against KMT-17 cells was found to be augmented in BLM-treated tumor bearing rats as compared with that in nontreated tumor bearing rats. The enhanced tumor neutralizing activity of spleen cells was not abolished by an anti-rat T-cell serum plus complement treatment and was present in an adherent macrophage enriched population. Similarly, an in vitro [125I]iododeoxyuridine release test enabled us to observe the enhancement of the cytotoxic activity of adherent spleen cells and adherent PC in BLM-treated rats. The cytotoxic activity of the PC of BLM-treated rats was not specific to KMT-17 cells alone but was also observed to operate against antigenically different tumor cells such as WFT-2N, KST-20, and K562 cells. An in vitro carrageenan treatment of PC taken from BLM-treated rats reduced their cytotoxic activity. At the same time, the combined administration of carrageenan and BLM also reduced the cytotoxic activity of PC. These results suggest that the tumoricidal activity of macrophages in tumor bearing rats is augmented after BLM therapy and that the activated tumoricidal macrophages may participate in the host-mediated antitumor effects of BLM. PMID:2416431

  4. 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 β-protein (Aβ) 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 Aβ-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 Aβ-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

  5. Compromised redox homeostasis, altered nitroso–redox balance, and therapeutic possibilities in atrial fibrillation

    PubMed Central

    Simon, Jillian N.; Ziberna, Klemen; Casadei, Barbara

    2016-01-01

    Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso–redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF. PMID:26786158

  6. Role of curcumin in idiopathic pulmonary arterial hypertension treatment: a new therapeutic possibility.

    PubMed

    Bronte, Enrico; Coppola, Giuseppe; Di Miceli, Riccardo; Sucato, Vincenzo; Russo, Antonio; Novo, Salvatore

    2013-11-01

    The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include systemic drugs such as prostanoids, phosphodiesterase inhibitors and antagonists of endothelin-1 (ERBs). Some researchers have long investigated the anti-inflammatory effects of curcumin. It shows a role for inactivation of NF-κB-mediated inflammation. On the basis of these findings we propose a potential role of curcumin and its pharmacologically fit derivatives for treatment of idiopathic pulmonary arterial hypertension.

  7. 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

  8. Compromised redox homeostasis, altered nitroso-redox balance, and therapeutic possibilities in atrial fibrillation.

    PubMed

    Simon, Jillian N; Ziberna, Klemen; Casadei, Barbara

    2016-04-01

    Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso-redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF.

  9. [Future cure of hearing disorders? Gene therapy and stem cell implantation are possible new therapeutic alternatives].

    PubMed

    Duan, M L; Ulfendahl, M; Ahlberg, A; Pyykkö, I; Borg, E

    2000-03-01

    Hearing loss is a very common disorder; nearly 10 per cent of the population is affected. Recently, a few findings such as the roles of neurotrophins, nitric oxide, reactive oxygen species and glutamate receptors in the peripheral hearing system have been highlighted. In this review, focus is set on possible mechanisms of peripheral hearing disorders, and on recent advances to prevent and treat hearing loss. Clinically useful treatment strategies, especially gene therapy and the use of embryonic stem cells, are particularly stressed.

  10. [Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate].

    PubMed

    Matolcsi, Judit; Rózsa, Csilla

    2015-01-30

    Dimethyl fumarate (DMF) is a novel oral therapy that has recently been approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Dimethyl fumarate shows anti-inflammatory and cytoprotective properties that are thought to be mediated primarily via activation of the nuclear factor (erythroid-derived 2)-like 2- Nrf2 transcriptional pathway, which up-regulates the genes involved in the cellular response to oxidative stress. The drug was evaluated in 2 large, randomized, double-blind, multicentric, multinational, 2-year, phase III clinical trials. The DEFINE and CONFIRM trials, conducted with over 2600 adult patients suffering from RRMS, unequivocally confirmed the efficacy of DMF (2 x 240 mg daily) in reducing the annualized relapse rate (ARR) and reducing the proportion of patients with MS relapse at 2 years. Significantly reduced sustained disability progression was observed with the drug versus placebo in DEFINE, while the same tendency was seen in CONFIRM. The MRI results of the studies were also convincing: DMF significantly reduced the number of new/enlarging T2-hyperintense lesions and the number of Gd-enhancing lesions compared to placebo. Dimethyl fumarate was generally well tolerated and no safety concern has been raised. Adverse events that occurred most frequently included flushing and gastrointestinal events. The long-term efficacy and tolerability of dimethyl fumarate is currently being investigated in the ENDORSE trial, with interim results demonstrating the same results as the two previous studies. In conclusion, although further, mostly comparative data are needed to fully establish the relative efficacy and tolerability of dimethyl fumarate compared with other therapies, dimethyl-fumarate is a valuable addition to the therapeutic options available for RRMS. PMID:25842911

  11. Mycophenolate Mofetil, a Possible Therapeutic Agent for Children with Juvenile Dermatomyositis

    PubMed Central

    Rouster-Stevens, Kelly A; Morgan, Gabrielle A; Wang, Deli; Pachman, Lauren M

    2010-01-01

    Objective To determine if mycophenolate mofetil (MMF) diminished skin and muscle disease activity in children with juvenile dermatomyositis (JDM) permitting decrease in corticosteroid dosage. Methods Retrospective data review for 50 JDM children identified the following: 38 (76%) girls, 39 (78%) white, 10 (20%) Hispanic, 1 (2%) black, mean age 12.2 ± 5.0 years who had been given MMF for 12 months. MMF dose and frequency, type of infection, white blood cell count (WBC), corticosteroid dose and validated disease activity score (DAS), (sub scores for skin [DAS-S], muscle [DAS-M]), were obtained. Results Twelve months after start of MMF, mean DAS-S decreased from 5.24 ± 0.29 to 3.72 ± 0.29 (p=0.001) and DAS-M dropped from 2.44 ± 0.39 to 1.17 ± 0.28 (p=0.002). Prednisone dose decreased from 0.39 mg/kg/day ± 0.06 mg to 0.23mg/kg/day ± 0.02 mg (p=0.0001), with resumption of linear growth (p=0.008). The WBC/lymphocyte count was unchanged over 12 months on MMF. Infection rate was assessed in a subset of 26 children with JDM followed for 12 months before start of MMF and compared with ensuing 12 months on MMF. There was no significant difference between pretreatment and first 6 months of MMF (p=0.44), but infection rate dropped in months 7–12 (p=0.001). Conclusions MMF appears to be worthy of consideration as an additional therapeutic modality for treatment of children with JDM. These data suggest that use of MMF decreases skin and muscle disease activity and is steroid sparing. MMF appears to be well tolerated, but patients should be monitored for infection. PMID:20521307

  12. Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications.

    PubMed

    Matin, Nassim; Tabatabaie, Omidreza; Falsaperla, Raffaele; Lubrano, Riccardo; Pavone, Piero; Mahmood, Fahad; Gullotta, Melissa; Serra, Agostino; Di Mauro, Paola; Cocuzza, Salvatore; Vitaliti, Giovanna

    2015-01-01

    Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1β intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1β/ IL-1β R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies. PMID:26260962

  13. Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications

    PubMed Central

    Matin, Nassim; Tabatabaie, Omidreza; Falsaperla, Raffaele; Lubrano, Riccardo; Pavone, Piero; Mahmood, Fahad; Gullotta, Melissa; Serra, Agostino; Mauro, Paola Di; Cocuzza, Salvatore; Vitaliti, Giovanna

    2015-01-01

    Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1β intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1β/ IL-1β R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies. PMID:26260962

  14. Heteromers of μ-δ opioid receptors: new pharmacology and novel therapeutic possibilities

    PubMed Central

    Fujita, Wakako; Gomes, Ivone; Devi, Lakshmi A

    2015-01-01

    Several studies suggest that heteromerization between μ (MOP) and δ (DOP) opioid receptors modulates the signalling properties of the individual receptors. For example, whereas activation of MOP receptors by an agonist induces G protein-mediated signalling, the same agonist induces β-arrestin-mediated signalling in the context of the MOP-DOP receptor heteromer. Moreover, heteromer-mediated signalling is allosterically modulated by a combination of MOP and DOP receptor ligands. This has implications in analgesia given that morphine-induced antinociception can be potentiated by DOP receptor ligands. Recently reagents selectively targeting the MOP-DOP receptor heteromer such as bivalent ligands, antibodies or membrane permeable peptides have been generated; these reagents are enabling studies to elucidate the contribution of endogenously expressed heteromers to analgesia as well as to the development of side-effects associated with chronic opioid use. Recent advances in drug screening technology have led to the identification of a MOP-DOP receptor heteromer-biased agonist that activates both G protein-mediated and β-arrestin-mediated signalling. Moreover, this heteromer-biased agonist exhibits potent antinociceptive activity but with reduced side-effects, suggesting that ligands targeting the MOP-DOP receptor heteromer form a basis for the development of novel therapeutics for the treatment of pain. In this review, we summarize findings regarding the biological and functional characteristics of the MOP-DOP receptor heteromer and the in vitro and in vivo properties of heteromer-selective ligands. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24571499

  15. Protein in St. John's Wort may suppress HIV-1 gene expression. Research suggests interesting possibilities.

    PubMed

    2005-12-01

    St. John's Wort contains a protein that inhibits HIV-1 replication, according to new research. Investigators who have spent more than a decade studying the mechanism of development of neurological disorders in AIDS patients decided to look at the impact St. John's Wort might have on neuronal cells, says Kamel Khalili, PhD, director of the Center for Neurovirology, professor, and acting chair of the department of neuroscience at Temple University's School of Medicine in Philadelphia, PA. PMID:16397939

  16. HIV

    PubMed Central

    Chawla, Sumit; Sahoo, Soumya Swaroop; Jain, Rambilas; Khanna, Pardeep; Mehta, Bharti; Singh, Inderjeet

    2014-01-01

    Getting to zero: zero new HIV infections, zero deaths from AIDS-related illness, zero discrimination is the theme of World AIDS Day 2012. Given the spread of the epidemic today, getting to zero may sound difficult, but significant progress is underway. The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India’s annual health expenditure in 2004. The additional loss due to loss of labor income and increased medical expenditure as measured by the external transfers, account for 5% of the country’s health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering. Despite the remarkable achievements in development of anti-retroviral therapies against HIV and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. PMID:24056755

  17. HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain.

    PubMed

    Tsantoulas, Christoforos; Mooney, Elizabeth R; McNaughton, Peter A

    2016-09-15

    Nociception - the ability to detect painful stimuli - is an invaluable sense that warns against present or imminent damage. In patients with chronic pain, however, this warning signal persists in the absence of any genuine threat and affects all aspects of everyday life. Neuropathic pain, a form of chronic pain caused by damage to sensory nerves themselves, is dishearteningly refractory to drugs that may work in other types of pain and is a major unmet medical need begging for novel analgesics. Hyperpolarisation-activated cyclic nucleotide (HCN)-modulated ion channels are best known for their fundamental pacemaker role in the heart; here, we review data demonstrating that the HCN2 isoform acts in an analogous way as a 'pacemaker for pain', in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states. Pharmacological block or genetic deletion of HCN2 in sensory neurons provides robust pain relief in a variety of animal models of inflammatory and neuropathic pain, without any effect on normal sensation of acute pain. We discuss the implications of these findings for our understanding of neuropathic pain pathogenesis, and we outline possible future opportunities for the development of efficacious and safe pharmacotherapies in a range of chronic pain syndromes. PMID:27621481

  18. Immune Responses in Age Related Macular Degeneration and a possible Long Term Therapeutic Strategy for Prevention

    PubMed Central

    Nussenblatt, Robert B.; Lee, Richard W.J.; Chew, Emily; Wei, Lai; Liu, Baoying; Sen, Nida; Dick, Andrew D.; Ferris, Frederick L.

    2014-01-01

    Purpose To describe the immune alterations associated with, age related macular degeneration (AMD). Based on these findings, to offer an approach to possibly prevent the expression of late disease. Design Perspective Methods Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients. Results Significant genetic associations have been identified and reported, but environmentally induced (including epigenetic) changes are also an important consideration. Immune alterations include a strong interleukin-17 family signature as well as marked expression of these molecules in the eye. Oxidative stress as well as other homeostatic altering mechanisms occurs throughout life. With this immune dysregulation there is a rationale for considering immunotherapy. Indeed immunotherapy has been shown to affect the late stages of AMD. Conclusion Immune dysregulation appears to be an underlying alteration in AMD as in other diseases thought to be degenerative and due to aging. Parainflammation and immunosensescence may importantly contribute to the development of disease. The role of complement factor H still needs to be better defined but in light of its association with ocular inflammatory conditions such as sarcoidosis, it does not appear to be unique to AMD but rather may be a marker for retinal pigment epithelium function. With the strong interleukin-17 family signature and the need to treat early on in the disease process, oral tolerance may be considered to prevent disease progression. PMID:24709810

  19. A review on possible therapeutic targets to contain obesity: The role of phytochemicals.

    PubMed

    Balaji, Meriga; Ganjayi, Muni Swamy; Hanuma Kumar, Gali E N; Parim, Brahma Naidu; Mopuri, Ramgopal; Dasari, Sreenivasulu

    2016-01-01

    The prevalence and severity of obesity has increased markedly in recent decades making it a global public health concern. Since obesity is a potential risk factor in the development of hypertension, type-2 diabetes, cardiovascular diseases, infertility, etc., it is no more viewed as a cosmetic issue. Currently, only a few FDA-approved anti-obesity drugs like Orlistat, Lorcaserin and Phentermine-topiramate are available in the market, but they have considerable side effects. On the other hand, bariatric surgery as an alternative is associated with high risk and expensive. In view of these there is a growing trend towards natural product-based drug intervention as one of the crucial strategies for management of obesity and related ailments. In Asian traditional medicine and Ayurvedic literature a good number of plant species have been used and quoted for possible lipid-lowering and anti-obesity effects; however, many of them have not been evaluated rigorously for a definite recommendation and also lack adequate scientific validation. This review explores and updates on various plant species, their used parts, bioactive components and focuses multiple targets/pathways to contain obesity which may pave the way to develop novel and effective drugs. We also summarised different drugs in use to treat obesity and their current status. Nature is future promise of our wellbeing. PMID:26740473

  20. 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 β-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.

  1. Experimental study of possible involvement of some apoptosis mechanisms in pathogenesis of the HIV infection: 2. The CD4+ T lymphocytes depletion in the HIV infection occurs through activation-induced apoptosis.

    PubMed

    Topârceanu, F; Bârnaure, F; Iucu, C T; Spulbăr, E; Pătru, C

    1999-01-01

    The present work is a part of a complex experimental study aimed at the demonstration of the two previously published hypotheses regarding the involvement of apoptosis in general in the viral infection and especially in HIV infection (1). Our researches have shown that the significant lowering of the number of peripheral CD4+ T lymphocytes in HIV-infected children is associated with a marked increase of the soluble interleukin 2-receptor (sIL2-R)# concentration, in comparison with HIV-negative, healthy or acute infections exhibiting controls. As sIL-2R is a circulating marker of cell activation, we investigated the role of monocytes (antigen-presenting cells) in the viability of peripheral lymphocytes isolated from HIV-infected children in comparison with the controls. Lymphocytes cultivation in the absence and in the presence of autologous monocytes led to the following conclusions: 1) freshly isolated lymphocytes from HIV-positive individuals undergo an accelerated spontaneous apoptosis in comparison with that of lymphocytes isolated from HIV-negative individuals: 2) the normal antiapoptotic effect of monocytes on lymphocytes diminishes gradually in the HIV infection, changing into a proapoptotic effect, corresponding to the sIL-2R augmentation to increasingly higher values. Our results show that peripheral CD4+ T-lymphocyte depletion in HIV infection occurs through apoptosis and the activation-induced cell death is one of the possible apoptosis mechanisms.

  2. Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

    PubMed Central

    Shankar, Esaki Muthu; Vignesh, Ramachandran; Murugavel, Kailapuri G; Balakrishnan, Pachamuthu; Sekar, Ramalingam; Lloyd, Charmaine AC; Solomon, Suniti; Kumarasamy, Nagalingeswaran

    2007-01-01

    Gut immune components are severely compromised among persons with AIDS, which allows increased translocation of bacterial lipopolysaccharides (LPS) into the systemic circulation. These microbial LPS are reportedly increased in chronically HIV-infected individuals and findings have correlated convincingly with measures of immune activation. Immune reconstitution inflammatory syndrome (IRIS) is an adverse consequence of the restoration of pathogen-specific immune responses in a subset of HIV-infected subjects with underlying latent infections during the initial months of highly active antiretroviral treatment (HAART). Whether IRIS is the result of a response to a high antigen burden, an excessive response by the recovering immune system, exacerbated production of pro-inflammatory cytokines or a lack of immune regulation due to inability to produce regulatory cytokines remains to be determined. We theorize that those who develop IRIS have a high burden of proinflammatory cytokines produced also in response to systemic bacterial LPS that nonspecifically act on latent mycobacterial antigens. We also hypothesize that subjects that do not develop IRIS could have developed either tolerance (anergy) to persistent LPS/tubercle antigens or could have normal FOXP3+ gene and that those with defective FOXP3+ gene or those with enormous plasma LPS could be vulnerable to IRIS. The measure of microbial LPS, anti-LPS antibodies and nonspecific plasma cytokines in subjects on HAART shall predict the role of these components in IRIS. PMID:18053126

  3. [Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection].

    PubMed

    Carella, E; Moschini, G L; Romanelli, F; Bossalini, G; Alberici, F; Viale, P; Ratti, G

    1997-05-01

    We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.

  4. Poly-S-Nitrosated Albumin as a Safe and Effective Multifunctional Antitumor Agent: Characterization, Biochemistry and Possible Future Therapeutic Applications

    PubMed Central

    Ishima, Yu; Kragh-Hansen, Ulrich; Maruyama, Toru; Otagiri, Masaki

    2013-01-01

    Nitric oxide (NO) is a ubiquitous molecule involved in multiple cellular functions. Inappropriate production of NO may lead to disease states. To date, pharmacologically active compounds that release NO within the body, such as organic nitrates, have been used as therapeutic agents, but their efficacy is significantly limited by unwanted side effects. Therefore, novel NO donors with better pharmacological and pharmacokinetic properties are highly desirable. The S-nitrosothiol fraction in plasma is largely composed of endogenous S-nitrosated human serum albumin (Mono-SNO-HSA), and that is why we are testing whether this albumin form can be therapeutically useful. Recently, we developed SNO-HSA analogs such as SNO-HSA with many conjugated SNO groups (Poly-SNO-HSA) which were prepared using chemical modification. Unexpectedly, we found striking inverse effects between Poly-SNO-HSA and Mono-SNO-HSA. Despite the fact that Mono-SNO-HSA inhibits apoptosis, Poly-SNO-HSA possesses very strong proapoptotic effects against tumor cells. Furthermore, Poly-SNO-HSA can reduce or perhaps completely eliminate the multidrug resistance often developed by cancer cells. In this review, we forward the possibility that Poly-SNO-HSA can be used as a safe and effective multifunctional antitumor agent. PMID:24490156

  5. Identification of Drug Targets in Helicobacter pylori by in silico Analysis: Possible Therapeutic Implications for Gastric cancer.

    PubMed

    Nammi, Deepthi; Srimath-Tirumala-Peddinti, Ravi C P K; Neelapu, Nageswara Rao R

    2016-01-01

    Helicobacter pylori colonize stomach, inducing gastritis, ulcers and gastric cancer. Drugs are used to relieve pain, but not H. pylori infections. Hence, there is a need for discovery of drug targets and drugs for H. pylori. An objective of this current study is to identify drug targets for H. pylori. RAST was used to compare genomes of 23 H. pylori strains with Homo sapiens sapiens, other Helicobacter species (H. acinonychis, H. hepaticus, H. mustalae) and among them, to identify 13471 unique genes. Bacterial genes which are non-homologous to humans and essential for pathogen are identified using BLASTp. Later, 29 potential drug targets were identified by subjecting these genes to property analysis. Eleven of the 29 drug targets are already experimentally validated, lending credence to our approach. These methods have enabled rapid identification of drug targets with possible therapeutic implications for gastric cancer.

  6. Ending the HIV/AIDS epidemic in low- and middle-income countries by 2030: is it possible?

    PubMed Central

    Harries, Anthony D.; Suthar, Amitabh B.; Takarinda, Kudakwashe C.; Tweya, Hannock; Kyaw, Nang Thu Thu; Tayler-Smith, Katie; Zachariah, Rony

    2016-01-01

    The international community has committed to ending the epidemics of HIV/AIDS, tuberculosis, malaria, and neglected tropical infections by 2030, and this bold stance deserves universal support. In this paper, we discuss whether this ambitious goal is achievable for HIV/AIDS and what is needed to further accelerate progress. The joint United Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets and the related strategy are built upon currently available health technologies that can diagnose HIV infection and suppress viral replication in all people with HIV. Nonetheless, there is much work to be done in ensuring equitable access to these HIV services for key populations and those who remain outside the rims of the traditional health services. Identifying a cure and a preventive vaccine would further help accelerate progress in ending the epidemic. Other disease control programmes could learn from the response to the HIV/AIDS epidemic.

  7. Ending the HIV/AIDS epidemic in low- and middle-income countries by 2030: is it possible?

    PubMed Central

    Harries, Anthony D.; Suthar, Amitabh B.; Takarinda, Kudakwashe C.; Tweya, Hannock; Kyaw, Nang Thu Thu; Tayler-Smith, Katie; Zachariah, Rony

    2016-01-01

    The international community has committed to ending the epidemics of HIV/AIDS, tuberculosis, malaria, and neglected tropical infections by 2030, and this bold stance deserves universal support. In this paper, we discuss whether this ambitious goal is achievable for HIV/AIDS and what is needed to further accelerate progress. The joint United Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets and the related strategy are built upon currently available health technologies that can diagnose HIV infection and suppress viral replication in all people with HIV. Nonetheless, there is much work to be done in ensuring equitable access to these HIV services for key populations and those who remain outside the rims of the traditional health services. Identifying a cure and a preventive vaccine would further help accelerate progress in ending the epidemic. Other disease control programmes could learn from the response to the HIV/AIDS epidemic. PMID:27703672

  8. 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

  9. Immunological and pharmacological strategies to reactivate HIV-1 from latently infected cells: a possibility for HIV-1 paediatric patients?

    PubMed

    Martínez-Bonet, M; Clemente, M I; Serramía, M J; Moreno, S; Muñoz, E; Muñoz-Fernández, M A

    2015-07-01

    The limitations to establishing a viral reservoir facilitated by early cART in children could play a critical role in achieving natural control of viral replication upon discontinuation of cART, which could be defined as 'functional cure'. Viral reservoirs could provide a persistent source of recrudescent viraemia after withdrawal of cART, despite temporary remission of HIV-1 infection, as observed in the 'Mississippi baby'. Intensification of cART has been proposed as a strategy to control residual replication and to diminish the reservoirs. The effects of cART intensification with maraviroc persisted after discontinuation of the drug in HIV-1-infected adults. However, in HIV-1-infected children, the emergence of CXCR4-using variants occurs very early, and the use of CCR5 antagonists in these children as intensification therapy may not be the best alternative. New treatments to eradicate HIV-1 are focused on the activation of viral production from latently infected cells to purge and clear HIV-1 reservoirs. This strategy involves the use of a wide range of small molecules called latency-reversing agents (LRAs). Histone deacetylase inhibitors (HDACi) such as givinostat, belinostat and panobinostat, and class I-selective HDACis that include oxamflatin, NCH-51 and romidepsin, are the most advanced in clinical testing for HIV-1 LRAs. Panobinostat and romidepsin show an efficient reactivation profile in J89GFP cells, a lymphocyte HIV-1 latently infected cell line considered a relevant model to study post-integration HIV-1 latency and reactivation. Clinical trials with panobinostat and romidepsin have been performed in children with other pathologies and it could be reasonable to design a clinical trial using these drugs in combination with cART in HIV-1-infected children.

  10. Retention and Treatment Outcomes of an Undernutrition Program for HIV patients involving Ready-to-Use Therapeutic Food at Gondar University Hospital, Ethiopia: A Cross-Sectional Study

    PubMed Central

    Bhagavathula, Akshaya Srikanth; Dawson, Angela; Elnour, Asim Ahmed; Shehab, Abdulla

    2016-01-01

    Introduction Despite global efforts to eradicate poverty and hunger, under-nutrition is still a major health problem, especially in Sub-Saharan Africa, where HIV/AIDS prevalence is also a serious burden. Aim To assess the retention and outcomes of under-nutrition treatment program in Gondar University Hospital, Ethiopia. Settings and Design: A cross-sectional study was conducted in HIV positive children and adults participating in the Ready-to-use Therapeutic Food (RUTF) treatment program at Gondar University Hospital ART clinic for one year from November 2012 to November 2013. Materials and Methods Six hundred and thirty six patient records were followed-up for one year. Outcome variables were Mid-Upper Arm Circumference (MUAC) values measured as severe, moderate acute malnutrition, normal after treatment, non-respondent, relapsed and lost to follow-up using the hospital records of HIV positive children and adults eligible for the program. Statistical Analysis: Univariate and multivariate analysis were performed to compute Crude Odds Ratio (COR) and Adjusted Odds Ratio (AOR). Statistical significance was set at p-value<0.05. Results Among 636 clients, 44.2% achieved MUAC measures ≥ 125 mm for children and ≥ 21 cm for adults at 4 and 6 months. 70.1% of those were children while 29.9% of the 281 were adults. Moreover, a more positive initial response to ready-to-use therapeutic food was found among children as there was significant increase (p<0.05) in MUAC value after the second month of initiating treatment while adults achieved a significant (p<0.05, p<0.01) in MUAC at the 4th and 6th month respectively. There was a significant association between age, nutrition status and treatment outcome, while sex, HIV status, education and residency were not associated with treatment outcome. Conclusion Recovery and weight gain rates were below 50%. Defaulter rates were higher than the Sphere standards and recovery was better in children than adults. Integrated RUTF and

  11. " … it's almost therapeutic, right? Because it's almost like that session that I never had": gay men's accounts of being a participant in HIV research.

    PubMed

    Grace, Daniel; Steinberg, Malcolm; Chown, Sarah A; Jollimore, Jody; Parry, Robin; Gilbert, Mark

    2016-10-01

    Limited research has explored how gay, bisexual and other men who have sex with men describe the impact of their involvement in HIV and sexual health research. We enrolled 166 gay and bisexual men who tested HIV-negative at a community sexual health clinic in Vancouver, British Columbia, into a year-long mixed methods study. Thirty-three of these participants who reported recent condomless anal intercourse were purposively recruited into an embedded qualitative study. Analysis revealed rich accounts of the self-described, interrelated impacts of study participation: (1) pride in contribution and community involvement (e.g., as a rationale for enrolment and an outcome of participation); (2) how one thinks about sexual behaviours and partnerships (e.g., encouraging reflection on the types and amount of sex they have had; in some cases the methods of quantitative data collection were said to have produced feelings of guilt or shame); and (3) experiencing research as a form of counselling (e.g., qualitative interviews were experienced as having a major therapeutic component to them). Our analysis underscores the importance of researchers being reflexive regarding how study participation in HIV research may impact participants, including unintended emotional and behavioural impacts.

  12. HIV chemotherapy

    NASA Astrophysics Data System (ADS)

    Richman, Douglas D.

    2001-04-01

    The use of chemotherapy to suppress replication of the human immunodeficiency virus (HIV) has transformed the face of AIDS in the developed world. Pronounced reductions in illness and death have been achieved and healthcare utilization has diminished. HIV therapy has also provided many new insights into the pathogenesis and the viral and cellular dynamics of HIV infection. But challenges remain. Treatment does not suppress HIV replication in all patients, and the emergence of drug-resistant virus hinders subsequent treatment. Chronic therapy can also result in toxicity. These challenges prompt the search for new drugs and new therapeutic strategies to control chronic viral replication.

  13. Carbohydrate-binding agents cause deletions of highly conserved glycosylation sites in HIV GP120: a new therapeutic concept to hit the achilles heel of HIV.

    PubMed

    Balzarini, Jan; Van Laethem, Kristel; Hatse, Sigrid; Froeyen, Matheus; Peumans, Willy; Van Damme, Els; Schols, Dominique

    2005-12-01

    Mannose-binding proteins derived from several plants (i.e. Hippeastrum hybrid and Galanthus nivalis agglutinin) or prokaryotes (i.e. cyanovirin-N) inhibit human immunodeficiency virus (HIV) replication and select for drug-resistant viruses that show profound deletion of N-glycosylation sites in the GP120 envelope (Balzarini, J., Van Laethem, K., Hatse, S., Vermeire, K., De Clercq, E., Peumans, W., Van Damme, E., Vandamme, A.-M., Bolmstedt, A., and Schols, D. (2004) J. Virol. 78, 10617-10627; Balzarini, J., Van Laethem, K., Hatse, S., Froeyen, M., Van Damme, E., Bolmstedt, A., Peumans, W., De Clercq, E., and Schols, D. (2005) Mol. Pharmacol. 67, 1556-1565). Here we demonstrated that the N-acetylglucosamine-binding protein from Urtica dioica (UDA) prevents HIV entry and eventually selects for viruses in which conserved N-glycosylation sites in GP120 were deleted. In contrast to the mannose-binding proteins, which have a 50-100-fold decreased antiviral activity against the UDA-exposed mutant viruses, UDA has decreased anti-HIV activity to a very limited extent, even against those mutant virus strains that lack at least 9 of 22 ( approximately 40%) glycosylation sites in their GP120 envelope. Therefore, UDA represents the prototype of a new conceptual class of carbohydrate-binding agents with an unusually specific and targeted drug resistance profile. It forces HIV to escape drug pressure by deleting the indispensable glycans on its GP120, thereby obligatorily exposing previously hidden immunogenic epitopes on its envelope.

  14. Humanized Mouse Models of HIV Infection

    PubMed Central

    Denton, Paul W.; Garcia, J. Victor

    2013-01-01

    Because of the limited tropism of HIV, in vivo modeling of this virus has been almost exclusively limited to other lentiviruses such as SIV that reproduce many important characteristics of HIV infection. However, there are significant genetic and biological differences among lentiviruses and some HIV-specific interventions are not effective against other lentiviruses in non-human hosts. For these reasons much emphasis has recently been placed on developing alternative animal models that support HIV replication and recapitulate key aspects of HIV infection and pathogenesis in humans. Humanized mice, CD34+ hematopoietic progenitor cell transplanted immunodeficient mice and in particular mice also implanted with human thymic/liver tissue (BLT mice) that develop a functional human immune system, have been the focus of a great deal of attention as possible models to study virtually all aspects of HIV biology and pathogenesis. Humanized mice are systemically reconstituted with human lymphoid cells offering rapid, reliable and reproducible experimental systems for HIV research. Peripheral blood of humanized mice can be readily sampled longitudinally to assess reconstitution with human cells and to monitor HIV replication permitting the evaluation of multiple parameters of HIV infection such as viral load levels, CD4+ T cell depletion, immune activation, as well as the effects of therapeutic interventions. Of high relevance to HIV transmission is the extensive characterization and validation of the reconstitution with human lymphoid cells of the female reproductive tract and of the gastrointestinal tract of humanized BLT mice that renders them susceptible to both vaginal and rectal HIV infection. Other important attributes of all types of humanized mice include: 1) their small size and cost that make them broadly accessible; 2) multiple cohorts of humanized mice can be made from multiple human donors and each cohort has identical human cells, permitting control of

  15. Exome analysis of HIV patients submitted to dendritic cells therapeutic vaccine reveals an association of CNOT1 gene with response to the treatment

    PubMed Central

    Moura, Ronald; Pontillo, Alessandra; D'Adamo, Pio; Pirastu, Nicola; Coelho, Antonio Campos; Crovella, Sergio

    2014-01-01

    Introduction With the aim of searching genetic factors associated with the response to an immune treatment based on autologous monocyte-derived dendritic cells pulsed with autologous inactivated HIV, we performed exome analysis by screening more than 240,000 putative functional exonic variants in 18 HIV-positive Brazilian patients that underwent the immune treatment. Methods Exome analysis has been performed using the ILLUMINA Infinium HumanExome BeadChip. zCall algorithm allowed us to recall rare variants. Quality control and SNP-centred analysis were done with GenABEL R package. An in-house implementation of the Wang method permitted gene-centred analysis. Results CCR4-NOT transcription complex, subunit 1 (CNOT1) gene (16q21), showed the strongest association with the modification of the response to the therapeutic vaccine (p=0.00075). CNOT1 SNP rs7188697 A/G was significantly associated with DC treatment response. The presence of a G allele indicated poor response to the therapeutic vaccine (p=0.0031; OR=33.00; CI=1.74–624.66), and the SNP behaved in a dominant model (A/A vs. A/G+G/G p=0.0009; OR=107.66; 95% CI=3.85–3013.31), being the A/G genotype present only in weak/transient responders, conferring susceptibility to poor response to the immune treatment. Discussion CNOT1 is known to be involved in the control of mRNA deadenylation and mRNA decay. Moreover, CNOT1 has been recently described as being involved in the regulation of inflammatory processes mediated by tristetraprolin (TTP). The TTP-CCR4-NOT complex (CNOT1 in the CCR4-NOT complex is the binding site for TTP) has been reported as interfering with HIV replication, through post-transcriptional control. Therefore, we can hypothesize that genetic variation occurring in the CNOT1 gene could impair the TTP-CCR4-NOT complex, thus interfering with HIV replication and/or host immune response. Conclusions Being aware that our findings are exclusive to the 18 patients studied with a need for replication

  16. [The usefulness of a genogram as a tool in therapeutic patient education: an exploratory study of parents of children living with HIV/AIDS in Benin].

    PubMed

    Juré, Estelle; Iguenane, Jacqueline; Toudonou, Annicette; Azondekon, Alain; Gagnayre, Rémi

    2010-01-01

    Understanding family dynamics and relationship is an important facet of care, therapeutic education and psychosocial support. As part of a therapeutic education program organized within a pediatric service in Cotonou, Benin, we have experimented with the genogram at the time of diagnosis and tested it as an educational tool. This study evaluates the usefulness of the genogram for therapeutic patient education, and its capacity to serve as an aid to better understand family structure and dynamics. The study was conducted in 2007 with 29 parents of children living with HIV / AIDS. Six professionals observed the conditions for the development and application of the genograms their effects on the production of information of an educational nature. The results indicate that it can provide families and caregivers benchmarks essential for understanding the role of the family and community in which the child-patient is situated and how they function. It facilitates the identification of key resource persons for the child and selfcare to be mobilized and fostered within the family.

  17. HIV and the gut microbiota, partners in crime: breaking the vicious cycle to unearth new therapeutic targets.

    PubMed

    Vyboh, Kishanda; Jenabian, Mohammad-Ali; Mehraj, Vikram; Routy, Jean-Pierre

    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.

  18. 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.

  19. [Summary of work session 4: Effects of calcitonin and somatostatin on the stomach and pancreas--a possible therapeutic principle].

    PubMed

    Goebell, H; Hotz, J

    1976-03-01

    Although calcitonin and somatostatin are polypeptid hormones of entirely different structure, in pharmacological doses they possess a similar effect to secretions of stomach and pancreas. Given intravenously, they generally inhibit the basal secretion of organs, stimulated by pentagastrin or pancreozymin, as well as the contraction of the gallbladder. Orally, calcitonin also suppresses by direct contact the secretion of the stomach. While calcitonin in higher doses shows only very slight and tolerable side effects (nausea, headache), somatostatin acts suppressively on many other hormone-regulated systems. Apart from this, disturbances of blood coagulation in monkeys and man were observed, findings which necessitate very careful application. Therapeutical trials appear reasonable with calcitonin in treating acute pancreatitis, in prophylaxis and treatment of stress ulcers with the danger of bleeding, in intensive care medicine, in preoperative procedure of Zollinger-Ellison syndrome as well as in duodenal ulcers (oral calcitonin). Double blind studies are carried out at present to answer most of these questions (acute pancreatitis, stress ulcers, duodenal ulcers), results of which should definitely be awaited.

  20. 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 Fcγ receptor (FcγR)-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

  1. Structural and electronic properties of new fullerene derivatives and their possible application as HIV-1 protease inhibitors

    NASA Astrophysics Data System (ADS)

    Ibrahim, Medhat; Saleh, Noha A.; Hameed, Ali Jameel; Elshemey, Wael M.; Elsayed, Anwar A.

    2010-02-01

    Density functional theory (DFT) calculations have been carried out at the hybrid Becke 3-Lee-Yang-Parr; B3LYP/3-21G** level of theory to study two series of hydroxy-chalca-acetic acid-(4-pyrrolidin-1-yl-phenyl) ester [C 60-C 2H 4N-(4-XCOCH 2OH)C 6H 4] and hydroxy-chalcoacetic acid-[2-(2-hydroxy-acetylchalcanyl)-4-pyrrolidin-1-yl-phenyl] ester[C 60-C 2H 4N-(3,4-XCOCH 2OH)C 6H 4]. The X atom is O, S or Se for the two series. The vibrational spectra, physical, chemical, thermodynamics and Quantitative Structure Activity Relationship (QSAR) properties of the studied molecules are calculated and discussed. We have evaluated these molecules as HIV-1 protease inhibitors based on the hydrogenation interaction between the hydroxymethylcarbonyl (HMC) groups and the two aspartic acid of the HIV-1 protease active site. Results show that some of the investigated fullerene-based derivatives can be considered promising as HIV-1 protease inhibitors.

  2. Is it possible to diagnose the therapeutic adherence of patients with COPD in clinical practice? A cohort study

    PubMed Central

    2011-01-01

    Background Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor. It is therefore necessary to determine the magnitude of non-adherence to develop strategies to correct this behaviour. The purpose of this study was to analyse the diagnostic validity of indirect adherence methods. Methods Sample: 195 COPD patients undergoing scheduled inhaled treatment attending 5 Primary Care Centres of Malaga, Spain. Variables: Sociodemographic profile, illness data, spirometry, quality of life (St. George Respiratory Questionnaire: SGRQ), and inhaled medication counting (count of dose/pill or electronic monitoring) were collected. The patient's knowledge of COPD (Batalla test:BT),their attitude towards treatment (Morisky-Green test: MGT) and their self-reported therapeutic adherence (Haynes-Sackett test: HST) were used as methods of evaluating adherence. The follow-up consisted four visits over one year (the recruitment visit: V0; and after 1 month:V1; 6 months:V2; and 1 year:V3). Results The mean age was 69.59 (95% CI, 68.29-70.89) years old and 93.8% were male. Other findings included: 85.4% had a low educational level, 23.6% were smokers, 71.5% mild-moderate COPD stage with a FEV1 = 56.86 (SD = 18.85); exacerbations per year = 1.41(95% CI, 1-1.8). The total SGRQ score was 44.96 (95% CI, 42.46-47.46), showing a mild self-perceived impairment in health. The prevalence of adherence (dose/pill count) was 68.1% (95% CI, 60.9-75.3) at V1, 80% (95% CI, 73-87) at V2 and 84% (95% CI, 77.9) at V3. The MGT showed a specificity of 67.34% at V1, 76.19% at V2 and 69.62% at V3. The sensitivity was 53.33% at V1, 66.66% at V2 and 33.33% at V3.The BT showed a specificity of 55.1% at V1, 70.23% at V2 and 67.09% at V3. The sensitivity was 68.88% at V1, 71.43% at V2 and 46.66% at V3. Considering both tests together, the specificity was 86.73% at V1, 94.04% at V2 and 92.49% at V3 and the sensitivity was 37.77% at V1, 47.62% at V2 and 13.3% at V3. Conclusions

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

    PubMed

    Oesterle, Adam; Bowman, Marion A Hofmann

    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.

  4. 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

  5. Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV in Overseas Job Seekers of Bangladesh with the Possible Routes of Transmission.

    PubMed

    Jobayer, M; Chowdhury, S S; Shamsuzzaman, S M; Islam, M S

    2016-07-01

    Hepatitis and AIDS are major public health problem globally. The aim of this study was to determine the sero-prevalence of hepatitis B, C virus and HIV infection among Bangladeshi overseas job seekers. This cross sectional study was carried out in the Department of Microbiology of Dhaka Medical College, Dhaka, Bangladesh from February 2013 to August 2013. A total of 2254 adult (18-45 years) male job seekers to Malaysia attending for health check up were enrolled. HBsAg, Anti-HCV, Anti-HIV were detected from venous blood by ELISA method using commercial kits. From the positive people, further history and information were collected by predesigned questionnaire. Prevalence of HBV was 2.35%, HCV was 0.13% and none was found positive for HIV. Prevalence of hepatitis was higher in the age group of 21-30 year and infection was more prevalent in married group. No significant relationship was found between hepatitis infection and religion, localities, profession. Only a few cases had history of possible major known route of transmission of virus. But most of them had history of taking injection or sharing blades in barber shop and history of circumcision. About 96% population had no history of hepatitis B vaccination. None was co-infected with HBV and HCV. Prevalence of hepatitis B virus infection in adult population appears to be on decline and hepatitis C and HIV infection is still low in Bangladesh. In majority of the positive person, routes of transmission of viruses were not well established. PMID:27612902

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

    PubMed

    Alias, A G

    2000-04-01

    .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.

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

    PubMed

    Alias, A G

    2000-04-01

    .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

  8. [Clinical, biological, therapeutic and evolving profile of patients with HIV infection hospitalized at Infectious and tropical diseases unit in Abidjan (Ivory Coast)].

    PubMed

    Kra, O; Aba, Y T; Yao, K H; Ouattara, B; Abouo, F; Tanon, K A; Eholié, S; Bissagnené, E

    2013-02-01

    The objective of this study is to describe the clinical, biological, therapeutic and evolving current profile of hospitalized patients with HIV infection in the cohort of the Infectious and Tropical Diseases Unit (ITDU) in the aim to improve their care management. This is a retrospective study, conducted on medical data of hospitalized cases of patients with HIV infection in the ITDU at the teaching hospital of Treichville (Abidjan) from 2006 to 2007. During the two years, 447 patients were included in the study. Their average age was 39 years [18 years-86 years] and sex ratio was 0.69. Of the 447 patients, 35% were unemployed and 67% were new patients who had never undergone antiretroviral therapy (ART). The duration of drug exposure was less than 6 months in 59% of treated patients. The average time to initiate ART was seven weeks. Among naive patients 41.9% were lost to follow up, 35.9% were waiting for treatment and 22.1% waiting for baseline biological test to initiate ART. At the initiation of ART, 79.6% of patients had a CD4 count less than 200/mm(3). The reasons of hospitalization defining AIDS were dominated by tuberculosis (34.2%), cerebral toxoplasmosis (17.9%) and neuromeningeal cryptococcosis (8%). The main reasons of hospitalization in classifying non-AIDS were pyelonephritis (6.5%), bacterial pneumonia (5.4%) and undetermined infectious encephalitis (4.9%). Hospital mortality was 24.4%. The leading causes of death were tuberculosis (22.9%), cerebral toxoplasmosis (20.2%), undetermined infectious encephalitis (18.3%) and cryptococcal meningitis (13.7%). The profile of PLHIV in hospital is characterized by profound immunosuppression due to late diagnosis and high mortality associated with severe opportunistic infections and late initiation of ART.

  9. 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

  10. 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 < 0.001); greater duration of cART did not predict obesity. Individual weight-time trends mostly showed slow long-term progressive weight gain. Investigating body-weight perception, we found that weight and adiposity were underestimated by obese subjects, who showed a greater disparity between perceived and actual adiposity (P < 0.001). Obese subjects targeted more obese target “ideal” body shapes (P < 0.01), but were less satisfied with their body shape overall (P = 0.02). Conclusion: Seropositive African women on antiretroviral treatment are at heightened risk of obesity. Although multifactorial, body-weight perception represents a potential target for intervention. PMID:25431572

  11. Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART

    PubMed Central

    Ensoli, Barbara; Bellino, Stefania; Tripiciano, Antonella; Longo, Olimpia; Francavilla, Vittorio; Marcotullio, Simone; Cafaro, Aurelio; Picconi, Orietta; Paniccia, Giovanni; Scoglio, Arianna; Arancio, Angela; Ariola, Cristina; Ruiz Alvarez, Maria J.; Campagna, Massimo; Scaramuzzi, Donato; Iori, Cristina; Esposito, Roberto; Mussini, Cristina; Ghinelli, Florio; Sighinolfi, Laura; Palamara, Guido; Latini, Alessandra; Angarano, Gioacchino; Ladisa, Nicoletta; Soscia, Fabrizio; Mercurio, Vito S.; Lazzarin, Adriano; Tambussi, Giuseppe; Visintini, Raffaele; Mazzotta, Francesco; Di Pietro, Massimo; Galli, Massimo; Rusconi, Stefano; Carosi, Giampiero; Torti, Carlo; Di Perri, Giovanni; Bonora, Stefano; Ensoli, Fabrizio; Garaci, Enrico

    2010-01-01

    Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4+ and CD8+ cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4+ T cells and B cells with reduction of CD8+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4+ and CD8+ T cells were accompanied by increases of CD4+ and CD8+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the

  12. Essential proteins and possible therapeutic targets of Wolbachia endosymbiont and development of FiloBase-a comprehensive drug target database for Lymphatic filariasis

    PubMed Central

    Sharma, Om Prakash; Kumar, Muthuvel Suresh

    2016-01-01

    Lymphatic filariasis (Lf) is one of the oldest and most debilitating tropical diseases. Millions of people are suffering from this prevalent disease. It is estimated to infect over 120 million people in at least 80 nations of the world through the tropical and subtropical regions. More than one billion people are in danger of getting affected with this life-threatening disease. Several studies were suggested its emerging limitations and resistance towards the available drugs and therapeutic targets for Lf. Therefore, better medicine and drug targets are in demand. We took an initiative to identify the essential proteins of Wolbachia endosymbiont of Brugia malayi, which are indispensable for their survival and non-homologous to human host proteins. In this current study, we have used proteome subtractive approach to screen the possible therapeutic targets for wBm. In addition, numerous literatures were mined in the hunt for potential drug targets, drugs, epitopes, crystal structures, and expressed sequence tag (EST) sequences for filarial causing nematodes. Data obtained from our study were presented in a user friendly database named FiloBase. We hope that information stored in this database may be used for further research and drug development process against filariasis. URL: http://filobase.bicpu.edu.in. PMID:26806463

  13. INTERACTIONS OF DIFFERENT INHIBITORS WITH ACTIVE-SITE ASPARTYL RESIDUES OF HIV-1 PROTEASE AND POSSIBLE RELEVANCE TO PEPSINS

    PubMed Central

    Sayer, Jane M.; Louis, John M.

    2008-01-01

    The importance of the active site region aspartyl residues 25 and 29 of the mature HIV-1 protease (PR) for the binding of five clinical and three experimental protease inhibitors (symmetric cyclic urea inhibitor DMP323, non-hydrolysable substrate analog (RPB) and the generic aspartic protease inhibitor acetyl-pepstatin (Ac-PEP)) was assessed by differential scanning calorimetry. ΔTm values, defined as the difference in Tm for a given protein in the presence and absence of inhibitor, for PR with DRV, ATV, SQV, RTV, APV, DMP323, RPB and Ac-PEP are 22.4, 20.8, 19.3, 15.6, 14.3, 14.7, 8.7, and 6.5 °C, respectively. Binding of APV and Ac-PEP is most sensitive to the D25N mutation, as shown by ΔTm ratios [ΔTm(PR)/ΔTm(PRD25N)] of 35.8 and 16.3, respectively, whereas binding of DMP323 and RPB (ΔTm ratios of 1-2) is least affected. Binding of the substrate-like inhibitors RPB and Ac-PEP is nearly abolished (ΔTm(PR)/ΔTm(PRD29N) ≥ 44) by the D29N mutation, whereas this mutation only moderately affects binding of the smaller inhibitors (ΔTm ratios of 1.4-2.2). Of the 9 FDA approved clinical HIV-1 protease inhibitors screened, APV, RTV and DRV competitively inhibit porcine pepsin with Ki values of 0.3, 0.6 and 2.14 μM, respectively. DSC results were consistent with this relatively weak binding of APV (ΔTm 2.7 °C) compared with the tight binding of AcPEP (ΔTm ≥17 °C). Comparison of superimposed structures of the PR/APV complex with those of PR/Ac-PEP and pepsin/pepstatin A complexes suggests a role for Asp215, Asp32 and Ser219 in pepsin, equivalent to Asp25, Asp25′ and Asp29 in PR, in the binding and stabilization of the pepsin/APV complex. PMID:18951411

  14. 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.

  15. HIV Vaccination, is Breakthrough Underway?

    PubMed

    Lu, Da-Yong; Wu, Hong-Ying; Lu, Ting-Ren; Xu, Bin; Ding, Jian

    2016-01-01

    After long defeats-almost no marked breakthrough in HIV vaccination campaign has been observed during the past two decades, and we still have not lost our faiths for the development of highly effective and low risk HIV vaccines. Many effective vaccines have been discovered and will certainly enter into the markets within the next 5 to 10 years. In order to promote HIV vaccine developments and clinical HIV therapeutic improvements, this perspective addresses the good and bad sides of currently available HIV vaccines, discusses many subjects of medical significance and finally provides up-to-date information in the field of HIV studies, in particular regarding vaccine developments and HIV pathogenesis.

  16. Pin1 liberates the human immunodeficiency virus type-1 (HIV-1): Must we stop it?

    PubMed

    Hou, Hai; Wang, Jing-Zhang; Liu, Bao-Guo; Zhang, Ting

    2015-07-01

    Acquired immune deficiency syndrome (AIDS) is mainly caused by the human immunodeficiency virus type-1 (HIV-1). To our knowledge, this is the first review focusing on the vital role of Pin1 in the infection of HIV-1 and the development of AIDS. We and others have demonstrated that Pin1, the only known cis-to-trans isomerase recognizing the pThr/pSer-Pro motifs in proteins, plays striking roles in several human diseases. Interestingly, recent evidence gradually indicates that Pin1 regulates several key steps of the life cycle of HIV-1, including the uncoating of the HIV-1 core, the reverse transcription of the RNA genome of HIV-1, and the integration of the HIV-1 cDNA into human chromosomes. Whereas inhibiting Pin1 suppresses all of these key steps and attenuates the replication of HIV-1, at the same time different PIN1 gene variants are correlated with the susceptibility to HIV-1 infection. Furthermore, Pin1 potentially promotes HIV-1 infection by activating multiple oncogenes and inactivating multiple tumor suppressors, extending the life span of HIV-infected cells. These descriptions suggest Pin1 as a promising therapeutic target for the prevention of HIV-1 and highlight the possibility of blocking the development of AIDS by Pin1 inhibitors.

  17. Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach

    PubMed Central

    2013-01-01

    In 2013 there will be an estimated 22,240 new diagnoses and 14,030 deaths from ovarian cancer in the United States. Despite the improved surgical approach and the novel active drugs that are available today in clinical practice, about 80% of women presenting with late-stage disease have a 5-year survival rate of only 30%. In the last years a growing scientific knowledge about the molecular pathways involved in ovarian carcinogenesis has led to the discovery and evaluation of several novel molecular targeted agents, with the aim to test alternative models of treatment in order to overcome the clinical problem of resistance. Cancer stem cells tend to be more resistant to chemotherapeutic agents and radiation than more differentiated cellular subtypes from the same tissue. In this context the study of ovarian cancer stem cells is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future. In our review, we focused our attention on the molecular characteristics of epithelial ovarian cancer stem cells, in particular on possible targets to hit with targeted therapies. PMID:23902592

  18. A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study.

    PubMed

    Pandey, Anand Kumar; Shukla, Swet Chand; Bhattacharya, Pallab; Patnaik, Ranjana

    2016-08-01

    The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. µ-Calpain, a calcium ion activated intracellular cysteine protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke. Hence, it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury. As the inhibitory property of µ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with µ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the µ-calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with μ-calpain. Affinity binding of quercetin with µ-calpain had a value of -28.73 kJ/mol and a Ki value of 35.87 µM that may be a probable reason to lead to altered functioning of µ-calpain. Hence, quercetin was found to be an inhibitor of µ-calpain which might have a possible therapeutic role in hypoxic injury. PMID:27651771

  19. A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study

    PubMed Central

    Pandey, Anand Kumar; Shukla, Swet Chand; Bhattacharya, Pallab; Patnaik, Ranjana

    2016-01-01

    The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. µ-Calpain, a calcium ion activated intracellular cysteine protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke. Hence, it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury. As the inhibitory property of µ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with µ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the µ-calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with μ-calpain. Affinity binding of quercetin with µ-calpain had a value of –28.73 kJ/mol and a Ki value of 35.87 µM that may be a probable reason to lead to altered functioning of µ-calpain. Hence, quercetin was found to be an inhibitor of µ-calpain which might have a possible therapeutic role in hypoxic injury.

  20. Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach.

    PubMed

    Tomao, Federica; Papa, Anselmo; Rossi, Luigi; Strudel, Martina; Vici, Patrizia; Lo Russo, Giuseppe; Tomao, Silverio

    2013-08-01

    In 2013 there will be an estimated 22,240 new diagnoses and 14,030 deaths from ovarian cancer in the United States. Despite the improved surgical approach and the novel active drugs that are available today in clinical practice, about 80% of women presenting with late-stage disease have a 5-year survival rate of only 30%. In the last years a growing scientific knowledge about the molecular pathways involved in ovarian carcinogenesis has led to the discovery and evaluation of several novel molecular targeted agents, with the aim to test alternative models of treatment in order to overcome the clinical problem of resistance. Cancer stem cells tend to be more resistant to chemotherapeutic agents and radiation than more differentiated cellular subtypes from the same tissue. In this context the study of ovarian cancer stem cells is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future. In our review, we focused our attention on the molecular characteristics of epithelial ovarian cancer stem cells, in particular on possible targets to hit with targeted therapies.

  1. A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study

    PubMed Central

    Pandey, Anand Kumar; Shukla, Swet Chand; Bhattacharya, Pallab; Patnaik, Ranjana

    2016-01-01

    The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. µ-Calpain, a calcium ion activated intracellular cysteine protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke. Hence, it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury. As the inhibitory property of µ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with µ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the µ-calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with μ-calpain. Affinity binding of quercetin with µ-calpain had a value of –28.73 kJ/mol and a Ki value of 35.87 µM that may be a probable reason to lead to altered functioning of µ-calpain. Hence, quercetin was found to be an inhibitor of µ-calpain which might have a possible therapeutic role in hypoxic injury. PMID:27651771

  2. The maturation of antibody technology for the HIV epidemic.

    PubMed

    Winnall, Wendy R; Beasley, Matthew D; Center, Rob J; Parsons, Matthew S; Kiefel, Ben R; Kent, Stephen J

    2014-08-01

    Antibodies are one of our most useful biological tools. Indeed, improvements in antibody-based technologies have ushered in a new era of antibody-based therapeutics, research and diagnostic tools. Although improved technologies have led to the development of therapeutic antibodies for treatment of malignancies and inflammatory conditions, the use of advanced antibody technology in the therapy of viral infections is in its infancy. Non-human primate studies have demonstrated that antibodies against the HIV envelope can both prevent viral infection and control viremia. Despite the obvious potential of antibody therapies against HIV, there remain limitations in production and purification capacity that require further research. Recent advances in recombinant antibody technology have led to the development of a range of novel antibody fragments, such as single-domain nanobodies and bispecific antibodies, that are capable of targeting cancer cells to cytotoxic T cells. Novel antibody production techniques have also been designed, allowing antibodies to be obtained from non-mammalian cells, bovine colostrum and the periplasm and cytoplasm of bacteria. These advances may allow large-scale production of HIV antibodies that are capable of protecting against HIV infection or serving as therapeutics that reduce the need for life-long antiretroviral treatment. This review summarises recent advances in antibody-based technologies and discusses the possibilities and challenges of using these advances to design prophylactics and therapeutics against HIV. PMID:24797582

  3. Yeast Genetic Analysis Reveals the Involvement of Chromatin Reassembly Factors in Repressing HIV-1 Basal Transcription

    PubMed Central

    Respaldiza, Iñaki; Rodríguez-Gil, Alfonso; Gómez-Herreros, Fernando; Jimeno-González, Silvia; Jordan, Albert; Chávez, Sebastián

    2009-01-01

    Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5′ end of HIV-1 transcribed region (5′HIV-TR), which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5′HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5′HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5′HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency. PMID:19148280

  4. Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs.

    PubMed

    Vermeire, Kurt; Schols, Dominique

    2005-08-01

    It is imperative to continue efforts to identify novel effective therapies that can assist in containing the spread of HIV. Recently acquired knowledge about the HIV entry process points to new strategies to block viral entry. For most HIV strains, the successful infection of their target cells is mainly dependent on the presence of the CD4 surface molecule, which serves as the primary virus receptor. The attachment of the viral envelope to this cellular CD4 receptor can be considered as an ideal target with multiple windows of opportunity for therapeutic intervention. Therefore, drugs that interfere with the CD4 receptor, and thus inhibit viral entry, may be promising agents for the treatment of AIDS. The CD4-targeted HIV entry inhibitors cyclotriazadisulfonamides represent a novel class of small molecule antiviral agents with a unique mode of action. The lead compound, CADA, specifically interacts with the cellular CD4 receptor and is active against a wide variety of HIV strains at submicromolar levels when evaluated in different cell-types such as T cells, monocytes and dendritic cells. Moreover, a strict correlation has been demonstrated between anti-HIV activity and CD4 interaction of about 20 different CADA analogues. In addition, CADA acted synergistically in combination with all other FDA-approved anti-HIV drugs as well as with compounds that target the main HIV co-receptors. In this article, the characteristics of cyclotriazadisulfonamide compounds are presented and the possible application of CADA as a microbicide is also discussed. PMID:15980096

  5. Suppression of HIV replication in the resting CD4+ T cell reservoir by autologous CD8+ T cells: Implications for the development of therapeutic strategies

    PubMed Central

    Chun, Tae-Wook; Justement, J. Shawn; Moir, Susan; Hallahan, Claire W.; Ehler, Linda A.; Liu, Shuying; McLaughlin, Mary; Dybul, Mark; Mican, JoAnn M.; Fauci, Anthony S.

    2001-01-01

    CD8+ T cell-mediated antiviral activity against HIV has been described consistently in infected individuals; however, the role of this activity in controlling replication of HIV in the latently infected, resting CD4+ T cell reservoir is unclear. By using an ex vivo system, we show that replication of HIV in this viral reservoir is effectively suppressed in coculture by autologous CD8+ T cells in long-term nonprogressors (LTNPs) and in patients whose viremia was controlled by highly active antiretroviral therapy (HAART), but not in therapy-naive patients who had substantial levels of plasma viremia. This antiviral activity was largely independent of cytotoxic CD8+ T lymphocytes (CTL). When the role of soluble CD8+ T cell-derived factors was examined, we found that CC-chemokines played a major role in inhibition of viral replication in the latent viral reservoir in some LTNPs and patients receiving HAART, but not in chronically infected patients who were not receiving antiretroviral therapy. Potent antiviral activity, independent of CC-chemokines, was found mainly in patients in whom HAART was initiated shortly after the acute phase of HIV infection. These results indicate that CD8+ T cells provide potent suppressive activity against HIV replication in the latent viral reservoir via direct cellular contact in patients who are naturally LTNPs or in those who are treated with HAART. Furthermore, the profound antiviral activity exerted by non-CC-chemokine soluble factors in infected patients who began HAART early in HIV infection suggests that preservation of this HIV-suppressive mechanism by early initiation of therapy may play an important role in the containment of viral replication in infected patients following interruption of therapy. PMID:11136258

  6. HIV/AIDS: a minority health issue.

    PubMed

    Cargill, Victoria A; Stone, Valerie E

    2005-07-01

    HIV infection among racial and ethnic minorities is an ongoing health crisis. The disproportionate impact of HIV infection on racial and ethnic minorities has affected communities already struggling with many social and economic challenges, such as poverty, substance abuse, homelessness,unequal access to health care, and unequal treatment once in the health care system. Superimposed on these challenges is HIV infection, the transmission of which is facilitated by many of these factors. Although the epidemic is disproportionately affecting all racial and ethnic minorities, within these minority populations women are particularly affected. The care and management of racial and ethnic minorities who have HIV infection has been complicated by the unequal access to health care and the unequal treatment once enrolled in health care. Health insurance status, lack of concordance between the race of the patient and the provider, and satisfaction with the quality of their care all impact on treatment outcomes in this population. In addition, the provider must be aware of the many comorbid conditions that may affect the delivery of care to minority patients living with HIV infection: depression, substance and alcohol abuse, and posttraumatic stress disorders. The impact of these comorbid conditions on the therapeutic relationship, including treatment and adherence, warrants screening for these disorders and treating them when identified. Because the patient provider relationship has been repeatedly identified as a predictor of higher adherence, developing and maintaining a strong therapeutic alliance is critical. Participation of racial and ethnic minorities in HIV clinical trials, as in other disease states, has been very poor. Racial and ethnic minorities have been chronically underrepresented in HIV clinical trials, despite their overrepresentation in the HIV epidemiology. This underrepresentation seems to be the result of a combination of factors including (1) provider

  7. 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

  8. Creating genetic resistance to HIV.

    PubMed

    Burnett, John C; Zaia, John A; Rossi, John J

    2012-10-01

    HIV/AIDS remains a chronic and incurable disease, in spite of the notable successes of combination antiretroviral therapy. Gene therapy offers the prospect of creating genetic resistance to HIV that supplants the need for antiviral drugs. In sight of this goal, a variety of anti-HIV genes have reached clinical testing, including gene-editing enzymes, protein-based inhibitors, and RNA-based therapeutics. Combinations of therapeutic genes against viral and host targets are designed to improve the overall antiviral potency and reduce the likelihood of viral resistance. In cell-based therapies, therapeutic genes are expressed in gene modified T lymphocytes or in hematopoietic stem cells that generate an HIV-resistant immune system. Such strategies must promote the selective proliferation of the transplanted cells and the prolonged expression of therapeutic genes. This review focuses on the current advances and limitations in genetic therapies against HIV, including the status of several recent and ongoing clinical studies.

  9. A systematic review of the effects of different types of therapeutic exercise on physiologic and functional measurements in patients with HIV/AIDS.

    PubMed

    Gomes-Neto, Mansueto; Conceição, Cristiano Sena; Oliveira Carvalho, Vitor; Brites, Carlos

    2013-01-01

    Several studies have reported the benefits of exercise training for adults with HIV, although there is no consensus regarding the most efficient modalities. The aim of this study was to determine the effects of different types of exercise on physiologic and functional measurements in patients with HIV using a systematic strategy for searching randomized controlled trials. The sources used in this review were the Cochrane Library, EMBASE, MEDLINE, and PEDro from 1950 to August 2012. We selected randomized controlled trials examining the effects of exercise on body composition, muscle strength, aerobic capacity, and/or quality of life in adults with HIV. Two independent reviewers screened the abstracts using the Cochrane Collaboration's protocol. The PEDro score was used to evaluate methodological quality. In total, 29 studies fulfilled the inclusion criteria. Individual studies suggested that exercise training contributed to improvement of physiologic and functional parameters, but that the gains were specific to the type of exercise performed. Resistance exercise training improved outcomes related to body composition and muscle strength, with little impact on quality of life. Aerobic exercise training improved body composition and aerobic capacity. Concurrent training produced significant gains in all outcomes evaluated, although moderate intensity and a long duration were necessary. We concluded that exercise training was shown to be a safe and beneficial intervention in the treatment of patients with HIV.

  10. The same site on the integrase-binding domain of lens epithelium–derived growth factor is a therapeutic target for MLL leukemia and HIV

    PubMed Central

    Murai, Marcelo J.; Pollock, Jonathan; He, Shihan; Miao, Hongzhi; Purohit, Trupta; Yokom, Adam; Hess, Jay L.; Muntean, Andrew G.; Grembecka, Jolanta

    2014-01-01

    Lens epithelium-derived growth factor (LEDGF) is a chromatin-associated protein implicated in leukemia and HIV type 1 infection. LEDGF associates with mixed-lineage leukemia (MLL) fusion proteins and menin and is required for leukemic transformation. To better understand the molecular mechanism underlying the LEDGF integrase-binding domain (IBD) interaction with MLL fusion proteins in leukemia, we determined the solution structure of the MLL-IBD complex. We found a novel MLL motif, integrase domain binding motif 2 (IBM2), which binds to a well-defined site on IBD. Point mutations within IBM2 abolished leukemogenic transformation by MLL-AF9, validating that this newly identified motif is essential for the oncogenic activity of MLL fusion proteins. Interestingly, the IBM2 binding site on IBD overlaps with the binding site for the HIV integrase (IN), and IN was capable of efficiently sequestering IBD from the menin-MLL complex. A short IBM2 peptide binds to IBD directly and inhibits both the IBD-MLL/menin and IBD-IN interactions. Our findings show that the same site on IBD is involved in binding to MLL and HIV-IN, revealing an attractive approach to simultaneously target LEDGF in leukemia and HIV. PMID:25305204

  11. Therapeutic perspectives

    PubMed Central

    Fiore, Carmelo E.; Pennisi, Pietra; Tinè, Marianna

    2008-01-01

    Osteoporosis and atherosclerosis are linked by biological association. This encourages the search for therapeutic strategies having both cardiovascular and skeletal beneficial effects. Among drugs that may concordantly enhance bone density and reduce the progression of atherosclerosis we can include bisphosphonates (BP), statins, β -blockers, and possibly anti-RANKL antibodies. Available data come from experimental animals and human studies. All these treatments however lack controlled clinical studies designed to demonstrate dual-action effects. PMID:22460845

  12. HIV-1 proteins, Tat and gp120, target the developing dopamine system.

    PubMed

    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

  13. 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

  14. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    PubMed

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus.

  15. Endothelial and platelet function alterations in HIV-infected patients.

    PubMed

    Gresele, P; Falcinelli, E; Sebastiano, M; Baldelli, F

    2012-03-01

    The HIV epidemic has huge dimensions: in 2009, 33.3million people worldwide, including 2.5million children, were affected by human immunodeficiency virus (HIV) infection. The introduction of Highly Active Anti-Retroviral Therapy (HAART) has significantly modified the course of HIV disease, with longer survival and improved quality of life, but it has simultaneously lead to the appearance of previously unrecognized complications, such as ischemic cardiovascular events. Many studies have shown a higher rate of premature atherosclerosis in patients with HIV infection, leading to coronary, cerebrovascular, or peripheral arterial disease. However, it is still debated whether cardiovascular complications are a consequence of HIV infection itself or of the long-term use of HAART. In particular, myocardial infarction has been suggested to be associated with the use of abacavir. Endothelial dysfunction and platelet activation are markers of atherosclerosis and of increased cardiovascular risk. Here we review the evidence that endothelial dysfunction and platelet alterations are associated with chronic HIV infection, the possible role of different HAARTs, and the possible pathophysiologic mechanisms. Potential therapeutic implications are also discussed.

  16. Are major reductions in new HIV infections possible with people who inject drugs? The case for low dead-space syringes in highly affected countries.

    PubMed

    Zule, William A; Cross, Harry E; Stover, John; Pretorius, Carel

    2013-01-01

    Circumstantial evidence from laboratory studies, mathematical models, ecological studies and bio behavioural surveys, suggests that injection-related HIV epidemics may be averted or reversed if people who inject drugs (PWID) switch from using high dead-space to using low dead-space syringes. In laboratory experiments that simulated the injection process and rinsing with water, low dead space syringes retained 1000 times less blood than high dead space syringes. In mathematical models, switching PWID from high dead space to low dead space syringes prevents or reverses injection-related HIV epidemics. No one knows if such an intervention is feasible or what effect it would have on HIV transmission among PWID. Feasibility studies and randomized controlled trials (RCTs) will be needed to answer these questions definitively, but these studies will be very expensive and take years to complete. Rather than waiting for them to be completed, we argue for an approach similar to that used with needle and syringe programs (NSP), which were promoted and implemented before being tested more rigorously. Before implementation, rapid assessments that involve PWID will need to be conducted to ensure buy-in from PWID and other local stakeholders. This commentary summarizes the existing evidence regarding the protective effects of low dead space syringes and estimates potential impacts on HIV transmission; it describes potential barriers to transitioning PWID from high dead space to low dead space needles and syringes; and it presents strategies for overcoming these barriers.

  17. HIV control in vivo: Dynamical analysis

    NASA Astrophysics Data System (ADS)

    Gumel, A. B.; Moghadas, S. M.

    2004-10-01

    A deterministic model for the immunological and therapeutic control of human immunodeficiency virus (HIV) in vivo is studied qualitatively. In addition to analyzing the local stability of the equilibria, the global stability of the infection-free equilibrium is established. The optimal efficacy level of anti-retroviral therapy needed to eradicate HIV from the body of an HIV-infected individual is obtained.

  18. [The use of computer psychosemantic analysis for diagnosis of possible relapse in patients with schizophrenia in the period of therapeutic remission forming].

    PubMed

    Tiuvina, N A; Krivtsov, K Iu

    2006-01-01

    Sixty-five patients with paranoid schizophrenia were studied using a method of computer psychosemantic analysis, which allowed to obtain significant evidence that in 21 patients without clinical symptoms of acute psychosis psychosemantic equivalents of psychotic experience remained actual. Using clinical and psychometric parameters, this was further confirmed by the negative dynamics of mental state in 15 cases (71.4%). Sensitivity of this method was estimated as 78.9%, reproducibility 84.6% and specificity 86.9%. These results suggest efficacy of the used diagnostic method for prognosis of psychosis relapse and assessment of therapeutic effect.

  19. Safety and therapeutic efficacy of the switch to maraviroc+darunavir/ritonavir in HIV/HCV coinfected patients: initial results from GUSTA study

    PubMed Central

    Gagliardini, Roberta; Rossetti, Barbara; Bianco, Claudia; Rusconi, Stefano; Colafigli, Manuela; Prinapori, Roberta; Francisci, Daniela; Fantauzzi, Alessandra; Orofino, Giancarlo; Vignale, Francesca; Di Giambenedetto, Simona; De Luca, Andrea

    2014-01-01

    Introduction HIV/HCV coinfection is a risk factor for hepatic injury in patients receiving HAART and previous studies support a favourable effect of antiretroviral regimens including maraviroc (MVC) on the course of coinfection compared with other antiretroviral drugs. There are few observations about MVC use in simplified treatment of coinfected patients.Objective: To evaluate the efficacy and the safety of simplification to darunavir (DRV)/ritonavir (r)/maraviroc (MVC) in virologically HIV-suppressed patients and to explore the effect of simplified treatment on coinfected patients. Material and Methods GUSTA study is a randomized two arms trial that compares the switch to DRV/r/MVC with standard HAART with three drugs. The study enrols patients with HIV-1 RNA<50cp/mL>6 months, R5 tropism, CD4>200 cells/mm. Survival analysis was used to analyze factors associated to time-to a single viral load (VL) over 50cp/mL and FIB-4>1.45. Results We included 62 patients with at least the 24 week follow-up for FIB-4 analysis: males 75.8%, heterosexuals 48.4%, HCV+12.9% median age 48.3 years (IQR41.1;53.5), time from HIV diagnosis 11.0 years (IQR7.3;16.7), CD4 cells 659/mm (IQR478;882), nadir CD4 203/mm (IQR115;286), FPR 46 (IQR30;70), baseline (BL) FIB-4 1.11 (IQR0.75;1.35). At BL no differences were observed in the two arms, except for platelets (−34.96 109/L, in the study arm, p=0.028) and CD4 at nadir (−70cell/µL, p0.051). After 24 weeks a significant reduction in total bilirubin (TB) (−0.55 mg/dL, p=0.025) and alkaline phosphatase(AP) (−12.96 UI/L, p=0.002) was observed in the study group. A statistically significant difference in mean change of TB (0.61 mg/dL, p=0.016) and AP (13.23 UI/L, p=0.04) at 24 week between control and study group was observed. No grade 3/4 transaminase elevation was observed for any patient even if HIV/HCV coinfected and receiving MVC. A single HCV negative patient in the control arm had grade 3 bilirubin increase. Including all patients

  20. Assessing the impact of substance use and hepatitis coinfection on atazanavir and lopinavir trough concentrations in HIV-infected patients during therapeutic drug monitoring.

    PubMed

    Slish, Judianne; Ma, Qing; Zingman, Barry S; Reichman, Richard C; Fischl, Margaret A; Gripshover, Barbara; Forrest, Alan; Brazeau, Dan; Boston, Naomi S; Catanzaro, Linda; DiFrancesco, Robin; Morse, Gene D

    2007-10-01

    Atazanavir (ATV) and lopinavir (LPV) are widely used HIV-1 protease inhibitors. Like with other protease inhibitors, careful monitoring of potential drug-drug and drug-disease interactions in clinical practice is necessary. The aim of this study was to assess the impact of substance use and hepatitis virus coinfection on plasma ATV and LPV trough concentrations in HIV-positive substance users and nonusers. Individuals established on ATV (300 mg and 100 mg ritonavir daily) or LPV (400 mg and 100 mg ritonavir twice daily)-containing regimens completed two clinical visits (trough and directly observed therapy) during which dosing characteristics, concomitant medication, and substance use were recorded. Trough plasma concentrations (22-26 hours for ATV and 10-14 hours for LPV) were measured using LCMSMS. The influence of substance use was evaluated by Kruskal-Wallis test. Substance use was associated with a marked decrease in trough LPV concentrations during the trough visit (median, 5.536 and 3.791 microg/mL for nonsubstance users and substance users, respectively, P = 0.029). Significantly lower LPV trough levels were also noted among patients with active hepatitis C virus coinfection evaluated as an independent variable (median, 2.253 and 5.927 microg/mL for active and inactive/no hepatitis C virus infection, respectively, P = 0.032). Substance use and hepatitis virus coinfection had limited effects on ATV trough levels. In this cohort, despite the wide interindividual variability of ATV and LPV trough concentrations, significant associations between substance use and active hepatitis C virus infection and low LPV trough concentrations were observed. Further work is needed to assess the optimal dosing regimen when using LPV in HIV-infected substance users.

  1. Importance of an Early HIV Antibody Differentiation Immunoassay for Detection of Dual Infection with HIV-1 and HIV-2

    PubMed Central

    Zbinden, Andrea; Dürig, Roland; Shah, Cyril; Böni, Jürg; Schüpbach, Jörg

    2016-01-01

    Background HIV-2 is primarily endemic in West Africa and India, however, in time of global migration, a possible HIV-2 infection or co-infection with HIV-1 should be recognized right at the time of HIV diagnosis, in order to enable optimized antiretroviral treatment. Laboratory HIV testing consists of a combined HIV1/2/O antibody + antigen screening test and subsequent confirmation and type differentiation by a serological test formatted as a multi-line or multi-spot assay. CDC has proposed a revised alternative HIV diagnostic strategy which, in case of a reactive result in a combined HIV1/2/O antibody + antigen screening test, comprises an HIV-1 nucleic acid test (NAT) for HIV confirmation instead of an antibody differentiation immunoassay (ADI). Only a negative NAT must be further investigated by an ADI, thus saving expenses for ADI in most instances. We have investigated this alternative strategy with respect to its recognition of dual HIV-1 and HIV-2 infection. Methods and Results Anonymized data of HIV notifications of patients newly diagnosed with HIV in Switzerland between 2007 and 2014 were analysed retrospectively. In a total of 4'679 notifications, we found 35 HIV-2 infections, 9 (25.7%) of which were dually infected with HIV-1. In 7 of the 9 dual HIV-1 and HIV-2 infections, HIV-1 RNA testing at the time of HIV diagnosis was positive with concentrations from 102 to 94'300 copies/mL plasma. HIV-1 RNA data were not available for the other two cases. Conclusions The alternative CDC strategy would have missed the concomitant HIV-2 infection in at least 7, but probably even more, of the 9 dually infected patients, as the detectable HIV-1 RNA would have precluded a supplemental ADI. Early ADI is mandatory for diagnosis of dual HIV-1/HIV-2 infection and guidance of appropriate therapy. PMID:27310138

  2. The change in cerebral glucose metabolism after electroacupuncture: a possible marker to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa

    PubMed Central

    Liu, Tao-Tao; Hong, Qing-Xiong; Xiang, Hong-Bing

    2015-01-01

    Some reports have demonstrated that deep brain stimulation (DBS) is a promising treatment for patients who suffer from intractable anorexia nervosa. However, the nature of DBS may not be viewed as a standard clinical treatment option for anorexia nervosa because of the unpredictable outcome before DBS. Just like DBS in the brain, electroacupuncture at acupoints is also efficient in treating refractory anorexia nervosa. Some neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) had revealed that both DBS and electroacupuncture at acupoints with electrical stimulation are related to the changes in cerebral glucose metabolism. Therefore, we hypothesize that the changes in cerebral glucose metabolism after electroacupuncture might be useful to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa. PMID:26770596

  3. [Epidemiological, clinical and therapeutics' data of HIV-infected patients placed on ART in the Segou hospital in Mali (2004-2011)].

    PubMed

    Koné, M C; Cissoko, Y; Diallo, M S; Traoré, B A; Mallé, K K

    2013-08-01

    This is a retrospective study on a cohort of 811 adult patients placed on ART between January 2004 and December 2011 at the hospital Nianankoro Fomba Segou in Mali, to describe their epidemiological, clinical and developmental profile for 48 months. The average age of patients was 35.2±9.4 years. The sex-ratio was 0.6. Approximately 58.3% of the patients were from rural areas. HIV1 represented 95.8%. Prolonged fever, weight loss and chronic diarrhea were the main reasons for testing. The majority of patients (64.5%) had stage III WHO. The mean CD4 cell count was 144±135.8/mm³ at screening. The evolution was favorable under immunological antiretroviral therapy. The survival rate at 48 months follow-up was 78% [64.1%-81.3%]. Patients followed in the structure are predominantly rural, female and young aged. They are diagnosed with advanced HIV infection. Antiretroviral therapy has led to the strengthening of the immune system and improved the clinical outcomes with a survival rate of 78%.

  4. Cross-Reactivity, Epitope Spreading, and De Novo Immune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines.

    PubMed

    Nakagawa, Mayumi; Greenfield, William; Moerman-Herzog, Andrea; Coleman, Hannah N

    2015-07-01

    Numerous versions of human papillomavirus (HPV) therapeutic vaccines designed to treat individuals with established HPV infection, including those with cervical intraepithelial neoplasia (CIN), are in development because approved prophylactic vaccines are not effective once HPV infection is established. As human papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV-18. While these two HPV types are responsible for approximately 70% of cervical cancer cases, there are other high-risk HPV types known to cause malignancy. Therefore, it would be of interest to assess whether these HPV therapeutic vaccines may confer cross-protection against other high-risk HPV types. Data available from a few clinical trials that enrolled subjects with CINs regardless of the HPV type(s) present demonstrated clinical responses, as measured by CIN regression, in subjects with both vaccine-matched and nonvaccine HPV types. The currently available evidence demonstrating cross-reactivity, epitope spreading, and de novo immune stimulation as possible mechanisms of cross-protection conferred by investigational HPV therapeutic vaccines is discussed.

  5. Barriers to HIV Cure.

    PubMed

    Stein, J; Storcksdieck Genannt Bonsmann, M; Streeck, H

    2016-10-01

    Since the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers. PMID:27620852

  6. Overview of HIV.

    PubMed

    Klimas, Nancy; Koneru, Anne O'Brien; Fletcher, Mary Ann

    2008-06-01

    This article provides an overview and reviews the HIV pandemic, the basic biology and immunology of the virus (e.g., genetic diversity of HIV and the viral life cycle), the phases of disease progression, modes of HIV transmission, HIV testing, immune response to the infection, and current therapeutic strategies. HIV is occurring in epidemic proportions, especially in Sub-Saharan Africa. In the US, men who have sex with men account for over half of AIDS diagnoses; racial and ethnic minorities are disproportionally affected. Factors influencing the progression and severity of HIV infection include type of immune response, coinfection (e.g., another sexually transmitted infection, including hepatitis B or C), age and behavioral and psychosocial factors. Antiretroviral therapies can achieve reduction in blood levels of the HIV virus below the limits of detection by current technology. However, effective treatment requires adherence to therapy. Patient failure to adhere to treatment regimens results in detectible circulating virus and in HIV disease progression, and is the primary cause of drug resistance. In addition to research on the immunology and virology of the disease, other studies focus on behavioral and psychosocial factors that may affect medication adherence and risk behaviors. PMID:18541903

  7. Prison Therapeutic Community Treatment for Female Offenders: Profiles and Preliminary Findings for Mental Health and Other Variables (Crime, Substance Use and HIV Risk)

    ERIC Educational Resources Information Center

    Sacks, Joann Y.; Sacks, Stanley; Mckendrick, Karen; Banks, Steven; Schoeneberger, Marlies; Hamilton, Zachary; Stommel, Joseph; Shoemaker, Joanie

    2008-01-01

    This random assignment study compared women in a prison Therapeutic Community (TC) program with those in a cognitive-behavioral intervention. Over two thirds of study subjects received a lifetime diagnosis of severe mental disorder, nearly one-half received a diagnosis of PTSD, and virtually all reported exposure to trauma. Preliminary analysis (n…

  8. Therapeutic insemination.

    PubMed

    Alexander, N J; Ackerman, S

    1987-12-01

    Except in special circumstances, therapeutic insemination with a husband's sample has a low success rate. Couples in whom oligozoospermia has been identified as the principal cause of infertility do not benefit from therapeutic insemination by husband. Because of this low success rate, intrauterine insemination to provide sperm in closer proximity to the egg has become popular, but intrauterine insemination also has a low success rate. We suggest that intrauterine insemination should be approached aggressively in cases of male factor infertility. The recipient should be stimulated to enhance egg production and closely monitored for ovulation. A semen specimen of not less than 1 X 10(6) motile sperm with antibiotics added should be placed in the uterus the day after ovulation. If no pregnancies occur within four cycles, alternate approaches should be considered. Therapeutic insemination by donor involves careful donor selection to avoid inheritance of malformations and familial diseases. Because of the possibilities of sexually transmitted diseases, careful and repeated screening should be conducted. A complete sexual history should be obtained, and donors should be excluded if they have had any homosexual contact since 1978, if they have been an intravenous drug user, if they come from a geographic area where the sex ratio of AIDS is close to 1:1, or if they have recently had multiple sexual partners. A permanent record preserving the confidentiality but allowing the tracing of genetic anomalies, even if not present at birth, should be kept. PMID:3328130

  9. 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 ± 0.84 mm in the TA group and 5.16 ± 1.04 mm 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

  10. HIV reservoirs as obstacles and opportunities for an HIV cure.

    PubMed

    Chun, Tae-Wook; Moir, Susan; Fauci, Anthony S

    2015-06-01

    The persistence of HIV reservoirs remains a formidable obstacle to achieving sustained virologic remission in HIV-infected individuals after antiretroviral therapy (ART) is discontinued, even if plasma viremia has been successfully suppressed for prolonged periods of time. Numerous approaches aimed at eradicating the virus, as well as maintaining its prolonged suppression in the absence of ART, have had little success. A better understanding of the pathophysiologic nature of HIV reservoirs and the impact of various interventions on their persistence is essential for the development of successful therapeutic strategies against HIV or the long-term control of infection. Here, we discuss the persistent HIV reservoir as a barrier to cure as well as the current therapeutic strategies aimed at eliminating or controlling the virus in the absence of ART.

  11. Nigella sativa concoction induced sustained seroreversion in HIV patient.

    PubMed

    Onifade, Abdulfatah Adekunle; Jewell, Andrew Paul; Adedeji, Waheed Adeola

    2013-01-01

    Nigella sativa had been documented to possess many therapeutic functions in medicine but the least expected is sero-reversion in HIV infection which is very rare despite extensive therapy with highly active anti-retroviral therapy (HAART). This case presentation is to highlight the complete recovery and sero-reversion of adult HIV patient after treatment with Nigella sativa concoction for the period of six months. The patient presented to the herbal therapist with history of chronic fever, diarrhoea, weight loss and multiple papular pruritic lesions of 3 months duration. Examination revealed moderate weight loss, and the laboratory tests of ELISA (Genscreen) and western blot (new blot 1 & 2) confirmed sero-positivity to HIV infection with pre-treatment viral (HIV-RNA) load and CD4 count of 27,000 copies/ml and CD4 count of 250 cells/ mm(3) respectively. The patient was commenced on Nigella sativa concoction 10 mls twice daily for 6 months.. He was contacted daily to monitor side-effects and drug efficacy. Fever, diarrhoea and multiple pruritic lesions disappeared on 5th, 7th and 20th day respectively on Nigella sativa therapy. The CD4 count decreased to 160 cells/ mm3 despite significant reduction in viral load (≤1000 copies/ml) on 30th day on N. sativa. Repeated EIA and Western blot tests on 187th day on Nigella sativa therapy was sero-negative. The post therapy CD4 count was 650 cells/ mm(3) with undetectable viral (HIV-RNA) load. Several repeats of the HIV tests remained sero-negative, aviraemia and normal CD4 count since 24 months without herbal therapy. This case report reflects the fact that there are possible therapeutic agents in Nigella sativa that may effectively control HIV infection.

  12. The neuropathology of adult HIV infection.

    PubMed

    Bell, J E

    1998-12-01

    . These may coexist with HIVE and may be difficult to diagnose in life. CMV gives rise to microglial nodular encephalitis, ventriculitis, necrotising encephalitis and myelo-radiculitis. Presymptomatic HIV positive patients do not show HIVE or opportunistic infections or lymphomas in the CNS. They frequently display a low-grade T-cell infiltrate in the leptomeninges and parenchyma, particularly around vessels. This lymphocytic infiltrate has been attributed to presumed early invasion of the CNS by HIV although the exact timing of entry is uncertain. It is possible that reported abnormalities in presymptomatic cases such as gliosis, microglial activation and rising proviral load may anticipate the onset of HIVE but most studies show that significant CNS damage and HIV-related pathology is confined to patients with AIDS. HIV-related pathology in the spinal cord includes not only HIV myelitis, opportunistic infections and lymphomas, but also vacuolar myelopathy (VM) which affects predominantly the dorsolateral white matter tracts. The cause of VM is not understood and has not been unequivocally linked with HIV infection. It is noted that none of these neuropathological features (including HIVE) correlates exactly with the clinical expression of AIDS-related dementia (ARD). The exact contribution of macrophage activation and cytokine release, astrocytic infection, neuronal loss and axonal damage to the neuropsychiatric syndromes of advanced HIV infection remain to be determined. While the current understanding of the pathogenesis of HIVE and ARD is beyond the scope of this review it is axiomatic that accurate documentation of neuropathology findings will help to resolve the outstanding dilemmas relating to HIV infection of the CNS. There is considerable optimism that progress in therapeutic regimes for HIV-infected patients will succeed in eliminating the virus from the blood and from lymphoid tissue. (ABSTRACT TRUNCATED)

  13. H3.3 G34R mutations in pediatric primitive neuroectodermal tumors of central nervous system (CNS-PNET) and pediatric glioblastomas: possible diagnostic and therapeutic implications?

    PubMed

    Gessi, Marco; Gielen, Gerrit H; Hammes, Jennifer; Dörner, Evelyn; Mühlen, Anja Zur; Waha, Andreas; Pietsch, Torsten

    2013-03-01

    Pediatric glioblastomas recently have been exon sequenced with evidence that approximately 30 % of cases harbour mutations of the histone H3.3 gene. Although studies to determinate their role in risk stratification are on-going, it remains to be determined whether H3.3 mutations could be found in other tumors such as pediatric primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) and whether the presence of H3.3 mutations in glioblastomas could be used as diagnostic tool in their differential diagnosis with CNS-PNETs. We performed a large mutational pyrosequencing-based screening on 123 pediatric glioblastomas and 33 CNS-PNET. The analysis revealed that 39/123 (31.7 %) glioblastomas carry H3.3 mutations. The K27M (AAG → ATG, lysine → methionine) mutation was found in 33 glioblastomas (26 %); the G34R (GGG → AGG, glycine → arginine) was observed in 6 glioblastomas (5.5 %). However, we also identified 4 of 33 cases (11 %) of CNS-PNETs harbouring a H3.3 G34R mutation. Multiplex ligation-dependent probe amplification analysis revealed PDGFR-alpha amplification and EGFR gain in two cases and N-Myc amplification in one case of H3.3 G34R mutated CNS-PNET. None of H3.3 mutated tumors presented a CDKN2A loss. In conclusion, because pediatric patients with glioblastoma and CNS-PNET are treated according to different therapeutic protocols, these findings may raise further concerns about the reliability of the histological diagnosis in the case of an undifferentiated brain tumor harbouring G34R H3.3 mutation. In this view, additional studies are needed to determine whether H3.3 G34 mutated CNS-PNET/glioblastomas may represent a defined tumor subtype. PMID:23354654

  14. 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 More information ... and brain Return to top More information on HIV symptoms Explore other publications and websites Basic Information ...

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

    PubMed

    Vo, Thanh-Sang; Kim, Se-Kwon

    2010-11-29

    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.

  16. 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

  17. HIV Prevention

    MedlinePlus

    ... to treat HIV infection (called antiretroviral therapy, or ART) the right way, every day and his or ... way, every day, the medicine to treat HIV (ART) reduces the amount of HIV (called “viral ...

  18. HIV: Cell Binding and Entry

    PubMed Central

    Wilen, Craig B.; Tilton, John C.; Doms, Robert W.

    2012-01-01

    The first step of the human immunodeficiency virus (HIV) replication cycle—binding and entry into the host cell—plays a major role in determining viral tropism and the ability of HIV to degrade the human immune system. HIV uses a complex series of steps to deliver its genome into the host cell cytoplasm while simultaneously evading the host immune response. To infect cells, the HIV protein envelope (Env) binds to the primary cellular receptor CD4 and then to a cellular coreceptor. This sequential binding triggers fusion of the viral and host cell membranes, initiating infection. Revealing the mechanism of HIV entry has profound implications for viral tropism, transmission, pathogenesis, and therapeutic intervention. Here, we provide an overview into the mechanism of HIV entry, provide historical context to key discoveries, discuss recent advances, and speculate on future directions in the field. PMID:22908191

  19. Reduction of painful area as new possible therapeutic target in post-herpetic neuropathic pain treated with 5% lidocaine medicated plaster: a case series.

    PubMed

    Casale, Roberto; Di Matteo, Maria; Minella, Cristina E; Fanelli, Guido; Allegri, Massimo

    2014-01-01

    Post-herpetic neuralgia (PHN) is neuropathic pain persisting after an acute episode of herpes zoster, and is associated with severe pain and sensory abnormalities that adversely affect the patient's quality of life and increase health care costs. Up to 83% of patients with PHN describe localized neuropathic pain, defined as "a type of neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain". Topical treatments have been suggested as a first-line treatment for localized neuropathic pain. Use of 5% lidocaine medicated plaster could reduce abnormal nervous peripheral discharge and via the plaster could have a "protective" function in the affected area. It has been suggested that use of this plaster could reduce pain as well as the size of the painful area. To evaluate this possible outcome, we retrospectively reviewed eight patients with PHN, treated using 5% lidocaine medicated plaster. During a follow-up period of 3 months, we observed good pain relief, which was associated with a 46% reduction in size of the painful area after one month (from 236.38±140.34 cm(2) to 128.80±95.7 cm(2)) and a 66% reduction after 3 months (81.38±59.19 cm(2)). Our study cohort was composed mainly of elderly patients taking multiple drugs to treat comorbidities, who have a high risk of drug-drug interactions. Such patients benefit greatly from topical treatment of PHN. Our observations confirm the effectiveness of lidocaine plasters in the treatment of PHN, indicating that 5% lidocaine medicated plaster could reduce the size of the painful area. This last observation has to be confirmed and the mechanisms clarified in appropriate larger randomized controlled trials.

  20. 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

  1. HIV-1 Infection of Bone Marrow Hematopoietic Progenitor Cells and Their Role in Trafficking and Viral Dissemination

    PubMed Central

    Alexaki, Aikaterini; Wigdahl, Brian

    2008-01-01

    Patients with HIV-1 often present with a wide range of hematopoietic abnormalities, some of which may be due to the presence of opportunistic infections and to therapeutic drug treatments. However, many of these abnormalities are directly related to HIV-1 replication in the bone marrow (BM). Although the most primitive hematopoietic progenitor cells (HPCs) are resistant to HIV-1 infection, once these cells begin to differentiate and become committed HPCs they become increasingly susceptible to HIV-1 infection and permissive to viral gene expression and infectious virus production. Trafficking of BM-derived HIV-1-infected monocytes has been shown to be involved in the dissemination of HIV-1 into the central nervous system (CNS), and it is possible that HIV-1 replication in the BM and infection of BM HPCs may be involved in the early steps leading to the development of HIV-1-associated dementia (HAD) as an end result of this cellular trafficking process. In addition, the growth and development of HPCs in the BM of patients with HIV-1 has also been shown to be impaired due to the presence of HIV-1 proteins and changes in the cytokine milieu, potentially leading to an altered maturation process and to increased cell death within one or more BM cell lineages. Changes in the growth and differentiation process of HPCs may be involved in the generation of monocyte populations that are more susceptible and/or permissive to HIV-1, and have potentially altered trafficking profiles to several organs, including the CNS. A monocyte subpopulation with these features has been shown to expand during the course of HIV-1 disease, particularly in HAD patients, and is characterized by low CD14 expression and the presence of cell surface CD16. PMID:19112504

  2. [HIV and reproductive choices].

    PubMed

    Boer, K; de Vries, J W; de Beaufort, I E

    1995-05-13

    It is estimated that there are about 120-150 hemophilic men infected with HIV in the Netherlands as well as 1000 men infected via intravenous drug use. The majority of them are in reproductive age with relationships with seronegative women. In the event they want to have a child, artificial insemination with donor sperm (KID) is an option. In 1994 there were 147 instances of insemination of 66 women with the processed semen of HIV-positive men and no infection resulted. The annual risk of HIV infection was 7.2% of a woman engaging in unprotected intercourse, according to a prospective Italian study. The risk of HIV infection per contact was estimated at 0.1-5.6%. However, it is not yet proven that processed sperm of an HIV-seropositive man can produce a pregnancy without the risk of infecting the woman. The risk of transmission of HIV to the fetus is higher in artificial insemination of a seropositive woman with the sperm of her partner. In vitro fertilization is not a sure method either for the prevention of HIV infection of the mother because of the possibility of an egg cell being infected before fertilization. HIV-infected pregnant women face the problems of caring for HIV-infected offspring. For HIV discordant couples the advice is to use both condoms for the prevention of infection and oral contraceptives for the prevention of pregnancy. In the case of a lesbian relationship, if the partners want to have a child, HIV infection is still a factor because of previous heterosexual contacts.

  3. 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

  4. HIV Associated Neurocognitive Disorders

    PubMed Central

    Zhou, Li; Saksena, Nitin K.

    2013-01-01

    Human immunodeficiency virus type 1 is associated with the development of neurocognitive disorders in many infected individuals, including a broad spectrum of motor impairments and cognitive deficits. Despite extensive research, the pathogenesis of HIV-associated neurocognitive disorders (HAND) is still not clear. This review provides a comprehensive view of HAND, including HIV neuroinvasion, HAND diagnosis and different level of disturbances, influence of highly-active antiretroviral therapy to HIV-associated dementia (HAD), possible pathogenesis of HAD, etc. Together, this review will give a thorough and clear understanding of HAND, especially HAD, which will be vital for future research, diagnosis and treatment. PMID:24470972

  5. Women and HIV

    MedlinePlus

    ... Consumer Information by Audience For Women Women and HIV Share Tweet Linkedin Pin it More sharing options ... HIV? What should pregnant women know about HIV? HIV Quick Facts What is HIV? HIV is the ...

  6. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    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.

  7. 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 ...

  8. HIV Molecular Immunology 2014

    SciTech Connect

    Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan; Koup, Richard; de Boer, Rob; Moore, John P.; Brander, Christian; Haynes, Barton F.; Walker, Bruce D.

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  9. HIV-1 cellular and tissue replication patterns in infected humanized mice.

    PubMed

    Araínga, Mariluz; Su, Hang; Poluektova, Larisa Y; Gorantla, Santhi; Gendelman, Howard E

    2016-01-01

    Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human. PMID:26996968

  10. HIV infection and the gastrointestinal immune system

    PubMed Central

    Brenchley, JM; Douek, DC

    2009-01-01

    There has recently been a resurgence of interest in the gastrointestinal pathology observed in patients infected with HIV. The gastrointestinal tract is a major site of HIV replication, which results in massive depletion of lamina propria CD4 T cells during acute infection. Highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of gastrointestinal CD4 T cells. The gastrointestinal pathology associated with HIV infection comprises significant enteropathy with increased levels of inflammation and decreased levels of mucosal repair and regeneration. Assessment of gut mucosal immune system has provided novel directions for therapeutic interventions that modify the consequences of acute HIV infection. PMID:19079157

  11. Get Tested for HIV

    MedlinePlus

    ... Print This Topic En español Get Tested for HIV Browse Sections The Basics Overview What Is HIV? ... 1 of 7 sections The Basics: What Is HIV? What is HIV? HIV stands for human immunodeficiency ...

  12. HIV Treatment: The Basics

    MedlinePlus

    HIV Treatment HIV Treatment: The Basics (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  13. Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.

    PubMed

    Tincati, Camilla; Douek, Daniel C; Marchetti, Giulia

    2016-01-01

    Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota. PMID:27073405

  14. Inhibitors of HIV-1 replication that inhibit HIV integrase.

    PubMed Central

    Robinson, W E; Reinecke, M G; Abdel-Malek, S; Jia, Q; Chow, S A

    1996-01-01

    HIV-1 replication depends on the viral enzyme integrase that mediates integration of a DNA copy of the virus into the host cell genome. This enzyme represents a novel target to which antiviral agents might be directed. Three compounds, 3,5-dicaffeoylquinic acid, 1-methoxyoxalyl-3,5-dicaffeoylquinic acid, and L-chicoric acid, inhibit HIV-1 integrase in biochemical assays at concentrations ranging from 0.06-0.66 microgram/ml; furthermore, these compounds inhibit HIV-1 replication in tissue culture at 1-4 microgram/ml. The toxic concentrations of these compounds are fully 100-fold greater than their antiviral concentrations. These compounds represent a potentially important new class of antiviral agents that may contribute to our understanding of the molecular mechanisms of viral integration. Thus, the dicaffeoylquinic acids are promising leads to new anti-HIV therapeutics and offer a significant advance in the search for new HIV enzyme targets as they are both specific for HIV-1 integrase and active against HIV-1 in tissue culture. Images Fig. 3 PMID:8692814

  15. Authentic HIV-1 integrase inhibitors

    PubMed Central

    Liao, Chenzhong; Marchand, Christophe; Burke, Terrence R; Pommier, Yves; Nicklaus, Marc C

    2010-01-01

    HIV-1 integrase (IN) is indispensable for HIV-1 replication and has become a validated target for developing anti-AIDS agents. In two decades of development of IN inhibition-based anti-HIV therapeutics, a significant number of compounds were identified as IN inhibitors, but only some of them showed antiviral activity. This article reviews a number of patented HIV-1 IN inhibitors, especially those that possess high selectivity for the strand transfer reaction. These compounds generally have a polar coplanar moiety, which is assumed to chelate two magnesium ions in the binding site. Resistance to those compounds, when given to patients, can develop as a result of IN mutations. We refer to those compounds as authentic IN inhibitors. Continued drug development has so far delivered one authentic IN inhibitor to the market (raltegravir in 2007). Current and future attention will be focused on the development of novel authentic IN inhibitors with the goal of overcoming viral resistance. PMID:21426159

  16. Stem cell transplantation in the context of HIV--how can we cure HIV infection?

    PubMed

    Bauer, Gerhard; Anderson, Joseph S

    2014-01-01

    All HIV target cells are derived from hematopoietic stem cells. More than two decades ago, a hypothesis was postulated that a cure for HIV may be possible by performing a transplant with HIV-resistant hematopoietic stem cells that would allow for an HIV-resistant immune system to arise. HIV-resistant stem cells could be generated by genetically modifying them with gene therapy vectors transferring anti-HIV genes. First attempts of stem cell gene therapy for HIV were carried out in the USA in the 1990s demonstrating safety, but also little efficacy at that time. The first demonstration that the postulated hypothesis was correct was the cure of an HIV-infected individual in Berlin in 2009 who received an allogeneic bone marrow transplant from a donor who lacked the CCR5 chemokine receptor, a naturally arising mutation rendering HIV target cells resistant to infection with macrophage tropic strains of HIV. In 2013, reports were published about a possible cure of HIV-infected individuals who received allogeneic bone marrow transplants with cells not resistant to HIV. We will review these stem cell transplant procedures and discuss their utility to provide a cure for HIV infection, including efficacious future stem cell gene therapy applications.

  17. Human Microbiome and HIV/AIDS

    PubMed Central

    Li, Yihong; Yang, Liying; Pei, Zhiheng; Poles, Michael; Abrams, William R.; Malamud, Daniel

    2013-01-01

    Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of “crosstalk” between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection. PMID:22193889

  18. Fighting with the enemy's weapons? the role of costimulatory molecules in HIV.

    PubMed

    De Keersmaecker, B; Thielemans, K; Aerts, J L

    2011-04-01

    HIV infection is characterized by a number of abnormalities in several components of the immune system. For example, during HIV infection, a massive decrease of CD4(+) T cells is observed, as well as a progressive depletion of naïve CD8(+) T cells. Furthermore, elevated numbers of apoptotic B and T cells are present in HIV-infected patients, and a systemic immune activation results in T-cell exhaustion. Finally, HIV infection is characterized by the presence of functionally impaired dendritic cells, with decreased expression of maturation markers, decreased secretion of cytokines and defects in antigen processing and presentation. All these characteristics result in the occurrence of non-functional cytotoxic T lymphocytes, that fail to control HIV-replication in most individuals during progressive disease. Costimulatory and co-inhibitory molecules are involved in the activation, differentiation and survival of several cell-types of the immune system. Each costimulatory receptor (generally expressed on effector cells) can conjugate with one or more specific ligands (expressed on antigen-presenting cells), which leads to an activation of intracellular signaling pathways inside the cells on which they are expressed. HIV infection is characterized by an aberrant expression of these molecules on cells of the immune system. Many of the immune deficiencies mentioned in the previous paragraph can be explained by abnormal expression of costimulatory molecules, and could consequently be overcome by interfering with their interactions. In this review, we give an overview of the functions and expression patterns of the receptor/ligand pairs of the tumor necrosis factor and the B7 super-families of costimulatory and co-inhibitory molecules in HIV-infected patients. We will also discuss possibilities for manipulating their signaling as a therapeutic anti-HIV tool.

  19. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

    PubMed Central

    Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

    2016-01-01

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  20. MACROMOLECULAR THERAPEUTICS

    PubMed Central

    Yang, Jiyuan; Kopeček, Jindřich

    2014-01-01

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

  1. Tuberculosis surveillance in a therapeutic community.

    PubMed

    Foley, M E; Ehr, A P; Raza, B; Devlin, C J

    1995-01-01

    Tuberculosis, a chronic communicable bacterial infection of epidemic proportions in the United States, is more common among debilitated and immunocompromised persons, for example, alcoholics, drug abusers, and HIV/AIDS patients, than among the general population. Daytop Village Inc., a drug free therapeutic community for chemical dependency treatment, initiated a program of tuberculosis (TB) surveillance and prevention education with grant support. Continuous educational sessions for staff and residents have raised awareness of the threat of TB. From March 1991 until September 1992, 2,932 clients screened for TB found 272 (9.2%) PPD positive. Of these 272, 125 also tested for HIV found 28 (22.4%) HIV positive. The TB screening program had no negative impact on the retention rate of Daytop residents. With sufficient fiscal and personnel support, tuberculosis education, screening, and treatment has been naturally integrated into the primary care agenda within the therapeutic community model of drug abuse rehabilitation.

  2. 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.

  3. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; 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'etre 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 multi-step 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.

  4. HIV-2 Genetic Evolution in Patients with Advanced Disease Is Faster than That in Matched HIV-1 Patients▿ †

    PubMed Central

    Skar, Helena; Borrego, Pedro; Wallstrom, Timothy C.; Mild, Mattias; Marcelino, José Maria; Barroso, Helena; Taveira, Nuno; Leitner, Thomas; Albert, Jan

    2010-01-01

    The objective of this study was to estimate and compare the evolutionary rates of HIV-2 and HIV-1. Two HIV-2 data sets from patients with advanced disease were compared to matched HIV-1 data sets. The estimated mean evolutionary rate of HIV-2 was significantly higher than the estimated rate of HIV-1, both in the gp125 and in the V3 region of the env gene. In addition, the rate of synonymous substitutions in gp125 was significantly higher for HIV-2 than for HIV-1, possibly indicating a shorter generation time or higher mutation rate of HIV-2. Thus, the lower virulence of HIV-2 does not appear to translate into a lower rate of evolution. PMID:20463072

  5. Responsibility for HIV prevention: patterns of attribution among HIV-seropositive gay and bisexual men.

    PubMed

    Offer, Claudine; Grinstead, Olga; Goldstein, Ellen; Mamary, Edward; Alvarado, Nicholas; Euren, Jason; Woods, William J

    2007-02-01

    The Seroconversion Narratives for AIDS Prevention (SNAP) study elicited narratives from recently infected seropositive gay and bisexual men that described the circumstances of their own seroconversion. This analysis of the narratives explored participants' attributions of responsibility for HIV prevention before and after they became infected. Before becoming infected with HIV, responsibility for prevention was often attributed to HIV-negative individuals themselves. These retrospective attributions revealed themes that included feelings of negligence, a sense of consequences, followed by regret. After seroconversion, responsibility for HIV prevention was primarily attributed to HIV-positive individuals themselves. Themes within these attributions included pledges to avoid HIV transmission, a strong sense of burden related to the possibility of infecting someone, and risk reduction strategies that they implemented in an attempt to avoid HIV transmission. Greater understanding of ideas related to responsibility has the potential to increase the effectiveness of HIV prevention interventions. PMID:17411387

  6. Waking up the sleepers: HIV latency and reactivation.

    PubMed

    Mok, Hoi Ping; Lever, Andrew

    2008-12-01

    In a patient infected with HIV-1, the presence of latently infected cells from which the virus can be reactivated and rekindle HIV infection in the patient necessitates lifelong administration of antiretroviral treatment. The biology of HIV latency and viral silencing is now becoming clearer at a molecular and cellular level. However, our understanding of HIV-1 latency in vivo is still inadequate. Attempts to therapeutically reactivate the virus in infected patients have yielded disappointing results. This article reviews the research and clinical findings and discusses current thinking on the subject of HIV latency and reactivation.

  7. HIV Transmission

    MedlinePlus

    ... pre-chewed by an HIV-infected person. The contamination occurs when infected blood from a caregiver’s mouth ... pre-chewed by an HIV-infected person. The contamination occurs when infected blood from a caregiver’s mouth ...

  8. The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the host cell

    PubMed Central

    Perrone, Rosalba; Butovskaya, Elena; Lago, Sara; Garzino-Demo, Alfredo; Pannecouque, Christophe; Palù, Giorgio; Richter, Sara N.

    2016-01-01

    AS1411 is a G-rich aptamer that forms a stable G-quadruplex structure and displays antineoplastic properties both in vitro and in vivo. This oligonucleotide has undergone phase 2 clinical trials. The major molecular target of AS1411 is nucleolin (NCL), a multifunctional nucleolar protein also present in the cell membrane where it selectively mediates the binding and uptake of AS1411. Cell-surface NCL has been recognised as a low-affinity co-receptor for human immunodeficiency virus type 1 (HIV-1) anchorage on target cells. Here we assessed the anti-HIV-1 properties and underlying mechanism of action of AS1411. The antiviral activity of AS1411 was determined towards different HIV-1 strains, host cells and at various times post-infection. Acutely, persistently and latently infected cells were tested, including HIV-1-infected peripheral blood mononuclear cells from a healthy donor. Mechanistic studies to exclude modes of action other than virus binding via NCL were performed. AS1411 efficiently inhibited HIV-1 attachment/entry into the host cell. The aptamer displayed antiviral activity in the absence of cytotoxicity at the tested doses, therefore displaying a wide therapeutic window and favourable selectivity indexes. These findings, besides validating cell-surface-expressed NCL as an antiviral target, open the way for the possible use of AS1411 as a new potent and promisingly safe anti-HIV-1 agent. PMID:27032748

  9. Strategies for universalistic and targeted HIV prevention.

    PubMed

    Des Jarlais, D C; Padian, N

    1997-10-01

    The controversy over "targeted" versus "universalistic" programs for HIV prevention has persisted throughout the history of the HIV/AIDS epidemic in the United States and in some European countries. Building on previous analyses, we outline methods for integrating universalistic and targeted HIV prevention programming. The outline considers possible synergy between targeted and universalistic programs, rather than a forced choice between the two. Components within this framework include a continuum of the intensity of targeted programs, specification of local risk behavior populations, categories of risk behavior, and HIV seroprevalence within local risk-behavior populations. Given the scarce resources currently available, preventing all new HIV infections is not a realistic public health goal, but with better use of current scientific knowledge, it should be possible to greatly reduce the rate of new HIV infections. PMID:9358108

  10. HIV Medication Adherence

    MedlinePlus

    HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  11. HIV among Transgender People

    MedlinePlus

    ... of transgender Virginians . Richmond, VA: Virginia HIV Community Planning Committee and Virginia Department of Health; 2007. Accessed April 14, 2016. Additional ... HIV/AIDS CDC HIV CDC HIV/AIDS ...

  12. [HIV lipodystrophy].

    PubMed

    Snopková, S; Matýsková, M; Povolná, K; Polák, P; Husa, P

    2010-12-01

    Combined antiretroviral therapy results in extraordinary decrease of morbidity and mortality of HIV-infected patients and in an essential change of the HIV/AIDS disease prognosis. However, long-term intake of antiretroviral medicaments is related to occurrence of metabolic and morphological abnormalities, of which some have been combined into a new syndrome--the so called HIV lipodystrophy. The HIV lipodystrophy syndrome covers metabolic and morphological changes. Metabolic changes include dyslipidaemia with hypercholesterolaemia and/or hypertriglyceridaemia, insulin resistance with hyperinsulinaemia and hyperlaktataemia. Morphological changes have the nature of lipoatrophia (loss of subcutaneous fat--on the cheeks, on extremities, on buttocks and marked prominence of surface veins) or lipohypertrophia (growth of fat tissue--on the chest, in the dorsocervical area, lipomatosis of visceral tissues and organs, fat accumulation in the abdominal area). Several HIV lipodystrophy features are very similar to the metabolic syndrome of the general population. That is why this new syndrome represents a prospective risk of premature atherosclerosis and increase of the cardiovascular risk in young HIV positive individuals. The article mentions major presented studies dealing with the relation of antiretroviral treatment and the cardiovascular risk. The conclusions of the studies are not unequivocal--this is, among others, given by the reason that their length is short from the viewpoint of atherogenesis. The major risk of subclinical atherosclerosis acceleration seems to be related to the deep immunodeficiency and low number of CD4+ lymphocytes and florid, uncontrolled HIV infection with a high number of HIV-1 RNA copies actually circulating in the plasma. The question, whether metabolic and morphological changes related to HIV and cART carry a similar atherogenic potential as in the general population, remains open for future. PMID:21261108

  13. 'I can coexist with HIV': a qualitative study of perceptions of HIV cure among people living with HIV in Guangzhou, China.

    PubMed

    Ma, Qingyan; Wu, Feng; Henderson, Gail; Rennie, Stuart; Rich, Zachary C; Cheng, Yu; Hu, Fengyu; Cai, Weiping; Tucker, Joseph D

    2016-07-01

    Little is known about perceptions of HIV cure among people living with HIV (PLHIV), despite them being crucial stakeholders in ongoing HIV cure research. A qualitative research study was conducted in Guangzhou, China, to explore the perceptions of HIV cure among PLHIV in relation to their views on HIV treatment, stigma and social identity. We conducted in-depth interviews with 22 PLHIV from September 2014 to June 2015. Our qualitative data revealed three major themes: (1) Representations of HIV cure: PLHIV generally thought HIV cure was distant from them; (2) Possibility of HIV cure: ideas about the possibility of HIV cure ranged from optimism to scepticism and pessimism; and (3) Life without HIV cure: some participants had adjusted well to the chronic condition of HIV and ART adherence. Although some PLHIV looked forward to HIV being cured, most of the PLHIV in our study had little interest in it. On the contrary, many felt it is more important and realistic to have access to better ART medication and more education for the general public to decrease HIV stigma today rather than develop a cure for tomorrow.

  14. Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4.

    PubMed

    Nicolás, David; Ambrosioni, Juan; Paredes, Roger; Marcos, M Ángeles; Manzardo, Christian; Moreno, Asunción; Miró, José M

    2015-08-01

    HIV-1 is the most prevalent retrovirus, with over 30 million people infected worldwide. Nevertheless, infection caused by other human retroviruses like HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4 is gaining importance. Initially confined to specific geographical areas, HIV-2, HTLV-1 and HTLV-2 are becoming a major concern in non-endemic countries due to international migration flows. Clinical manifestations of retroviruses range from asymptomatic carriers to life-threatening conditions, such as AIDS in HIV-2 infection or adult T-cell lymphoma/leukemia or tropical spastic paraparesis in HTLV-1 infection. HIV-2 is naturally resistant to some antiretrovirals frequently used to treat HIV-1 infection, but it does have effective antiretroviral therapy options. Unfortunately, HTLV still has limited therapeutic options. In this article, we will review the epidemiological, clinical, diagnostic, pathogenic and therapeutic aspects of infections caused by these human retroviruses.

  15. HIV among Women

    MedlinePlus

    ... testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS ... HIV infection—National HIV Behavioral Surveillance, 20 U.S. cities, 2013 . HIV Surveillance Special Report 13 . Accessed January ...

  16. T-cell therapies for HIV: Preclinical successes and current clinical strategies.

    PubMed

    Patel, Shabnum; Jones, R Brad; Nixon, Douglas F; Bollard, Catherine M

    2016-08-01

    Although antiretroviral therapy (ART) has been successful in controlling HIV infection, it does not provide a permanent cure, requires lifelong treatment, and HIV-positive individuals are left with social concerns such as stigma. The recent application of T cells to treat cancer and viral reactivations post-transplant offers a potential strategy to control HIV infection. It is known that naturally occurring HIV-specific T cells can inhibit HIV initially, but this response is not sustained in the majority of people living with HIV. Genetically modifying T cells to target HIV, resist infection, and persist in the immunosuppressive environment found in chronically infected HIV-positive individuals might provide a therapeutic solution for HIV. This review focuses on successful preclinical studies and current clinical strategies using T-cell therapy to control HIV infection and mediate a functional cure solution.

  17. T-cell therapies for HIV: Preclinical successes and current clinical strategies.

    PubMed

    Patel, Shabnum; Jones, R Brad; Nixon, Douglas F; Bollard, Catherine M

    2016-08-01

    Although antiretroviral therapy (ART) has been successful in controlling HIV infection, it does not provide a permanent cure, requires lifelong treatment, and HIV-positive individuals are left with social concerns such as stigma. The recent application of T cells to treat cancer and viral reactivations post-transplant offers a potential strategy to control HIV infection. It is known that naturally occurring HIV-specific T cells can inhibit HIV initially, but this response is not sustained in the majority of people living with HIV. Genetically modifying T cells to target HIV, resist infection, and persist in the immunosuppressive environment found in chronically infected HIV-positive individuals might provide a therapeutic solution for HIV. This review focuses on successful preclinical studies and current clinical strategies using T-cell therapy to control HIV infection and mediate a functional cure solution. PMID:27265874

  18. Therapeutic alliance.

    PubMed

    Fox, Valerie

    2002-01-01

    I have been very fortunate in my journey of mental illness. I respond well to medication, but I don't think that is the complete answer to living successfully with serious, persistent mental illness. I believe a person's environment is also of utmost importance, enabling the person suffering with mental illness to continually grow in life. I found early in my struggle with mental illness a psychiatrist with whom I have always had a very good rapport. Until recently I didn't know that what I have with this psychiatrist is professionally known as a therapeutic alliance. Over the years, when I need someone to talk over anything that is troubling to me, I seek my psychiatrist. A therapeutic alliance is non-judgmental; it is nourishing; and finally it is a relationship of complete trust. Perhaps persons reading this article who have never experienced this alliance will seek it. I believe it can make an insecure person secure; a frightened person less frightened; and allow a person to continue the journey of mental health with a sense of belief in oneself. PMID:12433224

  19. 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 ...

  20. [Microbiological diagnosis of HIV infection].

    PubMed

    López-Bernaldo de Quirós, Juan Carlos; Delgado, Rafael; García, Federico; Eiros, José M; Ortiz de Lejarazu, Raúl

    2007-12-01

    Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

  1. Stem cell based anti-HIV Gene therapy

    PubMed Central

    Kitchen, Scott G.; Shimizu, Saki; An, Dong Sung

    2011-01-01

    Human stem cell-based therapeutic intervention strategies for treating HIV infection have recently undergone a renaissance as a major focus of investigation. Unlike most conventional antiviral therapies, genetically engineered hematopoietic stem cells possess the capacity for prolonged self-renewal that would continuously produce protected immune cells to fight against HIV. A successful strategy therefore has the potential to stably control and ultimately eradicate HIV from patients by a single or minimal treatment. Recent progress in the development of new technologies and clinical trials sets the stage for the current generation of gene therapy approaches to combat HIV infection. In this review, we will discuss two major approaches that are currently underway in the development of stem cell-based gene therapy to target HIV: One that focuses on the protection of cells from productive infection with HIV, and the other that focuses on targeting immune cells to directly combat HIV infection. PMID:21247612

  2. Newer gene editing technologies toward HIV gene therapy.

    PubMed

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

    2013-11-01

    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.

  3. Adolescents with HIV and facial lipoatrophy: response to facial stimulation

    PubMed Central

    Gabana-Silveira, Jesus Claudio; Mangilli, Laura Davison; Sassi, Fernanda C.; Braga, Arnaldo Feitosa; Andrade, Claudia Regina Furquim

    2014-01-01

    OBJECTIVES: This study evaluated the effects of facial stimulation over the superficial muscles of the face in individuals with facial lipoatrophy associated with human immunodeficiency virus (HIV) and with no indication for treatment with polymethyl methacrylate. METHOD: The study sample comprised four adolescents of both genders ranging from 13 to 17 years in age. To participate in the study, the participants had to score six or less points on the Facial Lipoatrophy Index. The facial stimulation program used in our study consisted of 12 weekly 30-minute sessions during which individuals received therapy. The therapy consisted of intra- and extra-oral muscle contraction and stretching maneuvers of the zygomaticus major and minor and the masseter muscles. Pre- and post-treatment results were obtained using anthropometric static measurements of the face and the Facial Lipoatrophy Index. RESULTS: The results suggest that the therapeutic program effectively improved the volume of the buccinators. No significant differences were observed for the measurements of the medial portion of the face, the lateral portion of the face, the volume of the masseter muscle, or Facial Lipoatrophy Index scores. CONCLUSION: The results of our study suggest that facial maneuvers applied to the superficial muscles of the face of adolescents with facial lipoatrophy associated with HIV improved the facial area volume related to the buccinators muscles. We believe that our results will encourage future research with HIV patients, especially for patients who do not have the possibility of receiving an alternative aesthetic treatment. PMID:25141118

  4. 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

  5. Stem cell-based therapies for HIV/AIDS.

    PubMed

    Pernet, Olivier; Yadav, Swati Seth; An, Dong Sung

    2016-08-01

    One of the current focuses in HIV/AIDS research is to develop a novel therapeutic strategy that can provide a life-long remission of HIV/AIDS without daily drug treatment and, ultimately, a cure for HIV/AIDS. Hematopoietic stem cell-based anti-HIV gene therapy aims to reconstitute the patient immune system by transplantation of genetically engineered hematopoietic stem cells with anti-HIV genes. Hematopoietic stem cells can self-renew, proliferate and differentiate into mature immune cells. In theory, anti-HIV gene-modified hematopoietic stem cells can continuously provide HIV-resistant immune cells throughout the life of a patient. Therefore, hematopoietic stem cell-based anti-HIV gene therapy has a great potential to provide a life-long remission of HIV/AIDS by a single treatment. Here, we provide a comprehensive review of the recent progress of developing anti-HIV genes, genetic modification of hematopoietic stem progenitor cells, engraftment and reconstitution of anti-HIV gene-modified immune cells, HIV inhibition in in vitro and in vivo animal models, and in human clinical trials. PMID:27151309

  6. Complement and HIV-I infection/HIV-associated neurocognitive disorders.

    PubMed

    Liu, Fengming; Dai, Shen; Gordon, Jennifer; Qin, Xuebin

    2014-04-01

    The various neurological complications associated with HIV-1 infection, specifically HIV-associated neurocognitive disorders (HAND) persist as a major public health burden worldwide. Despite the widespread use of anti-retroviral therapy, the prevalence of HAND is significantly high. HAND results from the direct effects of an HIV-1 infection as well as secondary effects of HIV-1-induced immune reaction and inflammatory response. Complement, a critical mediator of innate and acquired immunity, plays important roles in defeating many viral infections by the formation of a lytic pore or indirectly by opsonization and recruitment of phagocytes. While the role of complement in the pathogenesis of HIV-1 infection and HAND has been previously recognized for over 15 years, it has been largely underestimated thus far. Complement can be activated through HIV-1 envelope proteins, mannose-binding lectins (MBL), and anti-HIV-1 antibodies. Complement not only fights against HIV-1 infection but also enhances HIV-1 infection. In addition, HIV-1 can hijack complement regulators such as CD59 and CD55 and can utilize these regulators and factor H to escape from complement attack. Normally, complement levels in brain are much lower than plasma levels and there is no or little complement deposition in brain cells. Interestingly, local production and deposition of complement are dramatically increased in HIV-1-infected brain, indicating that complement may contribute to the pathogenesis of HAND. Here, we review the current understanding of the role of complement in HIV-1 infection and HAND, as well as potential therapeutic approaches targeting the complement system for the treatment and eradications of HIV-1 infection.

  7. Study of blood groups in HIV seropositive patients.

    PubMed

    Sayal, S K; Das, A L; Nema, S K

    1996-01-01

    Blood groups in 104 cases of HIV infection and 300 normal persons were determined. A relatively increased incidence of HIV infection was observed in persons with blood group O and relativey lower incidence in blood group B. Incidence of HIV infection was also low in Rh negative subjects. These results suggest a possible relationship between the incidence of blood group and the natural defence mechanism against HIV infection.

  8. Family Wellness, Not HIV Prevention

    PubMed Central

    Swendeman, Dallas; Flannery, Diane

    2010-01-01

    HIV exceptionalism (and disease-specific programs generally) garner both unbalanced funding and the most talented personnel, distorting local health priorities. In support of HIV exceptionalism, the successful mobilization of significant global health sector resources was not possible prior to HIV. Both sides of the debate have merits; rather than perpetuating polarization, we suggest that sustained improvements in global health require creating a prevention infrastructure to meet multiple health challenges experienced by local communities. We propose four fundamental shifts in HIV and disease prevention: (1) horizontally integrating prevention at one site locally, with priorities tailored to local health challenges and managed by local community leaders; (2) using a family wellness metaphor for services, not disease prevention; (3) implementing evidence-based prevention programs (EBPP) based on common principles, factors, and processes, rather than replication of specific programs; and (4) utilizing the expertise of private enterprise to re-design EBPP into highly attractive, engaging, and accessible experiences. PMID:19148744

  9. "When in the body, it makes you look fat and HIV negative": the constitution of antiretroviral therapy in local discourse among youth in Kahe, Tanzania.

    PubMed

    Ezekiel, Mangi Job; Talle, Aud; Juma, James M; Klepp, Knut-Inge

    2009-03-01

    Antiretroviral therapy (ART) is becoming increasingly more accessible within the health care system in Tanzania. However, the impact of the increased availability of ART on local conceptions about medicines, health and physical wellbeing has not been fully explored. In this article we examine how ART is constituted within local discourses about treatment and healing. Based on 21 focus group discussions with young people aged 14-24 years in a rural area (Kahe), we examine how local terms and descriptions of antiretroviral therapy relate to wider definitions about the body, health, illness and drug efficacy. Findings illustrate how local understandings of ART draw on a wider discourse about the therapeutic functions of medicines and clinical dimensions of HIV/AIDS. Therapeutic efficacy of antiretroviral medication appeared to overlap and sometimes contradict locally shared understandings of the clinical functions of medicines in the body. Implications of ART on bodily appearance and HIV signs may influence conceptions about sick role, perpetuate stigma and affect local strategies for HIV prevention. Structural inequities in access, limited information on therapeutic efficacy of ART and perceived difficulties with status disclosure appear to inform local conceptions and possible implications of ART. Policy and programme interventions to foster public understanding and acceptability of ART should emphasize treatment education about the benefits and limitations of therapy and increased access to ART in rural areas, and should integrate voluntary status disclosure and HIV prevention.

  10. Macro-level Implicit HIV Prejudice and the Health of Community Residents with HIV

    PubMed Central

    Miller, Carol T.; Varni, Susan E.; Solomon, Sondra E.; DeSarno, Michael J.; Bunn, Janice Y.

    2016-01-01

    Objectives This study examined how community levels of implicit HIV prejudice are associated with the psychological and physical well-being of people with HIV living in those same communities. It also examined whether community motivation to control prejudice and/or explicit HIV prejudice moderates the relationship of implicit prejudice and well-being. Methods Participants were 206 people with HIV living in 42 different communities in New England who completed measures that assessed psychological distress, thriving, and physical well-being. Telephone surveys of 347 residents of these same communities (selected via random digit dialing) were used to assess community explicit HIV prejudice and motivation to control HIV prejudice. These community residents then completed an on-line measure of implicit prejudice toward people with HIV, the Implicit Association Test (IAT, Greenwald et al., 1998). Results Multilevel analyses showed that higher community implicit HIV prejudice was associated with greater psychological distress among residents with HIV living in that community. The physical well-being of participants with HIV was negatively related to community implicit HIV prejudice in communities in which residents were unmotivated to control HIV prejudice or had high levels of explicit HIV prejudice. Conclusions These findings indicate that implicit prejudice of residents of real-world communities may create an environment that may impair the well-being of stigmatized people. Implicit prejudice can therefore be considered an element of macro-level or structural stigma. The discussion considered the possible role of implicit HIV prejudice on a community’s social capital as one pathway by which it compromises the well-being of residents with HIV. PMID:27505199

  11. Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers

    PubMed Central

    Goda, Jayant S.; Pachpor, Tejaswini; Basu, Trinanjan; Chopra, Supriya; Gota, Vikram

    2016-01-01

    Cellular resistance in tumour cells to different therapeutic approaches has been a limiting factor in the curative treatment of cancer. Resistance to therapeutic radiation is a common phenomenon which significantly reduces treatment options and impacts survival. One of the mechanisms of acquiring resistance to ionizing radiation is the overexpression or activation of various oncogenes like the EGFR (epidermal growth factor receptor), RAS (rat sarcoma) oncogene or loss of PTEN (phosphatase and tensin homologue) which in turn activates the phosphatidyl inositol 3-kinase/protein kinase B (PI3-K)/AKT pathway responsible for radiation resistance in various tumours. Blocking the pathway enhances the radiation response both in vitro and in vivo. Due to the differential activation of this pathway (constitutively activated in tumour cells and not in the normal host cells), it is an excellent candidate target for molecular targeted therapy to enhance radiation sensitivity. In this regard, HIV protease inhibitors (HPIs) known to interfere with PI3-K/AKT signaling in tumour cells, have been shown to sensitize various tumour cells to radiation both in vitro and in vivo. As a result, HPIs are now being investigated as possible radiosensitizers along with various chemotherapeutic drugs. This review describes the mechanisms by which PI3-K/AKT pathway causes radioresistance and the role of HIV protease inhibitors especially nelfinavir as a potential candidate drug to target the AKT pathway for overcoming radioresistance and its use in various clinical trials for different malignancies. PMID:27121513

  12. Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers.

    PubMed

    Goda, Jayant S; Pachpor, Tejaswini; Basu, Trinanjan; Chopra, Supriya; Gota, Vikram

    2016-02-01

    Cellular resistance in tumour cells to different therapeutic approaches has been a limiting factor in the curative treatment of cancer. Resistance to therapeutic radiation is a common phenomenon which significantly reduces treatment options and impacts survival. One of the mechanisms of acquiring resistance to ionizing radiation is the overexpression or activation of various oncogenes like the EGFR (epidermal growth factor receptor), RAS (rat sarcoma) oncogene or loss of PTEN (phosphatase and tensin homologue) which in turn activates the phosphatidyl inositol 3-kinase/protein kinase B (PI3-K)/AKT pathway responsible for radiation resistance in various tumours. Blocking the pathway enhances the radiation response both in vitro and in vivo. Due to the differential activation of this pathway (constitutively activated in tumour cells and not in the normal host cells), it is an excellent candidate target for molecular targeted therapy to enhance radiation sensitivity. In this regard, HIV protease inhibitors (HPIs) known to interfere with PI3-K/AKT signaling in tumour cells, have been shown to sensitize various tumour cells to radiation both in vitro and in vivo. As a result, HPIs are now being investigated as possible radiosensitizers along with various chemotherapeutic drugs. This review describes the mechanisms by which PI3-K/AKT pathway causes radioresistance and the role of HIV protease inhibitors especially nelfinavir as a potential candidate drug to target the AKT pathway for overcoming radioresistance and its use in various clinical trials for different malignancies.

  13. Peptidomimetic inhibitors of HIV protease.

    PubMed

    Randolph, John T; DeGoey, David A

    2004-01-01

    There are currently (July, 2002) six protease inhibitors approved for the treatment of HIV infection, each of which can be classified as peptidomimetic in structure. These agents, when used in combination with other antiretroviral agents, produce a sustained decrease in viral load, often to levels below the limits of quantifiable detection, and a significant reconstitution of the immune system. Therapeutic regimens containing one or more HIV protease inhibitors thus provide a highly effective method for disease management. The important role of protease inhibitors in HIV therapy, combined with numerous challenges remaining in HIV treatment, have resulted in a continued effort both to optimize regimens using the existing agents and to identify new protease inhibitors that may provide unique properties. This review will provide an overview of the discovery and clinical trials of the currently approved HIV protease inhibitors, followed by an examination of important aspects of therapy, such as pharmacokinetic enhancement, resistance and side effects. A description of new peptidomimetic compounds currently being investigated in the clinic and in preclinical discovery will follow. PMID:15193140

  14. Herpes simplex virus type-2 stimulates HIV-1 replication in cervical tissues: implications for HIV-1 transmission and efficacy of anti-HIV-1 microbicides.

    PubMed

    Rollenhagen, C; Lathrop, M J; Macura, S L; Doncel, G F; Asin, S N

    2014-09-01

    Herpes Simplex virus Type-2 (HSV-2) increases the risk of HIV-1 acquisition, yet the mechanism for this viral pathogen to regulate the susceptibility of the cervicovaginal mucosa to HIV-1 is virtually unknown. Using ex vivo human ectocervical tissue models, we report greater levels of HIV-1 reverse transcription, DNA integration, RNA expression, and virions release in HIV-1/HSV-2 co-infected tissues compared with HIV-1 only infected tissues (P<0.05). Enhanced HIV-1 replication was associated with increased CD4, CCR5, and CD38 transcription (P<0.05) and increased number of CD4(+)/CCR5(+)/CD38(+) T cells in HIV-1/HSV-2 co-infected tissues compared with tissues infected with HIV-1 alone. Tenofovir (TFV) 1% gel, the leading microbicide candidate, demonstrated only partial protection against HIV-1, when applied vaginally before and after sexual intercourse. It is possible that mucosal inflammation, in particular that induced by HSV-2 infection, may have decreased TFV efficacy. HSV-2 upregulated the number of HIV-1-infected cells and elevated the concentration of TFV needed to decrease HIV-1 infection. Similarly, only high concentrations of TFV inhibited HSV-2 replication in HIV-1/HSV-2-infected tissues. Thus, HSV-2 co-infection and mucosal immune cell activation should be taken into consideration when designing preventative strategies for sexual transmission of HIV-1.

  15. Continuous antigenic stimulation of DO11.10 TCR transgenic mice in the presence or absence of IL-1β: possible implications for mechanisms of T cell depletion in HIV disease1

    PubMed Central

    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.

    2015-01-01

    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 context, but the quantitative contributions of these proposed mechanisms over time remains unclear. We turned to the DO11.10 TCR transgenic (tg) mouse model, where OVA is recognized in the context of H-2d, to explore the impact of chronic antigenic stimulation on CD4+ T cell dynamics. To model dichotomous states of persistent antigen exposure in the presence or absence of proinflammatory stimulation, we administered OVA peptide (OVAp) to these mice on a continuous basis with or without the prototypic proinflammatory cytokine, interleukin 1β (IL-1β). In both cases, circulating antigen-specific CD4+ T cells were depleted. However, in the absence of IL-1β, there was limited proliferation and effector/memory conversion of antigen-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 OVAp was administered in the presence of IL-1β, effector/memory phenotype T cells expanded and the typical symptoms of heightened immune activation were observed. Acknowledging the imperfect and incomplete relationship between antigen-stimulated DO11.10 TCR tg 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 antigen exposure in the absence of proinflammatory signals and/or appropriate antigen-presenting cell functions. PMID:26416271

  16. HIV Latency

    PubMed Central

    Siliciano, Robert F.; Greene, Warner C.

    2011-01-01

    HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4+ T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recognized as a major barrier to curing HIV-1 infection. The molecular mechanisms of latency are complex and include the absence in resting CD4+ T cells of nuclear forms of key host transcription factors (e.g., NFκB and NFAT), the absence of Tat and associated host factors that promote efficient transcriptional elongation, epigenetic changes inhibiting HIV-1 gene expression, and transcriptional interference. The presence of a latent reservoir for HIV-1 helps explain the presence of very low levels of viremia in patients on antiretroviral therapy. These viruses are released from latently infected cells that have become activated and perhaps from other stable reservoirs but are blocked from additional rounds of replication by the drugs. Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir. PMID:22229121

  17. Bacteriophage Procurement for Therapeutic Purposes.

    PubMed

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  18. Bacteriophage Procurement for Therapeutic Purposes

    PubMed Central

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  19. Heterosexual transmission of HIV.

    PubMed

    Johnson, A M; Laga, M

    1988-01-01

    Recent developments concerning heterosexual transmission of HIV (review of 1988 literature only) suggest improved understanding of the pattern of spread and role of risk behaviors and biological cofactors in its transmission. 3 distinct patterns if HIV infection are known: heterosexual spread in sub-Saharan Africa and the Caribbean, spread primarily among homosexuals and injecting drug users in Europe, North American and much of Latin America and Australia, and both homosexual and heterosexual transmission in Asia, the Pacific, the Middle East and Eastern Europe, where prevalence is low. In Africa an estimated 80% of cases are acquired heterosexually. Important risk factors are number of sex partners, sex with prostitutes, being a prostitute, being a sex partner of an infected person, and having a history of other sexually transmitted diseases. Prevalence rates have risen rapidly in Zaire and Kenya. In Africa, acquisition of HIV is related to sexual activity only. In contrast, in the U.S., heterosexual cases make up only 4% of all cases, and in Europe only 6%. Data on types of sexual transmission of HIV are mounting, in aggregate suggestive of a marked heterogeneity in infectivity and possibly susceptibility between individuals. Among couples where the man is positive, in some places individuals appear to be highly infective, notably those from Kinshasa, Zaire and Haiti, while other series of discordant couples the receptive partner remained seronegative for several years. Transmission from women to men appears to be less efficient than from men to women, as has been observed with other STDs such as gonorrhea. Biological cofactors implicated in enhanced HIV transmission appear to be advanced CDC Stage IV AIDS disease, with low T-helper lymphocyte counts and high antigenemia; concomitant STDS, especially those with genital ulceration; lack of circumcision; oral contraceptive use; practice of anal intercourse; inconsistent or no use of condoms. Theoretical models for

  20. Ex vivo gene therapy for HIV-1 treatment

    PubMed Central

    Scherer, Lisa J.; Rossi, John J.

    2011-01-01

    Until recently, progress in ex vivo gene therapy (GT) for human immunodeficiency virus-1 (HIV-1) treatment has been incremental. Long-term HIV-1 remission in a patient who received a heterologous stem cell transplant for acquired immunodeficiency syndrome-related lymphoma from a CCR5−/– donor, even after discontinuation of conventional therapy, has energized the field. We review the status of current approaches as well as future directions in the areas of therapeutic targets, combinatorial strategies, vector design, introduction of therapeutics into stem cells and enrichment/expansion of gene-modified cells. Finally, we discuss recent advances towards clinical application of HIV-1 GT. PMID:21505069

  1. Alcohol Consumption, Progression of Disease and Other Comorbidities, and Responses to Antiretroviral Medication in People Living with HIV

    PubMed Central

    Neuman, Manuela G.; Schneider, Michelle; Nanau, Radu M.; Parry, Charles

    2012-01-01

    The present paper describes the possible connection between alcohol consumption and adherence to medicine used to treat human deficiency viral (HIV) infection. Highly active antiretroviral therapy (HAART) has a positive influence on longevity in patients with HIV, substantially reducing morbidity and mortality, including resource-poor settings such as South Africa. However, in a systematic comparison of HAART outcomes between low-income and high-income countries in the treatment of HIV-patients, mortality was higher in resource-poor settings. Specifically, in South Africa, patients often suffer from concomitant tuberculosis and other infections that may contribute to these results. Alcohol influences the use of medicine for opportunistic infections (e.g., pneumonia, tuberculosis), or coinfections HIV-hepatitis viruses-B (HBV) and C (HCV), cytomegalovirus, or herpes simplex virus. Furthermore, alcohol use may negatively impact on medication adherence contributing to HIV progression. The materials used provide a data-supported approach. They are based on analysis of published (2006–2011) world literature and the experience of the authors in the specified topic. Intended for use by health care professionals, these recommendations suggest approaches to the therapeutic and preventive aspects of care. Our intention was to fully characterize the quality of evidence supporting recommendations, which are reflecting benefit versus risk, and assessing strength or certainty. PMID:22496971

  2. HIV-Associated Neurologic Disorders and Central Nervous System Opportunistic Infections in HIV.

    PubMed

    Le, Leah T; Spudich, Serena S

    2016-08-01

    Since the advent of combination antiretroviral therapy (cART), HIV has transformed from a fatal disease to a chronic illness that often presents with milder central nervous system (CNS) symptoms laced with related confounders. The immune recovery associated with access to cART has led to a new spectrum of immune-mediated presentations of infection, phenotypically distinct from the conditions observed in advanced disease.HIV-associated neurocognitive disorder (HAND) entails a categorized continuum of disorders reflecting an array of clinical presentation, outcome, and increasing level of severity: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). HAND is defined through an assessment of neurocognitive abilities and functional performance. Progressive neurologic symptoms detected in patients on cART with detectable CSF viral load and a suppressed plasma viral load, or CSF viral load 1 log10 greater than low detectable plasma viral load, characterize a phenomenon termed symptomatic CSF "escape." CD8+ T-cell encephalitis, possibly a form of CNS immune reconstitution inflammatory syndrome, resembles CNS "escape" as it presents in patients despite viral suppression with cART. Cerebral toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy, are AIDS defining conditions with associated high mortality risk. Cerebral toxoplasmosis and cryptococcal meningitis typically manifest in immunosuppressed patients (<200 CD4+ T-cells/μL), while PML can occur in patients with higher CD4+ T-cell counts.Neurologic conditions are increasingly interconnected with chronic diseases, and classic opportunistic infections may have altered phenotypes in the cART era. However, there exist promising diagnostic methods and therapeutic approaches, as well as associated pitfalls in diagnosis and treatment.

  3. HIV-Associated Neurologic Disorders and Central Nervous System Opportunistic Infections in HIV.

    PubMed

    Le, Leah T; Spudich, Serena S

    2016-08-01

    Since the advent of combination antiretroviral therapy (cART), HIV has transformed from a fatal disease to a chronic illness that often presents with milder central nervous system (CNS) symptoms laced with related confounders. The immune recovery associated with access to cART has led to a new spectrum of immune-mediated presentations of infection, phenotypically distinct from the conditions observed in advanced disease.HIV-associated neurocognitive disorder (HAND) entails a categorized continuum of disorders reflecting an array of clinical presentation, outcome, and increasing level of severity: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). HAND is defined through an assessment of neurocognitive abilities and functional performance. Progressive neurologic symptoms detected in patients on cART with detectable CSF viral load and a suppressed plasma viral load, or CSF viral load 1 log10 greater than low detectable plasma viral load, characterize a phenomenon termed symptomatic CSF "escape." CD8+ T-cell encephalitis, possibly a form of CNS immune reconstitution inflammatory syndrome, resembles CNS "escape" as it presents in patients despite viral suppression with cART. Cerebral toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy, are AIDS defining conditions with associated high mortality risk. Cerebral toxoplasmosis and cryptococcal meningitis typically manifest in immunosuppressed patients (<200 CD4+ T-cells/μL), while PML can occur in patients with higher CD4+ T-cell counts.Neurologic conditions are increasingly interconnected with chronic diseases, and classic opportunistic infections may have altered phenotypes in the cART era. However, there exist promising diagnostic methods and therapeutic approaches, as well as associated pitfalls in diagnosis and treatment. PMID:27643907

  4. Targeting the gastrointestinal tract to develop novel therapies for HIV.

    PubMed

    Reeves, R K; Burgener, A; Klatt, N R

    2015-10-01

    Despite the use of antiretroviral therapy (ART), which delays and/or prevents AIDS pathogenesis, human immunodeficiency virus (HIV)-infected individuals continue to face increased morbidities and mortality rates compared with uninfected individuals. Gastrointestinal (GI) mucosal dysfunction is a key feature of HIV infection, and is associated with mortality. In this study, we review current knowledge about mucosal dysfunction in HIV infection, and describe potential avenues for therapeutic targets to enhance mucosal function and decrease morbidities and mortalities in HIV-infected individuals.

  5. Oligodendrocytes Are Targets of HIV-1 Tat: NMDA and AMPA Receptor-Mediated Effects on Survival and Development

    PubMed Central

    Zou, Shiping; Fuss, Babette; Fitting, Sylvia; Hahn, Yun Kyung; Hauser, Kurt F.

    2015-01-01

    Myelin pallor in HIV+ individuals can occur very early during the disease process. While myelin damage might partly originate from HIV-induced vascular changes, the timing suggests that myelin and/or oligodendrocytes (OLs) may be directly affected. Histological (Golgi–Kopsch, electron microscopy) and biochemical studies have revealed an increased occurrence of abnormal OL/myelin morphology and dysregulated myelin protein expression in transgenic mice expressing the HIV-1 transactivator of transcription (Tat) protein. This suggests that viral proteins by themselves might cause OL injury. Since Tat interacts with NMDARs, we hypothesized that activation of NMDARs and subsequent disruption of cytoplasmic Ca2+ ([Ca2+]i) homeostasis might be one cause of white matter injury after HIV infection. In culture, HIV-1 Tat caused concentration-dependent death of immature OLs, while more mature OLs remained alive but had reduced myelin-like membranes. Tat also induced [Ca2+]i increases and Thr-287 autophosphorylation of Ca2+/calmodulin-dependent protein kinase II β (CaMKIIβ) in OLs. Tat-induced [Ca2+]i was attenuated by the NMDAR antagonist MK801, and also by the AMPA/kainate receptor antagonist CNQX. Importantly, both MK801 and CNQX blocked Tat-induced death of immature OLs, but only MK801 reversed Tat effects on myelin-like membranes. These results suggest that OLs can be direct targets of HIV proteins released from infected cells. Although viability and membrane production are both affected by glutamatergic receptor-mediated Ca2+ influx, and possibly the ensuing CaMKIIβ activation, the roles of AMPARs and NMDARs appear to be different and dependent on the stage of OL differentiation. SIGNIFICANCE STATEMENT Over 33 million individuals are currently infected by HIV. Among these individuals, ∼60% develop HIV-associated neurocognitive disorders. Myelin damage and white matter injury have been frequently reported in HIV patients but not extensively studied. Clinical studies

  6. Current Advances in Virus-Like Particles as a Vaccination Approach against HIV Infection

    PubMed Central

    Zhao, Chongbo; Ao, Zhujun; Yao, Xiaojian

    2016-01-01

    HIV-1 virus-like particles (VLPs) are promising vaccine candidates against HIV-1 infection. They are capable of preserving the native conformation of HIV-1 antigens and priming CD4+ and CD8+ T cell responses efficiently via cross presentation by both major histocompatibility complex (MHC) class I and II molecules. Progress has been achieved in the preclinical research of HIV-1 VLPs as prophylactic vaccines that induce broadly neutralizing antibodies and potent T cell responses. Moreover, the progress in HIV-1 dendritic cells (DC)-based immunotherapy provides us with a new vision for HIV-1 vaccine development. In this review, we describe updates from the past 5 years on the development of HIV-1 VLPs as a vaccine candidate and on the combined use of HIV particles with HIV-1 DC-based immunotherapy as efficient prophylactic and therapeutic vaccination strategies. PMID:26805898

  7. HIV Life Cycle

    MedlinePlus

    HIV Overview The HIV Life Cycle (Last updated 9/8/2016; last reviewed 9/8/2016) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

  8. Camp HIV.

    PubMed

    Grodeck, B

    1995-01-01

    Innovative retreats for HIV-positive travelers specialize in stress reduction and alternative healing. The author gives a first-hand account of experiencing a wellness vacation for the HIV-positive. Although wellness retreats are nothing new, a San Francisco-based travel company picked the island of Hawaii as the specialized testing ground. The retreats guarantee a safe environment with a dose of restoration. Individuals spend seven days at the retreat center, Kalani Honua. Stress management workshops focus on yoga, principles of meditation, psychic healings, acupressure, relationship and communication, and massage.

  9. A structurally plastic ribonucleoprotein complex mediates post-transcriptional gene regulation in HIV-1.

    PubMed

    Fernandes, Jason D; Booth, David S; Frankel, Alan D

    2016-07-01

    HIV replication requires the nuclear export of essential, intron-containing viral RNAs. To facilitate export, HIV encodes the viral accessory protein Rev which binds unspliced and partially spliced viral RNAs and creates a ribonucleoprotein complex that recruits the cellular Chromosome maintenance factor 1 export machinery. Exporting RNAs in this manner bypasses the necessity for complete splicing as a prerequisite for mRNA export, and allows intron-containing RNAs to reach the cytoplasm intact for translation and virus packaging. Recent structural studies have revealed that this entire complex exhibits remarkable plasticity at many levels of organization, including RNA folding, protein-RNA recognition, multimer formation, and host factor recruitment. In this review, we explore each aspect of plasticity from structural, functional, and possible therapeutic viewpoints. WIREs RNA 2016, 7:470-486. doi: 10.1002/wrna.1342 For further resources related to this article, please visit the WIREs website. PMID:26929078

  10. HIV-1 Capsid: The Multifaceted Key Player in HIV-1 infection

    PubMed Central

    Campbell, Edward M.; Hope, Thomas J.

    2016-01-01

    In a mature, infectious HIV-1 virion, the viral genome is housed within a conical capsid core comprised of 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

  11. 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 immunodeficiency 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.

  12. TALEN gene editing takes aim on HIV.

    PubMed

    Benjamin, Ronald; Berges, Bradford K; Solis-Leal, Antonio; Igbinedion, Omoyemwen; Strong, Christy L; Schiller, Martin R

    2016-09-01

    Transcription activator-like effector nucleases (TALENs) are one of several types of programmable, engineered nucleases that bind and cleave specific DNA sequences. Cellular machinery repairs the cleaved DNA by introducing indels. In this review, we emphasize the potential, explore progress, and identify challenges in using TALENs as a therapeutic tool to treat HIV infection. TALENs have less off-target editing and can be more effective at tolerating HIV escape mutations than CRISPR/Cas-9. Scientists have explored TALEN-mediated editing of host genes such as viral entry receptors (CCR5 and CXCR4) and a protein involved in proviral integration (LEDGF/p75). Viral targets include the proviral DNA, particularly focused on the long terminal repeats. Major challenges with translating gene therapy from bench to bedside are improving cleavage efficiency and delivery, while minimizing off-target editing, cytotoxicity, and immunogenicity. However, rapid improvements in TALEN technology are enhancing cleavage efficiency and specificity. Therapeutic testing in animal models of HIV infection will help determine whether TALENs are a viable HIV treatment therapy. TALENs or other engineered nucleases could shift the therapeutic paradigm from life-long antiretroviral therapy toward eradication of HIV infection.

  13. Clinical management of HIV-associated hematologic malignancies.

    PubMed

    Wang, Chia-Ching J; Kaplan, Lawrence D

    2016-01-01

    HIV is associated with an excess risk for lymphoid malignancies. Although the risk of lymphoma has decreased in HIV-infected individuals in the era of effective combination antiretroviral therapy, it remains high. Treatment outcomes have improved due to improvements in HIV and cancer therapeutics for the common HIV-associated lymphomas. R-CHOP/R-EPOCH are the standard of care for HIV-associated diffuse large B-cell lymphoma. HIV-infected patients with Burkitt lymphoma and good performance status should receive dose-intensive regimens. HIV-infected patients with primary central nervous system lymphoma can respond favorably to high-dose methotrexate-based therapy. In many cases, treatment and expected outcomes for HIV-infected patients with either Hodgkin or non-Hodgkin's lymphomas are very similar to HIV-negative patients. There is currently no standard treatment for HIV-associated multicentric Castleman disease or primary effusion lymphoma. For those hematologic cancers in which transplantation is part of standard care, this modality should be considered an option in those with well-controlled HIV infection. PMID:26652941

  14. Screening and diagnosis for HIV

    MedlinePlus

    HIV testing; HIV screening; HIV screening test; HIV confirmatory test ... Task Force. Final Update Summary: Human Immunodeficiency Virus (HIV) Infection: Screening. July 2015. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/ ...

  15. Naturally derived anti-HIV agents.

    PubMed

    Asres, Kaleab; Seyoum, Ameha; Veeresham, Ciddi; Bucar, Franz; Gibbons, Simon

    2005-07-01

    The urgent need for new anti-HIV/AIDS drugs is a global concern. In addition to obvious economical and commercial hurdles, HIV/AIDS patients are faced with multifarious difficulties associated with the currently approved anti-HIV drugs. Adverse effects, the emergence of drug resistance and the narrow spectrum of activity have limited the therapeutic usefulness of the various reverse transcriptase and protease inhibitors that are currently available on the market. This has driven many scientists to look for new anti-retrovirals with better efficacy, safety and affordability. As has always been the case in the search for cures, natural sources offer great promise. Several natural products, mostly of plant origin have been shown to possess promising activities that could assist in the prevention and/or amelioration of the disease. Many of these anti-HIV agents have other medicinal values as well, which afford them further prospective as novel leads for the development of new drugs that can deal with both the virus and the various disorders that characterize HIV/AIDS. The aim of this review is to report new discoveries and updates pertaining to anti-HIV natural products. In the review anti-HIV agents have been classified according to their chemical classes rather than their target in the HIV replicative cycle, which is the most frequently encountered approach. Perusal of the literature revealed that most of these promising naturally derived anti-HIV compounds are flavonoids, coumarins, terpenoids, alkaloids, polyphenols, polysaccharides or proteins. It is our strong conviction that the results and experiences with many of the anti-HIV natural products will inspire and motivate even more researchers to look for new leads from plants and other natural sources. PMID:16161055

  16. Sexual health for people living with HIV.

    PubMed

    Shapiro, Kathy; Ray, Sunanda

    2007-05-01

    Sexual health is defined in terms of well-being, but is challenged by the social, cultural and economic realities faced by women and men with HIV. A sexual rights approach puts women and men with HIV in charge of their sexual health. Accurate, accessible information to make informed choices and safe, pleasurable sexual relationships possible is best delivered through peer education and health professionals trained in empathetic approaches to sensitive issues. Young people with HIV especially need appropriate sex education and support for dealing with sexuality and self-identity with HIV. Women and men with HIV need condoms, appropriate services for sexually transmitted infections, sexual dysfunction and management of cervical and anogenital cancers. Interventions based on positive prevention, that combine protection of personal health with avoiding HIV/STI transmission to partners, are recommended. HIV counselling following a positive test has increased condom use and decreased coercive sex and outside sexual contacts among discordant couples. HIV treatment and care have reduced stigma and increased uptake of HIV testing and disclosure of positive status to partners. High adherence to antiretroviral therapy and safer sexual behaviour must go hand-in-hand. Sexual health services have worked with peer educators and volunteer groups to reach those at higher risk, such as sex workers. Technological advances in diagnosis of STIs, microbicide development and screening and vaccination for human papillomavirus must be available in developing countries and for those with the highest need globally.

  17. HIV Testing

    MedlinePlus

    ... the right way, every day. If you have health insurance, your insurer is required to cover some medicines ... to treat HIV. If you don’t have health insurance, or you’re unable to afford your co- ...

  18. HIV Transmission Risk Behavior Among HIV-Positive Patients Receiving Antiretroviral Therapy in KwaZulu-Natal, South Africa

    PubMed Central

    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.

    2014-01-01

    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

  19. [Therapeutic plasmas available worldwide].

    PubMed

    Martinaud, C; Cauet, A; Sailliol, A

    2013-05-01

    Therapeutic plasma is a current product; French guidelines were reviewed in 2012. Connections between more or less closed countries are frequent, during relief disasters as well as in war settings. This is associated with the increasing use of plasma in the management of casualties. Additionally, The real possibility of lack of plasma supply in some countries provides a fundamental interest of the knowledge of foreign blood supply organizations. We present here the main divergences and mutual point between plasmas available worldwide. We present the main characteristics of each product.

  20. Mannose-binding lectin in HIV infection

    PubMed Central

    Eisen, Sarah; Dzwonek, Agnieszka; Klein, Nigel J

    2010-01-01

    Infection with HIV represents a significant global health problem, with high infection rates and high mortality worldwide. Treatment with antiretroviral therapy is inaccessible to many patients and efficacy is limited by development of resistance and side effects. The interactions of HIV with the human immune system, both innate and humoral, are complex and complicated by the profound ability of the virus to disable the host immune response. Mannose-binding lectin, a component of the innate immune system, has been demonstrated to play a role in host-virus interactions. This protein may have a key role in determining host susceptibility to infection, pathogenesis and progression of disease, and may contribute to the extensive variability of host response to infection. Further understanding and manipulation of the mannose-binding lectin response may represent a target for immunomodulation in HIV infection, which may, in conjunction with highly active antiretroviral therapy, allow development of a novel therapeutic approach to HIV infection. PMID:21218140

  1. 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 ...

  2. Older People and HIV

    MedlinePlus

    ... common than they were before the use of anti-HIV drugs. It is difficult to know what is causing mental problems in older people with HIV. Is it normal aging, or is it HIV disease? Research studies have ...

  3. HIV/AIDS

    MedlinePlus

    HIV infection; Infection - HIV; Human immunodeficiency virus; Acquired immune deficiency syndrome ... Symptoms related to acute HIV infection (when a person is first infected) can be similar to the flu or other viral illnesses. They include: Fever and ...

  4. 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 ...

  5. 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/ ...

  6. 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 ...

  7. HIV/AIDS

    MedlinePlus

    ... at risk for serious infections and certain cancers. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most often spreads through unprotected sex with ...

  8. HIV/AIDS

    MedlinePlus

    ... HIV infections. HIV infection is often diagnosed through rapid diagnostic tests (RDTs), which detect the presence or absence of ... accuracy. It is important to note that serological tests detect antibodies produced ... pathogens, rather than direct detection of HIV itself. Most ...

  9. HIV testing in India.

    PubMed

    Tripathy, Srikanth; Pereira, Michael; Tripathy, Sriram Prasad

    2012-06-01

    The National AIDS Control Organization (NACO) has initiated programs for HIV/AIDS control in India. Algorithms for HIV testing have been developed for India. NACO programs have resulted in HIV situation improving over the last decade.

  10. Genotype dependent QSAR for HIV-1 protease inhibition.

    PubMed

    Boutton, Carlo W; De Bondt, Hendrik L; De Jonge, Marc R

    2005-03-24

    The development of drug-resistant viruses limits the therapeutic success of anti-HIV therapies. Some of these genetic HIV-variants display complex mutational patterns in their pol gene that codes for protease and reverse transcriptase, the most investigated molecular targets for antiretroviral therapy. In this paper, we present a computational structure-based approach to predict the resistance of a HIV-1 protease strain to amprenavir by calculating the interaction energy of the drug with HIV-1 protease. By considering the interaction energy per residue, we can identify what residue mutations contribute to drug-resistance. This approach is presented here as a structure-based tool for the prediction of resistance of HIV-1 protease toward amprenavir, with a view to use the drug-protein interaction-energy pattern in a lead-optimization procedure for the discovery of new anti-HIV drugs. PMID:15771454

  11. 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

  12. HIV-1 infection, microenvironment and endothelial cell dysfunction.

    PubMed

    Mazzuca, Pietro; Caruso, Arnaldo; Caccuri, Francesca

    2016-09-01

    HIV-1 promotes a generalized immune activation that involves the main targets of HIV-1 infection but also cells that are not sensitive to viral infection. ECs display major dysfunctions in HIV+ patients during long-standing viral infection that persist even in the current cART era, in which new-generation drugs have reduced dysmetabolic side effects and successfully impeded viral replication. In vivo studies have failed to demonstrate the presence of replicating virus in ECs suggesting that a direct role of the virus is unlikely, and implying that the mechanism accounting for vascular dysfunction may rely on the indirect action of molecules released in the microenvironment by HIV-1-infected cells. This article reviews the current understanding of how HIV-1 infection can contribute to vascular dysfunction. In particular, we discuss the emerging role played by different HIV-1 proteins in driving inflammation and EC dysregulation, and highlight the need to target them for therapeutic benefit. PMID:27602413

  13. HIV-1 differentially modulates autophagy in neurons and astrocytes.

    PubMed

    Mehla, Rajeev; Chauhan, Ashok

    2015-08-15

    Autophagy, a lysosomal degradative pathway that maintains cellular homeostasis, has emerged as an innate immune defense against pathogens. The role of autophagy in the deregulated HIV-infected central nervous system (CNS) is unclear. We have found that HIV-1-induced neuro-glial (neurons and astrocytes) damage involves modulation of the autophagy pathway. Neuro-glial stress induced by HIV-1 led to biochemical and morphological dysfunctions. X4 HIV-1 produced neuro-glial toxicity coupled with suppression of autophagy, while R5 HIV-1-induced toxicity was restricted to neurons. Rapamycin, a specific mTOR inhibitor (autophagy inducer) relieved the blockage of the autophagy pathway caused by HIV-1 and resulted in neuro-glial protection. Further understanding of the regulation of autophagy by cytokines and chemokines or other signaling events may lead to recognition of therapeutic targets for neurodegenerative diseases.

  14. Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size

    PubMed Central

    Cummins, Nathan W.; Sainski, Amy M.; Dai, Haiming; Natesampillai, Sekar; Pang, Yuan-Ping; Bren, Gary D.; de Araujo Correia, Maria Cristina Miranda; Sampath, Rahul; Rizza, Stacey A.; O'Brien, Daniel; Yao, Joseph D.

    2016-01-01

    ABSTRACT Understanding how some HIV-infected cells resist the cytotoxicity of HIV replication is crucial to enabling HIV cure efforts. HIV killing of CD4 T cells that replicate HIV can involve HIV protease-mediated cleavage of procaspase 8 to generate a fragment (Casp8p41) that directly binds and activates the mitochondrial proapoptotic protein BAK. Here, we demonstrate that Casp8p41 also binds with nanomolar affinity to the antiapoptotic protein Bcl-2, which sequesters Casp8p41 and prevents apoptosis. Further, we show that central memory CD4 T cells (TCM) from HIV-infected individuals have heightened expression of BCL-2 relative to procaspase 8, possibly explaining the persistence of HIV-infected TCM despite generation of Casp8p41. Consistent with this hypothesis, the selective BCL-2 antagonist venetoclax induced minimal killing of uninfected CD4 T cells but markedly increased the death of CD4 T cells and diminished cell-associated HIV DNA when CD4 T cells from antiretroviral therapy (ART)-suppressed HIV patients were induced with αCD3/αCD28 to reactivate HIV ex vivo. Thus, priming CD4 T cells from ART suppressed HIV patients with a BCL-2 antagonist, followed by HIV reactivation, achieves reductions in cell-associated HIV DNA, whereas HIV reactivation alone does not. IMPORTANCE HIV infection is incurable due to a long-lived reservoir of HIV+ memory CD4 T cells, and no clinically relevant interventions have been identified that reduce the number of these HIV DNA-containing cells. Since postintegration HIV replication can result in HIV protease generation of Casp8p41, which activates BAK, causing infected CD4 T cell death, we sought to determine whether this occurs in memory CD4 T cells. Here, we demonstrate that memory CD4 T cells can generate Casp8p41 and yet are intrinsically resistant to death induced by diverse stimuli, including Casp8p41. Furthermore, BCL-2 expression is relatively increased in these cells and directly binds and inhibits Casp8p41's

  15. The Therapeutic School.

    ERIC Educational Resources Information Center

    Rice, John Steadman

    2002-01-01

    Contributes to the recent research on specific institutional carriers of the therapeutic culture, such as the state, the corporation, and the self- help movement, defining therapeutic discourse and discussing the therapeutic ethic, the therapeutic school, schools of education and their critics, and disappointing results of therapeutic schooling.…

  16. Coevolution of risk perception, sexual behaviour, and HIV transmission in an agent-based model.

    PubMed

    Tully, Stephen; Cojocaru, Monica; Bauch, Chris T

    2013-11-21

    Risk perception shapes individual behaviour, and is in turn shaped by the consequences of that behaviour. Here we explore this dynamics in the context of human immunodeficiency virus (HIV) spread. We construct a simplified agent-based model based on a partner selection game, where individuals are paired with others in the population, and through a decision tree, agree on unprotected sex, protected sex, or no sex. An individual's choice is conditioned on their HIV status, their perceived population-level HIV prevalence, and the preferences expressed by the individual with whom they are paired. HIV is transmitted during unprotected sex with a certain probability. As expected, in model simulations, the perceived population-level HIV prevalence climbs along with actual HIV prevalence. During this time, HIV- individuals increasingly switch from unprotected sex to protected sex, HIV+ individuals continue practicing unprotected sex whenever possible, and unprotected sex between HIV+ and HIV- individuals eventually becomes rare. We also find that the perceived population-level HIV prevalence diverges according to HIV status: HIV- individuals develop a higher perceived HIV prevalence than HIV+ individuals, although this result is sensitive to how much information is derived from global versus local sources. This research illustrates a potential mechanism by which distinct groups, as defined by their sexual behaviour, HIV status, and risk perceptions, can emerge through coevolution of HIV transmission and risk perception dynamics. PMID:23988796

  17. African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia. An overview of evidence and pharmacology

    PubMed Central

    Mills, Edward; Cooper, Curtis; Seely, Dugald; Kanfer, Izzy

    2005-01-01

    In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment. PMID:15927053

  18. C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

    PubMed Central

    Aoki, Manabu; Hayashi, Hironori; Yedidi, Ravikiran S.; Martyr, Cuthbert D.; Takamatsu, Yuki; Aoki-Ogata, Hiromi; Nakamura, Teruya; Nakata, Hirotomo; Das, Debananda; Yamagata, Yuriko; Ghosh, Arun K.

    2015-01-01

    ABSTRACT We identified three nonpeptidic HIV-1 protease inhibitors (PIs), GRL-015, -085, and -097, containing tetrahydropyrano-tetrahydrofuran (Tp-THF) with a C-5 hydroxyl. The three compounds were potent against a wild-type laboratory HIV-1 strain (HIV-1WT), with 50% effective concentrations (EC50s) of 3.0 to 49 nM, and exhibited minimal cytotoxicity, with 50% cytotoxic concentrations (CC50) for GRL-015, -085, and -097 of 80, >100, and >100 μM, respectively. All the three compounds potently inhibited the replication of highly PI-resistant HIV-1 variants selected with each of the currently available PIs and recombinant clinical HIV-1 isolates obtained from patients harboring multidrug-resistant HIV-1 variants (HIVMDR). Importantly, darunavir (DRV) was >1,000 times less active against a highly DRV-resistant HIV-1 variant (HIV-1DRVRP51); the three compounds remained active against HIV-1DRVRP51 with only a 6.8- to 68-fold reduction. Moreover, the emergence of HIV-1 variants resistant to the three compounds was considerably delayed compared to the case of DRV. In particular, HIV-1 variants resistant to GRL-085 and -097 did not emerge even when two different highly DRV-resistant HIV-1 variants were used as a starting population. In the structural analyses, Tp-THF of GRL-015, -085, and -097 showed strong hydrogen bond interactions with the backbone atoms of active-site amino acid residues (Asp29 and Asp30) of HIV-1 protease. A strong hydrogen bonding formation between the hydroxyl moiety of Tp-THF and a carbonyl oxygen atom of Gly48 was newly identified. The present findings indicate that the three compounds warrant further study as possible therapeutic agents for treating individuals harboring wild-type HIV and/or HIVMDR. IMPORTANCE Darunavir (DRV) inhibits the replication of most existing multidrug-resistant HIV-1 strains and has a high genetic barrier. However, the emergence of highly DRV-resistant HIV-1 strains (HIVDRVR) has recently been observed in vivo and in

  19. ANAESTHETIC CONSIDERATIONS FOR THE HIV POSITIVE PARTURIENT

    PubMed Central

    Oluwabukola, Adesina; Adesina, Oladokun

    2009-01-01

    The HIV epidemic in children parallels that among women on account of perinatal transmission. A combination of antiretroviral therapy and elective caesarean section reduces the rate of vertical transmission to <2%. Elective caesarean section independent of antiretroviral therapy decreases the risk of HIV vertical transmission from mother to baby. However, a caesarean section is a major surgical intervention that has well-reported complications. Women infected with HIV have been reported to be more susceptible to such complications. The multi-organ nature of HIV poses challenges at the time of surgery and anesthesia. Preoperative evaluation will allow a good prediction for the perioperative risk of the HIV-patient. The anesthesiologist should be aware of the possible toxic side effects or the possible interaction of antiretroviral drugs with the anesthetics. Some of these adverse effects may mimic signs and symptoms of the HIV disease itself. Regional anesthesia has been shown to be associated with reduced morbidity and mortality in a wide range of patients, including HIV positive parturients. Finally, the possibility of transmission in the health care setting highlights the need for anesthetists to enforce rigorous infection control policies to protect themselves, other health workers and their patients. PMID:25161460

  20. Therapeutic Drug Monitoring

    MedlinePlus

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

  1. Laser palliation of the HIV+ patient

    NASA Astrophysics Data System (ADS)

    Convissar, Robert A.

    2003-12-01

    Many oral manifestations of HIV infection can be used as markers for degree of immunosupression. These manifestations may be treated with antibiotics, analgesics, and antineoplastics, which may interact and interfere with antiviral agents used to treat the disease, and possibly exacerbate it. Dentists will see more HIV-infected patients as medical research transforms this disease into a chronic illness. Lasers have been shown to be effective instruments in palliation of oral manifestations of HIV infection. The use of lasers to palliate the painful symptoms of three oral manifestations of HIV infection is described. The advantages and benefits to both patient and dentist will be discussed. The paper does not address the use of lasers as a modality to treat or cure HIV infection -- only to palliate some of its symptoms.

  2. Migration, Marital Change, and HIV Infection in Malawi

    PubMed Central

    Anglewicz, Philip

    2013-01-01

    Research on the relationship between migration and HIV infection in sub-Saharan Africa often suggests that migrants are at higher risk of HIV infection because they are more likely to engage in risk behavior than non-migrants, and tend to move to areas with a relatively higher HIV prevalence. While migration may be a risk factor for HIV infection, I instead focus on the possibility that the HIV positive are more likely to migrate. Using a longitudinal dataset of permanent rural residents and migrants from Malawi, I find that migrants originating from rural areas are indeed more likely than non-migrants to be HIV positive and to have engaged in HIV risk behavior. The increased HIV risk among migrants may be due to the selection of HIV positive individuals into migration; I find that HIV positive individuals are more likely migrate than those who are HIV negative. The explanation for this phenomenon appears to be marital instability, which occurs more frequently among HIV positive individuals and leads to migration after marital change. PMID:22109083

  3. Gut Microbiota Linked to Sexual Preference and HIV Infection.

    PubMed

    Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

    2016-03-01

    The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

  4. Gut Microbiota Linked to Sexual Preference and HIV Infection

    PubMed Central

    Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

    2016-01-01

    The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

  5. Dendritic cell based vaccines for HIV infection: the way ahead.

    PubMed

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

    2013-11-01

    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.

  6. 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.

  7. Two concepts of therapeutic optimism.

    PubMed

    Jansen, Lynn A

    2011-09-01

    Researchers and ethicists have long been concerned about the expectations for direct medical benefit expressed by participants in early phase clinical trials. Early work on the issue considered the possibility that participants misunderstand the purpose of clinical research or that they are misinformed about the prospects for medical benefit from these trials. Recently, however, attention has turned to the possibility that research participants are simply expressing optimism or hope about their participation in these trials. The ethical significance of this therapeutic optimism remains unclear. This paper argues that there are two distinct phenomena that can be associated with the term 'therapeutic optimism'-one is ethically benign and the other is potentially worrisome. Distinguishing these two phenomena is crucial for understanding the nature and ethical significance of therapeutic optimism. The failure to draw a distinction between these phenomena also helps to explain why different writers on the topic often speak past one another.

  8. HIV and infant feeding. Breastfeeding.

    PubMed

    1995-02-01

    The human immunodeficiency virus (HIV) can be passed to the infant during pregnancy, childbirth, or breast feeding. Most infants born to HIV positive mothers do not become infected with HIV. The virus is found in breast milk; available research suggests 1 out of 7 breast fed infants of HIV positive mothers will be infected from breast milk. Mothers with recent or advanced HIV infections have more virus in their body fluids, including breast milk; therefore, a baby is more likely to be infected if the mother becomes infected during pregnancy, childbirth, or breast feeding, or if she is ill with acquired immunodeficiency syndrome (AIDS) related illnesses. If a baby is already infected, breast feeding will help the infant stay healthier longer. Health workers should discuss the benefits of breast feeding with all pregnant women. Information about the spread of HIV and sexually transmitted disease (STD) should be given; safe sex (condom use or abstinence) is important during pregnancy and breast feeding. If a woman's status is unknown, she should be encouraged to breast feed. In most communities, counselling and testing are unavailable. Where these services are available, the risk of infection through breast feeding should never be used to put pressure on a woman to take a test. Counselling prepares her for the possibility of being positive and allows her to make an informed choice about breast feeding. In some situations (especially if she herself is ill), a woman who knows she is HIV positive should not breast feed. However, alternatives may be unavailable, and the benefits may outweigh the risks. Health workers should assist the woman in making an informed choice. Issues to be considered include: 1) access to clean water and ability to pay for fuel or electricity to sterilize feeding utensils; 2) support from family or friends; 3) access to animal milk or shops that carry formula milk; and 4) ability to pay for formula or animal milk. To feed an infant for 6 months

  9. 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-α, NF-κB, 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.

  10. 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

  11. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease.

    PubMed

    Tugizov, Sharof

    2016-01-01

    Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

  12. 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.

  13. HIV and AIDS

    MedlinePlus

    ... I Help a Friend Who Cuts? HIV and AIDS KidsHealth > For Teens > HIV and AIDS Print A A A Text Size What's in ... in human history. HIV causes a condition called acquired immunodeficiency syndrome — better known as AIDS . HIV destroys a type ...

  14. HIV protease inhibitors disrupt astrocytic glutamate transporter function and neurobehavioral performance

    PubMed Central

    Vivithanaporn, Pornpun; Asahchop, Eugene L.; Acharjee, Shaona; Baker, Glen B.; Power, Christopher

    2016-01-01

    Objective: The neurotoxic actions of the HIV protease inhibitors, amprenavir (APV) and lopinavir (LPV) were investigated. Design: With combination antiretroviral therapy (cART), HIV-infected persons exhibit neurocognitive impairments, raising the possibility that cART might exert adverse central nervous system (CNS) effects. We examined the effects of LPV and APV using in-vitro and in-vivo assays of CNS function. Methods: Gene expression, cell viability and amino-acid levels were measured in human astrocytes, following exposure to APV or LPV. Neurobehavioral performance, amino-acid levels and neuropathology were examined in HIV-1 Vpr transgenic mice after treatment with APV or LPV. Results: Excitatory amino-acid transporter-2 (EAAT2) expression was reduced in astrocytes treated with LPV or APV, especially LPV (P < 0.05), which was accompanied by reduced intracellular l-glutamate levels in LPV-treated cells (P < 0.05). Treatment of astrocytes with APV or LPV reduced the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 (P < 0.05) although cell survival was unaffected. Exposure of LPV to astrocytes augmented glutamate-evoked transient rises in [Cai] (P < 0.05). Vpr mice treated with LPV showed lower concentrations of l-glutamate, l-aspartate and l-serine in cortex compared with vehicle-treated mice (P < 0.05). Total errors in T-maze assessment were increased in LPV and APV-treated animals (P < 0.05). EAAT2 expression was reduced in the brains of protease inhibitor-treated animals, which was associated with gliosis (P < 0.05). Conclusion: These results indicated that contemporary protease inhibitors disrupt astrocyte functions at therapeutic concentrations with enhanced sensitivity to glutamate, which can lead to neurobehavioral impairments. ART neurotoxicity should be considered in future therapeutic regimens for HIV/AIDS. PMID:26558720

  15. Secondary HIV prevention.

    PubMed

    Temoshok, L R; Frerichs, R R

    1998-06-01

    Primary HIV prevention, preventing HIV exposure among uninfected persons, has been the focus of much attention. However, secondary HIV prevention, preventing HIV transmission from infected people to their uninfected contacts, has not received as much interest or attention from HIV researchers, clinicians, and policymakers. The concept of secondary HIV prevention, as distinguished from primary prevention, is clarified, and the current and future strategies to further secondary HIV prevention efforts are explored. Secondary prevention strategies can be incorporated into comprehensive programs and result in shifts in attitudes and behaviors. This could reduce the size of the epidemic, while also benefiting the individual and his or her close relationships.

  16. 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

  17. 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.

  18. Reducing the cost of HIV antibody testing.

    PubMed

    Tamashiro, H; Maskill, W; Emmanuel, J; Fauquex, A; Sato, P; Heymann, D

    1993-07-10

    Available tests to detect antibody to human immunodeficiency virus (HIV) have a range of applications, and injudicious selection and inappropriate use can add a significant financial burden to budgets for AIDS programmes in developing countries. There are several ways by which the cost of HIV antibody testing can be reduced; they include use of tests appropriate for existing laboratory capabilities; adoption of cost-effective testing strategies; pooling of serum samples before testing; and ensuring best possible purchase prices. Each approach can significantly reduce the cost of HIV antibody testing alone or in combination, which increases the potential sustainability of antibody testing programmes, even in settings of limited resources. PMID:8100916

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

    MedlinePlus

    ... HIV medicines. All HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class may cause lactic acidosis, but ... some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to ...

  20. Analysis of Michigan Medicaid costs to treat HIV infection.

    PubMed

    Solomon, D J; Hogan, A J; Bouknight, R R; Solomon, C T

    1989-01-01

    To obtain better understanding of the nature and cost of health care related to human immunodeficiency virus (HIV) infection, medical payment records were analyzed for 204 men, women, and children older than 60 months who had indications of HIV infection. The records were those of Michigan Medicaid, the General Assistance Medical Program, and the Resident County Hospitalization Program, with service dates on or after January 1, 1984, and which were processed by November 30, 1987. Patient payment records were coded according to whether the patient's condition was considered to be pre-HIV, HIV unrelated, possibly HIV related, or HIV related. Average monthly payments were found to be $150 for pre-HIV patient payment records, $114 for those HIV unrelated, $57 for those possibly related, and $1,213 for those related to HIV infection. HIV-related monthly payments rose from about $1,500 per month in the period 3 months prior to the patient's death to more than $8,000 in the last month of life. Men were found to have twice as many claims as women, and men's claims cost about three times as much. A higher percentage of women than men (91 percent versus 37 percent) received pre-HIV paid services, indicating a higher percentage of women were at least initially receiving Medicaid for reasons other than an HIV-related disability. Diagnostic categories that accounted for the bulk of the HIV-related health care utilization included infectious and parasitic diseases, acquired immunodeficiency syndrome, diseases of the respiratory system, and non-HIV-specific immunity disorders. Inpatient hospitalization accounted for more than 75 percent of the payments, followed by physician costs (11 percent), pharmacy costs (5 percent), and outpatient costs (3 percent). A total of 45, or about 22 percent of the recipients, received zidovudine (AZT) prescriptions at an average monthly cost of $404. PMID:2508170

  1. Review: [corrected] The changing face of the HIV epidemic in sub-Saharan Africa.

    PubMed

    Mutevedzi, Portia C; Newell, Marie-Louise

    2014-09-01

    The widespread roll-out of antiretroviral therapy (ART) has substantially changed the face of human immunodeficiency virus (HIV). Timely initiation of ART in HIV-infected individuals dramatically reduces mortality and improves employment rates to levels prior to HIV infection. Recent findings from several studies have shown that ART reduces HIV transmission risk even with modest ART coverage of the HIV-infected population and imperfect ART adherence. While condoms are highly effective in the prevention of HIV acquisition, they are compromised by low and inconsistent usage; male medical circumcision substantially reduces HIV transmission but uptake remains relatively low; ART during pregnancy, delivery and breastfeeding can virtually eliminate mother-to-child transmission but implementation is challenging, especially in resource-limited settings. The current HIV prevention recommendations focus on a combination of preventions approach, including ART as treatment or pre- or post-exposure prophylaxis together with condoms, circumcision and sexual behaviour modification. Improved survival in HIV-infected individuals and reduced HIV transmission risk is beginning to result in limited HIV incidence decline at population level and substantial increases in HIV prevalence. However, achievements in HIV treatment and prevention are threatened by the challenges of lifelong adherence to preventive and therapeutic methods and by the ageing of the HIV-infected cohorts potentially complicating HIV management. Although current thinking suggests prevention of HIV transmission through early detection of infection immediately followed by ART could eventually result in elimination of the HIV epidemic, controversies remain as to whether we can treat our way out of the HIV epidemic.

  2. Combination genetic therapy to inhibit HIV-1.

    PubMed

    Strayer, David S; Branco, Francisco; Landré, Julien; BouHamdan, Mohamad; Shaheen, Farida; Pomerantz, Roger J

    2002-01-01

    Compared with single agents, combination antilentiviral pharmacotherapy targets multiple HIV-1 functions simultaneously, maximizing efficacy and decreasing chances of escape mutations. Combination genetic therapy could theoretically enhance efficacy similarly, but delivery of even single genes to high percentages of hematopoietic cells or their derivatives has proven problematic. Because of their high efficiency of gene delivery, we tested recombinant SV40-derived vectors (rSV40s) for this purpose. We made six rSV40s, each carrying a different transgene that targeted a different lentiviral function. We tested the ability of these constructs, individually and in double and triple combinations, to protect SupT1 human T lymphoma cells from HIV-1 challenge. Single chain antibodies (SFv) against CXCR4 and against HIV-1 reverse transcriptase (RT) and integrase (IN) were used, as were polymeric TAR decoys (PolyTAR) and a dominant-negative mutant of HIV-1 Rev (RevM10). Immunostaining showed that virtually all doubly treated cells expressed both transgenes. All transgenes individually protected from HIV-1 but, except for anti-CXCR4 SFv, their effectiveness diminished as challenge doses increased from 40 through 2500 tissue culture infectious dose(50) (TCID(50))/10(6) cells. However, all combinations of transgenes protected target cells better than individual transgenes, even from the highest challenge doses. Thus, combination gene therapies may inhibit HIV-1 better than single agents, and rSV40s may facilitate delivery of multigene therapeutics.

  3. 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

  4. Exosomes: Implications in HIV-1 Pathogenesis.

    PubMed

    Madison, Marisa N; Okeoma, Chioma M

    2015-07-20

    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.

  5. Possible people.

    PubMed

    Hare, R M

    1988-10-01

    Where we have a choice between bringing someone into existence and not doing so, the interests of the possible person must be considered. The implications of this view for population policy are explored, concluding with a version of utilitarianism that proposes increasing the population of a society while increasing the total utility, without altering its proportionate distribution, until the lowest segment of the population comes below the break-even point at which life is just worth living. Questions of whether poverty is the chief cause of misery and how great an obligation is owed to reducing social and economic inequalities are examined.

  6. Slow Human Immunodeficiency Virus (HIV) Infectivity Correlated with Low HIV Coreceptor Levels

    PubMed Central

    Bristow, Cynthia L.

    2001-01-01

    The absolute number of CD4+ lymphocytes in blood is prognostic for disease progression, yet the cell surface density of CD4 receptors or chemokine receptors on a single cell has not previously been found to be predictive of human immunodeficiency virus (HIV) infectivity outcome. It has recently been shown that human leukocyte elastase (HLE) and its ligand α1 proteinase inhibitor (α1PI; α1 antitrypsin) act as HIV fusion cofactors. The present study shows that decreased HIV infectivity is significantly correlated with decreased cell surface density of HLE but not with decreased CD4 nor chemokine receptors. In vitro HIV infectivity outcome in this study was predicted by the surface density of HLE on mononuclear phagocytes but not on lymphocytes. The set point HLE surface density was in part determined by α1PI. Decreased circulating α1PI was correlated with increased cell surface HLE and with increased HIV infectivity. The correlation of HIV infectivity outcome with surface HLE and circulating α1PI supports the utility of these HIV cofactors in diagnostic analysis and therapeutic intervention. PMID:11527806

  7. Effect of mimetic CDK9 inhibitors on HIV-1 activated transcription

    PubMed Central

    Van Duyne, Rachel; Guendel, Irene; Jaworski, Elizabeth; Sampey, Gavin; Klase, Zachary; Chen, Hao; Zeng, Chen; Kovalskyy, Dmytro; el Kouni, Mahmoud H.; Lepene, Benjamin; Patanarut, Alexis; Nekhai, Sergei; Price, David H.; Kashanchi, Fatah

    2013-01-01

    Potent antiretroviral therapy (ART) has transformed HIV-1 infection into a chronic manageable disease; however drug resistance remains a common problem that limits the effectiveness and clinical benefits of this type of treatment. The discovery of viral reservoirs in the body, in which HIV-1 may persist, has helped to explain why therapeutic eradication of HIV-1 has proved so difficult. In the current study we utilized a combination of structure based analysis of Cyclin/CDK complexes with our previously published Tat peptide derivatives. We modeled the Tat peptide inhibitors with CDKs and found a particular pocket which showed the most stable binding site (Cavity 1) using in silico analysis. Furthermore, we were able to find peptide mimetics that bound to similar regions using in silico searches of a chemical library, followed by cell based biological assays. Using these methods we obtained the first generation mimetic drugs and tested these compounds on HIV-1 LTR activated transcription. Using biological assays followed by similar in silico analysis to find a 2nd generation drugs resembling the original mimetic, we found the new targets of Cavity 1 and Cavity 2 regions on CDK9. We examined the 2nd generation mimetic against various viral isolates, and observed a generalized suppression of most HIV-1 isolates. Finally, the drug inhibited viral replication in humanized mouse models of Rag2-/-γc-/- with no toxicity to the animals at tested concentrations. Our results suggest that it may be possible to model peptide inhibitors into available crystal structures and further find drug mimetics using in silico analysis. PMID:23247501

  8. HIV-1 Tat Upregulates Expression of Histone Deacetylase-2 (HDAC2) in Human Neurons: Implication for HIV-Associated Neurocognitive Disorder (HAND)

    PubMed Central

    Saiyed, Zainulabedin M.; Gandhi, Nimisha; Agudelo, Marisela; Napuri, Jessica; Samikkannu, Thangavel; Reddy, Pichili VB; Khatavkar, Pradnya; Yndart, Adriana; Saxena, Shailendra K.; Nair, Madhavan P.N.

    2011-01-01

    Histone deacetylases (HDACs) play a pivotal role in epigenetic regulation of transcription and homeostasis of protein acetylation in histones and other proteins involved in chromatin remodeling. Histone hypoacetylation and transcriptional dysfunction have been shown to be associated with a variety of neurodegenerative diseases. More recently, neuron specific overexpression of HDAC2 has been shown to modulate synaptic plasticity and learning behavior in mice. However, the role of HDAC2 in development of HIV-associated neurocognitive disorders (HAND) is not reported. Herein we report that HIV-1 Tat protein upregulate HDAC2 expression in neuronal cells leading to transcriptional repression of genes involved in synaptic plasticity and neuronal function thereby contributing to the progression of HAND. Our results indicate upregulation of HDAC2 by Tat treatment in dose and time dependant manner by human neuroblastoma SK-N-MC cells and primary human neurons. Further, HDAC2 overexpression was associated with concomitant downregulation in CREB and CaMKIIa genes that are known to regulate neuronal activity. These observed effects were completely blocked by HDAC2 inhibition. These results for the first time suggest the possible role of HDAC2 in development of HAND. Therefore, use of HDAC2 specific inhibitor in combination with HAART may be of therapeutic value in treatment of neurocognitive disorders observed in HIV-1 infected individuals. PMID:21315782

  9. Parotid manifestations of HIV infection.

    PubMed

    Zeitlen, S; Shaha, A

    1991-08-01

    A lump in the parotid region is generally a salivary tumor unless proved otherwise. Recently with an epidemic of acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), a large number of pathologies are noticed in the parotid region. These conditions generally involve the intraparotid and periparotid lymph nodes. Hyperplastic lymphadenopathy and the benign lymphoepithelial lesions are the most common variants. Our knowledge regarding these new conditions is just evolving. There remains a therapeutic dilemma starting from observation only to local excision and superficial or total parotidectomy. These lesions must be kept in mind when we evaluate a patient with risk factors for human immunodeficiency virus (HIV) infection.

  10. A Challenge for the Future: Aging and HIV Infection

    PubMed Central

    Rickabaugh, Tammy M.; Jamieson, Beth D.

    2010-01-01

    Older individuals (≥ 50 years of age) are increasingly becoming a new at-risk group for HIV-1 infection and, together with those surviving longer due to the introduction of anti-retroviral therapy (ART), it is predicted that more than half of all HIV-1-infected individuals in the U.S. will be greater than 50 years of age in the year 2015. Older individuals diagnosed with HIV-1 are prone to faster disease progression and reduced T-cell reconstitution despite successful virologic control with anti-retroviral therapy (ART). There is also growing evidence that the T-cell compartment in HIV-1+ adults displays an aged phenotype and HIV-1-infected individuals are increasingly diagnosed with clinical conditions more commonly seen in older uninfected persons. As aging in the absence of HIV infection is associated with alterations in T-cell function and immunosenescence, the combined impact of both HIV-1 infection and aging may provide an explanation for poorer clinical outcomes observed in older HIV-1-infected individuals. Thus, the development of novel therapeutics to stimulate immune function and delay immunosenescence is critical and would be beneficial to both the elderly and HIV-1 infected individuals. PMID:20734158

  11. HIV/AIDS and rheumatoid arthritis.

    PubMed

    Cunha, Bernardo M; Mota, Licia Maria H; Pileggi, Gecilmara S; Safe, Izabella P; Lacerda, Marcus V G

    2015-05-01

    The acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). It was first recognized in the United States in 1981, and the HIV/AIDS epidemic has since spread to affect all countries. The interface of HIV/AIDS with opportunistic infectious diseases is well characterized, but further research is required into the concurrence of other chronic diseases. The objective of this review was to identify possible interferences of HIV infection in the diagnosis and management of rheumatoid arthritis (RA). A review of the available evidence was conducted using the GRADE approach. Overall, the quality of evidence was low. Our main conclusions were: (1) the occurrence of rheumatoid-like arthritis in patients with HIV/AIDS is quite rare; therefore, it is not recommended that HIV infection be considered routinely as a differential diagnosis in this condition (C2); (2) HIV infection may lead to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity, but usually at low titers (C1); (3) RA might cause false-positive HIV serology and ELISA seems to be a more specific test for HIV in patients with RA (C2); (4) RA and AIDS may coexist, even in cases of severe immunosuppression (C1); (5) RA emergence may seldom occur during or after immune reconstitution (C1); and (6) there is insufficient safety data to recommend use of specific disease-modifying antirheumatic drugs (DMARDs) in RA patients with HIV/AIDS. Therefore, these drugs should be used cautiously (C1).

  12. HIV infection duration, social support and the level of trauma symptoms in a sample of HIV-positive Polish individuals.

    PubMed

    Rzeszutek, Marcin; Oniszczenko, Włodzimierz; Żebrowska, Magdalena; Firląg-Burkacka, Ewa

    2015-01-01

    The aim of this study was to investigate the relationship between the average HIV infection duration and the level of quantitatively rated post-traumatic stress disorder (PTSD) symptoms and social support dimensions in a sample of 562 Polish HIV+ adults. Possible moderating effects of social support on the relationship between the average HIV infection duration and the level of PTSD symptoms were also analysed. The results of this study suggest that the average HIV infection duration may intensify PTSD symptoms and deteriorate the perceived availability of social support in HIV+ individuals. However, a positive relationship between HIV infection duration and the level of trauma symptoms was observed only in the group of HIV+ individuals with low perceived available social support, but not in the group of HIV-infected individuals with high perceived available social support. This research provided some new insight into the psychological and social aspects of living with HIV. In particular, our results suggest that although HIV infection duration may intensify trauma symptoms and deteriorate social support, perceived available social support may act as a buffer against HIV-related trauma symptoms.

  13. HIV-1 and interferons: who's interfering with whom?

    PubMed

    Doyle, Tomas; Goujon, Caroline; Malim, Michael H

    2015-07-01

    The ability of interferons (IFNs) to inhibit HIV-1 replication in cell culture models has long been recognized, and the therapeutic administration of IFNα to HIV-1-infected patients who are not receiving antiretroviral therapy produces a clear but transient decrease in plasma viral load. Conversely, studies of chronic HIV-1 infection in humans and SIV-infected animal models of AIDS show positive correlations between elevated plasma levels of IFNs, increased expression of IFN-stimulated genes (ISGs), biomarkers of inflammation and disease progression. In this Review, we discuss the evidence that IFNs can control HIV-1 replication in vivo and debate the controversial role of IFNs in promoting the pathological sequelae of chronic HIV-1 infection.

  14. Novel therapeutic strategies for cardioprotection.

    PubMed

    Sluijter, Joost P G; Condorelli, Gianluigi; Davidson, Sean M; Engel, Felix B; Ferdinandy, Peter; Hausenloy, Derek J; Lecour, Sandrine; Madonna, Rosalinda; Ovize, Michel; Ruiz-Meana, Marisol; Schulz, Rainer; Van Laake, Linda W

    2014-10-01

    The morbidity and mortality from ischemic heart disease (IHD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of occluded coronary arteries. Although it is essential to re-open the artery as soon as possible, paradoxically this leads to additional myocardial injury, called acute ischemia-reperfusion injury (IRI), for which currently no effective therapy is available. Therefore, novel therapeutic strategies are required to protect the heart from acute IRI in order to reduce myocardial infarction size, preserve cardiac function and improve clinical outcomes in patients with IHD. In this review article, we will first outline the pathophysiology of acute IRI and review promising therapeutic strategies for cardioprotection. These include novel aspects of mitochondrial function, epigenetics, circadian clocks, the immune system, microvesicles, growth factors, stem cell therapy and gene therapy. We discuss the therapeutic potential of these novel cardioprotective strategies in terms of pharmacological targeting and clinical application. PMID:24837132

  15. Novel therapeutic strategies for cardioprotection.

    PubMed

    Sluijter, Joost P G; Condorelli, Gianluigi; Davidson, Sean M; Engel, Felix B; Ferdinandy, Peter; Hausenloy, Derek J; Lecour, Sandrine; Madonna, Rosalinda; Ovize, Michel; Ruiz-Meana, Marisol; Schulz, Rainer; Van Laake, Linda W

    2014-10-01

    The morbidity and mortality from ischemic heart disease (IHD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of occluded coronary arteries. Although it is essential to re-open the artery as soon as possible, paradoxically this leads to additional myocardial injury, called acute ischemia-reperfusion injury (IRI), for which currently no effective therapy is available. Therefore, novel therapeutic strategies are required to protect the heart from acute IRI in order to reduce myocardial infarction size, preserve cardiac function and improve clinical outcomes in patients with IHD. In this review article, we will first outline the pathophysiology of acute IRI and review promising therapeutic strategies for cardioprotection. These include novel aspects of mitochondrial function, epigenetics, circadian clocks, the immune system, microvesicles, growth factors, stem cell therapy and gene therapy. We discuss the therapeutic potential of these novel cardioprotective strategies in terms of pharmacological targeting and clinical application.

  16. Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications.

    PubMed

    Avettand-Fènoël, Véronique; Hocqueloux, Laurent; Ghosn, Jade; Cheret, Antoine; Frange, Pierre; Melard, Adeline; Viard, Jean-Paul; Rouzioux, Christine

    2016-10-01

    HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis. PMID:27559075

  17. 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

  18. HIV suppression by host restriction factors and viral immune evasion.

    PubMed

    Jia, Xiaofei; Zhao, Qi; Xiong, Yong

    2015-04-01

    Antiviral restriction factors are an integral part of the host innate immune system that protects cells from viral pathogens, such as human immunodeficiency virus (HIV). Studies of the interactions between restriction factors and HIV have greatly advanced our understanding of both the viral life cycle and basic cell biology, as well as provided new opportunities for therapeutic intervention of viral infection. Here we review the recent developments towards establishing the structural and biochemical bases of HIV inhibition by, and viral countermeasures of, the restriction factors TRIM5, MxB, APOBEC3, SAMHD1, and BST2/tetherin.

  19. Interactions of HIV-1 and HIV-2 envelope glycoproteins with sulphated polysaccharides and mannose-6-phosphate.

    PubMed

    Mbemba, E; Gluckman, J C; Gattegno, L

    1994-02-01

    Envelope glycoproteins of human immunodeficiency viruses (HIV-1 and HIV-2) can interact with high-mannose glycans and with the mannosyl or N-acetylglucosaminyl core of complex-type oligosaccharidic structures. HIV-1 glycoproteins also specifically bind sulphated polysaccharides such as dextran sulphate (DS) and heparin. Here, we show that the latter property is shared by HIV-2 recombinant gp140 (rgp140) precursor glycoprotein. Binding of rgp140 and of corresponding rgp160 of HIV-1 to heparin- and DS-substituted (sulphated dextran beads; SDB) affinity matrices was inhibited by the soluble specific ligand and also by fetuin, asialofetuin or the anionic simple carbohydrate derivative mannose-6-phosphate (M6P). Interaction of HIV-1 rgp120 subunit with the two affinity matrices was also inhibited by M6P, but only rgp120 binding to heparin-agarose, and not that to SDB, was affected by fetuin and asialofetuin. These results suggest that HIV-1 and HIV-2 envelope glycoproteins presumably display different sulphated polysaccharide and carbohydrate recognition sites. Some of these may be common or in close proximity: with respect to rgp160, for example, the sites may be common on the gp41 moiety and/or in a region of gp120 which would be more accessible when expressed on rgp160 than on processed gp120, while they may be distinct on the cleaved gp120 subunit. Finally, because M6P is a marker of lysosomal enzymes, we verified that HIV-1 and HIV-2 envelope glycoproteins could specifically bind in a M6P-inhibitable manner to a representative lysosomal enzyme, bovine liver beta-glucuronidase coupled to agarose, suggesting that they may possibly interfere with lysosomal enzyme sorting in HIV-infected cells.

  20. Immunotherapeutic restoration in HIV-infected individuals.

    PubMed

    Kim, June Myung; Han, Sang Hoon

    2011-02-01

    While the development of combined active antiretroviral therapy (cART) has dramatically improved life expectancies and quality of life in HIV-infected individuals, long-term clinical problems, such as metabolic complications, remain important constraints of life-long cART. Complete immune restoration using only cART is normally unattainable even in cases of sufficient plasma viral suppression. The need for immunologic adjuncts that complement cART remains, because while cART alone may result in the complete recovery of peripheral net CD4+ T lymphocytes, it may not affect the reservoir of HIV-infected cells. Here, we review current immunotherapies for HIV infection, with a particular emphasis on recent advances in cytokine therapies, therapeutic immunization, monoclonal antibodies, immune-modulating drugs, nanotechnology-based approaches and radioimmunotherapy.

  1. Cell-based gene therapy against HIV.

    PubMed

    Dey, R; Pillai, B

    2015-11-01

    The ability to integrate inside the host genome lays a strong foundation for HIV to play hide and seek with the host's immune surveillance mechanisms. Present anti-viral therapies, although successful in suppressing the virus to a certain level, fail to wipe it out completely. However, recent approaches in modifying stem cells and enabling them to give rise to potent/resistant T-cells against HIV holds immense hope for eradication of the virus from the host. In this review, we will briefly discuss previous landmark studies on engineering stem cells or T-cells that have been explored for therapeutic efficacy against HIV. We will also analyze potential benefits and pitfalls of some studies done recently and will share our opinion on emerging trends.

  2. The Warburg effect: molecular aspects and therapeutic possibilities.

    PubMed

    Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

    2015-04-01

    It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies. PMID:25253100

  3. [Probiotics: history, definition, requirements and possible therapeutic applications].

    PubMed

    Montalto, Massimo; Arancio, Fabiola; Izzi, Donatello; Cuoco, Lucio; Curigliano, Valentina; Manna, Raffaele; Gasbarrini, Giovanni

    2002-01-01

    The ingestion of probiotics is associated with various beneficial effects on human health and modifies the physiological homeostasis of the intestinal flora. Probiotics are microorganisms with some particular characteristics: human origin, safety in human use, bile and acid resistance, survival in the intestine, at least temporary colonization of the human gut, adhesion to the mucosa and bacteriocine production. Thanks to these characteristics, probiotics block the invasion of human intestinal cells by the enteroinvasive bacteria. Furthermore, they should be able to stimulate and modulate the intestinal immune response, and to protect and stabilize the mucosal barrier. Finally, the efficacy of probiotics should be evident and documented with valid studies. All their properties should be maintained during processing and storage. Probiotics are usually used to protect the host from pathogens. With regard to this, they are useful in the prevention of antibiotic and traveler's diarrhea and they may play a role in the management of gastric Helicobacter pylori infection. Furthermore, their efficacy in the treatment of infectious diarrhea, in inflammatory bowel diseases, in pouchitis and in food allergy has been shown. Probiotics can improve the symptoms of irritable bowel syndrome and of lactose malabsorption. Finally, it has been suggested that such microorganisms may play a role in the prevention of carcinogenesis and of tumor growth. PMID:12402663

  4. [Therapeutic possibilities in refractory epilepsy in tuberous sclerosis complex].

    PubMed

    Puertas-Martin, Verónica; Carreras-Saez, Inmaculada; Marana, Ana; Ruiz-Falco Rojas, M Luz; Cantarin-Extremera, Verónica; Calleja-Gero, M Lourdes

    2014-06-16

    Introduccion. El complejo esclerosis tuberosa (CET) cursa frecuentemente con epilepsia de dificil control, lo que condiciona la calidad de vida y el nivel cognitivo de estos pacientes. Objetivo. Describir las caracteristicas epidemiologicas, clinicas y el tratamiento de los pacientes afectos de CET con epilepsia. Pacientes y metodos. Se han revisado retrospectivamente las historias clinicas de 30 pacientes menores de 18 años, diagnosticados de CET y epilepsia registrados en nuestra base de datos. Resultados. La edad de inicio de la epilepsia en los pacientes con CET en nuestra serie esta comprendida entre el primer mes de vida y los 4 años. Todos comenzaron con crisis parciales. Dos presentaron sindrome de West y cuatro, espasmos infantiles sin hipsarritmia. En 19 de los pacientes, la epilepsia se comporto como farmacorresistente. Respecto al tratamiento con farmacos antiepilepticos, 11 estan en monoterapia, 10 en biterapia, siete en triterapia y uno con cuatro farmacos. Dos recibieron ACTH, dos tienen implantado un estimulador del nervio vago, cuatro reciben tratamiento con everolimus y ocho han sido sometidos a cirugia. Conclusiones. La epilepsia es un problema muy frecuente y de inicio en los primeros años de vida en el CET. Las opciones terapeuticas actuales son muchas, sin embargo el 63,3% de los pacientes tiene una epilepsia no controlada y la mayoria de ellos presenta crisis diarias. El mal control de las crisis se correlaciona con retraso mental y trastorno del espectro autista. Señalar la respuesta positiva obtenida con otras posibilidades terapeuticas: inhibidores de la via mTOR, cirugia y el estimulador del nervio vago.

  5. [Is it possible to combine fixed therapeutic associations?].

    PubMed

    Nordmann, J-P

    2009-03-01

    The number of fixed associations to treat intraocular pressure has increased over the recent years, to improve patient's treatment adherence. They are generally considered as comparable to the same components administered separately with, in some cases, less side effects. It could thus be appealing to combine fixed associations to reduce these side effects and retain efficacy. However, almost all fixed associations contain timolol, a beta blocker, with a risk of an excessive beta blocking dose and related systemic adverse drug reactions. Several fixed-associations contain a prostaglandin analogue. Their combination would not have a superior efficacy to one fixed combination taken alone. Furthermore, an increased risk or incidence of adverse drug reactions would appear. Specific clinical studies are required before recommending their use in daily clinical practice. PMID:19515336

  6. Dietary Phytochemicals in Neuroimmunoaging: A New Therapeutic Possibility for Humans?

    PubMed Central

    Corbi, Graziamaria; Conti, Valeria; Davinelli, Sergio; Scapagnini, Giovanni; Filippelli, Amelia; Ferrara, Nicola

    2016-01-01

    Although several efforts have been made in the search for genetic and epigenetic patterns linked to diseases, a comprehensive explanation of the mechanisms underlying pathological phenotypic plasticity is still far from being clarified. Oxidative stress and inflammation are two of the major triggers of the epigenetic alterations occurring in chronic pathologies, such as neurodegenerative diseases. In fact, over the last decade, remarkable progress has been made to realize that chronic, low-grade inflammation is one of the major risk factor underlying brain aging. Accumulated data strongly suggest that phytochemicals from fruits, vegetables, herbs, and spices may exert relevant immunomodulatory and/or anti-inflammatory activities in the context of brain aging. Starting by the evidence that a common denominator of aging and chronic degenerative diseases is represented by inflammation, and that several dietary phytochemicals are able to potentially interfere with and regulate the normal function of cells, in particular neuronal components, aim of this review is to summarize recent studies on neuroinflammaging processes and proofs indicating that specific phytochemicals may act as positive modulators of neuroinflammatory events. In addition, critical pathways involved in mediating phytochemicals effects on neuroinflammaging were discussed, exploring the real impact of these compounds in preserving brain health before the onset of symptoms leading to inflammatory neurodegeneration and cognitive decline. PMID:27790141

  7. New therapeutic possibilities in primary invasive breast cancer.

    PubMed Central

    Cady, B; Stone, M D; Wayne, J

    1993-01-01

    OBJECTIVE: Current therapy for small invasive breast cancer, particularly when discovered mammographically, was re-examined. Axillary dissection may be avoided when lymph node metastases incidence is low (< 10%) or when primary cancer features determine adjuvant therapy. Radiation therapy may be avoided when risk of recurrence is very low. SUMMARY BACKGROUND DATA: Recent studies by the Surveillance, Epidemiology, and End Results program (SEER) have shown increases in small invasive breast cancers (< 1 cm) attributable to mammographic screening. The incidence of axillary metastases in mammographically discovered small cancers (< 1 cm) may be less than 10%. Follow-up data from the Breast Cancer Detection Demonstration Project (BCDDP) indicate a disease-free survival rate exceeding 95% at 8 years if the cancer was discovered mammographically. METHODS: Maximum diameter and lymph node metastases of invasive breast cancer diagnosed between 1969 and 1988 were analyzed and compared to cases diagnosed between 1929 and 1968. One hundred thirty patients have been treated without either axillary dissection or radiation therapy since 1980. RESULTS: The mean and median diameters of invasive breast cancers decreased to 2.31 and 2.0 cm, respectively, between 1984 and 1988; 13% were less than 1 cm in diameter. Only 13% of patients had axillary metastases if the primary cancer was 1 cm or less in diameter in the last 10 years; 71% had only 1 or 2 nodes involved. Isolated local recurrence, total local recurrence, and distant metastases were unchanged when radiated and nonirradiated patients were compared. Axillary nodal recurrence was decreased in irradiated patients because the lower half of the axilla was treated. CONCLUSION: In selected patients with very small invasive breast cancers detected by mammography, breast conservation without axillary dissection or radiation therapy may be used. Entirely outpatient treatment markedly reduces morbidity and cost, and furthers the gains from screening programs. PMID:8373276

  8. American Therapeutic Recreation Association

    MedlinePlus

    ... Remember Me I forgot my password American Therapeutic Recreation Association Empowering Recreational Therapists Call for 2017 Webinars – ... http://ow.ly/qzAj304HTCi Join thousands of Therapeutic Recreation specialists today Join Now Renew your membership today ...

  9. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  10. Diagnosing and treating HIV-associated sensory neuropathy: a global perspective.

    PubMed

    Cherry, Catherine L; Wadley, Antonia L; Kamerman, Peter R

    2016-04-01

    HIV-associated sensory neuropathy (HIV-SN) is a common complication of HIV and remains highly prevalent even with modern HIV management strategies, causing debilitating pain in millions globally. We review HIV-SN diagnosis and management. We suggest most HIV-SN cases are easily recognized using clinical screening tools, with physician assessment and/or specialized testing prioritized for atypical cases. Management aims to prevent further nerve damage and optimize symptom control. Symptom relief is difficult and rarely complete, with a lack of proven pharmacological strategies. Work is needed to clarify optimal use of available medications. This includes understanding the marked placebo effect in HIV-SN analgesic trials and exploring 'responder phenotypes'. Limited data support nondrug strategies including hypnosis, meditation, psychology, physical activity and a positive therapeutic relationship. PMID:26988147

  11. Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound

    PubMed Central

    Smith, Kahli A.; Lin, Xionghao; Bolshakov, Oleg; Griffin, James; Niu, Xiaomei; Kovalskyy, Dmytro; Ivanov, Andrey; Jerebtsova, Marina; Taylor, Robert E.; Akala, Emmanuel; Nekhai, Sergei

    2015-01-01

    Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics. PMID:26839837

  12. Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound.

    PubMed

    Smith, Kahli A; Lin, Xionghao; Bolshakov, Oleg; Griffin, James; Niu, Xiaomei; Kovalskyy, Dmytro; Ivanov, Andrey; Jerebtsova, Marina; Taylor, Robert E; Akala, Emmanuel; Nekhai, Sergei

    2015-01-01

    Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics. PMID:26839837

  13. Latency: the hidden HIV-1 challenge

    PubMed Central

    Marcello, Alessandro

    2006-01-01

    Eradication of HIV-1 from an infected individual cannot be achieved by current regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy for a long time 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 transcriptionally silent provirus. Since the molecular mechanisms that permit long term transcriptional control of proviral gene expression in these cells are still obscure, this review aims at summarizing the various aspects of the problem that need to be considered. In particular, this review will focus the attention on the control of transcription imposed by chromatin through various epigenetic mechanisms. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication. PMID:16412247

  14. HIV surveillance among injecting drug users.

    PubMed

    Des Jarlais, D C; Dehne, K; Casabona, J

    2001-04-01

    Injecting drug users (IDUs) should be considered a 'partially hidden population' at high risk for HIV infection. In almost all locations it should be possible to locate and conduct research with IDUs, but it will probably never be possible to enumerate or draw random samples from an IDU population. Surveillance research studies with IDUs should include risk behaviors, as surveillance of HIV infection only will not be sufficiently time sensitive, and be used to develop and refine HIV prevention programming for the population. Contacts with IDUs can be developed at multiple settings, including voluntary treatment programs, law enforcement settings, and through 'street outreach.' Each type of setting has different advantages, disadvantages and ethical concerns. HIV testing as part of surveillance also raises additional important ethical concerns. The primary risk behaviors that should be included in surveillance studies are 'sharing' of drug injection equipment, the potential for rapid partner change among risk partners, and sexual risk behavior. Additional important objectives for surveillance research include: (1) the size of the local IDU population, (2) patterns of drug use, (3) availability injection equipment, (4) participation in prevention activities, and (5) access to and use of anti-retroviral treatments. HIV incidence is an ultimate objective for surveillance research, but there are no currently available cost-efficient methods for studying HIV incidence, so estimation from indirect measurements is usually required. PMID:11421178

  15. 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

  16. Smoking and HIV

    MedlinePlus

    ... 28, 2014 Select a Language: Fact Sheet 803 Smoking and HIV WHY IS SMOKING MORE DANGEROUS FOR ... It can also worsen liver problems like hepatitis. Smoking and Side Effects People with HIV who smoke ...

  17. HIV and Pregnancy

    MedlinePlus

    ... Pregnancy Patient Education FAQs HIV and Pregnancy Patient Education Pamphlets - Spanish HIV and Pregnancy FAQ113, December 2012 PDF Format ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  18. HIV and AIDS

    MedlinePlus

    ... that causes the disease AIDS. HIV Hurts the Immune System People who are HIV positive have been tested ... to everyone in the world. When the person's immune system has weakened and more of the blood's T ...

  19. Older People and HIV

    MedlinePlus

    ... Many older people believe that HIV only affects younger people Most older people get little training in ... diseases among older people, as they do for younger people. Physicians may not diagnose HIV infection in ...

  20. Testing for HIV

    MedlinePlus

    ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability (Biologics) HIV Home Test Kits Testing for HIV Share Tweet Linkedin Pin it More ...

  1. HIV and Cardiovascular Disease

    MedlinePlus

    ... CVD. ART can increase blood fats (cholesterol and triglycerides, see fact sheet 123.) It can also help ... disease. HIV infection decreases good cholesterol and increases triglycerides. HIV causes inflammation. This can also contribute to ...

  2. Microbiome in HIV infection

    PubMed Central

    Salas, January T.; Chang, Theresa L.

    2014-01-01

    HIV primary infection occurs at mucosa tissues, suggesting an intricate interplay between microbiome and HIV infection. Recent advanced technologies of high-throughput sequencing and bioinformatics allow researchers to explore nonculturable microbes including bacteria, virus and fungi and their association with diseases. HIV/SIV infection is associated with microbiome shifts and immune activation that may affect the outcome of disease progression. Similarly, altered microbiome and inflammation are associated with increased risks of HIV acquisition, suggesting the role of microbiome in HIV transmission. In this review, we will focus on microbiome in HIV infection at various mucosal compartments. Understanding the relationship between microbiome and HIV may offer insights into development of better strategies for HIV prevention and treatment. PMID:25439273

  3. Reduce HIV Risk

    MedlinePlus

    ... Control and Prevention (CDC) has used them as models, and Dr. Jemmott was invited to South Africa to help decrease HIV/AIDS there. "For the past 15 years, I have observed how the HIV/AIDS epidemic ...

  4. Neuroinflammation in treated HIV-positive individuals

    PubMed Central

    Guo, Qi; Cole, James H.; Boasso, Adriano; Greathead, Louise; Kelleher, Peter; Rabiner, Eugenii A; Kalk, Nicola; Bishop, Courtney; Gunn, Roger N.; Matthews, Paul M.; Winston, Alan

    2016-01-01

    Objective: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [11C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). Methods: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [11C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. Results: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). Conclusions: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment. PMID:26911637

  5. Therapeutic perspectives in atopic dermatitis.

    PubMed

    Misery, Laurent

    2011-12-01

    Therapy of atopic dermatitis should comprise emollients, topical glucocorticosteroids, or calcineurin inhibitors, phototherapies, immunosuppressants like cyclosporin A, and other treatments. All these treatments should be improved, thanks to research. But new therapeutic perspectives should be given by topical anti-inflammatory substances, selective glucocorticoid receptor agonists, probiotics, interferon γ, TNFα inhibitors, inhibition of T cells or B cells, inhibition of IgE binding, and many other possibilities.

  6. RNA-based Therapeutics- Current Progress and Future Prospects

    PubMed Central

    Burnett, John C.; Rossi, John J.

    2012-01-01

    Summary Recent advances of biological drugs have broadened the scope of therapeutic targets for a variety of human diseases. This holds true for dozens of RNA-based therapeutics currently under clinical investigation for diseases ranging from genetic disorders to HIV infection to various cancers. These emerging drugs, which include therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs), demonstrate the unprecedented versatility of RNA. However, RNA is inherently unstable, potentially immunogenic, and typically requires a delivery vehicle for efficient transport to the targeted cells. These issues have hindered the clinical progress of some RNA-based drugs and have contributed to mixed results in clinical testing. Nevertheless, promising results from recent clinical trials suggest that these barriers may be overcome with improved synthetic delivery carriers and chemical modifications of the RNA therapeutics. This review focuses on the clinical results of siRNA, RNA aptamer, and ribozyme therapeutics and the prospects for future successes. PMID:22284355

  7. Neisseria gonorrhoeae enhances HIV-1 infection of primary resting CD4+ T cells through TLR2 activation.

    PubMed

    Ding, Jian; Rapista, Aprille; Teleshova, Natalia; Mosoyan, Goar; Jarvis, Gary A; Klotman, Mary E; Chang, Theresa L

    2010-03-15

    Sexually transmitted infections increase the likelihood of HIV-1 transmission. We investigated the effect of Neisseria gonorrheae (gonococcus [GC]) exposure on HIV replication in primary resting CD4(+) T cells, a major HIV target cell during the early stage of sexual transmission of HIV. GC and TLR2 agonists, such as peptidylglycan (PGN), Pam(3)CSK(4), and Pam(3)C-Lip, a GC-derived synthetic lipopeptide, but not TLR4 agonists including LPS or GC lipooligosaccharide enhanced HIV-1 infection of primary resting CD4(+) T cells after viral entry. Pretreatment of CD4(+) cells with PGN also promoted HIV infection. Anti-TLR2 Abs abolished the HIV enhancing effect of GC and Pam(3)C-Lip, indicating that GC-mediated enhancement of HIV infection of resting CD4(+) T cells was through TLR2. IL-2 was required for TLR2-mediated HIV enhancement. PGN and GC induced cell surface expression of T cell activation markers and HIV coreceptors, CCR5 and CXCR4. The maximal postentry HIV enhancing effect was achieved when PGN was added immediately after viral exposure. Kinetic studies and analysis of HIV DNA products indicated that GC exposure and TLR2 activation enhanced HIV infection at the step of nuclear import. We conclude that GC enhanced HIV infection of primary resting CD4(+) T cells through TLR2 activation, which both increased the susceptibility of primary CD4(+) T cells to HIV infection as well as enhanced HIV-infected CD4(+) T cells at the early stage of HIV life cycle after entry. This study provides a molecular mechanism by which nonulcerative sexually transmitted infections mediate enhancement of HIV infection and has implication for HIV prevention and therapeutics. PMID:20147631

  8. Tertiary Element Interaction in HIV-1 TAR.

    PubMed

    Krawczyk, Konrad; Sim, Adelene Y L; Knapp, Bernhard; Deane, Charlotte M; Minary, Peter

    2016-09-26

    HIV-1 replication requires binding to occur between Trans-activation Response Element (TAR) RNA and the TAT protein. This TAR-TAT binding depends on the conformation of TAR, and therapeutic development has attempted to exploit this dynamic behavior. Here we simulate TAR dynamics in the context of mutations inhibiting TAR binding. We find that two tertiary elements, the apical loop and the bulge, can interact directly, and this interaction may be linked to the affinity of TAR for TAT. PMID:27500460

  9. A cure for HIV: is it in sight?

    PubMed

    Pace, Matthew; Frater, John

    2014-07-01

    HIV is a devastating disease affecting millions of people worldwide despite the advent of successful antiretroviral therapy (ART). However, ART does not result in a cure and has to be taken for life. Accordingly, researchers are turning towards cure efforts, particularly in the light of two patients whose HIV has been seemingly eradicated. Numerous approaches and strategies have been considered for curing HIV, but no scalable and safe solution has yet been reached. With newly discovered difficulties in measuring the HIV reservoir, the main barrier to a cure, the only true test of cure is to stop ART and see whether the virus becomes detectable. However, it is possible that this treatment interruption may be associated with certain risks for patients. Here, we compare the current major approaches and recent advances for curing HIV, as well as discuss ways of evaluating HIV cure and the safety concerns involved.

  10. 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.

  11. Is homeopathy possible?

    PubMed

    Milgrom, Lionel R

    2006-09-01

    As a therapeutic intervention, homeopathy is the target of increased scepticism because in the main, its remedies are diluted and succussed (potentized) out of material existence. This puts homeopathy seemingly at odds with the paradigm of conventional science, in particular, that atoms and molecules are the fundamental building blocks of all matter. Accordingly, homeopathy cannot work, so that any reported beneficial effects must, at best, be due to the placebo effect. The purpose of this article is to challenge that conclusion and to suggest that there may well be conventional science-based explanations of how homeopathy could be possible. Homeopathy's key principles are first described. Then the double-blind randomized controlled trial (RCT), the chief means by which homeopathic remedies and prescribing are tested, is shown to be based on a linear reductionism that is too blunt an instrument with which to test the efficacy of complex interventions such as homeopathy The memory of water hypothesis, as a mechanism for how potentized remedies might work, is reviewed, along with some evidence for its existence. A possible rationale for the water memory effect is proposed in terms of a dynamic 'ordering' of water's constantly switching network of intermolecular hydrogen bonds, induced by the manufacturing process of homeopathic remedies. This could lead to a long-range molecular 'coherence' between trillions of mobile water molecules. However, the water memory effect is an essentially pharmacological explanation of homeopathy's putative efficacy. It is pointed out that healing also entails an interaction between consenting beings. From this point of view, an explanation of any therapeutic procedure should include an attempt to describe the nature of the patient-practitioner interaction. From this perspective, a quantum theoretical treatment of the therapeutic process, involving a form of macro-entanglement between patient, practitioner and remedy (PPR), is advanced

  12. A Multiplex PCR Approach for Detecting Dual Infections and Recombinants Involving Major HIV Variants

    PubMed Central

    Cappy, Pierre; De Oliveira, Fabienne; Gueudin, Marie; Alessandri-Gradt, Elodie

    2016-01-01

    The cocirculation of different HIV types and groups can lead to dual infections and recombinants, which hinder diagnosis and therapeutic management. We designed two multiplex PCRs (mPCRs) coupled with capillary electrophoresis to facilitate the detection of such infections. The first, MMO2, targets three variants (HIV-1/M, HIV-1/O, and HIV-2), and the second, MMO, targets HIV-1/M and HIV-1/O. These mPCRs were validated on DNA and RNA extracts from 19 HIV-1/M, 12 HIV-1/O, and 13 HIV-2 cultures and from mixtures simulating dual infections. They were then assessed with DNA and RNA extracts from samples of 47 clinical monoinfections and HIV-1/M+O dual infections or infections with HIV-1/MO recombinants. Both mPCRs had excellent specificity. Sensitivities ranged from 80 to 100% for in vitro samples and from 58 to 100% for clinical samples, with the results obtained depending on the material used and the region of the genome concerned. Sensitivity was generally lower for DNA than for RNA and for amplifications of the integrase and matrix regions. In terms of global detection (at least one target gene for each strain), both mPCRs yielded a detection rate of 100% for in vitro samples. MMO2 detected 100% of the clinical strains from DNA and 97% from RNA, whereas MMO detected 100% of the strains from both materials. Thus, for in vitro and clinical samples, MMO2 was a useful tool for detecting dual infections with HIV-1 and HIV-2 (referred to as HIV-1+HIV-2) and HIV-1/M+O, and MMO was useful for detecting both MO dual infections and MO mosaic patterns. PMID:26912747

  13. HIV and the menopause.

    PubMed

    Fan, Maria D; Maslow, Bat-Sheva; Santoro, Nanette; Schoenbaum, Ellie

    2008-12-01

    Dramatic improvement in the survival of the HIV population has occurred with the ascendance of highly active antiretroviral therapy (HAART). In the foreseeable future, HIV-infected women who acquired disease during the peak years of the epidemic are expected to survive to experience menopause and even years beyond. The HIV epidemic may be viewed as 'mature', as its earlier victims become part of the geriatric population. Research about the process of menopause in HIV-infected women and, conversely, about HIV infection in women undergoing menopause is currently limited. Existing research suggests that the process of menopause is affected by HIV infection, inasmuch as infected women appear to experience menopause at an earlier age, with greater symptomatology, and with different reproductive hormone profiles compared with HIV-uninfected women. HIV infection also appears to affect bone mineral density, cardiovascular disease and cognition, with some age-related interactions. Lifestyle and demographic factors have pervasive importance for both HIV infection and the menopause in women. This article reviews the current state of knowledge about the menopausal process in HIV-infected women, and the common conditions in postmenopausal women that are likely to be affected by HIV infection. Clinicians should appreciate the potential role of HIV infection in caring for menopause-aged women. PMID:19037065

  14. HIV Disease: Current Concepts.

    ERIC Educational Resources Information Center

    Keeling, Richard P.

    1993-01-01

    Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…

  15. Behaviour change and competitive exclusion can explain the diverging HIV-1 and HIV-2 prevalence trends in Guinea-Bissau.

    PubMed

    Schmidt, W P; Van Der Loeff, M Schim; Aaby, P; Whittle, H; Bakker, R; Buckner, M; Dias, F; White, R G

    2008-04-01

    The aim of this study was to determine whether a temporary rise in sexual risk behaviour during war in Guinea-Bissau could explain the observed trends in HIV-1 and HIV-2 prevalence, and to explore the possible contribution of competitive elimination of HIV-2 by HIV-1. A simulation model of the heterosexual transmission of sexually transmitted infections was parameterized using demographic, behavioural and epidemiological data from rural Guinea-Bissau, and fitted to the observed HIV-1 and HIV-2 trends with and without a historic rise in risk behaviour. The observed trends could only be simulated by assuming a temporary rise in risk behaviour. Around 30% of the projected decline in HIV-2 prevalence from a peak of 8.7% to 4.3% in 2010 was due to competitive elimination by HIV-1. Importantly for public health, HIV-1 prevalence was predicted to continue increasing and to become the dominant HIV type by 2010. Data collection is required to validate this prediction.

  16. 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

  17. 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.

  18. The Janus kinase inhibitor ruxolitinib reduces HIV replication in human macrophages and ameliorates HIV encephalitis in a murine model.

    PubMed

    Haile, Woldeab B; Gavegnano, Christina; Tao, Sijia; Jiang, Yong; Schinazi, Raymond F; Tyor, William R

    2016-08-01

    A hallmark of persistent HIV-1 infection in the central nervous system is increased activation of mononuclear phagocytes and surrounding astrogliosis, conferring persistent HIV-induced inflammation. This inflammation is believed to result in neuronal dysfunction and the clinical manifestations of HIV-associated neurocognitive disorders (HAND). The Jak/STAT pathway is activated in macrophages/myeloid cells upon HIV-1 infection, modulating many pro-inflammatory pathways that result in HAND, thereby representing an attractive cellular target. Thus, the impact of ruxolitinib, a Janus Kinase (Jak) 1/2 inhibitor that is FDA approved for myelofibrosis and polycythemia vera, was assessed for its potential to inhibit HIV-1 replication in macrophages and HIV-induced activation in monocytes/macrophages in culture. In addition, a murine model of HIV encephalitis (HIVE) was used to assess the impact of ruxolitinib on histopathological features of HIVE, brain viral load, as well as its ability to penetrate the blood-brain-barrier (BBB). Ruxolitinib was found to inhibit HIV-1 replication in macrophages, HIV-induced activation of monocytes (CD14/CD16) and macrophages (HLA-DR, CCR5, and CD163) without apparent toxicity. In vivo, systemically administered ruxolitinib was detected in the brain during HIVE in SCID mice and markedly inhibited astrogliosis. Together, these data indicate that ruxolitinib reduces HIV-induced activation and infiltration of monocytes/macrophages in vitro, reduces the replication of HIV in vitro, penetrates the BBB when systemically administered in mice and reduces astrogliosis in the brains of mice with HIVE. These data suggest that ruxolitinib will be useful as a novel therapeutic to treat humans with HAND. PMID:26851503

  19. Streamlining HIV Testing for HIV Preexposure Prophylaxis

    PubMed Central

    Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M.

    2014-01-01

    HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT results. WB testing, however, causes delays in diagnosis and adds expense. The iPrEx study evaluated the safety and efficacy of daily oral emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and transgender women who have sex with men: HIV infection was assessed with two RTs plus WB confirmation, followed by HIV-1 plasma viral load testing. During the iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers using RTs: 142 (0.28%) had concordant positive results (100% were eventually confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were eventually determined to be HIV infected. A streamlined approach using only one RT to screen and a second RT to confirm (without WB) would have had nearly the same accuracy. Discrepant RT results are best evaluated with nucleic acid testing, which would also increase sensitivity. PMID:25378570

  20. Mononuclear phagocyte accumulation in visceral tissue in HIV encephalitis: evidence for increased monocyte/macrophage trafficking and altered differentiation.

    PubMed

    Fischer, Tracy; Wyatt, Christina M; D'Agati, Vivette D; Croul, Sidney; McCourt, Laura; Morgello, Susan; Rappaport, Jay

    2014-01-01

    The invasion of circulating monocytes/macrophages (MΦ)s from the peripheral blood into the central nervous system (CNS) appears to play an important role in the pathogenesis of HIV dementia (HIV-D), the most severe form of HIV-associated neurocognitive disorders (HAND), often confirmed histologically as HIV encephalitis (HIVE). In order to determine if trafficking of monocytes/MΦs is exclusive to the CNS or if it also occurs in organs outside of the brain, we have focused our investigation on visceral tissues of patients with HIVE. Liver, lymph node, spleen, and kidney autopsy tissues from the same HIVE cases investigated in earlier studies were examined by immunohistochemistry for the presence of CD14, CD16, CD68, Ki-67, and HIV-1 p24 expression. Here, we report a statistically significant increase in accumulation of MΦs in kidney, spleen, and lymph node tissues in specimens from patients with HIVE. In liver, we did not observe a significant increase in parenchymal macrophage accumulation, although perivascular macrophage accumulation was consistently observed with nodular lesions in 4 of 5 HIVE cases. We also observed an absence of CD14 expression on splenic MΦs in HIVE cases, which may implicate the spleen as a potential source of increased plasma soluble CD14 in HIV infection. HIV-1 p24 expression was observed in liver, lymph node and spleen but not kidney. Interestingly, renal pathology suggestive of chronic tubulointerstitial nephritis (possibly due to chronic pyelonephritis), including tubulointerstitial scarring, chronic interstitial inflammation and focal global glomerulosclerosis, without evidence of HIV-associated nephropathy (HIVAN), was seen in four of eight HIVE cases. Focal segmental and global glomerulosclerosis with tubular dilatation and prominent interstitial inflammation, consistent with HIVAN, was observed in two of the eight cases. Abundant cells expressing monocyte/MΦ cell surface markers, CD14 and CD68, were also CD16(+) and found

  1. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy

    PubMed Central

    Lee, Sulggi A.; Bacchetti, Peter; Chomont, Nicolas; Fromentin, Remi; Lewin, Sharon R.; O’Doherty, Una; Palmer, Sarah; Richman, Douglas D.; Siliciano, Janet D.; Yukl, Steven A.; Deeks, Steven G.; Burbelo, Peter D.

    2016-01-01

    Background A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the “reservoir”). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART). Methods We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables. Results Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results. Conclusions Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV

  2. 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

  3. Therapeutic depletion of natural killer cells controls persistent infection.

    PubMed

    Waggoner, Stephen N; Daniels, Keith A; Welsh, Raymond M

    2014-02-01

    Persistent viral infections are associated with host and viral factors that impair effective antiviral immunity. Natural killer (NK) cells contribute to establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection in mice through suppression of virus-specific T cell responses during the first few days of infection, but NK cell depletion during those early time points can enable severe T cell-mediated immune pathology and death of the host. Here we show that long after their peak in cytolytic activation, NK cells continue to support viral persistence at later times of infection. Delayed depletion of NK cells, 2 to 3 weeks after infection, enhanced virus-specific T cell responses and viral control. This enhancing effect of delayed NK cell depletion on antiviral immunity, in contrast to early NK cell depletion, was not associated with increased morbidity and mortality, and mice quickly regained weight after treatment. The efficacy of the depletion depended in part upon the size of the original virus inoculum, the viral load at the time of depletion, and the presence of CD4 T cells. Each of these factors is an important contributor to the degree of CD8 T cell dysfunction during viral persistence. Thus, NK cells may continuously contribute to exhaustion of virus-specific T cells during chronic infection, possibly by depleting CD4 T cells. Targeting of NK cells could thus be considered in combination with blockade of other immunosuppressive pathways, such as the interleukin-10 (IL-10) and programmed death 1 (PD-1) pathways, as a therapy to cure chronic human infections, including those with HIV or hepatitis C virus. IMPORTANCE Persistent virus infections are a major threat to global human health. The capacity of viruses, including HIV and hepatitis C virus, to overwhelm or subvert host immune responses contributes to a prolonged state of dampened antiviral immune functionality, which in turn facilitates viral persistence. Recent efforts have focused on

  4. Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection.

    PubMed

    Ramezani, Ali; Dubrovsky, Larisa; Pushkarsky, Tatiana; Sviridov, Dmitri; Karandish, Sara; Raj, Dominic S; Fitzgerald, Michael L; Bukrinsky, Michael

    2015-09-01

    Previous studies demonstrated that liver X receptor (LXR) agonists inhibit human immunodeficiency virus (HIV) replication by upregulating cholesterol transporter ATP-binding cassette A1 (ABCA1), suppressing HIV production, and reducing infectivity of produced virions. In this study, we extended these observations by analyzing the effect of the LXR agonist T0901317 [N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide] on the ongoing HIV infection and investigating the possibility of using LXR agonist for pre-exposure prophylaxis of HIV infection in a humanized mouse model. Pre-exposure of monocyte-derived macrophages to T0901317 reduced susceptibility of these cells to HIV infection in vitro. This protective effect lasted for up to 4 days after treatment termination and correlated with upregulated expression of ABCA1, reduced abundance of lipid rafts, and reduced fusion of the cells with HIV. Pre-exposure of peripheral blood leukocytes to T0901317 provided only a short-term protection against HIV infection. Treatment of HIV-exposed humanized mice with LXR agonist starting 2 weeks postinfection substantially reduced viral load. When eight humanized mice were pretreated with LXR agonist prior to HIV infection, five animals were protected from infection, two had viral load at the limit of detection, and one had viral load significantly reduced relative to mock-treated controls. T0901317 pretreatment also reduced HIV-induced dyslipidemia in infected mice. In conclusion, these results reveal a novel link between LXR stimulation and cell resistance to HIV infection and suggest that LXR agonists may be good candidates for development as anti-HIV agents, in particular for pre-exposure prophylaxis of HIV infection.

  5. HIV-1-Specific Antibody Response and Function after DNA Prime and Recombinant Adenovirus 5 Boost HIV Vaccine in HIV-Infected Subjects

    PubMed Central

    Gach, Johannes S.; Gorlani, Andrea; Dotsey, Emmanuel Y.; Becerra, Juan C.; Anderson, Chase T. M.; Berzins, Baiba; Felgner, Philip L.; Forthal, Donald N.; Deeks, Steven G.; Wilkin, Timothy J.; Casazza, Joseph P.; Koup, Richard A.; Katlama, Christine; Autran, Brigitte; Murphy, Robert L.; Achenbach, Chad J.

    2016-01-01

    Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir. PMID:27500639

  6. HIV-1-Specific Antibody Response and Function after DNA Prime and Recombinant Adenovirus 5 Boost HIV Vaccine in HIV-Infected Subjects.

    PubMed

    Gach, Johannes S; Gorlani, Andrea; Dotsey, Emmanuel Y; Becerra, Juan C; Anderson, Chase T M; Berzins, Baiba; Felgner, Philip L; Forthal, Donald N; Deeks, Steven G; Wilkin, Timothy J; Casazza, Joseph P; Koup, Richard A; Katlama, Christine; Autran, Brigitte; Murphy, Robert L; Achenbach, Chad J

    2016-01-01

    Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir. PMID:27500639

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

    PubMed

    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

  8. Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder

    PubMed Central

    2014-01-01

    Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. PMID:24886748

  9. 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

  10. HIV and maternal mortality.

    PubMed

    Lathrop, Eva; Jamieson, Denise J; Danel, Isabella

    2014-11-01

    The majority of the 17 million women globally that are estimated to be infected with HIV live in Sub-Saharan Africa. Worldwide, HIV-related causes contributed to 19 000-56 000 maternal deaths in 2011 (6%-20% of maternal deaths). HIV-infected pregnant women have two to 10 times the risk of dying during pregnancy and the postpartum period compared with uninfected pregnant women. Many of these deaths can be prevented with the implementation of high-quality obstetric care, prevention and treatment of common co-infections, and treatment of HIV with ART. The paper summarizes what is known about HIV disease progression in pregnancy, specific causes of HIV-related maternal deaths, and the potential impact of treatment with antiretroviral therapy on maternal mortality. Recommendations are proposed for improving maternal health and decreasing maternal mortality among HIV-infected women based on existing evidence.

  11. Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

    PubMed Central

    Bártolo, Inês; Marcelino, José Maria; Família, Carlos; Quintas, Alexandre; Taveira, Nuno

    2011-01-01

    Background Unlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infection. Methodology/Principal Findings We performed a side-by-side molecular, evolutionary and structural comparison of the C2, V3 and C3 envelope regions from HIV-1 and HIV-2. These regions contain major antigenic targets and are important for receptor binding. In HIV-2, these regions also have immune modulatory properties. We found that these regions are significantly more variable in HIV-1 than in HIV-2. Within each virus, C3 is the most entropic region followed by either C2 (HIV-2) or V3 (HIV-1). The C3 region is well exposed in the HIV-2 envelope and is under strong diversifying selection suggesting that, like in HIV-1, it may harbour neutralizing epitopes. Notably, however, extreme diversification of C2 and C3 seems to be deleterious for HIV-2 and prevent its transmission. Computer modelling simulations showed that in HIV-2 the V3 loop is much less exposed than C2 and C3 and has a retractile conformation due to a physical interaction with both C2 and C3. The concealed and conserved nature of V3 in the HIV-2 is consistent with its lack of immunodominancy in vivo and with its role in preventing immune activation. In contrast, HIV-1 had an extended and accessible V3 loop that is consistent with its immunodominant and neutralizing nature. Conclusions/Significance We identify significant structural and functional constrains to the diversification and evolution of C2, V3 and C3 in the HIV-2 envelope but not in HIV-1. These studies highlight fundamental differences in the biology and infection of HIV-1 and HIV-2 and in their mode of interaction with the human

  12. Thymic function in HIV-infection.

    PubMed

    Kolte, Lilian

    2013-04-01

    -infected patients independent of viral load, CD4 cell depletion or level of immune activation, and this may be due to increased thymic production of naïve Tregs. Alteration of thymic function in adults is possible, both by stimulation of thymopoiesis with rhGH therapy and as a result of pregnancy. Finally, immunological abnormalities detected in HIV-EU infants are recovered at 15 months of age, and even if diminished in size, thymic function is normalized at this age. PMID:23651726

  13. Basic HIV/AIDS Statistics

    MedlinePlus

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Collapse All How many people are diagnosed with HIV each year in the United States? In 2014, ...

  14. HIV Medicines and Side Effects

    MedlinePlus

    Side Effects of HIV Medicines HIV Medicines and Side Effects (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points HIV medicines help people with ... will depend on a person’s individual needs. Can HIV medicines cause side effects? HIV medicines help people ...

  15. Cost-effectiveness analysis of initial HIV treatment under Italian guidelines

    PubMed Central

    Colombo, Giorgio L; Colangeli, Vincenzo; Di Biagio, Antonio; Di Matteo, Sergio; Viscoli, Claudio; Viale, Pierluigi

    2011-01-01

    Introduction Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines. Patients and methods The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients’ characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. Results The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (€22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (€24,526), and TDF/emtricitabine (FTC) + nevirapine (€26,416), and TDF + FTC + EFV (€26,558); the remaining strategies have an incremental cost-effectiveness ratio (ICER) value varying from €28,000 to €41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario. Conclusion STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by

  16. Why is HIV not vector-borne?

    PubMed Central

    Day, Troy; Mideo, Nicole; Alizon, Samuel

    2008-01-01

    Abstract Many pathogens of humans are blood borne, including HIV, Malaria, Hepatitis B and C, West Nile virus, Dengue, and other viral hemorrhagic fevers. Although several of these pathogens are transmitted by blood-feeding arthropods, HIV is not. A number of properties of HIV and its life cycle have been identified as proximate explanations for the absence of arthropod transmission, but little consideration has been given to why HIV has not evolved this form of transmission. We consider the empirical evidence for arthropod transmission, and suggest that mechanical transmission has not evolved in HIV because such strains would induce a faster onset of AIDS during infection, which would thereby limit their ability to spread. On the other hand, it is not as clear why biological transmission has not occurred. Available data suggests that a lack of appropriate genetic variation in HIV is one explanation, but it is also possible that a conflict between natural selection occurring within and between infected individuals has prevented its evolution instead. We discuss the potential significance of these ideas, and argue that taking such an evolutionary perspective broadens our understanding of infectious diseases and the potential consequences of public health interventions. PMID:25567488

  17. Hematopoietic cell transplantation and HIV cure: where we are and what next?

    PubMed

    Zou, Shimian; Glynn, Simone; Kuritzkes, Daniel; Shah, Monica; Cook, Nakela; Berliner, Nancy

    2013-10-31

    The report of the so-called Berlin patient cured of HIV with hematopoietic stem cell transplantation and a few other studies raised tremendous hope, excitement, and curiosity in the field. The National Heart, Lung and Blood Institute of the National Institutes of Health convened a Working Group to address emerging heart, lung, and blood research priorities related to HIV infection. Hematopoietic cells could contribute to HIV cure through allogeneic or autologous transplantation of naturally occurring or engineered cells with anti-HIV moieties. Protection of central memory T cells from HIV infection could be a critical determinant of achieving a functional cure. HIV cure can only be achieved if the virus is eradicated from reservoirs in resting T cells and possibly other hematopoietic cells. The Working Group recommended multidisciplinary efforts leveraging HIV and cell therapy expertise to answer the critical need to support research toward an HIV cure.

  18. County-Level Correlates of CDC-Funded HIV Testing Events, United States, 2012.

    PubMed

    Hayek, Samah; Heitgerd, Janet L; Williams, Weston O; Krueger, Amy L; Dietz, Patricia M

    2015-10-01

    HIV prevalence and socio-demographic data were analyzed to assess the alignment of CDC-funded HIV testing activity in 2012 with its high-impact prevention approach. CDC-funded HIV-testing was conducted in counties with high HIV prevalence and in places potentially more affected by HIV as measured by urbanicity, percent black, percent poverty, and percent uninsured. The percent Hispanic/Latino was associated with a lower probability of HIV testing activity. Higher percentages of black and Hispanic/Latino in the population was positively associated with new HIV diagnoses. Analyzing county-level data confirmed the appropriateness of CDC-funded HIV testing activities under a high-impact prevention approach but also suggested areas for possible improvement.

  19. 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

  20. Foreign-Born Persons Diagnosed with HIV: Where are They From and Where Were They Infected?

    PubMed

    Wiewel, Ellen W; Torian, Lucia V; Hanna, David B; Bocour, Angelica; Shepard, Colin W

    2015-05-01

    We sought to calculate rates of HIV diagnoses by area of birth among foreign-born persons in a high-incidence US city with many immigrants, and determine probable place of HIV acquisition. Data from the New York City HIV surveillance registry and American Community Survey were used to calculate HIV diagnosis rates by area of birth and determine probable place of HIV acquisition among foreign-born diagnosed in 2006-2012. HIV diagnosis rates varied by area of birth and were highest among African-born persons; absolute numbers were highest among Caribbean-born persons. Probable place of acquisition was a foreign country for 23 % (from 9 % among Middle Easterners to 43 % among Africans), US for 61 % (from 34 % among Africans to 76 % among South Americans), and not possible to estimate for 16 %. HIV prevention and testing initiatives should take into account variability by foreign area of birth in HIV diagnosis rates and place of acquisition.

  1. [Sanitary safety of GMOs used in therapeutics].

    PubMed

    Trouvin, Jean-Hugues

    2002-01-01

    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 those 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 permitted considerable therapeutic progress without compromising health security. PMID:12669359

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

    PubMed

    Trouvin, J-H

    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. PMID:12668948

  3. [Sanitary safety of GMOs used in therapeutics].

    PubMed

    Trouvin, Jean-Hugues

    2002-01-01

    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 those 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 permitted considerable therapeutic progress without compromising health security.

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

    PubMed

    Trouvin, J-H

    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.

  5. [Study toward practical use of oligonucleotide therapeutics].

    PubMed

    Inoue, Takao; Yoshida, Tokuyuki

    2014-01-01

    Over the past decade, oligonucleotide-based therapeutics such as antisense oligonucleotides and small interfering RNAs (siRNAs) have been developed extensively. For example, mipomersen (Kynamro; ISIS Pharmaceuticals), which is a second-generation antisense oligonucleotide administered by subcutaneous injection, has recently been approved by the FDA for the treatment of homozygous familial hypercholesterolemia. On the other hands, methods for the evaluation of quality, efficacy and safety of oligonucleotide therapeutics have not been fully discussed. Furthermore, the regulatory guidance specific for oligonucleotide therapeutics has not been established yet. Under these circumstances, we started to collaborate with Osaka University and PMDA to discuss regulatory science focused on oligonucleotide therapeutics. Through the collaboration, we would like to propose the possible design of quality evaluation and preclinical safety-evaluation of oligonucleotide therapeutics. PMID:25707197

  6. Assessment of mucosal immunity to HIV-1.

    PubMed

    Jespers, Vicky; Harandi, Ali M; Hinkula, Jorma; Medaglini, Donata; Le Grand, Roger; Stahl-Hennig, Christiane; Bogers, Willy; El Habib, Raphaelle; Wegmann, Frank; Fraser, Carol; Cranage, Martin; Shattock, Robin J; Spetz, Anna-Lena

    2010-04-01

    A key gap in the development and evaluation of HIV-1 vaccines is insufficient knowledge with regard to sampling techniques and assessment of mucosal immune responses required for early prevention and inhibition of viral dissemination. In an attempt to start bridging this gap, the EUROPRISE network of scientists working on HIV-1 vaccine and microbicide research organized a workshop with the aim to review the types of mucosal responses/biomarkers currently measured in mucosal immunology and to define how the mucosal responses/biomarkers are measured and/or the assays and sampling methods used. The Workshop addressed two critical questions: first whether, with current knowledge, it would be possible to define a consensus set of mucosal sampling methods to facilitate cross-species comparisons and ensure standardized implementation in clinical trials; second to determine the remaining challenges (technical and logistical) and their possible solutions for assessing mucosal responses to HIV-1 vaccines. PMID:20370549

  7. 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 ...

  8. 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

  9. Differential regulation of human immunodeficiency viruses (HIVs): a specific regulatory element in HIV-2 responds to stimulation of the T-cell antigen receptor.

    PubMed Central

    Markovitz, D M; Hannibal, M; Perez, V L; Gauntt, C; Folks, T M; Nabel, G J

    1990-01-01

    The human immunodeficiency viruses (HIVs) types 1 and 2 have similar genetic organization but differ significantly in nucleic acid sequence. Although infection by either agent leads to symptoms of immunodeficiency, recent studies suggest potential differences in the time course and severity of these diseases. In this report, the transcriptional regulation and induction of these retroviruses were analyzed. We report that the regulation of HIV-2 differs from that of HIV-1: a distinct T-cell activation pathway, triggering of the CD3 component of the T-cell receptor complex, stimulates HIV-2 but not HIV-1 gene expression. The response to T-cell receptor stimulation in HIV-2 is mediated partly by an upstream regulatory element, termed CD3R, which is recognized by a sequence-specific DNA binding protein, NF-CD3R. Jurkat T leukemia cell lines containing HIV-2 provirus also showed increased viral replication after stimulation of the T-cell receptor complex, in contrast to HIV-1. These findings suggest that transcriptional regulation and induction of HIV-2 differ from HIV-1 and raise the possibility that different cofactors contribute to the activation of HIV-1- and HIV-2-associated AIDS. Images PMID:2147512

  10. Multilevel stigma as a barrier to HIV testing in Central Asia: a context quantified.

    PubMed

    Smolak, Alex; El-Bassel, Nabila

    2013-10-01

    Central Asia is experiencing one of the fastest growing HIV epidemics in the world, with some areas' infection rates doubling yearly since 2000. This study examines the impact of multilevel stigma (individual, family, and community) on uptake of HIV testing and receipt of HIV testing results among women in Central Asia. The sample consists of 38,884 ever-married, Central Asian women between the ages of 15 and 49. Using multilevel modeling (MLM), HIV stigma variables at the individual, family, and community levels were used to assess the significance of differences in HIV testing and receipt of HIV test results among participants while adjusting for possible confounding factors, such as age, wealth, and education. MLM results indicate that HIV stigma is significantly associated with decreased HIV testing uptake at the individual, family, and community levels and with a decrease in receipt at the community level. A one standard deviation increase in individual, family, and community level composite stigma score was associated with a respective 49 %, 59 %, and 94 % (p < 0.001) decrease in the odds of having been tested for HIV. A one standard deviation increase in community composite stigma score was associated with a 99 % (p < 0.001) decrease in the odds of test receipt. HIV stigma operates on the individual, family, and community levels to hinder HIV testing uptake and at the community level to hinder receipt. These findings have important interventions implications to improve uptake of HIV testing and receipt of HIV test results.

  11. Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in US hospital discharge records: a cross-sectional study

    PubMed Central

    Nouraie, Mehdi; Nekhai, Sergei; Gordeuk, Victor R

    2012-01-01

    Objective Some studies suggest that HIV infection progresses slowly in patients with sickle cell disease (SCD). The authors aimed to determine the relationships between SCD and HIV infection. Methods National Hospital Discharge Survey data from adult Africane–Americans in the period of 1997–2009 were analysed. The comorbidities of SCD with HIV infections in hospital discharges were analysed. Multiple logistic regression was used to test the association between SCD and HIV. For comparative purposes, the relationships of SCD with hepatitis B virus (HBV) and hepatitis C virus (HCV) were also assessed. Results 423 431 records were divided into two time periods 1997–2003 (53% of records) and 2004–2009 (47% of records). The frequency of HIV diagnosis was lower in patients with SCD (1.5% vs 3.3% in patients without SCD). In logistic regression, SCD diagnosis was associated with an OR of 0.24 (95% CI 0.18 to 0.32) for HIV diagnosis in the first period and with an OR of 0.31 (95% CI 0.22 to 0.42) in the second period. In contrast, SCD was associated with higher risk of HCV (OR=2.01, 95% CI 1.56 to 2.59 in the first period and OR=2.12, 95% CI 1.71 to 2.63 in the second period). SCD was also associated with a higher risk of HBV (OR=1.15, 95% CI 0.72 to 1.83 in the first period and OR=1.82, 95% CI 1.24 to 2.68 in the second period). Conclusions The lower risk of HIV comorbidity, but not HCV and HBV, with SCD is consistent with the possibility that SCD has a unique effect in altering the risk of HIV infection or progression. Investigation of how the haemolytic and immunological changes of SCD influence HIV might lead to new therapeutic or preventive approaches. PMID:22628662

  12. Increased longevity in HIV: caring for older HIV-infected adults.

    PubMed

    Ball, Susan C

    2014-01-01

    The demographics of the HIV-infected population in the United States have shifted in a way that few would have predicted 30 years ago when the tide of sick and dying patients largely consisted of young men. Effective ART has allowed those infected to live long, productive lives and to grow old with their disease. With the increase in life expectancy afforded by HIV treatment, the cause of death among HIV-infected individuals is far more likely to be from an HIV-associated non-AIDS condition. Nonetheless, HIV seems to accelerate the aging process, and care providers involved in the treatment of older patients with HIV need to be aware that their patients are at increased risk of developing various common disorders, compared to uninfected same-age patients. Clinicians need to remain vigilant to the possibility of a new diagnosis of HIV among their older patients. Awareness of current or distant risk, frank discussions of sexual practices, and willingness to offer routine testing are crucial to making this diagnosis, with the recognition that longevity for patients with HIV is directly linked to how soon they enter care. HIV infection adds another challenge to the management of older patients; geriatricians and HIV specialists need to coordinate their efforts to provide patients with comprehensive multidisciplinary care. Older patients with HIV also have social and psychological needs that extend beyond the medical office. Maintaining independence, acknowledging limitations, reducing risk of adverse events such as falls or medication errors, and supporting self-acceptance and awareness are only a few of the many areas where care providers outside the medical office can be important for patients' ongoing well-being. Accessing family support, community outreach, church affiliation, or other outpatient support networks can be useful for patients. The remarkable change in prognosis brought about by effective ART in the mid-1990s has meant that HIV is now, for many, a

  13. 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

  14. 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

  15. HIV/AIDS, conflict and security in Africa: rethinking relationships

    PubMed Central

    2008-01-01

    The effect of conflict on HIV transmission and regional and global security has been the subject of much recent discussion and debate. Many long held assumptions regarding these relationships are being reconsidered. Conflict has long been assumed to contribute significantly to the spread of HIV infection. However, new research is casting doubt on this assumption. Studies from Africa suggest that conflict does not necessarily predispose to HIV transmission and indeed, there is evidence to suggest that recovery in the "post-conflict" state is potentially dangerous from the standpoint of HIV transmission. As well, refugee populations have been previously considered as highly infected vectors of HIV transmission. But in light of new investigation this belief is also being reconsidered. There has additionally been concern that high rates of HIV infection among many of the militaries of sub-Saharan Africa poses a threat to regional security. However, data is lacking on both dramatically elevated prevalence amongst soldiers and a possible negative effect on regional security. Nevertheless, HIV/AIDS remain a serious threat to population health and economic well being in this region. These issues are of vital importance for HIV programming and health sector development in conflict and "post-conflict" societies and will constitute formidable challenges to the international community. Further research is required to better inform the discussion of HIV, conflict, and security in sub-Saharan Africa. PMID:19014653

  16. The Diagnosis of HIV Infection in Infants and Children.

    PubMed

    Abdollahi, Alireza; Saffar, Hana

    2016-01-01

    It is estimated that the number of HIV infected children globally has increased from 1.6 million in 2001 to 3.3 million in 2012. The number of children below 15 years of age living with HIV has increased worldwide. Published data from recent studies confirmed dramatic survival benefit for infants started anti-retroviral therapy (ART) as early as possible after diagnosis of HI. Early confirmation of HIV diagnosis is required in order to identify infants who need immediate ART. WHO has designed recommendations to improve programs for both early diagnoses of HIV infection and considering ART whenever indicated? It is strongly recommended that HIV virologocal assays for diagnosis of HIV have sensitivity of at least 95% and ideally greater than 98% and specificity of 98% or more under standardized and validated conditions. Timing of virological testing is also important. Infants infected at or around delivery may take short time to have detectable virus. Therefore, sensitivity of virological tests is lower at birth. In utero HIV infection, HIV DNA or RNA can be detected within 48 h of birth and in infants with peripartum acquisition it needs one to two weeks. Finally it is emphasized that all laboratories performing HIV tests should follow available services provided by WHO or CDC for quality assurance programs. Both clinicians and staffs providing laboratory services need regular communications, well-defined SOPs and nationally validated algorithms for optimal use of laboratory tests. Every country should use assays that have been validated by national reference laboratory. PMID:27499768

  17. 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

  18. Review of HIV Testing Efforts in Historically Black Churches

    PubMed Central

    Pichon, Latrice Crystal; Powell, Terrinieka Williams

    2015-01-01

    This paper aims to critically assess the state of HIV testing in African American churches. A comprehensive review of peer-reviewed publications on HIV testing in church-based settings was conducted by two independent coders. Twenty-six papers published between 1991 and 2015, representing 24 unique projects, were identified addressing at least one dimension of HIV testing. Thirteen faith-based projects have implemented HIV testing events or had clergy promote the importance of testing and knowing one’s HIV status, but empirical data and rigorous study designs were limited. Only eight papers reported onsite HIV testing in churches. Less than 5% of the studies reported the percentage of congregants who returned for their test results. Finally, no study has examined at baseline or post-intervention behavioral intentions to be screened for HIV. Future research is needed to evaluate the effectiveness of HIV testing in churches and to explore the possibilities of the role of the church and leadership structure in the promotion of HIV treatment and care. PMID:26030470

  19. Elevated Rates of Mild Cognitive Impairment in HIV Disease

    PubMed Central

    Sheppard, David P.; Iudicello, Jennifer E.; Bondi, Mark W.; Doyle, Katie L.; Morgan, Erin E.; Massman, Paul J.; Gilbert, Paul E.; Woods, Steven Paul

    2015-01-01

    With the rising number of individuals in their 50s and 60s who are infected with HIV, concerns have emerged about possible increases in the rates of non-HIV-associated dementias. The current study examined the prevalence of mild cognitive impairment (MCI) in older HIV-infected adults, since MCI is an intermediate state between typical cognitive aging and dementia that emerges in this age range. Participants included 75 adults with HIV disease aged 50 years and older who were on cART and had undetectable plasma viral loads and 80 demographically similar HIV seronegative comparison subjects. Participants completed a research neuropsychological evaluation that was used to classify MCI according to the comprehensive diagnostic scheme described by Bondi et al. (2014). HIV-infected persons were over seven times more likely to have an MCI designation (16%) than their seronegative counterparts (2.5%). Within the HIV+ cohort, MCI had minimal overlap with diagnoses of Asymptomatic Neurocognitive Impairment and was significantly associated with older age, lower Karnofsky Scale of Performance Scores, and mild difficulties performing instrumental activities of daily living (iADLs). HIV infection in older adults is associated with a notably elevated concurrent risk of MCI, which may increase the likelihood of developing non-HIV-associated dementias as this population ages further. PMID:26139019

  20. A lymphomagenic role for HIV beyond immune suppression?

    PubMed

    Dolcetti, Riccardo; Gloghini, Annunziata; Caruso, Arnaldo; Carbone, Antonino

    2016-03-17

    Despite the immune reconstitution promoted by combined antiretroviral therapy (cART), lymphomas still represent the most common type of cancer in HIV-infected individuals. Cofactors related to immunodeficiency such as oncogenic viruses, chronic antigenic stimulation, and cytokine overproduction are thought to be the main drivers of HIV lymphomagenesis, although the current scenario does not convincingly explain the still-high incidence of lymphomas and the occurrence of peculiar lymphoma histotypes in HIV-infected patients under cART. Recent findings are challenging the current view of a mainly indirect role of HIV in lymphoma development and support the possibility that HIV may directly contribute to lymphomagenesis. In fact, mechanisms other than immune suppression involve biologic effects mediated by HIV products that are secreted and accumulate in lymphoid tissues, mainly within lymph node germinal centers. Notably, HIV-infected patients with lymphomas, but not those not affected by these tumors, were recently shown to carry HIV p17 protein variants with enhanced B-cell clonogenic activity. HIV p17 protein variants were characterized by the presence of distinct insertions at the C-terminal region of the protein responsible for a structural destabilization and the acquisition of novel biologic properties. These data are changing the current paradigm assuming that HIV is only indirectly related to lymphomagenesis. Furthermore, these recent findings are consistent with a role of HIV as a critical microenvironmental factor promoting lymphoma development and pave the way for further studies that may lead to the design of more effective strategies for an early identification and improved control of lymphomas in the HIV setting.

  1. New drugs for HIV-1: challenges and novel candidates.

    PubMed

    Ward, Christopher James Kevin

    2010-10-01

    The XVIII International Conference of the International AIDS Society held in Vienna on the 18-23 July 2010 brought together scientists, clinicians, policymakers, people living with HIV/AIDS and journalists from across the globe. Keynote speakers relevant to the theme of this report included Sharon Lewin (Alfred Hospital, Melbourne, Australia) and Tae-Wook Chun (National Institute of Allergy and Infectious Diseases, MA, USA), among others. A total of 19,100 delegates from across 193 countries attended the conference, which comprised 248 sessions, accompanied by 6238 abstracts and posters. The remit was broad, covering scientific, social and political aspects of the HIV/AIDS epidemic. This article focuses on the issue of eliminating latent reservoirs of HIV-1 infection, highlighting selected potential novel therapeutic interventions in overcoming challenges in HIV-1 suppression.

  2. Challenges facing providers caring for HIV/HCV-coinfected patients

    PubMed Central

    Lekas, Helen-Maria; Siegel, Karolynn; Leider, Jason

    2015-01-01

    Despite the high prevalence of Hepatitis C virus (HCV) infection among injection drug users also infected with Human immunodeficiency virus (HIV), and the synergistic adverse effect of the two diseases on patients' health and survival, the research on the clinical management of these patients and particularly the low uptake of HCV therapy is limited. We conducted qualitative interviews with 17 HIV providers from two urban public hospitals. We discovered that the limitations of the current state of medical knowledge, the severe side effects of HIV and HCV therapies, and the psychosocial vulnerability of HIV/HCV-coinfected patients combined with their resistance to becoming informed about HCV posed significant challenges for providers. To contend with these challenges, providers incorporated key dimensions of patient-centered medicine in their practice such as considering their patients' psychosocial profiles and the meaning patients assign to being coinfected, and finding ways to engage their patients in a therapeutic alliance. PMID:21825278

  3. Molecular Characterization of Mexican HIV-1 Vif Sequences.

    PubMed

    Guerra-Palomares, Sandra E; Hernandez-Sanchez, Pedro G; Esparza-Perez, Mario A; Arguello, J Rafael; Noyola, Daniel E; Garcia-Sepulveda, Christian A

    2016-03-01

    The viral infectivity factor (Vif) is an HIV accessory protein that counteracts host antiviral proteins of the APOBEC3 family. Accumulating evidence highlights the pivotal role that accessory HIV proteins have on disease pathogenesis, a fact that has made them targets of interest for novel therapeutic and preventive strategies. Little is known about Vif sequence diversity outside of African or white populations. Mexico is home to Americas' third largest HIV-affected population and Mexican Hispanics represent an ever-increasing U.S. minority. This study provides a detailed analysis of the diversity seen in 77 Mexican Vif protein sequences. Phylogenetic analysis shows that most sequences cluster with HIV-1 subtype B, while less than 10% exhibit greater similarity to subtype D and A subtypes. Although most functional motifs are conserved among the Mexican sequences, substantial diversity was seen in some APOBEC binding sites, the nuclear localization inhibitory signal, and the CBFβ interaction sites.

  4. Epigenetic regulation and therapeutic approaches in cancer.

    PubMed

    Recillas-Targa, Félix

    2008-01-01

    The interdependency between genetic and epigenetic regulatory processes renders cancer therapeutics and translational clinic possible, even though they remain difficult tasks considering all the evidence supporting a central role of progenitor-stem cells as a causative source of cellular transformation. In contrast to genetic alterations, epigenetic processes are potentially reversible allowing a better action of complementary therapeutic compounds. Here I would first describe the plethora of interconnected epigenetic processes and targets to then discuss several therapeutic strategies on the basis of different compounds. I conclude that the advent of new and specific epigenetic target drugs will certainly contribute to better treatments and to the development of predictive protocols in a next future.

  5. 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, ...

  6. 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 ...

  7. 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, ...

  8. Women and HIV/AIDS

    MedlinePlus

    ... action on HIV/AIDS National Women and Girls HIV/AIDS Awareness Day – March 10 Programs Share your story Anonymous from Illinois says... Although I am HIV negative, I would like to share my story. ...

  9. 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 ...

  10. 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…

  11. Cannabis: its therapeutic use.

    PubMed

    Wall, J; Davis, S; Ridgway, S

    This article provides an overview of the issues surrounding the use of cannabis for therapeutic purposes. Examples of some of the ethical issues related to professional practice are discussed. The authors do not advocate legalising cannabis for all, but the therapeutic advantages and disadvantages of using cannabis are highlighted.

  12. Cytokines and therapeutic oligonucleotides.

    PubMed

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies.

  13. Cuba's response to the HIV epidemic.

    PubMed Central

    Pérez-Stable, E J

    1991-01-01

    BACKGROUND: Cuba's response to the human immunodeficiency virus (HIV) epidemic has been to conduct mass testing of the population to ascertain seroprevalence, to enforce mandatory relative quarantine of persons testing positive, and to implement educational interventions using media and school-based programs. METHODS: Interview with the Vice-Minister of Health and review of available data. RESULTS: Reports to date show a very low seroprevalence rate without evidence of a widespread epidemic. Sexual contact with foreign-born persons is the primary risk factor. Possible advantages of Cuba's policy include rapid reduction in the risk of HIV transmission by infected blood products, an opportunity for focused education and secondary prevention, and limitation of new infections. Possible disadvantages include the restriction of individual freedom in those who are not guilty of any illegal act, quarantine of persons with false positive HIV tests, and ongoing transmission because of the incomplete nature of the quarantine. The policy is expensive and may displace other public health priorities. The content of the media-based educational interventions has emphasized rational medical information in unimaginative formats with a limited focus on prevention. CONCLUSIONS: The issue of personal responsibility for behavioral change versus government imposed regulations is at the core of Cuba's HIV policy. The quarantine policy may paradoxically permit most Cubans to feel that they are personally invulnerable to the HIV epidemic. PMID:2014854

  14. An Empiric HIV Risk Scoring Tool to Predict HIV-1 Acquisition in African Women

    PubMed Central

    Brown, Elizabeth; Palanee, Thesla; Nair, Gonasagrie; Gafoor, Zakir; Zhang, Jingyang; Richardson, Barbra A.; Chirenje, Zvavahera M.; Marrazzo, Jeanne M.; Baeten, Jared M.

    2016-01-01

    Objective: To develop and validate an HIV risk assessment tool to predict HIV acquisition among African women. Design: Data were analyzed from 3 randomized trials of biomedical HIV prevention interventions among African women (VOICE, HPTN 035, and FEM-PrEP). Methods: We implemented standard methods for the development of clinical prediction rules to generate a risk-scoring tool to predict HIV acquisition over the course of 1 year. Performance of the score was assessed through internal and external validations. Results: The final risk score resulting from multivariable modeling included age, married/living with a partner, partner provides financial or material support, partner has other partners, alcohol use, detection of a curable sexually transmitted infection, and herpes simplex virus 2 serostatus. Point values for each factor ranged from 0 to 2, with a maximum possible total score of 11. Scores ≥5 were associated with HIV incidence >5 per 100 person-years and identified 91% of incident HIV infections from among only 64% of women. The area under the curve (AUC) for predictive ability of the score was 0.71 (95% confidence interval [CI]: 0.68 to 0.74), indicating good predictive ability. Risk score performance was generally similar with internal cross-validation (AUC = 0.69; 95% CI: 0.66 to 0.73) and external validation in HPTN 035 (AUC = 0.70; 95% CI: 0.65 to 0.75) and FEM-PrEP (AUC = 0.58; 95% CI: 0.51 to 0.65). Conclusions: A discrete set of characteristics that can be easily assessed in clinical and research settings was predictive of HIV acquisition over 1 year. The use of a validated risk score could improve efficiency of recruitment into HIV prevention research and inform scale-up of HIV prevention strategies in women at highest risk. PMID:26918545

  15. Engineering T Cells to Functionally Cure HIV-1 Infection.

    PubMed

    Leibman, Rachel S; Riley, James L

    2015-07-01

    Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1-resistant cells, redirecting HIV-1-specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1-specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy-mediated functional cure.

  16. Heat Shock Factor 1 Mediates Latent HIV Reactivation

    PubMed Central

    Pan, Xiao-Yan; Zhao, Wei; Zeng, Xiao-Yun; Lin, Jian; Li, Min-Min; Shen, Xin-Tian; Liu, Shu-Wen

    2016-01-01

    HSF1, a conserved heat shock factor, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. To our knowledge, it is not known whether HSF1 regulates viral transcription, particularly HIV-1 and its latent form. Here we reveal that HSF1 extensively participates in HIV transcription and is critical for HIV latent reactivation. Mode of action studies demonstrated that HSF1 binds to the HIV 5′-LTR to reactivate viral transcription and recruits a family of closely related multi-subunit complexes, including p300 and p-TEFb. And HSF1 recruits p300 for self-acetylation is also a committed step. The knockout of HSF1 impaired HIV transcription, whereas the conditional over-expression of HSF1 improved that. These findings demonstrate that HSF1 positively regulates the transcription of latent HIV, suggesting that it might be an important target for different therapeutic strategies aimed at a cure for HIV/AIDS. PMID:27189267

  17. Heat Shock Factor 1 Mediates Latent HIV Reactivation.

    PubMed

    Pan, Xiao-Yan; Zhao, Wei; Zeng, Xiao-Yun; Lin, Jian; Li, Min-Min; Shen, Xin-Tian; Liu, Shu-Wen

    2016-05-18

    HSF1, a conserved heat shock factor, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. To our knowledge, it is not known whether HSF1 regulates viral transcription, particularly HIV-1 and its latent form. Here we reveal that HSF1 extensively participates in HIV transcription and is critical for HIV latent reactivation. Mode of action studies demonstrated that HSF1 binds to the HIV 5'-LTR to reactivate viral transcription and recruits a family of closely related multi-subunit complexes, including p300 and p-TEFb. And HSF1 recruits p300 for self-acetylation is also a committed step. The knockout of HSF1 impaired HIV transcription, whereas the conditional over-expression of HSF1 improved that. These findings demonstrate that HSF1 positively regulates the transcription of latent HIV, suggesting that it might be an important target for different therapeutic strategies aimed at a cure for HIV/AIDS.

  18. Engineering T Cells to Functionally Cure HIV-1 Infection

    PubMed Central

    Leibman, Rachel S; Riley, James L

    2015-01-01

    Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1–resistant cells, redirecting HIV-1–specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1–specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy–mediated functional cure. PMID:25896251

  19. MicroRNAs and their potential involvement in HIV infection

    PubMed Central

    Sun, Guihua; Rossi, John J.

    2011-01-01

    Treatment and cure of human immunodeficiency virus-1(HIV-1) infection remains one of the greatest therapeutic challenges due to its persistent infection, which often leads to acquired immunodeficiency syndrome (AIDS). Although it has been 28 years since the discovery of the virus, the development of an effective vaccine is still years away. Relatively newly discovered microRNAs (miRNA) are a family of small non-coding RNAs that can regulate gene expression primarily by binding to the 3′ untranslated region (UTR) of targeted transcripts. Understanding how HIV-1 infection affects the host miRNA pathway could generate new insights into the basic mechanisms underlying HIV-1-mediated pathologies and T-lymphocyte depletion. Here, we review literature related to the biogenesis of HIV-1 encoded miRNAs, cellular miRNAs that can directly target HIV-1 or essential cellular factors required for HIV-1 replication. We also discuss the feasibility of using miRNAs for HIV-1 therapy. PMID:21862142

  20. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    PubMed Central

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  1. HIV incidence rates among drug users in northern Thailand, 1993-7.

    PubMed Central

    Jittiwutikarn, J.; Sawanpanyalert, P.; Rangsiveroj, N.; Satitvipawee, P.

    2000-01-01

    Drug use is a major mode of HIV transmission in Thailand. This study determined HIV incidence rates among drug users in a regional drug treatment centre in northern Thailand. A retrospective cohort of repeatedly-hospitalized drug users between 1993 and 1997 was formed and HIV incidence rates were calculated. The overall incidence was 11.44 per 100 person-years of observation. Gender, age, religion, ethnicity, education, employment, income, reasons for drug use, type of drugs, mode of use, spending on drugs, and referral for treatment are associated with HIV incidence. However, there are no associations between HIV incidence and history of treatment and mode of discharge from the centre. This implies that current treatment modality has no impact on HIV infection risk and other therapeutic approaches should be explored. PMID:11057970

  2. TALEN Knockout of the PSIP1 Gene in Human Cells: Analyses of HIV-1 Replication and Allosteric Integrase Inhibitor Mechanism

    PubMed Central

    Morrison, James H.; Saenz, Dyana T.; Fuchs, James R.; Kvaratskhelia, Mamuka; Ekker, Stephen C.

    2014-01-01

    ABSTRACT HIV-1 utilizes the cellular protein LEDGF/p75 as a chromosome docking and integration cofactor. The LEDGF/p75 gene, PSIP1, is a potential therapeutic target because, like CCR5, depletion of LEDGF/p75 is tolerated well by human CD4+ T cells, and knockout mice have normal immune systems. RNA interference (RNAi) has been useful for studying LEDGF/p75, but the potent cofactor activity of small protein residua can be confounding. Here, in human cells with utility for HIV research (293T and Jurkat), we used transcription activator-like effector nucleases (TALENs) to completely eradicate all LEDGF/p75 expression. We performed two kinds of PSIP1 knockouts: whole-gene deletion and deletion of the integrase binding domain (IBD)-encoding exons. HIV-1 integration was inhibited, and spreading viral replication was severely impaired in PSIP1−/− Jurkat cells infected at high multiplicity. Furthermore, frameshifting the gene in the first coding exon with a single TALEN pair yielded trace LEDGF/p75 levels that were virologically active, affirming the cofactor's potency and the value of definitive gene or IBD exon segment deletion. Some recent studies have suggested that LEDGF/p75 may participate in HIV-1 assembly. However, we determined that assembly of infectious viral particles is normal in PSIP1−/− cells. The potency of an allosteric integrase inhibitor, ALLINI-2, for rendering produced virions noninfectious was also unaffected by total eradication of cellular LEDGF/p75. We conclude that HIV-1 particle assembly and the main ALLINI mechanism are LEDGF/p75 independent. The block to HIV-1 propagation in PSIP1−/− human CD4+ T cells raises the possibility of gene targeting PSIP1 combinatorially with CCR5 for HIV-1 cure. IMPORTANCE LEDGF/p75 dependence is universally conserved in the retroviral genus Lentivirus. Once inside the nucleus, lentiviral preintegration complexes are thought to attach to the chromosome when integrase binds to LEDGF/p75. This tethering

  3. Comparison of the Cepheid GeneXpert and Abbott M2000 HIV-1 real time molecular assays for monitoring HIV-1 viral load and detecting HIV-1 infection.

    PubMed

    Ceffa, Susanna; Luhanga, Richard; Andreotti, Mauro; Brambilla, Davide; Erba, Fulvio; Jere, Haswel; Mancinelli, Sandro; Giuliano, Marina; Palombi, Leonardo; Marazzi, Maria Cristina

    2016-03-01

    Assessing treatment efficacy and early infant diagnosis (EID) are critical issues in HIV disease management. Point-of-care assays may greatly increase the possibility to access laboratory monitoring also in rural areas. Recently two new laboratory tests have been developed by Cepheid (Sunnyvale, California) the Xpert HIV-1 Viral Load for viral load determination and the Xpert HIV-1 Qualitative for early infant diagnosis. We conducted a study in Blantyre, Malawi, comparing the 2 methods versus the Abbott real time quantitative and qualitative assays, for viral load and EID respectively. We tested 300 plasma samples for viral load determination and 200 samples for infant diagnosis. HIV-1 RNA values of the 274 samples quantified by both assays were highly correlated (Pearson r=0.95, R(2)=0.90). In 90.9% of the cases the two methods were concordant in defining the HIV-1 RNA levels as detectable or undetectable. For EID, the Xpert HIV-1 Qualitative assay yielded the same identical results as the Abbott assay. Both the quantitative and the qualitative Xpert assays are promising tools to monitor treatment efficacy in HIV patients receiving treatment and for early diagnosis in HIV-exposed infants. PMID:26709099

  4. 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

  5. Reporting therapeutic discourse in a therapeutic community.

    PubMed

    Chapman, G E

    1988-03-01

    Research in nurses' communications has concentrated on nurse to patient interactions. Those few studies which focus on nurse to nurse communications seem to be generated by a pragmatic and normative concern with effective information sharing. In this paper, which describes one aspect of a larger case study of a hospital-based therapeutic community, the description and analysis of nurses' reports flows not from a normative model of professional practice, but rather an exploration of how professional practice is articulated as discourse in nurses' written accounts. Foucault's ideas about therapeutic discourse inform the theoretical framework of the research. Ethnomethodological concerns with the importance of documentary analysis provide the methodological rationale for examining nurses' 24-hour report documents, as official discourse, reflecting therapeutic practice in this setting. A content analysis of nurses' reports, collected over a period of 4 months, demonstrated the importance of domesticity and ordinary everyday activities in nurses' accounts of hospital life. Disruption to the 'life as usual' domesticity in the community seemed to be associated with admission to and discharge from the hospital when interpersonal and interactional changes between patients occur. It is suggested that nurses in general hospital wards and more orthodox psychiatric settings might usefully consider the impact of admissions and discharges on the group of patients they manage, and make this a discursive focus of their work. PMID:3372900

  6. Therapeutics in Huntington's Disease.

    PubMed

    Killoran, Annie; Biglan, Kevin M

    2012-02-01

    OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there

  7. ORTHOPEDIC COMPLICATIONS IN HIV PATIENTS

    PubMed Central

    Lima, Ana Lúcia Lei Munhoz; Godoy, Alexandre Leme; Oliveira, Priscila Rosalba Domingos; Gobbi, Ricardo Gomes; de Almeida Silva, Camila; Martino, Patricia Bernardelli; Gutierrez, Eliana Bataggia; Gianna, Maria Clara; Camanho, Gilberto Luis

    2015-01-01

    The considerable increase of the life expectancy of HIV-infected patients in the age of highly-powerful antiretroviral treatment results in important metabolic and bone-joint changes resulting from a long-lasting viral infection time and from this treatment. The most common orthopaedic complications are bone mineralization changes, osteonecrosis, carpal tunnel syndrome and gleno-humeral adhesive capsulitis, with different clinical presentation features, natural disease progression and therapeutic response compared to the overall population. Literature reports are initial, and the experience of the multidisciplinary service of the University of Sao Paulo's Institute of Orthopaedics and Traumatology enables us a more indepth knowledge about the various pathologies involved and the development of treatment protocols that are appropriate to these diagnoses. PMID:27004170

  8. [Current therapeutics in infectious dermatology].

    PubMed

    Lascaux, A S; Chosidow, O

    NEW AGENTS: Among new treatments used for infectious dermatology diseases, new agents for genital herpes, valaciclovir and famciclovir, have greatly simplified therapeutic schemes. Cidofovir has also been shown to be effective against aciclovir-resistant cutaneous and mucosal herpetic lesions and for the treatment of molluscum contagiosum. NEW ADMINISTRATION ROUTES: For genital papillomavirus infections, trials using systemic or intralesional administered interferon have not provided conclusive evidence but imiquimode appears to be quite promising. Itaconazole and fluconazole are effective for onchomycoses. NEW POSSIBILITIES: Ivermectine is effective against scabies, but must be reserved for particularly severe forms. Finally, the emergence of Neisseria gonorrhoeae strains resistant to fluoroquinolones is disquieting. PMID:10874915

  9. Hospital treatment of HIV patients.

    PubMed

    Ola, Samuel Olawale

    2006-12-01

    Treatment of patients with HIV/AIDS in Nigeria has progressed from the stage of inactivity, unconcern, abandonment and neglect to the present stage of holistic care involving treatment of the infection with Highly Active Anti Retroviral Agents, complications of the disease and side effects of antiretroviral therapy as well as that of human behavioural responses towards the disease with hope and promising outcome. The goal of the treatment is to prolong the patient's life while maintaining the best possible quality of health and life. It is now a continuum of care between the hospital and the different sectors of the community. Hospital treatment of patients with HIV-AIDS is complex and yet a simple task if there is healthy interaction of the patients and health care providers in a milieu of well equipped hospital setting with available treatment facilities for proper management of diseases. Similarly, for the care to achieve its goal, it requires a joint participation of the community and the commitment of the government not only on curtailment of the reservoir of HIV infection by antiretroviral therapy but total eradication of diseases, poverty and ignorance in all its entirety. PMID:18050774

  10. Genetic therapy for HIV/AIDS.

    PubMed

    Poluri, Ananthalakshmi; van Maanen, Marc; Sutton, Richard E

    2003-09-01

    Despite the tremendous success of highly active antiretroviral treatment (HAART) introduced nearly 8 years ago for the treatment of human immunodeficiency virus (HIV), innovative therapies, including gene transfer approaches, are still required for nearly half of the general patient population. A number of potential gene therapeutic targets for HIV have been identified and include both viral and cellular genes essential for viral replication. The diverse methods used to inhibit viral replication comprise RNA-based strategies such as ribozymes, RNA decoys, antisense messenger RNAs and small interfering RNA (siRNA) molecules. Other potential anti-HIV genes include dominant negative viral proteins, intracellular antibodies, intrakines and suicide genes, all of which have had a modicum of success in vitro. Cellular targets include CD4+ T cells, macrophages and their progenitors. The greatest gene transfer efficiency has been achieved using retroviral or, more recently, lentiviral vectors. A limited number of Phase I clinical trials suggest that the general method is safe. It is proposed that a national network for HIV gene therapy (similar to the AIDS Clinical Trial Groups) may be the best way to determine which approaches should proceed clinically.

  11. Ethical issues in HIV/AIDS research.

    PubMed

    Muthuswamy, Vasantha

    2005-04-01

    Globally the HIV/AIDS epidemic has presented unique health challenges to populations, including a host of ethical and moral issues related to human life and dignity. The disease has most affected the vulnerable groups of people in the world often leading to stigma and discrimination. Currently the critical areas of concern include access to treatment and developing newer, more effective therapeutic and prevention methods while taking care of ethical values in health care and research. The ethical issues mainly revolve around the standard of care, informed consent across cultures, privacy and confidentiality, stigma and discrimination, protection of vulnerable groups, community consultation, ethical review mechanisms, international collaboration, epidemiological studies, clinical trials and also sociobehavioural studies on HIV/AIDS. In addition major concerns are raised regarding HIV/AIDS vaccine trials, microbicidal trials as well as prevention of parent-to-child transmission (PPTCT) trials especially in resource-poor countries. For international collaborative research appropriate standard of care, community benefits, and host country needs must be kept in mind. Improving our understanding of the various ethical and societal concerns related to HIV/AIDS treatment and research would help in development of appropriate policies for disease control and prevention.

  12. 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

  13. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

    In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

  14. Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children.

    PubMed Central

    Matt, C.; Roger, M.

    2001-01-01

    It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis. PMID:11778647

  15. Maternal HIV disclosure to HIV-uninfected children in rural South Africa: a pilot study of a family-based intervention

    PubMed Central

    2013-01-01

    Background As access to treatment increases, large numbers of HIV-positive parents are raising HIV-negative children. Maternal HIV disclosure has been shown to have benefits for mothers and children, however, disclosure rates remain low with between 30-45% of mothers reporting HIV disclosure to their children in both observational and intervention studies. Disclosure of HIV status by parent to an HIV-uninfected child is a complex and challenging psychological and social process. No intervention studies have been designed and tested in Southern Africa to support HIV-positive parents to disclose their status, despite this region being one of the most heavily affected by the HIV epidemic. Method This paper describes the development of a family-centred, structured intervention to support mothers to disclose their HIV status to their HIV-negative school-aged children in rural South Africa, an area with high HIV prevalence. The intervention package includes printed materials, therapeutic tools and child-friendly activities and games to support age-appropriate maternal HIV disclosure, and has three main aims: (1) to benefit family relationships by increasing maternal HIV disclosure; (2) to increase children’s knowledge about HIV and health; (3) to improve the quality of custody planning for children with HIV-positive mothers. We provide the theoretical framework for the intervention design and report the results of a small pilot study undertaken to test its acceptability in the local context. Results The intervention was piloted with 24 Zulu families, all mothers were HIV-positive and had an HIV-negative child aged 6–9 years. Lay counsellors delivered the six session intervention over a six to eight week period. Qualitative data were collected on the acceptability, feasibility and the effectiveness of the intervention in increasing disclosure, health promotion and custody planning. All mothers disclosed something to their children: 11/24 disclosed fully using the

  16. HIV/AIDS, peacekeeping and conflict crises in Africa.

    PubMed

    Tripodi, Paolo; Patel, Preeti

    2004-01-01

    This article investigates the impact of the spread of HIV/AIDS on the African military and its ability to act as an effective instrument of conflict resolution in the continent. The capacity of African militaries is particularly important at a time when major powers are reluctant to engage in greater peacekeeping operations in the region. The widespread prevalence of HIV among military personnel threatens political and social stability more generally, and this study focuses on the link between peacekeeping and the disease. It considers how HIV-positive soldiers act as a vector in communities where they are deployed, and how soldiers deployed in locations with a high prevalence rate of HIV/AIDS may spread the disease in their home communities upon return. Possible recommendations on how to tackle HIV/AIDS prevention efforts with the aid of peacekeepers are offered. PMID:15508885

  17. The church and paediatric HIV care in rural South Africa: a qualitative study.

    PubMed

    Norder, Wilma A J; Peters, Remco P H; Kok, Maarten O; van Elsland, Sabine L; Struthers, Helen E; Tutu, Mpho A; van Furth, A Marceline

    2015-01-01

    Religion has substantial - positive and negative - influence on South Africa's HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences of various stakeholders including religious leaders, healthcare workers and people infected/affected with/by HIV were investigated through participant observation, semi-structured interviews and focus group discussions. During the research the original focus on paediatric HIV care shifted to HIV care in general in reaction to participant responses. Participants identified three main barriers to positive church engagement in HIV care: (a) stigma and disclosure; (b) sexual associations with HIV and (c) religious beliefs and practices. All participant groups appreciated the opportunity and relevance of strengthening church involvement in HIV care. Opportunities for positive church engagement in HIV care that participants identified included: (a) comprehensive and holistic HIV care when churches and clinics collaborate; (b) the wide social reach of churches and (c) the safety and acceptance in churches. Findings indicate that despite barriers great potential exists for increased positive church engagement in HIV care in rural South Africa. Recommendations include increased medical knowledge and dialogue on HIV/AIDS within church settings, and increased collaboration between churches and the medical sector. PMID:26679269

  18. Early-developed hand osteoarthritis in treated HIV-positive patients: Four cases.

    PubMed

    Larcher, Romaric; Mauboussin, Jean-Marc; Rouanet, Isabelle; Sotto, Albert

    2015-10-01

    We describe four cases of hand osteoarthritis in patients with HIV infection under antiretroviral treatment. A 36-year-old HIV-infected man came for consultation in 2007 with hand osteoarthritis. He was diagnosed HIV positive by sexual transmission in 1997. A 52-year-old HIV-infected woman came for consultation with hand osteoarthritis started in 2006. She was diagnosed HIV positive in 1986 by sexual transmission. A 57-year-old man presented hand osteoarthritis. This former IV drug user was diagnosed HIV positive in 1989. A 61-year-old HIV-infected man presented with hand osteoarthritis started in 2010. He had been contaminated with HIV in 1990 by sexual transmission. For all patients, there were neither clinical nor biological manifestations suggesting inflammatory arthritis. X-rays showed signs of hand osteoarthritis. CD4 cell count was over 500/mm(3) and the viral load was below 20 copies/mL under treatments. These four cases show osteoarthritis in HIV-infected patients. Hand osteoarthritis did not seem to be linked to aging or to an antiretroviral treatment's side effect, but rather to the HIV infection itself, and it may pass through a metabolic syndrome. We described a possible association between early-developed hand osteoarthritis and HIV-infected patients. Clinicians should consider osteoarthritis when they are confronted with HIV-infected patients with chronic hand pain.

  19. Engineering antibody therapeutics.

    PubMed

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  20. Testing (HIV). Quick test receives Singapore approval.

    PubMed

    1996-04-22

    Hema-Strip HIV 1/2 is a rapid HIV antibody immunoassay developed by Saliva Diagnostic Systems, Inc. (SDS) which can be used by anyone who can read the product insert. The test kit is comprised of a small lancet for a finger stick, a cylindrical tube with a capillary tip and a SDS diagnostic strip inside, and a vial of buffer. Once blood is drawn by the lancet, the capillary tip is placed upon the blood droplet and the blood is automatically drawn into the tube. The tube is then inserted tip first into the vial of buffer. The buffer and blood migrate over the diagnostic strip inside, yielding stable results within 15 minutes. Studies have found Hema-Strip HIV 1/2 to have a sensitivity and specificity greater than 99.4%, as accurate as most conventional HIV tests which require the use of laboratory equipment and trained staff, and possibly hours to produce results. Moreover, the test kit requires neither refrigeration nor special storage. Hema-Strip HIV 1/2 has received a certificate of free sale from the Ministry of Health in Singapore and is now being submitted for regulatory approval in Brazil, China, Russia, India, Malaysia, Thailand, and the UK. SDS products in production include Sero-Strip HIV 1/2, a rapid serum-based HIV antibody test; Omni-SAL, a saliva collector which is the principal sample collection device used by British insurance companies for HIV testing with other confirmatory tests; Omni-Swab, a serrated swab which collects body fluids or cells; Saliva-Sampler, a saliva collection device used for general testing purposes; and Saliva Check, a test which checks the composition of saliva samples. SDS is in the final stages of developing Saliva-Strip HIV-1/2, a rapid saliva-based HIV antibody test. The company also intends to complete development in 1996 of a rapid blood-based antibody test for the Helicobacter pylori bacteria, a pathogen linked to 80% of peptic ulcers and gastric cancers. PMID:12290908

  1. Eosinophilic pustular folliculitis: A published work-based comprehensive analysis of therapeutic responsiveness.

    PubMed

    Nomura, Takashi; Katoh, Mayumi; Yamamoto, Yosuke; Miyachi, Yoshiki; Kabashima, Kenji

    2016-08-01

    Eosinophilic pustular folliculitis (EPF) is a non-infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression-associated EPF, which is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non-HIV and infancy-associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non-HIV and infancy-associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei-to (a Chinese-Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin-resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.

  2. Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study.

    PubMed

    Papuchon, Jennifer; Pinson, Patricia; Guidicelli, Gwenda-Line; Bellecave, Pantxika; Thomas, Réjean; LeBlanc, Roger; Reigadas, Sandrine; Taupin, Jean-Luc; Baril, Jean Guy; Routy, Jean Pierre; Wainberg, Mark; Fleury, Hervé

    2014-01-01

    In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013) showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2) and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.

  3. ["Emerging infectious diseases". Dengue-fever, West-Nile-fever, SARS, avian influenza, HIV].

    PubMed

    Haas, W; Krause, G; Marcus, U; Stark, K; Ammon, A; Burger, R

    2004-06-01

    Some emerging infectious diseases have recently become endemic in Germany. Others remain confined to specific regions in the world. Physicians notice them only when travelers after infection in endemic areas present themselves with symptoms. Several of these emerging infections will be explained. HIV is an example for an imported pathogen which has become endemic in Germany. SARS and avian influenza are zoonoses with the potential to spread from person to person. Avian influenza in humans provides a possibility for the reassortment of a potential new pandemic strain. Outbreaks of dengue fever in endemic areas are reflected in increased infections in travelers returning from these areas. Currently, West-Nile-virus infections are only imported into Germany. The timely implementation of diagnostic, therapeutic and infection control measures requires physicians to include these diseases in their differential diagnosis. To achieve this goal, good cooperation between physicians, laboratories and the public health service is essential.

  4. 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 ...

  5. 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

  6. 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

  7. Are therapeutic communities therapeutic for women?

    PubMed Central

    Eliason, Michele J

    2006-01-01

    This paper addresses the growing phenomena of therapeutic community (TC) treatment approaches for women in correctional settings. Although rapidly increasing in number across the country, there is very little empirical research to support the effectiveness of TC treatment for women. Therefore, the literature on the efficacy and effectiveness of TC treatment for women is reviewed in relation to the literature on women's treatment issues. The literature review highlights the gaps where TC treatment ignores or exacerbates issues that are common to addicted women, or uses methods that may be contradictory to women's recovery. PMID:16722560

  8. Evaluation of Immune Survival Factors in Pediatric HIV-1 Infection

    PubMed Central

    SHEARER, WILLIAM T.; EASLEY, KIRK A.; GOLDFARB, JOHANNA; JENSON, HAL B.; ROSENBLATT, HOWARD M.; KOVACS, ANDREA; MCINTOSH, KENNETH

    2015-01-01

    Peripheral blood CD4+ and CD8+ T cells, CD19+/20+ B cells, and serum immunoglobulins (Igs) have been implicated as survival factors for pediatric HIV-1 infection. To determine which of these immune factors might be important in predicting survival, we studied HIV-1 vertically infected (HIV-1+) children over a 5-year period. Peripheral blood lymphocytes and Igs were measured in 298 HIV-1+ children, who were classified as survivors or nonsurvivors, and in 463 HIV-1 vertically exposed and noninfected (HIV-1–) children. Measurements of other possible survival factors were included in this study: albumin, hemoglobin, lactic dehydrogenase (LDH), and HIV-1 RNA levels. Survivors had significantly higher CD4+ T-cell, CD8+ T-cell, and CD19+/CD20+ B-cell counts and serum IgG levels, but lower serum IgA and IgM levels than nonsurvivors. Serum albumin and blood hemoglobin levels were higher, but serum LDH and HIV-1 RNA levels were lower in the survivors compared to non-survivors. In univariable analysis, factors affecting survival were baseline CD4+ T-cell and CD8+ T-cell counts, IgG, albumin, hemoglobin, LDH, and HIV-1 RNA (all p < 0.001). In multivariable analysis, high baseline CD4+ T-cell count, IgG and albumin levels, and low baseline HIV-1 RNA load remained important factors for survival. Serum IgG level has been identified as an immune factor that independently predicts survival, in addition to the already established CD4+ T-cell count. The HIV-1 RNA and serum albumin levels also predicted survival. PMID:11144332

  9. HIV-1 infection may be on the rise in Peru.

    PubMed

    The results of a national survey have indicated that "... HIV-1 infection is epidemic in Peru among groups at high risk of sexually and parenterally transmitted diseases," a multicenter group reported (AIDS 1996; 10: 1141-1145). Although the risk of infection appears to be very low in the general population, it may possibly be increasing, according to Dr. Michael C. McCarthy, US National Naval Medical Center in Bethesda, Maryland. McCarthy's group evaluated over 140,000 serum samples for antibodies to HIV-1 between January 1986 and December 1990 in Peru. HIV-1 antibody was detected in 26% of samples from homosexual men, 10% of samples from male sexually transmitted disease patients, and 13% of samples from drug users. 10% of the samples from hemophiliacs and unlicensed female prostitutes were positive for antibodies to HIV-1. In general, he concluded that the patterns of the HIV-1 epidemic in Peru are similar to those seen in Brazil and "... are also similar to initial transmission patterns of HIV-1 infection of North America." However, McCarthy also noted a substantial increase in the prevalence of HIV-1 infection between the beginning and the end of the survey period. Although there was a low prevalence of HIV-1 infection among military personnel and among women seen at prenatal clinics, a "low but rising prevalence of HIV-1 antibody" among military personnel points to a potential increase in the general population. "The fact that many HIV-1 antibody-positive men were married and reported bisexual behavior (28%) highlights the potential of this group to transmit HIV-1 to female partners," he added.

  10. Bioengineering Beige Adipose Tissue Therapeutics.

    PubMed

    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

  11. Bioengineering Beige Adipose Tissue Therapeutics.

    PubMed

    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

  12. 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

  13. CD4 immunophenotyping in HIV infection

    PubMed Central

    Barnett, David; Walker, Brooke; Landay, Alan; Denny, Thomas N.

    2009-01-01

    The ability to rapidly identify immune cell subsets such as CD4 cells, which became possible around the same time as the onset of the HIV/AIDS pandemic, was one of the greatest advances in clinical and diagnostic immunology. The evolution of this global pandemic and the subsequent development of treatment strategies to prolong the life of infected individuals mean that it is now more crucial than ever that we develop affordable, reliable and accurate methods for the enumeration of CD4 cells. Here, we provide an overview of the historical developments in CD4 enumeration technologies that are related to HIV infection, and summarize the current technological challenges that must be overcome to meet the needs of those living with HIV infection. PMID:18923413

  14. What Will It Take to Cure HIV?

    PubMed

    Ananworanich, Jintanat

    2015-01-01

    Investigational strategies to attempt HIV cure or remission include very early initiation of antiretroviral therapy to limit the latent HIV reservoir and preinfection vaccination. In the setting of viral suppression, strategies include reactivation of latently infected cells (eg, through "shock" therapy with histone deacetylase inhibitors or other agents); use of broadly neutralizing antibodies, therapeutic vaccines, immunotoxins, or other immune-based therapies to kill latently infected cells; and gene editing to induce target cell resistance (eg, by eliminating the CC chemokine receptor 5 [CCR5] coreceptor). Improved ability to detect and quantify very low levels of virus is needed. This article summarizes a presentation by Jintanat Ananworanich, MD, PhD, at the IAS-USA continuing education program held in New York, New York, in October 2014.

  15. 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

  16. Relationship of ethnicity, age, education, and reading level to speed and executive function among HIV+ and HIV- women: the Women's Interagency HIV Study (WIHS) Neurocognitive Substudy.

    PubMed

    Manly, Jennifer J; Smith, Clifford; Crystal, Howard A; Richardson, Jean; Golub, Elizabeth T; Greenblatt, Ruth; Robison, Esther; Martin, Eileen M; Young, Mary

    2011-10-01

    Use of neuropsychological tests to identify HIV-associated neurocognitive dysfunction must involve normative standards that are well suited to the population of interest. Norms should be based on a population of HIV-uninfected individuals as closely matched to the HIV-infected group as possible and must include examination of the potential effects of demographic factors on test performance. This is the first study to determine the normal range of scores on measures of psychomotor speed and executive function among a large group of ethnically and educationally diverse HIV-uninfected, high-risk women, as well as their HIV-infected counterparts. Participants (n = 1,653) were administered the Trail Making Test Parts A and B (Trails A and Trails B), the Symbol Digit Modalities Test (SDMT), and the Wide Range Achievement Test-3 (WRAT-3). Among HIV-uninfected women, race/ethnicity accounted for almost 5% of the variance in cognitive test performance. The proportions ofvariance in cognitive test performance accounted for by age (13.8%), years of school (4.1%), and WRAT-3 score (11.5%) were each significant, but did not completely account for the effect of race (3%). HIV-infected women obtained lower scores than HIV-uninfected women on time to complete Trails A and B, SDMT total correct, and SDMT incidental recall score, but after adjustment for age, years of education, racial/ethnic classification, and reading level, only the difference on SDMT total correct remained significant. Results highlight the need to adjust for demographic variables when diagnosing cognitive impairment in HIV-infected women. Advantages of demographically adjusted regression equations developed using data from HIV-uninfected women are discussed.

  17. Bone Marrow Gene Therapy for HIV/AIDS.

    PubMed

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-01

    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.

  18. Bone Marrow Gene Therapy for HIV/AIDS.

    PubMed

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-01

    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

  19. In Vitro Reactivation of Replication-Competent and Infectious HIV-1 by Histone Deacetylase Inhibitors

    PubMed Central

    Banga, Riddhima; Procopio, Francesco Andrea; Cavassini, Matthias

    2015-01-01

    ABSTRACT The existence of long-lived HIV-1-infected resting memory CD4 T cells is thought to be the primary obstacle to HIV-1 eradication. In the search for novel therapeutic approaches that may reverse HIV-1 latency, inhibitors of histone deacetylases (HDACis) have been tested to reactivate HIV-1 replication with the objective of rendering HIV-1-infected cells susceptible to elimination either by HIV-specific CD8 T cells or through virus-mediated cytopathicity. In the present study, we evaluated the efficiency of HDACis to reactivate HIV-1 replication from resting memory CD4 T cells isolated from aviremic long-term-treated HIV-1-infected subjects. We demonstrate that following prolonged/repeated treatment of resting memory CD4 T cells with HDACis, HIV-1 replication may be induced from primary resting memory CD4 T cells isolated from aviremic long-term-treated HIV-1-infected subjects. More importantly, we demonstrate that HIV-1 reactivated in the cell cultures was not only replication competent but also infectious. Interestingly, givinostat, an HDACi that has not been investigated in clinical trials, was more efficient than vorinostat, panobinostat, and romidepsin in reversing HIV-1 latency in vitro. Taken together, these results support further evaluation of givinostat as a latency-reversing agent (LRA) in aviremic long-term-treated HIV-1-infected subjects. IMPORTANCE The major barrier to HIV cure is the existence of long-lived latently HIV-1-infected resting memory CD4 T cells. Latently HIV-1-infected CD4 T cells are transcriptionally silent and are therefore not targeted by conventional antiretroviral therapy (ART) or the immune system. In this context, one strategy to target latently infected cells is based on pharmacological molecules that may force the virus to replicate and would therefore render HIV-1-infected cells susceptible to elimination either by HIV-specific CD8 T cells or through virus-mediated cytopathicity. In this context, we developed an

  20. [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