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1

Therapeutic HIV Vaccines What is a vaccine?  

E-print Network

Therapeutic HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate there are currently no vaccines to prevent or treat HIV, researchers are developing and testing potential HIV vaccines. HIV vaccines designed to prevent HIV infection in HIV negative people are called preventive vaccines

Levin, Judith G.

2

Is an HIV vaccine possible?  

PubMed

Although many new prevention modalities that include the use of antiretroviral drugs show promise, there is no question that a global solution to the HIV epidemic will not be economically or logistically feasible without the development of vaccine that provides durable protection. In the best case scenario, the vaccine has to protect against acquisition of infection, likely mediated by Env-specific B-cell responses combined with CD4+ T-cell responses to evoke full maturation and maintenance of protective antibodies. But HIV-specific CD8+ T-cell responses are also likely to be a key element, particularly for those inevitable situations in which full vaccine-induced protection from acquisition is not achieved, in which case durable control of established infection will be required. Although there is reason to be optimistic that an effective HIV vaccine is possible, one of the major constraints moving forward will likely be constraint on funding to support a diversity of concepts at a time that the correlates of protection from acquisition and disease progression are still unknown. Given the scope of the epidemic and the economic climate, we must strive to do much more with less and seek to access additional resources, both scientific and monetary, from every possible source. PMID:22772390

McElrath, M Juliana; Walker, Bruce D

2012-08-01

3

[Therapeutic possibilities after traumatic experiences].  

PubMed

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 acute crisis. In early interventions, substances blocking the norepinephric hyperactivity seem to be promising alternatives. Stress doses of hydrocortisone may be considered as an experimental pharmacological strategy so far. PMID:19011595

Kapfhammer, Hans-Peter

2008-12-01

4

Pharmacokinetic Enhancers in HIV Therapeutics.  

PubMed

Maximal and durable viral load suppression is one of the most important goals of HIV therapy and is directly related to adequate drug exposure. Protease inhibitors (PIs), an important component of the antiretroviral armada, were historically associated with poor oral bioavailability and high pill burden. However, because the PIs are metabolized by cytochrome P450 (CYP) 3A enzymes, intentional inhibition of these enzymes leads to higher drug exposure, lower pill burden, and therefore simplified dosing schedules with this class of drug. This is the basis of pharmacokinetic enhancement. In HIV therapy, two pharmacokinetic enhancers or boosting agents are used: ritonavir and cobicistat. Both agents inhibit CYP3A4, with cobicistat being a more specific CYP inhibitor than ritonavir. Unlike ritonavir, cobicistat does not have antiretroviral activity. Cobicistat has been evaluated in clinical trials and was recently approved in the USA as a fixed-dose combination with the integrase inhibitor, elvitegravir and two nucleos(t)ide analogs. Additional studies are examining cobicistat in fixed-dose combinations with various PIs. In this review, we summarize current knowledge of these agents and clinically relevant drug regimens and ongoing trials. Studies with elvitegravir and the novel PI TMC319011 are also discussed. PMID:25164142

Larson, Kajal B; Wang, Kun; Delille, Cecile; Otofokun, Igho; Acosta, Edward P

2014-10-01

5

Personalized Therapeutics: HIV Treatment in Adolescents  

PubMed Central

Adolescents infected with human immunodeficiency virus (HIV) represent a heterogeneous group of pubertal children and young adults. Antiretroviral therapy (ART) in adolescents is complex and depends on multiple factors. The continued use of higher (weight- or surface-based) pediatric doses can result in potentially toxic drug exposure, whereas early introduction of lower adult doses can lead to the development of drug resistance and virologic failure. The physiological and psychosocial changes during puberty create strong grounds for an individualized therapeutic approach in HIV-infected adolescents. PMID:18830226

Rakhmanina, NY; Capparelli, EV; van den Anker, JN

2009-01-01

6

Fighting HIV/AIDS: is success possible?  

PubMed Central

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

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

2001-01-01

7

Transplantation in HIV-infected subjects: is cure possible?  

PubMed

With the advent of effective antiretroviral therapy, the treatment of patients with HIV-related malignancies, especially lymphoma, has greatly improved, yielding results comparable to those seen in patients with lymphoma unrelated to HIV. The platform of transplantation of hematopoietic stem cells has facilitated studies of genetically modified stem cells engineered to express antiretroviral genes to resist infection by the HIV virus, testing the concept that engraftment of these cells will lead to HIV resistance and elimination of the reservoir of virus in the body. Results in patients with HIV and lymphoma have now led to studies that will test these principles in HIV patients without concomitant malignancy. In addition, in a patient with HIV and acute myeloid leukemia, the success of an allogeneic transplantation from an unrelated donor carrying a mutation in the CCR5 genes has demonstrated that, in principle, such an approach could also lead to cure of patients with HIV. Case studies in HIV patients with leukemia undergoing allogeneic transplantation also suggest that there may be a therapeutic effect on the HIV reservoir that could alter the natural history of HIV in the allogeneic setting. PMID:24319209

Zaia, John A; Forman, Stephen J

2013-01-01

8

Erythema nodosum leprosum and HIV infection: A therapeutic experience.  

PubMed

The relationship between leprosy and HIV infection is not yet fully understood, as not much is known about the natural history of the co-infected patients. The matter has become more confusing because of conflicting reports. Type-1 lepra reactions and neuritis appear to be severe and more frequent among them. But erythema nodosum leprosum too is not as uncommon among these patients as it was once thought. Management of these co-infected patients is often difficult for want of clear-cut guidelines on clinical care. We report here our experience of treating recurrent, severe erythema nodosum leprosum in a patient concurrently having leprosy and HIV infection. Early institution of antiretroviral therapy appears to provide an edge in improving the therapeutic outcome for him. It also suggests a direct and more complex interplay of HIV and Mycobacterium leprae infection. PMID:16830640

Sharma, Nand Lal; Mahajan, Vikram K; Sharma, Vikas C; Sarin, Sandip; Sharma, Ramesh Chander

2005-09-01

9

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

PubMed Central

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

Engelman, Alan; Cherepanov, Peter

2013-01-01

10

Fighting HIV\\/AIDS: is success possible?  

Microsoft Academic Search

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

Sam Okware; Alex Opio; Joshua Musinguzi; Paul Waibale

11

Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges  

PubMed Central

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

Nissapatorn, Veeranoot; Sawangjaroen, Nongyao

2011-01-01

12

Affect regulation and HIV risk among youth in therapeutic schools  

PubMed Central

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

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

2012-01-01

13

Pancreatic insufficiency in HIV: is it possible?  

PubMed

Pancreatic involvement in AIDS is very important and common, but there are few studies in the literature concerning the pancreas in AIDS. Therefore, our research involves an important issue in the pancreatic field. The objective of the study was to evaluate the profile of HIV-infected patients with probable exocrine pancreatic insufficiency and its relation to the degree of human immunodeficiency virus (HIV) infection. This is a cross-sectional study carried out at Faculdade de Medicina do ABC in partnership with the basic health care unit Vila Guiomar in Santo André. We selected 118 individuals divided into four groups (a control group and three other groups composed of AIDS patients, separated according to CD4 levels); participants had an interview, completed a questionnaire, and had laboratory and imaging tests. The only clinical variables with significant differences among the studied groups were the use of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections, the administration of chemoprophylaxis, and weight loss. There were no differences in the amylase, lipase, and steatocrit dosages among the groups. Levels of fecal elastase 1 were lower in the HIV patient groups (2, 3, and 4) when compared with the control group, although all of them showed average levels that were much higher than the cutoff point (200??g/g). Only nonalcoholic individuals showed a relationship between diarrhea and alterations in elastase levels. A relationship between the use of HAART and exocrine pancreatic insufficiency in different phases of HIV infection could not be verified. PMID:23088671

Chehter, Ethel Zimberg; Bacci, Marcelo Rodrigues; Alessi, Ruda; D'Oria, Pedro; Chicoli, Felipe; Salloto, Nicole; Maximiano, Fabio Luiz; Fonseca, Fernando Luiz Afonso

2013-03-01

14

Virus Maturation as a Novel HIV-1 Therapeutic Target  

PubMed Central

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

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

2009-01-01

15

Virus maturation as a new HIV-1 therapeutic target.  

PubMed

Development of novel therapeutic targets against HIV-1 is a high research priority owing to the serious clinical consequences associated with acquisition of resistance to current antiretroviral drugs. The HIV-1 structural protein Gag represents a potential new therapeutic target as it plays a central role in virus particle production yet is not targeted by any of the antiretroviral drugs approved at present. 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 new 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

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

2009-08-01

16

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

PubMed Central

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

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

2014-01-01

17

An HIV-1 Transmission Case Possibly Associated with Manicure Care.  

PubMed

Abstract 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. PMID:25354026

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

2014-11-01

18

Identification of HIV-1 Tat peptides for future therapeutic angiogenesis.  

PubMed

Therapeutic angiogenesis represents a novel approach to treat critical limb ischemia when revascularization is no more an option. The clinical use of the vascular endothelial growth factor is questioned, because of its side effects. This study was designed to identify and characterize human immunodeficiency virus type 1 (HIV-1) Tat-derived peptides based on their pro-angiogenic properties. A series of Tat-derived peptides were synthesized containing mutations in the basic domain. To minimize side effects Tat peptides were selected exerting no effects on the proteasome and on the viability of human umbilical vein endothelial cells (HUVEC). Tatpep5, 15, and 16 increased the endogenous levels of the pro-angiogenic transcription factors c-Jun and SP-1 as well as the production of the plasminogen activator inhibitor-1 (PAI-1) by HUVEC. A significant induction of endothelial cell invasion was observed upon treatment of HUVEC with Tat peptides. In addition, selected Tat peptides induced tube formation by HUVEC as visualized and quantified in a Matrigel matrix. Our data demonstrate that the selected Tat peptides fulfill essential criteria for pro-angiogenic substances. They represent the basis for the development of novel pro-angiogenic drugs for future therapeutic angiogenesis, which might be applied for treatment of unreconstructible critical limb ischemia. PMID:16800839

Ismail, Mahmoud; Henklein, Peter; Huang, Xiaohua; Braumann, Chris; Rückert, Ralph I; Dubiel, Wolfgang

2006-08-01

19

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

E-print Network

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

Batzoglou, Serafim

20

HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention  

Microsoft Academic Search

Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action. The compounds exhibit potent

Wade S. Blair; Chris Pickford; Stephen L. Irving; David G. Brown; Marie Anderson; Richard Bazin; Joan Cao; Giuseppe Ciaramella; Jason Isaacson; Lynn Jackson; Rachael Hunt; Anne Kjerrstrom; James A. Nieman; Amy K. Patick; Manos Perros; Andrew D. Scott; Kevin Whitby; Hua Wu; Scott L. Butler

2010-01-01

21

HIV-Associated Neurocognitive Disorder: Pathogenesis and Therapeutic Opportunities  

PubMed Central

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

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

2010-01-01

22

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

PubMed Central

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

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

2013-01-01

23

Can therapeutic drug monitoring improve pharmacotherapy of HIV infection in adolescents?  

PubMed

Currently, therapeutic drug monitoring (TDM) of antiretroviral therapy (ART) is not performed in the United States as part of routine clinical care of an HIV-infected adolescent patient. TDM is recommended to rule out subtherapeutic drug concentrations and to differentiate among malabsorption, drug interactions, poor adherence, or increased drug metabolism or clearance as possible causes of decreased drug exposure. The use of TDM is also considered to assist in finding the optimal dose of a drug in patients whose virus has shown reduced susceptibility to that drug. The dosing of antiretroviral (ARV) drugs in adolescent patients with HIV infection depends on the chronologic age, weight, height, and the stage of sexual maturation. As a result of the limited data on the pharmacokinetics of ART during puberty, the transition of a dosing regimen from higher pediatric (weight and surface-based) to adult (fixed) range is not well defined. Developmental pharmacokinetic differences contribute to high variability in pediatric and adolescent patients and an increased frequency of suboptimal ARV exposure as compared to in adults. Individualized, concentration-targeted optimal dosing of ARV medications can be beneficial to patients for whom only limited dosing guidelines are available. This article describes three cases of the application of TDM in treatment-experienced adolescent patients whose ART was optimized using ARV TDM. TDM of ARV drugs is useful in managing the pharmacotherapy of HIV in adolescent patients and is well received by the adolescent patients with HIV and their families. Among others, the benefits of TDM provide evidence for adherence interventions and create grounds for enhanced education of the adolescent patient and involved adult caregivers about ART. Finally, TDM in adolescents provides valuable information about the clinical pharmacology of ART during puberty. PMID:20445485

Rakhmanina, Natella Y; van den Anker, John N; Soldin, Steven J; van Schaik, Ron H; Mordwinkin, Nick; Neely, Michael N

2010-06-01

24

Diacylglycerol kinase as a possible therapeutic target for neuronal diseases  

PubMed Central

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. PMID:24708409

2014-01-01

25

[Therapeutic strategy for chronic myeloid leukemia: possibilities and prospects].  

PubMed

Over the past decade the clinical introduction of agents that directionally blocks the activity of BCR-ABL tumor tyrosine kinase (TK) has changed the prognosis of chronic myeloid leukemia. A significant malignant Ph'-positive clone inhibition and durable remissions have made it possible to increase overall and relapse-free survival. Due to their higher life expectancy, the number of patients is on the increase and their quality of life and working capacity remain good. According to the All-Russian Register of Chronic Myeloid Leukemia, there were more than 6500 cases in the Russian Federation in 2012. Of them, 93.1% were diagnosed with the chronic phase of the disease, 6.4 and 0.4% with its accelerated phase and blast crisis, respectively. Among the BCR-ABL TK inhibitors (TKI) registered in the Russian Federation and recommended for the treatment of chronic myeloid leukemia, there are 3 medications: imatinib, nilotinib, and dasatinib. The efficiency and safety of TKI therapy have been well studied. The most important principle of treatment is to permanently affect the Ph'-positive tumor cell clone by the long-term daily use of TKls. Regular cytogenetic and molecular genetic monitoring allows adequate estimation of the leukemic clone volume and it is essential in evaluating the therapeutic effectiveness. To choose a TKI for each specific patient with regard for its best tolerability and maximum efficiency permits individualized treatment. The prospect of therapy discontinuation can be discussed only in individual patients with a durable and stable complete molecular response and only within clinical trials. PMID:24137941

Turkina, A G; Chelysheva, E Iu

2013-01-01

26

HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.  

PubMed

The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication. PMID:24840331

Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

2014-07-01

27

Small molecules anti-HIV therapeutics targeting CXCR4.  

PubMed

HIV cellular entry is a multistep process that requires the interaction of a viral envelope glycoprotein (gp120) and a host receptor (CD4) followed by binding to a co-receptor. The CC-chemokine receptor 5 (CCR5) and CXC-chemokine receptor 4 (CXCR4) have been identified as the major HIV co-receptors and therefore are promising targets for the development of new anti-HIV drugs. CXCR4 is also involved in several diseases such as angiogenesis, metabolic and neurological disorders, rheumatoid arthritis and in different forms of metastatic cancer. Herein, we present a review focusing on small molecule CXCR4 antagonists. These compounds are divided into 11 classes that include cyclic penta- and tetrapeptides, diketopiperazine mimetics, bicyclams, non-bicyclams, tetrahydroquinolines, thiazolylisothiourea derivatives, benzodiazepines, alkyl amine analogs and non-peptides derivatives, dipicolylamine-zinc(II) complexes, ampelopsin and distamycin analogs. The most advanced CXCR4 antagonists documented are bicyclam derivatives, which are specific CXCR4 antagonists and exhibit potency in the nanomolar range. Further development of selective CXCR4 antagonists continues to be crucial for the design of second generation of anti-HIV drugs. We aim to provide a comprehensive summary of diverse structural templates that could be useful for optimization and discovery of novel CXCR4 antagonists. PMID:18289065

Grande, Fedora; Garofalo, Antonio; Neamati, Nouri

2008-01-01

28

Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges.  

PubMed

The incidence of AIDS-defining cancers (ADCs) - Kaposi sarcoma, primary central nervous system lymphoma, non-Hodgkin lymphoma, and cervical cancer - although on the decline since shortly after the introduction of HAART, has continued to be greater even in treated HIV-infected persons than in the general population. Although the survival of newly infected people living with HIV/AIDS now rivals that of the general population, morbidity and mortality associated with non-AIDS-defining cancers (NADCs) such as lung, liver, anal, and melanoma are significant and also continue to rise. Increasing age (i.e. longevity) is the greatest risk factor for NADCs, but longevity alone is not sufficient to fully explain these trends in cancer epidemiology. In this review, we briefly review the epidemiology and etiology of cancers seen in HIV/AIDS, and in this context, discuss preclinical research and broad treatment considerations. Investigation of these considerations provides insight into why malignancies continue to be a major problem in the current era of HIV/AIDS care. PMID:24401642

Rubinstein, Paul G; Aboulafia, David M; Zloza, Andrew

2014-02-20

29

HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention  

PubMed Central

Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action. The compounds exhibit potent antiviral activity against HIV-1 laboratory strains, clinical isolates, and HIV-2, and inhibit both early and late events in the viral replication cycle. We present mechanistic studies indicating that these early and late activities result from the compound affecting viral uncoating and assembly, respectively. We show that amino acid substitutions in the N-terminal domain of HIV-1 CA are sufficient to confer resistance to this class of compounds, identifying CA as the target in infected cells. A high-resolution co-crystal structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the N-terminal domain of the protein. Our data demonstrate that broad-spectrum antiviral activity can be achieved by targeting this new binding site and reveal HIV CA as a tractable drug target for HIV therapy. PMID:21170360

Irving, Stephen L.; Brown, David G.; Anderson, Marie; Bazin, Richard; Cao, Joan; Ciaramella, Giuseppe; Isaacson, Jason; Jackson, Lynn; Hunt, Rachael; Kjerrstrom, Anne; Nieman, James A.; Patick, Amy K.; Perros, Manos; Scott, Andrew D.; Whitby, Kevin; Wu, Hua; Butler, Scott L.

2010-01-01

30

HIV Preclinical–Clinical Therapeutics Research: Central Nervous System Approaches  

Microsoft Academic Search

The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals\\u000a who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that\\u000a are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to\\u000a substantively reduce an individual’s quality of

Kathy L. Kopnisky; Jing Bao

2007-01-01

31

Rational design of highly potent HIV-1 fusion inhibitory proteins: Implication for developing antiviral therapeutics  

SciTech Connect

Recombinant protein containing one heptad-repeat 1 (HR1) segment and one HR2 segment of the HIV-1 gp41 (HR1-HR2) has been shown to fold into thermally stable six-helix bundle, representing the fusogenic core of gp41. In this study, we have used the fusogenic core as a scaffold to design HIV-1 fusion inhibitory proteins by linking another HR1 to the C terminus of HR1-HR2 (HR121) or additional HR2 to the N terminus of HR1-HR2 (HR212). Both recombinant proteins could be abundantly and solubly expressed and easily purified, exhibiting high stability and potent inhibitory activity on HIV-1 fusion with IC{sub 50} values of 16.2 {+-} 2.8 and 2.8 {+-} 0.63 nM, respectively. These suggest that these rationally designed proteins can be further developed as novel anti-HIV-1 therapeutics.

Ni Ling [Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School of the Chinese Academy of Sciences (China); Gao, George F. [Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China)]. E-mail: ggao66@yahoo.com; Tien Po [Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China)]. E-mail: tienpo@sun.im.ac.cn

2005-07-08

32

NTPDase activity in human lymphocytes is not affected by therapeutic doses of anti-HIV drugs.  

PubMed

NTPDase (EC 3.6.1.5) is an enzyme that hydrolyzes extracellular nucleoside tri- and/or diphoshates forming AMP that can serve as a substrate for an ecto-5'-nucleotidase (EC 3.1.3.5) with liberation of adenosine, a modulator of vascular tone and inhibitor of platelet aggregation. These enzymes also occur in lymphocytes playing an important role in immune function. In this study, it was investigated if anti-HIV therapy could affect NTPDase activity in human lymphocytes. Samples of lymphocytes were incubated with different concentrations of anti-HIV drugs and NTPDase activity was determined by colorimetric assay with quantification of inorganic phosphate released. There is not significant difference of NTPDase activity among samples with therapeutic doses of anti-HIV drugs tested when compared with controls. NTPDase activity in peripheral human lymphocytes is not altered by anti-HIV therapy. PMID:21306861

Leal, Daniela B R; Schetinger, Maria R C; Leal, Claudio A M; Bertoncheli, Claudia de M; Morsch, Vera M

2011-12-01

33

Targeting therapeutics to an exposed and conserved binding element of the HIV-1 fusion protein  

PubMed Central

There is an urgent need for new drugs that can kill HIV type 1 (HIV-1)-infected cells. HIV-1 glycoprotein Env, which promotes viral membrane fusion through receptor-mediated conformational changes, is an attractive target for such agents because it is expressed on the surface of both virions and infected cells. Unfortunately, conserved binding elements on this protein frequently are buried under a canopy of flexible, glycosylated peptide loops or exposed only transiently during the fusion process. Here, we investigate the exposure of the C-terminal region of the Env ectodomain outside the context of membrane fusion. This binding element is the target of the 5-Helix protein, a designed entry inhibitor that disrupts conformational changes in Env subunit gp41, essential for the fusion process. We show that 5-Helix is capable of interacting with HIV-1 Env in a receptor-independent fashion and that a chimeric 5-Helix/Pseudomonas exotoxin protein recognizes cells expressing Env from a broad spectrum of HIV-1 strains including primary isolates from clades B, D, E, G, and H. This recombinant toxin selectively kills HIV-1-infected cells and blocks spreading infection while still maintaining potent inhibitory activity against membrane fusion. Our results demonstrate that the C-terminal region of the gp41 ectodomain is an accessible target on HIV-1-infected cells for the development of antiviral therapeutics and neutralizing antibodies. PMID:12702763

Root, Michael J.; Hamer, Dean H.

2003-01-01

34

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

PubMed Central

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

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

2013-01-01

35

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination.  

PubMed

We treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine (REMUNE, HIV-1 Immunogen) in an open label study. We then determined whether baseline parameters, such as CD4 cell count, viral load and IgG levels, were predictive of the magnitude of the HIV-specific lymphocyte proliferative responses (LPRs). We demonstrate herein that there is a significant enhancement from baseline for both HIV and p24 antigen-stimulated LPRs after immunization. Using a responder definition of a stimulation index of >5 on at least two post-immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38 (71%) responded to native p24 antigen. Viral load and total IgG were negatively correlated, while CD4 cell counts were positively associated with the magnitude of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best predictor of HIV antigen LPR post-immunization. PMID:11985528

Moss, R B; Wallace, M R; Steigbigel, R T; Morrison, S A; Giermakowska, W K; Nardo, C J; Diveley, J P; Carlo, D J

2002-05-01

36

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination  

PubMed Central

We treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine (Remune, HIV-1 Immunogen) in an open label study. We then determined whether baseline parameters, such as CD4 cell count, viral load and IgG levels, were predictive of the magnitude of the HIV-specific lymphocyte proliferative responses (LPRs). We demonstrate herein that there is a significant enhancement from baseline for both HIV and p24 antigen-stimulated LPRs after immunization. Using a responder definition of a stimulation index of >5 on at least two post-immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38 (71%) responded to native p24 antigen. Viral load and total IgG were negatively correlated, while CD4 cell counts were positively associated with the magnitude of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best predictor of HIV antigen LPR post-immunization. PMID:11985528

MOSS, R B; WALLACE, M R; STEIGBIGEL, R T; MORRISON, S A; GIERMAKOWSKA, W K; NARDO, C J; DIVELEY, J P; CARLO, D J

2002-01-01

37

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

PubMed

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

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

2013-01-01

38

New diagnostic and therapeutic possibilities for diastolic heart failure  

PubMed Central

Despite the fact that up to half of all heart failure occurs in patients without evidence of systolic cardiac dysfunction, there are no universally accepted diagnostic markers and no approved therapies for heart failure with preserved ejection fraction (HFpEF). HFpEF, otherwise known as diastolic heart failure, has nearly the same grim prognosis as systolic heart failure, and diastolic heart failure is increasing in incidence and prevalence. Major trials have shown that many of the treatments that are salutary in systolic heart failure have no beneficial effects in diastolic heart failure, suggesting different underlying mechanisms for these two disorders. Even criteria for diagnosis of HFpEF are still debated, and there is still no gold standard marker to detect diastolic dysfunction. Here, we will review some promising new insights into the pathogenesis of diastolic dysfunction that may lead to new diagnostic and therapeutic tools. PMID:24494212

Jeong, Euy-Myoung; Dudley, Samuel C.

2014-01-01

39

Targeting nicotine addiction: the possibility of a therapeutic vaccine.  

PubMed

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

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

2011-01-01

40

HIV transmission through breastfeeding: still possible in developed countries.  

PubMed

We describe here the case of a 13-month-old boy who acquired HIV infection postnatally through breastfeeding in a developed country in 2012. His mother had regular pregnancy follow-up and was found to be seronegative for HIV on 2 consecutive screening tests (during pregnancy and just after delivery). However, 1 year later, diagnosis of HIV infection arose in both of them after a pediatric emergency department visit for bronchitis when unexplained hepatosplenomegaly and inflammatory syndrome were noted. The negative maternal viral load found just after delivery confirmed that the mother's seroconversion occurred postnatally, which allowed for active HIV transmission during lactation and lack of the efficient preventive measures that have implemented in Belgium for years. We discuss this uncommon but still existing mode of HIV transmission in industrialized countries and highlight the importance of implementing new targeted health education interventions in addition to constant clinicians' awareness. PMID:25136040

Blumental, Sophie; Ferster, Alina; Van den Wijngaert, Sigi; Lepage, Philippe

2014-09-01

41

Raltegravir: The evidence of its therapeutic value in HIV-1 infection  

PubMed Central

Introduction: The antiretroviral treatment paradigm for human immunodeficiency virus-1 (HIV-1) infection has undergone a significant change with the addition of a new class of therapeutic agents targeting HIV-1 integrase (IN). IN inhibitors prevent the integration of viral DNA into the human genome and terminate the viral life cycle. As the first member of this new class of anti-HIV drugs, raltegravir has shown promising results in the clinic. Aims: To review the emerging evidence for the use of the IN inhibitor raltegravir in the treatment of HIV-1 infection. Evidence review: Strong evidence shows that raltegravir is effective in reducing the viral load to less than 50 copies/mL and increasing CD4 cell count in treatment-experienced patients with triple-drug class-resistant HIV-1 infection. Substantial evidence also indicates that while raltegravir is able to achieve treatment response in patients with drug-resistant HIV-1, it is susceptible to development of resistance. Raltegravir should be used with at least one other active drug. In addition to its use in salvage therapy upon failure of first-line antiretroviral treatment, a raltegravir-based treatment regimen may also be effective as initial therapy. Substantial evidence also shows that raltegravir-based treatment regimen is well tolerated with minimal clinically severe adverse events and toxicities. Modeling studies suggest a cost-effectiveness of US$21,339 per quality-adjusted life year gained with raltegravir use, though further direct evidence on quality of life and cost-effectiveness is needed. Place in therapy: Raltegravir shows significant and sustained virologic and immunologic response in combination with other antiretrovirals in treatment-experienced HIV-1 infected patients who show evidence of viral replication or multidrug-resistant HIV-1 strains, without any significant tolerability issues. PMID:20694070

Ramkumar, Kavya; Neamati, Nouri

2010-01-01

42

Cytokine production and dysregulation in HIV pathogenesis: Lessons for development of therapeutics and vaccines  

PubMed Central

Numerous studies have characterized the cytokine modulation observed in human immunodeficiency virus (HIV) infected individuals, from initial infection through chronic disease. Progressive and non-progressive HIV infection models show the cytokine milieu differs in terms of production and responsiveness in these two groups, suggesting an understanding of the role cytokines play during infection is necessary for directing the immune response toward viral control. This review will cover cytokine induction and dysfunction during HIV pathogenesis, with a focus on the interplay between cytokines and transcription factors, T cell activation, and exhaustion. We highlight cytokines that have either vaccine adjuvant or therapeutic potential and discuss the need to identify key factors required for prevention of progression, clearance of infection, or protection from acquisition. PMID:22743036

Reuter, Morgan A.; Pombo, Carolina; Betts, Michael R.

2012-01-01

43

Therapeutic Drug Monitoring of Indinavir in HIV-Infected Patients Undergoing HAART  

Microsoft Academic Search

Background: Therapeutic drug monitoring (TDM) of protease inhibitors (PI) is gaining increasing importance for the management of HIV-infected\\u000a patients undergoing highly active antiretroviral therapy (HAART). The PI indinavir (IDV) is widely used in HAART regimens.\\u000a Combinations of IDV with ritonavir (RTV) have been used to increase the plasma concentration of IDV. However, the desirable\\u000a IDV concentration range in clinical practice

P. Langmann; M. Zilly; B. Weißbrich; S. Desch; T. Väth; H. Klinker

2002-01-01

44

Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection.  

PubMed

Objective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection. Methods. Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48-72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA. Results. Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy. Conclusions. Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responses in vivo. PMID:22719767

Nowak, Piotr; Abdurahman, Samir; Lindkvist, Annica; Troseid, Marius; Sönnerborg, Anders

2012-01-01

45

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

PubMed

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. PMID:10658583

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

46

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

PubMed Central

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-?B 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

2009-01-01

47

HIV-1 Latency: An Update of Molecular Mechanisms and Therapeutic Strategies  

PubMed Central

The major obstacle towards HIV-1 eradication is the life-long persistence of the virus in reservoirs of latently infected cells. In these cells the proviral DNA is integrated in the host’s genome but it does not actively replicate, becoming invisible to the host immune system and unaffected by existing antiviral drugs. Rebound of viremia and recovery of systemic infection that follows interruption of therapy, necessitates life-long treatments with problems of compliance, toxicity, and untenable costs, especially in developing countries where the infection hits worst. Extensive research efforts have led to the proposal and preliminary testing of several anti-latency compounds, however, overall, eradication strategies have had, so far, limited clinical success while posing several risks for patients. This review will briefly summarize the more recent advances in the elucidation of mechanisms that regulates the establishment/maintenance of latency and therapeutic strategies currently under evaluation in order to eradicate HIV persistence. PMID:24736215

Battistini, Angela; Sgarbanti, Marco

2014-01-01

48

Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys  

PubMed Central

HIV-1-specific monoclonal antibodies (mAbs) with extraordinary potency and breadth have recently been described. In humanized mice, combinations of mAbs have been shown to suppress viremia, but the therapeutic potential of these mAbs has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific mAbs, as well as the single glycan-dependent mAb PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic virus SHIV-SF162P3. A single mAb infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance. Moreover, following mAb administration, host Gag-specific T lymphocyte responses exhibited improved functionality. Virus rebounded in the majority of animals after a median of 56 days when serum mAb titers had declined to undetectable levels, although a subset of animals maintained long-term virologic control in the absence of further mAb infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific mAbs in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of mAb therapy for HIV-1 in humans. PMID:24172905

Barouch, Dan H.; Whitney, James B.; Moldt, Brian; Klein, Florian; Oliveira, Thiago Y.; Liu, Jinyan; Stephenson, Kathryn E.; Chang, Hui-Wen; Shekhar, Karthik; Gupta, Sanjana; Nkolola, Joseph P.; Seaman, Michael S.; Smith, Kaitlin M.; Borducchi, Erica N.; Cabral, Crystal; Smith, Jeffrey Y.; Blackmore, Stephen; Sanisetty, Srisowmya; Perry, James R.; Beck, Matthew; Lewis, Mark G.; Rinaldi, William; Chakraborty, Arup K.; Poignard, Pascal; Nussenzweig, Michel C.; Burton, Dennis R.

2014-01-01

49

Lessons to be Learned from Natural Control of HIV - Future Directions, Therapeutic, and Preventive Implications  

PubMed Central

Accumulating data generated from persons who naturally control HIV without the need for antiretroviral treatment has led to significant insights into the possible mechanisms of durable control of AIDS virus infection. At the center of this control is the HIV-specific CD8 T cell response, and the basis for this CD8-mediated control is gradually being revealed. Genome wide association studies coupled with HLA sequence data implicate the nature of the HLA-viral peptide interaction as the major genetic factor modulating durable control of HIV, but host genetic factors account for only around 20% of the variability in control. Other factors including specific functional characteristics of the TCR clonotypes generated in vivo, targeting of vulnerable regions of the virus that lead to fitness impairing mutations, immune exhaustion, and host restriction factors that limit HIV replication all have been shown to additionally contribute to control. Moreover, emerging data indicate that the CD8+ T cell response may be critical for attempts to purge virus infected cells following activation of the latent reservoir, and thus lessons learned from elite controllers (ECs) are likely to impact the eradication agenda. On-going efforts are also needed to understand and address the role of immune activation in disease progression, as it becomes increasingly clear that durable immune control in ECs comes at a cost. Taken together, the research achievements in the attempt to unlock the mechanisms behind natural control of HIV will continue to be an important source of insights and ideas in the continuous search after an effective HIV vaccine, and for the attempts to achieve a sterilizing or functional cure in HIV positive patients with progressive infection. PMID:23805139

Shasha, David; Walker, Bruce D.

2013-01-01

50

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

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

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

51

Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications  

PubMed Central

Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients. PMID:17183414

Tsiodras, Sotirios; Mantzoros, Christos

2006-01-01

52

Chaperone proteins and brain tumors: Potential targets and possible therapeutics1  

PubMed Central

Chaperone proteins are most notable for the proteo- and cyotoprotective capacities they afford during cellular stress. Under conditions of cellular normalcy, chaperones still play integral roles in the folding of nascent polypeptides into functional entities, in assisting in intracellular/intraorganellar transport, in assembly and maintenance of multi-subunit protein complexes, and in aiding and abetting the degradation of senescent proteins. Tumors frequently have relatively enhanced needs for chaperone number and activity because of the stresses of rapid proliferation, increased metabolism, and overall genetic instability. Thus, it may be possible to take advantage of this reliance that tumor cells have on chaperones by pharmacologic and biologic means. Certain chaperones are abundant in the brain, which implies important roles for them. While it is presumed that the requirements of brain tumors for chaperone proteins are similar to those of any other cell type, tumor or otherwise, very little inquiry has been directed at the possibility of using chaperone proteins as therapeutic targets or even as therapeutic agents against central nervous system malignancies. This review highlights some of the research on the functions of chaperone proteins, on what can be done to modify those functions, and on the physiological responses that tumors and organisms can have to chaperone-targeted or chaperone-based therapies. In particular, this review will also underscore areas of research where brain tumors have been part of the field, although in general those instances are few and far between. This relative dearth of research devoted to chaperone protein targets and therapeutics in brain tumors reveals much untrodden turf to explore for potential treatments of these dreadfully refractive diseases. PMID:16053701

Graner, Michael W.; Bigner, Darell D.

2005-01-01

53

Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir  

PubMed Central

Summary The pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence. PMID:21364060

Caswell, R J; Phillips, D; Chaponda, M; Khoo, S H; Taylor, G P; Ghanem, M; Poulton, M; Welch, J; Gibbons, S; Jackson, V; Lambert, J S

2013-01-01

54

Incomplete Immune Recovery in HIV Infection: Mechanisms, Relevance for Clinical Care, and Possible Solutions  

PubMed Central

Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) usually results in diminished viral replication, increasing CD4+ cell counts, a reversal of most immunological disturbances, and a reduction in risk of morbidity and mortality. However, approximately 20% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution. Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution in HIV infection, including mechanisms, relevance for clinical care, and possible solutions. PMID:22474480

Gaardbo, Julie C.; Hartling, Hans J.; Gerstoft, Jan; Nielsen, Susanne D.

2012-01-01

55

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

ERIC Educational Resources Information Center

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…

Rule, Peter

2011-01-01

56

Immune and genetic mechanisms in COPD: possible targets for therapeutic interventions.  

PubMed

Genetic, immune and environmental interactions are key elements for the development of COPD. Cigarette smoking is considered the primary risk factor initiating inflammatory cascades in genetically susceptible individuals. The "danger signals" elicited by the injured cells of non-specific immunity induce the downstream activation of proinflammatory cascades and antigen-specific adaptive immune responses. The produced oxidative stress further damages the lung leading to acquired genetic changes (histone deacetylation, microsatellite DNA instability, DNA methylation, telomere shortening, miRNA alterations) due to an inefficient DNA repair machinery. On the other hand, augmented apoptosis, impaired efferocytosis and abnormal tissue remodeling contribute to the chronic inflammatory response and tissue destruction in COPD. This review focuses on the role of genetic, epigenetic and immune mechanisms in the development of COPD in order to put forward possible prognostic and therapeutic targets. PMID:23256714

Tzortzaki, Eleni G; Papi, Alberto; Neofytou, Eirini; Soulitzis, Nikolaos; Siafakas, Nikolaos M

2013-02-01

57

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

PubMed Central

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

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

2014-01-01

58

Complex DNA repair pathways as possible therapeutic targets to overcome temozolomide resistance in glioblastoma  

PubMed Central

Many conventional chemotherapeutic drugs exert their cytotoxic function by inducing DNA damage in the tumor cell. Therefore, a cell-inherent DNA repair pathway, which reverses the DNA-damaging effect of the cytotoxic drugs, can mediate therapeutic resistance to chemotherapy. The monofunctional DNA-alkylating agent temozolomide (TMZ) is a commonly used chemotherapeutic drug and the gold standard treatment for glioblastoma (GBM). Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been described as the main modulator to determine the sensitivity of GBM to TMZ, a subset of GBM does not respond despite MGMT inactivation, suggesting that another DNA repair mechanism may also modulate the tolerance to TMZ. Considerable interest has focused on MGMT, mismatch repair (MMR), and the base excision repair (BER) pathway in the mechanism of mediating TMZ resistance, but emerging roles for the DNA strand-break repair pathway have been demonstrated. In the first part of this review article, we briefly review the significant role of MGMT, MMR, and the BER pathway in the tolerance to TMZ; in the last part, we review the recent publications that demonstrate possible roles of DNA strand-break repair pathways, such as single-strand break repair and double-strand break repair, as well as the Fanconi anemia pathway in the repair process after alkylating agent-based therapy. It is possible that all of these repair pathways have a potential to modulate the sensitivity to TMZ and aid in overcoming the therapeutic resistance in the clinic. PMID:23227453

Yoshimoto, Koji; Mizoguchi, Masahiro; Hata, Nobuhiro; Murata, Hideki; Hatae, Ryusuke; Amano, Toshiyuki; Nakamizo, Akira; Sasaki, Tomio

2012-01-01

59

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

PubMed

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

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

2011-06-01

60

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

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.

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

2013-08-15

61

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

PubMed Central

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

Torres, Rebecca A; Lewis, William

2014-01-01

62

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

PubMed

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

Torres, Rebecca A; Lewis, William

2014-02-01

63

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

PubMed Central

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; ?9-tetrahydrocannabinol (?9-THC)) and Sativex (?9-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB2 receptors, and/or (v) adjunctive ‘multi-targeting’. PMID:23108552

Pertwee, Roger G.

2012-01-01

64

Monocyte/macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets?  

PubMed Central

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

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

2014-01-01

65

HIV screening for pregnant women in South Eastern France: evolution 1992–1994–1996  

Microsoft Academic Search

Objectives: To assess the evolution of the HIV screening practices towards pregnant women between 1992 and 1996, in relation with the 1993 French mandatory obligation to offer prenatal HIV testing and recent therapeutic possibilities to reduce HIV vertical transmission. Study design: Three successive surveys (January 1992, May 1994 and May 1996) about HIV screening policies among medical chiefs of all

Dominique Rey; Yolande Obadia; Maria-Patrizia Carrieri; Jean-Paul Moatti

1998-01-01

66

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

E-print Network

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

Barouch, Dan H.

67

Gelsolin Amyloidosis: Genetics, Biochemistry, Pathology and Possible Strategies for Therapeutic Intervention  

PubMed Central

Protein misassembly into aggregate structures, including cross-?-sheet amyloid fibrils, is linked to diseases characterized by the degeneration of post-mitotic tissue. While amyloid fibril deposition in the extracellular space certainly disrupts cellular and tissue architecture late in the course of amyloid diseases, strong genetic, pathological and pharmacologic evidence suggests that the process of amyloid fibril formation itself, known as amyloidogenesis, likely causes these maladies. It seems that the formation of oligomeric aggregates during the amyloidogenesis process causes the proteotoxicity and cytotoxicity characteristic of these disorders. Herein, we review what is known about the genetics, biochemistry and pathology of familial amyloidosis of Finnish Type (FAF) or gelsolin amyloidosis. Briefly, autosomal dominant D187N or D187Y mutations compromise Ca2+ binding in domain 2 of gelsolin, allowing domain 2 to sample unfolded conformations. When domain 2 is unfolded, gelsolin is subject to aberrant furin endoproteolysis as it passes through the Golgi on its way to the extracellular space. The resulting C-terminal 68kDa fragment (C68) is susceptible to extracellular endoproteolytic events, possibly mediated by a matrix metalloprotease, affording 8 and 5 kDa amyloidogenic fragments of gelsolin. These amyloidogenic fragments deposit systemically, causing a variety of symptoms, including corneal lattice dystrophy and neurodegeneration. The first murine model of the disease recapitulates the aberrant processing of mutant plasma gelsolin, amyloid deposition, and the degenerative phenotype. We use what we have learned from our biochemical studies, as well as insight from mouse and human pathology to propose therapeutic strategies that may halt the progression of FAF. PMID:22360545

Solomon, James P.; Page, Lesley J.; Balch, William E.; Kelly, Jeffery W.

2012-01-01

68

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

PubMed Central

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

Katz, Karol; Northrup, Veronika

2013-01-01

69

Do Men who have Sex with Men (MSM) in the United States Understand that HIV Serodiscordance is Possible?  

PubMed Central

Background Little is currently known about the extent to which US MSM understand the possibility that a long-term sex partner can have an HIV status different than one’s own status. This information is important in the adaptation of Couples Voluntary HIV Counseling and Testing (CVCT) for US MSM. Methods 428 US MSM completed an online survey using MySpace.com from March-April, 2009. Results Of 426 MSM with complete data, 21.1% (90) were not definitively aware that serodiscordance is possible. Factors associated with a lack of understanding that serodiscordance is possible were: never having tested for HIV (OR: 2.0; CI: 1.1, 3.8), compared to testing 0-6 months previously and having a high school education or less (OR: 2.2; CI: 1.1, 4.5), compared to men who had completed at least some college. Conclusions A large proportion of young, internet-using MSM in the United States may not understand that HIV serodiscordance is possible within sexual partnerships. Based on these results, we recommend that CVCT provided to male couples in the United States should include education on HIV serodiscordance. PMID:24133557

Wagenaar, Bradley H.; Grabbe, Kristina L.; Stephenson, Rob; Khosropour, Christine M.; Sullivan, Patrick S.

2013-01-01

70

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

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 (? = 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% of HIV-negative children achieved discharge Weight-For-Height (WFH) ? 80% of the NCHS reference median (p = 0.003). Clinical algorithms for diagnosing HIV in SAM children had poor sensitivity and specificity. Conclusion CTC is a potentially valuable entry point for providing HIV testing and care in the community to HIV infected children with SAM. PMID:18671876

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

2008-01-01

71

Therapeutic drug monitoring of HIV-protease inhibitors to assess noncompliance  

Microsoft Academic Search

Summary: Objective: To determine plasma concentration ratio limits (CORALS) for HIV-protease inhibitors outside of which random plasma concentrations reflect partial compliance or noncompliance. In the absence of a gold standard for measuring com- pliance and to avoid complex techniques, measuring plasma concentrations may be an objective and easy way to check noncompliance.

Patricia W. H. Hugen; David M. Burger; Rob E. Aarnoutse; Patricia A. Baede; Pythia T. Nieuwkerk; Peter P. Koopmans; Yechiel A. Hekster

2002-01-01

72

Direct Interaction of Antifungal Azole-Derivatives with Calmodulin: A Possible Mechanism for Their Therapeutic Activity  

Microsoft Academic Search

Azole derivatives, such as ketoconazole and bifonazole, are well-established antifungal drugs. Recently, these compounds have been reported to have therapeutic efficacy also in inflammatory skin disorders. These is increasing evidence that calmodulin is involved in fungal infections as well as in inflammatory skin diseases. Therefore, we investigated the effects of various antifungal drugs on calmodulin activity, using calmodulin-dependent phosphodiesterase as

Lutz Hegemann; Susan M. Toso; Khosrow L Lahijani; Guy F. Webster; Jouni Uitto

1993-01-01

73

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

PubMed Central

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 neurodegenerative diseases and the future promising prospects of using specific HAT based therapeutic approaches. PMID:23543406

Pirooznia, Sheila K.; Elefant, Felice

2013-01-01

74

Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions.  

PubMed

Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection. PMID:15383160

Geisbert, Thomas W; Hensley, Lisa E

2004-09-21

75

The therapeutic implications of timely linkage and early retention in HIV care.  

PubMed

Following HIV diagnosis, linkage to outpatient treatment, antiretroviral initiation, and longitudinal retention in care represent the foundation for successful treatment. While prior studies have evaluated these processes in isolation, a systematic evaluation of successive steps in the same cohort of patients has not yet been performed. To ensure optimal long-term outcomes, a better understanding of the interplay of these processes is needed. Therefore, a retrospective cohort study of patients initiating outpatient care at the University of Alabama at Birmingham 1917 HIV=AIDS Clinic between January 2000 and December 2005 was undertaken. Multivariable models determined factors associated with: late diagnosis=linkage to care (initial CD4 < 350 cells=mm3), timely antiretroviral initiation, and retention across the first two years of care. Delayed linkage was observed in two-thirds of the overall sample (n = 567) and was associated with older age (odds ratio [OR] = 1.31 per 10 years; 95%confidence interval [CI] = 1.06-1.62) and African American race (OR = 2.45; 95% CI = 1.60-3.74). Attending all clinic visits (hazard ratio [HR] = 6.45; 95% CI = 4.47-9.31) and lower initial CD4 counts led to earlier antiretroviral initiation. Worse retention in the first 2 years was associated with younger age (OR = 0.68 per 10 years;95% CI = 0.56-0.83), higher baseline CD4 count, and substance abuse (OR = 1.78; 95% CI = 1.16-2.73). Interventions to improve timely HIV diagnosis and linkage to care should focus on older patients and African Americans while efforts to improve retention should address younger patients, those with higher baseline CD4 counts, and substance abuse. Missed clinic visits represent an important obstacle to the timely initiation of antiretroviral therapy. These data inform development of interventions to improve linkage and retention in HIV care, an emerging area of growing importance. PMID:19055408

Ulett, Kimberly B; Willig, James H; Lin, Hui-Yi; Routman, Justin S; Abroms, Sarah; Allison, Jeroan; Chatham, Ashlee; Raper, James L; Saag, Michael S; Mugavero, Michael J

2009-01-01

76

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

ERIC Educational Resources Information Center

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,…

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

2013-01-01

77

Novel Recombinant Engineered gp41 N-terminal Heptad Repeat Trimers and Their Potential as Anti-HIV-1 Therapeutics or Microbicides*  

PubMed Central

Peptides derived from N-terminal heptad repeat (NHR) of the HIV-1 gp41 are generally poor inhibitors of HIV-1 entry, because they tend to aggregate and do not form a trimeric coiled-coil. In this study, we have fused portions of gp41 NHR, e.g. N36 or N28, to the T4 fibritin trimerization domain, Foldon (Fd), thus constructing novel NHR trimers, designated N36Fd or N28Fd, which could be expressed in Escherichia coli cells. The purified N36Fd and N28Fd exhibited SDS-resistant trimeric coiled-coil conformation with improved ?-helicity compared with the corresponding N-peptides. They could interact with a C-peptide (e.g. C34) to form stable six-helix bundle and possessed potent anti-HIV-1 activity against a broad spectrum of HIV-1 strains. N28Fd was effective against T20-resistant HIV-1 variants and more resistant to proteinase K compared with T20 (enfuvirtide), a C-peptide-based HIV fusion inhibitor. Therefore, N28Fd trimer has great potentials for further development as an affordable therapeutic or microbicide for treatment and prevention of HIV-1 infection. PMID:20538590

Chen, Xi; Lu, Lu; Qi, Zhi; Lu, Hong; Wang, Ji; Yu, Xiaoxia; Chen, Yinghua; Jiang, Shibo

2010-01-01

78

The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers  

PubMed Central

Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the research of TNBC is needed. This review aims to summarize the latest findings in TNBC in risk factors, possible therapeutic targets and possible prognostic makers.

Jiao, Qingli; Shao, Guoli; Peng, Haoyu; Wang, Mengchuan; Ji, Shufeng; Liu, Peng; Zhang, Jian

2014-01-01

79

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

PubMed

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

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

2014-08-01

80

POSSIBLE EXPLANATIONS OF THE WIDELY AGREED LOW IMPACT OF HIV\\/AIDS ON ECONOMIC GROWTH  

Microsoft Academic Search

While microeconomic impact of HIV\\/AIDS is clearly very high, the same cannot be said relatively to the macroeconomic sector. The objective of this paper is to study the impact of HIV\\/AIDS on economic growth: after a synthetic critical review of standard models on this topic, a deeper analysis of the impact on capital and labour will be made. A similar

Luca Tiberti

81

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

ERIC Educational Resources Information Center

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…

Kagotho, Njeri

2012-01-01

82

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

PubMed

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

Alon, D; Chowers, M

2012-04-01

83

Interactions between prostaglandins, leukotrienes and HIV-1: Possible implications for the central nervous system  

PubMed Central

In HIV-1-infected individuals, there is often discordance between viremia in peripheral blood and viral load found in the central nervous system (CNS). Although the viral burden is often lower in the CNS compartment than in the plasma, neuroinflammation is present in most infected individuals, albeit attenuated by the current combined antiretroviral therapy. The HIV-1-associated neurological complications are thought to result not only from direct viral replication, but also from the subsequent neuroinflammatory processes. The eicosanoids - prostanoids and leukotrienes - are known as potent inflammatory lipid mediators. They are often present in neuroinflammatory diseases, notably HIV-1 infection. Their exact modulatory role in HIV-1 infection is, however, still poorly understood, especially in the CNS compartment. Nonetheless, a handful of studies have provided evidence as to how these lipid mediators can modulate HIV-1 infection. This review summarizes findings indicating how eicosanoids may influence the progression of neuroAIDS. PMID:22236409

2012-01-01

84

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

PubMed

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

Crowder, Stephen A; Merritte, Kristin

2013-09-01

85

[Experimental analysis of therapeutic properties of Rhodiola rosea L. and its possible application in medicine].  

PubMed

The paper presents a review of the scientific publications on Rhodiola rosea L. known for its adaptogenic characteristics. Biologically active substances salidroside, rosin, rosavin, rosarin and tyrosol, which are mainly found in plant rhizomes, demonstrate therapeutic effect. These active components effect the central nervous system by increasing the ability to concentrate, the mental and physical power; they are efficient in the asthenic states and improve general resistance of the cells and the organism against the harmful outer influence. They also prevent the heart system from stress and arrhythmias, and posses some antioxidant activity. Some data confirm that the Rhodiola rosea L. preparations stop the growth of the malignant tumors and metastases in the liver. Some preclinical and clinical data of the golden root preparations are discussed in the survey. The interaction of the herb with other medicines, its usage and effect, recommended doses, and its side effects are also reviewed in the paper. PMID:15252224

Kucinskaite, Agne; Briedis, Vitalis; Savickas, Ar?nas

2004-01-01

86

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

PubMed Central

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

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

2011-01-01

87

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

PubMed

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

Elosta, Abdulhakim; Ghous, Tahseen; Ahmed, Nessar

2012-03-01

88

Role of ?-Catenin/TCF-4 Signaling in HIV Replication and Pathogenesis: Insights to Informing Novel Anti-HIV Molecular Therapeutics  

PubMed Central

A greater understanding of the interaction between HIV and host signaling pathways that restrict virus production may lead to new methods to purge virus from latent reservoirs and enhance survival/function of cells targeted by HIV. This review highlights the role of the Wnt/?-catenin pathway as a host factor that represses HIV replication in multiple targets, especially those relevant to HIV in the central nervous system. PMID:21384147

Henderson, Lisa J.

2013-01-01

89

Communication, recruitment and enrolment in the preventative and therapeutic phase I clinical trial against HIV/AIDS based on the recombinant HIV-1 Tat protein.  

PubMed

The role of volunteer recruitment in HIV vaccine trials has recently been considered particularly with respect to critical issues, such as motivation, psychological assessment and social impact. The preventative and therapeutic phase I trials based on the recombinant biologically active Tat vaccine candidate, sponsored in Italy by the Istituto Superiore di Sanità, included a specific centralised procedure (SCP) developed to support both the sponsor and the volunteers during trial enrolment and conduction. This process, which is an integrated, multidisciplinary, biomedical and psycho-socio-behavioural network, represented a novel and important aspect for the conduction and success of the clinical study. A specific flow of information from the sponsor to the population was developed through the SCP which started from the national announcement of the trials (through a press conference and a press release) to the enrolment of the volunteers. To this aim a telephone counselling intervention was performed to supply the scientific information translated in personalised message, allowing to select potential participants prior to the first contact with the clinical sites. Furthermore, the multi-step procedure contributed in reinforcing the motivation to participation and trial retention, providing important hints for the design of standardised enrolment procedures to be used in clinical studies. Indeed, this methodological approach, which foresees the joined participation of researchers and expert of communication, could be followed in future vaccine trials in order to improve the effectiveness of enrolment procedures. PMID:21390884

Luzi, Anna Maria; Gallo, Pietro; Colucci, Anna; Marcotullio, Simone; Bellino, Stefania; Longo, Olimpia; Ensoli, Barbara

2011-08-01

90

Therapeutic Possibilities of Ceftazidime Nanoparticles in Devastating Pseudomonas Ophthalmic Infections; Keratitis and Endophthalmitis  

PubMed Central

As the number of contact?lens wearers rises worldwide, Pseudomonas aeruginosa (PA) keratitis is attracting more attention as a major public health issue. Corneal lesions of PA, being the most intimidating complication of contact?lens wearer, can progress rapidly in spite of local antibiotic treatment, and may result in perforation and the permanent loss of vision. One of the explanations proposed for the evasion of the pathogen from immune responses of the host as well as antibacterial treatment is the fact that invasive clinical isolates of PA have the unusual ability to invade and replicate within surface corneal epithelial cells. In this manner, PA is left with an intracellular sanctuary. Endophthalmitis, albeit rare, is another ophthalmic infection faced by the challenge of drug delivery that can be potentially catastrophic. The present hypothesis is that nanoparticles can carry anti?pseudomonas antibiotics (e.g. ceftazidime) through the membranes, into the “hidden zone” of the pathogen, hence being an effective and potent therapeutic approach against pseudomonas keratitis and endophthalmitis. PMID:24600610

Mohammadpour, Mehrdad; Jabbarvand, Mahmood; Karimi, Nasser

2012-01-01

91

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

PubMed Central

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

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

2014-01-01

92

[Surgical and interventional therapeutic possibilities in aneurysms of the subclavian artery].  

PubMed

Aneurysms of the subclavian artery are extremely rare and most commonly caused by arteriosclerosis, trauma or thoracic outlet syndrome. Less frequently seen causes also include syphilis, cystic media necrosis or tuberculosis or congenital anomalies. The presence of a subclavian aneurysm can give rise to various symptoms such as a pulsating supraclavicular mass, peripheral embolism or brachial plexus compression. Generally, surgical intervention is undertaken involving ligation and extirpation of the aneurysm followed by interposition of either a saphenous vein- or synthetic vascular graft. Recent diversifications in potential therapeutic strategies include the clinical application of transluminally positioned stents for the treatment of vascular lesions. In the literature review we found more than 260 published cases of surgically treated subclavian aneurysms and additional 17 subclavian aneurysms treated by endoluminal stent application. From 1992-1997 5 subclavian aneurysms were resected in our hospital. In four cases a vein graft of the vena saphena magna and in one case a PTFE graft were used. The sensory ischaemic deficit regressed in the further follow up in four of the five cases. Patency was checked postoperatively by ultrasound sonography, angiography or MR-angiography. PMID:10703160

Brauer, R B; Naundorf, M; Maurer, P C

2000-01-01

93

The HIV epidemic in Southern Africa - Is an AIDS-free generation possible?  

PubMed

Southern Africa, home to about 20 % of the global burden of infection continues to experience high rates of new HIV infection despite substantial programmatic scale-up of treatment and prevention interventions. While several countries in the region have had substantial reductions in HIV infection, almost half a million new infections occurred in this region in 2012. Sexual transmission remains the dominant mode of transmission. A recent national household survey in Swaziland revealed an HIV prevalence of 14.3 % among 18-19 year old girls, compared to 0.8 % among their male peers. Expanded ART programmes in Southern Africa have resulted in dramatically decreased HIV incidence and HIV mortality rates. In South Africa alone, it is estimated that more than 2.1 million of the 6.1 million HIV-positive people were receiving ART by the end of 2012, and that this resulted in more than 2.7 million life-years saved, and hundreds of thousands of HIV infections averted. Biological, behavioural and structural factors all contribute to the ongoing high rates of new HIV infection; however, as the epidemic matures and mortality is reduced from increased ART coverage, epidemiological trends become hard to quantify. What is clear is that a key driver of the Southern African epidemic is the high incidence rate of infection in young women, a vulnerable population with limited prevention options. Moreover, whilst ongoing trials of combination prevention, microbicides and behavioural economics hold promise for further epidemic control, an AIDS-free generation will not be realised unless incident infections in key populations are reduced. PMID:24676559

Delva, Wim; Abdool Karim, Quarraisha

2014-06-01

94

School age children with HIV/AIDS: possible discrimination and attitudes against.  

PubMed

Survey-based study what purpose was to analyse respondents' opinions about contacts with HIV/AIDS-affected people. It was performed using a paper-pencil method during visits of respondents at primary care centres and on-line through a link to the questionnaire distributed among patients of primary care physicians. The study involved 302 respondents, 80% of whom were women; the average age was 34.48 years. The majority of respondents did not know anyone with HIV/AIDS (89.6%). About 83.3% claimed that they would not decrease contacts with HIV/AIDS-affected people. According to 64.1% of respondents, children with HIV/AIDS should go to kindergarten/public or non-public school. We selected a group of respondents, who previously were not but now are inclined to limit such contacts. These respondents can be a potential target group for HIV/AIDS educational programmes. Most respondents think that there is insufficient information about the HIV/AIDS in the mass media. PMID:24626355

Kurpas, Donata; Mroczek, Bozena; Sochocka, Lucyna; Church, Joseph

2013-12-01

95

Penicillin and vitamin A as possible therapeutic agents in pityriasis rubra pilaris.  

PubMed

Pityriasis rubra pilaris (PRP) is a rare skin disorder with versatile clinical presentations. A 62-year-old Caucasian woman with progressive erythroderma and classic adult (type I) PRP is presented. Treatment with systemic steroids and methotrexate produced no improvement. Clinical remission was achieved after systemic therapy with penicillin (both intravenous and intramuscular) and vitamin A. The therapy of PRP is reviewed, focusing on a possible infectious genesis of PRP as well as the role of antibiotics in its management. PMID:19912462

Popova, Ludmila; Darlenski, Razvigor; Tsankov, Nikolai

2010-05-01

96

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

PubMed

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

Sun, Yang; Lu, Hongzhou

2014-06-01

97

Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible involvement of D-serine  

PubMed Central

A unique feature of N-methyl-D-aspartate receptors (NMDARs) that distinguishes them from other ionic receptors is that their activation requires more than one agonist to bind simultaneously to distinct binding sites on the receptor. D-serine, a co-agonist binding to the glycine site of NMDARs, has been implicated in several NMDAR-dependent physiological processes, and altered D-serine levels under certain pathophysiological conditions contribute to neural dysfunction via NMDARs in the central nervous system. Entry of HIV-1 in the brain causes neuronal injury leading to cognitive, behavioral and motor impairments known as HIV-associated neurocognitive disorders (HAND). As HIV-1 does not infect neurons, neuronal injury is believed to be primarily mediated by an indirect mechanism,that is, HIV-1-infected and/or immune-activated macrophages and microglial cells release soluble molecules leading to neuronal injury or death. Among the soluble factors is D-serine. In this article we try to address recent progresses on the role D-serine might play in the pathogenesis of neurodegenerative disorders with a particular emphasis of the involvement of D-serine in HIV-1-associated neurotoxicity. PMID:24044033

Xia, Jianxun; Xiong, Huangui

2013-01-01

98

Local ELF-magnetic field: a possible novel therapeutic approach to psychology symptoms.  

PubMed

The recorded EEG of some brain regions of patients such as attention deficit hyperactivity disorder (ADHD), depression and etc. are different in comparison to healthy people. The disease improves with modifying the patient EEG that this is the basis of neurofeedback training. The main disadvantage of neurofeedback training demands patient's collaborative and active participation during treatment sessions, while some of patients such as addicts, depressed people and ADHD children cannot easily concentrate in direction of therapist's purpose. Furthermore, extremely low frequency magnetic fields (MFs) can affect brain signals and change them that in some cases lead to clinical effects. This report proposes if by locating small coils in desired region proceeds to local exposure of brain and happens in different frequencies or intensities and the effects of each MF in brain signals get analyzed then by knowing its effects we can make changes in patient voluntary without direct participation of patient in his/her brain signal changes. In the other words by changing type of the MF exposure and immediate record of brain signals we can fallow brain signals by observing the immediate record after exposure, with changes in the amplitude and the next exposure frequency, the therapist tries to direct the brain signal of desired region to the purpose. The possibility of approving this hypothesis in spite of contradictory effects about recovery or appearance of depression because of the MF and ability of local magnetic field exposures in changing of brain signals get reinforced to some extent. PMID:25073696

Shafiei, Seyed Ali; Firoozabadi, Seyed Mohammad

2014-11-01

99

Possible association between the stage of HIV disease, antiretroviral treatment and the nutrient composition of breast milk in the Mangaung area, South Africa  

PubMed Central

Introduction In South Africa where replacement feeding may not be affordable, feasible or sustainable, HIV-infected women are recommended to exclusively breastfeed their infants during the first six months of life. The question arises whether HIV disease progression and its metabolic impact on the mother will affect the nutrient composition of breast milk. The aim was to determine the possible association between HIV disease progression, as measured by the immunological markers, and the nutrient composition of breast milk. Methods The nutrient composition of breast milk of 100 HIV-infected and 50 non-infected volunteered (control group) lodging/day visiting mothers at Paediatric/Neonatal wards of National, Pelonomi and Universitas hospitals, Bloemfontein, were measured. The HIV-infected group was subdivided into HIV-naïve and HIV-ARV treatment group. Breast milk and blood samples were obtained. Macronutrients namely lactose, proteins, fat, total solids and the energy content of the breast milk and micronutrient namely calcium and phosphate were measured. Blood and immunological parameters comprised of CD4/CD8+T cell counts, viral loads and full blood counts. Results Protein levels amongst the HIV-infected group showed a significant elevation (p<0.0001) compared to the control group. The calcium levels of the HIV-infected group were significantly lower (p=0.0081) than the control group. No statistically significant differences were recorded of the measured nutrients between mothers receiving treatment and the HIV-naïve group. All the HIV patients were anaemic with haemoglobin, haematocrit and RDW below the normal range. The Spearman Correlation Coefficient was used to determine if HIV disease progression have an influence on the nutrient composition. For the HIV-naïve group, a significant correlation was found between the viral load and percentage total solids in breast milk. A correlation between the CD4+T cell count, the percentage total solids and energy content of the breast milk was determined in the HIV-ARV treatment group. No strong positive correlation could be established between the immunological markers, HIV disease progression and the nutrient composition in the breast milk. Conclusions HIV mothers can breastfeed their babies even at a more advanced stage of HIV disease progression, but emphasis has been placed on exclusive breastfeeding.

van den Heever, Wilhelmina; de Wet, Geta; Hattingh, Moira

2014-01-01

100

Preventive HIV Vaccines What is a vaccine?  

E-print Network

Preventive HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate infection or make you sick. What is the difference between a preventive HIV vaccine and a therapeutic HIV vaccine? Therapeutic HIV vaccines are designed to control HIV infection in people who are already HIV

Levin, Judith G.

101

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

PubMed Central

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

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

102

[AIDS throughout the world and possibilities of preventing the spread of HIV infection].  

PubMed

At the end of 1992, according the World Health Organization, 611,589 AIDS cases had been reported, but the actual number of cases reached about two million. The actual number of HIV-infected people in the world, according to WHO, in 1992 ranged between 10 and 12 million. It is estimated that by the year 2000 there will be 30-40 million infected people and about 12-18 million AIDS cases. In the 1980's the increase was especially great in Sub-Saharan Africa, with about 6 million infected cases of whom 1/3 were pregnant women in big city maternity wards. In recent years the steep increase of cases in Africa led to its appellation as the AIDS continent. The percentage of infected people is put at 15-20% and it is steadily increasing. On the American continents by the end of 1992, a total of 313,083 cases were reported, of which 242,000 were in the US (970 per 1 million inhabitants). In Brazil there were 31,000, in Mexico 11,000, and in Canada 7000 cases. The highest figure was in the Bahamas: 4087 per 1 million inhabitants. In Asia only 2582 AIDS cases were reported at the end of 1992, because HIV still had not exploded on this continent. The latest data indicated an increase of the infection in Asia among IV drug users and prostitutes, so that seropositive persons were estimated at half a million. The highest number of clinical cases were in Thailand (909), Japan (508), and in Israel (192). In Europe there were 88,810 cases reported, of which 21,487 were in France. At the end of 1992 in Yugoslavia 268 cases were registered (25 per 1 million inhabitants). In Serbia there were 262 cases (in Belgrade 75% of them) and in Montenegro 3 cases. It is worrisome that about 2000 HIV-positive persons have been detected since 1985. AZT (azidothymidine, zidovudin) and ddI (dideoxyinosine) are the main drugs for treatment. Since an effective vaccine is still unavailable, the only means of halting the spread of HIV infection is warning and education, beginning with prepubescents, about first intercourse and IV drug use. PMID:8212657

Litvinjenko, S; Pocek, B

1993-01-01

103

Infection of female primary lower genital tract epithelial cells after natural pseudotyping of HIV-1: possible implications for sexual transmission of HIV-1.  

PubMed

The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call "natural pseudotyping," expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus. PMID:25010677

Tang, Yuyang; George, Alvin; Nouvet, Franklin; Sweet, Stephanie; Emeagwali, Nkiruka; Taylor, Harry E; Simmons, Glenn; Hildreth, James E K

2014-01-01

104

Experimental and potential future therapeutic approaches for HIV1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin  

Microsoft Academic Search

Severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia\\u000a can occur after infection with the human immunodeficiency virus-1 (HIV-1). Infected peripheral immune-competent cells, in\\u000a particular macrophages, infiltrate the central nervous system (CNS) and provoke a neuropathological response involving all\\u000a cell types in the brain. HIV-1 infection results in activation of chemokine receptors, inflammatory mediators, extracellular

Marcus Kaul; Stuart A. Lipton

2005-01-01

105

Reduced viral burden amongst high responder patients following HIV1 p24 peptide-based therapeutic immunization  

Microsoft Academic Search

We have previously shown that HIV p24-like peptides (Vacc-4x) via activation of skin dendritic cells induced immune responses in 90% of HIV patients on highly active antiretroviral treatment (HAART). These patients (n=38) were here subjected to a final 14-week interruption of HAART. Patients with the highest delayed type hypersensitivity (DTH) responses to Vacc-4x-peptides before treatment interruption tended to achieve lower

Anne-Marte B. Kran; Maja A. Sommerfelt; Birger Sørensen; Jørgen Nyhus; Ingebjørg Baksaas; Johan N. Bruun; Dag Kvale

2005-01-01

106

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

PubMed Central

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

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

2014-01-01

107

Changes of the coagulation and fibrinolysis system in malignancy: their possible impact on future diagnostic and therapeutic procedures.  

PubMed

The interaction between malignant cell growth and the coagulation and fibrinolysis system has been a well known phenomenon for decades. During recent years, this area of research has received new attention. Experimental data suggest a role for the coagulation and fibrinolysis system in tumor development, progression and metastasis. Also, clinical research suggests that targeting the coagulation system or fibrinolysis system might influence the course of malignant disease beneficially. This paper reviews data on various hemostatic and fibrinolytic parameters in malignancy; the possible use of such parameters as risk markers in oncology patients; and possible targets of anti-neoplastic therapies using anticoagulant and/or antifibrinolytic strategies. Current evidence suggests that the tissue factor/factor VIIa pathway mediates the most abundant procoagulant stimulus in malignancy via the increase in thrombin generation. Tissue factor has been suggested to mediate pro-metastatic properties via coagulation-dependent and coagulation-independent pathways; tissue factor has also been implicated in tumor neo-angiogenesis. However, so far no model has been validated that would allow the use of tissue factor in its soluble or insoluble form as a marker for risk stratification in tumor patients. On the other hand, there is now good evidence that parts of the fibrinolytic system, such as urokinase-type plasminogen activator and its receptor ("uPAR"), can be used as strong predictors of outcome in several types of cancer, specifically breast cancer. Observation of various treatment options in patients with thromboembolic disease and cancer as well as attempts to use anticoagulants and/or therapies modulating the fibrinolytic system as anti-neoplastic treatment strategies have yielded exciting results. These data indicate that anticoagulant therapy, and specifically low molecular weight heparin therapy, is likely to have anti-neoplastic effects; and that their use in addition to chemotherapy will probably improve outcome of tumor treatment in certain types of cancer. However, the body of clinical data is still relatively small and the question whether or not we should routinely consider the coagulation and/or fibrinolysis system as therapeutic targets in cancer patients is yet to be answered. PMID:11071061

Korte, W

2000-08-01

108

A Case Series of HIV-Seropositive Patients and Hypercoagulable State-Is It Difficult to Treat Even with Therapeutic Anticoagulation?  

PubMed

Patients with human immunodeficiency virus (HIV) are at risk of developing thrombosis and are 8 to 10 times more likely to develop thrombosis than the general population. Moreover, if they have hypercoagulable state they can have severe thrombosis and life-threatening thrombotic events. The purpose of this retrospective study is to analyze hypercoagulable state in HIV-seropositive patients who have been diagnosed with venous thromboembolism (VTE). This study is a subgroup study of a larger cohort group of HIV-seropositive patients with VTE followed up with our vascular medicine outpatient clinic. The patients included for this study were HIV-seropositive patients with hypercoagulable state, analyzed over the past 3 years, and followed prospectively. HIV-seropositive patients with arterial thrombosis were excluded. These patients had minimum, regular follow-up of 3 months, with a Doppler scan in the beginning and last follow-up. All the patients were analyzed for hypercoagulable state and the patients selected in this study were those who were tested positive for hypercoagulable state. All patients were analyzed for age, gender, race, site of thrombosis, coagulation factors, lipid panel, type of antiretroviral treatment, past or present history of infections or malignancy, CD4 absolute and helper cell counts at the beginning of thrombosis, and response to treatment and outcome. Patients with HIV with arterial thrombosis were excluded. The study was approved by the ethics committee. Five patients were included in this study. The mean age was 47.8 years (range 38 to 58 years). All were male patients with lower limb thrombosis. Most common venous thrombosis was popliteal vein thrombosis, followed by common femoral, superficial femoral, and external iliac thrombosis. Two patients had deficiency of protein S, two had high homocysteine levels, one had deficiency of antithrombin 3, and one had increase in anticardiolipin immunoglobulin G antibody. All the patients were taking nucleoside and nonnucleoside inhibitors but only one patient was taking protease inhibitors. There was no history of malignancy but two patients had past history of tuberculosis. The mean absolute CD4 counts were 244 cells/UL (range 103 to 392 cells/UL) and helper CD4 counts were 19.6 cells/UL (range 15 to 30 cells/UL). All were anticoagulated with warfarin or enoxaparin. There was complete resolution of deep vein thrombosis only in one patient on long-term anticoagulation but there was no resolution of thrombosis in the other four patients despite of therapeutic anticoagulation for more than 6 months. All the patients are alive and on regular follow-up. Thrombosis in HIV patients is seen more commonly in middle aged, community ambulant male patients. The most common hypercoagulable state was noted as deficiency of protein S and hyperhomocysteinemia. Eighty percent of the patients did not respond to therapeutic anticoagulation. PMID:24436593

Sule, Ashish Anil; Pandit, Nihar; Handa, Pankaj; Chadachan, Veerandra; Tan, Endean; Sum, Faith Nadine Choo Yun; Joyce, Er Hui Ling; Chin, Tay Jam

2013-06-01

109

HIV chemotherapy  

NASA Astrophysics Data System (ADS)

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.

Richman, Douglas D.

2001-04-01

110

OA03.07. A comparative clinical study to evaluate the therapeutic effect of shivagutika in patients with H.I.V infection  

PubMed Central

Purpose: HIVAIDS is the most dreaded challenge that the today's medical world is facing! As patients do not have many options, they tend to look at ayurveda to help improve their condition clinical presentation of HIV is akin to the description of Rajayakshma characterized by involvement of multiple srotas and presenting with diarrhea, cough, fever and similar other symptoms. Shiva guttika is used here as a rasayana to improve the immunity. Method: A Single blind comparative clinical study with Pretest & Post test design. The patients were randomly categorized into two groups as shivagutika group and ART group consisting of 20 patients each Shivagutika group In this group the 20 patients were treated orally with shivagutika in a dose of 12 grams od, for 6 months ART group In this the patients were treated with ART for six months. Result: The criteria's selected for the evaluation like Cough, Dyspnoea, fever,body weight, HB%, ESR, CD4 count etc all were statistically analyzed. Following medication with shivagutika the value of cd4 count was 567 in comparison to initial value of 391. in the ART group the initial value of 417.6 increased to 447.6 following treatment. Conclusion: CD4 count affirms the therapeutic benefit of shivagutika in HIV infection /AIDS beyond doubt Various other vyadhi hara rasayanas can be used in the management of immuno compromised conditions and in reoccurant diseases.

Anil, L Abhishek; Acharya, G Shrinivasa

2013-01-01

111

Full validation of an analytical method for the HIV-protease inhibitor atazanavir in combination with 8 other antiretroviral agents and its applicability to therapeutic drug monitoring.  

PubMed

Because HIV medications are used in combination, it is important to develop multiplex assays to streamline the therapeutic drug monitoring process and provide rapid turnaround. This article reports full validation of an analytical method that combines atazanavir with 6 HIV-protease inhibitors (indinavir, amprenavir, saquinavir, nelfinavir, ritonavir, and lopinavir) and 2 nonnucleoside reverse transcriptase inhibitors (nevirapine and efavirenz). Using 200 microL of plasma and a simple liquid-liquid extraction method, this analytical method achieved a clean baseline and high extraction efficiencies (90.0% to 99.5%). A Zorbax C-18 (150 x 4.6 mm, 3.5 microm) analytical column was used along with a 27-minute linear gradient elution of the mobile phase to provide sharp peaks at 210 nm. This method was validated over a range of 25 to 10,000 ng/mL and is accurate (90.4% to 110.5%) and precise (precision within a day and between days ranged from 2.3% to 8.3%). Because this method is simple and inexpensive, it may have applicability in countries with low resources. PMID:16885719

Rezk, Naser L; Crutchley, Rustin D; Yeh, Rosa F; Kashuba, Angela D M

2006-08-01

112

Humanized Mouse Models of HIV Infection  

PubMed Central

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 intragenetic variables; 3) continuous de novo production of human immune cells from the transplanted CD34+ cells within each humanized mouse facilitates long term experiments; 4) both primary and laboratory HIV isolates can be used for experiments; and 5) in addition to therapeutic interventions, rectal and vaginal HIV prevention approaches can be studied. In summary, humanized mice can have an important role in virtually all aspects of HIV research including the analysis of HIV replication, the evaluation of HIV restriction factors, the characterization of successful biomedical HIV prevention strategies, the evaluation of new treatment regimens and the evaluation of novel HIV eradication strategies. PMID:21799532

Denton, Paul W.; Garcia, J. Victor

2013-01-01

113

Rhabdomyolysis: a case study exploring the possible side effect of lipid lowering medication by a HIV positive patient taking a protease inhibitor  

PubMed Central

This case study explores the incidence of rhabdomyolysis in a HIV positive patient that was taking a lipid lowering drug and a protease inhibitor concurrently while under chiropractic treatment for generalized muscular soreness. Dyslipidemia is a very common problem both in the general and HIV population, with many patients being prescribed lipid lowering drugs. While extremely rare, adverse effects of lipid lowering drugs have been documented to include myopathy such as rhabdomyolysis. It is imperative that chiropractors are aware of the possible adverse side effect of lipid lowering drug therapy in their patients complaining of musculoskeletal pain. It is even more important that chiropractors treating the HIV population are aware of the potential interactions between these medications and protease inhibitors to cause myopathy. PMID:19066698

De Carvalho, Diana; Citro, Mark; Tibbles, Anthony

2008-01-01

114

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

Microsoft Academic Search

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

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

2008-01-01

115

Use of a Rapid HIV Home Test to Screen Sexual Partners: An Evaluation of Its Possible Use and Relative Risk  

PubMed Central

We estimated the HIV risk reduction that could be attained by using a rapid HIV home test (HT) to screen sexual partners versus using condoms in different proportions of anal intercourse (AI) occasions among men who have sex with men (MSM). Special attention was paid to the role of the window period during which infected cases go undetected. Our results show that if MSM engage in AI without condoms following a non-reactive HT result, they have lower chances of becoming infected by someone still in the window period than by following heuristics and using condoms inconsistently. For MSM who do not use condoms, use of HT as a screening device may be a useful risk reduction strategy. This advantage increases with higher HIV population prevalence. With higher HIV incidence, this strategy will not provide any advantage if condoms are used in as little as one out of four occasions. PMID:19415483

Ventuneac, Ana; Carballo-Dieguez, Alex; Leu, Cheng-Shiun; Levin, Bruce; Bauermeister, Jose; Woodman-Maynard, Emily; Giguere, Rebecca

2009-01-01

116

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

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 OBS population. These findings support the use of Tat immunization to intensify HAART efficacy and to restore immune homeostasis. Trial registration ClinicalTrials.gov NCT00751595 PMID:21085635

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

117

Why don't young adults protect themselves against sexual transmission of HIV? Possible answers to a complex question.  

PubMed

Using theories of health behavior, this study aimed to advance the understanding of risk-taking regarding human immunodeficiency virus (HIV) infection among young adults by describing: (a) their representation (i.e., schema) about HIV infection, (b) their problems with use of condoms and comfort with safe-sex practices, and (c) situations associated with risky sexual behavior and reported reasons for risk-taking. Participants were 272 young adult college students whose average age was 19.3 years (SD = 2.4). They completed an extensive questionnaire developed for the study. The representation of HIV infection in this sample lacked the specific and detailed information necessary to guide sexual behavior. For example, participants were aware of the causes of sexual transmission of HIV, but many persons indicated uncertainty about the effectiveness of various preventive strategies (e.g., latex condoms, birth control devices). A number of specific problems with using condoms were identified or expected by participants. These included inadequate lubrication, poor fit, and breaks or leaks during intercourse. The majority of the sample (85.3%) reported at least one occurrence of unprotected sexual intercourse. For 60% of them, the stated reason for the risk-taking was that the intercourse was unplanned or spontaneous; 50% reported that they "just knew" the partner was safe and not infected with HIV. Implications for health education programs are discussed. PMID:8217474

Keller, M L

1993-01-01

118

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

PubMed Central

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 The prevalence of treatment adherence changes over time. Indirect methods (dose/pill count and self-reported) can be useful to detect non-adherence in COPD patients. The combination of MGT and BT is the best approach to test self-reported adherence. PMID:21261951

2011-01-01

119

Which Antibody Functions are Important for an HIV Vaccine?  

PubMed Central

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

Su, Bin; Moog, Christiane

2014-01-01

120

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

PubMed

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

Alias, A G

2000-04-01

121

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

NASA Astrophysics Data System (ADS)

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.

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

2010-02-01

122

HIV Type 1 Gag as a Target for Antiviral Therapy  

PubMed Central

Abstract The Gag proteins of HIV-1 are central players in virus particle assembly, release, and maturation, and also function in the establishment of a productive infection. Despite their importance throughout the replication cycle, there are currently no approved antiretroviral therapies that target the Gag precursor protein or any of the mature Gag proteins. Recent progress in understanding the structural and cell biology of HIV-1 Gag function has revealed a number of potential Gag-related targets for possible therapeutic intervention. In this review, we summarize our current understanding of HIV-1 Gag and suggest some approaches for the development of novel antiretroviral agents that target Gag. PMID:21848364

2012-01-01

123

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

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

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

2013-10-01

124

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

PubMed Central

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?

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

2014-01-01

125

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

PubMed Central

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

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

2014-01-01

126

The maturation of antibody technology for the HIV epidemic.  

PubMed

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

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

2014-08-01

127

Does over-expression of transforming growth factor-beta account for the increased morbidity in African-Americans?: possible clinical study and therapeutic implications.  

PubMed

African-Americans experience an excessive prevalence of a number of apparently disparate disorders that all appear to be, at least in part, mediated by the over-expression or activation of transforming growth factor-beta (TGF-beta) signaling pathways, and that certain genotypes including the codon 10 polymorphism occur more commonly among African-Americans and appears to predispose to these disorders. These disorders, fibrosing in nature, include hypertension, focal glomerulosclerosis, diabetic nephropathy, end stage renal disease, sarcoidosis, uterine leiomyoma, keloids, myocardial fibrosis, and glaucoma. The specific polymorphism for TGF-beta, codon 10, has been implicated in glomerulosclerosis and diabetic nephropathy as well as cardiac transplant rejection. Although TGF-beta over-expression is not the sole factor in these disorders, it is suggested that by designing future clinical studies that consider genomic differences in TGF-beta expression, a more complete understanding of these clinical disorders will be possible. A more thorough understanding of the genetic basis of disease will like promote improved therapeutic regimens and may help reduce the disparate health outcomes for African-Americans as well as improve treatment of individuals of various and diverse ethnic backgrounds. PMID:20457494

Eiser, Arnold R

2010-11-01

128

Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin.  

PubMed

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, nonhydrolyzable substrate analog (RPB) and the generic aspartic protease inhibitor acetyl-pepstatin (Ac-PEP)] was assessed by differential scanning calorimetry. DeltaT(m) values, defined as the difference in T(m) 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 degrees C, respectively. Binding of APV and Ac-PEP is most sensitive to the D25N mutation, as shown by DeltaT(m) ratios [DeltaT(m)(PR)/DeltaT(m)(PR(D25N))] of 35.8 and 16.3, respectively, whereas binding of DMP323 and RPB (DeltaT(m) ratios of 1-2) is least affected. Binding of the substrate-like inhibitors RPB and Ac-PEP is nearly abolished (DeltaT(m)(PR)/DeltaT(m)(PR(D29N)) > or = 44) by the D29N mutation, whereas this mutation only moderately affects binding of the smaller inhibitors (DeltaT(m) ratios of 1.4-2.2). Of the nine FDA-approved clinical HIV-1 protease inhibitors screened, APV, RTV, and DRV competitively inhibit porcine pepsin with K(i) values of 0.3, 0.6, and 2.14 microM, respectively. DSC results were consistent with this relatively weak binding of APV (DeltaT(m) 2.7 degrees C) compared with the tight binding of Ac-PEP (DeltaT(m) > or = 17 degrees 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

Sayer, Jane M; Louis, John M

2009-05-15

129

Therapeutic Immunization with HIV1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART  

Microsoft Academic Search

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

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

2010-01-01

130

Growth and Trophic Factors, pH and the Na+\\/H+ Exchanger in Alzheimer's Disease, Other Neurodegenerative Diseases and Cancer: New Therapeutic Possibilities and Potential Dangers  

Microsoft Academic Search

Abnormalities in the intricate intracellular signalling pathways play a key role in the deregulation of either spontaneous (normal or pathological) or induced (therapeutic) cell death mechanisms. Some of these pathways are in- creasingly becoming molecular therapeutic targets in different processes, ranging from neurodegenerative diseases to can- cer. Recent discoveries in research and treatment have shown that failure to induce selective

Salvador Harguindey; Stephan J. Reshkin; Gorka Orive; Jose Luis Arranz; Eduardo Anitua

2007-01-01

131

Differential cellular FGF2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy  

Microsoft Academic Search

BACKGROUND: The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and\\/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically

Karen F Coracini; Caio J Fernandes; Almir F Barbarini; César M Silva; Rodrigo T Scabello; Gabriela P Oliveira; Gerson Chadi

2010-01-01

132

HIV2 Infection and Chemokine Receptors Usage - Clues to Reduced Virulence of HIV2  

Microsoft Academic Search

Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) are the causative agents of Acquired Immunodeficiency Syndrome (AIDS). Without therapeutic intervention, HIV-1 or HIV-2 infections in humans are characterized by a gradual and irreversible immunologic failure that ultimately leads to the onset of a severe immunodeficiency that constitutes the hallmark of AIDS. In the last two decades AIDS has

José Miguel Azevedo-Pereira; José Moniz-Pereira

133

Cationic host defence peptides: potential as antiviral therapeutics.  

PubMed

There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics. PMID:23649937

Gwyer Findlay, Emily; Currie, Silke M; Davidson, Donald J

2013-10-01

134

Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies  

PubMed Central

Background: Natural Eggshell Membrane (NEM®) is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and inflexibility associated with joint and connective tissue disorders. Methods: Eleven (single-arm trial) and 28 (double-arm trial) patients received oral NEM® 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies). In the single-arm trial, range of motion (ROM) and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT) population within each study. Results: Single-arm trial: Supplementation with NEM® produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038) and at 30 days for general pain (72.5% reduction; P = 0.007), flexibility (43.7% increase; P = 0.006), and ROM-associated pain (75.9% reduction; P = 0.021). Double-arm trial: Supplementation with NEM® produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014). There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001). There were no adverse events reported during either study and the treatment was reported to be well tolerated by study participants. Conclusions: Natural Eggshell Membrane (NEM®) is a possible new effective and safe therapeutic option for the treatment of pain and inflexibility associated with joint and connective tissue (JCT) disorders. Supplementation with NEM®, 500 mg taken once daily, significantly reduced pain, both rapidly (seven days) and continuously (30 days). It also showed clinically meaningful results from a brief responder analysis, demonstrating that significant proportions of treated patients may be helped considerably from NEM® supplementation. The Clinical Trial Registration numbers for these trials are: NCT00750230 and NCT00750854. PMID:19554094

Ruff, Kevin J; DeVore, Dale P; Leu, Michael D; Robinson, Mark A

2009-01-01

135

HIV UPDATE: BOTSWANA HIV  

E-print Network

HIV UPDATE: BOTSWANA HIV CONFERENCE OCTOBER 2012, Issue 10 Tlaleletso is a monthly publication presentations from the Botswana HIV conference, which was held in Gaborone from September 19th to 22nd, 2012. Next month's Tlaleletso will discuss HIV and Cancer. If there are other topics you would like

Bushman, Frederic

136

HIV UPDATE: AGING & HIV  

E-print Network

HIV UPDATE: AGING & HIV SEPTEMBER 2012, Issue 9 Tlaleletso is a monthly publication produced-friendly format. This month's Taleletso provides an introduction to the topic of HIV and Aging. For a more is an invaluable resource for doctors managing HIV patients. Next month Tlaleletso will discuss the Management

Bushman, Frederic

137

Therapeutic Drug Monitoring and Pharmacogenetic Study of HIV-Infected Ethnic Chinese Receiving Efavirenz-Containing Antiretroviral Therapy with or without Rifampicin-Based Anti-Tuberculous Therapy  

PubMed Central

Objectives Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese. Methods HIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively. Results From October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P?=?0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33–0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97–9.59) in multivariate analysis. Conclusions Despite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations. PMID:24551111

Lee, Kuan-Yeh; Lin, Shu-Wen; Sun, Hsin-Yun; Kuo, Ching-Hua; Tsai, Mao-Song; Wu, Bing-Ru; Tang, Sue-Yo; Liu, Wen-Chun; Chang, Sui-Yuan; Hung, Chien-Ching

2014-01-01

138

Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy  

PubMed Central

Background The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system. Methods Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg-1). Animals were sacrificed seven days later. Results Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction. Conclusion FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy. PMID:21062430

2010-01-01

139

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

PubMed Central

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 with at least one follow-up HCV status was not associated with an increased risk of detectable VL (n=114, 4072 person-week-follow-up [IQR12;51.6]), nor with FIB-4>1.45 (n=98, 3513 person-week-follow-up [IQR11.4;50.9]). Conclusions The initial results from GUSTA study show that ART-regimen including MVC did not increase the incidence of adverse events or severe laboratory liver abnormalities in HIV-1-infected patients with or without HCV coinfection. Coinfected patients did not show an increased risk of failure on simplification treatment with MVC/DRV/r. PMID:25397562

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

140

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

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…

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

2008-01-01

141

Updating the use of synthetic peptides as inhibitors of HIV-1 entry.  

PubMed

The use of synthetic peptides as HIV-1 inhibitors has been the object of research over recent years. A large number of peptides that affect different stages of the HIV-1 life cycle have been and continue to be studied due to their possible clinical application in the fight against HIV-1 infection. The main advantages of synthetic peptides as therapeutic agents are their low systemic toxicity, the fact that structural modifications can be made to them and their resulting capacity to mimic certain substrates or epitopes. HIV-1-inhibiting peptides have been identified and/or developed using different methods. Some therapeutic peptides such as enfuvirtide-already approved for clinical use-are derived from HIV-1 itself. Others are natural peptides such as chemokines, defensins or the "virus inhibitory peptide"; while still others have been designed and synthesized based on crystallographic data on HIV-1 proteins or from peptide libraries. Initial attempts at therapeutic applications focused on HIV-coded enzymes (reverse transcriptase, protease and, more recently, integrase). However, structural HIV proteins and, more specifically, the mechanisms that involve the virus in cell infection and replication are now also considered therapeutic targets. Several chemical strategies to improve both the stability of peptides and their pharmacokinetics, including prolonging their half-life, have recently been described in the literature. There is growing an interest in inhibitors that prevent HIV entry into the host cell (fusion inhibitors) which could lead to the development of new antiviral agents. Knowledge of the mechanism of action of fusion inhibitors is essential not only for the development of future generations of entry inhibitors, but also to gain an understanding of the form and kinetics of membrane fusion induced by the virus. The physico-chemical processes involved at the interface between the lipid surface of cells and enveloped viruses (such as HIV-1) are essential to the action of peptides that prevent HIV-1 entry into the host cell. The interaction of these peptides with biological membranes may be related to their inhibition efficiency and to their mechanism of action, as the HIV-1 gp41 glycoprotein is bound and confined between the cellular membrane and the viral envelope. PMID:23931277

Gómara, María José; Haro, Isabel

2014-04-01

142

The burden of HIV experience and care among MSM having an HIV-positive seroconcordant steady partner: a possible research hypothesis. Results from the French VESPA ANRS EN12 study  

Microsoft Academic Search

ObjectivesPrevention fatigue, relapse into unsafe sex practices and sexual behaviour changes have been reported in the community of men who have sex with men (MSM) since the introduction of highly active antiretroviral therapy. Engaging in a relationship with a seroconcordant partner is perceived by some HIV-positive MSM as an alternative prevention strategy to consistent condom use. This study addresses whether

Marie Suzan-Monti; Marie Préau; Jérôme Blanche; Sandrine Cabut; Patrizia M Carrieri; France Lert; Yolande Obadia; Bruno Spire

2011-01-01

143

Dendritic Cells Exposed to MVA-Based HIV1 Vaccine Induce Highly Functional HIV1Specific CD8+ T Cell Responses in HIV1Infected Individuals  

Microsoft Academic Search

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1\\/AIDS prophylactic\\/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B

Núria Climent; Susana Guerra; Felipe García; Cristina Rovira; Laia Miralles; Carmen Elena Gómez; Núria Piqué; Cristina Gil; José María Gatell; Mariano Esteban; Teresa Gallart

2011-01-01

144

HIV transmission within marriage : findings from Tanzania  

Microsoft Academic Search

This thesis focuses on the influence of marriage on HIV transmission and factors associated with HIV transmission among married people in Tanzania, and to suggest possible and feasible solutions. The study questions are: 1) What are the reasons for HIV transmission among married people in Tanzania, 2) How Marriage influences the spread of HIV?, 3) What are the perceptions of

H. A. Diggos

2007-01-01

145

Increased risk of histologically-defined cancer subtypes in HIV-infected individuals: clues for possible immunosuppression-related or infectious etiology  

PubMed Central

Background Malignancies that occur in excess among HIV-infected individuals may be caused by immunosuppression or infections. Because histologically-defined cancer subtypes have not been systematically evaluated, we assessed their risk among people with AIDS. Methods Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 U.S. population-based HIV/AIDS and cancer registries during 1980–2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies) and time since AIDS (a proxy of immunosuppression). Results Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T-cell leukemia/lymphoma (SIR=11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR=10.7), giant cell carcinoma (SIR=7.51) and leukemia not otherwise specified (NOS) (SIR=6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma NOS, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia and myeloid leukemias. For several of these cancer subtypes, we observed significant declines in SIRs across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since AIDS (i.e., prolonged immunosuppression). Conclusions The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. PMID:22359254

Shiels, Meredith S.; Engels, Eric A.

2012-01-01

146

Potential Anti-HIV Agents from Marine Resources: An Overview  

PubMed Central

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

Vo, Thanh-Sang; Kim, Se-Kwon

2010-01-01

147

Inhibition of the effects of rheumatoid synovial fluid cells on chondrogenesis and cartilage breakdown in vitro: possible therapeutical conclusions. A morphological--biochemical study.  

PubMed

Short-term co-cultivation of blastemal cells from 12-day-old mouse limb buds and human rheumatoid synovial fluid cells in high density cultures (Trowell culture system) resulted, depending on when co-cultivation started, either in (1) an inhibition of chondrogenesis (co-cultivation right from the start) or in (2) an extensive breakdown of cartilaginous matrix (co-cultivation after formation of embryonic cartilage). These synovial effects were markedly impeded if Avarol (a dioxygenase inhibitor) was applied singly or in combination with PAI-2 (a u-PA-inhibitor). PAI-2 alone, however, had no effect on the synovial-induced inhibition of chondrogenesis, but produced a pronounced inhibitory effect on matrix breakdown. The effects of both inhibitors were studied electron microscopically and biochemically (determination of sulfated-glycosaminoglycans in the high density cultures by Alcian Blue binding assay). The results of this study are consistent with the presumption that rheumatoid synovial cells are capable of inhibiting chondrogenesis and enhancing the breakdown of the cartilaginous matrix. Amongst others, the possible mediators involved are prostaglandins and plasminogen activators. The response to the inhibitors Avarol and PAI-2 is compatible with their mode of action. The chondroprotective action of these substances may be useful in developing potential antirheumatic drugs. PMID:8401816

Mohamed-Ali, H; Scholz, P; Merker, H J

1993-01-01

148

Plasmids encoding therapeutic agents  

DOEpatents

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.

Keener, William K. (Idaho Falls, ID)

2007-08-07

149

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

PubMed Central

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 cm2 to 128.80±95.7 cm2) and a 66% reduction after 3 months (81.38±59.19 cm2). 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. PMID:25018649

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

2014-01-01

150

HIV / AIDS  

MedlinePLUS

... on. Read more information on enabling JavaScript. HIV/AIDS Skip Content Marketing Share this: Main Content Area ... are being affected by HIV/AIDS. Understanding HIV/AIDS Overview Cause Transmission Symptoms Testing and Diagnosis Treatment ...

151

HIV Life Cycle  

MedlinePLUS

... HIV life cycle. What is the connection between HIV medicines and the HIV life cycle? Without treatment, HIV infection gradually destroys ... the risk of HIV drug resistance . What is HIV drug resistance? Drug resistance is when HIV is ...

152

Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals  

PubMed Central

Background HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa. Methods Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT. Results In antiretroviral-naive mother–infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1–infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT. Conclusions CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants. PMID:18845960

Singh, Kumud K.; Hughes, Michael D.; Chen, Jie; Phiri, Kelesitse; Rousseau, Christine; Kuhn, Louise; Coutsoudis, Anna; Jackson, J. Brooks; Guay, Laura A.; Musoke, Philippa; Mmiro, Francis; Semba, Richard D.; Spector, Stephen A.

2009-01-01

153

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

PubMed Central

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

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

2014-01-01

154

Genome-wide search for the genes accountable for the induced resistance to HIV-1 infection in activated CD4+ T cells: apparent transcriptional signatures, co-expression networks and possible cellular processes  

PubMed Central

Background Upon co-stimulation with CD3/CD28 antibodies, activated CD4?+?T cells were found to lose their susceptibility to HIV-1 infection, exhibiting an induced resistant phenotype. This rather unexpected phenomenon has been repeatedly confirmed but the underlying cell and molecular mechanisms are still unknown. Methods We first replicated the reported system using the specified Dynal beads with PHA/IL-2-stimulated and un-stimulated cells as controls. Genome-wide expression and analysis were then performed by using Agilent whole genome microarrays and established bioinformatics tools. Results We showed that following CD3/CD28 co-stimulation, a homogeneous population emerged with uniform expression of activation markers CD25 and CD69 as well as a memory marker CD45RO at high levels. These cells differentially expressed 7,824 genes when compared with the controls on microarrays. Series-Cluster analysis identified 6 distinct expression profiles containing 1,345 genes as the representative signatures in the permissive and resistant cells. Of them, 245 (101 potentially permissive and 144 potentially resistant) were significant in gene ontology categories related to immune response, cell adhesion and metabolism. Co-expression networks analysis identified 137 “key regulatory” genes (84 potentially permissive and 53 potentially resistant), holding hub positions in the gene interactions. By mapping these genes on KEGG pathways, the predominance of actin cytoskeleton functions, proteasomes, and cell cycle arrest in induced resistance emerged. We also revealed an entire set of previously unreported novel genes for further mining and functional validation. Conclusions This initial microarray study will stimulate renewed interest in exploring this system and open new avenues for research into HIV-1 susceptibility and its reversal in target cells, serving as a foundation for the development of novel therapeutic and clinical treatments. PMID:23635305

2013-01-01

155

The HIV-Infected Adolescent  

Microsoft Academic Search

HIV-infected adolescents represent a unique, yet diverse, population requiring specialized medical and psychosocial HIV care.\\u000a Perinatally infected and behaviorally infected adolescents often have differing therapeutic needs, but may share common difficulties,\\u000a including medication nonadherence, high-risk sexual behavior, psychosocial stressors, and concomitant psychiatric disorders.\\u000a Addressing these needs within a culturally sensitive framework and in the context of a population-specific approach to

Allison C. Ross; Andres Camacho-Gonzalez; Sheryl Henderson; Francisca Abanyie; Rana Chakraborty

2010-01-01

156

Antisense Oligodeoxynucleotide Inhibition of HIV Gene Expression.  

National Technical Information Service (NTIS)

The goal of this work is to develop novel, efficacious, injectable, gene-specific therapeutics for treatment of human immunodeficiency virus (HIV) infection. These products will be nuclease resistant, stereospecific antisense inhibitors of human immunodef...

E. Wickstrom

1989-01-01

157

Human Immunodeficiency Virus (HIV) Research (AIDS).  

National Technical Information Service (NTIS)

This grant was awarded to fund clinical and laboratory research on therapeutic regimens which show promise of ameliorating the effects of HIV infection. Midway through the five year grant, an organizational structure is in place to conduct both basic and ...

B. C. Redington, M. B. Shaw

1991-01-01

158

HIV TAT Protein Transduction Domain Mediated Cell Binding and Intracellular Delivery of Nanoparticles  

Microsoft Academic Search

Intracellular delivery of non?transported therapeutic agents has traditionally been thought possible only for low molecular weight (<500 DA) hydrophobic molecules. Higher molecular weight agents including oligonucleotides, proteins, DNA, liposomes, and nanoparticles do not readily enter the cytoplasm. However, the human immunodeficiency virus (HIV) trans?acting transcriptional activator (TAT) protein enters the cytosol by way of an 11 amino acid cationic peptide (TATp).

J. Andrew MacKay; Francis C. Szoka Jr.

2003-01-01

159

A novel approach to develop anti-HIV drugs: adapting non-nucleoside anticancer chemotherapeutics.  

PubMed

Some anticancer drugs, but not all, inhibit replication of human immunodeficiency virus (HIV) and thus, exhibit a therapeutic potential. Such drugs, unlike the traditional HIV enzyme inhibitors, could suppress HIV strains that are resistant to inhibitors of viral enzymes, decrease proviral burden in vivo, or reduce reservoirs of infection via killing infected cells. Thus, they may be an effective adjunct therapy or perhaps result in a cure. The incidence of HIV infection and AIDS mortalities continue to increase worldwide, including the United States and parts of Africa, with a parallel increase in a number of other manifestations, including AIDS defining malignancies. The basis for continual spread of HIV presumably in large part stems from the viral resistance to previously successful drugs and the lack of curative antiretroviral drugs. To reverse these trends, other approaches for AIDS therapy must be developed. One possibility is the development of potent anticancer drugs, that exhibit anti-HIV activities. At least four chemically and pharmacologically distinct classes of anticancer drugs, i.e. certain cyclin-dependent kinase inhibitors (CDKIs), topoisomerase 1 enzyme (top 1) inhibitors, non-nucleoside antimetabolites, and estrogen receptor ligands are promising candidates. These drugs, at high doses are used for cancer therapy; at lower concentrations they exhibit anti-HIV activities in cultured cells. While the antiretroviral and the anticancer activities of the cdk inhibitor flavopiridol appear to be mutually exclusive and unrelated in cells and animal model(s) of HIV disease, the top 1 inhibitor 9-nitrocamptothecin, as well as the cdk-inhibitor roscovitine inhibit replication of HIV via selective sensitization of HIV-infected cells to apoptosis. In contrast, the inhibitory effects of these compounds are different from other cancer therapeutics that, at toxic concentrations, activate HIV either in cultured cells (such as certain ingenol and butyrate derivatives) and/or in patients (such as the widely used cyclophosmamide and cisplatin). This quality may lead to the eradication of proviral reservoirs, which is not accomplished by the currently available antiretroviral drugs. In this review, relevant available clinical and in vitro data that either support or discourage using certain anticancer drugs for treatment of HIV disease, and the rationales for developing novel antiretroviral drugs that may target infected cells rather than viral proteins are discussed. PMID:14670589

Sadaie, M Reza; Mayner, Ronald; Doniger, Jay

2004-01-01

160

HIV Testing Frequency  

MedlinePLUS

... HIV Testing Frequency Translate Text Size Print Share HIV Testing Frequency Testing Frequency How often should you ... local health department for proper care and information. HIV Testing HIV Test Locations HIV Test Types HIV ...

161

HIV Viral Load  

MedlinePLUS

... that an HIV viral load test detects HIV RNA. What is an HIV DNA test? The HIV ... HIV-1-Infected Adults and Adolescents, Plasma HIV RNA Testing. AIDSinfo On-line information]. Available online through ...

162

Lymphedema and Therapeutic Lymphangiogenesis  

PubMed Central

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. Lymphedema is divided into primary and secondary forms based on the underlying etiology. Despite substantial advances in both surgical and conservative techniques, therapeutic options for the management of lymphedema are limited. Although rarely lethal, lymphedema is a disfiguring and disabling condition with an associated decrease in the quality of life. The recent impressive expansion of knowledge on the molecular mechanisms governing lymphangiogenesis provides new possibilities for the treatment of lymphedema. This review highlights the lymphatic biology, the pathophysiology of lymphedema, and the therapeutic lymphangiogenesis using hepatocyte growth factor. PMID:24222916

Nakagami, Hironori; Kaneda, Yasufumi; Morishita, Ryuichi

2013-01-01

163

Human immunodeficiency virus (HIV) seropositivity in intravenous (i.v.) drug abusers in three cities of Italy: possible natural history of HIV infection in i.v. drug addicts in Italy.  

PubMed

The prevalence of human immunodeficiency virus (HIV) antibodies and the symptoms induced [persistent generalized lymphadenopathy (PGL), AIDS-related complex (ARC), acquired immunodeficiency syndrome (AIDS)] was evaluated in several groups of intravenous (IV) drug abusers in three large Italian cities (Milan, Bologna, and Rome). The earliest evidence of seropositivity in sera collected from patients with acute viral hepatitis dates back to 1979 in Milan and to 1981 in Bologna with peaks in 1983 in both cities. In two groups of IV drug addicts on methadone-maintenance treatment at assistance centers, the prevalence of seropositivity differed sharply between Rome (33.3%) and Milan (69.3%) in 1985. Rates of seroconversion were also found to be higher in Milan than in Bologna and Rome. When a population of IV drug abusers voluntarily attending centers for surveillance of AIDS and/or ARC were investigated, high levels (range 55.2-81.5%) of seropositivity were found in the three cities. ARC prevalence among seropositives was very high (range 48.1-64.2% in 1985) in the three cities. The evolution rate to AIDS in Milan was higher among those attending a center for AIDS surveillance (7.4%) than among those attending an assistance center for methadone treatment (0.9%). These data are compatible with the hypothesis that virus infection among IV drug abusers originated in and then spread widely in Northern Italy (Milan first and then Bologna). Both the first appearance and subsequent spread of virus infection are in keeping with the reported occurrence of AIDS cases in the corresponding three regions of Milan, Bologna, and Rome. PMID:3430144

Titti, F; Lazzarin, A; Costigliola, P; Oliva, C; Nicoletti, L; Negri, C; Ricchi, E; Donati, G; Uberti-Foppa, C; Re, M C

1987-11-01

164

Possible false-negative results on therapeutic drug monitoring of phenytoin using a particle enhanced turbidimetric inhibition immunoassay in a patient with a high level of IgM.  

PubMed

: In this report, the authors described the unusual case of a patient in whom the plasma phenytoin concentration was unexpectedly not detected on a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) technique, a typical immunoassay for phenytoin. The plasma concentration was measured using PETINIA and high-performance liquid chromatography in a 69-year-old male patient treated with fosphenytoin intravenously at the standard dose for 7 days. Although the plasma concentration of phenytoin was below the limit of detection (<0.5 mcg/mL) on PETINIA after the administration of fosphenytoin, the trough plasma concentration was estimated to be between 5 and 10 mg/L on high-performance liquid chromatography. When the plasma concentrations of IgM and IgG were measured using an enzyme-linked immunosorbent assay, the plasma IgG level was within the reference range, whereas the plasma IgM level was 2-3 times higher than the upper limit of the reference range. We concluded that the PETINIA method yielded a possible false-negative result regarding the phenytoin level in this patient, perhaps because of some hindrance to the measurement process by IgM. This case suggests that false-negative results should be considered when therapeutic drug monitoring reveals abnormally low values using PETINIA and that it is necessary to evaluate the plasma IgM level. PMID:24632808

Hirata, Kenshiro; Saruwatari, Junji; Enoki, Yuhuki; Iwata, Kazufumi; Urata, Yukino; Aizawa, Keiji; Ueda, Kentaro; Shirouzono, Takumi; Imamura, Motoki; Moriuchi, Hiroshi; Ishima, Yu; Kadowaki, Daisuke; Watanabe, Hiroshi; Hirata, Sumio; Maruyama, Toru; Fukunaga, Eiko

2014-10-01

165

Study the drug adherence and possible factor influencing drug adherence in HIV/AIDS patients in north eastern part of India  

PubMed Central

Background: Majority of HIV/AIDS patients who are on Highly Active Anti Retroviral Therapy (HAART), are not aware about drug adherence and its importance which is the most important factor for drug adherence. Objectives: To study the level of drug adherence in patients accessing antiretroviral therapy (ART) through the National program and factor influencing drug adherence. Materials and Methods: In present study, we enrolled 102 newly diagnosed patients, among them in 79 patients, ART was started. To study the drug adherence a pretested, semistructured questionnaire was formed and patients were followed up for 6 months of the study. Pretest and posttest counseling was done to all such patients. Results: A total of 28 patients missed the dose in 1st follow-up, nine patients missed in 2nd follow-up, eight patients missed in 3rd follow-up. Three patients lost follow-up in 2nd follow-up, three patients further lost follow-up in 3rd follow-up. Running out of pills (40.0%), side effect (15.5%), and family problem (13.3%), poor transport facility for taking drug (8.9%) and forgetfulness (11.1%) are five major causes related to miss dose. In females patients, drug adherence (69%) was initially less than male patients (76%) but latter on female patients (96.3%) had better adherence than males (95.2%). Conclusion: This study suggest that drug adherence can be increased by proper counseling and close monitoring of the patients which may have a great role in preventing the drug resistance and ART response. PMID:25013824

Meena, Lalit Prashant; Pandey, Shant Kumar; Rai, Madhukar; Bharti, Anju; Chakravarty, Jaya; Sundar, Shyam

2014-01-01

166

Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants.  

PubMed Central

The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1. PMID:8460144

Pollack, H; Zhan, M X; Ilmet-Moore, T; Ajuang-Simbiri, K; Krasinski, K; Borkowsky, W

1993-01-01

167

Therapeutic mammaplasty.  

PubMed

Therapeutic mammaplasty is a term for the oncoplastic application of breast reduction and mastopexy techniques to treat selected breast tumours by breast conserving surgery (BCS). It has the potential to increase the indications for BCS as well as achieve more acceptable aesthetic results from it in suitable women. Now an established technique in the range of oncoplastic options for women with breast cancer, it finds common application and is associated with good oncological and quality of life outcomes. PMID:24889526

Macmillan, R D; James, R; Gale, K L; McCulley, S J

2014-07-01

168

Association Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies  

PubMed Central

Background: Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. Methods: We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1–infected humanized mice treated with the antibody PGT128 and from untreated control mice. Results: For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1–infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). Conclusions: These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach. PMID:25072615

Walter, Hauke; Lengauer, Thomas

2014-01-01

169

HIV UPDATE: cancer & HIV  

E-print Network

description of the acquired immune deficiency syndrome (AIDS). Now, the World Health Organization predicts of CD4 cell counts but becomes increasingly more common as immune function declines. The progression may toxicity. In this edition of Tlaleletso we review the common cancers seen in people living with HIV

Bushman, Frederic

170

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 ...

171

HIV Prevention  

MedlinePLUS

... your HIV-positive partner is taking antiretroviral therapy (ART) consistently and correctly, especially if his/her viral ... your partner to get and stay on treatment. ART reduces the amount of HIV virus (viral load) ...

172

HIV Transmission  

MedlinePLUS

... the partner with HIV is using antiretroviral therapy (ART) consistently and correctly and whether the partner who ... the partner with HIV is taking antiretroviral therapy (ART) consistently and correctly, and if the partner who ...

173

HIV virus  

NSDL National Science Digital Library

HIV is a virus that can be transmitted through fluids exchanged in sexual activity. HIV eventually causes AIDS. AIDS patients have compromised immune systems and they eventually die from diseases that healthy humans would normally fight off very easily.

Carl Henderson (National Institutes of Health;)

2005-12-09

174

Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells  

PubMed Central

HIV-infected individuals currently cannot be completely cured because existing antiviral therapy regimens do not address HIV provirus DNA, flanked by long terminal repeats (LTRs), already integrated into host genome. Here, we present a possible alternative therapeutic approach to specifically and directly mediate deletion of the integrated full-length HIV provirus from infected and latently infected human T cell genomes by using specially designed zinc-finger nucleases (ZFNs) to target a sequence within the LTR that is well conserved across all clades. We designed and screened one pair of ZFN to target the highly conserved HIV-1 5?-LTR and 3?-LTR DNA sequences, named ZFN-LTR. We found that ZFN-LTR can specifically target and cleave the full-length HIV-1 proviral DNA in several infected and latently infected cell types and also HIV-1 infected human primary cells in vitro. We observed that the frequency of excision was 45.9% in infected human cell lines after treatment with ZFN-LTR, without significant host-cell genotoxicity. Taken together, our data demonstrate that a single ZFN-LTR pair can specifically and effectively cleave integrated full-length HIV-1 proviral DNA and mediate antiretroviral activity in infected and latently infected cells, suggesting that this strategy could offer a novel approach to eradicate the HIV-1 virus from the infected host in the future. PMID:23804764

Qu, Xiying; Wang, Pengfei; Ding, Donglin; Li, Lin; Wang, Haibo; Ma, Li; Zhou, Xin; Liu, Shaohui; Lin, Shiguan; Wang, Xiaohui; Zhang, Gongmin; Liu, Sijie; Liu, Lin; Wang, Jianhua; Zhang, Feng; Lu, Daru; Zhu, Huanzhang

2013-01-01

175

HIV chemotherapy  

Microsoft Academic Search

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.

Douglas D. Richman

2001-01-01

176

Protection against ischemic brain injury by protein therapeutics  

Microsoft Academic Search

Preventing massive cell death is an important therapeutic strategy for various injuries and disorders. Protein therapeutics have the advantage of delivering proteins in a short period. We have engineered the antiapoptotic bcl-x gene to generate the super antiapoptotic factor, FNK, with a more powerful cytoprotective activity. In this study, we fused the protein transduction domain (PTD) of the HIV\\/Tat protein

Sadamitsu Asoh; Ikuroh Ohsawa; Takashi Mori; Ken-Ichiro Katsura; Tomoharu Hiraide; Yasuo Katayama; Megumi Kimura; Daiya Ozaki; Kumi Yamagata; Shigeo Ohta

2002-01-01

177

Mesothelioma in an HIV\\/AIDS patient without history of asbestos exposure: possible role for immunosuppression in mesothelioma: a case report  

Microsoft Academic Search

We describe a 41-year-old African-American male who initially presented in respiratory distress. He had a positive history of asthma, cigarette smoking, and only recent possible asbestos exposure six months prior to onset of symptoms. Mesothelioma was suspected after chest radiography and PET-CT, and confirmed by immunohistochemical tissue analysis. We postulate that immunosuppression enhances susceptibility to mesothelioma, since weakened immune systems

Cleve Orian James; Ashanti W Woods; Payam Arya; Khadega Ahmed Abuelgasim; Lekidelu Taddesse Heath; Amy Sitapati

2009-01-01

178

HIV Protease Inhibitors Modulate Ca2+ Homeostasis and Potentiate Alcoholic Stress and Injury in Mice and Primary Mouse and Human Hepatocytes  

PubMed Central

A portion of HIV-infected patients under therapy with protease inhibitors (HIV PIs) concomitantly consume or abuse alcohol leading to hepatic injury. The underling mechanisms are not known. We hypothesize that HIV PI aggravates alcohol-induced liver injury through an endoplasmic reticulum (ER) stress mechanism. To address this, we treated mice and primary mouse and human hepatocytes (PMH and PHH respectively) with alcohol and the two HIV PIs: ritonavir and lopinavir. In mice, ritonavir and lopinavir (15 mg/kg body weight each) induced mild ER stress and inhibition of Sarco/ER Calcium-ATPase (SERCA) without significant increase in serum ALT levels. However, a single dose of alcohol by gavage (5g/kg body weight) plus the two HIV PIs caused a greater than 5-fold increase in serum ALT, a synergistic increase in alcohol-induced liver lipid accumulation and ER stress response, and a decrease of SERCA. Mice treated with chronic HIV PIs and alcohol developed moderate liver fibrosis. In PMH, the HIV drugs plus alcohol also inhibited SERCA expression and increased expression of GRP78, CHOP, SREBP1c and phosphorylated JNK2, which were accompanied by a synergistic increase in cell death compared to alcohol or the HIV drugs alone. In PHH, ritonavir and lopinavir or alcohol alone treatment increased mRNA of spliced Xbp1 and decreased SERCA, which were accompanied by reduced levels of intracellular calcium. Alcohol combined with the HIV drugs significantly reduced intracellular calcium levels and potentiated cell death, which was comparable to the cell death caused by the SERCA inhibitor-thapsigargin. Our findings suggest the possibility that HIV PIs potentiate alcohol-induced ER stress and injury through modulation of SERCA and maintaining calcium homeostasis should be a therapeutic aim for a better care of HIV patients. PMID:22407670

Kao, Eddy; Shinohara, Masao; Feng, Min; Lau, Mo Yin; Ji, Cheng

2012-01-01

179

Authentic HIV-1 integrase inhibitors  

PubMed Central

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

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

2010-01-01

180

Ingenol Derivates Promising for HIV Eradication.  

PubMed

The eradication of HIV is at this moment one of the greatest challenges in the fight against HIV/AIDS. Despite the prolonged effectiveness of current anti-HIV therapies, capable of keeping patients with undetectable viremia for long periods of time, HIV-infected patients cannot be cured due to the establishment of HIV latent reservoirs. Therefore, several therapeutic strategies are being evaluated to eliminate these viral reservoirs. One of these strategies, termed "shock and kill", aims to attack the latent reservoir by simultaneous treatment with HIV-activating agents to stimulate viral replication in latently infected cells and antiretroviral therapy to block new infections. A number of compounds have been suggested for the shock and kill strategy including histone deacetylase inhibitors (HDACI), histone methyltransferases (HMT), DNA methyltransferase inhibitors (DNMTI), and protein kinase C (PKC) activators. PMID:25373349

Poveda, Eva

2014-01-01

181

HIV Wellness Numbers  

MedlinePLUS Videos and Cool Tools

HIV Wellness Numbers Updated:Mar 22,2012 Featured Video The Basics of HIV Management Length: 2:37 ... Learn more about your important heart-health numbers . HIV and Your Heart • Home • About HIVHIV and ...

182

HIV Medicine: A Medical Texbook  

NSDL National Science Digital Library

HIV Medicine is an online medical textbook that provides comprehensive and timely information on HIV treatment. Chapters include background information on Acute HIV-1 Infection, and a detailed guide to HIV Therapy. There is also current information about side effects, Lipodystrophy Syndrome, and resistance testing. The online textbook includes an impressive, in-depth index of HIV drugs. Editors Christian Hoffmann and Bernd Sebastian Kamps have years of experience in the medical field and provide free and anonymous access of their text to the public. Collaborators include Nyasha Bakare, MD who has worked at the Research Institute for Genetic and Human Therapy (RIGHT) since 2001, and has been working on the clinical development of a therapeutic HIV vaccine. This Web site is easy to navigate and its layout nicely mirrors the organization of a paper textbook. It will be useful as a research tool for college and graduate students as well as for the layperson who desires more in-depth information on HIV and treatments. Join the mailing list to be notified of new chapters and updates. [TJS

Hoffmann, Christian; Kamps, Bernd S.

183

An efficient synthesis of a hydroxyethylamine (HEA) isostere and its ?-aminophosphonate and phosphoramidate derivatives as potential anti-HIV agents.  

PubMed

HIV protease is a promising drug target for AIDS therapy, and several potent HIV-1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possible emergence of therapeutic resistance. As HIV protease cleaves the peptide bond via a tetrahedral intermediate, various transition-state models such as hydroxyethylamine (HEA) have been designed. We therefore pursued an efficient synthesis of an HEA isostere; this was performed with a novel one-pot reduction-transimination-reduction reaction sequence as a key step. ?-Aminophosphonate and phosphoramidate derivatives of the HEA isostere were designed and synthesized, and all of the synthesized derivatives were assayed for their anti-HIV activities against wild-type and mutant HIV strains. Phosphoramidate derivative 15 a was found to be the most active of all synthesized compounds against the III(B) and RES056 strains. As phosphonates are known to exhibit physiological stability, good cell permeability, and other promising pharmacokinetic characteristics, our newly synthesized compounds have the potential as alternatives to existing therapeutics and diagnostics. PMID:22786810

Bhattacharya, Asish K; Rana, Kalpeshkumar C; Pannecouque, Christophe; De Clercq, Eric

2012-09-01

184

HIV1 Langerhans' Cell Tropism Associated with Heterosexual Transmission of HIV  

Microsoft Academic Search

Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1

Luis E. Soto-Ramirez; Boris Renjifo; Mary F. McLane; Richard Marlink; Carl O'Hara; Ruengpung Sutthent; Chantapong Wasi; Prakong Vithayasai; Vicharn Vithayasai; Chatchawann Apichartpiyakul; Prasert Auewarakul; Victor Pena Cruz; Dao-Shan Chui; Rapin Osathanondh; Kenneth Mayer; Tun-Hou Lee; Max Essex

1996-01-01

185

HIV Transmission Networks  

PubMed Central

Purpose of Review Over the past several years, one segment of the complex field of HIV transmission dynamics —heterosexual networks—has dominated theoretical and empirical investigation. This review provides an overview of recent work on HIV risks and networks, with a focus on recent findings in heterosexual network dynamics. Recent findings Qualitative (ethnographic) assessments have demonstrated the heterogeneity and complexity of heterosexual connections, particular in Africa where tradition, official polygamy, and unofficial multi-person arrangements lead to concurrency of sexual partnerships. A large, quantitative study on Likoma Island, Malawi, demonstrated the considerable, interlocking sexual connections that arise from a high-concurrency sexual setting, even with a low average number of partnerships (low-degree) of long duration. Such settings, as suggested by ethnographic studies, may be common in Africa and, coupled with newer information about transmissibility during acute and early infection, may provide a plausible explanation for endemic transmission and possibly for rapid HIV propagation. Summary Recognition of high- concurrency, low-degree networks is an important development for understanding HIV transmission dynamics. Their relevance to heterosexual transmission, and possible extension to other epidemiologic settings, reinforces the heterogeneity and complexity of HIV transmission dynamics. PMID:19532062

Rothenberg, Richard

2010-01-01

186

HIV Medicine  

NSDL National Science Digital Library

From Flying Publisher, _HIV Medicine 2005_ is a free, online "medical textbook that provides a comprehensive and up-to-date overview of the treatment of HIV Infection." This edition is an update of the 2003 version of the textbook (reported on in the June 13, 2003 NSDL Scout Report for Life Sciences). Chapter titles in the textbook include HIV Testing, HIV and Pulmonary Diseases, Mitochondrial Toxicity, HIV and HBV Coinfections, and Traveling with HIV, to name a few. The textbook is available in both German and English. Please note that while certain sections of the 2005 edition are currently available, many sections are still in the process of being published on the site. Sections from the 2003 edition are standing in for some of the forthcoming 2005 sections. The entire 352-page 2003 edition is available for download at this site as well.

187

Human immunodeficiency virus (HIV) type 2-mediated inhibition of HIV type 1: a new approach to gene therapy of HIV-infection.  

PubMed Central

Human immunodeficiency virus (HIV) type 2, the second AIDS-associated human retrovirus, differs from HIV-1 in its natural history, infectivity, and pathogenicity, as well as in details of its genomic structure and molecular behavior. We report here that HIV-2 inhibits the replication of HIV-1 at the molecular level. This inhibition was selective, dose-dependent, and nonreciprocal. The closely related simian immunodeficiency provirus also inhibited HIV-1. The selectivity of inhibition was shown by the observation that HIV-2 did not significantly downmodulate the expression of the unrelated murine leukemia virus; neither did the murine leukemia virus markedly affect HIV-1 or HIV-2 expression. Moreover, while HIV-2 potently inhibited HIV-1, the reverse did not happen, thus identifying yet another and remarkable difference between HIV-1 and HIV-2. Mutational analysis of the HIV-2 genome suggested that the inhibition follows a complex pathway, possibly involving multiple genes and redundant mechanisms. Introduction of inactivating mutations into the structural and regulatory/accessory genes did not render the HIV-2 provirus ineffective. Some of the HIV-2 gene defects, such as that of tat and rev genes, were phenotypically transcomplemented by HIV-1. The HIV-2 proviruses with deletions in the putative packaging signal and defective for virus replication were effective in inducing the suppressive phenotype. Though the exact mechanism remains to be defined, the inhibition appeared to be mainly due to an intracellular molecular event because it could not be explained solely on the basis of cell surface receptor mediated interference. The results support the notion that the inhibition likely occurred at the level of viral RNA, possibly involving competition between viral RNAs for some transcriptional factor essential for virus replication. Induction of a cytokine is another possibility. These findings might be relevant to the clinical-epidemiological data suggesting that infection with HIV-2 may offer some protection against HIV-1 infection. Images Fig. 3 PMID:8633095

Arya, S K; Gallo, R C

1996-01-01

188

T Cell Transcription Factors and Their Impact on HIV Expression  

PubMed Central

By targeting CD4+ effector T cells, HIV has a dramatic impact on the depletion, expansion and function of the different polarized T cell subsets. The maturation of T cell lineages is in part driven by intrinsic transcription factors that potentially influence how efficiently HIV replicates. In this review, we explore whether transcription factors that are required for polarizing T cells influence HIV replication. In particular, we examine provirus transcription as well as the establishment and maintenance of HIV latency. Furthermore, it is suggested these factors may provide novel cell-specific therapeutic strategies for targeting the HIV latent reservoir. PMID:24436634

Kaczmarek, Katarzyna; Morales, Ayana; Henderson, Andrew J.

2013-01-01

189

Postexposure prophylaxis for HIV.  

PubMed

Health care workers are at risk for human immunodeficiency virus (HIV) and other infectious pathogens through exposure to blood and body fluids. Antiretroviral medications have been prescribed for postexposure prophylaxis following occupational exposure to the HIV since the early 1990s. This practice has since been extended to nonoccupational situations, such as sexual assaults. The efficacy of prophylactic therapy may be highly time-dependent and should be initiated as soon as possible. Wound care management and referral for social, medical, or advocacy services remain important for all cases. PMID:20413023

Chin, Rachel L

2010-05-01

190

Focused assessment with sonography for HIV-associated tuberculosis (FASH): a short protocol and a pictorial review  

PubMed Central

Background Ultrasound can rapidly identify abnormal signs, which in high prevalence settings, are highly suggestive of extra-pulmonary tuberculosis (EPTB). Unfortunately experienced sonographers are often scarce in these settings. Methods A protocol for focused assessment with sonography for HIV-associated tuberculosis (FASH) which can be used by physicians who are relatively inexperienced in ultrasound was developed. Results The technique as well as normal and pathological findings are described and the diagnostic and possible therapeutic reasoning explained. The protocol is intended for settings where the prevalence of HIV/TB co-infected patients is high. Conclusion FASH is suitable for more rapid identification of EPTB even at the peripheral hospital level where other imaging modalities are scarce and most of the HIV and TB care will be delivered in the future. PMID:23171481

2012-01-01

191

The crystal structure of protease Sapp1p from Candida parapsilosis in complex with the HIV protease inhibitor ritonavir.  

PubMed

Secreted aspartic proteases (Saps) are extracellular proteolytic enzymes that enhance the virulence of Candida pathogens. These enzymes therefore represent possible targets for therapeutic drug design. Saps are inhibited by nanomolar concentrations of the classical inhibitor of aspartic proteases pepstatin A and also by the inhibitors of the HIV protease, but with the K(i) of micromolar values or higher. To contribute to the discussion regarding whether HIV protease inhibitors can act against opportunistic mycoses by the inhibition of Saps, we determined the structure of Sapp1p from Candida parapsilosis in complex with ritonavir (RTV), a clinically used inhibitor of the HIV protease. The crystal structure refined at resolution 2.4 Å proved binding of RTV into the active site of Sapp1p and provided the structural information necessary to evaluate the stability and specificity of the protein-inhibitor interaction. PMID:22146051

Dostál, Ji?í; Brynda, Ji?í; Hrušková-Heidingsfeldová, Olga; Pachl, Petr; Pichová, Iva; Rezá?ová, Pavlína

2012-02-01

192

HIV-1 Tat-Mediated Apoptosis in Human Blood-Retinal Barrier-Associated Cells  

PubMed Central

HIV-1-associated ocular complications, such as microvasculopathies, can lead to the loss of vision in HIV-1-infected patients. Even in patients under highly active antiretroviral therapy, ocular lesions are unavoidable. Ocular complications have been demonstrated to be closely related to the breakdown of the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear. The data from this study indicated that the HIV-1 Tat protein induced the apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB, respectively. In addition, this study found that the activation of N-methyl-D-aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected against the apoptosis induced by NMDAR activation and prevented the dysregulation of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications. PMID:24739951

Che, Xin; He, Fanglin; Deng, Yuan; Xu, Shiqiong; Fan, Xianqun; Gu, Ping; Wang, Zhiliang

2014-01-01

193

False negative HIV antibody test in HIV infected children who receive early antiretroviral treatment in a resource-limited setting.  

PubMed

With the implementation of 2010 World Health Organization guidelines, the number of infants from developing countries who will initiate antiretroviral therapy (ART) will increase considerably. In this study we describe the HIV antibody tests of 14 HIV infected children who initiated ART at age less than one year in a rural setting of India. The HIV rapid test was negative in seven and indeterminate in two cases, whereas the HIV enzyme-linked immunosorbent assay (ELISA) antibody test was negative in three and indeterminate in one case. In one child who had both negative HIV rapid test and ELISA initially, HIV serology turned positive after having a virological failure to ART, suggesting the possibility of utilizing HIV serology for monitoring ART effectiveness in children who experience HIV seroreversion. In conclusion, HIV seroreversion of children with early initiation of ART is common and should be considered for avoiding misdiagnosis of HIV infection. PMID:24470936

Alvarez-Uria, Gerardo; Naik, Praveen K; Midde, Manoranjan; Kannan, Shanmugamari; Reddy, Raghuprakash

2012-01-01

194

False negative HIV antibody test in HIV infected children who receive early antiretroviral treatment in a resource-limited setting  

PubMed Central

With the implementation of 2010 World Health Organization guidelines, the number of infants from developing countries who will initiate antiretroviral therapy (ART) will increase considerably. In this study we describe the HIV antibody tests of 14 HIV infected children who initiated ART at age less than one year in a rural setting of India. The HIV rapid test was negative in seven and indeterminate in two cases, whereas the HIV enzyme-linked immunosorbent assay (ELISA) antibody test was negative in three and indeterminate in one case. In one child who had both negative HIV rapid test and ELISA initially, HIV serology turned positive after having a virological failure to ART, suggesting the possibility of utilizing HIV serology for monitoring ART effectiveness in children who experience HIV seroreversion. In conclusion, HIV seroreversion of children with early initiation of ART is common and should be considered for avoiding misdiagnosis of HIV infection. PMID:24470936

Alvarez-Uria, Gerardo; Naik, Praveen K; Midde, Manoranjan; Kannan, Shanmugamari; Reddy, Raghuprakash

2012-01-01

195

Pharmacotherapy of Pediatric HIV Infection  

PubMed Central

SYNOPSIS With the ongoing epidemic of human immune deficiency virus (HIV) infections in the pediatric age group, the delivery of safe and effective antiretroviral therapy to children and adolescents is crucial to save the lives of millions of children worldwide. Antiretroviral drugs have been demonstrated to significantly decrease HIV-associated morbidity and mortality, assure normal growth and development, and improve survival and quality of life in children and adolescents. The immunologic response to HIV infection is closely related to the child’s development and creates age specific parameters for the evaluation of therapeutic response to antiretroviral therapy in pediatric HIV disease. In addition to the changes in immunological response to HIV infection, the development and maturation of organ systems involved in drug absorption, distribution, metabolism, and elimination determines significant changes in the pharmacokinetics of antiretroviral drugs throughout the childhood. Multiple factors including age-specific adherence barriers, changes in social and economical surroundings, and psychological and sexual maturation affect the choices and outcomes of the treatment of pediatric HIV disease. In this chapter we will review the evolution of antiretroviral treatment from early infancy through adolescence. PMID:23036246

Rakhmanina, Natella; Phelps, Ryan

2012-01-01

196

Myocardial and pericardial disease in HIV  

Microsoft Academic Search

Opinion statement  Cardiovascular complications are frequently encountered in the HIV-infected population. Cardiac care providers should implement\\u000a appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in this increasingly\\u000a treatable, chronic disease. All HIV-infected individuals should undergo periodic cardiac evaluation, including echocardiography,\\u000a in order to identify subclinical cardiac dysfunction. Left ventricular (LV) dysfunction can result from, or be

William G. Harmon; Gul H. Dadlani; Stacy D. Fisher; Steven E. Lipshultz

2002-01-01

197

Partner Characteristics Predicting HIV-1 Set Point in Sexually Acquired HIV-1 Among African Seroconverters  

PubMed Central

Abstract Plasma HIV-1 RNA set point is an important predictor of HIV-1 disease progression. We hypothesized that inoculum size and HIV-1 exposure prior to HIV-1 transmission may modulate set point. We evaluated predictors of set point among 141 African HIV-1 seroconverters and their HIV-1-infected study partners. We compared characteristics of seroconverters and their HIV-1-infected partners and HIV-1 set point. Data were from a clinical trial of genital HSV-2 suppression with acyclovir to reduce HIV-1 transmission in HIV-1 serodiscordant couples with HIV-1 transmission linkage assigned through virus sequencing. Our analysis includes data from all transmissions including those with transmission linkage to the HIV-1-infected “source partner” and those that were not linked to their HIV-1-infected study partner. In multivariable analysis, higher plasma HIV-1 in source partners was associated with higher seroconverter set point (+0.44 log10 copies/ml per log10 source partner plasma HIV-1, p<0.001). In addition, bacterial vaginosis (BV) among female source partners near the time of infection was associated with higher set point in their male seroconverters (+0.49 log10, p=0.04). Source partner characteristics associated with lower set point included male circumcision (?0.63 log10, p=0.03) and assignment to acyclovir (?0.44 log10, p=0.02). The proportion of variation in set point explained by plasma HIV-1 RNA of the source partner, after controlling for other factors, was 0.06. Source partner plasma HIV-1 level is the most significant predictor of seroconverter set point, possibly reflecting characteristics of the transmitted virus. Acyclovir use, BV among women source partners, and circumcision among male source partners may alter the set point by affecting transmitted virus inoculum in the source partners' genital compartment. PMID:23061422

Thomas, Katherine K.; Hughes, James P.; Baeten, Jared M.; Wald, Anna; Farquhar, Carey; de Bruyn, Guy; Fife, Kenneth H.; Campbell, Mary S.; Kapiga, Saidi; Mullins, James I.; Celum, Connie

2013-01-01

198

The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4 (FFA4/GPR120), Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism  

PubMed Central

TUG-891 [3-(4-((4-fluoro-4?-methyl-[1,1?-biphenyl]-2-yl)methoxy)phenyl)propanoic acid] was recently described as a potent and selective agonist for the long chain free fatty acid (LCFA) receptor 4 (FFA4; previously G protein–coupled receptor 120, or GPR120). Herein, we have used TUG-891 to further define the function of FFA4 and used this compound in proof of principle studies to indicate the therapeutic potential of this receptor. TUG-891 displayed similar signaling properties to the LCFA ?-linolenic acid at human FFA4 across various assay end points, including stimulation of Ca2+ mobilization, ?-arrestin-1 and ?-arrestin-2 recruitment, and extracellular signal-regulated kinase phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. While these latter events were associated with desensitization of the FFA4 signaling response, removal of TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and resensitization of the FFA4 Ca2+ signaling response. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species. Pharmacologic dissection of responses to TUG-891 in model murine cell systems indicated that activation of FFA4 was able to mimic many potentially beneficial therapeutic properties previously reported for LCFAs, including stimulating glucagon-like peptide-1 secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1 adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7 macrophages, which suggests promise for FFA4 as a therapeutic target for type 2 diabetes and obesity. Together, these results demonstrate both potential but also significant challenges that still need to be overcome to therapeutically target FFA4. PMID:23979972

Hudson, Brian D.; Shimpukade, Bharat; Mackenzie, Amanda E.; Butcher, Adrian J.; Pediani, John D.; Christiansen, Elisabeth; Heathcote, Helen; Tobin, Andrew B.; Ulven, Trond

2013-01-01

199

Assessment of HIV testing rates among HIV infected individuals using incidence data on HIV and AIDS diagnoses.  

PubMed

This paper considers estimation of the rate HIV diagnosis in a population of HIV positive individuals. A number of previous papers have studied the situation where time of first positive HIV test is available for AIDS cases, and possibly for individuals who have not yet developed AIDS. In this context, AIDS diagnoses are linked to prior HIV diagnoses. The present paper focuses on the case where AIDS incidence data, and data on new HIV diagnoses, are unlinked. Although there is less information available when there is no linking AIDS diagnosis and HIV tests, it is shown that a useful assessment can be made of the pattern of HIV testing over time. The methodology makes use of back-projection estimates of HIV incidence and involves fitting a model for HIV diagnosis to the observed pattern of new positive HIV tests. Smooth non-parametric estimates are obtained by minimizing a penalized residual sum of squares. In analysis of data on HIV diagnoses among the homosexual/bisexual population in the state of Victoria, Australia, we find strong evidence of a significant decrease in testing rates during the latter part of the 1980s. Subsequent testing rate estimates are subject to greater uncertainty, but are of a comparable magnitude to estimates based on linked data in other countries. PMID:8668874

Marschner, I C

1996-03-15

200

HIV/AIDS  

MedlinePLUS

HIV infection; Infection – HIV; Human immunodeficiency virus; Acquired immune deficiency syndrome ... Human immunodeficiency virus (HIV) causes HIV infection and AIDS. The virus attacks the immune system. As the immune system weakens, the body is ...

201

HIV and Your Heart  

MedlinePLUS

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

202

HIV among Latinos  

MedlinePLUS

... HIV/AIDS HIV A-Z Topics Share Compartir HIV Among Latinos Fast Facts Hispanics/Latinos are disproportionately ... of the total US population. The Numbers New HIV Infections c In 2010, Hispanic/Latino men accounted ...

203

"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

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. PMID:19136190

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

2009-03-01

204

Adolescents with HIV and facial lipoatrophy: response to facial stimulation  

PubMed Central

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

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

2014-01-01

205

HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury.  

PubMed

The present paper describes possible connections between antiretroviral therapies (ARTs) used to treat human immunodeficiency virus (HIV) infection and adverse drug reactions (ADRs) encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART) has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search) and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication. PMID:22506127

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

2012-01-01

206

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

PubMed Central

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

2013-01-01

207

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

PubMed Central

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

2013-01-01

208

HIV-Associated Venous Thromboembolism  

PubMed Central

HIV infection has been recognized as a prothrombotic condition and this association has now been proven by a large number of studies with a reported VTE frequency among HIV-infected patients ranging from 0.19% to 7,63 %/year. HIV infection is associated with a two to tenfold increased risk of venous thrombosis in comparison with a general population of the same age. Some risk factors demonstrated a strongest association with VTE such as, low CD4+ cell count especially in the presence of clinical AIDS, protein S deficiency, and protein C deficiency. Whereas other risk factors are still controversial like protease inhibitor therapy, presence of active opportunistic infections and presence of antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. Physicians caring for HIV positive patients should be able to recognize and treat not only the well-known opportunistic infections and malignancies associated with this chronic disease, but also be alert to the less well-known complications such as thromboses. Pulmonary embolism should be included in the differential diagnosis when patients with HIV/AIDS have unexplained dyspnea or hypoxemia. In younger individuals with VTE, especially men, without other identifiable risk factors for VTE, HIV should be considered. Because interactions between warfarin and antiretrovirals is possible, health care providers should also be alert to the potential of dangerously high or low INRs when they are giving anticoagulants to patients with HIV infection who are undergoing antiretroviral therapy. PMID:21869916

Bibas, Michele; Biava, Gianluigi; Antinori., Andrea

2011-01-01

209

Family Wellness, Not HIV Prevention  

PubMed Central

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

Swendeman, Dallas; Flannery, Diane

2010-01-01

210

HIV and AIDS  

NSDL National Science Digital Library

The Science Inside: HIV and AIDSThis booklet helps to explain what doctors and scientists know about the HIV and AIDS epidemic. It summarizes what HIV and AIDS are and what happens when HIV becomes AIDS, including the health problems that can result. The e-book explains how the diseases are spread, what groups suffer most from them, how they may be prevented, how they are treated, and what the latest research reveals.The Science Inside e-book series is intended to be a bridge between the consumer health brochure and the scientific paper, the booklets in this series focus on the science that is inside of, or behind, the disease its cause, its possible cure, its treatment, promising research, and so on. These booklets are designed to appeal to people who have not had the opportunity to study the science and to understand why they may have been given some of the advice that they have been given through some of the more consumer-oriented materials.

American Association for the Advancement of Science (;)

2004-01-01

211

Update on Human Immunodeficiency Virus (HIV)-2 Infection  

PubMed Central

Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges. PMID:21367732

Campbell-Yesufu, Omobolaji T.

2011-01-01

212

HIV?2 antibody detection after indeterminate or negative HIV?1 Western blot in Cuba, 2005-2008.  

PubMed

INTRODUCTION Differentiating between HIV-1 and HIV-2 infection is the first step to understanding HIV transmission, epidemiology and pathogenesis in geographical areas where both viruses circulate. In Cuba, positive results in mixed HIV-1/2 screening assays are confirmed by HIV-1 Western blot. Indeterminate results constitute the main limitation of this test and HIV-2 infection is among their possible causes; hence the importance of second-stage screening and confirmatory tests for HIV-2 infection. OBJECTIVE Investigate the contribution of HIV-2 antibodies to negative or indeterminate HIV-1 Western blot results in serum samples from 2005 through 2008 in Cuba. METHODS HIV-2 reactivity was studied using the ELISA DAVIH-VIH-2 diagnostic kit (Cuba) in 1723 serum samples with negative or indeterminate results for HIV-1 Western blot from January 2005 through December 2008. Duplicate sera reactive by ELISA were confirmed by HIV-2 Western blot, results interpreted according to WHO criteria. The epidemiological interview established by Cuba's National Program for Prevention and Control Sexually-Transmitted Diseases and HIV/AIDS was applied to HIV-2 Western blot-positive patients. RESULTS Among all sera studied, HIV-2 ELISA identified 12 reactive serum samples (0.70%) and 1711 non-reactive (99.30%). Western blot analysis of the 12 ELISA-reactive samples confirmed two positive samples (16.67%), 4 negative (33.33%) and 6 indeterminate (50%). Positive samples reacted against the p16, p26, gp36, p53, p56, p68 and gp105 proteins. All 12 ELISA-reactive samples belonged to the HIV-1 Western blot indeterminate group. The two HIV-2-positive samples showed well defined reactivity to gp160, p53, p55 and p34 of HIV-1. HIV-1 seroconversion was observed in all 10 remaining samples during serological followup. CONCLUSIONS Two new HIV-2 seropositive cases were diagnosed using DAVIH-VIH-2 and HIV-2 Western blot in indeterminate HIV-1 Western blot samples. Results support the recommendation that HIV-2 Western blot be included in the diagnostic algorithm for HIV-1/2 to followup negative or indeterminate HIV-1 Western blot results. KEYWORDS Diagnosis, laboratory techniques and procedures, antibodies, HIV-2, Western blot, enzyme-linked immunosorbent assay, algorithm, Cuba. PMID:22334109

Díaz, Dervel F; Ortiz, Eva; Martín, Dayamí; Nibot, Carmen; Rizo, Adis; Silva, Eladio

2012-01-01

213

Can TDM Improve Pharmacotherapy of HIV Infection in Adolescents?  

PubMed Central

Currently, therapeutic drug monitoring (TDM) of antiretroviral therapy (ART) is not performed in the US as part of routine clinical care of an HIV-infected adolescent patient. TDM is recommended to rule out subtherapeutic drug concentrations and to differentiate between malabsorption, drug interactions, poor adherence, or increased drug metabolism or clearance as possible causes of decreased drug exposure. The use of TDM is also considered to assist in finding the optimal dose of a drug in patients in patients whose virus has shown a reduced susceptibility to that drug. The dosing of antiretroviral (ARV) drugs in adolescent patients with HIV infection depends on the chronological age, weight, height and the stage of sexual maturation. Due to the limited data on the pharmacokinetics (PK) of ART during puberty the transition of a dosing regimen from higher pediatric (weight and surface-based) to adult (fixed) range is not well defined. Developmental PK differences contribute to high variability in pediatric and adolescent patients and an increased frequency of suboptimal ARV exposure than in adults. Individualized, concentration-targeted optimal dosing of ARV medications can be beneficial to patients for whom only limited dosing guidelines are available. This manuscript describes 3 cases of the application of TDM in treatment experienced adolescent patients whose ART was optimized using of ARV TDM. TDM of ARV drugs is useful in managing the pharmacotherapy of HIV in adolescent patients and is well received by the adolescent patients with HIV and their families. Among others, the benefits of TDM provide evidence for adherence interventions and create grounds for enhanced education of the adolescent patient and involved adult caregivers about ART. Finally, TDM in adolescents provides valuable information about the clinical pharmacology of ART during puberty. PMID:20445485

Rakhmanina, Natella Y.; van den Anker, John N.; Soldin, Steven J.; van Schaik, Ron H.; Mordwinkin, Nick; Neely, Michael N.

2010-01-01

214

Therapeutics Based On The Induced Internalization Of Surface Receptors  

Cancer.gov

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

215

Novel therapeutic strategies for cardioprotection.  

PubMed

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

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

216

Oligonucleotide conjugates for therapeutic applications  

PubMed Central

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

Winkler, Johannes

2013-01-01

217

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

PubMed Central

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

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

2005-01-01

218

Macrophage signaling in HIV-1 infection.  

PubMed

The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection. PMID:20380698

Herbein, Georges; Gras, Gabriel; Khan, Kashif Aziz; Abbas, Wasim

2010-01-01

219

HIV-related neuropathy: current perspectives  

PubMed Central

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

Schutz, Sonja G; Robinson-Papp, Jessica

2013-01-01

220

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

PubMed

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

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

2014-08-01

221

HIV at Work  

MedlinePLUS

... Rights : Workplace Translate Text Size Print Share Workplace HIV at Work The impact of the HIV/AIDS ... Workplace Issues Frequently Asked Questions I am an HIV/AIDS Service Provider. What resources are available to ...

222

HIV/AIDS  

MedlinePLUS

HIV stands for human immunodeficiency virus. It kills or damages the body's immune system cells. AIDS stands ... is the most advanced stage of infection with HIV. HIV most often spreads through unprotected sex with ...

223

HIV and AIDS  

MedlinePLUS

... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ... a serious infection. Continue How Many People Have HIV/AIDS? Since the discovery of the virus almost ...

224

HIV/AIDS Basics  

MedlinePLUS

... About CDC.gov . Act Against AIDS Share Compartir HIV/AIDS Basics Before we can stop any epidemic, ... before, AIDS is still a significant health issue. HIV 101 HIV/AIDS Basic Statistics Transmission Testing Prevention ...

225

Travelers' Health: HIV Infection  

MedlinePLUS

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

226

HIV Medication Adherence  

MedlinePLUS

... Before and After Starting HIV Medicines . What is medication adherence? Adherence means “to stick firmly.” So for ... future HIV regimen. What is the connection between medication adherence and drug resistance? Taking HIV medicines every ...

227

HIV-1 protease-induced apoptosis  

PubMed Central

Background Apoptosis is one of the presumptive causes of CD4+ T cell depletion during HIV infection and progression to AIDS. However, the precise role of HIV-1 in this process remains unexplained. HIV-1 protease (PR) has been suggested as a possible factor, but a direct link between HIV-1 PR enzymatic activity and apoptosis has not been established. Results Here, we show that expression of active HIV-1 PR induces death in HeLa and HEK-293 cells via the mitochondrial apoptotic pathway. This conclusion is based on in vivo observations of the direct localization of HIV-1 PR in mitochondria, a key player in triggering apoptosis. Moreover, we observed an HIV-1 PR concentration-dependent decrease in mitochondrial membrane potential and the role of HIV-1 PR in activation of caspase 9, PARP cleavage and DNA fragmentation. In addition, in vitro data demonstrated that HIV-1 PR mediates cleavage of mitochondrial proteins Tom22, VDAC and ANT, leading to release of AIF and Hsp60 proteins. By using yeast two-hybrid screening, we also identified a new HIV-1 PR interaction partner, breast carcinoma-associated protein 3 (BCA3). We found that BCA3 accelerates p53 transcriptional activity on the bax promoter, thus elevating the cellular level of pro-apoptotic Bax protein. Conclusion In summary, our results describe the involvement of HIV-1 PR in apoptosis, which is caused either by a direct effect of HIV-1 PR on mitochondrial membrane integrity or by its interaction with cellular protein BCA3. PMID:24886575

2014-01-01

228

Role of cellular iron and oxygen in the regulation of HIV-1 infection  

PubMed Central

Despite efficient antiretroviral therapy, eradication of HIV-1 infection is challenging and requires novel biological insights and therapeutic strategies. Among other physiological and environmental factors, intracellular iron greatly affects HIV-1 replication. Higher iron stores were shown to be associated with faster progression of HIV-1 infection and to inversely correlate with the survival of HIV-1 infected patients. Iron is required for several steps in the HIV-1 life cycle, including reverse transcription, HIV-1 gene expression and capsid assembly. Here, the authors present a comprehensive review of the molecular mechanisms involved in iron- and oxygen-mediated regulation of HIV-1 replication. We also propose key intracellular pathways that may be involved in regulating HIV-1 replication, via protein kinase complexes, CDK9/cyclin T1 and CDK 2/cyclin E, protein phosphatase-1 and other host factors. PMID:23678366

Nekhai, Sergei; Kumari, Namita; Dhawan, Subhash

2013-01-01

229

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

PubMed Central

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

Date, Abhijit A.; Destache, Christopher J.

2013-01-01

230

CCR5 as a Natural and Modulated Target for Inhibition of HIV  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection—this without detrimental effects to the host—and transplantation of CCR5-delta32 stem cells in a patient with HIV (“Berlin patient”) achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells. PMID:24381033

Burke, Bryan P.; Boyd, Maureen P.; Impey, Helen; Breton, Louis R.; Bartlett, Jeffrey S.; Symonds, Geoff P.; Hutter, Gero

2013-01-01

231

RNA-based Therapeutics- Current Progress and Future Prospects  

PubMed Central

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

Burnett, John C.; Rossi, John J.

2012-01-01

232

Subtype Classification of Iranian HIV-1 Sequences Registered in the HIV Databases, 2006-2013  

PubMed Central

Background The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory. Methods All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods. Results A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported. Conclusions Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies. PMID:25188443

Baesi, Kazem; Moallemi, Samaneh; Farrokhi, Molood; Alinaghi, Seyed Ahmad Seyed; Truong, Hong-Ha M.

2014-01-01

233

HIV Treatment as Prevention: Optimising the Impact of Expanded HIV Treatment Programmes  

Microsoft Academic Search

Until now, decisions about how to allocate ART have largely been based on maximising the therapeutic benefit of ART for patients. Since the results of the HPTN 052 study showed efficacy of antiretroviral therapy (ART) in preventing HIV transmission, there has been increased interest in the benefits of ART not only as treatment, but also in prevention. Resources for expanding

Wim Delva; Jeffrey W. Eaton; Fei Meng; Christophe Fraser; Richard G. White; Peter Vickerman; Marie-Claude Boily; Timothy B. Hallett

2012-01-01

234

Eosinophilic granuloma of the femur in an HIV-1-positive patient.  

PubMed

A case of eosinophilic granuloma in the right femur of an HIV-1-infected patient is described, and the possible pathogenetic role of HIV infection in eosinophilic granuloma formation is discussed. PMID:11945205

Panayiotakopoulos, G D; Sipsas, N V; Kontos, A; Patsouris, E; Korkolopoulou, P; Revenas, K; Dounis, E; Kordossis, T

2002-03-01

235

[Retrospective seroepidemiology of HIV-1].  

PubMed

Serum samples collected between 1974 and 1980 out of populations from the States of Pará and Goiás, Brazil, were tested for antibodies against HIV-1 through ELISA, immunofluorescence, and immunoblot. The aim was to describe the possibility of the virus presence in this country before the present epidemic. Four samples from an epidemiologically closed community, the Xicrin indians, gave positive reaction in the ELISA test, but were negative in the confirmatory tests. The negative results suggest the absence of HIV-1, in the groups tested, prior to the 1980's. PMID:2690308

Ishak, R; Ishak, M O; Tsiquaye, K; Cardoso, D D

1989-01-01

236

Laser palliation of the HIV+ patient  

NASA Astrophysics Data System (ADS)

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.

Convissar, Robert A.

2003-12-01

237

HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: implication for HIV-associated neurocognitive disorder (HAND).  

PubMed

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

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

2011-05-01

238

Take the HIV Wellness Quiz  

MedlinePLUS

... Wellness Checklist HIV Medications - Medications for Cardiovascular Wellness Systems for Cardiovascular Health Healthy Living and Wellness Goals - HIV and Smoking Cessation - HIV and a Healthy ...

239

Plasma membrane signaling in HIV-1 infection.  

PubMed

Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4+ T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking. PMID:23806647

Abbas, Wasim; Herbein, Georges

2014-04-01

240

Effect of mimetic CDK9 inhibitors on HIV-1 activated transcription  

PubMed Central

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-/-?c-/- 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

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

241

Transcriptome analysis of monocyte-HIV interactions  

PubMed Central

Background During HIV infection and/or antiretroviral therapy (ART), monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19) for the development of the abacavir hypersensitivity reaction were suggested. Conclusions Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. PMID:20546557

2010-01-01

242

The D-amino acid peptide D3 reduces amyloid fibril boosted HIV-1 infectivity  

PubMed Central

Background Amyloid fibrils such as Semen-Derived Enhancer of Viral Infection (SEVI) or amyloid-?-peptide (A?) enhance HIV-1 attachment and entry. Inhibitors destroying or converting those fibrils into non-amyloidogenic aggregates effectively reduce viral infectivity. Thus, they seem to be suitable as therapeutic drugs expanding the current HIV-intervening repertoire of antiretroviral compounds. Findings In this study, we demonstrate that the small D-amino acid peptide D3, which was investigated for therapeutic studies on Alzheimer’s disease (AD), significantly reduces both SEVI and A? fibril boosted infectivity of HIV-1. Conclusions Since amyloids could play an important role in the progression of AIDS dementia complex (ADC), the treatment of HIV-1 infected individuals with D3, that inhibits A? fibril formation and converts preformed A? fibrils into non-amyloidogenic and non-fibrillar aggregates, may reduce the vulnerability of the central nervous system of HIV patients for HIV associated neurological disorders. PMID:24422713

2014-01-01

243

The changing face of the HIV epidemic in sub-Saharan Africa.  

PubMed

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. PMID:24976370

Mutevedzi, Portia C; Newell, Marie-Louise

2014-09-01

244

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.

245

Mucosal Immunology of HIV Infection  

PubMed Central

Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

2013-01-01

246

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  

Microsoft Academic Search

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

Jennifer J. Manly; Clifford Smith; Howard A. Crystal; Jean Richardson; Elizabeth T. Golub; Ruth Greenblatt; Esther Robison; Eileen M. Martin; Mary Young

2011-01-01

247

The Two Human CXCR4 Isoforms Display Different HIV Receptor Activities: Consequences for the Emergence of X4 Strains.  

PubMed

CXCR4 is a chemokine receptor that plays key roles with its specific ligand, CXCL12, in stem cell homing and immune trafficking. It is also used as a coreceptor by some HIV-1 strains (X4 strains), whereas other strains (R5 strains) use an alternative coreceptor, CCR5. X4 strains mainly emerge at late stages of the infection and are linked to disease progression. Two isoforms of this coreceptor have been described in humans: CXCR4-A and CXCR4-B, corresponding to an unspliced and a spliced mRNA, respectively. In this study, we show that CXCR4-B, but not CXCR4-A, mediates an efficient HIV-1 X4 entry and productive infection. Yet, the chemotactic activity of CXCL12 on both isoforms was similar. Furthermore, HIV-R5 infection favored CXCR4-B expression over that of CXCR4-A. In vitro infection with an R5 strain increased CXCR4-B/CXCR4-A mRNA ratio in PBMCs, and this ratio correlated with HIV RNA plasma level in R5-infected individuals. In addition, the presence of the CXCR4-B isoform favored R5 to X4 switch more efficiently than did CXCR4-A in vitro. Hence, the predominance of CXCR4-B over CXCR4-A expression in PBMCs was linked to the ability of circulating HIV-1 strains to use CXCR4, as determined by genotyping. These data suggest that R5 to X4 switch could be favored by R5 infection-induced overexpression of CXCR4-B. Finally, we achieved a specific small interfering RNA-mediated knockdown of CXCR4-B. This represents a proof of concept for a possible gene-therapeutic approach aimed at blocking the HIV coreceptor activity of CXCR4 without knocking down its chemotactic activity. PMID:25230750

Duquenne, Charline; Psomas, Christina; Gimenez, Sandrine; Guigues, Adeline; Carles, Marie-Josée; Barbuat, Claudine; Lavigne, Jean-Philippe; Sotto, Albert; Reynes, Jacques; Guglielmi, Paul; Mettling, Clément; François, Vincent; Corbeau, Pierre

2014-10-15

248

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

PubMed Central

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

John, Mina; Gaudieri, Silvana

2014-01-01

249

T-Cell Signaling in HIV-1 Infection  

PubMed Central

HIV exploits the T-cell signaling network to gain access to downstream cellular components, which serves as effective tools to break the cellular barriers. Multiple host factors and their interaction with viral proteins contribute to the complexity of HIV-1 pathogenesis and disease progression. HIV-1 proteins gp120, Nef, Tat and Vpr alter the T-cell signaling pathways by activating multiple transcription factors including NF-?B, Sp1 and AP-1. HIV-1 evades the immune system by developing a multi-pronged strategy. Additionally, HIV-1 encoded proteins influence the apoptosis in the host cell favoring or blocking T-cell apoptosis. Thus, T-cell signaling hijacked by viral proteins accounts for both viral persistence and immune suppression during HIV-1 infection. Here, we summarize past and present studies on HIV-1 T-cell signaling with special focus on the possible role of T cells in facilitating viral infection and pathogenesis PMID:23986795

Abbas, Wasim; Herbein, Georges

2013-01-01

250

Therapeutic Devices for Epilepsy  

PubMed Central

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

Fisher, Robert S.

2011-01-01

251

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

E-print Network

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

Angin, Mathieu

252

Fast and simultaneous determination of darunavir and eleven other antiretroviral drugs for therapeutic drug monitoring: method development and validation for the determination of all currently approved HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in human plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.  

PubMed

For the quantification of all currently approved non-nucleoside reverse transcriptase inhibitors and protease inhibitors, including the new protease inhibitor darunavir and the active nelfinavir metabolite M8, an assay was developed, using liquid chromatography coupled with tandem mass spectrometry. The sample pretreatment consisted of a protein precipitation with a mixture of methanol and acetonitrile using only 100 microL plasma. Chromatographic separation was performed on a reversed-phase C18 column (150 x 2.0 mm, particle size 5 microm) with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.25 mL/min. The analytical run time was only 10 min. The triple quadrupole mass spectrometer was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over a range of 0.1 to 20 microg/mL for amprenavir, atazanavir, efavirenz, indinavir, lopinavir, nelfinavir, the active nelfinavir metabolite M8, nevirapine and ritonavir, a range of 0.05 to 10 microg/mL for saquinavir and darunavir and a range of 0.5 to 100 microg/mL for tipranavir, based on observed concentration ranges in patients treated with these drugs. D5-squinavir, D6-indinavir, 13C6-efavirenz and dibenzepine were used as internal standards. The method was proven to be specific, accurate, precise and robust. Accuracies ranged from 88.5% to 102.2% and all precisions were less than 9.5%. Furthermore, the assay demonstrates a high sensitivity for all analytes and the stepwise gradient allows addition of new analytes into the same method. The method is now successfully applied for routine therapeutic drug monitoring and pharmacokinetic studies in HIV-infected patients. PMID:17610214

ter Heine, Rob; Alderden-Los, Carolien G; Rosing, Hilde; Hillebrand, Michel J X; van Gorp, Eric C M; Huitema, Alwin D R; Beijnen, Jos H

2007-01-01

253

In vivo emergence of HIV1 variants resistant to multiple protease inhibitors  

Microsoft Academic Search

INHIBITORS of the human immunodeficiency virus type 1 (HIV-1) protease have entered clinical study as potential therapeutic agents for HIV-1 infection. The clinical efficacy of HIV-1 reverse transcriptase inhibitors has been limited by the emergence of resistant viral variants. Similarly, variants expressing resistance to protease inhibitors have been derived in cell culture1-10. We now report the characterization of resistant variants

Jon H. Condra; William A. Schleif; Olga M. Blahy; Lori J. Gabryelski; Donald J. Graham; Julio Quintero; Audrey Rhodes; Helen L. Robbins; Elizabeth Roth; Malathi Shivaprakash; Donna Titus; Tao Yang; Hedy Tepplert; Kathleen E. Squires; Paul J. Deutsch; Emilio A. Emini

1995-01-01

254

A BLUEPRINT FOR HIV VACCINE DISCOVERY  

PubMed Central

Despite numerous attempts over many years to develop an HIV vaccine based on classical strategies, none has convincingly succeeded to date. A number of approaches are being pursued in the field, including building upon possible efficacy indicated by the recent RV144 clinical trial, which combined two HIV vaccines. Here, we argue for an approach based, in part, on understanding the HIV envelope spike and its interaction with broadly neutralizing antibodies (bnAbs) at the molecular level and using this understanding to design immunogens as possible vaccines. BnAbs can protect against virus challenge in animal models and many such antibodies have been isolated recently. We further propose that studies focused on how best to provide T cell help to B cells that produce bnAbs are crucial for optimal immunization strategies. The synthesis of rational immunogen design and immunization strategies, together with iterative improvements, offers great promise for advancing toward an HIV vaccine. PMID:23084910

Burton, Dennis R.; Ahmed, Rafi; Barouch, Dan H.; Butera, Salvatore T.; Crotty, Shane; Godzik, Adam; Kaufmann, Daniel E.; McElrath, M. Juliana; Nussenzweig, Michel C.; Pulendran, Bali; Scanlan, Chris N.; Schief, William R.; Silvestri, Guido; Streeck, Hendrik; Walker, Bruce D.; Walker, Laura M.; Ward, Andrew B.; Wilson, Ian A.; Wyatt, Richard

2012-01-01

255

Celastrol Inhibits Tat-Mediated Human Immunodeficiency Virus (HIV) Transcription and Replication  

Microsoft Academic Search

Current drugs used for antiretroviral therapy against human immunodeficiency virus (HIV) have a narrow spectrum of activity and, more often, have associated toxicities and severe side effects in addition to developing resistance. Thus, there is a need to develop new therapeutic strategies against HIV\\/AIDS to complement the already existing ones. Surprisingly, transactivator of transcription (Tat), an early virus-encoded protein required

Vivek Narayan; Kodihalli C. Ravindra; Chris Chiaro; Daniele Cary; Bharat B. Aggarwal; Andrew J. Henderson; K. Sandeep Prabhu

2011-01-01

256

Advances in dendritic cell immunotherapies for HIV-1 infection.  

PubMed

Augmentation of adaptive immunity via HIV therapeutic vaccination may be a key component of curative strategies. Adoptive dendritic cell (DC) immunotherapies may prove useful in enhancing the success of these approaches by circumventing certain defects in DC function during HIV infection. Thus far, DC immunotherapies that utilize autologous, inactivated virus as an immunogen have provided the most promising results however, are beset with practical constraints. Consequently, alternative forms of immunogens are under investigation, with an emphasis on RNA-based approaches. Here we review the data from DC immunotherapy trials for HIV infection and discuss challenges and future directions in the field. PMID:25143151

Miller, Elizabeth; Bhardwaj, Nina

2014-11-01

257

Possible sensations  

E-print Network

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

Shin, Yae Jin

2013-01-01

258

HIV/AIDS Clinical Trials  

MedlinePLUS

... safe and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help ... related to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. ...

259

HIV Medicines and Side Effects  

MedlinePLUS

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

260

[New therapeutic possibilities for acquired clonal blood diseases and myelodysplasia].  

PubMed

Examples of patients are used as a basis for discussing the treatment of severe aplastic anaemia with clonal chromosomal aberrations in haematopoietic cells, the aplastic form of paroxysmal nocturnal haemoglobinuria and myelodysplasia, with allogeneic bone marrow transplantation. Transplantation with marrow from an HLA-identical sibling donor has curative potential in selected patients with these disorders. The procedure should preferably be carried out before the patients have received massive treatment for the complications of marrow failure. The use of matched unrelated bone marrow donors is still at the investigation stage. PMID:1412233

Brinch, L; Evensen, S A; Hammerstrøm, J; Blichfeldt, P

1992-08-10

261

Burning mouth syndrome: is acupuncture a therapeutic possibility?  

Microsoft Academic Search

Background Burning mouth syndrome is a chronic pathology of unknown ethiopathogenesis. The aim of this study was to evaluate whether acupuncture can produce a reduction of the burning sensation by influencing the oral microcirculation.Methods Thirty patients (10 male and 20 female; mean age ± SD = 65.4 ± 2.17) and 30 healthy subjects (10 male and 20 female; mean age

A. Ruggieri; F. Provenzano; P. Messina; G. A. Scardina

2010-01-01

262

[Impotence in diabetes mellitus. Etiological factors and therapeutic possibilities].  

PubMed

The neurovascular causes of diabetic impotence are presented. 55 men presenting impotence and diabetes mellitus were examined in an extended diagnostic program. Nocturnal penile tumescence and Papaverin-test showed psychogenic impotence in 10 of these men, which lead to psychosexual therapy of the couple. Because of regional erectile lesions (Mb. Peyronie, penile trauma, inborn penile deviation, Priapism) 8 further diabetics were successfully operated. The remaining 37 patients with diabetes mellitus showed vascular erectile lesions (increased venous drainage in 7 and decreased arterial inflow in 30 men) and were operated upon with the following methods: Microsurgical arterialisation of the penile vein via a V. saphena-graft to the iliaque artery was done in 4 patients. There was an amelioration in 2 and a longterm failure in the remaining 2 men. Vein ligation of both internal iliaque veins and lateral penile veins in 7 patients resulted in 2 short term improvements and 5 failures. Flexible penile prostheses (AMS- and Jonas-prostheses) in 26 patients showed good results in 24 and infectious complications in 2 of them (Explanation of both prostheses, ones partial penile amputation). Vascular interventions for diabetic impotence seem to be of questionable value and therefore the implantation of penile prostheses should be preferred. In diabetics, infection of the alloplastic implants is particularly dangerous and may lead to septicemia and penile amputation. PMID:3631559

Wagenknecht, L V; Shukfeh, F; Ballmajo, C J

1987-06-01

263

USING ART IN NARRATIVE THERAPY: ENHANCING THERAPEUTIC POSSIBILITIES  

Microsoft Academic Search

Narrative therapy attempts to help families “reauthor” their lives through a process of externalization, unique outcomes, and performance before an audience. The interventions in this model are accomplished mostly through language. This may make narrative therapy a complicated process for many therapists and clients. The purpose of this article is to show how applying art therapy techniques to the basic

Thomas D. Carlson

1997-01-01

264

Human endogenous retroviruses and cancer: Causality and therapeutic possibilities  

PubMed Central

A substantial part of the human genome is derived from transposable elements; remnants of ancient retroviral infections. Conservative estimates set the percentage of human endogenous retroviruses (HERVs) in the genome at 8%. For the most part, the interplay between mutations, epigenetic mechanisms and posttranscriptional regulations silence HERVs in somatic cells. We first highlight mechanisms by which activation of members of several HERV families may be associated with tumor development before discussing the arising chances for both diagnosis and therapy. It has been shown that at least in some cases, tumor cells expressing HERV open reading frames (ORFs) thus gain tumor-promoting functions. However, since these proteins are not expressed in healthy tissues, they become prime target structures. Of potential pharmacological interest are the prevention of HERV transposition, the inhibition of HERV-encoded protein expression and the interference with these proteins’ activities. Evidence from recent studies unequivocally proves that HERV ORFs represent a very interesting source of novel tumor-specific antigens with even the potential to surpass entity boundaries. The development of new tumor (immune-) therapies is a very active field and true tumor-specific targets are of outstanding interest since they minimize the risk of autoimmunity and could reduce side effects. Finally, we postulate on main future research streams in order to stimulate discussion on this hot topic. PMID:23155332

Mullins, Christina S; Linnebacher, Michael

2012-01-01

265

Analysis Using TCGA Data Identifies New Therapeutic Possibility  

Cancer.gov

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

266

The Possible Potential Therapeutic Targets for Drug Induced Gingival Overgrowth  

PubMed Central

Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-?, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth. PMID:23690667

Alitheen, Noorjahan Banu

2013-01-01

267

Latency: the hidden HIV-1 challenge  

PubMed Central

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

Marcello, Alessandro

2006-01-01

268

Interplay between HIV Entry and Transportin-SR2 Dependency  

Microsoft Academic Search

BACKGROUND: Transportin-SR2 (TRN-SR2, TNPO3, transportin 3) was previously identified as an interaction partner of human immunodeficiency virus type 1 (HIV-1) integrase and functions as a nuclear import factor of HIV-1. A possible role of capsid in transportin-SR2-mediated nuclear import was recently suggested by the findings that a chimeric HIV virus, carrying the murine leukemia virus (MLV) capsid and matrix proteins,

Wannes Thys; Stéphanie De Houwer; Jonas Demeulemeester; Oliver Taltynov; Renée Vancraenenbroeck; Melanie Gérard; Jan De Rijck; Rik Gijsbers; Frauke Christ; Zeger Debyser

2011-01-01

269

Sentinel surveillance for HIV-2 infection in high-risk US populations.  

PubMed Central

OBJECTIVES. We conducted sentinel surveillance in persons practicing behaviors known to transmit retroviruses to determine the US presence and extent of human immunodeficiency virus type 2 (HIV-2). METHODS. Sentinel surveillance for HIV-2 was conducted by testing 31,533 anonymous blood specimens from patients at sexually transmitted disease clinics, injecting drug users at treatment centers, and clients at HIV counseling and testing sites in 14 US cities where West African immigrants often settle. Specimens were tested by HIV-1 and HIV-2 whole virus and synthetic peptide enzyme immunoassay and confirmed by HIV-1 and HIV-2 Western blots. RESULTS. Nearly 10% of 31,533 sera were positive for HIV-1. Two heterosexual Black male sexually transmitted disease patients were infected with HIV-2. One of the HIV-2 positive specimens did not cross-react on HIV-1 enzyme immunoassay screening. One client had antibodies consistent with malarial infection in West Africa; the other, who had syphilis, did not have antibodies to malaria or to any of 20 arboviruses present in Africa. CONCLUSIONS. Clinics serving clients from HIV-2 endemic areas should test persons practicing risk behaviors for both HIV-1 and HIV-2. Sentinel surveillance for HIV-2 serves as an early warning system for the possible spread of this virus in the United States. PMID:8460726

Onorato, I M; O'Brien, T R; Schable, C A; Spruill, C; Holmberg, S D

1993-01-01

270

Ethical and regulatory considerations for the inclusion of adolescents in HIV biomedical prevention research.  

PubMed

Adolescents should be enrolled in ethically appropriate and scientifically rigorous HIV biomedical prevention research involving vaccines, pre-exposure prophylaxis, or microbicides. There is general agreement that children should only be enrolled in a clinical trial if the scientific objectives cannot be met either through enrolling adult subjects who can provide informed consent personally or through conducting research using animal models. In addition, the risks to which children are exposed in a clinical trial without the possibility of direct therapeutic benefit must be low. Children also should not be placed at a disadvantage after being enrolled in a clinical trial by, for example, being exposed to an unnecessarily risky intervention or by failing to receive a comparable treatment that would prevent significant morbidity or mortality. In light of this shared framework, we discuss the timing of enrolling adolescents in HIV prevention trials; some general study design considerations that may be necessary for adequate labeling of products for an adolescent indication; the use of data obtained from international studies for licensure applications in the United States; the role of parental permission and adolescent assent to research participation; and the inclusion of pregnant adolescents in HIV biomedical prevention research. PMID:20571419

Nelson, Robert M; Lewis, Linda L; Struble, Kimberly; Wood, Susan F

2010-07-01

271

FACT SHEETS HIV and Pregnancy  

E-print Network

. In areas with opt-out testing, HIV testing is automatically included as part of rou tine prenatal careFACT SHEETS HIV and Pregnancy HIV Testing and Pregnancy Mother-to-Child Transmission of HIV Anti in managing HIV dur ing pregnancy. Table of Contents 1. HIV Testing and Pregnancy 2. Mother

Levin, Judith G.

272

[HIV prophylaxis kits. A concept for emergency treatment in the context of postexposure prophylaxis].  

PubMed

Occupational transmission of HIV among healthcare personnel is rare but has repeatedly been published in the literature. Early initiation of postexposure HIV prophylaxis (HIV-PEP) is crucial to prevent virus transmission. For this reason the need for HIV-PEP has to be evaluated immediately and if necessary, started as soon as possible. This article presents an early intervention program in a university hospital which enables healthcare personnel immediate 24/7/365 access to a HIV-PEP prophylaxis kit following occupational HIV exposure. PMID:24292193

Wicker, S; Walcher, F; Wutzler, S; Marzi, I; Stephan, C

2014-01-01

273

Induction of HIV1 Replication by Type 1Like Cytokines, Interleukin (IL)-12 and IL15: Effect on Viral Transcriptional Activation, Cellular Proliferation, and Endogenous Cytokine Production  

Microsoft Academic Search

Cytokine dysregulation is evident in HIV-1 infection and it may play an important role in HIV-1 pathogenesis. Administration of T helper cytokines potentially may restore the functional abnormalities to the HIV-1 immune response. Type 1-like cytokines, IL-2, IL-12, and IL-15, are candidates for immune-based therapy for HIV. Given their potential therapeutic use, we determined the effects of IL-2, IL-12, and

Lena Al-Harthi; Kenneth A. Roebuck; Alan Landay

1998-01-01

274

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

PubMed Central

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.

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

2014-01-01

275

HIV/AIDS Review.  

PubMed

Many advances have been made in the prevention of HIV transmission and management of HIV/AIDS since the virus was discovered in the early 1980s. One of the most important discoveries has been antiretroviral treatment, which can halt the replication of HIV and ease symptoms, turning AIDS into a chronic condition instead of a rapidly terminal illness. Despite advances, HIV remains a major public health challenge. This article reviews the genus, life cycle, and transmission of HIV, as well as workplace issues surrounding the virus and the challenges of developing an HIV vaccine. PMID:23322863

Moss, Joseph Anthony

2013-01-01

276

Constitutional Possibilities  

Microsoft Academic Search

What are our constitutional possibilities? The importance of this question is illustrated by the striking breadth of recent discussions, ranging from the interpretation of the United States Constitution as a guarantee of fundamental economic equality and proposals to restore the lost constitution to arguments for the virtual abandonment of structural provisions of the Constitution of 1789. Such proposals are conventionally

Lawrence B. Solum

2008-01-01

277

HIV and Its Treatment Changing an HIV Treatment Regimen Changing an HIV Treatment Regimen  

E-print Network

HIV and Its Treatment ­ Changing an HIV Treatment Regimen Changing an HIV Treatment Regimen Will my HIV treatment regimen ever change? At some point, you may need to adjust or change your regimen an HIV treatment regimen? There are several reasons why a person may switch to another HIV regimen

Levin, Judith G.

278

Evolutionary origin on HIV zThe closest relatives of HIV-1 and HIV-2  

E-print Network

Evolutionary origin on HIV zThe closest relatives of HIV-1 and HIV-2 are simian immunodeficiency viruses (SIV). zThere is evidence for multiple transmissions from SIV into humans. zHIV-1 is very closely of virulence. #12;HIV is a quasispecies zViral replication is error prone. zHIV reverse transcriptase and RNA

Moehlis, Jeff

279

HIV Eradication: Combinatorial Approaches to Activate Latent Viruses  

PubMed Central

The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due to the presence of a reservoir of latent HIV infected cells, which persist in the presence of c-ART. Recently, pharmaceutical approaches have focused on the development of molecules able to induce HIV-1 replication from latently infected cells in order to render them susceptible to viral cytopathic effects and host immune responses. Alternative pathways and transcription complexes function to regulate the activity of the HIV promoter and might serve as molecular targets for compounds to activate latent HIV. A combined therapy coupling various depressors and activators will likely be the most effective in promoting HIV replication while avoiding pleiotropic effects at the cellular level. Moreover, in light of differences among HIV subtypes and variability in integration sites, the combination of multiple agents targeting multiple pathways will increase likelihood of therapeutic effectiveness and prevent mutational escape. This review provides an overview of the mechanisms that can be targeted to induce HIV activation focusing on potential combinatorial approaches. PMID:25421889

De Crignis, Elisa; Mahmoudi, Tokameh

2014-01-01

280

Establishing Restricted Expression of Caveolin-1 in HIV Infected Cells and Inhibition of Virus Replication  

PubMed Central

Background: Caveolin-1 (Cav-1) is the major protein of the caveolae and plays a role in multiple cellular functions and implicated to have anti-HIV activity. Regulated expression of Cav-1 is important for safe and effective use in order to exploit Cav-1 for HIV therapeutic applications. Methods: A series of Cav-1 and GFP expression vectors were constructed under the control of the HIV LTR for conditional expression or CMV promoter and the expression of Cav-1 was monitored in the presence or absence of Tat or HIV infection in order to establish the restricted expression of Cav-1 to HIV infected cells. Results: Cav-1 expression was evident under the control of the HIV LTR in the absence of Tat or HIV infection as demonstrated by immunoblot. Placing two internal ribosomal entry sequences (IRES) and a Rev response element, RRE (5’~ LTR-IRES-GFP-RRE-IRES-Cav-1~3’) resulted in no expression of Cav-1 in the absence of Tat with effective expression in the presence of Tat. Transduction of HIV permissive cells with this construct using a foamy virus vector show that Cav-1 was able to inhibit HIV replication by 82%. Cells that received LTR-IRES-GFP-RRE-IRES-Cav-1 remain healthy in the absence of Tat or HIV infection. Conclusion: These results taken together reveal the inclusion of two IRES establishes a significant reduction of leak through expression of Cav-1 in the absence of Tat or HIV infection. Such regulated expression will have therapeutic application of Cav-1 for HIV infection as well as broad applications which can be beneficial for other host-targeted interventions as therapeutics. PMID:25408776

Lo, Yung-Tsun; Nadeau, Peter E; Lin, Shanshan; Mergia, Ayalew

2014-01-01

281

Silence, Sexuality and HIV/AIDS in South African Schools  

ERIC Educational Resources Information Center

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

Morrell, Robert

2003-01-01

282

HIV-Positive Athletes. When Medicine Meets the Law.  

ERIC Educational Resources Information Center

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

Mitten, Matthew, J.

1994-01-01

283

HIV/AIDS--How to Maintain a Safe Environment.  

ERIC Educational Resources Information Center

Although there have been no documented cases of HIV transmission during athletic competition, the possibility exists. The use of universal precaution procedures reduces risk of HIV transmission. Athletic coaches and physical educators need training about such universal precautions to ensure student and staff safety. The article describes the…

Sutliff, Michael A.; Bomgardner, Richard

1994-01-01

284

High-affinity recognition of HIV-1 frameshift-stimulating RNA alters frameshifting in vitro and interferes with HIV-1 infectivity.  

PubMed

The life cycle of the human immunodeficiency virus type 1 (HIV-1) has an absolute requirement for ribosomal frameshifting during protein translation in order to produce the polyprotein precursor of the viral enzymes. While an RNA stem-loop structure (the "HIV-1 Frameshift Stimulating Signal", or HIV-1 FSS) controls the frameshift efficiency and has been hypothesized as an attractive therapeutic target, developing compounds that selectively bind this RNA and interfere with HIV-1 replication has proven challenging. Building on our prior discovery of a "hit" molecule able to bind this stem-loop, we now report the development of compounds displaying high affinity for the HIV-1 FSS. These compounds are able to enhance frameshifting more than 50% in a dual-luciferase assay in human embryonic kidney cells, and they strongly inhibit the infectivity of pseudotyped HIV-1 virions. PMID:24387306

Ofori, Leslie O; Hilimire, Thomas A; Bennett, Ryan P; Brown, Nathaniel W; Smith, Harold C; Miller, Benjamin L

2014-02-13

285

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 ...

286

Treatment of HIV Infection  

MedlinePLUS

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

287

HIV and employment.  

PubMed

According to 2009 statistics, the human immunodeficiency virus (HIV) infected an estimated 86,500 individuals within the UK, although around one-quarter were unaware of their infection. In the majority of cases, it is now considered a long-term controllable but incurable infection. Indeed, most HIV-positive individuals are able to work. Employment is across most, if not all, workforce sectors and protection against workplace discrimination is provided by the Equality Act 2010. Issues including confidentiality, workplace adjustments, vaccinations and travel restrictions may be relevant to the occupational health of HIV-positive workers. There are special considerations concerning HIV-infected health care workers, including avoidance of performing exposure-prone procedures. Prevention of HIV acquisition in the workplace is relevant to a diverse range of occupational environments, and HIV post-exposure prophylaxis should be considered after potential HIV exposure incidents. If a worker contracts HIV by occupational means, financial help may be available. PMID:22661659

McGoldrick, C

2012-06-01

288

HIV and Immunizations  

MedlinePLUS

... a disease outbreak. Is there a vaccine against HIV? Testing is underway on experimental vaccines to prevent ... can benefit from vaccines against other diseases. Can HIV infection affect the safety and effectiveness of vaccines? ...

289

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

SciTech Connect

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.

Peretti, Silvia [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy); Schiavoni, Ilaria [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy); Pugliese, Katherina [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy); Federico, Maurizio [AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy)]. E-mail: federico@iss.it

2006-02-05

290

Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications  

Microsoft Academic Search

BACKGROUND AND OBJECTIVE  Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated\\u000a the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective\\u000a of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients

Emily A. Wang; Kathleen A. McGinnis; David A. Fiellin; Joseph L. Goulet; Kendall Bryant; Cynthia L. Gibert; David A. Leaf; Kristin Mattocks; Lynn E. Sullivan; Nicholas Vogenthaler; Amy C. Justice

291

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

PubMed

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

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

2012-01-01

292

Current strategies and limitations of HIV vaccines.  

PubMed

There is currently no cure for HIV infection, and the possibility of developing a vaccine in the near future appears unlikely. With more than 33 million individuals living with HIV/AIDS worldwide, there is a distinct need for a prophylactic vaccine against HIV infection. However, conventional vaccine strategies aimed at eliciting antibody and T-cell responses have failed to protect against the virus. Current research has been directed toward the more realistic goal of controlling viral replication during the early stages of infection, thus reducing the viral setpoint, through the use of novel vaccine delivery systems and techniques. In this review, several of the key milestones achieved as a result of research efforts aimed at developing an effective HIV vaccine are identified, and future prospects are examined. PMID:20112169

Kawalekar, Omkar U; Shedlock, Devon J; Weiner, David B

2010-02-01

293

Maternal Health and HIV  

Microsoft Academic Search

The HIV\\/AIDS epidemic is one of the major factors affecting women's health, with 20 million women living with HIV and more than two million pregnancies in HIV-positive women each year. Most HIV infections in women are in resource-constrained settings where the risk of maternal morbidity and mortality is also unacceptably high, and where most of the 529,000 deaths from complications

James McIntyre

2005-01-01

294

HIV Disease: Current Concepts.  

ERIC Educational Resources Information Center

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…

Keeling, Richard P.

1993-01-01

295

Serodiagnosis of HIV Infection  

Microsoft Academic Search

Serologic assays have been an established method for the clinical diagnosis of HIV infection since the early 1980s. These techniques for detecting HIV infection have also been fundamental to the screening of blood donations and blood products, and to the epidemiologic monitoring of the severity and extent of the AIDS epidemic worldwide. The first laboratory methods to screen for HIV

Aissatou Guèye-Ndiaye

296

Relevance of Early Detection of HIV Type 1 SI/CXCR4-Using Viruses in Vertically Infected Children  

PubMed Central

Abstract The aim of the study was to investigate the prevalence and persistence of syncytium-inducing (SI) strains in HIV-1-infected children along time of infection and to evaluate the influence of antiretroviral therapy and host factors on viral tropism. This is a retrospective analysis carried out in 267 HIV-1 vertically infected children from an Argentinean cohort. The viral phenotype was screened in MT-2 cells and coreceptor usage confirmed by the GHOST cell assay. Also, CD4+ T cell count, viral load, antiretroviral therapy, and human CCR5-?32 and CCR2-64I genotypes were analyzed. A high frequency of HIV-1 SI/CXCR4-using variants (22%) was found among children within the first trimester of life, reaching 46% after 10 years of infection. At acute infection, zidovudine prophylaxis did not significantly affect the proportions of SI HIV-1 strains, while their presence was favored by the CCR5+/?32 genotype. Interestingly, the majority of the early SI strains did not persist over time, probably due to a higher susceptibility to antiretroviral (ARV) treatment or immunologic pressure. At the chronic stage, SI variants emerged even in the presence of HAART reaching 36% at 120 months of infection. Also the HIV-1 SI phenotype was associated with lower CD4+ T cell counts all along the course of infection. These findings highlight the need to evaluate the presence of SI/CXCR4 variants early at primary infection. This will make it possible to optimize the use of CCR5 inhibitors in children who are apparently carriers of the R5 virus preventing early therapeutic failure due to the reemergence of SI strains from reservoirs. PMID:22023092

Crudeli, Cintia M.; Aulicino, Paula C.; Rocco, Carlos A.; Bologna, Rosa; Mangano, Andrea

2012-01-01

297

HIV disclosure among adults living with HIV  

Microsoft Academic Search

Research on disclosure among heterosexual adult person(s) living with HIV (PLH) was reviewed, omitting disclosure of parental HIV to children. Disclosure has been studied within five additional relational contexts: with partners, family members, friends, healthcare professionals and in work settings. Disclosure is higher among women than men, among Latino and white compared to African-American families, and among younger compared to

E. Mayfield Arnold; E. Rice; D. Flannery; M. J. Rotheram-Borus

2008-01-01

298

High-efficiency Transduction of Rhesus Hematopoietic Repopulating Cells by a Modified HIV1-based Lentiviral Vector  

PubMed Central

Human immunodeficiency virus type 1 (HIV1) vectors poorly transduce rhesus hematopoietic cells due to species-specific restriction factors, including the tripartite motif-containing 5 isoform? (TRIM5?) which targets the HIV1 capsid. We previously developed a chimeric HIV1 (?HIV) vector system wherein the vector genome is packaged with the simian immunodeficiency virus (SIV) capsid for efficient transduction of both rhesus and human CD34+ cells. To evaluate whether ?HIV vectors could efficiently transduce rhesus hematopoietic repopulating cells, we performed a competitive repopulation assay in rhesus macaques, in which half of the CD34+ cells were transduced with standard SIV vectors and the other half with ?HIV vectors. As compared with SIV vectors, ?HIV vectors achieved higher vector integration, and the transgene expression rates were two- to threefold higher in granulocytes and red blood cells and equivalent in lymphocytes and platelets for 2 years. A recipient of ?HIV vector-only transduced cells reached up to 40% of transgene expression rates in granulocytes and lymphocytes and 20% in red blood cells. Similar to HIV1 and SIV vectors, ?HIV vector frequently integrated into gene regions, especially into introns. In summary, our ?HIV vector demonstrated efficient transduction for rhesus long-term repopulating cells, comparable with SIV vectors. This ?HIV vector should allow preclinical testing of HIV1-based therapeutic vectors in large animal models. PMID:22871664

Uchida, Naoya; Hargrove, Phillip W.; Lap, Coen J.; Evans, Molly E.; Phang, Oswald; Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.; Nguyen, Anh-Dao; Hsieh, Matthew M.; Wolfsberg, Tyra G.; Donahue, Robert E.; Persons, Derek A.; Tisdale, John F.

2012-01-01

299

Recent advances in humanized mice: accelerating the development of an HIV vaccine.  

PubMed

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

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

2013-11-01

300

Therapeutics for cognitive aging  

PubMed Central

This review summarizes the scientific talks presented at the conference “Therapeutics for Cognitive Aging,” hosted by the New York Academy of Sciences and the Alzheimer’s Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people—approximately 200 in all—the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease. PMID:20392284

Shineman, Diana W.; Salthouse, Timothy A.; Launer, Lenore J.; Hof, Patrick R.; Bartzokis, George; Kleiman, Robin; Luine, Victoria; Buccafusco, Jerry J.; Small, Gary W.; Aisen, Paul S.; Lowe, David A.; Fillit, Howard M.

2011-01-01

301

Inflammation After Stroke: Mechanisms and Therapeutic Approaches  

PubMed Central

Reperfusion of ischemic brain can reduce injury and improve outcome, but secondary injury due to inflammatory mechanisms limits the efficacy and time window of such treatments for stroke. This review summarizes the cellular and molecular basis of inflammation in ischemic injury as well as possible therapeutic strategies. PMID:20976117

Ahmad, Muzamil

2010-01-01

302

Is there a therapeutic role for cranioplasty?  

PubMed

Cranioplasty is often undertaken as a joint neurosurgical and maxillofacial procedure. The principal aims remain to improve cosmesis and to protect the underlying brain. We report two cases of cranioplasty with subsequent improvement in neurological function and discuss the possible therapeutic role of cranioplasty. PMID:23415243

Alibhai, M K; Balasundaram, I; Bridle, C; Holmes, S B

2013-05-01

303

Is homeopathy possible?  

PubMed

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 as another possible explanation of the homeopathy's efficacy. This shows that the reason double-blind RCTs deliver at best only equivocal results on homeopathy's efficacy is because it effectively breaks the PPR entangled state. A comparison is made between the entanglement-breaking effect of double-blind RCTs and the wave-function 'collapsing' effect of observation in orthodox quantum theory. The article concludes by suggesting that the memory of water and PPR entanglement are not competing but most likely complementary hypotheses, and that both are probably required in order to provide a complete description of the homeopathic process. While awaiting experimental evidence of these hypotheses, it is suggested that observations of clinical outcomes would be superior to RCTs for further testing homeopathy's efficacy. PMID:17004404

Milgrom, Lionel R

2006-09-01

304

FACT SHEETS HIV and Its Treatment  

E-print Network

FACT SHEETS HIV and Its Treatment HIV/AIDS: The Basics Testing for HIV Seeing an HIV Health Care of HIV/AIDS, recommended anti-HIV medications, and tips on how to successfully follow an anti-HIV regimen advice and care of medical professionals. Individuals seeking HIV/AIDS-related medical advice should

Levin, Judith G.

305

HIV and maternal mortality.  

PubMed

The majority of the 17million 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. PMID:25097142

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

2014-11-01

306

Leprosy in HIV infection: a study of three cases.  

PubMed

The course of leprosy in patients with HIV infection has been a controversial issue for a long time. It is still a matter of debate whether the HIV status of an individual has any impact on the natural history of leprosy and response to anti-leprosy treatment. We report here three HIV-positive leprosy cases (two BT and one BB) along with their CD4 counts and HIV staging with anti-leprosy therapeutic response. Both BT cases responded well to conventional WHO MDT (PB) for 6 months, whereas the BB case relapsed 3 months after completion of MDT (MB) for one year. However, he became inactive again following a further one-year course of MDT (MB). PMID:15242274

Rath, N; Kar, H K

2003-01-01

307

Simultaneous determination of 16 anti-HIV drugs in human plasma by high-performance liquid chromatography  

Microsoft Academic Search

Therapeutic drug monitoring (TDM) is pivotal to improve the management of HIV infection. Here, a HPLC–UV method has been developed to quantify simultaneously seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir; PIs), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine; NRTIs), and two non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine; NNRTIs)

Stefania Notari; Alessio Bocedi; Giuseppe Ippolito; Pasquale Narciso; Leopoldo Paolo Pucillo; Gianna Tossini; Raffaele Perrone Donnorso; Francesco Gasparrini; Paolo Ascenzi

2006-01-01

308

Infections in solid organ transplant HIV-infected patients.  

PubMed

Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and Europe indicates that 3- to 5-year survival in HIV/HCV-coinfected liver recipients is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected transplant patients (liver, kidney and heart) was similar to that of non-HIV-infected patients. Preliminary experience with lung transplantation and combined kidney and pancreas transplantation is also satisfactory. Infections in HIV-infected recipients during the post-transplant period are similar to those seen in non-HIV-infected patients, although the incidence rates of tuberculosis and fungal infections seem to be higher. HIV-infected patients who are being evaluated for SOT should follow the same recommendations as those used for non-HIV-infected patients in order to prevent infections during the pre-transplant period. After transplantation, HIV-infected SOT recipients must follow recommendations on post-SOT and anti-HIV immunization and on antimicrobial prophylaxis. The recommended antiretroviral regimen is one based on raltegravir or dolutegravir plus two nucleos(t)ide reverse transcriptase inhibitors (tenofovir + emtricitabine or abacavir + lamivudine), because it can prevent pharmacokinetic interactions between antiretroviral drugs, immunosuppressive drugs and some of the antimicrobial agents used to treat or prevent post-transplant infections. In this manuscript, we review current recommendations for preventing infections both before and after transplantation. We also analyse the incidence, aetiology and clinical characteristics of opportunistic and non-opportunistic bacterial, mycobacterial, fungal and viral infections in HIV-infected SOT recipients during the post-transplant period. PMID:25040016

Miro, J M; Agüero, F; Duclos-Vallée, J-C; Mueller, N J; Grossi, P; Moreno, A

2014-09-01

309

Complement-targeted therapeutics  

Microsoft Academic Search

The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic

Daniel Ricklin; John D Lambris

2007-01-01

310

Therapeutic Recombinant Monoclonal Antibodies  

ERIC Educational Resources Information Center

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

Bakhtiar, Ray

2012-01-01

311

Developing Therapeutic Listening  

ERIC Educational Resources Information Center

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

Lee, Billy; Prior, Seamus

2013-01-01

312

Processing the therapeutic relationship  

Microsoft Academic Search

The authors propose that if therapists and clients process their therapeutic relationship (i.e., directly address in the here and now feelings about each other and about the inevitable problems that emerge in the therapy relationship), feelings will be expressed and accepted, problems will be resolved, the relationship will be enhanced, and clients will transfer their learning to other relationships outside

Clara E. Hill; Sarah Knox

2009-01-01

313

Predictors of sustained therapeutic change  

Microsoft Academic Search

The authors integrate explorations by Blatt and colleagues of contributions of patient personality, therapeutic relationship, and change in mental representation to sustained therapeutic change. A pretreatment personality characteristic, self-critical perfectionism, a negative self-schema, significantly interfered with therapeutic progress in manual-directed, brief outpatient treatment for depression. The therapeutic relationship, however, facilitated changes in this negative self-representation, leading to sustained therapeutic change.

Sidney J. Blatt; David C. Zuroff; Lance L. Hawley; John S. Auerbach

2010-01-01

314

Why is HIV not vector-borne?  

PubMed Central

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.

Day, Troy; Mideo, Nicole; Alizon, Samuel

2008-01-01

315

[Therapeutic perspectives in heart failure  

PubMed

Many different diseases may lead to heart failure. Nevertheless, the symptoms and pathophysiological changes in heart failure are uniform as are the basic principles of treatment. Although significant progress has been achieved in understanding the biology of heart failure and the therapeutic options, the quality of life of heart failure patients and their survival are often poor. Since cardiac transplantation as a final therapeutic option is limited by the availability of donor organs, new strategies and technologies need to be explored to treat the failing heart effectively. Approaches to improve the medical therapy of heart failure mainly focus on strategies to escape the vicious circle of decreased contractility and neurohumoral activation. Substances with promising experimental and clinical results include neutral endopeptidase inhibitors, endothelin antagonists or cytokine inhibitors, e.g. TNF antagonists. Mechanical and electrical devices are under development such as left ventricular assist devices (LVADs), biventricular pacemakers and artificial hearts, which may become valuable alternative therapies. Gene therapy approaches aim to improve the vascularization of the heart, the Ca-homeostasis of the myocytes or the survival of cardiac cells in disease. Finally, cellular cardiomyoplasty is a relatively novel approach to replace or support the cardiomyocytes of the diseased heart by implanting new ones. Which cell type under which conditions will turn out to be the most suitable is still unknown and subject to debate. Ongoing clinical studies will only help to demonstrate the safety and feasibility of this technique but not determine its long-term efficacy. It is highly desirable that one of these new therapeutic strategies or a combination of them will have a significant impact on the future management of heart failure. Currently, our main clinical focus must be to treat as many patients as possible with drugs that are known to improve symptoms and survival, like ACE inhibitors, beta-blockers, cardiac glycosides, diuretics and spironolactone. PMID:12806818

Müller-Ehmsen, Jochen; Schwinger, Robert H

2003-04-01

316

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 ...

317

Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection  

PubMed Central

Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV. PMID:24865485

Mastroianni, Claudio M.; Lichtner, Miriam; Mascia, Claudia; Zuccala, Paola; Vullo, Vincenzo

2014-01-01

318

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

PubMed Central

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

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

2013-01-01

319

Dental Caries in HIV-seropositive Women  

Microsoft Academic Search

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV-women at baseline and 242 HIV+ and 66 HIV-women at

J. A. Phelan; R. Mulligan; E. Nelson; J. Brunelle; M. E. A. F. Alves; M. Navazesh; D. Greenspan

2004-01-01

320

Therapeutic targets for premature ejaculation.  

PubMed

Premature ejaculation (PE) is the most common male sexual complaint, and may exert a profound negative impact on the man's life and partnership. Using currently available treatment alternatives (e.g., selective serotonin uptake inhibitor, agents acting locally on the penis), PE can be treated in most, but not all patients. However, since long term success rates have been disappointing, and the only approved treatment so far is the short-acting selective serotonin re-uptake inhibitor dapoxetine, there is currently an intensive search for new treatment modalities. Selection of the most promising therapeutic targets from a host of current and potential candidates depends heavily on their roles in the pathophysiology of PE. Possible central nervous targets that will be discussed are serotonin transporters, and CNS receptors for 5-HT(IA) and 5-HT(1B), dopamine, oxytocin, opioids, neurokinin-1, and glutamate. Putative peripheral targets include ?(1)-adrenoceptors, phosphodiestrase enzymes, Rho kinases, purinergic (P2X) receptors, and penile sensory nerves. It is clear that exploiting the full therapeutic potential of these targets will require additional basic and clinical research. PMID:21816550

Andersson, Karl-Erik; Abdel-Hamid, Ibrahim A

2011-09-01

321

Increased longevity in HIV: caring for older HIV-infected adults.  

PubMed

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 manageable chronic illness. Clinicians and other care providers are changing their approach and goals of care as patients with HIV grow old. PMID:25118513

Ball, Susan C

2014-01-01

322

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

PubMed Central

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

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

2013-01-01

323

HIV/AIDS, conflict and security in Africa: rethinking relationships  

PubMed Central

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

2008-01-01

324

Hypothalamic-pituitary-adrenal axis in HIV infection and disease.  

PubMed

HIV infection induces hypothalamic-pituitary-adrenal (HPA) axis derangements. Partial glucocorticoid resistance has been observed in a subset of AIDS patients, possibly owing to HIV-induced altered cytokine secretion and action. Because glucocorticoids have immunomodulatory effects, the severity of the HPA axis disorder could play a central role in disease progression. The characteristic phenotype of AIDS patients (visceral obesity, lipodystrophy) may be owing to effects of HIV proteins on the HPA axis, including changes in glucocorticoid and insulin sensitivity of target tissues, as well as altered cytokine production and interaction with the HPA axis, genetic causes, comorbidities, and, possibly, use of antiretroviral agents. PMID:25169568

Chrousos, George P; Zapanti, Evangelia D

2014-09-01

325

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, ...

326

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, ...

327

HIV among African American Youth  

MedlinePLUS

... the groups most severely affected by HIV infection in the United States. In fact, black youth represent more than half ( ... million people estimated to be living with HIV in the United States (44 percent), and of new HIV infections each ...

328

Oral Sex and HIV Risk  

MedlinePLUS

... living with HIV and is taking antiretroviral therapy (ART) consistently and correctly. PrEP is a drug (Truvada) ... at substantial risk of HIV to prevent infection. ART is a combination of drugs to treat HIV ...

329

Depression and HIV/AIDS  

MedlinePLUS

... see the NIMH booklet on Depression . What is HIV/AIDS? Human immunodeficiency virus (HIV) is the virus ... they can function normally. How are depression and HIV/AIDS linked? Studies show that people who are ...

330

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

ERIC Educational Resources Information Center

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

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

2011-01-01

331

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

PubMed Central

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

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

2013-01-01

332

Therapeutics for neonatal brain injury.  

PubMed

Neonatal brain injury is an important cause of death and neurodevelopmental delay. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead to both early and late phases of cell damage and death. Therapies targeting these different pathways have shown potential in protecting the brain from ongoing injury. More recent therapies, such as growth factors, have demonstrated an ability to increase cell proliferation and repair over longer periods of time. Even though hypothermia, which decreases cerebral metabolism and possibly affects other mechanisms, may show some benefit in particular cases, no widely effective therapeutic interventions for human neonates exist. In this review, we summarize recent findings in neuroprotection and neurogenesis for the immature brain, including combination therapy to optimize repair. PMID:18718848

Gonzalez, Fernando F; Ferriero, Donna M

2008-10-01

333

HIV-1 transcription and latency: an update  

PubMed Central

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

2013-01-01

334

Complement-targeted therapeutics  

PubMed Central

The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic modalities have been developed. However, successful marketing of complement-targeted drugs has proved to be more difficult than initially expected, and many strategies have been discontinued. The US Food and Drug Administration’s approval of the first complement-specific drug, an antibody against complement component C5 (eculizumab; Soliris), in March 2007, was a long-awaited breakthrough in the field. Approval of eculizumab validates the complement system as therapeutic target and might facilitate clinical development of other promising drug candidates. PMID:17989689

Ricklin, Daniel; Lambris, John D

2010-01-01

335

Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children.  

PubMed Central

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

Matt, C.; Roger, M.

2001-01-01

336

Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children.  

PubMed

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

Matt, C; Roger, M

2001-09-01

337

Connection in therapeutic communities.  

PubMed

The success of therapeutic community treatment is based on trust. Trust underlies the willingness of residents to endorse and profit from confrontations of their denial. Lack of trust can be seen to underlie the high dropout rate of many therapeutic communities. Social learning theory, which is usually cited as a theoretical foundation for therapeutic communities, does not explain the role of trust. Instead, we need an explanation of trust based on a logic of emotion rather than the cognitive, calculating logic of social learning. This logic can be found in the process of connection. Trust, in the theoretical orientation of connection, grows out of the resident's perception that community members care. This caring is revealed in their empathy for the resident, their willingness to take responsibility for helping the resident, and their nurturance. The resident's level of trust determines his (her) willingness to be open and responsive to the community. The implications of the connection process for the development of trust between new residents and old residents and between residents and staff are developed. PMID:8188445

Bell, D C

1994-03-01

338

Therapeutic antibody engineering  

PubMed Central

It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.

Parren, Paul W.H.I.; Lugovskoy, Alexey A.

2013-01-01

339

Therapeutic targets for neuroblastomas  

PubMed Central

Introduction Neuroblastoma (NB) is the most common and deadly solid tumor in children. Despite recent improvements, the long-term outlook for high-risk NB is still < 50%. Further, there is considerable short- and long-term toxicity. More effective, less toxic therapy is needed, and the development of targeted therapies offers great promise. Areas covered Relevant literature was reviewed to identify current and future therapeutic targets that are critical to malignant transformation and progression of NB. The potential or actual NB therapeutic targets are classified into four categories: i) genes activated by amplification, mutation, translocation or autocrine overexpression; ii) genes inactivated by deletion, mutation or epigenetic silencing; iii) membrane-associated genes expressed on most NBs but few other tissues; or iv) common target genes relevant to NB as well as other tumors. Expert opinion Therapeutic approaches have been developed to some of these targets, but many remain untargeted at the present time. It is unlikely that single targeted agents will be sufficient for long-term cure, at least for high-risk NBs. The challenge will be how to integrate targeted agents with each other and with conventional therapy to enhance their efficacy, while simultaneously reducing systemic toxicity. PMID:24387342

Brodeur, Garrett M; lIyer, Radhika; Croucher, Jamie L; Zhuang, Tiangang; Higashi, Mayumi; Kolla, Venkatadri

2014-01-01

340

Mitochondria-directed therapeutics.  

PubMed

Mitochondria are key regulators of cell life and death and play an important role in a wide range of diseases, including cancer, diabetes, cardiovascular disease, and the age-related neurodegenerative diseases. The unique structural and functional characteristics of mitochondria enable the selective targeting of drugs designed to modulate the function of this organelle for therapeutic gain. This forum discusses (a) potential new mitochondrial targets for therapeutic intervention, including components of the electron transport chain, the permeability transition, and the membrane dynamics protein mitofusin-2; (b) the role of mitochondria-targeted antioxidants including MitoQ and SS peptides in modulating reactive oxygen and chlorine species induced mitochondrial permeabilization and cell death; and (c) the potential use of SS peptides in ischemia and reperfusion tissue injury. In the future, mitochondrial drug-targeting strategies will be expected to open up avenues for manipulating mitochondrial functions and allow for selective protection or eradication of cells for therapeutic gain in a variety of diseases. PMID:18092938

Armstrong, Jeffrey S

2008-03-01

341

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 Central

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. PMID:24964202

Papuchon, Jennifer; Pinson, Patricia; Guidicelli, Gwenda-Line; Bellecave, Pantxika; Thomas, Rejean; LeBlanc, Roger; Reigadas, Sandrine; Taupin, Jean-Luc; Baril, Jean Guy; Routy, Jean Pierre; Wainberg, Mark; Fleury, Herve

2014-01-01

342

The therapeutic transnosological use of psychotropic drugs  

PubMed Central

The current clinical use of psychotropic drugs is transnosologically oriented. This is facilitated by the current classification of mental disorders (International Classification of Diseases, 10th Revision [ICD-10]) and is perhaps justified if depression and psychosis (taken here as examples) are considered as being complex syndromes with heterogeneous etiologies, but common pathogenesis, more than specific entities. However, this approach does not identify possible differences between specific psychiatric entities, which could in turn mask differences in therapeutic responses and, therefore, therapeutic outcome. This is compounded by the current disharmony between the nosological classification of diseases, drug development, clinical research, and therapeutic uses of psychotropic drugs. Functional pharmacology targeting abnormal behavioral traits could represent an avenue for future research and treatment. PMID:22033800

Ackenheil, Manfred; Montane Jaime, Lazara Karelia

1999-01-01

343

Maternal HIV disclosure to HIV-uninfected children in rural South Africa: a pilot study of a family-based intervention  

PubMed Central

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 words "HIV" while 13/24 disclosed partially using the word "virus". Conclusion The pilot study found the intervention was feasible and acceptable to mothers and counsellors, and provides preliminary evidence that participation in the intervention encouraged disclosure and health promotion. The pilot methodology and small sample size has limitations and further research is required to test the potential of this intervention. A larger demonstration project with 300 families is currently underway. PMID:23418933

2013-01-01

344

Modeling an HIV Particle  

NSDL National Science Digital Library

This activity helps learners visualize the Human Immunodeficiency Virus (HIV) by constructing three-dimensional HIV particle models from paper. The model to be used is a 20-sided polyhedron (icosahedron) and represents a complete viral particle. Learners combine their finished models into one mass. This is a first step toward estimating how many HIV particles could be contained inside a white blood cell before being released into the blood stream to attack new cells.

Gregory L. Vogt, Ed D.; Moreno, Nancy P.

2011-01-01

345

HIV among transgendered people  

Microsoft Academic Search

This study explores HIV status and HIV-related risk factors among transgendered people. A needs assessment survey developed with the help of transgendered people was used to conduct face-to-face interviews with 81 transgendered persons, 49 male-to-females (MTFs) and 32 female-to-males (FTMs). The findings indicate that HIV\\/AIDS is a serious health concern facing the transgender community. The majority of respondents engaged in

G. P. Kenagy

2002-01-01

346

Multispot HIV-1/HIV-2 Rapid Test: advantages over other rapid HIV tests.  

PubMed

The Multispot HIV-1/HIV-2 Rapid Test is sensitive and specific for the detection and differentiation of HIV-1 and HIV-2. These attributes, along with best-in-class specificity among HIV-1 rapid tests, make its use attractive in a confirmatory capacity, especially in settings where HIV-2 is prevalent. Widespread use as a primary screening test is largely thwarted by moderate complexity and high cost. PMID:17892358

O'Conell, Robert J; Peel, Sheila A

2007-09-01

347

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

PubMed Central

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

Ambegaokar, Surendra S; Kolson, Dennis L

2014-01-01

348

Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection  

PubMed Central

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

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

349

Development of parallel scales to measure HIV-related stigma  

PubMed Central

HIV-related stigma is a multidimensional concept which has pervasive effects on the lives of HIV-infected people as well as serious consequences for the management of HIV/AIDS. In this research three parallel stigma scales were developed to assess personal views of stigma, stigma attributed to others, and internalized stigma experienced by HIV-infected individuals. The stigma scales were administered in two samples: a community sample of 1077 respondents and 317 HIV-infected pregnant women recruited at clinics from the same community in Tshwane (South Africa). A two-factor structure referring to moral judgment and interpersonal distancing was confirmed across scales and sample groups. The internal consistency of the scales was acceptable and evidence of validity is reported. Parallel scales to assess and compare different perspectives of stigma provide opportunities for research aimed at understanding of stigma, assessing the consequences or evaluating possible interventions aimed at reducing stigma. PMID:18266101

Visser, Maretha J.; Kershaw, Trace; Makin, Jennifer D.; Forsyth, Brian W.C.

2014-01-01

350

How Do You Get HIV or AIDS?  

MedlinePLUS

... Text Size Print Share How Do You Get HIV or AIDS? How Do You Get HIV? Certain body fluids from an HIV-infected person ... CDCâ??s HIV Basics: HIV Transmission . HOW is hiv spread? Approximately 50,000 new HIV infections occur ...

351

HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates.  

PubMed

The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish a rationale for eliminating HIV-1-infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the remnants of ancient infectious retroviruses. We show that the infection of CD4+ T cells with HIV-1 resulted in transcription of the HML-2 lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins. HERV-K(HML-2)-specific CD8+ T cells obtained from HIV-1-infected human subjects responded to HIV-1-infected cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of action, a HERV-K(HML-2)-specific CD8+ T cell clone exhibited comprehensive elimination of cells infected with a panel of globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV-1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies the consideration of HERV-K(HML-2)-specific and cross-reactive T cell responses in the natural control of HIV-1 infection and for exploring HERV-K(HML-2)-targeted HIV-1 vaccines and immunotherapeutics. PMID:23143309

Jones, R Brad; Garrison, Keith E; Mujib, Shariq; Mihajlovic, Vesna; Aidarus, Nasra; Hunter, Diana V; Martin, Eric; John, Vivek M; Zhan, Wei; Faruk, Nabil F; Gyenes, Gabor; Sheppard, Neil C; Priumboom-Brees, Ingrid M; Goodwin, David A; Chen, Lianchun; Rieger, Melanie; Muscat-King, Sophie; Loudon, Peter T; Stanley, Cole; Holditch, Sara J; Wong, Jessica C; Clayton, Kiera; Duan, Erick; Song, Haihan; Xu, Yang; SenGupta, Devi; Tandon, Ravi; Sacha, Jonah B; Brockman, Mark A; Benko, Erika; Kovacs, Colin; Nixon, Douglas F; Ostrowski, Mario A

2012-12-01

352

HERV-K–specific T cells eliminate diverse HIV-1/2 and SIV primary isolates  

PubMed Central

The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish a rationale for eliminating HIV-1–infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the remnants of ancient infectious retroviruses. We show that the infection of CD4+ T cells with HIV-1 resulted in transcription of the HML-2 lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins. HERV-K(HML-2)–specific CD8+ T cells obtained from HIV-1–infected human subjects responded to HIV-1–infected cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of action, a HERV-K(HML-2)–specific CD8+ T cell clone exhibited comprehensive elimination of cells infected with a panel of globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV-1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies the consideration of HERV-K(HML-2)–specific and cross-reactive T cell responses in the natural control of HIV-1 infection and for exploring HERV-K(HML-2)–targeted HIV-1 vaccines and immunotherapeutics. PMID:23143309

Jones, R. Brad; Garrison, Keith E.; Mujib, Shariq; Mihajlovic, Vesna; Aidarus, Nasra; Hunter, Diana V.; Martin, Eric; John, Vivek M.; Zhan, Wei; Faruk, Nabil F.; Gyenes, Gabor; Sheppard, Neil C.; Priumboom-Brees, Ingrid M.; Goodwin, David A.; Chen, Lianchun; Rieger, Melanie; Muscat-King, Sophie; Loudon, Peter T.; Stanley, Cole; Holditch, Sara J.; Wong, Jessica C.; Clayton, Kiera; Duan, Erick; Song, Haihan; Xu, Yang; SenGupta, Devi; Tandon, Ravi; Sacha, Jonah B.; Brockman, Mark A.; Benko, Erika; Kovacs, Colin; Nixon, Douglas F.; Ostrowski, Mario A.

2012-01-01

353

HIV-1 diversity, drug-resistant mutations, and viral evolution among high-risk individuals in phase II HIV vaccine trial sites in southern China.  

PubMed

HIV-1 prevalence in Guangxi, China, has been growing since 1996, when the first case was reported. Over half of HIV-1 positive patients in Guangxi Province were injecting drug users (IDUs), possibly because of the province's location near drug-trafficking routes. Since a phase II HIV vaccine trial is ongoing there, a current characterization of the subtypes of HIV-1 among IDUs in Guangxi would provide critical information for future HIV vaccine trials, as well as further control and prevention of HIV-1 transmission. Thus, we conducted a molecular epidemiological investigation of HIV-1 samples from 2008-2010 among IDUs in multiple cities in Guangxi Province. Our results, based on the gag/pol fragment, indicated a very high proportion (78.47%) of HIV-1 CRF08_BC recombinants, some CRF01_AE (15.38%) recombinants, and a low proportion of CRF07_BC (6.15%) recombinants among the IDUs. The high proportion of CRF08 HIV-1 strains among recent IDUs matches the vaccine candidate constructs. However, future vaccine development should also incorporate CRF01-targeted vaccine candidates. Distinct Env sequence evolution patterns were observed for CRF08_BC and CRF01_AE, indicating that different local selection pressures have been exerted on these two HIV-1 subtypes. Unique drug-resistant mutations were also detected, and our data indicate that HIV treatment programs should consider pre-existing drug-resistant mutations. PMID:23869225

Qi, Haiyan; Zhao, Ke; Xu, Fei; Zhang, Xuzhao; Zhang, Zhiyong; Yang, Li; Li, Chunling; Liang, Xu; Guo, Weigui; Chen, Shihai; Liu, Zhihao; Zhang, Wenyan; Yu, Xiao-Fang

2013-01-01

354

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

PubMed

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

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

2014-11-01

355

HCV versus HIV drug discovery: Déjà vu all over again?  

PubMed

Efforts to address HIV infection have been highly successful, enabling chronic suppression of viral replication with once-daily regimens. More recent research into HCV therapeutics have also resulted in very promising clinical candidates. This Digest explores similarities and differences in the two fields and compares the chronology of drug discovery relative to the availability of enabling tools, and concludes that safe and convenient, once-daily regimens are likely to reach approval much more rapidly for HCV than was the case for HIV. PMID:23489621

Watkins, William J; Desai, Manoj C

2013-04-15

356

HIV risk networks and HIV transmission among injecting drug users  

Microsoft Academic Search

The objective of this study was to demonstrate how injecting drug users’ (IDUs) HIV risk networks affect their risk for infection with HIV and influence their HIV risk behaviors. Concepts utilized in a network approach were specified. These concepts included: (1) the distinction between risk networks (the people with or among whom IDUs—or others at risk of infection with HIV—engage

A. Neaigus; S. R. Friedman; B. J. Kottiri; D. C. Des Jarlais

2001-01-01

357

Morphine Enhances HIV Infection of Human Blood Mononuclear Phagocytes through Modulation of ?-Chemokines and CCR5 Receptor  

PubMed Central

Background Injection drug use remains a significant risk for acquiring HIV infection. The mechanisms by which morphine enhances HIV infection of human immune cells are largely unknown. Objective In this study, we sought to determine the possible mechanisms by which morphine upregulates HIV infection of human blood monocyte-derived macrophages (MDM). Methods In this study, MDM were infected with the R5, X4, and R5X4 HIV strains. HIV replication was determined by performing reverse transcriptase activity assays. HIV receptors were determined by performing reverse transcriptase polymerase chain reactions and flow cytometry assays. ?-chemokines were analyzed by performing enzyme-linked immunosorbent assays. In addition, HIV R5 strain and murine leukemia virus envelope-pseudotyped HIV infection was performed to determine whether morphine affects HIV infection of macrophages at entry level. Results Morphine significantly enhanced HIV R5 strain infection of MDM but had little effect on X4 strain infection. The macrophage-tropic R5 strain envelope-pseudotyped HIV infection was markedly increased by morphine, whereas murine leukemia virus envelope-pseudotyped HIV infection was not significantly affected. Furthermore, morphine significantly upregulated CCR5 receptor expression and inhibited the endogenous production of ?-chemokines in MDM. The opioid receptor antagonist naltrexone blocked the effects of morphine on the production of ?-chemokines. Conclusion Opiates enhance HIV R5 strain infection of macrophages through the downregulation of ?-chemokine production and upregulation of CCR5 receptor expression and may have an important role in HIV immunopathogenesis. PMID:12425430

Guo, Chang-Jiang; Li, Yuan; Tian, Sha; Wang, Xu; Douglas, Steven D.; Ho, Wen-Zhe

2014-01-01

358

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

PubMed Central

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

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

2013-01-01

359

Towards Modeling HIV Long Term Behavior  

E-print Network

The precise mechanism that causes HIV infection to progress to AIDS is still unknown. This paper presents a mathematical model which is able to predict the entire trajectory of the HIV/AIDS dynamics, then a possible explanation for this progression is examined. A dynamical analysis of this model reveals a set of parameters which may produce two real equilibria in the model. One equilibrium is stable and represents those individuals who have been living with HIV for at least 7 to 9 years, and do not develop AIDS. The other one is unstable and represents those patients who developed AIDS in an average period of 10 years. However, further work is needed since the proposed model is sensitive to parameter variations.

Hernandez-Vargas, Esteban A; Middleton, Richard H

2011-01-01

360

Stable human immunodeficiency virus type 1 (HIV-1) resistance in transformed CD4+ monocytic cells treated with multitargeting HIV-1 antisense sequences incorporated into U1 snRNA.  

PubMed Central

We have approached the development of a human immunodeficiency virus type 1 (HIV-1) therapeutic product by producing immune cells stably resistant to HIV-1. Promonocytic CD4+ cells (U937) were made resistant to HIV-1 by the introduction of a DNA construct (pNDU1A,B,C) that contained three independent antisense sequences directed against two functional regions, transactivation response and tat/rev, of the HIV-1 target. Each sequence was incorporated into the transcribed region of a U1 snRNA gene to generate U1/HIV antisense RNA. Stably transfected cells expressed all three U1/HIV antisense transcripts, and these transcripts accumulated in the nucleus. These cells were subjected to two successive challenges with HIV-1 (BAL strain). The surviving cells showed normal growth characteristics and have retained their CD4+ phenotype. In situ hybridization assays showed that essentially all of the surviving cells produced U1/HIV antisense RNA. No detectable p24 antigen was observed, no syncytium formation was observed, and PCR-amplified HIV gag sequences were not detected. Rechallenge with HIV-1 (IIIB strain) similarly yielded no infection at a relatively high multiplicity of infection. As a further demonstration that the antisense RNA directed against HIV-1 was functioning in these transfected immune cells, Tat-activated expression of chloramphenicol acetyltransferase was shown to be specifically inhibited in cells expressing Tat and transactivation response region antisense sequences. PMID:9094686

Liu, D; Donegan, J; Nuovo, G; Mitra, D; Laurence, J

1997-01-01

361

Clinical Management of HIV Drug Resistance  

PubMed Central

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

362

ANTIOXIDANT THERAPEUTIC ADVANCES IN COPD  

PubMed Central

Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD. PMID:19124382

Rahman, Irfan

2009-01-01

363

Recently diagnosed gay men talk about HIV treatment decisions.  

PubMed

Background In recent years, there has been increasing evidence that early initiation of antiretroviral therapy (ART) may provide health benefits for those infected with HIV. There has also been significant discussion about the role of HIV treatment in preventing onward transmission of the virus. Early provision and uptake of ART to people recently diagnosed with HIV could achieve both individual and public health outcomes. The success of such an initiative relies, in part, on the preparedness of those recently diagnosed with HIV to engage with the therapy. Methods: The HIV Seroconversion Study collects both quantitative and qualitative data from people in Australia who have recently been diagnosed with HIV. During 2011-2012, 53 gay or bisexual men recruited across Australia took part in semistructured interviews as part of the study. The men were asked about their knowledge and experience of, and their decisions about whether or not to commence, HIV treatment. Results: The interviews identified differing levels of knowledge about HIV treatments and divergent views about the health and prevention benefits of ART. For some, treatments provided a sense of control over the virus; others were apprehensive and distrustful, and preferred to resist commencing treatments for as long as possible. Conclusions: If early initiation of treatment is to be encouraged, appropriate measures must be in place to ensure recently diagnosed individuals have access to the appropriate information and the support they need to enable them to make informed choices and, if necessary, to address their fears. PMID:24507432

Down, Ian; Prestage, Garrett; Triffitt, Kathy; Brown, Graham; Bradley, Jack; Ellard, Jeanne

2014-07-01

364

HIV and Communication  

ERIC Educational Resources Information Center

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

McNeilly, L.G.

2005-01-01

365

HIV and adolescents.  

PubMed

Human immunodeficiency virus has entered the adolescent population, and pediatricians will be caring for youngsters who are HIV positive or at risk of being infected. We should remember that it is risky sexual behavior and injection drug use that places a teen at risk for HIV infection, not their sexual orientation, ethnicity, or gender. Parents and their teenagers desire and expect their pediatricians to provide care and guidance for the diseases and problems that adolescents face. A screening psychosocial assessment of teenagers can identify those who need more in-depth counseling. Although the subjects of sex and drug use initially may be uncomfortable for a physician, practice using the HEADSS assessment will rapidly lead to comfort in discussing these important subjects. An understanding of HIV testing and pre- and post-test counseling will prepare the physician for the inevitable patient who wishes testing or who is HIV positive. Much of the treatment of HIV-positive adolescents involves patience and support while the adolescent grapples with the serious implications of being HIV positive. The initial history and physical exam establishes baselines regarding previous infections and illnesses that may bear on HIV infection, as well as determining which symptoms and signs of HIV infection are present. The initial laboratory tests further define the patient's current clinical state and will determine what therapies are immediately needed. Human immunodeficiency virus continues to evolve toward a manageable chronic illness that responds most favorably to early intervention. PMID:8414698

Anderson, M M; Morris, R E

1993-07-01

366

Smart HIV testing system.  

PubMed

The quick HIV testing method called "MiraWell Rapid HIV Test" uses a specialized testing kit to determine whether an individual's blood is contaminated with the HIV virus or not. When a drop of blood is placed on the center of the testing kit, a simple pattern will appear in the middle of the kit to indicate the test status, i.e., positive or negative. This HIV test should be done in a small clinic or in a lab and the test must be conducted by a trained technician. A smart HIV testing system was developed through this research to eliminate the human error that is associated with the use of the quick HIV testing kits. Also, the smart HIV system will improve the testing productivity in comparison to those achieved by the trained technicians. In this research, we have developed a cost-effective system that analyzes the image produced by the HIV kits. We have used a System-On-Chip (SOC) design approach based on the Field Programmable Gate Array (FPGA) technology and the Xilinx Virtex SOC chip in building the system's prototype. The system used a CMOS digital camera to capture the image and an FPGA chip to process the captured image and send the testing results to the display unit. The system can be used in small clinics and pharmacies and eliminates the need for trained technicians. The system has been tested successfully and 98% of the tests were correct. PMID:16078623

El Kateeb, Ali; Law, Peter; Chan, King

2005-06-01

367

Families living with HIV  

Microsoft Academic Search

Given the historical emergence of the AIDS epidemic first among gay men in the developed world, HIV interventions have primarily focused on individuals rather than families. Typically not part of traditional family structures, HIV-positive gay men in Europe and the US lived primarily in societies providing essential infrastructure for survival needs that highly value individual justice and freedom. Interventions were

M. J. Rotheram-Borus; D. Flannery; E. Rice; P. Lester

2005-01-01

368

Positive: HIV Affirmative Counseling.  

ERIC Educational Resources Information Center

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

Kain, Craig D.

369

After Hrs with HIV  

Microsoft Academic Search

To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multi- vesicular body (MVB) biogenesis. The HIV Gag protein mimics hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links mem- brane cargo recognition to its degradation after delivery to MVBs.

Ali Amara; Dan R. Littman

2003-01-01

370

Mental Health and HIV  

MedlinePLUS

... as by volunteering at an HIV/AIDS service organization. This may empower you and lessen your feelings of fear. Talk to your doctor about medicines for anxiety if the feelings don't lessen with time or if they get worse. Stress If you are HIV positive, you and your ...

371

Revisiting HIV1 uncoating  

Microsoft Academic Search

HIV uncoating is defined as the loss of viral capsid that occurs within the cytoplasm of infected cells before entry of the viral genome into the nucleus. It is an obligatory step of HIV-1 early infection and accompanies the transition between reverse transcription complexes (RTCs), in which reverse transcription occurs, and pre-integration complexes (PICs), which are competent to integrate into

Nathalie Arhel

2010-01-01

372

Biologic Characterization of HIV-2.  

National Technical Information Service (NTIS)

Our data on the biology of HIV-2 suggest that this virus may have a distinct biology from that of its close relative HIV-1. It Is therefore relevant to assess these differences In populations Infected with significant rates of both HIV-2 and HIV-1. Senega...

P. J. Kanki

1992-01-01

373

Living with HIV/AIDS  

MedlinePLUS

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

374

Natural Protection Against HIV1 Infection Provided by HIV2  

Microsoft Academic Search

Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in

Karin Travers; Souleymane Mboup; Richard Marlink; Aissatou Gueye-Ndiaye; Tidiane Siby; Ibou Thior; Ibrahima Traore; Abdoulaye Dieng-Sarr; Jean-Louis Sankale; Christopher Mullins; Ibrahima Ndoye; Chung-Cheng Hsieh; Max Essex; Phyllis Kanki

1995-01-01

375

HIV preferentially infects HIV-specific CD4+ T cells  

Microsoft Academic Search

HIV infection is associated with the progressive loss of CD4+ T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4+ T cells are preferentially affected. Here we show that HIV-specific memory CD4+ T cells in infected individuals contain more HIV viral DNA

Daniel C. Douek; Jason M. Brenchley; Michael R. Betts; David R. Ambrozak; Brenna J. Hill; Yukari Okamoto; Joseph P. Casazza; Janaki Kuruppu; Kevin Kunstman; Steven Wolinsky; Zvi Grossman; Mark Dybul; Annette Oxenius; David A. Price; Mark Connors; Richard A. Koup

2002-01-01

376

Interactions between HIV1 gp120, chemokines, and cultured adult microglial cells  

Microsoft Academic Search

HIV dementia (HIVD), a disease that is apparently mediated by neurotoxins and viral proteins secreted by HIV infected microglia,\\u000a is characterized neuropathologically by an increased number of activated microglia in the brains of affected individuals.\\u000a Consequently, the rational design of potential therapeutic strategies should take into account the mechanisms that lead to\\u000a microglial activation and to their increased prominence in

Andrew V. Albright; Julio Martón; Michael O’Connor; Francisco González-Scarano

2001-01-01

377

[Kidney and HIV infection].  

PubMed

Screening of chronic kidney disease (CKD) that includes estimation of the glomerular filtration rate (GFR) and evaluation proteinuria should be performed in all HIV-infected patients and these parameters have to be monitored annually in patients at higher risk for CKD. Black patients have a genetic predisposition to develop HIV-associated nephropathy. Suppression of HIV viral replication with antiretroviral therapy prevents the development of HIV-associated nephropathy or halts its progression. Kidney biopsy remains the most informative diagnosis test to differentiate various forms of kidney diseases in HIV-infected patients. Dosing antiretroviral agents with kidney metabolism should be adjusted when eGFR is bellow 50 mL/min/1.73 m(2). eGFR and serum phosphorus at baseline and during treatment should be carefully assessed in patients receiving tenofovir. Proximal renal tubular toxicity must be further evaluated in the presence of eGFR decrease and/or hypophosphatemia under tenofovir therapy. PMID:22245017

Plaisier, Emmanuelle; Lescure, François-Xavier; Ronco, Pierre

2012-03-01

378

HIV-Associated Tuberculosis  

PubMed Central

The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6. PMID:20871843

Naidoo, Kogieleum; Naidoo, Kasavan; Padayatchi, Nesri; Abdool Karim, Quarraisha

2011-01-01

379

Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals  

PubMed Central

We explored the possible augmenting effect of traumatic brain injury (TBI) history on HIV (human immunodeficiency virus) associated neurocognitive complications. HIV-infected participants with self-reported history of definite TBI were compared to HIV patients without TBI history. Groups were equated for relevant demographic and HIV-associated characteristics. The TBI group evidenced significantly greater deficits in executive functioning and working memory. N-acetylaspartate, a putative marker of neuronal integrity, was significantly lower in the frontal gray matter and basal ganglia brain regions of the TBI group. Together, these results suggest an additional brain impact of TBI over that from HIV alone. One clinical implication is that HIV patients with TBI history may need to be monitored more closely for increased risk of HIV-associated neurocognitive disorder signs or symptoms. PMID:21229435

Lin, Kenny; Taylor, Michael J; Heaton, Robert; Franklin, Donald; Jernigan, Terry; Fennema-Notestine, Christine; McCutchan, Allen; Atkinson, J Hampton; Ellis, Ronald J; McArthur, Justin; Morgello, Susan; Simpson, David; Collier, Ann C; Marra, Christina; Gelman, Benjamin; Clifford, David; Grant, Igor

2011-01-01

380

HIV/AIDS knowledge and attitudes among Chinese college students in the US.  

PubMed

This study assessed knowledge and attitudes about HIV/AIDS and sources of HIV/STI information among Chinese college students living in the USA and explored specific factors associated with knowledge levels and types of sources of information. We surveyed 133 Chinese students enrolled in three US universities. About 41.4 % believed that HIV could be contracted through mosquito bites, and 22.6 % were unaware that condoms could prevent HIV. Sources of HIV/STI information were the mass media. Males were more likely to demonstrate a higher HIV/AIDS knowledge level than females. Graduate students were more likely to cite television as a source of information, and less likely to mention school teachers, than were undergraduate students. These ethnic minority immigrant students held misconceptions about HIV transmission and prevention, and possibly utilized information of varying quality. Accordingly this study identifies specific objectives for education, including basic biology and diversity issues from evidence-based sources. PMID:22965498

Tung, Wei-Chen; Lu, Minggen; Cook, Daniel M

2013-08-01

381

The epidemiology of HIV infection in Morocco: systematic review and data synthesis  

PubMed Central

Summary Morocco has made significant strides in building its HIV research capacity. Based on a wealth of empirical data, the objective of this study was to conduct a comprehensive and systematic literature review and analytical synthesis of HIV epidemiological evidence in this country. Data were retrieved using three major sources of literature and data. HIV transmission dynamics were found to be focused in high-risk populations, with female sex workers (FSWs) and clients contributing the largest share of new HIV infections. There is a pattern of emerging epidemics among some high-risk populations, and some epidemics, particularly among FSWs, appear to be established and stable. The scale of the local HIV epidemics and populations affected show highly heterogeneous geographical distribution. To optimize the national HIV response, surveillance and prevention efforts need to be expanded among high-risk populations and in geographic settings where low intensity and possibly concentrated HIV epidemics are emerging or are already endemic. PMID:23970764

Kouyoumjian, S P; Mumtaz, G R; Hilmi, N; Zidouh, A; El Rhilani, H; Alami, K; Bennani, A; Gouws, E; Ghys, P D; Abu-Raddad, L J

2013-01-01

382

Pyroptosis drives CD4 T-cell depletion in HIV-1 infection  

PubMed Central

The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood. Apoptosis has been proposed as the key mechanism for CD4 T-cell loss. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of productively infected cells. The remaining >95% of quiescent lymphoid CD4 T-cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death where cytoplasmic contents and pro-inflammatory cytokines including IL-1?, are released. This death pathway thus links the two signature events in HIV infection––CD4 T-cell depletion and chronic inflammation––and creates a vicious pathogenic cycle where dying CD4 T-cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase-1 inhibitors shown to be safe in humans, raising the possibility of a new class of “anti-AIDS” therapeutics targeting the host rather than the virus. PMID:24356306

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

2014-01-01

383

Gene Therapy Targeting HIV Entry  

PubMed Central

Despite the unquestionable success of antiretroviral therapy (ART) in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT) using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection. PMID:24662607

Didigu, Chuka; Doms, Robert

2014-01-01

384

[Epidemiology of HIV].  

PubMed

Globally, an estimated 35 million people were living with HIV in 2012; of these, 69 % in sub-Saharan Africa. There were 2.3 million new HIV infections globally and 1.6 million AIDS deaths in 2012. As a result of large roll-out programs with integrated voluntary counselling and testing and prevention programs in resource limited settings, sexual transmission of HIV decreased substantially over the last years. However, the world is not on track to reduced HIV transmission among people who inject drugs. Especially in Eastern Europe and Asia prevention coverage for people who inject drugs remains low. In addition, effective prevention among these people is undermined by stigmatisation, discrimination, punitive policy frameworks and law enforcement practices, which discourage people from seeking the health and social services they need. Antiretroviral coverage among pregnant women living with HIV reached 62 % in 2012 resulting in a reduction of newly infected children by 35 % from 2009. In 2012, 9.7 million people in low and middle-income countries received antiretroviral therapy, representing 61 % of all who were eligible under the 2010 WHO HIV treatment guidelines. Under the 2013 guidelines, this represents only 34 % of the 28.3 million people eligible in 2013. A new concept to curb the HIV epidemic is "Test and Treat" which involves population-wide HIV tests with immediate initiation of antiretroviral therapy among all HIV infected individuals. However, there are concerns regarding the sustainability of such treatment programs for decades due to lost to follow up and insufficient adherence and the danger of a large increase of resistant HIV which jeopardize the effectiveness of affordable treatments. PMID:25093307

Ledergerber, Bruno; Battegay, Manuel

2014-08-01

385

AIDS\\/HIV in Pregnancy  

Microsoft Academic Search

Women are among the fastest growing populations of those infected with HIV and AIDS, and most infected women are of childbearing\\u000a age. Women who are both HIV-positive and pregnant are faced with a double burden both in terms of immunity and nutrition.\\u000a The HIV-infected pregnant woman is at increased nutritional risk compared to the HIV-uninfected pregnant woman. HIV-infected\\u000a pregnant women

Katherine Kunstel

386

[Humanized antibodies as therapeutics].  

PubMed

Since 1997, nine humanized antibodies received the approval of the FDA to be used as drugs for the treatment of various diseases including transplant rejections, metastatic breast and colon cancers, leukaemia, non-Hodgkin lymphomas, allergic conditions or multiple sclerosis. This review describes techniques used to engineer these antibodies and presents the recent evolutions of these techniques : SDRs grafting or < abbreviated > CDRs grafting. Based on the illustrative examples of several antibodies, Mylotarg, Herceptin or Xolair, the therapeutic effectiveness of humanized antibodies are underlined and, with the example of Tysabri, the sometimes dramatic adverse effects associated with their clinical use is stressed. In a second part, this review presents some future and realistic avenues to improve the effectiveness of the humanized antibodies, to decrease their immunogenicity and to reduce their cost. PMID:16324646

Bellet, Dominique; Dangles-Marie, Virginie

2005-12-01

387

Antimicrobial peptides: therapeutic potentials.  

PubMed

The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations. PMID:25371141

Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

2014-12-01

388

[Therapeutic education didactic techniques].  

PubMed

This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective. PMID:23157069

Valverde, Maite; Vidal, Mercè; Jansa, Margarida

2012-10-01

389

Missed opportunities: HIV and the 2010 FIFA World Cup.  

PubMed

The international community missed opportunities to raise HIV awareness and reduce transmission risk during the World Cup held in South Africa from 11 June-11 July 2010. With the tournament captivating the entire region, the public health community should have better applied our knowledge and evidence-based interventions to raise the profile of HIV prevention, care and treatment. More should have been done to prevent possible new infections fueled by visitors, alcohol and sports celebrations. Considering the impact of HIV in southern Africa and the amount of funds and effort that go into addressing the problem each year, we cannot afford to miss these opportunities for action. PMID:21907367

Beres, L K

2011-10-01

390

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

PubMed Central

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

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

2014-01-01

391

Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C  

PubMed Central

Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are the most prevalent deadly chronic viral diseases. HIV is treated by small molecule inhibitors. HBV is treated by immunomodulation and small molecule inhibitors. HCV is currently treated primarily by immunomodulation but many small molecules are in clinical development. Although HIV is a retrovirus, HBV is a double-stranded DNA virus, and HCV is a single-stranded RNA virus, antiviral drug resistance complicates the development of drugs and the successful treatment of each of these viruses. Although their replication cycles, therapeutic targets, and evolutionary mechanisms are different, the fundamental approaches to identifying and characterizing HIV, HBV, and HCV drug resistance are similar. This review describes the evolution of HIV, HBV, and HCV within individuals and populations and the genetic mechanisms associated with drug resistance to each of the antiviral drug classes used for their treatment. PMID:21243082

Margeridon-Thermet, Severine; Shafer, Robert W.

2010-01-01

392

Developing neuroprotective strategies for treatment of HIV-associated neurocognitive dysfunction  

PubMed Central

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

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

2009-01-01

393

HIV treatment for prevention.  

PubMed

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

Ambrosioni, Juan; Calmy, Alexandra; Hirschel, Bernard

2011-01-01

394

[Behçet's disease revealed by deep vein thrombosis in an HIV-1-infected patient].  

PubMed

Behçet's disease is a multisystemic vasculitis characterized by the association of recurrent oral and genital ulcers with systemic involvements, particularly ocular, nervous and vascular manifestations. The association of Behçet's disease and aids/HIV infection is rare. The role of HIV infection in the pathomechanism of both diseases is unclear. We report a 28-year-old HIV-positive patient who presented Behçet's disease complicated by deep vein thrombosis and left lateral sinus thrombosis. This rare association raises questions about the etiopathogenic process and therapeutic management. PMID:23068309

Marih, L; Sodqi, M; Marhoum El Filali, K; Chakib, A

2012-12-01

395

Unorthodox inhibitors of HIV protease: looking beyond active-site-directed peptidomimetics.  

PubMed

HIV protease (PR) is a key target for antiviral drugs, and HIV protease inhibitors (PIs) are a prime example of successful structure-based drug design. PIs show clear therapeutic benefits, but their efficacy can be compromised by poor bioavailabilitity, unwanted side effects, and most importantly, development of antiviral drug resistance. Therefore, the quest for novel, highly active compounds with improved resistance profiles, better pharmacokinetic properties, and fewer adverse effects continues. In particular, the problem of cross-resistance could be circumvented by identifying novel compounds that show different binding modes to HIV PR than the current clinical inhibitors. PMID:24001229

Schimer, Jiri; Konvalinka, Jan

2014-01-01

396

Silence, sexuality and HIV\\/AIDS in South African schools  

Microsoft Academic Search

In South Africa where there is a very high HIV infection rate among teenagers and young adults, it is surprising to find that\\u000a students and teachers are very unwilling to talk about the possibility of being or becoming HIV positive. While AIDS messages\\u000a dominate public discourse, there is a silence in schools about the personal in relation to AIDS. This

Robert Morrell

2003-01-01

397

Women Are at Risk of HIV  

MedlinePLUS

... of all races and ethnicities can get HIV Violence against women and HIV risk Alcohol and substance abuse and ... of all races and ethnicities can get HIV Violence against women and HIV risk Alcohol and substance abuse and ...

398

HIV/AIDS and Asian Americans  

MedlinePLUS

... Data > Minority Population Profiles > Asian American > HIV/AIDS HIV/AIDS and Asian Americans Asian Americans have slightly ... with HIV than White women. At a glance – HIV Infection Cases (Adults and Children) Estimated number of ...

399

Black Americans and HIV/AIDS  

MedlinePLUS

... Black Americans and HIV/AIDS Black Americans and HIV/AIDS Apr 25, 2014 Black Americans have been ... of Blacks living with an HIV diagnosis. 15 HIV Testing and Access to Prevention & Care Three quarters ( ...

400

HIV Vaccine Research Curriculum  

NSDL National Science Digital Library

This is a series of PDF files including an overview, a series of 5 lessons, assessments, an appendix and extended resources such as a lab activity. The lessons should span approximately 2 weeks, depending on the amount of activities and depth of review. This unit explores the scientific and ethical issues involved in clinical HIV vaccine trials using human research participants. The unit begins by examining studentsÃÂ current knowledge of HIV, and by reviewing HIV structure and transmission. Next, it familiarizes students with types of vaccines and with challenges related to creating an HIV vaccine. Students are encouraged to explore issues related to human research participants using basic ethical principles and historical case studies. Lastly, global issues regarding the pandemic are explored to give the students an understanding of cultural issues involved in the spread of HIV. This cultural context introduces students to ethical dilemmas inherent in the selection of human participants in global vaccine trials. The lessons culminate in having students design their own hypothetical HIV vaccine clinical trial, based upon knowledge of HIV structure, vaccine characteristics, human research participants considerations, and global contexts.

Joan Griswold (NWABR)

2007-01-01

401

HIV-specific CD8+ T cells: serial killers condemned to die?  

PubMed

An increasing body of evidence supports a key role for cytotoxic CD8+ T cells (CTL) in controlling HIV infection. Although a vigorous HIV-specific CD8+ T cell response is raised during the primary infection, these cells ultimately fail to control virus and prevent disease progression. The failure of CTL to control HIV infection has been attributed to a number of strategies HIV employs to evade the immune system. Recently, intrinsic defects in the CTL themselves have been proposed to contribute to the failure of CTL to control HIV. HIV-specific CD8+ T cells differ in their effector/memory phenotype from other virus-specific CD8+ T cells indicating that their differentiation status differs. This altered different