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Sample records for advanced human immunodeficiency

  1. Addressing Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Advanced Practice Nursing Education.

    ERIC Educational Resources Information Center

    Nokes, Kathleen M.; Stein, Gary L.

    1997-01-01

    A survey of 23 advanced practice nursing programs showed only 3 had HIV-specific graduate-level nursing courses. Recommendations were made for HIV-specific courses, integration of HIV content into other courses, use of Centers for Disease Control and Occupational Safety and Health Administration guidelines, and subspecialties in HIV nursing. (SK)

  2. Recent key advances in human immunodeficiency virus medicine and implications for China

    PubMed Central

    2010-01-01

    In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program. PMID:20500898

  3. Testing for Human Immunodeficiency Virus

    MedlinePlus

    ... incisions made in the mother’s abdomen and uterus. Human Immunodeficiency Virus (HIV): A virus that attacks certain cells of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS). Immune System: ...

  4. Human Immunodeficiency Virus Prevention.

    PubMed

    Davis, Teaniese Latham; DiClemente, Ralph

    2016-04-01

    Human immunodeficiency virus (HIV) is the virus that causes AIDS. Surveillance data from 2012 indicate an estimated 1.2 million people aged 13 years and older were living with HIV infection in the United States, and 12.8% do not know their status. There are approximately 50,000 new HIV infections annually. With no available cure for HIV, primary prevention to reduce incident cases of HIV is essential. Strategies to prevent HIV transmission include reducing sexual risk behavior and needle sharing. The Centers for Disease Control and Prevention has multiple resources available for primary and secondary prevention to reduce disease transmission and severity. PMID:26980130

  5. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A ... weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can cause AIDS ( ...

  6. Human immunodeficiency virus infection and pneumothorax

    PubMed Central

    Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

    2014-01-01

    Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

  7. Adolescents and human immunodeficiency virus infection.

    PubMed

    Anderson, J R

    1992-12-01

    As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to-female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills.

  8. Pediatric human immunodeficiency virus infection.

    PubMed Central

    Domachowske, J B

    1996-01-01

    In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies. PMID:8894346

  9. Screening for Human Immunodeficiency Virus (HIV)

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of this screening: (1) Everyone aged 15 to ... the disease to other people. Potential Benefits and Harms of Screening for Human Immunodeficiency Virus (HIV) The ...

  10. Acquired immunodeficiency syndrome and human immunodeficiency virus infection in Nevada.

    PubMed

    Jarvis, J Q; Semiatin, S L

    1991-01-01

    We summarize information from three sets of epidemiologic data: the Nevada AIDS [acquired immunodeficiency syndrome] Surveillance System, which contains information about every case identified within the state boundaries through September 1989; the human immunodeficiency virus (HIV) seroprevalence reporting systems, which currently include data on all HIV-positive reports submitted statewide to public health authorities; and surveys on the knowledge, attitudes, and behaviors of Nevadans concerning HIV-related disease. The Nevada State AIDS Task Force outlined major policy recommendations, nearly half of which concerned testing; only 2 dealt with preventing HIV transmission. Greater efforts should go into education, particularly directed toward groups at greatest risk of exposure to HIV, and to improve community-based care of infected persons.

  11. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults.

    PubMed

    Scott, Jake; Goetz, Matthew Bidwell

    2016-08-01

    Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities.

  12. Human Immunodeficiency Virus Vaccine Trials

    PubMed Central

    O’Connell, Robert J.; Kim, Jerome H.; Corey, Lawrence; Michael, Nelson L.

    2012-01-01

    More than 2 million AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/AIDS. Despite promising advances in prevention, an estimated 2.7 million new HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1 vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate vaccine strategies have been advanced to efficacy testing. The recombinant glycoprotein (rgp)120 subunit vaccines, AIDSVAX B/B and AIDSVAX B/E, and the Merck Adenovirus serotype (Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost vaccine combination of ALVAC-HIV vCP1521 and bivalent rgp120 (AIDSVAX B/E) showed 31% efficacy in protection from infection among community-risk Thai participants. A fifth efficacy trial testing a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1 infection. PMID:23209178

  13. Randomized Trial of Paclitaxel versus Pegylated Liposomal Doxorubicin for Advanced Human Immunodeficiency Virus-associated Kaposi’s Sarcoma: Evidence for Symptom Palliation from Chemotherapy

    PubMed Central

    Cianfrocca, Mary; Lee, Sandra; Von Roenn, Jamie; Tulpule, Anile; Dezube, Bruce J.; Aboulafia, David M.; Ambinder, Richard F.; Lee, Jeannette Y.; Krown, Susan E.; Sparano, Joseph A.

    2011-01-01

    Background Paclitaxel (PTX) and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency (HIV) associated Kaposi’s sarcoma (KS). We performed a randomized trial comparing the efficacy and toxicity of PTX and PLD, and determine the effects of therapy on symptom palliation and quality of life. Methods Patients with advanced HIV-associated KS were randomly assigned to receive PTX (100 mg/m2) IV every 2 weeks, or PLD 20 mg/m2 IV every 3 weeks. The KS Functional Assessment of HIV (FAHI) Quality of Life instrument was used before and after every other treatment cycle. Results The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the PTX arm and 37 in the PLD arm; 73% received highly active antiretroviral therapy (HAART) and 32% had undetectable viral load (<400 copies/mL). Treatment was associated with significant improvement in pain (P=0.024) and swelling (P<0.001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the PTX and PLD arms revealed comparable response rates (56% vs. 46%; p=0.49), median progression free survival (17.5 vs. 12.2 months; p=0.66), and 2-year survival (79% vs. 78%; p=0.75), but somewhat more grade 3–5 toxicity for PTX (84% vs. 66%, p=0.077). Conclusion Treatment with either PTX or PLD produces significant improvement in pain and swelling in patients with advanced, symptomatic, HIV-associated KS treated in the early HAART era. PMID:20564162

  14. Women at Risk for Human Immunodeficiency Virus.

    ERIC Educational Resources Information Center

    Quadagno, David; And Others

    This article reports results from a survey among women at risk for contracting Human Immunodeficiency Virus (HIV) as well as transmitting it in a vertical (to offspring) and horizontal (sexual partner or intravenous [IV] drug usage) mode. Little is known about the extent of HIV knowledge, sexual behaviors, and IV drug usage for women at risk for…

  15. Human Immunodeficiency Virus Infection and Pregnancy

    PubMed Central

    1994-01-01

    The human immunodeficiency virus (HIV) epidemic is clearly one of the most serious health-care crises in the professional lives of contemporary physicians. It cannot be regarded as a curiosity to be dealt with by inner-city infectious-disease experts, but rather must be considered a problem for all health-care providers and a problem in which the obstetrician-gynecologist has a special role to play. PMID:18475370

  16. Endemic mycosis complicating human immunodeficiency virus infection.

    PubMed Central

    Sarosi, G A; DAvies, S F

    1996-01-01

    Persons infected with the human immunodeficiency virus are prone to the development of many fungal diseases. Normal hosts with intact immunity usually recover from infection by these less-invasive fungi. In persons with compromised T-cell-mediated immunity, however, widespread dissemination from a pulmonary focus occurs. In this review, we discuss the epidemiology, clinical manifestations, diagnosis, and treatment of the three major North American mycoses, histoplasmosis, blastomycosis, and coccidioidomycosis. In most cases, amphotericin B is the initial drug of choice, followed by one of the azoles for lifelong maintenance therapy. PMID:8732733

  17. Lipid management in human immunodeficiency virus.

    PubMed

    Myerson, Merle

    2015-05-01

    The development and use of antiretroviral medications to treat patients infected with human immunodeficiency virus (HIV) has dramatically changed the course of this disease from one that was fatal to a chronic and more manageable condition. Recommendations and guidelines for the general population are presented in this review with suggestions as to how they may be applied to this patient population. Issues for which there is little or no information available are noted to highlight the many gaps in our knowledge regarding diagnosis and management of dyslipidemia for patients living with HIV.

  18. Depoliticize Human Immunodeficiency Virus Infection: A Commentary

    PubMed Central

    1994-01-01

    Public-health policy is inconsistent in its approach to the sexually transmitted disease human immunodeficiency virus (HIV). Nearly every health agency has politicized the reporting, finding, and contacting of HIV cases. There is also no consistency among the various state health departments and the various federal health agencies. Until we have a uniform health policy that treats HIV infection as every other reportable sexually transmitted disease, we will make little progress toward controlling its inevitable increase in both cases and costs. PMID:18475369

  19. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ... Development and Human Immunodeficiency Virus Cure Research; Reopening of Comment Period AGENCY: Food and Drug... Virus (HIV) Patient-Focused Drug Development and HIV Cure Research,'' published in the Federal Register of May 21, 2013 (78 FR 29755). In that notice, FDA requested public comment regarding...

  20. Ocular syphilis in patients with Human Immunodeficiency Virus infection.

    PubMed

    Mitchell, John P; Huang, Lynn L; Rosberger, Daniel F

    2015-06-01

    As Acquired Immunodeficiency Disease (AIDS) turns thirty-years old, much progress has been made. 56,000 new cases of the Human Immunodeficiency Virus (HIV) infection are expected in Americans this year. At least half or more will be in African Americans. Reports of the association between syphilis and HIV infection are well documented. We present a case of bilateral optic neuritis and panuveitis as the initial presentation in a previously undiagnosed patient with human immunodeficiency virus (HIV) and syphilis. PMID:27269502

  1. Human immunodeficiency virus induced oral candidiasis.

    PubMed

    Warrier, S Aravind; Sathasivasubramanian, S

    2015-08-01

    Human immunodeficiency virus (HIV) infection is a worldwide health problem, which affects in both developing and developed countries. The oral lesions caused due to this disease can drastically change the life of the patient, in terms of quality. We can also know the progression of the disease and also the important immune status of the patient. Lots of information on HIV is known in the developed countries and very less reports are available in the developing countries. The morbidity of HIV disease is due to its association with opportunistic fungal infection and the most common among them is oral candidiasis. Here, we present a case report on an apparently healthy male patient of 39 years, who had oral candidiasis and was one of the indicators for HIV infection.

  2. Inhibitors of human immunodeficiency virus integrase.

    PubMed Central

    Fesen, M R; Kohn, K W; Leteurtre, F; Pommier, Y

    1993-01-01

    In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of chemicals, including topoisomerase inhibitors, antimalarial agents, DNA binders, naphthoquinones, the flavone quercetin, and caffeic acid phenethyl ester as potential human immunodeficiency virus type 1 integrase inhibitors. Our results show that although several topoisomerase inhibitors--including doxorubicin, mitoxantrone, ellipticines, and quercetin--are potent integrase inhibitors, other topoisomerase inhibitors--such as amsacrine, etoposide, teniposide, and camptothecin--are inactive. Other intercalators, such as chloroquine and the bifunctional intercalator ditercalinium, are also active. However, DNA binding does not correlate closely with integrase inhibition. The intercalator 9-aminoacridine and the polyamine DNA minor-groove binders spermine, spermidine, and distamycin have no effect, whereas the non-DNA binders primaquine, 5,8-dihydroxy-1,4-naphthoquinone, and caffeic acid phenethyl ester inhibit the integrase. Caffeic acid phenethyl ester was the only compound that inhibited the integration step to a substantially greater degree than the initial cleavage step of the enzyme. A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed. Images Fig. 2 PMID:8460151

  3. Antiviral therapy for human immunodeficiency virus infections.

    PubMed Central

    De Clercq, E

    1995-01-01

    Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed. PMID:7542558

  4. [Cerebral infarction in human immunodeficiency virus infection].

    PubMed

    Blanche, P; Toulon, P; de La Blanchardière, A; Sicard, D

    1995-06-01

    Patients infected with the human immunodeficiency virus (HIV) appear to have a high risk of ischaemic cerebral events. We observed two cases of cerebral infarction in patients with acquired immune deficiency syndrome (AIDS). In the first case, a 38-year-old homosexual with no cardiovascular risk other than smoking presented with rapidly progressive hemiparesia. Brain CT-scan visualized two infarcts in the territory of the right sylvian artery and the arteriography an occlusion of the internal carotid artery. In the second, a 37-year-old homosexual, hospitalization was required for a left-sided pure sensitive epilepsy seizure. There was no cardiovascular risk other than smoking. Magnetic resonance imaging showed parietal ischaemia and thrombus in the left atrium without atrial hypertrophy was seen at transoesophageal echocardiography. In both cases, there was no evidence of endocarditis, dissection of the neck vessels or disseminated intravascular coagulation nor of associated viral or bacterial infectious complication of AIDS. Angiographic findings eliminated cerebral vascularitis. Among the perturbed haemostasis factors previously reported in HIV+ patients, we observed free proteins S deficiency (68 and 43%) and heparin cofactor II deficiency (54 and 40%). Serum albumin was 33 and 32 g/l respectively. Outcome was favourable in both cases with anticoagulant therapy. These coagulation anomalies would not appear sufficient to explain cerebral infarction. Other mechanisms including immune complexed deposition, direct HIV toxicity for endothelial cells or the effect of cytokines on smooth muscles fibres and fibroblasts are probably more important causal factors. PMID:7638144

  5. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

    PubMed

    Conte, Antonio Hernandez; Kittleson, Michelle M; Dilibero, Deanna; Hardy, W David; Kobashigawa, Jon A; Esmailian, Fardad

    2016-02-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

  6. Eosinophilia in Patients Infected with Human Immunodeficiency Virus

    PubMed Central

    Chou, Andrew; Serpa, Jose A.

    2015-01-01

    Eosinophilia is not uncommonly encountered in patients infected with human immunodeficiency virus (HIV); particularly at initiation of care or among those with advanced disease. The clinical manifestation most commonly associated with eosinophilia in this patient population is skin rash. Management of these patients is challenging due to a paucity of data evaluating diagnostic testing and therapeutic strategies. Patients born in or with significant travel to parasite-endemic countries are more likely to have tissue-invasive helminthes, such as Strongyloides or Schistosoma. Patients without such risk factors are unlikely to have parasitic infections and frequently will have self-resolution of eosinophilia. When a detailed history, physical exam and diagnostic work-up is unrevealing, we sometimes consider empirical therapy with ivermectin. Praziquantel may also be considered for those at risk for schistosomiasis. PMID:26126686

  7. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  8. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

    PubMed

    Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

    2016-03-01

    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression. PMID:26962942

  9. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

    PubMed

    Monaco, Cynthia L; Gootenberg, David B; Zhao, Guoyan; Handley, Scott A; Ghebremichael, Musie S; Lim, Efrem S; Lankowski, Alex; Baldridge, Megan T; Wilen, Craig B; Flagg, Meaghan; Norman, Jason M; Keller, Brian C; Luévano, Jesús Mario; Wang, David; Boum, Yap; Martin, Jeffrey N; Hunt, Peter W; Bangsberg, David R; Siedner, Mark J; Kwon, Douglas S; Virgin, Herbert W

    2016-03-01

    Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.

  10. Neuromuscular complications of human immunodeficiency virus infection and antiretroviral therapy.

    PubMed Central

    Miller, R G

    1994-01-01

    At least 4 distinct peripheral neuropathy syndromes occur in patients infected with the human immunodeficiency virus. The most common, painful sensory neuropathy, may be related to the viral infection or may be medication induced and is treated symptomatically. The other 3, chronic inflammatory demyelinating polyradiculoneuropathy, mononeuropathy multiplex (some patients), and the progressive polyradiculopathies related to the acquired immunodeficiency syndrome, may all respond to appropriate therapy. Both inflammatory myopathy and zidovudine myopathy also abate with early diagnosis and treatment. PMID:8048229

  11. Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3'-long terminal repeat transgene

    PubMed Central

    1994-01-01

    We have generated several transgenic mouse strains carrying a human immunodeficiency virus 1 (HIV-1) NEF/3' long terminal repeat (LTR) transgene under control of a T cell-specific promoter-enhancer element, showing a depletion of CD4+ T cells in the thymus and periphery. The immunological functions of the line with the most dramatic changes in lymphocyte populations, B6/338L, were analyzed in greater detail. The presence of the transgene in the heterozygous animal is associated with a dominant severe immunodeficiency. Older animals develop lymph- adenopathy and splenomegaly. CD4+CD8+ and CD4+CD8- single positive thymocytes already are depleted in these mice at the earliest stages in ontogeny, and peripheral T cells are reduced in frequency and present cell surface marker expression, which is characteristic for memory and activated T cells. The immunological response of B6/338L mice to several viral infections is also greatly impaired. Thus, the HIV-1 NEF/3' LTR as transgene in T cells can cause immunodeficiency and disease with striking similarities to a known retrovirus-induced immunodeficiency called murine AIDS (H. C. Morse III, S. K. Chattopadhyay, M. Makino, T. N. Frederickson, A. W. Hugin, and J. W. Hartley. 1992. AIDS. 6:607). PMID:8113676

  12. Health Administrator Perspectives on Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Prevention and Services at Historically Black Colleges and Universities

    ERIC Educational Resources Information Center

    Warren-Jeanpiere, Lari; Jones, Sandra; Sutton, Madeline Y.

    2011-01-01

    Objective: Due to the disproportionate impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) among African American young adults, the authors explored (1) number of historically black college and university (HBCU) campuses with existing HIV prevention policies and services and (2) perceived barriers for implementing…

  13. Brazilian response to the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic among injection drug users.

    PubMed

    Mesquita, Fábio; Doneda, Denise; Gandolfi, Denise; Nemes, Maria Inês Battistella; Andrade, Tarcísio; Bueno, Regina; Piconez e Trigueiros, Daniela

    2003-12-15

    The Brazilian response to the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic is being observed all over the world because of its success. Understanding the role of injection drug users (IDUs) in the epidemic and the political response thereto is a key factor in the control of the epidemic in Brazil. This paper summarizes some of the most important analyses of the Brazilian response to the HIV/AIDS epidemic among and from IDUs. Key elements of the response include the support of the Brazilian Universal Public Health System, the provision of universal access to highly active antiretroviral therapy, and the creation of harm reduction projects that are politically and financially supported by the federal government. The response among and from IDUs is a key element in overall control of the HIV/AIDS epidemic. The response to the epidemic among and from IDUs has been headed in the correct direction since its beginning and is now being intensively expanded.

  14. ACOG Committee Opinion No. 536: Human immunodeficiency virus and acquired immunodeficiency syndrome and women of color.

    PubMed

    2012-09-01

    In the United States, most new cases of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) occur among women of color (primarily African American and Hispanic women). Most women of color acquire the disease from heterosexual contact, often from a partner who has undisclosed risk factors for HIV infection. Safe sex practices, especially consistent condom use, must be emphasized for all women, including women of color. A combination of testing, education, and brief behavioral interventions can help reduce the rate of HIV infection and its complications among women of color. In addition,biomedical interventions such as early treatment of patients infected with HIV and pre-exposure antiretroviral prophylaxis of high-risk individuals offer promise for future reductions in infections.

  15. Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

    PubMed

    García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

    2015-05-01

    Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

  16. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda.

    PubMed

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  17. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.

    ERIC Educational Resources Information Center

    Fauci, Anthony S.

    1988-01-01

    Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

  18. Human Immunodeficiency Virus Associated Sporadic Nonfamilial Porphyria Cutanea Tarda

    PubMed Central

    Guha, Sibashish Kamal; Bandyopadhyay, Debabrata; Saha, Abanti; Lal, Niharika Ranjan

    2016-01-01

    Porphyria cutanea tarda (PCT), a relatively uncommon metabolic disease, is the most common cutaneous porphyria. Here, we present the case of a patient diagnosed with sporadic, nonfamilial PCT that presented with classical cutaneous findings and multiple risk factors, including alcohol abuse, human immunodeficiency virus/AIDS, that have been strongly associated with the sporadic form of PCT. PMID:27293254

  19. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke

    PubMed Central

    Piggott, Damani A.; Carroll, Karen C.; Lim, Michael; Melia, Michael T.

    2016-01-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  20. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. PMID:25577549

  1. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.

  2. Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus

    PubMed Central

    Chow, Dominic; Nakamoto, Beau K.; Sullivan, Katherine; Sletten, David M.; Fujii, Satomi; Umekawa, Sari; Kocher, Morgan; Kallianpur, Kalpana J.; Shikuma, Cecilia M.; Low, Phillip

    2015-01-01

    This retrospective study evaluated the frequencies of symptoms associated with autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients on stable combined antiretroviral therapy. Patients infected with HIV reported higher frequencies of dysautonomia symptoms compared with HIV-negative patients, particularly in the autonomic domains related to urinary, sleep, gastroparesis, secretomotor, pupillomotor, and male sexual dysfunction. PMID:26269797

  3. The Presidential Commission on the Human Immunodeficiency Virus Epidemic Report.

    ERIC Educational Resources Information Center

    Presidential Commission on the Human Immunodeficiency Virus Epidemic, Washington, DC.

    This document presents findings of the Presidential Commission on the Human Immunodeficiency Virus (HIV) epidemic. The executive summary lists 20 major findings and recommendations which together comprise a comprehensive national strategy for managing the HIV epidemic. The commission recommends: (1) replacement of the obsolete term "AIDS"…

  4. Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke.

    PubMed

    Piggott, Damani A; Carroll, Karen C; Lim, Michael; Melia, Michael T

    2016-04-01

    Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176

  5. Hemophagocytic Lymphohistiocytosis Secondary to Human Immunodeficiency Virus-Associated Histoplasmosis

    PubMed Central

    Castelli, Anthony A.; Rosenthal, David G.; Bender Ignacio, Rachel; Chu, Helen Y.

    2015-01-01

    Hemophagocytic lymphohistiocytosis (HLH) in immunocompromised hosts is a fulminant syndrome of immune activation with high rates of mortality that may be triggered by infections or immunodeficiency. Rapid diagnosis and treatment of the underlying disorder is necessary to prevent progression to multiorgan failure and death. We report a case of HLH in a patient with human immunodeficiency virus, disseminated histoplasmosis, Mycobacterium avium complex, and Escherichia coli bacteremia. We discuss management of acutely ill patients with HLH and treatment of the underlying infection versus initiation of HLH-specific chemotherapy. PMID:26566535

  6. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

    PubMed

    Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

    2016-06-01

    Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

  7. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  8. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  9. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  10. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  11. 21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Disease Agents § 610.46 Human immunodeficiency virus (HIV) “lookback” requirements. (a) If you are an... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Human immunodeficiency virus (HIV) âlookbackâ... calendar days after a donor tests reactive for evidence of human immunodeficiency virus (HIV)...

  12. Perinatally infected adolescents living with human immunodeficiency virus (perinatally human immunodeficiency virus)

    PubMed Central

    Cruz, Maria Leticia S; Cardoso, Claudete A

    2015-01-01

    The availability of highly potent antiretroviral treatment during the last decades has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents (PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubMed, located using the keywords “perinatally HIV-infected” AND “adolescents”. Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: “Puberal development and sexual maturation”, “Growth in weight and height”, “Bone metabolism during adolescence”, “Metabolic complications”, “Brain development, cognition and mental health”, “Reproductive health”, “Viral drug resistance” and “Transition to adult outpatient care”. We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment. PMID:26279988

  13. Advances in human genetics

    SciTech Connect

    Harris, H.; Hirschhorn, K.

    1993-01-01

    This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.

  14. Human T Follicular Helper Cells in Primary Immunodeficiency: Quality Just as Important as Quantity.

    PubMed

    Ma, Cindy S

    2016-05-01

    T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.

  15. The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: deficits in cognitive function.

    PubMed

    Griffin, William C; Middaugh, Lawrence D; Cook, Jennifer E; Tyor, William R

    2004-04-01

    The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features.

  16. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ... (78 FR 21613), FDA published a document that announced the disease ] areas for meetings in fiscal... immunodeficiency virus (HIV) Patient-Focused Drug Development and HIV Cure Research. Patient-Focused Drug... Fee Act (PDUFA V). FDA is interested in obtaining patient input on the impact of HIV on daily...

  17. Functional role of human immunodeficiency virus type 1 vpu.

    PubMed Central

    Terwilliger, E F; Cohen, E A; Lu, Y C; Sodroski, J G; Haseltine, W A

    1989-01-01

    To investigate the role of vpu in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product of vpu. The vpu-encoded protein is shown to decrease the rate of syncytium formation and cell killing in infected CD4+ human T cells, to increase greatly the export of virus particles from infected cells, and to reduce the rate of accumulation of cell-associated viral proteins. The vpu protein complements in trans the defect in a vpu- HIV-1 provirus but does not affect the simian immunodeficiency virus, which lacks vpu. These observations suggest that vpu may contribute to the AIDS epidemic by increasing the transmission efficiency of the virus. Images PMID:2472639

  18. Sicca complex and infection with human immunodeficiency virus.

    PubMed

    Couderc, L J; D'Agay, M F; Danon, F; Harzic, M; Brocheriou, C; Clauvel, J P

    1987-05-01

    Five male patients with the persistent generalized lymphadenopathy syndrome also had a sicca complex. Salivary gland biopsy specimens showed diffuse lymphocytic infiltration of the glandular parenchyma. Serum autoantibodies and rheumatoid factor were not detected. All patients had IgG antibodies to human immunodeficiency virus and IgG to the viral capsid antigen of Epstein-Barr virus. These five patients had benign lymphocytic infiltrates in other organs (lung, liver, and kidneys). Sicca complex may be one of the various manifestations of the lymphoid hyperplasia noted in human immunodeficiency virus-infected patients. In these patients, the sicca complex showed specific features related to male predominance, lack of serum autoantibodies, and peripheral-blood T-lymphocyte subset distribution.

  19. Immunoassay for detection of antibodies to simian immunodeficiency virus and human immunodeficiency virus in serum.

    PubMed

    Otsyula, M G; Yee, J A; Suleman, M A; Marx, P A; Jennings, M B

    1996-04-01

    We developed a simple, inexpensive, rapid assay for the detection of antibodies to simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in serum. The immunoassay uses inactivated SIV and HIV-1 gp41 transmembrane recombinant protein as antigenic adsorbents on a nitrocellulose filter membrane. Diluted serum, with the addition of Protein-A-Gold, is gravity-filtered through the filter membrane, blocked, and buffer-washed. Antibodies to HIV or SIV or both in serum bind to the appropriate antigen, and the resulting antigen-antibody complex reacts with Protein-A-Gold to produce a readable pink color. Field evaluation of the test on 30 human and 70 nonhuman primate sera in Kenya and Zaire indicated that the test had at least 93 and 90% correlation with Western blot sensitivity and specificity respectively. Prior refrigeration of the test kit and incubation of sera during testing were not required. This result indicates that the test may be a rapid, economical, and simple test for detecting HIV, SIV, or both in serum. This immunoassay can be useful for carrying out HIV and SIV serosurveys in countries with limited or no laboratory facilities. PMID:8723237

  20. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  1. From Immunodeficiency to Humanization: The Contribution of Mouse Models to Explore HTLV-1 Leukemogenesis

    PubMed Central

    Pérès, Eléonore; Bagdassarian, Eugénie; This, Sébastien; Villaudy, Julien; Rigal, Dominique; Gazzolo, Louis; Duc Dodon, Madeleine

    2015-01-01

    The first discovered human retrovirus, Human T-Lymphotropic Virus type 1 (HTLV-1), is responsible for an aggressive form of T cell leukemia/lymphoma. Mouse models recapitulating the leukemogenesis process have been helpful for understanding the mechanisms underlying the pathogenesis of this retroviral-induced disease. This review will focus on the recent advances in the generation of immunodeficient and human hemato-lymphoid system mice with a particular emphasis on the development of mouse models for HTLV-1-mediated pathogenesis, their present limitations and the challenges yet to be addressed. PMID:26690200

  2. Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome.

    PubMed

    Breen, Elizabeth Crabb

    2002-09-01

    In persons with human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS), the immune system becomes dysfunctional in many ways. There is both immunodeficiency due to the loss of CD4-positive T helper cells and hyperactivity as a result of B-cell activation. Likewise, both decreases and increases are seen in the production and/or activity of cytokines. Cytokine changes in HIV infection have been assessed by a variety of techniques, ranging from determination of cytokine gene expression at the mRNA level to secretion of cytokine proteins in vivo and in vitro. Changes in cytokine levels in HIV-infected persons can affect the function of the immune system, and have the potential to directly impact the course of HIV disease by enhancing or suppressing HIV replication. In particular, the balance between the pro-inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha, which up-regulate HIV expression, and IL-10, which can act both as an anti-inflammatory cytokine and a B-cell stimulatory factor, may play an important role in the progression to AIDS. In light of its ability to suppress the production of pro-inflammatory cytokines and, under some conditions, suppress HIV replication, increased IL-10 may be viewed as beneficial in slowing HIV disease progression. However, an association between increased IL-10 and the development of AIDS-associated B-cell lymphoma highlights the bifunctional nature of IL-10 as both an anti-inflammatory and B-cell-stimulatory cytokine that could have beneficial and detrimental effects on the course of HIV infection and AIDS.

  3. Recent advances in treatment of severe primary immunodeficiencies

    PubMed Central

    Gennery, Andrew

    2015-01-01

    Primary immunodeficiencies are rare, inborn errors that result in impaired, disordered or uncontrolled immune responses. Whilst symptomatic and prophylactic treatment is available, hematopoietic stem cell transplantation is an option for many diseases, leading to cure of the immunodeficiency and establishing normal physical and psychological health. Newborn screening for some diseases, whilst improving outcomes, is focusing research on safer and less toxic treatment strategies, which result in durable and sustainable immune function without adverse effects. New conditioning regimens have reduced the risk of hematopoietic stem cell transplantation, and new methods of manipulating stem cell sources should guarantee a donor for almost all patients. Whilst incremental enhancements in transplantation technique have gradually improved survival outcomes over time, some of these new applications are likely to radically alter our approach to treating primary immunodeficiencies. PMID:26918153

  4. Prevention and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome in resource-limited settings.

    PubMed Central

    Hogan, Daniel R.; Salomon, Joshua A.

    2005-01-01

    Strategies for confronting the epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have included a range of different approaches that focus on prevention and treatment. However, debate persists over what levels of emphasis are appropriate for the different components of the global response. This paper presents an overview of this debate and briefly summarizes the evidence on a range of interventions designed to prevent the spread of HIV infection, paying particular attention to voluntary counselling and testing, treatment for sexually transmitted infections and prevention of mother-to-child transmission. We also review the experience with antiretroviral therapy to date in terms of response rates and survival rates, adherence, drug resistance, behavioural change and epidemiological impact. Although various studies have identified strategies with proven effectiveness in reducing the risks of HIV infection and AIDS mortality, considerable uncertainties remain. Successful integration of treatment and prevention of HIV/AIDS will require a balanced approach and rigorous monitoring of the impact of programmes in terms of both individual and population outcomes. PMID:15744406

  5. Inflammatory joint disease and human immunodeficiency virus infection

    PubMed Central

    Forster, S M; Seifert, M H; Keat, A C; Rowe, I F; Thomas, B J; Taylor-Robinson, D; Pinching, A J; Harris, J R W

    1988-01-01

    Nine men positive for antibody to human immunodeficiency virus (HIV) who developed peripheral, non-erosive arthritis were followed up. The clinical features were compatible with reactive arthritis but were atypical in several respects: the joint symptoms were generally severe, persistent, and unresponsive to non-steroidal anti-inflammatory drugs. The onset of arthritis was associated with various infections, none of which are known to be associated with the development of reactive arthritis. HLA typing was performed for three patients, all of whom were positive for HLA-B27. HIV was isolated from the synovial fluid of one patient. No patient had AIDS before developing arthritis, but four progressed to having AIDS after a mean of 7·5 months, and two died. Arthritis resolved in only one patient. The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Synovitis in patients with severe immunodeficiency has important pathogenetic implications. PMID:3135044

  6. Thirty years of the human immunodeficiency virus epidemic and beyond

    PubMed Central

    Younai, Fariba S

    2013-01-01

    After more than 30 years of battling a global epidemic, the prospect of eliminating human immunodeficiency virus (HIV) as the most challenging infectious disease of the modern era is within our reach. Major scientific discoveries about the virus responsible for this immunodeficiency disease state, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention. Although these agents and many others still in development and testing are capable of effectively suppressing viral replication and survival, the medical management of HIV infection at the individual and the population levels remains challenging. Timely initiation of antiretroviral drugs, adherence to the appropriate therapeutic regimens, effective use of these agents in the pre and post-exposure prophylaxis contexts, treatment of comorbid conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations. PMID:24136672

  7. Idiopathic genital ulcers in women infected with human immunodeficiency virus.

    PubMed

    Anderson, J; Clark, R A; Watts, D H; Till, M; Arrastia, C; Schuman, P; Cohn, S E; Young, M; Bessen, L; Greenblatt, R; Vogler, M; Swindells, S; Boyer, P

    1996-12-01

    A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

  8. Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligodeoxynucleotides

    NASA Astrophysics Data System (ADS)

    Goodchild, John; Agrawal, Sudhir; Civeira, Maria P.; Sarin, Prem S.; Sun, Daisy; Zamecnik, Paul C.

    1988-08-01

    Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligomers complementary to sites within or near the sequence repeated at the ends of retrovirus RNA (R region) and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting virus replication was also investigated, and preliminary toxicity studies in mice show that these compounds are toxic only at high levels. The results indicate potential usefulness for these oligomers in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex either alone or in combination with other drugs.

  9. Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

    PubMed

    Rivera, J; Monteagudo, I; Lopez-Longo, J; Sanchez-Atrio, A

    1992-12-01

    We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.

  10. Plasmoblastic lymphoma associated with human immunodeficiency virus.

    PubMed

    Horváth, Emoke; Krenács, L; Bagdi, Eniko; Pávai, Z; Macarie, I; Nagy, Elod-Erno; Demian, Smaranda

    2008-01-01

    Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis.

  11. Plasmoblastic lymphoma associated with human immunodeficiency virus.

    PubMed

    Horváth, Emoke; Krenács, L; Bagdi, Eniko; Pávai, Z; Macarie, I; Nagy, Elod-Erno; Demian, Smaranda

    2008-01-01

    Plasmoblastic lymphoma (PBL) is a subtype of the diffuse large B-cell lymphoma, typically present as extranodal disease associated with human immune deficiency virus (HIV) infection. PBLs are often the initial manifestation of AIDS. Here we present a case of PBL concerning the oral cavity. A 34-year-old woman presented a tumor in the oral cavity that involved the maxilla and gingiva (confirmed by CT-scan). The gingival biopsy showed a massive infiltration by large lymphoid cells with round, vesicular nuclei, prominent nucleoli, fine chromatin and an significant amount of basophilic cytoplasm which express CD79a, CD138, cytoplasmic lambda light chain and LCA, without staining for CD20, CD38, CD3 and CTK. Serological analysis confirmed HIV positivity. PBLs lack most B-lineage markers, but many express CD79a in at least some of the cells, therefore generate difficulties in differential diagnosis. Overall assessment and correlation of the histopathological and immunohistochemical features with the clinical findings and serology investigation are the most helpful diagnostic tools and can lead to the final diagnosis. PMID:18758634

  12. Review of testing for human immunodeficiency virus.

    PubMed

    Bylund, D J; Ziegner, U H; Hooper, D G

    1992-06-01

    The performance of HIV testing requires meticulous attention to preanalytic, analytic, and postanalytic variables, especially matters of patient confidentiality. Laboratory directors must pay strict attention to quality control and quality assurance practices. Careful attention to these considerations can produce a screening program in low-prevalence populations that has an extremely low false-positive rate, with a positive predictive value of greater than 99%. Issuing a clear and concise laboratory report to the clinician is important. The Fifth Consensus Conference on Testing for Human Retroviruses of the Association of State and Territorial Public Health Laboratory Directors, March 1990, has recommended that ELISA be reported as reactive or nonreactive; IFA as reactive, nonreactive, or nonspecific, and WB as reactive, nonreactive, or indeterminate. It is recommended that the terms positive and negative be reserved for the summary interpretation given at the conclusion of the HIV-1 antibody testing algorithm. The testing algorithm used for HIV antibody screening at Scripps Clinic is shown in Figure 3. Other algorithms for complete testing on a single sample only or on two separate samples are reported. We agree with others that the patient should not be counseled for infection with HIV until a reactive confirmatory test(s) establishes a positive diagnosis. Certain special situations in diagnostic testing deserve comment. Establishing the diagnosis of HIV infection can be difficult in seronegative persons with acute infection. Polymerase chain reaction, viral culture or antigen detection may be useful tests in this situation. However, careful interpretation of test results and close correlation with patient risk factors are important to establish the proper diagnosis. Reports of seronegative persons, some remaining seronegative over a protracted time, have raised concerns over the transfusional risk of HIV infection. Blood donor screening programs are using

  13. Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia.

    PubMed

    Henry, M J; Stanley, M W; Cruikshank, S; Carson, L

    1989-02-01

    Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.

  14. Neuromyelitis optica in patients with coexisting human immunodeficiency virus infections.

    PubMed

    Feyissa, Anteneh M; Singh, Parbhdeep; Smith, Robert G

    2013-09-01

    Two patients with known human immunodeficiency virus (HIV) infections and receiving antiretroviral treatment developed neuromyelitis optica (Devic's disease). One patient tested positive for serum aquaporin-4 immunoglobulin G antibodies. Both patients were treated with high dose pulsed intravenous methylprednisolone followed by standard sessions of plasma exchange both at the onset attack and during disease relapses. For maintenance therapy, one patient received rituximab infusions and the second patient received mycophenolate mofetil orally. Despite treatment, both patients are currently wheelchair-bound due to severe paraparesis. Neuromyelitis optica can occur in the course of HIV infection and poses an ongoing therapeutic challenge.

  15. The human immunodeficiency virus reduces network capacity: acoustic noise effect

    PubMed Central

    Tomasi, Dardo; Chang, Linda; de Castro Caparelli, Elisabeth; Telang, Frank; Ernst, Thomas

    2008-01-01

    Increased acoustic noise (AN) during working memory (WM) leads to increased brain activation in healthy individuals, and may have greater impact in human immunodeficiency virus (HIV) patients. Compared to controls, HIV subjects showed reduced AN-activation and lower neuronal marker N-acetylaspartate in prefrontal and parietal cortices. Competing use of the WM network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients. These findings suggest reduced reserve capacity of the WM network in HIV patients and additional stress (e.g. AN) might exhaust the impaired network for more demanding tasks. PMID:16437575

  16. The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis

    NASA Astrophysics Data System (ADS)

    Fauci, Anthony S.

    1988-02-01

    Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.

  17. Management of dyslipidemia in patients with human immunodeficiency virus.

    PubMed

    Shalit, Peter

    2014-01-01

    Dyslipidemias are more common in the patient population with human immunodeficiency virus (HIV). Combination antiretroviral therapy (ART) has dramatically reduced HIV-associated morbidity and mortality and has transformed HIV disease into a chronic, manageable condition. As a result, non-AIDS-related illnesses, including cardiovascular diseases, are now the leading causes of death in the HIV-infected population. Optimizing fasting lipid parameters plays an important role in reducing cardiovascular risk in this population. This review focuses on the management of dyslipidemia in HIV-infected individuals treated with combination ART.

  18. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    PubMed

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  19. Seroprevalence of human herpesvirus 8 in human immunodeficiency virus 1-positive and human immunodeficiency virus 1-negative populations in Japan.

    PubMed

    Fujii, T; Taguchi, H; Katano, H; Mori, S; Nakamura, T; Nojiri, N; Nakajima, K; Tadokoro, K; Juji, T; Iwamoto, A

    1999-02-01

    To determine the seroprevalence of human herpesvirus 8 (HHV8) among human immunodeficiency virus 1 (HIV-1)-positive (HIV-1+) and HIV-1-negative (HIV-1-) populations in Japan, 276 HIV-1+ patients and 1,000 HIV-1- blood donors were enrolled in this study. Antibodies against HHV8 latency-associated nuclear antigen (LANA) were examined through indirect immunofluorescent assay by using a B-cell line that was infected latently with HHV8 (body cavity-based lymphoma 1). An HHV8- and Epstein-Barr virus-negative B-cell line (Ramos) was used as a control. Thirty-two seropositive cases against LANA (anti-LANA+) were identified among the 276 HIV-1+ patients who were studied. Five cases were foreigners living in Japan. The risk factor of all 27 Japanese cases was unprotected sexual intercourse, and the great majority of these cases (23 in 27; 85%) reported homosexual/bisexual behavior. Anti-LANA+ status correlated with the presence of sexually transmitted diseases, such as amoeba and HBV infection, further suggesting male homosexual behavior as the main route of HHV8 transmission in Japan. Only two LANA+ cases were identified among 1,000 HIV- blood donors in Japan; thus, seroprevalence of HHV8 identified by LANA was estimated to be 0.2% among HIV-1- populations in this country. PMID:9892401

  20. Cardiac dysfunction in patients seropositive for the human immunodeficiency virus.

    PubMed Central

    Johnson, J. E.; Slife, D. M.; Anders, G. T.; Bailey, S. R.; Blanton, H. M.; McAllister, C. K.; Latham, R. D.

    1991-01-01

    To confirm the presence of cardiac dysfunction in a group of patients seropositive for the human immunodeficiency virus with either dyspnea on exertion or a reduced anaerobic threshold, 9 patients with no history of opportunistic infection underwent exercise right-sided heart catheterization. When compared with 13 control patients previously exercised in the same manner, the patients showed elevated exercise pulmonary capillary wedge pressure (14.6 +/- 3.3 mm of mercury versus 9.9 +/- 3.3 mm of mercury; P less than .005) and right atrial pressure (10.1 +/- 2.1 mm of mercury versus 4.7 +/- 3.2 mm of mercury; P less than .001) at a similar exercise oxygen consumption and cardiac index. Of the 9 patients, 8 had at least 1 catheterization value outside the 95% confidence limits for the control group and 4 patients had multiple abnormalities. Values for blood CD4 lymphocytes were 0.2 x 10(9) per liter or more for 7 of the 9. One patient underwent endomyocardial biopsy with findings consistent with a cardiomyopathy. We conclude that cardiac disease may occur at any immunologic stage of human immunodeficiency virus infection. These observations suggest an effect of this disease on the heart. Images PMID:1771874

  1. Disinfection of Goldmann tonometers against human immunodeficiency virus type 1.

    PubMed

    Pepose, J S; Linette, G; Lee, S F; MacRae, S

    1989-07-01

    Goldmann tonometer tips were inoculated with 5 X 10(5) IU of cell-free or cell-associated human immunodeficiency virus type 1 (lymphadenopathy virus type 1 isolate) or 10(4) plaque-forming units of herpes simplex virus type 1 (McKrae strain) or type 2 (Hicks strain). In an effort to mimic a "worst case" clinical scenario, each respective virus was allowed to air dry on the tonometer tip for 10 minutes. Inoculated tonometers were then (1) not treated, (2) wiped with a disposable (Kim-wipe) tissue or sterile gauze; (3) wiped with sterile gauze soaked with 3% hydrogen peroxide; or (4) wiped with a 70% isopropyl alcohol swab. The hydrogen peroxide treatment and the alcohol wipes both completely disinfected the tonometer tips for human immunodeficiency virus type 1 and herpes simplex virus types 1 and 2, whereas wiping with a sterile gauze or tissue was not effective. Wiping the Goldmann tonometer tip with an isopropyl alcohol swab and then allowing the alcohol to evaporate provides a ready and efficient means of inactivating these three enveloped viruses.

  2. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    NASA Astrophysics Data System (ADS)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  3. Human immunodeficiency virus type 1 infection of neural xenografts.

    PubMed Central

    Cvetkovich, T A; Lazar, E; Blumberg, B M; Saito, Y; Eskin, T A; Reichman, R; Baram, D A; del Cerro, C; Gendelman, H E; del Cerro, M

    1992-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain. Images PMID:1594627

  4. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  5. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  6. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  7. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  8. 21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false In vitro human immunodeficiency virus (HIV) drug... Serological Reagents § 866.3950 In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay is a device that consists of nucleic acid...

  9. Oral lesions in infection with human immunodeficiency virus.

    PubMed Central

    Coogan, Maeve M.; Greenspan, John; Challacombe, Stephen J.

    2005-01-01

    This paper discusses the importance of oral lesions as indicators of infection with human immunodeficiency virus (HIV) and as predictors of progression of HIV disease to acquired immunodeficiency syndrome (AIDS). Oral manifestations are among the earliest and most important indicators of infection with HIV. Seven cardinal lesions, oral candidiasis, hairy leukoplakia, Kaposi sarcoma, linear gingival erythema, necrotizing ulcerative gingivitis, necrotizing ulcerative periodontitis and non-Hodgkin lymphoma, which are strongly associated with HIV infection, have been identified and internationally calibrated, and are seen in both developed and developing countries. They may provide a strong indication of HIV infection and be present in the majority of HIV-infected people. Antiretroviral therapy may affect the prevalence of HIV-related lesions. The presence of oral lesions can have a significant impact on health-related quality of life. Oral health is strongly associated with physical and mental health and there are significant increases in oral health needs in people with HIV infection, especially in children, and in adults particularly in relation to periodontal diseases. International collaboration is needed to ensure that oral aspects of HIV disease are taken into account in medical programmes and to integrate oral health care with the general care of the patient. It is important that all health care workers receive education and training on the relevance of oral health needs and the use of oral lesions as surrogate markers in HIV infection. PMID:16211162

  10. Follicular dendritic cells and human immunodeficiency virus infectivity

    NASA Astrophysics Data System (ADS)

    Heath, Sonya L.; Tew, J. Grant; Tew, John G.; Szakal, Andras K.; Burton, Gregory F.

    1995-10-01

    LARGE amounts of human immunodeficiency virus (HIV) localize on follicular dendritic cells (FDC) in the follicles of secondary lymphoid tissues following viral infection1,2. During clinical latency, active viral infection occurs primarily at these sites3,4. As HIV on FDC is in the form of immune complexes5, some of which may be formed with neutralizing antibody, we investigated whether HIV on FDC is infectious. We report here that HIV on FDC is highly infectious. Furthermore, FDC can convert neutralized HIV into an infectious form even in the presence of a vast excess of neutralizing antibody. Thus FDC may provide a mechanism whereby HIV infection can continue in the presence of neutralizing antibody.

  11. Multivariate analysis of human immunodeficiency virus type 1 neutralization data.

    PubMed Central

    Nyambi, P N; Nkengasong, J; Lewi, P; Andries, K; Janssens, W; Fransen, K; Heyndrickx, L; Piot, P; van der Groen, G

    1996-01-01

    We report on the use of spectral map analysis of the inter- and intraclade neutralization data of 14 sera of human immunodeficiency virus type 1 (HIV-1)-infected individuals and 16 primary isolates, representing genetic clades A to H in group M and group O. This multivariate analysis has been used previously to study the interaction between drugs and receptors and between viruses and antiviral compounds. The analysis reveals the existence of neutralization clusters, not correlated with the known genetic clades. The structural factors that have been identified may correlate with the most important neutralization epitopes. Three key primary HIV-1 isolates, which allow discrimination of sera that are likely or unlikely to neutralize primary isolates from most of the genetic clades, were identified. Our method of analysis will facilitate the evaluation as well as the design of suitable HIV-1 vaccines, which induce high-titer interclade cross-neutralizing antibodies. PMID:8709250

  12. Human immunodeficiency virus antibody test and seroprevalence in psychiatric patients.

    PubMed

    Naber, D; Pajonk, F G; Perro, C; Löhmer, B

    1994-05-01

    Psychiatric inpatients are at risk for human immunodeficiency virus (HIV) infection. Investigations in the United States revealed seroprevalence rates of 5.5-8.9%. Therefore, inclusion of HIV antibody testing in routine laboratory screening is sometimes suggested. To investigate this issue for inpatients in the Department of Psychiatry, University of Munich, the incidence, reason for HIV testing and results were analyzed. Of 12,603 patients, hospitalized from 1985 to 1993, 4.9% (623 patients, 265 in risk groups) underwent the HIV test after informed consent. Thirty patients (4.8% of those tested) were found to be positive, but only in 5 cases (all of risk groups) was infection newly detected. Data indicate that, in psychiatry, HIV testing is reasonable only in patients in risk groups or if clinical variables suggest HIV infection.

  13. Human immunodeficiency virus and migrant labor in South Africa.

    PubMed

    Jochelson, K; Mothibeli, M; Leger, J P

    1991-01-01

    The authors investigate the impact of the migrant labor system on heterosexual relationships on South African mines and assess the implications for the future transmission of human immunodeficiency virus (HIV) infection. The migrant labor system has created a market for prostitution in mining towns and geographic networks of relationships within and between urban and rural communities. A section of the migrant workforce and a group of women dependent on prostitution for economic support appear especially vulnerable to contracting HIV infection since they are involved in multiple sexual encounters with different, changing partners, usually without condom protection. Furthermore, sexually transmitted disease morbidity is extensive in the general and mineworker populations. Historically, migration facilitated the transmission of sexually transmitted diseases and may act similarly for HIV. Problems of combating the HIV epidemic in South Africa are discussed. PMID:2004869

  14. Seroprevalence of human immunodeficiency virus among inpatient pretrial detainees.

    PubMed

    Schwartz-Watts, D; Montgomery, L D; Morgan, D W

    1995-01-01

    Medical records of inpatients discharged from a forensic unit in Columbia, South Carolina, from January 1991 to December 1991 were reviewed to determine the incidence of human immunodeficiency virus (HIV) seropositivity. Results were linked to age, gender, ethnicity, history of intravenous drug use, and Axis I diagnoses. HIV status was obtained for 74 percent of patients 18 to 55 years of age. The incidence of HIV seropositivity among patients tested was 5.5 percent, which is greater than 40 times the incidence for the general population in South Carolina. Intravenous drug use was reported for 33 percent of the seropositive males. We conclude that inpatient pretrial detainees are at increased risk for HIV infection. HIV testing should be mandated at all facilities housing detainees. Further studies are needed to determine any factors about these patients that can be linked to seropositivity.

  15. Human immunodeficiency virus and migrant labor in South Africa.

    PubMed

    Jochelson, K; Mothibeli, M; Leger, J P

    1991-01-01

    The authors investigate the impact of the migrant labor system on heterosexual relationships on South African mines and assess the implications for the future transmission of human immunodeficiency virus (HIV) infection. The migrant labor system has created a market for prostitution in mining towns and geographic networks of relationships within and between urban and rural communities. A section of the migrant workforce and a group of women dependent on prostitution for economic support appear especially vulnerable to contracting HIV infection since they are involved in multiple sexual encounters with different, changing partners, usually without condom protection. Furthermore, sexually transmitted disease morbidity is extensive in the general and mineworker populations. Historically, migration facilitated the transmission of sexually transmitted diseases and may act similarly for HIV. Problems of combating the HIV epidemic in South Africa are discussed.

  16. Glanzmann Thrombasthenia Associated with Human Immunodeficiency Virus-Positive Patient

    PubMed Central

    Manne, Rakesh Kumar; Natarajan, Kannan; Patil, Rajendra; Prathi, Venkata Sarath; Beeraka, Swapna Sridevi; Kolaparthi, Venkata Suneel Kumar

    2014-01-01

    Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect characterized by normal platelet count, prolonged bleeding time and abnormal clot retraction. This disease typically presents in infancy or early childhood and has proven to have very good prognosis. In this case study, a 22-year-old GT patient who also developed human immunodeficiency virus (HIV) infection after sometime is reported. The patient showed oral manifestations of gingival hyperplasia and petechial lesions. Unfortunately the detection of both thrombasthenia and HIV were done at considerably late stages which contributed to a poor prognosis. The patient died of cardiopulmonary arrest secondary to HIV, thrombasthenia and thrombocytopenia. The importance of early detection, supportive care and communication between the general and oral physician in management of the GT is also discussed. PMID:24829739

  17. Primary pulmonary hypertension associated with human immunodeficiency virus infection.

    PubMed Central

    Golpe, R.; Fernandez-Infante, B.; Fernandez-Rozas, S.

    1998-01-01

    Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking. PMID:9799910

  18. Human immunodeficiency virus antibody test and seroprevalence in psychiatric patients.

    PubMed

    Naber, D; Pajonk, F G; Perro, C; Löhmer, B

    1994-05-01

    Psychiatric inpatients are at risk for human immunodeficiency virus (HIV) infection. Investigations in the United States revealed seroprevalence rates of 5.5-8.9%. Therefore, inclusion of HIV antibody testing in routine laboratory screening is sometimes suggested. To investigate this issue for inpatients in the Department of Psychiatry, University of Munich, the incidence, reason for HIV testing and results were analyzed. Of 12,603 patients, hospitalized from 1985 to 1993, 4.9% (623 patients, 265 in risk groups) underwent the HIV test after informed consent. Thirty patients (4.8% of those tested) were found to be positive, but only in 5 cases (all of risk groups) was infection newly detected. Data indicate that, in psychiatry, HIV testing is reasonable only in patients in risk groups or if clinical variables suggest HIV infection. PMID:8067276

  19. Inactivation of human immunodeficiency virus type 1 by alcohols.

    PubMed

    van Bueren, J; Larkin, D P; Simpson, R A

    1994-10-01

    Alcohols are commonly used as disinfectants for skin, surfaces and immersion of some medical instruments. Measurements of the activity of alcohols against human immunodeficiency virus type 1 (HIV-1) must take account of the compatibility of neutralizers used to stop the disinfectant reaction, and of toxicity to the cell line used to detect residual virus. We have developed protocols to measure the efficacy of alcohols against HIV in suspension and dried onto surfaces in the presence of high and low protein concentrations. High titres of HIV in suspension were rapidly inactivated by 70% ethanol, independent of the protein load. When virus was dried onto a glass surface, the rate of inactivation decreased when high levels of protein were present. Due to its rapid evaporation, a spray or a wipe with alcohol cannot be guaranteed to disinfect a surface contaminated with blood or other body fluids without preliminary cleaning.

  20. Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus

    PubMed Central

    Razonable, Raymund R.

    2011-01-01

    Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M2 protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti–human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M2 inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects. PMID

  1. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations AGENCY: Centers for Disease Control and... funding available to make awards under the Centers for Disease Control and Prevention Funding...

  2. Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

    PubMed

    Sharma, Prem L; Nurpeisov, Viktoria; Hernandez-Santiago, Brenda; Beltran, Thierry; Schinazi, Raymond F

    2004-01-01

    The development of novel compounds that can effectively inhibit both wild type and the most consensus resistant strains of human immunodeficiency virus type 1 (HIV-1) is the primary focus in HIV disease management. Combination therapy, comprising at least three classes of drugs, has become the standard of care for acquired immunodeficiency syndrome (AIDS) or HIV-infected individuals. The drug cocktail can comprise all three classes of HIV inhibitors, including nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). Due to their competitive mode of inhibition and requirement for metabolic activation, almost all NRTI drugs lack the virological potency of NNRTI or PI drugs. However, data from clinical trials indicate that sustained viral suppression could not be achieved with NRTI, NNRTI or PIs alone. Therefore, the NRTIs will remain essential components of highly active antiretroviral therapy (HAART) for the foreseeable future, because they enhance the virological potency of the regimen, they do not bind excessively to protein and most regimens are small pills/tablets given once a day. It has become apparent in recent years that the prolonged use of certain NRTIs exhibits adverse events as a class, limiting the length of time for which they can be safely used. Of major clinical concern is their association with the potentially fatal lactic acidaemia and hepatic steatosis. These class events, as well as individual drug effects, such as peripheral neuropathy, are linked to delayed mitochondrial destruction. In addition to toxicity, the development of resistance-conferring mutations against exposure to nucleoside analogs currently in use influences long-term therapeutic benefits. Of critical importance for the evaluation of new NRTIs are recent studies showing that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key

  3. Quantitation of human immunodeficiency virus type 1 infection kinetics.

    PubMed Central

    Dimitrov, D S; Willey, R L; Sato, H; Chang, L J; Blumenthal, R; Martin, M A

    1993-01-01

    Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle. PMID:8445728

  4. Inhibition of productive human immunodeficiency virus-1 infection by cobalamins.

    PubMed

    Weinberg, J B; Sauls, D L; Misukonis, M A; Shugars, D C

    1995-08-15

    Various cobalamins act as important enzyme cofactors and modulate cellular function. We investigated cobalamins for their abilities to modify productive human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro. We show that hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), and adenosylcobalamin Ado-Cbl (Ado-Cbl) inhibit HIV-1 infection of normal human blood monocytes and lymphocytes. The inhibitory effects were noted when analyzing the monocytotropic strains HIV-1-BaL and HIV-1-ADA as well as the lymphocytotropic strain HIV-1-LAI. Cobalamins did not modify binding of gp120 to CD4 or block early steps in viral life cycle, inhibit reverse transcriptase, inhibit induction of HIV-1 expression from cells with established or latent infection, or modify monocyte interferon-alpha production. Because of the ability to achieve high blood and tissue levels of cobalamins in vivo and the general lack of toxicity, cobalamins should be considered as potentially useful agents for the treatment of HIV-1 infection. PMID:7632933

  5. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease

    PubMed Central

    Flores, Sonia C.; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease. PMID:23662195

  6. Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation.

    PubMed Central

    Duesberg, P H

    1989-01-01

    AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch's postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch's postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive "AIDS test." (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS

  7. Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

    PubMed Central

    Morgello, S.

    1992-01-01

    The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems. Images Figure 1 Figure 2 PMID:1323221

  8. Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.

    PubMed Central

    Moore, P S; Jones, C J; Mahmood, N; Evans, I G; Goff, M; Cooper, R; Hay, A J

    1995-01-01

    Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree. PMID:7536411

  9. Phylogenetic Analysis of Human Immunodeficiency Virus Type 2 Group B

    PubMed Central

    Cella, Eleonora; Lo Presti, Alessandra; Giovanetti, Marta; Veo, Carla; Lai, Alessia; Dicuonzo, Giordano; Angeletti, Silvia; Ciotti, Marco; Zehender, Gianguglielmo; Ciccozzi, Massimo

    2016-01-01

    Context: Human immunodeficiency virus type 2 (HIV-2) infections are mainly restricted to West Africa; however, in the recent years, the prevalence of HIV-2 is a growing concern in some European countries and the Southwestern region of India. Despite the presence of different HIV-2 groups, only A and B Groups have established human-to-human transmission chains. Aims: This work aimed to evaluate the phylogeographic inference of HIV-2 Group B worldwide to estimate their data of origin and the population dynamics. Materials and Methods: The evolutionary rates, the demographic history for HIV-2 Group B dataset, and the phylogeographic analysis were estimated using a Bayesian approach. The viral gene flow analysis was used to count viral gene out/in flow among different locations. Results: The root of the Bayesian maximum clade credibility tree of HIV-2 Group B dated back to 1957. The demographic history of HIV-2 Group B showed that the epidemic remained constant up to 1970 when started an exponential growth. From 1985 to early 2000s, the epidemic reached a plateau, and then it was characterized by two bottlenecks and a new plateau at the end of 2000s. Phylogeographic reconstruction showed that the most probable location for the root of the tree was Ghana. Regarding the viral gene flow of HIV-2 Group B, the only observed viral gene flow was from Africa to France, Belgium, and Luxembourg. Conclusions: The study gives insights into the origin, history, and phylogeography of HIV-2 Group B epidemic. The growing number of infections of HIV-2 worldwide indicates the need for strengthening surveillance. PMID:27621561

  10. Phylogenetic Analysis of Human Immunodeficiency Virus Type 2 Group B

    PubMed Central

    Cella, Eleonora; Lo Presti, Alessandra; Giovanetti, Marta; Veo, Carla; Lai, Alessia; Dicuonzo, Giordano; Angeletti, Silvia; Ciotti, Marco; Zehender, Gianguglielmo; Ciccozzi, Massimo

    2016-01-01

    Context: Human immunodeficiency virus type 2 (HIV-2) infections are mainly restricted to West Africa; however, in the recent years, the prevalence of HIV-2 is a growing concern in some European countries and the Southwestern region of India. Despite the presence of different HIV-2 groups, only A and B Groups have established human-to-human transmission chains. Aims: This work aimed to evaluate the phylogeographic inference of HIV-2 Group B worldwide to estimate their data of origin and the population dynamics. Materials and Methods: The evolutionary rates, the demographic history for HIV-2 Group B dataset, and the phylogeographic analysis were estimated using a Bayesian approach. The viral gene flow analysis was used to count viral gene out/in flow among different locations. Results: The root of the Bayesian maximum clade credibility tree of HIV-2 Group B dated back to 1957. The demographic history of HIV-2 Group B showed that the epidemic remained constant up to 1970 when started an exponential growth. From 1985 to early 2000s, the epidemic reached a plateau, and then it was characterized by two bottlenecks and a new plateau at the end of 2000s. Phylogeographic reconstruction showed that the most probable location for the root of the tree was Ghana. Regarding the viral gene flow of HIV-2 Group B, the only observed viral gene flow was from Africa to France, Belgium, and Luxembourg. Conclusions: The study gives insights into the origin, history, and phylogeography of HIV-2 Group B epidemic. The growing number of infections of HIV-2 worldwide indicates the need for strengthening surveillance.

  11. [Antiretroviral therapy in human immunodeficiency virus infection: an update].

    PubMed

    Chaix, F; Goujard, C

    2009-06-01

    Since the onset of the human immunodeficiency virus (HIV) epidemic, the care of infected patients improved dramatically. Whereas the disease was almost always fatal, the development of new drugs and new therapeutic strategies now allow a prolonged survival. However, the complexity of patient care is increasing and physicians face new clinical events and treatment toxicities. Recent molecules and follow-up according to the recent French recommendations will be presented here. The objectives of the treatment is to decrease mortality and morbidity of the HIV infection, by restoring near normal CD4+ T cell counts and qualitative T CD4+ responses, associated with a sustained reduction in viral replication. This objective must be reached by minimizing toxicity of antiretroviral drugs. Newly developed drugs that are better-tolerated and new therapeutic classes should improve outcome at all stages of HIV infection. Whereas viral eradication remains unrealistic and protective vaccines will not be soon available, direct consequences of long term HIV infection and issues related to an ageing HIV infected population raise up new research topics. Prevention of new infections, improvement in the precocity of care by a better-targeted screening and assessment of therapy before an established immune deficiency appear as the main priorities for the coming years. PMID:19237230

  12. Tuberculous meningitis in patients infected with human immunodeficiency virus.

    PubMed

    Garg, Ravindra Kumar; Sinha, Manish Kumar

    2011-01-01

    Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory, radiographic findings, or the response to therapy. Still, some differences have been noted. For example, the histopathological examination of exudates in HIV-infected patients shows fewer lymphocytes, epithelioid cells, and Langhan's type of giant cells. Larger numbers of acid-fast bacilli may be seen in the cerebral parenchyma and meninges. The chest radiograph is abnormal in up to 46% of patients with tuberculous meningitis. Tuberculous meningitis is likely to present with cerebral infarcts and mass lesions. Cryptococcal meningitis is important in differential diagnosis. The recommended duration of treatment in HIV-infected patients is 9-12 months. The benefit of adjunctive corticosteroids is uncertain. Antiretroviral therapy and antituberculosis treatment should be initiated at the same time, regardless of CD4 cell counts. Tuberculous meningitis may be a manifestation of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. Some studies have demonstrated a significant impact of HIV co-infection on mortality from tuberculous meningitis. HIV-infected patients with multidrug-resistant tuberculous meningitis have significantly higher mortality. The best way to prevent HIV-associated tuberculous meningitis is to diagnose and isolate infectious cases of tuberculosis promptly and administer appropriate treatment.

  13. Kinetics of human immunodeficiency virus budding and assembly

    NASA Astrophysics Data System (ADS)

    Zhang, Rui; Nguyen, Toan

    2009-03-01

    Human immunodeficiency virus (HIV) belongs to a large family of RNA viruses, retroviruses. Unlike budding of regular enveloped viruses, retroviruses bud concurrently with the assembly of retroviral capsids on the cell membrane. The kinetics of HIV (and other retroviruses) budding and assembly is therefore strongly affected by the elastic energy of the membrane and fundamentally different from regular viruses. The main result of this work shows that the kinetics is tunable from a fast budding process to a slow and effectively trapped partial budding process, by varying the attractive energy of retroviral proteins (call Gags), relative to the membrane elastic energy. When the Gag-Gag attraction is relatively high, the membrane elastic energy provides a kinetic barrier for the two pieces of the partial capsids to merge. This energy barrier determines the slowest step in the kinetics and the budding time. In the opposite limit, the membrane elastic energy provides not only a kinetic energy barrier, but a free energy barrier. The budding and assembly is effectively trapped at local free energy minimum, corresponding to a partially budded state. The time scale to escape from this metastable state is exponentially large. In both cases, our result fit with experimental measurements pretty well.

  14. Testicular dysfunction in human immunodeficiency virus-infected men.

    PubMed

    Poretsky, L; Can, S; Zumoff, B

    1995-07-01

    This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system.

  15. Cytoskeletal proteins inside human immunodeficiency virus type 1 virions.

    PubMed Central

    Ott, D E; Coren, L V; Kane, B P; Busch, L K; Johnson, D G; Sowder, R C; Chertova, E N; Arthur, L O; Henderson, L E

    1996-01-01

    We have identified three types of cytoskeletal proteins inside human immunodeficiency virus type 1 (HIV-1) virions by analyzing subtilisin-digested particles. HIV-1 virions were digested with protease, and the treated particles were isolated by sucrose density centrifugation. This method removes both exterior viral proteins and proteins associated with microvesicles that contaminate virion preparations. Since the proteins inside the virion are protected from digestion by the viral lipid envelope, they can be isolated and analyzed after treatment. Experiments presented here demonstrated that this procedure removed more than 95% of the protein associated with microvesicles. Proteins in digested HIV-1(MN) particles from infected H9 and CEM(ss) cell lines were analyzed by high-pressure liquid chromatography, protein sequencing, and immunoblotting. The data revealed that three types of cytoskeletal proteins are present in virions at different concentrations relative to the molar level of Gag: actin (approximately 10 to 15%), ezrin and moesin (approximately 2%), and cofilin (approximately 2 to 10%). Our analysis of proteins within virus particles detected proteolytic fragments of alpha-smooth muscle actin and moesin that were cleaved at sites which might be recognized by HIV-1 protease. These cleavage products are not present in microvesicles from uninfected cells. Therefore, these processed proteins are most probably produced by HIV-1 protease digestion. The presence of these fragments, as well as the incorporation of a few specific cytoskeletal proteins into virions, suggests an active interaction between cytoskeletal and viral proteins. PMID:8892894

  16. Selective destruction of cells infected with human immunodeficiency virus

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2003-09-30

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  17. Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2006-03-28

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  18. Hepatitis B and human immunodeficiency virus co-infection

    PubMed Central

    Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

    2014-01-01

    Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

  19. Role of liver transplantation in human immunodeficiency virus positive patients

    PubMed Central

    Joshi, Deepak; Agarwal, Kosh

    2015-01-01

    End-stage liver disease (ESLD) is a leading cause of morbidity and mortality amongst human immunodeficiency virus (HIV)-positive individuals. Chronic hepatitis B and hepatitis C virus (HCV) infection, drug-induced hepatotoxicity related to combined anti-retro-viral therapy, alcohol related liver disease and non-alcohol related fatty liver disease appear to be the leading causes. It is therefore, anticipated that more HIV-positive patients with ESLD will present as potential transplant candidates. HIV infection is no longer a contraindication to liver transplantation. Key transplantation outcomes such as rejection and infection rates as well as medium term graft and patient survival match those seen in the non-HIV infected patients in the absence of co-existing HCV infection. HIV disease does not seem to be negatively impacted by transplantation. However, HIV-HCV co-infection transplant outcomes remain suboptimal due to recurrence. In this article, we review the key challenges faced by this patient cohort in the pre- and post-transplant period. PMID:26604639

  20. Update on kidney transplantation in human immunodeficiency virus infected recipients.

    PubMed

    Nashar, Khaled; Sureshkumar, Kalathil K

    2016-07-01

    Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV(+) donors to HIV(+) recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV(+) to HIV(+) kidney transplant in the United States and the first HIV(+) to HIV(+) liver transplant in the world were recently performed at the Johns Hopkins University Medical Center. PMID:27458559

  1. Recombination increases human immunodeficiency virus fitness, but not necessarily diversity.

    PubMed

    Vijay, N N V; Vasantika; Ajmani, Rahul; Perelson, Alan S; Dixit, Narendra M

    2008-06-01

    Recombination can facilitate the accumulation of mutations and accelerate the emergence of resistance to current antiretroviral therapies for human immunodeficiency virus (HIV) infection. Yet, since recombination can also dissociate favourable combinations of mutations, the benefit of recombination to HIV remains in question. The confounding effects of mutation, multiple infections of cells, random genetic drift and fitness selection that underlie HIV evolution render the influence of recombination difficult to unravel. We developed computer simulations that mimic the genomic diversification of HIV within an infected individual and elucidate the influence of recombination. We find, interestingly, that when the effective population size of HIV is small, recombination increases both the diversity and the mean fitness of the viral population. When the effective population size is large, recombination increases viral fitness but decreases diversity. In effect, recombination enhances (lowers) the likelihood of the existence of multi-drug resistant strains of HIV in infected individuals prior to the onset of therapy when the effective population size is small (large). Our simulations are consistent with several recent experimental observations, including the evolution of HIV diversity and divergence in vivo. The intriguing dependencies on the effective population size appear due to the subtle interplay of drift, selection and epistasis, which we discuss in the light of modern population genetics theories. Current estimates of the effective population size of HIV have large discrepancies. Our simulations present an avenue for accurate determination of the effective population size of HIV in vivo and facilitate establishment of the benefit of recombination to HIV.

  2. Syphilis, leprosy, and human immunodeficiency virus coinfection: a challenging diagnosis.

    PubMed

    Souza, Claudia Fd; Bornhausen-Demarch, Eduardo; Prata, Aline G; de Andrade, Felipe C; Fernandes, Mariana P; Lopes, Marcia Ra; Nery, José Ac

    2013-08-01

    The association between syphilis, leprosy, and human immunodeficiency virus (HIV) is not well documented, and the emergence of isolated cases raises the interest and indicates that this triple coinfection can occur. We report the case of a 42-year-old man from Rio de Janeiro, Brazil, who presented with erythematous papules on the trunk, back, and upper and lower extremities; an erythematous plaque on the upper abdomen; and an erythematous violaceous plaque on the right thigh with altered sensitivity. Laboratory investigation showed a reagent VDRL test (1:512) and positive test results for Treponema pallidum hemagglutination. Treatment with benzathine penicillin (2,400,000 U intramuscularly) was started (2 doses 1 week apart). On follow-up 40 days later, the lesions showed partial improvement with persistence of the plaques on the right thigh and upper abdomen as well as a new similar plaque on the back. Further laboratory examinations showed negative bacilloscopy, positive HIV test, and histologic findings consistent with tuberculoid leprosy. The patient was started on multidrug therapy for paucibacillary leprosy with clinical improvement; the patient also was monitored by the HIV/AIDS department. We emphasize the importance of clinical suspicion for a coinfection case despite the polymorphism of these diseases as well as the precise interpretation of laboratory and histopathology examinations to correctly manage atypical cases. PMID:24087779

  3. Update on kidney transplantation in human immunodeficiency virus infected recipients

    PubMed Central

    Nashar, Khaled; Sureshkumar, Kalathil K

    2016-01-01

    Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV+ donors to HIV+ recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV+ to HIV+ kidney transplant in the United States and the first HIV+ to HIV+ liver transplant in the world were recently performed at the Johns Hopkins University Medical Center. PMID:27458559

  4. Markers predicting progression of human immunodeficiency virus-related disease.

    PubMed Central

    Tsoukas, C M; Bernard, N F

    1994-01-01

    Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression. PMID:8118788

  5. Analysis of the human immunodeficiency virus-1 RNA packageome.

    PubMed

    Eckwahl, Matthew J; Arnion, Helene; Kharytonchyk, Siarhei; Zang, Trinity; Bieniasz, Paul D; Telesnitsky, Alice; Wolin, Sandra L

    2016-08-01

    All retroviruses package cellular RNAs into virions. Studies of murine leukemia virus (MLV) revealed that the major host cell RNAs encapsidated by this simple retrovirus were LTR retrotransposons and noncoding RNAs (ncRNAs). Several classes of ncRNAs appeared to be packaged by MLV shortly after synthesis, as precursors to tRNAs, small nuclear RNAs, and small nucleolar RNAs were all enriched in virions. To determine the extent to which the human immunodeficiency virus (HIV-1) packages similar RNAs, we used high-throughput sequencing to characterize the RNAs within infectious HIV-1 virions produced in CEM-SS T lymphoblastoid cells. We report that the most abundant cellular RNAs in HIV-1 virions are 7SL RNA and transcripts from numerous divergent and truncated members of the long interspersed element (LINE) and short interspersed element (SINE) families of retrotransposons. We also detected precursors to several tRNAs and small nuclear RNAs as well as transcripts derived from the ribosomal DNA (rDNA) intergenic spacers. We show that packaging of a pre-tRNA requires the nuclear export receptor Exportin 5, indicating that HIV-1 recruits at least some newly made ncRNAs in the cytoplasm. Together, our work identifies the set of RNAs packaged by HIV-1 and reveals that early steps in HIV-1 assembly intersect with host cell ncRNA biogenesis pathways. PMID:27247436

  6. Human immunodeficiency virus type 1 infection of the brain.

    PubMed Central

    Atwood, W J; Berger, J R; Kaderman, R; Tornatore, C S; Major, E O

    1993-01-01

    Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology. Images PMID:8269391

  7. Exercise dysfunction in patients seropositive for the human immunodeficiency virus

    SciTech Connect

    Johnson, J.E.; Anders, G.T.; Blanton, H.M.; Hawkes, C.E.; Bush, B.A.; McAllister, C.K.; Matthews, J.I. )

    1990-03-01

    To confirm the presence of exercise dysfunction in patients seropositive for the human immunodeficiency virus (HIV), 32 such patients without AIDS were evaluated with cardiopulmonary exercise testing, pulmonary function testing, bronchoalveolar lavage, chest roentgenography, and gallium scanning. No evidence of pulmonary opportunistic infection was found. When compared to an otherwise similar group of HIV-seronegative controls, the patients exercised to a significantly lower workload (195 +/- 30 versus 227 +/- 31 W, p less than 0.001). The ventilatory anaerobic threshold (VAT) values were also significantly lower for the patients (49.2 +/- 13.0 versus 61.9 +/- 9.1% of maximum predicted VO2, p less than 0.001). Nine of the patients had VAT values less than the 95% confidence interval for the controls. This subgroup exercised to a significantly lower maximum VO2 (69.9 +/- 11.2 versus 95.9 +/- 17.5% of maximum predicted VO2, p less than 0.001) and workload (165 +/- 21 versus 227 +/- 31 W) when compared to the control group. These patients demonstrated a mild tachypnea throughout exercise relative to the controls and had a significant increase in the slope of the heart rate to VO2 relationship. These findings are most consistent with a limitation of oxygen delivery to exercising muscles, which may represent occult cardiac disease in this group.

  8. Complementation of human immunodeficiency virus (HIV-1) gag particle formation.

    PubMed

    Zhoa, Y; Jones, I M; Hockley, D J; Nermut, M V; Roy, P

    1994-03-01

    The human immunodeficiency virus gag precursor protein Pr55Gag exhibits the ability of particle assembly when expressed using recombinant baculoviruses. In order to delineate the sequences required for particle formation, two mutants of Gag (D1 and D2) were constructed in which 10 amino acids within the CA domain were deleted. Both mutants yielded stable high levels of Gag antigen following expression in Spodoptera frugiperda insect cells. Electron microscopy of sections through infected cells revealed that neither mutant was able to assemble particles although targeting of the protein to the plasma membrane still occurred. The Gag antigen that accumulated beneath the plasma membrane exhibited distinctive morphologies when compared to each other and to parental (Pr46Gag) particles. Particle assembly was rescued when S. frugiperda cells were coinfected with both AcD1 and AcD2 viruses, or with AcD1 and a carboxyl-terminal deletion of Gag (Pr41.5) which was previously shown not to form particles (J.B.M., D.J. Hockley, M.V. Nermot, and I.M. Jones, 1992, J. Gen. Virol. 73, 3079-3086). The genetic complementation of Gag-driven assembly is discussed.

  9. Water, electrolytes, and acid-base alterations in human immunodeficiency virus infected patients

    PubMed Central

    Musso, Carlos G; Belloso, Waldo H; Glassock, Richard J

    2016-01-01

    The clinical spectrum of human immunodeficiency virus (HIV) infection associated disease has changed significantly over the past decade, mainly due to the wide availability and improvement of combination antiretroviral therapy regiments. Serious complications associated with profound immunodeficiency are nowadays fortunately rare in patients with adequate access to care and treatment. However, HIV infected patients, and particularly those with acquired immune deficiency syndrome, are predisposed to a host of different water, electrolyte, and acid-base disorders (sometimes with opposite characteristics), since they have a modified renal physiology (reduced free water clearance, and relatively increased fractional excretion of calcium and magnesium) and they are also exposed to infectious, inflammatory, endocrinological, oncological variables which promote clinical conditions (such as fever, tachypnea, vomiting, diarrhea, polyuria, and delirium), and may require a variety of medical interventions (antiviral medication, antibiotics, antineoplastic agents), whose combination predispose them to undermine their homeostatic capability. As many of these disturbances may remain clinically silent until reaching an advanced condition, high awareness is advisable, particularly in patients with late diagnosis, concomitant inflammatory conditions and opportunistic diseases. These disorders contribute to both morbidity and mortality in HIV infected patients. PMID:26788462

  10. Water, electrolytes, and acid-base alterations in human immunodeficiency virus infected patients.

    PubMed

    Musso, Carlos G; Belloso, Waldo H; Glassock, Richard J

    2016-01-01

    The clinical spectrum of human immunodeficiency virus (HIV) infection associated disease has changed significantly over the past decade, mainly due to the wide availability and improvement of combination antiretroviral therapy regiments. Serious complications associated with profound immunodeficiency are nowadays fortunately rare in patients with adequate access to care and treatment. However, HIV infected patients, and particularly those with acquired immune deficiency syndrome, are predisposed to a host of different water, electrolyte, and acid-base disorders (sometimes with opposite characteristics), since they have a modified renal physiology (reduced free water clearance, and relatively increased fractional excretion of calcium and magnesium) and they are also exposed to infectious, inflammatory, endocrinological, oncological variables which promote clinical conditions (such as fever, tachypnea, vomiting, diarrhea, polyuria, and delirium), and may require a variety of medical interventions (antiviral medication, antibiotics, antineoplastic agents), whose combination predispose them to undermine their homeostatic capability. As many of these disturbances may remain clinically silent until reaching an advanced condition, high awareness is advisable, particularly in patients with late diagnosis, concomitant inflammatory conditions and opportunistic diseases. These disorders contribute to both morbidity and mortality in HIV infected patients. PMID:26788462

  11. Exercise and Human Immunodeficiency Virus (HIV-1) Infection

    NASA Technical Reports Server (NTRS)

    Lawless, DeSales; Jackson, Catherine G. R.; Greenleaf, John E.

    1995-01-01

    The human immune system is highly efficient and remarkably protective when functioning properly. Similar to other physiological systems, it functions best when the body is maintained with a balanced diet, sufficient rest and a moderately stress-free lifestyle. It can be disrupted by inappropriate drug use and extreme emotion or exertion. The functioning of normal or compromised immune systems can be enhanced by properly prescribed moderate exercise conditioning regimens in healthy people, and in some human immunodeficiency virus (HIV-1)-infected patients but not in others who unable to complete an interval training program. Regular exercise conditioning in healthy people reduces cardiovascular risk factors, increases stamina, facilitates bodyweight control, and reduces stress by engendering positive feelings of well-being. Certain types of cancer may also be suppressed by appropriate exercise conditioning. Various exercise regimens are being evaluated as adjunct treatments for medicated patients with the HIV-1 syndrome. Limited anecdotal evidence from patients suggests that moderate exercise conditioning is per se responsible for their survival well beyond expectancy. HIV-1-infected patients respond positively, both physiologically and psychologically, to moderate exercise conditioning. However, the effectiveness of any exercise treatment programme depends on its mode, frequency, intensity and duration when prescribed o complement the pathological condition of the patient. The effectiveness of exercise conditioning regimens in patients with HIV-1 infection is reviewed in this article. In addition, we discuss mechanisms and pathways, involving the interplay of psychological and physiological factors, through which the suppressed immune system can be enhanced. The immune modulators discussed are endogenous opioids, cytokines, neurotransmitters and other hormones. Exercise conditioning treatment appears to be more effective when combined with other stress management

  12. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

    PubMed Central

    Santos, Lucianna Helene; Ferreira, Rafaela Salgado; Caffarena, Ernesto Raúl

    2015-01-01

    Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted. PMID:26560977

  13. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.

    PubMed

    Santos, Lucianna Helene; Ferreira, Rafaela Salgado; Caffarena, Ernesto Raúl

    2015-11-01

    Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted. PMID:26560977

  14. REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.

    PubMed

    Dami, N; Shehu, N Y; Dami, S; Iroezindu, M O

    2015-01-01

    The global scourge of human immunodeficiency virus (HIV) infection is inundating, especially in sub-Saharan Africa and in particular Nigeria which is home to 10% of the world's HIV-infected persons. The target of the millennium development goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in Nigeria was initially shrouded in denial and apathy. Subsequently, a more pragmatic approach was launched during the tenure of President Olusegun Obasanjo. Several policies were formulated. The national prevalence of HIV witnessed some progressive decline and is currently 4.1%. There is now improvement in both HIV awareness and counselling and testing. Greater access to antiretroviral therapy and other support services have also been witnessed with over 300,000 persons currently on drugs. Notable achievements have been recorded in prevention of mother to child transmission (PMTC). However, with increased access to antiretroviral therapy, antiretroviral drug resistance has become inevitable. Acquired drug resistance is high-82% and transmitted drug resistance ranges between 0.7 and 4.5%. The achievements were largely facilitated by international partnerships which have become more streamlined in recent years. A sustained shift to indigenously sourced financial and manpower resource has become imperative. It is also important to integrate HIV facilities with other existing health care facilities for sustainability and cost-effectiveness. In an attempt to strengthen the national response, President Goodluck Ebele Jonathan launched the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped that this well-articulated policy would be well implemented to significantly reverse the epidemic. PMID:27487603

  15. Declined Neural Efficiency in Cognitively Stable Human Immunodeficiency Virus Patients

    PubMed Central

    Ernst, Thomas; Yakupov, Renat; Nakama, Helenna; Crocket, Grace; Cole, Michael; Watters, Michael; Ricardo-Dukelow, Mary Lynn; Chang, Linda

    2009-01-01

    Objective To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)–infected and in HIV-seronegative control (SN) participants over a 1-year period. Methods Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations. Results Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. PMID:19334060

  16. Measuring domestic violence in human immunodeficiency virus-positive women

    PubMed Central

    Patrikar, Seema; Verma, AK; Bhatti, VK; Shatabdi, S

    2012-01-01

    Background Violence affects the lives of millions of women worldwide, in all socioeconomic classes. Violence and the fear of violence are emerging as important risk factor contributing to the vulnerability to human immunodeficiency virus (HIV) infection for women. The objective of the present cross sectional study is to compare the experiences of domestic violence between HIV-positive and HIV-negative married women seeking treatment in a tertiary care hospital. Methods The study is conducted in a tertiary care hospital in Pune on a randomly selected 150 married women (75 HIV-positive and 75 HIV-negative). Informed consent was obtained from all the women and also a trained counsellor was present during the process of data collection. The data was collected by interview method by taking precautions as laid down in the World Health Organization's ethical and safety recommendations for research on domestic violence and using modified conflict tactics scale (CTS). The definition of violence followed is as per the Declaration on the Elimination of Violence against Women, adopted by the United Nations General Assembly in 1993. Results The percentage of women reporting domestic violence is 44.7% (95% confidence interval [CI] = 36.84–52.68). The proportion of physical, emotional and sexual violence reported is 38% (95% CI = 30.49–45.96), 24% (95% CI = 17.67–31.31), and 14.7% (95% CI = 9.66–21.02), respectively. The odds of reporting violence of all forms is significantly higher among HIV-positive women than among HIV-negative women (P<0.05). Univariate and multivariate logistic regression is carried out to examine the possible predictors of domestic violence. Conclusion The findings suggest high proportion of HIV-positive women report violence then HIV-negative women which must be addressed through multilevel prevention approaches. PMID:24669053

  17. REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.

    PubMed

    Dami, N; Shehu, N Y; Dami, S; Iroezindu, M O

    2015-01-01

    The global scourge of human immunodeficiency virus (HIV) infection is inundating, especially in sub-Saharan Africa and in particular Nigeria which is home to 10% of the world's HIV-infected persons. The target of the millennium development goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in Nigeria was initially shrouded in denial and apathy. Subsequently, a more pragmatic approach was launched during the tenure of President Olusegun Obasanjo. Several policies were formulated. The national prevalence of HIV witnessed some progressive decline and is currently 4.1%. There is now improvement in both HIV awareness and counselling and testing. Greater access to antiretroviral therapy and other support services have also been witnessed with over 300,000 persons currently on drugs. Notable achievements have been recorded in prevention of mother to child transmission (PMTC). However, with increased access to antiretroviral therapy, antiretroviral drug resistance has become inevitable. Acquired drug resistance is high-82% and transmitted drug resistance ranges between 0.7 and 4.5%. The achievements were largely facilitated by international partnerships which have become more streamlined in recent years. A sustained shift to indigenously sourced financial and manpower resource has become imperative. It is also important to integrate HIV facilities with other existing health care facilities for sustainability and cost-effectiveness. In an attempt to strengthen the national response, President Goodluck Ebele Jonathan launched the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped that this well-articulated policy would be well implemented to significantly reverse the epidemic.

  18. Leishmania and human immunodeficiency virus coinfection: the first 10 years.

    PubMed Central

    Alvar, J; Cañavate, C; Gutiérrez-Solar, B; Jiménez, M; Laguna, F; López-Vélez, R; Molina, R; Moreno, J

    1997-01-01

    Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack

  19. Inducible human immunodeficiency virus type 1 packaging cell lines.

    PubMed Central

    Yu, H; Rabson, A B; Kaul, M; Ron, Y; Dougherty, J P

    1996-01-01

    Packaging cell lines are important tools for transferring genes into eukaryotic cells. Human immunodeficiency virus type 1 (HIV-1)-based packaging cell lines are difficult to obtain, in part owing to the problem that some HIV-1 proteins are cytotoxic in a variety of cells. To overcome this, we have developed an HIV-1-based packaging cell line which has an inducible expression system. The tetracycline-inducible expression system was utilized to control the expression of the Rev regulatory protein, which in turn controls the expression of the late proteins including Gag, Pol, and Env. Western blotting (immunoblotting) demonstrated that the expression of p24gag and gp120env from the packaging cells peaked on days 6 and 7 postinduction. Reverse transcriptase activity could be detected by day 4 after induction and also peaked on days 6 and 7. Defective vector virus could be propagated, yielding titers as high as 7 x 10(3) CFU/ml, while replication-competent virus was not detectable at any time. Thus, the cell line should enable the transfer of specific genes into CD4+ cells and should be a useful tool for studying the biology of HIV-1. We have also established an inducible HIV-1 Env-expressing cell line which could be used to propagate HIV-1 vectors that require only Env in trans. The env-minus vector virus titer produced from the Env-expressing cells reached 2 x 10(4) CFU/ml. The inducible HIV-1 Env-expressing cell line should be a useful tool for the study of HIV-1 Env as well. PMID:8676479

  20. Human Immunodeficiency Virus Type 1 Populations in Blood and Semen

    PubMed Central

    Delwart, Eric L.; Mullins, James I.; Gupta, Phalguni; Learn, Gerald H.; Holodniy, Mark; Katzenstein, David; Walker, Bruce D.; Singh, Mandaleshwar K.

    1998-01-01

    Transmission of human immunodeficiency virus type 1 (HIV-1) usually results in outgrowth of viruses with macrophage-tropic phenotype and consensus non-syncytium-inducing (NSI) V3 loop sequences, despite the presence of virus with broader host range and the syncytium-inducing (SI) phenotype in the blood of many donors. We examined proviruses in contemporaneous peripheral blood mononuclear cells (PBMC) and nonspermatozoal semen mononuclear cells (NSMC) of five HIV-1-infected individuals to determine if this preferential outgrowth could be due to compartmentalization and thus preferential transmission of viruses of the NSI phenotype from the male genital tract. Phylogenetic reconstructions of ∼700-bp sequences covering the second constant region through the fifth variable region (C2 to V5) of the viral envelope gene revealed distinct variant populations in the blood versus the semen in two patients with AIDS and in one asymptomatic individual (patient 613), whereas similar variant populations were found in both compartments in two other asymptomatic individuals. Variants with amino acids in the V3 loop that predict the SI phenotype were found in both AIDS patients and in patient 613; however, the distribution of these variants between the two compartments was not consistent. SI variants were found only in the PBMC of one AIDS patient but only in the NSMC of the other, while they were found in both compartments in patient 613. It is therefore unlikely that restriction of SI variants from the male genital tract accounts for the observed NSI transmission bias. Furthermore, no evidence for a semen-specific signature amino acid sequence was detected. PMID:9420266

  1. Human immunodeficiency virus type 1 populations in blood and semen.

    PubMed

    Delwart, E L; Mullins, J I; Gupta, P; Learn, G H; Holodniy, M; Katzenstein, D; Walker, B D; Singh, M K

    1998-01-01

    Transmission of human immunodeficiency virus type 1 (HIV-1) usually results in outgrowth of viruses with macrophage-tropic phenotype and consensus non-syncytium-inducing (NSI) V3 loop sequences, despite the presence of virus with broader host range and the syncytium-inducing (SI) phenotype in the blood of many donors. We examined proviruses in contemporaneous peripheral blood mononuclear cells (PBMC) and non-spermatozoal semen mononuclear cells (NSMC) of five HIV-1-infected individuals to determine if this preferential outgrowth could be due to compartmentalization and thus preferential transmission of viruses of the NSI phenotype from the male genital tract. Phylogenetic reconstructions of approximately 700-bp sequences covering the second constant region through the fifth variable region (C2 to V5) of the viral envelope gene revealed distinct variant populations in the blood versus the semen in two patients with AIDS and in one asymptomatic individual (patient 613), whereas similar variant populations were found in both compartments in two other asymptomatic individuals. Variants with amino acids in the V3 loop that predict the SI phenotype were found in both AIDS patients and in patient 613; however, the distribution of these variants between the two compartments was not consistent. SI variants were found only in the PBMC of one AIDS patient but only in the NSMC of the other, while they were found in both compartments in patient 613. It is therefore unlikely that restriction of SI variants from the male genital tract accounts for the observed NSI transmission bias. Furthermore, no evidence for a semen-specific signature amino acid sequence was detected.

  2. Pharmacologic management of human immunodeficiency virus wasting syndrome.

    PubMed

    Badowski, Melissa; Pandit, Neha Sheth

    2014-08-01

    Pharmacologic interventions for human immunodeficiency virus (HIV) wasting have been studied since the 1990s, but the results of these interventions have been difficult to compare because the studies used different HIV wasting definitions and assessed various patient outcomes. Thus, we performed a systematic review of the current literature to identify studies that evaluated pharmacologic management of HIV wasting and to compare and contrast treatment options. Further, we provide a comprehensive review of these treatment options and describe the definition of HIV wasting used in each study, the outcomes assessed, and whether antiretroviral therapy was used during the HIV wasting treatment. Literature searches of the PubMed/Medline (1946-2014) and Google Scholar databases were performed, and a review of the bibliographies of retrieved articles was performed to identify additional references. Only English-language articles pertaining to humans and HIV-infected individuals were evaluated. Thirty-six studies were identified that assessed pharmacologic interventions to treat HIV wasting. Appetite stimulants, such as megestrol acetate, have been shown to increase total body weight (TBW) and body mass index in HIV-infected patients with wasting. Studies evaluating dronabinol showed conflicting data on TBW increases, but the drug may have minimal benefit on body composition compared with other appetite stimulants. Testosterone has been shown to be effective in HIV wasting for those who suffer from hypogonadism. Recombinant human growth hormone has been evaluated for HIV wasting and has shown promising results for TBW and lean body mass increases. Thalidomide has been studied; however, its use is limited due to its toxicities. Although megestrol acetate and dronabinol are approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV wasting, it is important to recognize other comorbidities such as depression or hypogonadism that may contribute to the

  3. Treatment of acquired immunodeficiency syndrome with Chinese medicine in China: opportunity, advancement and challenges.

    PubMed

    Liu, Zhi-Bin; Wang, Xin; Liu, Hui-Juan; Jin, Yan-Tao; Guo, Hui-Jun; Jiang, Zi-Qiang; Li, Zhen; Xu, Li-Ran

    2013-08-01

    Chinese medicine (CM) has been used in the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) for 30 years and the demonstrated therapeutic effects of CM, such as reducing plasma HIV viral load, increasing CD4(+)T cell counts, promoting immunity reconstitution, ameliorating symptoms and signs, improving the health related quality of life (HRQOL) and counteracting against the effects of anti-retroviral drugs, were summarized and reviewed in this article. The authors point out that it had been a good opportunity to use CM for the treatment of HIV infection and AIDS in the past and also there are huge challenges ahead for CM research and clinicians to discover more effective CM and its underlying mechanisms for treatment of AIDS.

  4. Advances in Human B Cell Phenotypic Profiling

    PubMed Central

    Kaminski, Denise A.; Wei, Chungwen; Qian, Yu; Rosenberg, Alexander F.; Sanz, Ignacio

    2012-01-01

    To advance our understanding and treatment of disease, research immunologists have been called-upon to place more centralized emphasis on impactful human studies. Such endeavors will inevitably require large-scale study execution and data management regulation (“Big Biology”), necessitating standardized and reliable metrics of immune status and function. A well-known example setting this large-scale effort in-motion is identifying correlations between eventual disease outcome and T lymphocyte phenotype in large HIV-patient cohorts using multiparameter flow cytometry. However, infection, immunodeficiency, and autoimmunity are also characterized by correlative and functional contributions of B lymphocytes, which to-date have received much less attention in the human Big Biology enterprise. Here, we review progress in human B cell phenotyping, analysis, and bioinformatics tools that constitute valuable resources for the B cell research community to effectively join in this effort. PMID:23087687

  5. International military human immunodeficiency virus/acquired immunodeficiency syndrome policies and programs: strengths and limitations in current practice.

    PubMed

    Yeager, R; Hendrix, C W; Kingma, S

    2000-02-01

    A survey was conducted to evaluate military human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) policies and programs in 119 countries. Ninety-eight percent of the 62 respondents provide prevention education, 95% in group settings but only 53% individually. Predeployment briefings are more common than postdeployment briefings. Condoms are promoted more often than provided. Seventy-eight respondents report some form of mandatory HIV testing, and 58% perform mandatory recruit testing, with recruitment denied to HIV-positive individuals in 17%. Counseling accompanies mandatory testing less than voluntary testing. In-service care for AIDS patients is universal. Many military prevention programs can be improved through postdeployment briefings and proactive interventions involving education, condom distribution, and counseling combined with testing. Mandatory testing is often inconsistent with stated goals, and AIDS care policies may strain military budgets. Testing based on cost-benefit assessments may increase efficiency in military HIV control. Military budgets may benefit from greater civil-military cost sharing in AIDS care. PMID:10709366

  6. International military human immunodeficiency virus/acquired immunodeficiency syndrome policies and programs: strengths and limitations in current practice.

    PubMed

    Yeager, R; Hendrix, C W; Kingma, S

    2000-02-01

    A survey was conducted to evaluate military human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) policies and programs in 119 countries. Ninety-eight percent of the 62 respondents provide prevention education, 95% in group settings but only 53% individually. Predeployment briefings are more common than postdeployment briefings. Condoms are promoted more often than provided. Seventy-eight respondents report some form of mandatory HIV testing, and 58% perform mandatory recruit testing, with recruitment denied to HIV-positive individuals in 17%. Counseling accompanies mandatory testing less than voluntary testing. In-service care for AIDS patients is universal. Many military prevention programs can be improved through postdeployment briefings and proactive interventions involving education, condom distribution, and counseling combined with testing. Mandatory testing is often inconsistent with stated goals, and AIDS care policies may strain military budgets. Testing based on cost-benefit assessments may increase efficiency in military HIV control. Military budgets may benefit from greater civil-military cost sharing in AIDS care.

  7. New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.

    PubMed

    Ollague Sierra, Jose E; Ollague Torres, Jose M

    2013-04-01

    Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS.

  8. Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.

    PubMed

    Barbosa Júnior, Walter Lins; Ramos de Araújo, Paulo Sérgio; Dias de Andrade, Luiz; Aguiar Dos Santos, Ana Maria; Lopes da Silva, Maria Almerice; Dantas-Torres, Filipe; Medeiros, Zulma

    2015-11-01

    After the emergence of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)-HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH(®); DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test (KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL diagnosis was based on clinical findings, cytology, serology, parasite DNA, and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS patients. Only three patients were positive in bone marrow cytology, three patients were conventional polymerase chain reaction (PCR) positive, while six were real-time PCR positive. All patients were direct agglutination test (DAT) (Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to validate the use of the KAtex in the national public health laboratory network in Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this country.

  9. Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.

    PubMed

    Barbosa Júnior, Walter Lins; Ramos de Araújo, Paulo Sérgio; Dias de Andrade, Luiz; Aguiar Dos Santos, Ana Maria; Lopes da Silva, Maria Almerice; Dantas-Torres, Filipe; Medeiros, Zulma

    2015-11-01

    After the emergence of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)-HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH(®); DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test (KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL diagnosis was based on clinical findings, cytology, serology, parasite DNA, and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS patients. Only three patients were positive in bone marrow cytology, three patients were conventional polymerase chain reaction (PCR) positive, while six were real-time PCR positive. All patients were direct agglutination test (DAT) (Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to validate the use of the KAtex in the national public health laboratory network in Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this country. PMID:26416105

  10. Use of humanized severe combined immunodeficient mice for human vaccine development

    PubMed Central

    Koo, Gloria C; Hasan, Aisha; O’Reilly, Richard J

    2009-01-01

    The severe combined immunodeficient (SCID) mouse has no adaptive immunity, lacking mature T and B cells in the peripheral blood or the lymphoid organs. It has been used extensively in biomedical research as a valuable translational model for xeno-engraftment of human tissues and cells. This review focuses on the engraftment of human peripheral blood cells and tissues in SCID mice, as well as in the newly established and more permissive SCID mice deficient in the IL-2 receptor γ-chain. Human immune responses could be elicited and assessed in these humanized SCID mice upon vaccination or sensitization with allogeneic tissues. A translational model is proposed to attain preclinical data for testing human vaccines. PMID:19093778

  11. Role of Active and Inactive Cytotoxic Immune Response in Human Immunodeficiency Virus Dynamics

    PubMed Central

    Toro Zapata, Hernan Dario; Caicedo Casso, Angelica Graciela; Bichara, Derdei; Lee, Sunmi

    2014-01-01

    Objectives Mathematical models can be helpful to understand the complex dynamics of human immunodeficiency virus infection within a host. Most of work has studied the interactions of host responses and virus in the presence of active cytotoxic immune cells, which decay to zero when there is no virus. However, recent research highlights that cytotoxic immune cells can be inactive but never be depleted. Methods We propose a mathematical model to investigate the human immunodeficiency virus dynamics in the presence of both active and inactive cytotoxic immune cells within a host. We explore the impact of the immune responses on the dynamics of human immunodeficiency virus infection under different disease stages. Results Standard mathematical and numerical analyses are presented for this new model. Specifically, the basic reproduction number is computed and local and global stability analyses are discussed. Conclusion Our results can give helpful insights when designing more effective drug schedules in the presence of active and inactive immune responses. PMID:24955306

  12. 76 FR 72417 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... HUMAN SERVICES Centers for Disease Control and Prevention Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation AGENCY: Centers for Disease Control and Prevention (CDC),...

  13. 76 FR 58517 - Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... HUMAN SERVICES Centers for Disease Control and Prevention Public Health Service Guideline for Reducing Transmission of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) Through Solid Organ Transplantation AGENCY: Centers for Disease Control and Prevention (CDC),...

  14. Human immunodeficiency virus type 1 envelope-specific cytotoxic T lymphocytes response dynamics after prime-boost vaccine regimens with human immunodeficiency virus type 1 canarypox and pseudovirions.

    PubMed

    Arp, J; Rovinski, B; Sambhara, S; Tartaglia, J; Dekaban, G

    1999-01-01

    Virus-specific cytotoxic T lymphocytes (CTLs) may represent significant immune mechanisms in the control of human immunodeficiency virus (HIV) infection and, therefore, CTL induction may be a fundamental goal in the development of an efficacious acquired immunodeficiency syndrome (AIDS) vaccine. In the current study, prime-boost protocols were used to investigate the potential of noninfectious human immunodeficiency virus type 1 (HIV-1) pseudovirions (HIV PSV) in enhancing HIV-specific CTL responses in Balb/c mice primed with the recombinant canarypox vector, vCP205, encoding HIV-1 gp120 (MN strain) in addition to Gag/Protease (HIB strain). The prime-boost immunization regimens were administered intramuscularly and involved injections of vCP205 followed by boosts with HIV PSV. Previous vaccination strategies solely involving vCP205 had induced good cellular immune responses in uninfected human volunteers, despite some limitations. The use of genetically engineered HIV PSV was a logical step in the evaluation of whole noninfectious virus or inactivated virus vaccine strategies, particularly as a potential boosting agent for vCP205-primed recipients. Based on this current study, HIV PSV appeared to have the capability to effectively induce and boost cell-mediated HIV-1-specific responses. In order to observe the immune effects of HIV PSV in a prime-boost immunization strategy, both HIV vaccine immunogens required careful titration in vivo. This suggests that careful consideration should be given to the optimization of immunization protocols destined for human use.

  15. White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals.

    PubMed

    Gongvatana, Assawin; Schweinsburg, Brian C; Taylor, Michael J; Theilmann, Rebecca J; Letendre, Scott L; Alhassoon, Omar M; Jacobus, Joanna; Woods, Steven P; Jernigan, Terry L; Ellis, Ronald J; Frank, Lawrence R; Grant, Igor

    2009-04-01

    Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

  16. Practice Bulletin No. 167 Summary: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus.

    PubMed

    2016-10-01

    In the United States in 2013, there were an estimated 226,000 women and adolescents living with human immunodeficiency virus (HIV) infection (1). Women with HIV are living longer, healthier lives, so the need for routine and problem-focused gynecologic care has increased. The purpose of this document is to educate clinicians about basic health screening and care, family planning, prepregnancy care, and managing common gynecologic problems for women and adolescents who are infected with HIV. For information on screening guidelines, refer to the American College of Obstetricians and Gynecologists' Committee Opinion No. 596, Routine Human Immunodeficiency Virus Screening (2). PMID:27661642

  17. Practice Bulletin No. 167: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus.

    PubMed

    2016-10-01

    In the United States in 2013, there were an estimated 226,000 women and adolescents living with human immunodeficiency virus (HIV) infection (1). Women with HIV are living longer, healthier lives, so the need for routine and problem-focused gynecologic care has increased. The purpose of this document is to educate clinicians about basic health screening and care, family planning, prepregnancy care, and managing common gynecologic problems for women and adolescents who are infected with HIV. For information on screening guidelines, refer to the American College of Obstetricians and Gynecologists' Committee Opinion No. 596, Routine Human Immunodeficiency Virus Screening (2). PMID:27661659

  18. C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge

    PubMed Central

    Veazey, Ronald S.; Chatterji, Udayan; Bobardt, Michael; Russell-Lodrigue, Kasi E.; Li, Jian; Wang, Xiaolei

    2015-01-01

    A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. PMID:26552985

  19. The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives.

    PubMed

    Yasuno, Takumi; Ohe, Tomoyuki; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

    2015-08-15

    In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inhibition without cytotoxicity.

  20. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... partner and that the disclosure is necessary to protect the health of the spouse or sexual partner. (c) A... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject...

  1. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... partner and that the disclosure is necessary to protect the health of the spouse or sexual partner. (c) A... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject...

  2. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... partner and that the disclosure is necessary to protect the health of the spouse or sexual partner. (c) A... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject...

  3. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... indicating that a patient is infected with the HIV if the disclosure is made to the spouse of the patient,...

  4. 38 CFR 1.487 - Disclosure of information related to infection with the human immunodeficiency virus to the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... related to infection with the human immunodeficiency virus to the spouse or sexual partner of the patient... the human immunodeficiency virus to the spouse or sexual partner of the patient. (a) Subject to... indicating that a patient is infected with the HIV if the disclosure is made to the spouse of the patient,...

  5. Personal and psychosocial characteristics associated with psychiatric conditions among women with human immunodeficiency virus.

    PubMed

    Sherbourne, Cathy; Griffith Forge, Nell; Kung, Fuan-Yue; Orlando, Maria; Tucker, Joan

    2003-01-01

    This study presents information on correlates of mental health and substance abuse problems among women with human immunodeficiency virus (HIV), a particularly vulnerable, poor and minority population. Data are from 847 women in the HIV Cost and Services Utilization Study, a national probability sample of adults with known human immunodeficiency virus infection. Fifty-five percent of women manifested a probable psychiatric condition. Results indicated that increased risk for psychiatric conditions among these women was associated with younger age, having acquired immunodeficiency virus (rather than asymptomatic), using avoidant coping strategies, reporting increased conflict with others, and prior physical abuse, needing income assistance, and putting off going to the doctor because of caring for someone else. Findings suggest we need to address women's need for safety from assaultive partners and that we may need special programs for women burdened with having to care for others.

  6. The Interaction between Human Immunodeficiency Virus and Human Papillomaviruses in Heterosexuals in Africa.

    PubMed

    Williamson, Anna-Lise

    2015-04-02

    Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV infection and associated disease is very high in HIV-infected people and continues to be a problem even after anti-retroviral therapy. In the genital tract, the interaction between HPV and HIV is complex, with infection with multiple HPV types reported to make both women and men more susceptible to HIV infection. Besides the national programmes to vaccinate girls against HPV and screen women for cervical cancer, there should be targeted cervical cancer screening, treatment and prevention programmes introduced into HIV treatment centres. There is evidence that in high HIV prevalence areas, HIV-positive women could cause increases in the prevalence of genital HPV infection in HIV-negative men and so increase the HPV circulating in the community. Condom use and circumcision reduce the acquisition of HIV-1, and also to some extent of HPV. This review will highlight what is known about the interaction of HIV and HPV, with an emphasis on research in Africa.

  7. The Interaction between Human Immunodeficiency Virus and Human Papillomaviruses in Heterosexuals in Africa

    PubMed Central

    Williamson, Anna-Lise

    2015-01-01

    Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV infection and associated disease is very high in HIV-infected people and continues to be a problem even after anti-retroviral therapy. In the genital tract, the interaction between HPV and HIV is complex, with infection with multiple HPV types reported to make both women and men more susceptible to HIV infection. Besides the national programmes to vaccinate girls against HPV and screen women for cervical cancer, there should be targeted cervical cancer screening, treatment and prevention programmes introduced into HIV treatment centres. There is evidence that in high HIV prevalence areas, HIV-positive women could cause increases in the prevalence of genital HPV infection in HIV-negative men and so increase the HPV circulating in the community. Condom use and circumcision reduce the acquisition of HIV-1, and also to some extent of HPV. This review will highlight what is known about the interaction of HIV and HPV, with an emphasis on research in Africa. PMID:26239348

  8. The Interaction between Human Immunodeficiency Virus and Human Papillomaviruses in Heterosexuals in Africa.

    PubMed

    Williamson, Anna-Lise

    2015-01-01

    Sub-Saharan Africa has the highest incidence of human papillomavirus (HPV) and cervical cancer in the world, which is further aggravated by the burden of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) disease with invasive cervical cancer being an AIDS-defining cancer. The prevalence of HPV infection and associated disease is very high in HIV-infected people and continues to be a problem even after anti-retroviral therapy. In the genital tract, the interaction between HPV and HIV is complex, with infection with multiple HPV types reported to make both women and men more susceptible to HIV infection. Besides the national programmes to vaccinate girls against HPV and screen women for cervical cancer, there should be targeted cervical cancer screening, treatment and prevention programmes introduced into HIV treatment centres. There is evidence that in high HIV prevalence areas, HIV-positive women could cause increases in the prevalence of genital HPV infection in HIV-negative men and so increase the HPV circulating in the community. Condom use and circumcision reduce the acquisition of HIV-1, and also to some extent of HPV. This review will highlight what is known about the interaction of HIV and HPV, with an emphasis on research in Africa. PMID:26239348

  9. Limited Protection from a Pathogenic Chimeric Simian-Human Immunodeficiency Virus Challenge following Immunization with Attenuated Simian Immunodeficiency Virus

    PubMed Central

    Lewis, Mark G.; Yalley-Ogunro, Jake; Greenhouse, Jack J.; Brennan, Terry P.; Jiang, Jennifer Bo; VanCott, Thomas C.; Lu, Yichen; Eddy, Gerald A.; Birx, Deborah L.

    1999-01-01

    Two live attenuated single-deletion mutant simian immunodeficiency virus (SIV) constructs, SIV239Δnef and SIVPBj6.6Δnef, were tested for their abilities to stimulate protective immunity in macaques. During the immunization period the animals were examined for specific immune responses and virus growth. Each construct generated high levels of specific immunity in all of the immunized animals. The SIV239Δnef construct was found to grow to high levels in all immunized animals, with some animals remaining positive for virus isolation and plasma RNA throughout the immunization period. The SIVPBj6.6Δnef was effectively controlled by all of the immunized animals, with virus mostly isolated only during the first few months following immunization and plasma RNA never detected. Following an extended period of immunization of over 80 weeks, the animals were challenged with a pathogenic simian-human immunodeficiency virus (SHIV) isolate, SIV89.6PD, by intravenous injection. All of the SIV239Δnef-immunized animals became infected with the SHIV isolate; two of five animals eventually controlled the challenge and three of five animals, which failed to check the immunizing virus, progressed to disease state before the unvaccinated controls. One of five animals immunized with SIVPBj6.6Δnef totally resisted infection by the challenge virus, while three others limited its growth and the remaining animal became persistently infected and eventually died of a pulmonary thrombus. These data indicate that vaccination with attenuated SIV can protect macaques from disease and in some cases from infection by a divergent SHIV. However, if animals are unable to control the immunizing virus, potential damage that can accelerate the disease course of a pathogenic challenge virus may occur. PMID:9882330

  10. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus

    PubMed Central

    Lo, Janet; Lu, Michael T.; Kim, Elli A.; Nou, Eric; Hallett, Travis R.; Park, Jakob; Hoffmann, Udo; Grinspoon, Steven K.

    2016-01-01

    Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy. PMID:27419149

  11. Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique

    PubMed Central

    Wandeler, Gilles; Mulenga, Lloyd; Hobbins, Michael; Joao, Candido; Sinkala, Edford; Hector, Jonas; Aly, Musa; Chi, Benjamin H.; Egger, Matthias; Vinikoor, Michael J.

    2016-01-01

    Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication. PMID:27047986

  12. Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults

    PubMed Central

    Lindeman, Tara A.; Duggan, Joan M.; Sahloff, Eric G.

    2016-01-01

    This retrospective chart review evaluated changes in serum creatinine and creatinine clearance (CrCl) after initiation of an integrase inhibitor (INSTI)-based regimen as initial treatment in human immunodeficiency virus-infected adults. Serum creatinine and CrCl changes were similar to those seen in clinical trials for INSTIs. No renal-related serious adverse events or discontinuations occurred. PMID:27092314

  13. Human Immunodeficiency Virus (HIV) Testing and False Disclosures in Heterosexual College Students

    ERIC Educational Resources Information Center

    Marelich, William D.; Clark, Tonya

    2004-01-01

    The authors assessed factors that motivate individuals to report negative human immunodeficiency virus (HIV) antibody test results, although they had never been tested. In particular, they investigated sexual intimacy motives associated with the needs for affiliation, sex, and dominance as contributing factors for faulty disclosures. Participants…

  14. Case Study: Delirium in an Adolescent Girl with Human Immunodeficiency Virus-Associated Dementia

    ERIC Educational Resources Information Center

    Scharko, Alexander M.; Baker, Eva H.; Kothari, Priti; Khattak, Hina; Lancaster, Duniya

    2006-01-01

    Delirium and human immunodeficiency virus (HIV)-associated dementia are well recognized neuropsychiatric consequences of HIV infection in adults. Almost nothing is known regarding the management of delirium in HIV-infected children and adolescents. HIV-related progressive encephalopathy is thought to represent the pediatric form of HIV-associated…

  15. Prevalence of Human Immunodeficiency Virus Testing and Associated Risk Factors in College Students

    ERIC Educational Resources Information Center

    Dennison, Olivia; Wu, Qishan; Ickes, Melinda

    2014-01-01

    Objective: This study documents the prevalence of human immunodeficiency virus (HIV) testing in a sample of college students and examines associated demographic and behavioral characteristics. Participants: College students aged 18 or older were randomly selected to participate in a health behavior survey at a southeastern university in September…

  16. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus.

    PubMed

    Lo, Janet; Lu, Michael T; Kim, Elli A; Nou, Eric; Hallett, Travis R; Park, Jakob; Hoffmann, Udo; Grinspoon, Steven K

    2016-04-01

    Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy. PMID:27419149

  17. Kinetics and inhibition of reverse transcriptase from human and simian immunodeficiency viruses.

    PubMed Central

    Wu, J C; Chernow, M; Boehme, R E; Suttmann, R T; McRoberts, M J; Prisbe, E J; Matthews, T R; Marx, P A; Chuang, R Y; Chen, M S

    1988-01-01

    Reverse transcriptase from the simian immunodeficiency virus (SIV) was found to have kinetic behavior similar to that of enzyme from the human immunodeficiency virus (HIV). Michaelis constants for the substrates TTP and dGTP and inhibition constants for the inhibitors 3'-azido-3'-deoxythymidine 5'-triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, and 2'-3'-dideoxyguanosine 5'-triphosphate were obtained for SIV reverse transcriptase and were found to be similar to the corresponding values for HIV reverse transcriptase. Thus, the interaction of SIV reverse transcriptase with nucleotide analogs appears to be indistinguishable from that of the HIV enzyme, suggesting that SIV/simian acquired immunodeficiency syndrome (SAIDS) is a potentially good model of AIDS. PMID:2469388

  18. Association of infections with human immunodeficiency virus and human papillomavirus in Honduras.

    PubMed

    Ferrera, A; Melchers, W J; Velema, J P; Figueroa, M

    1997-08-01

    The etiologic role of the oncogenic types of human papillomavirus (HPV) in the development of cervical cancer has been widely proven. Since this cancer occurs more frequently in immunosuppressed individuals, we sought to evaluate the prevalence of HPV infection among human immunodeficiency virus (HIV)-infected and HIV-noninfected prostitutes in Tegucigalpa, Honduras. Cervical scrapes were collected from 23 HIV-seropositive and 28 HIV-seronegative prostitutes for HPV DNA detection by the polymerase chain reaction. Fifty-six percent of the HIV-seropositive women and only 18% of the seronegative women were HPV DNA positive (odds ratio = 6.0). In addition, there was a significant association between seropositivity for HIV with a history of sexually transmitted diseases (P < 0.01). Our data confirm the association between infections with HIV and HPV.

  19. A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus

    PubMed Central

    1989-01-01

    In vitro infection by the human immunodeficiency virus (HIV) of CD4+ H9 lymphoblasts is inhibited by a mannose-binding protein (MBP) purified from human serum. In addition, MBP is able to selectively bind to HIV- infected H9 cells and HIV-infected cells from the monocyte cell line U937. These results indicate MBP most likely recognizes high mannose glycans known to be present on gp120 in the domain that is recognized by CD4 and thereby inhibits viral entry to susceptible cells. In support of this contention, recombinant gp120 binds directly to MBP; the binding is saturable, mannan inhibitable, removed by N-glycanase treatment, and dependent on divalent cations. PMID:2909656

  20. Neuropathological sequelae of Human Immunodeficiency Virus and apathy: A review of neuropsychological and neuroimaging studies.

    PubMed

    McIntosh, Roger C; Rosselli, Monica; Uddin, Lucina Q; Antoni, Michael

    2015-08-01

    Apathy remains a common neuropsychiatric disturbance in the Human Immunodeficiency Virus (HIV-1) despite advances in anti-retroviral treatment (ART). The goal of the current review is to recapitulate findings relating apathy to the deleterious biobehavioral effects of HIV-1 in the post-ART era. Available literatures demonstrate that the emergence of apathy with other neurocognitive and neuropsychiatric symptoms may be attributed to neurotoxic effects of viral proliferation, e.g., aggregative effect of Tat and gp120 on apoptosis, transport and other enzymatic reactions amongst dopaminergic neurons and neuroglia. An assortment of neuroimaging modalities converge on the severity of apathy symptoms associated with the propensity of the virus to replicate within frontal-striatal brain circuits that facilitate emotional processing. Burgeoning research into functional brain connectivity also supports the effects of microvascular and neuro-inflammatory injury linked to aging with HIV-1 on the presentation of neuropsychiatric symptoms. Summarizing these findings, we review domains of HIV-associated neurocognitive and neuropsychiatric impairment linked to apathy in HIV. Taken together, these lines of research suggest that loss of affective, cognitive and behavioral inertia is commensurate with the neuropathology of HIV-1.

  1. Infectious and Non-infectious Etiologies of Cardiovascular Disease in Human Immunodeficiency Virus Infection

    PubMed Central

    Chastain, Daniel B.; King, Travis S.; Stover, Kayla R.

    2016-01-01

    Background: Increasing rates of HIV have been observed in women, African Americans, and Hispanics, particularly those residing in rural areas of the United States. Although cardiovascular (CV) complications in patients infected with human immunodeficiency virus (HIV) have significantly decreased following the introduction of antiretroviral therapy on a global scale, in many rural areas, residents face geographic, social, and cultural barriers that result in decreased access to care. Despite the advancements to combat the disease, many patients in these medically underserved areas are not linked to care, and fewer than half achieve viral suppression. Methods: Databases were systematically searched for peer-reviewed publications reporting infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. Relevant articles cited in the retrieved publications were also reviewed for inclusion. Results: A variety of outcomes studies and literature reviews were included in the analysis. Relevant literature discussed the manifestations, diagnosis, treatment, and outcomes of infectious and non-infectious etiologies of cardiovascular disease in HIV-infected patients. Conclusion: In these medically underserved areas, it is vital that clinicians are knowledgeable in the manifestations, diagnosis, and treatment of CV complications in patients with untreated HIV. This review summarizes the epidemiology and causes of CV complications associated with untreated HIV and provide recommendations for management of these complications. PMID:27583063

  2. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice

    PubMed Central

    Wu, Tao; Heuillard, Emilie; Lindner, Véronique; Bou About, Ghina; Ignat, Mihaela; Dillenseger, Jean-Philippe; Anton, Nicolas; Dalimier, Eugénie; Gossé, Francine; Fouré, Gael; Blindauer, Franck; Giraudeau, Céline; El-Saghire, Hussein; Bouhadjar, Mourad; Calligaro, Cynthia; Sorg, Tania; Choquet, Philippe; Vandamme, Thierry; Ferrand, Christophe; Marescaux, Jacques; Baumert, Thomas F.; Diana, Michele; Pessaux, Patrick; Robinet, Eric

    2016-01-01

    The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging. PMID:27739457

  3. Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

    PubMed Central

    Sun, Hsin-Yun; Sheng, Wang-Huei; Tsai, Mao-Song; Lee, Kuan-Yeh; Chang, Sui-Yuan; Hung, Chien-Ching

    2014-01-01

    Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients. PMID:25356024

  4. Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.

    PubMed Central

    Delwart, E L; Pan, H; Sheppard, H W; Wolpert, D; Neumann, A U; Korber, B; Mullins, J I

    1997-01-01

    The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies. PMID:9311829

  5. Molecular Characterization of the Human Immunodeficiency Virus Type 1 in Women and Their Vertically Infected Children.

    PubMed

    Vaz, Sara Nunes; Giovanetti, Marta; Rego, Filipe Ferreira de Almeida; Oliveira, Tulio de; Danaviah, Siva; Gonçalves, Maria Luiza Freire; Alcantara, Luiz Carlos Junior; Brites, Carlos

    2015-10-01

    Approximately 35 million people worldwide are infected with human immunodeficiency virus (HIV) around 3.2 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all infections in children. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Samples from 19 HIV-1-infected families were collected. DNA was extracted and fragments from gag, pol, and env were amplified and sequenced directly. Phylogenetic reconstruction was performed. Drug resistance analyses were performed in pol and env sequences. We found 82.1% of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance-associated mutations in pol sequences was identified. Of the drug-naive children 33.3% presented at least one mutation related to protease inhibitor/nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations. PMID:26200738

  6. Cost and safety of assisted reproductive technologies for human immunodeficiency virus-1 discordant couples.

    PubMed

    Wu, Ming-Yih; Ho, Hong-Nerng

    2015-05-12

    Due to significant advances in the treatment of human immunodeficiency virus type-1 (HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a normal life expectancy. Hence, more and more HIV-1 discordant couples in Taiwan and the rest of the world are seeking fertility assistance. Pre-treatment of highly active antiretroviral therapy (HAART) combined with sperm washing and RT-polymerase chain reaction examination for HIV-1 viral load has become the standard procedure to assist them to conceive. However, in order to reduce the transmission risk to the lowest level for the couple and to diminish the cost of health care for the insurance institutes or government, in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) therapy provides the ideal solution for HIV-1 discordant couples with infected men. Intrauterine insemination (IUI) theoretically introduces more than 10(7) times of sperm counts or semen volume to uninfected women vs IVF-ICSI. However, since some regimens of HAART may significantly decrease the sperm motility, compared to IVF-ICSI, IUI only produces 1/5 to 1/2 pregnancy rates per cycle. Given the risk of seroconversion of HIV infection which actually happens after successful treatment, IVF-ICSI for these HIV-1 seropositive men is more cost-effective and should be the first line treatment for these cases.

  7. Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures.

    PubMed Central

    Langhoff, E; Terwilliger, E F; Bos, H J; Kalland, K H; Poznansky, M C; Bacon, O M; Haseltine, W A

    1991-01-01

    The ability of the human immunodeficiency virus type 1 (HIV-1) to replicate in primary blood dendritic cells was investigated. Dendritic cells compose less than 1% of the circulating leukocytes and are nondividing cells. Highly purified preparations of dendritic cells were obtained using recent advances in cell fractionation. The results of these experiments show that dendritic cells, in contrast to monocytes and T cells, support the active replication of all strains of HIV-1 tested, including T-cell tropic and monocyte/macrophage tropic isolates. The dendritic cell cultures supported much more virus production than did cultures of primary unseparated T cells, CD4+ T cells, and adherent as well as nonadherent monocytes. Replication of HIV-1 in dendritic cells produces no noticeable cytopathic effect nor does it decrease total cell number. The ability of the nonreplicating dendritic cells to support high levels of replication of HIV-1 suggests that this antigen-presenting cell population, which is also capable of supporting clonal T-cell growth, may play a central role in HIV pathogenesis, serving as a source of continued infection of CD4+ T cells and as a reservoir of virus infection. Images PMID:1910172

  8. Committee opinion no: 635: Prenatal and perinatal human immunodeficiency virus testing: expanded recommendations.

    PubMed

    2015-06-01

    Given the enormous advances in the prevention of perinatal transmission of human immunodeficiency virus (HIV), it is clear that early identification and treatment of all pregnant women with HIV is the best way to prevent neonatal infection and also improve women's health. Furthermore, new evidence suggests that early initiation of antiretroviral therapy in the course of infection is beneficial for individuals infected with HIV and reduces the rate of sexual transmission to partners who are not infected. Screening should be performed after women have been notified that HIV screening is recommended for all pregnant patients and that they will receive an HIV test as part of the routine panel of prenatal tests unless they decline (opt-out screening). Obstetrician-gynecologists or other obstetric providers should follow opt-out prenatal HIV screening where legally possible. Repeat HIV testing in the third trimester is recommended for women in areas with high HIV incidence or prevalence and women known to be at risk of acquiring HIV infection. Women who were not tested earlier in pregnancy or whose HIV status is otherwise undocumented should be offered rapid screening on labor and delivery using the opt-out approach where allowed. If a rapid HIV test result in labor is reactive, antiretroviral prophylaxis should be immediately initiated while waiting for supplemental test results. If the diagnosis of HIV infection is established, the woman should be linked into ongoing care with a specialist in HIV care for comanagement.

  9. Molecular Characterization of the Human Immunodeficiency Virus Type 1 in Women and Their Vertically Infected Children

    PubMed Central

    Vaz, Sara Nunes; Giovanetti, Marta; Rego, Filipe Ferreira de Almeida; de Oliveira, Tulio; Danaviah, Siva; Gonçalves, Maria Luiza Freire; Alcantara, Luiz Carlos Junior

    2015-01-01

    Abstract Approximately 35 million people worldwide are infected with human immunodeficiency virus (HIV) around 3.2 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all infections in children. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Samples from 19 HIV-1-infected families were collected. DNA was extracted and fragments from gag, pol, and env were amplified and sequenced directly. Phylogenetic reconstruction was performed. Drug resistance analyses were performed in pol and env sequences. We found 82.1% of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance-associated mutations in pol sequences was identified. Of the drug-naive children 33.3% presented at least one mutation related to protease inhibitor/nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations. PMID:26200738

  10. Cost and safety of assisted reproductive technologies for human immunodeficiency virus-1 discordant couples.

    PubMed

    Wu, Ming-Yih; Ho, Hong-Nerng

    2015-05-12

    Due to significant advances in the treatment of human immunodeficiency virus type-1 (HIV-1), HIV-1 infection gradually has become a treatable chronic disease. Successfully treated HIV-positive individuals can have a normal life expectancy. Hence, more and more HIV-1 discordant couples in Taiwan and the rest of the world are seeking fertility assistance. Pre-treatment of highly active antiretroviral therapy (HAART) combined with sperm washing and RT-polymerase chain reaction examination for HIV-1 viral load has become the standard procedure to assist them to conceive. However, in order to reduce the transmission risk to the lowest level for the couple and to diminish the cost of health care for the insurance institutes or government, in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) therapy provides the ideal solution for HIV-1 discordant couples with infected men. Intrauterine insemination (IUI) theoretically introduces more than 10(7) times of sperm counts or semen volume to uninfected women vs IVF-ICSI. However, since some regimens of HAART may significantly decrease the sperm motility, compared to IVF-ICSI, IUI only produces 1/5 to 1/2 pregnancy rates per cycle. Given the risk of seroconversion of HIV infection which actually happens after successful treatment, IVF-ICSI for these HIV-1 seropositive men is more cost-effective and should be the first line treatment for these cases. PMID:25964879

  11. [Range of neuromuscular involvement in 47 patients infected with the human immunodeficiency virus].

    PubMed

    Ghika-Schmid, F; Kuntzer, T; Chave, J P; Miklossy, J; Regli, F

    1994-05-14

    Over a 30 month period, 47 out of 749 patients infected with the human immunodeficiency virus had various neuromuscular symptoms. Based on clinical and electrophysiological data, 47% had distal symmetric polyneuropathy, 11% chronic inflammatory demyelinating polyneuropathy (CIDP), 8.5% toxic neuropathy related to 2-3-dideoxyinosine (DDI), 8.5% cranial neuropathy, 8.5% mononeuropathy multiplex or isolated focal neuropathy, 8.5% progressive lumbosacral polyradiculopathy, and 8.5% myopathy. Half of the patients exhibited previous or concomitant signs of central nervous system involvement and 18 patients died during the study period. CIDP and cranial neuropathies usually appeared early in the course of the disease and consequently showed neurological improvement. Nerve conduction studies of DDI related toxic neuropathies showed distal axono-myelinic sensitivo-motor neuropathy, differing from CIDP by the absence of a conduction block. Distal symmetric polyneuropathies, frequent in the advanced systemic illness, do not systematically require an extended workup, but more unusual peripheral neuropathies which might be treatable necessitate further investigations (electromyography, radiology, serological blood tests; protein chemistry and routine workup of the cerebrospinal fluid). For example, progressive lumbosacral polyradiculopathies responded to early treatment, with a better outcome in one case of herpetic origin than in another case due to cytomegalovirus infection. Our observations suggest that myopathies in HIV infected patients should first be tackled by temporary interruption of virostatic medication, followed by muscle biopsy if the symptoms persist. PMID:8209201

  12. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in connection with the performance of any program or activity relating to infection with the HIV,...

  13. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... immunodeficiency virus to public health authorities. (a) In the case of any record which is maintained in connection with the performance of any program or activity relating to infection with the HIV,...

  14. Species-Specific Metastasis of Human Tumor Cells in the Severe Combined Immunodeficiency Mouse Engrafted with Human Tissue

    NASA Astrophysics Data System (ADS)

    Shtivelman, Emma; Namikawa, Reiko

    1995-05-01

    We have attempted to model human metastatic disease by implanting human target organs into the immunodeficient C.B-17 scid/scid (severe combined immunodeficiency; SCID) mouse, creating SCID-hu mice. Preferential metastasis to implants of human fetal lung and human fetal bone marrow occurred after i.v. injection of human small cell lung cancer (SCLC) cells into SCID-hu mice; the homologous mouse organs were spared. Clinically more aggressive variant SCLC cells metastasized more efficiently to human fetal lung implants than did cells from classic SCLC. Metastasis of variant SCLC to human fetal bone marrow was enhanced in SCID-hu mice exposed to γ-irradiation or to interleukin 1α. These data indicate that the SCID-hu mice may provide a model in which to study species- and tissue-specific steps of the human metastatic process.

  15. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock.

    PubMed

    Nandy, Sneha; Shah, Ira

    2015-01-01

    Human immunodeficiency virus (HIV)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), Cryptococcus neoformans, Kaposi's sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis. PMID:26985424

  16. Pre-exposure prophylaxis for human immunodeficiency virus: the past, present, and future.

    PubMed

    Castel, Amanda D; Magnus, Manya; Greenberg, Alan E

    2014-12-01

    This article presents an overview of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention. The authors describe the past animal and human research that has been conducted that informs our current understanding of PrEP; summarize ongoing research in the area, including describing new regimens and delivery mechanisms being studied for PrEP; and highlight key issues that must be addressed in order to implement and optimize the use of this HIV prevention tool.

  17. Molecular biology of the human immunodeficiency virus type 1

    SciTech Connect

    Haseltine, W.A. )

    1991-07-01

    The immunodeficiency virus type 1 ia a complex retrovirus. In addition to genes that specify the proteins of the virus particle and the replicative enzymes common to all retroviruses, HIV-1 specifies at least six additional proteins that regulate the virus cycle. Two of these regulatory genes, tat and rev, specify proteins essential for replication. These proteins bind to specific sequences of newly synthesized virus RNA and profoundly affect virus protein expression. Tat and rev appear to be prototypes of novel eukaryotic regulatory proteins. These two genes may play a central role in regulating the rate of virus replication. Three other viral genes, vif, vpu, and vpr, affect the assembly and replication capacity of newly made virus particles. These genes may play a critical role in spread of the virus from tissue to tissue and from person to person. Our understanding of the contribution of each of the virus structural proteins and regulatory genes to the complex life cycle of the virus in natural infections is incomplete. However, enough insight has been gained into the structure and function of each of these components to provide a firm basis for rational antiviral drug development.

  18. Effects of long terminal repeat mutations on human immunodeficiency virus type 1 replication.

    PubMed Central

    Lu, Y; Stenzel, M; Sodroski, J G; Haseltine, W A

    1989-01-01

    The effects of deletions within three functional regions of the long terminal repeat of human immunodeficiency virus type 1 upon the ability of the long terminal repeat to direct production of the chloramphenicol acetyltransferase gene product and upon the ability of viruses that carry the mutations to replicate in human cell lines was investigated. The results show that the enhancer and TATAA sequences were required for efficient virus replication. Deletion of the negative regulatory element (NRE) yielded a virus that replicated more rapidly than did an otherwise isogeneic NRE-positive virus. The suppressive effect of the NRE did not depend upon the negative regulatory gene (nef), as both NRE-positive and NRE-negative viruses were defective for nef. We conclude that factors specified by the cell interact with the NRE sequences to retard human immunodeficiency virus type 1 replication. PMID:2760991

  19. Infectious Simian/Human Immunodeficiency Virus with Human Immunodeficiency Virus Type 1 Subtype C from an African Isolate: Rhesus Macaque Model

    PubMed Central

    Ndung'u, Thumbi; Lu, Yichen; Renjifo, Boris; Touzjian, Neal; Kushner, Nicholas; Pena-Cruz, Victor; Novitsky, Vladimir A.; Lee, Tun-Hou; Essex, Max

    2001-01-01

    Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 56% of all infections in the HIV and AIDS pandemic. It is the predominant subtype in the rapidly expanding epidemic in southern Africa. To develop a relevant model that would facilitate studies of transmission, pathogenesis, and vaccine development for this subtype, we generated SHIVMJ4, a simian/human immunodeficiency virus (SHIV) chimera based on HIV-1 subtype C. SHIVMJ4 contains the majority of env, the entire second exon of tat, and a partial sequence of the second exon of rev, all derived from a CCR5-tropic, primary isolate envelope clone from southern Africa. SHIVMJ4 replicated efficiently in human, rhesus, and pig-tailed macaque peripheral blood mononuclear cells (PBMCs) in vitro but not in CEMx174 cells. To assess in vivo infectivity, SHIVMJ4 was intravenously inoculated into four rhesus macaques (Macaca mulatta). All four animals became infected as determined through virus isolation, PCR analysis, and viral loads of 107 to 108 copies of viral RNA per ml of plasma during the primary infection phase. We have established a CCR5-tropic SHIVMJ4/rhesus macaque model that may be useful in the studies of HIV-1 subtype C immunology and biology and may also facilitate the evaluation of vaccines to control the spread of HIV-1 subtype C in southern Africa and elsewhere. PMID:11689623

  20. Human CRM1 Augments Production of Infectious Human and Feline Immunodeficiency Viruses from Murine Cells

    PubMed Central

    Elinav, Hila; Wu, Yuanfei; Coskun, Ayse; Hryckiewicz, Katarzyna; Kemler, Iris; Hu, Yani; Rogers, Hilary; Hao, Bing; Ben Mamoun, Choukri; Poeschla, Eric

    2012-01-01

    Productive replication of human immunodeficiency virus type 1 (HIV-1) occurs efficiently only in humans. The posttranscriptional stages of the HIV-1 life cycle proceed poorly in mouse cells, with a resulting defect in viral assembly and release. Previous work has shown that the presence of human chromosome 2 increases HIV-1 production in mouse cells. Recent studies have shown that human chromosome region maintenance 1 (hCRM1) stimulates Gag release from rodent cells. Here we report that expressions of hCRM1 in murine cells resulted in marked increases in the production of infectious HIV-1 and feline immunodeficiency virus (FIV). HIV-1 production was also increased by hSRp40, and a combination of hCRM1 and hSRp40 resulted in a more-than-additive effect on HIV-1 release. In contrast, the overexpression of mouse CRM1 (mCRM1) minimally affected HIV-1 and FIV production and did not antagonize hCRM1. In the presence of hCRM1 there were large increases in the amounts of released capsid, which paralleled the increases in the infectious titers. Consistent with this finding, the ratios of unspliced to spliced HIV-1 mRNAs in mouse cells expressing hCRM1 and SRp40 became similar to those of human cells. Furthermore, imaging of intron-containing FIV RNA showed that hCRM1 increased RNA export to the cytoplasm.By testing chimeras between mCRM1 and hCRM1 and comparing those sequences to feline CRM1, we mapped the functional domain to HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) repeats 4A to 9A and a triple point mutant in repeat 9A, which showed a loss of function. Structural analysis suggested that this region of hCRM1 may serve as a binding site for viral or cellular factors to facilitate lentiviral RNA nuclear export. PMID:22933280

  1. The genetic immunodeficiency disease, leukocyte adhesion deficiency, in humans, dogs, cattle, and mice.

    PubMed

    Gu, Yu-Chen; Bauer, Thomas R; Ackermann, Mark R; Smith, C Wayne; Kehrli, Marcus E; Starost, Matthew F; Hickstein, Dennis D

    2004-08-01

    This review highlights the genotype-phenotype relationship of the genetic immunodeficiency disease leukocyte adhesion deficiency (LAD) in humans, dogs, cattle, and mice, and provides assessment of the opportunities that each animal species provides in the understanding of leukocyte biology and in developing new therapeutic approaches to LAD in humans. This comparison is important since animal models of genetic diseases in humans provide the opportunity to test new therapeutic approaches in an appropriate, disease-specific model. The success of this approach is dependent on the relationship of the phenotype in the animal to the phenotype of the disease in humans. PMID:15357315

  2. Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication.

    PubMed Central

    Romero, D L; Busso, M; Tan, C K; Reusser, F; Palmer, J R; Poppe, S M; Aristoff, P A; Downey, K M; So, A G; Resnick, L

    1991-01-01

    Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection. Images PMID:1717988

  3. kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

    PubMed Central

    Chao, C C; Gekker, G; Hu, S; Sheng, W S; Shark, K B; Bu, D F; Archer, S; Bidlack, J M; Peterson, P K

    1996-01-01

    Microglial cells, the resident macrophages of the brain, play an important role in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of kappa opioid receptors (KORs) in human fetal microglia and inhibition of HIV-1 expression in acutely infected microglial cell cultures treated with KOR ligands. Using reverse transcriptase-polymerase chain reaction and sequencing analyses, we found that mRNA for the KOR was constitutively expressed in microglia and determined that the nucleotide sequence of the open reading frame was identical to that of the human brain KOR gene. The expression of KOR in microglial cells was confirmed by membrane binding of [3H]U69,593, a kappa-selective ligand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1 SF162 strain. This antiviral effect of the kappa ligands was blocked by the specific KOR antagonist, nor-binaltrophimine. These findings suggest that kappa opioid agonists have immunomodulatory activity in the brain, and that these compounds could have potential in the treatment of HIV-1-associated encephalopathy. Images Fig. 2 Fig. 4 PMID:8755601

  4. Primary Neuritic Hansen's Disease presenting as Ulnar Nerve Abscess in a Human Immunodeficiency Virus Positive Patient.

    PubMed

    Karjigi, S; Herakal, K; Murthy, S C; Bathina, A; Kusuma, M R; Nikhil, K R Y

    2015-01-01

    Leprosy has been increasingly known to have an enigmatic relationship with human immunodeficiency virus infection. Co-infection may result in atypical manifestations of leprosy. A 45-year old human immunodeficiency virus-positive male; agricultural laborer presented with a swelling over right elbow, right hand deformity, generalized itching and recurrent vesicles overthe perinasal area. Clinical and investigational findings were consistent with mononeuritic type of Hansen's disease with right sided silent ulnar nerve abscess, partial claw hand. CD4+ count of the patientwas 430 cells/cmm. This patient also hadherpes simplex labialis, with HIV-associated pruritus. To the best of our knowledge such an atypical presentation has not been reported earlier. PMID:26999990

  5. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus.

    PubMed Central

    Garcia, J A; Wu, F K; Mitsuyasu, R; Gaynor, R B

    1987-01-01

    The human immunodeficiency virus (HIV) is a human retrovirus which is the etiologic agent of the acquired immunodeficiency syndrome. To study the cellular factors involved in the transcriptional regulation of this virus, we performed DNase I footprinting of the viral LTR using partially purified HeLa cell extracts. Five regions of the viral LTR appear critical for DNA binding of cellular proteins. These include the negative regulatory, enhancer, SP1, TATA and untranslated regions. Deletion mutagenesis of these binding domains has significant effects on the basal level of transcription and the ability to be induced by the viral tat protein. Mutations of either the negative regulatory or untranslated regions affect factor binding to the enhancer region. In addition, oligonucleotides complementary to several of the binding domains specifically compete for factor binding. These results suggest that interactions between several distinct cellular proteins are required for HIV transcriptional regulation. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 6. PMID:3428273

  6. Human immunodeficiency virus superinfection and recombination: current state of knowledge and potential clinical consequences.

    PubMed

    Blackard, Jason T; Cohen, Daniel E; Mayer, Kenneth H

    2002-04-15

    Superinfection with multiple strains or subtypes of the human and simian immunodeficiency viruses has been documented. Recent increases in the prevalences of both unprotected anal intercourse and sexually transmitted diseases among men who have sex with men indicate that these men continue to practice unsafe sex and, therefore, are at risk for superinfection with the human immunodeficiency virus (HIV). Recurrent exposure to HIV among seropositive individuals who engage in high-risk behaviors can have serious consequences, because superinfection is a necessary first step for viral recombination to occur. Recombination may produce more virulent viruses, drug-resistant viruses, or viruses with altered cell tropism. Additionally, recombinant viruses and superinfection can accelerate disease progression and increase the likelihood of sexual transmission by increasing virus load in the blood and genital tract. The extent of superinfection and recombination in persons living with HIV is unknown. The implications of HIV superinfection and the generation of recombinant viruses are discussed. PMID:11915000

  7. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus.

    PubMed

    Garcia, J A; Wu, F K; Mitsuyasu, R; Gaynor, R B

    1987-12-01

    The human immunodeficiency virus (HIV) is a human retrovirus which is the etiologic agent of the acquired immunodeficiency syndrome. To study the cellular factors involved in the transcriptional regulation of this virus, we performed DNase I footprinting of the viral LTR using partially purified HeLa cell extracts. Five regions of the viral LTR appear critical for DNA binding of cellular proteins. These include the negative regulatory, enhancer, SP1, TATA and untranslated regions. Deletion mutagenesis of these binding domains has significant effects on the basal level of transcription and the ability to be induced by the viral tat protein. Mutations of either the negative regulatory or untranslated regions affect factor binding to the enhancer region. In addition, oligonucleotides complementary to several of the binding domains specifically compete for factor binding. These results suggest that interactions between several distinct cellular proteins are required for HIV transcriptional regulation.

  8. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future.

    PubMed

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-05-12

    The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a "Mayo Model" of HIV care that exceeds national outcomes and may be applicable in other settings.

  9. A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization.

    PubMed Central

    Broliden, P A; Ljunggren, K; Hinkula, J; Norrby, E; Akerblom, L; Wahren, B

    1990-01-01

    Monoclonal antibodies (MAbs) were raised against human immunodeficiency virus type 1 gp120. One MAb, P4/D10, was found to mediate highly efficient antibody-dependent cellular cytotoxicity and virus neutralization. The reactivity was located to a major neutralizing region (amino acids 304 to 323) on gp120. Five other MAbs with a similar epitopic reactivity did not show any antibody-dependent cellulan cytotoxicity activity but had a virus-neutralizing capacity. PMID:2296090

  10. Human Immunodeficiency Virus Type 1 Coat Protein Neurotoxicity Mediated by Nitric Oxide in Primary Cortical Cultures

    NASA Astrophysics Data System (ADS)

    Dawson, Valina L.; Dawson, Ted M.; Uhl, George R.; Snyder, Solomon H.

    1993-04-01

    The human immunodeficiency virus type 1 coat protein, gp120, kills neurons in primary cortical cultures at low picomolar concentrations. The toxicity requires external glutamate and calcium and is blocked by glutamate receptor antagonists. Nitric oxide (NO) contributes to gp120 toxicity, since nitroarginine, an inhibitor of NO synthase, prevents toxicity as does deletion of arginine from the incubation medium and hemoglobin, which binds NO. Superoxide dismutase also attenuates toxicity, implying a role for superoxide anions.

  11. Human immunodeficiency virus testing for patient-based and population-based diagnosis.

    PubMed

    Albritton, W L; Vittinghoff, E; Padian, N S

    1996-10-01

    Laboratory testing for human immunodeficiency virus (HIV) has been introduced for individual patient-based diagnosis as well as high-risk and low-risk population-based screening. The choice of test, confirmatory algorithm, and interpretative criteria used depend on the clinical setting. In the context of general population-based testing, factors affecting test performance will have to be considered carefully in the development of testing policy. PMID:8843247

  12. Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins

    SciTech Connect

    Korber, Bette T.; Perkins, Simon; Bhattacharya, Tanmoy; Fischer, William M.; Theiler, James; Letvin, Norman; Haynes, Barton F.; Hahn, Beatrice H.; Yusim, Karina; Kuiken, Carla

    2012-02-21

    The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  13. Identification of three feline immunodeficiency virus (FIV) env gene subtypes and comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns.

    PubMed Central

    Sodora, D L; Shpaer, E G; Kitchell, B E; Dow, S W; Hoover, E A; Mullins, J I

    1994-01-01

    Feline immunodeficiency virus (FIV) is a lentivirus associated with AIDS-like illnesses in cats. As such, FIV appears to be a feline analog of human immunodeficiency virus (HIV). A hallmark of HIV infection is the large degree of viral genetic diversity that can develop within an infected individual and the even greater and continually increasing level of diversity among virus isolates from different individuals. Our goal in this study was to determine patterns of FIV genetic diversity by focusing on a 684-nucleotide region encompassing variable regions V3, V4, and V5 of the FIV env gene in order to establish parallels and distinctions between FIV and HIV type 1 (HIV-1). Our data demonstrate that, like HIV-1, FIV can be separated into distinct envelope sequence subtypes (three are described here). Similar to that found for HIV-1, the pairwise sequence divergence within an FIV subtype ranged from 2.5 to 15.0%, whereas that between subtypes ranged from 17.8 to 26.2%. However, the high number of synonymous nucleotide changes among FIV V3 to V5 env sequences may also include a significant number of back mutations and suggests that the evolutionary distances among FIV subtypes are underestimated. Although only a few subtype B viruses were available for examination, the pattern of diversity between the FIV A and B subtypes was found to be significantly distinct; subtype B sequences had proportionally fewer mutations that changed amino acids, compared with silent changes, suggesting a more advanced state of adaptation to the host. No similar distinction was evident for HIV-1 subtypes. The diversity of FIV genomes within individual infected cats was found to be as high as 3.7% yet twofold lower than that within HIV-1-infected people over a comparable region of the env gene. Despite these differences, significant parallels between patterns of FIV evolution and HIV-1 evolution exist, indicating that a wide array of potentially divergent virus challenges need to be considered

  14. Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type

    NASA Technical Reports Server (NTRS)

    He, X. M.; Ruker, F.; Casale, E.; Carter, D. C.

    1992-01-01

    The three-dimensional structure of a human monoclonal antibody (Fab), which binds specifically to a major epitope of the transmembrane protein gp41 of the human immunodeficiency virus type 1, has been determined by crystallographic methods to a resolution of 2.7 A. It has been previously determined that this antibody recognizes the epitope SGKLICTTAVPWNAS, belongs to the subclass IgG1 (kappa), and exhibits antibody-dependent cellular cytotoxicity. The quaternary structure of the Fab is in an extended conformation with an elbow bend angle between the constant and variable domains of 175 degrees. Structurally, four of the hypervariable loops can be classified according to previously recognized canonical structures. The third hypervariable loops of the heavy (H3) and light chain (L3) are structurally distinct. Hypervariable loop H3, residues 102H-109H, is unusually extended from the surface. The complementarity-determining region forms a hydrophobic binding pocket that is created primarily from hypervariable loops L3, H3, and H2.

  15. Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection

    PubMed Central

    Saunders, Kevin O.; Wang, Lingshu; Joyce, M. Gordon; Yang, Zhi-Yong; Balazs, Alejandro B.; Cheng, Cheng; Ko, Sung-Youl; Kong, Wing-Pui; Rudicell, Rebecca S.; Georgiev, Ivelin S.; Duan, Lijie; Foulds, Kathryn E.; Donaldson, Mitzi; Xu, Ling; Schmidt, Stephen D.; Todd, John-Paul; Baltimore, David; Roederer, Mario; Haase, Ashley T.; Kwong, Peter D.; Rao, Srinivas S.

    2015-01-01

    ABSTRACT Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 μg/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled. IMPORTANCE Sustained interventions that can prevent HIV-1 infection are needed to halt the spread of the HIV-1 pandemic. The protective capacity of anti-HIV antibody gene therapy has been established in mouse models of HIV-1 infection but has not been established for primates. We show here a proof-of-concept that gene transfer of anti-HIV antibody genes can protect against infection by viruses that cause AIDS in primates when host immune responses are controlled. PMID:26041300

  16. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    PubMed

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection.

  17. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    PubMed

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. PMID:27515208

  18. Malignancies in human immunodeficiency virus infected patients in India: Initial experience in the HAART era

    PubMed Central

    Sharma, Surendra K.; Soneja, Manish; Ranjan, Sanjay

    2015-01-01

    Background & objectives: Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India. Methods: Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done. Results: The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/µl compared to 164 (IQR 86-243) cells/µl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkin's lymphoma (16), carcinoma cervix (3), Hodgkin's lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposi's sarcoma. Interpretation & conclusions: Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies. PMID:26658591

  19. 1'S-1'-acetoxychavicol acetate isolated from Alpinia galanga inhibits human immunodeficiency virus type 1 replication by blocking Rev transport.

    PubMed

    Ye, Ying; Li, Baoan

    2006-07-01

    AIDS remains a major global health concern. Despite a number of therapeutic advancements, there is still an urgent need to develop a new class of therapy for human immunodeficiency virus (HIV). Here, it was shown that 1'S-1'-acetoxychavicol acetate (ACA), a small molecular compound isolated from the rhizomes of Alpinia galanga, inhibited Rev transport at a low concentration by binding to chromosomal region maintenance 1 and accumulating full-length HIV-1 RNA in the nucleus, resulting in a block in HIV-1 replication in peripheral blood mononuclear cells. Additionally, ACA and didanosine acted synergistically to inhibit HIV-1 replication. Thus, ACA may represent a novel treatment for HIV-1 infection, especially in combination with other anti-HIV drugs.

  20. Comparative analysis of genetically engineered immunodeficient mouse strains as recipients for human myoblast transplantation.

    PubMed

    Silva-Barbosa, Suse D; Butler-Browne, Gillian S; Di Santo, James P; Mouly, Vincent

    2005-01-01

    The development of an optimized animal model for the in vivo analysis of human muscle cells remains an important goal in the search of therapy for muscular dystrophy. Here we examined the efficiency of human myoblast xenografts in three distinct immunodeficient mouse models. We found that different conditioning regimes used to provoke host muscle regeneration (i.e., cardiotoxin versus cryodamage) had a marked impact on xenograft success. Tibialis anterior muscle of Rag2-, Rag-/gammac-, and Rag-/gammac-/C5- mice was treated by cardiotoxin or cryodamage, submitted to enzymatic digestion, and analyzed by cytofluorometry to quantitate inflammatory cells. Human myoblasts were injected into pretreated muscles from immunodeficient recipients and the cell engraftment evaluated by immunocytochemistry, 4-8 weeks after transplantation. Donor cell differentiation and dispersion within the host muscles was also investigated. Host regeneration in cardiotoxin-treated mice was accompanied by a higher inflammatory cell infiltration when compared to that induced by cryodamage. Accordingly, when compared to the cardiotoxin group, more human myogenic cells were found after cryodamage. When the distinct immunodeficient mice were compared, we found that the alymphoid strain lacking the complement component C5 (Rag-/gammac-/C5- mice) was the most efficient host for human muscle xenografts, when compared with C5(+)Rag-/gammac- mice or Rag- mice. Our results demonstrate that cryolesion-conditioned muscles of Rag-/gammac-/C5- mice provide the best environment for long-term in vivo human myoblast differentiation, opening the way for a novel approach to study the pathophysiology of human muscle disorders. PMID:16285254

  1. Aggregation of human immunodeficiency virus type 1 by human salivary secretions.

    PubMed

    Bergey, E J; Cho, M I; Hammarskjöld, M L; Rekosh, D; Levine, M J; Blumberg, B M; Epstein, L G

    1993-01-01

    Human immunodeficiency virus (HIV-1) is generally transmitted by parenteral contact with infected body secretions. Although extensive epidemiological data and familial studies have failed to provide any conclusive data that saliva may act as a vehicle for transmission of AIDS, both professional and public anxieties remain. The present study, as well as others, suggests that salivary secretions may act as inhibitors of HIV-1 replication in vitro. In our study, the inhibitory activity was determined to be associated mainly with secretions obtained from the human submandibular-sublingual glands. Human submandibular-sublingual (HSMSL) and parotid (HPS) salivas were collected and tested for their ability to modulate the replication of HIV-1, using a plaque assay on HeLa/CD4+ cell monolayers. Initial results examining freshly collected salivary samples from ten individuals confirmed the results previously obtained by Fox et al. (1988, 1989). An average plaque reduction of approximately 66% was obtained with HSMSL, in contrast to 34% reduction obtained with HPS. Titration of the inhibitory activity in HSMSL showed detectable levels at a 1:500 dilution. Comparison of inhibitory activity of dialyzed and lyophilized saliva to fresh saliva indicated little difference between the two samples when filtration occurred after the addition of HIV-1. However, the effect of filtration was significantly diminished in the lyophilized samples. Electron microscopic examination of the saliva-HIV incubates revealed the aggregation/entrapment of virus particles by salivary components. These results suggest that human salivary secretions (with HSMSL > HPS) may have a role in modulating the infectivity of HIV-1.

  2. [Gastric uptake of gallium67 in the human immunodeficiency virus infection].

    PubMed

    Escalera Temprado, T; Banzo Marraco, J; Abós Olivares, M D; Olave Rubio, M T; Prats Rivera, E; García López, F; Razola Alba, P

    2004-02-01

    Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease. In the frequent clinical situations with fever, lymph nodes and loss weight it is necessary to determine their etiology, for establishing a specific treatment. Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous process, which can accumulate Ga67, may be present in the patient with acquired immunodeficiency syndrome. We report 2 cases with gastric uptake in which endoscopy and biopsy was obtained. In the first one, with previous treatment with omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were normal and in the second patient an Helicobacter pylori infection was diagnosed. We think that gastric uptake of Ga67 in HIV patients, must indicate to the clinician to rule out associated pathologies.

  3. Psychological problems of families and health workers dealing with people infected with human immunodeficiency virus 1.

    PubMed

    Maj, M

    1991-03-01

    The psychological problems of the families of human immunodeficiency virus 1 (HIV-1)-infected people, and of the health workers taking care of them, have been addressed in a few empirical studies and in several anecdotal reports and theoretical contributions. Apparently, HIV-1 infection and acquired immunodeficiency syndrome (AIDS) are able to elicit a wide range of emotional reactions, from rejection and refusal to provide care to immersion in the infected person's needs and burnout. Since irrational fears and attitudes play an important role in conditioning these reactions, education may not be sufficient to change behaviour. Counselling sessions and mutual support groups are often the most appropriate contexts where fears and concerns can receive an individually tailored response, and where formal and informal caregivers can be helped to manage stress.

  4. Restoration of Viral Immunity in Immunodeficient Humans by the Adoptive Transfer of T Cell Clones

    NASA Astrophysics Data System (ADS)

    Riddell, Stanley R.; Watanabe, Kathe S.; Goodrich, James M.; Li, Cheng R.; Agha, Mounzer E.; Greenberg, Philip D.

    1992-07-01

    The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8^+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8^+ cytomegalovirus-specific CTL responses.

  5. Inactivation of human immunodeficiency virus (HIV) by ionizing radiation in body fluids and serological evidence

    SciTech Connect

    Bigbee, P.D.; Sarin, P.S.; Humphreys, J.C.; Eubanks, W.G.; Sun, D.; Hocken, D.G.; Thornton, A.; Adams, D.E.; Simic, M.G. )

    1989-11-01

    A method to use ionizing radiation to inactivate HIV (Human Immunodeficiency Virus) in human body fluids was studied in an effort to reduce the risk of accidental infection to forensic science laboratory workers. Experiments conducted indicate that an X-ray absorbed dose of 25 krad was required to completely inactivate HIV. This does not alter forensically important constituents such as enzymes and proteins in body fluids. This method of inactivation of HIV cannot be used on body fluids which will be subjected to deoxyribonucleic acid (DNA) typing.

  6. Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection.

    PubMed

    Yeaman, Grant R; Howell, Alexandra L; Weldon, Sally; Demian, Douglas J; Collins, Jane E; O'Connell, Denise M; Asin, Susana N; Wira, Charles R; Fanger, Michael W

    2003-05-01

    Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection.

  7. Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection.

    PubMed

    Yeaman, Grant R; Howell, Alexandra L; Weldon, Sally; Demian, Douglas J; Collins, Jane E; O'Connell, Denise M; Asin, Susana N; Wira, Charles R; Fanger, Michael W

    2003-05-01

    Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection. PMID:12709027

  8. Transcription analysis of class II human leukocyte antigen genes from normal and immunodeficient B lymphocytes, using polymerase chain reaction.

    PubMed Central

    Bull, M; van Hoef, A; Gorski, J

    1990-01-01

    The RNA transcript levels of all human leukocyte antigen class II loci were determined from class II congenital immunodeficient B cells by polymerase chain reaction amplification of cDNA. No mRNA was observed under conditions in which 0.01% normal levels could be visualized. Pre-mRNA could be amplified from normal B cells but not from immunodeficient B cells, indicating a transcription defect. Images PMID:2113177

  9. Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world.

    PubMed

    Kaplan, J E; Hu, D J; Holmes, K K; Jaffe, H W; Masur, H; De Cock, K M

    1996-07-01

    More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.

  10. Epidemiology and seroprevalence of human immunodeficiency virus type 2.

    PubMed

    Kashyap, Bineeta; Gautam, Hitender; Bhalla, Preena

    2011-01-01

    HIV-2 infection is detected sporadically mostly from the southern states of India. We did a retrospective analysis to find the seroprevalence of HIV-2 in and around Delhi. The study included all attendees of an integrated counseling and testing center (ICTC) from January 2004 to January 2009. As per NACO guidelines, samples showing positive results in three rapid tests were declared HIV-positive. Samples that were reactive for HIV-2 were further confirmed by Western blot assay. 8.8% (n = 1,938) of the clients were reactive for HIV-1, 0.03% (n = 6) were reactive for HIV-2 and 0.005% (n = 1) had HIV-1 and HIV-2 coinfection. Spouses of only 2 cases were tested, both resulting as nonreactive. History of travel or past stay to endemic states was present in 57% cases. The commonest risk factor revealed in them was sexual contact with commercial sex workers (86%). As such, seroprevalence of HIV-2 is very low but continued surveillance is needed for HIV-2 to understand the epidemiology and natural history of this complex human pathogen.

  11. Pregnancy and Human Herpesvirus 8 Reactivation in Human Immunodeficiency Virus Type 1-Infected Women▿

    PubMed Central

    Lisco, Andrea; Barbierato, Massimo; Fiore, Josè R.; Gasperini, Paola ; Favia, Anna; Volpe, Anna; Chironna, Maria; Pastore, Giuseppe; Chieco-Bianchi, Luigi; Calabrò, Maria Luisa

    2006-01-01

    To investigate the impact of pregnancy on human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus type 1 (HIV-1)-infected women, the HHV-8 DNA presence and load were analyzed in peripheral blood mononuclear cells (PBMCs) and cervicovaginal secretions (CVSs) from 15 pregnant women coinfected with HIV-1 and HHV-8. HHV-8 detection was analyzed in relation to anti-HHV-8 antibodies and HIV-1-related parameters. Nucleotide sequence analysis of an ORFK1 hypervariable region of the HHV-8 strains was performed. HHV-8 was detected in maternal PBMCs (5/15 women) from the second trimester and in CVSs (5/15 women) mainly from the third trimester. The HHV-8 load significantly increased late in pregnancy in both maternal compartments and was associated with a significant increase in HIV-1 shedding in the genital tract. Antilytic antibodies were significantly more common in HHV-8 DNA-positive women. An elevated HHV-8 load was found in the PBMCs of an infant born to a mother with large amounts of HHV-8 in both compartments at delivery. Different ORFK1 subtypes were found in maternal samples, whereas the same subtype was identified in the mother-child pair. These data suggest that pregnancy may induce HHV-8 replication in HIV-1-infected women. An augmented HHV-8 load may, in turn, influence mother-to-child transmission, since one of the HIV-1-infected mothers with HHV-8 reactivation transmitted her ORFK1 subtype to the infant, who showed a high level of HHV-8 viremia indicative of a primary infection. This finding documents for the first time the perinatal transmission of a specific HHV-8 subtype. Vertical transmission may thus play a role in HHV-8 spread also in areas of subendemicity among HIV-1-infected women. PMID:16943357

  12. Human papillomavirus detection from human immunodeficiency virus-infected Colombian women's paired urine and cervical samples.

    PubMed

    Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A

    2013-01-01

    Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.

  13. Disguising the taste of antiretrovirals for pediatric patients infected with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: creative flavor compounding and techniques, part 2.

    PubMed

    Horace, Alexis E; Akbarian-Tefagh, Jessica

    2013-01-01

    Adherence to antiretrovirals for pediatric patients is challenging for a variety of reasons, many of which are quite obvious. The medication's taste and texture may contribute to a child's resistance to following their regimen. To make the problem of compliance even more complex, there are fewer pediatric-friendly formulations available and fewer alternative options for antiretrovirals when compared to formulations and alternatives available to adults. For the sake of compliance, it is vital that parents and/or caregivers be offered innovative ways to disguise the taste of antiretrovirals for pediatric patients infected with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome. Compounding pharmacists can play an important role in finding answers to this situation. This article provides an in-depth discussion on some of the specific flavoring and taste-masking options that are available in the effort to increase adherence in the pediatric patient population.

  14. Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome.

    PubMed

    Grinspoon, S; Corcoran, C; Stanley, T; Rabe, J; Wilkie, S

    2001-09-01

    Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency

  15. Severe combined immunodeficiency mouse and human psoriatic skin chimeras. Validation of a new animal model.

    PubMed Central

    Nickoloff, B. J.; Kunkel, S. L.; Burdick, M.; Strieter, R. M.

    1995-01-01

    Research into the cause and pathophysiological mechanisms underlying expression of psoriatric skin lesions has been hampered by lack of an appropriate animal model for this common and enigmatic cutaneous disease. These studies characterize normal skin, pre-psoriatic skin, and psoriatic plaque skin samples transplanted onto severe combined immunodeficiency mice. In this report we document that 1), normal, prepsoriatic, and psoriatic plaque keratome skin samples can be transplanted onto severe combined immunodeficiency mice reliably with high rates of graft survival (> 85%) and with reproducible changes consistently observed over prolonged periods of engraftment; 2), after transplantation, by clinical assessment and routine light microscopy, normal skin remained essentially normal whereas pre-psoriatic skin became thicker, and psoriatic plaque skin retained its characteristic plaque-type elevation and scale; 3), by using a panel of antibodies and immunohistochemical analysis, the overall phenotype of human cell types (including immunocytes) that persisted in the transplanted skin was remarkably similar to the immunophenotype of pretransplanted skin samples; 4), clearly recognized interface zones between human and murine skin within the epidermal and dermal compartments could be identified by routine microscopy and immunostaining, with focal areas of chimerism; and 5), elevated interleukin 8 cytokine levels were present in transplanted pre-psoriatic and psoriatic plaque skin samples. We conclude that there are many similarities between pre- and post-transplanted human samples of normal and psoriatic skin that are grafted onto severe combined immunodeficiency mice. Thus, we propose that this new animal model is appropriate for additional mechanistic-type studies designed to reveal the underlying genetic/etiological abnormality, as well as better illuminate the pathophysiological basis, for this important skin disease. Images Figure 1 Figure 2 Figure 3 PMID:7887440

  16. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy

    PubMed Central

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART. PMID:26933317

  17. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    PubMed

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.

  18. Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

    PubMed Central

    Chapel, A; Bensussan, A; Vilmer, E; Dormont, D

    1992-01-01

    By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1. Images PMID:1374814

  19. Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

    PubMed

    Chapel, A; Bensussan, A; Vilmer, E; Dormont, D

    1992-06-01

    By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated from human immunodeficiency virus (HIV)-negative donors, have been characterized and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1). Infected clones possess integrated provirus. Only six are able to replicate HIV-1, while seven may normally grow without cytopathic effect and without viral replication. These results argue that all CD4+ lymphocyte clones may be infectable but that a heterogeneity exists regarding their abilities to replicate HIV-1.

  20. Vulvar carcinoma in a 12-year-old girl with vertically acquired human immunodeficiency virus infection.

    PubMed

    Giaquinto, C; Del Mistro, A; De Rossi, A; Bertorelle, R; Giacomet, V; Ruga, E; Minucci, D

    2000-10-01

    We report the first case of a girl with vertically acquired human immunodeficiency virus (HIV) infection, who developed invasive squamous cell carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis covered the perianal area as well. She underwent a nonmutilating surgical excision of the infiltrating lesion. More than 3 years later, her clinical condition is excellent, although dysplastic, noninfiltrating multifocal lesions persist. This case highlights the need to perform careful periodic genital examinations in all HIV-infected children and adolescents born to HIV-positive mothers.

  1. Counseling patients seropositive for human immunodeficiency virus. An approach for medical practice.

    PubMed Central

    Coates, T. J.; Lo, B.

    1990-01-01

    Persons at risk for infection with the human immunodeficiency virus are being encouraged to learn their serostatus. While such knowledge can help patients seek appropriate medical care, it can also be distressing. We describe an approach, based on crisis counseling, for physicians to use in working with patients infected with HIV. It can help physicians in assisting patients with emotional reactions to the diagnosis as well as in directing patients to manage practical issues of concern. Methods for discussing safer sex or injection practices are also presented. PMID:2293468

  2. Medication adherence feedback intervention predicts improved human immunodeficiency virus clinical markers.

    PubMed

    Reich, Warren A

    2013-12-01

    Thirty-three participants in a human immunodeficiency virus (HIV) medication adherence feedback (MAF) intervention were compared with 58 HIV-positive non-participants in laboratory-tested CD4 and viral load. The intervention provided adherence feedback and counselling based on a visual display from an electronic pill bottle (MEMS(TM) ). Multiple regression controlling for baseline CD4 and showed that postintervention CD4 was higher for MAF participants than for non-MAF participants. Non-MAF participants' CD4 significantly declined over time. MAF participants were also less likely than non-MAF participants to have a detectable postintervention viral load.

  3. Neurobehavioral Manifestations of Human Immunodeficiency Virus/AIDS: Diagnosis and Treatment.

    PubMed

    Singer, Elyse J; Thames, April D

    2016-02-01

    Behavioral disorders are common in persons infected with human immunodeficiency virus (HIV). The differential includes preexisting psychiatric diseases, substance abuse, direct effects of HIV infection, opportunistic infection, and the adverse effects of medical therapies. Many patients have more than one contributing or comorbid problem to explain these behavioral changes. The differential should always include consideration of psychosocial, genetic, and medical causes of disease. Treatment strategies must take into account the coadministration of antiretroviral therapy and the specific neurologic problems common in patients infected with HIV. PMID:26613994

  4. Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.

    PubMed

    Bryant, Malcolm; Beard, Jennifer

    2016-02-01

    In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade.

  5. Mechanism of selective inhibition of human immunodeficiency virus by ingenol triacetate.

    PubMed Central

    Fujiwara, M; Ijichi, K; Tokuhisa, K; Katsuura, K; Shigeta, S; Konno, K; Wang, G Y; Uemura, D; Yokota, T; Baba, M

    1996-01-01

    Ingenol 3,5,20-triacetate (ITA), one of the ingenol derivatives, is a selective inhibitor of human immunodeficiency virus (HIV) replication in vitro. ITA inhibited the replication of HIV strains in MT-4 cells at concentrations of 0.051 to 0.65 microM. This concentration was approximately 10(3)-fold lower than its cytotoxic threshold. The mechanism of action of ITA is primarily attributed to the inhibition of viral adsorption to the host cells, but it is distinct from the mechanism of inhibition by other adsorption inhibitors. PMID:8787923

  6. One approach to care for patients infected with human immunodeficiency virus in an academic medical center.

    PubMed Central

    Jacobs, J. L.; Damson, L. C.; Rogers, D. E.

    1996-01-01

    The human immunodeficiency virus (HIV) epidemic poses unprecedented challenges to the health-care system. Caregivers must contend both with the complicated clinical syndromes associated with HIV infection and with issues that are central to the epidemic, such as discrimination, isolation, poverty, and substance abuse. Our HIV treatment program combines and enhances the resources of an academic medical center in a multidisciplinary care model. All patients, regardless of payor class, are offered services from 10 different disciplines. The same team of clinicians follows patients in the clinic and hospital. The program is flexible, non-hierarchical, and open to community participation. This approach may be a useful model for other institutions. PMID:8982523

  7. Twenty years of human immunodeficiency virus care at the Mayo Clinic: Past, present and future

    PubMed Central

    Cummins, Nathan W; Badley, Andrew D; Kasten, Mary J; Sampath, Rahul; Temesgen, Zelalem; Whitaker, Jennifer A; Wilson, John W; Yao, Joseph D; Zeuli, John; Rizza, Stacey A

    2016-01-01

    The Mayo human immunodeficiency virus (HIV) Clinic has been providing patient centered care for persons living with HIV in Minnesota and beyond for the past 20 years. Through multidisciplinary engagement, vital clinical outcomes such as retention in care, initiation of antiretroviral therapy and virologic suppression are maximized. In this commentary, we describe the history of the Mayo HIV Clinic and its best practices, providing a “Mayo Model” of HIV care that exceeds national outcomes and may be applicable in other settings. PMID:27175350

  8. Bubble continuous positive airway pressure in a human immunodeficiency virus-infected infant

    PubMed Central

    McCollum, E. D.; Smith, A.; Golitko, C. L.

    2014-01-01

    SUMMARY World Health Organization-classified very severe pneumonia due to Pneumocystis jirovecii infection is recognized as a life-threatening condition in human immunodeficiency virus (HIV) infected infants. We recount the use of nasal bubble continuous positive airway pressure (BCPAP) in an HIV-infected African infant with very severe pneumonia and treatment failure due to suspected infection with P. jirovecii. We also examine the potential implications of BCPAP use in resource-poor settings with a high case index of acute respiratory failure due to HIV-related pneumonia, but limited access to mechanical ventilation. PMID:21396221

  9. Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes.

    PubMed

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Chan, Wai Yee

    2015-12-01

    Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome, has claimed innumerable lives in the past. Many biomolecules which suppress HIV replication and also other biomolecules that inhibit enzymes essential to HIV replication have been reported. Proteins including a variety of milk proteins, ribosome-inactivating proteins, ribonucleases, antifungal proteins, and trypsin inhibitors; peptides comprising cathelicidins, defensins, synthetic peptides, and others; polysaccharides and polysaccharopeptides; nucleosides, nucleotides, and ribozymes, demonstrated anti-HIV activity. In many cases, the mechanism of anti-HIV action has been elucidated. Strategies have been devised to augment the anti-HIV potency of these compounds.

  10. [Oral plasmablastic lymphoma in a human immunodeficiency virus positive child: a case report].

    PubMed

    Astolfo, María Florencia; D'Antonio, Federico; Dartiguelongue, Juan B; Arabolaza, María N; Cheistwer, Ariel; De Matteo, Elena; Torrado, Lidia; Martínez Iriart, Emilio

    2016-04-01

    Plasmablastic lymphoma is a rare and aggressive subtype of diffuse large B cell non-Hodgkin lymphoma, originally described in the oral cavity of male adults with acquired immune deficiency syndrome. It is composed of neoplastic ceils which resemble immunoblasts but present immunophenotype distinctive of plasma cell and Epstein-Barr virus latent infection. In children, it is an even rarer disease. We present a case of oral plasmablastic lymphoma in a vertically transmitted human immunodeficiency virus-positive five-year-old child.

  11. Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.

    PubMed Central

    Piras, G; Dutschman, G E; Im, G J; Pan, B C; Chu, S H; Cheng, Y C

    1995-01-01

    Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse transcriptases resistant to nevirapine (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at position 100 to isoleucine) are cross resistant to E-BPU analogs. Nevirapine- or TIBO R82150-resistant HIV-1 were cross resistant to E-BPU analogs but were inhibited at concentrations 11- to 135-fold lower than the cytotoxic doses. PMID:7537030

  12. Nodular Erythema Elevatum Diutinum Mimicking Kaposi's Sarcoma in a Human Immunodeficiency Virus Infected Patient

    PubMed Central

    Rao, G Raghurama; Joshi, Rajiv; Phaneendra Prasad, A Krishna; Amareswar, A; Sandhya, S; Sridevi, M

    2014-01-01

    Erythema elevatum diutinum (EED) has been emerging as a specific Human Immunodeficiency Virus (HIV) associated dermatosis in recent times. It is an extremely rare chronic disease of unknown origin and part of the spectrum of leukocytoclastic vasculitis. We describe a case of EED simulating Kaposi's sarcoma in a 52-year-old HIV infected female patient with no previous opportunistic infections and CD4+ count of 164/mm3. Therapy with oral dapsone (100 mg/day) for two weeks resulted in resolution of some lesions. PMID:25484391

  13. Diabetes mellitus type 2 and abnormal glucose metabolism in the setting of human immunodeficiency virus.

    PubMed

    Hadigan, Colleen; Kattakuzhy, Sarah

    2014-09-01

    As the modern era of combination antiretroviral therapy has increased life expectancy for individuals infected with the human immunodeficiency virus (HIV), type 2 diabetes mellitus and disorders of glucose metabolism have emerged as an important issue in the care of this population. Multiple mechanisms, both specific and nonspecific to HIV, underlie a significant prevalence. Although best-practice diagnostic testing remains unclear, the risks associated with diabetes in the setting of HIV are well characterized, ranging from organ-specific damage to socioeconomic decline. As population-specific treatment data are limited, current guidelines serve as a basis for ongoing management.

  14. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia.

    PubMed

    Churchill, Melissa J; Wesselingh, Steven L; Cowley, Daniel; Pardo, Carlos A; McArthur, Justin C; Brew, Bruce J; Gorry, Paul R

    2009-08-01

    Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction to detect HIV DNA in single astrocytes in vivo, we showed that astrocyte infection is extensive in subjects with HIV-associated dementia, occurring in up to 19% of GFAP+ cells. In addition, astrocyte infection frequency correlated with the severity of neuropathological changes and proximity to perivascular macrophages. Our data indicate that astrocytes can be extensively infected with HIV, and suggest an important role for HIV-infected astrocytes in HIV neuropathogenesis.

  15. Efficient magnesium-dependent human immunodeficiency virus type 1 integrase activity.

    PubMed Central

    Engelman, A; Craigie, R

    1995-01-01

    The integrase protein from human immunodeficiency virus type 1 (HIV-1) has generally been reported to require Mn2+ for efficient in vitro activity. We have reexamined the divalent metal ion requirements of HIV-1 integrase and find that the protein is capable of promoting efficient 3' processing and DNA strand transfer with either Mn2+ or Mg2+. The metal ion preference depended upon the reaction conditions. HIV-1 integrase displayed significantly less nonspecific nuclease activity in reaction mixtures containing Mg2+ than it did under the previously described reaction conditions with mixtures containing Mn2+. PMID:7637039

  16. Role of dendritic cells in immunopathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Weissman, D; Fauci, A S

    1997-01-01

    The role of dendritic cells (DC) in the pathogenesis of human immunodeficiency virus (HIV) disease has been a subject of considerable interest for several years. Initial studies focused on the infection, dysfunction, and depletion of DC in HIV-infected individuals. More recent studies have begun to identify the functional role of DC in the initiation and propagation of viral replication in T cells in HIV-infected individuals. This review discusses recent data regarding the role of DC in HIV disease with the aim of delineating basic immunopathogenic principles of infection and the development of therapeutic strategies. PMID:9105759

  17. Testing women for human immunodeficiency virus infection: who, when, and how?

    PubMed

    Clark, Jill; Lampe, Margaret A; Jamieson, Denise J

    2008-09-01

    Obstetrician-gynecologists provide comprehensive primary and preventive care for women and are ideally suited to provide human immunodeficiency virus (HIV) screening for their patients. This paper provides a summary and rationale for the current recommendations for HIV testing among women in the United States, emphasizing recommendations from the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists [corrected] Who should receive HIV testing, when and how often testing should be conducted, and how testing should be offered are discussed. These recommendations are described separately for general populations (including nonpregnant women) and for pregnant women and their infants.

  18. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    PubMed

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART. PMID:26933317

  19. Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.

    PubMed

    Bryant, Malcolm; Beard, Jennifer

    2016-02-01

    In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade. PMID:26613693

  20. Cardiovascular disease in human immunodeficiency virus infected patients: A true or perceived risk?

    PubMed Central

    Shahbaz, Shima; Manicardi, Marcella; Guaraldi, Giovanni; Raggi, Paolo

    2015-01-01

    After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus (HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease (CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial. PMID:26516417

  1. Can antiretroviral therapy be used to prevent sexual transmission of human immunodeficiency virus type 1?

    PubMed

    Hosseinipour, Mina; Cohen, Myron S; Vernazza, Pietro L; Kashuba, Angela D M

    2002-05-15

    Approximately 5 million people annually are newly infected with human immunodeficiency virus (HIV). Although education, behavior modification, and promotion of condom use are effective transmission-prevention measures, the severity of the pandemic demands that all possible prevention strategies be explored. Antiretroviral therapy has the potential to decrease sexual transmission of HIV type 1 by reducing levels of HIV RNA and thus decreasing the risk that infected persons will transmit the disease or by its use as preexposure or postexposure prophylaxis. In this article, we explore the rationale for using antiretroviral therapy to prevent sexual transmission of HIV, as well as the limitations of this approach. PMID:11981736

  2. Expression of Human Immunodeficiency Virus Type 1 Neutralizing Antibody Fragments Using Human Vaginal Lactobacillus

    PubMed Central

    Marcobal, Angela; Liu, Xiaowen; Zhang, Wenlei; Dimitrov, Antony S.; Jia, Letong; Lee, Peter P.; Fouts, Timothy R.; Parks, Thomas P.

    2016-01-01

    Abstract Eradication of human immunodeficiency virus type 1 (HIV-1) by vaccination with epitopes that produce broadly neutralizing antibodies is the ultimate goal for HIV prevention. However, generating appropriate immune responses has proven difficult. Expression of broadly neutralizing antibodies by vaginal colonizing lactobacilli provides an approach to passively target these antibodies to the mucosa. We tested the feasibility of expressing single-chain and single-domain antibodies (dAbs) in Lactobacillus to be used as a topical microbicide/live biotherapeutic. Lactobacilli provide an excellent platform to express anti-HIV proteins. Broadly neutralizing antibodies have been identified against epitopes on the HIV-1 envelope and have been made into active antibody fragments. We tested single-chain variable fragment m9 and dAb-m36 and its derivative m36.4 as prototype antibodies. We cloned and expressed the antibody fragments m9, m36, and m36.4 in Lactobacillus jensenii-1153 and tested the expression levels and functionality. We made a recombinant L. jensenii 1153-1128 that expresses dAb-m36.4. All antibody fragments m9, m36, and m36.4 were expressed by lactobacilli. However, we noted the smaller m36/m36.4 were expressed to higher levels, ≥3 μg/ml. All L. jensenii-expressed antibody fragments bound to gp120/CD4 complex; Lactobacillus-produced m36.4 inhibited HIV-1BaL in a neutralization assay. Using a TZM-bl assay, we characterized the breadth of neutralization of the m36.4. Delivery of dAbs by Lactobacillus could provide passive transfer of these antibodies to the mucosa and longevity at the site of HIV-1 transmission. PMID:26950606

  3. Temporal patterns of human immunodeficiency virus type 1 transcripts in human fetal astrocytes.

    PubMed Central

    Tornatore, C; Meyers, K; Atwood, W; Conant, K; Major, E

    1994-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the developing central nervous system results in a dementing process in children, termed HIV-1-associated encephalopathy. Infection of astroglial elements of the pediatric nervous system has been demonstrated and suggests that direct infection of some astrocytes may contribute to the neurologic deficit. In this model, HIV-1 establishes a persistent state of infection in astrocytes, which can be reactivated by the cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). To better understand the natural history of viral persistence in astroglial cells, we characterized infection at the transcriptional level. The most abundant viral transcript during the establishment of persistence was the subgenomic multiply spliced 2-kb message, similar to mononuclear cell models of HIV-1 latency. Following reactivation with TNF-alpha or IL-1 beta the multiply spliced 2-kb message remained the most abundant viral transcript, in contrast to infected mononuclear cells in which reactivation leads to the reemergence of the 9- and 4-kb transcripts. Further characterization of the persistent 2-kb transcript by PCR amplification of in vitro-synthesized viral cDNA showed that, in the absence of cytokine stimulation, the most abundant multiply spliced transcripts were the Nef- and Rev-specific messages. However, following cytokine stimulation, double- and triple-spliced Tat-, Rev-, and Nef-specific messages could be identified. Immunohistochemical staining demonstrated that, during viral persistence, astrocytes expressed Nef protein but few or no viral structural proteins. These results demonstrate that viral persistence in astrocytes at the transcriptional level is fundamentally different from that seen in mononuclear cells and could account for the virtual absence of astroglial expression of viral structural antigens in vivo. Images PMID:8254781

  4. Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line.

    PubMed

    Banerjee, R; Bekesi, J G; Tarcsafalvi, A; Sperber, K; Deak, G; Choi, H S; Paronetto, F; Holland, J F; Acs, G

    1992-11-01

    We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.

  5. Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference

    PubMed Central

    Coburn, Glen A.; Cullen, Bryan R.

    2002-01-01

    Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle. PMID:12186906

  6. Avian influenza: potential impact on sub-Saharan military populations with high rates of human immunodeficiency virus/acquired immunodeficiency syndrome.

    PubMed

    Feldman, Robert L; Nickell, Kent

    2007-07-01

    Several sub-Saharan militaries have large percentages of troops with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. With the arrival of avian influenza in Africa, the potential exists that some of those soldiers might also become infected with H5N1, the virus responsible for the disease. Two possible scenarios have been postulated regarding how such a coinfection of HIV and H5N1 might present. (1) Soldiers already weakened by HIV/acquired immunodeficiency syndrome rapidly succumb to H5N1. The cause of death is a "cytokine storm," essentially a runaway inflammatory response. (2) The weakened immune system prevents the cytokine storm from occurring; however, H5N1 is still present, replicating, and being shed, leading to the infection of others. A cytokine storm is particularly dangerous for individuals of military age, as evidenced by the large number of soldiers who died during the 1918 influenza epidemic. If large numbers of sub-Saharan soldiers suffer a similar fate from avian influenza, then military and political instability could develop.

  7. In vivo pathogenic properties of two clonal human immunodeficiency virus type 1 isolates.

    PubMed Central

    Jamieson, B D; Pang, S; Aldrovandi, G M; Zha, J; Zack, J A

    1995-01-01

    We have investigated the in vivo pathogenic properties of two molecularly cloned strains of human immunodeficiency virus type 1 (HIV-1), HIV-1NL4-3 and HIV-1JR-CSF, in human fetal thymus/liver implants in severe combined immunodeficient mice. Studies comparing their in vivo replication kinetics and abilities to induce CD4+ thymocyte depletion were performed. HIV-1NL4-3 replicated in vivo with faster kinetics and induced greater levels of CD4+ thymocyte depletion than did HIV-1JR-CSF. These results demonstrate that different viral isolates have different pathogenic properties in this system. In the SCID-hu model, this pathogenesis most likely occurs in the absence of an immune response. Therefore, we investigated whether the absence of immune selection resulted in extensive genetic variation and the generation of viral quasispecies. To this end, DNA corresponding to the fourth variable domain region of the viral envelope gp120 protein recovered from biopsy samples at 6 weeks postinfection was sequenced. Little genetic variation was noted in either HIV-1JR-CSF- or HIV-1NL4-3-infected implants. The mutation levels demonstrated in both viral strains were more reflective of the acute rather than the chronic phase of HIV-1 infection in humans. These results suggest that the SCID-hu mouse model can be used to study the in vivo pathogenicity of different HIV-1 isolates in the absence of host immune selective pressures. PMID:7666526

  8. Requirement of human immunodeficiency virus type 1 nef for in vivo replication and pathogenicity.

    PubMed Central

    Jamieson, B D; Aldrovandi, G M; Planelles, V; Jowett, J B; Gao, L; Bloch, L M; Chen, I S; Zack, J A

    1994-01-01

    The role of human immunodeficiency virus type 1 (HIV-1) accessory genes in pathogenesis has remained unclear because of the lack of a suitable in vivo model. The most controversial of these genes is nef. We investigated the requirement for Nef for in vivo replication and pathogenicity of two isolates of HIV-1 (HIV-1JR-CSF and HIV-1NL4-3) in human fetal thymus and liver implants in severe combined immunodeficient mice. HIV-1JR-CSF and HIV-1NL4-3 differ in their in vitro phenotypes in that HIV-1JR-CSF does not induce syncytia and is relatively noncytopathic, while HIV-1NL4-3 is highly cytopathic and readily induces syncytia. The nef mutants of both isolates grew with kinetics similar to those of parental virus strains in stimulated peripheral blood lymphocytes but demonstrated attenuated growth properties in vivo. HIV-1NL4-3 induced severe depletion of human thymocytes within 6 weeks of infection, whereas its nef mutant did not. Thus, HIV-1 Nef is required for efficient in vivo viral replication and pathogenicity. Images PMID:8189487

  9. Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs.

    PubMed

    Chang, R S; Yeung, H W

    1988-04-01

    Twenty-seven medicinal herbs reputed in ancient Chinese folklore to have anti-infective properties were extracted by boiling under reflux. The extracts were tested for inhibitory activity against the human immunodeficiency virus in the H9 cell line at concentrations nontoxic to growth of the H9 cells. Using a significant reduction (greater than 3 S. D. below the mean) in the percentage of cells positive for specific viral antigens in three successive assays as indicative of activity against the virus, 11 of the 27 extracts were found to be active. One of the extracts (Viola yedoensis) was studied in greater depth. At a subtoxic concentration, this extract shut off completely the growth of HIV in virtually all experiments. It did not inactivate HIV extracellularly, did not induce interferon and did not inhibit the growth of herpes simplex, polio or vesicular stomatitis viruses in human fibroblast culture. Chinese medicinal herbs appeared to be a rich source of potentially useful materials for the treatment of human immunodeficiency virus infection. PMID:2840849

  10. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  11. Inactivation of human immunodeficiency virus type I in human milk: effects of intrinsic factors in human milk and of pasteurization.

    PubMed

    Orloff, S L; Wallingford, J C; McDougal, J S

    1993-03-01

    Human milk was inoculated with human immunodeficiency virus type I (HIV-1) or with HIV-1-infected cells in volumes and containers typically used in human milk banks. The inoculated milk was pasteurized at 62.5 degrees C for 30 minutes in a water bath, i.e., conditions currently in use or proposed for human milk pasteurization. The process of HIV-1 inoculation and pasteurization effectively inactivated the infectivity of both cell-free HIV-1 and HIV-1-infected cells. No virus was recovered after the process, even after repeated subculturing in attempts to rescue the virus. Pasteurization reduced the infectious titer of cell-free HIV-1 and HIV-1-infected cells by more than 5 logs and 6 logs respectively. Human milk contains one or more components that inactive HIV-1 but that are not toxic for the cells used to replicate virus. These components have not been identified, but physical and solubility properties are consistent with characteristics of lipids.

  12. A Patient Presenting with Tuberculous Encephalopathy and Human Immunodeficiency Virus Infection

    PubMed Central

    Li, Jason; Afroz, Suraiya; French, Eric; Mehta, Anuj

    2016-01-01

    Patient: Male, 33 Final Diagnosis: Tuberculous meningitis, human immunodeficiency virus infection Symptoms: — Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases Objective: Rare disease Background: In the USA, Mycobacterium tuberculosis infection is more likely to be found in foreign-born individuals, and those co-infected with human immunodeficiency virus (HIV) are more likely to have tuberculous meningitis. The literature is lacking in details about the clinical workup of patients presenting with tuberculous meningitis with encephalopathic features who are co-infected with HIV. This report demonstrates a clinical approach to diagnosis and management of tuberculous meningitis. Case Report: A 33-year-old Ecuadorean man presented with altered consciousness and constitutional symptoms. During the workup he was found to have tuberculous meningitis with encephalopathic features and concurrent HIV infection. Early evidence for tuberculosis meningitis included lymphocytic pleocytosis and a positive interferon gamma release assay. A confirmatory diagnosis of systemic infection was made based on lymph node biopsy. Imaging studies of the neck showed scrofula and adenopathy, and brain imaging showed infarctions, exudates, and communicating hydrocephalus. Treatment was started for tuberculous meningitis, while antiretroviral therapy for HIV was started 5 days later in combination with prednisone, given the risk of immune reconstitution inflammatory syndrome (IRIS). Conclusions: A clinical picture consistent with tuberculous meningitis includes constitutional symptoms, foreign birth, lymphocytic pleocytosis, specific radiographic findings, and immunodeficiency. Workup for tuberculous meningitis should include MRI, HIV screening, and cerebral spinal fluid analysis. It is essential to treat co-infection with HIV and to assess for IRIS. PMID:27302013

  13. A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon.

    PubMed Central

    Gürtler, L G; Hauser, P H; Eberle, J; von Brunn, A; Knapp, S; Zekeng, L; Tsague, J M; Kaptue, L

    1994-01-01

    A new subtype (MVP-5180) of human immunodeficiency virus type 1 (HIV-1) was isolated from a Cameroonian AIDS patient. MVP-5180 was grown in several human T-cell lines and the monocytic U937 line. MVP-5180 DNA could not be amplified by nested primer PCR with conventional env primers and could be only very faintly amplified with gag and pol primers. Most German, Ivoirian, and Malawian anti-HIV-1 sera reacted faintly or moderately with Env proteins in an MVP-5180 immunoblot, whereas some Cameroonian sera reacted strongly. Of HIV-1-infected Cameroonians, 8% were identified by serological methods as infected with MVP-5180; 7% were positive when MVP-5180-specific PCR env primers were used. DNA sequence analysis of MVP-5180 showed that its genetic organization was that of HIV-1, with 65% similarity to HIV-1 and 56% similarity to HIV-2 consensus sequences. The env gene of MVP-5180 had similarities to HIV-1 and HIV-2 of 53 and of 49%, respectively. V3 loop analysis identified a crown of Gly-Pro-Met-Arg by using cloned DNA and Gly-Pro-Leu-Arg by using PCR-amplified DNA, neither of which configuration has been described for other HIV strains. In an analysis of relationships, MVP-5180 occupied a position distant to all other HIV-1 strains, including the chimpanzee simian immunodeficiency virus type 1 SIVcpz and the Uganda virus U455, and closer to the HIV-1/HIV-2 divergence node. MVP-5180, together with another Cameroonian isolate, ANT-70, constitutes a group subtype O of the most divergent HIV-1 isolates yet identified. Characterization of MVP-5180 is important for understanding the natural history of the primate immunodeficiency viruses and for the development of vaccines and diagnostics. PMID:8107219

  14. Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain

    PubMed Central

    2013-01-01

    Background We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). Methods We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. Results We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). Conclusion The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma. Virtual slides The virtual slide(s) for this article can be found here

  15. Plaque staining assay for non- or weakly cytotoxic human immunodeficiency virus.

    PubMed

    Matsui, T; Nakashima, H; Yoshiyama, H; Kobayashi, N; Yamamoto, N

    1987-07-01

    Cells infected with human immunodeficiency virus (HIV) were selectively stained with peroxidase-coupled antibodies in a recently developed plaque assay for HIV. The numbers of plaques formed with the human T-cell lymphotropic virus type III strain of HIV were exactly the same in stained (immunologically detectable) and unstained (visible) dishes. However, four times more plaques were visualized in stained dishes than in unstained dishes when the YU-6 and acquired immune deficiency syndrome-associated retrovirus strains of HIV were used. Linear relationship was observed between the number of stained plaques and the virus concentrations in the titration of human T-cell lymphotropic virus type III and YU-6. The assay should be useful for the titration of HIV, especially for non- or weakly cytopathic strains of HIV.

  16. Survival of Human Neurofibroma in Immunodeficient Mice and Initial Results of Therapy With Pirfenidone

    PubMed Central

    Babovic-Vuksanovic, Dusica

    2004-01-01

    Neurofibromatosis type I is a common tumor predisposing disease in humans. Surgical therapy can be applied only in selected patients with resectable masses. Hence, development of new therapies for this disease is urgent. We used human neurofibroma implants in mice with severe combined immunodeficiency (SCID) as a model to test the toxicity and potential efficacy of pirfenidone, a new therapeutic agent. Two hundred twelve human neurofibromas were transplanted into various locations in 59 experimental animals, and 30 mice with implants received oral pirfenidone for up to six weeks. Survival of neurofibromas in animals treated with pirfenidone was lower than in the control group (P=.02). Tumors did not change histologic appearance or vascularization in response to pirfenidone. Treatment with pirfenidone, a new antifibrotic agent, inhibits survival of some tumors without causing toxicity in animals. PMID:15240917

  17. Characterization to species level of Mycobacterium avium complex strains from human immunodeficiency virus-positive and -negative patients.

    PubMed Central

    Kyriakopoulos, A M; Tassios, P T; Matsiota-Bernard, P; Marinis, E; Tsaousidou, S; Legakis, N J

    1997-01-01

    Forty human clinical Mycobacterium avium-M. intracellulare complex strains isolated in Greece were characterized to the species level by PCR with three sets of primers specific for one or both species. M. avium predominated in both human immunodeficiency virus-positive and -negative patients, but the frequency of M. intracellulare isolation appeared to be higher in the latter. PMID:9350780

  18. Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

    PubMed Central

    Bellows, M.L.; Floudas, C.A.

    2010-01-01

    This paper provides an overview of computational de novo protein design methods, highlighting recent advances and successes. Four protein systems are described that are important targets for drug design: human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases. Target areas for drug design for each protein are described, along with known inhibitors, focusing on peptidic inhibitors, but also describing some small-molecule inhibitors. Computational design methods that have been employed in elucidating these inhibitors for each protein are outlined, along with steps that can be taken in order to apply computational protein design to a system that has mainly used experimental methods to date. PMID:20210752

  19. Successful treatment of spleen tuberculosis in a patient with human immunodeficiency virus infection.

    PubMed

    Maserati, R; Seminari, E; Scudeller, L; Rizzi, L; Benedetti, M; Minoli, L

    1999-04-01

    Tuberculosis in human immunodeficiency virus (HIV)-infected patients may act as a cofactor that accelerates the clinical course of HIV infection, and, indeed, HIV-infected patients with tuberculosis have a reduced survival rate compared to those without tuberculosis. Diagnosis of tuberculosis in HIV-positive patients can be difficult because of nonspecific symptoms and the time required for the identification of mycobacteria by means of culture techniques. Recently, antiretroviral combination therapies have improved the outcome of several acquired immune deficiency syndrome (AIDS)-associated conditions. Unfortunately, the use of antiretroviral therapy for patients coinfected with HIV and Mycobacterium tuberculosis is still to be fully evaluated. The complexity of side-effects due to antituberculosis medication and drug interaction represent important issues and combining an effective anti-HIV treatment with antituberculosis therapy is still a clinical challenge. We discuss here a case of spleen tuberculosis in a human immunodeficiency virus-positive patient who had a successful response after a diagnostic splenectomy and medical treatment that included classical antituberculosis treatment associated with antiretroviral therapy without protease inhibitors.

  20. Substrate inhibition of the human immunodeficiency virus type 1 reverse transcriptase.

    PubMed Central

    Furman, P A; Painter, G; Wilson, J E; Cheng, N; Hopkins, S

    1991-01-01

    Substrate inhibition was observed with the heterodimeric (p66/p51) and the homodimeric (p66/p66, p51/p51) forms of human immunodeficiency virus type 1 reverse transcriptase (RNA-dependent DNA polymerase, EC 2.7.7.49). An apparent Ki value of 195 +/- 37 microM was determined for dTTP using the bacterial cloned and expressed heterodimer. Similar values were obtained with the homodimeric and the virus-encoded enzymes. When poly-(rC).p(dG)10 was used as template-primer, dGTP exhibited substrate inhibition with an apparent Ki value of 189 +/- 32 microM. Substrate inhibition was not observed with dTTP when DNA.DNA template-primers were used. Hill coefficients for substrate binding determined in the presence of saturating concentrations of template-primer were equal to 1.0, suggesting that substrate inhibition of the heterodimer is not the result of an allosteric mechanism involving the p51 subunit. Furthermore, UV crosslinking experiments with [gamma-32P]dTTP showed crosslinking only to the p66 subunit. Substrate inhibition was not as pronounced with other retroviral reverse transcriptases as it was with human immunodeficiency type 1 reverse transcriptase. Images PMID:1712479

  1. Cyclospora infection in a young woman with human immunodeficiency virus in Hong Kong: a case report

    PubMed Central

    2013-01-01

    Background Cyclospora is an uncommon pathogen. The diagnosis of Cyclospora infection can be difficult because of its scarcity in developed countries, intracellular mode of life, small size of the parasite and its inability to take up routine microscopic stains. However, it is endemic in many countries in Asia, Africa, Central and South America. With the increase in travels to these areas, the number of cases is expected to increase. Moreover, it is found to be associated with numerous food-borne outbreaks. Case presentation We encountered a patient with human immunodeficiency virus presented with 6 months of diarrhoea. The initial investigation was unrevealing. The diagnosis of Cyclospora infection was finally made on the histological sample obtained by colonoscopy. Moreover, the initial therapy with ciprofloxacin was not effective, while trimethoprim/sulfamethoxazole resulted in final cure of the disease. Conclusion Travel and food histories are important for the suspicion of Cyclospora infection. Histological examination is more sensitive in making a diagnosis of Cyclospora infection of the gut than fecal microscopic examination. Trimethoprim/sulfamethoxazole is a more reliable therapy for Cyclospora infection in patients with human immunodeficiency virus. PMID:24321705

  2. Human Immunodeficiency Virus Type 1 (HIV-1) Tat Induces Nitric-oxide Synthase in Human Astroglia*

    PubMed Central

    Liu, Xiaojuan; Jana, Malabendu; Dasgupta, Subhajit; Koka, Sreenivas; He, Jun; Wood, Charles; Pahan, Kalipada

    2007-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1 tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-κB and C/EBPβ, transcription factors responsible for the induction of iNOS. Activation of NF-κB as well as C/EBPβ by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPβ, and inhibition of RSV-tat-induced production of NO by Δp65, a dominant-negative mutant of p65, and ΔC/EBPβ, a dominant-negative mutant of C/EBPβ, suggest that RSV-tat induces iNOS through the activation of NF-κB and C/EBPβ. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and ΔERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO

  3. Intra-Blood-Brain Barrier Synthesis of Human Immunodeficiency Virus Antigen and Antibody in Humans and Chimpanzees

    NASA Astrophysics Data System (ADS)

    Goudsmit, Jaap; Epstein, Leon G.; Paul, Deborah A.; van der Helm, Hayo J.; Dawson, George J.; Asher, David M.; Yanagihara, Richard; Wolff, Axel V.; Gibbs, Clarence J.; Carleton Gajdusek, D.

    1987-06-01

    The presence of human immunodeficiency virus (HIV) antigens in cerebrospinal fluid (CSF) was associated with progressive encephalopathy in adult and pediatric patients with acquired immunodeficiency syndrome (AIDS). HIV antigen was detected in CSF from 6 of 7 AIDS patients with progressive encephalopathy. By contrast, HIV antigen, whether free or complexed, was detected in CSF from only 1 of 18 HIV antibody seropositive patients without progressive encephalopathy and from 0 of 8 experimentally infected chimpanzees without clinical signs. Intra-blood-brain barrier synthesis of HIV-specific antibody was demonstrated in the majority of patients with AIDS (9/12) or at risk for AIDS (8/13) as well as in the experimentally infected chimpanzees, indicating HIV-specific B-cell reactivity in the brain without apparent neurological signs. In 6 of 11 patients with HIV infection, antibodies synthesized in the central nervous system were directed against HIV envelope proteins. Active viral expression appears to be necessary for both the immunodeficiency and progressive encephalopathy associated with HIV infection.

  4. Decreases in human immunodeficiency virus infection rates in Kombolcha, Ethiopia: a 10-year data review

    PubMed Central

    Shiferaw, Melashu Balew; Gebregergs, Gebremedhin Berhe; Sinishaw, Mulusew Alemneh; Yesuf, Yohannes Amede

    2016-01-01

    Introduction Acquired immunodeficiency syndrome is one of the most serious public health and development challenges in sub-Saharan Africa, including Ethiopia. A particular challenge for prevention strategies has been the emergence of hotspot areas. Therefore, human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome programs should not be based on national level statistics, but need to be more focused geographically. Kombolcha is one of the high spot areas with different projects and development corridors. Hence, the aim of this study is to assess the trend of HIV infection rates among patients who visited Africa Service Committee clinic from 2005 to 2014. Methods An institutional-based cross-sectional study was conducted from January 1 to January 30, 2016. All records of new patients enrolled from February 8, 2005 to December 31, 2014 were reviewed. Data on sociodemographic information, risky sexual behavior, and HIV test result were collected from each study participant using data collection format. Data were analyzed using SPSS version 20.0. A multivariate logistic regression model was used to identify risk factors of HIV infection. Results The overall HIV infection was 10.8% (2,233/20,674). The rate of infection varied from 13.3% in 2005 to 4.5% in 2014, and its trend had significantly declined from 2008 to 2014. Urban residence (adjusted odds ratio [AOR]: 2.53; 95% confidence interval [CI]: 1.22–5.25), patients who ever had intercourse with penetration (AOR: 5.62; 95% CI: 1.11–28.57), and those who had marriage experience (AOR: 11.65; 95% CI: 4.2–32.3) were more infected with HIV. Conclusion The trend of HIV infection significantly reduced in the last 10 years in Kombolcha area. However, the HIV infection still remains high (4.5%) that needs intervention of those who had marriage experience, risky sexual behavior, and urban dwellers. PMID:27462177

  5. Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1.

    PubMed Central

    Lu, Y C; Touzjian, N; Stenzel, M; Dorfman, T; Sodroski, J G; Haseltine, W A

    1990-01-01

    The negative regulatory element of human immunodeficiency virus type 1 is a 260-nucleotide-long sequence that decreases the rate of RNA transcription initiation specified by the long terminal repeat. This region has the potential to bind several cellular transcription factors. Here it is shown that sequences which recognize the NFAT-1 and USF cellular transcription factors contribute to this negative regulatory effect. The sequences within the negative regulatory element which resemble the AP-1 site and the URS do not negatively regulate human immunodeficiency virus long terminal repeat transcription initiation. PMID:2398545

  6. Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120.

    PubMed Central

    Arthur, L O; Bess, J W; Waters, D J; Pyle, S W; Kelliher, J C; Nara, P L; Krohn, K; Robey, W G; Langlois, A J; Gallo, R C

    1989-01-01

    The human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, infects humans and chimpanzees. To determine the efficacy of immunization for preventing infection, chimpanzees were immunized with gp120 purified from human T-cell lymphotrophic virus type IIIB (HTLV-IIIB)-infected cell membranes and challenged with the homologous virus, HTLV-IIIB. A challenge stock of HTLV-IIIB was prepared by using unconcentrated HTLV-IIIB produced in H9 cells. The titer of the virus from this stock on human and chimpanzee peripheral blood mononuclear cells and in human lymphoid cell lines was determined; a cell culture infectivity of 10(4) was assigned. All chimpanzees inoculated intravenously with 40 cell culture infectious units or more became infected, as demonstrated by virus isolation and seroconversion. One of two chimpanzees inoculated with 4 cell culture infectious units became infected. Chimpanzees immunized with gp120 formulated in alum developed antibodies which precipitated gp120 and neutralized HTLV-IIIB. Peripheral blood mononuclear cells from gp120-vaccinated and HIV-infected animals showed a significantly greater response in proliferation assays with HIV proteins than did peripheral blood mononuclear cells from nonvaccinated and non-HIV-infected chimpanzees. Two of the gp120-alum-immunized chimpanzees were challenged with virus from the HTLV-IIIB stock. One animal received 400 cell culture infectious units, and one received 40 infectious units. Both animals became infected with HIV, indicating that the immune response elicited by immunization with gp120 formulated in alum was not effective in preventing infection with HIV-1. PMID:2555541

  7. Human papillomavirus detection in women with and without human immunodeficiency virus infection in Colombia

    PubMed Central

    2014-01-01

    Background HIV infection leads to a decreasing immune response, thereby facilitating the appearance of other infections, one of the most important ones being HPV. However, studies are needed for determining associations between immunodeficiency caused by HIV and/or the presence of HPV during the course of cervical lesions and their degree of malignancy. This study describes the cytological findings revealed by the Papanicolaou test, laboratory characteristics and HPV molecular profile in women with and without HIV infection. Methods A total of 216 HIV-positive and 1,159 HIV-negative women were invited to participate in the study; PCR was used for the molecular detection of HPV in cervical samples. Statistical analysis (such as percentages, Chi-square test and Fisher’s exact test when applicable) determined human papillomavirus (HPV) infection frequency (single and multiple) and the distribution of six types of high-risk-HPV in women with and without HIV infection. Likewise, a logistic regression model was run to evaluate the relationship between HIV-HPV infection and different risk factors. Results An association was found between the frequency of HPV infection and infection involving 2 or more HPV types (also known as multiple HPV infection) in HIV-positive women (69.0% and 54.2%, respectively); such frequency was greater than that found in HIV-negative women (44.3% and 22.7%, respectively). Statistically significant differences were observed between both groups (p = 0.001) regarding HPV presence (both in infection and multiple HPV infection). HPV-16 was the most prevalent type in the population being studied (p = 0.001); other viral types had variable distribution in both groups (HIV-positive and HIV-negative). HPV detection was associated with <500 cell/mm3 CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV-DNA detection, <200 cell/mm3 CD4-count (p = 0.001), and higher HIV-viral-load (p = 0.001) were associated with

  8. Productive Infection of Human Peripheral Blood Mononuclear Cells by Feline Immunodeficiency Virus: Implications for Vector Development

    PubMed Central

    Johnston, James; Power, Christopher

    1999-01-01

    Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV-infected human PBMC, with detection of viral titers of 101.3 to 102.1 50% tissue culture infective doses/106 cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy. PMID:9971834

  9. Risk to human health from a plethora of simian immunodeficiency viruses in primate bushmeat.

    PubMed

    Peeters, Martine; Courgnaud, Valerie; Abela, Bernadette; Auzel, Philippe; Pourrut, Xavier; Bibollet-Ruche, Frederic; Loul, Severin; Liegeois, Florian; Butel, Cristelle; Koulagna, Denis; Mpoudi-Ngole, Eitel; Shaw, George M; Hahn, Beatrice H; Delaporte, Eric

    2002-05-01

    To assess human exposure to Simian immunodeficiency virus (SIV) in west central Africa, we looked for SIV infection in 788 monkeys that were hunted in the rainforests of Cameroon for bushmeat or kept as pets. Serologic reactivity suggesting SIV infection was found in 13 of 16 primate species, including 4 not previously known to harbor SIV. Overall, 131 sera (16.6%) reacted strongly and an additional 34 (4.3%) reacted weakly with HIV antigens. Molecular analysis identified five new phylogenetic SIV lineages. These data document for the first time that a substantial proportion of wild monkeys in Cameroon are SIV infected and that humans who hunt and handle bushmeat are exposed to a plethora of genetically highly divergent viruses.

  10. Thrombotic microangiopathy and human immunodeficiency virus in the era of eculizumab.

    PubMed

    Jin, Anna; Boroujerdi-Rad, Laleh; Shah, Gaurang; Chen, Joline L T

    2016-08-01

    Thrombotic microangiopathies (TMAs) include thrombotic thromobocytopenic purpura and hemolytic uremic syndrome (HUS). Among these conditions, atypical HUS is now recognized to be a disease of alternative complement pathway dysregulation. Eculizumab is a recombinant humanized monoclonal antibody that binds to the complement protein C5 and prevents the cleavage of C5 to C5a and C5b. Eculizumab has been used as a novel treatment for complement-mediated TMA. We present a case of a patient with human immunodeficiency virus infection who developed TMA and was successfully treated with eculizumab. The effect of long-term treatment with this new medication is unknown, and further studies are needed to establish guidelines in the management of this condition. PMID:27478600

  11. In Vivo Replication Capacity Rather Than In Vitro Macrophage Tropism Predicts Efficiency of Vaginal Transmission of Simian Immunodeficiency Virus or Simian/Human Immunodeficiency Virus in Rhesus Macaques

    PubMed Central

    Miller, Christopher J.; Marthas, Marta; Greenier, Jennifer; Lu, Ding; Dailey, Peter J.; Lu, Yichen

    1998-01-01

    We used the rhesus macaque model of heterosexual human immunodeficiency virus (HIV) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. A single atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in all rhesus macaques tested. However, vaginal inoculation with a dualtropic molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two rhesus macaques. It has previously been shown that 12 intravaginal inoculations with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99–107, 1992). In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rhesus macaques following multiple vaginal inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045–3050, 1996). These results demonstrate that in vitro measures of macrophage tropism do not predict if a SIV or SHIV will produce systemic infection after intravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous inoculation predicts the outcome of intravaginal inoculation with each virus. PMID:9525652

  12. Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector.

    PubMed Central

    Venkatesh, L K; Arens, M Q; Subramanian, T; Chinnadurai, G

    1990-01-01

    The human immunodeficiency viruses (HIVs) primarily infect CD4+ T lymphocytes, leading eventually to the development of a systemic immune dysfunction termed acquired immunodeficiency syndrome (AIDS). An attractive strategy to combat HIV-mediated pathogenesis would be to eliminate the initial pool of infected cells and thus prevent disease progression. We have engineered a replication-defective, conditionally cytotoxic adenovirus vector, Ad-tk, whose action is dependent on the targeted expression of the herpes simplex virus type 1 thymidine kinase gene (tk), cloned downstream of the HIV-1 long terminal repeat, in human cells expressing the HIV-1 transcriptional activator Tat. Infection of Tat-expressing human HeLa or Jurkat cells with Ad-tk resulted in high-level tk expression, which was not deleterious to the viability of these cells. However, in the presence of the antiherpetic nucleoside analog ganciclovir, Ad-tk infection resulted in a massive reduction in the viability of these Tat-expressing cell lines. As adenoviruses are natural passengers of the human lymphoid system, our results suggest adenovirus vector-based strategies for the targeted expression, under the control of cis-responsive HIV regulatory elements, of cytotoxic agents in HIV-infected cells for the therapy of HIV-mediated pathogenesis. Images PMID:2247444

  13. [The human immunodeficiency virus type 1 and the developing central nervous system].

    PubMed

    Henao, Jorge Alejandro; Vanegas, Nora; Cano, Oscar David; Hiromi, Juan Carlos; Rugeles, María Teresa

    2005-03-01

    Currently, at least 42 million people are infected worldwide with the human immunodeficiency virus type 1 (HIV-1). Of these, 3.2 million are children infected, in 90% of the cases, through vertical transmission. In Colombia, approximately 200,000 persons have been infected since the beginning of the pandemic, with an increasing trend in the seroprevalence among pregnant women. Although HIV-1 is basically lymphotropic, its capacity to invade the central nervous system (CNS) is well known, generating multiple neurological alterations, especially prominent in children, with encephalopathy being the most prevalent. Classically, two types of neurological disorders are recognized in children, consisting of early and late encephalopathies, each with differing clinical and immunological characteristics. HIV-1 infection of the CNS is limited to macrophages, microglia and astrocytes in a restricted manner. In patients with acquired immunodeficiency virus (AIDS), neurons are rarely infected, suggesting that cellular and viral soluble factors, are responsible for the neuronal damage. The conclusion is that the CNS in earlier stages of development is especially susceptible to HIV-1 infection. The epidemiological trends predict that these types of clinical manifestations of HIV-1 will increase in frequency, and increases the necessity for an understanding of the underlying neuropathogenesis.

  14. Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids.

    PubMed

    Zhu, K; Cordeiro, M L; Atienza, J; Robinson, W E; Chow, S A

    1999-04-01

    Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis.

  15. Heat shock protein-based therapeutic strategies against human immunodeficiency virus type 1 infection.

    PubMed Central

    Brenner, B G; Wainberg, M A

    1999-01-01

    Heat shock proteins (hsps) and cyclophilins (CypA) are intracellular chaperone molecules that facilitate protein folding and assembly. These proteins are selectively expressed in cells following exposure to a range of stress stimuli, including viral infection. Hsp species are highly immunogenic, eliciting humoral, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell responses against viruses, tumours, and infectious diseases. This review discusses the roles of stress proteins in immunity and viral life cycles, vis-à-vis the development of Hsp-based therapeutic strategies against human immunodeficiency virus type-1 (HIV-1) infection. Cumulative findings are cited implicating the requirement of CypA in HIV-1 replication and formation of infectious virions. Studies by our group show the upregulated expression of hsp27 and hsp70 during single-cycle HIV infections. These species redistribute to the cell surface following HIV-infection and heat stress, serving as targets for NK and antibody-dependent cellular cytotoxicity. Co-immunoprecipitation and Western blot studies show that hsp27, hsp70, and hsp78 complex with HIV-1 viral proteins intracellularly. Hsp70, hsp56, and CypA are assembled into HIV-1 virions. The ability of hsps to interact with HIV-1 viral proteins, combined with their inherent adjuvant and immunogenic properties, indicates that hsps may serve as vehicles for antigen delivery and the design of vaccines against acquired immunodeficiency syndrome. PMID:10231014

  16. Irreversible Inhibition of Human Immunodeficiency Virus Type 1 Integrase by Dicaffeoylquinic Acids†

    PubMed Central

    Zhu, Kai; Cordeiro, Mara L.; Atienza, Jocelyn; Robinson, W. Edward; Chow, Samson A.

    1999-01-01

    Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis. PMID:10074185

  17. Isolation of human immunodeficiency virus from genital ulcers in Nairobi prostitutes.

    PubMed

    Kreiss, J K; Coombs, R; Plummer, F; Holmes, K K; Nikora, B; Cameron, W; Ngugi, E; Ndinya Achola, J O; Corey, L

    1989-09-01

    Recent epidemiologic studies have implicated genital/anorectal ulcer disease as an important cofactor for acquisition and transmission of human immunodeficiency virus (HIV) during sexual intercourse. To better understand the mechanism for the association between genital ulcers and HIV, exudates from 62 genital ulcers of 56 HIV-seropositive prostitutes in Nairobi (Kenya) were cultured for HIV. Twenty-six ulcer cultures could not be evaluated for the presence of HIV because of bacterial or fungal contamination. HIV was isolated from 4 (11%) of the 36 remaining uncontaminated ulcer cultures (2 introital, 1 vaginal, and 1 cervical) from 4 separate women. HIV was isolated from the cervical os from only 2 of the 4 women. HIV p24 antigen was detected in exudate from 1 of the 4 culture-positive ulcers and 0 of 32 culture-negative ulcers. Genital ulcers in seropositive patients should be regarded as potential sources of HIV, which could be important in transmission of HIV during intercourse. Public health measures aimed at controlling sexually transmitted genital ulcer diseases should be an integral part of acquired immunodeficiency syndrome (AIDS) prevention programs.

  18. Effect of sexual behavior change on long-term human immunodeficiency virus prevalence among homosexual men.

    PubMed

    Morris, M; Dean, L

    1994-08-01

    Substantial changes in human immunodeficiency virus (HIV)-related sexual behavior have been reported by virtually every survey of homosexual/bisexual men in the last decade. This paper uses a behavior-based simulation to examine how such changes are likely to affect the long-term future of the acquired immunodeficiency syndrome (AIDS) epidemic among homosexual men. Data from the Longitudinal AIDS Impact Project in New York City are used to estimate age-specific patterns of unprotected anogenital contact and behavioral change from 1980 to 1991. Model projections are validated using New York City surveillance data on AIDS incidence from 1981 to 1991. The current levels of unsafe sex reported in the Longitudinal AIDS Impact Project are shown to be almost exactly on the epidemic threshold. If this behavior were maintained, HIV prevalence would slowly decline in the population, but with just one additional unsafe sexual partner per year HIV would instead become endemic, with seroprevalence of about 65% in the oldest group and about 25% in the youngest. Transmission dynamics in the youngest group are analyzed in detail. For this group, the assortative age-matching bias in partner selection patterns raises the unsafe behavior threshold slightly in the long run. PMID:8030625

  19. Current laboratory diagnosis of opportunistic enteric parasites in human immunodeficiency virus-infected patients.

    PubMed

    De, Anuradha

    2013-01-01

    Diarrhea is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are encountered in 30-60% of HIV seropositive patients in developed countries and in 90% of patients in developing countries. Once the CD4(+) cell count drops below 200 cells/μl, patients are considered to have developed acquired immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or opportunistic infection significantly increasing. Opportunistic enteric parasites encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and microsporidia; as well as those more commonly associated with gastrointestinal disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in India, opportunistic enteric parasites are becoming increasingly important and it has to be identified properly. Apart from wet mounts, concentration methods for stool samples and special staining techniques for identification of these parasites, commercially available fecal immunoassays are widely available for the majority of enteric protozoa. Molecular methods such as polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in the pipeline for early diagnosis of these infections. Proper disposal of the feces to prevent contamination of the soil and water, boiling/filtering drinking water along with improved personal hygiene might go a long way in preventing these enteric parasitic infections.

  20. Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus.

    PubMed

    Bessudo, A; Rassenti, L; Havlir, D; Richman, D; Feigal, E; Kipps, T J

    1998-08-15

    We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VH gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VH gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens.

  1. Current laboratory diagnosis of opportunistic enteric parasites in human immunodeficiency virus-infected patients.

    PubMed

    De, Anuradha

    2013-01-01

    Diarrhea is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are encountered in 30-60% of HIV seropositive patients in developed countries and in 90% of patients in developing countries. Once the CD4(+) cell count drops below 200 cells/μl, patients are considered to have developed acquired immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or opportunistic infection significantly increasing. Opportunistic enteric parasites encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and microsporidia; as well as those more commonly associated with gastrointestinal disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in India, opportunistic enteric parasites are becoming increasingly important and it has to be identified properly. Apart from wet mounts, concentration methods for stool samples and special staining techniques for identification of these parasites, commercially available fecal immunoassays are widely available for the majority of enteric protozoa. Molecular methods such as polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in the pipeline for early diagnosis of these infections. Proper disposal of the feces to prevent contamination of the soil and water, boiling/filtering drinking water along with improved personal hygiene might go a long way in preventing these enteric parasitic infections. PMID:23961436

  2. Current laboratory diagnosis of opportunistic enteric parasites in human immunodeficiency virus-infected patients

    PubMed Central

    De, Anuradha

    2013-01-01

    Diarrhea is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are encountered in 30-60% of HIV seropositive patients in developed countries and in 90% of patients in developing countries. Once the CD4+ cell count drops below 200 cells/μl, patients are considered to have developed acquired immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or opportunistic infection significantly increasing. Opportunistic enteric parasites encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and microsporidia; as well as those more commonly associated with gastrointestinal disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in India, opportunistic enteric parasites are becoming increasingly important and it has to be identified properly. Apart from wet mounts, concentration methods for stool samples and special staining techniques for identification of these parasites, commercially available fecal immunoassays are widely available for the majority of enteric protozoa. Molecular methods such as polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in the pipeline for early diagnosis of these infections. Proper disposal of the feces to prevent contamination of the soil and water, boiling/filtering drinking water along with improved personal hygiene might go a long way in preventing these enteric parasitic infections. PMID:23961436

  3. Diagnostic implications of Ga-67 chest-scan patterns in human immunodeficiency virus-seropositive patients

    SciTech Connect

    Kramer, E.L.; Sanger, J.H.; Garay, S.M.; Grossman, R.J.; Tiu, S.; Banner, H.

    1989-03-01

    Consecutive gallium-67 scans (n = 237) of 180 human immunodeficiency virus-seropositive patients with suspected pulmonary infections were evaluated for intensity and pattern of gallium distribution. Scan findings were correlated with the history, chest radiographic findings, and clinicopathologic diagnoses. Pneumocystis carinii pneumonia (PCP) occurred significantly more often with heterogeneous diffuse uptake than with homogeneous diffuse uptake. Heterogeneous diffuse uptake had an 87% positive predictive value for PCP, which was higher than that of other patterns. Localized pulmonary uptake was most commonly due to bacterial pneumonia or PCP; ill-defined, perihilar uptake, to cytomegalovirus or PCP; and focal (lymph node) uptake, to tuberculosis or lymphoma. The positive predictive value of any pulmonary uptake for lung pathology was 93%, and the negative predictive value of a negative scan was 96%. These findings confirm the utility of gallium scanning in the detection of lung pathology related to acquired immunodeficiency syndrome, particularly PCP. Furthermore, identification of a diffuse pattern may permit the use of a less invasive test more specifically directed at the confirmation of a diagnosis of PCP.

  4. Projection of human immunodeficiency virus among high-risk groups in Malaysia.

    PubMed

    Mondal, Md Nazrul Islam; Shitan, Mahendran

    2013-01-01

    Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) presents a serious healthcare threat to young individuals in Malaysia and worldwide. This study aimed to identify trends in HIV-related risk behaviors among recognized high-risk groups and to estimate HIV transmission up to the year 2015. Data and necessary information were obtained from the Ministry of Health Malaysia, published reports from the World Health Organization and United Nations Program on HIV/AIDS, and other articles. The Estimation and Projection Package was used to estimate HIV transmission. The results of the present study revealed that within the high-risk groups, intravenous drug users (IDUs) had the highest prevalence rate of HIV transmission, followed by patients with sexually transmitted infections (STIs), female sex workers (SWs), and men who have sex with men (MSM). Within these at-risk populations, patients with STIs have the highest prevalence of HIV, followed by IDUs, MSM, and SWs. If the transmission rate continues to increase, the situation will worsen; therefore, there is an urgent need for a comprehensive prevention program to control HIV transmission in Malaysia. PMID:24047742

  5. Human immunodeficiency virus infection in heterosexual intravenous drug users in San Francisco.

    PubMed Central

    Chaisson, R E; Moss, A R; Onishi, R; Osmond, D; Carlson, J R

    1987-01-01

    To investigate the risk of infection with the human immunodeficiency virus (HIV) in San Francisco, the prevalence of antibodies to HIV was determined in 281 heterosexual intravenous drug users recruited from community-based settings. Ten per cent of subjects had ELISA and Western blot confirmed seropositivity for antibodies (95 per cent CI 6.8-14.2 per cent). Analysis of behavioral factors revealed an increased risk of seropositivity in addicts who reported regularly sharing needles when injecting, particularly those sharing with two or more persons (odds ratio = 5.43; 95 per cent CI 1.08-52.5). Blacks and Latinos also had a greater prevalence of seropositivity than Whites, and this finding persisted after adjustment for needle sharing (adjusted odds ratio = 2.8; 95 per cent CI .84-8.59). Seropositivity was not associated with age, sex, duration of drug use, or history of prostitution. These data indicate that a new epidemic of AIDS (acquired immunodeficiency syndrome) in intravenous drug users, similar to that which has occurred among homosexuals in San Francisco, is possible. The relatively low seroprevalence in 1985 provides health officials an important opportunity to intervene and attempt to prevent widespread infection of drug users with HIV. PMID:3467596

  6. Salivary gland lymph nodes. The site of lymphadenopathies and lymphomas associated with human immunodeficiency virus infection.

    PubMed

    Ioachim, H L; Ryan, J R; Blaugrund, S M

    1988-12-01

    Normally, lymph nodes are intimately associated with the salivary glands, particularly the parotid gland. Several lymph nodes are embedded in the parotid gland, other lymph nodes are adjacent to the submaxillary gland, and ectopic salivary gland acini and ducts are commonly present in cervical lymph nodes. These salivary gland lymph nodes may become the primary site of the benign lymphadenopathy and the malignant lymphomas characteristically associated with human immunodeficiency virus (HIV) infection. This report of a series of HIV-associated lymphatic lesions originating in salivary gland lymph nodes comprises nine cases of salivary gland masses that were surgically excised, it includes six cases of lymphadenitides and three cases of lymphoma--all originating in salivary gland lymph nodes and showing the histologic lesions known to occur in association with the acquired immunodeficiency syndrome. The HIV-related infections and neoplasias located in the salivary gland lymph nodes raise interesting questions about the possible etiologic role of an oral portal of entry and of the virus-infected saliva. The recognition of their clinical and pathologic features is indispensable to enable correct diagnosis and treatment.

  7. The spectrum of human immunodeficiency virus infection in patients with factor IX deficiency (Christmas disease)

    PubMed

    Goldsmith, J M; Variakojis, D; Phair, J P; Green, D

    1987-06-01

    Early reports suggested that hemophiliacs with factor IX deficiency (Christmas Disease) may be at less risk for developing the acquired immunodeficiency syndrome (AIDS) than patients with classic hemophilia. We evaluated 12 factor IX deficient patients for clinical and immunologic abnormalities related to infection with the human immunodeficiency virus (HIV). Antibody to HIV was not detected in these patients prior to 1982. By 1985, 66 percent (eight of 12) patients were seropositive. All three concentrates available commercially before 1985 were associated with seropositivity. Furthermore, seropositive hemophiliacs had received on average significantly more factor IX concentrate than seronegative hemophiliacs (27,825 +/- 17,976 (S.D.) versus 1,250 +/- 1,500 factor units/year, (p less than 0.02). Half of the seropositive individuals had generalized lymphadenopathy with splenomegaly. Two seropositive patients have developed AIDS, one with cryptococcal meningitis and another with a large cell immunoblastic lymphoma. Infection with HIV has occurred with high frequency in hemophiliacs who received unmodified factor IX concentrates.

  8. An Orphan Seven-Transmembrane Domain Receptor Expressed Widely in the Brain Functions as a Coreceptor for Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus

    PubMed Central

    Edinger, Aimee L.; Hoffman, Trevor L.; Sharron, Matthew; Lee, Benhur; Yi, Yanji; Choe, Wonkyu; Kolson, Dennis L.; Mitrovic, Branka; Zhou, Yiqing; Faulds, Daryl; Collman, Ronald G.; Hesselgesser, Joseph; Horuk, Richard; Doms, Robert W.

    1998-01-01

    Both CD4 and an appropriate coreceptor are necessary for infection of cells by human immunodeficiency virus type 1 (HIV-1) and most strains of HIV-2. The chemokine receptors CCR5 and CXCR4 are the major HIV-1 coreceptors, although some virus strains can also utilize alternative coreceptors such as CCR3 to infect cells. In contrast, most if not all simian immunodeficiency virus (SIV) strains use CCR5 as a coreceptor, and many SIV strains can use CCR5 independently of CD4. In addition, several orphan seven-transmembrane receptors which can serve as HIV-1 and SIV coreceptors have been identified. Here we report that APJ, an orphan seven-transmembrane domain receptor with homology to the angiotensin receptor family, functions as a coreceptor for a number of HIV-1 and SIV strains. APJ was expressed widely in the human brain and in NT2N neurons. APJ transcripts were also detected by reverse transcription-PCR in the CD4-positive T-cell line C8166, but not in peripheral blood leukocytes, microglia, phytohemagglutinin (PHA)- or PHA/interleukin-2-stimulated peripheral blood mononuclear cells, monocytes, or monocyte-derived macrophages. The widespread distribution of APJ in the central nervous system coupled with its use as a coreceptor by some HIV-1 strains indicates that it may play a role in neuropathogenesis. PMID:9733831

  9. Comparison of Talaromyces marneffei Infection in Human Immunodeficiency Virus-positive and Human Immunodeficiency Virus-negative Patients from Fujian, China

    PubMed Central

    Li, Hong-Ru; Cai, Shao-Xi; Chen, Yu-Sheng; Yu, Mei-E; Xu, Neng-Luan; Xie, Bao-Song; Lin, Ming; Hu, Xin-Lan

    2016-01-01

    Background: Talaromyces (Penicillium) marneffei (TM) is an emerging dimorphic human pathogenic fungus that is endemic to Southeast Asia. TM mostly occurs as an opportunistic infection in patients with human immunodeficiency virus (HIV). The objective of this study was to compare the clinical and laboratory parameters of patients with TM infections who were HIV-positive and HIV-negative and to assess therapies and outcomes. Methods: This was a retrospective analysis of 26 patients diagnosed with disseminated TM infection from September 2005 to April 2014 at Fujian Provincial Hospital, China. Results: Patients with TM infection tend to present with fever, weight loss, and anemia. The time from symptom onset to confirmed diagnosis was greater for HIV-negative patients (n = 7; median: 60 days, range: 14–365 days) than for HIV-positive patients (n = 19; median: 30 days, range: 3–90 days, Mann–Whitney U = 31.50, P = 0.041). HIV-negative patients were more likely to have dyspnea (57.1% vs. 5.3%, χ2 = 8.86, P = 0.010), low neutrophil count (Mann–Whitney U = 27.00, P = 0.029), high CD4 count (Mann–Whitney U = 0.00, P = 0.009), and high lymphocyte count (Mann–Whitney U = 21.00, P = 0.009). There were no significant differences in other demographic, clinical, or biochemical characteristics. Among all the patients, 12 HIV-positive patient and 1 HIV-negative patient received amphotericin and fluconazole treatment, 9 of whom improved, 1 died, 2 had kidney damage, 1 had hypokalemia due to exceeded doses. Conclusions: HIV-negative patients with TM infections tend to have a longer diagnostic interval, a higher percentage of dyspnea, higher levels of CD4 and lymphocytes, and lower neutrophil counts than TM infection in HIV-positive patients. Treatment programs with amphotericin and fluconazole are mostly effective. PMID:27098791

  10. A new immunodeficient pigmented retinal degenerate rat strain to study transplantation of human cells without immunosuppression

    PubMed Central

    Seiler, Magdalene J.; Aramant, Robert B.; Jones, Melissa K.; Ferguson, Dave L.; Bryda, Elizabeth C.

    2015-01-01

    Purpose The goal of this study was to develop an immunodeficient rat model of retinal degeneration (RD nude rats) that will not reject transplanted human cells. Methods SD-Tg(S334ter)3Lav females homozygous for a mutated mouse rhodopsin transgene were mated with NTac:NIH-Whn (NIH nude) males homozygous for the Foxn1rnu allele. Through selective breeding, a new stock, SD-Foxn1 Tg(S334ter)3Lav (RD nude) was generated such that all animals were homozygous for the Foxn1rnu allele and either homo- or hemizygous for the S334ter transgene. PCR-based assays for both the Foxn1rnu mutation and the S334ter transgene were developed for accurate genotyping. Immunodeficiency was tested by transplanting sheets of hESC-derived neural progenitor cells to the subretinal space of RD nude rats, and, as a control, NIH nude rats. Rats were killed between 8 and 184 days after surgery, and eye sections were analyzed for human, neuronal, and glial markers. Results After transplantation to RD nude and to NIH nude rats, hESC-derived neural progenitor cells differentiated to neuronal and glial cells, and migrated extensively from the transplant sheets throughout the host retina. Migration was more extensive in RD nude than in NIH nude rats. Already 8 days after transplantation, donor neuronal processes were found in the host inner plexiform layer. In addition, host glial cells extended processes into the transplants. The host retina showed the same photoreceptor degeneration pattern as in the immunocompetent SD-Tg(S334ter)3Lav rats. Recipients survived well after surgery. Conclusions This new rat model is useful for testing the effect of human cell transplantation on the restoration of vision without interference of immunosuppression. PMID:24817311

  11. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... Disclosures Without Patient Consent § 1.486 Disclosure of information related to infection with the...

  12. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... Disclosures Without Patient Consent § 1.486 Disclosure of information related to infection with the...

  13. 38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Disclosure of information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1... Disclosures Without Patient Consent § 1.486 Disclosure of information related to infection with the...

  14. Trends in Human Immunodeficiency Virus-Related Risk Behaviors among High School Students--United States, 1991-2005

    ERIC Educational Resources Information Center

    Brener, Nancy; Kann, Laura; Lowry, Richard; Wechsler, Howell; Romero, Lisa

    2006-01-01

    This paper examined changes in human immunodeficiency virus (HIV)-related risk behaviors among high school students in the United States during 1991-2005. Data from 8 national Youth Risk Behavior Surveys conducted during that period were analyzed. During 1991-2005, the percentage of US high school students engaging in HIV-related sexual risk…

  15. Construction and Use of a Replication-Competent Human Immunodeficiency Virus (HIV-1) that Expresses the Chloramphenicol Acetyltransferase Enzyme

    NASA Astrophysics Data System (ADS)

    Terwilliger, E. F.; Godin, B.; Sodroski, J. G.; Haseltine, W. A.

    1989-05-01

    The construction and properties of an infectious human immunodeficiency virus (HIV) that expresses the bacterial gene chloramphenicol acetyltransferase are described. This virus can be used in vitro to screen for drugs that inhibit HIV infection. The marked virus may also be used to trace the routes of infection from the site of inoculation in animal experiments.

  16. Identification of Light-independent Inhibition of Human Immunodeficiency Virus-1 Infection through Bioguided Fractionation of Hypericum perforatum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not. Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (...

  17. A One-Session Human Immunodeficiency Virus Risk-Reduction Intervention in Adolescents with Psychiatric and Substance Use Disorders

    ERIC Educational Resources Information Center

    Thurstone, Christian; Riggs, Paula D.; Klein, Constance; Mikulich-Gilbertson, Susan K.

    2007-01-01

    Objective: To explore change in human immunodeficiency virus (HIV) risk among teens in outpatient treatment for substance use disorders (SUDs). Method: From December 2002 to August 2004, 50 adolescents (13-19 years) with major depressive disorder, conduct disorder, and one or more non-nicotine SUD completed the Teen Health Survey (THS) at the…

  18. A Glimpse of the Early Years of the Human Immunodeficiency Virus Epidemic: A Fellow's Experience in 2014

    PubMed Central

    Colasanti, Jonathan; Armstrong, Wendy S.

    2014-01-01

    Human immunodeficiency virus (HIV) is a manageable chronic disease in the United States, yet the first author's experience on a general infectious diseases (ID) consult service illustrates that certain areas of the United States still experience high rates of acquired immune deficiency syndrome-related complications. PMID:25734112

  19. Pharmacological pain control for human immunodeficiency virus—infected adults with a history of drug dependence

    PubMed Central

    Basu, Sanjay; Bruce, R. Douglas; Barry, Declan T.; Altice, Frederick L.

    2007-01-01

    Clinicians treating human immunodeficiency virus (HIV)-infected patients with substance use disorders often face the challenge of managing patients' acute or chronic pain conditions while keeping in mind the potential dangers of prescription opiate dependence. In this clinical review, we critically appraise the existing data concerning barriers to appropriate treatment of pain among HIV-infected patients with substance use disorders. We then analyze published studies concerning the choice of pharmacological pain control regimens for acute and chronic pain conditions in HIV-infected patients, keeping in mind HIV-specific issues related to drug interactions and substance use disorders. We summarize this information in the form of flowcharts for physicians approaching HIV-infected patients who present with complaints of pain, providing evidence-based guidance for the structuring of pain management services and for addressing aberrant drug-taking behaviors. PMID:17481463

  20. Immunobiology of the human immunodeficiency virus envelope and its relationship to vaccine strategies.

    PubMed

    Bolognesi, D P

    1990-02-01

    The envelope of human immunodeficiency virus (HIV) is an essential building block of the virus and it plays a major role in its life-cycle, particularly during the early stages of infection. It very likely determines, at least in part, the host range and tissue specificity of HIV, participates in pathogenic processes mediated by the virus and can itself be immunosuppressive. Because of its strategic location on the outer surface of the virion and the infected cell, it also represents an optimal (although not the only) target for immune attack and thus a prime candidate for development of vaccine and therapeutic strategies. Efforts to better understand its structural, functional and antigenic properties will thus be well worthwhile. Some of its principal features are reviewed herein and its role in vaccine strategies is discussed. PMID:2182967

  1. A Hairpin Ribozyme Inhibits Expression of Diverse Strains of Human Immunodeficiency Virus Type 1

    NASA Astrophysics Data System (ADS)

    Yu, Mang; Ojwang, Joshua; Yamada, Osamu; Hampel, Arnold; Rapapport, Jay; Looney, David; Wong-Staal, Flossie

    1993-07-01

    Ribozymes have enormous potential as antiviral agents. We have previously reported that a hairpin ribozyme expressed under the control of the β-actin promoter that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence can inhibit HIV-1 (pHXB2gpt) expression. For such a ribozyme in a retroviral vector delivery system to be useful in gene therapy for the treatment of HIV-1 infection, it must be able to inhibit the expression of multiple HIV-1 strains. We have now cloned this ribozyme into various regular expression vectors (including retroviral vectors) by using various gene expression control strategies. Here we show by transient transfection that inhibition of expression of diverse strains of HIV-1 can be achieved by this ribozyme expressed in the proper vectors. These data further support the potential of this hairpin ribozyme as a therapeutic agent for HIV-1.

  2. Normal Pressure Hydrocephalus in a Human Immunodeficiency Virus Type 1 Patient

    PubMed Central

    Regeti, Kalyani; Khan, Rafay; Jehangir, Waqas; Zafar, Shoaib; Yousif, Abdalla; Sen, Shuvendu

    2016-01-01

    Normal pressure hydrocephalus (NPH) is a relatively common disease of adulthood characterized by a typical combination of clinical and radiological findings. In this report, we discuss a 54-year-old female presenting with symptoms suggestive of NPH and found to have a history of human immunodeficiency virus (HIV) type 1. She was not treated as she was in denial state and developed NPH as a possible complication. In the literature, there has only been one reported case of HIV type 2 causing NPH; however, no relationship has been properly documented with HIV type 1. These findings bring about a question on whether NPH is associated or a complication of HIV with awareness of this association. Earlier screening of HIV can be done in patients presenting with such symptoms, thus to prevent further progression of its complications. PMID:27222676

  3. Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia.

    PubMed

    Harimurti, Kuntjoro; Saldi, Siti R F; Dewiasty, Esthika; Khoeri, Miftahuddin M; Yunihastuti, Evi; Putri, Tiara; Tafroji, Wisnu; Safari, Dodi

    2016-01-01

    This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia.

  4. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

    SciTech Connect

    Ealy, Julie B.; Sudol, Malgorzata; Krzeminski, Jacek; Amin, Shantu; Katzman, Michael

    2012-11-10

    Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

  5. Relative concordance of human immunodeficiency virus oligomeric and monomeric envelope in CCR5 coreceptor usage

    SciTech Connect

    Teeravechyan, Samaporn; Suphaphiphat, Pirada; Essex, Max; Lee, Tun-Hou

    2008-01-20

    A major difference between binding and fusion assays commonly used to study the human immunodeficiency virus (HIV) envelope is the use of monomeric envelope for the former assay and oligomeric envelope for the latter. Due to discrepancies in their readouts for some mutants, envelope regions involved in CCR5 coreceptor usage were systematically studied to determine whether the discordance is due to inherent differences between the two assays or whether it genuinely reflects functional differences at each entry step. By adding the binding inhibitor TAK-779 to delay coreceptor binding kinetics in the fusion assay, the readouts were found comparable between the assays for the mutants analysed in this study. Our finding indicates that monomeric binding reflects oligomeric envelope-CCR5 interaction, thus discordant results between binding and fusion assays do not necessarily indicate differences in coreceptor usage by oligomeric envelope and monomeric gp120.

  6. Effect of human immunodeficiency virus on blood-brain barrier integrity and function: an update

    PubMed Central

    Atluri, Venkata Subba Rao; Hidalgo, Melissa; Samikkannu, Thangavel; Kurapati, Kesava Rao Venkata; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan P. N.

    2015-01-01

    The blood-brain barrier (BBB) is a diffusion barrier that has an important role in maintaining a precisely regulated microenvironment protecting the neural tissue from infectious agents and toxins in the circulating system. Compromised BBB integrity plays a major role in the pathogenesis of retroviral associated neurological diseases. Human Immunodeficiency Virus (HIV) infection in the Central Nervous System (CNS) is an early event even before the serodiagnosis for HIV positivity or the initiation of antiretroviral therapy (ART), resulting in neurological complications in many of the infected patients. Macrophages, microglia and astrocytes (in low levels) are the most productively/latently infected cell types within the CNS. In this brief review, we have discussed about the effect of HIV infection and viral proteins on the integrity and function of BBB, which may contribute to the progression of HIV associated neurocognitive disorders. PMID:26113810

  7. Antiretroviral regimen and suboptimal medication adherence are associated with low-level human immunodeficiency virus viremia.

    PubMed

    Konstantopoulos, Christina; Ribaudo, Heather; Ragland, Kathleen; Bangsberg, David R; Li, Jonathan Z

    2015-01-01

    Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification. PMID:25884007

  8. Expanding human immunodeficiency virus testing and counseling to reach tuberculosis clients' partners and families.

    PubMed

    Courtenay-Quirk, C; Date, A; Bachanas, P; Baggaley, R; Getahun, H; Nelson, L; Granich, R

    2015-12-01

    Recent years have shown important increases in human immunodeficiency virus (HIV) testing and counseling (HTC), diagnosis, and coverage of antiretroviral therapy (ART) among HIV-infected tuberculosis (TB) patients. Expansion of HTC for partners and families are critical next steps to increase earlier HIV diagnoses and access to ART, and to achieve international goals for reduced TB and HIV-related morbidity, mortality, transmission and costs. TB and HIV programs should develop and evaluate feasible and effective strategies to increase access to HTC among the partners and families of TB patients, and ensure that newly diagnosed people living with HIV and HIV-infected TB patients who complete anti-tuberculosis treatment are successfully linked to ongoing HIV clinical care.

  9. Bispecific Antibodies that Mediate Killing of Cells Infected with Human Immunodeficiency Virus of Any Strain

    NASA Astrophysics Data System (ADS)

    Berg, Jorg; Lotscher, Erika; Steimer, Kathelyn S.; Capon, Daniel J.; Baenziger, Jurg; Jack, Hans-Martin; Wabl, Matthias

    1991-06-01

    Although AIDS patients lose human immunodeficiency virus (HIV)-specific cytotoxic T cells, their remaining CD8-positive T lymphocytes maintain cytotoxic function. To exploit this fact we have constructed bispecific antibodies that direct cytotoxic T lymphocytes of any specificity to cells that express gp120 of HIV. These bispecific antibodies comprise one heavy/light chain pair from an antibody to CD3, linked to a heavy chain whose variable region has been replaced with sequences from CD4 plus a second light chain. CD3 is part of the antigen receptor on T cells and is responsible for signal transduction. In the presence of these bispecific antibodies, T cells of irrelevant specificity effectively lyse HIV-infected cells in vitro.

  10. Reduction of human immunodeficiency virus-infected cells from donor blood by leukocyte filtration.

    PubMed

    Rawal, B D; Busch, M P; Endow, R; Garcia-de-Lomas, J; Perkins, H A; Schwadron, R; Vyas, G N

    1989-06-01

    Several filters for leukocyte removal were evaluated in terms of their ability to reduce the cell-associated human immunodeficiency virus (HIV) load in units of blood either inoculated in vitro with lymphocytes from a chronically infected cell line or collected directly from seropositive donors. Filtration of the experimentally inoculated units of blood resulted in a 5.9 log 10 mean reduction (95% confidence interval:7.4-4.5) of tissue culture infectious units (TCIU) as assayed by end-point titration using the coculture assay. Filtration of the units of blood from anti-HIV positive donors lowered the infectivity by over 2 logs, as detected by the coculture and polymerase chain reaction (PCR) techniques. However, residual cell-associated virus was detected in the majority of experiments. Clinical studies are warranted to determine if leukocyte filtration of blood will reduce the risk of transfusion transmitted viral infections.

  11. The human immunodeficiency virus type 1 Rev protein shuttles between the cytoplasm and nuclear compartments.

    PubMed Central

    Kalland, K H; Szilvay, A M; Brokstad, K A; Saetrevik, W; Haukenes, G

    1994-01-01

    A retroviral regulatory protein, Rev (regulator of virion protein expression), is made in cells infected by human immunodeficiency virus (HIV). Rev is essential for the completion of the retroviral life cycle and interacts with the host cell at some posttranscriptional step in order to express the incompletely spliced HIV mRNAs from which HIV structural proteins are translated. Neither the host cell components nor the mechanisms responsible for this important regulation have been defined. We now report that Rev is a nucleocytoplasmic shuttle protein which is continuously transported between the cytoplasm, the nucleoli, and nucleoplasmic speckles enriched in RNA splicing and processing factors. The results show that Rev has the potential to interfere specifically with the splicing of the HIV pre-mRNA in the nucleoplasm and, next, guide such mRNAs to the cytoplasm for translation. Images PMID:7935458

  12. [Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus].

    PubMed

    Iribarren-Díaz, Mauricio; Ocampo Hermida, Antonio; González-Carreró Fojón, Joaquín; Alonso-Parada, María; Rodríguez-Girondo, Mar

    2014-12-01

    Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia.

  13. Beta 2-microglobulin and neopterin: predictive markers for human immunodeficiency virus type 1 infection in children?

    PubMed Central

    Chan, M M; Campos, J M; Josephs, S; Rifai, N

    1990-01-01

    The value of beta 2-microglobulin and neopterin concentrations in serum for early diagnosis of infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers was assessed. Concentrations of both markers were measured in serum samples from pediatric patients (Centers for Disease Control classifications P0, P1, and P2), as well as in age-matched normal subjects. Both beta 2-microglobulin and neopterin were significantly increased in HIV-1-infected symptomatic subjects (P2) compared to controls. Seventy-five percent of asymptomatic patients (P1) also had increased values. On the other hand, a significant overlap in concentrations of both markers in serum was found between controls and P0 patients. Thirty-eight percent of the P0 patients had values comparable to those of the P2 group. Persistently high concentrations of both markers in P0 patients may be indicative of HIV-1 infection. PMID:2229344

  14. ADAR2 editing enzyme is a novel human immunodeficiency virus-1 proviral factor.

    PubMed

    Doria, Margherita; Tomaselli, Sara; Neri, Francesca; Ciafrè, Silvia Anna; Farace, Maria Giulia; Michienzi, Alessandro; Gallo, Angela

    2011-05-01

    The adenosine deaminases acting on RNA (ADAR) enzymes catalyse conversion of adenosine to inosine in dsRNA. A positive effect of ADAR1 on human immunodeficiency virus type 1 (HIV-1) replication has recently been reported. Here, we show that another ADAR enzyme, ADAR2, positively affects the replication process of HIV-1. We found that, analogously to ADAR1, ADAR2 enhances the release of progeny virions by an editing-dependent mechanism. However, differently from the ADAR1 enzyme, ADAR2 does not increase the infectious potential of the virus. Importantly, downregulation of ADAR2 in Jurkat cells significantly impairs viral replication. Therefore, ADAR2 shares some but not all proviral functions of ADAR1. These results suggest a novel role of ADAR2 as a viral regulator. PMID:21289159

  15. Evaluation of the disinfectant effect of Solprogel against human immunodeficiency virus type 1 (HIV-1).

    PubMed

    Hernández, A; Belda, F J; Domínguez, J; Matas, L; Gimenez, M; Caraballo, M; Ramil, C; Ausina, V

    1996-11-01

    The antiviral activities of sodium dichloroisocyanurate (NaDCC) and a commercial product (Solprogel 2%) against human immunodeficiency virus type 1 (HIV-1) were investigated using a quantitative suspension test method. Solprogel is a compound that contains NaDCC and a biodegradable polymer of acrylic acid. Viral suspensions were prepared containing 3.2 x 10(6) tissue culture infective dose 50 (TCID50) in culture media. Syncytium formation in the MT-2 line and HIV antigen p24 on the supernatant of the cultures were used to determine viral titre. Results indicate that satisfactory disinfection (1000-fold reduction in 5 min) can be achieved using NaDCC and Solprogel at concentrations of 100 and 120 ppm available chlorine, respectively. PMID:8923278

  16. Normal Pressure Hydrocephalus in a Human Immunodeficiency Virus Type 1 Patient.

    PubMed

    Regeti, Kalyani; Khan, Rafay; Jehangir, Waqas; Zafar, Shoaib; Yousif, Abdalla; Sen, Shuvendu

    2016-06-01

    Normal pressure hydrocephalus (NPH) is a relatively common disease of adulthood characterized by a typical combination of clinical and radiological findings. In this report, we discuss a 54-year-old female presenting with symptoms suggestive of NPH and found to have a history of human immunodeficiency virus (HIV) type 1. She was not treated as she was in denial state and developed NPH as a possible complication. In the literature, there has only been one reported case of HIV type 2 causing NPH; however, no relationship has been properly documented with HIV type 1. These findings bring about a question on whether NPH is associated or a complication of HIV with awareness of this association. Earlier screening of HIV can be done in patients presenting with such symptoms, thus to prevent further progression of its complications. PMID:27222676

  17. Condom use prevents genital ulcers in women working as prostitutes. Influence of human immunodeficiency virus infection.

    PubMed

    Cameron, D W; Ngugi, E N; Ronald, A R; Simonsen, J N; Braddick, M; Bosire, M; Kimata, J; Kamala, J; Ndinya-Achola, J O; Waiyaki, P G

    1991-01-01

    Control of genital ulcer disease (GUD) is a proposed intervention to slow the dissemination of human immunodeficiency virus (HIV) infection. Programs for the control of sexually transmitted diseases (STD) should focus on groups of high-frequency transmitters, such as prostitutes and their clientele. This study illustrates the interaction between the prevalence of chancroid, use of barrier prophylaxis against STDs, and HIV infection in a population of female prostitutes in Nairobi. Four hundred and twenty three women were evaluated. Despite the increased use of condoms, the prevalence of genital ulcers remained constant between 1986-87 and 1987-88. Genital ulcer disease was simultaneously associated with HIV infection (adjusted odds ratio: 3.7, P less than .01) whereas it was independently and inversely associated with more consistent condom use (P less than .01). The authors conclude that genital ulcer disease can be controlled in these populations but concurrent HIV infection increases the difficulty of this intervention.

  18. Human immunodeficiency virus type 1 seroconversion in women with genital ulcers.

    PubMed

    Plourde, P J; Pepin, J; Agoki, E; Ronald, A R; Ombette, J; Tyndall, M; Cheang, M; Ndinya-Achola, J O; D'Costa, L J; Plummer, F A

    1994-08-01

    Genital ulcers are implicated as a risk factor enhancing susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. A prospective study to determine the incidence of and risk factors associated with acquisition of HIV-1 in women with genital ulcers was done. HIV-1-seronegative women with genital ulcers attending a clinic for sexually transmitted diseases in Nairobi were followed to HIV-1 seroconversion over a 6-month period. Of 81 women, 10 seroconverted to HIV-1. The crude 6-month incidence of HIV-1 infection was 12%. Risk factors associated with seroconversion included cervical ectopy (rate ratio [RR], 4.9; 95% confidence interval [CI], 1.5-15.6) and pelvic inflammatory disease (RR, 6.3; 95% CI, 1.9-20.4). Thus, cervical ectopy and pelvic inflammatory disease may increase susceptibility to HIV-1 in women with genital ulcers.

  19. Retinal blood flow indices in patients infected with human immunodeficiency virus.

    PubMed Central

    Yung, C W; Harris, A; Massicotte, S; Chioran, G; Krombach, G; Danis, R; Wolf, S

    1996-01-01

    AIMS/BACKGROUND: Abnormal blood flow dynamics are believed to contribute to the development of retinal microvascular disease in patients infected with human immunodeficiency virus (HIV). In this study, the scanning laser ophthalmoscope (SLO) was used, combined with fluorescein angiography, to measure retinal blood flow indices in HIV seropositive patients. METHODS: Arteriovenous passage time (AVP) and perifoveal capillary blood flow velocity (CFV) were measured in 23 HIV infected patients and 23 control subjects with SLO fluorescein angiography. RESULTS: No significant difference in AVP was found between the two groups. However, CFV was significantly reduced in HIV infected patients (p = 0.013). CONCLUSION: Patients infected with HIV show abnormal haemodynamics at the level of the perifoveal capillaries. PMID:8949717

  20. Human Immunodeficiency Virus and Allergic Bronchopulmonary Aspergillosis: Case Report and Review of Literature

    PubMed Central

    Galiatsatos, Panagis; Melia, Michael T.; Silhan, Leann L.

    2016-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) results from a hypersensitivity response to airways colonization with Aspergillus fumigatus, and it occurs most often in individuals with asthma or cystic fibrosis. Allergic bronchopulmonary aspergillosis is an indolent, but potentially progressive, disease in patients. In patients infected with human immunodeficiency virus (HIV), ABPA is rare, and its description in the literature is limited to case reports. We describe the occurrence of ABPA in a 37-year-old woman with well controlled HIV infection. This represents the first documented case of ABPA in an HIV-infected patient whose only pulmonary comorbidity included the ramifications of prior acute respiratory distress syndrome due to Pneumocystis jirovecii pneumonia. We also review prior case reports of ABPA in HIV-infected patients and consider risk factors for its development. PMID:27419184

  1. Amebic liver abscess and human immunodeficiency virus infection: a report of three cases.

    PubMed

    Liu, C J; Hung, C C; Chen, M Y; Lai, Y P; Chen, P J; Huang, S H; Chen, D S

    2001-07-01

    Invasive amebiasis rarely occurs in homosexual men and human immunodeficiency virus (HIV)-infected individuals and has not been regarded as a beacon for concomitant HIV infection. We encountered a bisexual man with a protracted course of amebic liver abscess and amebic colitis. In the presence of fever, generalized lymphadenopathy, and elevated serum aminotransferase levels, HIV infection was suspected and then confirmed by a de novo seroconversion of HIV antibody. Subsequently, we noted two consecutive patients with amebic liver abscess, also later found to be infected with HIV. The ameba obtained from these three cases was identified as Entamoeba histolytica by amplification of 16S ribosomal RNA by polymerase chain reaction and direct sequencing. This observation suggests that amebic liver abscess and colitis can be presentations for HIV infection in the Far East. Thus, the local patients with invasive amebiasis, especially those with a protracted course or with risk factors of HIV infection, should be tested for HIV.

  2. Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: A preliminary report

    SciTech Connect

    Masdeu, J.C.; Yudd, A.; Van Heertum, R.L.; Grundman, M.; Hriso, E.; O'Connell, R.A.; Luck, D.; Camli, U.; King, L.N. )

    1991-08-01

    Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.

  3. Dual infection with dengue virus 3 and human immunodeficiency virus 1 in Havana, Cuba.

    PubMed

    Gonzalez, Daniel; Limonta, Daniel; Bandera, Juan Francisco; Perez, Jorge; Kouri, Gustavo; Guzman, Maria G

    2009-01-01

    Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.

  4. Antibodies to CD4 in individuals infected with human immunodeficiency virus type 1.

    PubMed Central

    Kowalski, M; Ardman, B; Basiripour, L; Lu, Y C; Blohm, D; Haseltine, W; Sodroski, J

    1989-01-01

    The attachment of human immunodeficiency virus type 1 (HIV-1) to target cells is mediated by a specific interaction between the viral envelope glycoprotein (gp120) and the CD4 receptor. Here we report that approximately 10% of HIV-1-infected individuals produce antibodies that recognize the extracellular portion of the CD4 molecule. Carboxyl-terminal deletions of CD4 that do not affect HIV-1 gp120 binding eliminate recognition of CD4 by patient antisera. In contrast, mutations in the amino-terminal domain of CD4 that attenuate HIV-1 gp120 binding do not diminish CD4 recognition by patient antisera. These results suggest that HIV-1 infection can generate antibodies directed against a region of the viral receptor distinct from the virus-binding domain. Images PMID:2541442

  5. Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques.

    PubMed Central

    Lu, Y; Brosio, P; Lafaile, M; Li, J; Collman, R G; Sodroski, J; Miller, C J

    1996-01-01

    Chimeric simian/human immunodeficiency viruses (SHIVs) that express the env genes derived from distinct HIV type 1 (HIV-1) isolates were tested for the ability to infect rhesus macaques following intravaginal inoculation. SHIVs containing either the HIV-1 HXBc2 or the HIV-1 89.6 envelope glycoproteins were capable of replicating in intravenously inoculated rhesus macaques. However, intravaginal inoculation of animals with these two SHIVs resulted in infection only with the SHIV containing the HIV-1 89.6 glycoprotein. Thus, properties conferred by the envelope glycoproteins in the chimeric virus affect the ability of particular SHIVs to initiate a systemic infection following vaginal inoculation. These results provide indirect support for the hypothesis that the selection of specific viral variants occurs in the genital tracts of individuals exposed to HIV by sexual contact. PMID:8627782

  6. Probiotics in Human Immunodeficiency Virus Infection: A Systematic Review and Evidence Synthesis of Benefits and Risks

    PubMed Central

    Carter, George M.; Esmaeili, Aryan; Shah, Hardikkumar; Indyk, Debbie; Johnson, Matthew; Andreae, Michael; Sacks, Henry S.

    2016-01-01

    People living with human immunodeficiency virus frequently use dietary supplements, including probiotics, but concern exists about ingesting live organisms. We performed a systematic review of the benefits of probiotics and a meta-analysis of sepsis risk. We undertook a protocol-driven, comprehensive review to identify all relevant studies, assess their quality, and summarize the evidence. Of 2068 references, 27 were analyzed. The data suggest possible benefits for CD4 count, recurrence or management of bacterial vaginosis, and diarrhea management. We examined randomized, controlled studies explicitly assessing sepsis in any patient population, and we found zero cases of supplement-associated bacteremia or fungemia in 39 randomized controlled trials comprising 9402 subjects. The estimated number needed to harm is 7369 in Bayesian approach (95% credible interval: 1689, ∞), which should reassure clinicians. No or mild adverse effects were reported. Longer duration studies investigating different individual and mixed strains for plausible indications are needed to establish best practices. PMID:27747250

  7. Associations among depression, suicidal behavior, and quality of life in patients with human immunodeficiency virus

    PubMed Central

    Serafini, Gianluca; Montebovi, Franco; Lamis, Dorian A; Erbuto, Denise; Girardi, Paolo; Amore, Mario; Pompili, Maurizio

    2015-01-01

    AIM: To investigate the potential associations among major depression, quality of life, and suicidal behavior in human immunodeficiency virus (HIV) patients. METHODS: A detailed MEDLINE search was carried out to identify all articles and book chapters in English published from January 1995 to January 2015. RESULTS: Based on the main findings, the prevalence of major depressive disorder (MDD) ranged from 14.0% to 27.2%. Furthermore, the prevalence of suicidal ideation varied from 13.6% to 31.0% whereas, attempted suicides were reported to range from 3.9% to 32.7%. Interestingly, various associated risk factors for both depression and suicide were identified in HIV patients. Finally, consistent associations were reported among MDD, suicidal ideation, and poor quality of life in individuals living with HIV. CONCLUSION: Although additional studies are needed to elucidate this complex association, our results suggest the importance of early detection of both MDD and suicidality in patients living with HIV. PMID:26279991

  8. Invasive Aspergillus Sinusitis in Human Immunodeficiency Virus Infection: Case Report and Review of the Literature

    PubMed Central

    Humphrey, John M.; Walsh, Thomas J.; Gulick, Roy M.

    2016-01-01

    Invasive Aspergillus (IA) sinusitis is a life-threatening opportunistic infection in immunocompromised individuals, but it is uncommon in human immunodeficiency virus (HIV) infection. To gain a better understanding of the characteristics of IA sinusitis in this population, we present a unique case of chronic IA sinusitis in an HIV-infected patient taking antiretroviral therapy and review the literature summarizing published cases of invasive aspergillosis of the paranasal (n = 41) and mastoid (n = 17) sinuses in HIV-infected individuals. Among these cases, only 4 were reported after 1999, and 98% of patients had acquired immune deficiency syndrome. Orbital invasion occurred in 54% of paranasal sinus cases, whereas intracranial invasion was reported in 53% of mastoid sinus cases. The overall mortality was 79%. We also discuss various clinical and immunologic factors that may play a role in the development of IA and consider the changing epidemiology of aspergillosis in the era of effective antiretroviral therapy. PMID:27800523

  9. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents

    PubMed Central

    Delagrèverie, Héloïse M.; Delaugerre, Constance; Lewin, Sharon R.; Deeks, Steven G.; Li, Jonathan Z.

    2016-01-01

    In chronic human immunodeficiency virus (HIV)-1 infection, long-lived latently infected cells are the major barrier to virus eradication and functional cure. Several therapeutic strategies to perturb, eliminate, and/or control this reservoir are now being pursued in the clinic. These strategies include latency reversal agents (LRAs) designed to reactivate HIV-1 ribonucleic acid transcription and virus production and a variety of immune-modifying drugs designed to reverse latency, block homeostatic proliferation, and replenish the viral reservoir, eliminate virus-producing cells, and/or control HIV replication after cessation of antiretroviral therapy. This review provides a summary of ongoing clinical trials of HIV LRAs and immunomodulatory molecules, and it highlights challenges in the comparison and interpretation of the expected trial results. PMID:27757411

  10. The human immunodeficiency virus and the cardiometabolic syndrome in the developing world: an African perspective.

    PubMed

    Mutimura, Eugene; Crowther, Nigel J; Stewart, Aimee; Cade, W Todd

    2008-01-01

    The advent of highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)/AIDS into a manageable chronic disorder. Clinical care, however, needs to address the metabolic, anthropometric, and cardiovascular changes associated with HIV infection and HAART. Studies in developing countries suggest an increasing incidence of HIV-associated cardiometabolic syndrome (CMS), especially in urban settings. Predictions indicate that the greatest increase in the prevalence of diabetes will occur in Africa over the next 2 decades due to lifestyle changes. This, coupled with increased access to HAART, may exponentially increase the prevalence of CMS in developing countries, where HIV infection is prevalent. Appropriate evaluation and intervention programs need to be implemented in the developing world, especially sub-Saharan Africa, to curtail HIV-related CMS. This should include routine cardiovascular risk assessments, management of HIV infection with more "metabolically friendly" HAART, and encouragement of lifestyle modifications, particularly smoking cessation, weight management, regular exercise, and adherence to a healthy diet.

  11. High Prevalence of Liver Fibrosis in Patients with Human Immunodeficiency Virus Monoinfection and Human Immunodeficiency Virus Hepatitis-B Co-infection as Assessed by Shear Wave Elastography: Study at a Teaching Hospital in Kenya

    PubMed Central

    Gitau, Samuel Nguku; Vinayak, Sudhir; Silaba, Micah; Adam, Rodney; Shah, Reena

    2016-01-01

    Objectives: The aim of this study was to determine the prevalence of liver fibrosis in patients with human immunodeficiency virus (HIV) monoinfection versus those with HIV hepatitis-B virus (HBV) co-infection as assessed with shear wave elastography (SWE) in a tertiary sub-Saharan Africa hospital. Materials and Methods: A total of 105 consecutive patients, 70 with HIV monoinfection and 35 with HIV-HBV co-infection, had liver elastography obtained using SWE to assess for the presence of liver fibrosis the cutoff of which was 5.6 kPa. Assessment of aspartate aminotransferase-to-platelet ratio index (APRI) score (a noninvasive serum biomarker of liver fibrosis) in these patients was also done. Results: The prevalence of liver fibrosis was significantly higher (P < 0.0001) in patients with HIV-HBV co-infection, 25.7%, compared to those with HIV monoinfection, 7.1%. APRI score was greater in patients with HIV-HBV co-infection than those with HIV monoinfection. HIV co-infection with HBV accelerates progression to liver fibrosis. Association of a low cluster of differentiation 4 (CD-4) count with advanced fibrosis supports earlier starting of antiretroviral therapy to prevent rapid progression of liver disease in HIV-positive patients. Conclusion: In view of the high prevalence of liver fibrosis in patients with HIV-HBV co-infection, regular monitoring of the disease progression is recommended. PMID:27403400

  12. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease

    SciTech Connect

    Weiser, B.; La Neve, D.; Eilbott, D.J.; Burger, H.; Seidman, R. ); Peress, N. Veterans Administration Medical Center, Northport, NY )

    1990-05-01

    To investigate human immunodeficiency virus type 1 (HIV-1) pathogenesis in infected individuals and examine the correlation of HIV-1 expression with extent of clinical and pathologic disease, the authors studied spinal cords from acquired immunodeficiency syndrome patients with a wide range of spinal cord pathology. By performing in situ hybridization with HIV-1-specific riboprobes, they detected HIV-1 RNA in all 10 cords from acquired immunodeficiency syndrome patients with a common, characteristic pathologic entity called vacuolar myelopathy but not in 10 control cords from HIV-1-infected and uninfected patients. In the cords from individuals with vacuolar myelopathy, the level of HIV-1 RNA expression correlated directly with extent of spinal cord pathology and clinical findings. These data support a role for HIV-1 int he pathogenesis of tissue damage and related clinical disease in infected individuals.

  13. Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual men.

    PubMed

    Croxson, T S; Chapman, W E; Miller, L K; Levit, C D; Senie, R; Zumoff, B

    1989-02-01

    Serum total testosterone, total 17 beta-estradiol, LH, FSH, and PRL concentrations were measured by RIA in 59 homosexual men infected with the human immunodeficiency virus (32 clinically healthy antibody-positive men (HH+), 20 men with acquired immune deficiency syndrome (AIDS), and 7 men with AIDS-related complex (ARC). The results were compared with those of 26 antibody-negative homosexual men (HH-) who served as controls. The mean serum total testosterone concentration was significantly lower in the men with AIDS [414 +/- 230 (+/- SD) ng/dL (14.5 +/- 8.0)] than in the HH- men [550 +/- 172 ng/dL (19.0 +/- 6.0 nmol/L); P less than 0.05]. The mean serum LH level was significantly higher in the men with AIDS (26 +/- 14 vs. 14 +/- 4 IU/L in HH- men; P less than 0.01) and slightly but significantly higher in the men with ARC (19 +/- 8 IU/L; 0.10 greater than P greater than 0.05). Serum FSH also was significantly higher in the men with AIDS (P less than 0.05). Serum PRL was significantly higher in the men with ARC (10 +/- 2 micrograms/L; P less than 0.05) and AIDS (16 +/- 10 micrograms/L; P less than 0.001) than in the HH- men (8 +/- 3 micrograms/L). Serum sex hormone-binding globulin levels were similar in HH- men and men with AIDS as were serum T responses to hCG administration for 2 days. These results suggest that alterations of the hypothalamic-pituitary-gonadal axis indicative of primary hypogonadism accompany human immunodeficiency virus infection in homosexual men.

  14. Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis.

    PubMed

    Dallasta, L M; Pisarov, L A; Esplen, J E; Werley, J V; Moses, A V; Nelson, J A; Achim, C L

    1999-12-01

    The blood-brain barrier (BBB) plays a critical role in regulating cell trafficking through the central nervous system (CNS) due to several unique anatomical features, including the presence of interendothelial tight junctions that form impermeable seals between the cells. Previous studies have demonstrated BBB perturbations during human immunodeficiency virus encephalitis (HIVE); however, the basis of these permeability changes and its relationship to infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes, a critical event in the pathogenesis of the disease, remains unclear. In this study, we examined CNS tissue from HIV-1-seronegative patients and HIV-1-infected patients, both with and without encephalitis, for alterations in BBB integrity via immunohistochemical analysis of the tight junction membrane proteins, occludin and zonula occludens-1 (ZO-1). Significant tight junction disruption (P < 0.001), as demonstrated by fragmentation or absence of immunoreactivity for occludin and ZO-1, was observed within vessels from subcortical white matter, basal ganglia, and, to a lesser extent, cortical gray matter in patients who died with HIVE. These alterations were also associated with accumulation of activated, HIV-1-infected brain macrophages, fibrinogen leakage, and marked astrocytosis. In contrast, no significant changes (P > 0.05) were observed in cerebellar tissue from patients with HIVE compared to HIV-seronegative patients or HIV-1-infected patients without encephalitis. Our findings demonstrate that tight junction disruption is a key feature of HIVE that occurs in regions of histopathological alterations in association with perivascular accumulation of activated HIV-1-infected macrophages, serum protein extravasation, and marked astrocytosis. We propose that disruption of this key BBB structure serves as the main route of HIV-1-infected monocyte entry into the CNS.

  15. The Effect of Human Immunodeficiency Virus Prevention and Reproductive Health Text Messages on Human Immunodeficiency Virus Testing Among Young Women in Rural Kenya

    PubMed Central

    Njuguna, Njambi; Ngure, Kenneth; Mugo, Nelly; Sambu, Carrole; Sianyo, Christopher; Gakuo, Stephen; Irungu, Elizabeth; Baeten, Jared; Heffron, Renee

    2016-01-01

    Background More than half of human immunodeficiency virus (HIV)–infected individuals in Kenya are unaware of their status, and young women carry a disproportionate burden of incident HIV infections. We sought to determine the effect of an SMS intervention on uptake of HIV testing among female Kenyan college students. Methods We conducted a quasi-experimental study to increase HIV testing among women 18 to 24 years old. Four midlevel training colleges in Central Kenya were allocated to have their study participants receive either weekly SMS on HIV and reproductive health topics or no SMS. Monthly 9-question SMS surveys were sent to all participants for 6 months to collect data on HIV testing, sexual behavior, and HIV risk perception. We used multivariate Cox proportional hazards regression to detect differences in the time to the first HIV test reported by women during the study period. Results We enrolled 600 women between September 2013 and March 2014 of whom 300 received weekly SMS and monthly surveys and 300 received only monthly surveys. On average, women were 21 years of age (interquartile range, 20–22), 71.50% had ever had sex and 72.62% had never tested for HIV. A total of 356 women reported testing for HIV within the 6 months of follow-up: 67% from the intervention arm and 51% from the control arm (hazard ratio, 1.57; 95% confidence interval, 1.28–1.92). Conclusions Use of weekly text messages about HIV prevention and reproductive health significantly increased rates of HIV testing among young Kenyan women and would be feasible to implement widely among school populations. PMID:27200519

  16. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique

    PubMed Central

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M.; Sidat, Mohsin; Vergara, Alfredo E.

    2014-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and anti-stigma interventions in Zambézia Province, Mozambique. Qualitative data gathering methods, including indepth key-informant interviews, community interviews and consensus group sessions, were utilized. Delphi methods and the strategic options development analysis technique were used to synthesize qualitative data. Key findings are that stigma enacted by the general public might be declining in tandem with the HIV/AIDS epidemic in Mozambique, but there is likely excessive residual fear of HIV disease and community attitudes that sustain high levels of perceived stigma. HIV-positive women accessing maternal and child health services appear to shoulder a disproportionate burden of stigma. Unintentional biases among healthcare providers are currently the critical frontier of stigmatization, but there are few interventions designed to address them. Culturally sensitive psychotherapies are needed to address psychological distress associated with internalized stigma and these interventions should complement current supports for voluntary counseling and testing. While advantageous for defining stakeholder priorities for stigma reduction efforts, confirmatory quantitative studies of these consensus positions are needed before the launch of specific interventions. PMID:24527744

  17. Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome and Cancer: Proceedings of the 8th Annual Texas Conference on Health Disparities

    PubMed Central

    Rajendiran, Smrithi; Kashyap, Meghana V.; Vishwanatha, Jamboor K.

    2013-01-01

    The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education and ongoing research about health disparities both in Texas and among the national population. The 2013 Texas Conference on Health Disparities brought together experts, in research, patient care and community outreach, on the “Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Cancer”. Smoking, HIV/AIDS and cancer are three individual areas of public health concern, each with its own set of disparities and risk factors based on race, ethnicity, gender, geography and socio-economic status. Disparities among patient populations, in which these issues are found to be comorbid, provide valuable information on goals for patient care. The conference consisted of three sessions addressing “Comorbidities and Treatment”, “Public Health Perspectives”, and “Best Practices”. This article summarizes the basic science, clinical correlates and public health data presented by the speakers. PMID:24227993

  18. [A case of non-acquired immunodeficiency syndrome-defining lung adenocarcinoma in a multidrug-resistant human immunodeficiency virus-positive patient].

    PubMed

    Mori, Naoyoshi; Maeda, Hikaru; Fujiwara, Kentarou; Taniguchi, Haruki

    2013-10-01

    We report a case of non-acquired immunodeficiency syndrome-defining lung adenocarcinoma in a multidrug-resistant human immunodeficiency virus (HIV)-positive patient. The patient was a 47-year-old Japanese woman who received salvage combination anti-retroviral therapy with darunavir plus ritonavir plus raltegravir plus tenofovir/emtricitabine in May 2009. She was diagnosed with lung adenocarcinoma (T3N3M1, stage IV) in November 2010 and was not found to possess any activating mutations in the epidermal growth factor receptor gene. Therefore, 6 courses of carboplatin plus pemetrexed and 3 courses of gemcitabine followed by erlotinib were administrated, and therapy was changed to home medical care. The only drug-related adverse event was grade 1 neutropenia, and drug interaction between the simultaneously administered anti-retroviral and chemotherapeutic agents was not confirmed. The patient battled lung adenocarcinoma for 1 year after the diagnosis and died of cancer progression in October 2011. Her performance status was stable and the CD4 (+) lymphocyte count and HIV load were well controlled throughout the course of treatment. In conclusion, the agents used for this patient show high tolerability and can be used as an effective treatment strategy for lung cancer occurring in HIV-positive patients.

  19. Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

    PubMed

    Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

    2014-02-01

    Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

  20. Consensus on context-specific strategies for reducing the stigma of human immunodeficiency virus/acquired immunodeficiency syndrome in Zambézia Province, Mozambique.

    PubMed

    Mukolo, Abraham; Torres, Isabel; Bechtel, Ruth M; Sidat, Mohsin; Vergara, Alfredo E

    2013-01-01

    Stigma has been implicated in poor outcomes of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) care. Reducing stigma is important for HIV prevention and long-term treatment success. Although stigma reduction interventions are conducted in Mozambique, little is known about the current nature of stigma and the efficacy and effectiveness of stigma reduction initiatives. We describe action research to generate consensus on critical characteristics of HIV stigma and anti-stigma interventions in Zambézia Province, Mozambique. Qualitative data gathering methods, including in-depth key-informant interviews, community interviews and consensus group sessions, were utilized. Delphi methods and the strategic options development analysis technique were used to synthesize qualitative data. Key findings are that stigma enacted by the general public might be declining in tandem with the HIV/AIDS epidemic in Mozambique, but there is likely excessive residual fear of HIV disease and community attitudes that sustain high levels of perceived stigma. HIV-positive women accessing maternal and child health services appear to shoulder a disproportionate burden of stigma. Unintentional biases among healthcare providers are currently the critical frontier of stigmatization, but there are few interventions designed to address them. Culturally sensitive psychotherapies are needed to address psychological distress associated with internalized stigma and these interventions should complement current supports for voluntary counseling and testing. While advantageous for defining stakeholder priorities for stigma reduction efforts, confirmatory quantitative studies of these consensus positions are needed before the launch of specific interventions.

  1. Efavirenz Therapy in Rhesus Macaques Infected with a Chimera of Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1

    PubMed Central

    Hofman, Michael J.; Higgins, Joanne; Matthews, Timothy B.; Pedersen, Niels C.; Tan, Chalet; Schinazi, Raymond F.; North, Thomas W.

    2004-01-01

    The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9 ± 4.5 nM, and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility. The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week. The virus load rebounded within 3 weeks in one treated animal and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz. PMID:15328115

  2. CXCR4 expression during lymphopoiesis: implications for human immunodeficiency virus type 1 infection of the thymus.

    PubMed Central

    Kitchen, S G; Zack, J A

    1997-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the human thymus results in depletion of CD4-bearing thymocytes. This depletion is initially manifested in the immature CD4+/CD8+ thymocyte subset. To determine cellular factors involved in HIV infection in the thymus, we examined the expression of the recently identified viral coreceptor, CXCR4, on fresh human thymocytes and on human cells from SCID-hu (Thy/Liv) mice. CXCR4 is a member of the chemokine receptor family which is required along with CD4 for entry into the cell of syncytium-inducing (SI) HIV-1 strains. Our analyses show that CXCR4 expression is modulated during T-lymphoid differentiation such that immature thymocytes display an increased frequency and higher surface density of the coreceptor than do more mature cells. In addition, using an SI strain of HIV-1 which directs expression of a reporter protein on the surface of infected cells, we have found that the immature CD4+/CD8+ thymocytes that express the highest levels of both CD4 and CXCR4 are the cells that are preferentially infected and depleted by the virus in vitro. Thus, high levels of both primary receptor and coreceptor may allow efficient infection of the thymus by certain HIV-1 strains. This in part may explain the rapid disease progression seen in some HIV-infected children, where the thymus is actively involved in the production of new T lymphocytes. PMID:9261420

  3. Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury

    PubMed Central

    Moser, Jill; van Ark, Joris; van Dijk, Marcory C.; Greiner, Dale L.; Shultz, Leonard D.; van Goor, Harry; Hillebrands, Jan-Luuk

    2016-01-01

    Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in the severity of injury influenced endothelial regeneration, neointima formation, and homing of human inflammatory and progenitor cells. In contrast to non-reconstituted mice, hPBMC reconstitution reduced neointima formation after femoral cuff injury whereas hPBMCs promoted neointima formation after carotid wire injury 4 weeks after induction of injury. Neointimal endothelium and smooth muscle cells in the injured arteries were of mouse origin. Our results indicate that the immune system may differentially respond to arterial injury depending on the severity of injury, which may also be influenced by the intrinsic properties of the arteries themselves, resulting in either minimal or aggravated neointima formation. PMID:27759053

  4. Frequency of Human Immunodeficiency Virus Infection Among Students of Tertiary and Secondary Institutions in An Endemic State

    PubMed Central

    Abubakar, Abdulazeez

    2012-01-01

    Background: Students are pivotal to manpower development and technological advancement of any nation. Nigerian nation was recently ranked third human immunodeficiency virus (HIV) most endemic nation in the world Aim: The study was designed to determine the frequency of HIV infection among Nigerian tertiary and secondary institution students. Materials and Methods: A HIV screening test was conducted on 1,978 apparently healthy students composed of 981 males and 997 females aged 11–35 years, randomly selected from some Nigerian tertiary and secondary institutions Results: Overall, the sero-prevalence rate of 13.7% was recorded consisting 9.9% in the tertiary and 3.8% in secondary institutions. The distribution of the infection showed no significant difference by age (χ2=1.07, P>0.05) and by gender (χ2=0.85, P>0.05). Also, the prevalence had no significant association with the settlement of students (χ2=0.96, P>0.05) and the status of educational institutions (χ2=1.42, P>0.05). Conclusion: The findings indicate a high HIV prevalence rate among students in this part of the globe. General behavioral changes about sex among the students are suggested. PMID:22536559

  5. Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain.

    PubMed Central

    Scott, C F; Silver, S; Profy, A T; Putney, S D; Langlois, A; Weinhold, K; Robinson, J E

    1990-01-01

    We describe a human IgG1 monoclonal antibody (N701.9b) derived by Epstein-Barr virus transformation of B cells from a human immunodeficiency virus-seropositive asymptomatic donor. This antibody was shown to recognize the principal neutralizing domain contained within the V3 region of gp120 of the MN strain of human immunodeficiency virus and MN-like strains, as determined by binding to the PB-1 fragment of MN gp120 and to synthetic peptides corresponding to the V3 region of MN and related virus strains. The epitope identified by monoclonal antibody N701.9b was mapped to a segment of V3 containing at least 7 amino acids (amino acids 316-322), which is located in the "tip" and "right" side of the V3 loop of the MN strain. Furthermore, this antibody manifested potent type-specific fusion-inhibitory activity against the MN strain but not against the IIIB or RF virus strains. This antibody also neutralized four virus isolates that had MN-like V3 region sequences and failed to neutralize three other strains containing unrelated V3 region sequences. Our findings confirm that the V3 region stimulates type-specific neutralizing antibody during natural human immunodeficiency virus infection in humans. The potential clinical use of this antibody is discussed. PMID:1700435

  6. Neuroprotective mechanisms of lithium in murine human immunodeficiency virus-1 encephalitis.

    PubMed

    Dou, Huanyu; Ellison, Brent; Bradley, Jennifer; Kasiyanov, Alexander; Poluektova, Larisa Y; Xiong, Huangui; Maggirwar, Sanjay; Dewhurst, Stephen; Gelbard, Harris A; Gendelman, Howard E

    2005-09-14

    Lithium (Li) has garnered considerable interest as a neuroprotective drug for a broad range of nervous system disorders. Its neuroprotective activities occur as a consequence of glycogen synthase kinase-3beta (GSK-3beta) inhibition leading to downstream blockade of beta-catenin and Tau phosphorylation. In the present study, we investigated Li-mediated neuroprotective mechanisms in laboratory and murine human immunodeficiency virus-1 (HIV-1) encephalitis (HIVE) models. In laboratory tests, Li protected neurons from neurotoxic secretions of HIV-1-infected monocyte-derived macrophages (MDMs). This neuroprotection was mediated, in part, through the phosphatidyl inositol 3-kinase/Akt and GSK-3beta pathways. To examine the effects of Li treatment in vivo, MDMs were injected into the basal ganglia of severe combined immunodeficient mice and then Li was administered (60 mg/kg/d). Seven days after MDM injection, mice were killed and CNS tissue was collected and subjected to immunocytochemical and Western blot assays for leukocyte and neural antigens, GSK-3beta, and key kinase substrates such as beta-catenin and Tau. Numbers of HIV-1 p24 antigen-positive MDMs were unaltered by Li treatment of HIVE mice. Similarly, the greatly increased extent of astrocyte and microglia activation in HIVE mice (10-fold and 16-fold, respectively, compared with unmanipulated controls) was also unaltered by Li. In contrast, Li restored HIVE-associated loss of microtubule-associated protein-2-positive neurites and synaptic density while reducing levels or activity of phospho-Tau Ser202, phospho-beta-catenin, and GSK-3beta. Electrophysiological recordings showed diminished long-term potentiation in hippocampal slices of HIVE mice that were restored by Li. Based on these data, the use of Li as an adjuvant for HIV-1-associated dementia is now being pursued.

  7. Inhibition of Human Immunodeficiency Virus Type 1 by Triciribine Involves the Accessory Protein Nef ▿

    PubMed Central

    Ptak, Roger G.; Gentry, Brian G.; Hartman, Tracy L.; Watson, Karen M.; Osterling, M. Clayton; Buckheit, Robert W.; Townsend, Leroy B.; Drach, John C.

    2010-01-01

    Triciribine (TCN) is a tricyclic nucleoside that inhibits human immunodeficiency virus type 1 (HIV-1) replication by a unique mechanism not involving the inhibition of enzymes directly involved in viral replication. This activity requires the phosphorylation of TCN to its 5′ monophosphate by intracellular adenosine kinase. New testing with a panel of HIV and simian immunodeficiency virus isolates, including low-passage-number clinical isolates and selected subgroups of HIV-1, multidrug resistant HIV-1, and HIV-2, has demonstrated that TCN has broad antiretroviral activity. It was active in cell lines chronically infected with HIV-1 in which the provirus was integrated into chromosomal DNA, thereby indicating that TCN inhibits a late process in virus replication. The selection of TCN-resistant HIV-1 isolates resulted in up to a 750-fold increase in the level of resistance to the drug. DNA sequence analysis of highly resistant isolate HIV-1H10 found five point mutations in the HIV-1 gene nef, resulting in five different amino acid changes. DNA sequencing of the other TCN-resistant isolates identified at least one and up to three of the same mutations observed in isolate HIV-1H10. Transfer of the mutations from TCN-resistant isolate HIV-1H10 to wild-type virus and subsequent viral growth experiments with increasing concentrations of TCN demonstrated resistance to the drug. We conclude that TCN is a late-phase inhibitor of HIV-1 replication and that mutations in nef are necessary and sufficient for TCN resistance. PMID:20086149

  8. Functional Differences between Human and Bovine Immunodeficiency Virus Tat Transcription Factors

    PubMed Central

    Bogerd, Hal P.; Wiegand, Heather L.; Bieniasz, Paul D.; Cullen, Bryan R.

    2000-01-01

    Transcriptional transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter element by the essential viral Tat protein requires recruitment of positive transcription elongation factor b (P-TEFb) to the viral TAR RNA target. The recruitment of P-TEFb, which has been proposed to be necessary and sufficient for activation of viral gene expression, is mediated by the highly cooperative interaction of Tat and cyclin T1, an essential component of P-TEFb, with the HIV-1 TAR element. Species, such as rodents, that encode cyclin T1 variants that are unable to support TAR binding by the Tat-cyclin T1 heterodimer are also unable to support HIV-1 Tat function. In contrast, we here demonstrate that the bovine immunodeficiency virus (BIV) Tat protein is fully able to bind to BIV TAR both in vivo and in vitro in the absence of any cellular cofactor. Nevertheless, BIV Tat can specifically recruit cyclin T1 to the BIV TAR element, and this recruitment is as essential for BIV Tat function as it is for HIV-1 Tat activity. However, because the cyclin T1 protein does not contribute to TAR binding, BIV Tat is able to function effectively in cells from several species that do not support HIV-1 Tat function. Thus, BIV Tat, while apparently dependent on the same cellular cofactor as the Tat proteins encoded by other lentiviruses, is nevertheless unique in terms of the mechanism used to recruit the BIV Tat-cyclin T1 complex to the viral LTR promoter. PMID:10775603

  9. Discordance at human leukocyte antigen-DRB3 and protection from human immunodeficiency virus type 1 transmission.

    PubMed

    Hader, Shannon L; Hodge, Thomas W; Buchacz, Kate A; Bray, Robert A; Padian, Nancy S; Rausa, Alfio; Slaviniski, Sally A; Holmberg, Scott D

    2002-06-15

    Host human leukocyte antigens (HLAs) integrated into the human immunodeficiency virus (HIV) type 1 envelope could theoretically determine, as in tissue transplants, whether HIV-1 is "rejected" by exposed susceptible persons, preventing transmission. HLA discordance (mismatch) was examined among 45 heterosexual partner pairs in which at least 1 partner was HIV-1 infected and exposure or transmission between partners had occurred. Immunologic discordance at class II HLA-DRB3 (present in the HIV donor partner but absent in the recipient partner) was associated with lack of transmission of HIV-1. Eight (35%) of 23 partner pairs in which HIV-1 transmission did not occur were immunologically discordant at HLA-DRB3, compared with 0 of 11 partner pairs in which HIV-1 transmission did occur (P=.027). Further investigation of the roles of class II HLAs in HIV-1 transmission and as possible components of HIV-1 vaccines should be pursued. PMID:12085318

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

    PubMed

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

    2015-07-01

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

  11. Autoreactive cytotoxic T lymphocytes in human immunodeficiency virus type 1-infected subjects

    PubMed Central

    1996-01-01

    A subtractive analysis of peptides eluted from major histocompatibility complex (MHC) class I human histocompatibility leukocyte antigen (HLA)- A2.1 molecules purified from either human immunodeficiency virus type-1 (HIV-1)-infected or uninfected cells was performed using micro high- performance liquid chromatography and mass spectrometry. Three peptides unique to infected cells were identified and found to derive from a single protein, human vinculin, a structural protein not known to be involved in viral pathogenesis. Molecular and cytofluorometric analyses revealed vinculin mRNA and vinculin protein overexpression in B and T lymphocytes from HIV-1-infected individuals. Vinculin peptide-specific CTL activity was readily elicited from peripheral blood lymphocytes of the majority of HLA-A2.1+, HIV+ patients tested. Our observations suggest that atypical vinculin expression and MHC class I-mediated presentation of vinculin-derived peptides accompany HIV infection of lymphoid cells in vivo, with a resultant induction of antivinculin CTL in a significant portion of HIV+ (HLA-A2.1+) individuals. PMID:8676071

  12. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia

    PubMed Central

    Boisson, Bertrand; Laplantine, Emmanuel; Dobbs, Kerry; Cobat, Aurélie; Tarantino, Nadine; Hazen, Melissa; Lidov, Hart G.W.; Hopkins, Gregory; Du, Likun; Belkadi, Aziz; Chrabieh, Maya; Itan, Yuval; Picard, Capucine; Fournet, Jean-Christophe; Eibel, Hermann; Tsitsikov, Erdyni; Pai, Sung-Yun; Abel, Laurent; Al-Herz, Waleed; Israel, Alain

    2015-01-01

    Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-κB activation are impaired in the patient’s fibroblasts stimulated by IL-1β or TNF. In contrast, the patient’s monocytes respond to IL-1β more vigorously than control monocytes. However, the activation and differentiation of the patient’s B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-1-deficient patients. Clinical differences between HOIL-1- and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells. PMID:26008899

  13. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia.

    PubMed

    Boisson, Bertrand; Laplantine, Emmanuel; Dobbs, Kerry; Cobat, Aurélie; Tarantino, Nadine; Hazen, Melissa; Lidov, Hart G W; Hopkins, Gregory; Du, Likun; Belkadi, Aziz; Chrabieh, Maya; Itan, Yuval; Picard, Capucine; Fournet, Jean-Christophe; Eibel, Hermann; Tsitsikov, Erdyni; Pai, Sung-Yun; Abel, Laurent; Al-Herz, Waleed; Casanova, Jean-Laurent; Israel, Alain; Notarangelo, Luigi D

    2015-06-01

    Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-κB activation are impaired in the patient's fibroblasts stimulated by IL-1β or TNF. In contrast, the patient's monocytes respond to IL-1β more vigorously than control monocytes. However, the activation and differentiation of the patient's B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-1-deficient patients. Clinical differences between HOIL-1- and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells. PMID:26008899

  14. The physical activity levels among people living with human immunodeficiency virus/acquired immunodeficiency syndrome receiving high active antiretroviral therapy in Rwanda.

    PubMed

    Frantz, J M; Murenzi, A

    2013-01-01

    The accessibility of high active antiretroviral therapy (HAART) for local human immunodeficiency virus (HIV) patients is improving in Rwanda. It is well known that this therapy is associated with serious adverse effects, such as metabolic and morphologic changes. One of the recommended preventive modalities for these complications is participation in physical activity. The current study aims to determine the anthropometric profile and physical activity levels among people living with HIV and receiving HAART in Kigali, Rwanda. The study was a cross-sectional, descriptive quantitative survey. The participant's levels of physical activity participation and their association with anthropometric profiles were measured, using a structured self-administered questionnaire for 407 clients passing through the clinics. Of the participants, approximately 70% were inactive and in addition, 40% were obese and 43% overweight. Obesity was found to be strongly associated with inactivity. Lack of motivation, and time as well as fear of worsening the disease were found to be barriers to participation in physical activity.

  15. Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study

    PubMed Central

    Xu, Shaoxia; Wang, Qiaofeng; Zhang, Weihong; Qiu, Zhifeng; Cui, Jingtao; Yan, Wenjuan; Ni, Anping

    2015-01-01

    Background The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health. Methods Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010–2011). Positive human immunodeficiency virus tests were confirmed via western blotting. Results Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively) than in women (4.45% and 0.021%, respectively). The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%), Emergency (1.71%), and Dermatology and Sexually Transmitted Diseases (1.12%) departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60–70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients. Conclusions During 2010–2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency

  16. Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates

    PubMed Central

    Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W.; Thiebaut, Rodolphe; Scarlatti, Gabriella

    2016-01-01

    ABSTRACT Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. IMPORTANCE There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no

  17. Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies.

    PubMed

    Fischer-Smith, Tracy; Bell, Christie; Croul, Sidney; Lewis, Mark; Rappaport, Jay

    2008-08-01

    Here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (HIV) in the central nervous system (CNS): (1) HIV infection in the CNS is a compartmentalized infection, with the virus-infected macrophages entering the CNS early, infecting resident microglia and astrocytes, and achieving a state of latency with evolution toward a fulminant CNS infection late in the course of disease; or alternatively, (2) events in the periphery lead to altered monocyte/macrophage (MPhi) homeostasis, with increased CNS invasion of infected and/or uninfected MPhis. Here the authors have reevaluated evidence presented in the favor of the latter model, with a discussion of phenotypic characteristics distinguishing normal resident microglia with those accumulating in HIV encephalitis (HIVE). CD163 is normally expressed by perivascular MPhi s but not resident microglia in normal CNS of humans and rhesus macaques. In agreement with other studies, the authors demonstrate expression of CD163 by brain MPhi s in HIVE and simian immunodeficiency virus encephalitis (SIVE). CNS tissues from HIV-sero positive individuals with HIVE or HIV-associated progressive multifocal leukoencephalopathy (PML) were also examined. In HIVE, the authors further demonstrate colocalization of CD163 and CD16 (Fcgamma III recptor) gene expression, the latter marker associated with HIV infection of monocyte in vivo and permissivity of infection. Indeed, CD163(+) MPhis and microglia are often productively infected in HIVE CNS. In SIV infected rhesus macaques, CD163(+) cells accumulate perivascularly, within nodular lesions and the parenchyma in animals with encephalitis. Likewise, parenchymal microglia and perivascular MPhi s are CD163(+) in HIVE. In contrast to HIVE, CD163(+)perivascular and parenchymal MPhi s in HIV-associated PML were only associated with areas of demyelinating lesions. Interestingly, SIV-infected rhesus macaques

  18. Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules.

    PubMed Central

    Gauduin, M C; Allaway, G P; Maddon, P J; Barbas, C F; Burton, D R; Koup, R A

    1996-01-01

    We tested the ability of human monoclonal antibodies (immunoglobulin G1b12 [IgG1b12] and 19b) and CD4-based molecules (CD4-IgG2 and soluble CD4 [sCD4]) to neutralize human immunodeficiency virus type 1 directly from the plasma of seropositive donors in an ex vivo neutralization assay. IgG1b12 and CD4-IgG2, at concentrations from 1 to 25 micrograms/ml, were found to be effective at reducing the HIV-1 titer in most plasma samples. When viruses recovered from plasma samples were expanded to produce virus stocks, no correlation between the neutralization sensitivities to IgG1b12 and CD4-IgG2 of the in vitro passaged stocks and those of the ex vivo neutralizations performed directly on the plasma was observed. These differences could be due to changes in neutralization sensitivity that occur after one passage of the virus in vitro, or they could be related to the presence of complement or antibodies in the plasma. Furthermore, differences in expression of adhesion molecules on plasma-derived and phytohemagglutinin-activated peripheral blood mononuclear cell-derived viruses could be involved. These studies suggest that IgG1b12 and CD4-IgG2 have broad and potent neutralizing activity in both in vitro and ex vivo neutralization assays and should be considered for use as potential immunoprophylactic or therapeutic agents. PMID:8642690

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

    PubMed Central

    Bristow, Cynthia L.

    2001-01-01

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

  20. Optimization of Azoles as Anti-Human Immunodeficiency Virus Agents Guided by Free-Energy Calculations

    PubMed Central

    Zeevaart, Jacob G.; Wang, Ligong; Thakur, Vinay V.; Leung, Cheryl S.; Tirado-Rives, Julian; Bailey, Christopher M.; Domaoal, Robert A.; Anderson, Karen S.; Jorgensen, William L.

    2009-01-01

    Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP “chlorine scan” was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. FEP calculations for additional substituent modifications and change of the core heterocycle readily led to oxazoles 28 and 29, which were confirmed as highly potent anti-HIV agents with activities in the 10–20 nM range. The designed compounds were also monitored for possession of desirable pharmacological properties by use of additional computational tools. Overall, the trends predicted by the FEP calculations were well borne out by the assay results. FEP-guided lead optimization is confirmed as a valuable tool for molecular design including drug discovery; chlorine scans are particularly attractive since they are both straightforward to perform and highly informative. PMID:18588301

  1. Two distinct CCR5 domains can mediate coreceptor usage by human immunodeficiency virus type 1.

    PubMed Central

    Doranz, B J; Lu, Z H; Rucker, J; Zhang, T Y; Sharron, M; Cen, Y H; Wang, Z X; Guo, H H; Du, J G; Accavitti, M A; Doms, R W; Peiper, S C

    1997-01-01

    The chemokine receptor CCR5 is the major fusion coreceptor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). To define the structures of CCR5 that can support envelope (Env)-mediated membrane fusion, we analyzed the activity of homologs, chimeras, and mutants of human CCR5 in a sensitive gene reporter cell-cell fusion assay. Simian, but not murine, homologs of CCR5 were fully active as HIV-1 fusion coreceptors. Chimeras between CCR5 and divergent chemokine receptors demonstrated the existence of two distinct regions of CCR5 that could be utilized for Env-mediated fusion, the amino-terminal domain and the extracellular loops. Dual-tropic Env proteins were particularly sensitive to alterations in the CCR5 amino-terminal domain, suggesting that this domain may play a pivotal role in the evolution of coreceptor usage in vivo. We identified individual residues in both functional regions, Asp-11, Lys-197, and Asp-276, that contribute to coreceptor function. Deletion of a highly conserved cytoplasmic motif rendered CCR5 incapable of signaling but did not abrogate its ability to function as a coreceptor, implying the independence of fusion and G-protein-mediated chemokine receptor signaling. Finally, we developed a novel monoclonal antibody to CCR5 to assist in future studies of CCR5 expression. PMID:9261347

  2. Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress In Vitro and In Vivo▿

    PubMed Central

    Zimmerman, Erik S.; Sherman, Michael P.; Blackett, Jana L.; Neidleman, Jason A.; Kreis, Christophe; Mundt, Pamela; Williams, Samuel A.; Warmerdam, Maria; Kahn, James; Hecht, Frederick M.; Grant, Robert M.; de Noronha, Carlos M. C.; Weyrich, Andrew S.; Greene, Warner C.; Planelles, Vicente

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) causes cell cycle arrest in G2. Vpr-expressing cells display the hallmarks of certain forms of DNA damage, specifically activation of the ataxia telangiectasia mutated and Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo or in the context of viral infection is still lacking. In the present study, we demonstrate that HIV-1 infection of primary, human CD4+ lymphocytes causes G2 arrest in a Vpr-dependent manner and that this response requires ATR, as shown by RNA interference. The event leading to ATR activation in CD4+ lymphocytes is the accumulation of replication protein A in nuclear foci, an indication that Vpr likely induces stalling of replication forks. Primary macrophages are refractory to ATR activation by Vpr, a finding that is consistent with the lack of detectable ATR, Rad17, and Chk1 protein expression in these nondividing cells. These observations begin to explain the remarkable resilience of macrophages to HIV-1-induced cytopathicity. To study the in vivo consequences of Vpr function, we isolated CD4+ lymphocytes from HIV-1-infected individuals and interrogated the cell cycle status of anti-p24Gag-immunoreactive cells. We report that infected cells in vivo display an aberrant cell cycle profile whereby a majority of cells have a 4N DNA content, consistent with the onset of G2 arrest. PMID:16956949

  3. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

    PubMed Central

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-01-01

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  4. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics.

    PubMed

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-08-12

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  5. Genetic characterisation of Langerin gene in human immunodeficiency virus-1-infected women from Bahia, Brazil

    PubMed Central

    Costa, Giselle Calasans de Souza; Jesus, Jaqueline Goes; Rego, Filipe Ferreira de Almeida; Santos, Edson Souza; Galvão-Castro, Bernardo; Gonçalves, Marilda de Souza; Alcantara, Luiz Carlos Júnior

    2014-01-01

    Studies on human genetic variations are a useful source of knowledge about human immunodeficiency virus (HIV)-1 infection. The Langerin protein, found at the surface of Langerhans cells, has an important protective role in HIV-1 infection. Differences in Langerin function due to host genetic factors could influence susceptibility to HIV-1 infection. To verify the frequency of mutations in the Langerin gene, 118 samples from HIV-1-infected women and 99 samples from HIV-1-uninfected individuals were selected for sequencing of the promoter and carbohydrate recognition domain (CRD)-encoding regions of the Langerin gene. Langerin promoter analysis revealed two single nucleotide polymorphisms (SNPs) and one mutation in both studied groups, which created new binding sites for certain transcription factors, such as NFAT5, HOXB9.01 and STAT6.01, according to MatInspector software analysis. Three SNPs were observed in the CRD-encoding region in HIV-1-infected and uninfected individuals: p.K313I, c.941C>T and c.983C>T. This study shows that mutations in the Langerin gene are present in the analysed populations at different genotypic and allelic frequencies. Further studies should be conducted to verify the role of these mutations in HIV-1 susceptibility. PMID:24676666

  6. Epidemiology of Sexually Transmitted Infections among Human Immunodeficiency Virus Positive United States Military Personnel.

    PubMed

    Tzeng, Jeff S; Clark, Leslie L; Garges, Eric C; Otto, Jean Lin

    2013-01-01

    Background. Minimal data exist that describe the epidemiology of sexually transmitted infections (STI) in human immunodeficiency virus (HIV) positive populations across the pre- and post-diagnosis periods for HIV. Purpose. The purpose of this study was to identify and describe the epidemiology of gonorrhea, chlamydia, syphilis, herpes simplex virus, and human papillomavirus in an HIV-positive population. Methods. All 1,961 HIV seropositive United States active duty military personnel from 2000-2010 were identified. STI diagnoses relative to HIV diagnosis from 1995, which was the earliest electronic medical record available, to 2010 were examined. Results. The incidence diagnosis rates of STI generally increased during the period leading up to eventual HIV diagnosis. The rates of STI during the post-HIV diagnosis period fluctuated, but remained elevated compared to pre-HIV diagnosis period. Approximately 45%-69% with an STI in the HIV seropositive military population were diagnosed with their first STI greater than one year after their HIV diagnosis. Of those who were diagnosed with an STI in the post-HIV diagnosis period, 70.6% had one STI diagnosis, 23.5% had two STI diagnoses, and 5.8% had three or more STI diagnoses. Conclusions. Despite aggressive counseling, high-risk sexual behavior continues to occur in the HIV-positive military population.

  7. Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

    SciTech Connect

    Arthur, L.O.; Pyle, S.W.; Nara, P.L.; Bess, J.W. Jr.; Gonda, M.A.; Kelliher, J.C.; Gilden, R.V.; Robey, W.G.; Bolognesi, D.P.; Gallo, R.C.

    1987-12-01

    The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4/sup +/ and T8/sup +/ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4/sup +/ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.

  8. Health care workers infected with the human immunodeficiency virus. The next steps.

    PubMed

    Lo, B; Steinbrook, R

    1992-02-26

    The tragedy of five patients who contracted human immunodeficiency virus (HIV) infection from a seropositive dentist has alarmed the public. The Centers for Disease Control (CDC) recently revised its recommendations for preventing the transmission of HIV infection to patients during invasive procedures. The CDC abandoned a previous plan to list exposure-prone invasive procedures that HIV-infected health care workers should not perform. The CDC said "expert review panels" should decide on a case-by-case basis whether seropositive health care workers may perform invasive procedures. As of February 1992, the revised recommendations were under review by the US Department of Health and Human Services. Many issues remain to be clarified, such as how these panels will operate and whether decisions will be consistent in similar cases. Disregarding the CDC guidelines or infection-control precautions may further erode public trust and lead to draconian restrictions on HIV-infected health care workers. Physicians and dentists should respond more effectively to public fears about HIV transmission. The challenge is to protect patients while respecting the privacy and livelihood of health care workers.

  9. The epidemiology of cancers in human immunodeficiency virus infection and after organ transplantation.

    PubMed

    Grulich, Andrew E; Vajdic, Claire M

    2015-04-01

    The authors provide an update on the association between immune deficiency and cancer risk in people with human immunodeficiency virus (HIV) and in solid organ transplant recipients. Over the past decade, it has become clear that a wider range of about 20 mostly infection-related cancers occur at increased rates in people with immune deficiency. The human herpes virus 8 (HHV8) and Epstein Barr Virus (EBV)-related cancers of Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) are most closely related to level of immune deficiency. Transplant recipients also have a greatly increased risk of squamous cell carcinoma (SCC) of the skin, related to direct carcinogenic effects of the pharmaceuticals used for immune suppression. For those three cancer types, the increased cancer risk is largely reversed when immune deficiency is decreased by treatment of HIV or by reduction of iatrogenic immune suppression. Other infection-related cancers also occur at increased rates, but it is not clear whether reduction of immune deficiency reduces cancer risk. Prostate and breast cancer do not occur at increased rates, providing strong evidence that these cancers are unlikely to be related to infection. Epidemiological and clinical trends in these two populations have led to substantial recent changes in cancer occurrence. PMID:25843729

  10. Epitope specificity of human immunodeficiency virus-1 antibody dependent cellular cytotoxicity [ADCC] responses.

    PubMed

    Pollara, Justin; Bonsignori, Mattia; Moody, M Anthony; Pazgier, Marzena; Haynes, Barton F; Ferrari, Guido

    2013-07-01

    Antibody dependent cellular cytotoxicity [ADCC] has been suggested to play an important role in control of Human Immunodeficiency Virus-1 [HIV-1] viral load and protection from infection. ADCC antibody responses have been mapped to multiple linear and conformational epitopes within the HIV-1 envelope glycoproteins gp120 and gp41. Many epitopes targeted by antibodies that mediate ADCC overlap with those recognized by antibodies capable of virus neutralization. In addition, recent studies conducted with human monoclonal antibodies derived from HIV-1 infected individuals and HIV-1 vaccine-candidate vaccinees have identified a number of antibodies that lack the ability to capture primary HIV-1 isolates or mediate neutralizing activity, but are able to bind to the surface of infected CD4+ T cells and mediate ADCC. Of note, the conformational changes in the gp120 that may not exclusively relate to binding of the CD4 molecule are important in exposing epitopes recognized by ADCC responses. Here we discuss the HIV-1 envelope epitopes targeted by ADCC antibodies in the context of the potential protective capacities of ADCC. PMID:24191939

  11. Highly efficient inhibition of human immunodeficiency virus type 1 reverse transcriptase by aptamers functionalized gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Shiang, Yen-Chun; Ou, Chung-Mao; Chen, Shih-Ju; Ou, Ting-Yu; Lin, Han-Jia; Huang, Chih-Ching; Chang, Huan-Tsung

    2013-03-01

    We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45-Au NPs shows inhibitory efficiency in the retroviral replication cycle with a decreasing infectivity (40.2%).We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45

  12. Didanosine reduces atevirdine absorption in subjects with human immunodeficiency virus infections.

    PubMed Central

    Morse, G D; Fischl, M A; Shelton, M J; Borin, M T; Driver, M R; DeRemer, M; Lee, K; Wajszczuk, C P

    1996-01-01

    Atevirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 and is currently in phase II clinical trials. Atevirdine is most soluble at a pH of < 2, and therefore, normal gastric acidity is most likely necessary for optimal bioavailability. Because of the rapid development of resistance in vitro, atevirdine is being evaluated in combination with didanosine and/or zidovudine in both two- and three-drug combination regimens. To examine the influence of concurrent didanosine (buffered tablet formulation) on the disposition of atevirdine, 12 human immunodeficiency virus type 1-infected subjects (mean CD4+ cell count, 199 cells per mm3; range, 13 to 447 cells/mm3) participated in a three-way, partially randomized, crossover, single-dose study to evaluate the pharmacokinetics of didanosine and atevirdine when each drug was given alone (treatments A and B, respectively) versus concurrently (treatment C). Concurrent administration of didanosine and atevirdine significantly reduced the maximum concentration of atevirdine in serum from 3.45 +/- 2.8 to 0.854 +/- 0.33 microM (P = 0.004). Likewise, the mean atevirdine area under the concentration-time curve from 0 to 24 h after administration of the combination was reduced to 6.47 +/- 2.2 microM.h (P = 0.004) relative to a value of 11.3 +/- 4.8 microM.h for atevirdine alone. Atevirdine had no statistically significant effect on the pharmacokinetic parameters of didanosine. Concurrent administration of single doses of atevirdine and didanosine resulted in a markedly lower maximum concentration of atevirdine in serum and area under the concentration-time curve, with a minimal effect on the disposition of didanosine. It is unknown whether an interaction of similar magnitude would occur under steady-state conditions; thus, combination regimens which include both atevirdine and didanosine should be designed so that their administration times are separated. Since

  13. Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus

    PubMed Central

    Crawford, John M.; Earl, Patricia L.; Moss, Bernard; Reimann, Keith A.; Wyand, Michael S.; Manson, Kelledy H.; Bilska, Miroslawa; Zhou, Jin Tao; Pauza, C. David; Parren, Paul W. H. I.; Burton, Dennis R.; Sodroski, Joseph G.; Letvin, Norman L.; Montefiori, David C.

    1999-01-01

    Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human immunodeficiency virus type 1 (HIV-1) are now available. One of the advantages of these chimeric viruses is their application to studies of HIV-1-specific neutralizing antibodies in preclinical AIDS vaccine studies in nonhuman primates. In this regard, an important consideration is the spectrum of antigenic properties exhibited by the different envelope glycoproteins used for SHIV construction. The antigenic properties of six SHIV variants were characterized here in neutralization assays with recombinant soluble CD4 (rsCD4), monoclonal antibodies, and serum samples from SHIV-infected macaques and HIV-1-infected individuals. Neutralization of SHIV variants HXBc2, KU2, 89.6, and 89.6P by autologous and heterologous sera from SHIV-infected macaques was restricted to an extent that these viruses may be considered heterologous to one another in their major neutralization determinants. Little or no variation was seen in the neutralization determinants on SHIV variants 89.6P, 89.6PD, and SHIV-KB9. Neutralization of SHIV HXBc2 by sera from HXBc2-infected macaques could be blocked with autologous V3-loop peptide; this was less true in the case of SHIV 89.6 and sera from SHIV 89.6-infected macaques. The poorly immunogenic but highly conserved epitope for monoclonal antibody IgG1b12 was a target for neutralization on SHIV variants HXBc2, KU2, and 89.6 but not on 89.6P and KB9. The 2G12 epitope was a target for neutralization on all five SHIV variants. SHIV variants KU2, 89.6, 89.6P, 89.6PD, and KB9 exhibited antigenic properties characteristic of primary isolates by being relatively insensitive to neutralization in peripheral blood mononuclear cells with serum samples from HIV-1-infected individuals and 12-fold to 38-fold less sensitive to inhibition with recombinant soluble CD4 than TCLA

  14. Food Security in Households of People Living With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: A Cross-sectional Study in a Subdivision of Darjeeling District, West Bengal

    PubMed Central

    2016-01-01

    Objectives: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) adversely impacts food security in households of people living with HIV/AIDS (PLWHA). Little research has focused on food insecurity among PLWHA in India. The purpose of this study was to identify the prevalence of and factors relating to food security in households of PLWHA in the Siliguri subdivision of Darjeeling, West Bengal, India. Methods: A cross-sectional community-based study was carried out among 173 PLWHA residing in Siliguri and registered at the Anti-retroviral Therapy Centre of North Bengal Medical College & Hospital. Data was collected at the household level with interviews of PLWHA using a food security survey instrument. We analyzed the associations using logistic regression. Results: The prevalence of household food security among the participants was 50.9% (88/173). Five years or more of schooling, higher socioeconomic class and males were found to be significantly associated with a higher likelihood of food security. A later stage of the disease and the presence of other family members with HIV/AIDS were significantly associated with a lower likelihood of food security. The major coping strategies to deal with food insecurity in the acute phase HIV infection included borrowing money (56.1%), followed by spousal support, loans from microfinance institutions, banks, or money lenders, borrowing food, or selling agricultural products. Conclusions: The present study revealed that only about half of households with PLWHA were food secure. Prior interventions relating to periods of food and economic crisis as well as strategies for sustaining food security and economic status are needed in this area. PMID:27499166

  15. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.

    PubMed

    Myint, Thein; Anderson, Albert M; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W; Jhaveri, Malhar; Greenberg, Richard N; Bamberger, David M; Rodgers, Mark; Crawford, Timothy N; Wheat, L Joseph

    2014-01-01

    Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91-55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL. Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

  16. What High School Students Who Are Mildly Mentally Retarded Know about the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

    ERIC Educational Resources Information Center

    Cobb, Hazel B.; Horn, Charles J., Jr.

    Alabama high school students (N=309) with mild mental retardation completed a questionnaire concerning their knowledge, attitudes, and sources of information about human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Students demonstrated some basic knowledge of HIV/AIDS, and expressed some concern about getting AIDS. They…

  17. Crystallization of the Fab from a human monoclonal antibody against gp 41 of human immunodeficiency virus type I

    NASA Technical Reports Server (NTRS)

    Casale, Elena; He, Xiao-Min; Snyder, Robert S.; Carter, Daniel C.; Wenisch, Elisabeth; Jungbauer, Alois; Tauer, Christa; Ruker, Florian; Righetti, Pier Giorgio

    1990-01-01

    A monoclonal IgG antibody directed against gp 41 from the human immunodeficiency virus (HIV-1) has been crystallized in both intact and Fab forms. Crystals of the intact antibody grow as tetragonal-like prisms too small for conventional X-ray analysis. However, the Fab portion of the antibody produces suitable platelike crystals which belong to the space group P2(1)2(1)2(1) with unit cell constants of a = 66.5 A, b = 74.3 A, and c = 105.3 A. There is one molecule of Fab in the asymmetric unit. The Fab crystals show diffraction to d-spacings less than 3.0 A.

  18. NMR structure of a biologically active peptide containing the RNA-binding domain of human immunodeficiency virus type 1 Tat.

    PubMed Central

    Mujeeb, A; Bishop, K; Peterlin, B M; Turck, C; Parslow, T G; James, T L

    1994-01-01

    The Tat protein of human immunodeficiency virus type 1 enhances transcription by binding to a specific RNA element on nascent viral transcripts. Binding is mediated by a 10-amino acid basic domain that is rich in arginines and lysines. Here we report the three-dimensional peptide backbone structure of a biologically active 25-mer peptide that contains the human immunodeficiency virus type 1 Tat basic domain linked to the core regulatory domain of another lentiviral Tat--i.e., that from equine infectious anemia virus. Circular dichroism and two-dimensional proton NMR studies of this hybrid peptide indicate that the Tat basic domain forms a stable alpha-helix, whereas the adjacent regulatory sequence is mostly in extended form. These findings suggest that the tendency to form stable alpha-helices may be a common property of arginine- and lysine-rich RNA-binding domains. Images PMID:8058789

  19. Chikungunya infection in a human immunodeficiency virus-infected kidney transplant recipient returning to Italy from the Dominican Republic.

    PubMed

    Dalla Gasperina, D; Balsamo, M L; Garavaglia, S D; Rovida, F; Baldanti, F; Grossi, P A

    2015-12-01

    Since December 2013, chikungunya virus (CHIKV) spread in many countries of the Western Hemisphere, and during the last year some cases of infected European travelers, coming back from the Caribbean, have been reported. The risk of acquiring severe travel-related illness is higher in immunocompromised subjects, such as patients with human immunodeficiency virus (HIV) infection or solid organ transplant recipients. We reported the first case, to our knowledge, of CHIKV infection in an HIV-infected kidney transplant recipient.

  20. Potential of a Simplified p24 Assay for Early Diagnosis of Infant Human Immunodeficiency Virus Type 1 Infection in Haiti▿

    PubMed Central

    George, Erik; Beauharnais, Carole Anne; Brignoli, Emilio; Noel, Francine; Bois, Gyrlande; De Matteis Rouzier, Patricia; Altenor, Martine; Lauture, Daniel; Hosty, Marlène; Mehta, Sapna; Wright, Peter F.; Pape, Jean W.

    2007-01-01

    With global efforts to scale up the prevention of mother-to-child transmission services and pediatric antiretroviral therapy, there is an urgent need to introduce a simple, low-cost infant human immunodeficiency virus test in the field. We postulated that the p24 antigen capture enzyme-linked immunosorbent assay could be simplified by eliminating signal amplification without compromising diagnostic accuracy. PMID:17670933

  1. Therapeutic Trial of Rifabutin After Rifampicin-Associated DRESS Syndrome in Tuberculosis-Human Immunodeficiency Virus Coinfected Patients.

    PubMed

    Lehloenya, Rannakoe J; Dlamini, Sipho; Muloiwa, Rudzani; Kakande, Betty; Ngwanya, Mzudumile R; Todd, Gail; Dheda, Keertan

    2016-09-01

    Elimination of a rifamycin from the treatment regimen for tuberculosis negatively impacts outcomes. Cross-reactivity between the rifamycins after drug eruptions is unclear. We report 6 consecutive human immunodeficiency virus-infected patients with rifampicin-associated drug rash with eosinophilia and systemic symptoms (DRESS) syndrome confirmed on diagnostic rechallenge. The patients subsequently tolerated rifabutin. These data inform clinical management of tuberculosis-associated drug reactions. PMID:27419190

  2. Therapeutic Trial of Rifabutin After Rifampicin-Associated DRESS Syndrome in Tuberculosis-Human Immunodeficiency Virus Coinfected Patients

    PubMed Central

    Lehloenya, Rannakoe J.; Dlamini, Sipho; Muloiwa, Rudzani; Kakande, Betty; Ngwanya, Mzudumile R.; Todd, Gail; Dheda, Keertan

    2016-01-01

    Elimination of a rifamycin from the treatment regimen for tuberculosis negatively impacts outcomes. Cross-reactivity between the rifamycins after drug eruptions is unclear. We report 6 consecutive human immunodeficiency virus-infected patients with rifampicin-associated drug rash with eosinophilia and systemic symptoms (DRESS) syndrome confirmed on diagnostic rechallenge. The patients subsequently tolerated rifabutin. These data inform clinical management of tuberculosis-associated drug reactions. PMID:27419190

  3. Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection

    PubMed Central

    Kim, Eun-Young; Lorenzo-Redondo, Ramon; Little, Susan J.; Chung, Yoon-Seok; Phalora, Prabhjeet K.; Maljkovic Berry, Irina; Archer, John; Penugonda, Sudhir; Fischer, Will; Richman, Douglas D.; Bhattacharya, Tanmoy; Malim, Michael H.; Wolinsky, Steven M.

    2014-01-01

    Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1) cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA)-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection. PMID:25080100

  4. Structural Insight into the Human Immunodeficiency Virus Vif SOCS Box and Its Role in Human E3 Ubiquitin Ligase Assembly

    SciTech Connect

    Stanley,B.; Ehrlich, E.; Short, L.; Yu, Y.; Xiao, Z.; Yu, X.; Xiong, Y.

    2008-01-01

    Human immunodeficiency virus (HIV) virion infectivity factor (Vif) causes the proteasome-mediated destruction of human antiviral protein APOBEC3G by tethering it to a cellular E3 ubiquitin ligase composed of ElonginB, ElonginC, Cullin5, and Rbx2. It has been proposed that HIV Vif hijacks the E3 ligase through two regions within its C-terminal domain: a BC box region that interacts with ElonginC and a novel zinc finger motif that interacts with Cullin5. We have determined the crystal structure of the HIV Vif BC box in complex with human ElonginB and ElonginC. This complex presents direct structural evidence of the recruitment of a human ubiquitin ligase by a viral BC box protein that mimics the conserved interactions of cellular ubiquitin ligases. We further mutated conserved hydrophobic residues in a region downstream of the Vif BC box. These mutations demonstrate that this region, the Vif Cullin box, composes a third E3-ligase recruiting site critical for interaction between Vif and Cullin5. Furthermore, our homology modeling reveals that the Vif Cullin box and zinc finger motif may be positioned adjacent to the N terminus of Cullin5 for interaction with loop regions in the first cullin repeat of Cullin5.

  5. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.

    PubMed Central

    Shirazi, Y; Pitha, P M

    1992-01-01

    In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages. Images PMID:1738192

  6. Effects of dimethyl prostaglandin A1 on herpes simplex virus and human immunodeficiency virus replication

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; McGrath, M. S.; Hanks, D.; Erickson, S.; Pulliam, L.

    1992-01-01

    We have investigated the direct effect of dimethyl prostaglandin A1 (dmPGA1) on the replication of herpes simplex virus (HSV) and human immunodeficiency virus type 1 (HIV-1). dmPGA1 significantly inhibited viral replication in both HSV and HIV infection systems at concentrations of dmPGA1 that did not adversely alter cellular DNA synthesis. The 50% inhibitory concentration (ID50) for several HSV type 1 (HSV-1) strains ranged from 3.8 to 5.6 micrograms/ml for Vero cells and from 4.6 to 7.3 micrograms/ml for human foreskin fibroblasts. The ID50s for two HSV-2 strains varied from 3.8 to 4.5 micrograms/ml for Vero cells; the ID50 was 5.7 micrograms/ml for human foreskin fibroblasts. We found that closely related prostaglandins did not have the same effect on the replication of HSV; dmPGE2 and dmPGA2 caused up to a 60% increase in HSV replication compared with that in untreated virus-infected cells. HIV-1 replication in acutely infected T cells (VB line) and chronically infected macrophages was assessed by quantitative decreases in p24 concentration. The effective ID50s were 2.5 micrograms/ml for VB cells acutely infected with HIV-1 and 5.2 micrograms/m for chronically infected macrophages. dmPGA1 has an unusual broad-spectrum antiviral activity against both HSV and HIV-1 in vitro and offers a new class of potential therapeutic agents for in vivo use.

  7. Induction of Murine Mucosal CCR5-Reactive Antibodies as an Anti-Human Immunodeficiency Virus Strategy

    PubMed Central

    Barassi, C.; Soprana, E.; Pastori, C.; Longhi, R.; Buratti, E.; Lillo, F.; Marenzi, C.; Lazzarin, A.; Siccardi, A. G.; Lopalco, L.

    2005-01-01

    The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear cells of these subjects. These antibodies recognize the 89-to-102 extracellular loop of CCR5 in its native conformation. The aim of this study was to induce infection-preventing mucosal anti-CCR5 autoantibodies in individuals at high risk of HIV infection. Thus, we generated chimeric immunogens containing the relevant CCR5 peptide in the context of the capsid protein of Flock House virus, a presentation system in which it is possible to engineer conformationally constrained peptide in a highly immunogenic form. Administered in mice via the systemic or mucosal route, the immunogens elicited anti-CCR5 IgG and IgA (in sera and vaginal fluids). Analogous to exposed seronegative individuals, mice producing anti-CCR5 autoantibodies express significantly reduced levels of CCR5 on the surfaces of CD4+ cells from peripheral blood and vaginal washes. In vitro studies have shown that murine IgG and IgA (i) specifically bind human and mouse CD4+ lymphocytes and the CCR5-transfected U87 cell line, (ii) down-regulate CCR5 expression of CD4+ cells from both humans and untreated mice, (iii) inhibit Mip-1β chemotaxis of CD4+ CCR5+ lymphocytes, and (iv) neutralize HIV R5 strains. These data suggest that immune strategies aimed at generating anti-CCR5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV-protective immunity. PMID:15890924

  8. Generation of hybrid human immunodeficiency virus utilizing the cotransfection method and analysis of cellular tropism.

    PubMed Central

    Velpandi, A; Nagashunmugam, T; Murthy, S; Cartas, M; Monken, C; Srinivasan, A

    1991-01-01

    Human immunodeficiency viruses (HIV) isolated from infected individuals show tremendous genetic and biologic diversity. To delineate the genetic determinants underlying specific biologic characteristics, such as rate of replication, cytopathic effects, and ability to infect macrophages and T4 lymphoid cells, generation of hybrid HIV using viruses which exhibit distinct biologic features is essential. To develop methods for generating hybrid HIV, we constructed truncated HIV proviral DNA plasmids. Upon digestion with restriction enzymes, these plasmid DNAs were cotransfected into human rhabdomyosarcoma cells to generate hybrid HIV. The hybrid HIVs derived by this method were infectious upon transmission to both phytohemagglutinin-stimulated peripheral blood lymphocytes and established human leukemic T-cell lines. The virus derived from molecular clone pHXB2 (HIVHTLV-III) productively infected CEMx174 cells. On the other hand, molecular clone pARV (HIVSF2)-derived virus did not show productive infection of CEMx174 cells when used as a cell-free virus. The hybrid HIV containing the 3' end of the genome from pARV and the 5' end of the genome from pHXB2 was effective in infecting CEMx174 cells, but the converse hybrid containing 5' pARV and 3' pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef play a role in the ability of the virus to infect a certain cell type. The intracellular ligation method should be useful in the analysis of related and unrelated HIV-1 isolates with common restriction enzyme cleavage sites. Images PMID:1678438

  9. Generation of hybrid human immunodeficiency virus utilizing the cotransfection method and analysis of cellular tropism.

    PubMed

    Velpandi, A; Nagashunmugam, T; Murthy, S; Cartas, M; Monken, C; Srinivasan, A

    1991-09-01

    Human immunodeficiency viruses (HIV) isolated from infected individuals show tremendous genetic and biologic diversity. To delineate the genetic determinants underlying specific biologic characteristics, such as rate of replication, cytopathic effects, and ability to infect macrophages and T4 lymphoid cells, generation of hybrid HIV using viruses which exhibit distinct biologic features is essential. To develop methods for generating hybrid HIV, we constructed truncated HIV proviral DNA plasmids. Upon digestion with restriction enzymes, these plasmid DNAs were cotransfected into human rhabdomyosarcoma cells to generate hybrid HIV. The hybrid HIVs derived by this method were infectious upon transmission to both phytohemagglutinin-stimulated peripheral blood lymphocytes and established human leukemic T-cell lines. The virus derived from molecular clone pHXB2 (HIVHTLV-III) productively infected CEMx174 cells. On the other hand, molecular clone pARV (HIVSF2)-derived virus did not show productive infection of CEMx174 cells when used as a cell-free virus. The hybrid HIV containing the 3' end of the genome from pARV and the 5' end of the genome from pHXB2 was effective in infecting CEMx174 cells, but the converse hybrid containing 5' pARV and 3' pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef play a role in the ability of the virus to infect a certain cell type. The intracellular ligation method should be useful in the analysis of related and unrelated HIV-1 isolates with common restriction enzyme cleavage sites.

  10. Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

    PubMed

    Frerich, Bernhard; Winter, Karsten; Scheller, Konstanze; Braumann, Ulf-Dietrich

    2012-03-01

    Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however

  11. Serotyping of primary human immunodeficiency virus type 1 isolates from diverse geographic locations by flow cytometry.

    PubMed Central

    Zolla-Pazner, S; O'Leary, J; Burda, S; Gorny, M K; Kim, M; Mascola, J; McCutchan, F

    1995-01-01

    The immunologic relatedness of the various human immunodeficiency virus type 1 (HIV-1) clades was determined with 13 human anti-HIV-1 monoclonal antibodies (MAbs) to six immunogenic regions of the HIV-1 structural proteins. The immunoreactivity of the native, oligomeric viral envelope glycoproteins expressed on the surfaces of human peripheral blood mononuclear cells infected in vitro with primary isolates from clades A through E was determined by flow cytometry. Some epitopes in the immunodominant region of gp41 and the C terminus of gp120 appear to be HIV-1 group specific in that they are expressed on the surfaces of cells in cultures infected with the majority of viruses tested from clades A to E. Epitopes within the V3 region appear to be clade restricted. Surprisingly, one MAb to an epitope in the C terminus of gp120 was entirely clade B specific. Staining with anti-V2 and anti-CD4 binding domain (CD4bd) reagents was infrequently detected. Anti-CD4bd MAbs stained only CD4-negative T cells because the CD4bd of gp120 appeared to be complexed with membrane CD4. When present, the epitopes of V2 and the CD4bd appeared to be expressed on cells infected with various clades. Thus, the results suggest that MAbs to gp41, the C terminus, and the V3 loop of gp120 are most useful in serotyping primary isolates of HIV-1, providing group-specific, clade-restricted, and clade-specific reagents. The use of the immunofluorescent method with the reagents described herein distinguishes infection with clade B from that with all other HIV-1 clades. With additional MAbs, this technique will allow a broadly applicable, reproducible, and practical method for serotyping HIV-1. PMID:7745728

  12. Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.

    PubMed Central

    Jordan, C A; Watkins, B A; Kufta, C; Dubois-Dalcq, M

    1991-01-01

    In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro. Images PMID:1702842

  13. Sensitive, hydrosoluble, macromolecular fluorogenic substrates for human immunodeficiency virus 1 proteinase.

    PubMed Central

    Anjuère, F; Monsigny, M; Lelièvre, Y; Mayer, R

    1993-01-01

    Hydrosoluble macromolecular fluorogenic substrates specific for the human immunodeficiency virus 1 (HIV-1) proteinase have been prepared. The fluoresceinyl peptide Ftc-epsilon-Ahx-Ser-Phe-Asn-Phe-Pro-Gln-Ile-Thr-(Gly)n, corresponding to the first cleavage site of HIV-1 gag-pol native precursor was linked to a water-soluble neutral (Lys)n derivative. The epsilon-aminohexanoyl residue (epsilon-Ahx) and the glycyl sequence were added in order to improve the stability of the substrate and the accessibility of the cleavage site to the HIV-1 proteinase respectively. This macro-molecular peptidic-substrate conjugate is significantly more water-soluble than the free peptide itself on a substrate molar concentration basis. The assay is based on the quantitative precipitation of the polymeric material by adding propan-2-ol whereas the fluorescent peptide moiety released upon proteolysis remains soluble in the supernatant. The proteinase activity is assessed by measuring the fluorescence of the supernatant. This assay allows the detection of a few fmol of HIV-1 proteinase, even in the presence of cell culture media, plasma or cell lysate and it gives accurate results within a large proteinase concentration range. The hydrosoluble macromolecular substrate is also suitable for determining the HIV-1 proteinase activity using 96-well microplates, allowing us to test accurately and rapidly numerous enzyme samples and/or the potency of new proteinase inhibitors. PMID:8489513

  14. Integrating women's perspectives on prenatal human immunodeficiency virus screening: toward a socially just policy.

    PubMed

    Mawn, B

    1998-12-01

    The purpose of this study was to include the voices of laywomen at risk for or living with human immunodeficiency virus (HIV) in the ongoing debate on prenatal and newborn HIV screening. A phenomenological approach based on Moustakas's heuristic model was used in order to explore women's lived experience. The investigator interviewed 33 women, half of whom were HIV-positive, using an open-ended, loosely structured interview guide. Two major domains were identified related to the women's views and experiences of HIV testing: the importance of a woman's awareness of her HIV status for both her own and her child's sake, and the need to maintain voluntary choice. Common themes emerging from the stories included paradoxical dimensions of living with the virus, such as fear of death, worry about health, concern over the pandemic itself, and loneliness, interspersed with faith and hope. Implications for health care providers include an enhanced understanding of the impact of the diagnosis, improvement in counseling techniques, and the importance of the establishment of trust. PMID:9839795

  15. "Frontal systems" behaviors in comorbid human immunodeficiency virus infection and methamphetamine dependency.

    PubMed

    Marquine, María J; Iudicello, Jennifer E; Morgan, Erin E; Brown, Gregory G; Letendre, Scott L; Ellis, Ronald J; Deutsch, Reena; Woods, Steven Paul; Grant, Igor; Heaton, Robert K

    2014-01-30

    Human immunodeficiency virus (HIV) infection and methamphetamine (MA) dependence are associated with neural injury preferentially involving frontostriatal circuits. Little is known, however, about how these commonly comorbid conditions impact behavioral presentations typically associated with frontal systems dysfunction. Our sample comprised 47 HIV-uninfected/MA-nondependent; 25 HIV-uninfected/MA-dependent; 36 HIV-infected/MA-nondependent; and 28 HIV-infected/MA-dependent subjects. Participants completed self-report measures of "frontal systems" behaviors, including impulsivity/disinhibition, sensation-seeking, and apathy. They also underwent comprehensive neurocognitive and neuropsychiatric assessments that allowed for detailed characterization of neurocognitive deficits and comorbid/premorbid conditions, including lifetime Mood and Substance Use Disorders, Attention-Deficit/Hyperactivity Disorder, and Antisocial Personality Disorder. Multivariable regression models adjusting for potential confounds (i.e., demographics and comorbid/premorbid conditions) showed that MA dependence was independently associated with increased impulsivity/disinhibition, sensation-seeking and apathy, and HIV infection with greater apathy. However, we did not see synergistic/additive effects of HIV and MA on frontal systems behaviors. Global neurocognitive impairment was relatively independent of the frontal systems behaviors, which is consistent with the view that these constructs may have relatively separable biopsychosocial underpinnings. Future research should explore whether both neurocognitive impairment and frontal systems behaviors may independently contribute to everyday functioning outcomes relevant to HIV and MA.

  16. Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.

    PubMed

    Kacani, L; Prodinger, W M; Sprinzl, G M; Schwendinger, M G; Spruth, M; Stoiber, H; Döpper, S; Steinhuber, S; Steindl, F; Dierich, M P

    2000-09-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.

  17. Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment.

    PubMed

    Woodham, Andrew W; Skeate, Joseph G; Sanna, Adriana M; Taylor, Julia R; Da Silva, Diane M; Cannon, Paula M; Kast, W Martin

    2016-07-01

    In the last three decades, extensive research on human immunodeficiency virus (HIV) has highlighted its capability to exploit a variety of strategies to enter and infect immune cells. Although CD4(+) T cells are well known as the major HIV target, with infection occurring through the canonical combination of the cluster of differentiation 4 (CD4) receptor and either the C-C chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4) coreceptors, HIV has also been found to enter other important immune cell types such as macrophages, dendritic cells, Langerhans cells, B cells, and granulocytes. Interestingly, the expression of distinct cellular cofactors partially regulates the rate in which HIV infects each distinct cell type. Furthermore, HIV can benefit from the acquisition of new proteins incorporated into its envelope during budding events. While several publications have investigated details of how HIV manipulates particular cell types or subtypes, an up-to-date comprehensive review on HIV tropism for different immune cells is lacking. Therefore, this review is meant to focus on the different receptors, coreceptors, and cofactors that HIV exploits to enter particular immune cells. Additionally, prophylactic approaches that have targeted particular molecules associated with HIV entry and infection of different immune cells will be discussed. Unveiling the underlying cellular receptors and cofactors that lead to HIV preference for specific immune cell populations is crucial in identifying novel preventative/therapeutic targets for comprehensive strategies to eliminate viral infection.

  18. Screening of Tanzanian medicinal plants against Plasmodium falciparum and human immunodeficiency virus.

    PubMed

    Maregesi, Sheila; Van Miert, Sabine; Pannecouque, Christophe; Feiz Haddad, Mohammed H; Hermans, Nina; Wright, Colin W; Vlietinck, Arnold J; Apers, Sandra; Pieters, Luc

    2010-02-01

    Medicinal plants used to treat infectious diseases in Bunda district, Tanzania, were screened for activity against Plasmodium falciparum and Human Immunodeficiency Virus Type 1 (HIV-1, IIIB strain) and Type 2 (HIV-2, ROD strain). Antiplasmodial activity was observed for the 80 % MeOH extract of Ormocarpum kirkii (root; MIC = 31.25 microg/mL), Combretum adenogonium (leaves), Euphorbia tirucalli (root), Harrisonia abyssinica (root), Rhynchosia sublobata (root), Sesbania sesban (root), Tithonia diversifolia (leaves), and Vernonia cinerascens (leaves; MIC value of 62.5 microg/mL). With regard to HIV, 80 % MeOH extracts of Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark), Elaeodedron schlechteranum (stem bark and root bark), Lannea schweinfurthii (stem bark), Terminalia mollis (stem bark and root bark), Acacia tortilis (stem bark), Ficus cycamorus (stem bark) and Indigofera colutea (shoot), as well as H2O extracts from Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark), and Terminalia mollis (stem bark and root bark) exhibited IC50 values below 10 microg/mL against HIV-1 (IIIB strain). The highest anti-HIV-1 activity value was obtained for the B. eranthemoides 80 % MeOH root extract (IC50 value 2.1 microg/mL). Only a few extracts were active against HIV-2, such as the 80 % MeOH extract from Lannea schweinfurthii (stem bark) and Elaeodedron schlechteranum (root bark), showing IC50 values < 10 microg/mL.

  19. The ocular manifestations of syphilis in the human immunodeficiency virus type 1-infected host.

    PubMed

    McLeish, W M; Pulido, J S; Holland, S; Culbertson, W W; Winward, K

    1990-02-01

    Nine patients with active ocular or optic nerve involvement by syphilis who also had concurrent human immunodeficiency virus type-1 (HIV-1) infection are described. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in four of nine cases. Fifteen eyes were affected. Ocular manifestations were: iridocyclitis in three eyes, vitreitis in one eye, retinitis or neuroretinitis in five eyes, papillitis in two eyes, optic perineuritis in two eyes, and retrobulbar optic neuritis in two eyes. Three patients diagnosed with acquired immune deficiency syndrome (AIDS) had the worst initial visual acuities. Six of nine patients had evidence of concomitant central nervous syndrome (CNS) involvement with syphilis. Benzathine penicillin was administered intramuscularly to three patients. All three had relapses. Seven of nine patients treated intravenously with high-dose penicillin had dramatic responses to therapy with improvement in vision and serologies and no evidence of relapse. Regimens accepted for the treatment of neurosyphilis appear to be adequate for the treatment of ocular syphilis in HIV-1-infected patients though further long-term follow-up will be required. PMID:2326008

  20. Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1

    PubMed Central

    Moore, Penny L.; Crooks, Emma T.; Porter, Lauren; Zhu, Ping; Cayanan, Charmagne S.; Grise, Henry; Corcoran, Paul; Zwick, Michael B.; Franti, Michael; Morris, Lynn; Roux, Kenneth H.; Burton, Dennis R.; Binley, James M.

    2006-01-01

    Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that bear functional trimers. The recent surprising observation that nonneutralizing antibodies can specifically capture HIV-1 may provide a clue relating to this paradox. Specifically, it was suggested that forms of Env, to which nonneutralizing antibodies can bind, exist on virus surfaces. Here, we present evidence that HIV-1 particles bear nonfunctional gp120/gp41 monomers and gp120-depleted gp41 stumps. Using a native electrophoresis band shift assay, we show that antibody-trimer binding predicts neutralization and that the nonfunctional forms of Env may account for virus capture by nonneutralizing antibodies. We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization. PMID:16474158

  1. Human Immunodeficiency Virus Integration Protein Expressed in Escherichia Coli Possesses Selective DNA Cleaving Activity

    NASA Astrophysics Data System (ADS)

    Sherman, Paula A.; Fyfe, James A.

    1990-07-01

    The human immunodeficiency virus (HIV) integration protein, a potential target for selective antiviral therapy, was expressed in Escherichia coli. The purified protein, free of detectable contaminating endonucleases, selectively cleaved double-stranded DNA oligonucleotides that mimic the U3 and the U5 termini of linear HIV DNA. Two nucleotides were removed from the 3' ends of both the U5 plus strand and the U3 minus strand; in both cases, cleavage was adjacent to a conserved CA dinucleotide. The reaction was metal-ion dependent, with a preference for Mn2+ over Mg2+. Reaction selectivity was further demonstrated by the lack of cleavage of an HIV U5 substrate on the complementary (minus) strand, an analogous substrate that mimics the U3 terminus of an avian retrovirus, and an HIV U5 substrate in which the conserved CA dinucleotide was replaced with a TA dinucleotide. Such an integration protein-mediated cleavage reaction is expected to occur as part of the integration event in the retroviral life cycle, in which a double-stranded DNA copy of the viral RNA genome is inserted into the host cell DNA.

  2. AIDS and prevalence of antibody to human immunodeficiency virus (HIV) in high risk groups in Thailand.

    PubMed

    Traisupa, A; Wongba, C; Taylor, D N

    1987-04-01

    Since September 1984, six cases of acquired immune deficiency syndrome (AIDS) and 11 cases of AIDS related complex (ARC) have been reported in Thailand. All people with AIDS were homosexual or bisexual men; two were Thai and the rest were European or American. Nine of the 11 people with ARC were homosexual or bisexual men, one was the female sexual partner of a man with AIDS, and one was a Thai man who had lived in the United States of America for several years, but denied having had any homosexual contact. Nine of the 11 people with ARC were Thai. In a survey in April 1985 at a resort area near Bangkok, antibodies to human immunodeficiency virus (HIV) (confirmed by western blot) were detected in 2.4% of 127 homosexual men and none of 77 female prostitutes. In a more extensive survey in October 1985, antibodies were detected in 0.8% of 720 homosexual men, but none of 2880 female prostitutes or 309 sexually active heterosexual men. HIV has been introduced into Thailand primarily by homosexual transmission. The public health policy of Thailand concerning AIDS is discussed.

  3. Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

    PubMed

    Prakash, Om; Mason, Andrew; Luftig, Ronald B; Bautista, Abraham P

    2002-07-01

    Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. PMID:12086918

  4. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.

    PubMed

    Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi

    2015-05-01

    Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.

  5. Evaluation of the Editing Process in Human Immunodeficiency Virus Type 1 Genotyping

    PubMed Central

    Huang, Diana D.; Eshleman, Susan H.; Brambilla, Donald J.; Palumbo, Paul E.; Bremer, James W.

    2003-01-01

    Sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping assays require subjective interpretation (editing) of sequence data from multiple primers to form consensus sequences and identify antiretroviral drug resistance mutations. We assessed interlaboratory variations in editing and their impact on the recognition of resistance mutations. Six samples were analyzed in a central laboratory by using a research-use-only HIV-1 genotyping system previously produced by Applied Biosystems. The electronic files of individual primer sequences from the samples were sent to 10 laboratories to compare sequence editing strategies. Each sequence data set included sequences from seven primers spanning protease codons 1 to 99 and reverse transcriptase codons 1 to 320. Each laboratory generated a consensus sequence for each sample and completed a questionnaire about editing strategy. The amount of editing performed, the concordance of consensus sequences among the laboratories, and the identification of resistance mutations were evaluated. Sequence agreement was high among the laboratories despite wide variations in editing strategies. All laboratories identified 66 (88%) of 75 resistance mutations in the samples. Nonconcordant identifications were made for 9 (12%) of the 75 mutations, all of which required editing for identification. These results indicate a need for standardized editing guidelines in genotyping assays. Proficiency in editing should be assessed in training and included in quality control programs for HIV-1 genotyping. PMID:12843074

  6. [Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

    PubMed

    Aguirrebengoa, Koldo

    2014-11-01

    Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs.

  7. The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels.

    PubMed Central

    Ewart, G D; Sutherland, T; Gage, P W; Cox, G B

    1996-01-01

    Vpu is a small phosphorylated integral membrane protein encoded by the human immunodeficiency virus type 1 genome and found in the endoplasmic reticulum and Golgi membranes of infected cells. It has been linked to roles in virus particle budding and degradation of CD4 in the endoplasmic reticulum. However, the molecular mechanisms employed by Vpu in performance of these functions are unknown. Structural similarities between Vpu and the M2 protein of influenza A virus have raised the question of whether the two proteins are functionally analogous: M2 has been demonstrated to form cation-selective ion channels in phospholipid membranes. In this paper we provide evidence that Vpu, purified after expression in Escherichia coli, also forms ion channels in planar lipid bilayers. The channels are approximately five- to sixfold more permeable to sodium and potassium cations than to chloride or phosphate anions. A bacterial cross-feeding assay was used to demonstrate that Vpu can also form sodium-permeable channels in vivo in the E. coli plasma membrane. PMID:8794357

  8. Human immunodeficiency virus 1 protease expressed in Escherichia coli behaves as a dimeric aspartic protease.

    PubMed Central

    Meek, T D; Dayton, B D; Metcalf, B W; Dreyer, G B; Strickler, J E; Gorniak, J G; Rosenberg, M; Moore, M L; Magaard, V W; Debouck, C

    1989-01-01

    Recombinant human immunodeficiency virus 1 (HIV-1) protease, purified from a bacterial expression system, processed a recombinant form of its natural substrate, Pr55gag, into protein fragments that possess molecular weights commensurate with those of the virion gag proteins. Molecular weights of the protease obtained under denaturing and nondenaturing conditions (11,000 and 22,000, respectively) and chemical crosslinking studies were consistent with a dimeric structure for the active enzyme. The protease appropriately cleaved the nonapeptide Ac-Arg-Ala-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 between the tyrosine and proline residues. HIV-1 protease was sensitive to inactivators of the aspartic proteases. The aspartic protease inactivator 1,2-epoxy-3-(4-nitrophenoxy)propane produced irreversible, time-dependent inactivation of the protease. The pH-dependent kinetics of this inactivator were consistent with the requirement of an unprotonated carboxyl group in the active site of the enzyme, suggesting that HIV-1 protease is also an aspartic protease. Images PMID:2648384

  9. Primary Radiation Therapy for Head-and-Neck Cancer in the Setting of Human Immunodeficiency Virus

    SciTech Connect

    Klein, Emily A.; Guiou, Michael; Farwell, D. Gregory; Luu, Quang; Lau, Derick H.; Stuart, Kerri; Vaughan, Andrew; Vijayakumar, Srinivasan; Chen, Allen M.

    2011-01-01

    Purpose: To analyze outcomes after radiation therapy for head-and-neck cancer among a cohort of patients with human immunodeficiency virus (HIV). Methods and Materials: The medical records of 12 patients with serologic evidence of HIV who subsequently underwent radiation therapy to a median dose of 68 Gy (range, 64-72 Gy) for newly diagnosed squamous cell carcinoma of the head and neck were reviewed. Six patients (50%) received concurrent chemotherapy. Intensity-modulated radiotherapy was used in 6 cases (50%). All patients had a Karnofsky performance status of 80 or 90. Nine patients (75%) were receiving antiretroviral therapies at the time of treatment, and the median CD4 count was 460 (range, 266-800). Toxicity was graded according to the Radiation Therapy Oncology Group / European Organization for the Treatment of Cancer toxicity criteria. Results: The 3-year estimates of overall survival and local-regional control were 78% and 92%, respectively. Acute Grade 3+ toxicity occurred in 7 patients (58%), the most common being confluent mucositis (5 patients) and moist skin desquamation (4 patients). Two patients experienced greater than 10% weight loss, and none experienced more than 15% weight loss from baseline. Five patients (42%) experienced treatment breaks in excess of 10 cumulative days, although none required hospitalization. There were no treatment-related fatalities. Conclusions: Radiation therapy for head-and-neck cancer seems to be relatively well tolerated among appropriately selected patients with HIV. The observed rates of toxicity were comparable to historical controls without HIV.

  10. Influence of membrane fluidity on human immunodeficiency virus type 1 entry

    SciTech Connect

    Harada, Shinji . E-mail: biodef@gpo.kumamoto-u.ac.jp; Yusa, Keisuke; Monde, Kazuaki; Akaike, Takaaki; Maeda, Yosuke

    2005-04-08

    For penetration of human immunodeficiency virus type 1 (HIV-1), formation of fusion-pores might be required for accumulating critical numbers of fusion-activated gp41, followed by multiple-site binding of gp120 with receptors, with the help of fluidization of the plasma membrane and viral envelope. Correlation between HIV-1 infectivity and fluidity was observed by treatment of fluidity-modulators, indicating that infectivity was dependent on fluidity. A 5% decrease in fluidity suppressed the HIV-1 infectivity by 56%. Contrarily, a 5% increase in fluidity augmented the infectivity by 2.4-fold. An increased temperature of 40 deg C or treatment of 0.2% xylocaine after viral adsorption at room temperature enhanced the infectivity by 2.6- and 1.5-fold, respectively. These were inhibited by anti-CXCR4 peptide, implying that multiple-site binding was accelerated at 40 deg C or by xylocaine. Thus, fluidity of both the plasma membrane and viral envelope was required to form the fusion-pore and to complete the entry of HIV-1.

  11. Compounds from rose (Rosa rugosa) flowers with human immunodeficiency virus type 1 reverse transcriptase inhibitory activity.

    PubMed

    Fu, M; Ng, T B; Jiang, Y; Pi, Z F; Liu, Z K; Li, L; Liu, F

    2006-09-01

    The aqueous extracts and ethanol precipitates of aqueous extracts of 18 medicinal herbs traditionally used in China were screened for their ability to inhibit human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) in-vitro. Among the samples screened at a concentration of 500 microg mL-1, dried rose (Rosa rugosa) flowers showed the strongest inhibition. The ethanol precipitate of the aqueous extract of R. rugosa was processed and two components (P1 and P2) were obtained after ion exchange chromatography on DEAE-cellulose. Then, P1-a (Mr 150 kDa) and P1-b (Mr 8 kDa) were isolated from P1 by gel filtration on Sephadex G-200. They inhibited the activity of HIV-1 RT with an IC50 of 158 nM and 148.16 microg mL-1 (18.5 microM), respectively. Further structural analyses revealed that P1-a was a polysaccharide-peptide complex, and P1-b was a polymer consisting of acteoside and acteoside derivatives identified by Fourier transform infrared spectroscopy, nuclear magnetic resonance, assays of carbohydrate and protein contents and high-performance liquid chromatography electrospray ionization mass spectrometry. PMID:16945187

  12. Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives.

    PubMed Central

    Baba, M; Okamoto, M; Makino, M; Kimura, Y; Ikeuchi, T; Sakaguchi, T; Okamoto, T

    1997-01-01

    We have found novel piperazinyloxoquinoline derivatives to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in both acutely and chronically infected cells. 8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-didehydro-7-[4-(2-met hoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12), the most potent congener of the series, completely inhibited HIV-1 replication in acutely infected MOLT-4 cells at a concentration of 0.16 to 0.8 microM without showing any cytotoxicity. The compound completely suppressed tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 expression in latently infected cells (OM-10.1) and constitutive viral production in chronically infected cells (MOLT-4/III(B)) at a concentration of 0.8 microM. K-12 could also inhibit HIV-1 antigen expression in OM-10.1 and MOLT-4/III(B) cells at this concentration. Northern blot analysis revealed that K-12 selectively prevented the accumulation of HIV-1 mRNA in MOLT-4/III(B) and TNF-alpha-treated OM-10.1 cells in a dose-dependent fashion. It was not inhibitory to HIV-1 Tat or the cellular transcription factors NF-kappaB and Sp1, suggesting that the piperazinyloxoquinoline derivatives are a group of HIV-1 transcription inhibitors with a unique mechanism of action. PMID:9174179

  13. Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog.

    PubMed Central

    Rosenwirth, B; Billich, A; Datema, R; Donatsch, P; Hammerschmid, F; Harrison, R; Hiestand, P; Jaksche, H; Mayer, P; Peichl, P

    1994-01-01

    (Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppressive activity but retains full capacity for binding to cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1) activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its antiviral activity against laboratory strains and against clinical isolates from geographically distinct regions in primary T4 lymphocytes and in primary monocytes (50% inhibitory concentration = 0.011 to 0.057 micrograms/ml) was demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus-specific enzyme functions, either free or bound to cyclophilin. The compound does not influence CD4 expression or inhibit fusion between virus-infected and uninfected cells. SDZ NIM 811 was, however, found to block formation of infectious particles from chronically infected cells. Oral administration to mice, rats, dogs, and monkeys resulted in levels in blood considerably exceeding the drug concentration, which completely blocked virus replication in primary cells. SDZ NIM 811 caused changes of toxicity parameters in rats to a smaller degree than cyclosporine (formerly cyclosporin A). Thus, the potent and selective anti-HIV-1 activity of SDZ NIM 811 and its favorable pharmacokinetic behavior together with its lower nephrotoxicity than that of cyclosporine make this compound a promising candidate for development as an anti-HIV drug. PMID:7527198

  14. Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells.

    PubMed Central

    Harakeh, S; Jariwalla, R J; Pauling, L

    1990-01-01

    We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions. Images PMID:1698293

  15. Charges of human immunodeficiency virus discrimination in the workplace: the Americans with Disabilities Act in action.

    PubMed

    Studdert, David M

    2002-08-01

    Congress enacted the Americans with Disabilities Act (ADA) to provide persons living with the human immunodeficiency virus (HIV) and other vulnerable populations with legal means of redress against discrimination, yet virtually nothing is known about how the intended beneficiaries have used these protections. This study aimed to describe the epidemiology of ADA charges alleging employment-related discrimination due to HIV and to investigate the charge-filing behavior of workers with HIV. Using a national database of all HIV discrimination charges filed since the inception of the ADA in 1991, the author described respondent employers, issues in dispute, and outcomes of charges. Next, he used multivariate regression analyses to compare the sociodemographic characteristics of charge filers with those of a nationally representative baseline sample of workers with HIV. Of the 3,520 HIV discrimination charges filed through 1999, 18.0% had merit and 14.1% received monetary compensation. Workers who were female (odds ratio (OR) = 0.79, p < 0.01), aged less than 25 years (OR = 0.36, p < 0.01), and aged 25-34 years (OR = 0.77, p < 0.01) filed disproportionately fewer charges. Controlling for underlying rates of discrimination in the baseline population magnified this "underclaiming" among young workers. The findings should help to target dissemination and support activities, designed to help workers take advantage of antidiscrimination protections, at the subgroups of workers who need them most.

  16. Precancerous Cervix in Human Immunodeficiency Virus Infected Women Thirty Years Old and above in Northern Uganda.

    PubMed

    Izudi, Jonathan; Adrawa, Norbert; Amongin, Dinah

    2016-01-01

    Background. Little is known about precancerous cervical lesion (PCCL), the precursor of cervical cancer among Human Immunodeficiency (HIV) infected women in a postconflict setting of Northern Uganda. Objective. To establish factors associated with PCCL among HIV infected women above thirty years of age in a postconflict setting of Northern Uganda. Method. This retrospective cohort study used electronic data from 995 HIV-positive women that attended cervical cancer screening during June 2014 and December 2015. Data on social, sexual, obstetric, and gynecological factors was analyzed at 95% confidence level. Multivariate analysis determined factors independently associated with positive PCCL. Probability value less than 5% was considered significant. Results. Prevalence of PCCL was 3.0% (95% confidence interval (CI): 2.0-4.3). A positive PCCL was significantly associated with absence of sexually transmitted diseases (STDs) during clinic visits (adjusted odds ratio, aOR = 0.24; 95% confidence interval (CI): 0.09-0.64; P = 0.004) and first pregnancy before the age of 20 years (aOR = 3.09; 95% CI: 1.21-7.89; P = 0.018). Conclusion. The prevalence of PCCL was low in the postconflict setting of Northern Uganda. HIV-positive women presenting with STDs and those with first pregnancy before the age of 20 years were at increased risk of PCCL. PMID:27478441

  17. Stimulated Emission Depletion Nanoscopy Reveals Time-Course of Human Immunodeficiency Virus Proteolytic Maturation.

    PubMed

    Hanne, Janina; Göttfert, Fabian; Schimer, Jiří; Anders-Össwein, Maria; Konvalinka, Jan; Engelhardt, Johann; Müller, Barbara; Hell, Stefan W; Kräusslich, Hans-Georg

    2016-09-27

    Concomitant with human immunodeficiency virus type 1 (HIV-1) budding from a host cell, cleavage of the structural Gag polyproteins by the viral protease (PR) triggers complete remodeling of virion architecture. This maturation process is essential for virus infectivity. Electron tomography provided structures of immature and mature HIV-1 with a diameter of 120-140 nm, but information about the sequence and dynamics of structural rearrangements is lacking. Here, we employed super-resolution STED (stimulated emission depletion) fluorescence nanoscopy of HIV-1 carrying labeled Gag to visualize the virion architecture. The incomplete Gag lattice of immature virions was clearly distinguishable from the condensed distribution of mature protein subunits. Synchronized activation of PR within purified particles by photocleavage of a caged PR inhibitor enabled time-resolved in situ observation of the induction of proteolysis and maturation by super-resolution microscopy. This study shows the rearrangement of subviral structures in a super-resolution light microscope over time, outwitting phototoxicity and fluorophore bleaching through synchronization of a biological process by an optical switch. PMID:27517329

  18. Prevalence of human immunodeficiency virus infection among transgender men in Rawalpindi (Pakistan)

    PubMed Central

    2012-01-01

    Background Transgender males are at high risk for sexually transmitted diseases including AIDS caused by the notorious Human Immunodeficiency Virus (HIV), yet little consideration is given by the policy makers, researchers and non-governmental organizations (NGOs) towards this sensitive issue in Pakistan. Methods In this study, we have investigated the prevalence of HIV infection among 306 transgender males with a median age of 29 years (range 15–64 years) residing in Rawalpindi, Pakistan. Rapid HIV antibody-screening methods including the strip test and Enzyme Linked Immuno-absorbent tests were employed to detect HIV antibodies among the subjects. For further confirmation, Polymerase Chain Reaction (PCR) was carried out. Statistical analytical techniques utilized included logistic regression and chi-square. Results HIV-1 was found to be the predominant viral subtype. PCR confirmed 21.6% (Confidence Interval 0.17-0.26) of the respondents were reported being HIV positive. 15.7% of the transgender men who shave at home and 13.7% of the transgender men who were educated below 5th grade were found to have HIV. Conclusion This study shows a very high prevalence of HIV among transgender males. Unawareness among these individuals about the ramifications of this infection owes largely to lack of education. The spread rate is alarming and HIV epidemic is imminent if awareness is not widespread. PMID:23039269

  19. Influence of human immunodeficiency virus type 1 subtype on mother-to-child transmission.

    PubMed

    Tàpia, Natàlia; Franco, Sandra; Puig-Basagoiti, Francesc; Menéndez, Clara; Alonso, Pedro Luis; Mshinda, Hassan; Clotet, Bonaventura; Saiz, Juan Carlos; Martínez, Miguel Angel

    2003-03-01

    The present study was designed to assess whether the subtype of human immunodeficiency virus type 1 (HIV-1) could affect the rate of HIV-1 mother-to-child transmission in a cohort of 31 HIV-1-seropositive pregnant Tanzanian women. In order to assign a subtype to the samples analysed, nucleotide sequencing of the HIV-1 long terminal repeat U3 and C2V3C3 envelope regions was performed from the sera of these 31 pregnant women. Except in three cases, amplification of both regions was achieved in all samples. Subtypes A (n=13, 46 %), C (n=6, 21 %) and D (n=2, 7 %), as well as a number (25 %) of A/C, C/A, D/A and C/D recombinant forms (n=3, 2, 1 and 1, respectively), were identified. Of the 31 HIV-1 seropositive pregnant women analysed, eight (26 %) transmitted HIV-1 to their infants. Among the eight transmitter mothers, four (4 of 13, 31 %) were infected with HIV-1 subtype A, one (1 of 6, 17 %) with HIV-1 subtype C, none (0 of 2, 0 %) with HIV-1 subtype D and three (3 of 7, 43 %) with HIV-1 subtype recombinant A/C. These findings show no significant differences in the mother-to-child transmissibility of HIV-1 subtypes A, C and D and detected recombinants forms.

  20. Targeting Tat Inhibitors in the Assembly of Human Immunodeficiency Virus Type 1 Transcription Complexes▿ †

    PubMed Central

    D'Orso, Iván; Grunwell, Jocelyn R.; Nakamura, Robert L.; Das, Chandreyee; Frankel, Alan D.

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) transcription is regulated by the viral Tat protein, which relieves a block to elongation by recruiting an elongation factor, P-TEFb, to the viral promoter. Here, we report the discovery of potent Tat inhibitors that utilize a localization signal to target a dominant negative protein to its site of action. Fusing the Tat activation domain to some splicing factors, particularly to the Arg-Ser (RS) domain of U2AF65, creates Tat inhibitors that localize to subnuclear speckles, sites where pre-mRNA processing factors are stored for assembly into transcription complexes. A U2AF65 fusion named T-RS interacts with the nonphosphorylated C-terminal domain of RNA polymerase II (RNAP II) via its RS domain and is loaded into RNAP II holoenzyme complexes. T-RS is recruited efficiently to the HIV-1 promoter in a TAR-independent manner before RNAP II hyperphosphorylation but not to cellular promoters. The “preloading” of T-RS into HIV-1 preinitiation complexes prevents the entry of active Tat molecules, leaving the complexes in an elongation-incompetent state and effectively suppressing HIV-1 replication. The ability to deliver inhibitors to transcription complexes through the use of targeting/localization signals may provide new avenues for designing viral and transcription inhibitors. PMID:18667497

  1. Hepatitis C Screening in People With Human Immunodeficiency Virus: Lessons Learned From Syphilis Screening.

    PubMed

    Wurcel, Alysse G; Chen, Daniel D; Fitzpatrick, Rosemary E; Grasberger, Paula E; Kirshner, Caleb H; Anderson, Jordan E; Chui, Kenneth K H; Knox, Tamsin A

    2016-01-01

    Background.  The incidence of hepatitis C virus (HCV) infection is increasing in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). New guidelines recommend annual screening for HCV, similar to recommendations for syphilis screening with rapid plasma reagin (RPR). Methods.  This study compares the frequency of repeat HCV antibody (Ab) testing to repeat RPR testing in a retrospective chart review of 359 HCVAb-negative people living with HIV (PLWH) observed in an Infectious Diseases clinic. Patients were classified into risk groups based on sexual risk factors. Results.  Although 85% of PLWH had repeat syphilis screening, less than two thirds had repeat HCVAb screening. The MSM status was associated with increased HCVAb and RPR testing (adjusted odds ratio, 2.6 and 5.9, respectively). Seven persons had incident HCV infection: 3 were MSM, and 4 had symptoms or abnormal laboratory results to prompt testing. Conclusions.  Failure to find incident HCV infection in PLWH represents missed opportunities to cure HCV infection and prevent progressive liver disease. Further quality improvement studies are necessary to develop physician-focused interventions to increase HCV screening rates in PLWH.

  2. Hepatitis C Screening in People With Human Immunodeficiency Virus: Lessons Learned From Syphilis Screening

    PubMed Central

    Wurcel, Alysse G.; Chen, Daniel D.; Fitzpatrick, Rosemary E.; Grasberger, Paula E.; Kirshner, Caleb H.; Anderson, Jordan E.; Chui, Kenneth K. H.; Knox, Tamsin A.

    2016-01-01

    Background. The incidence of hepatitis C virus (HCV) infection is increasing in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). New guidelines recommend annual screening for HCV, similar to recommendations for syphilis screening with rapid plasma reagin (RPR). Methods. This study compares the frequency of repeat HCV antibody (Ab) testing to repeat RPR testing in a retrospective chart review of 359 HCVAb-negative people living with HIV (PLWH) observed in an Infectious Diseases clinic. Patients were classified into risk groups based on sexual risk factors. Results. Although 85% of PLWH had repeat syphilis screening, less than two thirds had repeat HCVAb screening. The MSM status was associated with increased HCVAb and RPR testing (adjusted odds ratio, 2.6 and 5.9, respectively). Seven persons had incident HCV infection: 3 were MSM, and 4 had symptoms or abnormal laboratory results to prompt testing. Conclusions. Failure to find incident HCV infection in PLWH represents missed opportunities to cure HCV infection and prevent progressive liver disease. Further quality improvement studies are necessary to develop physician-focused interventions to increase HCV screening rates in PLWH. PMID:26885544

  3. An inducible transcription factor activates expression of human immunodeficiency virus in T cells

    NASA Astrophysics Data System (ADS)

    Nabel, Gary; Baltimore, David

    1987-04-01

    Human immunodeficiency virus (HIV) production from latently infected T lymphocytes can be induced with compounds that activate the cells to secrete lymphokines1,2. The elements in the HIV genome which control activation are not known but expression might be regulated through a variety of DNA elements. The cis-acting control elements of the viral genome are enhancer and promoter regions. The virus also encodes trans-acting factors specified by the tat-III (refs 3-6) and art genes7. We have examined whether products specific to activated T cells might stimulate viral transcription by binding to regions on viral DNA. Activation of T cells, which increases HIV expression up to 50-fold, correlated with induction of a DNA binding protein indistinguishable from a recognized transcription factor, called NF-κB (ref. 8), with binding sites in the viral enhancer. Mutation of these binding sites abolished inducibility. That NF-κB acts in synergy with the viral tat-III gene product to enhance HIV expression in T cells may have implications for the pathogenesis of AIDS (acquired immune deficiency syndrome).

  4. Insights into human immunodeficiency virus-hepatitis B virus co-infection in India

    PubMed Central

    Chakravarty, Runu; Pal, Ananya

    2015-01-01

    Shared routes of transmission lead to frequent human immunodeficiency virus (HIV)-hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study. PMID:26279986

  5. An integrated system to study multiply substituted human immunodeficiency virus type 1 reverse transcriptase.

    PubMed

    Boretto, J; Longhi, S; Navarro, J M; Selmi, B; Sire, J; Canard, B

    2001-05-01

    We describe a gene system allowing the facile production of multiply substituted reverse transcriptases (RTs), the enzymatic characterization of these purified RTs, and the study of these mutations in the defined genetic background of the macrophagetropic, non-laboratory-adapted human immunodeficiency virus type 1 (HIV-1) AD8 strain. Thirteen unique silent restriction sites were introduced in the pol gene encoding HIV-1 RT, allowing easy introduction of mutations. To simplify genetic manipulation and generate p66/p51 heterodimers in Escherichia coli, a gene construct of the viral protease alone was optimized for expression from a separate vector carrying a p15A origin of replication. Active-site titration experiments using pre-steady-state kinetics showed that our system yields a higher proportion of active enzyme than that obtained by alternate methods. To facilitate phenotype/genotype correlations, the modified RT gene was designed to be easily reintroduced into a recombinant proviral AD8 HIV-1 DNA. Infectious viruses made from this vector were undistinguishable from wild-type AD8 HIV-1, an isolate able to infect peripheral blood mononuclear cells and macrophages. Thus, the pol gene can tolerate many silent mutations in the polymerase domain without affecting the functionality of the HIV-1 genome. The system was validated biochemically and virologically using the V75T substitution associated with stavudine resistance.

  6. Susceptibility of human immunodeficiency virus to antiviral agents measured by infectious virus yield reduction.

    PubMed

    Dianzani, F; Capobianchi, M R; Antonelli, G; Amicucci, P; De Marco, F

    1989-01-01

    Under single growth cycle conditions in C8166 lymphoblastoid cells human immunodeficiency virus shows a replication curve which is completed at 24 h post-infection. At lower multiplicity of infection virus yield peaks at approximately 72 h post-infection but in both cases the titer of the virus released in the medium is negligible with respect to that which remains cell-associated. A method based on back-titration of virus in cryolysates of C8166 cells infected with HIV and treated with antiviral compounds has been used to evaluate HIV sensitivity to such agents. Under single growth cycle conditions dose response curves appear linear and permit rapid and accurate determination of the endpoint activity. Under multiple growth cycle conditions the inhibitory activity may be measured during the exponential growth phase, at 48 h post-infection. This method, which directly measures production of infectious virus rather than indirect probes of viral replication such as reverse transcriptase or antigen production, offers the advantage of a precise determination of the degree of activity of antivirals also acting on viral assembly or release.

  7. Replication and pathogenicity of attenuated human metapneumovirus F mutants in severe combined immunodeficiency mice.

    PubMed

    Yu, Chun-mei; Li, Rong-pei; Chen, Xin; Liu, Ping; Zhao, Xiao-dong

    2012-01-01

    This study was to evaluate the replication and pathogenicity of attenuated human metapneumovirus (HMPV) mutants in severe combined immunodeficiency (SCID) mice. SCID mice were intranasally infected with either wild type GFP-rHMPV (WT), or mutant viruses (M1, M2 and M4) with the N-linked glycosylation(s) of the F protein removed. The organs were collected for viral isolation, titration, pulmonary histopathology and mRNA detection by PCR at different time points. WT or mutant viruses were successfully isolated from the lungs of infected mice after inoculation. The titers of WT and M1 peaked on 5th day and remained detectable until 14th day post-inoculation. M2 reached approximately 4 logs lower titer on 5th and 9th day post-inoculation as compared to WT and M1. M4 showed similar growth kinetics to M2. Viral signal was never detected from the heart, liver, spleen, kidney and brain on 5th day post-inoculation. The pulmonary pathology score in the M1 infected mice was similar to WT infected mice but higher than in M2 or M4 infected mice. WT and HMPV mutants can thus only replicate in the lungs of SCID mice. Attenuated M2 and M4 may be considered as candidates for the preparation of vaccine against HMPV.

  8. How human immunodeficiency virus voluntary testing can contribute to tuberculosis control.

    PubMed Central

    Godfrey-Faussett, Peter; Maher, Dermot; Mukadi, Ya Diul; Nunn, Paul; Perriëns, Joseph; Raviglione, Mario

    2002-01-01

    Human immunodeficiency virus (HIV) is fueling the tuberculosis (TB) epidemic, particularly in sub-Saharan Africa. However, despite their close epidemiological links, the public health responses have largely been separate. WHO has set out a strategy to decrease the burden of HIV-related TB, comprising interventions against both TB and HIV. Voluntary counselling and testing (VCT) for HIV can link TB and HIV programme activities. The benefits of VCT for HIV to TB patients include referral for appropriate clinical care and support for those testing HIV-positive. Likewise, people attending a centre for VCT can benefit from TB screening: those found to be both HIV-positive and with active TB need referral for TB treatment; those without active TB should be offered TB preventive treatment with isoniazid. To explore how VCT for HIV can contribute to a more coherent response to TB, WHO is coordinating the ProTEST Initiative. The name "ProTEST" is derived from the Promotion of voluntary testing as an entry point for access to the core interventions of intensified TB case-finding and isoniazid preventive treatment. Other interventions may be added to provide finally a comprehensive range of HIV and TB prevention and care interventions. Under the ProTEST Initiative, pilot districts are establishing links between centres for VCT for HIV and TB prevention and care. This will pave the way for large-scale operationalization of the comprehensive range of interventions needed to control TB in settings with high HIV prevalence. PMID:12571721

  9. Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

    PubMed Central

    Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne; Lillevang, Søren Thue; Christensen, Peer B; Holm, Dorte Kinggaard

    2016-01-01

    AIM To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained. The samples were analyzed for HBsAg, anti-HBc, anti-HBs, anti-HCV, and anti-HIV levels as well as subjected to a combined nucleic acid test (NAT) for HBV DNA, HCV RNA and HIV RNA. RESULTS Samples from 404 subjects were screened (85 CHB, 116 CHC, 114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system. PMID:27672281

  10. Gender Reassignment Surgery in Human Immunodeficiency Virus-Positive Patients: A Report of Two Cases

    PubMed Central

    Choi, Ji-An; Kim, Myung-Hoon; Kim, Min-Su; Lee, Keun-Cheol

    2015-01-01

    It is believed that surgery on human immunodeficiency virus (HIV)-positive patients is dangerous and should be avoided due to the possibility of postoperative infection of the patients or HIV occupational transmission to the medical staff. We discuss here the preparations and measures needed to conduct surgery safely on HIV-positive patients, based on our experience. We performed sex reassignment surgery on two HIV-positive patients from January 2013 to January 2015. Both of them were receiving highly active antiretroviral therapy and were asymptomatic, with a normal CD4 count (>500 cells/µL). The HIV-RNA was undetectable within the bloodstream. All the staff wore protective clothing, glasses, and three pairs of protective gloves in the operating room because of the possibility of transmission. Prophylactic antibiotics were administered to the patients, and antiviral therapy was performed during their perioperative course. Neither of the patients had postoperative complications, and none of the medical staff experienced accidental exposure. Both patients had satisfactory surgery outcomes without complications. HIV-positive patients can undergo surgery safely without increased risk of postoperative complications or HIV transmission to the staff through the proper use of antibiotics, active antiretroviral therapy, and supplemental protective measures with post-exposure prophylaxis for the staff in case of HIV exposure. PMID:26618127

  11. Gender Reassignment Surgery in Human Immunodeficiency Virus-Positive Patients: A Report of Two Cases.

    PubMed

    Kim, Seok-Kwun; Choi, Ji-An; Kim, Myung-Hoon; Kim, Min-Su; Lee, Keun-Cheol

    2015-11-01

    It is believed that surgery on human immunodeficiency virus (HIV)-positive patients is dangerous and should be avoided due to the possibility of postoperative infection of the patients or HIV occupational transmission to the medical staff. We discuss here the preparations and measures needed to conduct surgery safely on HIV-positive patients, based on our experience. We performed sex reassignment surgery on two HIV-positive patients from January 2013 to January 2015. Both of them were receiving highly active antiretroviral therapy and were asymptomatic, with a normal CD4 count (>500 cells/µL). The HIV-RNA was undetectable within the bloodstream. All the staff wore protective clothing, glasses, and three pairs of protective gloves in the operating room because of the possibility of transmission. Prophylactic antibiotics were administered to the patients, and antiviral therapy was performed during their perioperative course. Neither of the patients had postoperative complications, and none of the medical staff experienced accidental exposure. Both patients had satisfactory surgery outcomes without complications. HIV-positive patients can undergo surgery safely without increased risk of postoperative complications or HIV transmission to the staff through the proper use of antibiotics, active antiretroviral therapy, and supplemental protective measures with post-exposure prophylaxis for the staff in case of HIV exposure.

  12. Purification and characterization of an active human immunodeficiency virus type 1 RNase H domain.

    PubMed Central

    Smith, J S; Roth, M J

    1993-01-01

    We have expressed and purified from Escherichia coli a human immunodeficiency virus type 1 (HIV-1) RNase H domain consisting of amino acids 400 to 560 of reverse transcriptase with either an N- or C-terminal polyhistidine tag. The native protease cleavage site of HIV-1 reverse transcriptase is between amino acids 440 and 441. Purification on Ni(2+)-nitrilotriacetate agarose resulted in a highly active RNase H domain dependent on MnCl2 rather than MgCl2. Activity was unambiguously attributed to the purified proteins by an in situ RNase H gel assay. Residues 400 to 426, which include a stretch of tryptophans, did not contribute to RNase H activity, and the polyhistidine tag was essential for activity. Despite the requirement for a histidine tag, the recombinant RNase H proteins retained characteristics of the wild-type heterodimer, as determined by examining activity in the presence of several known inhibitors of HIV-1 RNase H, including ribonucleoside vanadyl complexes, dAMP, and a monoclonal antibody. Importantly, the isolated RNase H domain produced the same specific cleavage in tRNA(3Lys) removal as HIV-1 heterodimer, leaving the 3'-rA (adenosine 5' phosphate) residue of a model tRNA attached to the adjacent U5 sequence. This HIV-1 RNase H domain sedimented as a monomer in a glycerol gradient. Images PMID:7685407

  13. Multiple Simultaneous Gastrointestinal Parasitic Infections in a Patient with Human Immunodeficiency Virus.

    PubMed

    Del Pilar-Morales, Esteban A; Cardona-Rodríguez, Zaydalee; Bertrán-Pasarell, Jorge; Soto-Malave, Ruth; De León-Borras, Rafeal

    2016-06-01

    Patients with the human immunodeficiency virus (HIV) infection are at high risk for gastrointestinal infections causing diarrhea, particularly when those infections are parasitic in nature. This propensity is more pronounced in AIDS, where opportunistic parasitic infections may cause severe diarrhea, marked absorptive dysfunction, and significant risk of mortality. There are scant data regarding parasitic infections among HIV patients in the developed world; most studies and research come from povertystricken areas of South Africa, India, Iran, and the South Pacific. Although multiple infections with the same or different parasites have been reported, simultaneous infections are rare. We present the case of a 35-year-old man who developed a co-infection with Giardia, Cryptosporidium, and Strongyloides, simultaneously, the diagnosis being made after the judicious evaluation of a stool sample. Given the associated morbidity, prompt diagnosis and treatment are needed to avoid further complications in patients with HIV. To our knowledge this is the first reported case of triple parasitic infection in a patient with HIV.

  14. Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor

    SciTech Connect

    Schols, D.; Baba, M.; Pauwels, R.; Desmyter, J.; De Clercq, E. )

    1989-05-01

    The triphenylmethane derivative aurintricarboxylic acid (ATA), but not aurin, selectively prevented the binding of OKT4A/Leu-3a monoclonal antibody (mAb) and, to a lesser extent, OKT4 mAb to the CD4 cell receptor for human immunodeficiency virus type 1 (HIV-1). The effect was seen within 1 min at an ATA concentration of 10 {mu}M in various T4{sup +} cells (MT-4, U-937, peripheral blood lymphocytes, and monocytes). It was dose-dependent and reversible. ATA prevented the attachment of radiolabeled HIV-1 particles to MT-4 cells, which could be expected as the result of its specific binding to the HIV/CD4 receptor. Other HIV inhibitors such as suramin, fuchsin acid, azidothymidine, dextran sulfate, heparin, and pentosan polysulfate did not affect OKT4A/Leu-3a mAb binding to the CD4 receptor, although the sulfated polysaccharides suppressed HIV-1 adsorption to the cells at concentrations required for complete protection against HIV-1 cytopathogenicity. Thus, ATA is a selective marker molecule for the CD4 receptor. ATA also interfered with the staining of membrane-associated HIV-1 glycoprotein gp120 by a mAb against it. These unusual properties of a small molecule of nonimmunological origin may have important implications for the study of CD4/HIV/AIDS pathogenesis and possibly treatment.

  15. Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

    PubMed Central

    Sagnelli, Caterina; Martini, Salvatore; Pisaturo, Mariantonietta; Pasquale, Giuseppe; Macera, Margherita; Zampino, Rosa; Coppola, Nicola; Sagnelli, Evangelista

    2015-01-01

    Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of non-invasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCV-coinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice. PMID:26523204

  16. Motor development of infants exposed to maternal human immunodeficiency virus (HIV) but not infected

    PubMed Central

    2013-01-01

    Background To assess the motor development of infants exposed to maternal human immunodeficiency virus (HIV). Methods Thirty infants were assessed in the period from November 2009 to March 2010 at the AIDS Reference and Training Centre, in São Paulo, Brazil. The assessment instrument used in the research was the Alberta Infant Motor Scale (AIMS). All 30 infants used the antiretroviral drug properly for 42 consecutive days, in accordance with the protocol of the World Health Organization. Results Out of the total number of infants, 27 (90%) had proper motor performance and 3 (10%) presented motor delay, according to the AIMS. Discussion This study demonstrated that only 10% of the assessed group had developmental delay and no relation with environmental variables was detected, such as maternal level of education, social and economic issues, maternal practices, attendance at the day care center, and drug use during pregnancy. It is important to emphasize the necessity of studies with a larger number of participants. PMID:24171763

  17. Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin.

    PubMed

    Nagy, G Sonia; Tsiodras, Sotirios; Martin, Lizabeth D; Avihingsanon, Anchalee; Gavrila, Alina; Hsu, William C; Karchmer, Adolf W; Mantzoros, Christos S

    2003-03-15

    The relationship between the adipocyte-derived hormone leptin, insulin resistance, and fat redistribution in patients with human immunodeficiency virus (HIV) infection has not been established. We classified a cohort of HIV type 1 (HIV-1)-infected patients with >or=6 months of antiretroviral exposure as having no lipodystrophy (51 patients [43% of the cohort]), lipoatrophy (23 patients [19% of the cohort]), mixed lipodystrophy (29 patients [24% of the cohort]), or lipohypertrophy (17 patients [14% of the cohort]), on the basis of physical examination, anthropometric measurements, and the findings of dual-emission x-ray absorptiometry and computed tomography. Measurements of insulin resistance were higher for patients with each category of lipodystrophy, compared with those observed for patients with no lipodystrophy (P<.001). Mean leptin levels (+/- standard deviation) were lowest in patients with lipoatrophy (1.76+/-1.20 ng/mL), highest in patients with lipohypertrophy (9.10+/-6.86 ng/mL), and significantly different from those in patients without lipodystrophy (3.14+/-2.30 ng/mL; both P<.01). In this cohort of antiretroviral-experienced HIV-infected patients, a low serum level of leptin was independently associated with insulin resistance in patients with lipoatrophy, after controlling for total and regional body fat.

  18. Clinical use of cobicistat as a pharmacoenhancer of human immunodeficiency virus therapy

    PubMed Central

    von Hentig, Nils

    2016-01-01

    The pharmacoenhancement of plasma concentrations of protease inhibitors by coadministration of so-called boosters has been an integral part of antiretroviral therapy for human immunodeficiency virus (HIV) for 1.5 decades. Nearly all HIV protease inhibitors are combined with low-dose ritonavir or cobicistat, which are able to effectively inhibit the cytochrome-mediated metabolism of HIV protease inhibitors in the liver and thus enhance the plasma concentration and prolong the dosing interval of the antiretrovirally active combination partners. Therapies created in this way are clinically effective regimens, being convenient for patients and showing a high genetic barrier to viral resistance. In addition to ritonavir, which has been in use since 1996, cobicistat, a new pharmacoenhancer, has been approved and is widely used now. The outstanding property of cobicistat is its cytochrome P450 3A-selective inhibition of hepatic metabolism of antiretroviral drugs, in contrast with ritonavir, which not only inhibits but also induces a number of cytochrome P450 enzymes, UDP-glucuronosyltransferase, P-glycoprotein, and other cellular transporters. This article reviews the current literature, and compares the pharmacokinetics, pharmacodynamics, and safety of both pharmacoenhancers and discusses the clinical utility of cobicistat in up-to-date and future HIV therapy. PMID:26730211

  19. Sociosexuality, human immunodeficiency virus (HIV) susceptibility, and sexual behavior among African American women

    PubMed Central

    Hall, Naomi M.

    2014-01-01

    Psychosocial correlation of risky sexual behavior is important for the design and implementation of human immunodeficiency virus (HIV)-related prevention and intervention studies. Sociosexuality (individual differences in endorsement of casual sexual behavior) and perceived susceptibility to HIV were examined for their relationship to each other, and in predicting risky sexual behavior among adult, heterosexual African American women using web-based and in-person surveys. This study included 275 geographically diverse women (mean age = 33.60 years), with 81% reported having at least a college degree, and over 50% reported incomes over $45,000. Results indicate that sociosexuality was significantly associated with perceived susceptibility, and both higher levels of sociosexuality and perceived susceptibility were significantly related to engagement in riskier sexual behavior. Age at first voluntary intercourse emerged as an important covariate in predicting risky sexual behavior among the participants. The need to include psychosocial variables associated with risky sexual behavior in sexually transmitted infection (STI) and HIV-related health promotion and intervention studies was discussed. PMID:25614851

  20. Spatial analysis of infection by the human immunodeficiency virus among pregnant women1

    PubMed Central

    de Holanda, Eliane Rolim; Galvão, Marli Teresinha Gimeniz; Pedrosa, Nathália Lima; Paiva, Simone de Sousa; de Almeida, Rosa Lívia Freitas

    2015-01-01

    OBJECTIVES: to analyze the spatial distribution of reported cases of pregnant women infected by the human immunodeficiency virus and to identify the urban areas with greater social vulnerability to the infection among pregnant women. METHOD: ecological study, developed by means of spatial analysis techniques of area data. Secondary data were used from the Brazilian National Disease Notification System for the city of Recife, Pernambuco. Birth data were obtained from the Brazilian Information System on Live Births and socioeconomic data from the 2010 Demographic Census. RESULTS: the presence of spatial self-correlation was verified. Moran's Index was significant for the distribution. Clusters were identified, considered as high-risk areas, located in grouped neighborhoods, with equally high infection rates among pregnant women. A neighborhood located in the Northwest of the city was distinguished, considered in an epidemiological transition phase. CONCLUSION: precarious living conditions, as evidenced by the indicators illiteracy, absence of prenatal care and poverty, were relevant for the risk of vertical HIV transmission, converging to the grouping of cases among disadvantaged regions. PMID:26155005

  1. Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

    PubMed Central

    Méndez, Catalina; Ahlenstiel, Chantelle L; Kelleher, Anthony D

    2015-01-01

    While human immunodeficiency virus 1 (HIV-1) infection is controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference (RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by non-coding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing (TGS), as well as fine-tuning their expression through post-transcriptional gene silencing (PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells. PMID:26279984

  2. Epidemic transmission of human immunodeficiency virus in renal dialysis centers in Egypt.

    PubMed

    El Sayed, N M; Gomatos, P J; Beck-Sagué, C M; Dietrich, U; von Briesen, H; Osmanov, S; Esparza, J; Arthur, R R; Wahdan, M H; Jarvis, W R

    2000-01-01

    In 1993 an epidemic of human immunodeficiency virus (HIV) infection occurred among 39 patients at 2 renal dialysis centers in Egypt. The centers, private center A (PCA) and university center A (UCA) were visited, HIV-infected patients were interviewed, seroconversion rates at UCA were calculated, and relatedness of HIV strains was determined by sequence analysis; 34 (62%) of 55 patients from UCA and 5 (42%) of 12 patients from PCA were HIV-infected. The HIV seroconversion risk at UCA varied significantly with day and shift of dialysis session. Practices that resulted in sharing of syringes among patients were observed at both centers. The analyzed V3 loop sequences of the HIV strain of 12 outbreak patients were >96% related to each other. V3 loop sequences from each of 8 HIV-infected Egyptians unrelated to the 1993 epidemic were only 76%-89% related to those from outbreak strains. Dialysis patients may be at risk for HIV infection if infection control guidelines are not followed.

  3. Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.

    PubMed Central

    Boyer, P L; Currens, M J; McMahon, J B; Boyd, M R; Hughes, S H

    1993-01-01

    A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been reported. Several lines of evidence, including the isolation of RT mutants that show cross resistance, suggest that, despite their structural diversity, many of these inhibitors bind to a common site on HIV-1 RT. We have recently reported that, on the basis of analyses of HIV-1/HIV-2 chimeras, the natural product calanolide A may interact with a different site or sites in HIV-1 RT. We have used BspMI cassette mutagenesis to prepare a collection of HIV-1 RT mutants that show resistance to the known members of the general class of nonnucleoside inhibitors. This collection of mutants can be used to determine whether a new drug will show cross resistance with known inhibitors and to define amino acid positions critical for the action of the drugs. The mutants were used to analyze calanolide A, 1H,3H-thiazolo[3,4-a]benzimidazole(4i), and the acyclic nucleoside analog 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. These analyses suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors. However, the drugs respond differently to the panel of drug-resistant HIV-1 RTs, indicating that while the binding sites of the drugs overlap they are not identical. PMID:7680393

  4. Refinement of linkage of human severe combined immunodeficiency (SCIDXI) to polymorphic markers in Xq13

    SciTech Connect

    Puck, J.M Univ. of Pennsylvania School of Medicine, Philadelphia, PA ); Conely, M.E. ); Bailey, L.C. )

    1993-07-01

    The most common form of human severe combined immunodeficiency (SCID) is inherited as an X-linked recessive genetic defect, MIM 300400. The disease locus, SCIDX1, has previously been placed in Xq13.1-q21.1 by demonstration of linkage to polymorphic markers between DXS159 and DXS3 and by exclusion from interstitial deletions of Xq21.1-q21.3. The authors report an extension of previous linkage studies, with new markers and a total of 25 SCIDX1 families including female carriers identified by nonrandom X chromosome inactivation in their T lymphocytes. SCIDX1 was nonrecombinant with DXS441, with a lod score of 17.96. Linkage relationships of new markers in the SCIDX1 families were consistent with the linkage map generated in the families of the Centre d'Etude du Polymorphisms Humain (CEPH) and with available physical map data. The most likely locus order was DXS1-(DXS159,DXS153)-DXS106-DXS132-DXS453-(SCIDX1,PGK1, DXS325,DXS347,DXS441)-DXS447-DXS72-DXYS1X-DXS3. The SCIDX1 region now spans approximately 10 Mb of DNA in Xq13; this narrowed genetic localization will assist efforts to identify gene candidates and will improve genetic management for families with SCID. 25 refs., 3 figs., 2 tabs.

  5. Evaluation of hypochlorite-releasing disinfectants against the human immunodeficiency virus (HIV).

    PubMed

    Bloomfield, S F; Smith-Burchnell, C A; Dalgleish, A G

    1990-04-01

    Using a quantitative suspension test method, the antiviral activity of sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) against human immunodeficiency virus (HIV) was investigated. Viral suspensions were prepared containing 10(4)-10(5) syncitial forming units ml-1 in 0.9% saline or 0.9% saline containing 10% v/v plasma to simulate clean and dirty conditions. A syncitial inhibition assay on C8166 lymphoblastoid line was used to determine viral titre. Results indicate that satisfactory disinfection (3-4 log reduction in 2 min) can be achieved using NaDCC and NaOCl at concentrations of 50 ppm and 2500 ppm available chlorine (AvCl2) for clean and soiled conditions respectively. For treatment of blood spillages, the addition of NaDCC and NaOCl solutions (10,000 ppm) to equal volumes of contaminated blood (giving a final AvCl2 concentration of 5000 ppm of blood) was sufficient to produce total kill within 2 min. For treatment of spillage material, chlorine-releasing powder formulations--which produce higher AVCl2 concentrations and achieve containment of spillage material--offer an effective alternative. PMID:1971634

  6. Mechanism of resistance of human immunodeficiency virus type 1 to 2',3'-dideoxyinosine.

    PubMed Central

    Martin, J L; Wilson, J E; Haynes, R L; Furman, P A

    1993-01-01

    A molecular clone containing the wild-type reverse transcriptase (RT) coding region of human immunodeficiency virus type 1 (HIV-1) was constructed, and site-directed mutagenesis was used to introduce mutations--Leu74-->Val (L74V), T215Y, and the combination L74V/T215Y--into the RT coding region. The proteins were purified by immunoaffinity chromatography. Assays were performed with mutant and wild-type RT to determine substrate and inhibitor specificity. All three mutant enzymes catalyzed the incorporation of substrate 2'-deoxynucleoside 5'-triphosphates (dNTPs) as efficiently as wild-type HIV-1 RT. Small changes were observed in the Km values for dNTPs with all three mutant enzymes, while more significant changes were noted in sensitivity to nucleoside 5'-triphosphate analogues that inhibit the enzyme activity. Results suggest that altered substrate recognition by the HIV-1 RT is involved in the mechanism of resistance. Images Fig. 1 PMID:7687061

  7. Derivation of a biologically contained replication system for human immunodeficiency virus type 1.

    PubMed Central

    Chen, H; Boyle, T J; Malim, M H; Cullen, B R; Lyerly, H K

    1992-01-01

    Human immunodeficiency virus type 1 (HIV-1) proviral mutants that lack viral regulatory genes are unable to replicate unless rescued by complementation in trans. Structurally intact virus can be produced by infecting recombinant cell lines expressing the deficient genes. A HIV-1 mutant functionally defective in tat and rev (vIIIB delta Tat/Rev), which replicates only in a recombinant T-cell line expressing tat and rev (CEMTART), is described in this report. Infection of the CEMTART cell line with vIIIB delta Tat/Rev permits the complete HIV-1 life cycle, including cytopathology, decreased expression of CD4, and production of viral structural proteins, to be biologically contained. Culture supernatants from infected CEMTART contain virus that is able to replicate only in uninfected CEMTART. No reversion of vIIIB delta Tat/Rev to wild-type HIV-1 was observed as measured either by sequencing proviral vIIIB delta Tat/Rev or by detecting the ability of vIIIB delta Tat/Rev to replicate in CEM or activated CD4-bearing T lymphocytes. Defective HIV-1 mutants produced by trans complementation of essential genes permit infection and analysis of defined genotypes on cellular function and phenotype. Authentic HIV-1 structural proteins and infected cells can be prepared in mass, and agents that interfere with the HIV-1 life cycle can be studied on a large scale with minimum risk of exposing workers to virulent HIV-1. PMID:1502183

  8. CT-2576, an inhibitor of phospholipid signaling, suppresses constitutive and induced expression of human immunodeficiency virus.

    PubMed Central

    Leung, D W; Peterson, P K; Weeks, R; Gekker, G; Chao, C C; Kaplan, A H; Balantac, N; Tompkins, C; Underiner, G E; Bursten, S

    1995-01-01

    Viruses such as human immunodeficiency virus (HIV) require cellular activation for expression. Cellular activation in lymphoid cells is associated with augmented accumulation of certain phosphatidic acid (PA) species derived from the hydrolysis of glycan phosphatidylinositol (GPI). This suggests that activation of a phospholipid pathway may play a role in initiation of viral replication. To test this hypothesis, we examined the effect of tat gene expression on the production of cellular PA species, as the Tat protein is essential for HIV expression and has been implicated in activating the expression of multiple host cellular genes. Expression of tat increased the expression of PA. We then tested whether synthetic inhibitors of PA metabolism would inhibit activation of the HIV long terminal repeat by Tat and tumor necrosis factor alpha (TNF-alpha). CT-2576 suppressed both PA generation induced by Tat and HIV long terminal repeat-directed gene expression in response to Tat or TNF-alpha at a posttranscriptional step. CT-2576 also inhibited constitutive as well as TNF-alpha- and interleukin 6-induced expression of HIV p24 antigen in chronically infected U1 cells and in peripheral blood lymphocytes acutely infected with a clinical isolate of HIV. Pharmacological inhibition of synthesis of selected PA species may therefore provide a therapeutic approach to suppression of HIV replication. Images Fig. 1 Fig. 3 Fig. 5 PMID:7761405

  9. Pneumocystis Pneumonia in Human Immunodeficiency Virus–infected Adults and Adolescents: Current Concepts and Future Directions

    PubMed Central

    Tasaka, Sadatomo

    2015-01-01

    Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus–infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim–sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern. PMID:26327786

  10. Transcriptional Activation of the Integrated Chromatin-Associated Human Immunodeficiency Virus Type 1 Promoter

    PubMed Central

    El Kharroubi, Aboubaker; Piras, Graziella; Zensen, Ralf; Martin, Malcolm A.

    1998-01-01

    The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression involves a complex interplay between cellular transcription factors, chromatin-associated proviral DNA, and the virus-encoded transactivator protein, Tat. Here we show that Tat transactivates the integrated HIV-1 long terminal repeat (LTR), even in the absence of detectable basal promoter activity, and this transcriptional activation is accompanied by chromatin remodeling downstream of the transcription initiation site, as monitored by increased accessibility to restriction endonucleases. However, with an integrated promoter lacking both Sp1 and NF-κB sites, Tat was unable to either activate transcription or induce changes in chromatin structure even when it was tethered to the HIV-1 core promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1 or NF-κB was bound to the promoter, implying that Tat functions subsequent to the formation of a specific transcription initiation complex. Unlike Tat, NF-κB failed to stimulate the integrated transcriptionally silent HIV-1 promoter. Histone acetylation renders the inactive HIV-1 LTR responsive to NF-κB, indicating that a suppressive chromatin structure must be remodeled prior to transcriptional activation by NF-κB. Taken together, these results suggest that Sp1 and NF-κB are required for the assembly of transcriptional complexes on the integrated viral promoter exhibiting a continuum of basal activities, all of which are fully responsive to Tat. PMID:9566873

  11. Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter.

    PubMed

    El Kharroubi, A; Piras, G; Zensen, R; Martin, M A

    1998-05-01

    The regulation of human immunodeficiency virus type 1 (HIV-1) gene expression involves a complex interplay between cellular transcription factors, chromatin-associated proviral DNA, and the virus-encoded transactivator protein, Tat. Here we show that Tat transactivates the integrated HIV-1 long terminal repeat (LTR), even in the absence of detectable basal promoter activity, and this transcriptional activation is accompanied by chromatin remodeling downstream of the transcription initiation site, as monitored by increased accessibility to restriction endonucleases. However, with an integrated promoter lacking both Sp1 and NF-kappaB sites, Tat was unable to either activate transcription or induce changes in chromatin structure even when it was tethered to the HIV-1 core promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1 or NF-kappaB was bound to the promoter, implying that Tat functions subsequent to the formation of a specific transcription initiation complex. Unlike Tat, NF-kappaB failed to stimulate the integrated transcriptionally silent HIV-1 promoter. Histone acetylation renders the inactive HIV-1 LTR responsive to NF-kappaB, indicating that a suppressive chromatin structure must be remodeled prior to transcriptional activation by NF-kappaB. Taken together, these results suggest that Sp1 and NF-kappaB are required for the assembly of transcriptional complexes on the integrated viral promoter exhibiting a continuum of basal activities, all of which are fully responsive to Tat. PMID:9566873

  12. Mutational analysis of human immunodeficiency virus type 1 protease suggests functional homology with aspartic proteinases.

    PubMed Central

    Loeb, D D; Hutchison, C A; Edgell, M H; Farmerie, W G; Swanstrom, R

    1989-01-01

    Processing of the retroviral gag and pol gene products is mediated by a viral protease. Bacterial expression systems have been developed which permit genetic analysis of the human immunodeficiency virus type 1 protease as measured by cleavage of the pol protein precursor. Deletion analysis of the pol reading frame locates the sequences required to encode a protein with appropriate proteolytic activity near the left end of the pol reading frame but largely outside the gag-pol overlap region, which is at the extreme left end of pol. Most missense mutations within an 11-amino-acid domain highly conserved among retroviral proteases and with sequence similarity to the active site of aspartic proteinases abolish appropriate processing, suggesting that the retrovirus proteases share a catalytic mechanism with aspartic proteinases. Substitution of the amino acids flanking the scissile bond at three of the processing sites encoded by pol demonstrates distinct sequence requirements for cleavage at these different sites. The inclusion of a charged amino acid at the processing site blocks cleavage. A subset of these substitutions also inhibits processing at the nonmutated sites. Images PMID:2642305

  13. An Update on Heart Transplantation in Human Immunodeficiency Virus-Infected Patients.

    PubMed

    Agüero, F; Castel, M A; Cocchi, S; Moreno, A; Mestres, C A; Cervera, C; Pérez-Villa, F; Tuset, M; Cartañà, R; Manzardo, C; Guaraldi, G; Gatell, J M; Miró, J M

    2016-01-01

    Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities. PMID:26523614

  14. Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2.

    PubMed

    Kacani, L; Prodinger, W M; Sprinzl, G M; Schwendinger, M G; Spruth, M; Stoiber, H; Döpper, S; Steinhuber, S; Steindl, F; Dierich, M P

    2000-09-01

    After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC. PMID:10933708

  15. Circadian rhythms of circulating NK cells in healthy and human immunodeficiency virus-infected men.

    PubMed

    Bourin, P; Mansour, I; Doinel, C; Roué, R; Rouger, P; Levi, F

    1993-08-01

    Antiviral immunity involves NK cells, which circulate rhythmically every 24 hours. We have investigated circadian and 12-hour rhythms in the peripheral count of circulating NK cells in 15 men infected with human immunodeficiency virus (HIV) and 13 healthy controls. We analyzed three phenotypes using double-labeling with monoclonal antibodies and flow cytometry assessment: CD3- CD16+, CD3-CD57+, and CD2+CD3-. A statistical validation of time-dependent differences was achieved if significance (p < 0.05) was validated both with analysis of variance and cosinor. The circadian rhythm had a similar asymmetric waveform for the three phenotypes and is homogeneous on an individual basis. The circulating NK cell count peaked in the early morning and was low at night. A circadian rhythm and a circahemidian harmonic characterized all phenotypes in healthy subjects. We considered two groups of HIV-infected men: those who were asymptomatic (eight) and those with acquired immune deficiency syndrome (AIDS) (seven). Circadian changes in NK cell count were similar in both subgroups and in healthy controls. The circadian pattern was also consistent among individual patients. Asymptomatic HIV-infected men (early-stage disease) exhibited more pronounced 12-hour rhythmicity than did patients with AIDS or controls. The circulation of NK cells does not appear to share the same synchronizer(s) as other circulating T- or B-lymphocyte subsets. Thus, HIV infection gradually abolished circadian rhythmicity in circulating T and B cells, whereas it did not disturb that in NK cells.

  16. Kinetic analysis of inhibition of human immunodeficiency virus type-1 reverse transcriptase by calanolide A.

    PubMed

    Currens, M J; Mariner, J M; McMahon, J B; Boyd, M R

    1996-11-01

    Calanolide A, first isolated from the tropical rain forest tree Calophyllum lanigerum, is a potent human immunodeficiency virus type-1 (HIV-1) specific reverse transcriptase (RT) inhibitor, broadly active against diverse HIV-1 strains, including nucleoside and nonnucleoside-resistant variants. We examined the biochemical mechanism of inhibition of HIV-1 RT by calanolide A. Two template/primer systems were examined: ribosomal RNA and homopolymeric rA-dT 12-18. Calanolide A inhibited HIV-1 RT by a complex mechanism involving two calanolide A binding sites. With respect to either deoxynucleotide triphosphate (dNTP) or template/primer binding, one site was competitive and the other was uncompetitive. The data indicated that calanolide A bound near the active site of the enzyme and interfered with dNTP binding. Calanolide A inhibited HIV-1 RT in a synergistic fashion with nevirapine, further distinguishing it from the general class of nonnucleoside RT inhibitors. At certain concentrations, calanolide A bound HIV-1 RT in a mutually exclusive fashion with respect to both the pyrophosphate analog, phosphonoformic acid and the acyclic nucleoside analog 1-ethoxymethyl-5-ethyl-6-phenylthio-2-thiouracil. This indicates that calanolide A shares some binding domains with both phosphonoformic acid and 1-ethoxymethyl-5-ethyl-6-phenylthio-2-thiouracil, presumably reflecting that it interacts with RT near both the pyrophosphate binding site and the active site of the enzyme.

  17. Corneal Ring Infiltrates Caused by Serratia marcescens in a Patient with Human Immunodeficiency Virus

    PubMed Central

    Chaidaroon, Winai; Supalaset, Sumet

    2016-01-01

    Purpose To describe corneal ring infiltrates caused by Serratia marcescens in a patient with human immunodeficiency virus (HIV-1) who wore contact lenses. Methods A case study of a patient with keratitis due to an infection caused by S. marcescens and exhibiting corneal ring infiltrates was reviewed for history, clinical manifestation, microscopic study, and management. Results A 29-year-old man who had a history of contact lens wear and HIV-1 infection was admitted to hospital because of blurred vision, redness, and corneal infiltrates in the shape of a ring in the left eye. The visual acuity (VA) in both eyes was hand movement (uncorrected). Corneal scrapings were performed. The culture results of the corneal specimens revealed S. marcescens. The culture results of the contact lens disclosed the same organism. The corneal ulcer responded well to treatment with topical gentamycin sulfate 14 mg/ml. The final VA remained hand movement. Conclusions S. marcescens can cause ring infiltrates in a HIV-1 patient who wears contact lenses. The treatment result for S. marcescens keratitis in a HIV-1 patient who wore contact lenses was favorable after intensive use of fortified topical antibiotics. PMID:27721784

  18. Prevalence of human immunodeficiency virus, syphilis, hepatitis B and C in blood donations in Namibia

    PubMed Central

    2014-01-01

    Background Transfusion Transmissible Infections (TTIs) such as Human Immunodeficiency Virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV) are infections which are common in some communities in Southern Africa. It is important to screen blood donations for these infections. Methods This is a retrospective study which involved reviewing of previous blood donation records for the year 2012 in Namibia. The records were analyzed to determine the prevalence of HIV, syphilis, Hepatitis B and C among blood donations with regard to gender, age and geographical region of the donors. Results The findings indicated a significantly low prevalence of HIV, syphilis, HBsAg and anti-Hepatitis C among the blood donations. A low infection rate of 1.3% by any of the four tested TTIs was found among the blood donations given by the donor population in Namibia in 2012. Conclusion The blood donations given by the donor population in Namibia has a low infection rate with the HIV, syphilis, HBsAg and anti-HCV. A strict screening regime must continue to be used as the infections are still present albeit in small numbers. PMID:24884633

  19. In vitro infection of natural killer cells with different human immunodeficiency virus type 1 isolates.

    PubMed Central

    Chehimi, J; Bandyopadhyay, S; Prakash, K; Perussia, B; Hassan, N F; Kawashima, H; Campbell, D; Kornbluth, J; Starr, S E

    1991-01-01

    Natural killer (NK) cells are a discrete subset of leukocytes, distinct from T and B lymphocytes. NK cells mediate spontaneous non-MHC-restricted killing of a wide variety of target cells without prior sensitization and appear to be involved in initial protection against certain viral infections. Depressed NK cell-mediated cytotoxicity, one of the many immunological defects observed in AIDS patients, may contribute to secondary virus infections. Here we report that clonal and purified polyclonal populations of NK cells, which expressed neither surface CD4 nor CD4 mRNA, were susceptible to infection with various isolates of human immunodeficiency virus type 1 (HIV-1). Viral replication was demonstrated by detection of p24 antigen intracellularly and in culture supernatants, by the presence of HIV DNA within infected cells, and by the ability of supernatants derived from HIV-infected NK cells to infect peripheral blood mononuclear cells or CD4+ cell lines. Infection of NK cells was not blocked by anti-CD4 or anti-Fc gamma RIII monoclonal antibodies. NK cells from HIV-infected and uninfected cultures were similar in their ability to lyse three different target cells. Considerable numbers of cells died in HIV-infected NK cell cultures. These results suggest that loss of NK cells in AIDS patients is a direct effect of HIV infection but that reduced NK cell function involves another mechanism. The possibility that NK cells serve as a potential reservoir for HIV-1 must be considered. Images PMID:1672164

  20. Genital ulcers: etiology, clinical diagnosis, and associated human immunodeficiency virus infection in Kingston, Jamaica.

    PubMed

    Behets, F M; Brathwaite, A R; Hylton-Kong, T; Chen, C Y; Hoffman, I; Weiss, J B; Morse, S A; Dallabetta, G; Cohen, M S; Figueroa, J P

    1999-05-01

    Individuals presenting consecutively with genital ulcers in Kingston, Jamaica, underwent serological testing for human immunodeficiency virus (HIV) infection, chlamydial infection, and syphilis. Ulcer material was analyzed by multiplex polymerase chain reaction (M-PCR) analysis. DNA from herpes simplex virus (HSV), Haemophilus ducreyi, and Treponema pallidum was detected in 158 (52.0%), 72 (23.7%), and 31 (10.2%) of 304 ulcer specimens. Of the 304 subjects, 67 (22%) were HIV-seropositive and 64 (21%) were T. pallidum-seroreactive. Granuloma inguinale was clinically diagnosed in nine (13.4%) of 67 ulcers negative by M-PCR analysis and in 12 (5.1%) of 237 ulcers positive by M-PCR analysis (P = .03). Lymphogranuloma venereum was clinically diagnosed in eight patients. Compared with M-PCR analysis, the sensitivity and specificity of a clinical diagnosis of syphilis, herpes, and chancroid were 67.7%, 53.8%, and 75% and 91.2%, 83.6%, and 75.4%, respectively. Reactive syphilis serology was 74% sensitive and 85% specific compared with M-PCR analysis. Reported contact with a prostitute in the preceding 3 months was associated with chancroid (P = .009), reactive syphilis serology (P = .011), and HIV infection (P = .007). The relatively poor accuracy of clinical and locally available laboratory diagnoses pleads for syndromic management of genital ulcers in Jamaica. Prevention efforts should be intensified.

  1. Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments.

    PubMed

    Nickle, David C; Jensen, Mark A; Shriner, Daniel; Brodie, Scott J; Frenkel, Lisa M; Mittler, John E; Mullins, James I

    2003-05-01

    In vivo virologic compartments are cell types or tissues between which there is a restriction of virus flow, while virologic reservoirs are cell types or tissues in which there is a relative restriction of replication. The distinction between reservoirs and compartments is important because therapies that would be effective against a reservoir may not be effective against viruses produced by a given compartment, and vice versa. For example, the use of cytokines to "flush out" long-lived infected cells in patients on highly active antiretroviral therapy (T. W. Chun, D. Engel, M. M. Berrey, T. Shea, L. Corey, and A. S. Fauci, Proc. Natl. Acad. Sci. USA 95:8869-8873, 1998) may be successful for a latent reservoir but may not impact a compartment in which virus continues to replicate because of poor drug penetration. Here, we suggest phylogenetic criteria to illustrate, define, and differentiate between reservoirs and compartments. We then apply these criteria to the analysis of simulated and actual human immunodeficiency virus type 1 sequence data sets. We report that existing statistical methods work quite well at detecting viral compartments, and we learn from simulations that viral divergence from a calculated most recent common ancestor is a strong predictor of viral reservoirs.

  2. The Roles of Genetic Polymorphisms and Human Immunodeficiency Virus Infection in Lipid Metabolism

    PubMed Central

    de Almeida, Elaine Regina Delicato; Reiche, Edna Maria Vissoci; Flauzino, Tamires; Watanabe, Maria Angelica Ehara

    2013-01-01

    Dyslipidemia has been frequently observed among individuals infected with human immunodeficiency virus type 1 (HIV-1), and factors related to HIV-1, the host, and antiretroviral therapy (ART) are involved in this phenomenon. This study reviews the roles of genetic polymorphisms, HIV-1 infection, and highly active antiretroviral therapy (HAART) in lipid metabolism. Lipid abnormalities can vary according to the HAART regimen, such as those with protease inhibitors (PIs). However, genetic factors may also be involved in dyslipidemia because not all patients receiving the same HAART regimen and with comparable demographic, virological, and immunological characteristics develop variations in the lipid profile. Polymorphisms in a large number of genes are involved in the synthesis of structural proteins, and enzymes related to lipid metabolism account for variations in the lipid profile of each individual. As some genetic polymorphisms may cause dyslipidemia, these allele variants should be investigated in HIV-1-infected patients to identify individuals with an increased risk of developing dyslipidemia during treatment with HAART, particularly during therapy with PIs. This knowledge may guide individualized treatment decisions and lead to the development of new therapeutic targets for the treatment of dyslipidemia in these patients. PMID:24319689

  3. Barriers to human immunodeficiency virus related risk reduction among male street prostitutes.

    PubMed

    Simon, P M; Morse, E V; Balson, P M; Osofsky, H J; Gaumer, H R

    1993-01-01

    Two hundred eleven male street prostitutes between the ages of 18 and 51 years were interviewed and tested for antibodies to the human immunodeficiency virus (HIV). Economic, social, and emotional barriers to the reduction of HIV-related risk behavior were examined within the context of several concepts present in the Health Belief Model (HBM). Three lifestyle factors were found to function as barriers to engaging in risk reduction behavior. Subjects who were more economically dependent on prostitution, perceived less control over the hustling encounter, and reported increased pleasure from sexual activity with their customers were more likely to engage in risk-taking behavior. Prostitutes' perception of the severity of HIV infection was not significantly associated with their risk behavior. Unexpected findings indicated that increases in perceived susceptibility to HIV and perceived benefit of condom use for HIV prevention were significantly related to increased risk-taking behavior. Practical applications of findings in the design and implementation of future HIV-related preventive health education programs are discussed. PMID:8491637

  4. Maternal human immunodeficiency virus 1 infection and intrauterine growth: a prospective cohort study in Butare, Rwanda.

    PubMed

    Bulterys, M; Chao, A; Munyemana, S; Kurawige, J B; Nawrocki, P; Habimana, P; Kageruka, M; Mukantabana, S; Mbarutso, E; Dushimimana, A

    1994-02-01

    A prospective cohort study of 318 human immunodeficiency virus 1 (HIV-1)-infected and 309 seronegative pregnant women was carried out in Butare, Rwanda. Birth weight was significantly lower among singleton infants born alive to HIV-1-infected mothers compared with those born alive to seronegative mothers (2706 g vs. 2825 g; P = 0.002). Crown-to-heel length, head circumference, chest circumference and placental weight were also reduced. Maternal HIV-1 infection was significantly associated with intrauterine growth retardation but not with preterm birth. Differences in the body mass index and weight/head ratio suggest that the adverse impact on live born infants may have been most severe towards the end of pregnancy, resulting in a lean infant with a relatively large head. The higher frequency of intrauterine growth retardation could not be explained by potential confounding factors such as maternal cigarette smoking, history of sexually transmitted diseases or sociodemographic characteristics. The neonatal physical examination did not reveal any differences in clinical signs or symptoms within 48 hours of birth except for the presence of conjunctivitis which was more common among infants of HIV-1-infected mothers. The perinatal and neonatal mortality rates were not significantly affected by maternal HIV-1 status. PMID:8190558

  5. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes.

    PubMed Central

    Vartanian, J P; Meyerhans, A; Asjö, B; Wain-Hobson, S

    1991-01-01

    Human immunodeficiency virus type 1 (HIV-1) isolates are genetically so heterogeneous that they must be described in terms of populations of related but distinct genomes called quasispecies. A recent study of the influence of ex vivo culturing on HIV-1 quasispecies demonstrated that usually low-abundance genomes outgrew the more prominent forms. Here it is shown that multiple passages of an HIV-1 isolate on peripheral blood mononuclear cells resulted in the outgrowth of very minor forms. A single passage of equal proportions of supernatants to either of the established lymphocyte and monocyte cell lines Molt-3 and U937-2, respectively, resulted in the isolation of different sets of minor forms. Recombination between component sequences was observed. Extensive and monotonous base substitutions of G----A (G----A hypermutation) were evident in many sequences. A strong preference for the transition within the GpA dinucleotide was observed. Dislocation mutagenesis, in this case, a -1 slippage or dislocation of the primer with respect to the template, during DNA synthesis by the HIV-1 reverse transcriptase would explain this bias. When the consequences of polymerase errors, recombination, hypermutation, and instability are added to the genetic description of HIV-1, the real complexity of this virus starts to become apparent. PMID:2002543

  6. Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors.

    PubMed Central

    Neamati, N; Mazumder, A; Zhao, H; Sunder, S; Burke, T R; Schultz, R J; Pommier, Y

    1997-01-01

    A majority of reported human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors are polyhydroxylated aromatic compounds containing two phenyl rings separated by aliphatic or aromatic linkers. Most inhibitors possessing a catechol moiety exhibit considerable toxicity in cellular assays. In an effort to identify nonhydroxylated analogs, a series of aromatic sulfones were tested for their ability to inhibit the 3' processing and strand transfer steps that are necessary for HIV replication. Several aromatic sulfones have previously been shown to have moderate activity against HIV-1 reverse transcriptase in cellular assays; however, their inhibitory potencies against IN have not been explored. In the present study, the inhibitory effect of a series of sulfones and sulfonamides against IN was determined. Among 52 diaryl sulfones tested, 4 were determined to be highly potent (50% inhibitory concentration [IC50], 0.8 to 10 micrograms/ml), 5 had good potencies (IC50, 11 to 50 micrograms/ml), 10 showed moderate potencies (IC50, 51 to 100 micrograms/ml), and 33 were inactive (IC50, > 100 micrograms/ml) against IN. All of the active compounds exhibited similar potencies against HIV-2 IN. Sulfa drugs, used extensively in treating Pneumocystis carinii pneumonia, a leading cause of morbidity and mortality in AIDs patients, were also examined. Among 19 sulfonamides tested, sulfasalazine (IC50, 50 micrograms/ml) was the most potent. We conclude that potent inhibitors of IN can be designed based on the results presented in this study. PMID:9021196

  7. Viral multiplicity of attachment and its implications for human immunodeficiency virus therapies.

    PubMed Central

    Spouge, J L

    1994-01-01

    The multiplicity of attachment (MOA) of a virion in any particular time interval is the average number of cellular attachment opportunities that must be blocked to keep the virion in suspension. MOA is usually proportional to incubation time and cell concentration. Low MOA (like low multiplicity of infection) is required for reproducible assay of adsorptive blockers, and high MOA by itself can produce spurious synergies between adsorptive blockers, e.g., soluble CD4 (sCD4) and some antibodies. Poliovirus and human immunodeficiency virus (HIV) data show that viral neutralization conforms quantitatively to MOA and kinetic theory over large ranges of incubation times and target cell concentrations. Extrapolating sCD4 data beyond conditions achievable in vitro to those in vivo predicts that sCD4 concentrations above the strain-specific sCD4-gp120 dissociation constant are required to block lymphoid HIV significantly, in at least semiquantitative agreement with clinical results. The extrapolation is applicable to humoral neutralization data as well. MOA analysis also indicates that although completely stopping the attachment of individual virions to cells may still be an effective therapeutic strategy against established HIV infection, merely retarding attachment probably is not. The concept of MOA holds great promise for improving the therapeutic relevance of in vitro data and can be applied to any infectious agent, to many processes that impair or enhance infection steps, and to many assay end points, not just infection. PMID:8107240

  8. Human immunodeficiency virus has similar effects on brain volumetrics and cognition in males and females.

    PubMed

    Behrman-Lay, Ashley M; Paul, Robert H; Heaps-Woodruff, Jodi; Baker, Laurie M; Usher, Christina; Ances, Beau M

    2016-02-01

    Most studies that have examined neuropsychological impairments associated with human immunodeficiency virus (HIV) have focused on males, yet females represent one of the largest groups of newly infected patients. Further, few studies have examined neuropsychological performance and neuroimaging outcomes among females compared to males in the modern era of highly active anti-retroviral therapy (HAART). The present study investigated neuropsychological performance and brain volumetrics among HIV+ males (n = 93) and females (n = 44) on stable HAART compared to HIV seronegative (HIV-) males (n = 42) and females (n = 49). Results revealed a significant effect of HIV on neuropsychological performance and neuroimaging measures. An effect of gender, independent of HIV status, was also observed for neuroimaging measures but not neuropsychological performance. Additionally, no significant differences in neuropsychological performance or brain volumetrics were seen between HIV+ males and females. No significant interaction was observed between HIV and gender on either neuropsychological or neuroimaging indices. Our results suggest that both HIV+ males and females treated with HAART experience similar outcomes in terms of brain integrity.

  9. Reactivation of Epstein-Barr virus during early infection with human immunodeficiency virus.

    PubMed Central

    Rahman, M A; Kingsley, L A; Atchison, R W; Belle, S; Breinig, M C; Ho, M; Rinaldo, C R

    1991-01-01

    Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV. PMID:1650790

  10. Molecular Characterization of Clinical Isolates of Human Immunodeficiency Virus Resistant to the Protease Inhibitor Darunavir

    SciTech Connect

    Sasková, Klára Grantz; Koíek, Milan; Rezácová, Pavlína; Brynda, Jirí; Yashina, Tatyana; Kagan, Ron M.; Konvalinka, Jan

    2010-03-04

    Darunavir is the most recently approved human immunodeficiency virus (HIV) protease (PR) inhibitor (PI) and is active against many HIV type 1 PR variants resistant to earlier-generation PIs. Darunavir shows a high genetic barrier to resistance development, and virus strains with lower sensitivity to darunavir have a higher number of PI resistance-associated mutations than viruses resistant to other PIs. In this work, we have enzymologically and structurally characterized a number of highly mutated clinically derived PRs with high levels of phenotypic resistance to darunavir. With 18 to 21 amino acid residue changes, the PR variants studied in this work are the most highly mutated HIV PR species ever studied by means of enzyme kinetics and X-ray crystallography. The recombinant proteins showed major defects in substrate binding, while the substrate turnover was less affected. Remarkably, the overall catalytic efficiency of the recombinant PRs (5% that of the wild-type enzyme) is still sufficient to support polyprotein processing and particle maturation in the corresponding viruses. The X-ray structures of drug-resistant PRs complexed with darunavir suggest that the impaired inhibitor binding could be explained by change in the PR-inhibitor hydrogen bond pattern in the P2 binding pocket due to a substantial shift of the aminophenyl moiety of the inhibitor. Recombinant virus phenotypic characterization, enzyme kinetics, and X-ray structural analysis thus help to explain darunavir resistance development in HIV-positive patients.

  11. Precancerous Cervix in Human Immunodeficiency Virus Infected Women Thirty Years Old and above in Northern Uganda

    PubMed Central

    Adrawa, Norbert; Amongin, Dinah

    2016-01-01

    Background. Little is known about precancerous cervical lesion (PCCL), the precursor of cervical cancer among Human Immunodeficiency (HIV) infected women in a postconflict setting of Northern Uganda. Objective. To establish factors associated with PCCL among HIV infected women above thirty years of age in a postconflict setting of Northern Uganda. Method. This retrospective cohort study used electronic data from 995 HIV-positive women that attended cervical cancer screening during June 2014 and December 2015. Data on social, sexual, obstetric, and gynecological factors was analyzed at 95% confidence level. Multivariate analysis determined factors independently associated with positive PCCL. Probability value less than 5% was considered significant. Results. Prevalence of PCCL was 3.0% (95% confidence interval (CI): 2.0–4.3). A positive PCCL was significantly associated with absence of sexually transmitted diseases (STDs) during clinic visits (adjusted odds ratio, aOR = 0.24; 95% confidence interval (CI): 0.09–0.64; P = 0.004) and first pregnancy before the age of 20 years (aOR = 3.09; 95% CI: 1.21–7.89; P = 0.018). Conclusion. The prevalence of PCCL was low in the postconflict setting of Northern Uganda. HIV-positive women presenting with STDs and those with first pregnancy before the age of 20 years were at increased risk of PCCL. PMID:27478441

  12. Modular total chemical synthesis of a human immunodeficiency virus type 1 protease.

    PubMed

    Johnson, Erik C B; Malito, Enrico; Shen, Yuequan; Rich, Dan; Tang, Wei-Jen; Kent, Stephen B H

    2007-09-19

    As part of our ongoing studies of the human immunodeficiency virus type 1 (HIV-1) protease enzyme, we set out to develop a modular chemical synthesis of the protein from multiple peptide segments. Our initial attempts were frustrated by the insolubility of intermediate peptide products. To overcome this problem, we designed a synthetic strategy combining the solubility-enhancing properties of C-terminal (Arg)n tags and the biological phenomenon of autoprocessing of the Gag-Pol polyprotein that occurs during maturation of the HIV-1 virus in vivo. Synthesis of a 119-residue peptide chain containing 10 residues of the reverse transcriptase (RT) open reading frame plus an (Arg)(10) tag at the C-terminus was straightforward by native chemical ligation followed by conversion of the Cys residues to Ala by Raney nickel desulfurization. The product polypeptide itself completed the final synthetic step by removing the C-terminal modification under folding conditions, to give the mature 99-residue polypeptide. High-purity homodimeric HIV-1 protease protein was obtained in excellent yield and had full enzymatic activity; the structure of the synthetic enzyme was confirmed by X-ray crystallography to a resolution of 1.07 A. This efficient modular synthesis by a biomimetic autoprocessing strategy will enable the facile synthesis of unique chemical analogues of the HIV-1 protease to further elucidate the molecular basis of enzyme catalysis.

  13. Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication.

    PubMed Central

    Engelman, A; Englund, G; Orenstein, J M; Martin, M A; Craigie, R

    1995-01-01

    The integration of a DNA copy of the human immunodeficiency virus type 1 (HIV-1) genome into a chromosome of an infected cell is a pivotal step in virus replication. Integration requires the activity of the virus-encoded integrase, which enters the cell as a component of the virion. Results of numerous mutagenesis studies have identified amino acid residues and protein domains of HIV-1 integrase critical for in vitro activity, but only a few of these mutants have been studied for their effects on HIV replication. We have introduced site-directed changes into an infectious DNA clone of HIV-1 and show that integrase mutations can affect virus replication at a variety of steps. We identified mutations that altered virion morphology, levels of particle-associated integrase and reverse transcriptase, and viral DNA synthesis. One replication-defective mutant virus which had normal morphology and protein composition displayed increased levels of circular viral DNA following infection of a T-cell line. This virus also had a significant titer in a CD4-positive indicator cell assay, which requires the viral Tat protein. Although unintegrated viral DNA can serve as a template for Tat expression in infected indicator cells, this level of expression is insufficient to support a spreading viral infection in CD4-positive lymphocytes. PMID:7535863

  14. Divergent transcriptional regulation among expanding human immunodeficiency virus type 1 subtypes.

    PubMed Central

    Montano, M A; Novitsky, V A; Blackard, J T; Cho, N L; Katzenstein, D A; Essex, M

    1997-01-01

    The current AIDS pandemic represents the uneven spread of multiple genetically related subtypes (A to J) of human immunodeficiency virus type 1 (HIV-1). Notably, HIV-1 E in southeast Asia and HIV-1 C in sub-Saharan Africa are expanding faster and are likely of greater global significance than the HIV-1 B subtype prevalent in the United States and Europe. While many studies have focused on genetic variation among structural genes, we chose to conduct a comparative analysis of the long terminal repeats of HIV-1 E and HIV-1 C isolates and report subtype-specific differences in enhancer copy numbers and sequences, as well as divergent activation in response to the cellular transcriptional activators Rel-p65 and NFATc and viral Tat. This study is the first to identify functional distinctions in promoter architecture between HIV-1 subtypes and raises the possibility that regulatory divergence among the subtypes of HIV-1 has occurred. Divergent transcriptional regulation may explain some of the epidemiologically observed differences in transmission and pathogenesis and underscores the need for further comparative analysis of HIV-1 regulation. PMID:9343223

  15. Human immunodeficiency virus (HIV) antigen testing to detect HIV infection in female sex workers in Singapore.

    PubMed

    Chan, R K; Ali, K; Thoe, S Y

    1995-07-01

    Human immunodeficiency virus (HIV) infection is characterised by seroconversion after a ¿window¿ period of 2 to 3 months. After this period antibodies are usually detectable by screening tests (enzyme immunoassay or particle agglutination) confirmed by Western blot analysis. We studied 1000 newly enrolled female sex workers who had not been previously tested for HIV to assess the usefulness of HIV antigen testing to improve the efficacy of HIV infection detection. Blood was taken at enrollment for HIV antigen and HIV antibody testing. The Abbott HIVAG-1 test was used to detect antigen; antibody detection was by the Abbott recombinant HIV-1/HIV-2 3rd generation enzyme immunoassay (EIA) test, the Fujirebio Serodia-HIV particle agglutination (PA) test for screening, and the Diagnostic Biotechnology HIV Blot 2.2 Western blot (WB) test for antibody confirmation. Of the 1000 samples, 26 were positive for HIV antibody testing (26/26 for EIA, 25/25 for PA, 26/26 for WB), giving a prevalence rate of 2.6%, Of these 26 seropositive samples 1 was positive on HIV antigen testing. There were no samples which were antigen-positive and antibody-negative. HIV antigen testing does not add to increased efficacy of HIV detection among female sex workers in Singapore.

  16. A case of plasmablastic lymphoma of the liver without human immunodeficiency virus infection

    PubMed Central

    Tani, Joji; Miyoshi, Hisaaki; Nomura, Takako; Yoneyama, Hirohito; Kobara, Hideki; Mori, Hirohito; Morishita, Asahiro; Himoto, Takashi; Masaki, Tsutomu

    2013-01-01

    Plasmablastic lymphoma (PBL) is a very rare B-cell lymphoproliferative disorder was with an aggressive clinical behavior that recently characterized by the World Health Organization. Although PBL is most commonly observed in the oral cavity of human immunodeficiency virus (HIV)-positive patients, it can also be observed at extra-oral sites in HIV-negative patients. Epstein-Barr virus (EBV) may be closely related the pathogenesis of PBL. PBL shows different clinicopathological characteristics between HIV-positive and -negative patients. Here, we report a case of PBL of the liver in a 79-year-old HIV-negative male. The patient died approximately 1.5 mo after examination and autopsy showed that the main lesion was a very large liver mass. Histopathological examination of the excised lesion showed large-cell lymphoma with plasmacytic differentiation diffusely infiltrating the liver and involving the surrounding organs. The neoplastic cells were diffusely positive for CD30, EBV, Bob-1, and CD38. The autopsy findings suggested a diagnosis of PBL. To our knowledge, the present case appears to be the first report of PBL with initial presentation of the liver in a patient without HIV infection. PMID:24115831

  17. [Performance Assessment of a Newly Developed Rapid Diagnostic Reagent for Human Immunodeficiency Virus].

    PubMed

    Nakagiri, Itsuhiro; Wada, Hideho; Tokunaga, Hirotoshi; Fukuda, Hirofumi; Tasaka, Taizo; Sugihara, Takashi

    2015-11-01

    Extremely early diagnosis of human immunodeficiency virus (HIV) infection has been considered highly important for its treatment. We conducted a performance assessment of a newly developed rapid diagnostic reagent for HIV by using a fourth-generation immunochromatographic assay (Alere HIV Combo). We used whole-blood, plasma, and serum samples obtained from 250 Japanese adults who visited the Kawasaki Medical School Hospital and underwent HIV screening tests. We also used 12 types of commercial HIV-1 sero- conversion panels and World Health Organization standard antigens. This method, which has a detection sensitivity of 100% and a specificity of 99.3%, was as accurate as the chemiluminescent immunoassay (CLIA) method. In a sensitivity test using seroconversion panels in the early phase of infection, the mean duration until positive conversion was 19.3 days. With this method having a high detection sensitivity for HIV-1p24 antigen, the results from whole-blood samples were the same as those from plasma and serum samples. Therefore, it can be considered as a useful rapid measurement method for general practice. PMID:26821522

  18. Envelope glycoproteins of human immunodeficiency virus type 1: profound influences on immune functions.

    PubMed Central

    Chirmule, N; Pahwa, S

    1996-01-01

    Infection by human immunodeficiency virus type 1 (HIV-1) leads to progressive destruction of the CD4+ T-cell subset, resulting in immune deficiency and AIDS. The specific binding of the viral external envelope glycoprotein of HIV-1, gp120, to the CD4 molecules initiates viral entry. In the past few years, several studies have indicated that the interaction of HIV-1 envelope glycoprotein with cells and molecules of the immune system leads to pleiotropic biological effects on immune functions, which include effects on differentiation of CD34+ lymphoid progenitor cells and thymocytes, aberrant activation and cytokine secretion patterns of mature T cells, induction of apoptosis, B-cell hyperactivity, inhibition of T-cell dependent B-cell differentiation, modulation of macrophage functions, interactions with components of complement, and effects on neuronal cells. The amino acid sequence homologies of the envelope glycoproteins with several cellular proteins have suggested that molecular mimicry may play a role in the pathogenesis of the disease. This review summarizes work done by several investigators demonstrating the profound biological effects of envelope glycoproteins of HIV-1 on immune system cells. Extensive studies have also been done on interactions of the viral envelope proteins with components of the immune system which may be important for eliciting a "protective immune response." Understanding the influences of HIV-1 envelope glycoproteins on the immune system may provide valuable insights into HIV-1 disease pathogenesis and carries implications for the trials of HIV-1 envelope protein vaccines and immunotherapeutics. PMID:8801439

  19. Good governance and good health: The role of societal structures in the human immunodeficiency virus pandemic.

    PubMed

    Menon-Johansson, Anatole S

    2005-04-25

    BACKGROUND: Only governments sensitive to the demands of their citizens appropriately respond to needs of their nation. Based on Professor Amartya Sen's analysis of the link between famine and democracy, the following null hypothesis was tested: "Human Immunodeficiency Virus (HIV) prevalence is not associated with governance". METHODS: Governance has been divided by a recent World Bank paper into six dimensions. These include Voice and Accountability, Political Stability and Absence of Violence, Government Effectiveness, Regulatory Quality, Rule of Law and the Control of Corruption. The 2002 adult HIV prevalence estimates were obtained from UNAIDS. Additional health and economic variables were collected from multiple sources to illustrate the development needs of countries. RESULTS: The null hypothesis was rejected for each dimension of governance for all 149 countries with UNAIDS HIV prevalence estimates. When these nations were divided into three groups, the median (range) HIV prevalence estimates remained constant at 0.7% (0.05 - 33.7%) and 0.75% (0.05% - 33.4%) for the lower and middle mean governance groups respectively despite improvements in other health and economic indices. The median HIV prevalence estimates in the higher mean governance group was 0.2% (0.05 - 38.8%). CONCLUSION: HIV prevalence is significantly associated with poor governance. International public health programs need to address societal structures in order to create strong foundations upon which effective healthcare interventions can be implemented.

  20. Metabolic stress in infected cells may represent a therapeutic target for human immunodeficiency virus infection.

    PubMed

    Alonso-Villaverde, Carlos; Menéndez, Javier A; Joven, Jorge

    2013-07-01

    Worldwide, there are thousands of new cases of human immunodeficiency virus-1 (HIV-1) infection per day. The effectiveness of current combination antiretroviral therapy (ART) is relative; to prioritize finding vaccines and/or cure-oriented initiatives should be reinforced because there is little room, if any, for procrastination. Basic and clinical findings on HIV-1 reservoirs suggest that disruption of virus latency is feasible. Because the goal is curing HIV-1 infection, we should be aware that the challenge is to eradicate the viruses of every single infected cell and consequently acting upon virus latency is necessary but not sufficient. The large majority of the virus reservoir, CD4(+) T lymphocytes, is readily accessible but other minor reservoirs, where ART does not diffuse, require innovative strategies. The situation closely resembles that currently faced in the treatment of cancer. Exploiting the fact that histone deacetylase inhibitors, mainly vorinostat, may disrupt the latency of HIV-1, we propose to supplement this effect with a programmed interference in the metabolic stress of infected cells. Metformin and chloroquine are cheap and accessible modulators of pro-survival mechanisms to which viruses are constantly confronted to generate alternative energy sources and maximize virus production. Metformin restrains the use of the usurped cellular biosynthetic machinery by viral genes and chloroquine contributes to death of infected cells. We suggest that the combination of vorinostat, chloroquine and metformin should be combined with ART to pursue viral eradication in infected cells. PMID:23639282