High genetic variability of HIV-1 in female sex workers from Argentina

Directory of Open Access Journals (Sweden)

Carr Jean K

2007-08-01

Full Text Available Abstract Background A cross-sectional study on 625 Female Sex Workers (FSWs was conducted between 2000 and 2002 in 6 cities in Argentina. This study describes the genetic diversity and the resistance profile of the HIV-infected subjects. Results Seventeen samples from HIV positive FSWs were genotyped by env HMA, showing the presence of 9 subtype F, 6 subtype B and 2 subtype C. Sequence analysis of the protease/RT region on 16 of these showed that 10 were BF recombinants, three were subtype B, two were subtype C, and one sample presented a dual infection with subtype B and a BF recombinant. Full-length genomes of five of the protease/RT BF recombinants were also sequenced, showing that three of them were CRF12_BF. One FSW had a dual HIV-1 infection with subtype B and a BF recombinant. The B sections of the BF recombinant clustered closely with the pure B sequence isolated from the same patient. Major resistance mutations to antiretroviral drugs were found in 3 of 16 (18.8% strains. Conclusion The genetic diversity of HIV strains among FSWs in Argentina was extensive; about three-quarters of the samples were infected with diverse BF recombinants, near twenty percent had primary ART resistance and one sample presented a dual infection. Heterosexual transmission of genetically diverse, drug resistant strains among FSWs and their clients represents an important and underestimated threat, in Argentina.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

NARCIS (Netherlands)

Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; de Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; de Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.; Gras, A. Luuk; van Wout, Angelique B.; Arnedo-Valero, Mireia; Sierra, Mariana de Paz; Rodriguez, Ana Torrecilla; Garcia, Juan Gonzalez; Arribas, Jose R.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Francioli, P.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hirschel, B.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Prins, Yerly S. J. M.; Kuijpers, T. W.; Scherpbier, H. J.; Boer, K.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Vrouenraets, S. M. E.; Pajkrt, D.; Bos, J. C.; van der Valk, M.; Schreij, G.; Lowe, S.; Oude Lashof, A.; Pronk, M. J. H.; Bravenboer, B.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; van der Feltz, M.; Nouwen, J. L.; Gelinck, L. B. S.; Verbon, A.; Rijnders, B. J. A.; van de Ven-de Ruiter, E. D.; Slobbe, L.; Haag, Den; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; Bouwhuis, J. W.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; van den Broek, P. J.; van Dissel, J. T.; Arend, S. M.; van Nieuwkoop, C.; de Boer, M. J. G.; Jolink, H.; den Hollander, J. G.; Pogany, K.; Bronsveld, W.; Kortmann, W.; van Twillert, G.; van Houte, D. P. F.; Polée, M. B.; van Vonderen, M. G. A.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; Juttmann, J. R.; van Kasteren, M. E. E.; Brouwer, A. E.; Mulder, J. W.; van Gorp, E. C. M.; Smit, P. M.; Weijer, S.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; van Assen, S.; Stek, C. J.; Hoepelman, I. M.; Mudrikova, T.; Schneider, M. M. E.; Jaspers, C. A. J. J.; Ellerbroek, P. M.; Peters, E. J. G.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; van der Hilst, J. C. H.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; Margolick, Joseph B.; Plankey, Michael; Crain, Barbara; Dobs, Adrian; Farzadegan, Homayoon; Gallant, Joel; Johnson-Hill, Lisette; Sacktor, Ned; Selnes, Ola; Shepard, James; Thio, Chloe; Phair, John P.; Wolinsky, Steven M.; Badri, Sheila; Conover, Craig; O'Gorman, Maurice; Ostrow, David; Palella, Frank; Ragin, Ann; Detels, Roger; Martínez-Maza, Otoniel; Aronow, Aaron; Bolan, Robert; Breen, Elizabeth; Butch, Anthony; Fahey, John; Jamieson, Beth; Miller, Eric N.; Oishi, John; Vinters, Harry; Visscher, Barbara R.; Wiley, Dorothy; Witt, Mallory; Yang, Otto; Young, Stephen; Zhang, Zuo Feng; Rinaldo, Charles R.; Becker, James T.; Cranston, Ross D.; Martinson, Jeremy J.; Mellors, John W.; Silvestre, Anthony J.; Stall, Ronald D.; Muñoz, Alvaro; Abraham, Alison; Althoff, Keri; Cox, Christopher; D'Souza, Gypsyamber; Gange, Stephen J.; Golub, Elizabeth; Schollenberger, Janet; Seaberg, Eric C.; Su, Sol; Huebner, Robin E.; Dominguez, Geraldina; Moroni, M.; Angarano, G.; Antinori, A.; Carosi, G.; Cauda, R.; Monforte, A. d'Arminio; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Sagnelli, E.; Viale, P. L.; Von Schlosser, F.; d'Arminio Monforte, A.; Ammassari, A.; Andreoni, M.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; de Luca, A.; Gargiulo, M.; Gervasoni, C.; Girardi, E.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Murri, R.; Mussini, C.; Puoti, M.; Torti, C.; Fanti, I.; Formenti, T.; Galli, Laura; Lorenzini, Patrizia; Montroni, M.; Giacometti, A.; Costantini, A.; Riva, A.; Tirelli, U.; Martellotta, F.; Ladisa, N.; Lazzari, G.; Verucchi, G.; Castelli, F.; Scalzini, A.; Minardi, C.; Bertelli, D.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Carnevale, G.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Leoncini, F.; Mazzotta, F.; Pozzi, M.; Cassola, G.; Viscoli, G.; Viscoli, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, P.; Rizzardini, G.; Ridolfo, A. L.; Foschi, A.; Salpietro, S.; Galli, A.; Bigoloni, A.; Spagnuolo, V.; Merli, S.; Carenzi, L.; Moioli, M. C.; Cicconi, P.; Bisio, L.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; de Marco, M.; Ferrari, C.; Borghi, R.; Baldelli, F.; Belfiori, B.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Narciso, P.; Tozzi, V.; Vullo, V.; d'Avino, A.; Zaccarelli, M.; Gallo, L.; Acinapura, R.; Capozzi, M.; Libertone, R.; Trotta, M. P.; Tebano, G.; Cattelan, A. M.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Raise, N. N.; Ebo, F.; Pellizzer, G.; Manfrin, V.; Law, M.; Petoumenos, K.; McManus, H.; Wright, S.; Bendall, C.; Moore, R.; Edwards, S.

2013-01-01

Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV

A Strong Case for Viral Genetic Factors in HIV Virulence

Directory of Open Access Journals (Sweden)

Joshua T. Herbeck

2011-03-01

Full Text Available HIV infections show great variation in the rate of progression to disease, and the role of viral genetic factors in this variation had remained poorly characterized until recently. Now a series of four studies [1–4] published within a year has filled this important gap and has demonstrated a robust effect of the viral genotype on HIV virulence.

Systems mapping of HIV-1 infection

Directory of Open Access Journals (Sweden)

Hou Wei

2012-10-01

Full Text Available Abstract Mathematical models of viral dynamics in vivo provide incredible insights into the mechanisms for the nonlinear interaction between virus and host cell populations, the dynamics of viral drug resistance, and the way to eliminate virus infection from individual patients by drug treatment. The integration of these mathematical models with high-throughput genetic and genomic data within a statistical framework will raise a hope for effective treatment of infections with HIV virus through developing potent antiviral drugs based on individual patients’ genetic makeup. In this opinion article, we will show a conceptual model for mapping and dictating a comprehensive picture of genetic control mechanisms for viral dynamics through incorporating a group of differential equations that quantify the emergent properties of a system.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

NARCIS (Netherlands)

Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the

Psoriasis Patients Are Enriched for Genetic Variants That Protect against HIV-1 Disease

Science.gov (United States)

Chen, Haoyan; Hayashi, Genki; Lai, Olivia Y.; Dilthey, Alexander; Kuebler, Peter J.; Wong, Tami V.; Martin, Maureen P.; Fernandez Vina, Marcelo A.; McVean, Gil; Wabl, Matthias; Leslie, Kieron S.; Maurer, Toby; Martin, Jeffrey N.; Deeks, Steven G.; Carrington, Mary; Bowcock, Anne M.; Nixon, Douglas F.; Liao, Wilson

2012-01-01

An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis. PMID:22577363

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

OpenAIRE

Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle

2013-01-01

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the ...

HIV genetic information and clonal growth

Science.gov (United States)

Based on an analysis of blood cells from five HIV-infected individuals, NCI researchers have identified more than 2,400 HIV DNA insertion sites. Analysis of these sites showed that there is extensive clonal expansion (growth) of HIV infected cells.

First evidence of genetic intraspecific variability and occurrence of Entamoeba gingivalis in HIV(+/AIDS.

Directory of Open Access Journals (Sweden)

Sibeli B S Cembranelli

Full Text Available Entamoeba gingivalis is considered an oral commensal but demonstrates a pathogenic potential associated with periodontal disease in immunocompromised individuals. Therefore, this study evaluated the occurrence, opportunistic conditions, and intraspecific genetic variability of E. gingivalis in HIV(+/AIDS patients. Entamoeba gingivalis was studied using fresh examination (FE, culture, and PCR from bacterial plaque samples collected from 82 HIV(+/AIDS patients. Genetic characterization of the lower ribosomal subunit of region 18S (18S-SSU rRNA was conducted in 9 positive samples using low-stringency single specific primer PCR (LSSP-PCR and sequencing analysis. Entamoeba gingivalis was detected in 63.4% (52/82 of the samples. No association was detected between the presence of E. gingivalis and the CD4(+ lymphocyte count (≤200 cells/mm(3 (p = 0.912 or viral load (p = 0.429. The LSSP-PCR results helped group E. gingivalis populations into 2 polymorphic groups (68.3% similarity: group I, associated with 63.6% (7/11 of the samples, and group II, associated with 36.4% (4/11 of the samples, which shared 74% and 83.7% similarity and association with C and E isolates from HIV(- individuals, respectively. Sequencing of 4 samples demonstrated 99% identity with the reference strain ATCC 30927 and also showed 2 divergent clusters, similar to those detected by LSSP-PCR. Opportunistic behavior of E. gingivalis was not detected, which may be related to the use of highly active antiretroviral therapy by all HIV(+/AIDS patients. The high occurrence of E. gingivalis in these patients can be influenced by multifactorial components not directly related to the CD4(+ lymphocyte counts, such as cholesterol and the oral microbiota host, which could mask the potential opportunistic ability of E. gingivalis. The identification of the 18S SSU-rRNA polymorphism by LSSP-PCR and sequencing analysis provides the first evidence of genetic variability in E. gingivalis

Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana.

Science.gov (United States)

Nii-Trebi, Nicholas Israel; Brandful, James Ashun Mensah; Ibe, Shiro; Sugiura, Wataru; Barnor, Jacob Samson; Bampoh, Patrick Owiredu; Yamaoka, Shoji; Matano, Tetsuro; Yoshimura, Kazuhisa; Ishikawa, Koichi; Ampofo, William Kwabena

2017-11-01

There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4 + T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic. HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.

The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes

NARCIS (Netherlands)

Vijver, D.A. van de; Wensing, A.M.J.; Angarano, G.; Asjo, B.; Balotta, C.; Camacho, R.; Chaix, M.; Costagliola, D.; De Luca, A.; Derdelinckx, I.; Grossman, Z.; Hamouda, O.; Hatzakis, A.; Hemmer, R.; Hoepelman, A.I.M.; Horban, A.; Korn, K.; Kücherer, C.; Leitner, T.; Loveday, C.; MacRae, E.; Maljkovic, I.; Mendoza, C. de; Meyer, L.; Nielsen, C.; Op de Coul, E.L.M.; Omaasen, V.; Paraskevis, D.; Perrin, L.; Puchhammer-Stöckl, E.; Salminen, M.; Schmit, J.; Scheider, F.; Schuurman, R.; Soriano, V.; Stanczak, G.; Stanojevic, M.; Vandamme, A.; Laethem, K. van; Violin, M.; Wilde, K.; Yerly, S.; Zazzi, M.; Boucher, C.A.B.

The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug

Clinical presentation and opportunistic infections in HIV-1, HIV-2 and HIV-1/2 dual seropositive patients in Guinea-Bissau

DEFF Research Database (Denmark)

Sørensen, Allan; Jespersen, Sanne; Katzenstein, Terese L

2016-01-01

HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Methods: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Sim~ao Mendes in Guinea......-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients. Results: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive...... antigen. Conclusion: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major...

A Systematic Review on Confidentiality, Disclosure, and Stigma in the United States: Lessons for HIV Care in Pregnancy From Reproductive Genetics.

Science.gov (United States)

Wilkinson, Barbara; Arora, Kavita Shah

2015-01-01

The fields of HIV care in pregnancy and reproductive genetics have always been 'exceptional' in that patients are highly concerned about the potential for stigma and the corresponding need for privacy and confidentiality. However, the two fields have diverged in how they have addressed these concerns. The systematic review analyzed 61 manuscripts for similarities and differences between the fields of HIV care in pregnancy and reproductive genetics in the United States, with respect to privacy, confidentiality, disclosure, and stigma. The systematic review revealed that the field of HIV care in pregnancy has insufficiently addressed patient concerns about privacy, confidentiality, and stigma compared to the field of reproductive genetics. Failure to adequately protect confidentiality of HIV-positive patients, and failure to reduce stigma associated with HIV testing and treatment are deficiencies in the delivery of care to HIV-positive pregnant woman and barriers to reducing vertical transmission of HIV. Improvements in care and policy should mirror the field of reproductive genetics.

Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example

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Tornesello Maria

2007-05-01

Full Text Available Abstract The Human Immunodeficiency Virus type 1 (HIV-1 is classified into genetic groups, subtypes and sub-subtypes which show a specific geographic distribution pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has traditionally affected the Intra-venous drug user (IDU and Homosexual (Homo risk groups and has been sustained by the genetic B subtype. In the last years, however, the HIV-1 transmission rate among heterosexuals has dramatically increased, becoming the prevalent transmission route. In fact, while the traditional risk groups have high levels of knowledge and avoid high-risk practices, the heterosexuals do not sufficiently perceive the risk of HIV-1 infection. This misperception, linked to the growing number of immigrants from non-Western Countries, where non-B clades and circulating recombinant forms (CRFs are prevalent, is progressively introducing HIV-1 variants of non-B subtype in the Italian epidemic. This is in agreement with reports from other Western European Countries. In this context, the Italian HIV-1 epidemic is still characterized by low subtype heterogeneity and represents a paradigmatic example of the European situation. The continuous molecular evolution of the B subtype HIV-1 isolates, characteristic of a long-lasting epidemic, together with the introduction of new subtypes as well as recombinant forms may have significant implications for diagnostic, treatment, and vaccine development. The study and monitoring of the genetic evolution of the HIV-1 represent, therefore, an essential strategy for controlling the local as well as global HIV-1 epidemic and for developing efficient preventive and therapeutic strategies.

Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2

Science.gov (United States)

Celum, Connie; Wald, Anna; Lingappa, Jairam R.; Magaret, Amalia S.; Wang, Richard S.; Mugo, Nelly; Mujugira, Andrew; Baeten, Jared M.; Mullins, James I.; Hughes, James P.; Bukusi, Elizabeth A.; Cohen, Craig R.; Katabira, Elly; Ronald, Allan; Kiarie, James; Farquhar, Carey; Stewart, Grace John; Makhema, Joseph; Essex, Myron; Were, Edwin; Fife, Kenneth H.; de Bruyn, Guy; Gray, Glenda E.; McIntyre, James A.; Manongi, Rachel; Kapiga, Saidi; Coetzee, David; Allen, Susan; Inambao, Mubiana; Kayitenkore, Kayitesi; Karita, Etienne; Kanweka, William; Delany, Sinead; Rees, Helen; Vwalika, Bellington; Stevens, Wendy; Campbell, Mary S.; Thomas, Katherine K.; Coombs, Robert W.; Morrow, Rhoda; Whittington, William L.H.; McElrath, M. Juliana; Barnes, Linda; Ridzon, Renee; Corey, Lawrence

2010-01-01

BACKGROUND Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, ≥250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir

Identification and genetic characterization of unique HIV-1 A1/C recombinant strain in South Africa.

Science.gov (United States)

Musyoki, Andrew M; Rakgole, Johnny N; Selabe, Gloria; Mphahlele, Jeffrey

2015-03-01

HIV isolates from South Africa are predominantly subtype C. Sporadic isolation of non-C strains has been reported mainly in cosmopolitan cities. HIV isolate j51 was recovered from a rural South African heterosexual female aged 51 years. Near full length amplification of the genome was attempted using PCR with primers targeting overlapping segments of the HIV genome. Analysis of 5593 bp (gag to vpu) at a bootstrap value greater than 70% found that all but the vpu gene was HIV-1 subtype A1. The vpu gene was assigned HIV-1 subtype C. The recombination breaking point was estimated at position 6035+/- 15 bp with reference to the beginning of the HXB2 reference strain. Isolate j51 revealed a unique genome constellation to previously reported recombinant strains with parental A/C backbones from South Africa though a common recombination with subtype C within the vpu gene. Identification of recombinant strains supports continued surveillance of HIV genetic diversity.

Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls

DEFF Research Database (Denmark)

McLaren, Paul J; Coulonges, Cédric; Ripke, Stephan

2013-01-01

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although...... of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6 × 10(-11)). However, restricting analysis to individuals with a known date of seroconversion suggested...... no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size....

Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

Science.gov (United States)

de Pina-Araujo, Isabel Inês M; Guimarães, Monick L; Bello, Gonzalo; Vicente, Ana Carolina P; Morgado, Mariza G

2014-01-01

HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1-75) and 47 (IQR = 12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented.

HIV-1 genetic diversity and its distribution characteristics among newly diagnosed HIV-1 individuals in Hebei province, China.

Science.gov (United States)

Lu, Xinli; Zhao, Cuiying; Wang, Wei; Nie, Chenxi; Zhang, Yuqi; Zhao, Hongru; Chen, Suliang; Cui, Ze

2016-01-01

Since the first HIV-1 case in 1989, Hebei province has presented a clearly rising trend of HIV-1 prevalence, and HIV-1 genetic diversity has become the vital barrier to HIV prevention and control in this area. To obtain detailed information of HIV-1 spread in different populations and in different areas of Hebei, a cross-sectional HIV-1 molecular epidemiological investigation was performed across the province. Blood samples of 154 newly diagnosed HIV-1 individuals were collected from ten prefectures in Hebei using stratified sampling. Partial gag and env genes were amplified and sequenced. HIV-1 genotypes were identified by phylogenetic tree analyses. Among the 139 subjects genotyped, six HIV-1 subtypes were identified successfully, including subtype B (41.0 %), CRF01_AE (40.3 %), CRF07_BC (11.5 %), CRF08_BC (4.3 %), unique recombinant forms (URFs) (1.4 %) and subtype C (1.4 %). Subtype B was identified as the most frequent subtype. Two URF recombination patterns were the same as CRF01_AE/B. HIV-1 genotype distribution showed a significant statistical difference in different demographic characteristics, such as source (P  0.05). The differences in HIV-1 genotype distribution were closely associated with transmission routes. Particularly, all six subtype strains were found in heterosexuals, showing that HIV-1 has spread from the high-risk populations to the general populations in Hebei, China. In addition, CRF01_AE instead of subtype B has become the major strain of HIV-1 infection among homosexuals. Our study revealed HIV-1 evolution and genotype distribution by investigating newly diagnosed HIV-1 individuals in Hebei, China. This study provides important information to enhance the strategic plan for HIV prevention and control in China.

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

Science.gov (United States)

Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P; Gottlieb, Geoffrey S; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d'Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N'gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Ostergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-Gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; Pac-Ci; Abidjan

2013-01-01

HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region. Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3). This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

Directory of Open Access Journals (Sweden)

Didier K Ekouevi

Full Text Available HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA.We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region.Data was merged for 1,754 patients (56% female, including 1,021 HIV-2 infected patients (551 on ART and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART. At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7 and 42.4 years, IQR (37.0-47.3 for dually seropositive patients (p = 0.048. Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C. The median CD4 count at the ART initiation is 166 cells/mm(3, IQR (83-247 among HIV-2 infected patients and 146 cells/mm(3, IQR (55-249 among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3 after 24 months on ART for HIV-2 patients and 169 cells/mm(3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3.This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.

Science.gov (United States)

Hauser, Kurt F; Knapp, Pamela E

2014-01-01

Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.

Combining epidemiological and genetic networks signifies the importance of early treatment in HIV-1 transmission.

Science.gov (United States)

Zarrabi, Narges; Prosperi, Mattia; Belleman, Robert G; Colafigli, Manuela; De Luca, Andrea; Sloot, Peter M A

2012-01-01

Inferring disease transmission networks is important in epidemiology in order to understand and prevent the spread of infectious diseases. Reconstruction of the infection transmission networks requires insight into viral genome data as well as social interactions. For the HIV-1 epidemic, current research either uses genetic information of patients' virus to infer the past infection events or uses statistics of sexual interactions to model the network structure of viral spreading. Methods for a reliable reconstruction of HIV-1 transmission dynamics, taking into account both molecular and societal data are still lacking. The aim of this study is to combine information from both genetic and epidemiological scales to characterize and analyse a transmission network of the HIV-1 epidemic in central Italy.We introduce a novel filter-reduction method to build a network of HIV infected patients based on their social and treatment information. The network is then combined with a genetic network, to infer a hypothetical infection transmission network. We apply this method to a cohort study of HIV-1 infected patients in central Italy and find that patients who are highly connected in the network have longer untreated infection periods. We also find that the network structures for homosexual males and heterosexual populations are heterogeneous, consisting of a majority of 'peripheral nodes' that have only a few sexual interactions and a minority of 'hub nodes' that have many sexual interactions. Inferring HIV-1 transmission networks using this novel combined approach reveals remarkable correlations between high out-degree individuals and longer untreated infection periods. These findings signify the importance of early treatment and support the potential benefit of wide population screening, management of early diagnoses and anticipated antiretroviral treatment to prevent viral transmission and spread. The approach presented here for reconstructing HIV-1 transmission networks

Loss and recovery of genetic diversity in adapting populations of HIV.

Directory of Open Access Journals (Sweden)

Pleuni S Pennings

2014-01-01

Full Text Available The evolution of drug resistance in HIV occurs by the fixation of specific, well-known, drug-resistance mutations, but the underlying population genetic processes are not well understood. By analyzing within-patient longitudinal sequence data, we make four observations that shed a light on the underlying processes and allow us to infer the short-term effective population size of the viral population in a patient. Our first observation is that the evolution of drug resistance usually occurs by the fixation of one drug-resistance mutation at a time, as opposed to several changes simultaneously. Second, we find that these fixation events are accompanied by a reduction in genetic diversity in the region surrounding the fixed drug-resistance mutation, due to the hitchhiking effect. Third, we observe that the fixation of drug-resistance mutations involves both hard and soft selective sweeps. In a hard sweep, a resistance mutation arises in a single viral particle and drives all linked mutations with it when it spreads in the viral population, which dramatically reduces genetic diversity. On the other hand, in a soft sweep, a resistance mutation occurs multiple times on different genetic backgrounds, and the reduction of diversity is weak. Using the frequency of occurrence of hard and soft sweeps we estimate the effective population size of HIV to be 1.5 x 10(5 (95% confidence interval [0.8 x 10(5,4.8 x 10(5]. This number is much lower than the actual number of infected cells, but much larger than previous population size estimates based on synonymous diversity. We propose several explanations for the observed discrepancies. Finally, our fourth observation is that genetic diversity at non-synonymous sites recovers to its pre-fixation value within 18 months, whereas diversity at synonymous sites remains depressed after this time period. These results improve our understanding of HIV evolution and have potential implications for treatment strategies.

Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...

African Journals Online (AJOL)

The presence of human immunodeficiency virus (HIV) type-1 diversity has an impact on vaccine efficacy and drug resistance. It is important to know the circulating genetic variants and associated drug-resistance mutations in the context of scale up of antiretroviral therapy (ART) in Nigeria. The objective of this study was to ...

Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls

Science.gov (United States)

Ripke, Stephan; van den Berg, Leonard; Buchbinder, Susan; Carrington, Mary; Cossarizza, Andrea; Dalmau, Judith; Deeks, Steven G.; Delaneau, Olivier; De Luca, Andrea; Goedert, James J.; Haas, David; Herbeck, Joshua T.; Kathiresan, Sekar; Kirk, Gregory D.; Lambotte, Olivier; Luo, Ma; Mallal, Simon; van Manen, Daniëlle; Martinez-Picado, Javier; Meyer, Laurence; Miro, José M.; Mullins, James I.; Obel, Niels; O'Brien, Stephen J.; Pereyra, Florencia; Plummer, Francis A.; Poli, Guido; Qi, Ying; Rucart, Pierre; Sandhu, Manj S.; Shea, Patrick R.; Schuitemaker, Hanneke; Theodorou, Ioannis; Vannberg, Fredrik; Veldink, Jan; Walker, Bruce D.; Weintrob, Amy; Winkler, Cheryl A.; Wolinsky, Steven; Telenti, Amalio; Goldstein, David B.; de Bakker, Paul I. W.; Zagury, Jean-François; Fellay, Jacques

2013-01-01

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10−11). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size. PMID:23935489

Association study of common genetic variants and HIV-1 acquisition in 6,300 infected cases and 7,200 controls.

Directory of Open Access Journals (Sweden)

Paul J McLaren

Full Text Available Multiple genome-wide association studies (GWAS have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1. After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6 × 10⁻¹¹. However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity. Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.

HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases

International Nuclear Information System (INIS)

Devroe, Eric; Silver, Pamela A.; Engelman, Alan

2005-01-01

Mammalian genomes encode two related serine-threonine kinases, nuclear Dbf2 related (NDR)1 and NDR2, which are homologous to the Saccharomyces cerevisiae Dbf2 kinase. Recently, a yeast genetic screen implicated the Dbf2 kinase in Ty1 retrotransposition. Since several virion-incorporated kinases regulate the infectivity of human immunodeficiency virus type 1 (HIV-1), we speculated that the human NDR1 and NDR2 kinases might play a role in the HIV-1 life cycle. Here we show that the NDR1 and NDR2 kinases were incorporated into HIV-1 particles. Furthermore, NDR1 and NDR2 were cleaved by the HIV-1 protease (PR), both within virions and within producer cells. Truncation at the PR cleavage site altered NDR2 subcellular localization and inhibited NDR1 and NDR2 enzymatic activity. These studies identify two new virion-associated host cell enzymes and suggest a novel mechanism by which HIV-1 alters the intracellular environment of human cells

Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

Science.gov (United States)

Neogi, Ujjwal; Sood, Vikas; Ronsard, Larence; Singh, Jyotsna; Lata, Sneh; Ramachandran, V G; Das, S; Wanchu, Ajay; Banerjea, Akhil C

2011-12-01

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy

DEFF Research Database (Denmark)

Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A

2013-01-01

HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework o...... of the International epidemiological Databases to Evaluate AIDS (IeDEA)....

Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

Science.gov (United States)

Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C; Gorelick, Robert J; Keele, Brandon F; Hu, Wei-Shau; Pathak, Vinay K

2016-05-01

Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic

HIV-1 group O infection in Cameroon from 2006 to 2013: Prevalence, genetic diversity, evolution and public health challenges

Science.gov (United States)

Villabona-Arenas, Christian Julian; Domyeum, Jenny; Mouacha, Fatima; Butel, Christelle; Delaporte, Eric; Peeters, Martine; Mpoudi-Ngole, Eitel; Aghokeng, Avelin Fobang

2015-01-01

The human immunodeficiency virus, HIV, is characterized by a tremendously high genetic diversity, leading to the currently known circulating HIV types, groups, subtypes, and recombinant forms. HIV-1 group O is one of the most diverse forms of HIV-1 and has been so far related to Cameroon or individuals originating from Cameroon. In this study, we investigated in Cameroon, the evolution of this viral group from 2006 to 2013, in terms of prevalence, genetic diversity and public health implications. Our results confirmed the predominance of HIV-1 group M (98.5%), a very low prevalence (O was found at around 0.6% (95% confidence interval: 0.4–0.8%), indicating that the frequency of this virus in Cameroon has remained stable over the last decades. However, we found an extensive high genetic diversity within this HIV-1 group, that resulted from previous steady increase on the effective number of HIV-1 group O infections through time, and the current distribution of the circulating viral strains still does not allow classification as subtypes. The frequency of dual infections with HIV-1 group M and group O was 0.8% (95% confidence interval: 0.6–1.0%), but we found no recombinant forms in co-infected patients. Natural resistance to integrase inhibitors was not identified, although we found several mutations considered as natural polymorphisms. Our study shows that infections with HIV-1 group O can be adequately managed in countries where the virus circulates, but this complex virus still represents a challenge for diagnostics and monitoring strategies. PMID:26371064

Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of The West African Database to evaluate AIDS collaboration

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Tchounga, Boris K; Inwoley, Andre; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Bado, Guillaume; Minga, Albert; Hawerlander, Denise; Kane, Coumba; Eholie, Serge P; Dabis, François; Ekouevi, Didier K

2014-01-01

Introduction West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first-line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV-2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. Method A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Côte d’Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Côte d’Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII® (HIV-1&2 ImmunoComb BiSpot – Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). Results A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4≥500 cells/mm3 and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII® and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII® and in-house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV-2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). Conclusions Patients with HIV-2 mono-infection are correctly

Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements

Energy Technology Data Exchange (ETDEWEB)

Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T., E-mail: a.t.das@amc.uva.nl

2016-01-15

Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

Directory of Open Access Journals (Sweden)

Damien C Tully

2016-05-01

Full Text Available Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU, we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

Fatal nevirapine-induced Stevens- Johnson syndrome with HIV ...

African Journals Online (AJOL)

2014-06-01

Jun 1, 2014 ... of Stevens-Johnson syndrome highlights the dilemmas and complications that may arise when prescribing multiple medications in HIV-associated ... HIV enters the central nervous system early in the course of HIV ... Affected individuals with SJS/TEN are genetically predisposed to developing severe ...

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.

Science.gov (United States)

Guidi, Monia; Foletti, Giuseppe; McLaren, Paul; Cavassini, Matthias; Rauch, Andri; Tarr, Philip E; Lamy, Olivier; Panchaud, Alice; Telenti, Amalio; Csajka, Chantal; Rotger, Margalida

2015-01-01

Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Neuro-HIV: Nervous System Manifestations of HIV Infection- A Review

African Journals Online (AJOL)

Neuro-HIV: Nervous System Manifestations of HIV Infection- A Review. ... Open Access DOWNLOAD FULL TEXT Subscription or Fee Access ... The early detection of neurological disease due to HIV infection is of paramount importance to the clinician as there are implications not just for management but also for prognosis.

HIV-1 transmission linkage in an HIV-1 prevention clinical trial

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Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

2009-01-01

HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

A study of HIV-1 genetic diversity in the Czech Republic: 1986-2007

Czech Academy of Sciences Publication Activity Database

Linka, M.; Brůčková, M.; Malý, M.; Vandasová, J.; Stanková, M.; Reiniš, Milan

2009-01-01

Roč. 16, č. 4 (2009), s. 175-177 ISSN 1210-7778 Grant - others:MZd ČR(CZ) NR7843 Institutional research plan: CEZ:AV0Z50520514 Keywords : HIV-1 subtyping * non-B subtypes * molecular epidemiology Subject RIV: EB - Genetics ; Molecular Biology

Biological and genetic evolution of HIV type 1 in two siblings with different patterns of disease progression.

Science.gov (United States)

Ripamonti, Chiara; Leitner, Thomas; Laurén, Anna; Karlsson, Ingrid; Pastore, Angela; Cavarelli, Mariangela; Antonsson, Liselotte; Plebani, Anna; Fenyö, Eva Maria; Scarlatti, Gabriella

2007-12-01

To investigate the immunological and virological factors that may lead to different patterns of disease progression characteristic of HIV-1-infected children, two HIV-1-infected siblings, a slow and a fast progressor, were followed prospectively before the onset of highly active antiretroviral therapy. Viral coreceptor usage, including the use of CCR5/CXCR4 chimeric receptors, macrophage tropism, and sensitivity to the CC-chemokine RANTES, has been studied. An autologous and heterologous neutralizing antibody response has been documented using peripheral blood mononuclear cells- and GHOST(3) cell line-based assays. Viral evolution was investigated by env C2-V3 region sequence analysis. Although both siblings were infected with HIV-1 of the R5 phenotype, their viruses showed important biological differences. In the fast progressor there was a higher RANTES sensitivity of the early virus, an increased trend to change the mode of CCR5 receptor use, and a larger genetic evolution. Both children developed an autologous neutralizing antibody response starting from the second year with evidence of the continuous emergence of resistant variants. A marked viral genetic and phenotypic evolution was documented in the fast progressor sibling, which is accompanied by a high viral RANTES sensitivity and persistent neutralizing antibodies.

Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

Science.gov (United States)

Joshi, Anjali; Lee, Raphael T. C.; Mohl, Jonathan; Sedano, Melina; Khong, Wei Xin; Ng, Oon Tek; Maurer-Stroh, Sebastian; Garg, Himanshu

2014-01-01

The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4+ T cell loss. However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. A specific role of these residues was also confirmed experimentally. These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4+ T cells. Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype. PMID:24265318

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

OpenAIRE

Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.

2010-01-01

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. W...

Frequency of HIV type 2 infections among blood donor population from India: A 10-year experience

Directory of Open Access Journals (Sweden)

Kannangai R

2010-01-01

Full Text Available Purpose: In India, HIV-2 epidemic is alongside with HIV-1. Blood banks are introducing nucleic acid testing (NAT for screening. The limitation of NAT systems is the inability to detect HIV-2. Materials and Method : An analysis of HIV screening of a blood bank at a tertiary care center from 1998 to 2007 was carried out. Results : A total of 175026 donors were screened by serological assays and 789 were reactive for HIV antibody. Only 478 (61% were confirmed positive by Western blot/immunoblot. There were 465 (97.2% donations positive for HIV-1, 6 (1.3% for HIV-2 (monotypic infection and 7 (1.5% for HIV-1 and HIV-2 (dual infection. Conclusion : We show the presence of HIV-2 infection among the blood donors and the need for incorporating HIV-2 detection also in the NAT systems.

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Science.gov (United States)

Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J; Telenti, Amalio; de Bakker, Paul I W; Walker, Bruce D; Ripke, Stephan; Brumme, Chanson J; Pulit, Sara L; Carrington, Mary; Kadie, Carl M; Carlson, Jonathan M; Heckerman, David; Graham, Robert R; Plenge, Robert M; Deeks, Steven G; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P; Guiducci, Candace; Gupta, Namrata; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L; Lemay, Paul; O'Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L; Vine, Seanna; Addo, Marylyn M; Allen, Todd M; Altfeld, Marcus; Henn, Matthew R; Le Gall, Sylvie; Streeck, Hendrik; Haas, David W; Kuritzkes, Daniel R; Robbins, Gregory K; Shafer, Robert W; Gulick, Roy M; Shikuma, Cecilia M; Haubrich, Richard; Riddler, Sharon; Sax, Paul E; Daar, Eric S; Ribaudo, Heather J; Agan, Brian; Agarwal, Shanu; Ahern, Richard L; Allen, Brady L; Altidor, Sherly; Altschuler, Eric L; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C; Benson, Anne M; Berger, Judith; Bernard, Nicole F; Bernard, Annette M; Birch, Christopher; Bodner, Stanley J; Bolan, Robert K; Boudreaux, Emilie T; Bradley, Meg; Braun, James F; Brndjar, Jon E; Brown, Stephen J; Brown, Katherine; Brown, Sheldon T; Burack, Jedidiah; Bush, Larry M; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H; Carmichael, J Kevin; Casey, Kathleen K; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T; Chez, Nancy; Chirch, Lisa M; Cimoch, Paul J; Cohen, Daniel; Cohn, Lillian E; Conway, Brian; Cooper, David A; Cornelson, Brian; Cox, David T; Cristofano, Michael V; Cuchural, George; Czartoski, Julie L; Dahman, Joseph M; Daly, Jennifer S; Davis, Benjamin T; Davis, Kristine; Davod, Sheila M; DeJesus, Edwin; Dietz, Craig A; Dunham, Eleanor; Dunn, Michael E; Ellerin, Todd B; Eron, Joseph J; Fangman, John J W; Farel, Claire E; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A; French, Neel K; Fuchs, Jonathan D; Fuller, Jon D; Gaberman, Jonna; Gallant, Joel E; Gandhi, Rajesh T; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C; Gaultier, Cyril R; Gebre, Wondwoosen; Gilman, Frank D; Gilson, Ian; Goepfert, Paul A; Gottlieb, Michael S; Goulston, Claudia; Groger, Richard K; Gurley, T Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W David; Harrigan, P Richard; Hawkins, Trevor N; Heath, Sonya; Hecht, Frederick M; Henry, W Keith; Hladek, Melissa; Hoffman, Robert P; Horton, James M; Hsu, Ricky K; Huhn, Gregory D; Hunt, Peter; Hupert, Mark J; Illeman, Mark L; Jaeger, Hans; Jellinger, Robert M; John, Mina; Johnson, Jennifer A; Johnson, Kristin L; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C; Kauffman, Carol A; Khanlou, Homayoon; Killian, Robert K; Kim, Arthur Y; Kim, David D; Kinder, Clifford A; Kirchner, Jeffrey T; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P Todd; Kurisu, Wayne; Kwon, Douglas S; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M; Lee, David M; Lee, Jean M L; Lee, Marah J; Lee, Edward T Y; Lemoine, Janice; Levy, Jay A; Llibre, Josep M; Liguori, Michael A; Little, Susan J; Liu, Anne Y; Lopez, Alvaro J; Loutfy, Mono R; Loy, Dawn; Mohammed, Debbie Y; Man, Alan; Mansour, Michael K; Marconi, Vincent C; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N; Martin, Harold L; Mayer, Kenneth Hugh; McElrath, M Juliana; McGhee, Theresa A; McGovern, Barbara H; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X; Menezes, Prema; Mesa, Greg; Metroka, Craig E; Meyer-Olson, Dirk; Miller, Andy O; Montgomery, Kate; Mounzer, Karam C; Nagami, Ellen H; Nagin, Iris; Nahass, Ronald G; Nelson, Margret O; Nielsen, Craig; Norene, David L; O'Connor, David H; Ojikutu, Bisola O; Okulicz, Jason; Oladehin, Olakunle O; Oldfield, Edward C; Olender, Susan A; Ostrowski, Mario; Owen, William F; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M; Perlmutter, Aaron M; Pierce, Michael N; Pincus, Jonathan M; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J; Rhame, Frank S; Richards, Constance Shamuyarira; Richman, Douglas D; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C; Rosenberg, Eric S; Rosenthal, Daniel; Ross, Polly E; Rubin, David S; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R; Sanchez, William C; Sanjana, Veeraf M; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M; Shalit, Peter; Shay, William; Shirvani, Vivian N; Silebi, Vanessa I; Sizemore, James M; Skolnik, Paul R; Sokol-Anderson, Marcia; Sosman, James M; Stabile, Paul; Stapleton, Jack T; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F Lisa; Stone, Valerie E; Stone, David R; Tambussi, Giuseppe; Taplitz, Randy A; Tedaldi, Ellen M; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A; Trinh, Phuong D; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J; Vecino, Isabel; Vega, Vilma M; Veikley, Wenoah; Wade, Barbara H; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J; Warner, Daniel A; Weber, Robert D; Webster, Duncan; Weis, Steve; Wheeler, David A; White, David J; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G; van't Wout, Angelique; Wright, David P; Yang, Otto O; Yurdin, David L; Zabukovic, Brandon W; Zachary, Kimon C; Zeeman, Beth; Zhao, Meng

2010-12-10

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Science.gov (United States)

Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J.; Telenti, Amalio; de Bakker, Paul I.W.; Walker, Bruce D.; Jia, Xiaoming; McLaren, Paul J.; Ripke, Stephan; Brumme, Chanson J.; Pulit, Sara L.; Telenti, Amalio; Carrington, Mary; Kadie, Carl M.; Carlson, Jonathan M.; Heckerman, David; de Bakker, Paul I.W.; Pereyra, Florencia; de Bakker, Paul I.W.; Graham, Robert R.; Plenge, Robert M.; Deeks, Steven G.; Walker, Bruce D.; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M.; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P.; Guiducci, Candace; Gupta, Namrata; Carrington, Mary; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Pereyra, Florencia; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L.; Lemay, Paul; O’Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L.; Vine, Seanna; Addo, Marylyn M.; Allen, Todd M.; Altfeld, Marcus; Henn, Matthew R.; Le Gall, Sylvie; Streeck, Hendrik; Walker, Bruce D.; Haas, David W.; Kuritzkes, Daniel R.; Robbins, Gregory K.; Shafer, Robert W.; Gulick, Roy M.; Shikuma, Cecilia M.; Haubrich, Richard; Riddler, Sharon; Sax, Paul E.; Daar, Eric S.; Ribaudo, Heather J.; Agan, Brian; Agarwal, Shanu; Ahern, Richard L.; Allen, Brady L.; Altidor, Sherly; Altschuler, Eric L.; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J.; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C.; Benson, Anne M.; Berger, Judith; Bernard, Nicole F.; Bernard, Annette M.; Birch, Christopher; Bodner, Stanley J.; Bolan, Robert K.; Boudreaux, Emilie T.; Bradley, Meg; Braun, James F.; Brndjar, Jon E.; Brown, Stephen J.; Brown, Katherine; Brown, Sheldon T.; Burack, Jedidiah; Bush, Larry M.; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H.; Carmichael, J. Kevin; Casey, Kathleen K.; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T.; Chez, Nancy; Chirch, Lisa M.; Cimoch, Paul J.; Cohen, Daniel; Cohn, Lillian E.; Conway, Brian; Cooper, David A.; Cornelson, Brian; Cox, David T.; Cristofano, Michael V.; Cuchural, George; Czartoski, Julie L.; Dahman, Joseph M.; Daly, Jennifer S.; Davis, Benjamin T.; Davis, Kristine; Davod, Sheila M.; Deeks, Steven G.; DeJesus, Edwin; Dietz, Craig A.; Dunham, Eleanor; Dunn, Michael E.; Ellerin, Todd B.; Eron, Joseph J.; Fangman, John J.W.; Farel, Claire E.; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A.; French, Neel K.; Fuchs, Jonathan D.; Fuller, Jon D.; Gaberman, Jonna; Gallant, Joel E.; Gandhi, Rajesh T.; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C.; Gaultier, Cyril R.; Gebre, Wondwoosen; Gilman, Frank D.; Gilson, Ian; Goepfert, Paul A.; Gottlieb, Michael S.; Goulston, Claudia; Groger, Richard K.; Gurley, T. Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W. David; Harrigan, P. Richard; Hawkins, Trevor N.; Heath, Sonya; Hecht, Frederick M.; Henry, W. Keith; Hladek, Melissa; Hoffman, Robert P.; Horton, James M.; Hsu, Ricky K.; Huhn, Gregory D.; Hunt, Peter; Hupert, Mark J.; Illeman, Mark L.; Jaeger, Hans; Jellinger, Robert M.; John, Mina; Johnson, Jennifer A.; Johnson, Kristin L.; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C.; Kauffman, Carol A.; Khanlou, Homayoon; Killian, Robert K.; Kim, Arthur Y.; Kim, David D.; Kinder, Clifford A.; Kirchner, Jeffrey T.; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P. Todd; Kurisu, Wayne; Kwon, Douglas S.; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M.; Lee, David M.; Lee, Jean M.L.; Lee, Marah J.; Lee, Edward T.Y.; Lemoine, Janice; Levy, Jay A.; Llibre, Josep M.; Liguori, Michael A.; Little, Susan J.; Liu, Anne Y.; Lopez, Alvaro J.; Loutfy, Mono R.; Loy, Dawn; Mohammed, Debbie Y.; Man, Alan; Mansour, Michael K.; Marconi, Vincent C.; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N.; Martin, Harold L.; Mayer, Kenneth Hugh; McElrath, M. Juliana; McGhee, Theresa A.; McGovern, Barbara H.; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X.; Menezes, Prema; Mesa, Greg; Metroka, Craig E.; Meyer-Olson, Dirk; Miller, Andy O.; Montgomery, Kate; Mounzer, Karam C.; Nagami, Ellen H.; Nagin, Iris; Nahass, Ronald G.; Nelson, Margret O.; Nielsen, Craig; Norene, David L.; O’Connor, David H.; Ojikutu, Bisola O.; Okulicz, Jason; Oladehin, Olakunle O.; Oldfield, Edward C.; Olender, Susan A.; Ostrowski, Mario; Owen, William F.; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M.; Perlmutter, Aaron M.; Pierce, Michael N.; Pincus, Jonathan M.; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C.; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J.; Rhame, Frank S.; Richards, Constance Shamuyarira; Richman, Douglas D.; Robbins, Gregory K.; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C.; Rosenberg, Eric S.; Rosenthal, Daniel; Ross, Polly E.; Rubin, David S.; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R.; Sanchez, William C.; Sanjana, Veeraf M.; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M.; Shalit, Peter; Shay, William; Shirvani, Vivian N.; Silebi, Vanessa I.; Sizemore, James M.; Skolnik, Paul R.; Sokol-Anderson, Marcia; Sosman, James M.; Stabile, Paul; Stapleton, Jack T.; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F. Lisa; Stone, Valerie E.; Stone, David R.; Tambussi, Giuseppe; Taplitz, Randy A.; Tedaldi, Ellen M.; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A.; Trinh, Phuong D.; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J.; Vecino, Isabel; Vega, Vilma M.; Veikley, Wenoah; Wade, Barbara H.; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J.; Warner, Daniel A.; Weber, Robert D.; Webster, Duncan; Weis, Steve; Wheeler, David A.; White, David J.; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G.; Wout, Angelique van’t; Wright, David P.; Yang, Otto O.; Yurdin, David L.; Zabukovic, Brandon W.; Zachary, Kimon C.; Zeeman, Beth; Zhao, Meng

2011-01-01

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection. PMID:21051598

Labeling of multiple HIV-1 proteins with the biarsenical-tetracysteine system.

Directory of Open Access Journals (Sweden)

Cândida F Pereira

Full Text Available Due to its small size and versatility, the biarsenical-tetracysteine system is an attractive way to label viral proteins for live cell imaging. This study describes the genetic labeling of the human immunodeficiency virus type 1 (HIV-1 structural proteins (matrix, capsid and nucleocapsid, enzymes (protease, reverse transcriptase, RNAse H and integrase and envelope glycoprotein 120 with a tetracysteine tag in the context of a full-length virus. We measure the impact of these modifications on the natural virus infection and, most importantly, present the first infectious HIV-1 construct containing a fluorescently-labeled nucleocapsid protein. Furthermore, due to the high background levels normally associated with the labeling of tetracysteine-tagged proteins we have also optimized a metabolic labeling system that produces infectious virus containing the natural envelope glycoproteins and specifically labeled tetracysteine-tagged proteins that can easily be detected after virus infection of T-lymphocytes. This approach can be adapted to other viral systems for the visualization of the interplay between virus and host cell during infection.

Performance comparison of the 4th generation Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA on the EVOLIS™ automated system versus Abbott ARCHITECT HIV Ag/Ab Combo, Ortho Anti-HIV 1+2 EIA on Vitros ECi and Siemens HIV-1/O/2 enhanced on Advia Centaur.

Science.gov (United States)

Mitchell, Elizabeth O; Stewart, Greg; Bajzik, Olivier; Ferret, Mathieu; Bentsen, Christopher; Shriver, M Kathleen

2013-12-01

A multisite study was conducted to evaluate the performance of the Bio-Rad 4th generation GS HIV Combo Ag/Ab EIA versus Abbott 4th generation ARCHITECT HIV Ag/Ab Combo. The performance of two 3rd generation EIAs, Ortho Diagnostics Anti-HIV 1+2 EIA and Siemens HIV 1/O/2 was also evaluated. Study objective was comparison of analytical HIV-1 p24 antigen detection, sensitivity in HIV-1 seroconversion panels, specificity in blood donors and two HIV false reactive panels. Analytical sensitivity was evaluated with International HIV-1 p24 antigen standards, the AFFSAPS (pg/mL) and WHO 90/636 (IU/mL) standards; sensitivity in acute infection was compared on 55 seroconversion samples, and specificity was evaluated on 1000 negative blood donors and two false reactive panels. GS HIV Combo Ag/Ab demonstrated better analytical HIV antigen sensitivity compared to ARCHITECT HIV Ag/Ab Combo: 0.41 IU/mL versus 1.2 IU/mL (WHO) and 12.7 pg/mL versus 20.1 pg/mL (AFSSAPS); GS HIV Combo Ag/Ab EIA also demonstrated slightly better specificity compared to ARCHITECT HIV Ag/Ab Combo (100% versus 99.7%). The 4th generation HIV Combo tests detected seroconversion 7-11 days earlier than the 3rd generation HIV antibody only EIAs. Both 4th generation immunoassays demonstrated excellent performance in sensitivity, with the reduction of the serological window period (7-11 days earlier detection than the 3rd generation HIV tests). However, GS HIV Combo Ag/Ab demonstrated improved HIV antigen analytical sensitivity and slightly better specificity when compared to ARCHITECT HIV Ag/Ab Combo assay, with higher positive predictive values (PPV) for low prevalence populations. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination.

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Jia, Lei; Li, Lin; Gui, Tao; Liu, Siyang; Li, Hanping; Han, Jingwan; Guo, Wei; Liu, Yongjian; Li, Jingyun

2016-09-21

With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination. Thus, the results revealed an unexpected disagreement between intersubtype similarity and breakpoint distribution, which were further confirmed by genetic similarity analysis. Our analysis reveals a critical conflict between results from natural HIV-1 isolates and those from HIV-1-based assay vectors in which genetic similarity has been shown to be a very critical factor promoting recombination. These results indicate the region with high-pairing probabilities may be a more fundamental factor affecting HIV-1 recombination than sequence similarity in natural HIV-1 infections. Our

Marcadores virológicos no convencionales en pacientes infectados con el virus de la inmunodeficiencia humana: ADN HIV-T, ADN HIV- 2LTR y ARN de HIV Non conventional virological markers in HIV-infected patients: T-HIV DNA, 2LTR-HIV DNA and HIV RNA

Directory of Open Access Journals (Sweden)

Rosana Gariglio

2004-10-01

Full Text Available La terapia antirretroviral de alta eficacia (TAAE induce una reducción marcada y persistente de la viremia plasmática, contribuyendo a disminuir la mortalidad y morbilidad de los pacientes HIV-positivos. Así, la carga viral (CV es el método de referencia para evaluar la eficacia terapéutica. Sin embargo, aun en presencia de una TAAE eficiente no se ha logrado la erradicación viral. En este estudio analizamos la presencia del ADN total de HIV (ADN HIV-T, del ADN no integrado con 2LTR (ADN HIV-2LTR y del ARN de HIV, en un grupo de 55 pacientes HIV-positivos en distintos estadios clínicos, con y sin TAAE, mediante ensayos de PCR con revelado colorimétrico en microplaca, optimizados en nuestro laboratorio. La sensibilidad clínica del ARN del HIV fue evaluada con el bDNA, resultando del 74% y del 64%, respectivamente, con una concordancia del 85%. Este ensayo podría ser utilizado en el seguimiento de pacientes bajo TAAE. El ADN HIV-2LTR resultó positivo en el 54% aunque estuvo ausente en pacientes con elevada CV. Este marcador se consideraba un producto lábil y su presencia se asociaba a infección reciente. Sin embargo, actuales evidencias ponen en discusión su estabilidad por lo que su significado clínico debe ser reconsiderado. La ausencia del ADN HIV-2LTR en pacientes con CV detectable puede relacionarse con la heterogeneidad de la secuencia utilizada para su detección. El ADN HIV-T estuvo presente en el 100% de las muestras y resultaría relevante como marcador de remisión cuando se dispongan de terapias que efectivamente erradiquen la infección.Highly active antiretroviral therapy (HAART induces a persistent reduction of the plasmatic viremia, contributing to decrease mortality and morbidity of infected people with human immunodeficiency virus (HIV. Thus, viral load (VL is the reference method to evaluate therapy effectiveness. However, even in the presence of efficient HAART viral eradication was yet not achieved. In this

Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

African Journals Online (AJOL)

out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web ...

Therapeutic Vaccine Against HIV, Viral Variability, Cytotoxic T Lymphocyte Epitopes, and Genetics of Patients.

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Fleury, Herve; Tumiotto, Camille; Bellecave, Pantxika; Recordon-Pinson, Patricia

2018-01-01

The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles. There is a need to find a balance between the conservation of cytotoxic T lymphocyte (CTL) epitopes and presentation by HLA alleles. The pathway is a narrow one between adaptation of the virus to HLA I restriction and the definition of conserved proviral CTL epitopes presentable by HLA I alleles. It is likely that the genetics of patients will need to be considered for HIV-1 vaccine studies and that multidisciplinary collaboration will be essential in this field of infectious diseases.

Building a durable response to HIV/AIDS: implications for health systems.

Science.gov (United States)

Atun, Rifat; Bataringaya, Jacqueline

2011-08-01

The remarkable rise in investments for HIV control programs in 2003-2010 enabled an unprecedented expansion of access to HIV services in low-income and middle-income countries. By the end of 2010, more than 5.2 million people were receiving antiretroviral therapy (ART), which transformed HIV infection, once a death sentence, into a long-term illness. The rapid expansion in the number of persons receiving ART means that health systems must continue to provide acute life-saving care for those with advanced HIV/AIDS although also providing chronic care services to expanding cohorts of more stable patients who are doing well on ART. This expansion also means a transition from an emergency response to the epidemic, characterized by a public health approach, to a more integrated and durable approach to HIV prevention, care, and treatment services that fosters individualized care for those requiring long-term antiretroviral treatment. Yet most low-income and middle-income countries, which have weak health systems, are poorly prepared to make this transition. In this article, we highlight the challenges health systems face in developing a sustained and durable response to HIV/AIDS. The article analyses the readiness of health systems to combine rapid expansion of ART access with long-term treatment and continuity of care for a growing cohort of patients. We argue that effective management of a transition from an emergency AIDS response to long-term programatic strategies will require a paradigm shift that enables leveraging investments in HIV to build sustainable health systems for managing large cohorts of patients receiving ART although meeting the immediate needs of those who remain without access to HIV treatment and care.

HIV type 2 epidemic in Spain: challenges and missing opportunities.

Science.gov (United States)

de Mendoza, Carmen; Cabezas, Teresa; Caballero, Estrella; Requena, Silvia; Amengual, María J; Peñaranda, María; Sáez, Ana; Tellez, Raquel; Lozano, Ana B; Treviño, Ana; Ramos, José M; Pérez, José L; Barreiro, Pablo; Soriano, Vicente

2017-06-19

: HIV type 2 (HIV-2) is a neglected virus despite estimates of 1-2 million people infected worldwide. HIV-2 is less efficiently transmitted than HIV-1 by sex and from mother to child. Although AIDS may develop in HIV-2 carriers, it takes longer than in HIV-1-infected patients. In contrast with HIV-1 infection, there is no global pandemic caused by HIV-2, as the virus is largely confined to West Africa. In a less extent and due to socioeconomic ties and wars, HIV-2 is prevalent in Portugal and its former colonies in Brazil, India, Mozambique and Angola. Globally, HIV-2 infections are steadily declining over time. A total of 338 cases of HIV-2 infection had been reported at the Spanish HIV-2 registry until December 2016, of whom 63% were men. Overall 72% were sub-Saharan Africans, whereas 16% were native Spaniards. Dual HIV-1 and HIV-2 coinfection was found in 9% of patients. Heterosexual contact was the most likely route of HIV-2 acquisition in more than 90% of cases. Roughly one-third presented with CD4 cell counts less than 200 cells/μl and/or AIDS clinical events. Plasma HIV-2 RNA was undetectable at baseline in 40% of patients. To date, one-third of HIV-2 carriers have received antiretroviral therapy, using integrase inhibitors 32 individuals. New diagnoses of HIV-2 in Spain have remained stable since 2010 with an average of 15 cases yearly. Illegal immigration from Northwestern African borders accounts for over 75% of new HIV-2 diagnoses. Given the relatively large community of West Africans already living in Spain and the continuous flux of immigration from endemic regions, HIV-2 infection either alone or as coinfection with HIV-1 should be excluded once in all HIV-seroreactive persons, especially when showing atypical HIV serological profiles, immunovirological disconnect (CD4 cell count loss despite undetectable HIV-1 viremia) and/or high epidemiological risks (birth in or sex partners from endemic regions).

Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected women receiving effective combination antiretroviral therapy.

Science.gov (United States)

Péré, Héléne; Rascanu, Aida; LeGoff, Jérome; Matta, Mathieu; Bois, Frédéric; Lortholary, Olivier; Leroy, Valériane; Launay, Odile; Bélec, Laurent

2016-03-01

The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women naive for antiretroviral therapy initiating cART and 5 women with virological failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive. Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from baseline after one month of cART, in parallel in paired plasma and cervicovaginal secretions. In contrast, HIV-1 DNA loads did not show significant variations from baseline up to 18 months of treatment in both systemic and genital compartments. HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV-2 shedding in the genital compartment was observed in 11% of cervicovaginal samples at baseline and in 16% after initiating or switching cART. Cervicovaginal HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time, but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2 replication frequently occurred despite effective cART in HSV-2-/HIV-1-co-infected women. Genital HSV-2 replication under cART does not influence cervicovaginal HIV-1 RNA or DNA shedding. © The Author(s) 2015.

Development of a unified web-based national HIV/AIDS information system in China.

Science.gov (United States)

Mao, Yurong; Wu, Zunyou; Poundstone, Katharine; Wang, Changhe; Qin, Qianqian; Ma, Ye; Ma, Wei

2010-12-01

In the past, many data collection systems were in operation for different HIV/AIDS projects in China. We describe the creation of a unified, web-based national HIV/AIDS information system designed to streamline data collection and facilitate data use. Integration of separate HIV/AIDS data systems was carried out in three phases. Phase 1, from January 2006 to December 2007, involved creating a set of unified data collection forms that took into account existing program needs and the reporting requirements of various international organizations. Phase 2, from January to October 2007, involved creating a web-based platform to host the integrated HIV/AIDS data collection system. Phase 3, from November to December 2007, involved pilot testing the new, integrated system prior to nationwide application. Eight web-based data collection subsystems based on one platform began operation on 1 January 2008. These eight subsystems cover: (i) HIV/AIDS case reporting; (ii) HIV testing and counselling; (iii) antiretroviral treatment (ART) for adults; (iv) ART for children; (v) behavioural interventions for high-risk groups; (vi) methadone maintenance treatment; (vii) sentinel and behavioural surveillance; and (viii) local county background information. The system provides real-time data to monitor HIV testing, prevention and treatment programs across the country. China's new unified, web-based HIV/AIDS information system has improved the efficiency of data collection, reporting, analysis and use, as well as data quality and security. It is a powerful tool to support policy making, program evaluation and implementation of the national HIV/AIDS program and, thus, may serve a model for other countries.

Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

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Wan-Lin Yang

2015-03-01

Full Text Available Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS. All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V to 2.7/100-person-years;[0.7, 10.9] (for 215D. RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs. When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic tuberculosis

DEFF Research Database (Denmark)

Seng, R; Gustafson, P; Gomes, VF

2002-01-01

BACKGROUND: HIV-1 infection is associated with an increased incidence of and mortality from tuberculosis. Few community studies have examined the effect of HIV-2 on tuberculosis. METHODS: We investigated the association between HIV-1, HIV-2 and active tuberculosis in four districts (population 42...

HIV-1 transmitted drug resistance and genetic diversity among patients from Piauí State, Northeast Brazil.

Science.gov (United States)

Moura, Maria Edileuza Soares; da Guarda Reis, Mônica Nogueira; Lima, Yanna Andressa Ramos; Eulálio, Kelsen Dantas; Cardoso, Ludimila Paula Vaz; Stefani, Mariane Martins Araújo

2015-05-01

HIV-1 transmitted-drug-resistance and genetic diversity are dynamic and may differ in distinct locations/risk groups. In Brazil, increased AIDS incidence and related mortality have been detected in the Northeast region, differently from the epicenter in the Southeast. This cross-sectional study describes transmitted-dru- resistance and HIV-1 subtypes in protease/PR and reverse transcriptase/RT regions among antiretroviral naïve patients from Piauí State, Northeast Brazil. Among 96 patients recruited 89 (92.7%) had HIV-1 PR/RT regions sequenced: 44 females and 45 males, 22 self-declared as men who have sex with men. Transmitted-drug-resistance was investigated by CPR tool (Stanford HIV-1 Drug Resistance/SDRM). HIV-1 subtypes were assigned by REGA and phylogenetic inference. Overall, transmitted-drug-resistance rate was 11.2% (10/89; CI 95%: 5.8-19.1%); 22.7% among men who have sex with men (5/22; CI 95%: 8.8-43.4%), 10% in heterosexual men (2/20; CI 95%: 1.7-29.3%) and 6.8% in women (3/44; CI 95%: 1.8-17.4%). Singleton mutations to protease-inhibitor/PI, nucleoside-reverse-transcriptase-inhibitor/NRTI or non-nucleoside-reverse-transcriptase-inhibitor/NNRTI predominated (8/10): PI mutations (M46L, V82F, L90M); NRTI mutations (M41L, D67N) and NNRTI mutations (K103N/S). Dual class resistance mutations to NRTI and NNRTI were observed: T215L (NRTI), Y188L (NNRTI) and T215N (NRTI), F227L (NNRTI). Subtype B prevailed (86.6%; 77/89), followed by subtype F1 (1.1%, 1/89) and subtype C (1.1%, 1/89). B/F1 and B/C intersubtype recombinants represented 11.2% (10/89). In Piauí State extensive testing of incidence and transmitted-drug-resistance in all populations with risk behaviors may help control AIDS epidemic locally. © 2015 Wiley Periodicals, Inc.

Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

Science.gov (United States)

Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

2010-09-01

With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tests (INNO-LIA HIV-I/II Score) and NEW LAV BLOT II (Bio-Rad). Four hundred and forty three sequential stored HIV-positive serum samples, of known HIV-type, were evaluated. Genie II HIV1/HIV2, Immunoflow HIV1-HIV2 and SD Bioline HIV 1/2 3.0 had 100% sensitivity (95% CI, 98.9-100%) while for First Response HIV Card Test 1-2.0 this was 99.5% (95% CI, 98.2%-99.9%). In terms of discriminatory capacity, Genie II HIV1/HIV2 identified 382/ 384(99.5%) HIV-1 samples, 49/ 52(95%) HIV-2 and 7/7(100%) HIV-positive untypable samples. Immunoflow HIV1-HIV2 identified 99% HIV-1, 67% HIV-2 and all HIV-positive untypable samples. First Response HIV Card Test 1-2.0 identified 94% HIV-1, 64% HIV-2 and 57% HIV-positive untypable samples. SD-Bioline HIV 1/2 3.0 was the worst overall performer identifying 65% HIV-1, 69% HIV-2 and all HIV-positive untypable samples. The use of SD Bioline HIV 1/2 3.0 (the current standard in Guinea-Conakry) as a discriminatory HIV test is poor and may be best replaced by Immunoflow HIV1-HIV2. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Lower genetic variability of HIV-1 and antiretroviral drug resistance in pregnant women from the state of Pará, Brazil.

Science.gov (United States)

Machado, Luiz Fernando Almeida; Costa, Iran Barros; Folha, Maria Nazaré; da Luz, Anderson Levy Bessa; Vallinoto, Antonio Carlos Rosário; Ishak, Ricardo; Ishak, Marluisa Oliveira Guimarães

2017-04-12

The present study aimed to describe the genetic diversity of HIV-1, as well as the resistance profile of the viruses identified in HIV-1 infected pregnant women under antiretroviral therapy in the state of Pará, Northern Brazil. Blood samples were collected from 45 HIV-1 infected pregnant to determine the virus subtypes according to the HIV-1 protease (PR) gene and part of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of these regions. Drug resistance mutations and susceptibility to antiretroviral drugs were analyzed by the Stanford HIV Drug Resistance Database. Out of 45 samples, only 34 could be amplified for PR and 30 for RT. Regarding the PR gene, subtypes B (97.1%) and C (2.9%) were identified; for the RT gene, subtypes B (90.0%), F (6.7%), and C (3.3%) were detected. Resistance to protease inhibitors (PI) was identified in 5.8% of the pregnant, and mutations conferring resistance to nucleoside reverse transcriptase inhibitors were found in 3.3%, while mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors were found in 3.3%. These results showed a low frequency of strains resistant to antiretroviral drugs, the prevalence of subtypes B and F, and the persistent low transmission of subtype C in pregnant of the state of Pará, Brazil.

Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

Science.gov (United States)

Jespersen, Sanne; Hønge, Bo Langhoff; Esbjörnsson, Joakim; Medina, Candida; da Silva Té, David; Correira, Faustino Gomes; Laursen, Alex Lund; Østergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian

2016-02-01

Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/μl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women. © 2015 John Wiley & Sons Ltd.

The changing HIV-1 genetic characteristics and transmitted drug resistance among recently infected population in Yunnan, China.

Science.gov (United States)

Chen, M; Jia, M H; Ma, Y L; Luo, H B; Chen, H C; Yang, C J; Dai, J; Yang, L; Dong, L J; Lu, R; Song, L J; Han, Y; Lu, J Y; Cheung, A K L; Chen, Z W; Lu, L

2018-04-01

Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991-1999 and 1994-1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994-1998 and 2001-2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

Characterization of LEDGF/p75 genetic variants and association with HIV-1 disease progression.

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Peter Messiaen

Full Text Available BACKGROUND: As Lens epithelium-derived growth factor (LEDGF/p75 is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs. Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 genetic variation, mRNA expression and HIV-1 disease progression in order to guide future clinical use of LEDGINs. METHODS: Samples were derived from a therapy-naïve cohort at Ghent University Hospital and a Spanish long-term-non-progressor cohort. High-resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs in the coding region, flanking intronic regions and full 3'UTR of LEDGF/p75. In addition, two intronic tagSNPs were screened based on previous indication of influencing HIV disease. LEDGF/p75 mRNA was quantified in patient peripheral blood mononuclear cells (PBMC using RT-qPCR. RESULTS: 325 samples were investigated from patients of Caucasian (n = 291 and African (n = 34 origin, including Elite (n = 49 and Viremic controllers (n = 62. 21 SNPs were identified, comprising five in the coding region and 16 in the non-coding regions and 3'UTR. The variants in the coding region were infrequent and had no major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828 was significantly under-represented in Caucasian patients (P<0.0001 compared to healthy controls (HapMap. Two SNPs showed a non-significant trend towards association with slower disease progression but not with LEDGF/p75 expression. The observed variation in LEDGF/p75 expression was not correlated with disease progression. CONCLUSIONS: LEDGF/p75 is a highly conserved protein. Two non-coding polymorphisms were identified indicating a correlation with disease outcome, but further

Worldwide molecular epidemiology of HIV

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Henry I Z Requejo

2006-04-01

Full Text Available Human immunodeficiency virus (HIV is the worldwide disseminated causative agent of acquired immunodeficiency syndrome (AIDS. HIV is a member of the Lentivirus genus of Retroviridae family and is grouped in two types named HIV-1 and HIV-2. These viruses have a notable ability to mutate and adapt to the new conditions of human environment. A large incidence of errors at the transcriptional level results in changes on the genetic bases during the reproductive cycle. The elevated genomic variability of HIV has carried important implications for the diagnosis, treatment and prevention as well as epidemiologic investigations. The present review describes important definitions and geographical distribution of subtypes, circulating recombinant forms and other genomic variations of HIV. The present study aimed at leading students of Biomedical Sciences and public health laboratory staff guidance to general and specific knowledge about the genomic variability of the HIV.

Interplay between HIV Entry and Transportin-SR2 Dependency

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Gijsbers Rik

2011-01-01

Full Text Available Abstract Background Transportin-SR2 (TRN-SR2, TNPO3, transportin 3 was previously identified as an interaction partner of human immunodeficiency virus type 1 (HIV-1 integrase and functions as a nuclear import factor of HIV-1. A possible role of capsid in transportin-SR2-mediated nuclear import was recently suggested by the findings that a chimeric HIV virus, carrying the murine leukemia virus (MLV capsid and matrix proteins, displayed a transportin-SR2 independent phenotype, and that the HIV-1 N74D capsid mutant proved insensitive to transportin-SR2 knockdown. Results Our present analysis of viral specificity reveals that TRN-SR2 is not used to the same extent by all lentiviruses. The DNA flap does not determine the TRN-SR2 requirement of HIV-1. We corroborate the TRN-SR2 independent phenotype of the chimeric HIV virus carrying the MLV capsid and matrix proteins. We reanalyzed the HIV-1 N74D capsid mutant in cells transiently or stably depleted of transportin-SR2 and confirm that the N74D capsid mutant is independent of TRN-SR2 when pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G. Remarkably, although somewhat less dependent on TRN-SR2 than wild type virus, the N74D capsid mutant carrying the wild type HIV-1 envelope required TRN-SR2 for efficient replication. By pseudotyping with envelopes that mediate pH-independent viral uptake including HIV-1, measles virus and amphotropic MLV envelopes, we demonstrate that HIV-1 N74D capsid mutant viruses retain partial dependency on TRN-SR2. However, this dependency on TRN-SR2 is lost when the HIV N74D capsid mutant is pseudotyped with envelopes mediating pH-dependent endocytosis, such as the VSV-G and Ebola virus envelopes. Conclusion Here we discover a link between the viral entry of HIV and its interaction with TRN-SR2. Our data confirm the importance of TRN-SR2 in HIV-1 replication and argue for careful interpretation of experiments performed with VSV-G pseudotyped viruses in

Mannose-binding Lectin and the Risk of HIV Transmission and Disease Progression in Children A Systematic Review

NARCIS (Netherlands)

Israëls, Joël; Scherpbier, Henriette J.; Frakking, Florine N. J.; van de Wetering, Marianne D.; Kremer, Leontien C. M.; Kuijpers, Taco W.

2012-01-01

Background: Mannose-binding lectin (MBL) can activate the complement system by binding to carbohydrates, such as those presented on the HIV virion surface. It is unclear whether genetically determined MBL deficiency is related to vertical HIV transmission and disease progression in HIV-infected

Genetic predictor of working memory and prefrontal function in women with HIV.

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Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H; Little, Deborah M; Meyer, Vanessa J; Martin, Eileen; Weber, Kathleen; Cohen, Mardge; Maki, Pauline M

2015-02-01

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p women performed significantly worse than HIV-uninfected controls across N-back conditions (p working memory deficits and altered prefrontal function in HIV-infected individuals.

Genetic modification of hematopoietic stem cells as a therapy for HIV/AIDS.

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Younan, Patrick; Kowalski, John; Kiem, Hans-Peter

2013-11-28

The combination of genetic modification and hematopoietic stem cell (HSC) transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.

Genetic Modification of Hematopoietic Stem Cells as a Therapy for HIV/AIDS

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Patrick Younan

2013-11-01

Full Text Available The combination of genetic modification and hematopoietic stem cell (HSC transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.

HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood.

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Du, Peiwei; Liu, An; Jiao, Yanmei; Liu, Cuie; Jiang, Taiyi; Zhu, Weijun; Zhu, Yunxia; Wu, Hao; Sun, Lijun

2016-03-01

The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

CYTOKINES GENETIC POLYMORPHISM: THE PAST AND THE FUTURE

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L. V. Puzyryova

2016-01-01

Full Text Available The molecular genetics opens the new horizons in modern medicine, especially now when many diseases are given huge value in a type of their prevalence among various groups of population. Extremely high interleukin genes polymorphism degrees are studied well especially genetic polymorphism of tumor necrosis factor. Patients with HIV infection in the territory of Russia cause now the highest degree of mortality that is the most actual and socially significant problem of healthcare. This problems studying attracts many researchers. Works in respect of genetic immunity to a virus and influence of cytokines production on the disease forecast are especially interesting. One of the HIV replication influencing factors are cytokines, some of which, including the tumor necrosis factor and interleukin-6 can promote replication of HIV, raising an expression of virus regulatory genes. During disease progress in parallel of anti-inflammatory cytokines level increase (causing in this case rather ineffective antibodies level increase there is an T-helpers suppression stimulating a strong cellular component. Cytokine network functioning during HIV infection depends on many reasons which the individual variation in cytokine production caused by a number of genetic features, as well as an existence of opportunistic infection. Cytokines polymorphism determination in HIV infected patients is necessary in clinical practice for disease progression forecast to adverse fast transition to AIDS that it is important to consider in a choice of tactics of the supporting therapy of HIV-positive patients. Considering insufficient efficiency of modern methods of treatment, restoration and modulation of cytokines balance will increase anti-virus activity of immune system, influencing the factors blocking replication of a HIV.

Quality control assessment of human immunodeficiency virus type 2 (HIV-2) viral load quantification assays: results from an international collaboration on HIV-2 infection in 2006

NARCIS (Netherlands)

Damond, Florence; Benard, Antoine; Ruelle, Jean; Alabi, Abraham; Kupfer, Bernd; Gomes, Perpetua; Rodes, Berta; Albert, Jan; Böni, Jürg; Garson, Jeremy; Ferns, Bridget; Matheron, Sophie; Chene, Geneviève; Brun-Vezinet, Françoise; Goubau, Patrick; Campa, Pauline; Descamps, Diane; Simon, François; Taieb, Audrey; Autran, Brigitte; Cotten, Matt; Jaye, Assan; Peterson, Kevin; Rowland-Jones, Sarah; Rockstroh, Jürgen; Schwarze-Zander, Carolynne; de Wolf, Frank; van Sighem, Ard; Reiss, Peter; van der Loeff, Maarten Schim; Schutten, Martin; Camacho, Ricardo; Mansinho, Kamal; Antunes, Francisco; Luis, Franca; Valadas, Emilia; Toro, Carlos; Soriano, Vicente; Gyllensten, Katarina; Sonnerborg, Anders; Yilmaz, Aylin; Gisslén, Magnus; Calmy, Alexandra; Rickenbach, Martin; Pillay, Deenan; Tosswill, Jennifer; Anderson, Jane; Chadwick, David

2008-01-01

Human immunodeficiency virus type 2 (HIV-2) RNA quantification assays used in nine laboratories of the ACHI(E)V(2E) (A Collaboration on HIV-2 Infection) study group were evaluated. In a blinded experimental design, laboratories quantified three series of aliquots of an HIV-2 subtype A strain, each

Performance of 3 Rapid Tests for Discrimination Between HIV-1 and HIV-2 in Guinea-Bissau, West Africa

DEFF Research Database (Denmark)

Hønge, Bo Langhoff; Bjarnason Obinah, Magnús Pétur; Jespersen, Sanne

2014-01-01

As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated ...... (agreement 90.9%) and SD Bioline HIV-1/2 3.0 (agreement 84.5%). Our results underscore the need for evaluation of tests in relevant populations before implementation....

Molecular and epidemiological characterization of HIV-1 subtypes among Libyan patients.

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Daw, Mohamed A; El-Bouzedi, Abdallah; Ahmed, Mohamed O; Dau, Aghnyia A

2017-04-28

The epidemiological and clinical aspects of human immunodeficiency virus subtypes are of great interest worldwide. These subtypes are rarely studied in North African countries. Libya is a large country with the longest coast on the Mediterranean Sea, facing the Southern European countries. Studies on the characterization of HIV-1 subtypes are limited in Libya. This study aimed to determine the magnitude of the HIV problem among the Libyan population and to better understand the genetic diversity and the epidemiologic dynamics of HIV 1, as well as to correlate that with the risk factors involved. A total of 159 HIV-1 strains were collected from 814 HIV positive patients from the four Libyan regions during a 16-year period (1995-2010). To determine the HIV-1 subtypes, genetic analysis and molecular sequencing were carried out using provirus polygene. Epidemiologic and demographic information was obtained from each participant and correlated with HIV-1 subtypes using logistic regression. The overall prevalence of HIV among Libyans ranged from 5 to 10 per 100,000 during the study period. It was higher among intravenous drug users (IVDUs) (53.9%), blood recipients (25.9%) and heterosexuals (17.6%) than by vertical transmission (2.6%). Prevalence was higher among males aged 20-40 years (M:F 1:6, P > 0.001). Among the 159 strains of HIV-1 available for typing, 117 strains (73.6%) were subtype B, 29 (18.2%) were CRF02_AG, and 13 (8.2%) were subtype A. HIV-1 subtype B was the most prevalent all over the country, and it was more prevalent in the Northern region, particularly among IVDUs (P HIV-1 infection is emerging in Libya with a shifting prevalence of subtypes associated with the changing epidemiology of HIV-1 among risk groups. A genetic analysis of HIV-1 strains demonstrated low subtype heterogeneity with the evolution of subtype B, and CRF_20 AG, as well as HIV-1 subtype A. Our study highlights the importance of expanded surveillance programs to control HIV

HIV populations are large and accumulate high genetic diversity in a nonlinear fashion.

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Maldarelli, Frank; Kearney, Mary; Palmer, Sarah; Stephens, Robert; Mican, JoAnn; Polis, Michael A; Davey, Richard T; Kovacs, Joseph; Shao, Wei; Rock-Kress, Diane; Metcalf, Julia A; Rehm, Catherine; Greer, Sarah E; Lucey, Daniel L; Danley, Kristen; Alter, Harvey; Mellors, John W; Coffin, John M

2013-09-01

HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation of diversity and the mechanisms involved are under intense study to provide useful information to understand immune evasion and the development of drug resistance. To characterize the development of viral diversity after infection, we carried out an in-depth analysis of single genome sequences of HIV pro-pol to assess diversity and divergence and to estimate replicating population sizes in a group of treatment-naive HIV-infected individuals sampled at single (n = 22) or multiple, longitudinal (n = 11) time points. Analysis of single genome sequences revealed nonlinear accumulation of sequence diversity during the course of infection. Diversity accumulated in recently infected individuals at rates 30-fold higher than in patients with chronic infection. Accumulation of synonymous changes accounted for most of the diversity during chronic infection. Accumulation of diversity resulted in population shifts, but the rates of change were low relative to estimated replication cycle times, consistent with relatively large population sizes. Analysis of changes in allele frequencies revealed effective population sizes that are substantially higher than previous estimates of approximately 1,000 infectious particles/infected individual. Taken together, these observations indicate that HIV populations are large, diverse, and slow to change in chronic infection and that the emergence of new mutations, including drug resistance mutations, is governed by both selection forces and drift.

[Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province].

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Deng, Yongyue; Zhang, Chunyang; Yan, Yansheng; Yan, Pingping; Wu, Shouli

2014-06-01

In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province. Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology, during 2011-2012. Viral sequences(n = 81) of HIV-1 gag, env, and pol segments were amplified by nested PCR. Subtypes B and four Circulating Recombinant Forms, (CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%) were the two main HIV-1 strains in Fujian province. Compared with previous data, the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly. Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.

Genetically determined ancestry is more informative than self-reported race in HIV-infected and -exposed children

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Spector, Stephen A.; Brummel, Sean S.; Nievergelt, Caroline M.; Maihofer, Adam X.; Singh, Kumud K.; Purswani, Murli U.; Williams, Paige L.; Hazra, Rohan; Van Dyke, Russell; Seage, George R.

2016-01-01

Abstract The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants. In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined. According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian. GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes. PMID:27603370

Analysis of HIV subtypes and the phylogenetic tree in HIV-positive samples from Saudi Arabia

International Nuclear Information System (INIS)

Al-Zahrani, Alhusain J.

2008-01-01

Objective was to assess the prevalence of HIV-1 genetic subtypes in Saudi Arabia in samples that are serologically positive for HIV-1 and compare the HIV-1 genetic subtypes prevalent in Saudi Arabia with the subtypes prevalent in other countries. Thirty-nine HIV-1 positive samples were analyzed for HIV-1 subtypes using molecular techniques. The study is retrospective study that was conducted in Dammam, Kingdom of Saudi Arabia and in Abbott laboratories (United States of America) from2004 to 2007. All samples were seropositive for HIV-1 group M. Of the 39 seropositive samples, only 12 were polymerase chain reaction positive. Subtype C is the most common virus strain as it occurred in 58% of these samples; subtype B occurred in 17%; subtypes A, D and G were found in 8% each. The phylogenetic tree was also identified for the isolates. Detection of HIV subtypes is important for epidemiological purposes and may help in tracing the source of HIV infections in the Kingdom of Saudi Arabia. (author)

Evaluation of HIV Surveillance System in Rivers State, Nigeria ...

African Journals Online (AJOL)

Background: Rivers State has been reported to have the highest HIV prevalence of all the thirty-six states in Nigeria. HIV surveillance system generates information for timely and appropriate public health action. Evaluation of the surveillance system is vital in ensuring that the purpose of the surveillance system is being met.

Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

OpenAIRE

Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

2010-01-01

With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tes...

Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

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Petropoulos Christos J

2005-11-01

Full Text Available Abstract Background Central nervous system (CNS exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1 progression of systemic infection, 2 CSF white blood cell (WBC count, 3 antiretroviral therapy (ART, and 4 neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL. CSF HIV viral loads (VLs correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.

Trends of HIV-1, HIV-2 and dual infection in women attending outpatient clinics in Senegal, 1990–2009

Science.gov (United States)

Heitzinger, K; Sow, P S; Badiane, N M Dia; Gottlieb, G S; N’Doye, I; Toure, M; Kiviat, N B; Hawes, S E

2013-01-01

Summary We assessed trends in the relative prevalences of HIV-1, HIV-2 and dual HIV-1/HIV-2 infection in 10,321 women attending outpatient clinics in Senegal between 1990 and 2009. The relative prevalence of HIV-1 (defined as the proportion of seropositive subjects having HIV-1) rose sharply from 38% in 1990 until 1993 (P Senegal. From 1993 to 2009, the relative prevalence of HIV-1 increased at a slower rate, while the relative prevalences of HIV-2 and dual infection decreased. These results confirm trends in HIV prevalence observed in other West African populations and provide a critical update on HIV transmission risk among women in Senegal. PMID:23104745

Association of HIV diversity and survival in HIV-infected Ugandan infants.

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Maria M James

2011-04-01

Full Text Available The level of viral diversity in an HIV-infected individual can change during the course of HIV infection, reflecting mutagenesis during viral replication and selection of viral variants by immune and other selective pressures. Differences in the level of viral diversity in HIV-infected infants may reflect differences in viral dynamics, immune responses, or other factors that may also influence HIV disease progression. We used a novel high resolution melting (HRM assay to measure HIV diversity in Ugandan infants and examined the relationship between diversity and survival through 5 years of age.Plasma samples were obtained from 31 HIV-infected infants (HIVNET 012 trial. The HRM assay was used to measure diversity in two regions in the gag gene (Gag1 and Gag2 and one region in the pol gene (Pol.HRM scores in all three regions increased with age from 6-8 weeks to 12-18 months (for Gag1: P = 0.005; for Gag2: P = 0.006; for Pol: P = 0.016. Higher HRM scores at 6-8 weeks of age (scores above the 75(th percentile were associated with an increased risk of death by 5 years of age (for Pol: P = 0.005; for Gag1/Gag2 (mean of two scores: P = 0.003; for Gag1/Gag2/Pol (mean of three scores: P = 0.002. We did not find an association between HRM scores and other clinical and laboratory variables.Genetic diversity in HIV gag and pol measured using the HRM assay was typically low near birth and increased over time. Higher HIV diversity in these regions at 6-8 weeks of age was associated with a significantly increased risk of death by 5 years of age.

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

Science.gov (United States)

Lu, Xinli; Kang, Xianjiang; Liu, Yongjian; Cui, Ze; Guo, Wei; Zhao, Cuiying; Li, Yan; Chen, Suliang; Li, Jingyun; Zhang, Yuqi; Zhao, Hongru

2017-01-01

New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China.

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Xinli Lu

Full Text Available New human immunodeficiency virus type 1 (HIV-1 diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF01_AE (53.4%, CRF07_BC (23.4%, subtype B (15.9%, and unique recombinant forms URFs (4.9%. Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx, unknown before in Hebei, were first found among men who have sex with men (MSM. All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%, CRF01_AE/B (23.3%, B/C (16.7%, CRF01_AE/C (13.3%, CRF01_AE/B/A2 (3.3% and CRF01_AE/BC/A2 (3.3%, plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China.

Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

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Todd, Jim; Riedner, Gabriele; Maboko, Leonard; Hoelscher, Michael; Weiss, Helen A; Lyamuya, Eligius; Mabey, David; Rusizoka, Mary; Belec, Laurent; Hayes, Richard

2013-01-01

To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV. Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined. Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, pgenital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

Second Generation of HIV Surveillance System: A Pattern for Iran

OpenAIRE

Nematollahi, M; Khalesi, N; Moghaddasi, H; Askarian, M

2012-01-01

Background For the purpose of minimizing the HIV/AIDS epidemic effects, one of the programs is the promotion of scientific methods and setting of the suitable surveillance systems. The present research was conducted to design the HIV/AIDS surveillance system in Iran applying WHO recommendations and the experience of some countries. Methods In 2009, based on the country's requirements, the HIV/AIDS surveillance system was proposed and designed for Iran. The Delphi technique was utilized to fin...

Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

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Spencer, LaShonda Y; Christiansen, Shawna; Wang, Chia-Hao H; Mack, Wendy J; Young, Mary; Strickler, Howard D; Anastos, Kathryn; Minkoff, Howard; Cohen, Mardge; Geenblatt, Ruth M; Karim, Roksana; Operskalski, Eva; Frederick, Toni; Homans, James D; Landay, Alan; Kovacs, Andrea

2016-02-01

Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV

Similarities and differences in the nucleic acid chaperone activity of HIV-2 and HIV-1 nucleocapsid proteins in vitro.

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Pachulska-Wieczorek, Katarzyna; Stefaniak, Agnieszka K; Purzycka, Katarzyna J

2014-07-03

The nucleocapsid domain of Gag and mature nucleocapsid protein (NC) act as nucleic acid chaperones and facilitate folding of nucleic acids at critical steps of retroviral replication cycle. The basic N-terminus of HIV-1 NC protein was shown most important for the chaperone activity. The HIV-2 NC (NCp8) and HIV-1 NC (NCp7) proteins possess two highly conserved zinc fingers, flanked by basic residues. However, the NCp8 N-terminal domain is significantly shorter and contains less positively charged residues. This study characterizes previously unknown, nucleic acid chaperone activity of the HIV-2 NC protein. We have comparatively investigated the in vitro nucleic acid chaperone properties of the HIV-2 and HIV-1 NC proteins. Using substrates derived from the HIV-1 and HIV-2 genomes, we determined the ability of both proteins to chaperone nucleic acid aggregation, annealing and strand exchange in duplex structures. Both NC proteins displayed comparable, high annealing activity of HIV-1 TAR DNA and its complementary nucleic acid. Interesting differences between the two NC proteins were discovered when longer HIV substrates, particularly those derived from the HIV-2 genome, were used in chaperone assays. In contrast to NCp7, NCp8 weakly facilitates annealing of HIV-2 TAR RNA to its complementary TAR (-) DNA. NCp8 is also unable to efficiently stimulate tRNALys3 annealing to its respective HIV-2 PBS motif. Using truncated NCp8 peptide, we demonstrated that despite the fact that the N-terminus of NCp8 differs from that of NCp7, this domain is essential for NCp8 activity. Our data demonstrate that the HIV-2 NC protein displays reduced nucleic acid chaperone activity compared to that of HIV-1 NC. We found that NCp8 activity is limited by substrate length and stability to a greater degree than that of NCp7. This is especially interesting in light of the fact that the HIV-2 5'UTR is more structured than that of HIV-1. The reduced chaperone activity observed with NCp8 may

Sieve analysis in HIV-1 vaccine efficacy trials.

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Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

2013-09-01

The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

A comparison of parallel pyrosequencing and sanger clone-based sequencing and its impact on the characterization of the genetic diversity of HIV-1.

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Binhua Liang

Full Text Available BACKGROUND: Pyrosequencing technology has the potential to rapidly sequence HIV-1 viral quasispecies without requiring the traditional approach of cloning. In this study, we investigated the utility of ultra-deep pyrosequencing to characterize genetic diversity of the HIV-1 gag quasispecies and assessed the possible contribution of pyrosequencing technology in studying HIV-1 biology and evolution. METHODOLOGY/PRINCIPAL FINDINGS: HIV-1 gag gene was amplified from 96 patients using nested PCR. The PCR products were cloned and sequenced using capillary based Sanger fluorescent dideoxy termination sequencing. The same PCR products were also directly sequenced using the 454 pyrosequencing technology. The two sequencing methods were evaluated for their ability to characterize quasispecies variation, and to reveal sites under host immune pressure for their putative functional significance. A total of 14,034 variations were identified by 454 pyrosequencing versus 3,632 variations by Sanger clone-based (SCB sequencing. 11,050 of these variations were detected only by pyrosequencing. These undetected variations were located in the HIV-1 Gag region which is known to contain putative cytotoxic T lymphocyte (CTL and neutralizing antibody epitopes, and sites related to virus assembly and packaging. Analysis of the positively selected sites derived by the two sequencing methods identified several differences. All of them were located within the CTL epitope regions. CONCLUSIONS/SIGNIFICANCE: Ultra-deep pyrosequencing has proven to be a powerful tool for characterization of HIV-1 genetic diversity with enhanced sensitivity, efficiency, and accuracy. It also improved reliability of downstream evolutionary and functional analysis of HIV-1 quasispecies.

Copy number variation of Fc gamma receptor genes in HIV-infected and HIV-tuberculosis co-infected individuals in sub-Saharan Africa.

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Lee R Machado

Full Text Available AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB, as HIV stimulates the reactivation of latent tuberculosis (TB. Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies. Given that Fcγ receptors are critical in mediating the non-neutralising effects of antibodies, analysis of the extensive variation at Fcγ receptor genes is important. Single nucleotide variation and copy number variation (CNV of Fcγ receptor genes affects the expression profile, activatory/inhibitory balance, and IgG affinity of the Fcγ receptor repertoire of each individual. In this study we investigated whether CNV of FCGR2C, FCGR3A and FCGR3B as well as the HNA1 allotype of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART and co-infection with TB. We confirmed an effect of TB-co-infection status on HIV load and response to HAART, but no conclusive effect of the genetic variants we tested. We observed a small effect, in Ethiopians, of FCGR3B copy number, where deletion was more frequent in HIV-TB co-infected patients than those infected with HIV alone.

Enrichment of intersubtype HIV-1 recombinants in a dual infection system using HIV-1 strain-specific siRNAs

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2011-01-01

Background Intersubtype HIV-1 recombinants in the form of unique or stable circulating recombinants forms (CRFs) are responsible for over 20% of infections in the worldwide epidemic. Mechanisms controlling the generation, selection, and transmission of these intersubtype HIV-1 recombinants still require further investigation. All intersubtype HIV-1 recombinants are generated and evolve from initial dual infections, but are difficult to identify in the human population. In vitro studies provide the most practical system to study mechanisms, but the recombination rates are usually very low in dual infections with primary HIV-1 isolates. This study describes the use of HIV-1 isolate-specific siRNAs to enrich intersubtype HIV-1 recombinants and inhibit the parental HIV-1 isolates from a dual infection. Results Following a dual infection with subtype A and D primary HIV-1 isolates and two rounds of siRNA treatment, nearly 100% of replicative virus was resistant to a siRNA specific for an upstream target sequence in the subtype A envelope (env) gene as well as a siRNA specific for a downstream target sequence in the subtype D env gene. Only 20% (10/50) of the replicating virus had nucleotide substitutions in the siRNA-target sequence whereas the remaining 78% (39/50) harbored a recombination breakpoint that removed both siRNA target sequences, and rendered the intersubtype D/A recombinant virus resistant to the dual siRNA treatment. Since siRNAs target the newly transcribed HIV-1 mRNA, the siRNAs only enrich intersubtype env recombinants and do not influence the recombination process during reverse transcription. Using this system, a strong bias is selected for recombination breakpoints in the C2 region, whereas other HIV-1 env regions, most notably the hypervariable regions, were nearly devoid of intersubtype recombination breakpoints. Sequence conservation plays an important role in selecting for recombination breakpoints, but the lack of breakpoints in many conserved

The molecular epidemiology of HIV in Asia.

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Weniger, B G; Takebe, Y; Ou, C Y; Yamazaki, S

1994-01-01

The human immunodeficiency virus (HIV) was introduced readily into Asia and has quickly spread between Asian states through both parenteral and sexual modes of transmission. Only 1 year after Thailand's epidemic wave among intravenous drug users (IDUs) in 1988, the virus spread to the adjacent Myanmar and Malaysia, and another year later IDUs were infected in parts of India and China bordering Myanmar. Several methods can be used to quantify the genetic diversity, divergence, or variation within or between subtypes, genotypes, or isolates. Consensus sequences, representing the most common nucleotide in the genome, are often generated for comparison. 8 subtypes A through F, H, and O have been described for HIV-1 based on the genetic similarities and differences in the env gene or viral envelope. Subtype A and D have been found primarily in central and western Africa. Subtype B is predominant in Europe, the Western hemisphere, Japan, and Australia. Subtype C has been found mostly in southern Africa, the Central African Republic, and India. Subtype E was first identified in Thailand and recently in the Central African Republic. Subtype F has been found in Romania and is a rare variant in Brazil. Isolates from Gabon and the Russian Federation were designated subtype H. An "outlier" subtype O containing 2 human and 2 chimpanzee isolates has been identified in Cameroon and Gabon. Sequencing of the relatively conserved gag gene of geographically diverse HIV-1 isolates yielded a classification with 7 subtypes A-D and F-H. Other topics discussed include genome characterization, comparison with foreign isolates, segregation by mode of transmission, and biologic properties of HIV-1 variants in Thailand; regional diversity of HIV-1 subtypes and substantial spread of HIV-2 in India; as well as HIV transmission and infections in Japan, Australia, Cambodia, China, Taiwan, Philippines, Malaysia, Myanmar, and in states created out of the former Soviet Union.

Incident HSV-2 Infections Are Common Among HIV-1-discordant Couples

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Muiru, Anthony N.; Guthrie, Brandon L.; Bosire, Rose; Merkel, Michele; Liu, Amy Y.; Choi, Robert Y.; Lohman-Payne, Barbara; Gatuguta, Ann; Mackelprang, Romel D.; Kiarie, James N.; Farquhar, Carey

2013-01-01

Background. The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. Methods. HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. Results. Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00–2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12–5.74). At least 30% of incident HSV-2 infections originated from an outside partner. Conclusions. The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population. PMID:23840044

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

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

2015-12-10

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

HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations among Patients from the North, Central and South Regions of Angola

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Afonso, Joana Morais; Bello, Gonzalo; Guimarães, Monick L.; Sojka, Marta; Morgado, Mariza G.

2012-01-01

Background Angola presents a very complex HIV-1 epidemic characterized by the co-circulation of several HIV-1 group M subtypes, intersubtype recombinants and unclassified (U) variants. The viral diversity outside the major metropolitan regions (Luanda and Cabinda) and the prevalence of transmitted drug resistance mutations (DRM) since the introduction of HAART in 2004, however, has been barely studied. Methods One hundred and one individuals from the Central (n = 44), North (n = 35), and South (n = 22) regions of Angola were diagnosed as HIV-1 positive and had their blood collected between 2008 and 2010, at one of the National Referral Centers for HIV diagnosis, the Kifangondo Medical Center, located in the border between the Luanda and Bengo provinces. Angolan samples were genotyped based on phylogenetic and bootscanning analyses of the pol (PR/RT) gene and their drug resistance profile was analyzed. Results Among the 101 samples analyzed, 51% clustered within a pure group M subtype, 42% were classified as intersubtype recombinants, and 7% were denoted as U. We observed an important variation in the prevalence of different HIV-1 genetic variants among country regions, with high frequency of subtype F1 in the North (20%), intersubtype recombinants in the Central (42%), and subtype C in the South (45%). Statistically significant difference in HIV-1 clade distribution was only observed in subtype C prevalence between North vs South (p = 0.0005) and Central vs South (p = 0.0012) regions. DRM to NRTI and/or NNRTI were detected in 16.3% of patients analyzed. Conclusions These results demonstrate a heterogeneous distribution of HIV-1 genetic variants across different regions in Angola and also revealed an unexpected high frequency of DRM to RT inhibitors in patients that have reported no antiretroviral usage, which may decrease the efficiency of the standard first-line antiretroviral regimens currently used in the country. PMID:22952625

Effect of genital herpes on cervicovaginal HIV shedding in women co-infected with HIV AND HSV-2 in Tanzania.

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Jim Todd

Full Text Available To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV.Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1 57 women at 70 clinic visits with clinical genital herpes; (2 39 of the same women at 46 clinic visits when asymptomatic; (3 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL, herpetic lesions, HSV shedding and other factors were examined.Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03. In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41-0.60, p<0.001 and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16-0.32, p<0.001 but not the presence of herpetic lesions (β = -0.10, 95%CI:-0.28-0.08, p = 0.27.HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.

CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea.

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Mehlotra, Rajeev K; Hall, Noemi B; Bruse, Shannon E; John, Bangan; Zikursh, Melinda J Blood; Stein, Catherine M; Siba, Peter M; Zimmerman, Peter A

2015-12-01

Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G >A, CCR5 -2459G >A and Δ32, and CXCL12 801G >A in PNG (n=258), North America (n=184), and five countries in West Africa (n=178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 -2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 -2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-valuesnew insights regarding CCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel AIDS/HIV intelligent medical consulting system based on expert systems.

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Ebrahimi, Alireza Pour; Toloui Ashlaghi, Abbas; Mahdavy Rad, Maryam

2013-01-01

The purpose of this paper is to propose a novel intelligent model for AIDS/HIV data based on expert system and using it for developing an intelligent medical consulting system for AIDS/HIV. In this descriptive research, 752 frequently asked questions (FAQs) about AIDS/HIV are gathered from numerous websites about this disease. To perform the data mining and extracting the intelligent model, the 6 stages of Crisp method has been completed for FAQs. The 6 stages include: Business understanding, data understanding, data preparation, modelling, evaluation and deployment. C5.0 Tree classification algorithm is used for modelling. Also, rational unified process (RUP) is used to develop the web-based medical consulting software. Stages of RUP are as follows: Inception, elaboration, construction and transition. The intelligent developed model has been used in the infrastructure of the software and based on client's inquiry and keywords related FAQs are displayed to the client, according to the rank. FAQs' ranks are gradually determined considering clients reading it. Based on displayed FAQs, test and entertainment links are also displayed. The accuracy of the AIDS/HIV intelligent web-based medical consulting system is estimated to be 78.76%. AIDS/HIV medical consulting systems have been developed using intelligent infrastructure. Being equipped with an intelligent model, providing consulting services on systematic textual data and providing side services based on client's activities causes the implemented system to be unique. The research has been approved by Iranian Ministry of Health and Medical Education for being practical.

Mucosal Immunogenicity of Genetically Modified Lactobacillus acidophilus Expressing an HIV-1 Epitope within the Surface Layer Protein.

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Akinobu Kajikawa

Full Text Available Surface layer proteins of probiotic lactobacilli are theoretically efficient epitope-displaying scaffolds for oral vaccine delivery due to their high expression levels and surface localization. In this study, we constructed genetically modified Lactobacillus acidophilus strains expressing the membrane proximal external region (MPER from human immunodeficiency virus type 1 (HIV-1 within the context of the major S-layer protein, SlpA. Intragastric immunization of mice with the recombinants induced MPER-specific and S-layer protein-specific antibodies in serum and mucosal secretions. Moreover, analysis of systemic SlpA-specific cytokines revealed that the responses appeared to be Th1 and Th17 dominant. These findings demonstrated the potential use of the Lactobacillus S-layer protein for development of oral vaccines targeting specific peptides.

1 original article diverse genetic subtypes of hiv-1 among female sex

African Journals Online (AJOL)

boaz

Keywords: Diverse, HIV, subtypes, Female Sex workers and Vaccine ... significant probability that infection with this subtype occurred with a short incubation period (p< 0.05). Conclusion: This study .... regression was used to adjust for potential cofounders. .... TABLE 2: DISTRIBUTION OF HIV-1 SUBTYPES AMONG FSWS.

[HIV encephalopathy due to drug resistance despite 2-year suppression of HIV viremia by cART].

Science.gov (United States)

Sekiya, Hiroaki; Kawamoto, Michi; Togo, Masaya; Yoshimura, Hajime; Imai, Yukihiro; Kohara, Nobuo

2014-01-01

A 57-year-old man presented with subacute progression of cognitive impairment (MMSE 22/30). He had been diagnosed as AIDS two years before and taking atazanavir, abacavir, and lamivudine. HIV RNA of plasma had been negative. On admission, HIV RNA was 4,700 copy/ml and 5,200 copy/ml in plasma and in cerebrospinal fluid respectively, suggesting treatment failure of cART. The brain magnetic resonance imaging showed high intensity areas in the white matter of the both frontal lobes and brain stem. The drug-resistance test revealed the resistance of lamivudine and abacavir. We introduced the CNS penetration effectiveness (CPE) score to evaluate the drug penetration of HIV drugs. As the former regimen had low points (7 points), we optimized the regimen to raltegravir, zidovudine, and darunavir/ritonavir (scoring 10 points). His cognitive function improved as normal (MMSE 30/30) in 2 weeks and HIV-RNA became undetectable both in plasma and CSF in a month. In spite of the cognitive improvement, the white matter hyperintensity expanded. To rule out malignant lymphoma or glioblastoma, the brain biopsy was performed from the right frontal lobe. It revealed microglial hyperplasia and diffuse perivascular infiltration by CD8+/CD4-lymphocytes. No malignant cells were found and the polymerase chain reaction analyses excluded other viruses. Considering the drug penetration to the central nervous system is important for treating HIV encephalopathy.

BI-2 destabilizes HIV-1 cores during infection and Prevents Binding of CPSF6 to the HIV-1 Capsid.

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Fricke, Thomas; Buffone, Cindy; Opp, Silvana; Valle-Casuso, Jose; Diaz-Griffero, Felipe

2014-12-11

The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74. This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core. Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.

The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico.

Science.gov (United States)

López, Pablo; Rivera-Amill, Vanessa; Rodríguez, Nayra; Vargas, Freddie; Yamamura, Yasuhiro

2015-12-23

HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B). However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945) were obtained from our "HIV Genotyping" test file, which has been generated over a period of 14 years (2001-2014). REGA subtyping tool found the following subtypes: B (90%), B-like (3%), B/D recombinant (6%), and D/B recombinant (0.6%). Though there were fewer cases, the following subtypes were also found (in the given proportions): A1B (0.3%), BF1 (0.2%), subtype A (01-AE) (0.1%), subtype A (A2) (0.1%), subtype F (12BF) (0.1%), CRF-39 BF-like (0.1%), and others (0.1%). Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world.

The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico

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Pablo López

2015-12-01

Full Text Available HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B. However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945 were obtained from our “HIV Genotyping” test file, which has been generated over a period of 14 years (2001–2014. REGA subtyping tool found the following subtypes: B (90%, B-like (3%, B/D recombinant (6%, and D/B recombinant (0.6%. Though there were fewer cases, the following subtypes were also found (in the given proportions: A1B (0.3%, BF1 (0.2%, subtype A (01-AE (0.1%, subtype A (A2 (0.1%, subtype F (12BF (0.1%, CRF-39 BF-like (0.1%, and others (0.1%. Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world.

A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

Science.gov (United States)

Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Mª Angeles; Mileto, Davide; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel

2017-07-01

Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System. ¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS ® AmpliPrep/COBAS ® TaqMan ® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log 10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log 10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log 10 cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log 10 cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS ® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay. Copyright © 2017 Elsevier B.V. All rights reserved.

HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study in a Spanish HIV-infected population.

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Laura Ibáñez

Full Text Available BACKGROUND: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection. METHODS & FINDINGS: In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009, ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004, CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015 and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018 associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008, IL1RN (rs380092 p = 0.002 and ALOX5AP (rs3885907 p = 0.02 genetic variants. CONCLUSIONS: In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals.

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

Science.gov (United States)

de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

2017-06-01

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

A novel CD4-conjugated ultraviolet light-activated photocatalyst inactivates HIV-1 and SIV efficiently.

Science.gov (United States)

Yamaguchi, Koushi; Sugiyama, Takahiro; Kato, Shinji; Kondo, Yoichi; Ageyama, Naohide; Kanekiyo, Masaru; Iwata, Misao; Koyanagi, Yoshio; Yamamoto, Naoki; Honda, Mitsuo

2008-08-01

In this study, we found that the electric potential derived from the redox reaction of ultraviolet (UV)-illuminated CD4-conjugated titanium dioxide (TiO2) inactivated a wide range of high-titered primary HIV-1 isolates, regardless of virus co-receptor usage or genetic clade. In vitro incubation of HIV-1 isolates with CD4-conjugated TiO2 (CD4-TiO2) followed by UV illumination led to inhibition of viral infectivity in both H9 cells and peripheral blood mononuclear cells as well as to the complete inactivation of plasma virions from HIV-1-infected individuals. Treatment with a newly established extra-corporeal circulation system with the photocatalyst in rhesus macaques completely inactivated plasma virus in the system and effectively reduced the infectious plasma viral load. Furthermore, plasma viremia and infectious viral loads were controlled following a second therapeutic photocatalyst treatment during primary SIV(mac239) infection of macaques. Our findings suggest that this therapeutic immunophysical strategy may help control human immunodeficiency viral infection in vivo.

Reliable reconstruction of HIV-1 whole genome haplotypes reveals clonal interference and genetic hitchhiking among immune escape variants

Science.gov (United States)

2014-01-01

Background Following transmission, HIV-1 evolves into a diverse population, and next generation sequencing enables us to detect variants occurring at low frequencies. Studying viral evolution at the level of whole genomes was hitherto not possible because next generation sequencing delivers relatively short reads. Results We here provide a proof of principle that whole HIV-1 genomes can be reliably reconstructed from short reads, and use this to study the selection of immune escape mutations at the level of whole genome haplotypes. Using realistically simulated HIV-1 populations, we demonstrate that reconstruction of complete genome haplotypes is feasible with high fidelity. We do not reconstruct all genetically distinct genomes, but each reconstructed haplotype represents one or more of the quasispecies in the HIV-1 population. We then reconstruct 30 whole genome haplotypes from published short sequence reads sampled longitudinally from a single HIV-1 infected patient. We confirm the reliability of the reconstruction by validating our predicted haplotype genes with single genome amplification sequences, and by comparing haplotype frequencies with observed epitope escape frequencies. Conclusions Phylogenetic analysis shows that the HIV-1 population undergoes selection driven evolution, with successive replacement of the viral population by novel dominant strains. We demonstrate that immune escape mutants evolve in a dependent manner with various mutations hitchhiking along with others. As a consequence of this clonal interference, selection coefficients have to be estimated for complete haplotypes and not for individual immune escapes. PMID:24996694

HIV subtype influences HLA-B*07:02-associated HIV disease outcome

DEFF Research Database (Denmark)

Kløverpris, Henrik N; Adland, Emily; Koyanagi, Madoka

2014-01-01

Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA......% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed....

The Immune System of HIV-Exposed Uninfected Infants.

Science.gov (United States)

Abu-Raya, Bahaa; Kollmann, Tobias R; Marchant, Arnaud; MacGillivray, Duncan M

2016-01-01

Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, haemophilus influenzae type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored.

Towards a Mobile Intelligent Information System with Application to HIV/AIDS.

Science.gov (United States)

Kopec, D; Eckhardt, R; Tamang, S; Reinharth, D

2005-01-01

The United Nations Security Council reports HIV/AIDS as the fastest growing threat to human development. In addition, the World Health Organization [1] reports that nearly 5 million persons (4.3 million adults and 700,000 children) are newly infected with HIV each year; more than 95% of them found in developing countries. Since STDs as a group are a personal problem which few people feel comfortable discussing, we believe that hand-held PDAs can provide an opportunity for learning about this disease while insuring anonymity. This device will employ the newest technologies including Bluetooth wireless technology, which can transmit and receive data via a short-range radio link using a globally available frequency band (2.4 GHz ISM band), enabling rapid and accurate synchronous and asynchronous data communication. The first generation of Bluetooth permits exchange of data up to a rate of 1 Mbps, even in areas with much electromagnetic disturbance. This emerging technology can facilitate HIV/AIDS outreach around the globe.Recent advances in learning have taken a particularly cognitive perspective and these findings have implications for education in general as well as for the development of intelligent tutoring systems in particular. In the past, effective SmartBookstrade markhave been developed for AIDS education to disseminate the critical knowledge relevant to this epidemic [2].Since 1993, the proliferation of the World Wide Web has created a plethora of new opportunities for the delivery of electronic distance learning systems. However, we feel that it is important that a whatever technology is employed is based on a sound educational theory. A new, comprehensive, web-based learning system called SmartTutor has been developed, at Brooklyn College of The City University of New York [3]. This technology provides a user-friendly, self-paced, easy to modify, software environment intended to serve the user's learning needs and is based on a generic Smart

Diagnosed HIV Infection in Transgender Adults and Adolescents: Results from the National HIV Surveillance System, 2009-2014.

Science.gov (United States)

Clark, Hollie; Babu, Aruna Surendera; Wiewel, Ellen Weiss; Opoku, Jenevieve; Crepaz, Nicole

2017-09-01

Publications on diagnosed HIV infection among transgender people have been limited to state- or local-level data. We analyzed data from the National HIV Surveillance System and present results from the first national-level analysis of transgender people with diagnosed HIV infection. From 2009 to 2014, HIV surveillance jurisdictions from 45 states plus the District of Columbia identified and reported at least one case of newly diagnosed HIV infection for transgender people; jurisdictions from 5 states reported no cases for transgender people. Of 2351 transgender people with newly diagnosed HIV infection during 2009-2014, 84.0% were transgender women (male-to-female), 15.4% were transgender men (female-to-male), and 0.7% were additional gender identity (e.g., gender queer, bi-gender). Over half of both transgender women (50.8%; 1002/1974) and men (58.4%; 211/361) with newly diagnosed HIV infection were non-Hispanic black/African American. Improvements in data collection methods and quality are needed to gain a better understanding of HIV burden among transgender people.

HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

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Angeline Rouers

2017-07-01

Full Text Available HIV-specific broadly neutralizing antibodies (bnAbs have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs, multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57− ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.

Population dynamics of HIV-2 in rural West Africa: comparison with HIV-1 and ongoing transmission at the heart of the epidemic

NARCIS (Netherlands)

de Silva, Thushan I.; van Tienen, Carla; Onyango, Clayton; Jabang, Abdoulie; Vincent, Tim; Loeff, Maarten F. Schim van der; Coutinho, Roel A.; Jaye, Assan; Rowland-Jones, Sarah; Whittle, Hilton; Cotten, Matthew; Hué, Stéphane

2013-01-01

To compare the population dynamics of HIV-2 and HIV-1, and to characterize ongoing HIV-2 transmission in rural Guinea-Bissau. Phylogenetic and phylodynamic analyses using HIV-2 gag and env, and HIV-1 env sequences, combined with epidemiological data from a community cohort. Samples were obtained

Scaling-up health information systems to improve HIV treatment: An assessment of initial patient monitoring systems in Mozambique.

Science.gov (United States)

Hochgesang, Mindy; Zamudio-Haas, Sophia; Moran, Lissa; Nhampossa, Leopoldo; Packel, Laura; Leslie, Hannah; Richards, Janise; Shade, Starley B

2017-01-01

The rapid scale-up of HIV care and treatment in resource-limited countries requires concurrent, rapid development of health information systems to support quality service delivery. Mozambique, a country with an 11.5% prevalence of HIV, has developed nation-wide patient monitoring systems (PMS) with standardized reporting tools, utilized by all HIV treatment providers in paper or electronic form. Evaluation of the initial implementation of PMS can inform and strengthen future development as the country moves towards a harmonized, sustainable health information system. This assessment was conducted in order to 1) characterize data collection and reporting processes and PMS resources available and 2) provide evidence-based recommendations for harmonization and sustainability of PMS. This baseline assessment of PMS was conducted with eight non-governmental organizations that supported the Ministry of Health to provide 90% of HIV care and treatment in Mozambique. The study team conducted structured and semi-structured surveys at 18 health facilities located in all 11 provinces. Seventy-nine staff were interviewed. Deductive a priori analytic categories guided analysis. Health facilities have implemented paper and electronic monitoring systems with varying success. Where in use, robust electronic PMS facilitate facility-level reporting of required indicators; improve ability to identify patients lost to follow-up; and support facility and patient management. Challenges to implementation of monitoring systems include a lack of national guidelines and norms for patient level HIS, variable system implementation and functionality, and limited human and infrastructure resources to maximize system functionality and information use. This initial assessment supports the need for national guidelines to harmonize, expand, and strengthen HIV-related health information systems. Recommendations may benefit other countries with similar epidemiologic and resource

New subtypes and genetic recombination in HIV type 1-infecting patients with highly active antiretroviral therapy in Peru (2008-2010).

Science.gov (United States)

Yabar, Carlos Augusto; Acuña, Maribel; Gazzo, Cecilia; Salinas, Gabriela; Cárdenas, Fanny; Valverde, Ada; Romero, Soledad

2012-12-01

HIV-1 subtype B is the most frequent strain in Peru. However, there is no available data about the genetic diversity of HIV-infected patients receiving highly active antiretroviral therapy (HAART) here. A group of 267 patients in the Peruvian National Treatment Program with virologic failure were tested for genotypic evidence of HIV drug resistance at the Instituto Nacional de Salud (INS) of Peru between March 2008 and December 2010. Viral RNA was extracted from plasma and the segments of the protease (PR) and reverse transcriptase (RT) genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), purified, and fully sequenced. Consensus sequences were submitted to the HIVdb Genotypic Resistance Interpretation Algorithm Database from Stanford University, and then aligned using Clustal X v.2.0 to generate a phylogenetic tree using the maximum likelihood method. Intrasubtype and intersubtype recombination analyses were performed using the SCUEAL program (Subtype Classification by Evolutionary ALgo-rithms). A total of 245 samples (91%) were successfully genotyped. The analysis obtained from the HIVdb program showed 81.5% resistance cases (n=198). The phylogenetic analysis revealed that subtype B was predominant in the population (98.8%), except for new cases of A, C, and H subtypes (n=4). Of these cases, only subtype C was imported. Likewise, recombination analysis revealed nine intersubtype and 20 intrasubtype recombinant cases. This is the first report of the presence of HIV-1 subtypes C and H in Peru. The introduction of new subtypes and circulating recombinants forms can make it difficult to distinguish resistance profiles in patients and consequently affect future treatment strategies against HIV in this country.

Population mobility and the changing epidemics of HIV-2 in Portugal

DEFF Research Database (Denmark)

Carvalho, A C; Valadas, E; França, L

2012-01-01

Portugal is the European country with the highest frequency of HIV-2 infection, which is mainly concentrated in West Africa. The cumulative number of notified HIV-2 infections in Portugal was 1813 by the end of December 2008. To better characterize the dynamics of HIV-2 infection in the country a...... and to obtain data that may be of use in the prevention of the spread of HIV-2, we evaluated a large pooled sample of patients....

The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol.

Science.gov (United States)

Durand, Madeleine; Chartrand-Lefebvre, Carl; Baril, Jean-Guy; Trottier, Sylvie; Trottier, Benoit; Harris, Marianne; Walmsley, Sharon; Conway, Brian; Wong, Alexander; Routy, Jean-Pierre; Kovacs, Colin; MacPherson, Paul A; Monteith, Kenneth Marc; Mansour, Samer; Thanassoulis, George; Abrahamowicz, Michal; Zhu, Zhitong; Tsoukas, Christos; Ancuta, Petronela; Bernard, Nicole; Tremblay, Cécile L

2017-09-11

With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals. The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the

The HIV-1 Rev/RRE system is required for HIV-1 5' UTR cis elements to augment encapsidation of heterologous RNA into HIV-1 viral particles

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Ma Hong

2011-06-01

Full Text Available Abstract Background The process of HIV-1 genomic RNA (gRNA encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (ψ. Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site from the 5' untranslated region (UTR. Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles. Results We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and ψ. Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons; however, the cDNA forms are episomes predominantly in the 1-LTR circle form. Conclusions Premised on encapsidation of a heterologous RNA into

Central nervous system manifestations of HIV infection in children

International Nuclear Information System (INIS)

George, Reena; Andronikou, Savvas; Plessis, Jaco du; Plessis, Anne-Marie du; Maydell, Arthur; Toorn, Ronald van

2009-01-01

Vertically transmitted HIV infection is a major problem in the developing world due to the poor availability of antiretroviral agents to pregnant women. HIV is a neurotrophic virus and causes devastating neurological insults to the immature brain. The effects of the virus are further compounded by the opportunistic infections and neoplasms that occur as a result of the associated immune suppression. This review focuses on the imaging features of HIV infection and its complications in the central nervous system. (orig.)

Central nervous system manifestations of HIV infection in children

Energy Technology Data Exchange (ETDEWEB)

George, Reena; Andronikou, Savvas; Plessis, Jaco du; Plessis, Anne-Marie du; Maydell, Arthur [University of Stellenbosch, Department of Radiology, Tygerberg Academic Hospital, Cape Town (South Africa); Toorn, Ronald van [University of Stellenbosch, Department of Paediatrics and Child Health, Tygerberg Academic Hospital, Cape Town (South Africa)

2009-06-15

Vertically transmitted HIV infection is a major problem in the developing world due to the poor availability of antiretroviral agents to pregnant women. HIV is a neurotrophic virus and causes devastating neurological insults to the immature brain. The effects of the virus are further compounded by the opportunistic infections and neoplasms that occur as a result of the associated immune suppression. This review focuses on the imaging features of HIV infection and its complications in the central nervous system. (orig.)

Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

Directory of Open Access Journals (Sweden)

Jairam R Lingappa

Full Text Available The Partners HSV-2/HIV-1 Transmission Study (Partners Study is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2 suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9 with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to <350, respectively, p<0.001.The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission.ClinicalTrials.gov NCT00194519.

Performance evaluation of the Bio-Rad Laboratories GS HIV Combo Ag/Ab EIA, a 4th generation HIV assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma.

Science.gov (United States)

Bentsen, Christopher; McLaughlin, Lisa; Mitchell, Elizabeth; Ferrera, Carol; Liska, Sally; Myers, Robert; Peel, Sheila; Swenson, Paul; Gadelle, Stephane; Shriver, M Kathleen

2011-12-01

A multi-center study was conducted to evaluate the Bio-Rad GS HIV Combo Ag/Ab EIA, a 4th generation HIV-1/HIV-2 assay for the simultaneous detection of HIV p24 antigen and antibodies to HIV-1 (groups M and O) and HIV-2 in human serum or plasma in adult and pediatric populations. The objectives of the study were to assess assay performance for the detection of acute HIV infections; sensitivity in known HIV positive samples; percent agreement with HIV status; specificity in low and high risk individuals of unknown HIV status; and to compare assay performance to a 3rd generation HIV assay. The evaluation included testing 9150 samples at four U.S. clinical trial sites, using three kit lots. Unlinked samples were from routine testing, repositories or purchased from vendors. GS HIV Combo Ag/Ab EIA detection in samples from individuals in two separate populations with acute HIV infection was 95.2% (20/21) and 86.4% (38/44). Sensitivity was 100% (1603/1603) in known antibody positive [HIV-1 Groups M and O, and HIV-2] samples. HIV p24 antigen detection was 100% (53/53) in HIV-1 culture supernatants. HIV-1 seroconversion panel detection improved by a range of 0-20 days compared to a 3rd generation HIV test. Specificity was 99.9% (5989/5996) in low risk, 99.9% (959/960) in high risk and 100% (100/100) in pediatric populations. The GS HIV Combo Ag/Ab EIA significantly reduced the diagnostic window when compared to the 3rd generation screening assay, enabling earlier diagnosis of HIV infection. The performance parameters of the Bio-Rad GS HIV Combo Ag/Ab EIA are well suited for use in HIV diagnostic settings. Copyright © 2011 Elsevier B.V. All rights reserved.

Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors

OpenAIRE

Hauser, Kurt F.; Knapp, Pamela E.

2014-01-01

Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome (neuroAIDS) and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individua...

Experimental evaluation of ontology-based HIV/AIDS frequently asked question retrieval system.

Science.gov (United States)

Ayalew, Yirsaw; Moeng, Barbara; Mosweunyane, Gontlafetse

2018-05-01

This study presents the results of experimental evaluations of an ontology-based frequently asked question retrieval system in the domain of HIV and AIDS. The main purpose of the system is to provide answers to questions on HIV/AIDS using ontology. To evaluate the effectiveness of the frequently asked question retrieval system, we conducted two experiments. The first experiment focused on the evaluation of the quality of the ontology we developed using the OQuaRE evaluation framework which is based on software quality metrics and metrics designed for ontology quality evaluation. The second experiment focused on evaluating the effectiveness of the ontology in retrieving relevant answers. For this we used an open-source information retrieval platform, Terrier, with retrieval models BM25 and PL2. For the measurement of performance, we used the measures mean average precision, mean reciprocal rank, and precision at 5. The results suggest that frequently asked question retrieval with ontology is more effective than frequently asked question retrieval without ontology in the domain of HIV/AIDS.

Evaluation Of Algorithms Of Anti- HIV Antibody Tests

Directory of Open Access Journals (Sweden)

Paranjape R.S

1997-01-01

Full Text Available Research question: Can alternate algorithms be used in place of conventional algorithm for epidemiological studies of HIV infection with less expenses? Objective: To compare the results of HIV sero- prevalence as determined by test algorithms combining three kits with conventional test algorithm. Study design: Cross â€" sectional. Participants: 282 truck drivers. Statistical analysis: Sensitivity and specificity analysis and predictive values. Results: Three different algorithms that do not include Western Blot (WB were compared with the conventional algorithm, in a truck driver population with 5.6% prevalence of HIV â€"I infection. Algorithms with one EIA (Genetic Systems or Biotest and a rapid test (immunocomb or with two EIAs showed 100% positive predictive value in relation to the conventional algorithm. Using an algorithm with EIA as screening test and a rapid test as a confirmatory test was 50 to 70% less expensive than the conventional algorithm per positive scrum sample. These algorithms obviate the interpretation of indeterminate results and also give differential diagnosis of HIV-2 infection. Alternate algorithms are ideally suited for community based control programme in developing countries. Application of these algorithms in population with low prevalence should also be studied in order to evaluate universal applicability.

HIV control through a single nucleotide on the HLA-B locus

DEFF Research Database (Denmark)

Kløverpris, Henrik N; Harndahl, Mikkel; Leslie, Alasdair J

2012-01-01

Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and str......Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells......:02, which differ by only a single amino acid. Crucially, they occur primarily on identical HLA class I haplotypes and, as Bw6 alleles, do not act as NK cell ligands and are therefore largely unconfounded by other genetic factors. We show that in an outbred cohort (n = 2,093) of HIV C......-clade-infected individuals, a single amino acid change at position 9 of the HLA-B molecule critically affects peptide binding and significantly alters the cytotoxic T lymphocyte (CTL) epitopes targeted, measured directly ex vivo by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay (P = 2 × 10...

S4HARA: System for HIV/AIDS resource allocation.

Science.gov (United States)

Lasry, Arielle; Carter, Michael W; Zaric, Gregory S

2008-03-26

HIV/AIDS resource allocation decisions are influenced by political, social, ethical and other factors that are difficult to quantify. Consequently, quantitative models of HIV/AIDS resource allocation have had limited impact on actual spending decisions. We propose a decision-support System for HIV/AIDS Resource Allocation (S4HARA) that takes into consideration both principles of efficient resource allocation and the role of non-quantifiable influences on the decision-making process for resource allocation. S4HARA is a four-step spreadsheet-based model. The first step serves to identify the factors currently influencing HIV/AIDS allocation decisions. The second step consists of prioritizing HIV/AIDS interventions. The third step involves allocating the budget to the HIV/AIDS interventions using a rational approach. Decision-makers can select from several rational models of resource allocation depending on availability of data and level of complexity. The last step combines the results of the first and third steps to highlight the influencing factors that act as barriers or facilitators to the results suggested by the rational resource allocation approach. Actionable recommendations are then made to improve the allocation. We illustrate S4HARA in the context of a primary healthcare clinic in South Africa. The clinic offers six types of HIV/AIDS interventions and spends US$750,000 annually on these programs. Current allocation decisions are influenced by donors, NGOs and the government as well as by ethical and religious factors. Without additional funding, an optimal allocation of the total budget suggests that the portion allotted to condom distribution be increased from 1% to 15% and the portion allotted to prevention and treatment of opportunistic infections be increased from 43% to 71%, while allocation to other interventions should decrease. Condom uptake at the clinic should be increased by changing the condom distribution policy from a pull system to a push

Frequency of human immunodeficiency virus type-2 in hiv infected patients in Maputo City, Mozambique

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Bhatt Nilesh

2011-08-01

Full Text Available Abstract The HIV/AIDS pandemic is primarily caused by HIV-1. Another virus type, HIV-2, is found mainly in West African countries. We hypothesized that population migration and mobility in Africa may have facilitated the introduction and spreading of HIV-2 in Mozambique. The presence of HIV-2 has important implications for diagnosis and choice of treatment of HIV infection. Hence, the aim of this study was to estimate the prevalence of HIV-2 infection and its genotype in Maputo, Mozambique. HIV-infected individuals (N = 1,200 were consecutively enrolled and screened for IgG antibodies against HIV-1 gp41 and HIV-2 gp36 using peptide-based enzyme immunoassays (pepEIA. Specimens showing reactivity on the HIV-2 pepEIA were further tested using the INNO-LIA immunoblot assay and HIV-2 PCR targeting RT and PR genes. Subtype analysis of HIV-2 was based on the protease gene. After screening with HIV-2 pepEIA 1,168 were non-reactive and 32 were reactive to HIV-2 gp36 peptide. Of this total, 30 specimens were simultaneously reactive to gp41 and gp36 pepEIA while two samples reacted solely to gp36 peptide. Only three specimens containing antibodies against gp36 and gp105 on the INNO-LIA immunoblot assay were found to be positive by PCR to HIV-2 subtype A. The proportion of HIV-2 in Maputo City was 0.25% (90%CI 0.01-0.49. The HIV epidemic in Southern Mozambique is driven by HIV-1, with HIV-2 also circulating at a marginal rate. Surveillance program need to improve HIV-2 diagnosis and consider periodical survey aiming to monitor HIV-2 prevalence in the country.

Genital herpes simplex virus type 2 infection in humanized HIV-transgenic mice triggers HIV shedding and is associated with greater neurological disease.

Science.gov (United States)

Nixon, Briana; Fakioglu, Esra; Stefanidou, Martha; Wang, Yanhua; Dutta, Monica; Goldstein, Harris; Herold, Betsy C

2014-02-15

Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

HIV-TRACE (Transmission Cluster Engine): a tool for large scale molecular epidemiology of HIV-1 and other rapidly evolving pathogens.

Science.gov (United States)

Kosakovsky Pond, Sergei L; Weaver, Steven; Leigh Brown, Andrew J; Wertheim, Joel O

2018-01-31

In modern applications of molecular epidemiology, genetic sequence data are routinely used to identify clusters of transmission in rapidly evolving pathogens, most notably HIV-1. Traditional 'shoeleather' epidemiology infers transmission clusters by tracing chains of partners sharing epidemiological connections (e.g., sexual contact). Here, we present a computational tool for identifying a molecular transmission analog of such clusters: HIV-TRACE (TRAnsmission Cluster Engine). HIV-TRACE implements an approach inspired by traditional epidemiology, by identifying chains of partners whose viral genetic relatedness imply direct or indirect epidemiological connections. Molecular transmission clusters are constructed using codon-aware pairwise alignment to a reference sequence followed by pairwise genetic distance estimation among all sequences. This approach is computationally tractable and is capable of identifying HIV-1 transmission clusters in large surveillance databases comprising tens or hundreds of thousands of sequences in near real time, i.e., on the order of minutes to hours. HIV-TRACE is available at www.hivtrace.org and from github.com/veg/hivtrace, along with the accompanying result visualization module from github.com/veg/hivtrace-viz. Importantly, the approach underlying HIV-TRACE is not limited to the study of HIV-1 and can be applied to study outbreaks and epidemics of other rapidly evolving pathogens. © The Author 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Assessing spatial patterns of HIV knowledge in rural Mozambique using geographic information systems.

Science.gov (United States)

Buehler, Charlotte P; Blevins, Meridith; Ossemane, Ezequiel B; González-Calvo, Lázaro; Ndatimana, Elisée; Vermund, Sten H; Sidat, Mohsin; Olupona, Omo; Moon, Troy D

2015-03-01

To conduct a cross-sectional mapping analysis of HIV knowledge in Zambézia Province, Mozambique, and to examine spatial patterns of HIV knowledge and associated household characteristics. A population-based cluster survey was administered in 2010; data were analysed from 201 enumeration areas in three geographically diverse districts: Alto Molócuè, Morrumbala and Namacurra. We assessed HIV knowledge scores (0-9 points) using previously validated assessment tools. Using geographic information systems (GIS), we mapped hot spots of high and low HIV knowledge. Our multivariable linear regression model estimated HIV knowledge associations with distance to nearest clinic offering antiretroviral therapy, respondent age, education, household size, number of children under five, numeracy, literacy and district of residence. We found little overall HIV knowledge in all three districts. People in Alto Molócuè knew comparatively most about HIV, with a median score of 3 (IQR 2-5) and 22 of 51 (43%) enumeration areas scoring ≥4 of 9 points. Namacurra district, closest to the capital city and expected to have the best HIV knowledge levels, had a median score of 1 (IQR 0-3) and only 3 of 57 (5%) enumeration areas scoring ≥4 points. More HIV knowledge was associated with more education, age, household size, numeracy and proximity to a health facility offering antiretroviral therapy. HIV knowledge is critical for its prevention and treatment. By pinpointing areas of poor HIV knowledge, programme planners can prioritize educational resources and outreach initiatives within the context of antiretroviral therapy expansion. © 2014 John Wiley & Sons Ltd.

Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

Science.gov (United States)

Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

2017-06-01

HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

Evaluation of the NucliSens EasyQ v2.0 assay in comparison with the Roche Amplicor v1.5 and the Roche CAP/CTM HIV-1 Test v2.0 in quantification of C-clade HIV-1 in plasma.

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Maximilian Muenchhoff

Full Text Available Human immunodeficiency virus type 1 (HIV-1 genetic diversity poses a challenge to reliable viral load monitoring. Discrepancies between different testing platforms have been observed, especially for non-clade-B virus. Therefore we compare, in antiretroviral therapy (ART-naïve South African subjects predominantly infected with HIV-1 clade-C, three commercially available assays: the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test version 2.0 by Roche (CAP/CTM v2.0, the BioMérieux NucliSens Version 2.0 Easy Q/Easy Mag (NucliSens v2.0 and the Roche COBAS Amplicor HIV-1 Monitor Test Version 1.5 (Amplicor v1.5. Strong linear correlation was observed and Bland-Altman analyses showed overall good agreement between the assays with mean viral load differences of 0.078 log cp/ml (NucliSens v2.0 - Amplicor v1.5, 0.260 log cp/ml (CAP/CTM v2.0 - Amplicor v1.5 and 0.164 log cp/ml (CAP/CTM v2.0 - NucliSens v2.0, indicating lower mean viral load results for the Amplicor v1.5 and higher mean readings for the CAP/CTM v2.0. Consistent with observations following previous comparisons of CAP/CTM v2.0 versus Amplicor v1.5, the CAP/CTM v2.0 assay detected low-level viremia (median 65 cp/ml in more than one-third of those in whom viremia had been undetectable (<20 cp/ml in assays using the NucliSens platform. These levels of viremia are of uncertain clinical significance but may be of importance in early detection of ART resistance in those on treatment. Overall the three assays showed good comparability of results but with consistent, albeit relatively small, discrepancies for HIV-1 clade-C samples, especially in the low-viremic range that should be taken into account when interpreting viral load data.

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility.

Science.gov (United States)

Chintalapudi, Sumana R; Maria, Doaa; Di Wang, Xiang; Bailey, Jessica N Cooke; Hysi, Pirro G; Wiggs, Janey L; Williams, Robert W; Jablonski, Monica M

2017-11-24

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.

Interleukin-2 therapy in patients with HIV infection

DEFF Research Database (Denmark)

Abrams, D; Lévy, Y; Losso, M H

2009-01-01

Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either...

ORIGINAL ARTICLES Huntington's disease: Genetic heterogeneity ...

African Journals Online (AJOL)

2008-03-01

Mar 1, 2008 ... African origin.5 HD is considered rare among South African blacks, with an ... functions, syphilis, HIV and other tests in selected patients. We .... The discovery of a second genetic locus, resulting in HDL2,7 suggests the need ...

Management of mental health disorders and central nervous system sequelae in HIV-positive children and adolescents

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R Nassen

2014-09-01

Full Text Available HIV-positive children and adolescents are at increased risk of both central nervous system (CNS sequelae and mental disorders owing to a number of factors, including the impact of HIV infection on the brain, social determinants of health (e.g. poverty and orphanhood and psychosocial stressors related to living with HIV. Every effort should be made to identify perinatally HIV-infected children and initiate them on antiretroviral therapy early in life. HIV clinicians should ideally screen for mental health and neurocognitive problems, as part of the routine monitoring of children attending antiretroviral clinics. This guideline is intended as a reference tool for HIV clinicians to support the early identification, screening and management of mental health disorders and/or CNS impairment in children and adolescents. This guideline covers mental disorders (section 1 and HIV-associated neurocognitive disorders (section 2 among children and adolescents.

HIV-1 and HIV-2 infections in Guinea-Bissau, West Africa : studies of immune responses, prevailing viruses and epidemiological trends

OpenAIRE

Andersson, Sören

1999-01-01

This thesis encompasses immunological, virological and epidemiological studies of HIV-1 and HIV-2 infections in Guinea-Bissau. We have established a robust and reliable diagnostic strategy based on a combination of enzyme-linked immunosorbent assays (ELISAs) and rapid simple tests. Evaluations showed that the strategy had a high capacity to discriminate between HIV-1 and HIV-2 and a high concordance with polymerase chain reaction (PCR) testing. Epidemiological studies in...

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau

DEFF Research Database (Denmark)

Holmgren, B; da Silva, Z; Larsen, Olav Ditlevsen

2003-01-01

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were...... interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated...... with a blood sample in the HIV prevalence analyses and 1581 individuals participated in the HTLV-I prevalence analyses. The overall prevalence was 2.1% for HIV-1, 13.5% for HIV-2 and 7.1% for HTLV-I. Comparing the

The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.

Science.gov (United States)

Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

2009-09-01

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

Developing strategies for HIV-1 eradication

Science.gov (United States)

Durand, Christine M.; Blankson, Joel N.; Siliciano, Robert F.

2014-01-01

Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication, transforming the outlook for infected patients. However, reservoirs of replication-competent forms of the virus persist during HAART, and when treatment is stopped, high rates of HIV-1 replication return. Recent insights into HIV-1 latency, as well as a report that HIV-1 infection was eradicated in one individual, have renewed interest in finding a cure for HIV-1 infection. Strategies for HIV-1 eradication include gene therapy and hematopoietic stem cell transplantation, stimulating host immunity to control HIV-1 replication, and targeting latent HIV-1 in resting memory CD4+ T cells. Future efforts should aim to provide better understanding of how to reconstitute the CD4+ T cell compartment with genetically engineered cells, exert immune control over HIV-1 replication, and identify and eliminate all viral reservoirs. PMID:22867874

Human anti-HIV IgM detection by the OraQuick ADVANCE® Rapid HIV 1/2 Antibody Test.

Science.gov (United States)

Guillon, Geraldine; Yearwood, Graham; Snipes, Casey; Boschi, Daniel; Reed, Michael R

2018-01-01

The Centers for Disease Control and Prevention (CDC) and many public health jurisdictions continue to advocate for the most sensitive rapid HIV test that is available. Currently, the recommendation is to utilize tests that can detect HIV infection biomarkers within 30 days of infection, when initial immune responses are mounted. The infected patient's IgM response is often used to detect acute infection within a 20-25 days window after infection. This requirement applies to lab-based testing with automated analyzers and rapid, point of care (POC) testing used for screening in a non-clinical setting. A recent study has demonstrated that POC tests using a Protein A-based detection system can detect samples with predominantly HIV-1 IgM reactivity (Moshgabadi et al., 2015). The OraQuick ADVANCE ® Rapid HIV-1/2 Antibody Test (OraQuick ADVANCE ®) also uses Protein A as the detection protein in the antibody-binding colloidal gold conjugate, so it is expected that the OraQuick ADVANCE ® Test will also detect samples with predominantly IgM reactivity. This report definitively demonstrates that the OraQuick ADVANCE ® Test can detect IgM antibodies during an acute infection window period of approximately 20-25 days after infection, and is therefore suitable for use in testing environments requiring adherence to current CDC recommendations.

Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

Science.gov (United States)

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

2009-04-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

Directory of Open Access Journals (Sweden)

Gretja Schnell

2009-04-01

Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

Directory of Open Access Journals (Sweden)

van Manen Daniëlle

2012-08-01

Full Text Available Abstract Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection. This review gives an overview of findings from the GWAS performed on HIV infection, within different cohorts, with variable patient and phenotype selection. Furthermore, novel techniques and strategies in research that might contribute to the complete understanding of virus-host interactions and its role on the pathogenesis of HIV infection are discussed.

S4HARA: System for HIV/AIDS resource allocation

Directory of Open Access Journals (Sweden)

Carter Michael W

2008-03-01

Full Text Available Abstract Background HIV/AIDS resource allocation decisions are influenced by political, social, ethical and other factors that are difficult to quantify. Consequently, quantitative models of HIV/AIDS resource allocation have had limited impact on actual spending decisions. We propose a decision-support System for HIV/AIDS Resource Allocation (S4HARA that takes into consideration both principles of efficient resource allocation and the role of non-quantifiable influences on the decision-making process for resource allocation. Methods S4HARA is a four-step spreadsheet-based model. The first step serves to identify the factors currently influencing HIV/AIDS allocation decisions. The second step consists of prioritizing HIV/AIDS interventions. The third step involves allocating the budget to the HIV/AIDS interventions using a rational approach. Decision-makers can select from several rational models of resource allocation depending on availability of data and level of complexity. The last step combines the results of the first and third steps to highlight the influencing factors that act as barriers or facilitators to the results suggested by the rational resource allocation approach. Actionable recommendations are then made to improve the allocation. We illustrate S4HARA in the context of a primary healthcare clinic in South Africa. Results The clinic offers six types of HIV/AIDS interventions and spends US$750,000 annually on these programs. Current allocation decisions are influenced by donors, NGOs and the government as well as by ethical and religious factors. Without additional funding, an optimal allocation of the total budget suggests that the portion allotted to condom distribution be increased from 1% to 15% and the portion allotted to prevention and treatment of opportunistic infections be increased from 43% to 71%, while allocation to other interventions should decrease. Conclusion Condom uptake at the clinic should be increased by

The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses.

Directory of Open Access Journals (Sweden)

Eliran Moshe Reuven

2014-08-01

Full Text Available HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD of the HIV-1 envelope (ENV directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.

The HIVToolbox 2 web system integrates sequence, structure, function and mutation analysis.

Directory of Open Access Journals (Sweden)

David P Sargeant

Full Text Available There is enormous interest in studying HIV pathogenesis for improving the treatment of patients with HIV infection. HIV infection has become one of the best-studied systems for understanding how a virus can hijack a cell. To help facilitate discovery, we previously built HIVToolbox, a web system for visual data mining. The original HIVToolbox integrated information for HIV protein sequence, structure, functional sites, and sequence conservation. This web system has been used for almost 40,000 searches. We report improvements to HIVToolbox including new functions and workflows, data updates, and updates for ease of use. HIVToolbox2, is an improvement over HIVToolbox with new functions. HIVToolbox2 has new functionalities focused on HIV pathogenesis including drug-binding sites, drug-resistance mutations, and immune epitopes. The integrated, interactive view enables visual mining to generate hypotheses that are not readily revealed by other approaches. Most HIV proteins form multimers, and there are posttranslational modification and protein-protein interaction sites at many of these multimerization interfaces. Analysis of protease drug binding sites reveals an anatomy of drug resistance with different types of drug-resistance mutations regionally localized on the surface of protease. Some of these drug-resistance mutations have a high prevalence in specific HIV-1 M subtypes. Finally, consolidation of Tat functional sites reveals a hotspot region where there appear to be 30 interactions or posttranslational modifications. A cursory analysis with HIVToolbox2 has helped to identify several global patterns for HIV proteins. An initial analysis with this tool identifies homomultimerization of almost all HIV proteins, functional sites that overlap with multimerization sites, a global drug resistance anatomy for HIV protease, and specific distributions of some DRMs in specific HIV M subtypes. HIVToolbox2 is an open-access web application available at

Glycosylation in HIV-1 envelope glycoprotein and its biological implications

KAUST Repository

Ho, Yung Shwen

2013-08-01

Glycosylation of HIV-1 envelope proteins (Env gp120/gp41) plays a vital role in viral evasion from the host immune response, which occurs through the masking of key neutralization epitopes and the presentation of the Env glycosylation as \\'self\\' to the host immune system. Env glycosylation is generally conserved, yet its continual evolution plays an important role in modulating viral infectivity and Env immunogenicity. Thus, it is believed that Env glycosylation, which is a vital part of the HIV-1 architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may assist in effectively designing Env-based immunogens and in clearly understanding HIV vaccines. This review provides an in-depth perspective of various aspects of Env glycosylation in the context of HIV-1 pathogenesis. © 2013 Future Medicine Ltd.

Genetic polymorphisms associated with fatty liver disease and fibrosis in HIV positive patients receiving combined antiretroviral therapy (cART)

Science.gov (United States)

Luda, Carolin; Schwarze-Zander, Carolynne; Boesecke, Christoph; Hansel, Cordula; Nischalke, Hans-Dieter; Lutz, Philipp; Mohr, Raphael; Wasmuth, Jan-Christian; Strassburg, Christian P.; Trebicka, Jonel; Rockstroh, Jürgen Kurt; Spengler, Ulrich

2017-01-01

Hepatic steatosis can occur with any antiretroviral therapy (cART). Although single nucleotide polymorphisms (SNPs) have been identified to predispose to alcoholic and non-alcoholic fatty liver disease, their role for treatment-associated steatosis in HIV-positive patients remains unclear. We determined the frequency of PNPLA3 (rs738409), CSPG3/NCAN (rs2228603), GCKR (rs780094), PPP1R3B (rs4240624), TM6SF (rs8542926), LYPLAL1 (rs12137855) and MBOAT7 (rs626283) by RT-PCR in 117 HIV-positive patients on cART and stratified participants based on their “controlled attenuation parameter” (CAP) into probable (CAP: 215–300 dB/m) and definite (CAP >300 dB/m) hepatic steatosis. We analyzed CAP values and routine metabolic parameters according to the allele frequencies. Sixty-five (55.6%) and 13 (11.1%) patients were allocated to probable and definite steatosis. CAP values (p = 0.012) and serum triglycerides (p = 0.043) were increased in carriers of the GCKR (rs780094) A allele. Cox logistic regression identified triglycerides (p = 0.006), bilirubin (p = 0.021) and BMI (p = 0.068), but not the genetic parameters as risk factors for the occurrence of hepatic steatosis. Taken together, according to the limited sample size, this exploratory study generates the hypothesis that genetic polymorphisms seem to exert minor effects on the risk for fatty liver disease in HIV-positive patients on cART. Nevertheless, SNPs may modify metabolic complications once metabolic abnormalities have developed. Hence, subsequent analysis of a larger cohort is needed. PMID:28594920

Traditional medicines, HIV, and related infections: workshop 2C.

Science.gov (United States)

Patel, M; Bessong, P; Liu, H

2011-04-01

Traditional medicines are an integral part of health care worldwide, even though their efficacy has not been scientifically proven. HIV-infected individuals may use them singularly or in combination with conventional medicines. Many in vitro studies have proven the anti-HIV, anti-Candida, and anti-herpes simplex virus potential of traditional plants and identified some of the mechanisms of action. Very few in vivo studies are available that involve a small number of participants and show controversial results. In addition, knowledge is limited of the role of traditional medicines in the enhancement of the immune system. The use of traditional medicines with antiretroviral drugs (ARVs) has created a problem because drug interactions compromise the efficacy of ARVs. Several currently popular plants have been studied in the laboratory for their interaction with ARVs, with disadvantageous results. Unfortunately, no clinical trials are available. The science of traditional medicines is relatively new and is at present being modernized worldwide. However, there are still ethical issues regarding traditional medicines that need to be addressed-for example, regulations regarding quality control and standardization of medicines, regulation and education of healers who deliver these medicines, and unregulated clinical trials. The workshop addressed the following questions about traditional medicine and their use in HIV infection: What are the mechanisms of action of anti-HIV traditional medicines? Should traditional medicines be used in conjunction with ARV? Do traditional medicines enhance the immune system? Should medicinal plants be used for the control of oral infections associated with HIV? What are the ethical issues surrounding the use of traditional medicines for the treatment of HIV and associated infections?

Dynamic of HIV-testing after arrival in France for migrants from sub-Saharan Africa: The role of both health and social care systems.

Science.gov (United States)

Limousi, Frédérike; Lert, France; Desgrées du Loû, Annabel; Dray-Spira, Rosemary; Lydié, Nathalie

2017-01-01

HIV testing is an important tool in the management of the HIV epidemic among key populations. We aimed to explore the dynamic of first-time HIV testing in France for sub-Saharan migrants after their arrival. ANRS-Parcours is a retrospective life-event survey conducted from 2012 to 2013 in healthcare facilities in the Paris region, among 926 sub-Saharan HIV-infected migrants and 763 non-infected migrants. After describing the time to first HIV test in France and associated circumstances, we performed a discrete-time logistic regression to analyze the influence of socioeconomic position, contact with the healthcare system and sexual behaviors, on first-time HIV testing in France in migrants who arrived after 2000. Median first-time HIV testing occurred during the second year spent in France for non-infected men and women in both groups, and during the first year for men of the HIV group. The probability of testing increased with hospitalization and pregnancy for women of both groups. For non-infected men unemployment and absence of a residence permit were associated with an increased probability of HIV testing [respectively, OR = 2.2 (1.2-4.1) and OR = 2.0 (1.1-3.5)]. Unemployment was also associated with an increased probability of first-time HIV-testing for women of the HIV group [OR: 1.7 (1.0-2.7)]. Occasional and multiple sexual relationships were associated with an increased probability of first-time testing only for HIV-infected women [OR: 2.2 (1.2-4.0) and OR = 2.4 (1.3-4.6)]. Access to first HIV testing in France is promoted by contact with the health care system and is facilitated for unemployed and undocumented migrants after arrival.However, testing should be offered more systematically and repeated in order to reduce time between HIV infection and diagnosis, especially for deprived people which are particularly vulnerable regarding HIV infection.

HIV-1 Resistant CDK2-Knockdown Macrophage-Like Cells Generated from 293T Cell-Derived Human Induced Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Kuan-Teh Jeang

2012-07-01

Full Text Available A major challenge in studies of human diseases involving macrophages is low yield and heterogeneity of the primary cells and limited ability of these cells for transfections and genetic manipulations. To address this issue, we developed a simple and efficient three steps method for somatic 293T cells reprogramming into monocytes and macrophage-like cells. First, 293T cells were reprogrammed into induced pluripotent stem cells (iPSCs through a transfection-mediated expression of two factors, Oct-4 and Sox2, resulting in a high yield of iPSC. Second, the obtained iPSC were differentiated into monocytes using IL-3 and M-CSF treatment. And third, monocytes were differentiated into macrophage-like cells in the presence of M-CSF. As an example, we developed HIV-1-resistant macrophage-like cells from 293T cells with knockdown of CDK2, a factor critical for HIV-1 transcription. Our study provides a proof-of-principle approach that can be used to study the role of host cell factors in HIV-1 infection of human macrophages.

Access to HIV community services by vulnerable populations: evidence from an enhanced HIV/AIDS surveillance system.

Science.gov (United States)

Madden, H C E; Phillips-Howard, P A; Hargreaves, S C; Downing, J; Bellis, M A; Vivancos, R; Morley, C; Syed, Q; Cook, P A

2011-05-01

HIV disproportionately affects vulnerable populations such as black and minority ethnic groups, men who have sex with men (MSM) and migrants, in many countries including those in the UK. Community organisations in the UK are charitable non-governmental organisations with a proportion of the workforce who volunteer, and provide invaluable additional support for people living with HIV (PLWHIV). Information on their contribution to HIV care in vulnerable groups is relatively sparse. Data generated from an enhanced HIV surveillance system in North West England, UK, was utilised for this study. We aimed to determine the characteristics of individuals who chose to access community services in addition to clinical services (1375 out of 4195 records of PLWHIV in clinical services). Demographic information, risk factors including residency status, uniquely gathered in this region, and deprivation scores were examined. Multivariate logistic regression modelling was conducted to predict the relative effect of patient characteristics on attendance at community services. Attendance at community services was highest in those living in the most, compared with least, deprived areas (p<0.001), and was most evident in MSM and heterosexuals. Compared to white UK nationals attendance was significantly higher in non-UK nationals of uncertain residency status (Adjusted odds ratio [AOR] = 21.91, 95% confidence interval [CI] 10.48-45.83; p<0.001), refugees (AOR = 5.75, 95% CI 3.3-10.03; p<0.001), migrant workers (AOR = 5.48, 95% CI 2.22-13.51; p<0.001) and temporary visitors (AOR = 3.44, 95% CI 1.68-7.05; p<0.001). Community services, initially established predominantly to support MSM, have responded to the changing demography of HIV and reach the most vulnerable members of society. Consequent to their support of migrant populations, community services are vital for the management of HIV in black and minority groups. Paradoxically, this coincides with increasing funding pressures on these

Glycosylphosphatidylinositol-Anchored Anti-HIV scFv Efficiently Protects CD4 T Cells from HIV-1 Infection and Deletion in hu-PBL Mice

Science.gov (United States)

Ye, Chaobaihui; Wang, Weiming; Cheng, Liang; Li, Guangming; Wen, Michael; Wang, Qi; Zhang, Qing; Li, Dan

2016-01-01

ABSTRACT Despite success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of the HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from a homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance in permissive cells. Here, we employed a glycosylphosphatidylinositol (GPI)-scFv X5 approach to confer resistance of human primary CD4 T cells to HIV-1. We showed that primary CD4 T cells expressing GPI-scFv X5 were resistant to CCR5 (R5)-, CXCR4 (X4)-, and dual-tropic HIV-1 and had a survival advantage compared to control cells ex vivo. In a hu-PBL mouse study, GPI-scFv X5-transduced CD4 T cells were selected in peripheral blood and lymphoid tissues upon HIV-1 infection. Finally, GPI-scFv X5-transduced CD4 T cells, after being cotransfused with HIV-infected cells, showed significantly reduced viral loads and viral RNA copy numbers relative to CD4 cells in hu-PBL mice compared to mice with GPI-scFv AB65-transduced CD4 T cells. We conclude that GPI-scFv X5-modified CD4 T cells could potentially be used as a genetic intervention against both R5- and X4-tropic HIV-1 infections. IMPORTANCE Blocking of HIV-1 entry is one of most promising approaches for therapy. Genetic disruption of the HIV-1 coreceptor CCR5 by nucleases in T cells is under 2 clinical trials and leads to reduced viremia in patients. However, the emergence of viruses using the CXCR4 coreceptor is a concern for therapies applying single-coreceptor disruption. Here, we report that HIV-1-permissive CD4 T cells engineered with GPI-scFv X5 are resistant to R5-, X4-, or dual-tropic virus infection ex vivo. In a preclinical study using hu-PBL mice, we show that CD4 T cells were protected and that GPI-scFv X5

Direct and dynamic detection of HIV-1 in living cells.

Directory of Open Access Journals (Sweden)

Jonas Helma

Full Text Available In basic and applied HIV research, reliable detection of viral components is crucial to monitor progression of infection. While it is routine to detect structural viral proteins in vitro for diagnostic purposes, it previously remained impossible to directly and dynamically visualize HIV in living cells without genetic modification of the virus. Here, we describe a novel fluorescent biosensor to dynamically trace HIV-1 morphogenesis in living cells. We generated a camelid single domain antibody that specifically binds the HIV-1 capsid protein (CA at subnanomolar affinity and fused it to fluorescent proteins. The resulting fluorescent chromobody specifically recognizes the CA-harbouring HIV-1 Gag precursor protein in living cells and is applicable in various advanced light microscopy systems. Confocal live cell microscopy and super-resolution microscopy allowed detection and dynamic tracing of individual virion assemblies at the plasma membrane. The analysis of subcellular binding kinetics showed cytoplasmic antigen recognition and incorporation into virion assembly sites. Finally, we demonstrate the use of this new reporter in automated image analysis, providing a robust tool for cell-based HIV research.

Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

Science.gov (United States)

Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

2009-01-01

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

Directory of Open Access Journals (Sweden)

Maia Hightower

Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

Soluble HIV-1 envelope immunogens derived from an elite neutralizer elicit cross-reactive V1V2 antibodies and low potency neutralizing antibodies.

Directory of Open Access Journals (Sweden)

Sara Carbonetti

Full Text Available We evaluated four gp140 Envelope protein vaccine immunogens that were derived from an elite neutralizer, subject VC10042, whose plasma was able to potently neutralize a wide array of genetically distinct HIV-1 isolates. We sought to determine whether soluble Envelope proteins derived from the viruses circulating in VC10042 could be used as immunogens to elicit similar neutralizing antibody responses by vaccination. Each gp140 was tested in its trimeric and monomeric forms, and we evaluated two gp140 trimer vaccine regimens in which adjuvant was supplied at all four immunizations or at only the first two immunizations. Interestingly, all four Envelope immunogens elicited high titers of cross-reactive antibodies that recognize the variable regions V1V2 and are potentially similar to antibodies linked with a reduced risk of HIV-1 acquisition in the RV144 vaccine trial. Two of the four immunogens elicited neutralizing antibody responses that neutralized a wide array of HIV-1 isolates from across genetic clades, but those responses were of very low potency. There were no significant differences in the responses elicited by trimers or monomers, nor was there a significant difference between the two adjuvant regimens. Our study identified two promising Envelope immunogens that elicited anti-V1V2 antibodies and broad, but low potency, neutralizing antibody responses.

HIV-1 transmission during early infection in men who have sex with men: a phylodynamic analysis.

Directory of Open Access Journals (Sweden)

Erik M Volz

2013-12-01

Full Text Available Conventional epidemiological surveillance of infectious diseases is focused on characterization of incident infections and estimation of the number of prevalent infections. Advances in methods for the analysis of the population-level genetic variation of viruses can potentially provide information about donors, not just recipients, of infection. Genetic sequences from many viruses are increasingly abundant, especially HIV, which is routinely sequenced for surveillance of drug resistance mutations. We conducted a phylodynamic analysis of HIV genetic sequence data and surveillance data from a US population of men who have sex with men (MSM and estimated incidence and transmission rates by stage of infection.We analyzed 662 HIV-1 subtype B sequences collected between October 14, 2004, and February 24, 2012, from MSM in the Detroit metropolitan area, Michigan. These sequences were cross-referenced with a database of 30,200 patients diagnosed with HIV infection in the state of Michigan, which includes clinical information that is informative about the recency of infection at the time of diagnosis. These data were analyzed using recently developed population genetic methods that have enabled the estimation of transmission rates from the population-level genetic diversity of the virus. We found that genetic data are highly informative about HIV donors in ways that standard surveillance data are not. Genetic data are especially informative about the stage of infection of donors at the point of transmission. We estimate that 44.7% (95% CI, 42.2%-46.4% of transmissions occur during the first year of infection.In this study, almost half of transmissions occurred within the first year of HIV infection in MSM. Our conclusions may be sensitive to un-modeled intra-host evolutionary dynamics, un-modeled sexual risk behavior, and uncertainty in the stage of infected hosts at the time of sampling. The intensity of transmission during early infection may have

Male Circumcision and the Epidemic Emergence of HIV-2 in West Africa

Science.gov (United States)

Hewlett, Barry Stephen; Camacho, Ricardo Jorge

2016-01-01

Background Epidemic HIV-2 (groups A and B) emerged in humans circa 1930–40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985–91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread. Male circumcision (MC) is known to correlate negatively with HIV-1 prevalence in Africa, but studies examining this issue for HIV-2 are lacking. Methods We reviewed published HIV-2 serosurveys for 30 cities of all West African countries and obtained credible estimates of real prevalence through Bayesian estimation. We estimated past MC rates of 218 West African ethnic groups, based on ethnographic literature and fieldwork. We collected demographic tables specifying the ethnic partition in cities. Uncertainty was incorporated by defining plausible ranges of parameters (e.g. timing of introduction, proportion circumcised). We generated 1,000 sets of past MC rates per city using Latin Hypercube Sampling with different parameter combinations, and explored the correlation between HIV-2 prevalence and estimated MC rate (both logit-transformed) in the 1,000 replicates. Results and Conclusions Our survey reveals that, in the early 20th century, MC was far less common and geographically more variable than nowadays. HIV-2 prevalence in 1985–91 and MC rates in 1950 were negatively correlated (Spearman rho = -0.546, IQR: -0.553–-0.546, p≤0.0021). Guinea-Bissau and Côte d'Ivoire cities had markedly lower MC rates. In addition, MC was uncommon in rural southwestern Côte d'Ivoire in 1930.The differential HIV-2 spread in West Africa correlates with different historical MC rates. We suggest HIV-2 only formed early substantial foci in cities with substantial uncircumcised

Nucleic acid amplification of HIV-1 integrase sequence subtypes CRF01_AE and B for development of HIV anti-integrase drug resistance genotyping assay

Science.gov (United States)

Adlar, F. R.; Bela, B.

2017-08-01

To anticipate the potential use of anti-integrase drugs in Indonesia for treatment of HIV-1 infection, the development of a drug resistance genotyping assay for anti-integrase is crucial in identifying the genetic drug resistance profile of Indonesian HIV-1 strains. This experiment aimed to amplify a target region in the integrase gene of Indonesian HIV-1 subtypes CRF01_AE and B that contain genetic mutations known to confer resistance to anti-integrase drug. Eleven archived plasma samples from individuals living with HIV-1 were obtained from the Virology and Cancer Pathobiology Research Center for Health Service (VCPRC FKUI-RSCM) laboratory. One of the plasma samples contained HIV-1 subtype B, and the remaining plasma samples contained subtype CRF01_AE. The target regions for all samples were amplified through RT-PCR, with an annealing temperature of 55 °C, using the primer pair AE_POL 4086F and AE_POL 5232R that were designed by VCPRC FKUI-RSCM. The results of this experiment show that 18.2% (2/11) of the samples were successfully amplified using the one-step RT-PCR. While the primer pair was effective in amplifying the target region in the integrase gene sequence for subtype B (100%; 1/1), it had a low efficacy (10%, 1/10) for subtype CRF01_AE. In conclusion, the primer pair can be used to amplify the target region in Indonesian HIV-1 strain subtypes CRF01_AE and B. However, optimization of the PCR condition and an increased number of samples would help to determine an accurate representation of the efficacy of the primer pair.

Laboratory Diagnosis Of Dual Hiv-1/Hiv-2 Infection In Ghanaian ...

African Journals Online (AJOL)

Objective: To determine the true prevalence of HIV dual infections in a previously characterised HIV seropositive patient group due to inconsistencies between different diagnostic methods. Design: A cross-sectional study of an HIV seropositive group with different diagnostic methods. Setting: Three hospitals in the Northern, ...

New inhibitors of HDAC to purge latent HIV-1 reservoir

Czech Academy of Sciences Publication Activity Database

Hejnar, Jiří; Hirsch, I.

2010-01-01

Roč. 2, č. 4 (2010), s. 505-506 ISSN 1750-1911 Institutional research plan: CEZ:AV0Z50520514 Keywords : HAART * HIV latency * HDAC inhibitor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.429, year: 2010

Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems

Science.gov (United States)

Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Forthal, Donald; Mao, Lingjun; -Abanto, Segundo Hernandez; Urban, Lori; Landucci, Gary; Fischer, Rainer; Jiang, Xiaoming

2013-01-01

Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain antibody construct (m9), for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production. PMID:23533588

Rapid high-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems.

Directory of Open Access Journals (Sweden)

Yvonne Rosenberg

Full Text Available Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT of simian/human immunodeficiency virus (SHIV in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6PΔ140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01 or a single chain antibody construct (m9, for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production.

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi

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Javier M. Urquiza

2017-08-01

Full Text Available The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV, the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.

CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

DEFF Research Database (Denmark)

Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

2017-01-01

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations...

Differential effects of sex in a West African cohort of HIV-1, HIV-2, and HIV-1/2 infected patients

DEFF Research Database (Denmark)

Jespersen, Sanne; Hønge, Bo Langhoff; Esbjörnsson, Joakim

2016-01-01

initiation of ART, death or loss to follow-up using Cox proportional hazard models. RESULTS: A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P

Evaluation of HIV Surveillance System in Rivers State, Nigeria ...

African Journals Online (AJOL)

Sony Computer (Iby)

HIV surveillance system generates information for timely and appropriate ..... active type of surveillance.14 Nonetheless, it requires training, supervision and motivation ... very effectively.14 The introduction of reward-system could be included.

Enhanced mucosal and systemic immune response with intranasal immunization of mice with HIV peptides entrapped in PLG microparticles in combination with Ulex Europaeus-I lectin as M cell target.

Science.gov (United States)

Manocha, Monika; Pal, Pramod Chandra; Chitralekha, K T; Thomas, Beena Elizabeth; Tripathi, Vinita; Gupta, Siddhartha Dutta; Paranjape, Ramesh; Kulkarni, Smita; Rao, D Nageswara

2005-12-01

The predominant route of HIV infection is through the sexual transmission via M cells. Most of the peptide and protein vaccines show poor transport across the epithelial barrier and are commonly administered by parenteral route. In the present study four HIV peptides from envelope (gp 41-LZ (leucine zipper), gp 41-FD (fusion domain) and gp120-C2) and regulatory (Nef) region in poly lactic-co-glycolide (PLG) micro-particle delivery were evaluated in mice of outbred and with different genetic background to compare immune response versus MHC restriction. Out of the combinational and single routes of immunization attempted, the single route maintained the IgG, IgA and sIgA in sera and washes for longer duration as compared to combinational routes in which the response was declined. The study demonstrated that single intranasal immunization offered significantly higher immune response (pPP>or=SP. The cytokine measurement profile of IL-2, IFN-gamma and IL-6 and low levels of IL-4 in the cultural supernatants of SP, PP and LP showed mixed CD4(+) Th1 and Th2 immune response. The p24 assay showed high percent inhibition of HIV-IIIB virus with sera and washes obtained from intranasal route. Thus, overall the study highlighted the combination of UEA-1 lectin with HIV peptides in micro-particles through intranasal immunization generated systemic as well as mucosal immune response.

[Comparison of the clinical performance of the ECLusys HIV combi assay with the Lumipulse f and HISCL 2000-i HIV-1/2 ab screening assays].

Science.gov (United States)

Sugiura, Aya; Iwahara, Kunihiro; Suga, Yasuyuki; Uchiyama, Sachinori; Maekawa, Masato

2012-04-01

We compared the ECLusys HIV combi assay (ECL HIV Ag/Ab) to the Lumipulse Forte (LPf HIV 1/2 Ab) and HISCL (HIS HIV 1/2 Ab) assays. In a dilution sensitivity test using dilution panels of WHO HIV antibody international reference panel (HIV-1 Subtype A, B, C, E, HIV-1 Group O, HIV-2) and HIV-1/2 Ab CE marked material(HIV-1, HIV-2) parent specimens, the ECL assay enabled detection at a higher level of sensitivity than either the LPf assay or the HIS assay for all dilution panels. In an early detection test in the early phase of infection in which a BBI HIV seroconversion panel was used, the ECL assay enabled detection 7 days after initial blood sample collection, whereas the LPf and HIS assays enabled detection after 27 days. In a specificity test using high RF positive specimens (n=33), pregnancy specimens (n=35), cytomegalovirus antibody positive specimens (n=36), and high M protein positive specimens (n=21) that were confirmed negative for HIV-1/2 antibodies by the LPf assay, negative results were obtained for all specimens on both the ECL assay and the HIS assay. In a correlation test using routinely collected clinical specimens (n=121), including positive stock specimens, the ECL and HIS assays demonstrated the highest agreement rate 98.3%. The above results confirmed that the fourth-generation reagent ECL assay, which simultaneously detects both HIV-1/2 antibodies and p24 antigens, is both highly sensitive and specific, and is a suitable assay for use in routine testing.

A Home Integral Telecare System for HIV/AIDS Patients.

Science.gov (United States)

Caceres, Cesar; Gomez, Enrique J; Garcia, Felipe; Chausa, Paloma; Guzman, Jorge; Del Pozo, Francisco; Gatell, Jose Maria

2005-01-01

VIHrtual Hospital is a telemedicine web system for improving home integral care of chronic HIV patients through the Internet. Using the videoconference, chat or messaging tools included in the system, patients can visit their healthcare providers (physician, psychologist, nurse, psychiatrist, pharmacist, and social worker), having these access to the Electronic Patient Record. The system also provides a telepharmacy service that controls treatment adherence and side effects, sending the medication to the patient's home by courier. A virtual community has been created, facilitating communication between patients and improving the collaboration between professionals, creating a care plan for each patient. As a complement, there is a virtual library where users can find validated HIV/AIDS information helping to enhance prevention. This system has been developed using low cost technologies in order to extend the number of patients involved in its trial. Thus, VIHrtual Hospital is now on trial in the Hospital Clinic (Barcelona, Spain) involving a hundred patients and twenty healthcare professionals during two years.Although we are still waiting for the final results of the trial, we can already say that the use of telemedicine systems developed ad hoc for a chronic disease, like HIV/AIDS, improve the quality of care of the patients and their care team. The system described is a good example of the possibilities that technologies are offering to create new chronic patient care models based on telemedicine.

Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression

DEFF Research Database (Denmark)

Ioannidis, J P; Rosenberg, P S; Goedert, J J

2001-01-01

BACKGROUND: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. OBJECTIVE: To examine postulated associations of genetic alleles with HIV-1 disease progression. DESIGN: Meta-analysis of individual-patient data....... SETTING: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. PATIENTS: Patients with HIV-1 infection who were of European or African descent. MEASUREMENTS: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after...... (relative hazard among seroconverters, 0.64 and 0.74; P HIV-1 RNA levels after seroconversion (difference, -0.18 log(10) copies/mL and -0.14 log(10) copies/mL; P

Primary and Chronic HIV Infection Differently Modulates Mucosal Vδ1 and Vδ2 T-Cells Differentiation Profile and Effector Functions.

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Eleonora Cimini

Full Text Available Gut-associated immune system has been identified as a major battlefield during the early phases of HIV infection. γδ T-cells, deeply affected in number and function after HIV infection, are able to act as a first line of defence against invading pathogens by producing antiviral soluble factors and by killing infected cells. Despite the relevant role in mucosal immunity, few data are available on gut-associated γδ T-cells during HIV infection. Aim of this work was to evaluate how primary (P-HIV and chronic (C-HIV HIV infection affects differentiation profile and functionality of circulating and gut-associated Vδ1 and Vδ2 T-cells. In particular, circulating and mucosal cells were isolated from respectively whole blood and residual gut samples from HIV-infected subjects with primary and chronic infection and from healthy donors (HD. Differentiation profile and functionality were analyzed by multiparametric flow cytometry. P-HIV and C-HIV were characterized by an increase in the frequency of effector Vδ1-T cells both in circulating and mucosal compartments. Moreover, during P-HIV mucosal Vδ1 T-cells expressed high levels of CD107a, suggesting a good effector cytotoxic capability of these cells in the early phase of infection that was lost in C-HIV. P-HIV induced an increase in circulating effector Vδ2 T-cells in comparison to C-HIV and HD. Notably, P-HIV as well as HD were characterized by the ability of mucosal Vδ2 T-cells to spontaneously produce IFN-γ that was lost in C-HIV. Altogether, our data showed for the first time a functional capability of mucosal Vδ1 and Vδ2 T-cells during P-HIV that was lost in C-HIV, suggesting exhaustion mechanisms induced by persistent stimulation.

Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients.

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Khodadadi, Iraj; Abdi, Mohammad; Ahmadi, Abbas; Wahedi, Mohammad Saleh; Menbari, Shahoo; Lahoorpour, Fariba; Rahbari, Rezgar

2011-08-01

To determine adenosine deaminase (ADA) activity as a possible diagnostic marker in HIV and HIV-HBV co-infected patients. Blood samples were collected from 72 healthy, 33 HIV positive and 30 HIV-HBV co-infected subjects. Blood CD4+ cell count was recorded and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total ADA, and ADA1 and ADA2 isoenzyme activities were determined. Serum ALT, AST, total ADA and ADA2 isoenzyme activities were significantly higher in HIV positive and HIV-HBV co-infected groups compare to the control (pADA activities (R(2)=0.589, pADA was significantly increased in HIV and HIV-HBV co-infections. Therefore, because of its low cost and simplicity to perform, ADA activity might be considered as a useful diagnostic tool among the other markers in these diseases. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

HIV/AIDS

Science.gov (United States)

HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

HIV subtype and drug resistance patterns among drug naïve ...

African Journals Online (AJOL)

SERVER

2007-08-20

Aug 20, 2007 ... 1Institute of Human Virology, University of Maryland, Baltimore, USA. 2PSSH, Jos ... INTRODUCTION. Many genetic subtypes of HIV-1 have been characterized ..... A comprehensive panel of near-full- length clones and ...

[Co-infections of HIV, syphilis and HSV-2 among men who have sex with men at the voluntary HIV counseling and testing clinics in Shanghai].

Science.gov (United States)

Liu, Y; Tang, H F; Ning, Z; Zheng, H; He, N; Zhang, Y Y

2017-10-10

Objective: To understand the prevalence rates of HIV-syphilis and HIV-herpes simplex virus 2 (HSV-2) co-infections and related factors among men having sex with men (MSM) who had visited the voluntary HIV counseling and testing (VCT) clinics in Shanghai, China. Methods: 756 eligible MSM who attended the VCT clinics of Shanghai Municipality and Putuo district during March to August, 2015 were recruited to participate in a cross-sectional survey with questionnaire interview and blood testing for HIV, syphilis and HSV-2. Results: A total of 732 participants completed a valid questionnaire survey. The prevalence rates were 3.3 % (24/732) for HIV/Syphilis co-infection, 1.9 % (14/732) for HIV/HSV-2 co-infection, and 0.7 % (5/732) for HIV/Syphilis/HSV-2 co-infection, respectively. HIV prevalence appeared significantly higher among syphilis-infected participants (45.3 % , 24/53) than those without Syphilis (7.2 % , 61/679) (χ(2)=63.11, P Syphilis co-infection. Those participants who had high middle school or lower levels of education ( OR =6.87, 95 %CI : 1.86-25.42; OR =9.82, 95 %CI : 2.25-42.85) were under risk on HIV and HSV-2 co-infection. Conclusion: HIV/Syphilis and HIV/HSV-2 co-infection were seen among MSM who attended the VCT clinics in Shanghai that called for special attention, especially on migrants, those with low education or illicit drug users.

Accuracy in HIV Rapid Testing among Laboratory and Non-laboratory Personnel in Zambia: Observations from the National HIV Proficiency Testing System.

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Sheila Mwangala

Full Text Available Despite rapid task-shifting and scale-up of HIV testing services in high HIV prevalence countries, studies evaluating accuracy remain limited. This study aimed to assess overall accuracy level and factors associated with accuracy in HIV rapid testing in Zambia.Accuracy was investigated among rural and urban HIV testing sites participating in two annual national HIV proficiency testing (PT exercises conducted in 2009 (n = 282 sites and 2010 (n = 488 sites. Testers included lay counselors, nurses, laboratory personnel and others. PT panels of five dry tube specimens (DTS were issued to testing sites by the national reference laboratory (NRL. Site accuracy level was assessed by comparison of reported results to the expected results. Non-parametric rank tests and multiple linear regression models were used to assess variation in accuracy between PT cycles and between tester groups, and to examine factors associated with accuracy respectively.Overall accuracy level was 93.1% (95% CI: 91.2-94.9 in 2009 and 96.9% (95% CI: 96.1-97.8 in 2010. Differences in accuracy were seen between the tester groups in 2009 with laboratory personnel being more accurate than non-laboratory personnel, while in 2010 no differences were seen. In both PT exercises, lay counselors and nurses had more difficulties interpreting results, with more occurrences of false-negative, false-positive and indeterminate results. Having received the standard HIV rapid testing training and adherence to the national HIV testing algorithm were positively associated with accuracy.The study showed an improvement in tester group and overall accuracy from the first PT exercise to the next. Average number of incorrect test results per 1000 tests performed was reduced from 69 to 31. Further improvement is needed, however, and the national HIV proficiency testing system seems to be an important tool in this regard, which should be continued and needs to be urgently strengthened.

HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

DEFF Research Database (Denmark)

Hove-Skovsgaard, Malene; Gaardbo, Julie Christine; Kolte, Lilian

2017-01-01

BACKGROUND: Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may...... contribute to elevated risk of CVD. METHODS: Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA 2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28...... without T2D (HIV-T2D-)). Groups were matched on age and sex. High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine...

Risk of myocardial infarction in parents of HIV-infected individuals: a population-based cohort study

DEFF Research Database (Denmark)

Rasmussen, Line D; Omland, Lars H; Pedersen, Court

2010-01-01

associated with the HIV disease and HAART or whether life-style related or genetic factors also increase the risk in this population. To establish whether the increased risk of myocardial infarction in HIV patients partly reflects an increased risk of MI in their families, we estimated the relative risk...... of MI in parents of HIV-infected individuals METHODS: From the Danish HIV Cohort Study and the Danish Civil Registration System we identified the parents of all HIV-infected patients born in Denmark after 1952 in whom a Danish born mother was identifiable. For each HIV patient, 4 matched population...... controls and their parents were identified. Cumulative incidence functions were constructed to illustrate time to first MI of the parents as registered in the Danish National Hospital Registry. Incidence rate ratios (IRR) were estimated by Cox's regression analyses. Due to the confidential type...

Anti-viral drug treatment along with immune activator IL-2: a control-based mathematical approach for HIV infection

Science.gov (United States)

Nath Chatterjee, Amar; Roy, Priti Kumar

2012-02-01

Recent development in antiretroviral treatment against HIV can help AIDS patients to fight against HIV. But the question that whether the disease is to be partially or totally eradicated from HIV infected individuals still remains unsolved. Usually, the most effective treatment for the disease is HAART which can only control the disease progression. But as the immune system becomes weak, the patients can not fight against other diseases. Immune cells are activated and proliferated by IL-2 after the identification of antigen. IL-2 production is impaired in HIV positive patients and intermitted administration of immune activator IL-2 together with HAART which is a more effective treatment to fight against the disease. Thus, its expediency is essential and is yet to be explored. In this article we anticipated a mathematical model of the effect of IL-2 together with RTIs therapy in HIV positive patients. Our analytical as well as numerical study shows that the optimal schedule of treatment for best result is to be obtained by systematic drug therapy. But at the last stage of treatment, the infection level raises again due to minimisation of drug dosage. Thus we study the perfect adherence of the drugs and found out if RTIs are taken with sufficient interval then for fixed interval of IL-2 therapy, certain amount of drug dosages may be able to sustain the immune system at pre-infection stage and the infected CD4+T cells are going towards extinction.

HIV test offers and acceptance: New York State findings from the behavioral risk factor surveillance system and the National HIV behavioral surveillance, 2011-2012.

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John Leung, Shu-Yin; Sinclair, Amber H; Battles, Haven B; Swain, Carol-Ann E; French, Patrick Tyler; Anderson, Bridget J; Sowizral, Mycroft J; Ruberto, Rachael; Brissette, Ian; Lillquist, Patricia; Smith, Lou C

2015-01-01

The New York State HIV testing law requires that patients aged 13-64 years be offered HIV testing in health care settings. We investigated the extent to which HIV testing was offered and accepted during the 24 months after law enactment. We added local questions to the Behavioral Risk Factor Surveillance System (BRFSS) and the National HIV Behavioral Surveillance (NHBS) surveys asking respondents aged 18-64 years whether they were offered an HIV test in health care settings, and whether they had accepted testing. Statewide prevalence estimates of test offers and acceptance were obtained from a combined 2011-2012 BRFSS sample (N = 6,223). Local estimates for 2 high-risk populations were obtained from NHBS 2011 men who have sex with men (N = 329) and 2012 injection drug users (N = 188) samples. BRFSS data showed that 73% of New Yorkers received care in any health care setting in the past 12 months, of whom 25% were offered an HIV test. Sixty percent accepted the test when offered. The levels of test offer increased from 20% to 29% over time, whereas acceptance levels decreased from 68% to 53%. NHBS data showed that 81% of men who have sex with men received care, of whom 43% were offered an HIV test. Eighty-eight percent accepted the test when offered. Eighty-five percent of injection drug users received care, of whom 63% were offered an HIV test, and 63% accepted the test when offered. We found evidence of partial and increasing implementation of the HIV testing law. Importantly, these studies demonstrated New Yorkers' willingness to accept an offered HIV test as part of routine care in health care settings.

Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

Science.gov (United States)

Shan, Liang; Siliciano, Robert F.

2014-01-01

Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

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V. B. Musatov

2015-01-01

Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

[Analysis on HIV-1 genetics and threshold of drug resistance in Dehong prefecture of Yunnan province in 2013].

Science.gov (United States)

Ma, Yanling; Wang, Jibao; Xing, Hui; Chen, Min; Yao, Shitang; Chen, Huichao; Yang, Jin; Li, Yanling; Duan, Song; Jia, Manhong

2015-06-01

To study the HIV-1 genotypes and transmitted drug resistance (TDR) in Dehong prefecture of Yunnan province in 2013. Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS), 54 plasma samples of recently reported HIV-infected individuals, aged between 16 and 25 years, were collected in Dehong prefecture from January to August 2013. Genotyping of partial pol gene was performed by using reverse transcriptional PCR. HIV-1 genotype. Prevalent levels of HIV-1 drug resistance transmission were analyzed. Forty-eight plasma samples were successfully sequenced and analyzed. Among them, 45.8% were Chinese and the rest 54.2% were all Burmese. Based on pol sequences, identified HIV genotypes included subtype C (41.7%), URF (31.3%), CRF01_AE (12.5%), CRF07_BC (10.4%), CRF08_BC (2.1%) and subtype B (2.1%), C subtype appeared dominated in Chinese while URF was dominated in Burmese. One drug resistant mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was detected in one sequence from Burmese. Based on the statistical method of HIVDR-TS, the prevalence of transmitted HIV-1 drug resistance was adjusted as scientific management for people living with HIV/AIDS should be strictly followed. Meanwhile, relevant surveillance, including drug resistance surveillance should also be performed among cross-border migrant population.

Aerobic endurance in HIV-positive young adults and HIV-negative ...

African Journals Online (AJOL)

2015-03-09

Mar 9, 2015 ... not taking antiretroviral medication and 78 HIV-negative participants (45 ... between groups were adjusted for age differences using analysis of ... habits, body composition, gender, age and genetic factors ..... Three meta - analyses ... Exercise Treadmill Test for the Assessment of Cardiac Risk Markers.

HIV infection results in ventral-striatal reward system hypo-activation during cue processing

NARCIS (Netherlands)

Plessis, Stéfan du; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

2015-01-01

OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

Science.gov (United States)

Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

2016-06-01

Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

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Gi Soo Youn

2017-08-01

Full Text Available Histone deacetylase 6 (HDAC6 likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat activates NADPH oxidase resulting in generation of reactive oxygen species (ROS, leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation. Keywords: HIV-1 Tat, HDAC6, NADPH oxidase, ROS, Inflammation, Astrocytes

Comparative Genetic Variability in HIV-1 Subtype C vpu Gene in Early Age Groups of Infants.

Science.gov (United States)

Sharma, Uma; Gupta, Poonam; Gupta, Sunil; Venkatesh, S; Husain, Mohammad

2018-01-01

Identifying the genetic variability in vertically transmitted viruses in early infancy is important to understand the disease progression. Being important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants was investigated to understand the viral characteristics. Blood samples were obtained from 80 HIV-1 positive infants, categorized in two age groups; acute (6-18 months). A total of 77 PCR positive samples, amplified for vpu gene, were sequenced and analyzed. 73 isolates belonged to subtype C. Analysis of heterogeneity of amino acid sequences in infant groups showed that in the sequences of acute age group both insertions and deletions were present while in the early age group only deletions were present. In the acute age group, a deletion of 3 residues (RAE) in the first alfa helix in one sequence and insertions of 1-2 residues (DM, GH, G and H) in the second alfa helix in 4 sequences were observed. In the early age group, deletion of 2 residues (VN) in the cytoplasmic tail region in 2 sequences was observed. Length of the amino terminal was observed to be gradually increasing with the increasing age of the infants. Protein Variation Effect Analyzer software showed that deleterious mutations were more in the acute than the early age group. Entropy analysis revealed that heterogeneity of the residues was comparatively higher in the sequences of acute than the early age group. Mutations observed in the helixes may affect the conformation and lose the ability to degrade CD4 receptors. Heterogeneity was decreasing with the increasing ages of the infants, indicating positive selection for robust virion survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structural investigation of HIV-1 nonnucleoside reverse transcriptase inhibitors: 2-Aryl-substituted benzimidazoles

Science.gov (United States)

Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

2009-11-01

Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is one of the most destructive epidemics in history. Inhibitors of HIV enzymes are the main targets to develop drugs against that disease. Nonnucleoside reverse transcriptase inhibitors of HIV-1 (NNRTIs) are potentially effective and nontoxic. Structural studies provide information necessary to design more active compounds. The crystal structures of four NNRTI derivatives of 2-aryl-substituted N-benzyl-benzimidazole are presented here. Analysis of the geometrical parameters shows that the structures of the investigated inhibitors are rigid. The important geometrical parameter is the dihedral angle between the planes of the π-electron systems of the benzymidazole and benzyl moieties. The values of these dihedral angles are in a narrow range for all investigated inhibitors. There is no significant difference between the structure of the free inhibitor and the inhibitor in the complex with RT HIV-1. X-ray structures of the investigated inhibitors are a good basis for modeling enzyme-inhibitor interactions in rational drug design.

Steady-State-Preserving Simulation of Genetic Regulatory Systems

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Ruqiang Zhang

2017-01-01

Full Text Available A novel family of exponential Runge-Kutta (expRK methods are designed incorporating the stable steady-state structure of genetic regulatory systems. A natural and convenient approach to constructing new expRK methods on the base of traditional RK methods is provided. In the numerical integration of the one-gene, two-gene, and p53-mdm2 regulatory systems, the new expRK methods are shown to be more accurate than their prototype RK methods. Moreover, for nonstiff genetic regulatory systems, the expRK methods are more efficient than some traditional exponential RK integrators in the scientific literature.

Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death.

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Sachin Verma

Full Text Available BACKGROUND: Genetic studies reveal that vpu is one of the most variable regions in HIV-1 genome. Functional studies have been carried out mostly with Vpu derived from laboratory adapted subtype B pNL 4-3 virus. The rationale of this study was to characterize genetic variations that are present in the vpu gene from HIV-1 infected individuals from North-India (Punjab/Haryana and determine their functional relevance. METHODS: Functionally intact vpu gene variants were PCR amplified from genomic DNA of HIV-1 infected individuals. These variants were then subjected to genetic analysis and unique representative variants were cloned under CMV promoter containing expression vector as well as into pNL 4-3 HIV-1 virus for intracellular expression studies. These variants were characterized with respect to their ability to promote virus release as well as cell death. RESULTS: Based on phylogenetic analysis and extensive polymorphisms with respect to consensus Vpu B and C, we were able to arbitrarily assign variants into two major groups (B and C. The group B variants always showed significantly higher virus release activity and exhibited moderate levels of cell death. On the other hand, group C variants displayed lower virus release activity but greater cell death potential. Interestingly, Vpu variants with a natural S61A mutation showed greater intracellular stability. These variants also exhibited significant reduction in their intracellular ubiquitination and caused greater virus release. Another group C variant that possessed a non-functional β-TrcP binding motif due to two critical serine residues (S52 and S56 being substituted with isoleucine residues, showed reduced virus release activity but modest cytotoxic activity. CONCLUSIONS: The natural variations exhibited by our Vpu variants involve extensive polymorphism characterized by substitution and deletions that contribute toward positive selection. We identified two major groups and an extremely

Impact of CCR5delta32 Host Genetic Background and Disease Progression on HIV-1 Intrahost Evolutionary Processes: Efficient Hypothesis Testing through Hierarchical Phylogenetic Models

NARCIS (Netherlands)

Edo-Matas, Diana; Lemey, Philippe; Tom, Jennifer A.; Serna-Bolea, Cèlia; van den Blink, Agnes E.; van 't Wout, Angélique B.; Schuitemaker, Hanneke; Suchard, Marc A.

2011-01-01

The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically

An HIV1/2 point of care test on sputum for screening TB/HIV co-infection in central India - Will it work?

Institute of Scientific and Technical Information of China (English)

Prabha Desikan; Sajal De; Nitika Pant Pai; Pradyumna K Mishra; Kaushal Kumar; Nikita Panwalkar; Mayanka Verma; Zia Ul Hasan; Kewal K Maudar

2013-01-01

Objective:To determine whether theOraQuick®HIV-1/2Assay(OraSureTechnologies, Inc.,Bethlehem,PA,USA) in sputum is a valid tool forHIV surveillance amongTB patients. Methods:A cross sectional study was carried out on sputa of patients diagnosed with tuberculosis.Sputa were tested for antibodies toHIV usingOraQuick®HIV-1/2Assay(OraSure Technologies,Inc.,Bethlehem,PA,USA).The results were compared with results of serum ELISA.Results:Compared to serumELISA, theOraQuick®HIV-1/2Assay in sputum specimens reported90% sensitivity(9/10) and100% specificity(307/307), with a positive predictive value of 100%(95%CI:66.37%-100.00%) and a negative predictive value of99.68%(95%CI:98.20%-99.99%). Conclusions:This testing method may provide a useful strategy for conductingHIV surveillance in possible co-infectedTB patients at peripheral centres.Since there is no investment on infrastructure, it may be possible for paramedical health professionals to carry out the test, particularly in areas with lowHIV endemicity.

Hili Inhibits HIV Replication in Activated T Cells.

Science.gov (United States)

Peterlin, B Matija; Liu, Pingyang; Wang, Xiaoyun; Cary, Daniele; Shao, Wei; Leoz, Marie; Hong, Tian; Pan, Tao; Fujinaga, Koh

2017-06-01

P-element-induced wimpy-like (Piwil) proteins restrict the replication of mobile genetic elements in the germ line. They are also expressed in many transformed cell lines. In this study, we discovered that the human Piwil 2 (Hili) protein can also inhibit HIV replication, especially in activated CD4 + T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express Hili, its expression was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of Hili increased levels of viral proteins and new viral particles. Further studies revealed that Hili binds to tRNA. Some of the tRNAs represent rare tRNA species, whose codons are overrepresented in the viral genome. Targeting tRNA Arg (UCU) with an antisense oligonucleotide replicated effects of Hili and also inhibited HIV replication. Finally, Hili also inhibited the retrotransposition of the endogenous intracysternal A particle (IAP) by a similar mechanism. Thus, Hili joins a list of host proteins that inhibit the replication of HIV and other mobile genetic elements. IMPORTANCE Piwil proteins inhibit the movement of mobile genetic elements in the germ line. In their absence, sperm does not form and male mice are sterile. This inhibition is thought to occur via small Piwi-interacting RNAs (piRNAs). However, in some species and in human somatic cells, Piwil proteins bind primarily to tRNA. In this report, we demonstrate that human Piwil proteins, especially Hili, not only bind to select tRNA species, including rare tRNAs, but also inhibit HIV replication. Importantly, T cell activation induces the expression of Hili in CD4 + T cells. Since Hili also inhibited the movement of an endogenous retrovirus (IAP), our finding shed new light on this intracellular resistance to exogenous and endogenous retroviruses as well as other mobile genetic elements. Copyright © 2017 American Society for Microbiology.

Central nervous system involvement in childhood HIV: CT findings

International Nuclear Information System (INIS)

Muro, D.; Sanguesa, C.; Perez, A.; Otero, C.

1997-01-01

To determine the neuroradiological findings disclosed by CT on children infected by the human immunodeficiency virus (HIV) and to analyze the different radiological changes observed in the presence and absence of HIV encephalopathy. Fifty-one children with vertically transmitted HIV infection were divided into two groups according to the presence or absence of neurological changes (groups I and II, respectively). All the patients underwent cranial CT at different phases during the course of the disease. The presence of cerebral atrophy, calcifications of the basal ganglia, lesions involving white matter, opportunistic infections, vascular lesions and tumors of the central nervous system (CNS) was assessed. Neurological signs were observed in 17 patients (group I) and were absent in 34 (group II). Seventy percent of the patients in group I presented abnormal cranial CT findings, the most common of which were cerebral atrophy (58.8%) and calcifications of the basal ganglia (47%). One patient presented focal white matte lesions, another had hemorrhagic infarction and subdural hematoma and a third presented aneurysmal dilation of the intracerebral arteries. The rate of mortality in children with encephalopathy was 82.3%. Of the 34 patients in group II, Three (8.8%) presented an increase in the size of the ventricular system and of the subarachnoid space. Neuroradiological changes are frequently observed in children with HIV encephalopathy. Diffuse cerebral atrophy and calcification of the basal ganglia and periventricular white matter are the most common findings. Although cerebral atrophy can precede the development of encephalopathy, its presence generally coincides with neurological deterioration. The onset of neurological signs in HIV-infected patients indicates a very poor prognosis for the outcome of the disease. (Author) 32 refs

HIV-positive migrants’ encounters with the Swedish health care system

DEFF Research Database (Denmark)

Mehdiyar, Manijeh; Andersson, Rune; Hjelm, Katarina

2016-01-01

of access and adversity’ was identified as the core category of the study. Three additional categories were ‘appreciation of free access to treatment’, ‘the impact of the Swedish Disease Act on everyday life’, and ‘encountering discrimination in the general health care system’. The main finding indicated......Background: There is limited knowledge about human immunodeficiency virus (HIV)-positive migrants and their experiences in the Swedish health care system. It is necessary to increase our knowledge in this field to improve the quality of care and social support for this vulnerable group of patients....... Objective: The aim of this study was to describe the experiences of HIV-positive migrants and their encounters with the health care system in Sweden. Design: This is a Grounded Theory study based on qualitative interviews with 14 HIV-positive migrants living in Sweden, aged 29–55 years. Results: ‘A hybrid...

Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA

International Nuclear Information System (INIS)

Wyatt, Linda S.; Belyakov, Igor M.; Earl, Patricia L.; Berzofsky, Jay A.; Moss, Bernard

2008-01-01

During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env, a few viral foci stained very prominently. Virus cloned from such foci replicated to higher titers than the parent and displayed enhanced genetic stability on passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env gene of the mutant that caused a frame shift and truncation of 115 amino acids from the cytoplasmic domain. The truncated Env was more highly expressed on the cell surface, induced higher antibody responses than the full-length Env, reacted with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor-dependent fusion. Intramuscular (IM), intradermal (ID) needleless, and intrarectal (IR) catheter inoculations gave comparable serum IgG responses. However, intraoral (IO) needleless injector route gave the highest IgA in lung washings and IR gave the highest IgA and IgG responses in fecal extracts. Induction of CTL responses in the spleens of individual mice as assayed by intracellular cytokine staining was similar with both the full-length and truncated Env constructs. Induction of acute and memory CTL in the spleens of mice immunized with the truncated Env construct by ID, IO, and IR routes was comparable and higher than by the IM route, but only the IR route induced CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines

HIV Transmission Dynamics Among Foreign-Born Persons in the United States.

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Valverde, Eduardo E; Oster, Alexandra M; Xu, Songli; Wertheim, Joel O; Hernandez, Angela L

2017-12-15

In the United States (US), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from US-born persons with diagnosed HIV infection. Understanding HIV transmission dynamics among foreign-born persons is important to guide HIV prevention efforts for these populations. We conducted molecular transmission network analysis to describe HIV transmission dynamics among foreign-born persons with diagnosed HIV. Using HIV-1 polymerase nucleotide sequences reported to the US National HIV Surveillance System for persons with diagnosed HIV infection during 2001-2013, we constructed a genetic distance-based transmission network using HIV-TRACE and examined the birth region of potential transmission partners in this network. Of 77,686 people, 12,064 (16%) were foreign born. Overall, 28% of foreign-born persons linked to at least one other person in the transmission network. Of potential transmission partners, 62% were born in the United States, 31% were born in the same region as the foreign-born person, and 7% were born in another region of the world. Most transmission partners of male foreign-born persons (63%) were born in the United States, whereas most transmission partners of female foreign-borns (57%) were born in their same world region. These finding suggests that a majority of HIV infections among foreign-born persons in our network occurred after immigrating to the United States. Efforts to prevent HIV infection among foreign-born persons in the United States should include information of the transmission networks in which these individuals acquire or transmit HIV to develop more targeted HIV prevention interventions.

Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients

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Kazem Baesi

2014-09-01

Full Text Available Objective: To identify the dominant subtype among the HIV-1 strains circulation in Iran. Methods: In this cross sectional study 100 HIV positive patients participated. HIV-1 RNA was extracted from plasma. RT nested-PCR was performed and the final products were sequenced and phylogenetically analyzed; reference sequences were downloaded from Los Alamos, aligned with Iranian pol sequences in the study and analyzed by neighbor-joining method. Results: The results of the phylogenetic analysis showed that HIV-1 subtype CRF-35AD was the dominant subtype among HIV-1 infected patients in Iran; this analysis also suggested a new circulating recombinant form that had not previously been identified in Iran: CRF-29BF. Conclusions: The impact of HIV diversity on pathogenesis, transmission and clinical management have been discussed in different studies; therefore, analyses of HIV genetic diversity is required to design effective antiretroviral strategies for different HIV subtypes.

Short communication: identification of a novel HIV type 1 subtype H/J recombinant in Canada with discordant HIV viral load (RNA) values in three different commercial assays.

Science.gov (United States)

Kim, John E; Beckthold, Brenda; Chen, Zhaoxia; Mihowich, Jennifer; Malloch, Laurie; Gill, Michael John

2007-11-01

The presence of HIV-1 non-B subtypes is increasing worldwide. This poses challenges to commercial diagnostic and viral load (RNA) monitoring tests that are predominantly based on HIV-1 subtype B strains. Based on phylogenetic analysis of the gag, pol, and env gene regions, we describe the first HIV-1 H/J recombinant in Canada that presented divergent viral load values. DNA sequence analysis of the gag gene region further revealed that genetic diversity between this H/J recombinant and the primers and probes used in the bio-Merieux Nuclisens HIV-1 QT (Nuclisens) and Roche Amplicor Monitor HIV-1, v1.5 (Monitor) viral RNA assays can erroneously lead to undetectable viral load values. This observation appears to be more problematic in the Nuclisens assay. In light of increasing genetic diversity in HIV worldwide we recommend that DNA sequencing of HIV, especially in the gag gene region targeted by primers and probes used in molecular diagnostic and viral load tests, be incorporated into clinical monitoring practices.

Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

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Julia K Bialek

Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

HIV-1 transcripts use IRES-initiation under conditions where Cap-dependent translation is restricted by poliovirus 2A protease.

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Raquel Amorim

Full Text Available The 30 different species of mRNAs synthesized during the HIV-1 replication cycle are all capped and polyadenilated. Internal ribosome entry sites have been recognized in the 5' untranslated region of some mRNA species of HIV-1, which would contribute to an alternative mechanism of initiation of mRNA translation. However, the Cap-dependent translation is assumed to be the main mechanism driving the initiation of HIV-1 protein synthesis. In this work, we describe a cell system in which lower to higher levels of transient expression of the poliovirus 2A protease strongly inhibited cellular Cap-dependent translation with no toxic effect to the cells during a 72-hour time frame. In this system, the synthesis of HIV-1 proteins was inhibited in a temporal dose-dependent way. Higher levels of 2A protease expression severely inhibited HIV-1 protein synthesis during the first 24 hours of infection consequently inhibiting viral production and infectivity. Intermediate to lower levels of 2A Protease expression caused the inhibition of viral protein synthesis only during the first 48 hours of viral replication. After this period both protein synthesis and viral release were recovered to the control levels. However, the infectivity of viral progeny was still partially inhibited. These results indicate that two mechanisms of mRNA translation initiation contribute to the synthesis of HIV-1 proteins; during the first 24-48 hours of viral replication HIV-1 protein synthesis is strongly dependent on Cap-initiation, while at later time points IRES-driven translation initiation is sufficient to produce high amounts of viral particles.

CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection

DEFF Research Database (Denmark)

Buggert, Marcus; Frederiksen, Juliet Wairimu; Lund, Ole

2016-01-01

cells are linked to such outcome. DESIGN: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion......, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell...... clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2...

Rationale and uses of a public HIV drug-resistance database.

Science.gov (United States)

Shafer, Robert W

2006-09-15

Knowledge regarding the drug resistance of human immunodeficiency virus (HIV) is critical for surveillance of drug resistance, development of antiretroviral drugs, and management of infections with drug-resistant viruses. Such knowledge is derived from studies that correlate genetic variation in the targets of therapy with the antiretroviral treatments received by persons from whom the variant was obtained (genotype-treatment), with drug-susceptibility data on genetic variants (genotype-phenotype), and with virological and clinical response to a new treatment regimen (genotype-outcome). An HIV drug-resistance database is required to represent, store, and analyze the diverse forms of data underlying our knowledge of drug resistance and to make these data available to the broad community of researchers studying drug resistance in HIV and clinicians using HIV drug-resistance tests. Such genotype-treatment, genotype-phenotype, and genotype-outcome correlations are contained in the Stanford HIV RT and Protease Sequence Database and have specific usefulness.

CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.

Science.gov (United States)

Kulkarni, Hemant; Agan, Brian K; Marconi, Vincent C; O'Connell, Robert J; Camargo, Jose F; He, Weijing; Delmar, Judith; Phelps, Kenneth R; Crawford, George; Clark, Robert A; Dolan, Matthew J; Ahuja, Sunil K

2008-09-08

Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management

Implementation and outcomes of an active defaulter tracing system for HIV, prevention of mother to child transmission of HIV (PMTCT), and TB patients in Kibera, Nairobi, Kenya.

Science.gov (United States)

Thomson, Kerry A; Cheti, Erastus O; Reid, Tony

2011-06-01

Retention of patients in long term care and adherence to treatment regimens are a constant challenge for HIV, prevention of mother to child transmission of HIV (PMTCT), and TB programmes in sub-Saharan Africa. This study describes the implementation and outcomes of an active defaulter tracing system used to reduce loss to follow-up (LTFU) among HIV, PMTCT, TB, and HIV/TB co-infected patients receiving treatment at three Médecins Sans Frontières clinics in the informal settlement of Kibera, Nairobi, Kenya. Patients are routinely contacted by a social worker via telephone, in-person visit, or both very soon after they miss an appointment. Patient outcomes identified through 1066 tracing activities conducted between 1 April 2008 and 31 March 2009 included: 59.4% returned to the clinic, 9.0% unable to return to clinic, 6.3% died, 4.7% refused to return to clinic, 4.5% went to a different clinic, and 0.8% were hospitalized. Fifteen percent of patients identified for tracing could not be contacted. LTFU among all HIV patients decreased from 21.2% in 2006 to 11.5% in 2009. An active defaulter tracing system is feasible in a resource poor setting, solicits feedback from patients, retains a mobile population of patients in care, and reduces LTFU among HIV, PMTCT, and TB patients. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Genetics Home Reference: complement component 2 deficiency

Science.gov (United States)

... Topic: Immune System and Disorders Health Topic: Lupus Genetic and Rare Diseases Information Center (1 link) Complement component 2 deficiency Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 ...

Mobilization of HIV Spread by Diaphanous 2 Dependent Filopodia in Infected Dendritic Cells

Science.gov (United States)

Aggarwal, Anupriya; Iemma, Tina L.; Shih, Ivy; Newsome, Timothy P.; McAllery, Samantha; Cunningham, Anthony L.; Turville, Stuart G.

2012-01-01

Paramount to the success of persistent viral infection is the ability of viruses to navigate hostile environments en route to future targets. In response to such obstacles, many viruses have developed the ability of establishing actin rich-membrane bridges to aid in future infections. Herein through dynamic imaging of HIV infected dendritic cells, we have observed how viral high-jacking of the actin/membrane network facilitates one of the most efficient forms of HIV spread. Within infected DC, viral egress is coupled to viral filopodia formation, with more than 90% of filopodia bearing immature HIV on their tips at extensions of 10 to 20 µm. Live imaging showed HIV filopodia routinely pivoting at their base, and projecting HIV virions at µm.sec−1 along repetitive arc trajectories. HIV filopodial dynamics lead to up to 800 DC to CD4 T cell contacts per hour, with selection of T cells culminating in multiple filopodia tethering and converging to envelope the CD4 T-cell membrane with budding HIV particles. Long viral filopodial formation was dependent on the formin diaphanous 2 (Diaph2), and not a dominant Arp2/3 filopodial pathway often associated with pathogenic actin polymerization. Manipulation of HIV Nef reduced HIV transfer 25-fold by reducing viral filopodia frequency, supporting the potency of DC HIV transfer was dependent on viral filopodia abundance. Thus our observations show HIV corrupts DC to CD4 T cell interactions by physically embedding at the leading edge contacts of long DC filopodial networks. PMID:22685410

Mobilization of HIV spread by diaphanous 2 dependent filopodia in infected dendritic cells.

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Anupriya Aggarwal

Full Text Available Paramount to the success of persistent viral infection is the ability of viruses to navigate hostile environments en route to future targets. In response to such obstacles, many viruses have developed the ability of establishing actin rich-membrane bridges to aid in future infections. Herein through dynamic imaging of HIV infected dendritic cells, we have observed how viral high-jacking of the actin/membrane network facilitates one of the most efficient forms of HIV spread. Within infected DC, viral egress is coupled to viral filopodia formation, with more than 90% of filopodia bearing immature HIV on their tips at extensions of 10 to 20 µm. Live imaging showed HIV filopodia routinely pivoting at their base, and projecting HIV virions at µm.sec⁻¹ along repetitive arc trajectories. HIV filopodial dynamics lead to up to 800 DC to CD4 T cell contacts per hour, with selection of T cells culminating in multiple filopodia tethering and converging to envelope the CD4 T-cell membrane with budding HIV particles. Long viral filopodial formation was dependent on the formin diaphanous 2 (Diaph2, and not a dominant Arp2/3 filopodial pathway often associated with pathogenic actin polymerization. Manipulation of HIV Nef reduced HIV transfer 25-fold by reducing viral filopodia frequency, supporting the potency of DC HIV transfer was dependent on viral filopodia abundance. Thus our observations show HIV corrupts DC to CD4 T cell interactions by physically embedding at the leading edge contacts of long DC filopodial networks.

[Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987-2015].

Science.gov (United States)

Lapovok, I A; Lopatukhin, A E; Kireev, D E; Kazennova, E V; Lebedev, A V; Bobkova, M R; Kolomeets, A N; Turbina, G I; Shipulin, G A; Ladnaya, N N; Pokrovsky, V V

To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987-2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988-1989. The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.

Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins

DEFF Research Database (Denmark)

Hansen, J E; Nielsen, C M; Nielsen, C

1989-01-01

The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba...

Use of a high resolution melting (HRM) assay to compare gag, pol, and env diversity in adults with different stages of HIV infection.

Science.gov (United States)

Cousins, Matthew M; Laeyendecker, Oliver; Beauchamp, Geetha; Brookmeyer, Ronald; Towler, William I; Hudelson, Sarah E; Khaki, Leila; Koblin, Beryl; Chesney, Margaret; Moore, Richard D; Kelen, Gabor D; Coates, Thomas; Celum, Connie; Buchbinder, Susan P; Seage, George R; Quinn, Thomas C; Donnell, Deborah; Eshleman, Susan H

2011-01-01

Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual. HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative), 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14-540 days), and 67 with non-recent HIV infection (HIV infected >2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env. Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection. The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined.

nef gene sequence variation among HIV-1-infected African children

Czech Academy of Sciences Publication Activity Database

Chakraborty, R.; Reiniš, Milan; Rostron, T.; Philpott, S.; Dong, T.; D'Agostino, A.; Musoke, R.; de Silva, E.; Stumpf, M.; Weiser, B.; Burger, H.; Rowland-Jones, S.L.

2006-01-01

Roč. 7, č. 2 (2006), s. 75-84 ISSN 1464-2662 Grant - others:Fogarty International Center, NIH(US) 3D43TW00915; NIH(US) RO1 AI 42555 Institutional research plan: CEZ:AV0Z50520514 Keywords : HIV-1 nef gene * non-clade B * Kenya Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.674, year: 2006

Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic

NARCIS (Netherlands)

Martinez-Steele, Euridice; Awasana, Akum Aveika; Corrah, Tumani; Sabally, Saihou; van der Sande, Marianne; Jaye, Assan; Togun, Toyin; Sarge-Njie, Ramu; McConkey, Samuel J.; Whittle, Hilton; Schim van der Loeff, Maarten F.

2007-01-01

Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections. To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and

Atypical presentations of genital herpes simplex virus in HIV-1 and HIV-2 effectively treated by imiquimod.

Science.gov (United States)

McKendry, Anna; Narayana, Srinivasulu; Browne, Rita

2015-05-01

Atypical presentations of genital herpes simplex virus have been described in HIV. We report two cases with hypertrophic presentations which were effectively treated with imiquimod, one of which is the first reported case occurring in a patient with HIV-2. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Nurturing the Continuum of HIV Testing, Treatment and Prevention Matrix Cascade in Reducing HIV Transmission.

Science.gov (United States)

Yah, Clarence S

2017-11-01

Despite the shift in antiretroviral therapy (ARVs) eligibility cascade from CD4 ≤ 200 to CD4 ≤ 350 to CD4 ≤ 500 mm 3 , HIV related morbidity and mortality continue to escalate annually, as do HIV infections. The new paradigm of treatment for all HIV positives individual irrespective of CD4 count may significantly reduce HIV and related illnesses. The author assumes that all HIV infected partners should be eligible for HIV treatment and care, irrespective of CD4 count. A second assumption is that high risk HIV negative partners have free access to continuum of HIV pre-exposure prophylaxis (PrEP), post exposure prophylaxis (PEP) and other prevention packages. A literature review search was used to extract evidence-based ARVs-HIV treatment and prevention interventions among HIV positives and high risk partners respectively. Only articles published in English and indexed in journal nuclei were used for the study. The information was used to nurture understanding of HIV treatment and prevention approaches as well as HIV incidence multiplier effect among HIV serodiscordant partners. The imputed HIV incident reference was assumed at 1.2 per 100 person-years (2). This was based on the imputation that retention in care, adherence and other predetermined factors are functions of an effective health care delivery system. The model showed a reduced HIV transmission from 1.2 per 100 person-years to 1.032 per 100 person-years in 6 months. The average threshold period of HIV suppressed partners on ARVs to an undetectable level. The combined multiplier protective-effect probability of transmitting HIV from HIV positive partners on ARVs-suppressed viremic load to HIV negative partners on PrEP/PEP-prevention was detected at 86. The model showed a significant reduction in HIV incidence. Placing serodiscordant sexual partners in HIV treatment and prevention plays a significant role in reducing and controlling HIV infection. Therefore, the policy of enrolling all HIV positives

Differential trends in the codon usage patterns in HIV-1 genes.

Directory of Open Access Journals (Sweden)

Aridaman Pandit

Full Text Available Host-pathogen interactions underlie one of the most complex evolutionary phenomena resulting in continual adaptive genetic changes, where pathogens exploit the host's molecular resources for growth and survival, while hosts try to eliminate the pathogen. Deciphering the molecular basis of host-pathogen interactions is useful in understanding the factors governing pathogen evolution and disease propagation. In host-pathogen context, a balance between mutation, selection, and genetic drift is known to maintain codon bias in both organisms. Studies revealing determinants of the bias and its dynamics are central to the understanding of host-pathogen evolution. We considered the Human Immunodeficiency Virus (HIV type 1 and its human host to search for evolutionary signatures in the viral genome. Positive selection is known to dominate intra-host evolution of HIV-1, whereas high genetic variability underlies the belief that neutral processes drive inter-host differences. In this study, we analyze the codon usage patterns of HIV-1 genomes across all subtypes and clades sequenced over a period of 23 years. We show presence of unique temporal correlations in the codon bias of three HIV-1 genes illustrating differential adaptation of the HIV-1 genes towards the host preferred codons. Our results point towards gene-specific translational selection to be an important force driving the evolution of HIV-1 at the population level.

Excision of HIV-1 proviral DNA by recombinant cell permeable tre-recombinase.

Directory of Open Access Journals (Sweden)

Lakshmikanth Mariyanna

Full Text Available Over the previous years, comprehensive studies on antiretroviral drugs resulted in the successful introduction of highly active antiretroviral therapy (HAART into clinical practice for treatment of HIV/AIDS. However, there is still need for new therapeutic approaches, since HAART cannot eradicate HIV-1 from the infected organism and, unfortunately, can be associated with long-term toxicity and the development of drug resistance. In contrast, novel gene therapy strategies may have the potential to reverse the infection by eradicating HIV-1. For example, expression of long terminal repeat (LTR-specific recombinase (Tre-recombinase has been shown to result in chromosomal excision of proviral DNA and, in consequence, in the eradication of HIV-1 from infected cell cultures. However, the delivery of Tre-recombinase currently depends on the genetic manipulation of target cells, a process that is complicating such therapeutic approaches and, thus, might be undesirable in a clinical setting. In this report we demonstrate that E.coli expressed Tre-recombinases, tagged either with the protein transduction domain (PTD from the HIV-1 Tat trans-activator or the translocation motif (TLM of the Hepatitis B virus PreS2 protein, were able to translocate efficiently into cells and showed significant recombination activity on HIV-1 LTR sequences. Tre activity was observed using episomal and stable integrated reporter constructs in transfected HeLa cells. Furthermore, the TLM-tagged enzyme was able to excise the full-length proviral DNA from chromosomal integration sites of HIV-1-infected HeLa and CEM-SS cells. The presented data confirm Tre-recombinase activity on integrated HIV-1 and provide the basis for the non-genetic transient application of engineered recombinases, which may be a valuable component of future HIV eradication strategies.

Validation of an automated system for aliquoting of HIV-1 Env-pseudotyped virus stocks.

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Schultz, Anke; Germann, Anja; Fuss, Martina; Sarzotti-Kelsoe, Marcella; Ozaki, Daniel A; Montefiori, David C; Zimmermann, Heiko; von Briesen, Hagen

2018-01-01

The standardized assessments of HIV-specific immune responses are of main interest in the preclinical and clinical stage of HIV-1 vaccine development. In this regard, HIV-1 Env-pseudotyped viruses play a central role for the evaluation of neutralizing antibody profiles and are produced according to Good Clinical Laboratory Practice- (GCLP-) compliant manual and automated procedures. To further improve and complete the automated production cycle an automated system for aliquoting HIV-1 pseudovirus stocks has been implemented. The automation platform consists of a modified Tecan-based system including a robot platform for handling racks containing 48 cryovials, a Decapper, a tubing pump and a safety device consisting of ultrasound sensors for online liquid level detection of each individual cryovial. With the aim to aliquot the HIV-1 pseudoviruses in an automated manner under GCLP-compliant conditions a validation plan was developed where the acceptance criteria-accuracy, precision as well as the specificity and robustness-were defined and summarized. By passing the validation experiments described in this article the automated system for aliquoting has been successfully validated. This allows the standardized and operator independent distribution of small-scale and bulk amounts of HIV-1 pseudovirus stocks with a precise and reproducible outcome to support upcoming clinical vaccine trials.

A feasibility study for a clinical decision support system prompting HIV testing.

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Chadwick, D R; Hall, C; Rae, C; Rayment, Ml; Branch, M; Littlewood, J; Sullivan, A

2017-07-01

Levels of undiagnosed HIV infection and late presentation remain high globally despite attempts to increase testing. The objective of this study was to evaluate a risk-based prototype application to prompt HIV testing when patients undergo routine blood tests. Two computer physician order entry (CPOE) systems were modified using the application to prompt health care workers (HCWs) to add an HIV test when other tests selected suggested that the patient was at higher risk of HIV infection. The application was applied for a 3-month period in two areas, in a large London hospital and in general practices in Teesside/North Yorkshire. At the end of the evaluation period, HCWs were interviewed to assess the usability and acceptability of the prompt. Numbers of HIV tests ordered in the general practice areas were also compared before and after the prompt's introduction. The system was found to be both useable and generally acceptable to hospital doctors, general practitioners and nurse practitioners, with little evidence of prompt/alert fatigue. The issue of the prompt appearing late in the patient consultation did lead to some difficulties, particularly around discussion of the test and consent. In the general practices, around 1 in 10 prompts were accepted and there was a 6% increase in testing rates over the 3-month study period (P = 0.169). Using a CPOE-based clinical decision support application to prompt HIV testing appears both feasible and acceptable to HCWs. Refining the application to provide more accurate risk stratification is likely to make it more effective. © 2016 British HIV Association.

HIV infection in the elderly

Directory of Open Access Journals (Sweden)

Nancy Nguyen

2008-09-01

Full Text Available Nancy Nguyen1, Mark Holodniy21University of the Pacific School of Pharmacy and Health Sciences, Stockton, CA, USA; 2VA Palo Alto Health Care System, Palo Alto, CA, USAAbstract: In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient.Keywords: HIV, epidemiology, treatment, aging, review

Inferring genetic interactions from comparative fitness data.

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Crona, Kristina; Gavryushkin, Alex; Greene, Devin; Beerenwinkel, Niko

2017-12-20

Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax , the fungus Aspergillus niger , and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial.

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Wijting, Ingeborg; Rokx, Casper; Boucher, Charles; van Kampen, Jeroen; Pas, Suzan; de Vries-Sluijs, Theodora; Schurink, Carolina; Bax, Hannelore; Derksen, Maarten; Andrinopoulou, Eleni-Rosalina; van der Ende, Marchina; van Gorp, Eric; Nouwen, Jan; Verbon, Annelies; Bierman, Wouter; Rijnders, Bart

2017-12-01

The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands. Eligible patients (aged ≥18 years) were on combination ART, had been virologically suppressed (HIV RNA <50 copies per mL) for at least 6 months, and had CD4 nadirs of 200 cells per μL or higher, HIV RNA zeniths of 100 000 copies per mL or less, and no history of virological failure. Patients were randomly assigned (1:1), via a web-based block randomisation method (variable block sizes of 4 and 6), to switch to dolutegravir monotherapy (50 mg once a day) either immediately or after a delay of 24 weeks of continued combination ART. Randomisation was stratified by HIV RNA zenith (<50 000 copies per mL vs 50 000-99 999 copies per mL). Investigators and patients were not masked to group allocation. The primary endpoint was the proportion of patients with plasma HIV RNA viral loads of less than 200 copies per mL at week 24, with a non-inferiority margin of 12%. We did analyses in the on-treatment and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, NCT02401828. Between March 10, 2015, and Feb 4, 2016, we randomly assigned 51 patients to the immediate switch group and 53 patients to the delayed switch group. One patient who received immediate monotherapy discontinued treatment at week 12 because of disturbed sleep. At week 24, dolutegravir monotherapy was non-inferior to combination ART, with plasma HIV RNA loads of 200 copies per mL or higher observed in 2% (1/50) of patients in the immediate switch group and in no patients in the delayed switch group (difference 2%, 95% CI

Radiological differences between HIV-positive and HIV-negative children with cholesteatoma.

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McGuire, J K; Fagan, J J; Wojno, M; Manning, K; Harris, T

2018-07-01

HIV-positive children are possibly more prone to developing cholesteatoma. Chronic inflammation of the middle ear cleft may be more common in patients with HIV and this may predispose HIV-positive children to developing cholesteatoma. There are no studies that describe the radiological morphology of the middle ear cleft in HIV-positive compared to HIV-negative children with cholesteatoma. Compare the radiological differences of the middle ear cleft in HIV-positive and HIV-negative children with cholesteatoma. A retrospective, cross-sectional, observational analytical review of patients with cholesteatoma at our institute over a 6 year period. Forty patients were included in the study, 11 of whom had bilateral cholesteatoma and therefore 51 ears were eligible for our evaluation. HIV-positive patients had smaller (p=0.02) mastoid air cell systems (MACS). Forty percent of HIV-positive patients had sclerotic mastoids, whereas the rate was 3% in HIV-negative ears (p<0.02). Eighty-two percent of the HIV-positive patients had bilateral cholesteatoma compared to 7% of the control group (p<0.02). There was no difference between the 2 groups with regards to opacification of the middle ear cleft, bony erosion of middle ear structures, Eustachian tube obstruction or soft tissue occlusion of the post-nasal space. HIV-positive paediatric patients with cholesteatoma are more likely to have smaller, sclerotic mastoids compared to HIV-negative patients. They are significantly more likely to have bilateral cholesteatoma. This may have implications in terms of surveillance of HIV-positive children, as well as, an approach to management, recurrence and follow-up. HIV infection should be flagged as a risk factor for developing cholesteatoma. Copyright © 2018. Published by Elsevier B.V.

HIV and AIDS

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... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2.

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LeGoff, J; Roques, P; Jenabian, M-A; Charpentier, C; Brochier, C; Bouhlal, H; Gresenguet, G; Frost, E; Pepin, J; Mayaud, P; Belec, L

2015-09-01

Clinical and subclinical genital herpes simplex virus type 2 (HSV-2) reactivations have been associated with increases in human immunodeficiency virus (HIV)-1 genital shedding. Whether HSV-2 shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1/HSV-2-co-infected women, including seven with HSV-2 genital reactivation, and seven without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The HSV-2 selection pressure on HIV was estimated according to the number of synonymous substitutions (dS), the number of non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No differences in dS, dN and the dS/dN ratio were observed between the study groups for either genital HIV-1 RNA or plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with HSV-2 genital reactivation (p genital HIV-1 DNA was slightly higher in patients with HSV-2 genital replication, indicating a trend for purifying selection (p 0.056). HSV-2 increased the genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Impact of Clinical Parameters in the Intrahost Evolution of HIV-1 Subtype B in Pediatric Patients: A Machine Learning Approach

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Rojas Sánchez, Patricia; Cobos, Alberto; Navaro, Marisa; Ramos, José Tomas; Pagán, Israel

2017-01-01

Abstract Determining the factors modulating the genetic diversity of HIV-1 populations is essential to understand viral evolution. This study analyzes the relative importance of clinical factors in the intrahost HIV-1 subtype B (HIV-1B) evolution and in the fixation of drug resistance mutations (DRM) during longitudinal pediatric HIV-1 infection. We recovered 162 partial HIV-1B pol sequences (from 3 to 24 per patient) from 24 perinatally infected patients from the Madrid Cohort of HIV-1 infected children and adolescents in a time interval ranging from 2.2 to 20.3 years. We applied machine learning classification methods to analyze the relative importance of 28 clinical/epidemiological/virological factors in the HIV-1B evolution to predict HIV-1B genetic diversity (d), nonsynonymous and synonymous mutations (dN, dS) and DRM presence. Most of the 24 HIV-1B infected pediatric patients were Spanish (91.7%), diagnosed before 2000 (83.3%), and all were antiretroviral therapy experienced. They had from 0.3 to 18.8 years of HIV-1 exposure at sampling time. Most sequences presented DRM. The best-predictor variables for HIV-1B evolutionary parameters were the age of HIV-1 diagnosis for d, the age at first antiretroviral treatment for dN and the year of HIV-1 diagnosis for ds. The year of infection (birth year) and year of sampling seemed to be relevant for fixation of both DRM at large and, considering drug families, to protease inhibitors (PI). This study identifies, for the first time using machine learning, the factors affecting more HIV-1B pol evolution and those affecting DRM fixation in HIV-1B infected pediatric patients. PMID:29044435

Marburg Virus Reverse Genetics Systems

Directory of Open Access Journals (Sweden)

Kristina Maria Schmidt

2016-06-01

Full Text Available The highly pathogenic Marburg virus (MARV is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

Dynamic modeling of genetic networks using genetic algorithm and S-system.

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Kikuchi, Shinichi; Tominaga, Daisuke; Arita, Masanori; Takahashi, Katsutoshi; Tomita, Masaru

2003-03-22

The modeling of system dynamics of genetic networks, metabolic networks or signal transduction cascades from time-course data is formulated as a reverse-problem. Previous studies focused on the estimation of only network structures, and they were ineffective in inferring a network structure with feedback loops. We previously proposed a method to predict not only the network structure but also its dynamics using a Genetic Algorithm (GA) and an S-system formalism. However, it could predict only a small number of parameters and could rarely obtain essential structures. In this work, we propose a unified extension of the basic method. Notable improvements are as follows: (1) an additional term in its evaluation function that aims at eliminating futile parameters; (2) a crossover method called Simplex Crossover (SPX) to improve its optimization ability; and (3) a gradual optimization strategy to increase the number of predictable parameters. The proposed method is implemented as a C program called PEACE1 (Predictor by Evolutionary Algorithms and Canonical Equations 1). Its performance was compared with the basic method. The comparison showed that: (1) the convergence rate increased about 5-fold; (2) the optimization speed was raised about 1.5-fold; and (3) the number of predictable parameters was increased about 5-fold. Moreover, we successfully inferred the dynamics of a small genetic network constructed with 60 parameters for 5 network variables and feedback loops using only time-course data of gene expression.

Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

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van Manen, Daniëlle; van 't Wout, Angélique B.; Schuitemaker, Hanneke

2012-01-01

Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication

ORIGINAL ARTICLES Atopy in HIV-infected children in Pretoria

African Journals Online (AJOL)

Both atopic and HIV-related diseases are common in South. Africa. Atopy is a genetic .... tree mix, dog hair dander, cat hair dander, standard mite .... incidence of dermatitis;16 this may present as inflammatory or eczematous .... during intestinal nematode infections: what it takes to make a Th2 cell in vivo. Immunol Rev. 2004 ...

In vitro modeling of HIV proviral activity in microglia.

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Campbell, Lee A; Richie, Christopher T; Zhang, Yajun; Heathward, Emily J; Coke, Lamarque M; Park, Emily Y; Harvey, Brandon K

2017-12-01

Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection. We utilized clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology and integrated a modified HIV provirus into CHME-5 immortalized microglia to create HIV-NanoLuc CHME-5. In the modified provirus, the Gag-Pol region is replaced with the coding region for NanoLuciferase (NanoLuc), which allows for the rapid assay of HIV long terminal repeat activity using a luminescent substrate, while still containing the necessary genetic material to produce established neurotoxic viral proteins (e.g. tat, nef, gp120). We confirmed that HIV-NanoLuc CHME-5 microglia express NanoLuc, along with the HIV viral protein Nef. We subsequently exposed these cells to a battery of experiments to modulate the activity of the provirus. Proviral activity was enhanced by treating the cells with pro-inflammatory factors lipopolysaccharide (LPS) and tumor necrosis factor alpha and by overexpressing the viral regulatory protein Tat. Conversely, genetic modification of the toll-like receptor-4 gene by CRISPR/Cas9 reduced LPS-mediated proviral activation, and pharmacological application of NF-κB inhibitor sulfasalazine similarly diminished proviral activity. Overall, these data suggest that HIV-NanoLuc CHME-5 may be a useful tool in the study of HIV-mediated neuropathology and proviral regulation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

The HIV/AIDS epidemic in Cuba: description and tentative explanation of its low HIV prevalence

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Clémençon Stéphan

2007-11-01

Full Text Available Abstract Background The Cuban HIV/AIDS epidemic has the lowest prevalence rate of the Caribbean region. The objective of this paper is to give an overview of the HIV/AIDS epidemic in Cuba and to explore the reasons for this low prevalence. Methods Data were obtained from the Cuban HIV/AIDS programme established in 1983. This programme has an extensive adult HIV testing policy, including testing of all pregnant women. HIV and AIDS cases have been recorded since 1986. Persons found to be HIV-positive are interviewed on their sexual behaviour and partners. Tracing and voluntary testing of these partners are organised. Epidemiological description of this epidemic was obtained from analysis of this data set. Using elementary mathematical analyses, we estimated the coverage of the detection system (percentage of HIV-positive adults detected and the average period between HIV infection and detection. Estimated HIV prevalence rates were corrected to account for the coverage. Results HIV prevalence has increased since 1996. In 2005, the prevalence among pregnant women was 1.2 per 10,000 (16/137000. Estimated HIV prevalence among 15- to 49-year-olds was 8.1 per 10,000 (4913/6065000; 95%CI: 7.9 per 10,000 – 8.3 per 10,000. Most (77% of the HIV-positive adults were men, most (85.1% of the detected HIV-positive men were reported as having sex with men (MSM, and most of the HIV-positive women reported having had sex with MSM. The average period between HIV infection and detection was estimated to be 2.1 years (IQR = 1.7 – 2.2 years. We estimated that, for the year 2005, 79.6% (IQR: 77.3 – 81.4% of the HIV-positive persons were detected. Conclusion MSM drive the HIV epidemic in Cuba. The extensive HIV testing policy may be an important factor in explaining the low HIV prevalence. To reduce the HIV epidemic in Cuba, the epidemic among MSM should be addressed. To understand this epidemic further, data on sexual behaviour should be collected. Now that

Transfer of the amino-terminal nuclear envelope targeting domain of human MX2 converts MX1 into an HIV-1 resistance factor.

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Goujon, Caroline; Moncorgé, Olivier; Bauby, Hélène; Doyle, Tomas; Barclay, Wendy S; Malim, Michael H

2014-08-01

-stimulated genes (ISGs). The human MX2 protein has been identified as a key effector in the suppression of HIV-1 infection by IFN. Here, we describe a molecular genetic approach, using a collection of chimeric MX proteins, to identify protein domains of MX2 that specify HIV-1 inhibition. The amino-terminal 91-amino-acid domain of human MX2 confers HIV-1 suppressor capabilities upon human and mouse MX proteins and also promotes protein accumulation at the nuclear envelope. Therefore, these studies correlate the cellular location of MX proteins with anti-HIV-1 function and help establish a framework for future mechanistic analyses of MX-mediated virus control. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision support.

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Döring, Matthias; Borrego, Pedro; Büch, Joachim; Martins, Andreia; Friedrich, Georg; Camacho, Ricardo Jorge; Eberle, Josef; Kaiser, Rolf; Lengauer, Thomas; Taveira, Nuno; Pfeifer, Nico

2016-12-20

CCR5-coreceptor antagonists can be used for treating HIV-2 infected individuals. Before initiating treatment with coreceptor antagonists, viral coreceptor usage should be determined to ensure that the virus can use only the CCR5 coreceptor (R5) and cannot evade the drug by using the CXCR4 coreceptor (X4-capable). However, until now, no online tool for the genotypic identification of HIV-2 coreceptor usage had been available. Furthermore, there is a lack of knowledge on the determinants of HIV-2 coreceptor usage. Therefore, we developed a data-driven web service for the prediction of HIV-2 coreceptor usage from the V3 loop of the HIV-2 glycoprotein and used the tool to identify novel discriminatory features of X4-capable variants. Using 10 runs of tenfold cross validation, we selected a linear support vector machine (SVM) as the model for geno2pheno[coreceptor-hiv2], because it outperformed the other SVMs with an area under the ROC curve (AUC) of 0.95. We found that SVMs were highly accurate in identifying HIV-2 coreceptor usage, attaining sensitivities of 73.5% and specificities of 96% during tenfold nested cross validation. The predictive performance of SVMs was not significantly different (p value 0.37) from an existing rules-based approach. Moreover, geno2pheno[coreceptor-hiv2] achieved a predictive accuracy of 100% and outperformed the existing approach on an independent data set containing nine new isolates with corresponding phenotypic measurements of coreceptor usage. geno2pheno[coreceptor-hiv2] could not only reproduce the established markers of CXCR4-usage, but also revealed novel markers: the substitutions 27K, 15G, and 8S were significantly predictive of CXCR4 usage. Furthermore, SVMs trained on the amino-acid sequences of the V1 and V2 loops were also quite accurate in predicting coreceptor usage (AUCs of 0.84 and 0.65, respectively). In this study, we developed geno2pheno[coreceptor-hiv2], the first online tool for the prediction of HIV-2 coreceptor

Impact of global health governance on country health systems: the case of HIV initiatives in Nigeria.

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Chima, Charles Chikodili; Homedes, Nuria

2015-06-01

Three global health initiatives (GHIs) - the US President's Emergency Plan for AIDS Relief, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and the World Bank Multi-Country HIV/AIDS Program - finance most HIV services in Nigeria. Critics assert that GHIs burden fragile health systems in resource-poor countries and that health system limitations in these countries constrain the achievement of the objectives of GHIs. This study analyzed interactions between HIV GHIs and the Nigerian Health System and explored how the impact of the GHIs could be optimized. A country case study was conducted using qualitative methods, including: semi-structured interviews, direct observation, and archival review. Semi-structured interviews were held with key informants selected to reach a broad range of stakeholders including policymakers, program managers, service providers, representatives of donor agencies and their implementing partners; the WHO country office in Nigeria; independent consultants; and civil society organizations involved in HIV work. The fieldwork was conducted between June and August 2013. HIV GHIs have had a mixed impact on the health system. They have enhanced availability of and access to HIV services, improved quality of services, and strengthened health information systems and the role of non-state actors in health care. On the negative end, HIV donor funding has increased dependency on foreign aid, widened disparities in access to HIV services, done little to address the sustainability of the services, crowded out non-HIV health services, and led to the development of a parallel supply management system. They have also not invested significantly in the production of new health workers and have not addressed maldistribution problems, but have rather contributed to internal brain drain by luring health workers from the public sector to non-governmental organizations and have increased workload for existing health workers. There is poor policy direction

Genetic Diversity within Alphaherpesviruses: Characterization of a Novel Variant of Herpes Simplex Virus 2.

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Burrel, Sonia; Désiré, Nathalie; Marlet, Julien; Dacheux, Laurent; Seang, Sophie; Caumes, Eric; Bourhy, Hervé; Agut, Henri; Boutolleau, David

2015-12-01

Very low levels of variability have been reported for the herpes simplex virus 2 (HSV-2) genome. We recently described a new genetic variant of HSV-2 (HSV-2v) characterized by a much higher degree of variability for the UL30 gene (DNA polymerase) than observed for the HG52 reference strain. Retrospective screening of 505 clinical isolates of HSV-2 by a specific real-time PCR assay targeting the UL30 gene led to the identification of 13 additional HSV-2v isolates, resulting in an overall prevalence of 2.8%. Phylogenetic analyses on the basis of microsatellite markers and gene sequences showed clear differences between HSV-2v and classical HSV-2. Thirteen of the 14 patients infected with HSV-2v originated from West or Central Africa, and 9 of these patients were coinfected with HIV. These results raise questions about the origin of this new virus. Preliminary results suggest that HSV-2v may have acquired genomic segments from chimpanzee alphaherpesvirus (ChHV) by recombination. This article deals with the highly topical question of the origin of this new HSV-2 variant identified in patients with HIV coinfection originating mostly from West or Central Africa. HSV-2v clearly differed from classical HSV-2 isolates in phylogenetic analyses and may be linked to simian ChHV. This new HSV-2 variant highlights the possible occurrence of recombination between human and simian herpesviruses under natural conditions, potentially presenting greater challenges for the future. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

An Evaluation of Phylogenetic Methods for Reconstructing Transmitted HIV Variants using Longitudinal Clonal HIV Sequence Data

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McCloskey, Rosemary M.; Liang, Richard H.; Harrigan, P. Richard; Brumme, Zabrina L.

2014-01-01

difficult to isolate since newly infected individuals are often unaware of their status for months or years, by which time the virus population has evolved substantially. Here, we report on the potential use of evolutionary methods to reconstruct the genetic sequence of the transmitted/founder virus from its descendants at later stages of an infection. These methods can recover this ancestral sequence with an overall error rate of about 2.3%—about 15% more information than if we had ignored the evolutionary relationships among viruses. Although there is no substitute for sampling infections at earlier points in time, these methods can provide useful information about the genetic makeup of transmitted/founder HIV. PMID:24648453

Characterization of HIV Transmission in South-East Austria.

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Hoenigl, Martin; Chaillon, Antoine; Kessler, Harald H; Haas, Bernhard; Stelzl, Evelyn; Weninger, Karin; Little, Susan J; Mehta, Sanjay R

2016-01-01

To gain deeper insight into the epidemiology of HIV-1 transmission in South-East Austria we performed a retrospective analysis of 259 HIV-1 partial pol sequences obtained from unique individuals newly diagnosed with HIV infection in South-East Austria from 2008 through 2014. After quality filtering, putative transmission linkages were inferred when two sequences were ≤1.5% genetically different. Multiple linkages were resolved into putative transmission clusters. Further phylogenetic analyses were performed using BEAST v1.8.1. Finally, we investigated putative links between the 259 sequences from South-East Austria and all publicly available HIV polymerase sequences in the Los Alamos National Laboratory HIV sequence database. We found that 45.6% (118/259) of the sampled sequences were genetically linked with at least one other sequence from South-East Austria forming putative transmission clusters. Clustering individuals were more likely to be men who have sex with men (MSM; pAustria had at least one putative inferred linkage with sequences from a total of 69 other countries. In conclusion, analysis of HIV-1 sequences from newly diagnosed individuals residing in South-East Austria revealed a high degree of national and international clustering mainly within MSM. Interestingly, we found that a high number of heterosexual males clustered within MSM networks, suggesting either linkage between risk groups or misrepresentation of sexual risk behaviors by subjects.

Pharmacogenetic considerations in the treatment of HIV.

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Mattevi, Vanessa S; Tagliari, Carmela Fs

2017-01-01

After the introduction of highly active antiretroviral therapy in the 1990s, the perception of the diagnosis of HIV infection gradually shifted from a 'death sentence' to a chronic disease requiring long-term treatment. The host genetic variability has been shown to play a relevant role in both antiretroviral drugs bioavailability and adverse effects susceptibility. Knowledge about pharmacogenetics role in HIV infection treatment has largely increased over the last years, and is reviewed in the present report, as well as future perspectives for the inclusion of pharmacogenetics information in the directing of HIV infection treatment.

Recommendations for the classification of HIV associated neuromanifestations in the German DRG system.

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Evers, Stefan; Fiori, W; Brockmeyer, N; Arendt, G; Husstedt, I-W

2005-09-12

HIV associated neuromanifestations are of growing importance in the in-patient treatment of HIV infected patients. In Germany, all in-patients have to be coded according to the ICD-10 classification and the German DRG-system. We present recommendations how to code the different primary and secondary neuromanifestations of HIV infection. These recommendations are based on the commentary of the German DRG procedures and are aimed to establish uniform coding of neuromanifestations.

Use of a high resolution melting (HRM assay to compare gag, pol, and env diversity in adults with different stages of HIV infection.

Directory of Open Access Journals (Sweden)

Matthew M Cousins

Full Text Available Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative, 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14-540 days, and 67 with non-recent HIV infection (HIV infected >2 years. HRM scores were generated for two regions in gag, one region in pol, and three regions in env.Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection.The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined.

Clinical correlates of HIV-associated neurocognitive disorders in South Africa.

Science.gov (United States)

Joska, John A; Fincham, Dylan S; Stein, Dan J; Paul, Robert H; Seedat, Soraya

2010-04-01

Human immunodeficiency virus-associated neurocognitive disorders (HAND) occurs globally and across different genetic clades of the virus. However, few studies have examined HAND in South Africa, despite the prevalence of HIV in this region of the world, and the predominance of clade C. The present study examined the relationship between a number of demographic and clinical variables in a sample of 536 patients attending HIV clinics in South Africa. HAND was present in 23.5% of the sample and was associated with older age, a low educational level among those with post-traumatic stress disorder (PTSD) and alcohol abuse among those with many months since diagnosis. These results suggest that HAND is common among patients in South Africa, and is associated with clinical variables such as PTSD and alcohol abuse. This underlines the impact of HIV on the nervous system and the importance of screening for co morbid mental health conditions.

Fluorine Substituted 1,2,4-Triazinones as Potential Anti-HIV-1 and CDK2 Inhibitors

Directory of Open Access Journals (Sweden)

Mohammed S. I. Makki

2014-01-01

Full Text Available Fluorine substituted 1,2,4-triazinones have been synthesized via alkylation, amination, and/or oxidation of 6-(2-amino-5-fluorophenyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H-one 1 and 4-fluoro-N-(4-fluoro-2-(5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-ylphenylbenzamide 5 as possible anti-HIV-1 and CDK2 inhibitors. Alkylation on positions 2 and 4 in 1,2,4-triazinone gave compounds 6–8. Further modification was performed by selective alkylation and amination on position 3 to form compounds 9–15. However oxidation of 5 yielded compounds 16–18. Structures of the target compounds have been established by spectral analysis data. Five compounds (5, 11, 14, 16, and 17 have shown very good anti-HIV activity in MT-4 cells. Similarly, five compounds (1, 3, and 14–16 have exhibited very significant CDK2 inhibition activity. Compounds 14 and 16 were found to have dual anti-HIV and anticancer activities.

Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

Science.gov (United States)

Schiffer, Joshua T; Gottlieb, Sami L

2017-09-25

Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village

Directory of Open Access Journals (Sweden)

Ricard Dominique

2010-05-01

Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given

Variability of HIV-1 genomes among children and adolescents from Sao Paulo, Brazil.

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Sabri Saeed Sanabani

Full Text Available BACKGROUND: Genetic variability is a major feature of the human immunodeficiency virus type 1 (HIV-1 and considered the key factor to frustrating efforts to halt the virus epidemic. In this study, we aimed to investigate the genetic variability of HIV-1 strains among children and adolescents born from 1992 to 2009 in the state of Sao Paulo, Brazil. METHODOLOGY: Plasma and peripheral blood mononuclear cells (PBMC were collected from 51 HIV-1-positive children and adolescents on ART followed between September 1992 and July 2009. After extraction, the genetic materials were used in a polymerase chain reaction (PCR to amplify the viral near full length genomes (NFLGs from 5 overlapped fragments. NFLGs and partial amplicons were directly sequenced and data were phylogenetically inferred. RESULTS: Of the 51 samples studied, the NFLGs and partial fragments of HIV-1 from 42 PBMCs and 25 plasma were successfully subtyped. Results based on proviral DNA revealed that 22 (52.4% patients were infected with subtype B, 16 (38.1% were infected with BF1 mosaic variants and 4 (9.5% were infected with sub-subtype F1. All the BF1 recombinants were unique and distinct from any previously identified unique or circulating recombinant forms in South America. Evidence of dual infections was detected in 3 patients coinfected with the same or distinct HIV-1 subtypes. Ten of the 31 (32.2% and 12 of the 21 (57.1% subjects with recovered proviral and plasma, respectively, protease sequences were infected with major mutants resistant to protease inhibitors. The V3 sequences of 14 patients with available sequences from PBMC/or plasma were predicted to be R5-tropic virus except for two patients who harbored an X4 strain. CONCLUSIONS: The high proportion of HIV-1 BF1 recombinant, coinfection rate and vertical transmission in Brazil merits urgent attention and effective measures to reduce the transmission of HIV among spouses and sex partners.

Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.

Directory of Open Access Journals (Sweden)

Mary S Campbell

2011-03-01

Full Text Available Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519 was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners.We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥ 50%. Adjudicators classified each seroconversion, finding 108 (71.5% linked, 40 (26.5% unlinked, and 3 (2.0% indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%. Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters.In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner

Drugs + HIV, Learn the Link

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Full Text Available ... Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental Health Military Opioid Overdose ... be transmitted between users. Other infections, such as hepatitis C, can also be spread this way. Hepatitis ...

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Full Text Available ... Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental ... and alcohol even once can have serious health consequences. We also work to reach parents and teachers— ...

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Full Text Available ... Drugs and the Brain Genetics Global Health Health Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ...

[Survey on the transmission of HIV drug resistance in Kunming, Yunnan province in 2010].

Science.gov (United States)

Chen, Min; Ma, Yan-ling; Chu, Cheng-xia; Xing, Hui; Xu, Yan-sheng; Su, Ying-zhen; Yang, Ying; Chen, Hui-chao; Luo, Hong-bing; Jia, Man-hong; Lu, Lin

2012-01-01

To study the HIV drug resistance (HIVDR) transmission in Kunming city of Yunnan province in 2010. Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS) set by WHO, 62 plasma samples of recently reported HIV-infected individuals who were older than 25 years of age, were collected from January to August 2010. Genotyping of pol genetic mutations associated with HIVDR with reverse transcriptional PCR was performed and the prevalence of HIV-1 drug resistance transmission was evaluated. Of the 62 plasma samples, 54 were successfully sequenced and genotyped on pol sequence. Based on the pol sequences, HIV subtypes including CRF08_BC (53.2%), CRF07_BC (25.5%), CRF01_AE (19.1%) and C (2.1%) were identified. According to the time of sampling, the first 47 sequenced samples were used for drug resistance prevalence analysis. A protease inhibitor (PI) relative mutation was found in one sample. Based on the WHO standard, the prevalence of transmitted HIV-1 drug resistance was scientific management to AIDS patients seemed to be quite important.

Diabetes mellitus and impaired fasting glucose in ART-naïve patients with HIV-1, HIV-2 and HIV-1/2 dual infection in Guinea-Bissau

DEFF Research Database (Denmark)

Steiniche, Ditte; Jespersen, Sanne; Erikstrup, Christian

2016-01-01

BACKGROUND: The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau. METHODS: Patients were consecutively included. D...... age and a family history of DM apply also for ART-naïve patients with HIV.......BACKGROUND: The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau. METHODS: Patients were consecutively included....... Demographic and lifestyle data were collected and one fasting blood glucose (FBG) measurement was used to diagnose DM (FBG≥7.0 mmol/L) and impaired fasting glucose (IFG) (FBG≥6.1 and ART-naïve patients with HIV had been included in the study of whom 893...

[The comparative study of specificity of test-systems in diagnostic of HIV-infection on categories of samples of blood serum of pregnant women].

Science.gov (United States)

Sharipova, I N; Khodak, N M; Puzirev, V F; Burkov, A N; Ulanova, T I

2015-03-01

The detection of false positive serological reactions (FPSR) on HIV-infection under screening examination of pregnant women is an actual problem of practical health care. The original observations testify that under analysis of the same samples of blood serum of pregnant women using screening immune enzyme test-systems of various manufacturers the unmatched data concerning FPSR can be obtained. The purpose of this study was to implement comparative evaluation of specificity of immune enzyme test-systems of three different manufacturers: "DS-IFA-HIV-AGAT-SCREEN" ("Diagnostic Systems"), "Genscreen Ultra HIV Ag-Ab" "Bio Rad" France) and "The CombiBest HIV-1,2 AG/AT" ("Vector-Best" Novosibirsk). The sampling of 440 samples of blood serums of pregnant women from various medical institutions of Nizhnii Novgorod was analyzed. The results of the study demonstrated that FPSR were detected in all test-systems and at that spectrum of samples differed. The identical specificity of compared test-systems amounted to 98.64%. The alternative approach to FPSR to HIV issue under screening examinations of pregnant women was proposed. The proposed mode consisted of consistent application of two test-systems of fourth generation with different format of setup of reaction.

Re-visioning local biologies: HIV-2 and the pattern of differential valuation in biomedical research.

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Gilbert, Hannah

2013-01-01

The discovery of HIV-2, a distinctly West African variant of HIV, is often portrayed as the result of a straightforward, if serendipitous, error. This article reframes the history of how HIV-2 came to be a knowable scientific identity. Relying on narratives from an African laboratory and clinic, it suggests that the rise and fall of HIV-2 as a viable research entity is indicative of a differential visibility and valuation of both human bodies and viruses. Understanding how HIV-2 emerged as a local biology reveals the complex set of relations that contemporary African scientists face in navigating local moral economies and the mercurial politics of the contemporary global health industry.

HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study.

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Omori, Ryosuke; Nagelkerke, Nico; Abu-Raddad, Laith J

2017-12-04

To investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy. An individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and miscapture of high-risk individuals was assessed through sensitivity analyses. Assuming no HIV/HSV-2 biological interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners over last year, over lifetime and for both partner numbers simultaneously reduced the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54 (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction, the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI 7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90), 3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under-reporting of partners reduced the confounder-adjustment effects. Miscapture of high-risk individuals considerably lowered the estimated ORs. It is difficult to control for sexual-behaviour confounding in observational studies. The observed HIV/HSV-2 association appears more consistent with two infections sharing the same mode of transmission, rather than with HSV-2 enhancing HIV acquisition. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Feasibility testing of a web-based symptom self-management system for persons living with HIV.

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Schnall, Rebecca; Wantland, Dean; Velez, Olivia; Cato, Kenrick; Jia, Haomiao

2014-01-01

The purpose of this study was to explore the feasibility of using a Web-based tool to provide tailored symptom management strategies for persons living with HIV (PLWH) and to estimate the effect size of the tool for future studies. Testing the components of the Web-based system was done by incorporating a repeated-measures design measuring the outcomes of symptom frequency and intensity, use of symptom management strategies, and engagement with health care providers. We recruited 42 PLWH; participants were enrolled in the study for 12 weeks and were asked to use the system and complete the questionnaires every 2 weeks. Our results showed that participants who used the strategies were more likely to have a decrease in symptom frequency and intensity. Findings from this feasibility study provide preliminary evidence for the use of a Web-based HIV symptom management tool with self-management strategies for individuals living with HIV infection. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

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Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa

Science.gov (United States)

Freeman, Esther E.; White, Richard G.; Bakker, Roel; Orroth, Kate K.; Weiss, Helen A.; Buvé, Anne; Hayes, Richard J.; Glynn, Judith R.

2009-01-01

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30–40% after 20 years (range 4–66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine. PMID:19071187

Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

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Hammond Robert R

2004-05-01

Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

Slow progression of paediatric HIV disease: Selective adaptation or ...

African Journals Online (AJOL)

In the European Caucasian populations, the chemokine-cell receptor variant CCR5 \\"Delta 32\\" is a the genetic determinant of HIV disease progression that is believed to have been selected for in the general population by exposure to antigens closely interlinked to HIV like Yersinia pestis or small pox virus. Among African ...

[Detecting the markers of HIV infection with the new enzyme immunoassay diagnostic kit "DS-EIA-HIV-AB-AG-SPECTRUM" at the laboratories of AIDS prevention and control centers in the Volga Federal District].

Science.gov (United States)

Ivanova, N I; Peksheva, O Iu

2009-03-01

A possibility of simultaneously detecting specific antibodies to HIV-1 and HIV-2 by enzyme immunoassay (EIA) at lower concentrations than those by immunoblotting (IB), and well as an additional possibility of earlier diagnosis of HIV infection, by identifying the HIV-1 antigen p24 lay the foundation of the "DS-EIA-HIV-AB-AG-SPECTRUM" test system made by OOO "Research-and-Production Association "Diagnosticheskiye Sistemy" (Diagnostic Systems). These peculiarities were compared with those of IB at a number of laboratories of AIDS prevention and control centers in the Volga Federal District, by using native serum/plasma samples and a specially designed control panel. The analysis of the conducted studies to identify HIV-1 and HIV-2 antibodies and HIV-1 antigen p24 in 65 plasma/serum samples in the "DS-EIA-HIV-AB-AG-SPECTRUM" and "LIA-HIV-1/2" (OOO "Niarmedik plus") test systems while confirming the positive result indicated agreement in 57 (87.7%) cases. The diagnostic possibilities of the "DS-EIA-HIV-AB-AG-SPECTRUM" test system versus the "New Lav-Blot I" one to make a laboratory diagnosis of HIV infection were studied. Irrefragable answers as to the availability of HIV-1 markers in the study serum samples on the enciphered panel were provided by IB in 73.3% of cases and EIA in 92%.

Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

DEFF Research Database (Denmark)

Knudsen, T B; Kristiansen, T B; Katzenstein, T L

2001-01-01

/G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently......HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A...

HSV-2 Infection as a Cause of Female/Male and Racial/Ethnic Disparities in HIV Infection.

Directory of Open Access Journals (Sweden)

Don C Des Jarlais

Full Text Available To examine the potential contribution of herpes simplex virus 2 (HSV-2 infection to female/male and racial/ethnic disparities in HIV among non-injecting heroin and cocaine drug users. HSV-2 infection increases susceptibility to HIV infection by a factor of two to three.Subjects were recruited from entrants to the Beth Israel drug detoxification program in New York City 2005-11. All subjects reported current use of heroin and/or cocaine and no lifetime injection drug use. A structured questionnaire was administered and serum samples collected for HIV and HSV-2 testing. Population-attributable risk percentages (PAR%s were calculated for associations between HSV-2 infection and increased susceptibility to HIV.1745 subjects were recruited from 2005-11. Overall HIV prevalence was 14%. Females had higher prevalence than males (22% vs. 12% (p<0.001, African-Americans had the highest prevalence (15%, Hispanics an intermediate prevalence (12%, and Whites the lowest prevalence (3% (p<.001. There were parallel variations in HSV-2 prevalence (females 86%, males 51%, African-Americans 66%, Hispanics 47%, Whites 36%, HSV-2 prevalence was strongly associated with HIV prevalence (OR  =  3.12 95% CI 2.24 to 4.32. PAR%s for HSV-2 as a cause of HIV ranged from 21% for Whites to 50% for females. Adjusting for the effect of increased susceptibility to HIV due to HSV-2 infection greatly reduced all disparities (adjusted prevalence  =  males 8%, females 11%; Whites 3%, African-Americans 10%, Hispanics 9%.Female/male and racial/ethnic variations in HSV-2 infection provide a biological mechanism that may generate female/male and racial/ethnic disparities in HIV infection among non-injecting heroin and cocaine users in New York City. HSV-2 infection should be assessed as a potential contributing factor to disparities in sexually transmitted HIV throughout the US.

Combining social and genetic networks to study HIV transmission in mixing risk groups

NARCIS (Netherlands)

Zarrabi, N.; Prosperi, M.C.F.; Belleman, R.G.; Di Giambenedetto, S.; Fabbiani, M.; De Luca, A.; Sloot, P.M.A.

2013-01-01

Reconstruction of HIV transmission networks is important for understanding and preventing the spread of the virus and drug resistant variants. Mixing risk groups is important in network analysis of HIV in order to assess the role of transmission between risk groups in the HIV epidemic. Most of the

HIV/AIDS in Women

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HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV often ...

Is the HIV sentinel surveillance system adequate in China? Findings from an evaluation of the national HIV sentinel surveillance system

Directory of Open Access Journals (Sweden)

Marc Bulterys

2012-11-01

Full Text Available Background: An external evaluation was conducted to assess the performance of the national HIV sentinel surveillance system (HSS, identify operational challenges at national and local levels and provide recommendations for improvement.Methods: The United States Centers for Disease Control and Prevention’s (CDC Updated Guidelines for Evaluating Public Health Surveillance Systems were followed to assess the key attributes of HSS. Comprehensive assessment activities were conducted, including: using a detailed checklist to review surveillance guidelines, protocols and relevant documents; conducting self-administered, anonymous surveys with 286 local China CDC staff; and carrying out field observations in 32 sentinel sites in four provinces.Results: China has built an extensive HSS with 1888 sentinel sites to monitor HIV epidemic trends by population groups over time. The strengths of HSS lie in its flexibility, simplicity, usefulness and increase in coverage in locations and populations. With its rapid expansion in 2010, HSS faces challenges in maintaining acceptability, timeliness, data quality, representativeness and sustainability.Recommendations: Implementation of the national guidelines should be standardized by strengthening training, monitoring and supervision of all staff involved, including community-based organizations. National surveillance guidelines need to be revised to strengthen data quality and representativeness, particularly to include specific instructions on HIV testing result provision, collection of identifying information, sample size and sampling methods particularly for men who have sex with men (MSM, collection of refusal information, and data interpretation. Sustainability of China’s HSS could be strengthened by applying locally tailored surveillance strategies, strengthening coordination and cooperation among government agencies and ensuring financial and human resources.

Genetic factors associated with slow progression of HIV among perinatally-infected Indian children.

Science.gov (United States)

Chaudhuri, Riya Pal; Neogi, Ujjwal; Rao, Shwetha D; Shet, Anita

2014-10-01

To study the association between common AIDS restriction genes and slow disease progression among perinatally-infected children in India. ART-naïve children were identified and selected host factors including CCR5-∆32, SDF1-3'A, CCR5-59029G, HLA-B*27, B*57 were studied using allele-specific PCR-RFLP and SSPGo HLA typing kits. Among 165 children, 10 (6%) long-term non-progressors and 8 (5%) slow progressors were identified. For comparison, 12 children with normal progression of HIV were included. The frequencies of CCR5-∆32 deletion, SDF1-3'A and CCR5-59029G did not differ significantly. HLA-B*27 and B*57 were observed only in long-term non-progressors or slow progressors, who also harbored either SDF1-3'A and/or CCR5-59029G. There is an association between host genetic factors and slow disease progression in this population.

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Science.gov (United States)

Coulonges, Cedric; Bartha, István; Lenz, Tobias L.; Deutsch, Aaron J.; Bashirova, Arman; Buchbinder, Susan; Carrington, Mary N.; Cossarizza, Andrea; Dalmau, Judith; De Luca, Andrea; Goedert, James J.; Gurdasani, Deepti; Haas, David W.; Herbeck, Joshua T.; Johnson, Eric O.; Kirk, Gregory D.; Lambotte, Olivier; Luo, Ma; Mallal, Simon; van Manen, Daniëlle; Martinez-Picado, Javier; Meyer, Laurence; Miro, José M.; Mullins, James I.; Obel, Niels; Poli, Guido; Sandhu, Manjinder S.; Schuitemaker, Hanneke; Shea, Patrick R.; Theodorou, Ioannis; Walker, Bruce D.; Weintrob, Amy C.; Winkler, Cheryl A.; Wolinsky, Steven M.; Raychaudhuri, Soumya; Goldstein, David B.; Telenti, Amalio; de Bakker, Paul I. W.; Zagury, Jean-François; Fellay, Jacques

2015-01-01

Previous genome-wide association studies (GWAS) of HIV-1–infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation—mostly in the HLA and CCR5 regions—explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward. PMID:26553974

HIV/AIDS, Drug Abuse Treatment, and the Correctional System.

Science.gov (United States)

Lipton, Douglas S.

1997-01-01

Discusses in-prison prevalence and transmission of Human Immunodeficiency Virus (HIV). Focuses on epidemiology in prison settings, the role of ethnicity and gender in transmission, screening for HIV, segregating the HIV-positive inmate, condom distribution, medical treatment for HIV-positive inmates, HIV education and prevention, and tuberculosis…

Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

DEFF Research Database (Denmark)

Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete

2014-01-01

.g. metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index...... investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...

Vaginal microbiota and its role in HIV transmission and infection.

Science.gov (United States)

Petrova, Mariya I; van den Broek, Marianne; Balzarini, Jan; Vanderleyden, Jos; Lebeer, Sarah

2013-09-01

The urogenital tract appears to be the only niche of the human body that shows clear differences in microbiota between men and women. The female reproductive tract has special features in terms of immunological organization, an epithelial barrier, microbiota, and influence by sex hormones such as estrogen. While the upper genital tract is regarded as free of microorganisms, the vagina is colonized by bacteria dominated by Lactobacillus species, although their numbers vary considerably during life. Bacterial vaginosis is a common pathology characterized by dysbiosis, which increases the susceptibility for HIV infection and transmission. On the other hand, HIV infections are often characterized by a disturbed vaginal microbiota. The endogenous vaginal microbiota may protect against HIV by direct production of antiviral compounds, through blocking of adhesion and transmission by ligands such as lectins, and/or by stimulation of immune responses. The potential role of probiotics in the prevention of HIV infections and associated symptoms, by introducing them to the vaginal and gastrointestinal tract (GIT), is also discussed. Of note, the GIT is a site of considerable HIV replication and CD4(+) T-cell destruction, resulting in both local and systemic inflammation. Finally, genetically engineered lactobacilli show promise as new microbicidal agents against HIV. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

[HIV and syphilis coinfection in pregnancy and vertical HIV transmission: a study based on epidemiological surveillance data].

Science.gov (United States)

Acosta, Lisiane M W; Gonçalves, Tonantzin Ribeiro; Barcellos, Nêmora Tregnago

2016-12-01

To estimate the rate of HIV and syphilis coinfection among pregnant women living in Porto Alegre, Brazil, as well as the association of coinfection with vertical HIV transmission and socioeconomic variables. This analytical retrospective cross-sectional study employed data from the regular epidemiological surveillance system for the period from 2010 to 2013. Data were obtained regarding pregnant women with HIV and exposed children, syphilis in pregnancy, and congenital syphilis. The study population included 1 500 HIV-positive women with deliveries from 2010 to 2013. Of these, 155 (10.3%) were also infected with syphilis, corresponding to an HIV and syphilis coinfection rate of 10.2% (± 1.5%). The coinfected group had lower education levels, higher prevalence of black women, and greater HIV exposure related to drug use by the woman or a partner. Coinfected women had more delayed HIV diagnosis (for example, during childbirth) and greater prevalence of lacking prenatal care (44%). Crude analysis showed an association between vertical HIV transmission and HIV and syphilis co-infection (PR = 2.1; 95%CI: 1.21-3.74; P = 0.01) that persisted in the adjusted analysis. A profile of increased vulnerability was identified among pregnant women with HIV and syphilis coinfection. A positive impact of the treatment to reduce congenital syphilis and eliminate vertical transmission of HIV depends on enhanced access to qualified health care.

Cyclophilin B enhances HIV-1 infection.

Science.gov (United States)

DeBoer, Jason; Madson, Christian J; Belshan, Michael

2016-02-01

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. Copyright © 2015 Elsevier Inc. All rights reserved.

Administrative integration of vertical HIV monitoring and evaluation into health systems: a case study from South Africa.

Science.gov (United States)

Kawonga, Mary; Fonn, Sharon; Blaauw, Duane

2013-01-24

In light of an increasing global focus on health system strengthening and integration of vertical programmes within health systems, methods and tools are required to examine whether general health service managers exercise administrative authority over vertical programmes. To measure the extent to which general health service (horizontal) managers, exercise authority over the HIV programme's monitoring and evaluation (M&E) function, and to explore factors that may influence this exercise of authority. This cross-sectional survey involved interviews with 51 managers. We drew ideas from the concept of 'exercised decision-space' - traditionally used to measure local level managers' exercise of authority over health system functions following decentralisation. Our main outcome measure was the degree of exercised authority - classified as 'low', 'medium' or 'high' - over four M&E domains (HIV data collection, collation, analysis, and use). We applied ordinal logistic regression to assess whether actor type (horizontal or vertical) was predictive of a higher degree of exercised authority, independent of management capacity (training and experience), and M&E knowledge. Relative to vertical managers, horizontal managers had lower HIV M&E knowledge, were more likely to exercise a higher degree of authority over HIV data collation (OR 7.26; CI: 1.9, 27.4), and less likely to do so over HIV data use (OR 0.19; CI: 0.05, 0.84). A higher HIV M&E knowledge score was predictive of a higher exercised authority over HIV data use (OR 1.22; CI: 0.99, 1.49). There was no association between management capacity and degree of authority. This study demonstrates a HIV M&E model that is neither fully vertical nor integrated. The HIV M&E is characterised by horizontal managers producing HIV information while vertical managers use it. This may undermine policies to strengthen integrated health system planning and management under the leadership of horizontal managers.

Strengthening Health Systems for Chronic Care: Leveraging HIV Programs to Support Diabetes Services in Ethiopia and Swaziland

Directory of Open Access Journals (Sweden)

Miriam Rabkin

2012-01-01

Full Text Available The scale-up of HIV services in sub-Saharan Africa has catalyzed the development of highly effective chronic care systems. The strategies, systems, and tools developed to support life-long HIV care and treatment are locally owned contextually appropriate resources, many of which could be adapted to support continuity care for noncommunicable chronic diseases (NCD, such as diabetes mellitus (DM. We conducted two proof-of-concept studies to further the understanding of the status of NCD programs and the feasibility and effectiveness of adapting HIV program-related tools and systems for patients with DM. In Swaziland, a rapid assessment illustrated gaps in the approaches used to support DM services at 15 health facilities, despite the existence of chronic care systems at HIV clinics in the same hospitals, health centers, and clinics. In Ethiopia, a pilot study found similar gaps in DM services at baseline and illustrated the potential to rapidly improve the quality of care and treatment for DM by adapting HIV-specific policies, systems, and tools.

Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility

DEFF Research Database (Denmark)

Walter, Brandon L; Armitage, Andrew E; Graham, Stephen C

2009-01-01

BACKGROUND: Despite the existence of over 50 subtypes and circulating recombinant forms of HIV-1, subtype C dominates the heterosexual pandemic causing approximately 56% of all infections. OBJECTIVE: To evaluate whether viral genetic factors may contribute to the observed subtype-C predominance. ....... CONCLUSION: As CD4-CCR5-T cells are key targets for genital HIV infection and cervical selection can favor compact V1-V2 loops and 316T, which increase viral infectivity, we propose that these conserved subtype-C motifs may contribute to transmission and spread of this subtype....

Hairpin-induced tRNA-mediated (HITME) recombination in HIV-1

NARCIS (Netherlands)

Konstantinova, Pavlina; de Haan, Peter; Das, Atze T.; Berkhout, Ben

2006-01-01

Recombination due to template switching during reverse transcription is a major source of genetic variability in retroviruses. In the present study we forced a recombination event in human immunodeficiency virus type 1 (HIV-1) by electroporation of T cells with DNA from a molecular HIV-1 clone that

Circumcision status and incident herpes simplex virus type 2 infection, genital ulcer disease, and HIV infection

Science.gov (United States)

Mehta, Supriya D.; Moses, Stephen; Parker, Corette B.; Agot, Kawango; Maclean, Ian; Bailey, Robert C.

2013-01-01

Objective We assessed the protective effect of medical male circumcision (MMC) against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD) incidence. Design Two thousand, seven hundred and eighty-seven men aged 18–24 years living in Kisumu, Kenya were randomly assigned to circumcision (n=1391) or delayed circumcision (n =1393) and assessed by HIV and HSV-2 testing and medical examinations during follow-ups at 1, 3, 6, 12, 18, and 24 months. Methods Cox regression estimated the risk ratio of each outcome (incident HIV, GUD, HSV-2) for circumcision status and multivariable models estimated HIV risk associated with HSV-2, GUD, and circumcision status as time-varying covariates. Results HIV incidence was 1.42 per 100 person-years. Circumcision was 62% protective against HIV [risk ratio =0.38; 95% confidence interval (CI) 0.22–0.67] and did not change when controlling for HSV-2 and GUD (risk ratio =0.39; 95% CI 0.23–0.69). GUD incidence was halved among circumcised men (risk ratio =0.52; 95% CI 0.37–0.73). HSV-2 incidence did not differ by circumcision status (risk ratio =0.94; 95% CI 0.70–1.25). In the multivariable model, HIV seroconversions were tripled (risk ratio =3.44; 95% CI 1.52–7.80) among men with incident HSV-2 and seven times greater (risk ratio =6.98; 95% CI 3.50–13.9) for men with GUD. Conclusion Contrary to findings from the South African and Ugandan trials, the protective effect of MMC against HIV was independent of GUD and HSV-2, and MMC had no effect on HSV-2 incidence. Determining the causes of GUD is necessary to reduce associated HIV risk and to understand how circumcision confers protection against GUD and HIV PMID:22382150

Reporting of HIV-infected pregnant women: estimates from a Brazilian study.

Science.gov (United States)

Domingues, Rosa Maria Soares Madeira; Saraceni, Valéria; Leal, Maria do Carmo

2018-01-01

To estimate the coverage of the reporting of cases of HIV-infected pregnant women, to estimate the increase in the coverage of the reporting with the routine search of data in other Brazilian health information systems, and to identify missed opportunities for identification of HIV-infected pregnant women in Brazilian maternity hospitals. This is a descriptive study on the linkage of Brazilian databases with primary data from the "Nascer no Brasil" study and secondary database collection from national health information systems. The "Nascer no Brasil" is a national-based study carried out in 2011-2012 with 23,894 pregnant women, which identified HIV-infected pregnant women using prenatal and medical records. We searched for cases of HIV-infected pregnant women identified in the "Nascer no Brasil" study in the Information System of Notifiable Diseases, the Control System for Laboratory Tests of the National CD4+/CD8+ Lymphocyte Count and HIV Viral Load Network, and the Logistics Control System for Medications. We used the OpenRecLink software for the linkage of databases. We estimated the notification coverage, with the respective confidence interval, of the evaluated Brazilian health information systems. We estimated the coverage of the reporting of HIV-infected pregnant women in the Information System of Notifiable Diseases as 57.1% (95%CI 42.9-70.2), and we located 89.3% of the HIV-infected pregnant women (95%CI 81.2-94.2) in some of the Brazilian health information systems researched. The search in other national health information systems would result in an increase of 57.1% of the reported cases. We identified no missed opportunities for the diagnosis of HIV+ in pregnant women in the maternity hospitals evaluated by the "Nascer no Brasil" study. The routine search for information in other Brazilian health information systems, a procedure carried out by the Ministry of Health for cases of AIDS in adults and children, should be adopted for cases of HIV in

Seroprevalence of Herpes Simplex Virus type-2 (HSV-2) among pregnant women who participated in a national HIV surveillance activity in Haiti.

Science.gov (United States)

Domercant, Jean Wysler; Jean Louis, Frantz; Hulland, Erin; Griswold, Mark; Andre-Alboth, Jocelyne; Ye, Tun; Marston, Barbara J

2017-08-18

Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted.

Using Genetic Algorithms for Building Metrics of Collaborative Systems

Directory of Open Access Journals (Sweden)

Cristian CIUREA

2011-01-01

Full Text Available he paper objective is to reveal the importance of genetic algorithms in building robust metrics of collaborative systems. The main types of collaborative systems in economy are presented and some characteristics of genetic algorithms are described. A genetic algorithm was implemented in order to determine the local maximum and minimum points of the relative complexity function associated to a collaborative banking system. The intelligent collaborative systems based on genetic algorithms, representing the new generation of collaborative systems, are analyzed and the implementation of auto-adaptive interfaces in a banking application is described.

New Highly Sensitive Real-Time PCR Assay for HIV-2 Group A and Group B DNA Quantification.

Science.gov (United States)

Bertine, Mélanie; Gueudin, Marie; Mélard, Adeline; Damond, Florence; Descamps, Diane; Matheron, Sophie; Collin, Fidéline; Rouzioux, Christine; Plantier, Jean-Christophe; Avettand-Fenoel, Véronique

2017-09-01

HIV-2 infection is characterized by a very low replication rate in most cases and low progression. This necessitates an approach to patient monitoring that differs from that for HIV-1 infection. Here, a new highly specific and sensitive method for HIV-2 DNA quantification was developed. The new test is based on quantitative real-time PCR targeting the long terminal repeat (LTR) and gag regions and using an internal control. Analytical performance was determined in three laboratories, and clinical performance was determined on blood samples from 63 patients infected with HIV-2 group A ( n = 35) or group B ( n = 28). The specificity was 100%. The 95% limit of detection was three copies/PCR and the limit of quantification was six copies/PCR. The within-run coefficients of variation were between 1.03% at 3.78 log 10 copies/PCR and 27.02% at 0.78 log 10 copies/PCR. The between-run coefficient of variation was 5.10%. Both manual and automated nucleic acid extraction methods were validated. HIV-2 DNA loads were detectable in blood cells from all 63 patients. When HIV-2 DNA was quantifiable, median loads were significantly higher in antiretroviral-treated than in naive patients and were similar for groups A and B. HIV-2 DNA load was correlated with HIV-2 RNA load ( r = 0.68; 95% confidence interval [CI], 0.4 to 0.8; P < 0.0001). Our data show that this new assay is highly sensitive and quantifies the two main HIV-2 groups, making it useful for the diagnosis of HIV-2 infection and for pathogenesis studies on HIV-2 reservoirs. Copyright © 2017 American Society for Microbiology.

Cyclophilin B enhances HIV-1 infection

Energy Technology Data Exchange (ETDEWEB)

DeBoer, Jason; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln, NE (United States)

2016-02-15

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

Cyclophilin B enhances HIV-1 infection

International Nuclear Information System (INIS)

DeBoer, Jason; Madson, Christian J.; Belshan, Michael

2016-01-01

Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

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

Directory of Open Access Journals (Sweden)

Sulggi A Lee

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

Molecular docking of (5E)-3-(2-aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione on HIV-1 reverse transcriptase: novel drug acting on enzyme.

Science.gov (United States)

Seniya, Chandrabhan; Yadav, Ajay; Uchadia, Kuldeep; Kumar, Sanjay; Sagar, Nitin; Shrivastava, Priyanka; Shrivastava, Shilpi; Wadhwa, Gulshan

2012-01-01

The study of Human immunodeficiency virus (HIV) in humans and animal models in last 31 years suggested that it is a causative agent of AIDS. This causes serious pandemic public health concern globally. It was reported that the HIV-1 reverse transcriptase (RT) played a critical role in the life cycle of HIV. Therefore, inhibition of HIV-1RT enzyme is one of the major and potential targets in the treatment of AIDS. The enzyme (HIV-1RT) was successfully targeted by non nucleotide reverse transcriptase inhibitors (NNRTIs). But frequent application of NNRTIs led drug resistance mutation on HIV infections. Therefore, there is a need to search new NNRTIs with appropriate pharmacophores. For the purpose, a virtually screened 3D model of unliganded HIV-1RT (1DLO) was explored. The unliganded HIV-1RT (1DLO) was docked with 4-thiazolidinone and its derivatives (ChemBank Database) by using AutoDock4. The best seven docking solutions complex were selected and analyzed by Ligplot. The analysis showed that derivative (5E)-3-(2- aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione (CID 3087795) has maximum potential against unliganded HIV-1RT (1DLO). The analysis was done on the basis of scoring and binding ability. The derivative (5E)-3-(2- aminoethyl)-5-(2- thienylmethylene)-1, 3-thiazolidine-2, 4-dione (CID 3087795) indicated minimum energy score and highest number of interactions with active site residue and could be a promising inhibitor for HIV-1 RT as Drug target.

Role of HIV-2 envelope in Lv2-mediated restriction

International Nuclear Information System (INIS)

Reuter, Sandra; Kaumanns, Patrick; Buschhorn, Sabine B.; Dittmar, Matthias T.

2005-01-01

We have characterized envelope protein pseudotyped HIV-2 particles derived from two HIV-2 isolates termed prCBL23 and CBL23 in order to define the role of the envelope protein for the Lv2-mediated restriction to infection. Previously, it has been described that the primary isolate prCBL23 is restricted to infection of several human cell types, whereas the T cell line adapted isolate CBL23 is not restricted in these cell types. Molecular cloning of the two isolates revealed that the env and the gag gene are responsible for the observed phenotype and that this restriction is mediated by Lv2, which is distinct from Ref1/Lv1 (Schmitz, C., Marchant, D., Neil, S.J., Aubin, K., Reuter, S., Dittmar, M.T., McKnight, A., Kizhatil, K., Albritton, L.M., 2004. Lv2, a novel postentry restriction, is mediated by both capsid and envelope. J. Virol. 78 (4), 2006-2016). We generated pseudotyped viruses consisting of HIV-2 (ROD-AΔenv-GFP, ROD-AΔenv-RFP, or ROD-AΔenv-REN) and the prCBL23 or CBL23 envelope proteins as well as chimeric proteins between these envelopes. We demonstrate that a single amino acid exchange at position 74 in the surface unit of CBL23-Env confers restriction to infection. This single point mutation causes tighter CD4 binding, resulting in a less efficient fusion into the cytosol of the restricted cell line. Prevention of endosome formation and prevention of endosome acidification enhance infectivity of the restricted particles for GHOST/X4 cells indicating a degradative lysosomal pathway as a cause for the reduced cytosolic entry. The described restriction to infection of the primary isolate prCBL23 is therefore largely caused by an entry defect. A remaining restriction to infection (19-fold) is preserved when endosomal acidification is prevented. This restriction to infection is also dependent on the presence of the point mutation at position 74 (G74E)

Asymptomatic HIV infection

Science.gov (United States)

... of HIV/AIDS during which there are no symptoms of HIV infection. During this phase, the immune system in someone with HIV slowly weakens, but the person has no symptoms. How long this phase lasts depends on how ...

Cutaneous manifestation of HIV/AIDS: Part 2 | Dlova | Southern ...

African Journals Online (AJOL)

These can be localised, widespread, confined to the skin, or systemic. They can cause mild though disfiguring lesions such as molluscum contagiosum (MCV), or lead to life-threatening infections such as human papillomavirus (HPV-induced squamous cell carcinoma. Southern African Journal of HIV Medicine Vol.

Prevalence, incidence and determinants of herpes simplex virus type 2 infection among HIV-seronegative women at high-risk of HIV infection: a prospective study in Beira, Mozambique

NARCIS (Netherlands)

Meque, Ivete; Dubé, Karine; Feldblum, Paul J.; Clements, Archie C. A.; Zango, Arlinda; Cumbe, Fidelina; Chen, Pai Lien; Ferro, Josefo J.; van de Wijgert, Janneke H.

2014-01-01

To estimate the prevalence, incidence and determinants of herpes simplex type 2 (HSV-2) infection, and associations between HSV-2 and incident HIV infection, among women at higher risk for HIV infection in Beira, Mozambique. Between 2009 and 2012, 411 women aged 18-35 years at higher risk of HIV

Discovery and optimization of 2-pyridinone aminal integrase strand transfer inhibitors for the treatment of HIV.

Science.gov (United States)

Schreier, John D; Embrey, Mark W; Raheem, Izzat T; Barbe, Guillaume; Campeau, Louis-Charles; Dubost, David; McCabe Dunn, Jamie; Grobler, Jay; Hartingh, Timothy J; Hazuda, Daria J; Klein, Daniel; Miller, Michael D; Moore, Keith P; Nguyen, Natalie; Pajkovic, Natasa; Powell, David A; Rada, Vanessa; Sanders, John M; Sisko, John; Steele, Thomas G; Wai, John; Walji, Abbas; Xu, Min; Coleman, Paul J

2017-05-01

HIV integrase strand transfer inhibitors (InSTIs) represent an important class of antiviral therapeutics with proven efficacy and excellent tolerability for the treatment of HIV infections. In 2007, Raltegravir became the first marketed strand transfer inhibitor pioneering the way to a first-line therapy for treatment-naïve patients. Challenges with this class of therapeutics remain, including frequency of the dosing regimen and the genetic barrier to resistance. To address these issues, research towards next-generation integrase inhibitors has focused on imparting potency against RAL-resistent mutants and improving pharmacokinetic profiles. Herein, we detail medicinal chemistry efforts on a novel class of 2-pyridinone aminal InSTIs, inpsired by MK-0536, which led to the discovery of important lead molecules for our program. Systematic optimization carried out at the amide and aminal positions on the periphery of the core provided the necessary balance of antiviral activity and physiochemical properties. These efforts led to a novel aminal lead compound with the desired virological profile and preclinical pharmacokinetic profile to support a once-daily human dose prediction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developing a surveillance system for HIV/AIDS in Pakistan

International Nuclear Information System (INIS)

Emmanuel, F.; Bokhari, A.

2006-01-01

Apart from other interventions, surveillance remains a major focus of the national response to HIV/AIDS. However, with a shift in the epidemic pattern, the existing surveillance strategies are barely insufficient and long-term structural changes are desirable. This article provides a conceptual framework for developing a scientific system for HIV surveillance in Pakistan. Second generation surveillance system including repeated cross-sectional surveys in high risk population groups are suggested to collect behavioral and serological data at regular intervals on an annual basis to monitor the epidemic trend as well as the associated behaviors. In addition, multiple data resources have been highlighted, which could be coordinated to describe the epidemic pattern in the country. This information should form the basis for national prevention planning and ought to be used for making sensible choices through which prevention efforts are most likely to reduce new infections. (author)

2D-QSAR study of fullerene nanostructure derivatives as potent HIV-1 protease inhibitors

Science.gov (United States)

Barzegar, Abolfazl; Jafari Mousavi, Somaye; Hamidi, Hossein; Sadeghi, Mehdi

2017-09-01

The protease of human immunodeficiency virus1 (HIV-PR) is an essential enzyme for antiviral treatments. Carbon nanostructures of fullerene derivatives, have nanoscale dimension with a diameter comparable to the diameter of the active site of HIV-PR which would in turn inhibit HIV. In this research, two dimensional quantitative structure-activity relationships (2D-QSAR) of fullerene derivatives against HIV-PR activity were employed as a powerful tool for elucidation the relationships between structure and experimental observations. QSAR study of 49 fullerene derivatives was performed by employing stepwise-MLR, GAPLS-MLR, and PCA-MLR models for variable (descriptor) selection and model construction. QSAR models were obtained with higher ability to predict the activity of the fullerene derivatives against HIV-PR by a correlation coefficient (R2training) of 0.942, 0.89, and 0.87 as well as R2test values of 0.791, 0.67and 0.674 for stepwise-MLR, GAPLS-MLR, and PCA -MLR models, respectively. Leave-one-out cross-validated correlation coefficient (R2CV) and Y-randomization methods confirmed the models robustness. The descriptors indicated that the HIV-PR inhibition depends on the van der Waals volumes, polarizability, bond order between two atoms and electronegativities of fullerenes derivatives. 2D-QSAR simulation without needing receptor's active site geometry, resulted in useful descriptors mainly denoting ;C60 backbone-functional groups; and ;C60 functional groups; properties. Both properties in fullerene refer to the ligand fitness and improvement van der Waals interactions with HIV-PR active site. Therefore, the QSAR models can be used in the search for novel HIV-PR inhibitors based on fullerene derivatives.

A prospective cohort study comparing the effect of single-dose 2 g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women.

Science.gov (United States)

Balkus, Jennifer E; Richardson, Barbra A; Mochache, Vernon; Chohan, Vrasha; Chan, Jeannie D; Masese, Linnet; Shafi, Juma; Marrazzo, Jeanne; Farquhar, Carey; McClelland, R Scott

2013-06-01

This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women. Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole. All women on antiretroviral therapy (ART) used nevirapine-based regimens. Generalized estimating equations with a logit link were used to compare the frequency of persistent TV (defined as the presence of motile trichomonads by saline microscopy at the next examination visit within 60 days) by HIV status. Three-hundred sixty participants contributed 570 infections to the analysis (282 HIV-seropositive and 288 HIV-seronegative). There were 42 (15%) persistent infections among HIV-seropositive participants versus 35 (12%) among HIV-seronegative participants (adjusted odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.87). Persistent TV was highest among HIV-seropositive women using ART (21/64 [33%]) compared with HIV-seropositive women not using ART (21/217 [10%]). Concurrent bacterial vaginosis (BV) at TV diagnosis was associated with an increased likelihood of persistent TV (adjusted odds ratio, 1.90; 95% confidence interval, 1.16-3.09). The frequency of persistent TV infection after treatment with single-dose 2 g oral metronidazole was similar by HIV status. Alternative regimens including multiday antibiotic treatment may be necessary to improve cure rates for women using nevirapine-based ART and women with TV and concurrent BV.

Forensic application of phylogenetic analyses - Exploration of suspected HIV-1 transmission case.

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Siljic, Marina; Salemovic, Dubravka; Cirkovic, Valentina; Pesic-Pavlovic, Ivana; Ranin, Jovan; Todorovic, Marija; Nikolic, Slobodan; Jevtovic, Djordje; Stanojevic, Maja

2017-03-01

Transmission of human immunodeficiency virus (HIV) between individuals may have important legal implications and therefore may come to require forensic investigation based upon phylogenetic analysis. In criminal trials results of phylogenetic analyses have been used as evidence of responsibility for HIV transmission. In Serbia, as in many countries worldwide, exposure and deliberate transmission of HIV are criminalized. We present the results of applying state of the art phylogenetic analyses, based on pol and env genetic sequences, in exploration of suspected HIV transmission among three subjects: a man and two women, with presumed assumption of transmission direction from one woman to a man. Phylogenetic methods included relevant neighbor-joining (NJ), maximum likelihood (ML) and Bayesian methods of phylogenetic trees reconstruction and hypothesis testing, that has been shown to be the most sensitive for the reconstruction of epidemiological links mostly from sexually infected individuals. End-point limiting-dilution PCR (EPLD-PCR) assay, generating the minimum of 10 sequences per genetic region per subject, was performed to assess HIV quasispecies distribution and to explore the direction of HIV transmission between three subjects. Phylogenetic analysis revealed that the viral sequences from the three subjects were more genetically related to each other than to other strains circulating in the same area with the similar epidemiological profile, forming strongly supported transmission chain, which could be in favour of a priori hypothesis of one of the women infecting the man. However, in the EPLD based phylogenetic trees for both pol and env genetic region, viral sequences of one subject (man) were paraphyletic to those of two other subjects (women), implying the direction of transmission opposite to the a priori assumption. The dated tree in our analysis confirmed the clustering pattern of query sequences. Still, in the context of unsampled sequences and

A therapeutic HIV vaccine using coxsackie-HIV recombinants: a possible new strategy.

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Halim, S S; Collins, D N; Ramsingh, A I

2000-10-10

The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.

Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

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Min Chen

Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

Health Systems Integration of Sexual and Reproductive Health and HIV Services in Sub-Saharan Africa: A Scoping Study

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Kendall, Tamil; Langer, Ana; Bärnighausen, Till

2014-01-01

Objective: Both sexual and reproductive health (SRH) services and HIV programs in sub-Saharan Africa are typically delivered vertically, operating parallel to national health systems. The objective of this study was to map the evidence on national and international strategies for integration of SRH and HIV services in sub-Saharan Africa and to develop a research agenda for future health systems integration. Methods: We examined the literature on national and international strategies to integrate SRH and HIV services using a scoping study methodology. Current policy frameworks, national HIV strategies and research, and gray literature on integration were mapped. Five countries in sub-Saharan Africa with experience of integrating SRH and HIV services were purposively sampled for detailed thematic analysis, according to the health systems functions of governance, policy and planning, financing, health workforce organization, service organization, and monitoring and evaluation. Results: The major international health policies and donor guidance now support integration. Most integration research has focused on linkages of SRH and HIV front-line services. Yet, the common problems with implementation are related to delayed or incomplete integration of higher level health systems functions: lack of coordinated leadership and unified national integration policies; separate financing streams for SRH and HIV services and inadequate health worker training, supervision and retention. Conclusions: Rigorous health systems research on the integration of SRH and HIV services is urgently needed. Priority research areas include integration impact, performance, and economic evaluation to inform the planning, financing, and coordination of integrated service delivery. PMID:25436826

Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.

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Zoe Moodie

Full Text Available The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study.HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo were estimated by Cox models.Of the 695 eligible, 465 (67% enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections. The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001 but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62.The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women.clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Home; Journals; Journal of Genetics. STEFANOS BONOVAS. Articles written in Journal of Genetics. Volume 97 Issue 1 March 2018 pp 235-251 RESEARCH ARTICLE. Interleukin gene polymorphisms and susceptibility to HIV-1 infection: a meta-analysis · CHRISSA G TSIARA GEORGIOS K. NIKOLOPOULOS NIKI L. DIMOU ...

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Home; Journals; Journal of Genetics. Aridaman Pandit. Articles written in Journal of Genetics. Volume 92 Issue 3 December 2013 pp 403-412 Research Article. Analysis of dinucleotide signatures in HIV-1 subtype B genomes · Aridaman Pandit Jyothirmayi Vadlamudi Somdatta Sinha · More Details Abstract Fulltext PDF.