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  1. The unusual nucleotide content of the HIV RNA genome results in a biased amino acid composition of HIV proteins

    NARCIS (Netherlands)

    Berkhout, B.; van Hemert, F. J.

    1994-01-01

    Extremely high frequencies of the A nucleotide are found in the RNA genomes of the lentivirus group of retroviruses. It is presently unknown what molecular force is responsible for this A-pressure. In this manuscript, we demonstrate a correlation between this 'A-pressure' and the amino acid-usage of

  2. DBR1 siRNA inhibition of HIV-1 replication

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    Naidu Yathi

    2005-10-01

    Full Text Available Abstract Background HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1 expression would specifically inhibit HIV-1 replication. Results We designed three short interfering RNA (siRNA molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. Conclusion These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

  3. Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype.

    Science.gov (United States)

    Patterson, B K; Mosiman, V L; Cantarero, L; Furtado, M; Bhattacharya, M; Goolsby, C

    1998-04-01

    Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.

  4. HIV-1 nef suppression by virally encoded microRNA

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    Brisibe Ebiamadon

    2004-12-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are 21~25-nucleotides (nt long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi, depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs inhibited the transcription of HIV-1. Results Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA that corresponded to a predicted nef miRNA (~25 nt, miR-N367 can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2. In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. Conclusions These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.

  5. Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population.

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    Peters, Philip J; Westheimer, Emily; Cohen, Stephanie; Hightow-Weidman, Lisa B; Moss, Nicholas; Tsoi, Benjamin; Hall, Laura; Fann, Charles; Daskalakis, Demetre C; Beagle, Steve; Patel, Pragna; Radix, Asa; Foust, Evelyn; Kohn, Robert P; Marmorino, Jenni; Pandori, Mark; Fu, Jie; Samandari, Taraz; Gay, Cynthia L

    2016-02-16

    Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Number and proportion with acute HIV infections detected. Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both

  6. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1–Seropositive Kenyan Men

    Science.gov (United States)

    Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L.; Sanders, Eduard J.; Peshu, Norbert M.; Krieger, John N.; Muller, Charles H.; Coombs, Robert W.; Fredricks, David N.; Graham, Susan M.

    2017-01-01

    Introduction: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. Methods: We analyzed semen samples from 42 HIV-1–seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Results: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: −0.77, 95% CI: −1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Conclusion: Most of these HIV-1–infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission. PMID:27861240

  7. Levels and patterns of HIV RNA viral load in untreated pregnant women

    DEFF Research Database (Denmark)

    NN, NN; Patel, Deven; Thorne, Claire

    2008-01-01

    OBJECTIVE: To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race. METHODS: Data on > or = 1 antenatal HIV RNA measurements were available for 333 untreated HIV......-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested...... random effects term accounting for measurement variability within women and period of sample collection. RESULTS: The change in HIV RNA over pregnancy varied significantly by race (p=0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies...

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

    Science.gov (United States)

    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.

  9. Dynamics of HIV-1 RNA Near the Plasma Membrane during Virus Assembly.

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    Sardo, Luca; Hatch, Steven C; Chen, Jianbo; Nikolaitchik, Olga; Burdick, Ryan C; Chen, De; Westlake, Christopher J; Lockett, Stephen; Pathak, Vinay K; Hu, Wei-Shau

    2015-11-01

    To increase our understanding of the events that lead to HIV-1 genome packaging, we examined the dynamics of viral RNA and Gag-RNA interactions near the plasma membrane by using total internal reflection fluorescence microscopy. We labeled HIV-1 RNA with a photoconvertible Eos protein via an RNA-binding protein that recognizes stem-loop sequences engineered into the viral genome. Near-UV light exposure causes an irreversible structural change in Eos and alters its emitted fluorescence from green to red. We studied the dynamics of HIV-1 RNA by photoconverting Eos near the plasma membrane, and we monitored the population of photoconverted red-Eos-labeled RNA signals over time. We found that in the absence of Gag, most of the HIV-1 RNAs stayed near the plasma membrane transiently, for a few minutes. The presence of Gag significantly increased the time that RNAs stayed near the plasma membrane: most of the RNAs were still detected after 30 min. We then quantified the proportion of HIV-1 RNAs near the plasma membrane that were packaged into assembling viral complexes. By tagging Gag with blue fluorescent protein, we observed that only a portion, ∼13 to 34%, of the HIV-1 RNAs that reached the membrane were recruited into assembling particles in an hour, and the frequency of HIV-1 RNA packaging varied with the Gag expression level. Our studies reveal the HIV-1 RNA dynamics on the plasma membrane and the efficiency of RNA recruitment and provide insights into the events leading to the generation of infectious HIV-1 virions. Nascent HIV-1 particles assemble on plasma membranes. During the assembly process, HIV-1 RNA genomes must be encapsidated into viral complexes to generate infectious particles. To gain insights into the RNA packaging and virus assembly mechanisms, we labeled and monitored the HIV-1 RNA signals near the plasma membrane. Our results showed that most of the HIV-1 RNAs stayed near the plasma membrane for only a few minutes in the absence of Gag, whereas

  10. Dynamics of breast milk HIV-1 RNA with unilateral mastitis or abscess.

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    Semrau, Katherine; Kuhn, Louise; Brooks, Daniel R; Cabral, Howard; Sinkala, Moses; Kankasa, Chipepo; Thea, Donald M; Aldrovandi, Grace M

    2013-03-01

    Mastitis and abscess in HIV-infected women increase the risk of breastfeeding transmission of HIV. Guidelines encourage women to stop breastfeeding on the affected breast and feed on the contralateral breast. However, impact of breast pathology on breast milk HIV dynamics is unknown. HIV RNA was quantified in 211 breast milk samples collected before, during, and after a clinical mastitis or an abscess diagnosis from 38 HIV-infected women participating in a Zambian breastfeeding study. HIV RNA quantity was compared between affected and unaffected breasts over time using generalized estimating equation models. A sample of 115 women without breast pathology was selected as a control group. In the affected breast, breast milk HIV RNA quantity increased from the pre- to during-pathology period by log(10) 0.45 copies per milliliter [95% confidence interval (CI): 0.16 to 0.74], and after symptom resolution, HIV RNA levels were no different from prepathology levels (log10 -0.04 copies per milliliter 95% CI: -0.33 to 0.25). In the contralateral, unaffected breast, HIV RNA quantity did not significantly increase (log(10) 0.15 copies per milliliter, 95% CI: -0.41 to 0.10). Increase was more marked in women with abscess or with a greater number of mastitis symptoms. HIV RNA was not significantly different between affected and unaffected women, except at the time of diagnosis. Breast milk HIV RNA increased modestly in the affected breast with unilateral mastitis or abscess and returned to prepathology levels with symptom resolution. Contralateral HIV RNA was not affected. Results support guidelines encouraging feeding from the contralateral breast to minimize the risk of HIV transmission associated with unilateral breast pathology.

  11. Diagnosing acute HIV infection: The performance of quantitative HIV-1 RNA testing (viral load) in the 2014 laboratory testing algorithm.

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    Wu, Hsiu; Cohen, Stephanie E; Westheimer, Emily; Gay, Cynthia L; Hall, Laura; Rose, Charles; Hightow-Weidman, Lisa B; Gose, Severin; Fu, Jie; Peters, Philip J

    2017-08-01

    New recommendations for laboratory diagnosis of HIV infection in the United States were published in 2014. The updated testing algorithm includes a qualitative HIV-1 RNA assay to resolve discordant immunoassay results and to identify acute HIV-1 infection (AHI). The qualitative HIV-1 RNA assay is not widely available; therefore, we evaluated the performance of a more widely available quantitative HIV-1 RNA assay, viral load, for diagnosing AHI. We determined that quantitative viral loads consistently distinguished AHI from a false-positive immunoassay result. Among 100 study participants with AHI and a viral load result, the estimated geometric mean viral load was 1,377,793copies/mL. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in ...

    African Journals Online (AJOL)

    Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in a tertiary health facility in Maiduguri, Northeastern Nigeria. ... This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) ... HOW TO USE AJOL.

  13. Micro RNA in Exosomes from HIV-Infected Macrophages

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    William W. Roth

    2015-12-01

    Full Text Available Exosomes are small membrane-bound vesicles secreted by cells that function to shuttle RNA and proteins between cells. To examine the role of exosomal micro RNA (miRNA during the early stage of HIV-1 infection we characterized miRNA in exosomes from HIV-infected macrophages, compared with exosomes from non-infected macrophages. Primary human monocytes from uninfected donors were differentiated to macrophages (MDM which were either mock-infected or infected with the macrophage-tropic HIV-1 BaL strain. Exosomes were recovered from culture media and separated from virus particles by centrifugation on iodixanol density gradients. The low molecular weight RNA fraction was prepared from purified exosomes. After pre-amplification, RNA was hybridized to microarrays containing probes for 1200 miRNA species of known and unknown function. We observed 48 miRNA species in both infected and uninfected MDM exosomes. Additionally, 38 miRNAs were present in infected-cell exosomes but not uninfected-cell exosomes. Of these, 13 miRNAs were upregulated in exosomes from HIV-infected cells, including 4 miRNA species that were increased by more than 10-fold. Though numerous miRNA species have been identified in HIV-infected cells, relatively little is known about miRNA content in exosomes from these cells. In the future, we plan to investigate whether the upregulated miRNA species we identified are increased in exosomes from HIV-1-positive patients.

  14. Impact of collection method on assessment of semen HIV RNA viral load.

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    Brendan J W Osborne

    Full Text Available The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load.Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM either undiluted (Visit 1 or directly into transport medium (Visit 2. Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples.The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.

  15. HIV Infection Status as a Predictor of Hepatitis C Virus RNA Testing in Primary Care

    Science.gov (United States)

    Yartel, Anthony K.; Morgan, Rebecca L.; Rein, David B.; Brown, Kimberly Ann; Kil, Natalie B.; Massoud, Omar I.; Fallon, Michael B.; Smith, Bryce D.

    2015-01-01

    Introduction Receipt of hepatitis C virus (HCV) RNA testing following a positive HCV antibody (anti-HCV+) test result to establish current infection is a quality indicator for HCV-related care. This study examines HIV infection status as a predictor of HCV RNA test receipt after an anti-HCV+ result in the primary care setting. Methods Electronic medical records of anti-HCV+ patients from a multisite retrospective study of patients aged ≥18 years who utilized one or more primary care outpatient services during 2005–2010 were analyzed in 2014. A multivariable logistic regression model examined the independent relationships between patient characteristics and receipt of HCV RNA testing. Results Among 1,115 anti-HCV+ patients, 133 (11.9%) were also HIV-positive. Of these, 77.4% (n=103) underwent HCV RNA testing to determine current infection status. By contrast, 66.7% (n=654/980) of anti-HCV+ patients who were HIV-negative received HCV RNA testing. Following multivariable adjustment, the odds of receiving HCV RNA testing were higher among anti-HCV+ patients who were also HIV-positive (AOR=1.9, 95% CI=1.2, 3.0), compared with their HIV-negative counterparts. Elevated alanine aminotransferase level was also associated with receipt of HCV RNA testing (AOR=1.9, 95% CI=1.4, 2.4). Black race was associated with decreased odds of receiving HCV RNA testing (AOR=0.7, 95% CI=0.5, 1.0). Conclusions HIV infection status is independently associated with the likelihood of receiving HCV RNA testing following an anti-HCV+ result. One quarter of anti-HCV+ patients who were also HIV-positive and one third of their HIV-negative counterparts, respectively, did not receive testing to establish active HCV infection, which is imperative for appropriate care and treatment. PMID:25896194

  16. Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries

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    Daniela Toro-Ascuy

    2016-11-01

    Full Text Available The human immunodeficiency virus type-1 (HIV-1 unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation. During its journey, the HIV-1 unspliced mRNA assembles into highly specific messenger ribonucleoproteins (mRNPs containing many different host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay pathways such as up-frameshift suppressor 1 homolog (UPF1, Staufen double-stranded RNA binding protein 1/2 (STAU1/2, or components of miRNA-induced silencing complex (miRISC and processing bodies (PBs. More recently, the HIV-1 unspliced mRNA was shown to contain N6-methyladenosine (m6A, allowing the recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2, an m6A reader host protein involved in mRNA decay. Interestingly, these host proteins involved in mRNA decay were shown to play positive roles in viral gene expression and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication. This review summarizes the state of the art in terms of the interactions between HIV-1 unspliced mRNA and components of different host mRNA decay machineries.

  17. HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking.

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    Jing Jin

    Full Text Available Retroviral Gag polyproteins are necessary and sufficient for virus budding. Productive HIV-1 Gag assembly takes place at the plasma membrane. However, little is known about the mechanisms by which thousands of Gag molecules are targeted to the plasma membrane. Using a bimolecular fluorescence complementation (BiFC assay, we recently reported that the cellular sites and efficiency of HIV-1 Gag assembly depend on the precise pathway of Gag mRNA export from the nucleus, known to be mediated by Rev. Here we describe an assembly deficiency in human cells for HIV Gag whose expression depends on hepatitis B virus (HBV post-transcriptional regulatory element (PRE mediated-mRNA nuclear export. PRE-dependent HIV Gag expressed well in human cells, but assembled with slower kinetics, accumulated intracellularly, and failed to associate with a lipid raft compartment where the wild-type Rev-dependent HIV-1 Gag efficiently assembles. Surprisingly, assembly and budding of PRE-dependent HIV Gag in human cells could be rescued in trans by co-expression of Rev-dependent Gag that provides correct membrane targeting signals, or in cis by replacing HIV matrix (MA with other membrane targeting domains. Taken together, our results demonstrate deficient membrane targeting of PRE-dependent HIV-1 Gag and suggest that HIV MA function is regulated by the trafficking pathway of the encoding mRNA.

  18. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men.

    Science.gov (United States)

    Korhonen, Christine J; Srinivasan, Sujatha; Huang, Dandi; Ko, Daisy L; Sanders, Eduard J; Peshu, Norbert M; Krieger, John N; Muller, Charles H; Coombs, Robert W; Fredricks, David N; Graham, Susan M

    2017-03-01

    HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

  19. Cell-associated HIV DNA measured early during infection has prognostic value independent of serum HIV RNA measured concomitantly

    DEFF Research Database (Denmark)

    Katzenstein, Terese L; Oliveri, Roberto S; Benfield, Thomas

    2002-01-01

    Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided...... of serum HIV RNA (p normal allele (p

  20. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

    Science.gov (United States)

    Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

    2009-01-01

    Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4+ T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5′ untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1. PMID:19651874

  1. Cervical Shedding of HIV-1 RNA Among Women With Low Levels of Viremia While Receiving Highly Active Antiretroviral Therapy

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    Neely, Michael N.; Benning, Lorie; Xu, Jiaao; Strickler, Howard D.; Greenblatt, Ruth M.; Minkoff, Howard; Young, Mary; Bremer, James; Levine, Alexandra M.; Kovacs, Andrea

    2011-01-01

    Background Among women with low o r undetectable quantities of HIV-1 RNA in plasma, factors associated with genital HIV-1 RNA shedding, including choice of treatment regimen, are poorly characterized. Methods We measured HIV-1 RNA in cervical swab specimens obtained from participants in the Women’s Interagency HIV Study who had concurrent plasma viral RNA levels <500 copies/mL, and we assessed factors associated with genital HIV shedding. The study was powered to determine the relative effects of antiretroviral protease inhibitors (PIs) versus nonnucleoside reverse transcriptase inhibitors (NNRTIs) on viral RNA shedding. Results Overall, 44 (15%) of 290 women had detectable HIV-1 RNA in cervical specimens. In the final multivariate model, shedding was independently associated with NNRTI (vs. PI) use (odds ratio [OR], 95% confidence interval [CI]: 2.24, 1.13 to 4.45) and illicit drug use (OR, 95% CI: 2.41, 0.96 to 5.69). Conclusions This is the largest study to define risks for genital HIV-1 RNA shedding in women with low/undetectable plasma virus. Shedding in this population was common, and NNRTI-based highly active antiretroviral therapy (HAART) (vs. PI-based HAART) was associated with genital HIV shedding. Further study is required to determine the impact of these findings on transmission of HIV from mother to child or to sexual partners. PMID:17106279

  2. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  3. Physician experience and rates of plasma HIV-1 RNA suppression among illicit drug users: an observational study

    Directory of Open Access Journals (Sweden)

    Sangsari Sassan

    2012-01-01

    Full Text Available Abstract Background Despite the availability of antiretroviral therapy (ART, suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART. Methods Using data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA Results Between May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85% achieved a plasma HIV RNA Conclusions In this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.

  4. Receptor-targeted aptamer-siRNA conjugate-directed transcriptional regulation of HIV-1

    Science.gov (United States)

    Zhou, Jiehua; Lazar, Daniel; Li, Haitang; Xia, Xin; Satheesan, Sangeetha; Charlins, Paige; O'Mealy, Denis; Akkina, Ramesh; Saayman, Sheena; Weinberg, Marc S.; Rossi, John J.; Morris, Kevin V.

    2018-01-01

    Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR). TGS differs from traditional RNA interference (RNAi) in that it is characterized by concomitant silent-state epigenetic marks on histones and DNA. To deliver TGS-inducing RNAs, we developed functional RNA conjugates based on the previously reported dual function of the gp120 (A-1) aptamer conjugated to 27-mer Dicer-substrate anti-HIV-1 siRNA (dsiRNA), LTR-362. Results: We demonstrate here that high levels of processed guide RNAs localize to the nucleus in infected T lymphoblastoid CEM cell line and primary human CD4+ T-cells. Treatment of the aptamer-siRNA conjugates induced TGS with an ~10-fold suppression of viral p24 levels as measured at day 12 post infection. To explore the silencing efficacy of aptamer-siRNA conjugates in vivo, HIV-1-infected humanized NOD/SCID/IL2 rγnull mice (hu-NSG) were treated with the aptamer-siRNA conjugates. Systemic delivery of the A-1-stick-LTR-362 27-mer siRNA conjugates suppressed HIV-1 infection and protected CD4+ T cell levels in viremia hu-NSG mice. Principle conclusions: Collectively these data suggest that the gp120 aptamer-dsiRNA conjugate design is suitable for systemic delivery of small RNAs that can be used to suppress HIV-1. PMID:29556342

  5. RRE-dependent HIV-1 Env RNA effects on Gag protein expression, assembly and release

    International Nuclear Information System (INIS)

    López, Claudia S.; Sloan, Rachel; Cylinder, Isabel; Kozak, Susan L.; Kabat, David; Barklis, Eric

    2014-01-01

    The HIV-1 Gag proteins are translated from the full-length HIV-1 viral RNA (vRNA), whereas the envelope (Env) protein is translated from incompletely spliced Env mRNAs. Nuclear export of vRNAs and Env mRNAs is mediated by the Rev accessory protein which binds to the rev-responsive element (RRE) present on these RNAs. Evidence has shown there is a direct or indirect interaction between the Gag protein, and the cytoplasmic tail (CT) of the Env protein. Our current work shows that env gene expression impacts HIV-1 Gag expression and function in two ways. At the protein level, full-length Env expression altered Gag protein expression, while Env CT-deletion proteins did not. At the RNA level, RRE-containing Env mRNA expression reduced Gag expression, processing, and virus particle release from cells. Our results support models in which Gag is influenced by the Env CT, and Env mRNAs compete with vRNAs for nuclear export. - Highlights: • At the protein level, full-length HIV-1 Env alters Gag protein expression. • HIV-1 Env RNA expression reduces Gag levels and virus release. • Env RNA effects on Gag are dependent on the RRE. • RRE-containing Env RNAs compete with vRNAs for nuclear export

  6. The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation

    NARCIS (Netherlands)

    Abbink, Truus E. M.; Ooms, Marcel; Haasnoot, P. C. Joost; Berkhout, Ben

    2005-01-01

    The untranslated leader RNA is the most conserved part of the human immunodeficiency virus type I (HIV-1) genome. It contains many regulatory motifs that mediate a variety of steps in the viral life cycle. Previous work showed that the full-length leader RNA can adopt two alternative structures: a

  7. Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

    Science.gov (United States)

    Hoffman, Jennifer C.; Anton, Peter A.; Baldwin, Gayle Cocita; Elliott, Julie; Anisman-Posner, Deborah; Tanner, Karen; Grogan, Tristan; Elashoff, David; Sugar, Catherine; Yang, Otto O.

    2014-01-01

    Abstract Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (pplasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission. PMID:25209674

  8. The relative prognostic value of plasma HIV RNA levels and CD4 lymphocyte counts in advanced HIV infection

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Katzenstein, T L; Ullum, H

    1998-01-01

    . RESULTS: The plasma HIV RNA (median 101410 copies/ml; range (range 200-7200000) and the CD4 lymphocyte count (median 250 cells x 10(6)/l; range 1-1247) were negatively correlated (Pearson r = -0.53; P

  9. 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

    Directory of Open Access Journals (Sweden)

    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

  10. Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1.

    Science.gov (United States)

    Darlix, J L; Gabus, C; Nugeyre, M T; Clavel, F; Barré-Sinoussi, F

    1990-12-05

    The retroviral genome consists of two identical RNA molecules joined at their 5' ends by the Dimer Linkage Structure (DLS). To study the mechanism of dimerization and the DLS of HIV-1 RNA, large amounts of bona fide HIV-1 RNA and of mutants have been synthesized in vitro. We report that HIV-1 RNA forms dimeric molecules and that viral nucleocapsid (NC) protein NCp15 greatly activates dimerization. Deletion mutagenesis in the RNA 5' 1333 nucleotides indicated that a small domain of 100 nucleotides, located between positions 311 to 415 from the 5' end, is necessary and sufficient to promote HIV-1 RNA dimerization. This dimerization domain encompasses an encapsidation element located between the 5' splice donor site and initiator AUG of gag and shows little sequence variations in different strains of HIV-1. Furthermore, cross-linking analysis of the interactions between NC and HIV-1 RNA (311 to 415) locates a major contact site in the encapsidation element of HIV-1 RNA. The genomic RNA dimer is tightly associated with nucleocapsid protein molecules in avian and murine retroviruses, and this ribonucleoprotein structure is believed to be the template for reverse transcription. Genomic RNA-protein interactions have been analyzed in human immunodeficiency virus (HIV) virions and results showed that NC protein molecules are tightly bound to the genomic RNA dimer. Since retroviral RNA dimerization and packaging appear to be under the control of the same cis element, the encapsidation sequences, and trans-acting factor, the NC protein, they are probably related events in the course of virion assembly.

  11. Undetectable hepatitis C virus RNA during syphilis infection in two HIV/HCV-co-infected patients

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Knudsen, Andreas; Krarup, Henrik Bygum

    2014-01-01

    BACKGROUND: Treponema pallidum, the causative agent of syphilis, elicits a vigorous immune response in the infected host. This study sought to describe the impact of syphilis infection on hepatitis C virus (HCV) RNA levels in patients with HIV and chronic HCV infection. METHODS: Patients......-α), interferon gamma (IFN-γ), and IFN-γ-inducible protein 10 kDa (IP-10). RESULTS: Undetectable HCV RNA at the time of early latent syphilis infection was observed in 2 patients with HIV and chronic HCV infection. After treatment of the syphilis infection, HCV RNA levels increased again in patient 1, whereas...... patient 2 initiated HCV therapy and remained HCV RNA-negative. Available plasma samples obtained before and after the episode with undetectable HCV RNA were phylogenetically identical, making the possibility of spontaneous clearance and HCV reinfection less likely. The IL-10, TNF-α, and IP-10 levels...

  12. Distribution of HIV RNA in CSF and Blood is linked to CD4/CD8 Ratio During Acute HIV.

    Science.gov (United States)

    Chan, Phillip; Patel, Payal; Hellmuth, Joanna; Colby, Donn J; Kroon, Eugène; Sacdalan, Carlo; Pinyakorn, Suteeraporn; Jagodzinski, Linda; Krebs, Shelly; Ananworanich, Jintanat; Valcour, Victor; Spudich, Serena

    2018-05-07

    HIV RNA levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection but their dynamics have not been characterized during acute infection. This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. CSF immune markers were compared between groups with different PCratio. 117 mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had median age 28 years and an estimated median 18 days duration of infection; forty-three (37%) were Fiebig stages I/II. Twenty-seven (23%) had CSF HIV RNA CSF HIV RNA and PCratio of 3.76 and 2.36 Log10 copies/mL, respectively. HIV RNA peaked at Fiebig III in plasma and Fiebig IV in CSF. In multivariable analyses, plasma HIV RNA and CD4/CD8 ratio independently correlated with CSF HIV RNA (pCSF neopterin, sCD163, IL-6 and sCD14 levels (all pCSF HIV RNA and PCratio, suggesting that immune responses modulate CNS viral entry at early infection.

  13. Dried blood spot HIV-1 RNA quantification using open real-time systems in South Africa and Burkina Faso.

    Science.gov (United States)

    Viljoen, Johannes; Gampini, Sandrine; Danaviah, Sivapragashini; Valéa, Diane; Pillay, Sureshnee; Kania, Dramane; Méda, Nicolas; Newell, Marie-Louise; Van de Perre, Philippe; Rouet, François

    2010-11-01

    There is an urgent need to assess the accuracy/feasibility of using dried blood spots (DBS) for monitoring of HIV-1 viral load in resource-limited settings. A total of 892 DBS from HIV-1-positive pregnant women and their neonates enrolled in the Kesho Bora prevention of mother-to-child transmission trial conducted in Durban (South Africa) and Bobo-Dioulasso (Burkina Faso) between May 2005 and July 2008 were tested for HIV-1 RNA. The combination Nuclisens extraction method (BioMérieux)/Generic HIV Viral Load assay (Biocentric) was performed using one DBS (in Durban) versus 2 DBS (in Bobo-Dioulasso) on 2 distinct open real-time polymerase chain reaction instruments. DBS HIV-1 RNA results were compared with plasma HIV-1 RNA and HIV serology results used as the gold standards. The limits of detection of assays on DBS were 3100 and 1550 copies per milliliter in Durban and Bobo-Dioulasso, respectively. DBS HIV-1 RNA values correlated significantly with plasma levels (n = 327; R = 0.7351) and were uniformly distributed according to duration of DBS storage at -20°C (median duration, 280 days). For early infant diagnosis, the sensitivity and specificity were 100% (95% confidence interval: 97.2 to 100.0 and 96.5 to 100.0, respectively). HIV-1 viral load kinetics in DNase-pretreated DBS were similar to those obtained in plasma specimens among 13 patients receiving antiretroviral treatment. HIV-1 RNA findings from serial infant DBS collected prospectively (n = 164) showed 100% concordance with HIV serology at 18 months of life. Our findings strongly advocate the implementation of DBS HIV-1 RNA testing in remote areas from low-income and middle-income countries.

  14. Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging

    Directory of Open Access Journals (Sweden)

    Das Atze T

    2012-07-01

    Full Text Available Abstract Background The TAR hairpin is present at both the 5′ and 3′ end of the HIV-1 RNA genome. The 5′ element binds the viral Tat protein and is essential for Tat-mediated activation of transcription. We recently observed that complete TAR deletion is allowed in the context of an HIV-1 variant that does not depend on this Tat-TAR axis for transcription. Mutations that open the 5′ stem-loop structure did however affect the leader RNA conformation and resulted in a severe replication defect. In this study, we set out to analyze which step of the HIV-1 replication cycle is affected by this conformational change of the leader RNA. Results We demonstrate that opening the 5′ TAR structure through a deletion in either side of the stem region caused aberrant dimerization and reduced packaging of the unspliced viral RNA genome. In contrast, truncation of the TAR hairpin through deletions in both sides of the stem did not affect RNA dimer formation and packaging. Conclusions These results demonstrate that, although the TAR hairpin is not essential for RNA dimerization and packaging, mutations in TAR can significantly affect these processes through misfolding of the relevant RNA signals.

  15. Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Kara G Lassen

    2006-07-01

    Full Text Available HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART. We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications.

  16. Decrease in Seminal HIV-1 RNA Load After Praziquantel Treatment of Urogenital Schistosomiasis Coinfection in HIV-Positive Men—An Observational Study

    DEFF Research Database (Denmark)

    Midzi, Nicholas; Mduluza, Takafira; Mudenge, Boniface

    2017-01-01

    BACKGROUND: Urogenital schistosomiasis due to Schistosoma hematobium infection is hypothesized to cause increased HIV-1 RNA shedding in semen in HIV co-infected men as result of chronic egg-induced inflammation in the prostate and the seminal vesicles. The effect of treatment with the antihelmint...... targeting praziquantel as a supplementary preventive measure of sexual transmission of HIV-1 in S. haematobium endemic areas in sub-Saharan Africa....

  17. Analytical Performances of Human Immunodeficiency Virus Type 1 RNA-Based Amplix® Real-Time PCR Platform for HIV-1 RNA Quantification

    Directory of Open Access Journals (Sweden)

    Christian Diamant Mossoro-Kpinde

    2016-01-01

    Full Text Available Objectives. We evaluated the performances of Amplix real-time PCR platform developed by Biosynex (Strasbourg, France, combining automated station extraction (Amplix station 16 Dx and real-time PCR (Amplix NG, for quantifying plasma HIV-1 RNA by lyophilized HIV-1 RNA-based Amplix reagents targeting gag and LTR, using samples from HIV-1-infected adults from Central African Republic. Results. Amplix real-time PCR assay showed low limit of detection (28 copies/mL, across wide dynamic range (1.4–10 log copies/mL, 100% sensitivity and 99% specificity, high reproducibility, and accuracy with mean bias < 5%. The assay showed excellent correlations and concordance of 95.3% with the reference HIV-1 RNA load assay (Roche, with mean absolute bias of +0.097 log copies/mL by Bland-Altman analysis. The assay was able to detect and quantify the most prevalent HIV-1 subtype strains and the majority of non-B subtypes, CRFs of HIV-1 group M, and HIV-1 groups N and O circulating in Central Africa. The Amplix assay showed 100% sensitivity and 99.6% specificity to diagnose virological failure in clinical samples from antiretroviral drug-experienced patients. Conclusions. The HIV-1 RNA-based Amplix real-time PCR platform constitutes sensitive and reliable system for clinical monitoring of HIV-1 RNA load in HIV-1-infected children and adults, particularly adapted to intermediate laboratory facilities in sub-Saharan Africa.

  18. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing.

    Science.gov (United States)

    Jones, Christopher P; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-02-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.

  19. Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy

    NARCIS (Netherlands)

    Gisolf, E. H.; van Praag, R. M.; Jurriaans, S.; Portegies, P.; Goudsmit, J.; Danner, S. A.; Lange, J. M.; Prins, J. M.

    2000-01-01

    Only limited data on cerebrospinal fluid (CSF) HIV-1 RNA responses and markers of local inflammation in CSF during antiretroviral therapy are available. HIV-RNA, soluble tumor necrosis factor (TNF)-receptor (sTNFr)-II, monocyte chemoattractant protein (MCP)-1, and interferon-gamma-inducible protein

  20. A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA

    Directory of Open Access Journals (Sweden)

    Robert J Scarborough

    2014-01-01

    Full Text Available Antisense-based molecules targeting HIV-1 RNA have the potential to be used as part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA was screened to identify more conserved and accessible target sites for ribozymes based on the hepatitis delta virus motif. Using a quantitative screen for effects on HIV-1 production, we identified a ribozyme targeting a highly conserved site in the Gag coding sequence with improved inhibitory potential compared to our previously described candidates targeting the overlapping Tat/Rev coding sequence. We also demonstrate that this target site is highly accessible to short hairpin directed RNA interference, suggesting that it may be available for the binding of antisense RNAs with different modes of action. We provide evidence that this target site is structurally conserved in diverse viral strains and that it is sufficiently different from the human transcriptome to limit off-target effects from antisense therapies. We also show that the modified hepatitis delta virus ribozyme is more sensitive to a mismatch in its target site compared to the short hairpin RNA. Overall, our results validate the potential of a new target site in HIV-1 RNA to be used for the development of antisense therapies.

  1. The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes

    International Nuclear Information System (INIS)

    Fang Jianhua; Acheampong, Edward; Dave, Rajnish; Wang Fengxiang; Mukhtar, Muhammad; Pomerantz, Roger J.

    2005-01-01

    Productive infection by human immunodeficiency virus type I (HIV-1) in the central nervous system (CNS) involves mainly macrophages and microglial cells. A frequency of less than 10% of human astrocytes is estimated to be infectable with HIV-1. Nonetheless, this relatively low percentage of infected astrocytes, but associated with a large total number of astrocytic cells in the CNS, makes human astrocytes a critical part in the analyses of potential HIV-1 reservoirs in vivo. Investigations in astrocytic cell lines and primary human fetal astrocytes revealed that limited HIV-1 replication in these cells resulted from low-level viral entry, transcription, viral protein processing, and virion maturation. Of note, a low ratio of unspliced versus spliced HIV-1-specific RNA was also investigated, as Rev appeared to act aberrantly in astrocytes, via loss of nuclear and/or nucleolar localization and diminished Rev-mediated function. Host cellular machinery enabling Rev function has become critical for elucidation of diminished Rev activity, especially for those factors leading to RNA metabolism. We have recently identified a DEAD-box protein, DDX1, as a Rev cellular co-factor and now have explored its potential importance in astrocytes. Cells were infected with HIV-1 pseudotyped with envelope glycoproteins of amphotropic murine leukemia viruses (MLV). Semi-quantitative reverse transcriptase-polymerase chain reactions (RT-PCR) for unspliced, singly-spliced, and multiply-spliced RNA clearly showed a lower ratio of unspliced/singly-spliced over multiply-spliced HIV-1-specific RNA in human astrocytes as compared to Rev-permissive, non-glial control cells. As well, the cellular localization of Rev in astrocytes was cytoplasmically dominant as compared to that of Rev-permissive, non-glial controls. This endogenous level of DDX1 expression in astrocytes was demonstrated directly to lead to a shift of Rev sub-cellular distribution dominance from nuclear and/or nucleolar to

  2. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA:Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged......Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable...... in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle...

  3. A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1 infected women

    Science.gov (United States)

    Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M.

    2014-01-01

    Background In HIV-1 infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy (ART), it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. Methods In a prospective study among 2269 HIV-1 infected ART-naïve women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum and non-pregnant periods. Results Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% CI 39-73) cells/mm3 lower during pregnant compared to non-pregnant periods and 70 (95% CI 53-88) cells/mm3 lower during pregnant compared to postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and non-pregnant periods (p=0.9) or pregnant and postpartum periods (p=0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared to non-pregnant periods. Conclusion CD4 count declines among HIV-1 infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short term impact on plasma HIV-1 RNA concentrations. PMID:24442226

  4. An RNA-binding compound that stabilizes the HIV-1 gRNA packaging signal structure and specifically blocks HIV-1 RNA encapsidation.

    Science.gov (United States)

    Ingemarsdotter, Carin K; Zeng, Jingwei; Long, Ziqi; Lever, Andrew M L; Kenyon, Julia C

    2018-03-14

    NSC260594, a quinolinium derivative from the NCI diversity set II compound library, was previously identified in a target-based assay as an inhibitor of the interaction between the HIV-1 (ψ) stem-loop 3 (SL3) RNA and Gag. This compound was shown to exhibit potent antiviral activity. Here, the effects of this compound on individual stages of the viral lifecycle were examined by qRT-PCR, ELISA and Western blot, to see if its actions were specific to the viral packaging stage. The structural effects of NSC260594 binding to the HIV-1 gRNA were also examined by SHAPE and dimerization assays. Treatment of cells with NSC260594 did not reduce the number of integration events of incoming virus, and treatment of virus producing cells did not affect the level of intracellular Gag protein or viral particle release as determined by immunoblot. However, NSC260594 reduced the incorporation of gRNA into virions by up to 82%, without affecting levels of gRNA inside the cell. This reduction in packaging correlated closely with the reduction in infectivity of the released viral particles. To establish the structural effects of NSC260594 on the HIV-1 gRNA, we performed SHAPE analyses to pinpoint RNA structural changes. NSC260594 had a stabilizing effect on the wild type RNA that was not confined to SL3, but that was propagated across the structure. A packaging mutant lacking SL3 did not show this effect. NSC260594 acts as a specific inhibitor of HIV-1 RNA packaging. No other viral functions are affected. Its action involves preventing the interaction of Gag with SL3 by stabilizing this small RNA stem-loop which then leads to stabilization of the global packaging signal region (psi or ψ). This confirms data, previously only shown in analyses of isolated SL3 oligonucleotides, that SL3 is structurally labile in the presence of Gag and that this is critical for the complete psi region to be able to adopt different conformations. Since replication is otherwise unaffected by NSC260594

  5. Probing the HIV-1 genomic RNA trafficking pathway and dimerization by genetic recombination and single virion analyses.

    Directory of Open Access Journals (Sweden)

    Michael D Moore

    2009-10-01

    Full Text Available Once transcribed, the nascent full-length RNA of HIV-1 must travel to the appropriate host cell sites to be translated or to find a partner RNA for copackaging to form newly generated viruses. In this report, we sought to delineate the location where HIV-1 RNA initiates dimerization and the influence of the RNA transport pathway used by the virus on downstream events essential to viral replication. Using a cell-fusion-dependent recombination assay, we demonstrate that the two RNAs destined for copackaging into the same virion select each other mostly within the cytoplasm. Moreover, by manipulating the RNA export element in the viral genome, we show that the export pathway taken is important for the ability of RNA molecules derived from two viruses to interact and be copackaged. These results further illustrate that at the point of dimerization the two main cellular export pathways are partially distinct. Lastly, by providing Gag in trans, we have demonstrated that Gag is able to package RNA from either export pathway, irrespective of the transport pathway used by the gag mRNA. These findings provide unique insights into the process of RNA export in general, and more specifically, of HIV-1 genomic RNA trafficking.

  6. Impact of tuberculosis treatment on CD4 cell count, HIV RNA, and p24 antigen in patients with HIV and tuberculosis

    DEFF Research Database (Denmark)

    Wejse, Christian; Furtado, A.; Camara, C.

    2013-01-01

    To describe HIV RNA levels during tuberculosis (TB) infection in patients co-infected with TB and HIV. Moreover, to examine the p24 antigen profile during TB treatment.......To describe HIV RNA levels during tuberculosis (TB) infection in patients co-infected with TB and HIV. Moreover, to examine the p24 antigen profile during TB treatment....

  7. A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women.

    Science.gov (United States)

    Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M

    2014-02-01

    In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. In a prospective study among 2269 HIV-1-infected antiretroviral therapy-naive women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum, and nonpregnant periods. Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% confidence interval: 39 to 73) cells/mm lower during pregnant compared with nonpregnant periods and 70 (95% confidence interval: 53 to 88) cells/mm lower during pregnant compared with postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and nonpregnant periods (P = 0.9) or pregnant and postpartum periods (P = 0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared with nonpregnant periods. CD4 count declines among HIV-1-infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short-term impact on plasma HIV-1 RNA concentrations.

  8. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.

    Science.gov (United States)

    Baroncelli, Silvia; Pirillo, Maria F; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Degli Antoni, Anna; Galluzzo, Clementina M; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

    2015-07-01

    There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

  9. HIV-1 RNAs are Not Part of the Argonaute 2 Associated RNA Interference Pathway in Macrophages.

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    Valentina Vongrad

    Full Text Available MiRNAs and other small noncoding RNAs (sncRNAs are key players in post-transcriptional gene regulation. HIV-1 derived small noncoding RNAs (sncRNAs have been described in HIV-1 infected cells, but their biological functions still remain to be elucidated. Here, we approached the question whether viral sncRNAs may play a role in the RNA interference (RNAi pathway or whether viral mRNAs are targeted by cellular miRNAs in human monocyte derived macrophages (MDM.The incorporation of viral sncRNAs and/or their target RNAs into RNA-induced silencing complex was investigated using photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP as well as high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP, which capture Argonaute2-bound miRNAs and their target RNAs. HIV-1 infected monocyte-derived macrophages (MDM were chosen as target cells, as they have previously been shown to express HIV-1 sncRNAs. In addition, we applied small RNA deep sequencing to study differential cellular miRNA expression in HIV-1 infected versus non-infected MDMs.PAR-CLIP and HITS-CLIP data demonstrated the absence of HIV-1 RNAs in Ago2-RISC, although the presence of a multitude of HIV-1 sncRNAs in HIV-1 infected MDMs was confirmed by small RNA sequencing. Small RNA sequencing revealed that 1.4% of all sncRNAs were of HIV-1 origin. However, neither HIV-1 derived sncRNAs nor putative HIV-1 target sequences incorporated into Ago2-RISC were identified suggesting that HIV-1 sncRNAs are not involved in the canonical RNAi pathway nor is HIV-1 targeted by this pathway in HIV-1 infected macrophages.

  10. Deciphering the role of the Gag-Pol ribosomal frameshift signal in HIV-1 RNA genome packaging.

    Science.gov (United States)

    Nikolaitchik, Olga A; Hu, Wei-Shau

    2014-04-01

    A key step of retroviral replication is packaging of the viral RNA genome during virus assembly. Specific packaging is mediated by interactions between the viral protein Gag and elements in the viral RNA genome. In HIV-1, similar to most retroviruses, the packaging signal is located within the 5' untranslated region and extends into the gag-coding region. A recent study reported that a region including the Gag-Pol ribosomal frameshift signal plays an important role in HIV-1 RNA packaging; deletions or mutations that affect the RNA structure of this signal lead to drastic decreases (10- to 50-fold) in viral RNA packaging and virus titer. We examined here the role of the ribosomal frameshift signal in HIV-1 RNA packaging by studying the RNA packaging and virus titer in the context of proviruses. Three mutants with altered ribosomal frameshift signal, either through direct deletion of the signal, mutation of the 6U slippery sequence, or alterations of the secondary structure were examined. We found that RNAs from all three mutants were packaged efficiently, and they generate titers similar to that of a virus containing the wild-type ribosomal frameshift signal. We conclude that although the ribosomal frameshift signal plays an important role in regulating the replication cycle, this RNA element is not directly involved in regulating RNA encapsidation. To generate infectious viruses, HIV-1 must package viral RNA genome during virus assembly. The specific HIV-1 genome packaging is mediated by interactions between the structural protein Gag and elements near the 5' end of the viral RNA known as packaging signal. In this study, we examined whether the Gag-Pol ribosomal frameshift signal is important for HIV-1 RNA packaging as recently reported. Our results demonstrated that when Gag/Gag-Pol is supplied in trans, none of the tested ribosomal frameshift signal mutants has defects in RNA packaging or virus titer. These studies provide important information on how HIV-1

  11. What do we measure when we measure cell-associated HIV RNA.

    Science.gov (United States)

    Pasternak, Alexander O; Berkhout, Ben

    2018-01-29

    Cell-associated (CA) HIV RNA has received much attention in recent years as a surrogate measure of the efficiency of HIV latency reversion and because it may provide an estimate of the viral reservoir size. This review provides an update on some recent insights in the biology and clinical utility of this biomarker. We discuss a number of important considerations to be taken into account when interpreting CA HIV RNA measurements, as well as different methods to measure this biomarker.

  12. Discordant HIV Test Results: Implications on Perinatal and Haemotransfusion Screening for HIV Infection, Cape Coast, Ghana.

    Science.gov (United States)

    Tetteh, Ato Kwamena; Agyarko, Edward

    2017-01-01

    Screening results of 488 pregnant women aged 15-44 years whose blood samples had been tested on-site, using First Response® HIV 1/2, and confirmed with INNO-LIA™ HIV I/II Score were used. Of this total, 178 were reactive (HIV I, 154; HIV II, 2; and HIV I and HIV II, 22). Of the 154 HIV I-reactive samples, 104 were confirmed to be HIV I-positive and 2 were confirmed to be HIV II-positive, while 48 were confirmed to be negative [false positive rate = 17.44% (13.56-21.32)]. The two HIV II samples submitted were confirmed to be negative with the confirmatory test. For the 22 HIV I and HIV II samples, 7 were confirmed to be HIV I-positive and 1 was confirmed to be HIV I- and HIV II-positive, while 14 were confirmed to be negative. Of the 310 nonreactive samples, 6 were confirmed to be HIV I-positive and 1 was confirmed to be HIV II-positive [false negative rate = 5.79% (1.63-8.38)], while 303 were negative. False negative outcomes will remain unconfirmed, with no management options for the client. False negative rate of 5.79% requires attention, as its resultant implications on control of HIV/AIDS could be dire.

  13. Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA.

    Directory of Open Access Journals (Sweden)

    Jana Ferdin

    Full Text Available To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects.We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort.This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort. We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects.Here, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects.Since plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.

  14. Cell-associated HIV DNA measured early during infection has prognostic value independent of serum HIV RNA measured concomitantly

    DEFF Research Database (Denmark)

    Katzenstein, Terese L; Oliveri, Roberto S; Benfield, Thomas

    2002-01-01

    Using data from the Danish AIDS Cohort of HIV-infected homosexual men established in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts and CCR5 genotypes were determined. The patients were divided...... into 3 groups, according to whether their cell-associated HIV DNA load was or = 2,500 DNA copies/10(6) peripheral blood mononuclear cells. Clinical progression rates differed significantly between the groups (p value independent...... of serum HIV RNA (p value. Patients heterozygous for the CCR5 delta 32 allele had significantly lower HIV DNA loads than those homozygous for the normal allele (p

  15. The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1.

    Science.gov (United States)

    Gabus, C; Derrington, E; Leblanc, P; Chnaiderman, J; Dormont, D; Swietnicki, W; Morillas, M; Surewicz, W K; Marc, D; Nandi, P; Darlix, J L

    2001-06-01

    Transmissible spongiform encephalopathies are fatal neurodegenerative diseases associated with the accumulation of a protease-resistant form of the prion protein (PrP). Although PrP is conserved in vertebrates, its function remains to be identified. In vitro PrP binds large nucleic acids causing the formation of nucleoprotein complexes resembling human immunodeficiency virus type 1 (HIV-1) nucleocapsid-RNA complexes and in vivo MuLV replication accelerates the scrapie infectious process, suggesting possible interactions between retroviruses and PrP. Retroviruses, including HIV-1 encode a major nucleic acid binding protein (NC protein) found within the virus where 2000 NC protein molecules coat the dimeric genome. NC is required in virus assembly and infection to chaperone RNA dimerization and packaging and in proviral DNA synthesis by reverse transcriptase (RT). In HIV-1, 5'-leader RNA/NC interactions appear to control these viral processes. This prompted us to compare and contrast the interactions of human and ovine PrP and HIV-1 NCp7 with HIV-1 5'-leader RNA. Results show that PrP has properties characteristic of NCp7 with respect to viral RNA dimerization and proviral DNA synthesis by RT. The NC-like properties of huPrP map to the N-terminal region of huPrP. Interestingly, PrP localizes in the membrane and cytoplasm of PrP-expressing cells. These findings suggest that PrP is a multifunctional protein possibly participating in nucleic acid metabolism.

  16. Comparison of HIV DNA and RNA in gut-associated lymphoid tissue of HIV-infected controllers and noncontrollers.

    Science.gov (United States)

    Hatano, Hiroyu; Somsouk, Ma; Sinclair, Elizabeth; Harvill, Kara; Gilman, Lee; Cohen, Michelle; Hoh, Rebecca; Hunt, Peter W; Martin, Jeffrey N; Wong, Joseph K; Deeks, Steven G; Yukl, Steven A

    2013-09-10

    HIV-infected controllers have provided novel insights into mechanisms of viral control. We investigated the degree to which HIV DNA and RNA are present in gut-associated lymphoid tissue (GALT) of controllers. Cross-sectional cohort study. Colorectal biopsy pieces were obtained from five untreated noncontrollers, five ART-suppressed patients, and nine untreated controllers. Rectal HIV DNA was lower in controllers (median 496 copies/10(6) CD4 T cells) than in untreated noncontrollers (117483 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (6116 copies/10(6) CD4 T cells, P = 0.004). Similarly, rectal HIV RNA was lower in controllers (19 copies/10(6) CD4 T cells) than in noncontrollers (15210 copies/10(6) CD4+ T cells, P = 0.001) and ART-suppressed patients (1625 copies/10(6) CD4+ T cells, P = 0.0599). Rectal HIV RNA/DNA ratios were not statistically different between the three groups. Despite being able to maintain very low plasma HIV RNA levels in the absence of antiretroviral therapy (ART), HIV-infected controllers have readily measurable levels of HIV DNA and RNA in GALT. As expected, controllers had lower rectal HIV DNA and RNA compared with untreated noncontrollers and ART-suppressed individuals. Compared with the mechanisms of 'natural' viral control of controllers, long-term ART does not reduce the total HIV reservoir to the level of controllers.

  17. Maternal characteristics during pregnancy and risk factors for positive HIV RNA at delivery: a single-cohort observational study (Brescia, Northern Italy

    Directory of Open Access Journals (Sweden)

    Magoni Michele

    2011-02-01

    Full Text Available Abstract Background Detectable HIV RNA in mothers at delivery is an important risk factor for HIV transmission to newborns. Our hypothesis was that, in migrant women, the risk of detectable HIV RNA at delivery is greater owing to late HIV diagnosis. Therefore, we examined pregnant women by regional provenance and measured variables that could be associated with detectable HIV RNA at delivery. Methods A observational retrospective study was conducted from January 1999 to May 2008. Univariate and multivariable regression analyses (generalized linear models were used, with detectable HIV RNA at delivery as dependent variable. Results The overall population comprised 154 women (46.8% migrants. Presentation was later in migrant women than Italians, as assessed by CD4-T-cell count at first contact (mean 417/mm3 versus 545/mm3, respectively; p = 0.003. Likewise, HIV diagnosis was made before pregnancy and HAART was already prescribed at the time of pregnancy in more Italians (91% and 75%, respectively than migrants (61% and 42.8%, respectively. A subgroup of women with available HIV RNA close to term (i.e., ≤30 days before labour was studied for risk factors of detectable HIV RNA (≥50 copies/ml at delivery. Among 93 women, 25 (26.9% had detectable HIV RNA. A trend toward an association between non-Italian nationality and detectable HIV RNA at delivery was demonstrated by univariate analysis (relative risk, RR = 1.86; p = 0.099. However, by multivariable regression analysis, the following factors appeared to be more important: lack of stable (i.e., ≥14 days antiretroviral therapy at the time of HIV RNA testing (RR = 4.3; p 3, RR = 0.94; p = 0.038. Conclusions These results reinforce the importance of extensive screening for HIV infection, earlier initiation of antiretroviral therapy and stricter monitoring of pregnant women to reduce the risk of detectable HIV RNA at delivery. Public health interventions should be particularly targeted to migrant

  18. Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment

    OpenAIRE

    Baroncelli, Silvia; Pirillo, Maria F.; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Antoni, Anna Degli; Galluzzo, Clementina M.; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

    2015-01-01

    There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According ...

  19. APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

    Science.gov (United States)

    Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

    2014-07-29

    Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. 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

    study, we analyzed the presence of total HIV DNA (T-HIV DNA, non-integrated DNA with 2LTR (2LTR-HIV DNA and HIV RNA in a group of 55 HIV-positive subjects from Rosario City, with different clinical stages, with and without HAART. All markers were evaluated by PCR assays optimized in our laboratory that included colorimetric detection in microplate. HIV RNA clinical sensitivity was compared with a reference test, bDNA, resulting in 74% and 64% respectively, with an 85% of agreement. Thus, our HIV RNA assay could be used to monitor patients under HAART and at risk of infection. The 2LTR-HIV DNA was 54% positive although it was absent in patients with high VL. This marker was considered a labile product therefore its presence was associated with recent infection. However, current evidences question its stability. Thus, its clinical significance should be reconsidered. The absence of 2LTR-HIV DNA in patients with detectable VL may relate to the heterogeneity of the sequence used for its detection. T-HIV DNA was present in 100% of the samples and could be a relevant remission marker when therapies that effectively eradicate the infection became available.

  1. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. Methods: WLWH between 18...

  2. Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era

    Directory of Open Access Journals (Sweden)

    Aleixo Agdemir W

    2007-12-01

    Full Text Available Abstract Background In the central nervous system, HIV replication can occur relatively independent of systemic infection, and intrathecal replication of HIV-1 has been observed in patients with HIV-related and opportunistic neurological diseases. The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF of patients with opportunistic neurological diseases, or the effect of opportunistic diseases on CSF HIV levels in patients under HAART has not been well defined. We quantified CSF and plasma viral load in HIV-infected patients with and without different active opportunistic neurological diseases, determined the characteristics that led to a higher detection rate of HIV RNA in CSF, and compared these two compartments. Methods A prospective study was conducted on 90 HIV-infected patients submitted to lumbar puncture as part of a work-up for suspected neurological disease. Seventy-one patients had active neurological diseases while the remaining 19 did not. Results HIV-1 RNA was quantified in 90 CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in patients with neurological diseases, in those with a CD4 count lower than 200 cells/mm3, and in those not receiving antiretroviral therapy, as well as in patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF than in plasma in the total population, in patients without neurological diseases, and in patients with toxoplasmic encephalitis, while no significant difference between the two compartments was observed for patients with cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in those not receiving HAART. Conclusion Detection of HIV-1 RNA in CSF was more frequent in patients with neurological disease, a CD4 count lower than 200 cells/mm3 and detectable plasma HIV-1. Median HIV-1 RNA levels were generally lower in CSF than in

  3. The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV.

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    Hanumant S Tanwar

    2017-02-01

    Full Text Available The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0 that is further enhanced by the oligomerization of Pr55Gag. The change in enthalpy (ΔH widens sequentially from: (1 Pr55Gag-Psi RNA binding during HIV genome selection; to (2 Pr55Gag-Guanosine Uridine (GU-containing RNA binding in cytoplasm/plasma membrane; and then to (3 Pr55Gag-Adenosine(A-containing RNA binding in immature HIV. These data imply the stepwise increments of heat being released during HIV biogenesis may help to facilitate the process of viral assembly. By mimicking the interactions between A-containing RNA and oligomeric Pr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficient than full-length Pr55Gag in this thermodynamic process. These data suggest a potential unknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction during HIV assembly. Our data provide direct evidence on how nucleic acid sequences and the oligomeric state of Pr55Gag regulate HIV assembly.

  4. Nuclear Factor 90, a cellular dsRNA binding protein inhibits the HIV Rev-export function

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    St-Laurent Georges

    2006-11-01

    Full Text Available Abstract Background The HIV Rev protein is known to facilitate export of incompletely spliced and unspliced viral transcripts to the cytoplasm, a necessary step in virus life cycle. The Rev-mediated nucleo-cytoplasmic transport of nascent viral transcripts, dependents on interaction of Rev with the RRE RNA structural element present in the target RNAs. The C-terminal variant of dsRNA-binding nuclear protein 90 (NF90ctv has been shown to markedly attenuate viral replication in stably transduced HIV-1 target cell line. Here we examined a mechanism of interference of viral life cycle involving Rev-NF90ctv interaction. Results Since Rev:RRE complex formations depend on protein:RNA and protein:protein interactions, we investigated whether the expression of NF90ctv might interfere with Rev-mediated export of RRE-containing transcripts. When HeLa cells expressed both NF90ctv and Rev protein, we observed that NF90ctv inhibited the Rev-mediated RNA transport. In particular, three regions of NF90ctv protein are involved in blocking Rev function. Moreover, interaction of NF90ctv with the RRE RNA resulted in the expression of a reporter protein coding sequences linked to the RRE structure. Moreover, Rev influenced the subcellular localization of NF90ctv, and this process is leptomycin B sensitive. Conclusion The dsRNA binding protein, NF90ctv competes with HIV Rev function at two levels, by competitive protein:protein interaction involving Rev binding to specific domains of NF90ctv, as well as by its binding to the RRE-RNA structure. Our results are consistent with a model of Rev-mediated HIV-1 RNA export that envisions Rev-multimerization, a process interrupted by NF90ctv.

  5. How the RNA isolation method can affect microRNA microarray results

    DEFF Research Database (Denmark)

    Podolska, Agnieszka; Kaczkowski, Bogumil; Litman, Thomas

    2011-01-01

    RNA microarray analysis on porcine brain tissue. One method is a phenol-guanidine isothiocyanate-based procedure that permits isolation of total RNA. The second method, miRVana™ microRNA isolation, is column based and recovers the small RNA fraction alone. We found that microarray analyses give different results...... that depend on the RNA fraction used, in particular because some microRNAs appear very sensitive to the RNA isolation method. We conclude that precautions need to be taken when comparing microarray studies based on RNA isolated with different methods.......The quality of RNA is crucial in gene expression experiments. RNA degradation interferes in the measurement of gene expression, and in this context, microRNA quantification can lead to an incorrect estimation. In the present study, two different RNA isolation methods were used to perform micro...

  6. Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop

    Science.gov (United States)

    Upert, Gregory; Di Giorgio, Audrey; Upadhyay, Alok; Manvar, Dinesh; Pandey, Nootan; Pandey, Virendra N.; Patino, Nadia

    2012-01-01

    Human immunodeficiency virus-1 (HIV-1) replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR), to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP) cation-based vectors that efficiently deliver nucleotide analogs (PNAs) into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins. PMID:23029603

  7. Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop

    Directory of Open Access Journals (Sweden)

    Gregory Upert

    2012-01-01

    Full Text Available Human immunodeficiency virus-1 (HIV-1 replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR, to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP cation-based vectors that efficiently deliver nucleotide analogs (PNAs into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins.

  8. Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA and HIV-1 nef Genes in Escherichia coli.

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    Siti Aisyah Mualif

    Full Text Available Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef, HIV-1 p24 (ca, and HIV-1 vif in NiCo21(DE3 E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes.

  9. Comparison of droplet digital PCR and seminested real-time PCR for quantification of cell-associated HIV-1 RNA

    NARCIS (Netherlands)

    Kiselinova, Maja; Pasternak, Alexander O.; de Spiegelaere, Ward; Vogelaers, Dirk; Berkhout, Ben; Vandekerckhove, Linos

    2014-01-01

    Cell-associated (CA) HIV-1 RNA is considered a potential marker for assessment of viral reservoir dynamics and antiretroviral therapy (ART) response in HIV-infected patients. Recent studies employed sensitive seminested real-time quantitative (q)PCR to quantify CA HIV-1 RNA. Digital PCR has been

  10. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S

    2017-01-01

    in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18......-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes...... RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies...

  11. MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1 seropositive individuals

    Directory of Open Access Journals (Sweden)

    Smith Stephen M

    2008-12-01

    Full Text Available Abstract MicroRNAs (miRNAs play diverse roles in regulating cellular and developmental functions. We have profiled the miRNA expression in peripheral blood mononuclear cells from 36 HIV-1 seropositive individuals and 12 normal controls. The HIV-1-positive individuals were categorized operationally into four classes based on their CD4+ T-cell counts and their viral loads. We report that specific miRNA signatures can be observed for each of the four classes.

  12. Distinct binding interactions of HIV-1 Gag to Psi and non-Psi RNAs: implications for viral genomic RNA packaging.

    Science.gov (United States)

    Webb, Joseph A; Jones, Christopher P; Parent, Leslie J; Rouzina, Ioulia; Musier-Forsyth, Karin

    2013-08-01

    Despite the vast excess of cellular RNAs, precisely two copies of viral genomic RNA (gRNA) are selectively packaged into new human immunodeficiency type 1 (HIV-1) particles via specific interactions between the HIV-1 Gag and the gRNA psi (ψ) packaging signal. Gag consists of the matrix (MA), capsid, nucleocapsid (NC), and p6 domains. Binding of the Gag NC domain to ψ is necessary for gRNA packaging, but the mechanism by which Gag selectively interacts with ψ is unclear. Here, we investigate the binding of NC and Gag variants to an RNA derived from ψ (Psi RNA), as well as to a non-ψ region (TARPolyA). Binding was measured as a function of salt to obtain the effective charge (Zeff) and nonelectrostatic (i.e., specific) component of binding, Kd(1M). Gag binds to Psi RNA with a dramatically reduced Kd(1M) and lower Zeff relative to TARPolyA. NC, GagΔMA, and a dimerization mutant of Gag bind TARPolyA with reduced Zeff relative to WT Gag. Mutations involving the NC zinc finger motifs of Gag or changes to the G-rich NC-binding regions of Psi RNA significantly reduce the nonelectrostatic component of binding, leading to an increase in Zeff. These results show that Gag interacts with gRNA using different binding modes; both the NC and MA domains are bound to RNA in the case of TARPolyA, whereas binding to Psi RNA involves only the NC domain. Taken together, these results suggest a novel mechanism for selective gRNA encapsidation.

  13. Co-occurrence of Trichomonas vaginalis and bacterial vaginosis and vaginal shedding of HIV-1 RNA.

    Science.gov (United States)

    Fastring, Danielle R; Amedee, Angela; Gatski, Megan; Clark, Rebecca A; Mena, Leandro A; Levison, Judy; Schmidt, Norine; Rice, Janet; Gustat, Jeanette; Kissinger, Patricia

    2014-03-01

    Trichomonas vaginalis (TV) and bacterial vaginosis (BV) are independently associated with increased risk of vaginal shedding in HIV-positive women. Because these 2 conditions commonly co-occur, this study was undertaken to examine the association between TV/BV co-occurrence and vaginal shedding of HIV-1 RNA. HIV-positive women attending outpatient HIV clinics in 3 urban US cities underwent a clinical examination; were screened for TV, BV, Neisseria gonorrhoeae, Chlamydia trachomatis, and vulvovaginal candidiasis; and completed a behavioral survey. Women shedding HIV-1 RNA vaginally (≥50 copies/mL) were compared with women who had an undetectable (women who were TV positive and BV positive or had co-occurrence of TV/BV had higher odds of shedding vaginally when compared with women who did not have these conditions. In this sample of 373 HIV-positive women, 43.1% (n = 161) had co-occurrence of TV/BV and 33.2% (n = 124) were shedding HIV-1 RNA vaginally. The odds of shedding HIV vaginally in the presence of TV alone or BV alone and when TV/BV co-occurred were 4.07 (95% confidence interval [CI], 1.78-9.37), 5.65 (95% CI, 2.64-12.01), and 18.63 (95% CI, 6.71-51.72), respectively, when compared with women with no diagnosis of TV or BV, and after adjusting for age, antiretroviral therapy status, and plasma viral load. T. vaginalis and BV were independently and synergistically related to vaginal shedding of HIV-1 RNA. Screening and prompt treatment of these 2 conditions among HIV-positive women are important not only clinically but for HIV prevention, as well.

  14. Repeat testing of low-level HIV-1 RNA: assay performance and implementation in clinical trials.

    Science.gov (United States)

    White, Kirsten; Garner, Will; Wei, Lilian; Eron, Joseph J; Zhong, Lijie; Miller, Michael D; Martin, Hal; Plummer, Andrew; Tran-Muchowski, Cecilia; Lindstrom, Kim; Porter, James; Piontkowsky, David; Light, Angela; Reiske, Heinz; Quirk, Erin

    2018-05-15

    Assess the performance of HIV-1 RNA repeat testing of stored samples in cases of low-level viremia during clinical trials. Prospective and retrospective analysis of randomized clinical trial samples and reference standards. To evaluate assay variability of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, v2.0, three separate sources of samples were utilized: the World Health Organization (WHO) HIV reference standard (assayed using 50 independent measurements at six viral loads <200 copies/ml), retrospective analysis of four to six aliquots of plasma samples from four clinical trial participants, and prospective repeat testing of 120 samples from participants in randomized trials with low-level viremia. The TaqMan assay on the WHO HIV-1 RNA standards at viral loads <200 copies/ml performed within the expected variability according to assay specifications. However, standards with low viral loads of 36 and 18 copies/ml reported values of ≥ 50 copies/ml in 66 and 18% of tests, respectively. In participants treated with antiretrovirals who had unexpected viremia of 50-200 copies/ml after achieving <50 copies/ml, retesting of multiple aliquots of stored plasma found <50 copies/ml in nearly all cases upon retesting (14/15; 93%). Repeat testing was prospectively implemented in four clinical trials for all samples with virologic rebound of 50-200 copies/ml (n = 120 samples from 92 participants) from which 42% (50/120) had a retest result of less than 50 copies/ml and 58% (70/120) retested ≥ 50 copies/ml. The TaqMan HIV-1 RNA assay shows variability around 50 copies/ml that affects clinical trial results and may impact clinical practice. In participants with a history of viral load suppression, unexpected low-level viremia may be because of assay variability rather than low drug adherence or true virologic failure. Retesting a stored aliquot of the same sample may differentiate between assay variability and virologic failure as the source of viremia

  15. RNA interactions in the 5' region of the HIV-1 genome

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Andersen, Ebbe Sloth; Knudsen, Bjarne

    2004-01-01

    The untranslated leader of the dimeric HIV-1 RNA genome is folded into a complex structure that plays multiple and essential roles in the viral replication cycle. Here, we have investigated secondary and tertiary structural elements within the 5' 744 nucleotides of the HIV-1 genome using...... a combination of bioinformatics, enzymatic probing, native gel electrophoresis, and UV-crosslinking experiments. We used a recently developed RNA folding algorithm (Pfold) to predict the common secondary structure of an alignment of 20 divergent HIV-1 sequences. Combining this analysis with biochemical data, we...

  16. Distinct binding interactions of HIV-1 Gag to Psi and non-Psi RNAs: Implications for viral genomic RNA packaging

    OpenAIRE

    Webb, Joseph A.; Jones, Christopher P.; Parent, Leslie J.; Rouzina, Ioulia; Musier-Forsyth, Karin

    2013-01-01

    The mechanism underlying the selective packaging of genomic RNA into HIV-1 virions is not known. This paper provides important new biophysical insights into the nature of protein–RNA interactions responsible for HIV-1 genome packaging by quantifying the electrostatic and hydrophobic contributions to specific and nonspecific RNA.

  17. Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

    Science.gov (United States)

    Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA?

    Science.gov (United States)

    Subramanya, Sandesh; Kim, Sang-Soo; Manjunath, N; Shankar, Premlata

    2010-02-01

    Despite the clinical benefits of highly active antiretroviral therapy (HAART), the prospect of life-long antiretroviral treatment poses significant problems, which has spurred interest in developing new drugs and strategies to treat HIV infection and eliminate persistent viral reservoirs. RNAi has emerged as a therapeutic possibility for HIV. We discuss progress in overcoming hurdles to translating transient and stable RNAi enabling technologies to clinical application for HIV; covering the past 2 - 3 years. HIV inhibition can be achieved by transfection of chemically or enzymatically synthesized siRNAs or by DNA-based vector systems expressing short hairpin RNAs (shRNAs) that are processed intracellularly into siRNA. We compare these approaches, focusing on technical and safety issues that will guide the choice of strategy for clinical use. Introduction of synthetic siRNA into cells or its stable endogenous production using vector-driven shRNA have been shown to suppress HIV replication in vitro and, in some instances, in vivo. Each method has advantages and limitations in terms of ease of delivery, duration of silencing, emergence of escape mutants and potential toxicity. Both appear to have potential as future therapeutics for HIV, once the technical and safety issues of each approach are overcome.

  19. HIV surveillance in MENA: recent developments and results.

    Science.gov (United States)

    Bozicevic, Ivana; Riedner, Gabriele; Calleja, Jesus Maria Garcia

    2013-11-01

    To provide an overview of the current level of development and results from the national HIV surveillance systems of the 23 countries of the Middle East and North Africa (MENA), and to assess the quality of HIV surveillance systems in the period 2007-2011. A questionnaire was used to collect the information about the structure, activities and the results of HIV surveillance systems from the National AIDS Programmes. Assessment of the quality was based on four indicators: timeliness of data collection, appropriateness of populations under surveillance, consistency of the surveillance sites and groups measured over time, and coverage of the surveillance system. Only in four countries did surveillance systems enable assessment of epidemic trends in the same populations and locations over time, such as in pregnant women (Morocco, Iran), injecting drug users (Iran, Pakistan), female sex workers (Djibouti, Morocco) and male sex workers (Pakistan). There is increasing evidence of HIV infection being firmly established in at least one of the populations most at risk of HIV in nine MENA countries, while lower risk populations show elevated HIV prevalence in South Sudan, Djibouti and some parts of Somalia. The performance of HIV surveillance systems in several of the MENA countries has improved in recent years. The extent of HIV epidemics in the populations most at risk of HIV is still largely unknown in 10 countries. Multiple data sources that most of the countries still lack would enable indirectly estimation not only of the patterns of HIV epidemics but also the effectiveness of HIV responses.

  20. Combinatorial RNA-based gene therapy for the treatment of HIV/AIDS.

    Science.gov (United States)

    Chung, Janet; DiGiusto, David L; Rossi, John J

    2013-03-01

    HIV/AIDS continues to be a worldwide health problem and viral eradication has been an elusive goal. HIV+ patients are currently treated with combination antiretroviral therapy (cART) which is not curative. For many patients, cART is inaccessible, intolerable or unaffordable. Therefore, a new class of therapeutics for HIV is required to overcome these limitations. Cell and gene therapy for HIV has been proposed as a way to provide a functional cure for HIV in the form of a virus/infection resistant immune system. In this review, the authors describe the standard therapy for HIV/AIDS, its limitations, current areas of investigation and the potential of hematopoietic stem cells modified with anti-HIV RNAs as a means to affect a functional cure for HIV. Cell and gene therapy for HIV/AIDS is a promising alternative to antiviral drug therapy and may provide a functional cure. In order to show clinical benefit, multiple mechanisms of inhibition of HIV entry and lifecycle are likely to be required. Among the most promising antiviral strategies is the use of transgenic RNA molecules that provide protection from HIV infection. When these molecules are delivered as gene-modified hematopoietic stem and progenitor cells, long-term repopulation of the patient's immune system with gene-modified progeny has been observed.

  1. Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region

    Directory of Open Access Journals (Sweden)

    Masako Nomaguchi

    2017-12-01

    Full Text Available Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1. We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3. We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level.

  2. Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

    Science.gov (United States)

    Wessman, Maria; Thorsteinsson, Kristina; Jensen, Jørgen S; Storgaard, Merete; Rönsholt, Frederikke F; Johansen, Isik S; Pedersen, Gitte; Nørregård Nielsen, Lars; Bonde, Jesper; Katzenstein, Terese L; Weis, Nina; Lebech, Anne-Mette

    2017-05-31

    Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

  3. Alterations in messenger RNA and small nuclear RNA metabolism resulting from fluorouracil incorporation

    International Nuclear Information System (INIS)

    Armstrong, R.D.; Cadman, E.C.

    1985-01-01

    Studies were completed to examine the effect of 5-fluorouracil (FUra) incorporation on messenger RNA (mRNA) and small molecular weight nuclear RNA (SnRNA) metabolism. Studies of mRNA were completed using cDNA-mRNA hybridization methods to specifically examine dihydrofolate reductase (DHFR) mRNA. C 3 -L5178Y murine leukemia cells which are gene-amplified for DHFR, were exposed to FUra for 6, 12 or 24 hr, and the nuclear and cytoplasmic levels of DHFR-mRNA determined by hybridization with 32 P-DHFR-cDNA. FUra produced a dose-dependent increase in nuclear DHFR-mRNA levels, while total cytoplasmic DHFR-mRNA levels appeared to be unchanged. To examine only mRNA synthesized during FUra exposure, cells were also treated concurrently with [ 3 H] cytidine, and the [ 3 H]mRNA-cDNA hybrids measured following S 1 -nuclease treatment. FUra produced a concentration-dependent increase in nascent nuclear DHFR-mRNA levels, and a decrease in nascent cytoplasmic DHFR-mRNAs levels. These results suggest that FUra produces either an inhibition of mRNA processing, or an inhibition of nuclear-cytoplasmic transport. Preliminary experiments to examine ATP-dependent mRNA transport were completed with isolated nuclei from cells treated with FUra for 1 or 24 hr and then pulse-labeled for 1 hr with [ 3 H] cytidine. The results demonstrate a FUra-concentration and time-dependent inhibition of ATP-mediated mRNA efflux

  4. Rational design of micro-RNA-like bifunctional siRNAs targeting HIV and the HIV coreceptor CCR5.

    Science.gov (United States)

    Ehsani, Ali; Saetrom, Pål; Zhang, Jane; Alluin, Jessica; Li, Haitang; Snøve, Ola; Aagaard, Lars; Rossi, John J

    2010-04-01

    Small-interfering RNAs (siRNAs) and micro-RNAs (miRNAs) are distinguished by their modes of action. SiRNAs serve as guides for sequence-specific cleavage of complementary mRNAs and the targets can be in coding or noncoding regions of the target transcripts. MiRNAs inhibit translation via partially complementary base-pairing to 3' untranslated regions (UTRs) and are generally ineffective when targeting coding regions of a transcript. In this study, we deliberately designed siRNAs that simultaneously direct cleavage and translational suppression of HIV RNAs, or cleavage of the mRNA encoding the HIV coreceptor CCR5 and suppression of translation of HIV. These bifunctional siRNAs trigger inhibition of HIV infection and replication in cell culture. The design principles have wide applications throughout the genome, as about 90% of genes harbor sites that make the design of bifunctional siRNAs possible.

  5. HIV-1 Tat C-mediated regulation of tumor necrosis factor receptor-associated factor-3 by microRNA 32 in human microglia

    Directory of Open Access Journals (Sweden)

    Mishra Ritu

    2012-06-01

    Full Text Available Abstract Background HIV-1 Tat protein is known to be associated with neuroinflammation, a condition that develops in almost half of patients infected with HIV-1. HIV-1 Tat can alter glial neuroprotective functions, leading to neurotoxicity within the CNS. HIV-1 Tat is known to be secreted from productively infected cells and can affect neighboring uninfected cells by modulating cellular gene expression in a bystander fashion. Methods We were interested to study whether exogenous exposure to HIV-1 Tat-C protein perturbs the microRNA (miRNA expression profile of human microglial cells, leading to altered protein expression. We used protein expression and purification, miRNA overexpression, miRNA knockdown, transfection, site-directed mutagenesis, real-time PCR, luciferase assay and western blotting techniques to perform our study. Results HIV-1 Tat-C treatment of human microglial cells resulted in a dose-dependent increase in miR-32 expression. We found that tumor necrosis factor-receptor–associated factor 3 TRAF3 is a direct target for miR-32, and overexpression of miR-32 in CHME3 cells decreased TRAF3 both at the mRNA and the protein level. Recovery of TRAF3 protein expression after transfection of anti-miR-32 and the results of the luciferase reporter assay provided direct evidence of TRAF3 regulation by miR-32. We found that the regulation of interferon regulatory factor 3 (IRF3 and IRF7 is controlled by cellular levels of TRAF3 protein in microglial cells, as after overexpression of miR-32 and application of anti-miR-32, expression levels of IRF3 and IRF7 were inversely regulated by expression levels of TRAF3. Thus, our results suggest a novel miRNA mediated mechanism for regulation of TRAF3 in human microglial cells exposed to HIV-1 Tat C protein. These results may help to elucidate the detrimental neuroinflammatory consequences of HIV-1 Tat C protein in bystander fashion. Conclusion HIV-1 Tat protein can modulate TRAF3 expression through

  6. A miRNA Signature for Cognitive Deficits and Alcohol Use Disorder in Persons Living with HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Dorota Wyczechowska

    2017-11-01

    Full Text Available HIV-associated neurocognitive disorders (HAND affects more than half of persons living with HIV-1/AIDS (PLWHA. Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have evaluated this miRNA signature in PLWHA with alcohol use disorder (AUD at LSU Health Sciences Center (LSUHSC. The results show that AUD is a potential confounding factor for the miRNAs associated with cognitive impairment in PLWHA. Furthermore, we have investigated the miRNA signature associated with cognitive impairment in an independent cohort of PLWHA using plasma samples from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER program. Despite differences between the two cohorts in socioeconomic status, AUD, and likely misuse of illicit or prescription drugs, we validated a miRNA signature for cognitive deficits found at LSUHSC in the CHARTER samples.

  7. Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

    Science.gov (United States)

    Dravid, Ameet N; Natrajan, Kartik; Kulkarni, Milind M; Saraf, Chinmay K; Mahajan, Uma S; Kore, Sachin D; Rathod, Niranjan M; Mahajan, Umakant S; Wadia, Rustom S

    2018-02-01

    Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.

  8. Chimeric peptide-mediated siRNA transduction to inhibit HIV-1 infection.

    Science.gov (United States)

    Bivalkar-Mehla, Shalmali; Mehla, Rajeev; Chauhan, Ashok

    2017-04-01

    Persistent human immunodeficiency virus 1 (HIV-1) infection provokes immune activation and depletes CD4 +  lymphocytes, leading to acquired immunodeficiency syndrome. Uninterrupted administration of combination antiretroviral therapy (cART) in HIV-infected patients suppresses viral replication to below the detectable level and partially restores the immune system. However, cART-unresponsive residual HIV-1 infection and elusive transcriptionally silent but reactivatable viral reservoirs maintain a permanent viral DNA blue print. The virus rebounds within a few weeks after interruption of suppressive therapy. Adjunct gene therapy to control viral replication by ribonucleic acid interference (RNAi) is a post-transcriptional gene silencing strategy that could suppress residual HIV-1 burden and overcome viral resistance. Small interfering ribonucleic acids (siRNAs) are efficient transcriptional inhibitors, but need delivery systems to reach inside target cells. We investigated the potential of chimeric peptide (FP-PTD) to deliver specific siRNAs to HIV-1-susceptible and permissive cells. Chimeric FP-PTD peptide was designed with an RNA binding domain (PTD) to bind siRNA and a cell fusion peptide domain (FP) to enter cells. FP-PTD-siRNA complex entered and inhibited HIV-1 replication in susceptible cells, and could be a candidate for in vivo testing.

  9. Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.

    Science.gov (United States)

    García, F; Niebla, G; Romeu, J; Vidal, C; Plana, M; Ortega, M; Ruiz, L; Gallart, T; Clotet, B; Miró, J M; Pumarola, T; Gatell, J M

    1999-08-20

    To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l. Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured. The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001). HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.

  10. Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by HIV-1.

    Directory of Open Access Journals (Sweden)

    Luis Apolonia

    2015-01-01

    Full Text Available The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G (A3G and APOBEC3F (A3F, act as potent human immunodeficiency virus type-1 (HIV-1 restriction factors. These proteins require packaging into HIV-1 particles to exert their antiviral activities, but the molecular mechanism by which this occurs is incompletely understood. The nucleocapsid (NC region of HIV-1 Gag is required for efficient incorporation of A3G and A3F, and the interaction between A3G and NC has previously been shown to be RNA-dependent. Here, we address this issue in detail by first determining which RNAs are able to bind to A3G and A3F in HV-1 infected cells, as well as in cell-free virions, using the unbiased individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP method. We show that A3G and A3F bind many different types of RNA, including HIV-1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs. Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV-1 genomic RNA (gRNA and 7SL RNA are reduced, implying that these RNAs are not essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles formed with Gag lacking the NC domain (Gag ΔNC fail to encapsidate A3G/F. Here, we exploit this system by demonstrating that the addition of an assortment of heterologous RNA-binding proteins and domains to Gag ΔNC efficiently restored A3G/F packaging, indicating that A3G and A3F have the ability to engage multiple RNAs to ensure viral encapsidation. We propose that the rather indiscriminate RNA binding characteristics of A3G and A3F promote functionality by enabling recruitment into a wide range of retroviral particles whose packaged RNA genomes comprise divergent sequences.

  11. Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR RNA.

    Directory of Open Access Journals (Sweden)

    Matthew S Lalonde

    2011-05-01

    Full Text Available The RNA response element TAR plays a critical role in HIV replication by providing a binding site for the recruitment of the viral transactivator protein Tat. Using a structure-guided approach, we have developed a series of conformationally-constrained cyclic peptides that act as structural mimics of the Tat RNA binding region and block Tat-TAR interactions at nanomolar concentrations in vitro. Here we show that these compounds block Tat-dependent transcription in cell-free systems and in cell-based reporter assays. The compounds are also cell permeable, have low toxicity, and inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic L50 exhibited an IC(50 ∼250 nM. Surprisingly, inhibition of LTR-driven HIV-1 transcription could not account for the full antiviral activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic inhibition curve with the first phase occurring after HIV-1 entry into the host cell and during the initiation of HIV-1 reverse transcription. The second phase coincides with inhibition of HIV-1 transcription. Reconstituted reverse transcription assays confirm that HIV-1 (- strand strong stop DNA synthesis is blocked by L50-TAR RNA interactions in-vitro. These findings are consistent with genetic evidence that TAR plays critical roles both during reverse transcription and during HIV gene expression. Our results suggest that antiviral drugs targeting TAR RNA might be highly effective due to a dual inhibitory mechanism.

  12. Cytoplasmic HIV-1 RNA is mainly transported by diffusion in the presence or absence of Gag protein

    DEFF Research Database (Denmark)

    Chen, Jianbo; Grunwald, David; Sardo, Luca

    2014-01-01

    . In this report, we visualized HIV-1 RNA and monitored its movement in the cytoplasm by using single-molecule tracking. We observed that most of the HIV-1 RNA molecules move in a nondirectional, random-walk manner, which does not require an intact cytoskeletal structure, and that the mean-squared distance...... traveled by the RNA increases linearly with time, indicative of diffusive movement. We also observed that a single HIV-1 RNA molecule can move at various speeds when traveling through the cytoplasm, indicating that its movement is strongly affected by the immediate environment. To examine the effect of Gag...

  13. Novel RNA Duplex Locks HIV-1 in a Latent State via Chromatin-mediated Transcriptional Silencing

    Directory of Open Access Journals (Sweden)

    Chantelle Ahlenstiel

    2015-01-01

    Full Text Available Transcriptional gene silencing (TGS of mammalian genes can be induced by short interfering RNA (siRNA targeting promoter regions. We previously reported potent TGS of HIV-1 by siRNA (PromA, which targets tandem NF-κB motifs within the viral 5′LTR. In this study, we screened a siRNA panel with the aim of identifying novel 5′LTR targets, to provide multiplexing potential with enhanced viral silencing and application toward developing alternate therapeutic strategies. Systematic examination identified a novel siRNA target, si143, confirmed to induce TGS as the silencing mechanism. TGS was prolonged with virus suppression >12 days, despite a limited ability to induce post- TGS. Epigenetic changes associated with silencing were suggested by partial reversal by histone deacetylase inhibitors and confirmed by chromatin immunoprecipitation analyses, which showed induction of H3K27me3 and H3K9me3, reduction in H3K9Ac, and recruitment of argonaute-1, all characteristic marks of heterochromatin and TGS. Together, these epigenetic changes mimic those associated with HIV-1 latency. Further, robust resistance to reactivation was observed in the J-Lat 9.2 cell latency model, when transduced with shPromA and/or sh143. These data support si/shRNA-mediated TGS approaches to HIV-1 and provide alternate targets to pursue a functional cure, whereby the viral reservoir is locked in latency following antiretroviral therapy cessation.

  14. Single-Cell RNA-Seq Reveals Transcriptional Heterogeneity in Latent and Reactivated HIV-Infected Cells.

    Science.gov (United States)

    Golumbeanu, Monica; Cristinelli, Sara; Rato, Sylvie; Munoz, Miguel; Cavassini, Matthias; Beerenwinkel, Niko; Ciuffi, Angela

    2018-04-24

    Despite effective treatment, HIV can persist in latent reservoirs, which represent a major obstacle toward HIV eradication. Targeting and reactivating latent cells is challenging due to the heterogeneous nature of HIV-infected cells. Here, we used a primary model of HIV latency and single-cell RNA sequencing to characterize transcriptional heterogeneity during HIV latency and reactivation. Our analysis identified transcriptional programs leading to successful reactivation of HIV expression. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. HIV-Infected Ugandan Women on Antiretroviral Therapy Maintain HIV-1 RNA Suppression Across Periconception, Pregnancy, and Postpartum Periods.

    Science.gov (United States)

    Matthews, Lynn T; Ribaudo, Heather B; Kaida, Angela; Bennett, Kara; Musinguzi, Nicholas; Siedner, Mark J; Kabakyenga, Jerome; Hunt, Peter W; Martin, Jeffrey N; Boum, Yap; Haberer, Jessica E; Bangsberg, David R

    2016-04-01

    HIV-infected women risk sexual and perinatal HIV transmission during conception, pregnancy, childbirth, and breastfeeding. We compared HIV-1 RNA suppression and medication adherence across periconception, pregnancy, and postpartum periods, among women on antiretroviral therapy (ART) in Uganda. We analyzed data from women in a prospective cohort study, aged 18-49 years, enrolled at ART initiation and with ≥1 pregnancy between 2005 and 2011. Participants were seen quarterly. The primary exposure of interest was pregnancy period, including periconception (3 quarters before pregnancy), pregnancy, postpartum (6 months after pregnancy outcome), or nonpregnancy related. Regression models using generalized estimating equations compared the likelihood of HIV-1 RNA ≤400 copies per milliliter, pregnancy, and 89% of postpartum visits, and was more likely during periconception (adjusted odds ratio, 2.15) compared with nonpregnant periods. Average ART adherence was 90% [interquartile range (IQR), 70%-98%], 93% (IQR, 82%-98%), 92% (IQR, 72%-98%), and 88% (IQR, 63%-97%) during nonpregnant, periconception, pregnant, and postpartum periods, respectively. Average adherence pregnancy were virologically suppressed at most visits, with an increased likelihood of suppression and high adherence during periconception follow-up. Increased frequency of 72-hour gaps suggests a need for increased adherence support during postpartum periods.

  16. Potential for false positive HIV test results with the serial rapid HIV testing algorithm

    Directory of Open Access Journals (Sweden)

    Baveewo Steven

    2012-03-01

    Full Text Available Abstract Background Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Results Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold. However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2% were HIV negative. Conclusion Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

  17. Ebola Virus RNA in Semen from an HIV-Positive Survivor of Ebola.

    Science.gov (United States)

    Purpura, Lawrence J; Rogers, Emerson; Baller, April; White, Stephen; Soka, Moses; Choi, Mary J; Mahmoud, Nuha; Wasunna, Christine; Massaquoi, Moses; Kollie, Jomah; Dweh, Straker; Bemah, Philip; Ladele, Victor; Kpaka, Jonathan; Jawara, Mary; Mugisha, Margaret; Subah, Onyekachi; Faikai, Mylene; Bailey, Jeff A; Rollin, Pierre; Marston, Barbara; Nyenswah, Tolbert; Gasasira, Alex; Knust, Barbara; Nichol, Stuart; Williams, Desmond

    2017-04-01

    Ebola virus is known to persist in semen of male survivors of Ebola virus disease (EVD). However, maximum duration of, or risk factors for, virus persistence are unknown. We report an EVD survivor with preexisting HIV infection, whose semen was positive for Ebola virus RNA 565 days after recovery from EVD.

  18. Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain

    DEFF Research Database (Denmark)

    Sükösd, Zsuzsanna; Andersen, Ebbe Sloth; Seemann, Ernst Stefan

    2015-01-01

    of the HIV-1 genome is highly variable in most regions, with a limited number of stable and conserved RNA secondary structures. Most interesting, a set of long distance interactions form a core organizing structure (COS) that organize the genome into three major structural domains. Despite overlapping...

  19. Forced evolution of a regulatory RNA helix in the HIV-1 genome

    NARCIS (Netherlands)

    Berkhout, B.; Klaver, B.; Das, A. T.

    1997-01-01

    The 5'and 3'end of the HIV-1 RNA genome forms a repeat (R) element that encodes a double stem-loop structure (the TAR and polyA hairpins). Phylogenetic analysis of the polyA hairpin in different human and simian immunodeficiency viruses suggests that the thermodynamic stability of the helix is

  20. Potential for false positive HIV test results with the serial rapid HIV testing algorithm.

    Science.gov (United States)

    Baveewo, Steven; Kamya, Moses R; Mayanja-Kizza, Harriet; Fatch, Robin; Bangsberg, David R; Coates, Thomas; Hahn, Judith A; Wanyenze, Rhoda K

    2012-03-19

    Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

  1. HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector

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    Akkina Ramesh

    2005-01-01

    Full Text Available Abstract Background RNA interference (RNAi mediated by small interfering RNAs (siRNAs has proved to be a highly effective gene silencing mechanism with great potential for HIV/AIDS gene therapy. Previous work with siRNAs against cellular coreceptors CXCR4 and CCR5 had shown that down regulation of these surface molecules could prevent HIV-1 entry and confer viral resistance. Since monospecific siRNAs targeting individual coreceptors are inadequate in protecting against both T cell tropic (X4 and monocyte tropic (R5 viral strains simultaneously, bispecific constructs with dual specificity are required. For effective long range therapy, the bispecific constructs need to be stably transduced into HIV-1 target cells via integrating viral vectors. Results To achieve this goal, lentiviral vectors incorporating both CXCR4 and CCR5 siRNAs of short hairpin design were constructed. The CXCR4 siRNA was driven by a U6 promoter whereas the CCR5 siRNA was driven by an H1 promoter. A CMV promoter driven EGFP reporter gene is also incorporated in the bispecific construct. High efficiency transduction into coreceptor expressing Magi and Ghost cell lines with a concomitant down regulation of respective coreceptors was achieved with lentiviral vectors. When the siRNA expressing transduced cells were challenged with X4 and R5 tropic HIV-1, they demonstrated marked viral resistance. HIV-1 resistance was also observed in bispecific lentiviral vector transduced primary PBMCs. Conclusions Both CXCR4 and CCR5 coreceptors could be simultaneously targeted for down regulation by a single combinatorial lentiviral vector incorporating respective anti-coreceptor siRNAs. Stable down regulation of both the coreceptors protects cells against infection by both X4 and R5 tropic HIV-1. Stable down regulation of cellular molecules that aid in HIV-1 infection will be an effective strategy for long range HIV gene therapy.

  2. HIV-1 pre-mRNA commitment to Rev mediated export through PSF and Matrin 3

    International Nuclear Information System (INIS)

    Kula, Anna; Gharu, Lavina; Marcello, Alessandro

    2013-01-01

    Human immunodeficiency virus gene expression and replication are regulated at several levels. Incompletely spliced viral RNAs and full-length genomic RNA contain the RRE element and are bound by the viral trans-acting protein Rev to be transported out of the nucleus. Previously we found that the nuclear matrix protein MATR3 was a cofactor of Rev-mediated RNA export. Here we show that the pleiotropic protein PSF binds viral RNA and is associated with MATR3. PSF is involved in the maintenance of a pool of RNA available for Rev activity. However, while Rev and PSF bind the viral pre-mRNA at the site of viral transcription, MATR3 interacts at a subsequent step. We propose that PSF and MATR3 define a novel pathway for RRE-containing HIV-1 RNAs that is hijacked by the viral Rev protein.

  3. RNA glycosidase and other agents target Tat to inhibit HIV-1 transcription.

    Science.gov (United States)

    Harrich, David; Jin, Hongping

    2018-03-20

    The HIV-1 tat gene encodes a small 86-104 amino acid protein depending on the HIV-1 strain. Tat is essential for HIV-1 replication through interactions with numerous cellular transcription factors. The interaction between Tat and P-TEFb, which is a cellular protein complex composed of cyclin T1 and CDK9, delivers P-TEFb to the newly transcribed viral mRNAs where phosphorylation of RNA polymerase II by CDK9 leads to highly efficient mRNA transcription. It has long been recognized that Tat is a potential anti-HIV-1 target and possibly a viral Achilles' heel. However, specifically targeting Tat without affecting normal host cell functions has been challenging. Means to inactivate Tat have been reported that includes small compounds, transdominant negative Tat proteins, and by plant-derived antivirals. Investigations of these agents have reported encouraging outcomes that inform and may hopefully affect strategies for a functional HIV-1 cure. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  4. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals

    DEFF Research Database (Denmark)

    Grint, D; Tedaldi, Ellen; Peters, L

    2017-01-01

    OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among tho...

  5. Dissection of specific binding of HIV-1 Gag to the 'packaging signal' in viral RNA.

    Science.gov (United States)

    Comas-Garcia, Mauricio; Datta, Siddhartha Ak; Baker, Laura; Varma, Rajat; Gudla, Prabhakar R; Rein, Alan

    2017-07-20

    Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis -acting RNA element called the 'packaging signal' (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding of recombinant HIV-1 Gag protein to Cy5-tagged 190-base RNAs. At physiological ionic strength, Gag binds with very similar, nanomolar affinities to both Ψ-containing and control RNAs. We challenged these interactions by adding excess competing tRNA; introducing mutations in Gag; or raising the ionic strength. These modifications all revealed high specificity for Ψ. This specificity is evidently obscured in physiological salt by non-specific, predominantly electrostatic interactions. This nonspecific activity was attenuated by mutations in the MA, CA, and NC domains, including CA mutations disrupting Gag-Gag interaction. We propose that gRNA is selectively packaged because binding to Ψ nucleates virion assembly with particular efficiency.

  6. Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India

    Science.gov (United States)

    Neogi, Ujjwal; Gupta, Soham; Rodridges, Rashmi; Sahoo, Pravat Nalini; Rao, Shwetha D.; Rewari, Bharat B.; Shastri, Suresh; De Costa, Ayesha; Shet, Anita

    2012-01-01

    Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (−0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally. PMID:23391790

  7. Preclinical safety and efficacy of an anti–HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor

    Directory of Open Access Journals (Sweden)

    Orit Wolstein

    2014-01-01

    Full Text Available Gene transfer has therapeutic potential for treating HIV-1 infection by generating cells that are resistant to the virus. We have engineered a novel self-inactivating lentiviral vector, LVsh5/C46, using two viral-entry inhibitors to block early steps of HIV-1 cycle. The LVsh5/C46 vector encodes a short hairpin RNA (shRNA for downregulation of CCR5, in combination with the HIV-1 fusion inhibitor, C46. We demonstrate here the effective delivery of LVsh5/C46 to human T cell lines, peripheral blood mononuclear cells, primary CD4+ T lymphocytes, and CD34+ hematopoietic stem/progenitor cells (HSPC. CCR5-targeted shRNA (sh5 and C46 peptide were stably expressed in the target cells and were able to effectively protect gene-modified cells against infection with CCR5- and CXCR4-tropic strains of HIV-1. LVsh5/C46 treatment was nontoxic as assessed by cell growth and viability, was noninflammatory, and had no adverse effect on HSPC differentiation. LVsh5/C46 could be produced at a scale sufficient for clinical development and resulted in active viral particles with very low mutagenic potential and the absence of replication-competent lentivirus. Based on these in vitro results, plus additional in vivo safety and efficacy data, LVsh5/C46 is now being tested in a phase 1/2 clinical trial for the treatment of HIV-1 disease.

  8. Concerted motions in HIV-1 TAR RNA may allow access to bound state conformations: RNA dynamics from NMR residual dipolar couplings.

    Science.gov (United States)

    Al-Hashimi, Hashim M; Gosser, Yuying; Gorin, Andrey; Hu, Weidong; Majumdar, Ananya; Patel, Dinshaw J

    2002-01-11

    Ground-state dynamics in RNA is a critical precursor for structural adaptation observed ubiquitously in protein-RNA recognition. A tertiary conformational analysis of the stem-loop structural element in the transactivation response element (TAR) from human immunodeficiency virus type 1 (HIV-I) RNA is presented using recently introduced NMR methods that rely on the measurement of residual dipolar couplings (RDC) in partially oriented systems. Order matrix analysis of RDC data provides evidence for inter-helical motions that are of amplitude 46(+/-4) degrees, of random directional character, and that are executed about an average conformation with an inter-helical angle between 44 degrees and 54 degrees. The generated ensemble of TAR conformations have different organizations of functional groups responsible for interaction with the trans-activator protein Tat, including conformations similar to the previously characterized bound-state conformation. These results demonstrate the utility of RDC-NMR for simultaneously characterizing RNA tertiary dynamics and average conformation, and indicate an avenue for TAR complex formation involving tertiary structure capture. Copyright 2001 Academic Press.

  9. Associations between HIV-RNA-based indicators and virological and clinical outcomes

    DEFF Research Database (Denmark)

    Laut, Kamilla G; Shepherd, Leah C; Pedersen, Court

    2016-01-01

    OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with at least three viral load measureme......OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with at least three viral load...... measurements after baseline (the latest of 01/01/2001 or entry into EuroSIDA). Using multivariate Poisson regression, we modelled the association between short-term (resistance, triple-class failure) and long-term (all-cause mortality, any AIDS/non-AIDS clinical event) outcomes and the indicators: viraemia...

  10. The role of Vif oligomerization and RNA chaperone activity in HIV-1 replication.

    Science.gov (United States)

    Batisse, Julien; Guerrero, Santiago; Bernacchi, Serena; Sleiman, Dona; Gabus, Caroline; Darlix, Jean-Luc; Marquet, Roland; Tisné, Carine; Paillart, Jean-Christophe

    2012-11-01

    The viral infectivity factor (Vif) is essential for the productive infection and dissemination of HIV-1 in non-permissive cells that involve most natural HIV-1 target cells. Vif counteracts the packaging of two cellular cytidine deaminases named APOBEC3G (A3G) and A3F by diverse mechanisms including the recruitment of an E3 ubiquitin ligase complex and the proteasomal degradation of A3G/A3F, the inhibition of A3G mRNA translation or by a direct competition mechanism. In addition, Vif appears to be an active partner of the late steps of viral replication by participating in virus assembly and Gag processing, thus regulating the final stage of virion formation notably genomic RNA dimerization and by inhibiting the initiation of reverse transcription. Vif is a small pleiotropic protein with multiple domains, and recent studies highlighted the importance of Vif conformation and flexibility in counteracting A3G and in binding RNA. In this review, we will focus on the oligomerization and RNA chaperone properties of Vif and show that the intrinsic disordered nature of some Vif domains could play an important role in virus assembly and replication. Experimental evidence demonstrating the RNA chaperone activity of Vif will be presented. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

    Science.gov (United States)

    Grint, D; Tedaldi, E; Peters, L; Mocroft, A; Edlin, B; Gallien, S; Klinker, H; Boesecke, C; Kokordelis, P; Rockstroh, J K

    2017-07-01

    Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype. © 2016 British HIV Association.

  12. Comparison of sampling methods to measure HIV RNA viral load in female genital tract secretions.

    Science.gov (United States)

    Jaumdally, Shameem Z; Jones, Heidi E; Hoover, Donald R; Gamieldien, Hoyam; Kriek, Jean-Mari; Langwenya, Nontokozo; Myer, Landon; Passmore, Jo-Ann S; Todd, Catherine S

    2017-03-01

    How does menstrual cup (MC) compare to other genital sampling methods for HIV RNA recovery? We compared HIV RNA levels between MC, endocervical swab (ECS), and ECS-enriched cervicovaginal lavage (eCVL) specimens in 51 HIV-positive, antiretroviral therapy-naive women at enrollment, 3 and 6 months, with order rotated by visit. Paired comparisons were analyzed with McNemar's exact tests, signed-rank tests, and an extension of Somer's D for pooled analyses across visits. MC specimens had the highest proportion of quantifiable HIV VL at enrollment and month 3, but more MC specimens (n=12.8%) were insufficient for testing, compared with ECS (2%, P=0.006) and eCVL (0%, P<0.001). Among sufficient specimens, median VL was significantly higher for MC (2.62 log 10 copies/mL) compared to ECS (1.30 log 10 copies/mL, P<0.001) and eCVL (1.60 log 10 copies/mL, P<0.001) across visits. MC may be more sensitive than eCVL and CVS, provided insufficient specimens are reduced. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Novel HIV-1 knockdown targets identified by an enriched kinases/phosphatases shRNA library using a long-term iterative screen in Jurkat T-cells.

    Directory of Open Access Journals (Sweden)

    Sylvie Rato

    2010-02-01

    Full Text Available HIV-1 is a complex retrovirus that uses host machinery to promote its replication. Understanding cellular proteins involved in the multistep process of HIV-1 infection may result in the discovery of more adapted and effective therapeutic targets. Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells. Here, we focused on the discovery of kinases and phosphatases that are essential for HIV-1 replication but dispensable for cell viability. We performed an iterative screen in Jurkat T-cells with a short-hairpin-RNA (shRNA library highly enriched for human kinases and phosphatases. We identified 14 new proteins essential for HIV-1 replication that do not affect cell viability. These proteins are described to be involved in MAPK, JNK and ERK pathways, vesicular traffic and DNA repair. Moreover, we show that the proteins under study are important in an early step of HIV-1 infection before viral integration, whereas some of them affect viral transcription/translation. This study brings new insights for the complex interplay of HIV-1/host cell and opens new possibilities for antiviral strategies.

  14. Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.

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    Gene-Errol E Ringpis

    Full Text Available Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA. However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains. As such, combination approaches targeting additional steps in the virus lifecycle are required. We screened a panel of previously published shRNAs targeting highly conserved regions and identified a potent shRNA targeting the R-region of the HIV-1 long terminal repeat (LTR. Here, we report that human CD4(+ T-cells derived from transplanted HSPC engineered to co-express shRNAs targeting CCR5 and HIV-1 LTR are resistant to CCR5- and CXCR4- tropic HIV-1-mediated depletion in vivo. Transduction with the combination vector suppressed CXCR4- and CCR5- tropic viral replication in cell lines and peripheral blood mononuclear cells in vitro. No obvious cytotoxicity or interferon response was observed. Transplantation of combination vector-transduced HSPC into hu-BLT mice resulted in efficient engraftment and subsequent stable gene marking and CCR5 down-regulation in human CD4(+ T-cells within peripheral blood and systemic lymphoid tissues, including gut-associated lymphoid tissue, a major site of robust viral replication, for over twelve weeks. CXCR4- and CCR5- tropic HIV-1 infection was effectively inhibited in hu-BLT mouse spleen-derived human CD4(+ T-cells ex vivo. Furthermore, levels of gene-marked CD4(+ T-cells in peripheral blood increased despite systemic infection with either

  15. Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting.

    Science.gov (United States)

    Anema, Aranka; Kerr, Thomas; Milloy, M-J; Feng, Cindy; Montaner, Julio S G; Wood, Evan

    2014-04-01

    Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

  16. Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA

    Directory of Open Access Journals (Sweden)

    Soros Vanessa

    2008-10-01

    Full Text Available Abstract HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68ΔC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively. While investigating the inhibition of incompletely spliced HIV-1 mRNAs by Sam68ΔC, we determined that the effect was independent of the perinuclear bundling of the viral RNA. Inhibition was dependent upon the nuclear export pathway used, as translation of viral RNA exported via the Tap/CTE export pathway was not blocked by Sam68ΔC. We demonstrate that inhibition of HIV expression by Sam68ΔC is correlated with a loss of PABP1 binding with no attendant change in polyadenosine tail length of the affected RNAs. The capacity of Sam68ΔC to selectively inhibit translation of HIV-1 RNAs exported by Crm1 suggests that it is able to recognize unique characteristics of these viral RNPs, a property that could lead to new therapeutic approaches to controlling HIV-1 replication.

  17. 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

  18. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states.

    Directory of Open Access Journals (Sweden)

    Kevin A Wilkinson

    2008-04-01

    Full Text Available Replication and pathogenesis of the human immunodeficiency virus (HIV is tightly linked to the structure of its RNA genome, but genome structure in infectious virions is poorly understood. We invent high-throughput SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension technology, which uses many of the same tools as DNA sequencing, to quantify RNA backbone flexibility at single-nucleotide resolution and from which robust structural information can be immediately derived. We analyze the structure of HIV-1 genomic RNA in four biologically instructive states, including the authentic viral genome inside native particles. Remarkably, given the large number of plausible local structures, the first 10% of the HIV-1 genome exists in a single, predominant conformation in all four states. We also discover that noncoding regions functioning in a regulatory role have significantly lower (p-value < 0.0001 SHAPE reactivities, and hence more structure, than do viral coding regions that function as the template for protein synthesis. By directly monitoring protein binding inside virions, we identify the RNA recognition motif for the viral nucleocapsid protein. Seven structurally homologous binding sites occur in a well-defined domain in the genome, consistent with a role in directing specific packaging of genomic RNA into nascent virions. In addition, we identify two distinct motifs that are targets for the duplex destabilizing activity of this same protein. The nucleocapsid protein destabilizes local HIV-1 RNA structure in ways likely to facilitate initial movement both of the retroviral reverse transcriptase from its tRNA primer and of the ribosome in coding regions. Each of the three nucleocapsid interaction motifs falls in a specific genome domain, indicating that local protein interactions can be organized by the long-range architecture of an RNA. High-throughput SHAPE reveals a comprehensive view of HIV-1 RNA genome structure, and further

  19. Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load

    DEFF Research Database (Denmark)

    Kallestrup, Per; Zinyama, Rutendo; Gomo, Exnevia

    2005-01-01

    To determine whether treatment of schistosomiasis has an effect on the course of human immunodeficiency virus type 1 (HIV-1) infection, individuals with schistosomiasis and with or without HIV-1 infection were randomized to receive praziquantel treatment at inclusion or after a delay of 3 months......; 287 participants were included in the study, and 227 (79%) were followed up. Among the 130 participants who were coinfected, those who received early treatment (n=64) had a significantly lower increase in plasma HIV-1 RNA load than did those who received delayed treatment (n=66) (P...

  20. The RNA binding protein HuR does not interact directly with HIV-1 reverse transcriptase and does not affect reverse transcription in vitro

    Directory of Open Access Journals (Sweden)

    Gronenborn Angela M

    2010-05-01

    Full Text Available Abstract Background Lemay et al recently reported that the RNA binding protein HuR directly interacts with the ribonuclease H (RNase H domain of HIV-1 reverse transcriptase (RT and influences the efficiency of viral reverse transcription (Lemay et al., 2008, Retrovirology 5:47. HuR is a member of the embryonic lethal abnormal vision protein family and contains 3 RNA recognition motifs (RRMs that bind AU-rich elements (AREs. To define the structural determinants of the HuR-RT interaction and to elucidate the mechanism(s by which HuR influences HIV-1 reverse transcription activity in vitro, we cloned and purified full-length HuR as well as three additional protein constructs that contained the N-terminal and internal RRMs, the internal and C-terminal RRMs, or the C-terminal RRM only. Results All four HuR proteins were purified and characterized by biophysical methods. They are well structured and exist as monomers in solution. No direct protein-protein interaction between HuR and HIV-1 RT was detected using NMR titrations with 15N labeled HuR variants or the 15N labeled RNase H domain of HIV-1 RT. Furthermore, HuR did not significantly affect the kinetics of HIV-1 reverse transcription in vitro, even on RNA templates that contain AREs. Conclusions Our results suggest that HuR does not impact HIV-1 replication through a direct protein-protein interaction with the viral RT.

  1. Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones.

    Science.gov (United States)

    Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

    2013-06-01

    RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous 'polyamide amino acids' (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy-entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets.

  2. 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.

  3. HIV RNA Suppression during and after Pregnancy among Women in the HIV Outpatient Study, 1996 to 2015.

    Science.gov (United States)

    Patel, Monita; Tedaldi, Ellen; Armon, Carl; Nesheim, Steven; Lampe, Margaret; Palella, Frank; Novak, Richard; Sutton, Madeline; Buchacz, Kate

    2018-01-01

    To examine HIV viral suppression during/after pregnancy. Prospective observational cohort. We identified pregnancies from 1996 to 2015. We examined HIV RNA viral load (VL), VL suppression (≤500 copies/mL), and antiretroviral therapy (ART) status at pregnancy start, end, and 6 months postpartum. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for VL nonsuppression. Among 253 pregnancies analyzed, 34.8% of women exhibited VL suppression at pregnancy start, 60.1% at pregnancy end, and 42.7% at 6 months postpartum. Median VL (log 10 copies/mL) was 2.80 (interquartile range [IQR]: 1.40-3.85) at pregnancy start, 1.70 (IQR: 1.40-2.82) at pregnancy end, and 2.30 (IQR: 1.40-3.86) at postpartum. Risk of postpartum VL nonsuppression was also lower among women on ART and with VL suppression at pregnancy end (versus those not; adjusted RR = 0.30, 95% CI: 0.17-0.53). Maintaining VL suppression among US women remains a challenge, particularly during postpartum. Achieving VL suppression earlier during pregnancy benefits women subsequently.

  4. SL1 revisited: functional analysis of the structure and conformation of HIV-1 genome RNA.

    Science.gov (United States)

    Sakuragi, Sayuri; Yokoyama, Masaru; Shioda, Tatsuo; Sato, Hironori; Sakuragi, Jun-Ichi

    2016-11-11

    The dimer initiation site/dimer linkage sequence (DIS/DLS) region of HIV is located on the 5' end of the viral genome and suggested to form complex secondary/tertiary structures. Within this structure, stem-loop 1 (SL1) is believed to be most important and an essential key to dimerization, since the sequence and predicted secondary structure of SL1 are highly stable and conserved among various virus subtypes. In particular, a six-base palindromic sequence is always present at the hairpin loop of SL1 and the formation of kissing-loop structure at this position between the two strands of genomic RNA is suggested to trigger dimerization. Although the higher-order structure model of SL1 is well accepted and perhaps even undoubted lately, there could be stillroom for consideration to depict the functional SL1 structure while in vivo (in virion or cell). In this study, we performed several analyses to identify the nucleotides and/or basepairing within SL1 which are necessary for HIV-1 genome dimerization, encapsidation, recombination and infectivity. We unexpectedly found that some nucleotides that are believed to contribute the formation of the stem do not impact dimerization or infectivity. On the other hand, we found that one G-C basepair involved in stem formation may serve as an alternative dimer interactive site. We also report on our further investigation of the roles of the palindromic sequences on viral replication. Collectively, we aim to assemble a more-comprehensive functional map of SL1 on the HIV-1 viral life cycle. We discovered several possibilities for a novel structure of SL1 in HIV-1 DLS. The newly proposed structure model suggested that the hairpin loop of SL1 appeared larger, and genome dimerization process might consist of more complicated mechanism than previously understood. Further investigations would be still required to fully understand the genome packaging and dimerization of HIV.

  5. A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Lacour Nedra

    2008-07-01

    Full Text Available Abstract HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4% shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment.

  6. Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras

    Science.gov (United States)

    Wheeler, Lee Adam; Trifonova, Radiana; Vrbanac, Vladimir; Basar, Emre; McKernan, Shannon; Xu, Zhan; Seung, Edward; Deruaz, Maud; Dudek, Tim; Einarsson, Jon Ivar; Yang, Linda; Allen, Todd M.; Luster, Andrew D.; Tager, Andrew M.; Dykxhoorn, Derek M.; Lieberman, Judy

    2011-01-01

    The continued spread of the HIV epidemic underscores the need to interrupt transmission. One attractive strategy is a topical vaginal microbicide. Sexual transmission of herpes simplex virus type 2 (HSV-2) in mice can be inhibited by intravaginal siRNA application. To overcome the challenges of knocking down gene expression in immune cells susceptible to HIV infection, we used chimeric RNAs composed of an aptamer fused to an siRNA for targeted gene knockdown in cells bearing an aptamer-binding receptor. Here, we showed that CD4 aptamer-siRNA chimeras (CD4-AsiCs) specifically suppress gene expression in CD4+ T cells and macrophages in vitro, in polarized cervicovaginal tissue explants, and in the female genital tract of humanized mice. CD4-AsiCs do not activate lymphocytes or stimulate innate immunity. CD4-AsiCs that knock down HIV genes and/or CCR5 inhibited HIV infection in vitro and in tissue explants. When applied intravaginally to humanized mice, CD4-AsiCs protected against HIV vaginal transmission. Thus, CD4-AsiCs could be used as the active ingredient of a microbicide to prevent HIV sexual transmission. PMID:21576818

  7. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation.

    Science.gov (United States)

    Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W

    2014-09-24

    Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score. Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.

  8. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

    Science.gov (United States)

    Booth, David S; Cheng, Yifan; Frankel, Alan D

    2014-12-08

    The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

  9. Association of mitochondrial lysyl-tRNA synthetase with HIV-1 GagPol involves catalytic domain of the synthetase and transframe and integrase domains of Pol

    Directory of Open Access Journals (Sweden)

    Shalak V. F.

    2011-10-01

    Full Text Available Aim. Analyze the interaction between Lysyl-tRNA synthetase (LysRS and HIV-1 GagPol to know whether a particular N-terminal sequence of mitochondrial LysRS triggers a specific recognition with GagPol. Methods. Yeast two-hybrid analysis, immunoprecipitation. Results. We have shown that LysRS associates with the Pol domain of GagPol. Conclusions. A model of the assembly of the LysRS:tRNA3Lys:GagPol packaging complex is proposed.

  10. Patterns of repeated anal cytology results among HIV-positive and HIV-negative men who have sex with men

    Directory of Open Access Journals (Sweden)

    Hilary A. Robbins

    2018-06-01

    Full Text Available Background: Men who have sex with men (MSM are at increased risk for anal cancer. In cervical cancer screening, patterns of repeated cytology results are used to identify low- and high-risk women, but little is known about these patterns for anal cytology among MSM. Methods: We analyzed Multicenter AIDS Cohort Study (MACS data for MSM who were offered anal cytology testing annually (HIV-positive or every 2 years (HIV-negative for 4 years. Results: Following an initial negative (normal cytology, the frequency of a second negative cytology was lower among HIV-positive MSM with CD4 ≥ 500 (74% or CD4 < 500 (68% than HIV-negative MSM (83% (p < 0.001. After an initial abnormal cytology, the frequency of a second abnormal cytology was highest among HIV-positive MSM with CD4 < 500 (70% compared to CD4 ≥ 500 (53% or HIV-negative MSM (46% (p = 0.003. Among HIV-positive MSM with at least three results, 37% had 3 consecutive negative results; 3 consecutive abnormal results were more frequent among CD4 < 500 (22% than CD4 ≥ 500 (10% (p = 0.008. Conclusions: More than one-third of HIV-positive MSM have consistently negative anal cytology over three years. Following abnormal anal cytology, a repeated cytology is commonly negative in HIV-negative or immunocompetent HIV-positive men, while persistent cytological abnormality is more likely among HIV-positive men with CD4 < 500. Keywords: Anal cancer, Anal cytology, HIV, MSM, Anal cancer screening

  11. Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis

    DEFF Research Database (Denmark)

    Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy G.

    2015-01-01

    and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine). Methods Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks...... postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant. Results HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median...... (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg...

  12. Employment discrimination and HIV stigma: survey results from civil society organisations and people living with HIV in Africa.

    Science.gov (United States)

    Sprague, Laurel; Simon, Sara; Sprague, Courtenay

    2011-01-01

    The article presents findings from three surveys of people living with HIV (PLHIV) and civil society organisations about the experience of employment discrimination and stigma in the workplace. The work seeks to contribute to efforts by businesses and other organisations to effectively respond to the HIV epidemic within the world of work, and to deepen our understanding of the ways in which HIV stigma and employment discrimination persist in the workplace. The findings of global and regional surveys indicate the existence of high levels of employment discrimination based on HIV status worldwide, including forced disclosure of HIV status, exclusion in the workplace, refusals to hire or promote, and terminations of people known to be living with HIV. The survey findings show that employment discrimination based on HIV status is experienced in all African subregions. Country-level surveys conducted in Kenya and Zambia indicated that PLHIV face marked barriers to employment, including discrimination in hiring, loss of promotions, and termination because of HIV status. Additionally, large variances were found in the degree of support versus discrimination that employees living with HIV in those two countries received following their disclosure. The discussion emphasises the importance of the workplace as a site for intervention and behaviour change. To address this, we introduce a conceptual framework - the employment continuum - that maps multiple points of entry within the workplace to address HIV-related stigma and discrimination. Additional recommendations include: actions to ensure equal opportunity in hiring for PLHIV; ensuring that HIV testing is voluntary, never mandatory, and that disclosure is not necessary for employment; ensuring confidentiality of HIV status; communicating and enforcing HIV-related antidiscrimination policies; establishing support groups in the workplace; providing safe and confidential processes for resolving complaints of employment

  13. Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

    OpenAIRE

    Friew, Yeshitila N; Boyko, Vitaly; Hu, Wei-Shau; Pathak, Vinay K

    2009-01-01

    Abstract Background Host restriction factor APOBEC3G (A3G) blocks human immunodeficiency virus type 1 (HIV-1) replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC) to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Ga...

  14. Expression of Herpes Simplex Virus Thymidine Kinase/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells

    Directory of Open Access Journals (Sweden)

    Carin K. Ingemarsdotter

    2017-06-01

    Full Text Available Antiviral strategies targeting hijacked cellular processes are less easily evaded by the virus than viral targets. If selective for viral functions, they can have a high therapeutic index. We used RNA trans-splicing to deliver the herpes simplex virus thymidine kinase-ganciclovir (HSV-tk/GCV cell suicide system into HIV-producing cells. Using an extensive in silico bioinformatics and RNA structural analysis approach, ten HIV RNA trans-splicing constructs were designed targeting eight different HIV splice donor or acceptor sites and were tested in cells expressing HIV. Trans-spliced mRNAs were identified in HIV-expressing cells using qRT-PCR with successful detection of fusion RNA transcripts between HIV RNA and the HSV-tk RNA transcripts from six of ten candidate RNA trans-splicing constructs. Conventional PCR and Sanger sequencing confirmed RNA trans-splicing junctions. Measuring cell viability in the presence or absence of GCV expression of HSV-tk by RNA trans-splicing led to selective killing of HIV-producing cells using either 3′ exon replacement or 5′ exon replacement in the presence of GCV. Five constructs targeting four HIV splice donor and acceptor sites, D4, A5, A7, and A8, involved in regulating the generation of multiple HIV RNA transcripts proved to be effective for trans-splicing mediated selective killing of HIV-infected cells, within which individual constructs targeting D4 and A8 were the most efficient.

  15. Detection of HIV and HCV RNA in semen from Brazilian coinfected men using multiplex PCR before and after semen washing Detecção do RNA do HIV e HCV em sêmen de homens brasileiros, usando PCR multiplex antes e depois do "semen washing"

    Directory of Open Access Journals (Sweden)

    Cynthia Liliane Motta do Canto

    2006-08-01

    Full Text Available INTRODUCTION: Prolonged survival of patients under HAART has resulted in new demands for assisted reproductive technologies. HIV serodiscordant couples wish to make use of assisted reproduction techniques in order to avoid viral transmission to the partner or to the newborn. It is therefore essential to test the effectiveness of techniques aimed at reducing HIV and HCV loads in infected semen using molecular biology tests. METHODS: After seminal analysis, semen samples from 20 coinfected patients were submitted to cell fractioning and isolation of motile spermatozoa by density gradient centrifugation and swim-up. HIV and HCV RNA detection tests were performed with RNA obtained from sperm, seminal plasma and total semen. RESULTS: In pre-washing semen, HIV RNA was detected in 100% of total semen samples, whereas HCV RNA was concomitantly amplified in only one specimen. Neither HIV nor HCV were detected either in the swim-up or in the post-washing semen fractions. CONCLUSIONS: Reduction of HIV and/or HCV shedding in semen by density gradient centrifugation followed by swim-up is an efficient method. These findings lead us to believe that, although semen is rarely found to contain HCV, semen processing is highly beneficial for HIV/HCV coinfected individuals.O aumento da sobrevida dos pacientes que utilizam terapêutica antiretroviral altamente eficaz (HAART- Highly Active Antiretroviral Therapy trouxe uma nova demanda de casais sorodiscordantes que desejam filhos. Como esses casais não podem abandonar o uso de preservativos, torna-se indispensável tratar o sêmen infectado com técnicas laboratoriais eficazes que além de isolar os melhores espermatozóides, reduzam a carga viral do HIV e HCV a níveis indetectáveis. Para isso, são utilizadas técnicas de semen washing, associadas a testes ultra sensíveis de biologia molecular. Após análise seminal, sêmen de 20 pacientes co-infectados HIV-HCV foram submetidos a fracionamento celular e

  16. Isolation and characterization of 20'-F-RNA aptamers against whole HIV-1 subtype C envelope pseudovirus

    CSIR Research Space (South Africa)

    London, GM

    2015-01-01

    Full Text Available Aptamers, which are artificial nucleic acid ligands akin to antibodies in function, represent a new class of molecules that can prevent HIV infection. In this study, we isolated RNA aptamers against whole HV-1CAP45 enveloped pseudotyped virus...

  17. Implications of HIV PrEP Trials Results

    Science.gov (United States)

    Anton, Peter; Fletcher, Courtney V.; DeGruttola, Victor; McGowan, Ian; Becker, Stephen; Zwerski, Sheryl; Burns, David

    2011-01-01

    Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop. PMID:20969483

  18. Neurocognitive and neuroinflammatory correlates of PDYN and OPRK1 mRNA expression in the anterior cingulate in postmortem brain of HIV-infected subjects.

    Science.gov (United States)

    Yuferov, Vadim; Butelman, Eduardo R; Ho, Ann; Morgello, Susan; Kreek, Mary Jeanne

    2014-01-09

    Chronic inflammation may contribute to neuropsychological impairments in individuals with HIV, and modulation of this inflammatory response by opiate receptor ligands is important in light of the prevalence of drug use in HIV populations. Exogenous MOR and KOR agonists have differential effects on central nervous system (CNS) immunity and, while some data suggest KOR agonists are immunosuppressive, the KOR agonist dynorphin has been shown to stimulate human monocyte chemotaxis. In this study, we examined mRNA levels of endogenous opioid receptors OPRK1 and OPRM1, prodynorphin (PDYN), macrophage scavenger receptor CD163, and microglia/macrophage marker CD68 in the caudate and anterior cingulate of postmortem brains from HIV-positive and HIV-negative subjects. Brain tissues of HIV-infected (n = 24) and control subjects (n = 15) were obtained from the Manhattan HIV Brain Bank. Quantification of the gene mRNA was performed using SYBR Green RT-PCR. CD68 and CD163 were increased in HIV-positive (HIV+) compared to HIV-negative (HIV-) individuals in both brain regions. There were higher OPRK1 (P <0.005), and lower PDYN mRNA (P <0.005) levels in the anterior cingulate of HIV+ compared to HIV- subjects. This difference between the clinical groups was not found in the caudate. There was no difference in the levels of OPRM1 mRNA between HIV+ and HIV- subjects. Using linear regression analysis, we examined the relationship of OPRK1 and PDYN mRNA levels in the HIV+ subjects with seven cognitive domain T scores of a neuropsychological test battery. Within the HIV+ subjects, there was a positive correlation between anterior cingulate PDYN mRNA levels and better T-scores in the motor domain. Within the HIV+ subjects there were also positive correlations of both OPRK1 and PDYN mRNA levels with the anti-inflammatory marker CD163, but not with proinflammatory CD68 levels. In this setting, decreased PDYN mRNA may reflect a homeostatic mechanism to reduce monocyte

  19. Routine monitoring and assessment of adults living with HIV: results of the British HIV Association (BHIVA) national audit 2015.

    Science.gov (United States)

    Molloy, A; Curtis, H; Burns, F; Freedman, A

    2017-09-13

    The clinical care of people living with HIV changed fundamentally as a result of the development of effective antiretroviral therapy (ART). HIV infection is now a long-term treatable condition. We report a national audit to assess adherence to British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals. All UK sites known as providers of adult HIV outpatient services were invited to complete a case-note review and a brief survey of local clinic practices. Participating sites were asked to randomly select 50-100 adults, who attended for specialist HIV care during 2014 and/or 2015. Each site collected data electronically using a self-audit spreadsheet tool. This included demographic details (gender, ethnicity, HIV exposure, and age) and whether 22 standardised and pre-defined clinical audited outcomes had been recorded. Data were collected on 8258 adults from 123 sites, representing approximately 10% of people living with HIV reported in public health surveillance as attending UK HIV services. Sexual health screening was provided within 96.4% of HIV services, cervical cytology and influenza vaccination within 71.4% of HIV services. There was wide variation in resistance testing across sites. Only 44.9% of patients on ART had a documented 10-year CVD risk within the past three years and fracture risk had been assessed within the past three years for only 16.7% patients aged over 50 years. There was high participation in the national audit and good practice was identified in some areas. However improvements can be made in monitoring of cardiovascular risk, bone and sexual health.

  20. Changes in rRNA levels during stress invalidates results from mRNA blotting: Fluorescence in situ rRNA hybridization permits renormalization for estimation of cellular mRNA levels

    DEFF Research Database (Denmark)

    Hansen, M.C.; Nielsen, A.K.; Molin, Søren

    2001-01-01

    obtained by these techniques are compared between experiments in which differences in growth rates, strains, or stress treatments occur, the normalization procedure may have a significant impact on the results. In this report we present a solution to the normalization problem in RNA slot blotting...... the relative level of rRNA per cell, and slot blotting to rRNA probes, which estimates the level of rRNA per extracted total RNA, the amount of RNA per cell was calculated in a series of heat shock experiments with the gram-positive bacterium Lactococcus lactis. It was found that the level of rRNA per cell...... decreased to 30% in the course of the heat shock. This lowered ribosome level led to a decrease in the total RNA content, resulting in a gradually increasing overestimation of the mRNA levels throughout the experiment. Using renormalized cellular mRNA levels, the HrcA-mediated regulation of the genes...

  1. 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.

  2. Control of HIV-1 env RNA splicing and transport: investigating the role of hnRNP A1 in exon splicing silencer (ESS3a) function

    International Nuclear Information System (INIS)

    Asai, Kengo; Platt, Craig; Cochrane, Alan

    2003-01-01

    The control of HIV-1 viral RNA splicing and transport plays an important role in the successful replication of the virus. Previous studies have identified both an exon splicing enhancer (ESE) and a bipartite exon splicing silencer (ESS3a and ESS3b) within the terminal exon of HIV-1 that are involved in modulating both splicing and Rev-mediated export of viral RNA. To define the mechanism of ESS3a function, experiments were carried out to better define the cis and trans components required for ESS3a activity. Mutations throughout the 30-nt element resulted in partial loss of ESS function. Combining mutations was found to have an additive effect, suggesting the presence of multiple binding sites. Analysis of interacting factors identified hnRNP A1 as one component of the complex that modulates ESS3a activity. However, subsequent binding analyses determined that hnRNP A1 interacts with only one portion of ESS3a, suggesting the involvement of another host factor. Parallel analysis of the effect of the mutations on Rev-mediated export determined that there is not a direct correlation between the effect of the mutations on splicing and RNA transport. Consistent with this hypothesis, replacement of ESS3a with consensus hnRNP A1 binding sites was found to be insufficient to block Rev-mediated RNA export

  3. Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes.

    Science.gov (United States)

    Gu, Jijin; Al-Bayati, Karam; Ho, Emmanuel A

    2017-08-01

    RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands. In this study, chitosan nanoparticles (CS-NPs) were prepared by a complex coacervation method in the presence of siRNA, and antibody was chemically conjugated to the nanoparticles. The antibody-modified chitosan nanoparticles (Ab-CS-NPs) were spherical in shape, with an average particle size of 235.7 ± 10.2 nm and a zeta potential of 22.88 ± 1.78 mV. The therapeutic potential of the nanoparticles was evaluated based on their cellular uptake and gene silencing efficiency. Cellular accumulation and gene silencing efficiency of Ab-CS-NPs in astrocytes were significantly improved compared to non-modified CS-NPs and single-antibody-modified CS-NPs. These results suggest that the combination of anti-Tf antibody and anti-B2 antibody significantly increased the knockdown effect of siRNA-loaded nanoparticles. Thus, antibody-mediated dual-targeting nanoparticles are an efficient and promising delivery strategy for inhibiting HIV replication in astrocytes. Graphical abstract Graphic representation of dual-antibody-conjugated chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier (BBB) for inhibiting HIV replication in astrocytes. a Nanoparticle delivery to the BBB and penetration. b Tf

  4. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

    Science.gov (United States)

    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  5. Molecular dynamics and MM/GBSA-integrated protocol probing the correlation between biological activities and binding free energies of HIV-1 TAR RNA inhibitors.

    Science.gov (United States)

    Peddi, Saikiran Reddy; Sivan, Sree Kanth; Manga, Vijjulatha

    2018-02-01

    The interaction of HIV-1 transactivator protein Tat with its cognate transactivation response (TAR) RNA has emerged as a promising target for developing antiviral compounds and treating HIV infection, since it is a crucial step for efficient transcription and replication. In the present study, molecular dynamics (MD) simulations and MM/GBSA calculations have been performed on a series of neamine derivatives in order to estimate appropriate MD simulation time for acceptable correlation between ΔG bind and experimental pIC 50 values. Initially, all inhibitors were docked into the active site of HIV-1 TAR RNA. Later to explore various conformations and examine the docking results, MD simulations were carried out. Finally, binding free energies were calculated using MM/GBSA method and were correlated with experimental pIC 50 values at different time scales (0-1 to 0-10 ns). From this study, it is clear that in case of neamine derivatives as simulation time increased the correlation between binding free energy and experimental pIC 50 values increased correspondingly. Therefore, the binding energies which can be interpreted at longer simulation times can be used to predict the bioactivity of new neamine derivatives. Moreover, in this work, we have identified some plausible critical nucleotide interactions with neamine derivatives that are responsible for potent inhibitory activity. Furthermore, we also provide some insights into a new class of oxadiazole-based back bone cyclic peptides designed by incorporating the structural features of neamine derivatives. On the whole, this approach can provide a valuable guidance for designing new potent inhibitors and modify the existing compounds targeting HIV-1 TAR RNA.

  6. Employment discrimination and HIV stigma: survey results from civil ...

    African Journals Online (AJOL)

    The article presents findings from three surveys of people living with HIV (PLHIV) and civil society organisations about the experience of employment discrimination and stigma in the workplace. The work seeks to contribute to efforts by businesses and other organisations to effectively respond to the HIV epidemic within the ...

  7. Endogenous MCM7 microRNA cluster as a novel platform to multiplex small interfering and nucleolar RNAs for combinational HIV-1 gene therapy.

    Science.gov (United States)

    Chung, Janet; Zhang, Jane; Li, Haitang; Ouellet, Dominique L; DiGiusto, David L; Rossi, John J

    2012-11-01

    Combinational therapy with small RNA inhibitory agents against multiple viral targets allows efficient inhibition of viral production by controlling gene expression at critical time points. Here we explore combinations of different classes of therapeutic anti-HIV-1 RNAs expressed from within the context of an intronic MCM7 (minichromosome maintenance complex component-7) platform that naturally harbors 3 microRNAs (miRNAs). We replaced the endogenous miRNAs with anti-HIV small RNAs, including small interfering RNAs (siRNAs) targeting HIV-1 tat and rev messages that function to induce post-transcriptional gene silencing by the RNA interference pathway, a nucleolar-localizing RNA ribozyme that targets the conserved U5 region of HIV-1 transcripts for degradation, and finally nucleolar trans-activation response (TAR) and Rev-binding element (RBE) RNA decoys designed to sequester HIV-1 Tat and Rev proteins inside the nucleolus. We demonstrate the versatility of the MCM7 platform in expressing and efficiently processing the siRNAs as miRNA mimics along with nucleolar small RNAs. Furthermore, three of the combinatorial constructs tested potently suppressed viral replication during a 1-month HIV challenge, with greater than 5-log inhibition compared with untransduced, HIV-1-infected CEM T lymphocytes. One of the most effective constructs contains an anti-HIV siRNA combined with a nucleolar-localizing U5 ribozyme and TAR decoy. This represents the first efficacious example of combining Drosha-processed siRNAs with small nucleolar ribonucleoprotein (snoRNP)-processed nucleolar RNA chimeras from a single intron platform for effective inhibition of viral replication. Moreover, we demonstrated enrichment/selection for cells expressing levels of the antiviral RNAs that provide optimal inhibition under the selective pressure of HIV. The combinations of si/snoRNAs represent a new paradigm for combinatorial RNA-based gene therapy applications.

  8. Intergenic mRNA molecules resulting from trans-splicing.

    Science.gov (United States)

    Finta, Csaba; Zaphiropoulos, Peter G

    2002-02-22

    Accumulated recent evidence is indicating that alternative splicing represents a generalized process that increases the complexity of human gene expression. Here we show that mRNA production may not necessarily be limited to single genes, as human liver also has the potential to produce a variety of hybrid cytochrome P450 3A mRNA molecules. The four known cytochrome P450 3A genes in humans, CYP3A4, CYP3A5, CYP3A7, and CYP3A43, share a high degree of similarity, consist of 13 exons with conserved exon-intron boundaries, and form a cluster on chromosome 7. The chimeric CYP3A mRNA molecules described herein are characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 or CYP3A5 exons. Because the CYP3A43 gene is in a head-to-head orientation with the CYP3A4 and CYP3A5 genes, bypassing transcriptional termination can not account for the formation of hybrid CYP3A mRNAs. Thus, the mechanism generating these molecules has to be an RNA processing event that joins exons of independent pre-mRNA molecules, i.e. trans-splicing. Using quantitative real-time polymerase chain reaction, the ratio of one CYP3A43/3A4 intergenic combination was estimated to be approximately 0.15% that of the CYP3A43 mRNAs. Moreover, trans-splicing has been found not to interfere with polyadenylation. Heterologous expression of the chimeric species composed of CYP3A43 exon 1 joined to exons 2-13 of CYP3A4 revealed catalytic activity toward testosterone.

  9. Surprising results: HIV testing and changes in contraceptive practices among young women in Malawi

    Science.gov (United States)

    Sennott, Christie; Yeatman, Sara

    2015-01-01

    This study uses eight waves of data from the population-based Tsogolo la Thanzi study (2009–2011) in rural Malawi to examine changes in young women’s contraceptive practices, including the use of condoms, non-barrier contraceptive methods, and abstinence, following positive and negative HIV tests. The analysis factors in women’s prior perceptions of their HIV status that may already be shaping their behaviour and separates surprise HIV test results from those that merely confirm what was already believed. Fixed effects logistic regression models show that HIV testing frequently affects the contraceptive practices of young Malawian women, particularly when the test yields an unexpected result. Specifically, women who are surprised to test HIV positive increase their condom use and are more likely to use condoms consistently. Following an HIV negative test (whether a surprise or expected), women increase their use of condoms and decrease their use of non-barrier contraceptives; the latter may be due to an increase in abstinence following a surprise negative result. Changes in condom use following HIV testing are robust to the inclusion of potential explanatory mechanisms including fertility preferences, relationship status, and the perception that a partner is HIV positive. The results demonstrate that both positive and negative tests can influence women’s sexual and reproductive behaviours, and emphasise the importance of conceptualizing of HIV testing as offering new information only insofar as results deviate from prior perceptions of HIV status. PMID:26160156

  10. Correlation of immune activation with HIV-1 RNA levels assayed by real-time RT-PCR in HIV-1 Subtype C infected patients in Northern India

    Science.gov (United States)

    Agarwal, Atima; Sankaran, Sumathi; Vajpayee, Madhu; Sreenivas, V; Seth, Pradeep; Dandekar, Satya

    2014-01-01

    Background Assays with specificity and cost effectiveness are needed for the measurement of HIV-1 burden to monitor disease progression or response to anti-retroviral therapy (ART) in HIV-1 subtype C infected patients. Objectives The objective of this study was to develop and validate an affordable; one step Real-Time RT-PCR assay with high specificity and sensitivity to measure plasma HIV-1 loads in HIV-1 subtype C infected patients. Results We developed an RT-PCR assay to detect and quantitate plasma HIV-1 levels in HIV-1 subtype C infected patients. An inverse correlation between plasma viral loads (PVL) and CD4+ T-cell numbers was detected at all CDC stages. Significant correlations were found between CD8+ T-cell activation and PVL, as well as with the clinical and immunological status of the patients. Conclusions The RT-PCR assay provides a sensitive method to measure PVL in HIV-1 subtype C infected patients. Viral loads correlated with immune activation and can be used to monitor HIV care in India. PMID:17962068

  11. Trans-activation of the 5' to 3' viral DNA strand transfer by nucleocapsid protein during reverse transcription of HIV1 RNA.

    Science.gov (United States)

    Darlix, J L; Vincent, A; Gabus, C; de Rocquigny, H; Roques, B

    1993-08-01

    Two DNA strand transfer reactions take place during reverse transcription of the retroviral genome. The first transfer, that of the minus-strand strong stop DNA from the 5' end of the viral RNA to the 3' end, has been studied in vitro with two RNAs mimicking the 5' and 3' regions of the HIV1 genome and with nucleocapsid protein, NCp7, and reverse transcriptase. The results show that NCp7 strongly activates the 5' to 3' DNA strand transfer during reverse transcription while a basic peptide resembling NCp7 is inactive. Activation of the first transfer by several NCp7 derived peptides and the influence of the terminal redundancies (R) present at the 5' and 3' ends of HIV1 RNA were also examined. The first transfer is optimal in the presence of intact NCp7 and necessitates R on both the 5' and 3' RNAs. Sequencing of full length viral DNA products reveals approximately 40% misincorporations at the first nucleotide beyond the transfer point. If such base misincorporations occur during proviral DNA synthesis with possible homologous recombinations it may well contribute to the high level of genetic variability of HIV.

  12. Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Grint, D; Peters, L; Reekie, J

    2013-01-01

    Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals.......Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals....

  13. An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G.

    Science.gov (United States)

    Ejima, Tomohiko; Hirota, Mayuko; Mizukami, Tamio; Otsuka, Masami; Fujita, Mikako

    2011-10-01

    Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome. This finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that 5 µM SN-2 increases the expression of A3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. The proteasome inhibitor MG-132 increased the level of both A3G and Vif expression. These results demonstrate that A3G is ubiquitinated and degraded in the proteasome by a factor other than Vif, and that SN-2 selectively inhibits these processes. Furthermore, 5 µM SN-2 significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.

  14. ORIGINAL ARTICLES Epidemiology of HIV in South Africa - results ...

    African Journals Online (AJOL)

    The Nelson MandelaiHuman Sciences Research Council. (HSRC) study of HIV I AIDS5 ..... This study was funded by the Nelson Mandela Foundation, ... Cape Town: Centre for Actuarial Research, Medical Research Council and the Actuarial ...

  15. High rate of hepatitis C virus (HCV) recurrence in HIV-infected individuals with spontaneous HCV RNA clearance

    DEFF Research Database (Denmark)

    Peters, L; Mocroft, A; Soriano, V

    2014-01-01

    OBJECTIVES: Following resolution of hepatitis C virus (HCV) infection, recurrence has been shown to occur in some persons with repeated exposure to HCV. We aimed to investigate the rate and factors associated with HCV RNA recurrence among HIV-1-infected patients with prior spontaneous HCV RNA cle......-up. Our findings underline the importance of maintaining focus on preventive measures to reduce IDU and sharing of contaminated needles. Clinicians should maintain a high degree of vigilance to identify patients with new HCV infection early....

  16. HIV vaccine development: would more (public) money bring quicker results?

    Science.gov (United States)

    Winsbury, R

    1999-01-01

    Globally, $200-250 million/year are devoted to HIV vaccine research. Most of those funds pay for basic research rather than product development. Moreover, most of the funds are aimed at the HIV strain commonly found in the US and Europe, and not at the strains common to Africa and other developing countries. While US President Bill Clinton set in 1997 a 10-year target for the development of an HIV vaccine, that target date is looking increasingly unlikely. International vaccine and pharmaceutical companies typically drive vaccine research and development. However, concern over the ultimate profitability of developing and marketing an HIV vaccine, and the fear of major litigation should an eventual vaccine go awry have caused such firms to shy away from investing large amounts of money into HIV vaccine development. These companies somehow have to be attracted back into the field. A World Bank special task force is slated to present its report by mid-1999 on possible funding mechanisms to promote HIV vaccine development. It remains to be resolved whether public funds could and should be used, perhaps through a pooled international vaccine development fund. 2 new International AIDS Vaccine Initiative projects are described.

  17. RNA.

    Science.gov (United States)

    Darnell, James E., Jr.

    1985-01-01

    Ribonucleic acid (RNA) converts genetic information into protein and usually must be processed to serve its function. RNA types, chemical structure, protein synthesis, translation, manufacture, and processing are discussed. Concludes that the first genes might have been spliced RNA and that humans might be closer than bacteria to primitive…

  18. Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

    Directory of Open Access Journals (Sweden)

    Paulo Pereira Christo

    2011-08-01

    Full Text Available The question of whether HIV-1 RNA in cerebrospinal fluid (CSF is derived from viral replication in the central nervous system or simply reflects the transit of infected lymphocytes from the blood compartment has long been a matter of debate. Some studies found no correlation between CSF and plasma viral load, whereas others did. The lack of a correlation between the two compartments suggests that the presence of HIV-1 RNA is not simply due to the passive passage of the virus from blood to CSF but rather due to intrathecal replication. To evaluate the correlation between plasma and CSF HIV-1 RNA levels and to identify situations in which there is no correlation between the two compartments, seventy patients were prospectively studied. The association between CSF and plasma viral load was evaluated in the total population and in subgroups of patients with similar characteristics. A correlation between the CSF and plasma compartments was observed for patients undergoing highly active antiretroviral therapy (HAART, those with a CD4 T lymphocyte count lower than 200 cells/mm³, and those with increased CSF protein content. On the other hand, no correlation was observed for patients without adequate virological control, who had a CD4 count higher than 200 cells/mm³ and who did not use HAART. The correlation between the two compartments observed in some patients suggests that CSF HIV-1 RNA levels may reflect plasma levels in these subjects. In contrast, the lack of a correlation between the two compartments in patients who were not on HAART and who had normal CSF proteins and a poor virological control possibly indicates compartmentalization of the virus in CSF and, consequently, plasma-independent intrathecal viral replication.

  19. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    Directory of Open Access Journals (Sweden)

    Sandhya Boyapalle

    Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

  20. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up

    DEFF Research Database (Denmark)

    Lundgren, Jens; Babiker, Abdel; El-Sadr, Wafaa

    2008-01-01

    BACKGROUND AND METHODS: The SMART study compared 2 strategies for using antiretroviral therapy-drug conservation (DC) and viral suppression (VS)-in 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL. Rates and predictors of opportunistic disease...... or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported. RESULTS: During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count ...%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow- up with a CD4+ cell count

  1. Mechanisms of human immunodeficiency virus type 2 RNA packaging

    DEFF Research Database (Denmark)

    Ni, Na; Nikolaitchik, Olga A; Dilley, Kari A

    2011-01-01

    do not support the cis-packaging hypothesis but instead indicate that trans packaging is the major mechanism of HIV-2 RNA packaging. To further characterize the mechanisms of HIV-2 RNA packaging, we visualized HIV-2 RNA in individual particles by using fluorescent protein-tagged RNA-binding proteins......Human immunodeficiency virus type 2 (HIV-2) has been reported to have a distinct RNA packaging mechanism, referred to as cis packaging, in which Gag proteins package the RNA from which they were translated. We examined the progeny generated from dually infected cell lines that contain two HIV-2...... proviruses, one with a wild-type gag/gag-pol and the other with a mutant gag that cannot express functional Gag/Gag-Pol. Viral titers and RNA analyses revealed that mutant viral RNAs can be packaged at efficiencies comparable to that of viral RNA from which wild-type Gag/Gag-Pol is translated. These results...

  2. Deletions in cox2 mRNA result in loss of splicing and RNA editing and gain of novel RNA editing sites.

    Directory of Open Access Journals (Sweden)

    Stefanie Grüttner

    Full Text Available As previously demonstrated, the maize cox2 RNA is fully edited in cauliflower mitochondria. Use of constructs with a deleted cox2 intron, however, led to a loss of RNA editing at almost all editing sites, with only a few sites still partially edited. Likewise, one deletion in exon 1 and three in exon 2 abolish RNA editing at all cox2 sites analyzed. Furthermore, intron splicing is abolished using these deletions. Mutation of a cytosine residue, which is normally edited and localized directly adjacent to the intron, to thymidine did not result in restoration of splicing, indicating that the loss of splicing was not due to loss of RNA editing. One deletion in exon 2 did not lead to loss of splicing. Instead, most editing sites were found to be edited, only three were not edited. Unexpectedly, we observed additional RNA editing events at new sites. Thus it appears that deletions in the cox2 RNA sequence can have a strong effect on RNA processing, leading to loss of splicing, loss of editing at all sites, or even to a gain of new editing sites. As these effects are not limited to the vicinity of the respective deletions, but appear to be widespread or even affect all editing sites, they may not be explained by the loss of PPR binding sites. Instead, it appears that several parts of the cox2 transcript are required for proper RNA processing. This indicates the roles of the RNA sequence and structural elements in the recognition of the editing sites.

  3. Changes in HIV-1 subtypes B and C genital tract RNA in women and men after initiation of antiretroviral therapy.

    Science.gov (United States)

    Fiscus, Susan A; Cu-Uvin, Susan; Eshete, Abel Tilahun; Hughes, Michael D; Bao, Yajing; Hosseinipour, Mina; Grinsztejn, Beatriz; Badal-Faesen, Sharlaa; Dragavon, Joan; Coombs, Robert W; Braun, Ken; Moran, Laura; Hakim, James; Flanigan, Timothy; Kumarasamy, N; Campbell, Thomas B

    2013-07-01

    Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype. HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cART regimens. One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype B and 76% subtype C). Despite similar baseline CD4(+) cell counts and blood plasma viral loads, women with subtype C had the highest GTVL (median, 5.1 log10 copies/mL) compared to women with subtype B and men with subtype C or B (4.0, 4.0, and 3.8 log10 copies/mL, respectively; P female genital tract may serve as a reservoir of persistent HIV-1 replication during cART and affect the use of cART to prevent sexual and perinatal transmission of HIV-1.

  4. HIV-1 splicing is controlled by local RNA structure and binding of splicing regulatory proteins at the major 5' splice site

    NARCIS (Netherlands)

    Mueller, Nancy; Berkhout, Ben; Das, Atze T.

    2015-01-01

    The 5' leader region of the human immunodeficiency virus 1 (HIV-1) RNA genome contains the major 5' splice site (ss) that is used in the production of the many spliced viral RNAs. This splice-donor (SD) region can fold into a stable stem-loop structure and the thermodynamic stability of this RNA

  5. Persistent CSF but not Plasma HIV RNA, is Associated with Increased Risk of New-onset Moderate-to-Severe Depressive Symptoms; A Prospective Cohort Study

    Science.gov (United States)

    Hammond, Edward R.; Crum, Rosa M.; Treisman, Glenn J.; Mehta, Shruti H.; Clifford, David B.; Ellis, Ronald J.; Gelman, Benjamin B.; Grant, Igor; Letendre, Scott L.; Marra, Christina M; Morgello, Susan; Simpson, David M.; McArthur, Justin C.

    2016-01-01

    Major depressive disorder is the most common neuropsychiatric complication in human immunodeficiency virus (HIV) infections and is associated with worse clinical outcomes. We determined if detectable cerebrospinal fluid (CSF) HIV ribonucleic acid (RNA) at threshold ≥50 copies/ml is associated with increased risk of depression. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort is a six-center US-based prospective cohort with bi-annual follow-up 674 participants. We fit linear mixed models (N=233) and discrete-time survival models (N=154; 832 observations), to evaluate trajectories of Beck Depression Inventory (BDI) II scores, and the incidence of new-onset moderate-to-severe depressive symptoms (BDI≥17) among participants, on combination antiretroviral therapy (cART), who were free of depression at study entry, and received a minimum of three CSF examinations over 2,496 person-months follow-up. Detectable CSF HIV RNA (threshold ≥50 copies/ml) at any visit was associated with a 4.7-fold increase in new-onset depression at subsequent visits adjusted for plasma HIV RNA and treatment adherence; hazard ratio (HR)=4.76, (95% CI: 1.58–14.3); P=0.006. Depression (BDI) scores were 2.53 points higher (95% CI: 0.47–4.60; P=0.02) over 6 months if CSF HIV RNA was detectable at a prior study visit in fully adjusted models including age, sex, race, education, plasma HIV RNA, duration and adherence of cART, and lifetime depression diagnosis by DSM-IV criteria. Persistent CSF but not plasma HIV RNA, is associated with an increased risk for new-onset depression. Further research evaluating the role of immune activation and inflammatory markers may improve our understanding of this association. PMID:26727907

  6. Sustained progress, but no room for complacency: Results of 2015 HIV estimations in India

    Science.gov (United States)

    Pandey, Arvind; Dhingra, Neeraj; Kumar, Pradeep; Sahu, Damodar; Reddy, D.C.S.; Narayan, Padum; Raj, Yujwal; Sangal, Bhavna; Chandra, Nalini; Nair, Saritha; Singh, Jitenkumar; Chavan, Laxmikant; Srivastava, Deepika Joshi; Jha, Ugra Mohan; Verma, Vinita; Kant, Shashi; Bhattacharya, Madhulekha; Swain, Pushpanjali; Haldar, Partha; Singh, Lucky; Bakkali, Taoufik; Stover, John; Ammassari, Savina

    2017-01-01

    Background & objectives: Evidence-based planning has been the cornerstone of India's response to HIV/AIDS. Here we describe the process, method and tools used for generating the 2015 HIV estimates and provide a summary of the main results. Methods: Spectrum software supported by the UNAIDS was used to produce HIV estimates for India as a whole and its States/Union Territories. This tool takes into consideration the size and HIV prevalence of defined population groups and programme data to estimate HIV prevalence, incidence and mortality over time as well as treatment needs. Results: India's national adult prevalence of HIV was 0.26 per cent in 2015. Of the 2.1 million people living with HIV/AIDS, the largest numbers were in Andhra Pradesh, Maharashtra and Karnataka. New HIV infections were an estimated 86,000 in 2015, reflecting a decline by around 32 per cent from 2007. The declining trend in incidence was mirrored in most States, though an increasing trend was detected in Assam, Chandigarh, Chhattisgarh, Gujarat, Sikkim, Tripura and Uttar Pradesh. AIDS-related deaths were estimated to be 67,600 in 2015, reflecting a 54 per cent decline from 2007. There were variations in the rate and trend of decline across India for this indicator also. Interpretation & conclusions: While key indicators measured through Spectrum modelling confirm success of the National AIDS Control Programme, there is no room for complacency as rising incidence trends in some geographical areas and population pockets remain the cause of concern. Progress achieved so far in responding to HIV/AIDS needs to be sustained to end the HIV epidemic. PMID:29168464

  7. Health and budget impact of combined HIV prevention - first results of the BELHIVPREV model.

    Science.gov (United States)

    Vermeersch, Sebastian; Callens, Steven; De Wit, Stéphane; Goffard, Jean-Christophe; Laga, Marie; Van Beckhoven, Dominique; Annemans, Lieven

    2018-02-01

    We developed a pragmatic modelling approach to estimate the impact of treatment as prevention (TasP); outreach testing strategies; and pre-exposure prophylaxis (PrEP) on the epidemiology of HIV and its associated pharmaceutical expenses. Our model estimates the incremental health (in terms of new HIV diagnoses) and budget impact of two prevention scenarios (outreach+TasP and outreach+TasP+PrEP) against a 'no additional prevention' scenario. Model parameters were estimated from reported Belgian epidemiology and literature data. The analysis was performed from a healthcare payer perspective with a 15-year-time horizon. It considers subpopulation differences, HIV infections diagnosed in Belgium having occurred prior to migration, and the effects of an ageing HIV population. Without additional prevention measures, the annual number of new HIV diagnoses rises to over 1350 new diagnoses in 2030 as compared to baseline, resulting in a budget expenditure of €260.5 million. Implementation of outreach+TasP and outreach+TasP+PrEP results in a decrease in the number of new HIV diagnoses to 865 and 663 per year, respectively. Respective budget impacts decrease by €20.6 million and €33.7 million. Foregoing additional investments in prevention is not an option. An approach combining TasP, outreach and PrEP is most effective in reducing the number of new HIV diagnoses and the HIV treatment budget. Our model is the first pragmatic HIV model in Belgium estimating the consequences of a combined preventive approach on the HIV epidemiology and its economic burden assuming other prevention efforts such as condom use and harm reduction strategies remain the same.

  8. Improved detection of CXCR4-using HIV by V3 genotyping: application of population-based and "deep" sequencing to plasma RNA and proviral DNA.

    Science.gov (United States)

    Swenson, Luke C; Moores, Andrew; Low, Andrew J; Thielen, Alexander; Dong, Winnie; Woods, Conan; Jensen, Mark A; Wynhoven, Brian; Chan, Dennison; Glascock, Christopher; Harrigan, P Richard

    2010-08-01

    Tropism testing should rule out CXCR4-using HIV before treatment with CCR5 antagonists. Currently, the recombinant phenotypic Trofile assay (Monogram) is most widely utilized; however, genotypic tests may represent alternative methods. Independent triplicate amplifications of the HIV gp120 V3 region were made from either plasma HIV RNA or proviral DNA. These underwent standard, population-based sequencing with an ABI3730 (RNA n = 63; DNA n = 40), or "deep" sequencing with a Roche/454 Genome Sequencer-FLX (RNA n = 12; DNA n = 12). Position-specific scoring matrices (PSSMX4/R5) (-6.96 cutoff) and geno2pheno[coreceptor] (5% false-positive rate) inferred tropism from V3 sequence. These methods were then independently validated with a separate, blinded dataset (n = 278) of screening samples from the maraviroc MOTIVATE trials. Standard sequencing of HIV RNA with PSSM yielded 69% sensitivity and 91% specificity, relative to Trofile. The validation dataset gave 75% sensitivity and 83% specificity. Proviral DNA plus PSSM gave 77% sensitivity and 71% specificity. "Deep" sequencing of HIV RNA detected >2% inferred-CXCR4-using virus in 8/8 samples called non-R5 by Trofile, and <2% in 4/4 samples called R5. Triplicate analyses of V3 standard sequence data detect greater proportions of CXCR4-using samples than previously achieved. Sequencing proviral DNA and "deep" V3 sequencing may also be useful tools for assessing tropism.

  9. 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

  10. Trends in HIV & syphilis prevalence and correlates of HIV infection: results from cross-sectional surveys among women attending ante-natal clinics in Northern Tanzania

    Directory of Open Access Journals (Sweden)

    Kumogola Yusufu

    2010-09-01

    Full Text Available Abstract Background Sentinel surveillance for HIV in ante-natal clinics (ANC remains the primary method for collecting timely trend data on HIV prevalence in most of sub-Saharan Africa. We describe prevalence of HIV and syphilis infection and trends over time in HIV prevalence among women attending ante-natal clinics (ANC in Magu district and Mwanza city, part of Mwanza region in Northern Tanzania. HIV prevalence from ANC surveys in 2000 and 2002 was 10.5% and 10.8% respectively. In previous rounds urban residence, residential mobility, the length of time sexually active before marriage, time since marriage and age of the partner were associated with HIV infection. Methods A third round of HIV sentinel surveillance was conducted at ante-natal clinics in Mwanza region, Tanzania during 2006. We interviewed women attending 27 ante-natal clinics. In 15 clinics we also anonymously tested women for syphilis and HIV infection and linked these results to the questionnaire data. Results HIV prevalence was 7.6% overall in 2006 and 7.4% at the 11 clinics used in previous rounds. Geographical variations in HIV prevalence, apparent in previous rounds, have largely disappeared but syphilis prevalence is still higher in rural clinics. HIV prevalence has declined in urban clinics and is stable in rural clinics. The correlates of HIV infection have changed over time. In this round older age, lower gravidity, remarriage, duration of marriage, sexual activity before marriage, long interval between last birth and pregnancy and child death were all associated with infection. Conclusions HIV prevalence trends concur with results from a community-based cohort in the region. Correlates of HIV infection have also changed and more proximate, individual level factors are now more important, in line with the changing epidemiology of infection in this population.

  11. Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription

    International Nuclear Information System (INIS)

    Kusano, Shuichi; Eizuru, Yoshito

    2013-01-01

    Highlights: •PLSCR1 specifically interacted with HIV-1 Tat in vitro and in vivo. •PLSCR1 repressed Tat-dependent transactivation of the HIV-1 LTR. •Suppression of PLSCR1 expression enhanced the levels of HIV-1 transcripts. •PLSCR1 reduced the nuclear localization of Tat. -- Abstract: Human phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)-stimulated gene and possesses an IFN-mediated antiviral function. We show here that PLSCR1 directly interacts with human immunodeficiency virus type-1 (HIV-1) Tat. This interaction occurs both in vitro and in vivo through amino acids 160–250 of PLSCR1. Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. In addition, shRNA-mediated suppression of endogenous PLSCR1 expression enhances the levels of gag mRNA in an HIV-1-infected T-cell line. These findings indicate that PLSCR1 negatively regulates the Tat-dependent transactivation of the HIV-1 LTR during HIV-1 infection

  12. African American Clergy Perspectives About the HIV Care Continuum: Results From a Qualitative Study in Jackson, Mississippi.

    Science.gov (United States)

    Nunn, Amy; Parker, Sharon; McCoy, Katryna; Monger, Mauda; Bender, Melverta; Poceta, Joanna; Harvey, Julia; Thomas, Gladys; Johnson, Kendra; Ransome, Yusuf; Sutten Coats, Cassandra; Chan, Phil; Mena, Leandro

    2018-01-01

    Mississippi has some of the most pronounced racial disparities in HIV infection in the country; African Americans comprised 37% of the Mississippi population but represented 80% of new HIV cases in 2015. Improving outcomes along the HIV care continuum, including linking and retaining more individuals and enhancing adherence to medication, may reduce the disparities faced by African Americans in Mississippi. Little is understood about clergy's views about the HIV care continuum. We assessed knowledge of African American pastors and ministers in Jackson, Mississippi about HIV and the HIV care continuum. We also assessed their willingness to promote HIV screening and biomedical prevention technologies as well as efforts to enhance linkage and retention in care with their congregations. Four focus groups were conducted with 19 African American clergy. Clergy noted pervasive stigma associated with HIV and believed they had a moral imperative to promote HIV awareness and testing; they provided recommendations on how to normalize conversations related to HIV testing and treatment. Overall, clergy were willing to promote and help assist with linking and retaining HIV positive individuals in care but knew little about how HIV treatment can enhance prevention or new biomedical technologies such as pre-exposure prophylaxis (PrEP). Clergy underscored the importance of building coalitions to promote a collective local response to the epidemic. The results of this study highlight important public health opportunities to engage African American clergy in the HIV care continuum in order to reduce racial disparities in HIV infection.

  13. Knowledge, attitudes and practices of HIV-positive patients regarding disclosure of HIV results at Betesda Clinic in Namibia

    Directory of Open Access Journals (Sweden)

    Penelope Tom

    2013-02-01

    Full Text Available Background: This study examined the practices, knowledge, attitudes, and the reasons for disclosure and non-disclosure of HIV-positive patients with regard to the disclosure of HIV results at Betesda Clinic in Windhoek, Namibia.Objectives: The objectives of the study were to determine knowledge, attitudes, and practices of HIV-positive patients regarding the disclosure of HIV status at Betesda Clinic in Namibia, and to determine the reasons for disclosure and non-disclosure.Methods: This was a cross-sectional descriptive study and 263 HIV-positive patients were enrolled in the study.Results: Analyses revealed that knowledge on disclosure was good, with 68% who thought it was important. The majority (73% have disclosed and 60% disclosed within 1 week of receiving their results. The most common reasons for disclosure were that 32% needed help, 25% wanted his or her partner to go for testing, and 20% wanted to let relatives know. Reasons for non-disclosure were mainly the fear of gossip (79%. Seventy-three per cent had disclosed to their partners, and 23% had disclosed to more than one person. People’s reactions were supportive in 43%, whereas 29% understood, 9% accepted and 6% were angry. Upon disclosure 40% received help, 24% of partners were tested, 23% received psychological support and 5% were stigmatised. Disclosure was higher amongst the married and cohabitating.Conclusion: The attitude was positive with regard to knowledge of disclosure, with most participants thinking that disclosure was important and good. The attitudes and actual practices of disclosure were encouraging; however, people are disclosing only to trustedindividuals in the society and the fear of stigma is still present although the actual stigma was very low.

  14. Five-year trends in epidemiology and prevention of mother-to-child HIV transmission, St. Petersburg, Russia: results from perinatal HIV surveillance

    Directory of Open Access Journals (Sweden)

    Kissin Dmitry M

    2011-10-01

    Full Text Available Abstract Background The HIV epidemic in Russia has increasingly involved reproductive-aged women, which may increase perinatal HIV transmission. Methods Standard HIV case-reporting and enhanced perinatal HIV surveillance systems were used for prospective assessment of HIV-infected women giving birth in St. Petersburg, Russia, during 2004-2008. Trends in social, perinatal, and clinical factors influencing mother-to-child HIV transmission stratified by history of injection drug use, and rates of perinatal HIV transmission were assessed using two-sided χ2 or Cochran-Armitage tests. Results Among HIV-infected women who gave birth, the proportion of women who self-reported ever using injection drugs (IDUs decreased from 62% in 2004 to 41% in 2008 (P P P P for trend Conclusions Reduced proportion of IDUs and improved clinical services among HIV-infected women giving birth were accompanied by decreased perinatal HIV transmission, which can be further reduced by increasing outreach and HIV testing of women before and during pregnancy.

  15. HIV-1 in the RNA world: Transcription regulation, miRNAs and antiviral RNAs

    NARCIS (Netherlands)

    Harwig, A.

    2015-01-01

    All organisms, from bacteria to human, use three biological molecules that each serve critical functions in the expression of genes in the cell. These are deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins. RNA is synthesized from DNA in a process called transcription. RNA differs from

  16. Virological and immunological response to antiretroviral regimens containing maraviroc in HIV type 1-infected patients in clinical practice: role of different tropism testing results and of concomitant treatments.

    Science.gov (United States)

    Rossetti, Barbara; Bianco, Claudia; Bellazzi, Lara Ines; Bruzzone, Bianca; Colao, Grazia; Corsi, Paola; Monno, Laura; Pagano, Gabriella; Paolucci, Stefania; Punzi, Grazia; Setti, Maurizio; Zazzi, Maurizio; De Luca, Andrea

    2014-01-01

    We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA immunological response as time to a CD4 cell count increase of ≥ 100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05-1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96-4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch.

  17. STI patients are effective recruiters of undiagnosed cases of HIV: results of a social contact recruitment study in Malawi.

    Science.gov (United States)

    Rosenberg, Nora E; Kamanga, Gift; Pettifor, Audrey E; Bonongwe, Naomi; Mapanje, Clement; Rutstein, Sarah E; Ward, Michelle; Hoffman, Irving F; Martinson, Francis; Miller, William C

    2014-04-15

    Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection. In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 "seeds" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social "contacts" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices. Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds. Social contact recruitment by newly diagnosed STI patients efficiently led to new HIV diagnoses. Research to replicate findings and guide implementation is needed.

  18. High rates of HIV seroconversion in pregnant women and low reported levels of HIV testing among male partners in Southern Mozambique: results from a mixed methods study.

    Directory of Open Access Journals (Sweden)

    Caroline De Schacht

    Full Text Available INTRODUCTION: Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner's HIV testing. METHODS: Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2-3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n = 94 with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing. RESULTS: HIV incidence rate was estimated at 4.28/100 women-years (95%CI: 2.33-7.16. Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95%CI: 1.04-13.78, p = 0.04 and living in Maputo Province (RR 4.35, 95%CI: 0.97-19.45, p = 0.05. Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner, 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator. CONCLUSIONS: HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners' HIV status remains low. Knowledge of both partners' HIV status is critical for maximal effectiveness of prevention and treatment services to reach

  19. Potential of RNA aptamers in the prevention of HIV-1 subtype C infections

    CSIR Research Space (South Africa)

    London, GM

    2014-10-01

    Full Text Available Compounds that have been used to prevent human immunodeficiency virus type-I (HIV-1) infections include synthetic chemicals, plant extras and monoclonal antibodies. Although most of these compounds have potent antiviral activity, they often fail...

  20. Study of bantam miRNA expression in brain tumour resulted due to ...

    Indian Academy of Sciences (India)

    ANIMESH BANERJEE

    2017-06-19

    Jun 19, 2017 ... these genes lead to an inappropriate segregation of cell fate determinants ... ground could possibly be a consequence of brain tumour resulting ... Expression of bantam miRNA in Drosophila brain tumour. Figure 1. Bantam is ...

  1. Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD)

    Science.gov (United States)

    Zhou, J; Li, PCK; Kumarasamy, N; Boyd, M; Chen, YMA; Sirisanthana, T; Sungkanuparph, S; Oka, S; Tau, G; Phanuphak, P; Saphonn, V; Zhang, FJ; Omar, SFS; Lee, CKC; Ditangco, R; Merati, TP; Lim, PL; Choi, JY; Law, MG; Pujari, S

    2010-01-01

    Objective The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD). Methods Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria. Results Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person-years (7.8 per 100 person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person-years). There was no difference between patients from high- and low-income countries [adjusted hazard ratio (HR) 1.02; P = 0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P = 0.040], a lower CD4 count (≥ 51 cells/μL vs. ≤ 50 cells/μL; adjusted HR 0.61, P = 0.022) and a higher HIV viral load (≥ 400 HIV-1 RNA copies/mL vs. failure. Compared with patients from low-income countries, patients from high-income countries were more likely to change two or more drugs (67% vs. 49%; P = 0.009) and to change to a protease-inhibitor-containing regimen (48% vs. 16%; Pfailure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second-line treatment. There is a need to scale up the availability of second-line regimens and virological monitoring in this region. PMID:19601993

  2. Incidence of syphilis seroconversion among HIV-infected persons in Asia: results from the TREAT Asia HIV Observational Database.

    Science.gov (United States)

    Ahn, Jin Young; Boettiger, David; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Huy, Bui Vu; Wong, Wing Wai; Ditangco, Rossana; Lee, Man Po; Oka, Shinichi; Durier, Nicolas; Choi, Jun Yong

    2016-01-01

    Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, psyphilis diagnosis (IRR 5.15, 95% CI 3.69-7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706-0.997) were significantly associated with syphilis seroconversion. We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population.

  3. Acute HIV Discovered During Routine HIV Screening With HIV Antigen-Antibody Combination Tests in 9 US Emergency Departments.

    Science.gov (United States)

    White, Douglas A E; Giordano, Thomas P; Pasalar, Siavash; Jacobson, Kathleen R; Glick, Nancy R; Sha, Beverly E; Mammen, Priya E; Hunt, Bijou R; Todorovic, Tamara; Moreno-Walton, Lisa; Adomolga, Vincent; Feaster, Daniel J; Branson, Bernard M

    2018-01-05

    Newer combination HIV antigen-antibody tests allow detection of HIV sooner after infection than previous antibody-only immunoassays because, in addition to HIV-1 and -2 antibodies, they detect the HIV-1 p24 antigen, which appears before antibodies develop. We determine the yield of screening with HIV antigen-antibody tests and clinical presentations for new diagnoses of acute and established HIV infection across US emergency departments (EDs). This was a retrospective study of 9 EDs in 6 cities with HIV screening programs that integrated laboratory-based antigen-antibody tests between November 1, 2012, and December 31, 2015. Unique patients with newly diagnosed HIV infection were identified and classified as having either acute HIV infection or established HIV infection. Acute HIV infection was defined as a repeatedly reactive antigen-antibody test result, a negative HIV-1/HIV-2 antibody differentiation assay, or Western blot result, but detectable HIV ribonucleic acid (RNA); established HIV infection was defined as a repeatedly reactive antigen-antibody test result and a positive HIV-1/HIV-2 antibody differentiation assay or Western blot result. The primary outcomes were the number of new HIV diagnoses and proportion of patients with laboratory-defined acute HIV infection. Secondary outcomes compared reason for visit and the clinical presentation of acute HIV infection. In total, 214,524 patients were screened for HIV and 839 (0.4%) received a new diagnosis, of which 122 (14.5%) were acute HIV infection and 717 (85.5%) were established HIV infection. Compared with patients with established HIV infection, those with acute HIV infection were younger, had higher RNA and CD4 counts, and were more likely to have viral syndrome (41.8% versus 6.5%) or fever (14.3% versus 3.4%) as their reason for visit. Most patients with acute HIV infection displayed symptoms attributable to acute infection (median symptom count 5 [interquartile range 3 to 6]), with fever often

  4. mRNA profiling for the identification of blood-Results of a collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, Cordula; Hanson, E; Bär, W

    2010-01-01

    of the laboratories had no prior experience with RNA. Despite some expected variation in sensitivity between laboratories, the method proved to be reproducible and sensitive using different analysis strategies. The results of this collaborative exercise support the potential use of mRNA profiling as an alternative......A collaborative exercise on mRNA profiling for the identification of blood was organized by the European DNA Profiling Group (EDNAP). Seven blood samples and one blood dilution series were analyzed by the participating laboratories for the reportedly blood-specific markers HBB, SPTB and PBGD, using...

  5. mRNA profiling for the identification of blood--Results of a collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, C.; Hanson, E.; Bär, W.

    2011-01-01

    of the laboratories had no prior experience with RNA. Despite some expected variation in sensitivity between laboratories, the method proved to be reproducible and sensitive using different analysis strategies. The results of this collaborative exercise support the potential use of mRNA profiling as an alternative......A collaborative exercise on mRNA profiling for the identification of blood was organized by the European DNA Profiling Group (EDNAP). Seven blood samples and one blood dilution series were analyzed by the participating laboratories for the reportedly blood-specific markers HBB, SPTB and PBGD, using...

  6. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA in blood donors

    Directory of Open Access Journals (Sweden)

    Felicidade Mota Pereira

    2014-01-01

    Full Text Available Introduction: Hepatitis C virus (HCV infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. Methods: A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany, the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA, the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA and line probe assay (LiPA - Siemens, Tarrytown, NY, USA genotyping for HCV diagnosis. Results: Of these new samples, 38.2% (39/102 were positive, 57.8% (59/102 were negative and 3.9% (4/102 were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102 of the samples. RIBA results were positive in 58.1% (25/43, negative in 9.3% (4/43 and indeterminate in 32.6% (14/43 of the samples. The prevailing genotypes were 1 (78.3%, 18/23, 3 (17.4%, 4/23 and 2 (4.3%, 1/23. All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL. Of these samples, 71.4% (10/14 were reevaluated six months later. Eighty percent (8/10 of these samples remained indeterminate by RIBA, and 20% (2/10 were negative. Conclusions: In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

  7. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA) in blood donors.

    Science.gov (United States)

    Pereira, Felicidade Mota; Zarife, Maria Alice Sant'ana; Reis, Eliana Almeida Gomes; G Reis, Mitermayer

    2014-01-01

    Hepatitis C virus (HCV) infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA) and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA) at the Hematology and Hemotherapy Foundation of Bahia (HEMOBA) were later assessed with new samples using the Abbott Architect anti-HCV test (Abbott Diagnostics, Wiesbaden, Germany), the RIBA III test (Chiron RIBA HCV 3.0 SIA, Chiron Corp., Emeryville, CA, USA), the polymerase chain reaction (PCR; COBAS® AMPLICOR HCV Roche Diagnostics Corp., Indianapolis, IN, USA) and line probe assay (LiPA - Siemens, Tarrytown, NY, USA) genotyping for HCV diagnosis. Of these new samples, 38.2% (39/102) were positive, 57.8% (59/102) were negative and 3.9% (4/102) were indeterminate for anti-HCV; HCV-RNA was detected in 22.5% (23/102) of the samples. RIBA results were positive in 58.1% (25/43), negative in 9.3% (4/43) and indeterminate in 32.6% (14/43) of the samples. The prevailing genotypes were 1 (78.3%, 18/23), 3 (17.4%, 4/23) and 2 (4.3%, 1/23). All 14 samples with indeterminate RIBA results had undetectable viral loads (detection limit ≤50 IU/mL). Of these samples, 71.4% (10/14) were reevaluated six months later. Eighty percent (8/10) of these samples remained indeterminate by RIBA, and 20% (2/10) were negative. In this study, individuals with indeterminate RIBA results had no detectable HCV-RNA.

  8. Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study.

    Science.gov (United States)

    Scagnolari, Carolina; Corano Scheri, Giuseppe; Selvaggi, Carla; Schietroma, Ivan; Najafi Fard, Saeid; Mastrangelo, Andrea; Giustini, Noemi; Serafino, Sara; Pinacchio, Claudia; Pavone, Paolo; Fanello, Gianfranco; Ceccarelli, Giancarlo; Vullo, Vincenzo; d'Ettorre, Gabriella

    2016-09-27

    Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients' quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial.

  9. Nanoparticles containing siRNA to silence CD4 and CCR5 reduce expression of these receptors and inhibit HIV-1 infection in human female reproductive tract tissue explants

    Directory of Open Access Journals (Sweden)

    Susan K. Eszterhas

    2011-09-01

    Full Text Available Human Immunodeficiency Virus-type 1 (HIV- 1 binds to CD4 and CCR5 receptors on target cells in the human female reproductive tract. We sought to determine whether reducing levels of messenger RNA (mRNA transcripts that encode these receptors in female reproductive tract cells could protect mucosal tissue explants from HIV- 1 infection. Explants prepared from the endometrium, endocervix, and ectocervix of hysterectomy tissues from HIV-1 sero-negative women were exposed to nanoparticles containing CD4- and CCR5-specific short-interfering RNA (siRNA sequences. Explants were then exposed two days later to HIV-1, and HIV-1 reverse transcripts were measured five days post-infection. Explants treated with nanoparticles containing CD4- and CCR5-specific siRNA showed reduced levels of CD4 and CCR5 transcripts, and significantly lower levels of HIV-1 reverse transcripts compared to those treated with an irrelevant siRNA. In female reproductive tract explants and in peripheral blood cell cultures, siRNA transfection induced the secretion of IFN-alpha (IFN-α, a potent antiviral cytokine. In female mice, murine-specific Cd4-siRNA nanoparticles instilled within the uterus significantly reduced murine Cd4 transcripts by day 3. Our findings demonstrate that siRNA nanoparticles reduce expression of HIV-1 infectivity receptors in human female reproductive tract tissues and also inhibit HIV-1 infection. Murine studies demonstrate that nanoparticles can penetrate the reproductive tract tissues in vivo and silence gene expression. The induction of IFN-α after siRNA transfection can potentially contribute to the antiviral effect. These findings support the therapeutic development of nanoparticles to deliver siRNA molecules to silence host cell receptors in the female reproductive tract as a novel microbicide to inhibit mucosal HIV-1 transmission.

  10. Knowledge, attitudes and practices of HIV-positive patients regarding disclosure of HIV results at Betesda Clinic in Namibia

    Directory of Open Access Journals (Sweden)

    Penelope Tom

    2013-02-01

    Objectives: The objectives of the study were to determine knowledge, attitudes, and practices of HIV-positive patients regarding the disclosure of HIV status at Betesda Clinic in Namibia, and to determine the reasons for disclosure and non-disclosure. Methods: This was a cross-sectional descriptive study and 263 HIV-positive patients were enrolled in the study. Results: Analyses revealed that knowledge on disclosure was good, with 68% who thought it was important. The majority (73% have disclosed and 60% disclosed within 1 week of receiving their results. The most common reasons for disclosure were that 32% needed help, 25% wanted his or her partner to go for testing, and 20% wanted to let relatives know. Reasons for non-disclosure were mainly the fear of gossip (79%. Seventy-three per cent had disclosed to their partners, and 23% had disclosed to more than one person. People’s reactions were supportive in 43%, whereas 29% understood, 9% accepted and 6% were angry. Upon disclosure 40% received help, 24% of partners were tested, 23% received psychological support and 5% were stigmatised. Disclosure was higher amongst the married and cohabitating. Conclusion: The attitude was positive with regard to knowledge of disclosure, with most participants thinking that disclosure was important and good. The attitudes and actual practices of disclosure were encouraging; however, people are disclosing only to trusted individuals in the society and the fear of stigma is still present although the actual stigma was very low.

  11. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  12. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  13. 2012 HIV Diagnostics Conference: the molecular diagnostics perspective.

    Science.gov (United States)

    Branson, Bernard M; Pandori, Mark

    2013-04-01

    2012 HIV Diagnostic Conference Atlanta, GA, USA, 12-14 December 2012. This report highlights the presentations and discussions from the 2012 National HIV Diagnostic Conference held in Atlanta (GA, USA), on 12-14 December 2012. Reflecting changes in the evolving field of HIV diagnostics, the conference provided a forum for evaluating developments in molecular diagnostics and their role in HIV diagnosis. In 2010, the HIV Diagnostics Conference concluded with the proposal of a new diagnostic algorithm which included nucleic acid testing to resolve discordant screening and supplemental antibody test results. The 2012 meeting, picking up where the 2010 meeting left off, focused on scientific presentations that assessed this new algorithm and the role played by RNA testing and new developments in molecular diagnostics, including detection of total and integrated HIV-1 DNA, detection and quantification of HIV-2 RNA, and rapid formats for detection of HIV-1 RNA.

  14. MicroRNA-210, MicroRNA-331, and MicroRNA-7 Are Differentially Regulated in Treated HIV-1–Infected Individuals and Are Associated With Markers of Systemic Inflammation

    DEFF Research Database (Denmark)

    Ballegaard, Vibe; Ralfkiaer, Ulrik; Pedersen, Karin K.

    2017-01-01

    in inflammation and CVD risk and to investigate associations between these and systemic inflammation. Methods: In a screening cohort including 14 HIV-1-infected individuals and 9 uninfected controls, microarray profiling was performed using peripheral blood mononuclear cells (PBMCs). Differentially regulated mi......-sensitivity C-reactive protein, lipopolysaccharide (LPS), cytomegalovirus immunoglobulin G, lipids, and fasting glucose were measured, and associations with validated miRNAs were assessed with multiple linear regression analysis. Results: Upregulation of miR-210, miR-7, and miR-331 was found in PBMCs from HIV-1...... with tumor necrosis factor-alpha (P = 0.004). MiR-7 in PBMC was positively associated with interleukin-6 (P = 0.025) and fasting glucose (P = 0.005), whereas miR-331 was negatively associated with LPS (P = 0.006). In PBMCs from HIV-1-infected individuals with low cytomegalovirus immunoglobulin G, miR-7, mi...

  15. HIV-1 Viral RNA Dynamics at the Plasma Membrane May Provide Insight into Viral Assembly | Poster

    Science.gov (United States)

    Many aspects of how infectious viruses assemble in cells have yet to be completely deciphered. However, as reported in a recent Journal of Virology paper, researchers may be one step closer to understanding how HIV-1, the virus that causes AIDS, assembles and replicates.

  16. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression

    International Nuclear Information System (INIS)

    Nguyen, Kim-Lien; Llano, Manuel; Akari, Hirofumi; Miyagi, Eri; Poeschla, Eric M.; Strebel, Klaus; Bour, Stephan

    2004-01-01

    Two HIV-1 accessory proteins, Vpu and Vif, are notoriously difficult to express autonomously in the absence of the viral Tat and Rev proteins. We examined whether the codon bias observed in the vpu and vif genes relative to highly expressed human genes contributes to the Rev dependence and low expression level outside the context of the viral genome. The entire vpu gene as well as the 5' half of the vif gene were codon optimized and the resulting open reading frames (ORFs) (vphu and hvif, respectively) were cloned in autonomous expression vectors under the transcriptional control of the CMV promoter. Codon optimization efficiently removed the expression block observed in the native genes and allowed high levels of Rev- and Tat-independent expression of Vpu and Vif. Most of the higher protein levels detected are accounted for by enhanced steady-state levels of the mRNA encoding the optimized species. Nuclear run-on experiments show for the first time that codon optimization has no effect on the rate of transcriptional initiation or elongation of the vphu mRNA. Instead, optimization of the vpu gene was found to stabilize the vphu mRNA in the nucleus and enhance its export to the cytoplasm. This was achieved by allowing the optimized mRNA to use a new CRM1-independent nuclear export pathway. This work provides a better understanding of the molecular mechanisms underlying the process of codon optimization and introduces novel tools to study the biological functions of the Vpu and Vif proteins independently of other viral proteins

  17. Abacavir/Lamivudine plus Rilpivirine Is an Effective and Safe Strategy for HIV-1 Suppressed Patients: 48 Week Results of the SIMRIKI Retrospective Study.

    Directory of Open Access Journals (Sweden)

    Jesús Troya

    Full Text Available Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV treatment in virologically suppressed HIV-1-infected patients.We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT, missing = failure and on-treatment (OT analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations.Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients. The main reasons for switching were drug toxicity/poor tolerability (60.5% and simplification (20%. At week 48, the primary objective was achieved by 187 out of 205 (91.2% patients by ITT analysis, and 187 out of 192 (97.4% patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/μL (-50 to 189 and 1.2% (-1.3% to 4.1%, respectively, P<0.001. Thirty-eight adverse events (AE were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 [2.4%], toxicity

  18. Lack of knowledge of HIV status a major barrier to HIV prevention, care and treatment efforts in Kenya: results from a nationally representative study.

    Directory of Open Access Journals (Sweden)

    Peter Cherutich

    Full Text Available BACKGROUND: We analyzed HIV testing rates, prevalence of undiagnosed HIV, and predictors of testing in the Kenya AIDS Indicator Survey (KAIS 2007. METHODS: KAIS was a nationally representative sero-survey that included demographic and behavioral indicators and testing for HIV, HSV-2, syphilis, and CD4 cell counts in the population aged 15-64 years. We used gender-specific multivariable regression models to identify factors independently associated with HIV testing in sexually active persons. RESULTS: Of 19,840 eligible persons, 80% consented to interviews and blood specimen collection. National HIV prevalence was 7.1% (95% CI 6.5-7.7. Among ever sexually active persons, 27.4% (95% CI 25.6-29.2 of men and 44.2% (95% CI 42.5-46.0 of women reported previous HIV testing. Among HIV-infected persons, 83.6% (95% CI 76.2-91.0 were unaware of their HIV infection. Among sexually active women aged 15-49 years, 48.7% (95% CI 46.8-50.6 had their last HIV test during antenatal care (ANC. In multivariable analyses, the adjusted odds ratio (AOR for ever HIV testing in women ≥35 versus 15-19 years was 0.2 (95% CI: 0.1-0.3; p<0.0001. Other independent associations with ever HIV testing included urban residence (AOR 1.6, 95% CI: 1.2-2.0; p = 0.0005, women only, highest wealth index versus the four lower quintiles combined (AOR 1.8, 95% CI: 1.3-2.5; p = 0.0006, men only, and an increasing testing trend with higher levels of education. Missed opportunities for testing were identified during general or pregnancy-specific contacts with health facilities; 89% of adults said they would participate in home-based HIV testing. CONCLUSIONS: The vast majority of HIV-infected persons in Kenya are unaware of their HIV status, posing a major barrier to HIV prevention, care and treatment efforts. New approaches to HIV testing provision and education, including home-based testing, may increase coverage. Targeted interventions should involve sexually active men, sexually

  19. First line treatment response in patients with transmitted HIV drug resistance and well defined time point of HIV infection: updated results from the German HIV-1 seroconverter study.

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    Fabia Zu Knyphausen

    Full Text Available BACKGROUND: Transmission of drug-resistant HIV-1 (TDR can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. METHODS: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. RESULTS: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667 in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0% and decreased significantly over time (OR = 0.92, CI = 0.87-0.98, p = 0.01. Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92-1.09, p = 0.96 and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17 remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41. CONCLUSION: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were

  20. CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

    Science.gov (United States)

    Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

    2014-01-01

    CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

  1. Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study

    Science.gov (United States)

    Castagna, Antonella; Maggiolo, Franco; Penco, Giovanni; Wright, David; Mills, Anthony; Grossberg, Robert; Molina, Jean-Michel; Chas, Julie; Durant, Jacques; Moreno, Santiago; Doroana, Manuela; Ait-Khaled, Mounir; Huang, Jenny; Min, Sherene; Song, Ivy; Vavro, Cindy; Nichols, Garrett; Yeo, Jane M.; Aberg, J.; Akil, B.; Arribas, J. R.; Baril, J.-G.; Blanco Arévalo, J. L.; Blanco Quintana, F.; Blick, G.; Boix Martínez, V.; Bouchaud, O.; Branco, T.; Bredeek, U. F.; Castro Iglesias, M.; Clumeck, N.; Conway, B.; DeJesus, E.; Delassus, J.-L.; De Truchis, P.; Di Perri, G.; Di Pietro, M.; Duggan, J.; Duvivier, C.; Elion, R.; Eron, J.; Fish, D.; Gathe, J.; Haubrich, R.; Henderson, H.; Hicks, C.; Hocqueloux, L.; Hodder, S.; Hsiao, C.-B.; Katlama, C.; Kozal, M.; Kumar, P.; Lalla-Reddy, S.; Lazzarin, A.; Leoncini, F.; Llibre, J. M.; Mansinho, K.; Morlat, P.; Mounzer, K.; Murphy, M.; Newman, C.; Nguyen, T.; Nseir, B.; Philibert, P.; Pialoux, G.; Poizot-Martin, I.; Ramgopal, M.; Richmond, G.; Salmon Ceron, D.; Sax, P.; Scarsella, A.; Sension, M.; Shalit, P.; Sighinolfi, L.; Sloan, L.; Small, C.; Stein, D.; Tashima, K.; Tebas, P.; Torti, C.; Tribble, M.; Troisvallets, D.; Tsoukas, C.; Viciana Fernández, P.; Ward, D.; Wheeler, D.; Wilkin, T.; Yeni, G.-P.; Louise Martin-Carpenter, J.; Uhlenbrauck, Gina

    2014-01-01

    Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was −1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574). PMID:24446523

  2. Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT

    Directory of Open Access Journals (Sweden)

    Ross Lisa L

    2008-03-01

    Full Text Available Abstract Background Once-daily (QD ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100 or atazanavir 300 mg (ATV/r100, plus tenofovir/emtricitabine (TDF/FTC 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an open-label, multicenter 48-week study (ALERT in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log10 copies/mL; CD4+ count 191 cells/mm3 randomly assigned to the FPV/r100 or ATV/r100 regimens. Results At baseline, the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA (median, 4.9 log10 copies/mL [both], CD4+ count (mean, 176 vs 205 cells/mm3. At week 48, intent-to-treat: missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 (HIV-1 RNA 3, p = 0.398 [Wilcoxon rank sum test]. Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar, although week 48 median fasting triglycerides were higher with FPV/r100 (150 vs 131 mg/dL. FPV/r100-treated patients experienced fewer treatment-related grade 2–4 adverse events (15% vs 57%, with differences driven by ATV-related hyperbilirubinemia. Three patients discontinued TDF/FTC because their GFR decreased to Conclusion The all-QD regimens of FPV/r100 and ATV/r100, plus TDF/FTC, provided similar virologic, CD4+ response, and fasting total/LDL/HDL-cholesterol changes through 48 weeks. Fewer FPV/r100-treated patients experienced treatment-related grade 2–4 adverse events.

  3. Factors Associated with Participation in HIV Antibody Screening and Results Disclosure.

    Science.gov (United States)

    Silvestre, Anthony J.; And Others

    1993-01-01

    Identified differences among 110 gay and bisexual men who decided whether to be tested for antibodies to human immunodeficiency virus (HIV) and, if so, whether to return for results. Fifty percent refused testing. Of those tested, only 35% returned to obtain test results. Education was significantly and inversely related to being tested and to…

  4. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    , a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral...... to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...

  5. Health Care Use and HIV-Related Behaviors of Black and Latina Transgender Women in 3 US Metropolitan Areas: Results From the Transgender HIV Behavioral Survey.

    Science.gov (United States)

    Denson, Damian J; Padgett, Paige M; Pitts, Nicole; Paz-Bailey, Gabriela; Bingham, Trista; Carlos, Juli-Ann; McCann, Pamela; Prachand, Nikhil; Risser, Jan; Finlayson, Teresa

    2017-07-01

    HIV prevalence estimates among transgender women in the United States are high, particularly among racial/ethnic minorities. Despite increased HIV risk and evidence of racial disparities in HIV prevalence among transgender women, few data are available to inform HIV prevention efforts. A transgender HIV-related behavioral survey conducted in 2009 in 3 US metropolitan areas (Chicago, Houston, and Los Angeles County), used respondent-driven sampling to recruit 227 black (n = 139) and Latina (n = 88) transgender women. We present descriptive statistics on sociodemographic, health care, and HIV-risk behaviors. Of 227 transgender women enrolled, most were economically and socially disadvantaged: 73% had an annual income of less than $15,000; 62% lacked health insurance; 61% were unemployed; and 46% reported being homeless in the past 12 months. Most (80%) had visited a health care provider and over half (58%) had tested for HIV in the past 12 months. Twenty-nine percent of those who reported having an HIV test in the past 24 months self-reported being HIV positive. Most of the sample reported hormone use (67%) in the past 12 months and most hormone use was under clinical supervision (70%). Forty-nine percent reported condomless anal sex in the past 12 months and 16% reported ever injecting drugs. These findings reveal the socioeconomic challenges and behavioral risks often associated with high HIV risk reported by black and Latina transgender women. Despite low health insurance coverage, the results suggest opportunities to engage transgender women in HIV prevention and care given their high reported frequency of accessing health care providers.

  6. Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates Efeito das drogas anti-retrovirais sobre os valores dos linfócitos TCD4, RNA do HIV-1 e parâmetros antropométricos de neonatos de gestantes portadoras do HIV-1

    Directory of Open Access Journals (Sweden)

    Patrícia El Beitune

    2005-06-01

    Full Text Available PURPOSE: To study the effect of antiretroviral drugs administered during pregnancy on CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women and on the anthropometric parameters of their neonates. METHODS: A prospective study was conducted on 57 pregnant women and their neonates divided into 3 groups: ZDV Group, HIV-infected mothers taking zidovudine (n = 20; triple therapy (TT Group, mothers taking zidovudine + lamivudine + nelfinavir (n = 25, and Control Group, normal women (n = 12. CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women were analyzed during two periods of pregnancy. The perinatal prognosis took into account preterm rates, birth weight, intrauterine growth restriction, perinatal death, and vertical transmission of HIV-1. Data were analyzed statistically using the nonparametric chi-square, Mann-Whitney, Friedman, Kruskal-Wallis, and Wilcoxon matched pairs tests, with the level of significance set at P OBJETIVOS: Estudar o efeito das drogas anti-retrovirais sobre a quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV-1 e parâmetros antropométricos de seus neonatos. MÉTODOS: Estudo prospectivo avaliando 57 gestantes e seus neonatos em três grupos: Grupo AZT, gestantes portadoras do HIV utilizando zidovudina (n=20; Grupo TT, mães utilizando zidovudina+lamivudina+nelfinavir (n=25, e Grupo Controle, mulheres saudáveis (n=12. A quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV foi analisada em dois períodos durante a gestação. O prognóstico perinatal levou em consideração as taxas de pré-termos, restrição de crescimento intra-útero, mortalidade perinatal e transmissão vertical do HIV-1. Os dados foram analisados utilizando-se testes não paramétricos de qui-quadrado, Mann-Whitney, Friedman, Kruskal-Wallys e Wilcoxon para amostras pareadas, considerando-se significativos valores associados a p<0,05. RESULTADOS: Observou-se homogeneidade entre

  7. Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism.

    Science.gov (United States)

    Marquet, R; Baudin, F; Gabus, C; Darlix, J L; Mougel, M; Ehresmann, C; Ehresmann, B

    1991-05-11

    The retroviral genome consists of two identical RNA molecules joined close to their 5' ends by the dimer linkage structure. Recent findings indicated that retroviral RNA dimerization and encapsidation are probably related events during virion assembly. We studied the cation-induced dimerization of HIV-1 RNA and results indicate that all in vitro generated HIV-1 RNAs containing a 100 nucleotide domain downstream from the 5' splice site are able to dimerize. RNA dimerization depends on the concentration of RNA, mono- and multivalent cations, the size of the monovalent cation, temperature, and pH. Up to 75% of HIV-1 RNA is dimeric in the presence of spermidine. HIV-1 RNA dimer is fairly resistant to denaturing agents and unaffected by intercalating drugs. Antisense HIV-1 RNA does not dimerize but heterodimers can be formed between HIV-1 RNA and either MoMuLV or RSV RNA. Therefore retroviral RNA dimerization probably does not simply proceed through mechanisms involving Watson-Crick base-pairing. Neither adenine and cytosine protonation, nor quartets containing only guanines appear to determine the stability of the HIV-1 RNA dimer, while quartets involving both adenine(s) and guanine(s) could account for our results. A consensus sequence PuGGAPuA found in the putative dimerization-encapsidation region of all retroviral genomes examined may participate in the dimerization process.

  8. Comparación de los métodos de cuantificación de carga viral de VIH: COBAS® AmpliPrep/COBAS® TaqMan HIV-1 test, v 2.0, y VERSANT HIV-1 RNA 1.0 Assay (kPCR Comparison of COBAS® AmpliPrep/COBAS® TaqMan HIV-1 test, v 2.0 and VERSANT HIV-1 RNA 1.0 (kPCR assays for HIV-1 plasma viral load

    Directory of Open Access Journals (Sweden)

    María Isabel Múnera-Jaramillo

    2012-03-01

    processed for quantification of HIV-1 RNA by both techniques. A regression analysis, the Pearson correlation coefficient and agreement of Lin were done. The agreement between the two techniques was evaluated with the Bland Altman analysis. Results: The mean viral load by CAP/CTM was 3.2 ± 1.4 long10 copies/ml and by kPCR it was 3.0±1.3 10 copies/ml. Most samples (86.7% showed differences between the two methods lower than 0.5 long10 copies/ml, and 13.3% presented greater differences. The Pearson correlation coefficient between the two methods was 0.97 (95% CI 0.95-0.99 and the weighted kappa index between the two methods, in different ranges of concentration, was 0.91 (95% CI 0.87-0.96. The average difference between measurements by both techniques was 0.22 long10 copies/ml, (IC 95% -0.45-0.89. Conclusion: Both techniques were comparable, although lower values of viral load were observed with kPCR.

  9. A collaborative European exercise on mRNA-based body fluid/skin typing and interpretation of DNA and RNA results

    DEFF Research Database (Denmark)

    van den Berge, M; Carracedo, A; Gomes, I

    2014-01-01

    The European Forensic Genetics Network of Excellence (EUROFORGEN-NoE) undertook a collaborative project on mRNA-based body fluid/skin typing and the interpretation of the resulting RNA and DNA data. Although both body fluids and skin are composed of a variety of cell types with different function...

  10. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study

    DEFF Research Database (Denmark)

    Viard, Jean-Paul; Souberbielle, Jean-Claude; Kirk, Ole

    2011-01-01

    BACKGROUND:: We examined the association between vitamin D [25(OH)D] level and disease progression in HIV infection. METHODS:: Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored plasma samples closest to study entry. 25(OH)D results were stratified...

  11. False-negative syphilis treponemal enzyme immunoassay results in an HIV-infected case-patient.

    Science.gov (United States)

    Katz, Alan R; Komeya, Alan Y; Tomas, Juval E

    2017-06-01

    We present a case report of a false-negative syphilis treponemal enzyme immunoassay test result in an HIV-infected male. While treponemal tests are widely considered to be more sensitive and specific than non-treponemal tests, our findings point to potential challenges using the reverse sequence syphilis screening algorithm.

  12. The connection domain in reverse transcriptase facilitates the in vivo annealing of tRNALys3 to HIV-1 genomic RNA

    Directory of Open Access Journals (Sweden)

    Niu Meijuan

    2004-10-01

    Full Text Available Abstract The primer tRNA for reverse transcription in HIV-1, tRNALys3, is selectively packaged into the virus during its assembly, and annealed to the viral genomic RNA. The ribonucleoprotein complex that is involved in the packaging and annealing of tRNALys into HIV-1 consists of Gag, GagPol, tRNALys, lysyl-tRNA synthetase (LysRS, and viral genomic RNA. Gag targets tRNALys for viral packaging through Gag's interaction with LysRS, a tRNALys-binding protein, while reverse transcriptase (RT sequences within GagPol (the thumb domain bind to tRNALys. The further annealing of tRNALys3 to viral RNA requires nucleocapsid (NC sequences in Gag, but not the NC sequences GagPol. In this report, we further show that while the RT connection domain in GagPol is not required for tRNALys3 packaging into the virus, it is required for tRNALys3 annealing to the viral RNA genome.

  13. Phosphate-methylated DNA aimed at HIV-1 RNA loops and integrated DNA inhibits viral infectivity

    NARCIS (Netherlands)

    Buck, H. M.; Koole, L. H.; van Genderen, M. H.; Smit, L.; Geelen, J. L.; Jurriaans, S.; Goudsmit, J.

    1990-01-01

    Phosphate-methylated DNA hybridizes strongly and specifically to natural DNA and RNA. Hybridization to single-stranded and double-stranded DNA leads to site-selective blocking of replication and transcription. Phosphate-methylated DNA was used to interrupt the life cycle of the human

  14. Results of the Abbott RealTime HIV-1 Assay for Specimens Yielding “Target Not Detected” Results by the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test▿

    OpenAIRE

    Babady, N. Esther; Germer, Jeffrey J.; Yao, Joseph D. C.

    2009-01-01

    No significantly discordant results were observed between the Abbott RealTime HIV-1 assay and the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (CTM) among 1,190 unique clinical plasma specimens obtained from laboratories located in 40 states representing all nine U.S. geographic regions and previously yielding “target not detected” results by CTM.

  15. Results of the Abbott RealTime HIV-1 assay for specimens yielding "target not detected" results by the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test.

    Science.gov (United States)

    Babady, N Esther; Germer, Jeffrey J; Yao, Joseph D C

    2010-03-01

    No significantly discordant results were observed between the Abbott RealTime HIV-1 assay and the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (CTM) among 1,190 unique clinical plasma specimens obtained from laboratories located in 40 states representing all nine U.S. geographic regions and previously yielding "target not detected" results by CTM.

  16. The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome.

    Directory of Open Access Journals (Sweden)

    Nikki van Bel

    Full Text Available The viral integrase (IN is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs. Although designed to interfere with the IN-LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV-1 replication, the major impact was surprisingly found on the process of virus maturation during the late phase, causing a reverse transcription defect upon infection of target cells. Virus particles produced in the presence of an ALLINI are misformed with the ribonucleoprotein located outside the virus core. Virus assembly and maturation are highly orchestrated and regulated processes in which several viral proteins and RNA molecules closely interact. It is therefore of interest to study whether ALLINIs have unpredicted pleiotropic effects on these RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication and that the produced virus is non-infectious. Furthermore, we show that the wild-type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a dimeric state. The tRNAlys3 primer for reverse transcription was properly placed on this genomic RNA and could be extended ex vivo. In addition, the packaged reverse transcriptase enzyme was fully active when extracted from virions. As the RNA and enzyme components for reverse transcription are properly present in virions produced in the presence of BI-D, the inhibition of reverse transcription is likely to reflect the mislocalization of the components in the aberrant virus particle.

  17. The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome.

    Science.gov (United States)

    van Bel, Nikki; van der Velden, Yme; Bonnard, Damien; Le Rouzic, Erwann; Das, Atze T; Benarous, Richard; Berkhout, Ben

    2014-01-01

    The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs). Although designed to interfere with the IN-LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV-1 replication, the major impact was surprisingly found on the process of virus maturation during the late phase, causing a reverse transcription defect upon infection of target cells. Virus particles produced in the presence of an ALLINI are misformed with the ribonucleoprotein located outside the virus core. Virus assembly and maturation are highly orchestrated and regulated processes in which several viral proteins and RNA molecules closely interact. It is therefore of interest to study whether ALLINIs have unpredicted pleiotropic effects on these RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication and that the produced virus is non-infectious. Furthermore, we show that the wild-type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a dimeric state. The tRNAlys3 primer for reverse transcription was properly placed on this genomic RNA and could be extended ex vivo. In addition, the packaged reverse transcriptase enzyme was fully active when extracted from virions. As the RNA and enzyme components for reverse transcription are properly present in virions produced in the presence of BI-D, the inhibition of reverse transcription is likely to reflect the mislocalization of the components in the aberrant virus particle.

  18. Perception of taste in HIV-positive individuals in treatment antiretroviral: results of a case-control study.

    Science.gov (United States)

    Henn, Indiara Welter; da Silva, Ruann Oswaldo Carvalho; Chaiben, Cassiano Lima; Fernandes, Ângela; Naval Machado, Maria Ângela; de Lima, Antonio Adilson Soares

    2017-01-01

    The aim of this study was to evaluate the perception of taste in HIV-infected patients. One hundred males and females (11 to 60 years old) were divided into two groups (50 patients infected by HIV and 50 controls) and evaluated for gustatory function. The results revealed that the mean score in the evaluation of taste was significantly lower in individuals with HIV when compared to controls for both sides of the tongue (p < 0.05). Patients with HIV infection had difficulty recognizing the bitter taste, followed by salty and sweet. When each side of the tongue was evaluated separately and compared, the Wilcoxon test showed that there was no significant difference on the tongue of individuals with HIV. The prevalence of hypogeusia was 20% in individuals with this disease. Individuals with HIV infection may have a deficit in taste that can affect your general and oral health. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

  19. HIV status: the prima facie right not to know the result.

    Science.gov (United States)

    Chan, Tak Kwong

    2016-02-01

    When a patient regains consciousness from Cryptococcus meningitis, the clinician may offer an HIV test (in case it has not already been done) (scenario 1) or offer to tell the patient his HIV status (in case the test has already been performed with a positive result while the patient was unconscious) (scenario 2). Youngs and Simmonds proposed that the patient has the prima facie right to refuse an HIV test in scenario 1 but not the prima facie right not to be told the HIV status in scenario 2. I submit that the claims to the right of refusal in both scenarios are similarly strong as they should both be grounded in privacy, self determination or dignity. But a conscientious agent should bear in mind that members of the public also have the right not to be harmed. When the circumstance allows, a proper balance of the potential benefits and harm for all the competing parties should guide the clinical decision as to whose right should finally prevail. Where a full ethical analysis is not possible, the presumption should favour respecting the patient's right of refusal in both scenarios. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Deep-sequencing protocols influence the results obtained in small-RNA sequencing.

    Directory of Open Access Journals (Sweden)

    Joern Toedling

    Full Text Available Second-generation sequencing is a powerful method for identifying and quantifying small-RNA components of cells. However, little attention has been paid to the effects of the choice of sequencing platform and library preparation protocol on the results obtained. We present a thorough comparison of small-RNA sequencing libraries generated from the same embryonic stem cell lines, using different sequencing platforms, which represent the three major second-generation sequencing technologies, and protocols. We have analysed and compared the expression of microRNAs, as well as populations of small RNAs derived from repetitive elements. Despite the fact that different libraries display a good correlation between sequencing platforms, qualitative and quantitative variations in the results were found, depending on the protocol used. Thus, when comparing libraries from different biological samples, it is strongly recommended to use the same sequencing platform and protocol in order to ensure the biological relevance of the comparisons.

  1. Self-Reported HIV-Positive Status But Subsequent HIV-Negative Test Result Using Rapid Diagnostic Testing Algorithms Among Seven Sub-Saharan African Military Populations

    Science.gov (United States)

    2017-07-07

    analysis, data interpretation, or writing of the report. Leidos provided support in the form of salaries for JH, BRT, AGT, MBJ and JM but did not have any...have data on a QA process. The survey used for all seven partner mili- taries was based on a standardized modular survey, which assessed HIV risk... Technical considerations Technical limitations have been shown to increase false-positive HIV test results in voluntary counseling and testing centers

  2. Conformations of flanking bases in HIV-1 RNA DIS kissing complexes studied by molecular dynamics

    Czech Academy of Sciences Publication Activity Database

    Réblová, Kamila; Fadrná, E.; Sarzynska, J.; Kulinski, T.; Kulhánek, P.; Ennifar, E.; Koča, J.; Šponer, Jiří

    2007-01-01

    Roč. 93, č. 11 (2007), s. 3932-3949 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LC06030; GA ČR(CZ) GA203/05/0009; GA ČR(CZ) GA203/05/0388; GA AV ČR(CZ) 1QS500040581 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : molecular dynamics * RNA * virus Subject RIV: BO - Biophysics Impact factor: 4.627, year: 2007

  3. Can a short film impact HIV-related risk and stigma perceptions? Results from an experiment in Abuja, Nigeria.

    Science.gov (United States)

    Lapinski, Maria Knight; Nwulu, Paul

    2008-09-01

    HIV/AIDS-related stigma is believed to result in negative social consequences for people with the disease and to be a deterrent to HIV serostatus testing. The ability of communicators to change people's stigma perceptions and subsequently impact decisions to test, however, is not well understood. Based on the entertainment-education approach, this article presents the results of a field experiment conducted in Abuja, Nigeria, testing a mediated intervention designed to reduce HIV-related stigma and risk perceptions. The results indicate that the intervention was effective relative to a control in impacting perceptions of the severity of HIV and some stigma-related attitudes, particularly for male participants; and that for this sample, risk and stigma perceptions significantly impact intentions to test for HIV. It also showed that severity perceptions mediated the relationship between viewing the film and testing intent.

  4. Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

    Directory of Open Access Journals (Sweden)

    Nadia Bakkour

    2007-10-01

    Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

  5. Markovian negentropies in bioinformatics. 1. A picture of footprints after the interaction of the HIV-1 Psi-RNA packaging region with drugs.

    Science.gov (United States)

    Díaz, Humberto González; de Armas, Ronal Ramos; Molina, Reinaldo

    2003-11-01

    Many experts worldwide have highlighted the potential of RNA molecules as drug targets for the chemotherapeutic treatment of a range of diseases. In particular, the molecular pockets of RNA in the HIV-1 packaging region have been postulated as promising sites for antiviral action. The discovery of simpler methods to accurately represent drug-RNA interactions could therefore become an interesting and rapid way to generate models that are complementary to docking-based systems. The entropies of a vibrational Markov chain have been introduced here as physically meaningful descriptors for the local drug-nucleic acid complexes. A study of the interaction of the antibiotic Paromomycin with the packaging region of the RNA present in type-1 HIV has been carried out as an illustrative example of this approach. A linear discriminant function gave rise to excellent discrimination among 80.13% of interacting/non-interacting sites. More specifically, the model classified 36/45 nucleotides (80.0%) that interacted with paromomycin and, in addition, 85/106 (80.2%) footprinted (non-interacting) sites from the RNA viral sequence were recognized. The model showed a high Matthews' regression coefficient (C = 0.64). The Jackknife method was also used to assess the stability and predictability of the model by leaving out adenines, C, G, or U. Matthews' coefficients and overall accuracies for these approaches were between 0.55 and 0.68 and 75.8 and 82.7, respectively. On the other hand, a linear regression model predicted the local binding affinity constants between a specific nucleotide and the aforementioned antibiotic (R2 = 0.83,Q2 = 0.825). These kinds of models may play an important role either in the discovery of new anti-HIV compounds or in the elucidation of their mode of action. On request from the corresponding author (humbertogd@cbq.uclv.edu.cu or humbertogd@navegalia.com).

  6. Correlates of HIV-1 genital shedding in Tanzanian women.

    Directory of Open Access Journals (Sweden)

    Clare Tanton

    2011-03-01

    Full Text Available Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo in Tanzania.Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load.Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load.RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

  7. Indeterminate RIBA results were associated with the absence of hepatitis C virus RNA (HCV-RNA) in blood donors

    OpenAIRE

    Pereira, Felicidade Mota; Zarife, Maria Alice Sant'ana; Reis, Eliana Almeida Gomes; G. Reis, Mitermayer

    2014-01-01

    Introduction: Hepatitis C virus (HCV) infection is diagnosed by the presence of antibodies and is supplemented by confirmatory testing methods, such as recombinant immunoblot assay (RIBA) and HCV-RNA detection. This study aimed to evaluate the efficacy of RIBA testing to diagnose HCV infection in blood donors positive for anti-HCV antibodies. Methods: A total of 102 subjects positive for anti-HCV determined by enzyme-linked immunosorbent assay (ELISA) at the Hematology and Hemotherapy Found...

  8. Lost opportunities to identify and treat HIV-positive patients: results from a baseline assessment of provider-initiated HIV testing and counselling (PITC) in Malawi.

    Science.gov (United States)

    Ahmed, Saeed; Schwarz, Monica; Flick, Robert J; Rees, Chris A; Harawa, Mwelura; Simon, Katie; Robison, Jeff A; Kazembe, Peter N; Kim, Maria H

    2016-04-01

    To assess implementation of provider-initiated testing and counselling (PITC) for HIV in Malawi. A review of PITC practices within 118 departments in 12 Ministry of Health (MoH) facilities across Malawi was conducted. Information on PITC practices was collected via a health facility survey. Data describing patient visits and HIV tests were abstracted from routinely collected programme data. Reported PITC practices were highly variable. Most providers practiced symptom-based PITC. Antenatal clinics and maternity wards reported widespread use of routine opt-out PITC. In 2014, there was approximately 1 HIV test for every 15 clinic visits. HIV status was ascertained in 94.3% (5293/5615) of patients at tuberculosis clinics, 92.6% (30,675/33,142) of patients at antenatal clinics and 49.4% (6871/13,914) of patients at sexually transmitted infection clinics. Reported challenges to delivering PITC included test kit shortages (71/71 providers), insufficient physical space (58/71) and inadequate number of HIV counsellors (32/71) while providers from inpatient units cited the inability to test on weekends. Various models of PITC currently exist at MoH facilities in Malawi. Only antenatal and maternity clinics demonstrated high rates of routine opt-out PITC. The low ratio of facility visits to HIV tests suggests missed opportunities for HIV testing. However, the high proportion of patients at TB and antenatal clinics with known HIV status suggests that routine PITC is feasible. These results underscore the need to develop clear, standardised PITC policy and protocols, and to address obstacles of limited health commodities, infrastructure and human resources. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  9. Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

    Science.gov (United States)

    Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2016-07-01

    Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

  10. HISTOPLASMIN SURVEY IN HIV-POSITIVE PATIENTS: RESULTS FROM AN ENDEMIC AREA IN NORTHEASTERN BRAZIL

    Directory of Open Access Journals (Sweden)

    Fabricia Salvador Bezerra

    2013-07-01

    Full Text Available SUMMARY Background. Disseminated histoplasmosis is common in AIDS patients with advanced immunosuppression in Ceará, Northeastern Brazil. The goal of this study was to determine the prevalence of Histoplasma infection in patients with HIV/AIDS living in Fortaleza, the capital of Ceará. Methods. Intradermal tests with histoplasmin (mycelial phase were performed in 161 HIV patients with CD4 ≥ 350 cells/mm 3 . Evidence of recent illness was evaluated with immunodiffusion (ID tests in 76 of these individuals. Results. A total of 11.8% of patients reacted to histoplasmin and 2.63% had ID test positive to Histoplasma. The presence of mango trees (Mangifera indica in the patient neighborhood (OR = 2.870; 95% CI = 1.081-7.617; p = 0.040 and past activity involving soil (OR = 2.834; 95% CI = 1.045-7.687; p = 0.045 or visits to a farm (OR = 3.869; 95% CI = 1.189-12.591; p = 0.033 were significantly associated with Histoplasma infection. Conclusions. Patients with HIV living in Fortaleza have an expressive prevalence of infection with Histoplasma.

  11. "Know Your Status": results from a novel, student-run HIV testing initiative on college campuses.

    Science.gov (United States)

    Milligan, Caitlin; Cuneo, C Nicholas; Rutstein, Sarah E; Hicks, Charles

    2014-08-01

    Know Your Status (KYS), a novel, student-run program offered free HIV-testing at a private university (PU) and community college (CC). Following completion of surveys of risk behaviors/reasons for seeking testing, students were provided with rapid, oral HIV-testing. We investigated testing history, risk behaviors, and HIV prevalence among students tested during the first three years of KYS. In total, 1408 tests were conducted, 5 were positive: 4/408 CC, 1/1000 PU (1% vs. 0.1%, p=0.01). Three positives were new diagnoses, all black men-who-have-sex-with-men (MSM). Over 50% of students were tested for the first time and 59% reported risk behaviors. CC students were less likely to have used condoms at last sex (a surrogate for risk behavior) compared to PU (OR 0.73, CI [0.54, 0.98]). Race, sexual identity, and sex were not associated with condom use. These results demonstrate that KYS successfully recruited large numbers of previously untested, at-risk students, highlighting the feasibility and importance of testing college populations.

  12. Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients

    Directory of Open Access Journals (Sweden)

    Samuel I. Anyanwu

    2018-01-01

    Full Text Available Background. Extracellular vesicles (EVs are membrane bound, secreted by cells, and detected in bodily fluids, including urine, and contain proteins, RNA, and DNA. Our goal was to identify HIV and human proteins (HPs in urinary EVs from HIV+ patients and compare them to HIV− samples. Methods. Urine samples were collected from HIV+ (n=35 and HIV− (n=12 individuals. EVs were isolated by ultrafiltration and characterized using transmission electron microscopy, tandem mass spectrometry (LC/MS/MS, and nanoparticle tracking analysis (NTA. Western blots confirmed the presence of HIV proteins. Gene ontology (GO analysis was performed using FunRich and HIV Human Interaction database (HHID. Results. EVs from urine were 30–400 nm in size. More EVs were in HIV+ patients, P<0.05, by NTA. HIV+ samples had 14,475 HPs using LC/MS/MS, while only 111 were in HIV−. HPs in the EVs were of exosomal origin. LC/MS/MS showed all HIV+ samples contained at least one HIV protein. GO analysis showed differences in proteins between HIV+ and HIV− samples and more than 50% of the published HPs in the HHID interacted with EV HIV proteins. Conclusion. Differences in the proteomic profile of EVs from HIV+ versus HIV− samples were found. HIV and HPs in EVs could be used to detect infection and/or diagnose HIV disease syndromes.

  13. Pregnancy does not affect HIV incidence test results obtained using the BED capture enzyme immunoassay or an antibody avidity assay.

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    Oliver Laeyendecker

    2010-10-01

    Full Text Available Accurate incidence estimates are needed for surveillance of the HIV epidemic. HIV surveillance occurs at maternal-child health clinics, but it is not known if pregnancy affects HIV incidence testing.We used the BED capture immunoassay (BED and an antibody avidity assay to test longitudinal samples from 51 HIV-infected Ugandan women infected with subtype A, C, D and intersubtype recombinant HIV who were enrolled in the HIVNET 012 trial (37 baseline samples collected near the time of delivery and 135 follow-up samples collected 3, 4 or 5 years later. Nineteen of 51 women were also pregnant at the time of one or more of the follow-up visits. The BED assay was performed according to the manufacturer's instructions. The avidity assay was performed using a Genetic Systems HIV-1/HIV-2 + O EIA using 0.1M diethylamine as the chaotropic agent.During the HIVNET 012 follow-up study, there was no difference in normalized optical density values (OD-n obtained with the BED assay or in the avidity test results (% when women were pregnant (n = 20 results compared to those obtained when women were not pregnant (n = 115; for BED: p = 0.9, generalized estimating equations model; for avidity: p = 0.7, Wilcoxon rank sum. In addition, BED and avidity results were almost exactly the same in longitudinal samples from the 18 women who were pregnant at only one study visit during the follow-up study (p = 0.6, paired t-test.These results from 51 Ugandan women suggest that any changes in the antibody response to HIV infection that occur during pregnancy are not sufficient to alter results obtained with the BED and avidity assays. Confirmation with larger studies and with other HIV subtypes is needed.

  14. p24 as a predictor of mortality in a cohort of HIV-1-infected adults in rural Africa

    DEFF Research Database (Denmark)

    Erikstrup, C.; Kallestrup, P.; Zinyama-Gutsire, R.B.

    2008-01-01

    in a cohort of HIV-1-infected individuals in Zimbabwe. METHODS: Treatment-naive HIV-1-infected individuals (n=198) from the Mupfure Schistosomiasis and HIV Cohort were followed until death or censoring (3-4.3 years). At baseline, p24, HIV-RNA, CD4 cell counts, and clinical staging (Centers for Disease Control...... and Prevention classification) were assessed. RESULTS: p24 correlated with HIV-RNA (PDisease Control and Prevention category (P... regression. p24 predicted mortality in univariate Cox analysis (Pstudy to evaluate the prognostic strength of p24 in an area with a predominance of HIV subtype C infections. p24 correlated...

  15. Enhancing patient safety with an electronic results checking system in a large HIV outpatient service.

    Science.gov (United States)

    Nugent, D B; Uthayakumar, N; Ferrand, R A; Edwards, S G; Miller, R; Benn, P

    2013-08-01

    To establish whether an automated electronic tracker system for reporting blood results would expedite clinician review of abnormal results in HIV-positive outpatients and to pilot the use of this system in routine clinical practice. An outpatient service in central London providing specialist HIV-related care to 3900 HIV positive patients. A comparison of the time taken from sampling to identification and clinician review of abnormal blood results for biochemical tests between the original paper-based checking system and an automated electronic system during a 3-week pilot. Of 513 patients undergoing one or more blood tests, 296 (57%) had one or more biochemical abnormalities identified by electronic checking system. Out of 371 biochemical abnormalities, 307 (82.7%) were identified simultaneously by the paper-based system. Of the 307, 33 (10.7%) were classified as urgent, 130 (42.3%) as non-urgent and 144 (46.9%) as not clinically significant. The median interval between sampling and receipt of results was 1 (interquartile range 1-2) vs 4 days ( interquartile range 3-5), P interquartile range 1-4) vs 3 days (interquartile range 3-6), Pinterquartile range 1-4) vs 10 days ( interquartile range 9-12), P=0.136, for electronic and paper-based systems respectively. Seven (11%) of the missing paper-based system results were classified as urgent. The electronic system missed three abnormalities as a result of a software processing error which was subsequently corrected. The electronic tracker system allows faster identification of biochemical abnormalities and allowed faster review of these results by clinicians. The pilot study allowed for a software error to be identified and corrected before full implementation. The system has since integrated successfully into routine clinical practice.

  16. Differences in labour participation between people living with HIV and the general population: Results from Spain along the business cycle.

    Science.gov (United States)

    Peña Longobardo, Luz María; Oliva-Moreno, Juan

    2018-01-01

    HIV/AIDS (Human immunodeficiency virus/Acquired immune deficiency syndrome) not only has a strong impact on the health of the worldwide population but also affects the labour status of HIV-positive people. The primary aim of this paper is to compare the labour participation of people living with HIV (PlwHIV) with the labour participation of the general population along the last business cycle in Spain. The data used are from the Hospital Survey on HIV-AIDS, with a total sample size of 4,651 PlwHIV and the Labour Force Survey from 2001 to 2010, with a total sample size of 660,674 individuals as general population. Propensity Score Matching method was used to analyse the differences between the labour participation of PlwHIV and the general population. Additionally, several specific models categorised into different subgroups (gender, education, source of infection and level of defences) were also performed. We identified a convergence in labour participation across the period in the two populations considered: PlwHIV was 23% less likely to have a job than the general population during 2001-2002 and 14% less likely during 2009-2010. This convergence is mainly explained by two facts: first, the positive evolution of people infected by sex; second, the change in the PlwHIV population composition with a decreasing weight of people infected by drug use throughout the decade. Thereby, at the end of period, there was no statistical difference in the employment rate between PlwHIV infected through sex and the general population but there was strongly difference in PlwHIV infected through drugs. Inmunological status, source of infection and level of education play a relevant role among the PlwHIV population when comparing their labour participation with the general population. In spite of this positive result, the likelihood of being employed in HIV-positive people continues to be different from that of non-carriers. Our study shows that institutional features of labour

  17. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort.

    Science.gov (United States)

    Bruyand, Mathias; Thiébaut, Rodolphe; Lawson-Ayayi, Sylvie; Joly, Pierre; Sasco, Annie Jeanne; Mercié, Patrick; Pellegrin, Jean Luc; Neau, Didier; Dabis, François; Morlat, Philippe; Chêne, Geneviève; Bonnet, Fabrice

    2009-10-01

    Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.

  18. South Africa’s private sector investment in training and its erosion as a result of HIV and AIDS

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    Gavin George

    2014-03-01

    Full Text Available South Africa’s economic prospects depend on the productivity of its labour, and productivity can only be maximised when the labour force possess the appropriate skills. Business is playing its part by offering training opportunities to employees. Collectively, they are spending more than the government’s mandated level on training. However, the HIV and AIDS epidemic is eroding this investment in southern Africa where the HIV epidemic is at its worst. While there has been empirical work that provides estimates on the cost of HIV and AIDS to business, there is very little data on the actual amounts large companies spend on training, and how much of this investment is eroded as a result of HIV and AIDS deaths. Using an estimate of the HIV and AIDS death rate in the private sector and survey data which identifies training expenditure by sector, the authors estimate the extent to which HIV and AIDS has potentially eroded this investment. The loss for all sectors was estimated at almost R10 million (R9,871,732 during the study year, which equates to USD1,183,661 per annum. This amount represented on average 0.73 per cent of the actual investment in training. The real costs of HIV and AIDS on business, which includes absenteeism, declining productivity and other costs are difficult to quantify, but they are likely to significantly exceed this lost training investment as a result of increasing morbidity and mortality rates due to HIV. It is therefore in a company’s best interest to: (1 ensure that a sound HIV and AIDS policy is in place; (2 invest in effective prevention programmes; and (3 provide the appropriate ARV treatment to infected employees if this treatment is not easily accessible through the public health sector.

  19. Mixed results: the protective role of schooling in the HIV epidemic in ...

    African Journals Online (AJOL)

    It is recognised that young women, especially adolescents, are particularly vulnerable to HIV infection and bear a disproportionate burden of HIV incidence. The HIV data from Swaziland show the ... although there are challenges. Keywords: dropouts, education, orphans and vulnerable children, repeaters, young women ...

  20. Effects of a Community-Based HIV Risk Reduction Intervention Among HIV-Positive Individuals: Results of a Quasi-Experimental Study in Nepal.

    Science.gov (United States)

    Poudel, Krishna C; Buchanan, David R; Poudel-Tandukar, Kalpana

    2015-06-01

    We evaluated the efficacy of a sexual risk reduction intervention utilizing protection motivation and social cognitive theories to address knowledge, threat and coping appraisals, and condom use intentions among HIV-positive individuals in Nepal. Using a quasi-experimental research design, we assigned 277 participants to intervention (n=146) and control (n=131) groups. The intervention group received six sessions on sexual risk reduction strategies and the control group six sessions on medication adherence, smoking, and mental health. Data were collected at baseline and immediately after the intervention. Results indicate that the sexual risk reduction intervention produced a significant increase in HIV transmission knowledge, perceived threat and coping appraisals, and intentions to use condoms with regular, HIV-positive, and HIV-negative partners. The positive effects of the intervention remained significant after adjusting for baseline scores and other potential confounders. In conclusion, our theory-based sexual risk reduction intervention was effective in improving HIV transmission knowledge, perceived threat and coping appraisals, and condom use intentions. Further studies are needed to evaluate the long-term efficacy of the intervention in increasing protection motivation and maintaining preventive behaviors.

  1. Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

    Directory of Open Access Journals (Sweden)

    D Raben

    Full Text Available European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC. Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC, HIV test accepted (% of tests performed/% of tests offered and new HIV diagnosis rate (%. There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97, lowest in Northern Europe (median 44%, IQR 22-68% and highest in Eastern Europe (median 99%, IQR 86-100. Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9, with 29 audits (60.4% having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14. A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

  2. Differences in HIV Type 1 RNA Plasma Load Profile of Closely Related Cocirculating Ethiopian Subtype C Strains: C and C '

    NARCIS (Netherlands)

    Ayele, Workenesh; Mekonnen, Yared; Messele, Tsehaynesh; Mengistu, Yohannes; Tsegaye, Aster; Bakker, Margreet; Berkhout, Ben; Dorigo-Zetsma, Wendelien; Wolday, Dawit; Goudsmit, Jaap; Coutinho, Roel; de Baar, Michel; Paxton, William A.; Pollakis, Georgios

    2010-01-01

    Two HIV-1 subtype C subclusters have been identified in Ethiopia (C and C') with little knowledge regarding their biological or clinical differences. We longitudinally monitored HIV-1 viral loads and CD4(+) T cell counts for 130 subtype C-infected individuals from Ethiopia over 5 years. The genetic

  3. Prevalence, Recurrence, and Incidence of Current Depressive Symptoms among People Living with HIV in Ontario, Canada: Results from the Ontario HIV Treatment Network Cohort Study

    Science.gov (United States)

    Choi, Stephanie K. Y.; Boyle, Eleanor; Cairney, John; Collins, Evan J.; Gardner, Sandra; Bacon, Jean; Rourke, Sean B.

    2016-01-01

    Introduction Current studies of depression among people living with HIV focus on describing its point prevalence. Given the fluctuating nature of depression and its profound impacts on clinical and quality-of-life outcomes, this study aimed to examine the prevalence, recurrence and incidence of current depressive symptoms and its underlying catalysts longitudinally and systematically among these individuals. Methods We conducted a prospective cohort study between October 1, 2007 and December 31, 2012 using longitudinal linked data sources. Current depressive symptoms was identified using the Centre for Epidemiologic Studies Depression Scale or the Kessler Psychological Distress Scale, first at baseline and again during follow-up interviews. Multivariable regressions were used to characterize the three outcomes. Results Of the 3,816 HIV-positive participants, the point prevalence of depressive symptoms was estimated at 28%. Of the 957 participants who were identified with depressive symptoms at baseline and who had at least two years of follow-up, 43% had a recurrent episode. The cumulative incidence among 1,745 previously depressive symptoms free participants (at or prior to baseline) was 14%. During the five-year follow-up, our multivariable models showed that participants with greater risk of recurrent cases were more likely to feel worried about their housing situation. Participants at risk of developing incident cases were also likely to be younger, gay or bisexual, and unable to afford housing-related expenses. Conclusions Depressive symptoms are prevalent and likely to recur among people living with HIV. Our results support the direction of Ontario’s HIV/AIDS Strategy to 2026, which addresses medical concerns associated with HIV (such as depression) and the social drivers of health in order to enhance the overall well-being of people living with or at risk of HIV. Our findings reinforce the importance of providing effective mental health care and

  4. Prevalence, Recurrence, and Incidence of Current Depressive Symptoms among People Living with HIV in Ontario, Canada: Results from the Ontario HIV Treatment Network Cohort Study.

    Science.gov (United States)

    Choi, Stephanie K Y; Boyle, Eleanor; Cairney, John; Collins, Evan J; Gardner, Sandra; Bacon, Jean; Rourke, Sean B

    2016-01-01

    Current studies of depression among people living with HIV focus on describing its point prevalence. Given the fluctuating nature of depression and its profound impacts on clinical and quality-of-life outcomes, this study aimed to examine the prevalence, recurrence and incidence of current depressive symptoms and its underlying catalysts longitudinally and systematically among these individuals. We conducted a prospective cohort study between October 1, 2007 and December 31, 2012 using longitudinal linked data sources. Current depressive symptoms was identified using the Centre for Epidemiologic Studies Depression Scale or the Kessler Psychological Distress Scale, first at baseline and again during follow-up interviews. Multivariable regressions were used to characterize the three outcomes. Of the 3,816 HIV-positive participants, the point prevalence of depressive symptoms was estimated at 28%. Of the 957 participants who were identified with depressive symptoms at baseline and who had at least two years of follow-up, 43% had a recurrent episode. The cumulative incidence among 1,745 previously depressive symptoms free participants (at or prior to baseline) was 14%. During the five-year follow-up, our multivariable models showed that participants with greater risk of recurrent cases were more likely to feel worried about their housing situation. Participants at risk of developing incident cases were also likely to be younger, gay or bisexual, and unable to afford housing-related expenses. Depressive symptoms are prevalent and likely to recur among people living with HIV. Our results support the direction of Ontario's HIV/AIDS Strategy to 2026, which addresses medical concerns associated with HIV (such as depression) and the social drivers of health in order to enhance the overall well-being of people living with or at risk of HIV. Our findings reinforce the importance of providing effective mental health care and demonstrate the need for long-term support and

  5. Prevalence, Recurrence, and Incidence of Current Depressive Symptoms among People Living with HIV in Ontario, Canada: Results from the Ontario HIV Treatment Network Cohort Study.

    Directory of Open Access Journals (Sweden)

    Stephanie K Y Choi

    Full Text Available Current studies of depression among people living with HIV focus on describing its point prevalence. Given the fluctuating nature of depression and its profound impacts on clinical and quality-of-life outcomes, this study aimed to examine the prevalence, recurrence and incidence of current depressive symptoms and its underlying catalysts longitudinally and systematically among these individuals.We conducted a prospective cohort study between October 1, 2007 and December 31, 2012 using longitudinal linked data sources. Current depressive symptoms was identified using the Centre for Epidemiologic Studies Depression Scale or the Kessler Psychological Distress Scale, first at baseline and again during follow-up interviews. Multivariable regressions were used to characterize the three outcomes.Of the 3,816 HIV-positive participants, the point prevalence of depressive symptoms was estimated at 28%. Of the 957 participants who were identified with depressive symptoms at baseline and who had at least two years of follow-up, 43% had a recurrent episode. The cumulative incidence among 1,745 previously depressive symptoms free participants (at or prior to baseline was 14%. During the five-year follow-up, our multivariable models showed that participants with greater risk of recurrent cases were more likely to feel worried about their housing situation. Participants at risk of developing incident cases were also likely to be younger, gay or bisexual, and unable to afford housing-related expenses.Depressive symptoms are prevalent and likely to recur among people living with HIV. Our results support the direction of Ontario's HIV/AIDS Strategy to 2026, which addresses medical concerns associated with HIV (such as depression and the social drivers of health in order to enhance the overall well-being of people living with or at risk of HIV. Our findings reinforce the importance of providing effective mental health care and demonstrate the need for long

  6. HIV seroprevalence among Mexicans age 15 to 49: results from the National Health and Nutrition Survey 2012

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    Juan Pablo Gutiérrez

    2014-07-01

    Full Text Available Objective. To estimate the HIV seroprevalence among Mexicans aged 15 to 49 years old and living in households, and to describe the profile of serorreactive individuals. Materials and methods. Cross-sectional study with a national probabilistic sample of individuals aged 15 to 49 years with behavioral data from direct interview (face-to-face at households and HIV screening using capillary blood collected from the same individuals. Results. A seroprevalence of 0.15% (95%CI 0.09-0.21 was estimated for Mexicans aged 15 to 49; seroprevalence among women was 0.07% (95%CI 0.03-0.11 and 0.24% (95%CI 0.11-0.36 for men. HIV serorreactive population is composed of younger men, with a higher socioeconomic level compared to the general population, and with a higher insurance coverage –social protection on health in general and social security in particular. Only 50% of the serorreactive individuals may be aware of their status as living with HIV. Conclusions. The estimated HIV seroprevalence in the NHNS 2012 suggests a stable pattern since 2000. The estimated prevalence among individuals 15 to 49 years was adjusted both for selection bias correction and to include MSM estimations (under the assumption that MSM is a population hard to reach in a household survey, resulting in a total seroprevalence of 0.23% and an estimated number of people with HIV of 140000

  7. Disclosure of HIV positive result to a sexual partner among adult clinical service users in Kemissie district, northeast Ethiopia.

    Science.gov (United States)

    Seid, Mohammed; Wasie, Belaynew; Admassu, Mengesha

    2012-03-01

    HIV Status disclosure is vital for HIV prevention efforts and the couple's health in the context of accelerated highly active antiretroviral therapy. This study aimed to identify factors associated with disclosure of HIV Status to a sexual partner and its outcomes. A facility based cross-sectional study was conducted at Kemissie Health center on 360 HIV positive individuals selected by systematic random sampling. Data were collected using a structured, interviewer administered questionnaire. The level of disclosure to a sexual partner was 93.1%. Among those who disclosed, 74.5% were accepted, 10.8% minor challenges or suspicion of result and the last 7.8% faced physical abuse and blame. The main reasons for not disclosing were fear of divorce [32%], fear of stigma and discrimination [32%] and fear of physical abuse [16%]. Prior discussion, disclosure to family, smooth relationship and knowing partner status were significantly associated with disclosure. HIV prevention programs and counseling efforts should focus on mutual disclosure of HIV test results, by encouraging discussion, reduction of stigma, for better disclosure and continuing care.

  8. Characteristics of HIV infected individuals traveling abroad. Results from the +REDIVI Collaborative Network.

    Science.gov (United States)

    Pérez-Molina, Jose A; Martinez-Perez, Angela; Serre, Nuria; Treviño, Begoña; Ruiz-Giardín, José Manuel; Torrús, Diego; Goikoetxea, Josune; Echevarría, Esteban Martín; Malmierca, Eduardo; Rojo, Gerardo; Calabuig, Eva; Gutierrez, Belén; Norman, Francesca; Lopez-Velez, Rogelio

    2016-02-01

    The improvement in the prognosis of HIV infection, coupled with the increase in international travel and migration, has led to a rising number of HIV infected travelers. The objective of this study was to describe the epidemiological and clinical features of returning travelers, according to their HIV status. An observational prospective study was conducted including travelers and immigrants who traveled to visit friends and relatives (VFRs) registered in the +REDIVI collaborative network (January-2009; October-2014). +REDIVI is a national network that registers information regarding infections imported by travelers and immigrants at 21 different centers using a standardized protocol. A total of 3464 travellers were identified: 72 were HIV+ (2.1%) and 3.392 HIV- (98%). HIV+ vs. HIV- travelers were often older (40.5y vs. 34.2y P=.001), VFRs (79.1% vs. 44.4%; Ptravel advice (27% vs. 37%; P=.078). The main destinations for both groups were sub-Saharan Africa and Latin America. The most frequent reasons for consultation after travel were fever, request for a health examination, gastrointestinal complaints, and abnormal laboratory tests (mainly eosinophilia and anemia), which differed between groups. The most frequent diagnoses in HIV+ travelers were malaria (38.8%), newly diagnosed HIV infection (25%), and intestinal parasites (19.4%), while for HIV- travelers the main diagnoses were "healthy" (17.9%), malaria (14%), and intestinal parasites (17.3%). The typical profile of an HIV+ traveler in +REDIVI was that of a VFR traveler who did not seek pre-travel advice and made high-risk trips. This may increase the chance of acquiring travel-related infections which may pose a special risk for HIV-infected travelers. The post-travel visit was a good opportunity for HIV infection screening. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Assessing effects of a media campaign on HIV/AIDS awareness and prevention in Nigeria: results from the VISION Project

    Directory of Open Access Journals (Sweden)

    Adewuyi Alfred

    2006-05-01

    Full Text Available Abstract Background In response to the growing HIV epidemic in Nigeria, the U.S. Agency for International Development (USAID initiated the VISION Project, which aimed to increase use of family planning, child survival, and HIV/AIDS services. The VISION Project used a mass-media campaign that focused on reproductive health and HIV/AIDS prevention. This paper assesses to what extent program exposure translates into increased awareness and prevention of HIV/AIDS. Methods This analysis is based on data from the 2002 and 2004 Nigeria (Bauchi, Enugu, and Oyo Family Planning and Reproductive Health Surveys, which were conducted among adults living in the VISION Project areas. To correct for endogeneity, two-stage logistic regression is used to investigate the effect of program exposure on 1 discussion of HIV/AIDS with a partner, 2 awareness that consistent condom use reduces HIV risk, and 3 condom use at last intercourse. Results Exposure to the VISION mass media campaign was high: 59%, 47%, and 24% were exposed to at least 1 VISION radio, printed advertisement, or TV program about reproductive health, respectively. The differences in outcome variables between 2002 baseline data and the 2004 follow-up data were small. However, those with high program exposure were almost one and a half (Odds Ratio [O.R.] = 1.47, 95% Confidence Interval [C.I.] 1.01–2.16 times more likely than those with no exposure to have discussed HIV/AIDS with a partner. Those with high program exposure were over twice (O.R. = 2.20, C.I. 1.49–3.25 as likely as those with low exposure to know that condom use can reduce risk of HIV infection. Program exposure had no effect on condom use at last sex. Conclusion The VISION Project reached a large portion of the population and exposure to mass media programs about reproductive health and HIV prevention topics can help increase HIV/AIDS awareness. Programs that target rural populations, females, and unmarried individuals, and

  11. What do Key Stakeholders Think About HIV Self-Testing in Canada? Results from a Cross-Sectional Survey.

    Science.gov (United States)

    Pai, N Pant; Smallwood, M; Gulati, D; Lapczak, N; Musten, A; Gaydos, C; Johnston, C; Steben, M; Wong, T; Engel, N; Kim, J

    2018-02-01

    Human immunodeficiency virus (HIV) self-testing presents an empowering alternative to facility-based testing for reaching undiagnosed HIV infected individuals, but is not currently available in Canada. We surveyed stakeholders (clinical providers, public health professionals, researchers) engaged in HIV testing initiatives nationwide to identify the concerns, opportunities and challenges to implementing HIV self-testing in Canada. An online cross-sectional survey was disseminated by the Canadian Institutes of Health Research Centre for REACH 2.0 National HIV & sexually transmitted and blood borne infections working group to stakeholders nationwide, with a target sample size of 200. Quantitative and qualitative data were analyzed using a mixed-methods, respondent-informed approach, to inform subsequent HIV self-testing in a country where self-testing is not yet accessible. A total of 183 responses were received. A majority (70.7%) (128/181) felt that self-testing was a necessary investment to reach the undiagnosed. 64.6% (117/181) felt that self-tests should be made available to their clients and 71.5% (128/179) of respondents agreed that self-test instructions required improvements. However, 50% (90/180) felt that self-testing will pose an economic challenge to current HIV testing models. Regardless, 21% urged for timely action and availability of HIV self-tests. Thematic analyses reflected the following concerns: (a) need for affordable self-tests, (b) need for expedited, customized, and accessible linkages to counselling, (c) concern for patients to cope with positive self-test results, (d) accuracy of self-tests to detect acute HIV and (e) liability in the context of non-disclosure. Stakeholders agreed to the provision of an option of HIV self-testing to reach the undiagnosed individuals. Concerns regarding costs and accuracy of self-tests, expedited linkages to counselling, and integration of self-test within prevailing HIV testing models, will need to be

  12. T cell subset distribution in HIV-1 infected patients after 12 years of treatment induced viraemic suppression

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L

    2012-01-01

    healthy controls. METHODS:: Several different subsets of naïve, memory and activated T cells were analyzed in fresh whole blood by 6-color flowcytometry and ultra sensitive quantification of HIV RNA was performed. RESULTS:: HIV-infected patients (HIV+) had lower absolute and relative CD4 T cell counts...

  13. Perceived viral load, but not actual HIV-1-RNA load, is associated with sexual risk behaviour among HIV-infected homosexual men

    NARCIS (Netherlands)

    Stolte, Ineke G.; de Wit, John B. F.; van Eeden, Arne; Coutinho, Roel A.; Dukers, Nicole H. T. M.

    2004-01-01

    BACKGROUND: Increases in sexual risk behaviour and sexually transmitted infections among HIV-infected homosexual men after the introduction of highly active antiretroviral therapy (HAART) confirm the need for innovative prevention activities. The present study focused on time trends in sexual risk

  14. Characterization of RNA isolated from eighteen different human tissues: results from a rapid human autopsy program.

    Science.gov (United States)

    Walker, Douglas G; Whetzel, Alexis M; Serrano, Geidy; Sue, Lucia I; Lue, Lih-Fen; Beach, Thomas G

    2016-09-01

    Many factors affect the integrity of messenger RNA from human autopsy tissues including postmortem interval (PMI) between death and tissue preservation and the pre-mortem agonal and disease states. In this communication, we describe RNA isolation and characterization of 389 samples from 18 different tissues from elderly donors who were participants in a rapid whole-body autopsy program located in Sun City, Arizona ( www.brainandbodydonationprogram.org ). Most tissues were collected within a PMI of 2-6 h (median 3.15 h; N = 455), but for this study, tissue from cases with longer PMIs (1.25-29.25 h) were included. RNA quality was assessed by RNA integrity number (RIN) and total yield (ng RNA/mg tissue). RIN correlated with PMI for heart (r = -0.531, p = 0.009) and liver (r = -558, p = 0.0017), while RNA yield correlated with PMI for colon (r = -485, p = 0.016) and skin (r = -0.460, p = 0.031). RNAs with the lowest integrity were from skin and cervix where 22.7 and 31.4 % of samples respectively failed to produce intact RNA; by contrast all samples from esophagus, lymph node, jejunum, lung, stomach, submandibular gland and kidney produced RNA with measurable RINs. Expression levels in heart RNA of 4 common housekeeping normalization genes showed significant correlations of Ct values with RIN, but only one gene, glyceraldehyde-3 phosphate dehydrogenase, showed a correlation of Ct with PMI. There were no correlations between RIN values obtained for liver, adrenal, cervix, esophagus and lymph node and those obtained from corresponding brain samples. We show that high quality RNA can be produced from most human autopsy tissues, though with significant differences between tissues and donors. The RNA stability and yield did not depend solely on PMI; other undetermined factors are involved, but these do not include the age of the donor.

  15. 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

  16. Dealing with a positive result: routine HIV testing of pregnant women in Vietnam

    NARCIS (Netherlands)

    Oosterhoff, P.; Hardon, A.P.; Nguyen, T.A.; Pham, N.Y.; Wright, P.

    2008-01-01

    HIV testing is an essential component of PMTCT. It can be offered to pregnant women through different testing models, ranging from voluntary counseling and testing (VCT) to routine and mandatory testing. This study was conducted in Hanoi, Vietnam, where HIV-prevalence is low among the general

  17. Disclosure of their HIV status to perinatally infected youth using the adapted Blasini disclosure model in Haiti and the Dominican Republic: preliminary results

    Science.gov (United States)

    Beck-Sagué, Consuelo M.; Dévieux, Jessy; Pinzón-Iregui, Maria Claudia; Lerebours-Nadal, Leonel; Abreu-Pérez, Rosa; Bertrand, Rachel; Rouzier, Vanessa; Gaston, Stephanie; Ibanez, Gladys; Halpern, Mina; Pape, Jean W.; Dorceus, Patricia; Preston, Sharice M.; Dean, Andrew G.; Nicholas, Stephen W.; Blasini, Ileana

    2015-01-01

    Objectives To assess the safety, acceptability, and preliminary efficacy of a culturally-adapted disclosure intervention for perinatally HIV-infected combined antiretroviral therapy patients in Haiti and the Dominican Republic. Design A quasi-experimental trial was conducted comparing caregiver–youth pairs who completed the intervention [adapted Blasini disclosure model (aBDM)] to pairs who discontinued aBDM participation before disclosure. aBDM consists of five components: structured healthcare worker training; one-on one pre-disclosure intervention/education sessions for youth (describing pediatric chronic diseases including cancer, diabetes and HIV) and for caregivers (strengthening capacity for disclosure); a scheduled supportive disclosure session; and one-on-one postdisclosure support for caregivers and youth. Methods Caregivers of nondisclosed combined antiretroviral therapy patients aged 10.0–17.8 years were invited to participate. Data were collected by separate one-on-one face-to-face interviews of caregivers and youth by study staff and medical record review by pediatricians at enrollment and 3 months after disclosure or after intervention discontinuation. Results To date, 65 Dominican Republic and 27 Haiti caregiver–youth pairs have enrolled. At enrollment, only 46.4% of youth had viral suppression and 43.4% of caregivers had clinically significant depressive symptomatology. To date, two serious study-related adverse events have occurred. Seven of the 92 (7.6%, 6 in the Dominican Republic) enrolled pairs discontinued participation before disclosure and 39 had completed postdisclosure participation. Median plasma HIV-RNA concentration was lower in youth who completed aBDM than in youth who discontinued participation before aBDM disclosure (<40 versus 8673 copies/ml; P = 0.027). Completers expressed considerable satisfaction with aBDM. Conclusion Preliminary results suggest safety, acceptability, and possible effectiveness of the aBDM. PMID:26049543

  18. Determination of HIV Status in African Adults With Discordant HIV Rapid Tests.

    Science.gov (United States)

    Fogel, Jessica M; Piwowar-Manning, Estelle; Donohue, Kelsey; Cummings, Vanessa; Marzinke, Mark A; Clarke, William; Breaud, Autumn; Fiamma, Agnès; Donnell, Deborah; Kulich, Michal; Mbwambo, Jessie K K; Richter, Linda; Gray, Glenda; Sweat, Michael; Coates, Thomas J; Eshleman, Susan H

    2015-08-01

    In resource-limited settings, HIV infection is often diagnosed using 2 rapid tests. If the results are discordant, a third tie-breaker test is often used to determine HIV status. This study characterized samples with discordant rapid tests and compared different testing strategies for determining HIV status in these cases. Samples were previously collected from 173 African adults in a population-based survey who had discordant rapid test results. Samples were classified as HIV positive or HIV negative using a rigorous testing algorithm that included two fourth-generation tests, a discriminatory test, and 2 HIV RNA tests. Tie-breaker tests were evaluated, including rapid tests (1 performed in-country), a third-generation enzyme immunoassay, and two fourth-generation tests. Selected samples were further characterized using additional assays. Twenty-nine samples (16.8%) were classified as HIV positive and 24 of those samples (82.8%) had undetectable HIV RNA. Antiretroviral drugs were detected in 1 sample. Sensitivity was 8.3%-43% for the rapid tests; 24.1% for the third-generation enzyme immunoassay; 95.8% and 96.6% for the fourth-generation tests. Specificity was lower for the fourth-generation tests than the other tests. Accuracy ranged from 79.5% to 91.3%. In this population-based survey, most HIV-infected adults with discordant rapid tests were virally suppressed without antiretroviral drugs. Use of individual assays as tie-breaker tests was not a reliable method for determining HIV status in these individuals. More extensive testing algorithms that use a fourth-generation screening test with a discriminatory test and HIV RNA test are preferable for determining HIV status in these cases.

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

    Science.gov (United States)

    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

  20. Need to improve routine HIV testing of U.S. Veterans in care: results of an Internet survey.

    Science.gov (United States)

    Valdiserri, Ronald O; Nazi, Kim; McInnes, D Keith; Ross, David; Kinsinger, Linda

    2010-06-01

    Late diagnosis of HIV infection contributes to poor medical outcomes and helps sustain continued transmission of virus. Published evidence suggests that despite current public health recommendations, patients receiving care in the Veterans Health Administration (VHA) system are not being routinely tested for HIV infection. Using a sample of computer-literate veterans, we conducted a survey of recent testing experiences. My HealtheVet (MHV) is a secure website allowing registered Veterans to access limited personal VHA health information. Using the American Customer Satisfaction Index (ACSI) Survey, an electronic questionnaire on "health screening" was conducted in late Fall/early winter 2008-2009. A random sample (4%) of MHV users were surveyed; approximately 17% completed the survey and responses ranged from 31,237 to 33,074. Only 9% of the respondents indicated that they had been offered a test for HIV in the last 12 months compared to 83% who had been offered cholesterol screening, 65% blood sugar screening and 19% who had been offered testing for Hepatitis C virus (HCV). Of those who had been offered HIV testing, 91% indicated that they'd had the test performed. Of note, the percentage of respondents who indicated that they would "very likely" accept a test, if offered, was similar for HIV (73%), HCV (79%), cholesterol (75%), and blood sugar (75%). Although these results cannot be generalized to all Veterans in care, they suggest that routine testing for HIV has not been taking place and support recent VHA policy changes to remove barriers to HIV testing.

  1. Ethical issues in using social media to deliver an HIV prevention intervention: Results from the HOPE Peru Study

    Science.gov (United States)

    Garett, Renee; Menacho, Luis; Young, Sean D.

    2017-01-01

    Social media technologies have become increasingly useful tools for research-based interventions. However, participants and social media users have expressed ethical concerns with these studies, such as risks and benefits of participation, as well as privacy, confidentiality, and informed consent issues. This study was designed to follow up with and assess experiences and perceptions of ethics-related issues among a sample of 211 men who have sex with men who participated in the Harnessing Online Peer Education (HOPE) Peru study, a randomized controlled HIV prevention intervention conducted in Peru. We found that after adjusting for age, highest educational attainment, race, sexual orientation, and prior HIV research experience, participants in the intervention group were more likely than those in the control group to have safe sex (p = 0.0051) and get tested for HIV regularly (p = 0.0051). As a result of their participation, those in the intervention group benefited more positively than participants in the control group in improving HIV care (p = 0.0077) and learning where to receive sexual health services (p = 0.0021). Participants in the intervention group expressed higher levels of comfort than those in the control group in joining and seeing other people in the Facebook group (p = 0.039), seeing other people’s posts (p = 0.038), and having other group members talk to them online (p = 0.040). We discuss the implications of these results as they relate to social media–based HIV research. PMID:27933425

  2. Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival

    Science.gov (United States)

    Chen, Marcelo; Wong, Wing-Wai; Law, Matthew G.; Kiertiburanakul, Sasisopin; Yunihastuti, Evy; Merati, Tuti Parwati; Lim, Poh Lian; Chaiwarith, Romanee; Phanuphak, Praphan; Lee, Man Po; Kumarasamy, Nagalingeswaran; Saphonn, Vonthanak; Ditangco, Rossana; Sim, Benedict L. H.; Nguyen, Kinh Van; Pujari, Sanjay; Kamarulzaman, Adeeba; Zhang, Fujie; Pham, Thuy Thanh; Choi, Jun Yong; Oka, Shinichi; Kantipong, Pacharee; Mustafa, Mahiran; Ratanasuwan, Winai; Durier, Nicolas; Chen, Yi-Ming Arthur

    2016-01-01

    Background We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region. Methods Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test. Results A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive. Conclusion In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality. PMID:26933963

  3. HIV and schistosomiasis in rural Zimbabwe

    DEFF Research Database (Denmark)

    Kotzé, Sebastian Ranzi; Zinyama-Gutsire, Rutendo; Kallestrup, Per

    2015-01-01

    BACKGROUND: Vitamin A has widespread effects on immune function and is therefore interesting in HIV-infection. Retinol-binding protein (RBP or RBP4) is a negative acute-phase protein and a marker of vitamin A status. Our aim was to investigate the association of RBP with HIV progression, infection...... with schistosomiasis, inflammatory cytokines, and mortality. METHODS: The study included 192 HIV-infected and 177 HIV-uninfected individuals from Mupfure in rural Zimbabwe. Of these, 208 were infected with Schistosoma haematobium, 27 with S. mansoni and 48 with both. Plasma RBP, HIV-RNA, CD4 cell count, haemoglobin......, cytokines, clinical staging (CDC category), self-reported level of function (Karnoffsky Performance Score, KPS) and schistosomiasis status were assessed at baseline. Participants were followed up for survival 3-4 years post-enrolment. RESULTS: RBP levels were lower in HIV-infected individuals(p

  4. Integration of HIV and TB Services Results in Improved TB Treatment Outcomes and Earlier Prioritized ART Initiation in a Large Urban HIV Clinic in Uganda

    NARCIS (Netherlands)

    Hermans, Sabine M.; Castelnuovo, Barbara; Katabira, Catherine; Mbidde, Peter; Lange, Joep M. A.; Hoepelman, Andy I. M.; Coutinho, Alex; Manabe, Yukari C.

    2012-01-01

    Background: The World Health Organization recommends that treatment of tuberculosis (TB) in HIV-infected patients should be integrated with HIV care. In December 2008, a separate outdoor-integrated TB/HIV clinic was instituted for attendees of a large urban HIV clinic in Uganda. We sought to

  5. 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.

  6. Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

    Science.gov (United States)

    Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

    2016-11-01

    Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.

  7. Adverse childhood experiences, gender, and HIV risk behaviors: Results from a population-based sample

    Directory of Open Access Journals (Sweden)

    Lin Fang

    2016-12-01

    Full Text Available Recent HIV research suggested assessing adverse childhood experiences (ACEs as contributing factors of HIV risk behaviors. However, studies often focused on a single type of adverse experience and very few utilized population-based data. This population study examined the associations between ACE (individual and cumulative ACE score and HIV risk behaviors. We analyzed the 2012 Behavioral Risk Factor Surveillance Survey (BRFSS from 5 states. The sample consisted of 39,434 adults. Eight types of ACEs that included different types of child abuse and household dysfunctions before the age of 18 were measured. A cumulative score of ACEs was also computed. Logistic regression estimated of the association between ACEs and HIV risk behaviors using odds ratio (OR with 95% confidence intervals (CIs for males and females separately. We found that ACEs were positively associated with HIV risk behaviors overall, but the associations differed between males and females in a few instances. While the cumulative ACE score was associated with HIV risk behaviors in a stepwise manner, the pattern varied by gender. For males, the odds of HIV risk increased at a significant level as long as they experienced one ACE, whereas for females, the odds did not increase until they experienced three or more ACEs. Future research should further investigate the gender-specific associations between ACEs and HIV risk behaviors. As childhood adversities are prevalent among general population, and such experiences are associated with increased risk behaviors for HIV transmission, service providers can benefit from the principles of trauma-informed practice.

  8. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    International Nuclear Information System (INIS)

    Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Romerio, Fabio; Kashanchi, Fatah

    2015-01-01

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4"+ T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4"+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4"+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation (IR) increases

  9. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Iordanskiy, Sergey [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Van Duyne, Rachel [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Romerio, Fabio [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Kashanchi, Fatah, E-mail: fkashanc@gmu.edu [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States)

    2015-11-15

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4{sup +} T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4{sup +} T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4{sup +} T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation

  10. Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

    Directory of Open Access Journals (Sweden)

    Joseph C Sanchez

    2017-10-01

    Full Text Available A form of dwarfism known as Meier-Gorlin syndrome (MGS is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5. These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45. The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C. We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

  11. Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

    Science.gov (United States)

    Sanchez, Joseph C; Kwan, Elizabeth X; Pohl, Thomas J; Amemiya, Haley M; Raghuraman, M K; Brewer, Bonita J

    2017-10-01

    A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45). The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C). We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA) locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

  12. Nurse-delivered counselling intervention for parental HIV disclosure: Results from a pilot randomized controlled trial in China

    Science.gov (United States)

    Simoni, Jane M.; Yang, Joyce P.; Shiu, Cheng-Shi; Chen, Wei-ti; Udell, Wadiya; Bao, Meijuan; Zhang, Lin; Lu, Hongzhou

    2016-01-01

    Objective The objective of this study was to design and conduct a preliminary evaluation of an intervention to assist parents in decision-making about disclosure of their HIV diagnosis to their children. Design This was a pilot randomized controlled trial (RCT) with blinded assessment. Participants were randomized to intervention or treatment-as-usual (TAU) arms. Setting The study occurred at an outpatient HIV primary care centre in Shanghai, China. Participants Participants were 20 HIV-positive outpatients with at least one child (13–25 years old) who was unaware of the parent’s HIV diagnosis. Intervention The nurse-delivered intervention involved three, hour-long, individual sessions over 4 weeks. Intervention content comprised family assessment, discussion of advantages and disadvantages of disclosure, psycho-education about cognitive, social and emotional abilities of children at different developmental stages, and disclosure planning and practicing via role-plays. Main outcome measure(s) Primary study outcomes for intervention versus TAU arms were self-reported disclosure distress, self-efficacy and behaviours along a continuum from no disclosure to full disclosure and open communication about HIV. Results In all cross-sectional (Wald tests) and longitudinal (general estimating equations) analyses, at both postintervention (4 weeks) and follow-up (13 weeks), effects were in the hypothesized directions. Despite the small sample size, most of these between-arm comparisons were statistically significant, with at least one result for each outcome indicating a ‘large’ effect size. Conclusion Our results suggest that nurses are able to deliver a counselling intervention in a clinic setting with the potential to alleviate parental distress around HIV disclosure to their children. Findings warrant future trials powered for efficacy. PMID:26049544

  13. Improving clinical laboratory efficiency: a time-motion evaluation of the Abbott m2000 RealTime and Roche COBAS AmpliPrep/COBAS TaqMan PCR systems for the simultaneous quantitation of HIV-1 RNA and HCV RNA.

    Science.gov (United States)

    Amendola, Alessandra; Coen, Sabrina; Belladonna, Stefano; Pulvirenti, F Renato; Clemens, John M; Capobianchi, M Rosaria

    2011-08-01

    Diagnostic laboratories need automation that facilitates efficient processing and workflow management to meet today's challenges for expanding services and reducing cost, yet maintaining the highest levels of quality. Processing efficiency of two commercially available automated systems for quantifying HIV-1 and HCV RNA, Abbott m2000 system and Roche COBAS Ampliprep/COBAS TaqMan 96 (docked) systems (CAP/CTM), was evaluated in a mid/high throughput workflow laboratory using a representative daily workload of 24 HCV and 72 HIV samples. Three test scenarios were evaluated: A) one run with four batches on the CAP/CTM system, B) two runs on the Abbott m2000 and C) one run using the Abbott m2000 maxCycle feature (maxCycle) for co-processing these assays. Cycle times for processing, throughput and hands-on time were evaluated. Overall processing cycle time was 10.3, 9.1 and 7.6 h for Scenarios A), B) and C), respectively. Total hands-on time for each scenario was, in order, 100.0 (A), 90.3 (B) and 61.4 min (C). The interface of an automated analyzer to the laboratory workflow, notably system set up for samples and reagents and clean up functions, are as important as the automation capability of the analyzer for the overall impact to processing efficiency and operator hands-on time.

  14. HIV Infection Is Not Associated With Aortic Stiffness. Traditional Cardiovascular Risk Factors Are the Main Determinants-Cross-sectional Results of INI-ELSA-BRASIL.

    Science.gov (United States)

    Moreira, Rodrigo C; Mill, José G; Grinsztejn, Beatriz; Veloso, Valdilea; Fonseca, Maria de Jesus; Griep, Rosane H; Bensenor, Isabela; Cardoso, Sandra W; Lotufo, Paulo; Chor, Dora; Pacheco, Antonio G

    2018-05-01

    Aortic stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) is a marker of subclinical atherosclerosis. We propose to assess whether HIV infection is associated with arterial stiffness and their determinants in HIV-infected subjects. We compared data from an HIV cohort (644 patients, HIV+) in Rio de Janeiro with 2 groups: 105 HIV-negative (HIV-) individuals and 14,873 participants of the ELSA-Brasil study. We used multivariable linear regression to investigate factors associated with cf-PWV and whether HIV was independently associated with aortic stiffness and propensity score weighting to control for imbalances between groups. From 15,860 participants, cf-PWV was obtained in 15,622 (98.5%). Median age was 51 (interquartile range 45-58), 44.41 (35.73, 54.72), and 43.60 (36.01, 50.79) years (P ELSA-Brasil, HIV- and HIV+, respectively (P ELSA-Brasil [β = -0.05; 95% confidence interval (CI) = -0.23; P = 0.12; P = 0.52] or with the HIV- groups (β = 0.10; 95% CI = -0.10; 0, 31; P = 0.32). Traditional risk factors were associated with higher cf-PWV levels in the HIV+ group, particularly waist-to-hip ratio (β = 0.20; 95% CI = 0.10; 0.30; P < 0.001, result per one SD change). HIV infection was not associated with higher aortic stiffness according to our study. In HIV-infected subjects, the stiffness of large arteries is mainly associated with traditional risk factors and not to the HIV infection per se.

  15. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    , a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral......OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD...... therapy. RESULTS: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette...

  16. HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification

    DEFF Research Database (Denmark)

    Tenzer, Stefan; Crawford, Hayley; Pymm, Phillip

    2014-01-01

    these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions...... of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak T cell responses, this most likely results in both population-level immune evasion and inadequate responses in most...

  17. Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program.

    Science.gov (United States)

    Maggino, Tiziano; Sciarrone, Rocco; Murer, Bruno; Dei Rossi, Maria Rosa; Fedato, Chiara; Maran, Michela; Lorio, Melania; Soldà, Marika; Zago, Fiorella; Giorgi Rossi, Paolo; Zorzi, Manuel

    2016-08-23

    HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy. From October 2011 to May 2014, women aged 25-64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects. Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8%; relative rate (RR) 1.11, 95% confidence interval (CI) 1.05-1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6%; RR 2.02, 95% CI 1.82-2.25) but similar to the HPV DNA programs (4.8%; RR 1.02; 95% CI 0.96-1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19-1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40-1.16). The overall RR was 1.29 (95% CI 1.05-1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰; RR 2.50, 95% CI 1.76-3.62). A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.

  18. Frequency of indeterminate results from an interferon-gamma release assay among HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    Sandra Maria do Valle Leone de Oliveira

    Full Text Available ABSTRACT Objective: To evaluate the frequency of and factors associated with indeterminate interferon-gamma release assay (IGRA results in people living with HIV/AIDS (PLWHA. Methods: We tested 81 PLWHA in the central-west region of Brazil, using the tuberculin skin test and an IGRA. Information on sociodemographic and clinical variables was gathered through the use of questionnaires and from medical records. The association of those variables with indeterminate results was analyzed by calculating the adjusted ORs in a multivariate logistic regression model. Concordance was evaluated by determining the kappa statistic. Results: Among the 81 patients evaluated, the tuberculin skin test results were positive in 18 (22.2% of the patients, and the IGRA results were positive in 10 (12.3%, with a kappa of 0.62. The IGRA results were indeterminate in 22 (27.1% of the patients (95% CI: 17.8-38.1%. The odds of obtaining indeterminate results were significantly higher in smokers (adjusted OR = 6.0; 95% CI: 1.4-26.7 and in samples stored for less than 35 days (adjusted OR = 14.0; 95% CI: 3.1-64.2. Patients with advanced immunosuppression (CD4+ T-cell count < 200 cells/mm3 were at a higher risk for indeterminate results (OR adjusted for smoking and inadequate duration of sample storage = 4.7; 95% CI: 0.91-24.0, although the difference was not significant. Conclusions: The high prevalence of indeterminate results can be a major limitation for the routine use of IGRAs in PLWHA. The need to repeat the test increases its costs and should be taken into account in cost-effectiveness studies. The processing of samples can significantly alter the results.

  19. Nurse-delivered counselling intervention for parental HIV disclosure: results from a pilot randomized controlled trial in China.

    Science.gov (United States)

    Simoni, Jane M; Yang, Joyce P; Shiu, Cheng-Shi; Chen, Wei-Ti; Udell, Wadiya; Bao, Meijuan; Zhang, Lin; Lu, Hongzhou

    2015-06-01

    The objective of this study was to design and conduct a preliminary evaluation of an intervention to assist parents in decision-making about disclosure of their HIV diagnosis to their children. This was a pilot randomized controlled trial (RCT) with blinded assessment. Participants were randomized to intervention or treatment-as-usual (TAU) arms. The study occurred at an outpatient HIV primary care centre in Shanghai, China. Participants were 20 HIV-positive outpatients with at least one child (13-25 years old) who was unaware of the parent's HIV diagnosis. The nurse-delivered intervention involved three, hour-long, individual sessions over 4 weeks. Intervention content comprised family assessment, discussion of advantages and disadvantages of disclosure, psycho-education about cognitive, social and emotional abilities of children at different developmental stages, and disclosure planning and practicing via role-plays. Primary study outcomes for intervention versus TAU arms were self-reported disclosure distress, self-efficacy, and behaviours along a continuum from no disclosure to full disclosure and open communication about HIV. In all cross-sectional (Wald tests) and longitudinal (general estimating equations) analyses, at both postintervention (4 weeks) and follow-up (13 weeks), effects were in the hypothesized directions. Despite the small sample size, most of these between-arm comparisons were statistically significant, with at least one result for each outcome indicating a 'large' effect size. Our results suggest that nurses are able to deliver a counselling intervention in a clinic setting with the potential to alleviate parental distress around HIV disclosure to their children. Findings warrant future trials powered for efficacy.

  20. Determinants of HIV testing and receipt of test results among adolescent girls in Nigeria: the role of assets and decision-making.

    Science.gov (United States)

    Iwelunmor, Juliet; Blackstone, Sarah; Jennings, Larissa; Converse, Donaldson; Ehiri, John; Curley, Jami

    2018-04-09

    Purpose Many adolescent girls in Nigeria do not test for HIV despite being at high risk. While the influence of psychosocial factors on HIV testing has been examined, there is less evidence regarding the impact of assets and control of assets on HIV testing. This study investigated the protective effects of specific adolescent girls' assets on decision-making regarding HIV testing. Methods Cross-sectional data from the 2013 Nigeria Demographic and Health Survey was analyzed. The main outcome variables were self-reports of having been tested for HIV and knowledge of a place that offers HIV testing. Binary logistic regression was used with employment, education, wealth index, home ownership, land ownership and decision making as potential predictors. Demographic characteristics were controlled in the analysis. Results Age [odds ratio (OR = 1.49)], employment (OR = 3.38), education (OR = 3.16), wealth index (OR = 1.33) and decision making (OR = 3.16) were positively associated with HIV testing. Age (OR = 1.20), employment (OR = 1.33), education (OR = 1.38), wealth (OR = 1.64), land ownership (OR = 1.42), and decision making (OR = 1.26) were positively associated with knowledge of an HIV testing location. Conclusion Our findings suggest that assets play an important role with HIV testing decisions for adolescent girls. Further research to elucidate the specific asset-based needs of adolescent girls will be needed to enhance decisions surrounding uptake of HIV testing and receipt of test results in Nigeria.

  1. Disclosure of HIV Positive Result to a Sexual Partner among Adult ...

    African Journals Online (AJOL)

    HP

    360 HIV positive individuals selected by systematic random sampling. ... The main reasons for not disclosing were fear of divorce [32%], fear of stigma and .... associated with having children and high self- .... negative effect on service provided.

  2. TGF-β1 resulting in differential microRNA expression in bovine granulosa cells.

    Science.gov (United States)

    Xu, Yefen; Niu, Jiaqiang; Xi, Guangying; Niu, Xuezhi; Wang, Yuheng; Guo, Ming; Yangzong, Qiangba; Yao, Yilong; Sizhu, Suo Lang; Tian, Jianhui

    2018-07-15

    To explore the expression profile of the cellular miRNAs in bovine ovarian granulosa cells responding to transforming growth factor-β1 (TGF-β1), the effect of TGF-β1 on cell proliferation was firstly investigated by CCK-8 method and the results showed that there was a significant inhibitory effect on bovine granulosa cell proliferation treated with 5/10 ng/mL human recombinant TGF-β1 for 24 h compared to the control (P cells stimulated with or without 10 ng/mL human recombinant TGF-β1. A total of 13,257,248 and 138,726,391 clean reads per library were obtained from TGF-β1 and control groups, respectively. There were 498 and 499 bovine-specific exist miRNAs (exist miRNAs), 627 and 570 conserved known miRNAs (known miRNAs), and 593 and 585 predicted novel miRNAs in TGF-β1 and control groups, respectively. A total of 78 miRNAs with significant differential expression, including 39 up-regulated miRNAs and 39 down-regulated miRNAs were identified in the TGF-β1 group compared with the control. Real-time quantitative PCR analyses of bta-miR-106a and bta-miR-1434-5p showed that their up-expressions were interrupted by SB431542, an inhibitor that blocks TGFβ1/Smad signaling, which supported the sequencing data. GO analysis showed involvement of the predicted genes of the differentially expressed miRNAs in a broad spectrum of cell biological processes, cell components, and molecular functions. KEGG pathway analysis of the predicted miRNA targets further indicated that these differentially expressed miRNAs are involved in various signaling pathways, such as Wnt, MAPK, and TGF-β signaling, which might be involved in follicular development. These results provide valuable information on the composition, expression, and function of miRNAs in bovine granulosa cells responding to TGF-β1, and will aid in understanding the molecular mechanisms of TGF-β1 in granulosa cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Masese Linnet N

    2011-11-01

    Full Text Available Abstract Background Trichomonas vaginalis has been associated with increased vaginal HIV-1 RNA shedding in antiretroviral therapy (ART-naïve women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that T. vaginalis infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels. Methods We conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g. Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation. Results Among 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI 4% - 30%], 4 (13% [95% CI 4% - 30%], and 5 (16% [95% confidence interval {CI} 5% - 34%] women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7. In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45, p = 0.6. Conclusion Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection.

  4. Combining Results from Distinct MicroRNA Target Prediction Tools Enhances the Performance of Analyses

    Directory of Open Access Journals (Sweden)

    Arthur C. Oliveira

    2017-05-01

    Full Text Available Target prediction is generally the first step toward recognition of bona fide microRNA (miRNA-target interactions in living cells. Several target prediction tools are now available, which use distinct criteria and stringency to provide the best set of candidate targets for a single miRNA or a subset of miRNAs. However, there are many false-negative predictions, and consensus about the optimum strategy to select and use the output information provided by the target prediction tools is lacking. We compared the performance of four tools cited in literature—TargetScan (TS, miRanda-mirSVR (MR, Pita, and RNA22 (R22, and we determined the most effective approach for analyzing target prediction data (individual, union, or intersection. For this purpose, we calculated the sensitivity, specificity, precision, and correlation of these approaches using 10 miRNAs (miR-1-3p, miR-17-5p, miR-21-5p, miR-24-3p, miR-29a-3p, miR-34a-5p, miR-124-3p, miR-125b-5p, miR-145-5p, and miR-155-5p and 1,400 genes (700 validated and 700 non-validated as targets of these miRNAs. The four tools provided a subset of high-quality predictions and returned few false-positive predictions; however, they could not identify several known true targets. We demonstrate that union of TS/MR and TS/MR/R22 enhanced the quality of in silico prediction analysis of miRNA targets. We conclude that the union rather than the intersection of the aforementioned tools is the best strategy for maximizing performance while minimizing the loss of time and resources in subsequent in vivo and in vitro experiments for functional validation of miRNA-target interactions.

  5. Yeast tRNAPhe expressed in human cells can be selected by HIV-1 for use as a reverse transcription primer

    International Nuclear Information System (INIS)

    Kelly, Nathan J.; Morrow, Casey D.

    2003-01-01

    All naturally occurring human immune deficiency viruses (HIV-1) select and use tRNA Lys,3 as the primer for reverse transcription. Studies to elucidate the mechanism of tRNA selection from the intracellular milieu have been hampered due to the difficulties in manipulating the endogenous levels of tRNA Lys,3 . We have previously described a mutant HIV-1 with a primer binding site (PBS) complementary to yeast tRNA Phe (psHIV-Phe) that relies on transfection of yeast tRNA Phe for infectivity. To more accurately recapitulate the selection process, a cDNA was designed for the intracellular expression of the yeast tRNA Phe . Increasing amounts of the plasmid encoding tRNA Phe resulted in a corresponding increase in levels of yeast tRNA Phe in the cell. The yeast tRNA Phe isolated from cells transfected with the cDNA for yeast tRNA Phe , or in the cell lines expressing yeast tRNA Phe , were aminoacylated, indicating that the expressed yeast tRNA Phe was incorporated into tRNA biogenesis pathways and translation. Increasing the cytoplasmic levels of tRNA Phe resulted in increased encapsidation of tRNA Phe in viruses with a PBS complementary to tRNA Phe (psHIV-Phe) or tRNA Lys,3 (wild-type HIV-1). Production of infectious psHIV-Phe was dependent on the amount of cotransfected tRNA Phe cDNA. Increasing amounts of plasmids encoding yeast tRNA Phe produced an increase of infectious psHIV-Phe that plateaued at a level lower than that from the transfection of the wild-type genome, which uses tRNA Lys,3 as the primer for reverse transcription. Cell lines were generated that expressed yeast tRNA Phe at levels approximately 0.1% of that for tRNA Lys,3 . Even with this reduced level of yeast tRNA Phe , the cell lines complemented psHIV-Phe over background levels. The results of these studies demonstrate that intracellular levels of primer tRNA can have a direct effect on HIV-1 infectivity and further support the role for PBS-tRNA complementarity in the primer selection process

  6. Heterophilic interference in specimens yielding false-reactive results on the Abbott 4th generation ARCHITECT HIV Ag/Ab Combo assay.

    Science.gov (United States)

    Lavoie, S; Caswell, D; Gill, M J; Kadkhoda, K; Charlton, C L; Levett, P N; Hatchette, T; Garceau, R; Maregmen, J; Mazzulli, T; Needle, R; Kadivar, K; Kim, J

    2018-04-12

    False-reactivity in HIV-negative specimens has been detected in HIV fourth-generation antigen/antibody or 'combo' assays which are able to detect both anti-HIV-1/HIV-2 antibodies and HIV-1 antigen. We sought to characterize these specimens and determine the effect of heterophilic interference. Specimens previously testing as false-reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay and re-tested on a different (Siemens ADVIA Centaur HIV Ag/Ab) assay. A subset of these specimens were also pre-treated with heterophilic blocking agents and re-tested on the Abbott assay. Here we report that 95% (252/264) of clinical specimens that were repeatedly reactive on the Abbott ARCHITECT HIV Ag/Ab combo assay (S/Co range, 0.94-678) were negative when re-tested on a different fourth generation HIV combo assay (Siemens ADVIA Centaur HIV Ag/Ab). All 264 samples were subsequently confirmed to be HIV negative. On a small subset (57) of specimens with available volume, pre-treatment with two different reagents (HBT; Heterophilic Blocking Tube, NABT; Non-Specific Blocking Tube) designed to block heterophilic antibody interference either eliminated (HBT) or reduced (NABT) the false reactivity when re-tested on the ARCHITECT HIV Ag/Ab combo assay. Our results suggest that the Abbott ARCHITECT HIV Ag/Ab combo assay can be prone to heterophilic antibody interference. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  7. Stigma, discrimination, and sexual (dis)satisfaction among people living with HIV: results from the "AIDES et toi" survey.

    Science.gov (United States)

    Rojas Castro, D; Le Gall, J M; Andreo, C; Spire, B

    2010-08-01

    The effects of HIV-related stigma and discrimination have been studied in several areas, such as access to testing, quality of care quality, and access to work. Nevertheless, the effects of stigma and discrimination on the sexual life of people living with HIV/AIDS (PLWHA) have not been studied enough. AIDES, a French community-based organization, has developed a biannual survey which assesses several socioeconomical and psychosocial dimensions of the people in contact with this organization. A focus on the results concerning sexual (dis)satisfaction and the factors associated are presented here. A convenience sample of 521 HIV-positive men having sex with men, heterosexual men and women was analyzed. A logistic regression was performed to examine which factors were significantly associated with sexual dissatisfaction. Results showed that being older, not having a full-time job, not having a steady sexual partner, lower frequency of sexual intercourse, discrimination in the sexual relationship setting, and the perception of loneliness were independently associated with sexual dissatisfaction. A quality health approach must include the aspects linked to sexual life and sexual satisfaction. Given the potentially harmful effects that HIV-related stigma and discrimination have on PLWHA's well-being, more specific actions and advocacy in this direction should be developed and implemented.

  8. Sex workers clients in Italy: results of a phone survey on HIV risk behaviour and perception

    Directory of Open Access Journals (Sweden)

    Ilaria Mulieri

    2014-12-01

    Full Text Available INTRODUCTION: Sex workers (SW clients represent a bridge population for HIV transmission from high risk to low risk general population. MATERIALS AND METHODS: A cross-sectional anonymous telephone survey was carried out at the AIDS and Sexually Transmitted Infections Helpline of National Institute of Health in Italy. The questionnaire was proposed on a voluntary basis to a sample of 119 subjects from helpline users. RESULTS: The 119 participants were all males, aged between 19 and 59 years and mostly accessed female prostitutes. Vaginal intercourses with SW were more frequently reported, followed by passive oral, active oral sex and active anal intercourses. Cumulatively, 86.6% and 84.6% of vaginal and anal intercourses were respectively reported as regularly protected by condom. DISCUSSION: The telephone interview allowed an eased access, a high response rate and a standardised evaluation of questions CONCLUSIONS: It is necessary a constant monitoring of the characteristics, behaviour, risk perception and testing of SW clients in Italian and other populations.

  9. Randomized controlled trials of HIV/AIDS prevention and treatment in Africa: results from the Cochrane HIV/AIDS Specialized Register.

    Directory of Open Access Journals (Sweden)

    Babalwa Zani

    Full Text Available INTRODUCTION: To effectively address HIV/AIDS in Africa, evidence on preventing new infections and providing effective treatment is needed. Ideally, decisions on which interventions are effective should be based on evidence from randomized controlled trials (RCTs. Our previous research described African RCTs of HIV/AIDS reported between 1987 and 2003. This study updates that analysis with RCTs published between 2004 and 2008. OBJECTIVES: To describe RCTs of HIV/AIDS conducted in Africa and reported between 2004 and 2008. METHODS: We searched the Cochrane HIV/AIDS Specialized Register in September 2009. Two researchers independently evaluated studies for inclusion and extracted data using standardized forms. Details included location of trials, interventions, methodological quality, location of principal investigators and funders. RESULTS: Our search identified 834 RCTs, with 68 conducted in Africa. Forty-three assessed prevention-interventions and 25 treatment-interventions. Fifteen of the 43 prevention RCTs focused on preventing mother-to-child HIV transmission. Thirteen of the 25 treatment trials focused on opportunistic infections. Trials were conducted in 16 countries with most in South Africa (20, Zambia (12 and Zimbabwe (9. The median sample size was 628 (range 33-9645. Methods used for the generation of the allocation sequence and allocation concealment were adequate in 38 and 32 trials, respectively, and 58 reports included a CONSORT recommended flow diagram. Twenty-nine principal investigators resided in the United States of America (USA and 18 were from African countries. Trials were co-funded by different agencies with most of the funding obtained from USA governmental and non-governmental agencies. Nineteen pharmaceutical companies provided partial funding to 15 RCTs and African agencies co-funded 17 RCTs. Ethical approval was reported in 65 trials and informed consent in 61 trials. CONCLUSION: Prevention trials dominate the trial

  10. Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from TAHOD

    Directory of Open Access Journals (Sweden)

    Jialun Zhou

    2012-01-01

    Full Text Available This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned and temporary LTFU (re-entered later, and these groups compared. A total of 3626 patients were included (71% male. No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%. During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years. Patients LFTU were younger (P=0.002, had HIV viral load ≥500 copies/mL or missing (P=0.021, had shorter history of HIV infection (P=0.048, and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P<0.001. 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P<0.001, missing recent HIV viral load (P<0.001, negative hepatitis C test (P=0.025, and previous temporary LTFU episodes (P<0.001. Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced.

  11. Plasma HIV-1 RNA viral load rebound among people who inject drugs receiving antiretroviral therapy (ART) in a Canadian setting: an ethno-epidemiological study.

    Science.gov (United States)

    Small, Will; Milloy, M J; McNeil, Ryan; Maher, Lisa; Kerr, Thomas

    2016-01-01

    People who inject drugs (PWID) living with HIV often experience sub-optimal antiretroviral therapy (ART) treatment outcomes, including HIV plasma viral load (PVL) rebound. While previous studies have identified risk factors for PVL rebound among PWID, no study has examined the perspectives of PWID who have experienced PVL rebound episodes. We conducted an ethno-epidemiological study to investigate the circumstances surrounding the emergence of rebound episodes among PWID in Vancouver, BC, Canada. Comprehensive clinical records linked to a community-based prospective observational cohort of HIV-positive drug users were used to identify PWID who had recently experienced viral rebound. In-depth qualitative interviews with 16 male and 11 female participants explored participant perspectives regarding the emergence of viral rebound. A timeline depicting each participant's HIV viral load and adherence to ART was used to elicit discussion of circumstances surrounding viral rebound. Viral rebound episodes were shaped by interplay between various individual, social, and environmental factors that disrupted routines facilitating adherence. Structural-environmental influences resulting in non-adherence included housing transitions, changes in drug use patterns and intense drug scene involvement, and inadequate care for co-morbid health conditions. Social-environmental influences on ART adherence included poor interactions between care providers and patients producing non-adherence, and understandings of HIV treatment that fostered intentional treatment discontinuation. This study describes key pathways which led to rebound episodes among PWID receiving ART and illustrates how environmental forces may increase vulnerability for non-adherence leading to treatment failure. Our findings have potential to help inform interventions and supports that address social-structural forces that foster non-adherence among PWID.

  12. Characteristics of participants in an HIV prevention intervention for youth in Rwanda: results from a longitudinal study

    Directory of Open Access Journals (Sweden)

    Hanne Celis

    2014-08-01

    Full Text Available Introduction. This paper studies determinants of participation in a peer-led school-based HIV prevention intervention in Rwanda. Methods. A baseline survey among 1071 students (mean age 17 years assessed potential determinants of participation, while a follow-up six months in the intervention measured actual participation in the intervention. Statistical models were built using multivariate linear and multinomial regression analysis predicting overall participation, par- ticipation in group discussions and individual counseling. Results. Those who recently had sex, had been tested for HIV, feel more susceptible to HIV, have a higher sexual self-concept, a more positive future perspective (only for non-sexually active, and boys, were more likely to participate in group activities. Also students from the same class as the peer educator and boarding school students were more likely to participate in group activities. Older students and those with low external health locus of control participated more in individual counseling. Discussion. Participation could be increased by investing in general well-being of young people, organizing girls-only activities, and diversifying activities. Key words: selection bias, HIV prevention, participation rate, young people, Rwanda

  13. Long-term results after cardiac surgery in patients infected with the human immunodeficiency virus type-1 (HIV-1).

    Science.gov (United States)

    Mestres, Carlos A; Chuquiure, Javier E; Claramonte, Xavier; Muñoz, Josefa; Benito, Natividad; Castro, Miguel A; Pomar, José L; Miró, José M

    2003-06-01

    Assessment of long-term results of immunodeficiency virus type-1 (HIV-1)-infected patients undergoing cardiac surgery. Retrospective analysis of profile and outcomes of 31 HIV-1-infected patients (35 operations, 1985-2002). Twenty-seven males and four females (mean age 34.67) in three groups: acute infective endocarditis (AIE) 21 (67.74%), coronary (CAD) 5 (16.13%) and non-infective valvular disease (NIVD) 5 (16.13%). HIV factors: drug addiction (23-74.19%), homosexuality (5-16.12%), heterosexuality (3-9.67%), hemodialysis (1-3.22%). HIV stage: A (17), B (2), C (2) in AIE; A (2), B (3) in CAD and A (3), C (2) in NIVD. Mean preoperative CD4 count was 278 cells/microL (12infected patients requiring cardiac surgery, a decrease in AIE, however NIVD and CAD increasingly seen. Cardiac surgery did not blunt CD4 response induced by antiretrovirals. The late cause of death were not AIDS-related events.

  14. Social media use and HIV transmission risk behavior among ethnically diverse HIV-positive gay men: results of an online study in three U.S. states.

    Science.gov (United States)

    Hirshfield, Sabina; Grov, Christian; Parsons, Jeffrey T; Anderson, Ian; Chiasson, Mary Ann

    2015-10-01

    Though Black and Hispanic men who have sex with men (MSM) are at an increased risk for HIV, few HIV risk reduction interventions that target HIV-positive MSM, and even fewer that use technology, have been designed to target these groups. Despite similar rates of social media and technology use across racial/ethnic groups, online engagement of minority MSM for HIV prevention efforts is low. Since minority MSM tend to have less representation in online HIV prevention studies, the goals of this online anonymous study of HIV-positive gay-identified men were to test the feasibility of conducting targeted recruitment by race/ethnicity and sexual orientation, to assess technology and social media use, and to assess global HIV transmission risk. In 2011, an anonymous online survey was conducted among 463 members of an HIV-positive personals website. Emails were sent to a subset of HIV-positive male members who self-identified as gay. While 57 % were White, substantial proportions of participants were Black (20 %) or Hispanic (18 %). Median age was 46 (range 18-79). Men who reported using 3 or more websites or apps to meet sex partners were significantly more likely to report anal intercourse (AOR 4.43, p social media use, and sexual risk among a diverse sample of HIV-positive gay men. Efficacy trials of technology-based HIV prevention interventions targeting high-risk minority HIV-positive MSM are warranted.

  15. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

    NARCIS (Netherlands)

    Mocroft, Amanda; Lundgren, Jens D.; Sabin, Miriam Lewis; Monforte, Antonella d'Arminio; Brockmeyer, Norbert; Casabona, Jordi; Castagna, Antonella; Costagliola, Dominique; Dabis, Francois; de Wit, Stéphane; Fätkenheuer, Gerd; Furrer, Hansjakob; Johnson, Anne M.; Lazanas, Marios K.; Leport, Catherine; Moreno, Santiago; Obel, Niels; Post, Frank A.; Reekie, Joanne; Reiss, Peter; Sabin, Caroline; Skaletz-Rorowski, Adriane; Suarez-Lozano, Ignacio; Torti, Carlo; Warszawski, Josiane; Zangerle, Robert; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Kirk, Ole; Lundgren, Jens; Sabin, Miriam; Johnson, Anne; Lazanas, Mario; Post, Frank; Suarez-Loano, Ignacio; Johnson, Hansjakob Furrer Anne; Touloumi, Giota; Meyer, Laurence; Dabis, François; Krause, Murielle Mary; Ghosn, Jade; de Wolf, Frank; Prins, Maria; Bucher, Heiner; Gibb, Diana; Hamouda, Osamah; Bartmeyer, Barbara; del Amo, Julia

    2013-01-01

    Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV

  16. Relationship of HIV Reservoir Characteristics with Immune Status and Viral Rebound Kinetics in an HIV Therapeutic Vaccine Study

    Science.gov (United States)

    Li, Jonathan Z.; Heisey, Andrea; Ahmed, Hayat; Wang, Hongying; Zheng, Lu; Carrington, Mary; Wrin, Terri; Schooley, Robert T.; Lederman, Michael M.; Kuritzkes, Daniel R.

    2014-01-01

    Objectives To evaluate the impact of therapeutic HIV vaccination on the HIV reservoir, and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics. Design Retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine. Methods Participants received vaccine/placebo at weeks 0, 4, and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia (RV) were quantified at weeks 0, 8, and 38. HIV-specific CD4+/CD8+ activity were assessed by an intracellular cytokine staining assay. Results At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4+ interferon-γ-producing cells (CA-RNA: r = −0.23, P=0.03 and CA-DNA: r = −0.28, P<0.01, N=93). Therapeutic HIV vaccination induced HIV-specific CD4+ activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable RV at week 8 had higher frequencies of HIV-specific CD4+ and CD8+ interferon-γ-producing cells (undetectable versus detectable RV: 277 versus 161 CD4+ cells/106 lymphocytes, P=0.03 and 1326 versus 669 CD8+ cells/106 lymphocytes, P=0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P<0.01 and CA-DNA: r = 0.47, P<0.01). Conclusions Vaccine-induced T-cell responses were associated with a modest transient effect on RV, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics. PMID:25254301

  17. Cardiovascular Risk Reduction in Persons Living With HIV: Treatment Development, Feasibility, and Preliminary Results.

    Science.gov (United States)

    Cioe, Patricia A; Guthrie, Kate M; Freiberg, Matthew S; Williams, David M; Kahler, Christopher W

    Persons living with HIV (PLWH) have elevated risks for cardiovascular disease (CVD). Our goal was to develop and pilot test a tailored intervention to improve CVD risk perception and the adoption of heart-healthy behaviors. In-depth qualitative interviews were conducted with 30 PLWH participants to examine learning needs and preferences. An intervention manual was developed and tested in an open pilot with eight participants. Participants were stable on antiretroviral therapy and were recruited from two urban HIV clinics in the northeastern United States. Thematic analysis identified five major themes: (a) tailored structure and design for PLWH, (b) learning needs (specific to HIV), (c) desire for prompts/reminders (to exercise), (d) importance of participant resources, and (e) need for personal evaluation and goal setting. Feasibility and acceptability of the intervention were demonstrated with high session attendance and treatment satisfaction. Further testing is warranted. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  18. Scaling up integration: development and results of a participatory assessment of HIV/TB services, South Africa

    Directory of Open Access Journals (Sweden)

    Caldwell Judy

    2010-07-01

    Full Text Available Abstract Background In South Africa the need to integrate HIV, TB and STI programmes has been recognised at a policy and organisation level; the challenge is now one of translating policies into relevant actions and monitoring implementation to ensure that the anticipated benefits of integration are achieved. In this research, set in public primary care services in Cape Town, South Africa, we set out to determine how middle level managers could be empowered to monitor the implementation of an effective, integrated HIV/TB/STI service. Methods A team of managers and researchers designed an evaluation tool to measure implementation of key components of an integrated HIV/TB/STI package with a focus on integration. They used a comprehensive health systems framework based on conditions for programme effectiveness and then identified and collected tracer indicators. The tool was extensively piloted in two rounds involving 49 clinics in 2003 and 2004 to identify data necessary for effective facility-level management. A subsequent evaluation of 16 clinics (2 per health sub district, 12% of all public primary care facilities was done in February 2006. Results 16 clinics were reviewed and 635 records sampled. Client access to HIV/TB/STI programmes was limited in that 50% of facilities routinely deferred clients. Whilst the physical infrastructure and staff were available, there was problem with capacity in that there was insufficient staff training (for example, only 40% of clinical staff trained in HIV care. Weaknesses were identified in quality of care (for example, only 57% of HIV clients were staged in accordance with protocols and continuity of care (for example, only 24% of VCT clients diagnosed with HIV were followed up for medical assessment. Facility and programme managers felt that the evaluation tool generated information that was useful to manage the programmes at facility and district level. On the basis of the results facility managers drew

  19. Ethical Issues in Using Social Media to Deliver an HIV Prevention Intervention: Results from the HOPE Peru Study.

    Science.gov (United States)

    Garett, Renee; Menacho, Luis; Young, Sean D

    2017-02-01

    Social media technologies have become increasingly useful tools for research-based interventions. However, participants and social media users have expressed ethical concerns with these studies, such as risks and benefits of participation, as well as privacy, confidentiality, and informed consent issues. This study was designed to follow up with and assess experiences and perceptions of ethics-related issues among a sample of 211 men who have sex with men who participated in the Harnessing Online Peer Education (HOPE) Peru study, a randomized controlled HIV prevention intervention conducted in Peru. We found that after adjusting for age, highest educational attainment, race, sexual orientation, and prior HIV research experience, participants in the intervention group were more likely than those in the control group to have safe sex (p = 0.0051) and get tested for HIV regularly (p = 0.0051). As a result of their participation, those in the intervention group benefited more positively than participants in the control group in improving HIV care (p = 0.0077) and learning where to receive sexual health services (p = 0.0021). Participants in the intervention group expressed higher levels of comfort than those in the control group in joining and seeing other people in the Facebook group (p = 0.039), seeing other people's posts (p = 0.038) and having other group members talk to them online (p = 0.040). We discuss the implications of these results as they relate to social media-based HIV research.

  20. Cancer, immunodeficiency and antiretroviral treatment: results from the Australian HIV Observational Database (AHOD).

    Science.gov (United States)

    Petoumenos, K; van Leuwen, M T; Vajdic, C M; Woolley, I; Chuah, J; Templeton, D J; Grulich, A E; Law, M G

    2013-02-01

    The objective of the study was to conduct a within-cohort assessment of risk factors for incident AIDS-defining cancers (ADCs) and non-ADCs (NADCs) within the Australian HIV Observational Database (AHOD). A total of 2181 AHOD registrants were linked to the National AIDS Registry/National HIV Database (NAR/NHD) and the Australian Cancer Registry to identify those with a notified cancer diagnosis. Included in the current analyses were cancers diagnosed after HIV infection. Risk factors for cancers were also assessed using logistic regression methods. One hundred and thirty-nine cancer cases were diagnosed after HIV infection among 129 patients. More than half the diagnoses (n = 68; 60%) were ADCs, of which 69% were Kaposi's sarcoma and 31% non-Hodgkin's lymphoma. Among the NADCs, the most common cancers were melanoma (n = 10), lung cancer (n = 6), Hodgkin's lymphoma (n = 5) and anal cancer (n = 5). Over a total of 21021 person-years (PY) of follow-up since HIV diagnosis, the overall crude cancer incidence rate for any cancer was 5.09/1000 PY. The overall rate of cancers decreased from 15.9/1000 PY [95% confidence interval (CI) 9.25-25.40/1000 PY] for CD4 counts 350 cells/μL. Lower CD4 cell count and prior AIDS diagnoses were significant predictors for both ADCs and NADCs. ADCs remain the predominant cancers in this population, although NADC rates have increased in the more recent time period. Immune deficiency is a risk factor for both ADCs and NADCs. © 2012 British HIV Association.

  1. Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over Rev peptide is mainly enthalpic in origin.

    Science.gov (United States)

    Kumar, Santosh; Bose, Debojit; Suryawanshi, Hemant; Sabharwal, Harshana; Mapa, Koyeli; Maiti, Souvik

    2011-01-01

    Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT(m) = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a K(a) = 16.2±0.6×10(7) M(-1) where enthalpic change ΔH = -13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = -2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (K(a) = 3.1±0.4×10(7) M(-1)) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding.

  2. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells.

    Science.gov (United States)

    Oufir, Mouhssin; Bisset, Leslie R; Hoffmann, Stefan R K; Xue, Gongda; Klauser, Stephan; Bergamaschi, Bianca; Gervaix, Alain; Böni, Jürg; Schüpbach, Jörg; Gutte, Bernd

    2011-01-01

    An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  3. Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

    Directory of Open Access Journals (Sweden)

    Mouhssin Oufir

    2011-01-01

    Full Text Available An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

  4. RT-PCR Detection of HIV in Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Golubinka Bosevska

    2008-11-01

    Full Text Available The aim of the study was to detect HIV RNA in seropositive patients using RT-PCR method and thus, to establish PCR methodology in the routine laboratory works.The total of 33 examined persons were divided in two groups: 1 13 persons seropositive for HIV; and 2 20 healthy persons - randomly selected blood donors that made the case control group. The subjects age was between 25 and 52 years (average 38,5.ELFA test for combined detection of HIV p24 antigen and anti HIV-1 + 2 IgG and ELISA test for detection of antibodies against HIV-1 and HIV-2, were performed for each examined person. RNA from the whole blood was extracted using a commercial kit based on salt precipitation. Detection of HIV RNA was performed using RT-PCR kit. Following nested PCR, the product was separated by electrophoresis in 1,5 % agarose gel. The result was scored positive if the band of 210bp was visible regardless of intensity Measures of precaution were taken during all the steps of the work and HIV infected materials were disposed of accordingly.In the group of blood donors ELFA, ELISA and RT-PCR were negative. Assuming that prevalence of HIV infection is zero, the clinical specificity of RT-PCR is 100 %. The analytical specificity of RT-PCR method was tested against Hepatitis C and B, Human Papiloma Virus, Cytomegalovirus, Herpes Simplex Virus, Rubella Virus, Mycobacterium tuberculosis, Chlamydia trachomatis. None of these templates yielded amplicon. In the group of 13 seropositive persons, 33 samples were analyzed. HIV RNA was detected in 15 samples. ELISA and ELFA test were positive in all samples. Different aliquots of the samples were tested independently and showed the same results. After different periods of storing the RNA samples at -70°C, RT-PCR reaction was identical to the one performed initially. The obtained amplicons were maintained frozen at -20°C for a week and the subsequently performed electrophoresis was identical to the previous one. The reaction is

  5. HIV-infected individuals with the CCR delta32/CCR5 genotype have lower HIV RNA levels and higher CD4 cell counts in the early years of the infection than do patients with the wild type. Copenhagen AIDS Cohort Study Group

    DEFF Research Database (Denmark)

    Katzenstein, T L; Eugen-Olsen, J; Hofmann, B

    1997-01-01

    The relations among serum HIV RNA levels, CD4 cell counts, presence of the mutant CCR5-allele in heterozygous form, and clinical outcome was analyzed in 96 patients from the Copenhagen AIDS Cohort. In the early years of the infection, patients with the CCR5 delta32/CCR5 genotype had significantly...

  6. Declining prevalence of undiagnosed HIV in Melbourne : results from community-based bio-behavioural studies of gay and bisexual men

    NARCIS (Netherlands)

    Stoové, Mark; Asselin, Jason; Pedrana, Alisa; Lea, Toby; Hellard, Margaret; Wilson, David B; Prestage, Garrett; de Wit, John; Holt, Martin

    OBJECTIVE: To measure changes in undiagnosed HIV among gay and bisexual men (GBM) in Melbourne. METHODS: Undiagnosed HIV was compared between GBM recruited anonymously in 2008 in gay venues only and GBM anonymously or confidentially (results delivery) recruited in 2014 at gay venues and a community

  7. stability results of a mathematical model for the control of hiv/aids ...

    African Journals Online (AJOL)

    DJFLEX

    Subthreshold Domain of Bistable Equilibria for a Model of. HIV Epidemiology. International Journal of Mathematics and Mathematical Sciences, 58, 3679-3698. David R. M., 1997. Introduction to Theory of Stability. Springer-Verlag, New York, Inc. USA. Family Health International, 2007. How the Female Condom Affects Male ...

  8. Evolving treatment implementation among HIV-infected pregnant women and their partners: results from a national surveillance study in Italy, 2001-2015.

    Science.gov (United States)

    Floridia, Marco; Frisina, Valentina; Ravizza, Marina; Marconi, Anna Maria; Pinnetti, Carmela; Cetin, Irene; Sansone, Matilde; Molinari, Atim; Cervi, Francesca; Meloni, Alessandra; Luzi, Kety; Masuelli, Giulia; Tamburrini, Enrica

    2017-06-01

    -negative partners. The results suggest good implementation of antiretroviral treatment among HIV-positive women and their HIV-positive partners, but no implementation, even in recent years, of Pre-Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.

  9. HIV prevalence and factors associated with HIV infection among transgender women in Cambodia: results from a national Integrated Biological and Behavioral Survey.

    Science.gov (United States)

    Chhim, Srean; Ngin, Chanrith; Chhoun, Pheak; Tuot, Sovannary; Ly, Cheaty; Mun, Phalkun; Pal, Khondyla; Macom, John; Dousset, Jean-Philippe; Mburu, Gitau; Yi, Siyan

    2017-08-11

    To examine factors associated with HIV infection among transgender women in Cambodia. Cross-sectional study. HIV high-burden sites including the capital city and 12 provinces. This study included 1375 sexually active transgender women with a mean age of 25.9 years (SD 7.1), recruited by using respondent-driven sampling for structured questionnaire interviews and rapid finger-prick HIV testing. HIV infection detected by using Determine antibody test. HIV prevalence among this population was 5.9%. After adjustment for other covariates, participants living in urban areas were twice as likely to be HIV infected as those living in rural areas. Participants with primary education were 1.7 times as likely to be infected compared with those with high school education. HIV infection increased with age; compared with those aged 18-24 years, the odds of being HIV infected were twice as high among transgender women aged 25-34 years and 2.8 times higher among those aged ≥35 years. Self-injection of gender affirming hormones was associated with a fourfold increase in the odds of HIV infection. A history of genital sores over the previous 12 months increased the odds of HIV infection by threefold. Transgender women with stronger feminine identity, dressing as a woman all the time, were twice as likely to be HIV infected compared with those who did not dress as a woman all the time. Having never used online services developed for transgender women in the past six months was also associated with higher odds of being HIV infected. Transgender women in Cambodia are at high risk of HIV. To achieve the goal of eliminating HIV in Cambodia, effective combination prevention strategies addressing the above risk factors among transgender women should be strengthened. © 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.

  10. Human endogenous retrovirus K Gag coassembles with HIV-1 Gag and reduces the release efficiency and infectivity of HIV-1.

    Science.gov (United States)

    Monde, Kazuaki; Contreras-Galindo, Rafael; Kaplan, Mark H; Markovitz, David M; Ono, Akira

    2012-10-01

    Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K(CON) Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-K(CON) Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K(CON) Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-K(CON) Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-K(CON) Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-K(CON) Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-K(CON) Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-K(CON) Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-K(CON) Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation- and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.

  11. Rapid testing may not improve uptake of HIV testing and same day results in a rural South African community: a cohort study of 12,000 women.

    Directory of Open Access Journals (Sweden)

    Ntombizodumo B Mkwanazi

    Full Text Available Rapid testing of pregnant women aims to increase uptake of HIV testing and results and thus optimize care. We report on the acceptability of HIV counselling and testing, and uptake of results, before and after the introduction of rapid testing in this area.HIV counsellors offered counselling and testing to women attending 8 antenatal clinics, prior to enrolment into a study examining infant feeding and postnatal HIV transmission. From August 2001 to April 2003, blood was sent for HIV ELISA testing in line with the Prevention of Mother-to-Child Transmission (PMTCT programme in the district. From May 2003 to September 2004 women were offered a rapid HIV test as part of the PMTCT programme, but also continued to have ELISA testing for study purposes. Of 12,323 women counselled, 5,879 attended clinic prior to May 2003, and 6,444 after May 2003 when rapid testing was introduced; of whom 4,324 (74.6% and 4,810 (74.6% agreed to have an HIV test respectively. Of the 4,810 women who had a rapid HIV test, only 166 (3.4% requested to receive their results on the same day as testing, the remainder opted to return for results at a later appointment. Women with secondary school education were less likely to agree to testing than those with no education (AOR 0.648, p35 years (AOR 0.756, p<0.01 compared to those <20 years.Contrary to other reports, few women who had rapid tests accepted their HIV results the same day. Finding strategies to increase the proportion of pregnant women knowing their HIV results is critical so that appropriate care can be given.

  12. Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study.

    Science.gov (United States)

    Akil, Bisher; Blick, Gary; Hagins, Debbie P; Ramgopal, Moti N; Richmond, Gary J; Samuel, Rafik M; Givens, Naomi; Vavro, Cindy; Song, Ivy H; Wynne, Brian; Ait-Khaled, Mounir

    2015-01-01

    The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG. VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8. The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was 
-1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; PVIKING-3 study.

  13. Perceived Family Support and Antiretroviral Adherence in HIV-Positive Individuals: Results from a Community-Based Positive Living With HIV Study.

    Science.gov (United States)

    Poudel, Krishna C; Buchanan, David R; Amiya, Rachel M; Poudel-Tandukar, Kalpana

    2015-01-01

    The purpose of this study was to examine the association between perceived family support, either positive or negative, and adherence to antiretroviral medication regimens among HIV-positive individuals in the Kathmandu Valley, Nepal. We measured past 3-month antiretroviral adherence among 233 HIV-positive individuals, in relation to perceived family support, both positive (in terms of emotional and instrumental support) and negative (in the form of negative interactions), using the 10-item Nepali Family Support and Difficulty Scale. Medium and high levels of perceived emotional support from family were associated with reduced risk of antiretroviral nonadherence, compared with low levels of perceived emotional support (adjusted odds ratio [AOR]  = 0.37, 95% confidence interval [CI] [0.16, 0.88], and AOR  = 0.23, 95% CI [0.08, 0.64], respectively). Conversely, higher levels of felt emotional distance (AOR  = 1.46, 95% CI [1.00, 2.14]) and experienced physical harm (AOR  = 2.04, 95% CI [1.07, 3.91]) were associated with increased risk of nonadherence. The results support the recommendation that service providers need to be aware of the significant role of family support in shaping antiretroviral adherence and to consider ways to strengthen positive family support while minimizing negative family interactions to increase adherence rates. © The Author(s) 2015.

  14. HIV-1 protease mutations and inhibitor modifications. Results from a series of X-ray structures

    Czech Academy of Sciences Publication Activity Database

    Skálová, Tereza; Dohnálek, Jan; Dušková, Jarmila; Petroková, Hana; Hašek, Jindřich

    2006-01-01

    Roč. 13, č. 3 (2006), s. 142 ISSN 1211-5894. [Czech and Slovak Crystallographic Colloquium. 22.06.2006-24.06.2006, Grenoble] R&D Projects: GA AV ČR KJB4050312; GA AV ČR IAA4050811; GA MŠk 1K05008 Keywords : HIV-1 protease * X-ray diffraction Subject RIV: EB - Genetics ; Molecular Biology http://www. xray .cz/ms/default.htm

  15. HIV Serostatus Disclosure to Sexual Partners Among Sexually Active People Living with HIV in South Africa: Results from the 2012 National Population-Based Household Survey.

    Science.gov (United States)

    Simbayi, Leickness C; Zungu, Nompumelelo; Evans, Meredith; Mehlomakulu, Vuyelwa; Kupamupindi, Takura; Mafoko, Goitseone; Zuma, Khangelani

    2017-01-01

    This paper explores the prevalence and correlates of HIV seropositive status disclosure to sexual partners by people living with HIV (PLHIV) in South Africa. Secondary analysis of the 2012 South African National HIV Prevalence, Incidence and Behaviour Survey was conducted on data obtained from 934 sexually active PLHIV aged 15 years and older who responded to the question about HIV seropositive status disclosure. Overall, a large majority of respondents (77.1 %) reported disclosing their HIV-positive status to all their current sex partners. Multiple regression analysis, after adjustments for sex, marital status and locality type, revealed that those who were living together, going steady, and those who were single were all 60 % [adjusted odds ratio (AOR) = 0.4, 95 % CIs 0.20-0.78; AOR = 0.4, 95 % CIs 0.24-0.77; and AOR = 0.4, 95 % CIs 0.19-1.00, all ps < 0.05] less likely to disclose their HIV positive status to their partners compared to those who were married. Those who lived in rural formal areas were 70 % less likely to disclose their HIV status to their partners compared to those who stayed in urban formal areas (AOR = 0.3, 95 % CI 0.17-0.69, p < 0.001). Those who had correct HIV knowledge and rejection of myths were 2.0 times more likely to disclose their HIV status to their partners compared to those who did not have correct HIV knowledge and rejection of myths (AOR = 2.0, 95 % CI 1.04-3.68, p < 0.05). In conclusion, intervention programmes which help improve HIV seropositive status disclosure are needed by PLHIV who are not married, live in rural formal areas, and have incorrect HIV knowledge and rejection of myths.

  16. The Study of HIV and Antenatal Care Integration in Pregnancy in Kenya: Design, Methods, and Baseline Results of a Cluster-Randomized Controlled Trial

    Science.gov (United States)

    Turan, Janet M.; Steinfeld, Rachel L.; Onono, Maricianah; Bukusi, Elizabeth A.; Woods, Meghan; Shade, Starley B.; Washington, Sierra; Marima, Reson; Penner, Jeremy; Ackers, Marta L.; Mbori-Ngacha, Dorothy; Cohen, Craig R.

    2012-01-01

    Background Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma. Methodology/Principal Findings A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009– March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines. Conclusions/Significance This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery

  17. The study of HIV and antenatal care integration in pregnancy in Kenya: design, methods, and baseline results of a cluster-randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Janet M Turan

    Full Text Available Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT, HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma.A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment. During June 2009- March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines.This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving

  18. Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation.

    Directory of Open Access Journals (Sweden)

    Boris V Skryabin

    2007-12-01

    Full Text Available Prader-Willi syndrome (PWS [MIM 176270] is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonadism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScr(m-/p+ are indistinguishable from wild-type littermates. All those with the paternally inherited allele (PWScr(m+/p- consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6, but not FVB/N crosses. This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype.

  19. Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.

    Science.gov (United States)

    Lindbäck, S; Karlsson, A C; Mittler, J; Blaxhult, A; Carlsson, M; Briheim, G; Sönnerborg, A; Gaines, H

    2000-10-20

    To study the natural course of viremia during primary HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.

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

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    Ole S Søgaard

    2015-09-01

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

  1. Exploring the impact of the side-chain length on peptide/RNA binding events.

    Science.gov (United States)

    Sbicca, Lola; González, Alejandro López; Gresika, Alexandra; Di Giorgio, Audrey; Closa, Jordi Teixido; Tejedor, Roger Estrada; Andréola, Marie-Line; Azoulay, Stéphane; Patino, Nadia

    2017-07-19

    The impact of the amino-acid side-chain length on peptide-RNA binding events has been investigated using HIV-1 Tat derived peptides as ligands and the HIV-1 TAR RNA element as an RNA model. Our studies demonstrate that increasing the length of all peptide side-chains improves unexpectedly the binding affinity (K D ) but reduces the degree of compactness of the peptide-RNA complex. Overall, the side-chain length appears to modulate in an unpredictable way the ability of the peptide to compete with the cognate TAR RNA partner. Beyond the establishment of non-intuitive fundamental relationships, our results open up new perspectives in the design of effective RNA ligand competitors, since a large number of them have already been identified but few studies report on the modulation of the biological activity by modifying in the same way the length of all chains connecting RNA recognition motives to the central scaffold of a ligand.

  2. High Prevalence of HIV Drug Resistance Among Newly Diagnosed Infants Aged <18 Months: Results From a Nationwide Surveillance in Nigeria.

    Science.gov (United States)

    Inzaule, Seth C; Osi, Samuels J; Akinbiyi, Gbenga; Emeka, Asadu; Khamofu, Hadiza; Mpazanje, Rex; Ilesanmi, Oluwafunke; Ndembi, Nicaise; Odafe, Solomon; Sigaloff, Kim C E; Rinke de Wit, Tobias F; Akanmu, Sulaimon

    2018-01-01

    WHO recommends protease-inhibitor-based first-line regimen in infants because of risk of drug resistance from failed prophylaxis used in prevention of mother-to-child transmission (PMTCT). However, cost and logistics impede implementation in sub-Saharan Africa, and >75% of children still receive nonnucleoside reverse transcriptase inhibitor-based regimen (NNRTI) used in PMTCT. We assessed the national pretreatment drug resistance prevalence of HIV-infected children aged resistance surveillance protocol. We used remnant dried blood spots collected between June 2014 and July 2015 from 15 early infant diagnosis facilities spread across all the 6 geopolitical regions of Nigeria. Sampling was through a probability proportional-to-size approach. HIV drug resistance was determined by population-based sequencing. Overall, in 48% of infants (205 of 430) drug resistance mutations (DRM) were detected, conferring resistance to predominantly NNRTIs (45%). NRTI and multiclass NRTI/NNRTI resistance were present at 22% and 20%, respectively, while resistance to protease inhibitors was at 2%. Among 204 infants with exposure to drugs for PMTCT, 57% had DRMs, conferring NNRTI resistance in 54% and multiclass NRTI/NNRTI resistance in 29%. DRMs were also detected in 34% of 132 PMTCT unexposed infants. A high frequency of PDR, mainly NNRTI-associated, was observed in a nationwide surveillance among newly diagnosed HIV-infected children in Nigeria. PDR prevalence was equally high in PMTCT-unexposed infants. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected young children regardless of PMTCT history and underscore the need to accelerate implementation of the newly disseminated guideline in Nigeria.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. Bacterial vaginosis, alterations in vaginal flora and HIV genital shedding among HIV-1-infected women in Mozambique

    Directory of Open Access Journals (Sweden)

    Robert D Kirkcaldy

    2011-05-01

    Full Text Available Objectives. We investigated whether abnormal vaginal flora, including bacterial vaginosis (BV, are associated with detection of cervical HIV-1 RNA among HIV-infected women in Mozambique. Methods. We obtained clinical data and vaginal specimens from HIV-infected women registering for their first visit at one of two HIV care clinics in Mozambique. We compared women with detectable cervical HIV viral load (≥40 copies/ml with women with undetectable cervical HIV. Results. We enrolled 106 women. Women with abnormal vaginal flora (intermediate Nugent scores, 4 - 6 were more likely to have detectable cervical HIV RNA then women with normal vaginal flora (adjusted odds ratio 7.2 (95% confidence interval 1.8 - 29.1, adjusted for CD4 count. Women with BV had a non-significantly higher likelihood of detectable cervical HIV than women with normal flora. Conclusions. Abnormal vaginal flora were significantly associated with cervical HIV expression. Further research is needed to confirm this relationship.

  5. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.

    Science.gov (United States)

    Castagna, Antonella; Maggiolo, Franco; Penco, Giovanni; Wright, David; Mills, Anthony; Grossberg, Robert; Molina, Jean-Michel; Chas, Julie; Durant, Jacques; Moreno, Santiago; Doroana, Manuela; Ait-Khaled, Mounir; Huang, Jenny; Min, Sherene; Song, Ivy; Vavro, Cindy; Nichols, Garrett; Yeo, Jane M

    2014-08-01

    The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574). © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  6. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.

    Science.gov (United States)

    Eron, Joseph J; Clotet, Bonaventura; Durant, Jacques; Katlama, Christine; Kumar, Princy; Lazzarin, Adriano; Poizot-Martin, Isabelle; Richmond, Gary; Soriano, Vincent; Ait-Khaled, Mounir; Fujiwara, Tamio; Huang, Jenny; Min, Sherene; Vavro, Cindy; Yeo, Jane

    2013-03-01

    Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1-infected subjects with genotypic evidence of RAL resistance. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL.

  7. Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo

    International Nuclear Information System (INIS)

    Anesti, Anna-Maria; Simpson, Guy R; Price, Toby; Pandha, Hardev S; Coffin, Robert S

    2010-01-01

    Delivery of small interfering RNA (siRNA) to tumours remains a major obstacle for the development of RNA interference (RNAi)-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV) OncoVEX GM-CSF , we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV. To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA) or artificial microRNA (miRNA) against the reporter genes green fluorescent protein (eGFP) and β-galactosidase (lacZ). These vectors were tested in non-tumour cell lines in vitro and tumour cells that are moderately susceptible to HSV infection both in vitro and in mice xenografts in vivo. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting. Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cells in vitro and tumours in vivo, with the viruses expressing artificial miRNA being comprehensibly more effective. This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cells in vitro and in vivo. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen in human clinical trials

  8. Structure of the 30 kDa HIV-1 RNA Dimerization Signal by a Hybrid Cryo-EM, NMR, and Molecular Dynamics Approach.

    Science.gov (United States)

    Zhang, Kaiming; Keane, Sarah C; Su, Zhaoming; Irobalieva, Rossitza N; Chen, Muyuan; Van, Verna; Sciandra, Carly A; Marchant, Jan; Heng, Xiao; Schmid, Michael F; Case, David A; Ludtke, Steven J; Summers, Michael F; Chiu, Wah

    2018-03-06

    Cryoelectron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy are routinely used to determine structures of macromolecules with molecular weights over 65 and under 25 kDa, respectively. We combined these techniques to study a 30 kDa HIV-1 dimer initiation site RNA ([DIS] 2 ; 47 nt/strand). A 9 Å cryo-EM map clearly shows major groove features of the double helix and a right-handed superhelical twist. Simulated cryo-EM maps generated from time-averaged molecular dynamics trajectories (10 ns) exhibited levels of detail similar to those in the experimental maps, suggesting internal structural flexibility limits the cryo-EM resolution. Simultaneous inclusion of the cryo-EM map and 2 H-edited NMR-derived distance restraints during structure refinement generates a structure consistent with both datasets and supporting a flipped-out base within a conserved purine-rich bulge. Our findings demonstrate the power of combining global and local structural information from these techniques for structure determination of modest-sized RNAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  10. Different patterns of HIV-1 DNA after therapy discontinuation

    Directory of Open Access Journals (Sweden)

    Ghinelli Florio

    2005-09-01

    Full Text Available Abstract Background By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16 – 24 weeks to study the possible relationship between DNA and RNA viral load. Methods The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load. Results Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. Conclusion Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.

  11. Psychological factors, including alexithymia, in the prediction of cardiovascular risk in HIV infected patients: results of a cohort study.

    Directory of Open Access Journals (Sweden)

    Giustino Parruti

    Full Text Available Psychological factors are known predictors of cardiovascular disease in many clinical settings, but data are lacking for HIV infection. We carried out a prospective cohort study to evaluate potential psychological predictors of preclinical and clinical vascular disease in HIV patients.HIV patients were consecutively enrolled. Demographics, viral and immune parameters and traditional cardiovascular predictors were considered; Intima-Media Thickness (c-IMT, continuous measure and Carotid Plaques (CPs, focal thickening ≥1.5 mm were investigated by B-mode ultrasonography; depressive symptoms by the Beck Depression Inventory (BDI-II, Type D personality (Distressed Personality or Type D by the DS14, alexithymia by the Toronto Alexithymia Scale (TAS-20. Vascular outcomes included transient ischemic attacks or stroke, acute coronary syndrome, myocardial or other organ infarction. We enrolled 232 HIV subjects, 73.9% males, aged 44.5±9.9 y, 38.2% with AIDS diagnosis, 18.3% untreated. Mean Nadir CD4 T-cell counts were 237.5±186.2/mmc. Of them, 224 (96.5% attended IMT measurements; 201 (86.6% attended both IMT assessment and psychological profiling. Mean follow-up was 782±308 days. Fifty-nine patients (29.4% had CPs at baseline. Nineteen patients (9.5% had ≥1 vascular event; 12 (6.0% died due to such events (n = 4 or any cause. At baseline cross-sectional multivariate analysis, increasing age, total cholesterol, current smoking and Alexithymia score≥50 were significantly associated with both increased cIMT (linear regression and CPs (logistic regression. At follow-up analysis, log-rank tests and Cox's regression revealed that only older age (p = 0.001, current smoking (p = 0.019 and alexithymia score≥50 (p = 0.013 were independently associated with vascular events.In HIV-infected subjects, the Alexithymic trait emerges as a strong predictor of increased IMT, presence of CPs and vascular events. Such results are preliminary and require

  12. Repeat confirmatory testing for persons with discordant whole blood and oral fluid rapid HIV test results: findings from post marketing surveillance.

    Science.gov (United States)

    Wesolowski, Laura G; Mackellar, Duncan A; Ethridge, Steven F; Zhu, Julia H; Owen, S Michele; Sullivan, Patrick S

    2008-02-06

    Reactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB), immunofluorescent assay (IFA) or approved nucleic acid amplification test (NAAT)). When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result), repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results. Post-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing. Of 167,371 rapid tests conducted, 2589 (1.6%) were reactive: of these, 2417 (93%) had positive WB/IFA, 172 (7%) had negative or indeterminate WB/IFA. Of 89/172 (52%) persons with a repeat confirmatory test: 17 (19%) were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81%) were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative) (ptest [adjusted OR 2.6, 95% CI (1.3, 4.9)]. Though only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for persons with discordant results. Because of the lower sensitivity of oral fluid WBs, confirmatory testing following a reactive rapid test should be conducted using serum or plasma, when possible.

  13. The Coding Causes of Death in HIV (CoDe) Project: initial results and evaluation of methodology

    DEFF Research Database (Denmark)

    Kowalska, Justyna D; Friis-Møller, Nina; Kirk, Ole

    2011-01-01

    The Coding Causes of Death in HIV (CoDe) Project aims to deliver a standardized method for coding the underlying cause of death in HIV-positive persons, suitable for clinical trials and epidemiologic studies.......The Coding Causes of Death in HIV (CoDe) Project aims to deliver a standardized method for coding the underlying cause of death in HIV-positive persons, suitable for clinical trials and epidemiologic studies....

  14. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    Science.gov (United States)

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

  15. Factors associated with presenting late or with advanced HIV disease in the Netherlands, 1996–2014: results from a national observational cohort

    Science.gov (United States)

    Op de Coul, Eline L M; van Sighem, Ard; Brinkman, Kees; van Benthem, Birgit H; van der Ende, Marchina E; Geerlings, Suzanne; Reiss, Peter

    2016-01-01

    Objectives Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. Methods HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Results Of 20 965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Conclusions Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥50 years and certain regions in the Netherlands. PMID:26729389

  16. CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.

    Science.gov (United States)

    Abdel-Mohsen, Mohamed; Kuri-Cervantes, Leticia; Grau-Exposito, Judith; Spivak, Adam M; Nell, Racheal A; Tomescu, Costin; Vadrevu, Surya Kumari; Giron, Leila B; Serra-Peinado, Carla; Genescà, Meritxell; Castellví, Josep; Wu, Guoxin; Del Rio Estrada, Perla M; González-Navarro, Mauricio; Lynn, Kenneth; King, Colin T; Vemula, Sai; Cox, Kara; Wan, Yanmin; Li, Qingsheng; Mounzer, Karam; Kostman, Jay; Frank, Ian; Paiardini, Mirko; Hazuda, Daria; Reyes-Terán, Gustavo; Richman, Douglas; Howell, Bonnie; Tebas, Pablo; Martinez-Picado, Javier; Planelles, Vicente; Buzon, Maria J; Betts, Michael R; Montaner, Luis J

    2018-04-18

    The persistence of HIV reservoirs, including latently infected, resting CD4 + T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4 + T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4 + T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV + or SIV + subjects, we found that most of the circulating memory CD32 + CD4 + T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a T H 2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4 + T cells in peripheral blood or lymphoid tissue; isolated CD32 + resting CD4 + T cells accounted for less than 3% of the total HIV DNA in CD4 + T cells. Cell-associated HIV DNA and RNA loads in CD4 + T cells positively correlated with the frequency of CD32 + CD69 + CD4 + T cells but not with CD32 expression on resting CD4 + T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4 + T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4 + T cells enriched for transcriptionally active HIV after long-term ART. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Integration of HIV and TB services results in improved TB treatment outcomes and earlier prioritized ART initiation in a large urban HIV clinic in Uganda.

    Science.gov (United States)

    Hermans, Sabine M; Castelnuovo, Barbara; Katabira, Catherine; Mbidde, Peter; Lange, Joep M A; Hoepelman, Andy I M; Coutinho, Alex; Manabe, Yukari C

    2012-06-01

    The World Health Organization recommends that treatment of tuberculosis (TB) in HIV-infected patients should be integrated with HIV care. In December 2008, a separate outdoor-integrated TB/HIV clinic was instituted for attendees of a large urban HIV clinic in Uganda. We sought to evaluate associated TB and HIV treatment outcomes. Routinely collected clinical, pharmacy, and laboratory data were merged with TB clinic data for patients initiating TB treatment in 2009 and with TB register data for patients in 2007. TB treatment outcomes and (timing of) antiretroviral therapy (ART) initiation in ART-naive patients [overall and stratified by CD4+ T cell (CD4) count] in 2007 and 2009 were compared. Nosocomial transmission rates could not be assessed. Three hundred forty-six patients were initiated on TB treatment in 2007 and 366 in 2009. Median CD4 counts at TB diagnosis did not differ. TB treatment cure or completion increased from 62% to 68%, death or default decreased from 33% to 25% (P ART-naive TB patients were initiated on ART in 2009 versus 2007 (57% and 66%, P = 0.031), but this decrease was only in patients with CD4 counts >250 cells per cubic millimeter (19% vs. 48%, P = 0.003). More patients were started on ART during TB treatment (94% vs. 78%, P ART initiation. This supports rollout of a fully integrated TB/HIV service delivery model throughout high-prevalence TB and HIV settings.

  18. Sociodemographic factors and prejudice toward HIV and hepatitis B/C status in a working-age population: results from a national, cross-sectional study in Japan.

    Directory of Open Access Journals (Sweden)

    Hisashi Eguchi

    Full Text Available BACKGROUND: In many countries, HIV, hepatitis B virus (HBV, and hepatitis C virus (HCV infected individuals may face discrimination and mistreatment from coworkers. Effective interventions to reduce workplace discrimination are therefore needed to protect these vulnerable populations. The current study investigated potential associations between sociodemographic factors and prejudice toward HIV and HBV/HCV infected colleagues within a Japanese working population. METHODS: An online anonymous, nationwide internet survey was administered to a cross-section of approximately 3,000 individuals in Japan. The survey comprised 14 questions focusing on demographics (five items, basic HIV or HBV/HCV knowledge (eight items, and potential prejudice toward HIV or HBV/HCV infected colleagues (one item. The sociodemographic characteristics evaluated were sex, age, educational level, employment status, and individual income; with multiple logistic regression used for the analysis. RESULTS: In total, 3,055 individuals were recruited for the HIV related survey and 3,129 for the HBV/HCV related survey. Older age was significantly and positively associated with prejudice toward HIV infected colleagues (p<0.01 and negatively associated with prejudice toward HBV/HCV infected colleagues (p<0.01. Statistically significant associations were not observed between other sociodemographic characteristics and potential prejudice toward HIV and HBV/HCV infected coworkers. CONCLUSION: Overall, this study suggests that age may be associated with prejudice toward HIV and HBV/HCV infected colleagues among the working age population of Japan. As such, policy makers should consider the age of participants when formulating efforts to reduce prejudice toward HIV and HBV/HCV infected workers.

  19. Factors associated with presenting late or with advanced HIV disease in the Netherlands, 1996-2014: results from a national observational cohort.

    Science.gov (United States)

    Op de Coul, Eline L M; van Sighem, Ard; Brinkman, Kees; van Benthem, Birgit H; van der Ende, Marchina E; Geerlings, Suzanne; Reiss, Peter

    2016-01-04

    Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Of 20,965 patients, 53% presented with late-stage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥ 50 years and certain regions in the Netherlands. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. HIV/AIDS case management tasks and activities: the results of a functional analysis study.

    Science.gov (United States)

    Grube, B; Chernesky, R H

    2001-01-01

    Functional analysis, a variation of the time study technique, was used to examine how HIV/AIDS case managers in the tri-county region of New York State spend their time-the actual tasks and activities they choose to perform relative to the total universe of activities and tasks subsumed in the general category of case management. The picture developed was of a system operating primarily in a crisis mode, spending relatively brief amounts of time completing a range of activities and providing an extensive scope of services for or on behalf of clients. The bulk of the work was client centered, not administrative, and involved providing disease management and essential services (e.g., family and mental health). The implications of these findings are discussed, with particular attention paid to the potential influence of client profiles and worker demographics.

  1. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Nittaya Phanuphak

    Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  2. The Alphabet Soup of HIV Reservoir Markers.

    Science.gov (United States)

    Sharaf, Radwa R; Li, Jonathan Z

    2017-04-01

    Despite the success of antiretroviral therapy in suppressing HIV, life-long therapy is required to avoid HIV reactivation from long-lived viral reservoirs. Currently, there is intense interest in searching for therapeutic interventions that can purge the viral reservoir to achieve complete remission in HIV patients off antiretroviral therapy. The evaluation of such interventions relies on our ability to accurately and precisely measure the true size of the viral reservoir. In this review, we assess the most commonly used HIV reservoir assays, as a clear understanding of the strengths and weaknesses of each is vital for the accurate interpretation of results and for the development of improved assays. The quantification of intracellular or plasma HIV RNA or DNA levels remains the most commonly used tests for the characterization of the viral reservoir. While cost-effective and high-throughput, these assays are not able to differentiate between replication-competent or defective fractions or quantify the number of infected cells. Viral outgrowth assays provide a lower bound for the fraction of cells that can produce infectious virus, but these assays are laborious, expensive and substantially underestimate the potential reservoir of replication-competent provirus. Newer assays are now available that seek to overcome some of these problems, including full-length proviral sequencing, inducible HIV RNA assays, ultrasensitive p24 assays and murine adoptive transfer techniques. The development and evaluation of strategies for HIV remission rely upon our ability to accurately and precisely quantify the size of the remaining viral reservoir. At this time, all current HIV reservoir assays have drawbacks such that combinations of assays are generally needed to gain a more comprehensive view of the viral reservoir. The development of novel, rapid, high-throughput assays that can sensitively quantify the levels of the replication-competent HIV reservoir is still needed.

  3. Economic evaluation of HIV testing for men who have sex with men in community-based organizations - results from six European cities.

    Science.gov (United States)

    Perelman, Julian; Rosado, Ricardo; Amri, Omar; Morel, Stéphane; Rojas Castro, Daniela; Chanos, Sophocles; Cigan, Bojan; Lobnik, Miha; Fuertes, Ricardo; Pichon, François; Kaye, Per Slaaen; Agustí, Cristina; Fernàndez-López, Laura; Lorente, Nicolas; Casabona, Jordi

    2017-08-01

    The non-decreasing incidence of HIV among men who have sex with men (MSM) has motivated the emergence of Community Based Voluntary Counselling and Testing (CBVCT) services specifically addressed to MSM. The CBVCT services are characterized by facilitated access and linkage to care, a staff largely constituted by voluntary peers, and private not-for-profit structures outside the formal health system institutions. Encouraging results have been measured about their effectiveness, but these favourable results may have been obtained at high costs, questioning the opportunity to expand the experience. We performed an economic evaluation of HIV testing for MSM at CBVCT services, and compared them across six European cities. We collected retrospective data for six CBVCT services from six cities (Copenhagen, Paris, Lyon, Athens, Lisbon, and Ljubljana), for the year 2014, on the number of HIV tests and HIV reactive tests, and on all expenditures to perform the testing activities. The total costs of CBVCTs varied from 54,390€ per year (Ljubljana) to 245,803€ per year (Athens). The cost per HIV test varied from to 41€ (Athens) to 113€ (Ljubljana). The cost per HIV reactive test varied from 1966€ (Athens) to 9065€ (Ljubljana). Our results show that the benefits of CBVCT services are obtained at an acceptable cost, in comparison with the literature (values, mostly from the USA, range from 1600$ to 16,985$ per HIV reactive test in clinical and non-clinical settings). This result was transversal to several European cities, highlighting that there is a common CBVCT model, the cost of which is comparable regardless of the epidemiological context and prices. The CBVCT services represent an effective and "worth it" experience, to be continued and expanded in future public health strategies towards HIV.

  4. Downregulation of cinnamyl-alcohol dehydrogenase in switchgrass by RNA silencing results in enhanced glucose release after cellulase treatment.

    Directory of Open Access Journals (Sweden)

    Aaron J Saathoff

    Full Text Available Cinnamyl alcohol dehydrogenase (CAD catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. "Alamo" with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2. The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin.

  5. Downregulation of cinnamyl-alcohol dehydrogenase in switchgrass by RNA silencing results in enhanced glucose release after cellulase treatment.

    Science.gov (United States)

    Saathoff, Aaron J; Sarath, Gautam; Chow, Elaine K; Dien, Bruce S; Tobias, Christian M

    2011-01-27

    Cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. "Alamo" with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2. The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin.

  6. Factors Associated With HIV Testing Among Men in Haiti: Results From the 2012 Demographic and Health Survey.

    Science.gov (United States)

    Conserve, Donaldson F; Iwelunmor, Juliet; Whembolua, Guy-Lucien; Sofolahan-Oladeinde, Yewande; Teti, Michelle; Surkan, Pamela J

    2017-09-01

    HIV testing serves as the gateway to HIV prevention and treatment. However, research examining men's HIV testing behaviors in the Caribbean remains limited. The Andersen Behavioral Model of Health Services Utilization was used to examine factors associated with HIV testing among 7,354 men who participated in the 2012 Demographic and Health Survey conducted in Haiti. Few men (35%) reported having ever been tested for HIV. Logistic regression analyses revealed that HIV testing increased with education and wealth. Marital status was associated with HIV testing, with married men more likely to have been tested (adjusted odds ratio: 2.57, 95% CI [2.07, 3.19]) than unmarried men. Positive attitudes toward people living with HIV, indicated by willing to care for a relative who has HIV/AIDS, was also correlated with higher odds of having been tested (adjusted odds ratio: 1.28, 95% CI [1.08, 1.51]). Men who reported condom use during last sex were more likely to have been tested (odds ratio: 1.58, 95% CI [1.33, 1.88). The findings indicate that HIV testing rates remain low among men in Haiti and more efforts are needed to increase HIV testing among men who are not married, have low level of education, and engage in unprotected sex.

  7. Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts

    DEFF Research Database (Denmark)

    Nielsen, S. D.; Jeppesen, D. L.; Kolte, L.

    2001-01-01

    and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P ...). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T...... cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function....

  8. HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study.

    Science.gov (United States)

    Sungkanuparph, Somnuek; Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Li, Patrick C K; Kantipong, Pacharee; Lee, Christopher K C; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G; Phanuphak, Praphan

    2011-04-15

    Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.

  9. HIV prevention among male clients of female sex workers in Kaolack, Senegal: results of a peer education program.

    Science.gov (United States)

    Leonard, L; Ndiaye, I; Kapadia, A; Eisen, G; Diop, O; Mboup, S; Kanki, P

    2000-02-01

    This article reports the results of a peer-led HIV prevention education and condom promotion program among transport workers in Kaolack, Senegal. As part of a 2-year longitudinal follow-up study, changes in men's AIDS-related knowledge, sexual behavior, condom use, and perceived barriers to condom use were evaluated by self-reports obtained from a systematic sample of transport workers interviewed before and after intervention. In addition to men's self-reports, preintervention and postintervention data on men's sexual and condom use behavior were gathered from a sample of licensed, commercial sex workers, who cited transport workers as their primary source of clients. Significant increases in men's HIV-related knowledge, previous use of condoms (from 30.4% to 53.5%), and consistent condom use with regular sex partners were documented over the study period, as were significant declines in perceived barriers to condom use. Though men reported significantly fewer sexual encounters with casual and commercial partners at follow-up compared to baseline, these data were unreliable. Women's postintervention reports indicate that a greater proportion of clients (including, but not limited to transport workers) "always" agree to use condoms (p money for unprotected sex (p taking greater initiative in the mechanics of condom use (supplying the condom, putting it on, and taking it off) than they did prior to the intervention, and significantly (p < .05) fewer women think that most of their clients know how to use a condom. The findings indicate that the peer-mediated intervention had a positive impact on several important outcomes measured and suggest that HIV prevention efforts need to focus on male client groups despite the logistical and methodological challenges.

  10. Impact of HIV Type 1 DNA Levels on Spontaneous Disease Progression: A Meta-Analysis

    DEFF Research Database (Denmark)

    Tsiara, Chrissa G; Nikolopoulos, Georgios K; Bagos, Pantelis G

    2012-01-01

    Abstract Several studies have reported the prognostic strength of HIV-1 DNA with variable results however. The aims of the current study were to estimate more accurately the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) or death...... of primary studies indicated that HIV-1 DNA was a significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1 disease progression...

  11. A high HIV-1 strain variability in London, UK, revealed by full-genome analysis: Results from the ICONIC project

    Science.gov (United States)

    Frampton, Dan; Gallo Cassarino, Tiziano; Raffle, Jade; Hubb, Jonathan; Ferns, R. Bridget; Waters, Laura; Tong, C. Y. William; Kozlakidis, Zisis; Hayward, Andrew; Kellam, Paul; Pillay, Deenan; Clark, Duncan; Nastouli, Eleni; Leigh Brown, Andrew J.

    2018-01-01

    Background & methods The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker. Results The pipeline generated sequences of at least 1Kb of length (median = 7.46Kb, IQR = 4.01Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n = 149, 40.8%) and C (n = 77, 21.1%) and the circulating recombinant form CRF02_AG (n = 32, 8.8%). We found 14 different CRFs (n = 66, 18.1%) and multiple URFs (n = 32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RT pol region, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similar pol sequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset. Conclusions

  12. HIV/AIDS and the health of older people in the slums of Nairobi, Kenya: results from a cross sectional survey

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    Zulu Eliya

    2009-05-01

    Full Text Available Abstract Background The proportion of older people is increasing worldwide. Globally, it is estimated that older people (those 60 years or older constitute more than 11% of the population. As the HIV/AIDS pandemic rages in sub-Saharan Africa (SSA, its impact on older people needs closer attention given the increased economic and social roles older people have taken on as a result of increased mortality among adults in the productive age groups. Few studies have looked at older people and their health in SSA or indeed the impact of HIV/AIDS on their health. This study aims to assess the effect of being directly or indirectly affected by HIV/AIDS on the health of older people in two Nairobi slums. Methods Data were collected from residents of the Nairobi Urban Health and Demographic Surveillance area aged 50 years and above on 1st October 2006. Health status was assessed using the short SAGE (Study on Global AGEing and Adult Health form and two outcome measures – self-rated health and a composite health score – were generated. To assess HIV/AIDS affected status, respondents were asked: Have you personally been affected by HIV/AIDS? If yes, a follow up question: "How have you been personally affected by HIV/AIDS?" was asked. Ordinallogistic regression was used in models with self-rated health and linear regression in models with the health score. Results About 18% of respondents reported being affected by HIV/AIDS in at least one way, although less than 1% reported being infected with HIV. Nearly 60% of respondents reported being in good health, 27% in fair health and 14% in poor health. The overall mean health score was 70.6 (SD: 13.9 with females reporting worse health outcomes than males. Respondents directly or indirectly affected by HIV/AIDS reported worse health outcomes than those not affected: mean health score: 68.5 and 71.1 respectively (t = 3.21, p = 0.0007, and an adjusted odds ratio of reporting poor health of 1.42 (95%CI: 1.12–1

  13. Comparison between Roche and Xpert in HIV-1 RNA quantitation: A high concordance between the two techniques except for a CRF02_AG subtype variant with high viral load titters detected by Roche but undetected by Xpert.

    Science.gov (United States)

    Avidor, Boaz; Matus, Natalia; Girshengorn, Shirley; Achsanov, Svetlana; Gielman, Simona; Zeldis, Irene; Schweitzer, Inbal; Adler, Amos; Turner, Dan

    2017-08-01

    HIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. To compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory. A total of 383 plasma samples of HIV-1 infected patients previously tested by Roche, were retrospectively tested by Xpert to determine concordance between the two assays. Samples included a diversity of HIV-1 subtypes and a wide range of VLs. There was a high concordance between the two assays, except for a CRF02_AG subtype variant with high VL titters, that was detected by Roche but undetected by Xpert. The 5' long terminal repeat gene region of this virus, targeted by the Xpert assay, was amplified and sequenced. A 25 nucleotide insert was identified, but was unmatched to any known sequences of HIV-1. This particular insert, however could not explain the false-negativity by the Xpert assay. This study underlines the challenge to routine VL testing due to the high genetic diversity of HIV-1. Clinicians should, therefore be advised that a negative VL in cases where the clinical picture does not match the laboratory report, might in fact be, a false-negative result of the VL assay. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Effects of unplanned treatment interruptions on HIV treatment failure– results from TAHOD

    Science.gov (United States)

    Jiamsakul, Awachana; Kerr, Stephen J.; Ng, Oon Tek; Lee, Man Po; Chaiwarith, Romanee; Yunihastuti, Evy; Van Nguyen, Kinh; Pham, Thuy Thanh; Kiertiburanakul, Sasisopin; Ditangco, Rossana; Saphonn, Vonthanak; Sim, Benedict L. H.; Merati, Tuti Parwati; Wong, Wingwai; Kantipong, Pacharee; Zhang, Fujie; Choi, Jun Yong; Pujari, Sanjay; Kamarulzaman, Adeeba; Oka, Shinichi; Mustafa, Mahiran; Ratanasuwan, Winai; Petersen, Boondarika; Law, Matthew; Kumarasamy, Nagalingeswaran

    2016-01-01

    Objectives Treatment interruptions (TI) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia. Methods Patients initiating cART between 2006-2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Co-variables with p30 days were associated with failure (31-180 days HR=2.66, 95%CI (1.70-4.16); 181-365 days HR=6.22, 95%CI (3.26-11.86); and >365 days HR=9.10, 95% CI (4.27-19.38), all pfailure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption. PMID:26950901

  16. Community-based interventions that work to reduce HIV stigma and discrimination: results of an evaluation study in Thailand.

    Science.gov (United States)

    Jain, Aparna; Nuankaew, Ratana; Mongkholwiboolphol, Nungruthai; Banpabuth, Arunee; Tuvinun, Rachada; Oranop Na Ayuthaya, Pakprim; Richter, Kerry

    2013-11-13

    HIV stigma and discrimination are major issues affecting people living with HIV in their everyday lives. In Thailand, a project was implemented to address HIV stigma and discrimination within communities with four activities: (1) monthly banking days; (2) HIV campaigns; (3) information, education and communication (IEC) materials and (4) "Funfairs." This study evaluates the effect of project interventions on reducing community-level HIV stigma. A repeated cross-sectional design was developed to measure changes in HIV knowledge and HIV-related stigma domains among community members exposed to the project. Two cross-sectional surveys were implemented at baseline (respondent n=560) and endline (respondent n=560). T-tests were employed to assess changes on three stigma domains: fear of HIV infection through daily activity, shame associated with having HIV and blame towards people with HIV. Baseline scales were confirmed at endline, and each scale was regressed on demographic characteristics, HIV knowledge and exposure to intervention activities. No differences were observed in respondent characteristics at baseline and endline. Significant changes were observed in HIV transmission knowledge, fear of HIV infection and shame associated with having HIV from baseline to endline. Respondents exposed to three specific activities (monthly campaign, Funfair and IEC materials) were less likely to exhibit stigma along the dimensions of fear (3.8 points lower on average compared to respondents exposed to none or only one intervention; 95% CI: -7.3 to -0.3) and shame (4.1 points lower; 95% CI: -7.7 to -0.6), net of demographic controls and baseline levels of stigma. Personally knowing someone with HIV was associated with low fear and shame, and females were less likely to possess attitudes of shame compared to males. The multivariate linear models suggest that a combination of three interventions was critical in shifting community-level stigma--monthly campaign, Funfair and IEC

  17. Can family-centered programing mitigate HIV risk factors among orphaned and vulnerable adolescents? Results from a pilot study in South Africa.

    Science.gov (United States)

    Thurman, Tonya Renee; Nice, Johanna; Luckett, Brian; Visser, Maretha

    2018-04-01

    Let's Talk is a structured, family-centered adolescent HIV prevention program developed for use in South Africa using key components adapted from programs successfully implemented in the US and South Africa. It is designed to address individual HIV transmission risk factors common among orphaned and vulnerable adolescents, including elevated risk for poor psychological health and sexual risk behavior. These efforts are accentuated through parallel programing to support caregivers' mental health and parenting skills. Twelve Let's Talk groups, each serving approximately 10 families, were piloted by two local community-based organizations in Gauteng and Kwa-Zulu Natal provinces, South Africa. Face-to-face interviews were conducted among participating caregivers and adolescents at baseline and three months post-intervention to explore the potential effects of the program on intermediate outcomes that may support HIV preventive behavior. Specifically, generalized estimation equations were used to estimate average change on HIV prevention knowledge and self-efficacy, caregiver and adolescent mental health, and family dynamics. Among the 105 adolescents and their 95 caregivers who participated in Let's Talk and completed both surveys, statistically significant improvements were found for adolescents' HIV and condom use knowledge as well as condom negotiation self-efficacy, but not sexual refusal self-efficacy. Both caregivers and adolescents demonstrated significantly better mental health at post-test. Adolescent/caregiver connection and communication about healthy sexuality also improved. These preliminary results highlight the potential of HIV prevention interventions that engage caregivers alongside the vulnerable adolescents in their care to mitigate adolescent HIV risk factors. A more rigorous evaluation is warranted to substantiate these effects and identify their impact on adolescents' risk behavior and HIV incidence.

  18. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected...... patients (HCV genotype 1 (n = 16), 2 (n = 2), and 3 (n = 3)). Lower baseline IP-10 was significantly associated with a rapid decline in HCV RNA, in particular with the first phase reduction, and similar cut-off levels ( 600 pg/ml) as in HCV mono-infected patients apply. In conclusion, baseline IP......-10 infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  19. HIV/AIDS and the health of older people in the slums of Nairobi, Kenya: results from a cross sectional survey.

    Science.gov (United States)

    Kyobutungi, Catherine; Ezeh, Alex C; Zulu, Eliya; Falkingham, Jane

    2009-05-27

    The proportion of older people is increasing worldwide. Globally, it is estimated that older people (those 60 years or older) constitute more than 11% of the population. As the HIV/AIDS pandemic rages in sub-Saharan Africa (SSA), its impact on older people needs closer attention given the increased economic and social roles older people have taken on as a result of increased mortality among adults in the productive age groups. Few studies have looked at older people and their health in SSA or indeed the impact of HIV/AIDS on their health. This study aims to assess the effect of being directly or indirectly affected by HIV/AIDS on the health of older people in two Nairobi slums. Data were collected from residents of the Nairobi Urban Health and Demographic Surveillance area aged 50 years and above on 1st October 2006. Health status was assessed using the short SAGE (Study on Global AGEing and Adult Health) form and two outcome measures--self-rated health and a composite health score--were generated. To assess HIV/AIDS affected status, respondents were asked: Have you personally been affected by HIV/AIDS? If yes, a follow up question: "How have you been personally affected by HIV/AIDS?" was asked. Ordinallogistic regression was used in models with self-rated health and linear regression in models with the health score. About 18% of respondents reported being affected by HIV/AIDS in at least one way, although less than 1% reported being infected with HIV. Nearly 60% of respondents reported being in good health, 27% in fair health and 14% in poor health. The overall mean health score was 70.6 (SD: 13.9) with females reporting worse health outcomes than males. Respondents directly or indirectly affected by HIV/AIDS reported worse health outcomes than those not affected: mean health score: 68.5 and 71.1 respectively (t = 3.21, p = 0.0007), and an adjusted odds ratio of reporting poor health of 1.42 (95%CI: 1.12-1.80). Poor health outcomes among older people affected by

  20. RNA/DNA co-analysis from human skin and contact traces – results of a sixth collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, C; Hanson, E; Banemann, R

    2015-01-01

    The European DNA profiling group (EDNAP) organized a sixth collaborative exercise on RNA/DNA co-analysis for body fluid/tissue identification and STR profiling. The task was to identify skin samples/contact traces using specific RNA biomarkers and test three housekeeping genes for their suitabili...

  1. Measuring HIV- and AIDS-related stigma and discrimination in Nicaragua: results from a community-based study.

    Science.gov (United States)

    Ugarte, William J; Högberg, Ulf; Valladares, Eliette C; Essén, Birgitta

    2013-04-01

    Psychometric properties of external HIV-related stigma and discrimination scales and their predictors were investigated. A cross-sectional community-based study was carried out among 520 participants using an ongoing health and demographic surveillance system in León, Nicaragua. Participants completed an 18-item HIV stigma scale and 19 HIV and AIDS discrimination-related statements. A factor analysis found that 15 of the 18 items in the stigma scale and 18 of the 19 items in the discrimination scale loaded clearly into five- and four-factor structures, respectively. Overall Cronbach's alpha of .81 for the HIV stigma scale and .91 for the HIV discrimination scale provided evidence of internal consistency. Hierarchical multiple linear regression analysis identified that females, rural residents, people with insufficient HIV-related transmission knowledge, those not tested for HIV, those reporting an elevated self-perception of HIV risk, and those unwilling to disclose their HIV status were associated with higher stigmatizing attitudes and higher discriminatory actions towards HIV-positive people. This is the first community-based study in Nicaragua that demonstrates that overall HIV stigma and discrimination scales were reliable and valid in a community-based sample comprised of men and women of reproductive age. Stigma and discrimination were reported high in the general population, especially among sub-groups. The findings in the current study suggest community-based strategies, including the monitoring of stigma and discrimination, and designing and implementing stigma reduction interventions, are greatly needed to reduce inequities and increase acceptance of persons with HIV.

  2. HIV and STI control in El Salvador: results from an integrated behavioural survey among men who have sex with men.

    Science.gov (United States)

    Creswell, Jacob; Guardado, Maria Elena; Lee, Janet; Nieto, Ana Isabel; Kim, Andrea A; Monterroso, Edgar; Paz-Bailey, Gabriela

    2012-12-01

    This cross-sectional study investigates HIV, other sexually transmitted infections (STI), and risk behaviours among men who have sex with men (MSM) in two cities in El Salvador. Respondent-driven sampling (RDS) was used to recruit MSM in the cities of San Salvador and San Miguel, El Salvador. Participants responded to questions about HIV risk behaviours; and blood, urine and anal swabs were collected. Blood samples were tested for herpes simplex type 2, syphilis and HIV infection. Urine and anal samples were tested by polymerase chain reaction (PCR) for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium. HIV-positive samples were tested with the BED capture enzyme immunoassay to distinguish recent from longstanding HIV infection. We estimated population-adjusted prevalence of behavioural variables, STI and HIV, and identified risk factors for HIV. The final sample included 596 and 195 MSM in San Salvador and San Miguel, respectively. Consistent condom use was low across all partner types as was recent HIV testing. RDS-adjusted HIV prevalence was 10.8% (95% CI 7.4% to 14.7%) in San Salvador, and 8.8% (95% CI 4.2% to 14.5%) in San Miguel. The proportion of recent testing among HIV-positive samples was 20%. Prevalence of any bacterial STI by PRC testing was 12.7% (95% CI 8.2% to 17.5%) in San Salvador, and 9.6% (95% CI 4.9% to 15.4%) in San Miguel. We found a high prevalence of HIV, high levels of recent infection, and low condom usage. In El Salvador, targeted interventions towards MSM are needed to promote condom use, as well as to diagnose, treat and prevent HIV and other STIs.

  3. HIV-DNA in the genital tract of women on long-term effective therapy is associated to residual viremia and previous AIDS-defining illnesses.

    Directory of Open Access Journals (Sweden)

    Thierry Prazuck

    Full Text Available OBJECTIVES: To assess the impact of long-term combined antiretroviral therapy (cART on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL; to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission. METHODS: Women with undetectable PVL (6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL. Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated. RESULTS: Eighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%. There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08. In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2-61 and current residual viremia (20HIV-DNA detection in CVL. Twenty-eight percent of the women had unprotected intercourse with their regular HIV-seronegative male partner, for between 8 and 158 months. None of their male partners became infected, after a total of 14 000 exposures. CONCLUSION: In our experience, HIV-RNA was undetectable in the genital tract of women with sustained control of PVL on cART. HIV-DNA shedding persisted in about one third of cases, with no substantial evidence of residual infectiousness.

  4. The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity

    NARCIS (Netherlands)

    Amadori, Céline; Ubeles van der Velden, Yme; Bonnard, Damien; Orlov, Igor; van Bel, Nikki; Le Rouzic, Erwann; Miralles, Laia; Brias, Julie; Chevreuil, Francis; Spehner, Daniele; Chasset, Sophie; Ledoussal, Benoit; Mayr, Luzia; Moreau, François; García, Felipe; Gatell, José; Zamborlini, Alessia; Emiliani, Stéphane; Ruff, Marc; Klaholz, Bruno P.; Moog, Christiane; Berkhout, Ben; Plana, Montserrat; Benarous, Richard

    2017-01-01

    HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF

  5. Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

    Science.gov (United States)

    Mocroft, Amanda; Lundgren, Jens D.; Sabin, Miriam Lewis; Monforte, Antonella d'Arminio; Brockmeyer, Norbert; Casabona, Jordi; Castagna, Antonella; Costagliola, Dominique; Dabis, Francois; De Wit, Stéphane; Fätkenheuer, Gerd; Furrer, Hansjakob; Johnson, Anne M.; Lazanas, Marios K.; Leport, Catherine; Moreno, Santiago; Obel, Niels; Post, Frank A.; Reekie, Joanne; Reiss, Peter; Sabin, Caroline; Skaletz-Rorowski, Adriane; Suarez-Lozano, Ignacio; Torti, Carlo; Warszawski, Josiane; Zangerle, Robert; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Kirk, Ole

    2013-01-01

    Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP. Please see later in the article for the Editors' Summary PMID:24137103

  6. Identifying HIV-1 dual infections

    Directory of Open Access Journals (Sweden)

    Cornelissen Marion

    2007-09-01

    Full Text Available Abstract Transmission of human immunodeficiency virus (HIV is no exception to the phenomenon that a second, productive infection with another strain of the same virus is feasible. Experiments with RNA viruses have suggested that both coinfections (simultaneous infection with two strains of a virus and superinfections (second infection after a specific immune response to the first infecting strain has developed can result in increased fitness of the viral population. Concerns about dual infections with HIV are increasing. First, the frequent detection of superinfections seems to indicate that it will be difficult to develop a prophylactic vaccine. Second, HIV-1 superinfections have been associated with accelerated disease progression, although this is not true for all persons. In fact, superinfections have even been detected in persons controlling their HIV infections without antiretroviral therapy. Third, dual infections can give rise to recombinant viruses, which are increasingly found in the HIV-1 epidemic. Recombinants could have increased fitness over the parental strains, as in vitro models suggest, and could exhibit increased pathogenicity. Multiple drug resistant (MDR strains could recombine to produce a pan-resistant, transmittable virus. We will describe in this review what is presently known about super- and re-infection among ambient viral infections, as well as the first cases of HIV-1 superinfection, including HIV-1 triple infections. The clinical implications, the impact of the immune system, and the effect of anti-retroviral therapy will be covered, as will as the timing of HIV superinfection. The methods used to detect HIV-1 dual infections will be discussed in detail. To increase the likelihood of detecting a dual HIV-1 infection, pre-selection of patients can be done by serotyping, heteroduplex mobility assays (HMA, counting the degenerate base codes in the HIV-1 genotyping sequence, or surveying unexpected increases in the

  7. NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.

    Directory of Open Access Journals (Sweden)

    Shahin Ranjbar

    2006-12-01

    Full Text Available To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5, which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS.

  8. Interference RNA (RNAi)-based silencing of endogenous thrombopoietin receptor (Mpl) in Dami cells resulted in decreased hNUDC-mediated megakaryocyte proliferation and differentiation

    International Nuclear Information System (INIS)

    Pang, Shi-Feng; Li, Xiao-Kun; Zhang, Qiang; Yang, Fang; Xu, Peilin

    2009-01-01

    Recently our laboratory reported evidence showing that hNUDC acts as an additional cytokine for thrombopoietin receptor (Mpl). Previously known as the human homolog of a fungal nuclear migration protein, hNUDC plays a critical role in megakaryocyte differentiation and maturation. Here we sought to further clarify the hNUDC-Mpl ligand-receptor relationship by utilizing interference RNA (RNAi) to knockdown Mpl expression in a megakaryocyte cell line. We created U6 promoter driven constructs to express short hairpin RNAs (shRNA) with affinity for different sites on Mpl mRNA. By including Mpl-EGFP fusion protein in these constructs, we were able to effectively screen the shRNA that was most efficient in inhibiting Mpl mRNA expression. This shRNA was subsequently transferred into a lentivirus vector and transduced into Dami cells, a cell line which constitutively expresses endogenous Mpl. This lentiviral vector was also designed to simultaneously express EGFP to monitor transfection efficiency. Our results show that lentivirus can be used to effectively deliver shRNAs into Dami cells and cause specific inhibition of Mpl protein expression after transduction. Furthermore, we show the functional effects of shRNA-mediated Mpl silencing by demonstrating reduced hNUDC stimulated megakaryocyte proliferation and differentiation. Thus, the use of a RNAi knockdown strategy has allowed us to pinpoint the connection of hNUDC with Mpl in the regulation of megakaryocyte maturation.

  9. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, T F; Christensen, René dePont; Andersen, R F

    2013-01-01

    Background:This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC).Methods:A total of 230 patients......-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry.Results:High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95...... on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics....

  10. Cytoplasmic Dynein Promotes HIV-1 Uncoating

    Directory of Open Access Journals (Sweden)

    Paulina Pawlica

    2014-11-01

    Full Text Available Retroviral capsid (CA cores undergo uncoating during their retrograde transport (toward the nucleus, and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted dynein heavy chain (DHC using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we observed an increase in amounts of intact (pelletable CA cores upon DHC depletion or p50 over-expression. Results from these two complementary assays suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating in infected cells, indicating the existence of a functional link between HIV-1 transport and uncoating.

  11. Trofile HIV co-receptor usage assay.

    Science.gov (United States)

    Low, Andrew J; McGovern, Rachel A; Harrigan, P Richard

    2009-03-01

    The introduction of CCR5 antagonists increases the options available for constructing therapeutic drug regimens for HIV-positive patients. However, as these drugs do not inhibit HIV variants that use the CXCR4 co-receptor, a pretreatment test is required to determine accurately HIV co-receptor usage (tropism) before initiating CCR5 antagonist-based therapy. To discuss the Monogram Trofile assay as a diagnostic tool for determining HIV tropism by critically reviewing reported literature and available data. Monogram Trofile has become, largely by default, the de facto standard for HIV tropism assay. However, there is significant room for improvement in the speed, cost and availability of the test. Furthermore, the test is not quantitative, requires high-input HIV RNA viral loads, and produces results that are less biologically stable than expected. These technical considerations may limit the use of CCR5 antagonists in therapy. Nevertheless, this test is likely to remain the most widely used tropism diagnostic for the short term. We expect that a more practical and possibly more accurate method for measuring HIV tropism can be developed.

  12. 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.

  13. Case Report: HIV test misdiagnosis

    African Journals Online (AJOL)

    Case Study: HIV test misdiagnosis 124. Case Report: HIV ... A positive rapid HIV test does not require ... 3 College of Medicine - Johns Hopkins Research Project, Blantyre,. Malawi ... test results: a pilot study of three community testing sites.

  14. The Mpumalanga Men's Study (MPMS: results of a baseline biological and behavioral HIV surveillance survey in two MSM communities in South Africa.

    Directory of Open Access Journals (Sweden)

    Tim Lane

    Full Text Available The Mpumalanga Men's Study (MPMS is the assessment of the Project Boithato HIV prevention intervention for South African MSM. Boithato aims to increase consistent condom use, regular testing for HIV-negative MSM, and linkage to care for HIV-positive MSM. The MPMS baseline examined HIV prevalence and associated risk behaviors, and testing, care, and treatment behaviors among MSM in Gert Sibande and Ehlanzeni districts in Mpumalanga province, South Africa in order to effectively target intervention activities. We recruited 307 MSM in Gert Sibande and 298 in Ehlanzeni through respondent-driven sampling (RDS between September 2012-March 2013. RDS-adjusted HIV prevalence estimates are 28.3% (95% CI 21.1%-35.3% in Gert Sibande, and 13.7% (95% CI 9.1%-19.6% in Ehlanzeni. Prevalence is significantly higher among MSM over age 25 [57.8% (95% CI 43.1%-72.9% vs. 17.9% (95% CI 10.6%-23.9%, P<0.001 in Gert Sibande; 34.5% (95%CI 20.5%-56.0% vs. 9.1% (95% CI 4.6%-13.9%, P<0.001 in Ehlanzeni]. In Gert Sibande, prevalence is higher among self-identified gay and transgender MSM vs. other MSM [39.3% (95%CI, 28.3%-47.9%, P<0.01], inconsistent condom users [38.1% (18.1%-64.2%, P<0.05], those with a current regular male partner [35.0% (27.1%-46.4%, P<0.05], and those with lifetime experience of intimate partner violence with men [40.4%, (95%CI 28.9%-50.9%, P<0.05]. Prevalence of previous HIV testing was 65.8% (95%CI 58.8%-74.0% in Gert Sibande, and 69.3% (95%CI 61.9%-76.8% in Ehlanzeni. Regular HIV testing was uncommon [(34.6%, (95%CI 27.9%-41.4% in Gert Sibande; 31.0% (95%CI 24.9%-37.8% in Ehlanzeni]. Among HIV-positive participants, few knew their status (28.1% in Gert Sibande and 14.5% in Ehlanzeni, or were appropriately linked to care (18.2% and 11.3%, respectively, or taking antiretroviral therapy (13.6% and 9.6% respectively. MPMS results demonstrate the importance of implementing interventions for MSM to increase consistent condom use, regular HIV testing, and

  15. Inequities in access to HIV prevention services for transgender men: results of a global survey of men who have sex with men.

    Science.gov (United States)

    Scheim, Ayden I; Santos, Glenn-Milo; Arreola, Sonya; Makofane, Keletso; Do, Tri D; Hebert, Patrick; Thomann, Matthew; Ayala, George

    2016-01-01

    globally found that most reported inadequate access to basic prevention services and that they were less likely than cisgender MSM to have access to HIV testing and lubricants. Results indicate the need to enhance access to basic HIV prevention services for trans MSM, including MSM-specific services.

  16. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Weber, Rainer; Reiss, Peter

    2003-01-01

    OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD, ...

  17. Knowledge and causal attributions for mental disorders in HIV-positive children and adolescents: results from rural and urban Uganda.

    Science.gov (United States)

    Nalukenge, W; Martin, F; Seeley, J; Kinyanda, E

    2018-05-02

    Increasing availability of antiretroviral treatment (ART) has led HIV to be considered a chronic disease, shifting attention to focus on quality of life including mental wellbeing. We investigated knowledge and causal attributions for mental disorders in HIV-positive children and adolescents in rural and urban Uganda. This qualitative study was nested in an epidemiological mental health study among HIV-positive children and adolescents aged 5-17 years in rural and urban Uganda. In-depth interviews were conducted with caregivers of HIV-positive children (5-11 years) and adolescents (12-17 years) in HIV care. Interviews were audio recorded with permission from participants and written consent and assent sought before study procedures. Thirty eight participants (19 caregivers, 19 children/adolescents) were interviewed. Age range of caregivers was 28-69 years; majority were female (17). Caregivers had little knowledge on mental disorders ;only 3 related the vignette to a mental problem  and attributed it to: improper upbringing, violence, poverty and bereavement. Five adolescents identified vignettes as portraying mental disorders caused by: ill-health of parents, bereavement, child abuse, discrimination, HIV and poverty. Caregivers are not knowledgeable about behavioural and emotional challenges in HIV-positive children/adolescents. Mental health literacy programmes at HIV care clinics are essential to enhance treatment-seeking for mental health.

  18. The complex interplay of social networks, geography and HIV risk among Malaysian Drug Injectors: Results from respondent-driven sampling.

    Science.gov (United States)

    Zelenev, Alexei; Long, Elisa; Bazazi, Alexander R; Kamarulzaman, Adeeba; Altice, Frederick L

    2016-11-01

    HIV is primarily concentrated among people who inject drugs (PWID) in Malaysia, where currently HIV prevention and treatment coverage is inadequate. To improve the targeting of interventions, we examined HIV clustering and the role that social networks and geographical distance play in influencing HIV transmission among PWID. Data were derived from a respondent-driven survey sample (RDS) collected during 2010 of 460 PWID in greater Kuala Lumpur. Analysis focused on socio-demographic, clinical, behavioural, and network information. Spatial probit models were developed based on a distinction between the influence of peers (individuals nominated through a recruitment network) and neighbours (residing a close distance to the individual). The models were expanded to account for the potential influence of the network formation. Recruitment patterns of HIV-infected PWID clustered both spatially and across the recruitment networks. In addition, HIV-infected PWID were more likely to have peers and neighbours who inject with clean needles were HIV-infected and lived nearby (applied to identify injection network structures, and this provides an important mechanism for improving public health surveillance, accessing high-risk populations, and implementing risk-reduction interventions to slow HIV transmission. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

    Directory of Open Access Journals (Sweden)

    Dobson Wendy

    2011-06-01

    Full Text Available Abstract Background RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK family of SR protein kinases on HIV-1 expression and RNA processing was examined. Results Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication. Conclusions Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

  20. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE).

    Science.gov (United States)

    Mocroft, Amanda; Lundgren, Jens D; Sabin, Miriam Lewis; Monforte, Antonella d'Arminio; Brockmeyer, Norbert; Casabona, Jordi; Castagna, Antonella; Costagliola, Dominique; Dabis, Francois; De Wit, Stéphane; Fätkenheuer, Gerd; Furrer, Hansjakob; Johnson, Anne M; Lazanas, Marios K; Leport, Catherine; Moreno, Santiago; Obel, Niels; Post, Frank A; Reekie, Joanne; Reiss, Peter; Sabin, Caroline; Skaletz-Rorowski, Adriane; Suarez-Lozano, Ignacio; Torti, Carlo; Warszawski, Josiane; Zangerle, Robert; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Kirk, Ole

    2013-01-01

    Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further

  1. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE.

    Directory of Open Access Journals (Sweden)

    Amanda Mocroft

    Full Text Available Few studies have monitored late presentation (LP of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE as HIV diagnosis with a CD4 count <350/mm(3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%. LP was highest in heterosexual males (66.1%, Southern European countries (57.0%, and persons originating from Africa (65.1%. LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97. LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70 and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43.LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and

  2. HIV serostatus knowledge and serostatus disclosure with the most recent anal intercourse partner in a European MSM sample recruited in 13 cities: results from the Sialon-II study

    Directory of Open Access Journals (Sweden)

    Ulrich Marcus

    2017-11-01

    Full Text Available Abstract Background Knowledge of HIV status can be important in reducing the risk of HIV exposure. In a European sample of men-who-have-sex-with-men (MSM, we aimed to identify factors associated with HIV serostatus disclosure to the most recent anal intercourse (AI partner. We also aimed to describe the impact of HIV serostatus disclosure on HIV exposure risks. Methods During 2013 and 2014, 4901 participants were recruited for the bio-behavioural Sialon-II study in 13 European cities. Behavioural data were collected with a self-administered paper questionnaire. Biological specimens were tested for HIV antibodies. Factors associated with HIV serostatus disclosure with the most recent AI partner were examined using bivariate and multilevel multivariate logistic regression analysis. We also describe the role of serostatus disclosure for HIV exposure of the most recent AI partner. Results Thirty-five percent (n = 1450 of the study participants reported mutual serostatus disclosure with their most recent AI partner or disclosed having HIV to their partner. Most of these disclosures occurred between steady partners (74%, n = 1077. In addition to the type of partner and HIV diagnosis status, other factors positively associated with HIV serostatus disclosure in the multilevel multivariate logistic regression model were recent testing, no condom use, and outness regarding sexual orientation. Disclosure rates were lowest in three south-eastern European cities. Following condom use (51%, n = 2099, HIV serostatus disclosure (20%, n = 807 was the second most common prevention approach with the most recent AI partner, usually resulting in serosorting. A potential HIV exposure risk for the partner was reported by 26% (111/432 of HIV antibody positive study participants. In 18% (20/111 of exposure episodes, an incorrect HIV serostatus was unknowingly communicated. Partner exposures were equally distributed between steady and non-steady partners

  3. Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort

    DEFF Research Database (Denmark)

    Hansen, T F; Kjær-Frifeldt, S; Christensen, R D

    2014-01-01

    Background:The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients.Methods:A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based.......001). The overall survival (OS) index identified three different subgroups (Pcolon cancer. Furthermore...... on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves.Results:High miRNA-21 expression...

  4. Cost effectiveness of screening strategies for early identification of HIV and HCV infection in injection drug users.

    Directory of Open Access Journals (Sweden)

    Lauren E Cipriano

    Full Text Available To estimate the cost, effectiveness, and cost effectiveness of HIV and HCV screening of injection drug users (IDUs in opioid replacement therapy (ORT.Dynamic compartmental model of HIV and HCV in a population of IDUs and non-IDUs for a representative U.S. urban center with 2.5 million adults (age 15-59.We considered strategies of screening individuals in ORT for HIV, HCV, or both infections by antibody or antibody and viral RNA testing. We evaluated one-time and repeat screening at intervals from annually to once every 3 months. We calculated the number of HIV and HCV infections, quality-adjusted life years (QALYs, costs, and incremental cost-effectiveness ratios (ICERs.Adding HIV and HCV viral RNA testing to antibody testing averts 14.8-30.3 HIV and 3.7-7.7 HCV infections in a screened population of 26,100 IDUs entering ORT over 20 years, depending on screening frequency. Screening for HIV antibodies every 6 months costs $30,700/QALY gained. Screening for HIV antibodies and viral RNA every 6 months has an ICER of $65,900/QALY gained. Strategies including HCV testing have ICERs exceeding $100,000/QALY gained unless awareness of HCV-infection status results in a substantial reduction in needle-sharing behavior.Although annual screening for antibodies to HIV and HCV is modestly cost effective compared to no screening, more frequent screening for HIV provides additional benefit at less cost. Screening individuals in ORT every 3-6 months for HIV infection using both antibody and viral RNA technologies and initiating ART for acute HIV infection appears cost effective.

  5. RNA/DNA co-analysis from human saliva and semen stains--results of a third collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, Claus; Hanson, E; Anjos, M J

    2013-01-01

    samples of human or non-human origin were analyzed by 20 participating laboratories using an RNA extraction or RNA/DNA co-extraction method. Two novel mRNA multiplexes were used: a saliva triplex (HTN3, STATH and MUC7) and a semen pentaplex (PRM1, PRM2, PSA, SEMG1 and TGM4). The laboratories used......A third collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Twenty saliva and semen stains, four dilution series (10-0.01 µl saliva, 5-0.01 µl semen) and, optionally, bona fide or mock casework...... different chemistries and instrumentation and a majority (16/20) were able to successfully isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and DNA from individual stains not only permitted a confirmation of the presence of saliva/semen (i.e. tissue/fluid source of origin...

  6. A Comparison of RNA-Seq Results from Paired Formalin-Fixed Paraffin-Embedded and Fresh-Frozen Glioblastoma Tissue Samples.

    Directory of Open Access Journals (Sweden)

    Anna Esteve-Codina

    Full Text Available The molecular classification of glioblastoma (GBM based on gene expression might better explain outcome and response to treatment than clinical factors. Whole transcriptome sequencing using next-generation sequencing platforms is rapidly becoming accepted as a tool for measuring gene expression for both research and clinical use. Fresh frozen (FF tissue specimens of GBM are difficult to obtain since tumor tissue obtained at surgery is often scarce and necrotic and diagnosis is prioritized over freezing. After diagnosis, leftover tissue is usually stored as formalin-fixed paraffin-embedded (FFPE tissue. However, RNA from FFPE tissues is usually degraded, which could hamper gene expression analysis. We compared RNA-Seq data obtained from matched pairs of FF and FFPE GBM specimens. Only three FFPE out of eleven FFPE-FF matched samples yielded informative results. Several quality-control measurements showed that RNA from FFPE samples was highly degraded but maintained transcriptomic similarities to RNA from FF samples. Certain issues regarding mutation analysis and subtype prediction were detected. Nevertheless, our results suggest that RNA-Seq of FFPE GBM specimens provides reliable gene expression data that can be used in molecular studies of GBM if the RNA is sufficiently preserved.

  7. Repeat confirmatory testing for persons with discordant whole blood and oral fluid rapid HIV test results: findings from post marketing surveillance.

    Directory of Open Access Journals (Sweden)

    Laura G Wesolowski

    Full Text Available BACKGROUND: Reactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB, immunofluorescent assay (IFA or approved nucleic acid amplification test (NAAT. When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result, repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results. METHODOLOGY: Post-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing. PRINCIPAL FINDINGS: Of 167,371 rapid tests conducted, 2589 (1.6% were reactive: of these, 2417 (93% had positive WB/IFA, 172 (7% had negative or indeterminate WB/IFA. Of 89/172 (52% persons with a repeat confirmatory test: 17 (19% were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81% were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative (p<0.001 and having an initial oral fluid WB (vs. serum (p<0.001. Persons who had male-female sex (vs. male-male sex were at increased risk for not having a repeat test [adjusted OR 2.6, 95% CI (1.3, 4.9]. CONCLUSIONS: Though only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for

  8. Risk Factors for Non-Adherence to cART in Immigrants with HIV Living in the Netherlands: Results from the ROtterdam ADherence (ROAD Project.

    Directory of Open Access Journals (Sweden)

    Sabrina K Been

    Full Text Available In the Netherlands, immigrant people living with HIV (PLWH have poorer psychological and treatment outcomes than Dutch PLWH. This cross-sectional field study examined risk factors for non-adherence to combination Antiretroviral Therapy (cART among immigrant PLWH. First and second generation immigrant PLWH attending outpatient clinics at two HIV-treatment centers in Rotterdam were selected for this study. Socio-demographic and clinical characteristics for all eligible participants were collected from an existing database. Trained interviewers subsequently completed questionnaires together with consenting participants (n = 352 to gather additional data on socio-demographic characteristics, psychosocial variables, and self-reported adherence to cART. Univariable and multivariable logistic regression analyses were conducted among 301 participants who had used cART ≥6 months prior to inclusion. Independent risk factors for self-reported non-adherence were (I not having attended formal education or only primary school (OR = 3.25; 95% CI: 1.28-8.26, versus University, (II experiencing low levels of social support (OR = 2.56; 95% CI: 1.37-4.82, and (III reporting low treatment adherence self-efficacy (OR = 2.99; 95% CI: 1.59-5.64. Additionally, HIV-RNA >50 copies/ml and internalized HIV-related stigma were marginally associated (P<0.10 with non-adherence (OR = 2.53; 95% CI: 0.91-7.06 and OR = 1.82; 95% CI: 0.97-3.43. The findings that low educational attainment, lack of social support, and low treatment adherence self-efficacy are associated with non-adherence point to the need for tailored supportive interventions. Establishing contact with peer immigrant PLWH who serve as role models might be a successful intervention for this specific population.

  9. HIV serostatus knowledge and serostatus disclosure with the most recent anal intercourse partner in a European MSM sample recruited in 13 cities: results from the Sialon-II study.

    Science.gov (United States)

    Marcus, Ulrich; Schink, Susanne Barbara; Sherriff, Nigel; Jones, Anna-Marie; Gios, Lorenzo; Folch, Cinta; Berglund, Torsten; Nöstlinger, Christiana; Niedźwiedzka-Stadnik, Marta; Dias, Sonia F; Gama, Ana F; Naseva, Emilia; Alexiev, Ivailo; Staneková, Danica; Toskin, Igor; Pitigoi, Daniela; Rafila, Alexandru; Klavs, Irena; Mirandola, Massimo

    2017-11-25

    Knowledge of HIV status can be important in reducing the risk of HIV exposure. In a European sample of men-who-have-sex-with-men (MSM), we aimed to identify factors associated with HIV serostatus disclosure to the most recent anal intercourse (AI) partner. We also aimed to describe the impact of HIV serostatus disclosure on HIV exposure risks. During 2013 and 2014, 4901 participants were recruited for the bio-behavioural Sialon-II study in 13 European cities. Behavioural data were collected with a self-administered paper questionnaire. Biological specimens were tested for HIV antibodies. Factors associated with HIV serostatus disclosure with the most recent AI partner were examined using bivariate and multilevel multivariate logistic regression analysis. We also describe the role of serostatus disclosure for HIV exposure of the most recent AI partner. Thirty-five percent (n = 1450) of the study participants reported mutual serostatus disclosure with their most recent AI partner or disclosed having HIV to their partner. Most of these disclosures occurred between steady partners (74%, n = 1077). In addition to the type of partner and HIV diagnosis status, other factors positively associated with HIV serostatus disclosure in the multilevel multivariate logistic regression model were recent testing, no condom use, and outness regarding sexual orientation. Disclosure rates were lowest in three south-eastern European cities. Following condom use (51%, n = 2099), HIV serostatus disclosure (20%, n = 807) was the second most common prevention approach with the most recent AI partner, usually resulting in serosorting. A potential HIV exposure risk for the partner was reported by 26% (111/432) of HIV antibody positive study participants. In 18% (20/111) of exposure episodes, an incorrect HIV serostatus was unknowingly communicated. Partner exposures were equally distributed between steady and non-steady partners. The probability of HIV exposure through condomless AI

  10. High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    José Ernesto Vidal

    Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

  11. High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    José Ernesto Vidal

    2013-02-01

    Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

  12. Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda.

    Science.gov (United States)

    Ssebugenyi, I; Kizza, A; Mpoza, B; Aluma, G; Boaz, I; Newell, K; Laeyendecker, O; Shott, J P; Serwadda, D; Reynolds, S J

    2011-07-01

    The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ≥ six months and 147 from ART-naïve patients. The Roche assay detected ≥400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ≥400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ≥400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ≥400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ≥400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.

  13. Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study.

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    Gisela Leierer

    Full Text Available In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV and virological failure (VF under combined antiretroviral therapy (cART.We analysed patients receiving standard regimens between 1st July 2012 and 1st July 2013 with at least one viral load (VL measurement below the quantification limit (BLQ in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥ 200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models.Of 2276 participants, 1972 (86.6% were BLQ, 222 (9.8% showed LLV and 82 (3.6% had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI: 4.19 (2.07-8.49; for 10.000-99.999 copies/mL: aOR (95% CI: 2.52 (1.23-5.19] and shorter cART duration [for <9 months: aOR (95% CI: 2.59 (1.38-4.86]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI: 2.76 (1.03-7.35; for 30-50 years: aOR (95% CI: 2.70 (1.26-5.79], people originating from high prevalence countries [aOR (95% CI: 2.20 (1.09-4.42] and in male injecting drug users [aOR (95% CI: 2.72 (1.38-5.34].For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.

  14. A comparative analysis of costs of single and dual rapid HIV and syphilis diagnostics: results from a randomised controlled trial in Colombia.

    Science.gov (United States)

    Obure, Carol Dayo; Gaitan-Duarte, Hernando; Losada Saenz, Ricardo; Gonzalez, Lina; Angel-Muller, Edith; Laverty, Maura; Perez, Freddy

    2017-11-01

    HIV and congenital syphilis are major public health burdens contributing to substantial perinatal morbidity and mortality globally. Although studies have reported on the costs and cost-effectiveness of rapid diagnostic tests (RDTs) for syphilis screening within antenatal care in a number of resource-constrained settings, empirical evidence on country-specific cost and estimates of single RDTs compared with dual RDTs for HIV and syphilis are limited. A cluster randomised controlled study design was used to compare the incremental costs of two testing algorithms: (1) single RDTs for HIV and syphilis and (2) dual RDTs for HIV and syphilis, in 12 health facilities in Bogota and Cali, Colombia. The costs of single HIV and syphilis RDTs and dual HIV and syphilis RDTs were collected from each of the health facilities. The economic costs per woman tested for HIV and syphilis and costs per woman treated for syphilis defined as the total costs required to test and treat one woman for syphilis were estimated. A total of 2214 women were tested in the study facilities. Cost per pregnant woman tested and cost per woman treated for syphilis were US$10.26 and US$607.99, respectively in the single RDT arm. For the dual RDTs, the cost per pregnant woman tested for HIV and syphilis and cost per woman treated for syphilis were US$15.89 and US$1859.26, respectively. Overall costs per woman tested for HIV and syphilis and cost per woman treated for syphilis were lower in Cali compared with Bogota across both intervention arms. Staff costs accounted for the largest proportion of costs while treatment costs comprised <1% of the preventive programme. Findings show lower average costs for single RDTs compared with dual RDTs with costs sensitive to personnel costs and the scale of output at the health facilities. NCT02454816; results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. A psycho-educational HIV/STI prevention intervention for internally displaced women in Leogane, Haiti: results from a non-randomized cohort pilot study.

    Directory of Open Access Journals (Sweden)

    Carmen H Logie

    impacts of HIV prevention strategies in disaster contexts. Study results may inform HIV prevention interventions among internally displaced women in Haiti and can be tested for applicability with internally displaced women globally. ClinicalTrials.gov: Identifier NCT01492829, URL: http://clinicaltrials.gov/ct2/show/NCT01492829?term=logie&rank=1.

  16. Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells

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    Giacaman Rodrigo A

    2008-07-01

    Full Text Available Abstract Background Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner. Results To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Δenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral blood mononuclear cells (PBMCs or MOLT4 cells (CD4+ CCR5+ by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also trans infected HIV-1 to permissive cells in a donor-specific manner. Conclusion Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.

  17. Prevalence and prognostic significance of ECG abnormalities in HIV-infected patients: results from the Strategies for Management of Antiretroviral Therapy study

    DEFF Research Database (Denmark)

    Soliman, Elsayed Z; Prineas, Ronald J; Roediger, Mollie P

    2011-01-01

    BACKGROUND: It remains debated whether to include resting electrocardiogram (ECG) in the routine care of human immunodeficiency virus (HIV)-infected patients. METHODS: This analysis included 4518 HIV-infected patients (28% women and 29% blacks) from the Strategies for Management of Antiretroviral...... Therapy study, a clinical trial aimed to compare 2 HIV treatment strategies. ECG abnormalities were classified using the Minnesota Code. Cox proportional hazards analysis was used to examine the association between baseline ECG abnormalities and incident cardiovascular disease (CVD). RESULTS: More than...... half of the participants (n = 2325, or 51.5%) had either minor or major ECG abnormalities. Minor ECG abnormalities (48.6%) were more common than major ECG abnormalities (7.7%). During a median follow-up of 28.7 months, 155 participants (3.4%) developed incident CVD. After adjusting for the study...

  18. The HCV and HIV coinfected patient: what have we learned about pathophysiology?

    Science.gov (United States)

    Talal, Andrew H; Canchis, P Wilfredo; Jacobson, Ira

    2002-02-01

    Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

  19. Retrovirus-specific differences in matrix and nucleocapsid protein-nucleic acid interactions: implications for genomic RNA packaging.

    Science.gov (United States)

    Sun, Meng; Grigsby, Iwen F; Gorelick, Robert J; Mansky, Louis M; Musier-Forsyth, Karin

    2014-01-01

    Retroviral RNA encapsidation involves a recognition event between genomic RNA (gRNA) and one or more domains in Gag. In HIV-1, the nucleocapsid (NC) domain is involved in gRNA packaging and displays robust nucleic acid (NA) binding and chaperone functions. In comparison, NC of human T-cell leukemia virus type 1 (HTLV-1), a deltaretrovirus, displays weaker NA binding and chaperone activity. Mutation of conserved charged residues in the deltaretrovirus bovine leukemia virus (BLV) matrix (MA) and NC domains affects virus replication and gRNA packaging efficiency. Based on these observations, we hypothesized that the MA domain may generally contribute to NA binding and genome encapsidation in deltaretroviruses. Here, we examined the interaction between HTLV-2 and HIV-1 MA proteins and various NAs in vitro. HTLV-2 MA displays higher NA binding affinity and better chaperone activity than HIV-1 MA. HTLV-2 MA also binds NAs with higher affinity than HTLV-2 NC and displays more robust chaperone function. Mutation of two basic residues in HTLV-2 MA α-helix II, previously implicated in BLV gRNA packaging, reduces NA binding affinity. HTLV-2 MA binds with high affinity and specificity to RNA derived from the putative packaging signal of HTLV-2 relative to nonspecific NA. Furthermore, an HIV-1 MA triple mutant designed to mimic the basic character of HTLV-2 MA α-helix II dramatically improves binding affinity and chaperone activity of HIV-1 MA in vitro and restores RNA packaging to a ΔNC HIV-1 variant in cell-based assays. Taken together, these results are consistent with a role for deltaretrovirus MA proteins in viral RNA packaging.

  20. HIV gender-based vulnerabilities of women using drugs in long-term heterosexual relationships: baseline results from a randomized trial in Ukraine

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    Shulga, Liudmyla

    2012-07-01

    Full Text Available BACKGROUND: Sexual way of HIV transmission in Ukraine outweighs parenteral route since 2007. In response to situation change couple’s counseling for IDUs was introduced and is currently tested within randomized trial.METHODS: Baseline data were collected in June-September 2011: 548 IDU couples in 10 cities were surveyed and screened for HIV and Hepatitis C. Participants were recruited using respondent-driven sampling method. RESULTS: The average age of participants varied between 30 – 33 years old with women being 3 years younger. On many aspects drug using couples in long-term relationships share the same values as non-drug using couples. However, drug use resulted into specific HIV/STIs risks for the couple. Common reasons of being with the current partner included mutual understanding (98%; similar life styles (90%; understanding life with addiction (88%; and love (87%. At the same time, looking at the quality time partners spend together, it was found that mostly, they are connected by their drug use, fear of social exclusion and economical reasons. Although these factors are important for both men and women, they have a bigger impact on women and put them into more vulnerable position: 25% have children who in 59% of cases mostly live with mother and her partner; 40% live in a partner’s house; 30% are financially supported by partners; 77% women get drugs from partners and only 20% are first one to be injected. Trust also seems to be an issue. Thus, 83% of respondents believe that they know the HIV/STI status of their partner and 90% of those believe it to be negative, while 20% of those surveyed appeared to be HIV positive and about 30% Hepatitis C positive. CONCLUSIONS: Understanding characteristics of sexual partners is crucial for HIV prevention programme design and implementation.

  1. Reduction of adenovirus E1A mRNA by RNAi results in enhanced recombinant protein expression in transiently transfected HEK293 cells.

    Science.gov (United States)

    Hacker, David L; Bertschinger, Martin; Baldi, Lucia; Wurm, Florian M

    2004-10-27

    Human embryonic kidney 293 (HEK293) cells, a widely used host for large-scale transient expression of recombinant proteins, are transformed with the adenovirus E1A and E1B genes. Because the E1A proteins function as transcriptional activators or repressors, they may have a positive or negative effect on transient transgene expression in this cell line. Suspension cultures of HEK293 EBNA (HEK293E) cells were co-transfected with a reporter plasmid expressing the GFP gene and a plasmid expressing a short hairpin RNA (shRNA) targeting the E1A mRNAs for degradation by RNA interference (RNAi). The presence of the shRNA in HEK293E cells reduced the steady state level of E1A mRNA up to 75% and increased transient GFP expression from either the elongation factor-1alpha (EF-1alpha) promoter or the human cytomegalovirus (HCMV) immediate early promoter up to twofold. E1A mRNA depletion also resulted in a twofold increase in transient expression of a recombinant IgG in both small- and large-scale suspension cultures when the IgG light and heavy chain genes were controlled by the EF-1alpha promoter. Finally, transient IgG expression was enhanced 2.5-fold when the anti-E1A shRNA was expressed from the same vector as the IgG light chain gene. These results demonstrated that E1A has a negative effect on transient gene expression in HEK293E cells, and they established that RNAi can be used to enhance recombinant protein expression in mammalian cells.

  2. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial.

    Science.gov (United States)

    Hansen, T F; Christensen, R dP; Andersen, R F; Sørensen, F B; Johnsson, A; Jakobsen, A

    2013-09-03

    This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC). A total of 230 patients from a randomised phase III study were included. The primary microRNA-126 (pri-miRNA-126) A24G single-nucleotide polymorphism and the mature miRNA-126 were analysed by PCR using genomic DNA (full blood) and formalin-fixed paraffin-embedded tissue sections, respectively. The epidermal growth factor-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry. High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio=0.49, 95% confidence interval=0.29-0.84, P=0.009). Although not significant, a relationship between EGFL7 expression and response rates is suggested, with EGFL7 expression at the invasive front being lower in responding patients than in the non-responders (P=0.063). The results validate the previous findings on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics.

  3. [An application of the strategy results cycle to HIV/AIDS strategic planning in Latin America].

    Science.gov (United States)

    Rodríguez-García, Rosalía; Rosenberg, Hernán

    2013-07-01

    To describe the Strategy Results Cycle (SRC), a model that approaches planning as an ongoing cycle of seven phases that continually responds and adapts to existing evidence. Reliable sources were used for the preparation of databases and expenditure-costing data for resources needs analysis. The planning process 6-9 months to complete a national strategic plan that was informed by evidence, focused on results and costed. Knowledge transfer facilitated national leadership and stakeholders' participation. Between 2007 and 2011, 13 of 16 countries adopted the Strategy Results Cycle model. The evidence supported the identification of results and the expenditure-costing analysis improved budget allocation efficiency. The SRC facilitated purposeful participation and added value to previous planning approaches by connecting "thinking" and "doing" which resulted in national strategic plans that are designed by stakeholders, relevant to local conditions, and can guide implementation and resource mobilization.

  4. The management of isolated positive syphilis enzyme immunoassay results in HIV-negative patients attending a sexual health clinic.

    Science.gov (United States)

    Thorley, Nicola; Adebayo, Michael; Smit, Erasmus; Radcliffe, Keith

    2016-08-01

    An unconfirmed positive treponemal enzyme immunoassay (enzyme immunoassay positive, Treponema pallidum particle agglutination negative and rapid plasma reagin negative) presents a clinical challenge to distinguish early syphilis infection from false-positive results. These cases are referred for syphilis line assay (INNO-LIA) and recalled for repeat syphilis serology. We performed a retrospective audit to establish the proportion of HIV-negative cases with unconfirmed positive enzyme immunoassay results, the proportion of these cases that received an INNO-LIA test and repeat syphilis serology testing and reviewed the clinical outcomes; 0.35% (80/22687) cases had an unconfirmed positive treponemal enzyme immunoassay result. Repeat syphilis serology was performed in 80% (64/80) cases, but no additional cases of syphilis were identified. Eighty-eight per cent (70/80) received an INNO-LIA test; 14% (5/37) unconfirmed enzyme immunoassay-positive cases with no prior history of syphilis were confirmed on INNO-LIA assay, supporting a diagnosis of latent syphilis. As a confirmatory treponemal test, the INNO-LIA assay may be more useful than repeat syphilis serological testing. © The Author(s) 2016.

  5. Assessing effects of a media campaign on HIV/AIDS awareness and prevention in Nigeria: results from the VISION Project.

    Science.gov (United States)

    Keating, Joseph; Meekers, Dominique; Adewuyi, Alfred

    2006-05-03

    In response to the growing HIV epidemic in Nigeria, the U.S. Agency for International Development (USAID) initiated the VISION Project, which aimed to increase use of family planning, child survival, and HIV/AIDS services. The VISION Project used a mass-media campaign that focused on reproductive health and HIV/AIDS prevention. This paper assesses to what extent program exposure translates into increased awareness and prevention of HIV/AIDS. This analysis is based on data from the 2002 and 2004 Nigeria (Bauchi, Enugu, and Oyo) Family Planning and Reproductive Health Surveys, which were conducted among adults living in the VISION Project areas. To correct for endogeneity, two-stage logistic regression is used to investigate the effect of program exposure on 1) discussion of HIV/AIDS with a partner, 2) awareness that consistent condom use reduces HIV risk, and 3) condom use at last intercourse. Exposure to the VISION mass media campaign was high: 59%, 47%, and 24% were exposed to at least 1 VISION radio, printed advertisement, or TV program about reproductive health, respectively. The differences in outcome variables between 2002 baseline data and the 2004 follow-up data were small. However, those with high program exposure were almost one and a half (Odds Ratio [O.R.] = 1.47, 95% Confidence Interval [C.I.] 1.01-2.16) times more likely than those with no exposure to have discussed HIV/AIDS with a partner. Those with high program exposure were over twice (O.R. = 2.20, C.I. 1.49-3.25) as likely as those with low exposure to know that condom use can reduce risk of HIV infection. Program exposure had no effect on condom use at last sex. The VISION Project reached a large portion of the population and exposure to mass media programs about reproductive health and HIV prevention topics can help increase HIV/AIDS awareness. Programs that target rural populations, females, and unmarried individuals, and disseminate information on where to obtain condoms, are needed to reduce

  6. A stable CC-chemokine receptor (CCR)-5 tropic virus is correlated with the persistence of HIV RNA at less than 2.5 copies in successfully treated naïve subjects.

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Andreis, Samantha; Mengoli, Carlo; Scaggiante, Renzo; Cruciani, Mario; Ferretto, Roberto; Manfrin, Vinicio; Panese, Sandro; Basso, Monica; Boldrin, Caterina; Bressan, Stefania; Sarmati, Loredana; Andreoni, Massimo; Palù, Giorgio

    2013-07-11

    To determine if tropism for CXCR4 or CCR5 correlates with cellular HIV DNA load, residual viraemia and CD4 count in 219 successfully treated naive subjects with HIV infection enrolled in five infectious diseases units in Northeastern Italy. A subset of subjects, achieving plasma HIV RNA level <50 copies/ml after initiation of first-line therapy and maintaining it until follow-up time points, was retrospectively selected from a prospective cohort. Blood samples were collected before the beginning of therapy (T0), at the first follow-up time (T1) and, when available, at a second (T2) follow-up time. HIV DNA, CD4 count and plasma viraemia were available from all 219 patients at T0 and T1, and in 86 subjects at T2, while tropism determinations were available from 109 subjects at T0, 219 at T1, and from 86 subjects at T2. Achieving residual viraemia <2.5 copies/ml at T1 correlated with having the same condition at T2 (p = 0.0007). X4 tropism at T1 was negatively correlated with the possibility of achieving viraemia<2.5 copies/ml at T2 (p = 0.0076). T1-T2 tropism stability was significant (p <0.0001). T0 tropism correlated with T1 and T2 tropism (p < 0.001); therefore the stability of the tropism over the two follow-up periods was significant (p = 0.0003). An effective viremic suppression (viraemia<2.5 copies/ml) correlated with R5 coreceptor affinity (p= 0.047). The tropism of archived virus was stable during an effective treatment, with 15-18% of subjects switching over time, despite a viraemia<50 copies/ml. R5 tropism and its stability were related to achieving and maintaining viraemia<2.5 copies/ml.

  7. Examining the link between patient satisfaction and adherence to HIV care: a structural equation model.

    Directory of Open Access Journals (Sweden)

    Bich N Dang

    Full Text Available INTRODUCTION: Analogous to the business model of customer satisfaction and retention, patient satisfaction could serve as an innovative, patient-centered focus for increasing retention in HIV care and adherence to HAART, and ultimately HIV suppression. OBJECTIVE: To test, through structural equation modeling (SEM, a model of HIV suppression in which patient satisfaction influences HIV suppression indirectly through retention in HIV care and adherence to HAART. METHODS: We conducted a cross-sectional study of adults receiving HIV care at two clinics in Texas. Patient satisfaction was based on two validated items, one adapted from the Consumer Assessment of Healthcare Providers and Systems survey ("Would you recommend this clinic to other patients with HIV? and one adapted from the Delighted-Terrible Scale, ("Overall, how do you feel about the care you got at this clinic in the last 12 months?". A validated, single-item question measured adherence to HAART over the past 4 weeks. Retention in HIV care was based on visit constancy in the year prior to the survey. HIV suppression was defined as plasma HIV RNA <48 copies/mL at the time of the survey. We used SEM to test hypothesized relationships. RESULTS: The analyses included 489 patients (94% of eligible patients. The patient satisfaction score had a mean of 8.5 (median 9.2 on a 0- to 10- point scale. A total of 46% reported "excellent" adherence, 76% had adequate retention, and 70% had HIV suppression. In SEM analyses, patient satisfaction with care influences retention in HIV care and adherence to HAART, which in turn serve as key determinants of HIV suppression (all p<.0001. CONCLUSIONS: Patient satisfaction may have direct effects on retention in HIV care and adherence to HAART. Interventions to improve the care experience, without necessarily targeting objective clinical performance measures, could serve as an innovative method for optimizing HIV outcomes.

  8. Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults : results of the "COPA" pilot randomized trial

    NARCIS (Netherlands)

    Gori, A.; Rizzardini, G.; van't Land, B.; Amor, K. B.; van Schaik, J.; Torti, C.; Quirino, T.; Tincati, C.; Bandera, A.; Knol, J.; Benlhassan-Chahour, K.; Trabattoni, D.; Bray, D.; Vriesema, A.; Welling, G.; Garssen, J.; Clerici, M.

    Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4(+) T-cell depletion, deterioration of gut lining, and fecal microbiota composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active

  9. RNA/DNA co-analysis from blood stains--Results of a second collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, C.; Hanson, E.; Anjos, M.J.

    2012-01-01

    A second collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Six human blood stains, two blood dilution series (5-0.001 [mu]l blood) and, optionally, bona fide or mock casework samples of human or...

  10. Yellow fever vaccine for patients with HIV infection.

    Science.gov (United States)

    Barte, Hilary; Horvath, Tara H; Rutherford, George W

    2014-01-23

    Yellow fever (YF) is an acute viral haemorrhagic disease prevalent in tropical Africa and Latin America. The World Health Organization (WHO) estimates that there are 200,000 cases of YF and 30,000 deaths worldwide annually. Treatment for YF is supportive, but a live attenuated virus vaccine is effective for preventing infection. WHO recommends immunisation for all individuals > 9 months living in countries or areas at risk. However, the United States Advisory Committee on Immunization Practices (ACIP) advises that YF vaccine is contraindicated in individuals with HIV. Given the large populations of HIV-infected individuals living in tropical areas where YF is endemic, YF vaccine may be an important intervention for preventing YF in immunocompromised populations. To assess the risk and benefits of YF immunisation for people infected with HIV. We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Randomised controlled trials and cohort studies of individuals with HIV infection who received YF vaccine (17DD or 17D-204). Two authors screened abstracts of references identified by electronic or bibliographic searches according to inclusion and exclusion criteria as detailed in the protocol. We identified 199 references and examined 19 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Three cohort studies were included in the review. They examined 484 patients with HIV infection who received YF immunisation. Patients with HIV infection developed significantly lower concentrations of neutralising antibodies in the first year post immunisation compared to uninfected patients, though decay patterns were similar for recipients regardless of HIV infection. No study patient with HIV infection suffered serious adverse events as a result of YF vaccination. YF vaccination can produce protective levels of neutralising antibodies in

  11. Validity of measures of pain and symptoms in HIV/AIDS infected households in resources poor settings: results from the Dominican Republic and Cambodia

    Directory of Open Access Journals (Sweden)

    Morineau Guy

    2006-03-01

    Full Text Available Abstract Background HIV/AIDS treatment programs are currently being mounted in many developing nations that include palliative care services. While measures of palliative care have been developed and validated for resource rich settings, very little work exists to support an understanding of measurement for Africa, Latin America or Asia. Methods This study investigates the construct validity of measures of reported pain, pain control, symptoms and symptom control in areas with high HIV-infected prevalence in Dominican Republic and Cambodia Measures were adapted from the POS (Palliative Outcome Scale. Households were selected through purposive sampling from networks of people living with HIV/AIDS. Consistencies in patterns in the data were tested used Chi Square and Mantel Haenszel tests. Results The sample persons who reported chronic illness were much more likely to report pain and symptoms compared to those not chronically ill. When controlling for the degrees of pain, pain control did not differ between the chronically ill and non-chronically ill using a Mantel Haenszel test in both countries. Similar results were found for reported symptoms and symptom control for the Dominican Republic. These findings broadly support the construct validity of an adapted version of the POS in these two less developed countries. Conclusion The results of the study suggest that the selected measures can usefully be incorporated into population-based surveys and evaluation tools needed to monitor palliative care and used in settings with high HIV/AIDS prevalence.

  12. HIV-1/2 indeterminate Western blot results: follow-up of asymptomatic blood donors in Belo Horizonte, Minas Gerais, Brazil

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    CARNEIRO-PROIETTI A.B.F.

    1999-01-01

    Full Text Available The clinical and public health importance of indeterminate results in HIV-1/2 testing is still difficult to evaluate in volunteer blood donors. At Fundação Hemominas, HIV-1/2 ELISA is used as the screening test and, if reactive, is followed by Western blot (WB. We have evaluated 84 blood donors who had repeatedly reactive ELISA tests for HIV-1/2, but indeterminate WB results. Sixteen of the 84 donors (19.0% had history of sexually transmitted diseases; 18/84 (21.4% informed receiving or paying for sex; 3/84 (3.6% had homosexual contact; 2/26 women (7.6% had past history of multiple illegal abortions and 3/84 (3.6% had been previously transfused. Four out of 62 donors (6.5% had positive anti-nuclear factor (Hep2, with titles up to 1:640. Parasitological examination of the stool revealed eggs of S. mansoni in 4/62 (6.4% donors and other parasites in 8/62 (12.9%. Five (5.9% of the subjects presented overt seroconversion for HIV-1/2, 43/84 (51.2% had negative results on the last visit, while 36/84 (42.9% remained WB indeterminate. Although some conditions could be found associated with the HIV-1/2 indeterminate WB results and many donors had past of risky behavior, the significance of the majority of the results remains to be determined.

  13. A psycho-educational HIV/STI prevention intervention for internally displaced women in Leogane, Haiti: results from a non-randomized cohort pilot study.

    Science.gov (United States)

    Logie, Carmen H; Daniel, CarolAnn; Newman, Peter A; Weaver, James; Loutfy, Mona R

    2014-01-01

    Little evidence exists regarding efficacious HIV and sexually transmitted infections (STI) prevention interventions with internally displaced populations. Internally displaced women are at elevated risk for HIV/STI due to limited access to health services, heightened poverty and social network breakdown. The FASY (Famn an Aksyon Pou Sante' Yo) (Women Taking Action For Their Health) study examined the effectiveness of a peer health worker (PHW) delivered psycho-educational HIV/STI pilot study with internally displaced women in Leogane, Haiti. This was a non-randomized cohort pilot study. Participants completed a computer-assisted pre-test programmed on Android tablet PCs followed by an HIV/STI educational video-based session and a 6-week psycho-educational group program of weekly meetings. Participants completed a post-test upon completion of group sessions. The primary outcome was HIV knowledge; our pre-specified index of clinically significant change was an effect size of 0.30. Secondary outcomes included: STI knowledge, condom use, social support, resilient coping, depression and relationship control. We used mixed-effects regression to calculate mean outcome pre-post score change. This study was registered (clinicaltrials.gov, NCT01492829). Between January 1-April 30, 2012 we assigned 200 participants to the study. The majority of participants (n = 176, 88%) completed the study and were followed up at 8 weeks, finishing April 30, 2012. Adjusted for socio-demographic characteristics, HIV knowledge (β = 4.81; 95% CI 4.36-5.26), STI knowledge (β = 0.84; 95% CI 0.70-0.99), condom use (AOR = 4.05, 95% CI 1.86-8.83), and depression (β = -0.63, 95% CI -0.88--0.39) scores showed statistically significant change post-intervention (pHaiti. Pilot studies are an important approach to understand feasibility and scientific impacts of HIV prevention strategies in disaster contexts. Study results may inform HIV prevention interventions among internally displaced women in

  14. 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

  15. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART during acute HIV-1 infection: An observational study.

    Directory of Open Access Journals (Sweden)

    Timothy J Henrich

    2017-11-01

    Full Text Available It is unknown if extremely early initiation of antiretroviral therapy (ART may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male and 12 days (Participant B; 31-year-old male after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI following 32 weeks of continuous ART.Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF, plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA. Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse, but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input

  16. Effectiveness of cellulose sulfate vaginal gel for the prevention of HIV infection: results of a Phase III trial in Nigeria.

    Directory of Open Access Journals (Sweden)

    Vera Halpern

    Full Text Available This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection.This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1:1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events.The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10 than on placebo (13, a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3-1.8; p = 0.56. Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5-1.1; p = 0.19 for the combined STI outcome. Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported.Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV.ClinicalTrials.gov NCT00120770.

  17. Cascade detection for the extraction of localized sequence features; specificity results for HIV-1 protease and structure-function results for the Schellman loop.

    Science.gov (United States)

    Newell, Nicholas E

    2011-12-15

    The extraction of the set of features most relevant to function from classified biological sequence sets is still a challenging problem. A central issue is the determination of expected counts for higher order features so that artifact features may be screened. Cascade detection (CD), a new algorithm for the extraction of localized features from sequence sets, is introduced. CD is a natural extension of the proportional modeling techniques used in contingency table analysis into the domain of feature detection. The algorithm is successfully tested on synthetic data and then applied to feature detection problems from two different domains to demonstrate its broad utility. An analysis of HIV-1 protease specificity reveals patterns of strong first-order features that group hydrophobic residues by side chain geometry and exhibit substantial symmetry about the cleavage site. Higher order results suggest that favorable cooperativity is weak by comparison and broadly distributed, but indicate possible synergies between negative charge and hydrophobicity in the substrate. Structure-function results for the Schellman loop, a helix-capping motif in proteins, contain strong first-order features and also show statistically significant cooperativities that provide new insights into the design of the motif. These include a new 'hydrophobic staple' and multiple amphipathic and electrostatic pair features. CD should prove useful not only for sequence analysis, but also for the detection of multifactor synergies in cross-classified data from clinical studies or other sources. Windows XP/7 application and data files available at: https://sites.google.com/site/cascadedetect/home. nacnewell@comcast.net Supplementary information is available at Bioinformatics online.

  18. MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, T F; Christensen, René dePont; Andersen, R F

    2013-01-01

    Background:This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC).Methods:A total of 230 patients...... on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics....

  19. Performance of the BioPlex 2200 HIV Ag-Ab assay for identifying acute HIV infection.

    Science.gov (United States)

    Eshleman, Susan H; Piwowar-Manning, Estelle; Sivay, Mariya V; Debevec, Barbara; Veater, Stephanie; McKinstry, Laura; Bekker, Linda-Gail; Mannheimer, Sharon; Grant, Robert M; Chesney, Margaret A; Coates, Thomas J; Koblin, Beryl A; Fogel, Jessica M

    Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to screen for HIV infection. To compare the performance of the BioPlex 2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of acute HIV infection. Samples were obtained from 24 individuals (18 from the US, 6 from South Africa); these individuals were classified as having acute infection based on the following criteria: positive qualitative RNA assay; two negative rapid tests; negative discriminatory test. The samples were tested with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV Combo Ag-Ab EIA test, and a viral load assay. Twelve (50.0%) of 24 samples had RNA detected only ( > 40 to 13,476 copies/mL). Ten (43.5%) samples had reactive results with all three Ag/Ab assays, one sample was reactive with the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag positive/Ab negative by the BioPlex assay. Detection of acute HIV infection was similar for the BioPlex assay and two other Ag/Ab assays. All three tests were less sensitive than a qualitative RNA assay and only detected HIV Ag when the viral load was high. The BioPlex assay detected acute infection in about half of the cases, and identified most of those infections as Ag positive/Ab negative. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy

    Directory of Open Access Journals (Sweden)

    Hong-Hao Yu

    2016-10-01

    Full Text Available Dystrophinopathy, including Duchenne muscle dystrophy (DMD and Becker muscle dystrophy (BMD is an incurable X-linked hereditary muscle dystrophy caused by a mutation in the DMD gene in coding dystrophin. Advances in further understanding DMD/BMD for therapy are expected. Studies on mdx mice and dogs with muscle dystrophy provide limited insight into DMD disease mechanisms and therapeutic testing because of the different pathological manifestations. Miniature pigs share similar physiology and anatomy with humans and are thus an excellent animal model of human disease. Here, we successfully achieved precise DMD targeting in Chinese Diannan miniature pigs by co-injecting zygotes with Cas9 mRNA and sgRNA targeting DMD. Two piglets were obtained after embryo transfer, one of piglets was identified as DMD-modified individual via traditional cloning, sequencing and T7EN1 cleavage assay. An examination of targeting rates in the DMD-modified piglet revealed that sgRNA:Cas9-mediated on-target mosaic mutations were 70% and 60% of dystrophin alleles in skeletal and smooth muscle, respectively. Meanwhile, no detectable off-target mutations were found, highlighting the high specificity of genetic modification using CRISPR/Cas9. The DMD-modified piglet exhibited degenerative and disordered phenotypes in skeletal and cardiac muscle, and declining thickness of smooth muscle in the stomach and intestine. In conclusion, we successfully generated myopathy animal model by modifying the DMD via CRISPR/Cas9 system in a miniature pig.

  1. Prophylaxis and treatment of HIV-1 infection in pregnancy - Swedish Recommendations 2017.

    Science.gov (United States)

    Navér, Lars; Albert, Jan; Carlander, Christina; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Svedhem-Johansson, Veronica; Sönnerborg, Anders; Westling, Katarina; Yilmaz, Aylin; Pettersson, Karin

    2018-01-24

    Prophylaxis and treatment with antiretroviral drugs have resulted in a very low rate of mother-to-child transmission (MTCT) of HIV during recent years. Registration of new antiretroviral drugs, modification of clinical praxis, updated general treatment guidelines and increasing knowledge about MTCT have necessitated regular revisions of the recommendations for 'Prophylaxis and treatment of HIV-1 infection in pregnancy'. The Swedish Reference Group for Antiviral Therapy (RAV) has updated the recommendations from 2013 at an expert meeting 19 September 2017. In the new text, current treatment guidelines for non-pregnant are considered. The most important revisions are that: (1) Caesarean section and infant prophylaxis with three drugs are recommended when maternal HIV RNA >150 copies/mL (previously >50 copies/mL). The treatment target of undetectable HIV RNA remains unchanged <50 copies/mL; (2) Obstetric management and mode of delivery at premature rupture of the membranes and rupture of the membranes at full term follow the same procedures as in HIV negative women; (3) Vaginal delivery is recommended to a well-treated woman with HIV RNA <150 copies/mL regardless of gestational age, if no obstetric contraindications are present; (4) Treatment during pregnancy should begin as soon as possible and should continue after delivery; (5) Ongoing well-functioning HIV treatment at pregnancy start should usually be retained; (6) Recommended drugs and drug combinations have been updated.

  2. Self-reported health-related quality of life in persons with HIV infection: results from a multi-site interview project

    Directory of Open Access Journals (Sweden)

    Nakashima Allyn K

    2003-04-01

    Full Text Available Abstract Background To examine demographic and behavioral associations with self-reported health-related quality of life (HRQOL among persons with HIV infection or AIDS. Methods Analysis of interviews with persons ≥ 18 years of age reported through routine disease surveillance with HIV infection or AIDS to nine state and local health departments from January 1995 through December 1996. Scales were constructed from validated measures of HRQOL, and mean scores were calculated (lower scores signified poorer HRQOL. Measures of HRQOL included Overall Health, Pain, Physical Functioning, Role Functioning, Social Functioning, Mental Health, Energy/Fatigue, and Cognitive Functioning. Differences in HRQOL were examined by various demographic and behavioral factors, including taking antiretroviral medication. Results HRQOL data were available for 3778 persons. Factors associated with lower HRQOL scores included older age, female sex, black or Hispanic race/ethnicity, injection drug use, lower education and income, no private health insurance, and lower CD4 count. In multivariate analysis, lower CD4 count was the factor most consistently associated with lower HRQOL. Taking antiretroviral medication was not associated with differences in HRQOL regardless of CD4 count. Conclusions Perception of HRQOL varied in a population with HIV infection or AIDS. On most HRQOL measures, lower CD4 count was associated with lower HRQOL. Measurement of HRQOL can assist in understanding the long-term effects of disease and treatment on persons with HIV.

  3. A Peer-Educator Network HIV Prevention Intervention Among Injection Drug Users: Results of a Randomized Controlled Trial in St. Petersburg, Russia

    Science.gov (United States)

    Latkin, Carl A.; Kukhareva, Polina V.; Malov, Sergey V.; Batluk, Julia V.; Shaboltas, Alla V.; Skochilov, Roman V.; Sokolov, Nicolay V.; Verevochkin, Sergei V.; Hudgens, Michael G.; Kozlov, Andrei P.

    2014-01-01

    We evaluated the efficacy of a peer-educator network intervention as a strategy to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or sexual networks. A randomized controlled trial was conducted in St. Petersburg, Russia among IDU index participants and their risk network participants. Network units were randomized to the control or experimental intervention. Only the experimental index participants received training sessions to communicate risk reduction techniques to their network members. Analysis includes 76 index and 84 network participants who were HIV uninfected. The main outcome measure was HIV sero-conversion. The incidence rates in the control and experimental groups were 19.57 (95 % CI 10.74–35.65) and 7.76 (95 % CI 3.51–17.19) cases per 100 p/y, respectively. The IRR was 0.41 (95 % CI 0.15–1.08) without a statistically significant difference between the two groups (log rank test statistic X2 = 2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the loss due to incarceration or death. The results show a promising trend that this strategy would be successful in reducing the acquisition of HIV among IDUs. PMID:23881187

  4. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li

    2011-11-01

    Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

  5. Effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda: results from a non-randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Michielsen Kristien

    2012-09-01

    Full Text Available Abstract Background While the HIV epidemic is levelling off in sub-Saharan Africa, it remains at an unacceptably high level. Young people aged 15-24 years remain particularly vulnerable, resulting in a regional HIV prevalence of 1.4% in young men and 3.3% in young women. This study assesses the effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda on young people’s sexual behavior, HIV knowledge and attitudes. Methods In a non-randomized longitudinal controlled trial, fourteen schools were selected in two neighboring districts in Rwanda Bugesera (intervention and Rwamagana (control. Students (n = 1950 in eight intervention and six control schools participated in three surveys (baseline, six and twelve months in the intervention. Analysis was done using linear and logistic regression using generalized estimation equations adjusted for propensity score. Results The overall retention rate was 72%. Time trends in sexual risk behavior (being sexually active, sex in last six months, condom use at last sex were not significantly different in students from intervention and control schools, nor was the intervention associated with increased knowledge, perceived severity or perceived susceptibility. It did significantly reduce reported stigma. Conclusions Analyzing this and other interventions, we identified several reasons for the observed limited effectiveness of peer education: 1 intervention activities (spreading information are not tuned to objectives (changing behavior; 2 young people prefer receiving HIV information from other sources than peers; 3 outcome indicators are not adequate and the context of the relationship in which sex occurs and the context in which sex occurs is ignored. Effectiveness of peer education may increase through integration in holistic interventions and redefining peer educators’ role as focal points for sensitization and referral to experts and services. Finally, we argue that a

  6. Shamba Maisha: Pilot agricultural intervention for food security and HIV health outcomes in Kenya: design, methods, baseline results and process evaluation of a cluster-randomized controlled trial.

    Science.gov (United States)

    Cohen, Craig R; Steinfeld, Rachel L; Weke, Elly; Bukusi, Elizabeth A; Hatcher, Abigail M; Shiboski, Stephen; Rheingans, Richard; Scow, Kate M; Butler, Lisa M; Otieno, Phelgona; Dworkin, Shari L; Weiser, Sheri D

    2015-01-01

    Despite advances in treatment of people living with HIV, morbidity and mortality remains unacceptably high in sub-Saharan Africa, largely due to parallel epidemics of poverty and food insecurity. We conducted a pilot cluster randomized controlled trial (RCT) of a multisectoral agricultural and microfinance intervention (entitled Shamba Maisha) designed to improve food security, household wealth, HIV clinical outcomes and women's empowerment. The intervention was carried out at two HIV clinics in Kenya, one randomized to the intervention arm and one to the control arm. HIV-infected patients >18 years, on antiretroviral therapy, with moderate/severe food insecurity and/or body mass index (BMI) loan (~$150) to purchase the farming commodities, 2) a micro-irrigation pump, seeds, and fertilizer, and 3) trainings in sustainable agricultural practices and financial literacy. Enrollment of 140 participants took four months, and the screening-to-enrollment ratio was similar between arms. We followed participants for 12 months and conducted structured questionnaires. We also conducted a process evaluation with participants and stakeholders 3-5 months after study start and at study end. Baseline results revealed that participants at the two sites were similar in age, gender and marital status. A greater proportion of participants at the intervention site had a low BMI in comparison to participants at the control site (18% vs. 7%, p = 0.054). While median CD4 count was similar between arms, a greater proportion of participants enrolled at the intervention arm had a detectable HIV viral load compared with control participants (49% vs. 28%, respectively, p loans, agricultural challenges due to weather patterns, and a challenging partnership with the microfinance institution. We expect the results from this pilot study to provide useful data on the impacts of livelihood interventions and will help in the design of a definitive cluster RCT. This trial is registered at Clinical

  7. The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome

    NARCIS (Netherlands)

    van Bel, Nikki; van der Velden, Yme; Bonnard, Damien; Le Rouzic, Erwann; Das, Atze T.; Benarous, Richard; Berkhout, Ben

    2014-01-01

    The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs). Although designed to

  8. Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements

    NARCIS (Netherlands)

    Lanoy, Emilie; May, Margaret; Mocroft, Amanda; Phillips, Andrew; Justice, Amy; Chene, Genevieve; Furrer, Hansjakob; Sterling, Timothy; D'Arminio Monforte, Antonella; Force, Lluis; Gill, John; Harris, Ross; Hogg, Robert S.; Rockstroh, Juergen; Saag, Mike; Khaykin, Pavel; de Wolf, Frank; Sterne, Jonathan A. C.; Costagliola, Dominique

    2009-01-01

    Objectives: CD4 cell count and plasma viral load are well known predictors of AIDS and mortality in