Demonstration of a novel HIV-1 restriction phenotype from a human T cell line.

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Yanxing Han

2008-07-01

Full Text Available Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5alpha, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized by viral proteins Vif and Vpu. So far, no human gene has been found to effectively block wild type HIV-1 replication under natural condition. Thus, identification of such a gene product would be of great medical importance for the development of HIV therapies.In this study, we discovered a new type of host restriction against the wild type HIV-1 from a CD4/CXCR4 double-positive human T cell line. We identified a CEM-derived cell line (CEM.NKR that is highly resistant to productive HIV-1 infection. Viral production was reduced by at least 1000-fold when compared to the other permissive human T cell lines such as H9, A3.01, and CEM-T4. Importantly, this resistance was evident at extremely high multiplicity of infection. Further analyses demonstrated that HIV-1 could finish the first round of replication in CEM.NKR cells, but the released virions were poorly infectious. These virions could enter the target cells, but failed to initiate reverse transcription. Notably, this restriction phenotype was also present in CEM.NKR and 293T heterokaryons.These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s. Further characterization of this novel gene product(s will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1.

The influence of different helminth infection phenotypes on immune responses against HIV in co-infected adults in South Africa

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Mabaso Musawenkosi LH

2011-10-01

Full Text Available Abstract Background The convergent distribution of the Human Immunodeficiency Virus (HIV and helminth infections has led to the suggestion that infection with helminths exacerbates the HIV epidemic in developing countries. In South Africa, it is estimated that 57% of the population lives in poverty and carries the highest burden of both HIV and helmith infections, however, the disease interactions are under-researched. Methods We employed both coproscopy and Ascaris lumbricoides-specific serum IgE to increase diagnostic sensitivity and to distinguish between different helminth infection phenotypes and their effects on immune responses in HIV co-infected individuals. Coproscopy was done by formol ether and Kato Katz methods. HIV positive and negative adults were stratified according to the presence or absence of A. lumbricoides and/or Trichuris trichuria eggs with or without elevated Ascaris IgE. Lymphocyte subsets were phenotyped by flow cytometry. Viral loads, serum total IgE and eosinophils were also analysed. Lymphocyte activation markers (CCR5, HLA-DR, CD25, CD38 and CD71 were determined. Non parametric statistics were used to describe differences in the variables between the subgroups. Results Helminth prevalence ranged between 40%-60%. Four distinct subgroups of were identified, and this included egg positive/high Ascaris-specific IgE (egg+IgEhi, egg positive/low IgE (egg+IgElo, egg negative/high IgE (egg-IgEhi and egg negative/low IgE (egg-IgElo individuals. The egg+IgEhi subgroup displayed lymphocytopenia, eosinophilia, (low CD4+ counts in HIV- group, high viral load (in HIV+ group, and an activated lymphocyte profile. High Ascaris IgE subgroups (egg+IgEhi and egg-IgEhi had eosinophilia, highest viral loads, and lower CD4+ counts in the HIV- group. Egg excretion and low IgE (egg+IgElo status demonstrated a modified Th2 immune profile with a relatively competent response to HIV. Conclusions People with both helminth egg excretion and high

HIV infection is associated with preservation of MAIT cells in the lungs but alteration of their phenotype and T cell receptor repertoire

DEFF Research Database (Denmark)

Wong, E. B.; Xulu, B.; Prakadan, S.

2016-01-01

Tuberculosis remains the leading cause of death in HIV-positive people. A better understanding of the impact of HIV on lung immunity may lead to novel immunotherapeutic interventions. MAIT cells are tissue-homing donor-unrestricted T cells with broad anti-microbial activity. HIV infection causes ...... to determine the mechanisms underlying the altered phenotypes of lung-resident MAITs and whether these can be targeted to improve anti-microbial lung immunity in people living with HIV....

Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source

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Sullivan John S

2007-07-01

Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with attenuated, nef-deleted variants of human immunodeficiency virus type 1 (HIV-1 acquired from a single source. Long-term prospective studies have demonstrated that the SBBC now comprises slow progressors (SP as well as long-term nonprogressors (LTNP. Convergent evolution of nef sequences in SBBC SP and LTNP indicates the in vivo pathogenicity of HIV-1 in SBBC members is dictated by factors other than nef. To better understand mechanisms underlying the pathogenicity of nef-deleted HIV-1, we examined the phenotype and env sequence diversity of sequentially isolated viruses (n = 2 from 3 SBBC members. Results The viruses characterized here were isolated from two SP spanning a three or six year period during progressive HIV-1 infection (subjects D36 and C98, respectively and from a LTNP spanning a two year period during asymptomatic, nonprogressive infection (subject C18. Both isolates from D36 were R5X4 phenotype and, compared to control HIV-1 strains, replicated to low levels in peripheral blood mononuclear cells (PBMC. In contrast, both isolates from C98 and C18 were CCR5-restricted. Both viruses isolated from C98 replicated to barely detectable levels in PBMC, whereas both viruses isolated from C18 replicated to low levels, similar to those isolated from D36. Analysis of env by V1V2 and V3 heteroduplex tracking assay, V1V2 length polymorphisms, sequencing and phylogenetic analysis showed distinct intra- and inter-patient env evolution. Conclusion Independent evolution of env despite convergent evolution of nef may contribute to the in vivo pathogenicity of nef-deleted HIV-1 in SBBC members, which may not necessarily be associated with changes in replication capacity or viral coreceptor specificity.

Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

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Bhardwaj, Suvercha; Ahmad, Fareed; Wedemeyer, Heiner; Cornberg, Marcus; Schulze Zur Wiesch, Julian; van Lunzen, Jan; Sarin, Shiv K; Schmidt, Reinhold E; Meyer-Olson, Dirk

2016-04-18

HIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56(bright) NK cells. Sixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry. We observed an expansion of CD56(bright) NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56(bright) NK cells in comparison to healthy controls while not differing amongst themselves. The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56(bright) NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56(bright) NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56(bright) NK cells was increased in HIV-HCV co-infection in comparison

Alterations of HIV-1 envelope phenotype and antibody-mediated neutralization by signal peptide mutations.

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Chitra Upadhyay

2018-01-01

Full Text Available HIV-1 envelope glycoprotein (Env mediates virus attachment and entry into the host cells. Like other membrane-bound and secreted proteins, HIV-1 Env contains at its N terminus a signal peptide (SP that directs the nascent Env to the endoplasmic reticulum (ER where Env synthesis and post-translational modifications take place. SP is cleaved during Env biosynthesis but potentially influences the phenotypic traits of the Env protein. The Env SP sequences of HIV-1 isolates display high sequence variability, and the significance of such variability is unclear. We postulate that changes in the Env SP influence Env transport through the ER-Golgi secretory pathway and Env folding and/or glycosylation that impact on Env incorporation into virions, receptor binding and antibody recognition. We first evaluated the consequences of mutating the charged residues in the Env SP in the context of infectious molecular clone HIV-1 REJO.c/2864. Results show that three different mutations affecting histidine at position 12 affected Env incorporation into virions that correlated with reduction of virus infectivity and DC-SIGN-mediated virus capture and transmission. Mutations at positions 8, 12, and 15 also rendered the virus more resistant to neutralization by monoclonal antibodies against the Env V1V2 region. These mutations affected the oligosaccharide composition of N-glycans as shown by changes in Env reactivity with specific lectins and by mass spectrometry. Increased neutralization resistance and N-glycan composition changes were also observed when analogous mutations were introduced to another HIV-1 strain, JRFL. To the best of our knowledge, this is the first study showing that certain residues in the HIV-1 Env SP can affect virus neutralization sensitivity by modulating oligosaccharide moieties on the Env N-glycans. The HIV-1 Env SP sequences thus may be under selective pressure to balance virus infectiousness with virus resistance to the host antibody

The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

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Poulton Joanna

2009-04-01

Full Text Available Abstract Background The mitochondrial DNA (mtDNA T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV. Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93, gender (males 60% vs 53%, P = 0.54, and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21. The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30 in the HIV-associated cardiomyopathy cases and 13.5% (5/37 in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11. Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.

T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection.

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Marcus Buggert

2014-07-01

Full Text Available CD8(+ T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing CD8(+ T cell differentiation, T-bet and Eomesodermin (Eomes, have previously been shown in mice to differentially regulate T cell exhaustion in part through direct modulation of PD-1. Here, we examined the relationship between these transcription factors and the expression of several inhibitory receptors (PD-1, CD160, and 2B4, functional characteristics and memory differentiation of CD8(+ T cells in chronic and treated HIV infection. The expression of PD-1, CD160, and 2B4 on total CD8(+ T cells was elevated in chronically infected individuals and highly associated with a T-bet(dimEomes(hi expressional profile. Interestingly, both resting and activated HIV-specific CD8(+ T cells in chronic infection were almost exclusively T-bet(dimEomes(hi cells, while CMV-specific CD8(+ T cells displayed a balanced expression pattern of T-bet and Eomes. The T-bet(dimEomes(hi virus-specific CD8(+ T cells did not show features of terminal differentiation, but rather a transitional memory phenotype with poor polyfunctional (effector characteristics. The transitional and exhausted phenotype of HIV-specific CD8(+ T cells was longitudinally related to persistent Eomes expression after antiretroviral therapy (ART initiation. Strikingly, these characteristics remained stable up to 10 years after ART initiation. This study supports the concept that poor human viral-specific CD8(+ T cell functionality is due to an inverse expression balance between T-bet and Eomes, which is not reversed despite long-term viral control through ART. These results aid to explain the inability of HIV-specific CD8(+ T cells to control the viral replication post-ART cessation.

Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention.

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Lajoie, Julie; Mwangi, Lucy; Fowke, Keith R

2017-09-12

For over three decades, HIV infection has had a tremendous impact on the lives of individuals and public health. Microbicides and vaccines studies have shown that immune activation at the genital tract is a risk factor for HIV infection. Furthermore, lower level of immune activation, or what we call immune quiescence, has been associated with a lower risk of HIV acquisition. This unique phenotype is observed in highly-exposed seronegative individuals from different populations including female sex workers from the Pumwani cohort in Nairobi, Kenya. Here, we review the link between immune activation and susceptibility to HIV infection. We also describe a new concept in prevention where, instead of targeting the virus, we modulate the host immune system to resist HIV infection. Mimicking the immune quiescence phenotype might become a new strategy in the toolbox of biomedical methods to prevent HIV infection. Clinical trial registration on clinicaltrial.gov: #NCT02079077.

Mucosal Blood Group Antigen Expression Profiles and HIV Infections: A Study among Female Sex Workers in Kenya.

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Nadia Musimbi Chanzu

Full Text Available The ABO blood group antigens are carbohydrate moieties expressed on human red blood cells however; these antigens can also be expressed on some other cells particularly the surface of epithelial cells and may be found in mucosal secretions. In many human populations 80% secrete ABO antigens (termed 'secretors' while 20% do not (termed 'non-secretors'. Furthermore, there are disease conditions that are associated with secretor status.To investigate correlations between secretor status and HIV infection among female sex workers in Nairobi, Kenya.This cross-sectional study recruited 280 female sex workers aged 18-65 years from the Pumwani Majengo cohort, Kenya. Blood typing was determined by serological techniques using monoclonal antibodies to the ABO blood group antigens. Secretor phenotyping was determined using anti-H specific lectins specific to salivary, vaginal and cervical blood group H antigen using the agglutination inhibition technique and correlated to individual HIV sero-status. Participants were additionally screened for Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis.Out of the 280 participants, 212 (75.7% were secretors and 68 (24.3% were non-secretors. The incidence of all infections: HIV, Bacterial vaginosis, Neisseria gonorrhoea and Trichomonas vaginalis was higher among secretors compared to non-secretors. However, this difference was only statistically significant for HIV infection incidence rates: HIV infected secretors (83.7% versus HIV un-infected secretors (71.8% (p = 0.029 Based on ABO phenotype stratification, the incidence of HIV infection was higher among blood group A secretors (26/52 = 50%, in comparison to B (12/39 = 33.3%: p = 0.066, AB (3/9 = 33.3%: p = 0.355, and O secretors (36/112 = 32.1%: p = 0.028.This is the first report to document the variable expression of the ABH blood group antigens profiling secretor and non-secretor phenotypes in the female genital tract among a high-risk population

Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

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Nabatanzi, Rose; Cose, Stephen; Joloba, Moses; Jones, Sarah Rowland; Nakanjako, Damalie

2018-03-15

HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery.

Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals

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Catherine Riou

2017-08-01

Full Text Available Several immune-based assays have been suggested to differentiate latent from active tuberculosis (TB. However, their relative performance as well as their efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In a study of 81 individuals, divided into four groups based on their HIV-1 status and TB disease activity, we compared the differentiation (CD27 and KLRG1, activation (HLA-DR, homing potential (CCR4, CCR6, CXCR3, and CD161 and functional profiles (IFNγ, IL-2, and TNFα of Mycobacterium tuberculosis (Mtb-specific CD4+ T cells using flow cytometry. Active TB disease induced major changes within the Mtb-responding CD4+ T cell population, promoting memory maturation, elevated activation and increased inflammatory potential when compared to individuals with latent TB infection. Moreover, the functional profile of Mtb-specific CD4+ T cells appeared to be inherently related to their degree of differentiation. While these specific cell features were all capable of discriminating latent from active TB, irrespective of HIV status, HLA-DR expression showed the best performance for TB diagnosis [area-under-the-curve (AUC = 0.92, 95% CI: 0.82–1.01, specificity: 82%, sensitivity: 84% for HIV− and AUC = 0.99, 95% CI: 0.98–1.01, specificity: 94%, sensitivity: 93% for HIV+]. In conclusion, these data support the idea that analysis of T cell phenotype can be diagnostically useful in TB.

Short communication: Phenotypic protease inhibitor resistance and cross-resistance in the clinic from 2006 to 2008 and mutational prevalences in HIV from patients with discordant tipranavir and darunavir susceptibility phenotypes.

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Bethell, Richard; Scherer, Joseph; Witvrouw, Myriam; Paquet, Agnes; Coakley, Eoin; Hall, David

2012-09-01

To test tipranavir (TPV) or darunavir (DRV) as treatment options for patients with phenotypic resistance to protease inhibitors (PIs), including lopinavir, saquinavir, atazanavir, and fosamprenavir, the PhenoSense GT database was analyzed for susceptibility to DRV or TPV among PI-resistant isolates. The Monogram Biosciences HIV database (South San Francisco, CA) containing 7775 clinical isolates (2006-2008) not susceptible to at least one first-generation PI was analyzed. Phenotypic responses [resistant (R), partially susceptible (PS), or susceptible (S)] were defined by upper and lower clinical cut-offs to each PI. Genotypes were screened for amino acid substitutions associated with TPV-R/DRV-S and TPV-S/DRV-R phenotypes. In all, 4.9% (378) of isolates were resistant to all six PIs and 31.0% (2407) were resistant to none. Among isolates resistant to all four first-generation PIs, DRV resistance increased from 21.2% to 41.9% from 2006 to 2008, respectively, and resistance to TPV remained steady (53.9 to 57.3%, respectively). Higher prevalence substitutions in DRV-S/TPV-R isolates versus DRV-R/TPV-S isolates, respectively, were 82L/T (44.4% vs. 0%) and 83D (5.8% vs. 0%). Higher prevalence substitutions in DRV-R/TPV-S virus were 50V (0.0% vs. 28.9%), 54L (1.0% vs. 36.1%), and 76V (0.4% vs. 15.5%). Mutations to help predict discordant susceptibility to DRV and TPV in isolates with reduced susceptibility to other PIs were identified. DRV resistance mutations associated with improved virologic response to TPV were more prevalent in DRV-R/TPV-S isolates. TPV resistance mutations were more prevalent in TPV-R and DRV-S isolates. These results confirm the impact of genotype on phenotype, illustrating how HIV genotype and phenotype data assist regimen optimization.

Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

NARCIS (Netherlands)

Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

1999-01-01

Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

IDEPI: rapid prediction of HIV-1 antibody epitopes and other phenotypic features from sequence data using a flexible machine learning platform.

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N Lance Hepler

2014-09-01

Full Text Available Since its identification in 1983, HIV-1 has been the focus of a research effort unprecedented in scope and difficulty, whose ultimate goals--a cure and a vaccine--remain elusive. One of the fundamental challenges in accomplishing these goals is the tremendous genetic variability of the virus, with some genes differing at as many as 40% of nucleotide positions among circulating strains. Because of this, the genetic bases of many viral phenotypes, most notably the susceptibility to neutralization by a particular antibody, are difficult to identify computationally. Drawing upon open-source general-purpose machine learning algorithms and libraries, we have developed a software package IDEPI (IDentify EPItopes for learning genotype-to-phenotype predictive models from sequences with known phenotypes. IDEPI can apply learned models to classify sequences of unknown phenotypes, and also identify specific sequence features which contribute to a particular phenotype. We demonstrate that IDEPI achieves performance similar to or better than that of previously published approaches on four well-studied problems: finding the epitopes of broadly neutralizing antibodies (bNab, determining coreceptor tropism of the virus, identifying compartment-specific genetic signatures of the virus, and deducing drug-resistance associated mutations. The cross-platform Python source code (released under the GPL 3.0 license, documentation, issue tracking, and a pre-configured virtual machine for IDEPI can be found at https://github.com/veg/idepi.

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

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Shafer, Robert W

2006-09-15

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

Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition

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Limou, Sophie; Delaneau, Olivier; van Manen, Daniëlle; An, Ping; Sezgin, Efe; Le Clerc, Sigrid; Coulonges, Cédric; Troyer, Jennifer L.; Veldink, Jan H.; van den Berg, Leonard H.; Spadoni, Jean-Louis; Taing, Lieng; Labib, Taoufik; Montes, Matthieu; Delfraissy, Jean-François; Schachter, François; O’Brien, Stephen J.; Buchbinder, Susan; van Natta, Mark L.; Jabs, Douglas A.; Froguel, Philippe; Schuitemaker, Hanneke; Winkler, Cheryl A.

2012-01-01

Background. To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10−5 in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: Pcombined = 7.76 × 10−8. Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation. PMID:22362864

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

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Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

2018-01-01

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

Tools for Visualizing HIV in Cure Research.

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Niessl, Julia; Baxter, Amy E; Kaufmann, Daniel E

2018-02-01

The long-lived HIV reservoir remains a major obstacle for an HIV cure. Current techniques to analyze this reservoir are generally population-based. We highlight recent developments in methods visualizing HIV, which offer a different, complementary view, and provide indispensable information for cure strategy development. Recent advances in fluorescence in situ hybridization techniques enabled key developments in reservoir visualization. Flow cytometric detection of HIV mRNAs, concurrently with proteins, provides a high-throughput approach to study the reservoir on a single-cell level. On a tissue level, key spatial information can be obtained detecting viral RNA and DNA in situ by fluorescence microscopy. At total-body level, advancements in non-invasive immuno-positron emission tomography (PET) detection of HIV proteins may allow an encompassing view of HIV reservoir sites. HIV imaging approaches provide important, complementary information regarding the size, phenotype, and localization of the HIV reservoir. Visualizing the reservoir may contribute to the design, assessment, and monitoring of HIV cure strategies in vitro and in vivo.

In vitro HIV-1 evolution in response to triple reverse transcriptase inhibitors & in silico phenotypic analysis.

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Barbara A Rath

Full Text Available Effectiveness of ART regimens strongly depends upon complex interactions between the selective pressure of drugs and the evolution of mutations that allow or restrict drug resistance.Four clinical isolates from NRTI-exposed, NNRTI-naive subjects were passaged in increasing concentrations of NVP in combination with 1 µM 3 TC and 2 µM ADV to assess selective pressures of multi-drug treatment. A novel parameter inference procedure, based on a stochastic viral growth model, was used to estimate phenotypic resistance and fitness from in vitro combination passage experiments.Newly developed mathematical methods estimated key phenotypic parameters of mutations arising through selective pressure exerted by 3 TC and NVP. Concentrations of 1 µM 3 TC maintained the M184V mutation, which was associated with intrinsic fitness deficits. Increasing NVP concentrations selected major NNRTI resistance mutations. The evolutionary pathway of NVP resistance was highly dependent on the viral genetic background, epistasis as well as stochasticity. Parameter estimation indicated that the previously unrecognized mutation L228Q was associated with NVP resistance in some isolates.Serial passage of viruses in the presence of multiple drugs may resemble the selection of mutations observed among treated individuals and populations in vivo and indicate evolutionary preferences and restrictions. Phenotypic resistance estimated here "in silico" from in vitro passage experiments agreed well with previous knowledge, suggesting that the unique combination of "wet-" and "dry-lab" experimentation may improve our understanding of HIV-1 resistance evolution in the future.

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

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

2000-10-10

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

Short communication prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV type 1 resistance testing in the United States.

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Picchio, Gaston; Vingerhoets, Johan; Tambuyzer, Lotke; Coakley, Eoin; Haddad, Mojgan; Witek, James

2011-12-01

Abstract The prevalence of susceptibility to etravirine was investigated among clinical samples submitted for routine clinical testing in the United States using two separate weighted genotypic scoring systems. The presence of etravirine mutations and susceptibility to etravirine by phenotype of clinical samples from HIV-1-infected patients, submitted to Monogram Biosciences for routine resistance testing between June 2008 and June 2009, were analyzed. Susceptibility by genotype was determined using the Monogram and Tibotec etravirine-weighted genotypic scoring systems, with scores of ≤3 and ≤2, respectively, indicating full susceptibility. Susceptibility by phenotype was determined using the PhenoSense HIV assay, with lower and higher clinical cut-offs of 2.9 and 10, respectively. The frequency of individual etravirine mutations and the impact of the K103N mutation on susceptibility to etravirine by genotype were also determined. Among the 5482 samples with ≥1 defined nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations associated with resistance, 67% were classed as susceptible to etravirine by genotype by both scoring systems. Susceptibility to etravirine by phenotype was higher (76%). The proportion of first-generation NNRTI-resistant samples with (n=3598) and without (n=1884) K103N with susceptibility to etravirine by genotype was 77% and 49%, respectively. Among samples susceptible to first-generation NNRTIs (n=9458), >99% of samples were susceptible to etravirine by phenotype (FC <2.9); the remaining samples had FC ≥2.9-10. In summary, among samples submitted for routine clinical testing in the United States, a high proportion of samples with first-generation NNRTI resistance was susceptible to etravirine by genotype and phenotype. A higher proportion of NNRTI-resistant samples with K103N than without was susceptible to etravirine.

Clinical aspects of headache in HIV.

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Sheikh, Huma U; Cho, Tracey A

2014-05-01

Headaches are commonly seen in those patients with human immunodeficiency virus (HIV) and are the most common form of pain reported among HIV patients. There have been relatively few studies attempting to determine the rates and phenotypes of the headaches that occur in patients with HIV. Patients with HIV are susceptible to a much broader array of secondary headache causes, sometimes with atypical manifestations due to a dampened inflammatory response. The investigation of a headache in the HIV patient should be thorough and focused on making sure that secondary and HIV-specific causes are either ruled out or treated if present. An effective treatment plan should incorporate the use of appropriate pharmacological agents along with the integration of non-pharmacological therapies, such as relaxation and lifestyle regulation. When treating for headaches in patients with HIV, it is important to keep in mind comorbidities and other medications, especially combination antiretroviral therapy. For those with complicated headache histories, referral to a specialized headache center may be appropriate. © 2014 American Headache Society.

Viral phenotype, antiretroviral resistance and clinical evolution in human immunodeficiency virus-infected children.

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Mellado, M J; Cilleruelo, M J; Ortiz, M; Villota, J; García, M; Perez-Jurado, M L; Barreiro, G; Martín-Fontelos, P; Bernal, A

1997-11-01

The syncytium-inducing (SI) viral phenotype and the emergence of viral strains resistant to zidovudine have been described in persons infected with HIV, and in some cases they have been associated with poor prognosis. HIV isolates obtained from 37 HIV-infected children were analyzed to determine whether the SI viral phenotype and the mutation on the 215 position of the reverse transcriptase (M215) could be used as markers of disease progression. We performed peripheral blood coculture mononuclear cells, and we analyzed the induction of syncytia using the MT-2 cell line. The emergence of mutations on the 215 position was determined by PCR. We found a statistically significant association (P < 0.05) between SI viral phenotype and (1) recurrent serious bacterial infections, (2) absolute CD4+ cell counts <2 SD, (3) progression to AIDS and (4) death. Sixty percent of the children treated with zidovudine developed 215 mutant viral strains without statistically significant association with clinical or immunologic findings. The SI viral phenotype was statistically associated with the presence of the 215 mutation (P < 0.05). SI viral phenotype is a marker associated with a poor clinical and immunologic progression of the disease and it may facilitate the emergence of mutant strains in children treated with zidovudine.

EFFECT OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON VAGINAL Candida spp. ISOLATION IN HIV-INFECTED COMPARED TO HIV-UNINFECTED WOMEN

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Silvia de Souza Dantas ALCZUK

2015-04-01

Full Text Available Vulvovaginal candidiasis (VVC in HIV-infected women contributed to the impairment of their quality of life. The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART use on the vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women. This cross-sectional study included 178 HIV-infected (HIV group and 200 HIV-uninfected women (control that were studied at the Specialized Assistance Service (SAE for sexually transmitted diseases (STD/AIDS of the city of Maringá, Brazil, from April 1 to October 30, 2011. The yeasts were isolated and identified by phenotypic and molecular methods. The in vitro antifungal susceptibility to fluconazole, itraconazole, nystatin and amphotericin B was tested by the reference microdilution method. Higher frequencies of total vaginal Candida spp. isolation were found in the HIV-infected group than in the control group. However, both groups showed a similar frequency of colonization and VVC. Although C. albicans was the most frequent and sensitive to azolics and polyenes in both HIV-infected and uninfected women, the emerging resistance of C. glabrata to amphotericin B in the HIV-infected women was observed. Although higher frequency of vaginal Candida spp. isolation had been observed in the HIV-infected than in HIV-uninfected women, colonization and VVC showed similar frequency in both groups, indicating that HAART appears to protect against vaginal colonization and VVC.

Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication

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Belhumeur Pierre

2008-11-01

Full Text Available Abstract Background HIV-1 integrase (IN is a key viral enzymatic molecule required for the integration of the viral cDNA into the genome. Additionally, HIV-1 IN has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. Interestingly, previous studies have demonstrated that the expression of HIV-1 IN induces the lethal phenotype in some strains of Saccharomyces cerevisiae. In this study, we performed mutagenic analyses of the C-terminal region of the catalytic core domain of HIV-1 IN in order to delineate the critical amino acid(s and/or motif(s required for the induction of the lethal phenotype in the yeast strain HP16, and to further elucidate the molecular mechanism which causes this phenotype. Results Our study identified three HIV-1 IN mutants, V165A, A179P and KR186,7AA, located in the C-terminal region of the catalytic core domain of IN that do not induce the lethal phenotype in yeast. Chromatin binding assays in yeast and mammalian cells demonstrated that these IN mutants were impaired for the ability to bind chromatin. Additionally, we determined that while these IN mutants failed to interact with LEDGF/p75, they retained the ability to bind Integrase interactor 1. Furthermore, we observed that VSV-G-pseudotyped HIV-1 containing these IN mutants was unable to replicate in the C8166 T cell line and this defect was partially rescued by complementation with the catalytically inactive D64E IN mutant. Conclusion Overall, this study demonstrates that three mutations located in the C-terminal region of the catalytic core domain of HIV-1 IN inhibit the IN-induced lethal phenotype in yeast by inhibiting the binding of IN to the host chromatin. These results demonstrate that the C-terminal region of the catalytic core domain of HIV-1 IN is important for binding to host chromatin and is crucial for both viral replication and the promotion of

HIV: current opinion in escapology.

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Klenerman, Paul; Wu, Ying; Phillips, Rodney

2002-08-01

Much recent work strongly supports the hypothesis that CD8(+) T lymphocytes (CTLs) exert important immune control over HIV and so are a major selective force in its evolution. We analyse this host-pathogen interplay and focus on new data that describe the overall 'effectiveness' of CTL responses (strength, spread, specificity and 'stamina') and the mechanisms by which HIV may evade this suppressive activity. CTLs directed against HIV recognise very large numbers of distinct epitopes across the genome, are largely functional, turn over rapidly, and possess a phenotype that is distinct from CD8(+) lymphocytes specific for other viruses. Mutation of HIV epitopes that alters or abolishes CTL recognition altogether appears to be the most important immune escape mechanism, as the variation that HIV generates defies the limits of the T cell repertoire. However, this immune evasion is still only well-studied in a few patients. The rules that govern immune escape, and the ultimate limits of CTL capacity to deal with the variant epitopes that currently circulate, are not understood. This information will determine the feasibility of current vaccine approaches that, so far, make no provision for the enormous antigenic plasticity of HIV.

Phenotypic and functional analysis of CD1a+ dendritic cells from cats chronically infected with feline immunodeficiency virus.

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Zhang, Lin; Reckling, Stacie; Dean, Gregg A

2015-10-01

Numerous studies suggest dendritic cell (DC) dysfunction is central to the dysregulated immune response during HIV infection; however, in vivo studies are lacking. In the present study we used feline immunodeficiency virus (FIV) infection of cats as a model for HIV-1 infection to assess the maturation and function of dendritic cells, in vivo and in vitro. We compared CD1a+ DC migration, surface phenotype, endocytosis, mixed leukocyte reaction (MLR) and regulatory T cell (Treg) phenotype induction by CD1a+ cells isolated from lymph nodes of FIV-infected and control cats. Results showed that resident CD1a+ DC in lymph nodes of chronically FIV-infected cats are phenotypically mature, can stimulate normal primary T cell proliferation, override Treg suppression and do not skew toward Treg induction. In contrast, FIV infection had deleterious effects on antigen presentation and migratory capacity of CD1a+ cells in tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.

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Cavarelli, Mariangela; Karlsson, Ingrid; Zanchetta, Marisa; Antonsson, Liselotte; Plebani, Anna; Giaquinto, Carlo; Fenyö, Eva Maria; De Rossi, Anita; Scarlatti, Gabriella

2008-09-29

HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad) viruses), was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT) of HIV-1 and pediatric disease progression. Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting) and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow) phenotype (n = 20), but R5(broad) and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad) and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3) or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad) phenotype, however, the presence of the R5(broad) virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad) viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad) phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant. Our results show that R5(broad) viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow) phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.

Meloxicam blocks neuroinflammation, but not depressive-like behaviors, in HIV-1 transgenic female rats.

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Christina L Nemeth

Full Text Available Adolescents living with human immunodeficiency virus (HIV comprise approximately 12% of the HIV-positive population worldwide. HIV-positive adolescents experience a higher rate of clinical depression, a greater risk of sexual and drug abuse behaviors, and a decreased adherence to highly active antiretroviral therapies (HAART. Using adolescent HIV-1 transgenic rats (HIV-1 tg that display related immune response alterations and pathologies, this study tested the hypothesis that developmental expression of HIV-1-related proteins induces a depressive-like phenotype that parallels a decrease in hippocampal cell proliferation and an increase in pro-inflammatory cytokine expression in the hippocampus. Consistent with this hypothesis, adolescent HIV-1 tg rats demonstrated a depressive-like behavioral phenotype, had decreased levels of cell proliferation, and exhibited elevated expression of monocyte chemotactic protein-1 (Mcp-1 in the hippocampus relative to controls. Subsequently, we tested the ability of meloxicam, a selective COX-2 inhibitor, to attenuate behavioral deficits via inflammatory mechanisms. Daily meloxicam treatments did not alter the behavioral profile despite effectively reducing hippocampal inflammatory gene expression. Together, these data support a biological basis for the co-morbid manifestation of depression in HIV-positive patients as early as in adolescence and suggest that modifications in behavior manifest independent of inflammatory activity in the hippocampus.

NKT cell depletion in humans during early HIV infection.

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Fernandez, Caroline S; Kelleher, Anthony D; Finlayson, Robert; Godfrey, Dale I; Kent, Stephen J

2014-08-01

Natural killer T (NKT) cells bridge across innate and adaptive immune responses and have an important role in chronic viral infections such as human immunodeficiency virus (HIV). NKT cells are depleted during chronic HIV infection, but the timing, drivers and implications of this NKT cell depletion are poorly understood. We studied human peripheral blood NKT cell levels, phenotype and function in 31 HIV-infected subjects not on antiretroviral treatment from a mean of 4 months to 2 years after HIV infection. We found that peripheral CD4(+) NKT cells were substantially depleted and dysfunctional by 4 months after HIV infection. The depletion of CD4(+) NKT cells was more marked than the depletion of total CD4(+) T cells. Further, the early depletion of NKT cells correlated with CD4(+) T-cell decline, but not HIV viral levels. Levels of activated CD4(+) T cells correlated with the loss of NKT cells. Our studies suggest that the early loss of NKT cells is associated with subsequent immune destruction during HIV infection.

CXCR4-using HIV variants in a cohort of Black men who have sex with men: HIV Prevention Trials Network 061.

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Chen, Iris; Huang, Wei; Connor, Matthew B; Frantzell, Arne; Cummings, Vanessa; Beauchamp, Geetha G; Griffith, Sam; Fields, Sheldon D; Scott, Hyman M; Shoptaw, Steven; Del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Tieu, Hong-Van; Wheeler, Darrell P; Mayer, Kenneth H; Koblin, Beryl A; Eshleman, Susan H

2016-07-01

To evaluate factors associated with HIV tropism among Black men who have sex with men (MSM) in the United States enrolled in a clinical study (HIV Prevention Trials Network 061). HIV tropism was analyzed using a phenotypic assay (Trofile assay, Monogram Biosciences). Samples were analyzed from 43 men who were HIV infected at enrollment and reported either exclusive insertive intercourse or exclusive receptive intercourse; samples were also analyzed from 20 men who were HIV uninfected at enrollment and seroconverted during the study. Clonal analysis of individual viral variants was performed for seroconverters who had dual/mixed (DM) viruses. DM viruses were detected in samples from 11 (26%) of the 43 HIV-infected men analyzed at the enrollment visit; HIV tropism did not differ between those reporting exclusive insertive vs receptive intercourse. DM viruses were also detected in five (25%) of the 20 seroconverters. DM viruses were associated with lower CD4 cell counts. Seroconverters with DM viruses had dual-tropic viruses only or mixed populations of CCR5- and dual-tropic viruses. DM viruses were frequently detected among Black MSM in this study, including seroconverters. Further studies are needed to understand factors driving transmission and selection of CXCR4- and dual-tropic viruses among Black MSM.

Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

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MC Portela

1997-07-01

Full Text Available This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

Motivators of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies.

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Dhalla, Shayesta; Poole, Gary

2011-11-01

HIV vaccine preparedness studies (VPS) are important precursors to HIV vaccine trials. As well, they contribute to an understanding of motivators and barriers for participation in hypothetical HIV vaccine trials. Motivators can take the form of altruism and a desire for social benefits. Perceived personal benefits, including psychological, personal, and financial well-being, may also motivate participation. The authors performed a systematic review of HIV VPS using the Cochrane Database for Systematic Reviews, Medline, PubMed, Embase, and Google Scholar. The authors independently searched the literature for individual HIV VPS that examined motivators of participation in a hypothetical HIV vaccine trial, using the same search strategy. As the denominators employed in the literature varied across studies, the denominators were standardized to the number of respondents per survey item, regardless of their willingness to participate (WTP) in an HIV vaccine trial. The authors retrieved eight studies on social benefits (i.e., altruism) and 11 studies on personal benefits conducted in the Organization for Economic Co-operation and Development (OECD) countries, as well as 19 studies on social benefits and 20 studies on personal benefits in the non-OECD countries. Various different forms of altruism were found to be the major motivators for participation in an HIV vaccine trial in both the OECD and the non-OECD countries. In a large number of studies, protection from HIV was cited as a personal motivator for participation in a hypothetical HIV vaccine trial in the OECD and the non-OECD countries. Knowledge of motivators can inform and target recruitment for HIV vaccine trials, although it must be remembered that hypothetical motivators may not always translate into motivators in an actual vaccine trial.

Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.

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Morris, Sheldon R; Woods, Steven Paul; Deutsch, Reena; Little, Susan J; Wagner, Gabriel; Morgan, Erin E; Heaton, Robert K; Letendre, Scott L; Grant, Igor; Smith, Davey M

2013-10-01

HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.

Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection

DEFF Research Database (Denmark)

Evangelou, Evangelos; Fellay, Jacques; Colombo, Sara

2011-01-01

infected with human immunodeficiency virus type 1 (HIV-1) to assess whether differences in type of population (622 seroconverters vs. 636 seroprevalent subjects) or the number of measurements available for defining the phenotype resulted in differences in the effect sizes of associations between single...... nucleotide polymorphisms and the phenotype, HIV-1 viral load at set point. The effect estimate for the top 100 single nucleotide polymorphisms was 0.092 (95% confidence interval: 0.074, 0.110) log(10) viral load (log(10) copies of HIV-1 per mL of blood) greater in seroconverters than in seroprevalent...... available, particularly among seroconverters and for variants that achieved genome-wide significance. Differences in phenotype definition and ascertainment may affect the estimated magnitude of genetic effects and should be considered in optimizing power for discovering new associations....

HIV-1 with multiple CCR5/CXCR4 chimeric receptor use is predictive of immunological failure in infected children.

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Mariangela Cavarelli

Full Text Available BACKGROUND: HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5(broad viruses, was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT of HIV-1 and pediatric disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Viral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5(narrow phenotype (n = 20, but R5(broad and R5X4 viruses were also found in seven and one case, respectively. The presence of R5(broad and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3 or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5(broad phenotype, however, the presence of the R5(broad virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5(broad viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5(broad phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant. CONCLUSIONS/SIGNIFICANCE: Our results show that R5(broad viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5(narrow phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.

Interplay between HIV Entry and Transportin-SR2 Dependency

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Gijsbers Rik

2011-01-01

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

Chorioamnionitis in pregnancy: a comparative study of HIV-positive and HIV-negative parturients.

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Ocheke, Amaka N; Agaba, Patricia A; Imade, Godwin E; Silas, Olugbenga A; Ajetunmobi, Olanrewaju I; Echejoh, Godwins; Ekere, Clement; Sendht, Ayuba; Bitrus, James; Agaba, Emmanuel I; Sagay, Atiene S

2016-03-01

Chorioamnionitis is an important risk factor for vertical transmission of HIV/AIDS. We compared the prevalence and correlates of histologic chorioamnionitis (HCA) in HIV-positive and HIV-negative pregnant women. HIV-positive and -negative parturients were interviewed, examined and had their placentas examined histologically for chorioamnionitis. Data regarding HIV were also retrieved from their hospital records. A total of 298 parturients (150 HIV positive and 148 HIV negative) were enrolled. The two groups were similar in socio-demographic and obstetric parameters except for age. The prevalence of HCA was 57.1% in HIV-positive women and 61.6% in HIV-negative women (p = 0.43). HCA staging was associated with the number of intrapartum vaginal examinations in HIV-positive subjects and nulliparity in HIV-negative subjects. The number of intrapartum vaginal examinations and coitus in the week prior to delivery significantly affected the grade of HCA in HIV-negative subjects. The prevalence of HCA in both HIV-positive and HIV-negative is high. Most variables did not affect the occurrence of HCA in both groups studied except number of intrapartum examinations, coitus in the preceding one week and nulliparity, which were related to severity of the disease. © The Author(s) 2016.

Adrenaline-induced mobilization of T cells in HIV-infected patients

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Søndergaard, S R; Cozzi-Lepri, A; Ullum, H

2000-01-01

The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline...... infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45......RO+CD45RA- and CD8+CD28-cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect...

Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

DEFF Research Database (Denmark)

Sørensen, A M; Nielsen, C; Arendrup, M

1994-01-01

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes

DEFF Research Database (Denmark)

Sørensen, A M; Nielsen, C; Arendrup, M

1994-01-01

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

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Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane

2015-01-01

ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are

Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells

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Marielle Cavrois

2017-07-01

Full Text Available To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes. In HIV-infected patients, CD127-expressing cells preferentially localize to extrafollicular lymphoid regions with limited viral replication. Thus, CyTOF-based phenotyping, combined with analytical approaches to distinguish between selective infection and receptor modulation by viruses, can be used as a discovery tool.

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

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Lane, Jérôme; McLaren, Paul J.; Dorrell, Lucy; Shianna, Kevin V.; Stemke, Amanda; Pelak, Kimberly; Moore, Stephen; Oldenburg, Johannes; Alvarez-Roman, Maria Teresa; Angelillo-Scherrer, Anne; Boehlen, Francoise; Bolton-Maggs, Paula H.B.; Brand, Brigit; Brown, Deborah; Chiang, Elaine; Cid-Haro, Ana Rosa; Clotet, Bonaventura; Collins, Peter; Colombo, Sara; Dalmau, Judith; Fogarty, Patrick; Giangrande, Paul; Gringeri, Alessandro; Iyer, Rathi; Katsarou, Olga; Kempton, Christine; Kuriakose, Philip; Lin, Judith; Makris, Mike; Manco-Johnson, Marilyn; Tsakiris, Dimitrios A.; Martinez-Picado, Javier; Mauser-Bunschoten, Evelien; Neff, Anne; Oka, Shinichi; Oyesiku, Lara; Parra, Rafael; Peter-Salonen, Kristiina; Powell, Jerry; Recht, Michael; Shapiro, Amy; Stine, Kimo; Talks, Katherine; Telenti, Amalio; Wilde, Jonathan; Yee, Thynn Thynn; Wolinsky, Steven M.; Martinson, Jeremy; Hussain, Shehnaz K.; Bream, Jay H.; Jacobson, Lisa P.; Carrington, Mary; Goedert, James J.; Haynes, Barton F.; McMichael, Andrew J.; Goldstein, David B.; Fellay, Jacques

2013-01-01

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979–1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population. PMID:23372042

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

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

2016-12-20

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

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

DEFF Research Database (Denmark)

Seng, R; Gustafson, P; Gomes, VF

2002-01-01

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

Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.

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Maria L Alcaide

Full Text Available Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163, microbial translocation (LPS and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10 were evaluated.T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.

Determination of HIV-1 co-receptor usage.

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Cavarelli, Mariangela; Scarlatti, Gabriella

2014-01-01

Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly the β-chemokine receptor 5 (CCR5) and the α-chemokine receptor 4 (CXCR4). Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. In this chapter, methods to determine the co-receptor usage of HIV-1 variants are described.

Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.

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Cummins, Nathan W; Rizza, Stacey; Litzow, Mark R; Hua, Stephane; Lee, Guinevere Q; Einkauf, Kevin; Chun, Tae-Wook; Rhame, Frank; Baker, Jason V; Busch, Michael P; Chomont, Nicolas; Dean, Patrick G; Fromentin, Rémi; Haase, Ashley T; Hampton, Dylan; Keating, Sheila M; Lada, Steven M; Lee, Tzong-Hae; Natesampillai, Sekar; Richman, Douglas D; Schacker, Timothy W; Wietgrefe, Stephen; Yu, Xu G; Yao, Joseph D; Zeuli, John; Lichterfeld, Mathias; Badley, Andrew D

2017-11-01

Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

HIV protein sequence hotspots for crosstalk with host hub proteins.

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Mahdi Sarmady

Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1 Serodiscordant Couples

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MUGO, Nelly R.; HEFFRON, Renee; DONNELL, Deborah; WALD, Anna; WERE, Edwin O.; REES, Helen; CELUM, Connie; KIARIE, James N.; COHEN, Craig R.; KAYINTEKORE, Kayitesi; BAETEN, Jared M.

2011-01-01

Background Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1 infected women to male partners. Methods In a prospective study of African HIV-1 serodiscordant couples, we evaluated the relationship between pregnancy and the risk of 1) HIV-1 acquisition among women and 2) HIV-1 transmission from women to men. Results 3321 HIV-1 serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and non-pregnant periods (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.33–4.09). This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted HR 1.71, 95% CI 0.93–3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (HR 2.31, 95% CI 1.22–4.39). This effect was not attenuated in adjusted analysis (adjusted HR 2.47, 95% CI 1.26–4.85). Conclusions HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness. PMID:21785321

CD4 Cell Counts at HIV Diagnosis among HIV Outpatient Study Participants, 2000–2009

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Kate Buchacz

2012-01-01

Full Text Available Background. It is unclear if CD4 cell counts at HIV diagnosis have improved over a 10-year period of expanded HIV testing in the USA. Methods. We studied HOPS participants diagnosed with HIV infection ≤6 months prior to entry into care during 2000–2009. We assessed the correlates of CD4 count <200 cells/mm3 at HIV diagnosis (late HIV diagnosis by logistic regression. Results. Of 1,203 eligible patients, 936 (78% had a CD4 count within 3 months after HIV diagnosis. Median CD4 count at HIV diagnosis was 299 cells/mm3 and did not significantly improve over time (P=0.13. Comparing periods 2000-2001 versus 2008-2009, respectively, 39% and 35% of patients had a late HIV diagnosis (P=0.34. Independent correlates of late HIV diagnosis were having an HIV risk other than being MSM, age ≥35 years at diagnosis, and being of nonwhite race/ethnicity. Conclusions. There is need for routine universal HIV testing to reduce the frequency of late HIV diagnosis and increase opportunity for patient- and potentially population-level benefits associated with early antiretroviral treatment.

Recommendations for using standardised phenotypes in genetic association studies

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Naylor Melissa G

2009-07-01

Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

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Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

2017-12-01

Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

Exploring HIV-related stigma among HIV-infected men who have sex with men in Beijing, China: a correlation study.

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Li, Zhen; Hsieh, Evelyn; Morano, Jamie P; Sheng, Yu

2016-11-01

Human immunodeficiency virus (HIV)-related stigma among HIV-infected men who have sex with men (MSM) has been associated with adverse health outcomes, including poor adherence to antiretroviral therapy and care, and increased participation in behaviors linked to higher rates of HIV transmission. In China, the incidence of HIV is growing more rapidly among MSM than among other subgroups. This study characterizes and quantifies HIV stigma among HIV-infected MSM in Beijing, China, which arguably may be driving this epidemic. A cross-sectional survey study was performed among 266 HIV-positive MSM in Beijing, China, in 2014. The Berger HIV Stigma Scale was used to measure levels of HIV-related stigma. Participants additionally answered questions regarding socio-demographic characteristics and HIV-associated risk factors; previously validated Mandarin-language scales assessed depression, coping style, and social support networks. Multivariable linear regression models were used to identify variables significantly associated with HIV stigma. The mean overall HIV stigma score among the study population was 112.78 ± 18.11 (score range: 40-160). Higher HIV stigma scores were positively associated with depression (β = 7.99, 95% CI:3.69, 12.29, p stigma. The results of this study can inform the development of culturally sensitive interventions to reduce HIV-related stigma among MSM with HIV in China, with the overarching goal of reducing HIV transmission in this vulnerable population.

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

DEFF Research Database (Denmark)

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

2016-01-01

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

[Epidemiological study on HIV/AIDS in Cambodia seroprevalence of HIV/STD among commercial sex workers].

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Ohshige, K; Morio, S; Mizushima, S; Kitamura, K; Tajima, K; Ito, A; Suyama, A; Usuku, S; Phalla, T; Leng, H B; Sopheab, H; Eab, B; Soda, K

1999-01-01

To describe epidemiological features of HIV prevalence among female commercial sex workers (CSWs) in Cambodia, a cross-sectional study using a questionnaire study and serological tests was carried out from December 1997 to January 1998. We report the main results of the analyses of serological tests in this article. Two hundred ninety six CSWs working in Sisophon and Poi Pet, located in northwest Cambodia, Bantey Mean Chey province, were recruited for interview based on a questionnaire on sexual behavior, and serological tests. The blood samples were examined for HIV antibody, Chlamydia trachomatis IgG antibody, TPHA, Hepatitis B surface antigen, and Hepatitis B surface antibody. The relationship between HIV and the other STD's was analyzed by using logistic regression analysis. The HIV seroprevalence rate was 43.9% (130 out of 296). The seropositive rate of Chlamydia trachomatis IgG antibody (C.T.-IgG-Ab) was 73.3% (217 out of 296). Logistic regression analysis showed a significant association between C.T.-IgG-Ab positive and HIV prevalence. (Odds Ratio: 5.33; 95% Confidence Interval, 2.82-10.07). This study suggests that the existence of Chlamydia trachomatis is closely related with HIV prevalence among CSWs in Cambodia. Other STDs may also increase susceptibility to male-to-female sexual transmission of HIV. This suggests that appropriate prevention against STDs will be needed for the control of HIV prevalence in Cambodia.

Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.

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Recordon-Pinson, Patricia; Soulié, Cathia; Flandre, Philippe; Descamps, Diane; Lazrek, Mouna; Charpentier, Charlotte; Montes, Brigitte; Trabaud, Mary-Anne; Cottalorda, Jacqueline; Schneider, Véronique; Morand-Joubert, Laurence; Tamalet, Catherine; Desbois, Delphine; Macé, Muriel; Ferré, Virginie; Vabret, Astrid; Ruffault, Annick; Pallier, Coralie; Raymond, Stéphanie; Izopet, Jacques; Reynes, Jacques; Marcelin, Anne-Geneviève; Masquelier, Bernard

2010-08-01

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.

Brugia malayi Antigen (BmA Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells.

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Emily E I M Mouser

Full Text Available One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA and excretory-secretory product 62 (ES-62 from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs.

Human embryonic stem cell (hES derived dendritic cells are functionally normal and are susceptible to HIV-1 infection

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Bandi Sriram

2008-01-01

Full Text Available Abstract Background Human embryonic stem (hES cells hold considerable promise for cell replacement and gene therapies. Their remarkable properties of pluripotency, self-renewal, and tractability for genetic modification potentially allows for the production of sizeable quantities of therapeutic cells of the hematopoietic lineage. Dendritic cells (DC arise from CD34+ hematopoietic progenitor cells (HPCs and are important in many innate and adaptive immune functions. With respect to HIV-1 infection, DCs play an important role in the efficient capture and transfer of the virus to susceptible cells. With an aim of generating DCs from a renewable source for HIV-1 studies, here we evaluated the capacity of hES cell derived CD34+ cells to give rise to DCs which can support HIV-1 infection. Results Undifferentiated hES cells were cultured on S17 mouse bone marrow stromal cell layers to derive CD34+ HPCs which were subsequently grown in specific cytokine differentiation media to promote the development of DCs. The hES derived DCs (hES-DC were subjected to phenotypic and functional analyses and compared with DCs derived from fetal liver CD34+ HPC (FL-DC. The mature hES-DCs displayed typical DC morphology consisting of veiled stellate cells. The hES-DCs also displayed characteristic phenotypic surface markers CD1a, HLA-DR, B7.1, B7.2, and DC-SIGN. The hES-DCs were found to be capable of antigen uptake and stimulating naïve allogeneic CD4+ T cells in a mixed leukocyte reaction assay. Furthermore, the hES-DCs supported productive HIV-1 viral infection akin to standard DCs. Conclusion Phenotypically normal and functionally competent DCs that support HIV-1 infection can be derived from hES cells. hES-DCs can now be exploited in applied immunology and HIV-1 infection studies. Using gene therapy approaches, it is now possible to generate HIV-1 resistant DCs from anti-HIV gene transduced hES-CD34+ hematopoietic progenitor cells.

Fluconazole Resistance Patterns in Candida Species that Colonize Women with HIV Infection

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Lulu Zhang, MD

2014-12-01

Conclusions: Systemic antifungal therapy, including a vaginal topical regimen in women with HIV infection correlated with reduced fluconazole susceptibility of oral and vaginal isolates. Genotype profiling has disclosed that a majority of isolates from the same individual are clustered together, suggesting the likelihood of an original strain with some microevolution. We observed a change from a susceptibility dose dependent to a resistant phenotype of isolates in 2 women with HIV infection, even though no treatments were received during the 4-month study and the prior 2 years.

Risk of Breast Cancer with CXCR4-using HIV Defined by V3-Loop Sequencing

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Goedert, James J.; Swenson, Luke C.; Napolitano, Laura A.; Haddad, Mojgan; Anastos, Kathryn; Minkoff, Howard; Young, Mary; Levine, Alexandra; Adeyemi, Oluwatoyin; Seaberg, Eric C.; Aouizerat, Bradley; Rabkin, Charles S.; Harrigan, P. Richard; Hessol, Nancy A.

2014-01-01

Objective Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures. Methods A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIVgp120-V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencing-based HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [False-Positive-Rate (FPR 3.5) and 2% X4 cutoff], and lower stringency DS (FPR 5.75, 15% X4 cut-off). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (κ) statistics. Case-control comparisons used exact P-values and conditional logistic regression. Results In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P=0.06, odds ratio 0.14, confidence interval 0.003-1.03). Smaller case-control prevalence differences were found with high-stringency DS (21% vs 36%, P=0.32), lower-stringency DS (16% vs 35%, P=0.18), and phenotyping (11% vs 31%, P=0.10). HIV-X4-tropism concordance was best between PS and lower-stringency DS (93%, κ=0.83). Other pairwise concordances were 82%-92% (κ=0.56-0.81). Concordance was similar among cases and controls. Conclusions HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency deep sequencing and was significantly associated with lower odds of breast cancer. PMID:25321183

Why do marital partners of people living with HIV not test for HIV? A qualitative study in Lusaka, Zambia

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Maurice Musheke

2016-08-01

Full Text Available Abstract Background Knowledge of HIV status is crucial for HIV prevention and management in marital relationships. Yet some marital partners of people living with HIV decline HIV testing despite knowing the HIV-positive status of their partners. To date, little research has explored the reasons for this. Methods An exploratory qualitative study was undertaken in Lusaka, Zambia, between March 2010 and September 2011, nested within a larger ethnographic study. In-depth interviews were held with individuals who knew the HIV-positive status of their marital partners but never sought HIV testing (n = 30 and HIV service providers of a public sector clinic (n = 10. A focus group discussion was also conducted with eight (8 lay HIV counsellors. Data was transcribed, coded and managed using ATLAS.ti and analysed using latent content analysis. Results The overarching barrier to uptake of HIV testing was study participants’ perception of their physical health, reinforced by uptake of herbal remedies and conventional non-HIV medication to mitigate perceived HIV-related symptoms. They indicated willingness to test for HIV if they noticed a decline in physical health and other alternative forms of care became ineffective. Also, some study participants viewed themselves as already infected with HIV on account of the HIV-positive status of their marital partners, with some opting for faith healing to get ‘cured’. Other barriers were the perceived psychological burden of living with HIV, modulated by lay belief that knowledge of HIV-positive status led to rapid physical deterioration of health. Perceived inability to sustain uptake of life-long treatment – influenced by a negative attitude towards treatment – further undermined uptake of HIV testing. Self-stigma, which manifested itself through fear of blame and a need to maintain moral credibility in marital relationships, also undermined uptake of HIV testing. Conclusions Improving uptake of HIV

Why do marital partners of people living with HIV not test for HIV? A qualitative study in Lusaka, Zambia.

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Musheke, Maurice; Merten, Sonja; Bond, Virginia

2016-08-25

Knowledge of HIV status is crucial for HIV prevention and management in marital relationships. Yet some marital partners of people living with HIV decline HIV testing despite knowing the HIV-positive status of their partners. To date, little research has explored the reasons for this. An exploratory qualitative study was undertaken in Lusaka, Zambia, between March 2010 and September 2011, nested within a larger ethnographic study. In-depth interviews were held with individuals who knew the HIV-positive status of their marital partners but never sought HIV testing (n = 30) and HIV service providers of a public sector clinic (n = 10). A focus group discussion was also conducted with eight (8) lay HIV counsellors. Data was transcribed, coded and managed using ATLAS.ti and analysed using latent content analysis. The overarching barrier to uptake of HIV testing was study participants' perception of their physical health, reinforced by uptake of herbal remedies and conventional non-HIV medication to mitigate perceived HIV-related symptoms. They indicated willingness to test for HIV if they noticed a decline in physical health and other alternative forms of care became ineffective. Also, some study participants viewed themselves as already infected with HIV on account of the HIV-positive status of their marital partners, with some opting for faith healing to get 'cured'. Other barriers were the perceived psychological burden of living with HIV, modulated by lay belief that knowledge of HIV-positive status led to rapid physical deterioration of health. Perceived inability to sustain uptake of life-long treatment - influenced by a negative attitude towards treatment - further undermined uptake of HIV testing. Self-stigma, which manifested itself through fear of blame and a need to maintain moral credibility in marital relationships, also undermined uptake of HIV testing. Improving uptake of HIV testing requires a multi-pronged approach that addresses self-stigma, lay risk

Visceral leishmaniasis and leishmaniasis-HIV coinfection: comparative study

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João Victor Soares Coriolano Coutinho

Full Text Available Abstract INTRODUCTION: This study aimed to draw clinical and epidemiological comparisons between visceral leishmaniasis (VL and VL associated with human immunodeficiency virus (HIV infection. METHOD: Retrospective study. RESULTS: Of 473 cases of VL, 5.5% were coinfected with HIV. The highest proportion of cases of both VL and VL/HIV were found among men. A higher proportion of VL cases was seen in children aged 0-10 years, whereas coinfection was more common in those aged 18-50 years. CONCLUSIONS: VL/HIV coinfected patients presented slightly differently to and had a higher mortality rate than those with VL only.

ART drugs help reduce HIV transmission, Chinese study finds ...

International Development Research Centre (IDRC) Digital Library (Canada)

International Development Research Centre Government of Canada ... ART drugs help reduce HIV transmission, Chinese study finds ... where only one person has HIV can reduce HIV transmission rates, at least in the short term, a Chinese study has found. ... Ecohealth Field-building Leadership Initiative in Southeast Asia.

Research on Candida dubliniensis in a Brazilian yeast collection obtained from cardiac transplant, tuberculosis, and HIV-positive patients, and evaluation of phenotypic tests using agar screening methods.

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Ribeiro, Patrícia Monteiro; Querido, Silvia Maria Rodrigues; Back-Brito, Graziela Nueremberg; Mota, Adolfo José; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

2011-09-01

The aim of this study was to research Candida dubliniensis among isolates present in a Brazilian yeast collection and to evaluate the main phenotypic methods for discrimination between C. albicans and C. dubliniensis from oral cavity. A total of 200 isolates, presumptively identified as C. albicans or C. dubliniensis obtained from heart transplant patients under immunosuppressive therapy, tuberculosis patients under antibiotic therapy, HIV-positive patients under antiretroviral therapy, and healthy subjects, were analyzed using the following phenotypic tests: formation and structural arrangement of chlamydospores on corn meal agar, casein agar, tobacco agar, and sunflower seed agar; growth at 45 °C; and germ tube formation. All strains were analyzed by polymerase chain reaction (PCR). In a preliminary screen for C. dubliniensis, 48 of the 200 isolates on corn meal agar, 30 of the 200 on casein agar, 16 of the 200 on tobacco agar, and 15 of the 200 on sunflower seed agar produced chlamydoconidia; 27 of the 200 isolates showed no or poor growth at 45 °C. All isolates were positive for germ tube formation. These isolates were considered suggestive of C. dubliniensis. All of them were subjected to PCR analysis using C. dubliniensis-specific primers. C. dubliniensis isolates were not found. C. dubliniensis isolates were not recovered in this study done with immunocompromised patients. Sunflower seed agar was the medium with the smallest number of isolates of C. albicans suggestive of C. dubliniensis. None of the phenotypic methods was 100% effective for discrimination between C. albicans and C. dubliniensis. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2016-12-01

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

Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

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Qiong Yang

2012-01-01

Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration

NARCIS (Netherlands)

Olson, Ashley D.; Meyer, Laurence; Prins, Maria; Thiebaut, Rodolphe; Gurdasani, Deepti; Guiguet, Marguerite; Chaix, Marie-Laure; Amornkul, Pauli; Babiker, Abdel; Sandhu, Manjinder S.; Porter, Kholoud; del Amo, Julia; Bucher, Heiner C.; Chêne, Geneviève; Hamouda, Osamah; Pillay, Deenan; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Olson, Ashley; Coughlin, Kate; Walker, Sarah; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kelleher, Tony; Cooper, David; Grey, Pat; Finlayson, Robert; Bloch, Mark; Ramacciotti, Tim; Gelgor, Linda; Smith, Don; Zangerle, Robert; Gill, John; Lutsar, Irja; Dabis, Francois; Masquelier, Bernard; Costagliola, Dominique; Vanhems, Philippe; Ghosn, Jade; Boufassa, Faroudy; Kücherer, Claudia; Bartmeyer, Barbara; Paparizos, V.; Gargalianos-Kakolyris, P.; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke; Reiss, Peter

2014-01-01

Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. We assessed a number of EC definitions used in the

Contrasting HIV phylogenetic relationships and V3 loop protein similarities

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Korber, B. (Los Alamos National Lab., NM (United States) Santa Fe Inst., NM (United States)); Myers, G. (Los Alamos National Lab., NM (United States))

1992-01-01

At least five distinct sequence subtypes of HIV-I can be identified from the major centers of the AMS pandemic. While it is too early to tell whether these subtypes are serologically or phenotypically similar or distinct in terms of properties such as pathogenicity and transmissibility, we can begin to investigate their potential for phenotypic divergence at the protein sequence level. Phylogenetic analysis of HIV DNA sequences is being widely used to examine lineages of different viral strains as they evolve and spread throughout the globe. We have identified five distinct HIV-1 subtypes (designated A-E), or clades, based on phylogenetic clustering patterns generated from genetic information from both the gag and envelope (env) genes from a spectrum of international isolates. Our initial observations concerning both HIV-1 and HIV-2 sequences indicate that conserved patterns in protein chemistry may indeed exist across distant lineages. Such patterns in V3 loop amino acid chemistry may be indicative of stable lineages or convergence within this highly variable, though functionally and immunologically critical, region. We think that there may be parallels between the apparently stable HIV-2 V3 lineage and the previously mentioned HIV-1 V3 loops which are very similar at the protein level despite being distant by cladistic analysis, and which do not possess the distinctive positively charged residues. Highly conserved V3 loop protein sequences are also encountered in SIVAGMs and CIVs (chimpanzee viral strains), which do not appear to be pathogenic in their wild-caught natural hosts.

Contrasting HIV phylogenetic relationships and V3 loop protein similarities

Energy Technology Data Exchange (ETDEWEB)

Korber, B. [Los Alamos National Lab., NM (United States)]|[Santa Fe Inst., NM (United States); Myers, G. [Los Alamos National Lab., NM (United States)

1992-12-31

At least five distinct sequence subtypes of HIV-I can be identified from the major centers of the AMS pandemic. While it is too early to tell whether these subtypes are serologically or phenotypically similar or distinct in terms of properties such as pathogenicity and transmissibility, we can begin to investigate their potential for phenotypic divergence at the protein sequence level. Phylogenetic analysis of HIV DNA sequences is being widely used to examine lineages of different viral strains as they evolve and spread throughout the globe. We have identified five distinct HIV-1 subtypes (designated A-E), or clades, based on phylogenetic clustering patterns generated from genetic information from both the gag and envelope (env) genes from a spectrum of international isolates. Our initial observations concerning both HIV-1 and HIV-2 sequences indicate that conserved patterns in protein chemistry may indeed exist across distant lineages. Such patterns in V3 loop amino acid chemistry may be indicative of stable lineages or convergence within this highly variable, though functionally and immunologically critical, region. We think that there may be parallels between the apparently stable HIV-2 V3 lineage and the previously mentioned HIV-1 V3 loops which are very similar at the protein level despite being distant by cladistic analysis, and which do not possess the distinctive positively charged residues. Highly conserved V3 loop protein sequences are also encountered in SIVAGMs and CIVs (chimpanzee viral strains), which do not appear to be pathogenic in their wild-caught natural hosts.

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

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

2013-01-01

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

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

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Didier K Ekouevi

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

Linkage to HIV care, postpartum depression, and HIV-related stigma in newly diagnosed pregnant women living with HIV in Kenya: a longitudinal observational study.

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Turan, Bulent; Stringer, Kristi L; Onono, Maricianah; Bukusi, Elizabeth A; Weiser, Sheri D; Cohen, Craig R; Turan, Janet M

2014-12-03

While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effects of antiretroviral therapy. We examined associations between linkage to HIV care, postpartum depression, and internalized stigma in a population with a high risk of depression: newly diagnosed HIV-positive pregnant women. In this prospective observational study, data were obtained from 135 HIV-positive women from eight antenatal clinics in the rural Nyanza Province of Kenya at their first antenatal visit (prior to testing HIV-positive for the first time) and subsequently at 6 weeks after giving birth. At 6 weeks postpartum, women who had not linked to HIV care after testing positive at their first antenatal visit had higher levels of depression and internalized stigma, compared to women who had linked to care. Internalized stigma mediated the effect of linkage to care on depression. Furthermore, participants who had both linked to HIV care and initiated antiretroviral therapy reported the lowest levels of depressive symptoms. These results provide further support for current efforts to ensure that women who are newly diagnosed with HIV during pregnancy become linked to HIV care as early as possible, with important benefits for both physical and mental health.

Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies.

Science.gov (United States)

Rockstroh, Jürgen K; Teppler, Hedy; Zhao, Jing; Sklar, Peter; Miller, Michael D; Harvey, Charlotte M; Strohmaier, Kim M; Leavitt, Randi Y; Nguyen, Bach-Yen T

2011-07-17

We evaluated the long-term efficacy of raltegravir according to HIV-1 subtype (B and non-B) using data from three phase III studies in treatment-experienced (BENCHMRK-1 and 2) and treatment-naive (STARTMRK) HIV-infected patients. HIV-1 subtypes were identified from baseline plasma specimens using genotypic data of the PhenoSense GT test (Monogram Biosciences, South San Francisco, California, USA). Non-B subtypes were combined for the current analyses due to small numbers of each specific subtype. An observed failure approach was used (only discontinuations due to lack of efficacy were treated as failures). Resistance evaluation was performed in patients with documented virologic failure. Seven hundred and forty-three patients received raltegravir and 519 received comparator (efavirenz in STARTMRK; optimized background therapy in BENCHMRK). Non-B subtype virus (A, A/C, A/D, A/G, A1, AE, AG, B/G, BF, C, D, D/F, F, F1, G, and complex) was isolated at baseline in 98 (13%) raltegravir recipients and 62 (12%) comparator recipients. Subtypes AE and C were most common, isolated in 41 and 43 patients, respectively. The proportion of raltegravir recipients achieving HIV RNA less than 50 copies/ml was similar between non-B and B subtypes (STARTMRK: 94.5 vs. 88.7%; BENCHMRK-1 and 2: 66.7 vs. 60.7%); change in CD4 cell count also was similar between non-B and B subtypes (STARTMRK: 243 vs. 221 cells/μl; BENCHMRK-1 and 2: 121 vs. 144 cells/μl). Phenotypic resistance to raltegravir in non-B virus was associated with integrase mutations observed previously in subtype B virus. In phase III studies in treatment-naive and treatment-experienced patients, raltegravir showed comparable and potent clinical efficacy against B and non-B HIV-1 subtypes.

Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing.

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Szu-Wei Huang

Full Text Available The usefulness of ultra-deep pyrosequencing (UDPS for the diagnosis of HIV-1 drug resistance (DR remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF 07_BC among injection drug users (IDUs in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005 and 3 from late epidemic (collected in 2008 were obtained from treatment-naïve patient's peripheral blood mononuclear cells. Viral RNA was extracted directly from patient's plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs (4.4-47.3 fold. Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01-0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.

M. tuberculosis genotypic diversity and drug susceptibility pattern in HIV- infected and non-HIV-infected patients in northern Tanzania

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van Soolingen Dick

2007-05-01

Full Text Available Abstract Background Tuberculosis (TB is a major health problem and HIV is the major cause of the increase in TB. Sub-Saharan Africa is endemic for both TB and HIV infection. Determination of the prevalence of M. tuberculosis strains and their drug susceptibility is important for TB control. TB positive culture, BAL fluid or sputum samples from 130 patients were collected and genotyped. The spoligotypes were correlated with anti-tuberculous drug susceptibility in HIV-infected and non-HIV patients from Tanzania. Results One-third of patients were TB/HIV co-infected. Forty-seven spoligotypes were identified. Fourteen isolates (10.8% had new and unique spoligotypes while 116 isolates (89.2% belonged to 33 known spoligotypes. The major spoligotypes contained nine clusters: CAS1-Kili 30.0%, LAM11- ZWE 14.6%, ND 9.2%, EAI 6.2%, Beijing 5.4%, T-undefined 4.6%, CAS1-Delhi 3.8%, T1 3.8% and LAM9 3.8%. Twelve (10.8% of the 111 phenotypically tested strains were resistant to anti-TB drugs. Eight (7.2% were monoresistant strains: 7 to isoniazid (INH and one to streptomycin. Four strains (3.5% were resistant to multiple drugs: one (0.9% was resistant to INH and streptomycin and the other three (2.7% were MDR strains: one was resistant to INH, rifampicin and ethambutol and two were resistant to all four anti-TB drugs. Mutation in the katG gene codon 315 and the rpoB hotspot region showed a low and high sensitivity, respectively, as predictor of phenotypic drug resistance. Conclusion CAS1-Kili and LAM11-ZWE were the most common families. Strains of the Beijing family and CAS1-Kili were not or least often associated with resistance, respectively. HIV status was not associated with spoligotypes, resistance or previous TB treatment.

HIV-1 co-receptor usage:influence on mother-to-child transmission and pediatric infection

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Cavarelli Mariangela

2010-01-01

Full Text Available Abstract Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5narrow and R5broad resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

HIV-1 co-receptor usage: influence on mother-to-child transmission and pediatric infection.

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Cavarelli, Mariangela; Scarlatti, Gabriella

2011-01-27

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

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

Science.gov (United States)

Rochat, Tamsen J; Mkwanazi, Ntombizodumo; Bland, Ruth

2013-02-18

As access to treatment increases, large numbers of HIV-positive parents are raising HIV-negative children. Maternal HIV disclosure has been shown to have benefits for mothers and children, however, disclosure rates remain low with between 30-45% of mothers reporting HIV disclosure to their children in both observational and intervention studies. Disclosure of HIV status by parent to an HIV-uninfected child is a complex and challenging psychological and social process. No intervention studies have been designed and tested in Southern Africa to support HIV-positive parents to disclose their status, despite this region being one of the most heavily affected by the HIV epidemic. This paper describes the development of a family-centred, structured intervention to support mothers to disclose their HIV status to their HIV-negative school-aged children in rural South Africa, an area with high HIV prevalence. The intervention package includes printed materials, therapeutic tools and child-friendly activities and games to support age-appropriate maternal HIV disclosure, and has three main aims: (1) to benefit family relationships by increasing maternal HIV disclosure; (2) to increase children's knowledge about HIV and health; (3) to improve the quality of custody planning for children with HIV-positive mothers. We provide the theoretical framework for the intervention design and report the results of a small pilot study undertaken to test its acceptability in the local context. The intervention was piloted with 24 Zulu families, all mothers were HIV-positive and had an HIV-negative child aged 6-9 years. Lay counsellors delivered the six session intervention over a six to eight week period. Qualitative data were collected on the acceptability, feasibility and the effectiveness of the intervention in increasing disclosure, health promotion and custody planning. All mothers disclosed something to their children: 11/24 disclosed fully using the words "HIV" while 13/24 disclosed

Linkage to HIV care, postpartum depression, and HIV-related stigma in newly diagnosed pregnant women living with HIV in Kenya: a longitudinal observational study

OpenAIRE

Turan, Bulent; Stringer, Kristi L; Onono, Maricianah; Bukusi, Elizabeth A; Weiser, Sheri D; Cohen, Craig R; Turan, Janet M

2014-01-01

Background While studies have suggested that depression and HIV-related stigma may impede access to care, a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV. However, this has not been investigated in postpartum women living with HIV. Furthermore, linkage to care itself may have additional impacts on postpartum depression beyond the effect...

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.

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

Science.gov (United States)

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

2017-09-11

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

Copenhagen comorbidity in HIV infection (COCOMO) study

DEFF Research Database (Denmark)

Ronit, Andreas; Haissman, Judith Melchior; Kirkegaard-Klitbo, Ditte Marie

2016-01-01

BACKGROUND: Modern combination antiretroviral therapy (cART) has improved survival for people living with HIV (PLWHIV). Non-AIDS comorbidities have replaced opportunistic infections as leading causes of mortality and morbidity, and are becoming a key health concern as this population continues....../DESIGN: The Copenhagen comorbidity in HIV-infection (COCOMO) study is an observational, longitudinal cohort study. The study was initiated in 2015 and recruitment is ongoing with the aim of including 1500 PLWHIV from the Copenhagen area. Follow-up examinations after 2 and 10 years are planned. Uninfected controls...... (PBMC), urine, and stool samples are collected in a biobank for future studies. Data will be updated through periodical linking to national databases. DISCUSSION: As life expectancy for PLWHIV improves, it is essential to study long-term impact of HIV and cART. We anticipate that findings from...

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

Science.gov (United States)

Eshleman, Susan H; Laeyendecker, Oliver; Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C; Serwadda, David; Reynolds, Steven J; Kiwanuka, Noah; Quinn, Thomas C; Gray, Ronald; Wawer, Maria

2009-04-27

To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults.

Directory of Open Access Journals (Sweden)

Juliet Mpendo

Full Text Available Strategies to enhance the immunogenicity of DNA vaccines in humans include i co-administration of molecular adjuvants, ii intramuscular administration followed by in vivo electroporation (IM/EP and/or iii boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG plasmid DNA (pDNA vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12 (GENEVAX IL-12 given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs were reported. T cell and antibody response rates after HIVMAG (x3 prime-Ad35 (x1 boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ ELISPOT responses was highest after HIVMAG (x3 without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3 prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.ClinicalTrials.gov NCT01496989.

Sociodemographic differences among HIV-positive and HIV-negative recently pregnant women in Mexico City: A case-control study.

Science.gov (United States)

Aguilar-Zapata, Daniel; Piñeirúa-Menéndez, Alicia; Volkow-Fernández, Patricia; Rodríguez-Zulueta, Patricia; Ramos-Alamillo, Ubaldo; Cabrera-López, Teresita; Martin-Onraet, Alexandra

2017-07-01

National HIV preventive programs in Mexico focus on high-risk groups that do not consider women, apart from prenatal screening. Nonetheless, the epidemic in women is growing, and there is a need to better understand sociodemographic factors in women living with HIV (WLH). We performed a case-control study in Mexico City, including HIV+ and HIV- women with a recent pregnancy to compare their sociodemographic characteristics and describe the circumstances of diagnosis in HIV+ women, as well as prenatal screening frequency in both groups. Fifty cases and 102 controls were interviewed. HIV+ women were more frequently the only economic support of the family (20% vs 0%, P history of sexually transmitted diseases, substance abuse, history of violence, and civil status. Only 6% of controls were tested for HIV during prenatal follow-up. WLH in this study faced important social vulnerability. Targeting women living in these social contexts might increase early diagnosis and could tailor HIV prevention strategies. Prenatal coverage needs to be improved and should represent a national priority.

The role of virologic and immunologic factors in mother-to-child transmission of HIV-1.

Science.gov (United States)

Colognesi, C; Halapi, E; Jansson, M; Hodara, V; Steuer, G; Tresoldi, E; Leitner, T; Scarlatti, G

1997-09-01

More than 90% of human immunodeficiency virus type 1 (HIV-1) infection in children is acquired by mother-to-child transmission. However, infection of the child occurs in between 14 and 35% of cases. To understand the mechanisms involved in HIV-1 transmission, we have investigated the antigenic, molecular, and phenotypic characteristics of the virus harbored in infected mothers and their children. A clear correlation was observed between the transmission of the virus and the isolation of viral variants with a rapidly replicating and syncytium-inducing phenotype from the mother. Furthermore, non-transmitting mothers were able to neutralize several primary isolates more frequently than transmitting mothers. The comparison of the viral phenotype and genotype of mother-child pairs showed that the transmitted virus did not have common features, suggesting that transmission is usually not a selective process. This study suggests that transmission is governed by an interaction of both viral and immunological factors. The results obtained indicate that different strategies can be applied for the prevention of transmission.

Cardiovascular Diseases in HIV-infected Subjects (HIV-HEART Study)

Science.gov (United States)

2010-05-07

Detection of Frequency, Severity and Progression of Cardiovascular Diseases in Patients With HIV-infection.; Effect on Cardiovascular Risk and Life Quality by Age, Gender, Classic Cardiovascular Risk Factors,; HIV-specific Cardiovascular Risk Factors, Cardiovascular Medication, Antiretroviral Medication

A cross-sectional study of the magnitude, barriers, and outcomes of HIV status disclosure among women participating in a perinatal HIV transmission study, "the Nevirapine Repeat Pregnancy study".

Science.gov (United States)

Kiweewa, Flavia M; Bakaki, Paul M; McConnell, Michelle S; Musisi, Maria; Namirembe, Constance; Nakayiwa, Frances; Kusasira, Fiona; Nakintu, Dorothy; Mubiru, Michael C; Musoke, Philippa; Fowler, Mary Glenn

2015-09-29

HIV status disclosure is a difficult emotional task for HIV-infected persons and may create the opportunity for both social support and rejection. In this study, we evaluated the proportions, patterns, barriers and outcomes of HIV- 1 status disclosure among a group of women in Uganda. An exit interview was conducted one year post-partum for 85 HIV-infected women who participated in a study of HIV-1 transmission rates among NVP-experienced compared with NVP-naïve women in "The Nevirapine Repeat Pregnancy (NVP-RP) Study" at the Makerere University-Johns Hopkins University Research Collaboration, Kampala-Uganda, between June 2004 and June 2006. Of the 85 women interviewed, 99 % had disclosed their HIV status to at least one other person. Disclosure proportions ranged between 1 % to employer(s) and 69 % to a relative other than a parent. Only 38 % of the women had disclosed to their sex partners. Women with an HIV-infected baby were more likely than those with an uninfected baby to disclose to their sex partner, OR 4.9 (95 % CI, 2.0 -11.2), and women were less likely to disclose to a partner if they had previously disclosed to another relative than if they had not, OR 0.19 (95 % CI, 0.14-0.52). The most common reasons for non-disclosure included fear of separation from the partner and subsequent loss of financial support 34 %, and not living with the partner (not having opportunities to disclose) 26 %. While most women (67 %) reported getting social support following disclosure, 22 % reported negative outcomes (neglect, separation from their partners, and loss of financial support). Following disclosure of HIV status, 9 % of women reported that their partner (s) decided to have an HIV test. Results from this study show high overall HIV disclosure proportions and how this disclosure of HIV status can foster social support. However, proportions of disclosure specifically to male sex partners were low, which suggests the need for interventions aimed at increasing male

HIV tropism and decreased risk of breast cancer.

Directory of Open Access Journals (Sweden)

Nancy A Hessol

2010-12-01

Full Text Available During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR and 95% confidence intervals (CI for breast cancer were estimated by exact conditional logistic regression. Two (9% of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28% of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84 and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83. Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked

HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study.

Science.gov (United States)

Sengayi, Mazvita; Babb, Chantal; Egger, Matthias; Urban, Margaret I

2015-03-18

HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children associated with previous HIV testing. In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

Flexible use of CCR5 in the absence of CXCR4 use explains the immune deficiency in HIV-1 infected children.

Science.gov (United States)

Cavarelli, Mariangela; Karlsson, Ingrid; Ripamonti, Chiara; Plebani, Anna; Fenyo, Eva Maria; Scarlatti, Gabriella

2010-10-23

CCR5-using HIV-1 (R5 viruses) are usually isolated during acute infection from both adults and children. We have recently demonstrated that R5 viruses with a flexible use of CCR5 (called R5broad) can be detected in children close to birth and are predictive of a fast immunological failure. The aim of the present work was to investigate viral phenotype variation during disease progression in HIV-1 infected children, six slow and eight fast progressors. A total of 74 viral isolates obtained sequentially from 14 HIV-1 infected children were tested for their ability to infect U87.CD4 cells expressing a set of six different CCR5/CXCR4 chimeric receptors or wild-type coreceptors. The sensitivity of 35 R5 viruses to inhibition with the CC-chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated in a peripheral blood mononuclear cells based assay. Viral evolution to R5broad or to R5X4 phenotype occurred with one exception, in all children, although at a different time point according to rate of disease progression. Immune deficiency in the children was significantly associated with the appearance of R5broad phenotype or R5X4 viruses. Analysis of the sensitivity to inhibition by RANTES revealed a significant correlation between the R5broad phenotype and an augmented resistance to this CC-chemokine. We demonstrate that the viral evolution to a more flexible CCR5-use is sufficient to explain the immunological failure in the absence of CXCR4 usage. These results warrant detailed analysis of the R5 phenotype in forthcoming clinical studies introducing CCR5 inhibitors for the treatment of pediatric HIV-1 infection.

Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

NARCIS (Netherlands)

Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Steingrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, José A. M.; Miedema, Frank

2008-01-01

It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

Restoration of the CD4 T cell compartment after long-term highly active Antiretroviral therapy without phenotypical signs of accelerated immunological aging

NARCIS (Netherlands)

Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Stemgrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, Jose A. M.; Miedema, Frank

2008-01-01

It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

KAUST Repository

Tawe, Leabaneng

2018-03-14

Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

KAUST Repository

Tawe, Leabaneng; Motshoge, Thato; Ramatlho, Pleasure; Mutukwa, Naledi; Muthoga, Charles Waithaka; Dongho, Ghyslaine Bruna Djeunang; Martinelli, Axel; Peloewetse, Elias; Russo, Gianluca; Quaye, Isaac Kweku; Paganotti, Giacomo Maria

2018-01-01

Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

A CLINICAL STUDY OF OCULAR MANIFESTATIONS IN HIV PATIENTS

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Ravinder

2015-12-01

Full Text Available BACKGROUND HIV/AIDS is a multi system disorder with ocular involvement is about 70-80% of HIV patient occupational exposure to HIV is a significant health hazard for the treating clinicians including Eye Surgeons. AIM To study and evaluation of ocular manifestation in HIV patients attending out patient. MATERIALS AND METHODS It is observational study of 104 HIV+ve cases for a period of 1 year those patients who attended ophthalmic out patient department. RESULTS 73 were males (70.19% and 31 were females (29.80%. Majority of the patients belongs to age group of 15-50 years. Out of 104 patients 83(79.80% were married and 21(20.20% were unmarried. HIV was predominantly seen in labourers 41(32.42%. The predominant mode of transmission of sexual (Hetero Sexual transmission. HIV infection was predominantly seen in uneducated patients 64(61.53%. Total No. of ocular findings in 51 cases out of 75 with anterior Uveitis, Conjunctival microvasculopathy, Herpes Simplex Keratitis and Conjunctivitis are the most common anterior segment manifestation. CMV retinitis, HIV Microvasculopathy are the most common posterior segment manifestation. CONCLUSIONS Ophthalmologists should be familiar with common and uncommon ocular manifestations of AIDS+ve cases and their diagnosis and treatment, as early and proper treatment can Salvage their vision and improve the quality of life.

Advanced phenotyping and phenotype data analysis for the plant growth and development study

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Md. Matiur eRahaman

2015-08-01

Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age.

Science.gov (United States)

Rinaldi, Stefano; Pallikkuth, Suresh; George, Varghese K; de Armas, Lesley R; Pahwa, Rajendra; Sanchez, Celeste M; Pallin, Maria Fernanda; Pan, Li; Cotugno, Nicola; Dickinson, Gordon; Rodriguez, Allan; Fischl, Margaret; Alcaide, Maria; Gonzalez, Louis; Palma, Paolo; Pahwa, Savita

2017-04-01

Combination antiretroviral therapies (cART)can lead to normal life expectancy in HIV-infected persons, and people aged >50 yrs represent the fastest growing HIV group. Although HIV and aging are independently associated with impaired humoral immunity, immune status in people aging with HIV is relatively unexplored. In this study influenza vaccination was used to probe age associated perturbations in the B cell compartment of HIV-negative "healthy controls" (HC) and virologically controlled HIV-infected participants on cART (HIV) (n=124), grouped by age as young (aged (40-59yrs) or old ( > 60 yrs). H1N1 antibody response at d21 post-vaccination correlated inversely with age in both HC and HIV. Immunophenotyping of cryopreserved PBMC demonstrated increased frequencies of double negative B cells and decreased plasmablasts in old compared to young HC. Remarkably, young HIV were different from young HC but similar to old HC in B cell phenotype, influenza specific spontaneous (d7) or memory (d21) antibody secreting cells. We conclude that B cell immune senescence is a prominent phenomenon in young HIV in comparison to young HC, but distinctions between old HIV and old HC are less evident though both groups manifest age-associated B cell dysfunction.

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

Science.gov (United States)

George, Varghese K.; de Armas, Lesley R.; Pahwa, Rajendra; Sanchez, Celeste M.; Pallin, Maria Fernanda; Pan, Li; Cotugno, Nicola; Dickinson, Gordon; Rodriguez, Allan; Fischl, Margaret; Alcaide, Maria; Gonzalez, Louis; Palma, Paolo; Pahwa, Savita

2017-01-01

Combination antiretroviral therapies (cART) can lead to normal life expectancy in HIV-infected persons, and people aged >50 yrs represent the fastest growing HIV group. Although HIV and aging are independently associated with impaired humoral immunity, immune status in people aging with HIV is relatively unexplored. In this study influenza vaccination was used to probe age associated perturbations in the B cell compartment of HIV-negative “healthy controls” (HC) and virologically controlled HIV-infected participants on cART (HIV) (n=124), grouped by age as young (<40 yrs), middle-aged (40-59yrs) or old (≥60 yrs). H1N1 antibody response at d21 post-vaccination correlated inversely with age in both HC and HIV. Immunophenotyping of cryopreserved PBMC demonstrated increased frequencies of double negative B cells and decreased plasmablasts in old compared to young HC. Remarkably, young HIV were different from young HC but similar to old HC in B cell phenotype, influenza specific spontaneous (d7) or memory (d21) antibody secreting cells. We conclude that B cell immune senescence is a prominent phenomenon in young HIV in comparison to young HC, but distinctions between old HIV and old HC are less evident though both groups manifest age-associated B cell dysfunction. PMID:28448963

Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection

DEFF Research Database (Denmark)

Evangelou, Evangelos; Fellay, Jacques; Colombo, Sara

2011-01-01

Discussion on improving the power of genome-wide association studies to identify candidate variants and genes is generally centered on issues of maximizing sample size; less attention is given to the role of phenotype definition and ascertainment. The authors used genome-wide data from patients...... infected with human immunodeficiency virus type 1 (HIV-1) to assess whether differences in type of population (622 seroconverters vs. 636 seroprevalent subjects) or the number of measurements available for defining the phenotype resulted in differences in the effect sizes of associations between single...... available, particularly among seroconverters and for variants that achieved genome-wide significance. Differences in phenotype definition and ascertainment may affect the estimated magnitude of genetic effects and should be considered in optimizing power for discovering new associations....

An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration

DEFF Research Database (Denmark)

Olson, Ashley D; Meyer, Laurence; Prins, Maria

2014-01-01

ratios ranged from 12.5-19.0 for non-ECs compared to ECs). CONCLUSIONS: ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90......BACKGROUND: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. METHODS: We assessed a number of EC...... definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). RESULTS...

A comparison of HAART outcomes between the US military HIV Natural History Study (NHS and HIV Atlanta Veterans Affairs Cohort Study (HAVACS.

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Jodie L Guest

Full Text Available INTRODUCTION: The Department of Defense (DoD and the Department of Veterans Affairs (VA provide comprehensive HIV treatment and care to their beneficiaries with open access and few costs to the patient. Individuals who receive HIV care in the VA have higher rates of substance abuse, homelessness and unemployment than individuals who receive HIV care in the DoD. A comparison between individuals receiving HIV treatment and care from the DoD and the VA provides an opportunity to explore the impact of individual-level characteristics on clinical outcomes within two healthcare systems that are optimized for clinic retention and medication adherence. METHODS: Data were collected on 1065 patients from the HIV Atlanta VA Cohort Study (HAVACS and 1199 patients from the US Military HIV Natural History Study (NHS. Patients were eligible if they had an HIV diagnosis and began HAART between January 1, 1996 and June 30, 2010. The analysis examined the survival from HAART initiation to all-cause mortality or an AIDS event. RESULTS: Although there was substantial between-cohort heterogeneity and the 12-year survival of participants in NHS was significantly higher than in HAVACS in crude analyses, this survival disparity was reduced from 21.5% to 1.6% (mortality only and 26.8% to 4.1% (combined mortality or AIDS when controlling for clinical and demographic variables. CONCLUSION: We assessed the clinical outcomes for individuals with HIV from two very similar government-sponsored healthcare systems that reduced or eliminated many barriers associated with accessing treatment and care. After controlling for clinical and demographic variables, both 12-year survival and AIDS-free survival rates were similar for the two study cohorts who have open access to care and medication despite dramatic differences in socioeconomic and behavioral characteristics.

Genome-wide association scan in HIV-1-infected individuals identifying variants influencing disease course.

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Daniëlle van Manen

Full Text Available BACKGROUND: AIDS develops typically after 7-11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years. To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. METHODS: The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. RESULTS: Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. CONCLUSIONS: Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection.

Genome-Wide Association Scan in HIV-1-Infected Individuals Identifying Variants Influencing Disease Course

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van Manen, Daniëlle; Delaneau, Olivier; Kootstra, Neeltje A.; Boeser-Nunnink, Brigitte D.; Limou, Sophie; Bol, Sebastiaan M.; Burger, Judith A.; Zwinderman, Aeilko H.; Moerland, Perry D.; van 't Slot, Ruben; Zagury, Jean-François; van 't Wout, Angélique B.; Schuitemaker, Hanneke

2011-01-01

Background AIDS develops typically after 7–11 years of untreated HIV-1 infection, with extremes of very rapid disease progression (15 years). To reveal additional host genetic factors that may impact on the clinical course of HIV-1 infection, we designed a genome-wide association study (GWAS) in 404 participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Methods The association of SNP genotypes with the clinical course of HIV-1 infection was tested in Cox regression survival analyses using AIDS-diagnosis and AIDS-related death as endpoints. Results Multiple, not previously identified SNPs, were identified to be strongly associated with disease progression after HIV-1 infection, albeit not genome-wide significant. However, three independent SNPs in the top ten associations between SNP genotypes and time between seroconversion and AIDS-diagnosis, and one from the top ten associations between SNP genotypes and time between seroconversion and AIDS-related death, had P-values smaller than 0.05 in the French Genomics of Resistance to Immunodeficiency Virus cohort on disease progression. Conclusions Our study emphasizes that the use of different phenotypes in GWAS may be useful to unravel the full spectrum of host genetic factors that may be associated with the clinical course of HIV-1 infection. PMID:21811574

Perceptions of molecular epidemiology studies of HIV among stakeholders

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Cynthia Schairer

2017-12-01

Full Text Available Background: Advances in viral sequence analysis make it possible to track the spread of infectious pathogens, such as HIV, within a population. When used to study HIV, these analyses (i.e., molecular epidemiology potentially allow inference of the identity of individual research subjects. Current privacy standards are likely insufficient for this type of public health research. To address this challenge, it will be important to understand how stakeholders feel about the benefits and risks of such research. Design and Methods: To better understand perceived benefits and risks of these research methods, in-depth qualitative interviews were conducted with HIV-infected individuals, individuals at high-risk for contracting HIV, and professionals in HIV care and prevention. To gather additional perspectives, attendees to a public lecture on molecular epidemiology were asked to complete an informal questionnaire. Results: Among those interviewed and polled, there was near unanimous support for using molecular epidemiology to study HIV. Questionnaires showed strong agreement about benefits of molecular epidemiology, but diverse attitudes regarding risks. Interviewees acknowledged several risks, including privacy breaches and provocation of anti-gay sentiment. The interviews also demonstrated a possibility that misunderstandings about molecular epidemiology may affect how risks and benefits are evaluated. Conclusions: While nearly all study participants agree that the benefits of HIV molecular epidemiology outweigh the risks, concerns about privacy must be addressed to ensure continued trust in research institutions and willingness to participate in research.

HIV in females: A clinico-epidemiological study

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Mahesha Padyana

2013-01-01

Full Text Available Background: Human Immunodeficiency Virusinfected women account for almost half the number of cases of HIV worldwide. Despite reduction in HIV prevalence among the population, the percentage of Indian women contracting the disease seems to have increased. The social implications are also different in females. Materials and Methods: This prospective observational study was conducted from September 2009 to July 2011 at tertiary care hospitals attached to the Kasturba Medical College Mangalore, on a group of 200 HIV-positive patients. Patients above 18 years of age diagnosed with HIV as per National AIDS Control Organisation guidelines were included in the study. Clinical profile among women and men was compared with respect to clinical presentation, disease detection, CD4 count and response of family and society. Results: Clinical presentation was similar among both men and women. Eighty-one percent men had promiscual sexual exposure, 19% of women had so. Males were identified to be HIV-positive earlier than their spouse (tested later, time lag being 27.6 weeks. After detection of positivity 77% of females felt being less cared for by the in-laws. CD4 count less than 50 was detected in more number of females as compared to men (11% females and 1% males. Death of spouse was seen more often in females (among 35% of women and 11% of men. Conclusion: Most of the females were likely to acquire infection from their spouse. Females tend to seek and get medical attention at the late stage of disease as compared to men. HIV in females has different social implications which includes discrimination within the family.

Characteristics of HIV target CD4 T cells collected using different sampling methods from the genital tract of HIV seronegative women.

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Iyer, Smita S; Sabula, Michael J; Mehta, C Christina; Haddad, Lisa B; Brown, Nakita L; Amara, Rama R; Ofotokun, Igho; Sheth, Anandi N

2017-01-01

Understanding the immune profile of CD4 T cells, the primary targets for HIV, in the female genital tract (FGT) is critical for evaluating and developing effective biomedical HIV prevention strategies in women. However, longitudinal investigation of HIV susceptibility markers expressed by FGT CD4 T cells has been hindered by low cellular yield and risk of sampling-associated trauma. We investigated three minimally invasive FGT sampling methods to characterize and compare CD4 T cell yield and phenotype with the goal of establishing feasible sampling strategies for immune profiling of mucosal CD4 T cells. FGT samples were collected bimonthly from 12 healthy HIV negative women of reproductive age in the following order: 1) Cervicovaginal lavage (CVL), 2) two sequential endocervical flocked swabs (FS), and 3) two sequential endocervical cytobrushes (CB1, CB2). Cells were isolated and phentoyped via flow cytometry. CD4 T cell recovery was highest from each individual CB compared to either CVL or FS (p sampling method, expressed CCR5 relative to peripheral blood (p samples. Using three different mucosal sampling methods collected longitudinally we demonstrate that CD4 T cells within the FGT express CCR5 and α4β7 and are highly activated, attributes which could act in concert to facilitate HIV acquisition. FS and CB sampling methods can allow for investigation of strategies to reduce HIV target cells in the FGT and could inform the design and interpretation microbicide and vaccine studies in women.

Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections.

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Damien Portevin

Full Text Available It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4(+ and CD8(+ T cells in relation to age, HIV and active Tuberculosis (TB co-infection in a cohort of Tanzanian volunteers (≤ 16 years of age, n = 108 and ≥ 18 years, n = 79. Independent of HIV co-infection, IFNγ(+ CMVpp65-specific CD4(+ T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27(low phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.

Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

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Melikian, George L; Rhee, Soo-Yon; Taylor, Jonathan; Fessel, W Jeffrey; Kaufman, David; Towner, William; Troia-Cancio, Paolo V; Zolopa, Andrew; Robbins, Gregory K; Kagan, Ron; Israelski, Dennis; Shafer, Robert W

2012-05-01

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

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

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Andersson, Sören

1999-01-01

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

In "Step" with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study.

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Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.

Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD).

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Chadburn, A; Hyjek, E M; Tam, W; Liu, Y; Rengifo, T; Cesarman, E; Knowles, D M

2008-11-01

Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative. Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.

CLINICAL AND LABORATORY PROFILE OF SPUTUM POSITIVE PULMONARY TUBERCULOSIS AMONG HIV SEROPOSITIVE AND HIV SERONEGATIVE PATIENTS- A CROSS-SECTIONAL STUDY

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Amit Govind Kamat

2017-05-01

Full Text Available BACKGROUND The global impact of the converging dual epidemics of TB and HIV is one of the major public health challenges. The increasing rate of HIV infection in many countries has had an impact on TB epidemiology. As the prevalence of pulmonary tuberculosis is increasing among HIV seropositive patients with a wide range of immune status and clinical presentations, the present study was undertaken to assess the clinical and laboratory profile of sputum positive pulmonary tuberculosis among HIV seropositive and HIV seronegative patients. MATERIALS AND METHODS The present one year cross-sectional study was conducted in the Department of Medicine, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belgaum on 104 patients with sputum positive pulmonary tuberculosis patients during the period of January 2009 to December 2009. Routine investigations such as blood group, haemogram that is haemoglobin, total count, differential count, erythrocyte sedimentation rate, sputum smears for AFB and chest x-ray were done. RESULTS Seroprevalence of HIV among pulmonary tuberculosis patients was 23.08%. On examination anaemia, undernourishment, lymphadenopathy and the presence of opportunistic infections like oral candidiasis, herpes zoster stain and genital lesions were more predominant among HIV seropositives compared to HIV seronegatives. Mean Hb and TLC were significantly low among HIV seropositives compared to HIV seronegatives. Chest x-ray showed varied presentation. Upper zone infiltration, cavitation and fibrosis were more commonly involved among HIV seronegatives compared to HIV seropositives. CONCLUSION HIV seropositive PTB patients commonly present with fever, weight loss and loss of appetite, while cough with expectoration, haemoptysis, breathlessness were more common with HIV seronegative patients. Cavitation, fibrosis and fibrocavitary lesions were predominantly seen among HIV seronegatives, while infiltration and miliary mottling was

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

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Petrovas, Constantinos; Mueller, Yvonne M; Katsikis, Peter D

2004-04-01

An increasing body of evidence supports a key role for cytotoxic CD8+ T cells (CTL) in controlling HIV infection. Although a vigorous HIV-specific CD8+ T cell response is raised during the primary infection, these cells ultimately fail to control virus and prevent disease progression. The failure of CTL to control HIV infection has been attributed to a number of strategies HIV employs to evade the immune system. Recently, intrinsic defects in the CTL themselves have been proposed to contribute to the failure of CTL to control HIV. HIV-specific CD8+ T cells differ in their effector/memory phenotype from other virus-specific CD8+ T cells indicating that their differentiation status differs. This altered differentiation may affect effector functions as well as homing properties of these cells. Other studies have indicated that activation of HIV-specific CTL may be impaired and this contributes to their dysfunction. The effector function of these CTL may also be affected. There are conflicting reports about their ability to kill, whereas IFNgamma production does not appear to be impaired in these cells. In this review we focus on recent work indicating that apoptosis may be an important mechanism through which HIV evades the CTL response. In particular, HIV-specific CD8+ T cells are highly susceptible to CD95/Fas-induced apoptosis. This leads to the hypothesis that virus-specific cytotoxic T cells can be eliminated upon binding CD95L/FasL on HIV-infected cells. Understanding the intrinsic defects of CTL in HIV infection could lead to new therapeutic strategies and optimized vaccination protocols that enhance the HIV-specific cytotoxic response.

Appreciating HIV-1 diversity: subtypic differences in ENV

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Gnanakaran, S [Los Alamos National Laboratory; Shen, Tongye [Los Alamos National Laboratory; Lynch, Rebecca M [NON LANL; Derdeyn, Cynthia A [NON LANL

2008-01-01

Human immunodeficiency virus type 1 (HIV-1) group M is responsible for the current AIDS pandemic and exhibits exceedingly high levels of viral genetic diversity around the world, necessitating categorization of viruses into distinct lineages, or subtypes. These subtypes can differ by around 35% in the envelope (Env) glycoproteins of the virus, which are displayed on the surface of the virion and are targets for both neutralizing antibody and cell-mediated immune responses. This diversity reflects the remarkable ability of the virus to adapt to selective pressures, the bulk of which is applied by the host immune response, and represents a serious obstacle for developing an effective vaccine with broad coverage. Thus, it is important to understand the underlying biological consequences of inter-subtype diversity. Recent studies have revealed that the HIV-1 subtypes exhibit phenotypic differences that result from subtle differences in Env structure, particularly within the highly immunogenic V3 domain, which participates directly in viral entry. This review will therefore explore current research that describes subtypic differences in Env at the genetic and phenotypic level, focusing in particular on V3, and highlighting recent discoveries about the unique features of subtype C Env, which is the most prevalent subtype globally.

Predictors of Delayed Entry into Medical Care of Children Diagnosed with HIV Infection: Data from an HIV Cohort Study in India

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Gerardo Alvarez-Uria

2013-01-01

Full Text Available Data about the attrition before entry into care of children diagnosed with HIV in low- or middle-income countries are scarce. The aim of this study is to describe the attrition before engagement in HIV medical care in 523 children who were diagnosed with HIV from 2007 to 2012 in a cohort study in India. The cumulative incidence of children who entered into care was 87.2% at one year, but most children who did not enter into care within one year were lost to followup. The mortality before entry into care was low (1.3% at one year and concentrated during the first three months after HIV diagnosis. Factors associated with delayed entry into care were being diagnosed after mother’s HIV diagnosis, belonging to scheduled castes, age 90 minutes from the HIV centre. Children whose parents were alive and were living in a rented house were at a higher risk of delayed entry into care than those who were living in an owned house. The results of this study can be used to improve the linkage between HIV testing and HIV care of children diagnosed with HIV in India.

Transcriptome analysis of monocyte-HIV interactions

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Tran Huyen

2010-06-01

macrophages can contribute to sustained chronic immune activation during HIV infection, e.g. through the perturbation of cytokine and chemokine networks 141516. With the acknowledged notion of chronic immune activation as a paradoxical driving force of immune suppression 17, this pro-inflammatory macrophage phenotype during HIV infection may be a crucial parameter in disease progression. Yet other macrophage dysfunctions are associated with more peripheral HIV- or ART-associated disorders such as atherosclerosis 18, lipodystrophy 19, and metabolic syndrome during HIV infection and/or combination ART 2021. Monocytes, for their part, are much less permissive to infection with HIV, both in vitro 22 and in vivo, where estimates of infected circulating monocytes are consistently low 2324. Circulating monocytes represent the most accessible primary model for macrophage dysfunction during HIV infection, however, and are furthermore of sufficient importance to study in their own right. Infectious virus can be recovered from circulating monocytes, both in untreated patients 24 and in patients undergoing long-term successful combination ART 25. Additionally, the circulating monocyte pool as a whole does seem to be affected during HIV infection, despite the low frequency of actually infected monocytes. Transcriptome studies, in particular, show a form of hybrid phenotype exhibiting both increased and decreased pro-inflammatory features 2627. This modulation of the non-infected monocyte population could be due to the virus itself through mechanisms which do not require direct infection 28, or to other factors contributing to (aberrant immune activation occurring during HIV infection, such as perturbed cytokine networks 29 or other inflammatory stimulants 30. Several key factors in the described dysregulated processes have been identified 1831, but many molecular components remain elusive. Furthermore, other aspects of HIV and combination ART pathogenesis in which monocyte

Caffeine and Insomnia in People Living With HIV From the Miami Adult Studies on HIV (MASH) Cohort.

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Ramamoorthy, Venkataraghavan; Campa, Adriana; Rubens, Muni; Martinez, Sabrina S; Fleetwood, Christina; Stewart, Tiffanie; Liuzzi, Juan P; George, Florence; Khan, Hafiz; Li, Yinghui; Baum, Marianna K

We explored the relationship between caffeine consumption, insomnia, and HIV disease progression (CD4+ T cell counts and HIV viral loads). Caffeine intake and insomnia levels were measured using the Modified Caffeine Consumption Questionnaire and the Pittsburgh Insomnia Rating Scale (PIRS) in 130 clinically stable participants who were living with HIV, taking antiretroviral therapy, and recruited from the Miami Adult Studies on HIV cohort. Linear regressions showed that caffeine consumption was significantly and adversely associated with distress score, quality-of-life score, and global PIRS score. Linear regression analyses also showed that global PIRS score was significantly associated with lower CD4+ T cell counts and higher HIV viral loads. Caffeine could have precipitated insomnia in susceptible people living with HIV, which could be detrimental to their disease progression states. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection.

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Godelieve J de Bree

Full Text Available Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks.Primo-SHM trial patients selected for the present study were untreated (n = 23 or treated for 24 weeks (n = 24. Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks before (re-initiation of treatment.At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006. In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point.These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.

HIV screening among TB patients and co-trimoxazole preventive therapy for TB/HIV patients in Addis Ababa: facility based descriptive study.

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Denegetu, Amenu Wesen; Dolamo, Bethabile Lovely

2014-01-01

Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa. A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings. The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up. HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.

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

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Jairam R Lingappa

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

TUBERCULOSIS AND HIV COINFECTION: A TERTIARY CARE HOSPITAL STUDY

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Vivek

2016-02-01

Full Text Available OBJECTIVE The aim of the present study is to record the clinical, radiological profile of pulmonary and extra pulmonary tuberculosis (EPTB in HIV positive patients. To win the battle against AIDS we have to fight against TB. Unlike HIV/AIDS, TB is completely curable in the vast majority of cases. MATERIALS AND METHODS This prospective study was conducted in the department of pulmonary medicine, Gadag institute of medical sciences, Gadag. All newly diagnosed HIV patients during the study period were included and screened for TB. HIV infection was confirmed by enzyme linked immunosorbent assay using two different antigens and a rapid test as recommended by NACO. RESULTS Among 370 newly diagnosed HIV positive patients, 113(30.54% patients were diagnosed to have TB. Most common affected age group was 31-40years with a mean age of 38.08 years. Unprotected heterosexual contact was the most common mode of HIV transmission. Fever, weight loss and cough were the commonest symptoms at presentation. Pulmonary TB was diagnosed in 85(22.97% patients, EPTB in 21(5.67% and disseminated TB in 7(1.8% patients. Among the EPTB patients, 2(9.5% patients had extra thoracic lymphadenopathy. Cervical lymph node was the commonest lymph node involved. 14(66.66% patients had pleural effusion, 3(14.28% had abdominal TB, 1(4.76% had tubercular meningitis and 1(4.76% patient had TB testis. CONCLUSION The prevalence of HIV–TB co-infection was high. Moreover, HIV positive patients need early diagnosis and treatment of active TB. However large sample size prospective studies are needed to correlate the clinical and CD4 count with the occurrence of different types of tuberculosis.

Pregnancy outcomes in HIV-positive women: a retrospective cohort study.

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Arab, Kholoud; Spence, Andrea R; Czuzoj-Shulman, Nicholas; Abenhaim, Haim A

2017-03-01

In the United States, an estimated 8500 HIV (human immunodeficiency virus) positive women gave birth in 2014. This rate appears to be increasing annually. Our objective is to examine obstetrical outcomes of pregnancy among HIV-positive women. A population-based cohort study was conducted using the Nationwide Inpatient Sample database (2003-2011) from the United States. Pregnant HIV-positive women were identified and compared to pregnant women without HIV. Multivariate logistic regression was used to estimate the adjusted effect of HIV status on obstetrical and neonatal outcomes. Among 7,772,999 births over the study period, 1997 were in HIV-positive women (an incidence of 25.7/100,000 births). HIV-infected patients had greater frequency of pre-existing diabetes and chronic hypertension, and use of cigarettes, drugs, and alcohol during pregnancy (p HIV-infected women had greater likelihood of antenatal complications: preterm premature rupture of membranes (OR 1.35, 95% CI 1.14-1.60) and urinary tract infections (OR 3.02, 95% CI 2.40-3.81). Delivery and postpartum complications were also increased among HIV-infected women: cesarean delivery (OR 3.06, 95% CI 2.79-3.36), postpartum sepsis (OR 8.05, 95% CI 5.44-11.90), venous thromboembolism (OR 2.21, 95% CI 1.46-3.33), blood transfusions (OR 3.67, 95% CI 3.01-4.49), postpartum infection (OR 3.00, 95% CI 2.37-3.80), and maternal mortality (OR 21.52, 95% CI 12.96-35.72). Neonates born to these mothers were at higher risk of prematurity and intrauterine growth restriction. Pregnancy in HIV-infected women is associated with adverse maternal and newborn complications. Pregnant HIV-positive women should be followed in high-risk healthcare centers.

Using two on-going HIV studies to obtain clinical data from before, during and after pregnancy for HIV-positive women

Directory of Open Access Journals (Sweden)

Huntington Susie E

2012-07-01

Full Text Available Abstract Background The UK Collaborative HIV Cohort (UK CHIC is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone. Results Women in UK CHIC receiving HIV-clinical care in 1996–2009, were found in the NSHPC dataset by initially ‘linking’ records with identical date-of-birth, linked records were then accepted as a genuine ‘match’, if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932. Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009. There was bias towards matching women with repeat pregnancies (35.9% (741/2063 of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869 of women in NSHPC only and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063 compared to 47.7% (3278/6869, respectively. Conclusions Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.

HIV-1 Promoter Single Nucleotide Polymorphisms Are Associated with Clinical Disease Severity.

Directory of Open Access Journals (Sweden)

Michael R Nonnemacher

Full Text Available The large majority of human immunodeficiency virus type 1 (HIV-1 markers of disease progression/severity previously identified have been associated with alterations in host genetic and immune responses, with few studies focused on viral genetic markers correlate with changes in disease severity. This study presents a cross-sectional/longitudinal study of HIV-1 single nucleotide polymorphisms (SNPs contained within the viral promoter or long terminal repeat (LTR in patients within the Drexel Medicine CNS AIDS Research and Eradication Study (CARES Cohort. HIV-1 LTR SNPs were found to associate with the classical clinical disease parameters CD4+ T-cell count and log viral load. They were found in both defined and undefined transcription factor binding sites of the LTR. A novel SNP identified at position 108 in a known COUP (chicken ovalbumin upstream promoter/AP1 transcription factor binding site was significantly correlated with binding phenotypes that are potentially the underlying cause of the associated clinical outcome (increase in viral load and decrease in CD4+ T-cell count.

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study.

Science.gov (United States)

Dutta, Anupriya; Uno, Hajime; Holman, Alex; Lorenz, David R; Gabuzda, Dana

2017-07-01

African American men have the highest incidence of prostate cancer among ethnic groups, and racial disparity is highest in younger men. Prostate cancer prevalence is rising in HIV-infected men due to improved survival on antiretroviral therapies, yet little is known about racial differences in prostate cancer risk by HIV-infection status and age. This is a prospective cohort study of prostate cancer risk in 2,800 HIV-infected and -uninfected men who have sex with men (MSM) aged 40-70 years (22% African American) who were enrolled in the multicenter AIDS cohort study from 1996 to 2010. Poisson regression models were used to examine associations between race and HIV-infection status and prostate cancer risk among men aged 40-70, 40-55, and 56-70 years. Among men aged 40-70 years, incidence rates (IR) per 100,000 person-years were 169 among all men and 276 among African American HIV-infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0, 95% CI 0.55-1.82), but nearly threefold higher in African Americans compared to non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36-5.18 and 1.27-8.16 for all or HIV-infected men, respectively). Racial disparity in prostate cancer risk was greatest in African American men aged 40-55 years (adjusted IRR 3.31, 95% CI 1.19-9.22). Prostate cancer risk showed associations with family history of prostate cancer (p = 0.001), but not heavy smoking, androgen supplement use, or HIV-related factors. Among MSM, African American HIV-positive and HIV-negative men aged 40-55 years have threefold increased risk of young-onset prostate cancer compared to non-African American men, highlighting the need to make informed decisions about screening in this population.

Reduced Expression of Siglec-7, NKG2A, and CD57 on Terminally Differentiated CD56-CD16+ Natural Killer Cell Subset Is Associated with Natural Killer Cell Dysfunction in Chronic HIV-1 Clade C Infection.

Science.gov (United States)

Zulu, Michael Z; Naidoo, Kewreshini K; Mncube, Zenele; Jaggernath, Manjeetha; Goulder, Philip J R; Ndung'u, Thumbi; Altfeld, Marcus; Thobakgale, Christina F

2017-12-01

HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status, and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. NK cell phenotypic profiles were characterized by assessing sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7), NKG2A, and NKG2C markers on frozen peripheral blood mononuclear cells from viremic, antiretroviral therapy (ART)-naive HIV-1 chronically infected participants (n = 23), HIV-1 chronically infected participants who had been on combination antiretroviral therapy (cART) for at least 12 months (n = 23) compared with healthy donors (n = 23). NK cell differentiation was assessed by measurement of killer immunoglobulin receptor (KIR) and NKG2A expression; CD57 and CD107a measurements were carried out in HIV viremic and healthy donors. All phenotypic and functional assessments were analyzed by using multicolor flow cytometry. HIV-1-infected participants displayed greater frequencies of the CD56 - CD16 + (CD56negative) NK cell subset compared with healthy donors (p < .0001). Downregulation of Siglec-7 and NKG2A and upregulation of NKG2C were more pronounced in the CD56negative NK cell subset of viremic participants. The CD56negative subset demonstrated a differentiated (KIR + NKG2A - ) phenotype with reduced CD57 expression and lower degranulation capacity in HIV-1-infected participants compared with healthy donors. HIV-1 infection induces the expansion of the CD56negative NK cell subset marked by altered receptor expression profiles that are indicative of impaired function and may explain the overall NK cell dysfunction observed in chronic HIV-1 infection.

Exploring the role, needs and challenges of relatives of mothers with HIV or HIV and psychosis: A qualitative study

NARCIS (Netherlands)

Spies, Ruan; Derks, Olivia K.; Sterkenburg, Paula S.; Schuengel, Carlo; van Rensburg, Esme

2016-01-01

This study explored types and nature of supports by relatives of mothers living with HIV and psychosis in comparison to mothers with HIV only. Interview data on their experiences of their roles, needs and challenges were collected from 33 relatives on mothers with HIV and psychosis (n=12,

Isolation of Candida dubliniensis for the first time in Cali, Colombia, and its identification with phenotyping methods.

Science.gov (United States)

Alvarez, María Inés; Suárez, Blanca Lynne; Caicedo, Luz Dary

2009-01-01

Candida dubliniensis is an emerging pathogenic yeast isolated mainly from the oral cavity of HIV-infected patients. The close phenotypic and genotypic relationship between C. albicans and C. dubliniensis has led to incorrectly identifying isolates of C. dubliniensis as C. albicans. The oral cavities of 107 diabetic patients were studied in Cali, Colombia, and 72 colonies of Candida, with shades of green on CHROMagar Candida culture media, were obtained. Various phenotypic tests were carried out, which included germ tube formation and production of chlamydospores on corn meal Agar. Additionally, growth studies were carried out at 42 degrees C and 45 degrees C and on Sabouraud agar with 6.5%, sodium chloride. Identification of C. dubliniensis with these tests was confirmed with API 20C Aux. We identified 65 and 7 colonies of C. albicans and C. dubliniensis, respectively. This is the first time that C. dubliniensis is identified with phenotypic methods in Colombia.

HIV-Infected Children Have Elevated Levels of PD-1+ Memory CD4 T Cells With Low Proliferative Capacity and High Inflammatory Cytokine Effector Functions.

Science.gov (United States)

Foldi, Julia; Kozhaya, Lina; McCarty, Bret; Mwamzuka, Mussa; Marshed, Fatma; Ilmet, Tiina; Kilberg, Max; Kravietz, Adam; Ahmed, Aabid; Borkowsky, William; Unutmaz, Derya; Khaitan, Alka

2017-09-15

During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation. Second, in vitro CD4 T-cell proliferative and cytokine responses to HIV-specific and -nonspecific stimuli were assessed with and without PD-1 blockade. HIV-infected children have increased frequencies of PD-1+ memory CD4 T cells that fail to normalize with antiretroviral treatment. These cells are comprised of central and effector memory subsets and correlate with HIV disease progression, measured by viral load, CD4 percentage, CD4:CD8 T-cell ratio, and immune activation. Last, PD-1+ CD4 T cells predict impaired proliferative potential yet preferentially secrete the Th1 and Th17 cytokines interferon-γ and interleukin 17A, and are unresponsive to in vitro PD-1 blockade. This study highlights differences in PD-1+ CD4 T-cell memory phenotype and response to blockade between HIV-infected children and adults, with implications for potential immune checkpoint therapies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Perspectives of HIV-related stigma in a community in Vietnam: a qualitative study.

Science.gov (United States)

Gaudine, Alice; Gien, Lan; Thuan, Tran T; Dung, Do V

2010-01-01

While HIV/AIDS is increasing in Vietnam, very few published studies focus on HIV-related stigma in Vietnam. This study reports on findings from a community development project to reduce HIV-related stigma within one community in Vietnam. The purpose of this qualitative study is to describe HIV-related stigma from the perspective of three groups within one community in Vietnam: people living with HIV, their family members, and community members and leaders, including health care professionals. SETTING, PARTICIPANTS AND METHODS: Fifty-eight individuals from a poor, industrial district on the outskirts of a large city participated in the study and were asked to describe HIV-related stigma. Interviews were conducted with 10 people living with HIV, 10 family members of a person living with HIV, and 10 community members and 5 community leaders including health care professionals. We also conducted three focus groups, one with people living with HIV (n=8), one with family members of people living with HIV (n=8), and one with community leaders including health care professionals (n=7). Stigma across the three groups is characterized by four dimensions of HIV-related stigma: feeling shamed and scorned, behaving differently, stigma due to association, and fear of transmission. The manifestation of these dimensions differs for each group. Four themes of HIV-related stigma as described by people living with HIV are: being avoided, experiencing anger and rejection, being viewed as a social ill, and hiding the illness. Seven themes of HIV-related stigma as described by family members are: shunned by neighbors, viewed as poor parents, discriminated by health professionals, overhearing discussions about people with HIV, maintaining the secret, financial hardship for family, and fear of contracting HIV. Four themes of HIV-related stigma as described by community members and leaders including health professionals are: stigma as a fair reward, avoidance and shunning by neighbors

Premarital HIV testing in Malaysia: a qualitative exploratory study on the views of major stakeholders involved in HIV prevention.

Science.gov (United States)

Barmania, Sima; Aljunid, Syed Mohamed

2017-05-10

HIV screening has existed in numerous methods as an important part of HIV prevention efforts over the years. Premarital HIV testing for couples who wish to marry has been implemented in a number of regions, which often operate in a mandatory rather than voluntary basis and is considered a contentious issue, with viewpoints held in favour and against. One such region is Malaysia which has a policy of mandatory premarital HIV testing of prospective Muslim married couples. The purpose of this study is to understand stakeholders' views on premarital HIV testing given the Malaysian Islamic context. 35 in-depth face to face semi-structured interviews were undertaken with key stakeholder groups involved in HIV prevention policy in Malaysia, namely, officials from the Ministry of Health, religious leaders and people living with HIV. Participants were recruited from the Klang Valley area, from July to December 2013, using purposive sampling techniques. Inclusion criteria necessitated that participants were over the age of 18 and provided full consent. Interviews were audiotaped, followed a standardised topic guide, transcribed verbatim and analysed using a framework analysis. Participants identified pre-marital HIV testing as an effective HIV prevention policy implemented in Malaysia and was viewed, for the most part, as a positive initiative across all stakeholders. Religious leaders were supportive of testing as it provides a protective mechanism, in line with the teachings of the Shariah, while Ministry of Health officials considered it a normal part of their HIV prevention screening initiatives. However, there were concerns surrounding issues such as confidentiality, counselling and discrimination surrounding the test described by the PLHIV group. The findings of this study show that among the participants interviewed was strong support for mandatory premarital HIV testing, which could possibly expose the vulnerability to HIV, reluctance to test and other areas in the

Applications of the FIV Model to Study HIV Pathogenesis

Directory of Open Access Journals (Sweden)

Craig Miller

2018-04-01

Full Text Available Feline immunodeficiency virus (FIV is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS. Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV. In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and the mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data that highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked, resource for advancing therapies and the management of HIV/AIDS.

A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

Science.gov (United States)

Du, Sean X.; Xu, Li; Zhang, Wenge; Tang, Susan; Boenig, Rebecca I.; Chen, Helen; Mariano, Ellaine B.; Zwick, Michael B.; Parren, Paul W. H. I.; Burton, Dennis R.; Wrin, Terri; Petropoulos, Christos J.; Ballantyne, John A.; Chambers, Michael; Whalen, Robert G.

2011-01-01

A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. PMID:21738594

The implementation of isoniazid preventive therapy in HIV clinics: the experience from the TB/HIV in Rio (THRio) study.

Science.gov (United States)

Durovni, Betina; Cavalcante, Solange C; Saraceni, Valeria; Vellozo, Vitoria; Israel, Giselle; King, Bonnie S; Cohn, Silvia; Efron, Anne; Pacheco, Antonio G; Moulton, Lawrence H; Chaisson, Richard E; Golub, Jonathan E

2010-11-01

The TB/HIV in Rio (THRio) study was launched in September 2005 to assess the impact of integrated tuberculosis (TB) and HIV treatment strategies in 29 HIV clinics in Rio de Janeiro, Brazil. THRio is a cluster-randomized trial (CRT) to determine whether routine screening for and treatment of latent TB in HIV clinic patients with access to antiretroviral therapy will reduce TB incidence at the clinic level. THRio is part of the Consortium to Respond Effectively to AIDS/TB Epidemic that is implementing research studies to assess the impact of bold, new public health paradigms for controlling the AIDS/TB epidemic. Twenty-nine public primary HIV clinics were randomly assigned a date to begin implementing TB screening procedures and provision of isoniazid preventive therapy (IPT) for TB/HIV coinfected patients. Final analysis of the CRT is expected in 2011. Starting at date of tuberculin skin test (TST)/IPT implementation at each clinic through August 2010, 1670 HIV-infected patients initiated IPT, of which 215 are still receiving treatment. Of the remaining 1455 patients, 1230 (85%) completed therapy and only 20 (1.2%) patients initiating IPT reported adverse reactions leading to discontinuation of therapy. IPT completion was higher among HIV-infected patients receiving HAART (87%) than those not yet receiving HAART (79%, P effort requires a package of activities including training, advocacy and reorganization of services.

The Perinatal Guidelines Evaluation Project HIV and Pregnancy Study: overview and cohort description.

Science.gov (United States)

Ethier, Kathleen A.; Ickovics, Jeannette R.; Fernandez, M. Isabel; Wilson, Tracey E.; Royce, Rachel A.; Koenig, Linda J.

2002-01-01

OBJECTIVE: The HIV and Pregnancy Study of the Perinatal Guidelines Evaluation Project is a prospective, longitudinal, multisite study established to: (a) assess the implementation of Public Health Service guidelines regarding the prevention of perinatal HIV transmission and (b) evaluate the psychosocial consequences of HIV infection among pregnant women. A distinctive aspect of the study is the use of an HIV-negative comparison group. This article describes the methodology of the study and baseline characteristics of the study sample. Methods and Results. HIV-infected (n = 336) and uninfected (n = 298) pregnant women were enrolled from four geographic areas: Connecticut, North Carolina, Brooklyn, NY, and Miami, FL. The study included three structured face-to-face interviews from late pregnancy to six months postpartum for HIV-infected and uninfected women. Additional self-reports of medication adherence were collected for the HIV-infected participants, and the medical records of infected mothers and their infants were reviewed. Electronic monitoring of medication adherence was conducted for a subset of the infected women. The groups were successfully matched on self-reported characteristics, including HIV-risk behaviors. More than half of the uninfected women reported a high-risk sexual partner. Baseline comparisons indicated that both the HIV-infected and uninfected women had high levels of depressive symptoms, stress, and recent negative life events. CONCLUSIONS: This study provides a unique description of the psychosocial and behavioral characteristics of a population of low-income women. The results of this study suggest that HIV infection is one of many stressors faced by the women in this study. PMID:12356998

SigniSite: Identification of residue-level genotype-phenotype correlations in protein multiple sequence alignments

DEFF Research Database (Denmark)

Jessen, Leon Ivar; Hoof, Ilka; Lund, Ole

2013-01-01

Site does not require any pre-definition of subgroups or binary classification. Input is a set of protein sequences where each sequence has an associated real number, quantifying a given phenotype. SigniSite will then identify which amino acid residues are significantly associated with the data set......) using a set of human immunodeficiency virus protease-inhibitor genotype–phenotype data and corresponding resistance mutation scores from the Stanford University HIV Drug Resistance Database, and a data set of protein families with experimentally annotated SDPs. For both data sets, SigniSite was found...

Next-generation in situ hybridization approaches to define and quantify HIV and SIV reservoirs in tissue microenvironments.

Science.gov (United States)

Deleage, Claire; Chan, Chi N; Busman-Sahay, Kathleen; Estes, Jacob D

2018-01-09

The development of increasingly safe and effective antiretroviral treatments for human immunodeficiency virus (HIV) over the past several decades has led to vastly improved patient survival when treatment is available and affordable, an outcome that relies on uninterrupted adherence to combination antiretroviral therapy for life. Looking to the future, the discovery of an elusive 'cure' for HIV will necessitate highly sensitive methods for detecting, understanding, and eliminating viral reservoirs. Next-generation, in situ hybridization (ISH) approaches offer unique and complementary insights into viral reservoirs within their native tissue environments with a high degree of specificity and sensitivity. In this review, we will discuss how modern ISH techniques can be used, either alone or in conjunction with phenotypic characterization, to probe viral reservoir establishment and maintenance. In addition to focusing on how these techniques have already furthered our understanding of HIV reservoirs, we discuss potential avenues for how high-throughput, next-generation ISH may be applied. Finally, we will review how ISH could allow deeper phenotypic and contextual insights into HIV reservoir biology that should prove instrumental in moving the field closer to viral reservoir elimination needed for an 'HIV cure' to be realized.

Mapping and characterization of vicriviroc resistance mutations from HIV-1 isolated from treatment-experienced subjects enrolled in a phase II study (VICTOR-E1).

Science.gov (United States)

McNicholas, Paul M; Mann, Paul A; Wojcik, Lisa; Qiu, Ping; Lee, Erin; McCarthy, Michael; Shen, Junwu; Black, Todd A; Strizki, Julie M

2011-03-01

In the phase 2 VICTOR-E1 study, treatment-experienced subjects receiving 20 mg or 30 mg of the CCR5 antagonist vicriviroc (VCV), with a boosted protease containing optimized background regimen, experienced significantly greater reductions in HIV-1 viral load compared with control subjects. Among the 79 VCV-treated subjects, 15 experienced virologic failure, and of these 5 had VCV-resistant virus. This study investigated the molecular basis for the changes in susceptibility to VCV in these subjects. Sequence analysis and phenotypic susceptibility testing was performed on envelope clones from VCV-resistant virus. For select clones, an exchange of mutations in the V3 loop was performed between phenotypically resistant clones and the corresponding susceptible clones. Phenotypic resistance was manifest by reductions in the maximum percent inhibition. Clonal analysis of envelopes from the 5 subjects identified multiple amino acid changes in gp160 that were exclusive to the resistant clones, however, none of the changes were conserved between subjects. Introduction of V3 loop substitutions from the resistant clones into the matched susceptible clones was not sufficient to reproduce the resistant phenotype. Likewise, changing the substitutions in the V3 loops from resistant clones to match susceptible clones only restored susceptibility in 1 clone. There were no clearly conserved patterns of mutations in gp160 associated with phenotypic resistance to VCV and mutations both within and outside of the V3 loop contributed to the resistance phenotype. These data suggest that genotypic tests for VCV susceptibility may require larger training sets and additional information beyond V3 sequences.

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

An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

Science.gov (United States)

Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

2018-04-01

Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

OpenAIRE

Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

2009-01-01

There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 a...

Relationship of race-, sexual orientation-, and HIV-related discrimination with adherence to HIV treatment: a pilot study.

Science.gov (United States)

Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L

2008-10-01

Adherence to highly active antiretroviral therapy (HAART) must be close to perfect in order to maintain suppression of HIV viral load, and to prevent the development of drug resistant strains of HIV. People living with HIV (PLWH) often report low levels of adherence. One variable that has been linked to poor adherence is perceived discrimination; however, research has generally not considered the possible unique effects of different types of discrimination on adherence. The present pilot study aimed to examine the association of three types of discrimination (due to HIV+ status, race, or sexual orientation) with adherence among 57 PLWH. Logistic regression analyses were conducted to demonstrate the relationships between each type of discrimination and self-reported adherence. Racial discrimination significantly predicted lower adherence levels, whereas sexual orientation- and HIV-related discrimination did not. Results underscore the importance of addressing discrimination issues, specifically racial, when designing interventions to improve adherence to HAART.

Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

Science.gov (United States)

Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

2014-07-21

Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

Prevalence of human Papilloma Virus in HIV-positive and HIV-negative patients in the State of Bahia: a pilot study

Directory of Open Access Journals (Sweden)

Conceição Queiroz

Full Text Available Human Papilloma Virus (HPV plays a central role in the development of cervical cancer. However, other coexisting factors, such as HIV infection, must be present for this to occur. We evaluated the prevalence of HPV in HIV-positive and HIV-negative patients in the city of Salvador , Bahia, Brazil, and determined the most prevalent types of HPV in these patients. Fifty-five cases were selected from among patients attending three institutions providing cervical pathology services in the city of Salvador. HIV testing (Elisa/WB, HPV-DNA testing by PCR, colposcopy, cytology and biopsy were carried out in all patients. The histopathological results were classified as follows: 11 cases were normal/negative for neoplasia, 15 were diagnosed as cervical intraepithelial neoplasia grade 1 (CIN 1, 10 were CIN 2, 15 cases were CIN 3 and there were four cases of invasive squamous cell carcinoma. Among the 55 patients studied, 43 tested positive for HPV-DNA and 20 for HIV. All HIV-positive patients were positive for HPV-DNA. The most prevalent types of HPV were HPV 16, 52, 58, 53, 54, 33 and 51, and there was little difference between the groups of HIV-positive and HIV-negative patients with respect to the type of HPV encountered. The HIV-positive patients were found to be infected with a greater number of types of HPV than the HIV-negative patients. This study corroborates the existence of regional variations in the distribution of certain types of HPV, which is probably due to the particular ethnic constitution found in this region of Brazil.

Phenotype Variation in Human Immunodeficiency virus Type 1 Transmission and Disease Progression

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Mariangela Cavarelli

2009-01-01

Full Text Available Human immunodeficiency virus type I (HIV-1 infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.

Phenotype variation in human immunodeficiency virus type 1 transmission and disease progression.

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Cavarelli, Mariangela; Scarlatti, Gabriella

2009-01-01

Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.

Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

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Teresa H Evering

2012-02-01

Full Text Available Mucosal mononuclear (MMC CCR5+CD4+ T cells of the gastrointestinal (GI tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART, gut-associated lymphoid tissue (GALT CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment

Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

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Evering, Teresa H; Mehandru, Saurabh; Racz, Paul; Tenner-Racz, Klara; Poles, Michael A; Figueroa, Amir; Mohri, Hiroshi; Markowitz, Martin

2012-02-01

Mucosal mononuclear (MMC) CCR5+CD4+ T cells of the gastrointestinal (GI) tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART), gut-associated lymphoid tissue (GALT) CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd) biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd) GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS) were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment during

Phenotypic Characteristics Associated with Virulence of Clinical Isolates from the Sporothrix Complex

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Almeida-Paes, Rodrigo; de Oliveira, Luã Cardoso; Oliveira, Manoel Marques Evangelista; Gutierrez-Galhardo, Maria Clara; Nosanchuk, Joshua Daniel; Zancopé-Oliveira, Rosely Maria

2015-01-01

The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with a wide spectrum of clinical manifestations. Several specific phenotypic characteristics are associated with virulence in many fungi, but studies in this field involving the Sporothrix complex species are scarce. Melanization, thermotolerance, and production of proteases, catalase, and urease were investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains. The S. brasiliensis strains showed a higher expression of melanin and urease compared with S. schenckii. These two species, however, presented similar thermotolerances. Our S. globosa strain had low expression of all studied virulence factors. The relationship between these phenotypes and clinical aspects of sporotrichosis was also evaluated. Strains isolated from patients with spontaneous regression of infection were heavily melanized and produced high urease levels. Melanin was also related to dissemination of internal organs and protease production was associated with HIV-coinfection. A murine sporotrichosis model showed that a S. brasiliensis strain with high expression of virulence factors was able to disseminate and yield a high fungal burden in comparison with a control S. schenckii strain. Our results show that virulence-related phenotypes are variably expressed within the Sporothrix complex species and might be involved in clinical aspects of sporotrichosis. PMID:25961005

In “Step” with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study

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Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373

The role of social support on HIV testing and treatment adherence: A qualitative study of HIV-infected refugees in southwestern Uganda.

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Rouhani, Shada A; O'Laughlin, Kelli N; Faustin, Zikama M; Tsai, Alexander C; Kasozi, Julius; Ware, Norma C

2017-08-01

Little is known about the factors that encourage or discourage refugees to test for HIV, or to access and adhere to HIV care. In non-refugee populations, social support has been shown to influence HIV testing and utilisation of services. The present study enrolled HIV-infected refugees on anti-retroviral therapy (ART) in Uganda, who participated in qualitative interviews on HIV testing, treatment, and adherence. Interviews were analysed for themes about four types of social support: emotional, informational, instrumental, and appraisal support. A total of 61 interviews were analysed. Four roles for these types of social support were identified: (1) informational support encouraged refugees to test for HIV; (2) emotional support helped refugees cope with a diagnosis of HIV; (3) instrumental support facilitated adherence to ART and (4) after diagnosis, HIV-infected refugees provided informational and emotional support to encourage other refugees to test for HIV. These results suggest that social support influences HIV testing and treatment among refugees. Future interventions should capitalise on social support within a refugee settlement to facilitate testing and treatment.

Circulating Cxcr5-Expressing Cd8+T-Cells are Major Producers of Il-21 and Associate with Limited Hiv Replication.

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Perdomo-Celis, Federico; Taborda, Natalia A; Rugeles, Maria T

2018-04-10

Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication. and methods: By flow cytometry, we characterized the phenotype and function of circulating CXCR5-expressing CD8T-cells in HIV-infected patients with natural or HAART-induced control of HIV replication. Circulating CXCR5-expressing CD8T-cells exhibited low or null expression of the C-C chemokine receptor type 7 (CCR7) and had a transitional memory phenotype. Particular redistributions of CXCR5-expressing CD8T-cells were found in HIV-infected patients, and they were partially restored by HAART. The frequency of CXCR5CCR7CD8T-cells was higher in spontaneous HIV controllers and negatively correlated with plasma HIV RNA levels. Total and HIV-specific CXCR5CD8T-cells were major producers of interleukin-21, and this function was positively associated with their interferon-γ production. Circulating CXCR5-expressing CD8T-cells are associated with low level HIV replication, could be novel correlates of protection and potentially useful in the eradication of HIV reservoirs.

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

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

2018-01-01

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

A qualitative study exploring attitudes and perceptions of HIV ...

African Journals Online (AJOL)

Aim The study explored knowledge, attitudes and practices of HIV positive women who were instructed to stop breastfeeding at 6 months to prevent the transmission of HIV to their children. Methods We used qualitative methods consisting of key informant interviews (KII), critical incidence narratives (CINs), focus group ...

A cross-sectional study of bacterial vaginosis, intravaginal practices and HIV genital shedding; implications for HIV transmission and women's health.

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Alcaide, Maria L; Chisembele, Maureen; Malupande, Emeria; Arheart, Kristopher; Fischl, Margaret; Jones, Deborah L

2015-11-09

Bacterial vaginosis (BV) is associated with an increased risk of HIV transmission, and intravaginal practices (IVP) are an important risk factor for developing BV. The relationship between IVP, BV and HIV lower genital shedding, responsible for HIV transmission, has not been examined in women receiving antiretrovirals in Zambia. Cross-sectional study. Community Health Center in Lusaka, Zambia. Participants were HIV-infected women receiving antiretroviral therapy and engaging in IVP (n=128). Participants completed audio computer-administered self-interviews to assess IVP and underwent a vaginal examination. BV was diagnosed using Nugent criteria. HIV-1 lower genital shedding was assessed by measuring HIV-1 RNA in cervicovaginal lavages. Most women engaged in IVP daily (114, 89.0%) and 81 (63.3%) of the participants had BV. HIV-1 genital shedding was detected in 18 (14.2%) participants. BV was associated with daily use of IVP (prevalence ratio, PR=4.58, CI 1.26 to 16.64, p=0.02) and weekly use of traditional medicines for IVP (PR=1.33, CI 1.05 to 1.68, p=0.02). The only factor associated with HIV-1 lower genital shedding was plasma viraemia (PR=4.61, CI 2.02 to 10.54, pHIV shedding. Despite the frequency of IVP and high prevalence of BV, plasma viraemia was the primary factor associated with HIV lower genital shedding. These findings support early initiation of antiretrovirals as an HIV prevention tool. Given adverse health outcomes associated with BV, the association between frequent IVP and BV, and the powerful local norms and traditions encouraging IVP, there is a need for studies assessing culturally tailored interventions to decrease BV in high-prevalence settings. 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/

Placental vascular complications in HIV-infected pregnant women: a case-control study

OpenAIRE

CANLORBE, Geoffroy

2012-01-01

Background: Data from international literature suggest a link between HIV infection and placental vascular complications during pregnancy. Current studies on the subject are conflicting.Objective: The aim of the study was to evaluate the incidence of placental vascular complications during pregnancy among HIV+ and HIV- patients.Study Design: It is a single-center case-control study comparing the rates of gestational hypertension, preeclampsia, eclampsia and vascular intrauterine growth retard...

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Perceived HIV-associated stigma among HIV-seropositive men: psychometric study of HIV stigma scale

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Adrian eValle

2015-07-01

Full Text Available Objectives: To assess the internal consistency and factor structure of the abridged Spanish version of the Berger HIV Stigma Scale (HSS-21, provide evidence for its convergent and discriminant validity, and describe perceived stigma in an urban population from northeast Mexico. Methods: Seventy five HIV-positive men who have sex with men (MSM were recruited. Participants answered the Spanish versions of three Likert-type scales: HSS-21, Robsenberg’s self-esteem scale, and the abbreviated version of the Zung’s Depression Scale.Results: HSS-21 showed high reliability and validity; its factor structure included four components: concern with public attitudes; negative self-image; disclosure concerns; and enacted stigma. The level of stigma was high in 27 out of 75 (36% participants; nevertheless, the score found in the component related to disclosure concerns indicated high level of stigma in 68% of participants. The score of HSS-21 was positively correlated with the score of depression and negatively correlated with the score of self-esteem. Conclusion: Results demonstrated high reliability for the HSS-21; correlations with other scales supported its validity. This scale demonstrated to be a practical tool for assessing stigma among Mexican HIV-positive MSM. High level of stigma was found only in the factor related to disclosure concerns. Policy Implications: Identifying HIV-associated stigma through a short, reliable and validated instrument will allow the development of interventions that cope and manage stigma in HIV-positive MSM. HSS-21 distinguishes between different dimensions of stigma and will contribute to a better understanding of this phenomenon.

HIV infection returning to Mexico with migrant workers: an exploratory study.

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Sowell, Richard L; Holtz, Carol S; Velasquez, Gabriela

2008-01-01

Men migrating to the United States are at high risk of acquiring HIV and spreading it to their wives and children in Mexico. Yet there is limited understanding of this phenomenon from the perspective of these men and their wives. This exploratory study used face-to-face interviews to gain insight into factors influencing the increased risk of Mexican men migrating to the United States for contracting HIV as well as the consequences of their infections on returning to Mexico. Transcripts from audiotaped interviews provided the data for analysis. Thematic analysis revealed two overall categories and six interrelated themes. Categories were HIV Risk and Living with HIV. Study themes included social isolation, lack of knowledge/denial, machismo, powerlessness, and making the best of it. Results provide new insight into the spread of HIV in rural Mexico.

HIV Interventions to Reduce HIV/AIDS Stigma: A Systematic Review

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Banks, Bahby; Jonas, Dan; Miles, Margaret Shandor; Smith, Giselle Corbie

2011-01-01

We reviewed the literature to determine the effectiveness of HIV-related interventions in reducing HIV/AIDS stigma. Studies selected had randomized controlled trial (RCT), pretest–posttest with a non-randomized control group, or pretest–posttest one group study designs in which HIV-related interventions were being evaluated, and in which HIV/AIDS stigma was one of the outcomes being measured. A checklist was used to extract data from accepted studies, assess their internal validity, and overall quality. Data were extracted from 19 studies, and 14 of these studies demonstrated effectiveness in reducing HIV/ AIDS stigma. Only 2 of these 14 effective studies were considered good studies, based on quality, the extent to which the intervention focused on reducing HIV/AIDS stigma, and the statistics reported to demonstrate effectiveness. Future studies to reduce HIV/AIDS stigma could improve by designing interventions that pay greater attention to internal validity, use validated HIV/AIDS stigma instruments, and achieve both statistical and public health significance. PMID:21088989

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

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

2017-07-01

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

Hormonal levels among HIV-1-seropositive women compared with high-risk HIV-seronegative women during the menstrual cycle. Women's Health Study (WHS) 001 and WHS 001a Study Team.

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Cu-Uvin, S; Wright, D J; Anderson, D; Kovacs, A; Watts, D H; Cohn, J; Landay, A; Reichelderfer, P S

2000-10-01

There is a paucity of normative data on hormonal levels among HIV-infected women. Hormonal levels may influence fertility and HIV-related immunological and virological factors. The objective of this study was to determine progesterone and estradiol levels during the menstrual cycle in HIV-seropositive women compared with high-risk seronegative women. The study enrolled 55 HIV-infected and 10 high-risk uninfected women with self-reported regular menstrual cycles (25-30-day cycles). Progesterone and estradiol levels were determined on a weekly basis for 8 weeks. The analysis included evaluations from the first complete menstrual cycle for the 54 HIV-infected and 9 uninfected women who had at least one complete cycle. The median age was 35 years for HIV-infected women and 36 years for uninfected women. The median CD4+ count for HIV-seropositive women was 210 cells/mm3. The median menstrual cycle length was 28 days (range 22-49 days) for HIV-infected women and 25 days (range 24-44 days) for uninfected women. The maximum progesterone level during the luteal phase was normal (>3.0 ng/ml) for 52 (96%) of 54 HIV-seropositive women and 7 (78%) of 9 HIV-seronegative women (p = 0.09, Fisher's exact test). The median maximum progesterone level was 12.2 ng/ml in HIV-seropositive women and 7.2 ng/ml in HIV-seronegative women (p = 0.07, Wilcoxon test). The median maximum estradiol value during the follicular phase was 148 pg/ml for HIV-seropositive women and 111 pg/ml for HIV-seronegative women (p = 0.04, Wilcoxon test). Among HIV-infected women, there were no significant differences in progesterone and estradiol levels by antiretroviral therapy, baseline plasma viral load, or median CD4+ cell count. We conclude that HIV-infected women with self-reported normal menstrual cycles have normal levels of progesterone and estradiol during the menstrual cycle.

The Internet and HIV study: design and methods

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Elford Jonathan

2004-09-01

Full Text Available Abstract Background The Internet provides a new meeting ground, especially for gay men, that did not exist in the early 1990s. Several studies have found increased levels of high risk sexual behaviour and sexually transmissible infections (STI among gay men who seek sex on the Internet, although the underlying processes are not fully understood. Research funded by the UK Medical Research Council (2002–2004 provided the opportunity to consider whether the Internet represents a new sexual risk environment for gay and bisexual men living in London. Methods The objectives of the Internet and HIV study are to: (i measure the extent to which gay men living in London seek sexual partners on the Internet; (ii compare the characteristics of London gay men who do and do not seek sex on the Internet; (iii examine whether sex with Internet-partners is less safe than with other sexual partners; (iv compare use of the Internet with other venues where men meet sexual partners; (v establish whether gay men use the Internet to actively seek partners for unprotected anal intercourse; (vi determine the potential for using the Internet for HIV prevention. These objectives have been explored using quantitative and qualitative research methods in four samples of London gay men recruited and interviewed both online and offline. The four samples were: (i gay men recruited through Internet chat rooms and profiles; (ii HIV positive gay men attending an NHS hospital outpatients clinic; (iii gay men seeking an HIV test in an NHS HIV testing or sexual health clinic; (iv gay men recruited in the community. Results Quantitative data were collected by means of confidential, anonymous self-administered questionnaires (n>4000 completed on-line by the Internet sample. Qualitative data were collected by means of one-to-one interviews (n = 128 conducted either face-to-face or on-line. Conclusion The strength of the Internet and HIV study is its methodological plurality, drawing

A qualitative study of vulnerability to HIV infection: Places and ...

African Journals Online (AJOL)

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Methods: A qualitative study employing Focus Group Discussions (FGDs) and ... cope and are subjects to the threats for HIV infection. (2-4). In the era of HIV .... Table 1: Characteristics of participants in focus group discussions. Variable.

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART during acute HIV-1 infection: An observational study.

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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

Protecting HIV information in countries scaling up HIV services: a baseline study.

Science.gov (United States)

Beck, Eduard J; Mandalia, Sundhiya; Harling, Guy; Santas, Xenophon M; Mosure, Debra; Delay, Paul R

2011-02-06

Individual-level data are needed to optimize clinical care and monitor and evaluate HIV services. Confidentiality and security of such data must be safeguarded to avoid stigmatization and discrimination of people living with HIV. We set out to assess the extent that countries scaling up HIV services have developed and implemented guidelines to protect the confidentiality and security of HIV information. Questionnaires were sent to UNAIDS field staff in 98 middle- and lower-income countries, some reportedly with guidelines (G-countries) and others intending to develop them (NG-countries). Responses were scored, aggregated and weighted to produce standard scores for six categories: information governance, country policies, data collection, data storage, data transfer and data access. Responses were analyzed using regression analyses for associations with national HIV prevalence, gross national income per capita, OECD income, receiving US PEPFAR funding, and being a G- or NG-country. Differences between G- and NG-countries were investigated using non-parametric methods. Higher information governance scores were observed for G-countries compared with NG-countries; no differences were observed between country policies or data collection categories. However, for data storage, data transfer and data access, G-countries had lower scores compared with NG-countries. No significant associations were observed between country score and HIV prevalence, per capita gross national income, OECD economic category, and whether countries had received PEPFAR funding. Few countries, including G-countries, had developed comprehensive guidelines on protecting the confidentiality and security of HIV information. Countries must develop their own guidelines, using established frameworks to guide their efforts, and may require assistance in adapting, adopting and implementing them.

The effect of HIV infection and HCV viremia on inflammatory mediators and hepatic injury-The Women's Interagency HIV Study.

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Sheila M Keating

Full Text Available Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18, ART-treated HIV-controlled (ARTc, n = 20, uncontrolled on anti-retroviral therapy (ARTuc, n = 21 and elite HIV controllers (Elite, n = 20. All were HCV seroreactive and had either resolved (HCV RNA-; <50IU/mL or had chronic HCV infection (HCV RNA+. In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.

Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

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Pérez, Yolanda; Gómara, Maria José; Yuste, Eloísa; Gómez-Gutierrez, Patricia; Pérez, Juan Jesús; Haro, Isabel

2017-08-25

Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.

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Romiti, M L; Colognesi, C; Cancrini, C; Mas, A; Berrino, M; Salvatori, F; Orlandi, P; Jansson, M; Palomba, E; Plebani, A; Bertran, J M; Hernandez, M; de Martino, M; Amoroso, A; Tovo, P A; Rossi, P; Espanol, T; Scarlatti, G

2000-01-01

A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults. To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors. No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010). Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.

Sero-prevalence of latent Toxoplasma gondii infection among HIV-infected and HIV-uninfected people in Addis Ababa, Ethiopia: A comparative cross-sectional study

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Tegbaru Belete

2009-10-01

Full Text Available Abstract Background Toxoplasmosis in immuno-compromised hosts manifests primarily as a life threatening condition, toxoplasmic encephalitis. However, there is scarce information about the magnitude of Toxoplasma gondii infection among HIV-infected people in Ethiopia. This study was, therefore, conducted to determine the sero-prevalence of T. gondii infection among HIV-infected and HIV-uninfected subjects. Findings Sera were collected from people with and without HIV infection for the purpose of studying hepatitis B virus (HBV at St. Paul Hospital, Addis Ababa, Ethiopia from 24 January 2007 to 15 February 2007. Among these sera, the first 330 consecutive sera, 165 from each HIV sero-group, were selected and tested for anti-T. gondii IgG antibodies using Enzyme Linked Immunosorbent Assay. The seroprevalence of Toxoplasma infection was assessed against socio-demographic characteristics, HIV and HBV serostatus and HBV-related risk factors. The overall sero-prevalence of latent T. gondii infection among the study subjects was 90.0%. Toxoplasma infection was observed with respective prevalence of 93.3% and 86.7% among HIV-infected and HIV-uninfected people. Though Toxoplasma infection seems to be influenced by age, gender and HIV serostatus, only HBV serostatus was significantly associated (OR 2.71, CI 1.12 to 6.57 in multivariate logistic regression analysis. Conclusion The seroprevalence of latent T. gondii infection is high and similar by HIV status. Educating people to prevent acquisition of new Toxoplasma infection and minimizing the risk of disease manifestations among HIV-Toxoplasma co-infected individuals is important.

HIV Latency Reversing Agents have diverse effects on Natural Killer Cell Function

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Carolina Garrido

2016-09-01

Full Text Available In an effort to clear persistent HIV infection, and achieve a durable therapy-free remission of HIV disease, extensive pre-clinical studies and early pilot clinical trials are underway to develop and test agents that can reverse latent HIV infection and present viral antigen to the immune system for clearance. It is therefore critical to understand the impact of latency reversing agents (LRAs on the function of immune effectors needed to clear infected cells. We assessed the impact of LRAs on the function of natural killer (NK cells, the main effector cells of the innate immune system. We studied the effects of three histone deacetylase inhibitors (SAHA or vorinostat, romidepsin and panobinostat and two protein kinase C (PKC agonists (prostratin and ingenol on the antiviral activity, cytotoxicity, cytokine secretion, phenotype and viability of primary NK cells. We found that ex vivo exposure to vorinostat had minimal impact on all parameters assessed, while panobinostat caused a decrease in NK cell viability, antiviral activity and cytotoxicity. Prostratin caused NK cell activation and interestingly, improved antiviral activity. Overall, we found that LRAs can alter the function and fate of NK cells, and these effects must be carefully considered as strategies are developed to clear persistent HIV infection.

Pilot study of risk behaviour, voluntary HIV counselling and HIV antibody testing from saliva among inmates of prisons in Slovakia.

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Staneková, D; Ondrejka, D; Habeková, M; Wimmerová, S; Kucerková, S

2001-05-01

To implement a pilot study of risk behaviour and HIV infection using HIV antibody testing from saliva to improve the situation as regards HIV/AIDS infection in prison institutions in the Slovak Republic. The study comprised adult and juvenile males of grade one correction categories and prisoners from the prison for juveniles in Martin, as well as females prisoners in Nitra. Preventive activities were implemented in May 1998 in the form of discussions concerning topics related to HIV/AIDS infection. Saliva was collected for the presence of HIV antibodies and a questionnaire regarding sexual practice was completed. 32 persons [8 adult males (25%), 6 juvenile males (18.7%) and 18 females (56%)] were voluntarily tested for the presence of HIV antibodies in saliva. Nobody was HIV-positive. 75 persons (20 adult males, 30 juvenile males and 25 females) were involved in the study of risk behaviour. 40.8% participants had primary education, 28.2% secondary education, 2.8% were students of universities and 28.2% were apprenticies. 60% inmates (mostly females) were religious. Juvenile males reported the highest number of partners while females the smallest (p prison while 19%, 5.6% and 8.3% in the prison, respectively. Paid sexual services were offered by 9.1% females, 15.8% adult males and 25% juvenile males. Outside prison adult and juvenile males used non-sterile used syringes as well as tattooing more often than females (p prisoners.

Urine-Based Nested PCR for the Diagnosis of Mycobacterium tuberculosis: A Comparative Study Between HIV-Positive and HIV-Negative Patients.

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Jamshidi Makiani, Mahin; Davoodian, Parivash; Baghershiroodi, Mahnaz; Nejatizadeh, Abdol Azim; Fakkhar, Farideh; Zangeneh, Mehrangiz; Jahangiri, Nadia

2016-08-01

While tuberculosis (TB) can be diagnosed by microscopy and culture, the sensitivity of Ziehl-Neelsen staining is variable and culture results require 4 - 8 weeks to be determined. Polymerase chain reaction (PCR) and its modifications, including nested PCR, might be promising methods for the rapid diagnosis of TB. This study aimed to evaluate the performance of nested PCR on urine samples of human immunodeficiency virus (HIV)-positive and -negative patients with different manifestations of clinical TB. In a prospective study, three early-morning urine samples from 100 patients with pulmonary TB (PTB) or extrapulmonary TB (EPTB) were evaluated using a molecular target with insertion element IS6110, specific to the Mycobacterium tuberculosis genome, and nested PCR was performed. The results were analyzed with SPSS version 22. A total of 100 patients, including 74 (74%) with PTB and 26 (26%) with EPTB, were enrolled. Positive smears were seen in 38 patients (38%). Lymph nodes were the most commonly involved organ in 14 of the 26 (53.8%) EPTB patients (13.5%). Seven (23.1%) of the EPTB patients were HIV-positive. Urine PCR was positive in only 28 patients (28%). Seven HIV-positive patients with PTB showed positive urine PCR results. Moreover, PCR results were positive in only one of the seven HIV-positive subjects with EPTB. Positive PCR results were found in 20 of the 73 HIV-negative patients (27.4%) and in 8 of the 27 HIV-positive patients (29.6%). Therefore, there was no significant difference between the HIV-negative and HIV-positive patients for urine PCR (sensitivity 29.6%, specificity 72.6%; positive and negative predictive values 28% and 72%, respectively; P = 0.138). Nested PCR showed the same sensitivity in HIV-positive and HIV-negative patients. It can be applied as a rapid technique for the diagnosis of TB.

High frequency of Fredrickson's phenotypes IV and IIb in Brazilians infected by human immunodeficiency virus

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Oliveira Helena CF

2005-06-01

Full Text Available Abstract Background Human immunodeficiency virus (HIV infection is very prevalent in Brazil. HIV therapy has been recently associated with coronary heart disease (CHD. Dyslipidemia is a major risk factor for CHD that is frequently described in HIV positive patients, but very few studies have been conducted in Brazilian patients evaluating their lipid profiles. Methods In the present work, we evaluated the frequency and severity of dyslipidemia in 257 Brazilian HIV positive patients. Two hundred and thirty-eight (93% were submitted to antiretroviral therapy (224 treated with protease inhibitors plus nucleoside reverse transcriptase inhibitors, 14 treated only with the latter, 12 naive and 7 had no records of treatment. The average time on drug treatment with antiretroviral therapy was 20 months. None of the patients was under lipid lowering drugs. Cholesterol, triglyceride, phospholipid and free fatty acids were determined by enzymatic colorimetric methods. Lipoprotein profile was estimated by the Friedewald formula and Fredrickson's phenotyping was obtained by serum electrophoresis on agarose. Apolipoprotein B and AI and lipoprotein "a" were measured by nephelometry. Results The Fredrickson phenotypes were: type IIb (51%, IV (41%, IIa (7%. In addition one patient was type III and another type V. Thirty-three percent of all HIV+ patients presented serum cholesterol levels ≥ 200 mg/dL, 61% LDL-cholesterol ≥ 100 mg/dL, 65% HDL-cholesterol below 40 mg/dL, 46% triglycerides ≥ 150 mg/dL and 10% have all these parameters above the limits. Eighty-six percent of patients had cholesterol/HDL-cholesterol ratio ≥ 3.5, 22% increased lipoprotein "a", 79% increased free fatty acids and 9% increased phospholipids. The treatment with protease inhibitors plus nucleoside reverse transcriptase inhibitors increased the levels of cholesterol and triglycerides in these patients when compared with naïve patients. The HDL-cholesterol (p = 0.01 and

Computer vision and machine learning for robust phenotyping in genome-wide studies.

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Zhang, Jiaoping; Naik, Hsiang Sing; Assefa, Teshale; Sarkar, Soumik; Reddy, R V Chowda; Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh K

2017-03-08

Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems.

Two-year prospective study of major depressive disorder in HIV-infected men.

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Atkinson, J Hampton; Heaton, Robert K; Patterson, Thomas L; Wolfson, Tanya; Deutsch, Reena; Brown, Stephen J; Summers, J; Sciolla, A; Gutierrez, R; Ellis, Ronald J; Abramson, Ian; Hesselink, John R; McCutchan, J Allen; Grant, Igor

2008-06-01

The risks and factors contributing to major depressive episodes in HIV infection remain unclear. This 2-year prospective study compared cumulative rates and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297) and uninfected (HIV-) risk-group controls (N=90). By design participants at entry were without current major depression, substance dependence or major anxiety disorder. Standardized neuromedical, neuropsychological, neuroimaging, life events, and psychiatric assessments (Structured Clinical Interview for DSM III-R) were conducted semi-annually for those with AIDS, and annually for all others. Lifetime prevalence of major depression or other psychiatric disorder did not differ at baseline between HIV+ men and controls. On a two-year follow-up those with symptomatic HIV disease were significantly more likely to experience a major depressive episode than were asymptomatic HIV+ individuals and HIV-controls (pdepression. After baseline disease stage and medical variables associated with HIV infection were controlled, a lifetime history of major depression, or of lifetime psychiatric comorbidity (two or more psychiatric disorders), predicted subsequent major depressive episode (pdepressive episode. Research cohort of men examined before era of widespread use of advanced anti-HIV therapies. Symptomatic HIV disease, but not HIV infection itself, increases intermediate-term risk of major depression. Prior psychiatric history most strongly predicted future vulnerability.

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

NARCIS (Netherlands)

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

2012-01-01

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

Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

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Archer, John; Weber, Jan; Henry, Kenneth; Winner, Dane; Gibson, Richard; Lee, Lawrence; Paxinos, Ellen; Arts, Eric J; Robertson, David L; Mimms, Larry; Quiñones-Mateu, Miguel E

2012-01-01

HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences) and genotypic (e.g., population sequencing linked to bioinformatic algorithms) assays are the most widely used. Although several next-generation sequencing (NGS) platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences), Illumina®, and Ion Torrent™ (Life Technologies). Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels) and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

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John Archer

Full Text Available HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5 viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences and genotypic (e.g., population sequencing linked to bioinformatic algorithms assays are the most widely used. Although several next-generation sequencing (NGS platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences, Illumina®, and Ion Torrent™ (Life Technologies. Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used, compared to Trofile (80% and population sequencing (70%. In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

Sample size calculation in metabolic phenotyping studies.

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Billoir, Elise; Navratil, Vincent; Blaise, Benjamin J

2015-09-01

The number of samples needed to identify significant effects is a key question in biomedical studies, with consequences on experimental designs, costs and potential discoveries. In metabolic phenotyping studies, sample size determination remains a complex step. This is due particularly to the multiple hypothesis-testing framework and the top-down hypothesis-free approach, with no a priori known metabolic target. Until now, there was no standard procedure available to address this purpose. In this review, we discuss sample size estimation procedures for metabolic phenotyping studies. We release an automated implementation of the Data-driven Sample size Determination (DSD) algorithm for MATLAB and GNU Octave. Original research concerning DSD was published elsewhere. DSD allows the determination of an optimized sample size in metabolic phenotyping studies. The procedure uses analytical data only from a small pilot cohort to generate an expanded data set. The statistical recoupling of variables procedure is used to identify metabolic variables, and their intensity distributions are estimated by Kernel smoothing or log-normal density fitting. Statistically significant metabolic variations are evaluated using the Benjamini-Yekutieli correction and processed for data sets of various sizes. Optimal sample size determination is achieved in a context of biomarker discovery (at least one statistically significant variation) or metabolic exploration (a maximum of statistically significant variations). DSD toolbox is encoded in MATLAB R2008A (Mathworks, Natick, MA) for Kernel and log-normal estimates, and in GNU Octave for log-normal estimates (Kernel density estimates are not robust enough in GNU octave). It is available at http://www.prabi.fr/redmine/projects/dsd/repository, with a tutorial at http://www.prabi.fr/redmine/projects/dsd/wiki. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Testing HIV positive in pregnancy: A phenomenological study of women's experiences.

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Lingen-Stallard, Andrew; Furber, Christine; Lavender, Tina

2016-04-01

globally women receive HIV testing in pregnancy; however, limited information is available on their experiences of this potentially life-changing event. This study aims to explore women's experiences of receiving a positive HIV test result following antenatal screening. a qualitative, phenomenological approach. two public National Health Service (NHS) hospitals and HIV support organisations. a purposive sampling strategy was used. Thirteen black African women with a positive HIV result, in England, participated. data were collected using in-depth semi-structured interviews. An interpretive phenomenological approach to data analysis was used. the emergent phenomenon was transition and transformation of 'being,' as women accepted HIV as part of their lives. Paired themes support the phenomenon: shock and disbelief; anger and turmoil; stigma and confidentiality issues; acceptance and resilience. Women had extreme reactions to their positive HIV diagnosis, compounded by the cultural belief that they would die. Initial disbelief of the unexpected result developed into sadness at the loss of their old self. Turmoil was evident, as women considered termination of pregnancy, self-harm and suicide. Women felt isolated from others and relationship breakdowns often occurred. Most reported the pervasiveness of stigma, and how this was managed alongside living with HIV. Coping strategies included keeping HIV 'secret' and making their child(ren) the prime focus of life. Growing resilience was apparent with time. this study gives midwives unique understanding of the complexities and major implications for women who tested positive for HIV. Women's experiences resonated with processes of bereavement, providing useful insight into a transitional and transformational period, during which appropriate support can be targeted. midwives are crucial in improving the experience of women when they test HIV positive and to do this they need to be appropriately trained. Midwives need to

a comparative study among HIV sero-positive and HIV sero-negative

African Journals Online (AJOL)

ABEOLUGBENGAS

Effects of malaria and human immunodeficiency virus co-infection during pregnancy. International Journal of. Health Sciences.2009;2(3):237-243. 2. Whitworth J. Malaria and HIV. Available from: http://hivinsite.ucsf.edu/insite? Page=kb05/04-. 04. [Last accessed on 2013 Jul 15]. 3. Abu-Raddad L. HIV and malaria: a vicious.

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

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

2007-12-01

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

Prediction of disease and phenotype associations from genome-wide association studies.

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Stephanie N Lewis

Full Text Available Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases.Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits.The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV pseudovirions

International Nuclear Information System (INIS)

Devitt, Gerard; Emerson, Vanessa; Holtkotte, Denise; Pfeiffer, Tanya; Pisch, Thorsten; Bosch, Valerie

2007-01-01

Low level incorporation of the viral glycoprotein (Env) into human immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies against HIV/AIDS in which HIV particles are used as immunogen. Within this study, we have examined two strategies aimed at achieving higher levels of Env incorporation into non-infectious pseudovirions (PVs). First, we have generated chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of simian immunodeficiency virus (SIV)mac239-Env767 stop , which mediates strongly increased incorporation of SIV-Env into SIV particles. In a second strategy, we have employed a truncated HIV-Env protein (Env-Tr752 N750K ) which we have previously demonstrated to be incorporated into HIV virions, generated in infected T-cells, to a higher level than that of Wt-HIV-Env. Although the chimeric HIV/SIV Env proteins were expressed at the cell surface and induced increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env-Tr752 N750K exhibited significantly higher (threefold) levels of incorporation into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the large-scale preparation of non-infectious PVs for vaccine studies aimed at inducing Env humoral responses

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.

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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.

Potential roles for uncoupling proteins in HIV lipodystrophy.

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Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

Factors associated with delayed entry into HIV medical care after HIV diagnosis in a resource-limited setting: Data from a cohort study in India

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Gerardo Alvarez-Uria

2013-06-01

Full Text Available Studies from sub-Saharan Africa have shown that a substantial proportion of patients diagnosed with HIV enter into HIV medical care late. However, data from low or middle-income countries outside Africa are scarce. In this study, we investigated risk factors associated with delayed entry into care stratified by gender in a large cohort study in India. 7701 patients were diagnosed with HIV and 5410 entered into care within three months of HIV diagnosis. Nearly 80% entered into care within a year, but most patients who did not enter into care within a year remained lost to follow up or died. Patient with risk factors related to having a low socio-economic status (poverty, being homeless, belonging to a disadvantaged community and illiteracy were more likely to enter into care late. In addition, male gender and being asymptomatic at the moment of HIV infection were factors associated with delayed entry into care. Substantial gender differences were found. Younger age was found to be associated with delayed entry in men, but not in women. Widows and unmarried men were more likely to enter into care within three months. Women belonging to disadvantaged communities or living far from a town were more likely to enter into care late. The results of this study highlight the need to improve the linkage between HIV diagnosis and HIV treatment in India. HIV programmes should monitor patients diagnosed with HIV until they engage in HIV medical care, especially those at increased risk of attrition.

HIV associated hypocalcaemia among diarrheic patients in northwest Ethiopia: a cross sectional study.

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Moges, Beyene; Amare, Bemnet; Yabutani, Timoki; Kassu, Afework

2014-07-04

Hypocalcaemia, defined by serum calcium level less than 8.5 mg/dl, could be caused by human immunodeficiency virus (HIV) and diarrheal diseases. In Ethiopia, while morbidities from diarrheal diseases and HIV are serious health problems, studies assessing the interactions amongst of the three do not exist. Therefore, the present study was undertaken to investigate the level of calcium among diarrheic patients with and without HIV co-infection. Consecutive diarrheic patients attending Gondar University Hospital in Ethiopia were enrolled and screened for HIV, intestinal parasites, Shigella and Salmonella. Concentration of calcium in serum was determined using an inductively coupled plasma mass spectrometer. A total of 206 diarrheic patients were included in the study (109 = HIV positive, 97 = HIV negative). Intestinal parasites and Shigella species were detected in 32.2% and 8.5% of the patients, respectively. The serum calcium levels in the patients who were found positive for Shigella species or intestinal parasites was not significantly different by the presence or absence of HIV co-infection. HIV infected diarrheic patients had significantly lower mean serum calcium levels (7.82 ± 1.23 mg/dl) than those negative for HIV (8.38 ± 1.97) (P = 0.015). The age groups 25-35 and greater than 45 years showed significantly lower mean serum calcium levels (7.77 ± 1.55 mg/dl) in comparison to the other age groups (7.84 ± 1.41 mg/dl, P = 0.009). On the other hand, females presented with significantly lower mean serum calcium levels (7.79 ± 1.60 mg/dl, P = 0.044) than males (8.26 ± 1.65 mg/dl). There is high prevalence of hypocalcaemia among diarrheic patients in northwest Ethiopia. And HIV stood out to be a major risk factor for development of hypocalcaemia among the diarrheic patients in northwest Ethiopia. Further studies are required to substantiate and characterize the mechanisms and consequences of calcium metabolism disorders among HIV infected individuals in the

HIV/AIDS among American Indians/Alaska Natives Living in Montana: A Descriptive Study

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Sondag, K. Ann; Strike, Carrie

2011-01-01

This study examined the epidemiology of HIV among AI/ANs in Montana. Barriers to HIV testing and motivations to test also were explored. Analysis of data revealed that there were no significant changes in regard to HIV/AIDS case rates, demographic characteristics, or risk behaviors of AI/ANs infected with HIV/AIDS since reporting began in 1985.…

Gastrointestinal viral load and enteroendocrine cell number are associated with altered survival in HIV-1 infected individuals.

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Guido van Marle

Full Text Available Human immunodeficiency virus type 1 (HIV-1 infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS. The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM enrolled pre-HAART (Highly Active Antiretroviral Therapy. We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum and somatostatin (duodenum and colon immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.

Targeting cFMS signaling to restore immune function and eradicate HIV reservoirs

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Gerngross, Lindsey

While combination anti-retroviral therapy (cART) has improved the length and quality of life of individuals living with HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HAND) has increased and remains a significant clinical concern. The neuropathogenesis of HAND is not completely understood, however, latent HIV infection in the central nervous system (CNS) and chronic neuroinflammation are believed to play a prominent role. CNS-associated macrophages and resident microglia are significant contributors to CNS inflammation and constitute the chief reservoir of HIV-1 infection in the CNS. Previous studies from our lab suggest monocyte/macrophage invasion of the CNS in HIV may be driven by altered monocyte/macrophage homeostasis. We have reported expansion of a monocyte subset (CD14+CD16 +CD163+) in peripheral blood of HIV+ patients that is phenotypically similar to macrophages/microglia that accumulate in the CNS as seen in post-mortem tissue. The factors driving the expansion of this monocyte subset are unknown, however, signaling through cFMS, a type III receptor tyrosine kinase (RTK), may play a role. Macrophage-colony stimulating factor (M-CSF), a ligand of cFMS, has been shown to be elevated in the cerebral spinal fluid (CSF) of individuals with the most severe form of HAND, HIV-associated dementia (HAD). M-CSF promotes a Macrophage-2-like phenotype and increases CD16 and CD163 expression in cultured monocytes. M-CSF has also been shown to increase the susceptibility of macrophages to HIV infection and enhance virus production. These findings, in addition to the known function of M-CSF in promoting macrophage survival, supports a role for M-CSF in the development and maintenance of macrophage viral reservoirs in tissues where these cells accumulate, including the CNS. Interestingly, a second ligand for cFMS, IL-34, was recently identified and reported to share some functions with M-CSF, suggesting that both ligands may contribute to HIV

Salivary IgA and dental caries in HIV patients: A pilot study.

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Acharya, Sonu; Mandal, Pradip Kumar

2016-01-01

The interrelationship of human immunodeficiency virus (HIV) infection and dental caries, as well as Salivary IgA (S-IgA) level, appear to remain underexplored while a manual and electronic search of the literature was made. Hence, this study was undertaken to assess the relationship of S-IgA and dental caries status in HIV +ve children. The aim of this study was to find out the relationship of S-IgA antibody with dental caries by measuring the concentration of IgA in saliva of HIV +ve and HIV -ve children and to determine the dental caries status in HIV +ve and HIV -ve children, which may help in treatment planning and prevention of the same. Twenty-eight HIV +ve children aged between 6 and 14 years and 28 age matched HIV -ve children were included in this study, and both samples were randomly selected from the same nongovernmental organization (NGO). The HIV status of both these samples was confirmed from their medical records provided by the NGO. 2 cc of unstimulated saliva was collected from both groups in special tubes coded numerically using the method described by Collins and Dawes, and the samples were analyzed to measure the concentration of IgA using commercially available ELISA kit (DRG Diagnostics, Germany). Examination of dental caries was carried out according to the WHO criteria (1997) using a flat mouth mirror and Community periodontal index (CPI) probe. In HIV +ve group, mean salivary IgA level was calculated as 81.61 ± 6.20 μg/ml, mean decayed, missing, filled teeth (DMFT) was 3.86 ± 3.37, mean decayed, extracted and filled teeth (deft) was 4.75 ± 2.86. In HIV -ve group, the mean salivary IgA level was calculated as 145.57 ±17.83 μg/ml, mean DMFT was 2.54 ± 0.69, mean deft was 2.43 ± 2.01. Strong -ve correlation between S-IgA and DMFT (r = -0.781, t = 6.38, P 0.05) between S-IgA and deft was found in HIV +ve group. Strong -ve correlation between S-IgA and DMFT (r = -0.655, t = 4.42, P caries than normal individuals.

Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa.

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Goodall, Ruth L; Dunn, David T; Nkurunziza, Peter; Mugarura, Lincoln; Pattery, Theresa; Munderi, Paula; Kityo, Cissy; Gilks, Charles; Kaleebu, Pontiano; Pillay, Deenan; Gupta, Ravindra K

2017-05-01

Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-treated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 (3.4, P  =   0.01). There was a small reduction in tenofovir susceptibility (FC 0.7 and 1.0, respectively, P  =   0.18). Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV-1 phenotype

NARCIS (Netherlands)

Schellekens, P. T.; Tersmette, M.; Roos, M. T.; Keet, R. P.; de Wolf, F.; Coutinho, R. A.; Miedema, F.

1992-01-01

To determine the kinetics of decline of CD4+ lymphocytes in HIV-1-infected asymptomatic homosexual men. CD4+ lymphocytes were enumerated in a cohort of 187 HIV-1-infected initially asymptomatic homosexual men seen at 3-month intervals over 5 years. During follow-up, 45 men progressed to AIDS

Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

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Enkhmaa, Byambaa; Anuurad, Erdembileg; Zhang, Wei; Li, Chin-Shang; Kaplan, Robert; Lazar, Jason; Merenstein, Dan; Karim, Roksana; Aouizerat, Brad; Cohen, Mardge; Butler, Kenneth; Pahwa, Savita; Ofotokun, Igho; Adimora, Adaora A; Golub, Elizabeth; Berglund, Lars

2017-05-01

In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear. The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level ( P =0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4 + T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) ( P =0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes ( P =0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness. Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection. © 2017 American Heart Association, Inc.

A systematic review of measures of HIV/AIDS stigma in paediatric HIV-infected and HIV-affected populations

Science.gov (United States)

McAteer, Carole Ian; Truong, Nhan-Ai Thi; Aluoch, Josephine; Deathe, Andrew Roland; Nyandiko, Winstone M; Marete, Irene; Vreeman, Rachel Christine

2016-01-01

Introduction HIV-related stigma impacts the quality of life and care management of HIV-infected and HIV-affected individuals, but how we measure stigma and its impact on children and adolescents has less often been described. Methods We conducted a systematic review of studies that measured HIV-related stigma with a quantitative tool in paediatric HIV-infected and HIV-affected populations. Results and discussion Varying measures have been used to assess stigma in paediatric populations, with most studies utilizing the full or variant form of the HIV Stigma Scale that has been validated in adult populations and utilized with paediatric populations in Africa, Asia and the United States. Other common measures included the Perceived Public Stigma Against Children Affected by HIV, primarily utilized and validated in China. Few studies implored item validation techniques with the population of interest, although scales were used in a different cultural context from the origin of the scale. Conclusions Many stigma measures have been used to assess HIV stigma in paediatric populations, globally, but few have implored methods for cultural adaptation and content validity. PMID:27717409

A Controlled Study of an HIV/AIDS/STI/TB Intervention with Faith ...

African Journals Online (AJOL)

The aim of the study was to develop an HIV and AIDS training manual, and to evaluate the knowledge, attitudes and management of faith healers of Apostolic churches regarding HIV and AIDS, before and after they attended an HIV and AIDS training programme. A quasi-experimental intervention design was used with faith ...

A serological study of cysticercosis in patients with HIV Estudo sorológico da cisticercose em pacientes com HIV

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Subhash Chandra Parija

2009-08-01

Full Text Available Neurocysticercosis (NCC has attained the importance of one of the most common cause of focal brain lesions in patients infected with HIV (human immunodeficiency virus. Adequate data regarding the rate of this co-infection is lacking. Therefore, the present study was carried out to determine the prevalence of cysticercosis among HIV patients residing in Puducherry or its neighboring districts of Tamil Nadu State, India. A total of one hundred blood samples were collected from HIV seropositive cases visiting JIPMER hospital, Puducherry, between June 2007 and May 2008. Enzyme immunotransfer blot (EITB and enzyme linked immunosorbent assay (ELISA were used to demonstrate anti- T. solium larval stage antibodies and Co-agglutination (Co-A test was used to detect T. solium larval stage antigens in sera. Two HIV seropositive cases were found positive for anti-T. solium larval stage antibody by EITB and four were positive by ELISA. Only one sample was positive by both EITB and ELISA. No serum sample was found positive for T. solium larval stage antigen by Co-A test. The overall seropositivity detected by all the methods was 5% in this study group. The accurate clinical diagnosis of NCC in HIV is difficult due to deranged immunological parameters in the HIV infected patients. The results of this study provides important data on the prevalence of cysticercosis in HIV positive patients in Puducherry and neighboring areas which was previously unknown. This study will also increase awareness among physicians and public health agencies about T. solium cysticercosis in the selected group.Neurocisticercose (NCC tem alcançado a importância de uma das mais comuns causas de lesões focais no cérebro em pacientes infectados pelo HIV (vírus da imunodeficiência adquirida. Dados adequados relativos à frequencia desta co-infecção estão faltando. Portanto, o presente estudo foi realizado para determinar a prevalência da cisticercose entre pacientes com HIV

HIV incidence from the first population-based cohort study in India.

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Dandona, Lalit; Kumar, G Anil; Lakshmi, Vemu; Ahmed, G Md Mushtaq; Akbar, Mohammed; Ramgopal, Sri P; Sudha, Talasila; Alary, Michel; Dandona, Rakhi

2013-07-17

Understanding about who acquires new HIV infection and the determinants of why some persons get infected and others do not is fundamental to controlling HIV in the population. We assess HIV incidence and its associations in the population of a high HIV burden district in Andhra Pradesh state in southern India by a population-based longitudinal cohort study. We re-surveyed a population-based cohort of 12,617 adults in Guntur district of Andhra Pradesh for which we had reported a baseline HIV prevalence of 1.72% (rural 1.64%, urban 1.89%) among the 15-49 years age group in 2004-2005. We conducted interviews to assess risk behaviour and performed HIV testing again in 2010-2011. We assessed the rate of new HIV infection and its associations using multiple logistic regression. The participation rate in the follow-up was 74.9% and 63.9% of the baseline rural and urban samples, respectively. Over a mean follow-up of 5.63 years, the incidence of HIV was 1.26 per 1000 person-years (95% CI 0.83-1.69), after adjusting for slight compositional bias in the follow-up sample. The incidence per 1000 person-years was higher among rural men (1.68) than urban men (0.85), and among rural women (1.28) than urban women (0.54). The strongest association with incidence was a HIV positive spouse in the baseline for both men (odds ratio 266, 95% CI 62-1137) and women (odds ratio 28, 95% CI 9-88). Among men the other significant associations with HIV incidence were frequent use of condom for sex over the past 6 months, non-circumcision, more than one lifetime woman sex partner or ever visited sex worker, and transport-related occupation; for women the other significant associations were having had HIV testing other than antenatal check-up, previously married but currently not, and tobacco use. These first population-based cohort incidence data from India suggest that rural areas of high HIV burden states would need more attention to prevent new HIV infections, and that spouses of HIV

Clinical Improvement by Switching to an Integrase Strand Transfer Inhibitor in Hemophiliac Patients with HIV: The Japan Cohort Study of HIV Patients Infected through Blood Products.

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Kawado, Miyuki; Hashimoto, Shuji; Oka, Shin-Ichi; Fukutake, Katsuyuki; Higasa, Satoshi; Yatsuhashi, Hiroshi; Ogane, Miwa; Okamoto, Manabu; Shirasaka, Takuma

2017-01-01

This study aimed to determine improvement in HIV RNA levels and the CD4 cell count by switching to an antiretroviral regimen with an integrase strand transfer inhibitor (INSTI) in patients with HIV. This study was conducted on Japanese patients with HIV who were infected by blood products in the 1980s. Data were collected between 2007 and 2014. Data of 564 male hemophiliac patients with HIV from the Japan Cohort Study of HIV Patients Infected through Blood Products were available. Changes in antiretroviral regimen use, HIV RNA levels, and the CD4 cell count between 2007 and 2014 were examined. From 2007 to 2014, the proportion of use of a regimen with an INSTI increased from 0.0% to 41.0%. For patients with HIV who used a regimen, including an INSTI, the proportion of HIV RNA levels products. This suggests that performing this switch in clinical practice will lead to favorable effects.

Caregiver perceptions and motivation for disclosing or concealing the diagnosis of HIV infection to children receiving HIV care in Mbarara, Uganda: a qualitative study.

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Julius Kiwanuka

Full Text Available Disclosure of the diagnosis of HIV to HIV-infected children is challenging for caregivers. Despite current recommendations, data suggest that levels of disclosure of HIV status to HIV-infected children receiving care in resource-limited settings are very low. Few studies describe the disclosure process for children in these settings, particularly the motivators, antecedent goals, and immediate outcomes of disclosure to HIV-infected children. This study examined caregivers' perception of the disclosure concept prior to disclosure, their motivation towards or away from disclosure, and their short- and long-term intentions for disclosure to their HIV-infected children.In-depth interviews were conducted with primary caregivers of 40 HIV-infected children (ages 5-15 years who were receiving HIV care but did not know their HIV status.Caregivers of HIV-infected children mainly perceived disclosure as a single event rather than a process of gradual delivery of information about the child's illness. They viewed disclosure as potentially beneficial both to children and themselves, as well as an opportunity to explain the parents' role in the transmission of HIV to the children. Caregivers desired to personally conduct the disclosure; however, most reported being over-whelmed with fear of negative outcomes and revealed a lack of self-efficacy towards managing the disclosure process. Consequently, most cope by deception to avoid or delay disclosure until they perceive their own readiness to disclose.Interventions for HIV disclosure should consider that caregivers may desire to be directly responsible for disclosure to children under their care. They, however, need to be empowered with practical skills to recognize opportunities to initiate the disclosure process early, as well as supported to manage it in a phased, developmentally appropriate manner. The potential role for peer counselors in the disclosure process deserves further study.

An advanced BLT-humanized mouse model for extended HIV-1 cure studies.

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Lavender, Kerry J; Pace, Craig; Sutter, Kathrin; Messer, Ronald J; Pouncey, Dakota L; Cummins, Nathan W; Natesampillai, Sekar; Zheng, Jim; Goldsmith, Joshua; Widera, Marek; Van Dis, Erik S; Phillips, Katie; Race, Brent; Dittmer, Ulf; Kukolj, George; Hasenkrug, Kim J

2018-01-02

Although bone marrow, liver, thymus (BLT)-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: evaluate the GVHD-resistant C57 black 6 (C57BL/6) recombination activating gene 2 (Rag2)γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. Determine whether TKO-BLT mice could be maintained on antiretroviral therapy (ART) for extended periods of time. Assess the rapidity of viral rebound following therapy interruption. TKO-BLT mice were HIV-1 infected, treated with various ART regimens over extended periods of time and assayed for viral rebound following therapy interruption. Daily subcutaneous injection and oral ART-mediated suppression of HIV-1 infection was tested at various doses in TKO-BLT mice. Mice were monitored for suppression of viremia and cellular HIV-1 RNA and DNA prior to and following therapy interruption. Mice remained healthy for 45 weeks posthumanization and could be treated with ART for up to 18 weeks. Viremia was suppressed to less than 200 copies/ml in the majority of mice with significant reductions in cellular HIV-1 RNA and DNA. Treatment interruption resulted in rapid viral recrudescence. HIV-1 latency can be maintained in TKO-BLT mice over extended periods on ART and rapid viral rebound occurs following therapy removal. The additional 15-18 weeks of healthy longevity compared with other BLT models provides sufficient time to examine the decay kinetics of the latent reservoir as well as observe delays in recrudescence in HIV-1 cure studies.

The naked truth about HIV and risk taking in Swedish prisons: A qualitative study.

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Sigrid J A Lindbom

Full Text Available This qualitative study explores former prison inmates' perceptions and attitudes towards HIV risk inside Swedish prisons.In 2014, eight semi-structured interviews were conducted with former male prisoners to gain a deeper understanding of situations perceived to be associated with risk of HIV transmission. The material gathered from the interviews was analyzed by manifest and latent qualitative content analysis.The findings revealed that risky behavioral practices, such as sharing needles, unprotected sexual activity, and lack of openness about HIV status represented potential health threats with regard to the risk of HIV transmission.Evidence from the study indicates that educational interventions regarding HIV and the transmission routes are required for HIV prevention in Swedish prisons.

HIV/AIDS Knowledge, Attitudes and Behaviors Assessment of Chinese Students: A Questionnaire Study

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Chaojun Xie

2007-09-01

Full Text Available The objective of this study was to assess students' knowledge, attitudes and practices on HIV and AIDS. A questionnaire was administered to a cross section of 259 Chinese undergraduates. Respondents were asked to provide information about knowledge and attitudes about HIV/AIDS. Study results indicated that the majority of undergraduates had a moderate level of HIV and AIDS knowledge, acceptance and attitudes towards people with HIV and AIDS. Boys had more acceptance and positive attitudes towards people with HIV and AIDS than girls. Students majoring in medicine performed better (more knowledgeable and accepting than non-medical students. Differences between students with various monthly expenditures were found-- 6.2% of students had 3-5 sexual partners which has rarely been found in Chinese students; most students did not know HIV VCT centers and most students did not show their confidence for controlling of HIV and AIDS in China. In conclusion, students’ knowledge about HIV/AIDS was uneven. A peer educational program to talk about self esteem, healthy sexual attitudes, being human-accepting and loving should be developed in the near future.

Advancing gender equality to improve HIV prevention: A study of practice

OpenAIRE

Mannell, J. C.

2016-01-01

Addressing gender inequality as a social driver of HIV risk and vulnerability has become a key activity of non-governmental organisations (NGOs) in South Africa. This paper sheds light on the factors that influence gender and HIV prevention activities in this context. A multisite ethnographic study including 150 hours of participant observation and 32 in-depth interviews was conducted with 26 NGOs carrying out gender and HIV prevention interventions. Using thematic network a...

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

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Laura Ibáñez

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

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

Platelet function and HIV: a case-control study.

LENUS (Irish Health Repository)

Satchell, Claudette S

2010-03-13

Cardiovascular disease and myocardial infarction are of increasing concern in HIV-infected populations. Although platelets mediate arterial thrombosis, central to myocardial infarction, data on platelet function in HIV infection are lacking. We hypothesized that HIV-infected patients would have altered platelet reactivity.

Depression among HIV/AIDS Sudanese patients: a cross-sectional analytic study.

Science.gov (United States)

Elbadawi, Abdulateef; Mirghani, Hyder

2017-01-01

Depression and HIV/AIDS are common morbid health problems; the relationship is bidirectional exacerbating each other with deleterious consequences. There are limited studies on this topic in Sudan. In this study, we investigated depression among HIV/AIDS in Sudan. A cross-sectional analytic study was conducted among 362 HIV/AIDS patients from three centers in Khartoum, Sudan. Data were collected by the Hospital Depression and Anxiety (HADS) questionnaire. Chi-square was used for testing the significance and a P. Value of ≥ 0.05 was considered as statistically significant. Depression was evident in 332 (63.1%) of patients 68 (19.3%) had mild depression, 114 (32.4%) moderate depression, and 40 (11.4%) severe depression. Depression was commoner among women, illiterate, married/widowed, not receiving counseling, delaying the result of the test, P-value 0.05. Depression was prevalent among HIV/AIDS patients, especially females, low level of education, and widowed/married patients, and those not receiving counseling and post diagnosis sessions.

Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

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

2014-01-01

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

HIV drug resistance testing among patients failing second line antiretroviral therapy. Comparison of in-house and commercial sequencing.

Science.gov (United States)

Chimukangara, Benjamin; Varyani, Bhavini; Shamu, Tinei; Mutsvangwa, Junior; Manasa, Justen; White, Elizabeth; Chimbetete, Cleophas; Luethy, Ruedi; Katzenstein, David

2017-05-01

HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database. Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens. The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

Qualitative study of HIV related stigma and discrimination: What women say in Iran.

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Oskouie, Fatemeh; Kashefi, Farzaneh; Rafii, Forough; Gouya, Mohammad Mehdi

2017-07-01

HIV-related stigma is a major social problem of people living with HIV. Stigma against these people, especially women, interferes with the prevention, diagnosis and treatment of HIV. This study examined the experiences of HIV infected women who were stigmatized, as well as the strategies used to tackle the issue. Twenty-five women living with HIV were examined using in-depth, semi-structured interviews. The data obtained was analyzed using content analysis method in MAXQDA10. The finding of this study was classified into four themes: fear, shame, rejection by family or friends and feelings of frustration. The participant strategies adopted to the perceived stigma and discrimination included isolation, nondisclosure, and loss of follow-up. HIV in women has different social interposition. It is necessary to intervene, so as to alleviate the effect of stigma on HIV infected women, in order that they gain the ability to accomplish wellness, increase life span and improve quality of life. Nurses, midwives and other professionals need to be involved to ensure public policy in providing supportive environments, and decrease stigma.

Modeling viral coevolution: HIV multi-clonal persistence and competition dynamics

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Bagnoli, F.; Liò, P.; Sguanci, L.

2006-07-01

The coexistence of different viral strains (quasispecies) within the same host are nowadays observed for a growing number of viruses, most notably HIV, Marburg and Ebola, but the conditions for the formation and survival of new strains have not yet been understood. We present a model of HIV quasispecies competition, which describes the conditions of viral quasispecies coexistence under different immune system conditions. Our model incorporates both T and B cells responses, and we show that the role of B cells is important and additive to that of T cells. Simulations of coinfection (simultaneous infection) and superinfection (delayed secondary infection) scenarios in the early stages (days) and in the late stages of the infection (years) are in agreement with emerging molecular biology findings. The immune response induces a competition among similar phenotypes, leading to differentiation (quasispeciation), escape dynamics and complex oscillations of viral strain abundance. We found that the quasispecies dynamics after superinfection or coinfection has time scales of several months and becomes even slower when the immune system response is weak. Our model represents a general framework to study the speed and distribution of HIV quasispecies during disease progression, vaccination and therapy.

Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans.

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Min Ni

2013-09-01

Full Text Available Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome. In contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug resistance and enables rapid adaptive evolution. We report here that sexual reproduction generates phenotypic and genotypic diversity in the human pathogenic yeast Cryptococcus neoformans, which is globally distributed and commonly infects individuals with compromised immunity, such as HIV/AIDS patients, causing life-threatening meningoencephalitis. C. neoformans has a defined a-α opposite sexual cycle; however, >99% of isolates are of the α mating type. Interestingly, α cells can undergo α-α unisexual reproduction, even involving genotypically identical cells. A central question is: Why would cells mate with themselves given that sex is costly and typically serves to admix preexisting genetic diversity from genetically divergent parents? In this study, we demonstrate that α-α unisexual reproduction frequently generates phenotypic diversity, and the majority of these variant progeny are aneuploid. Aneuploidy is responsible for the observed phenotypic changes, as chromosome loss restoring euploidy results in a wild-type phenotype. Other genetic changes, including diploidization, chromosome length polymorphisms, SNPs, and indels, were also generated. Phenotypic/genotypic changes were not observed following asexual mitotic reproduction. Aneuploidy was also detected in progeny from a-α opposite-sex congenic mating; thus, both homothallic and heterothallic sexual reproduction can generate phenotypic diversity de novo. Our study suggests that the ability to undergo unisexual reproduction may be an evolutionary strategy for eukaryotic microbial pathogens, enabling de novo genotypic and phenotypic plasticity and facilitating rapid adaptation to novel environments.

Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

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Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Li, Ruili; Li, Hongjun [Capital Medical University, Department of Radiology, Beijing Youan Hospital, Beijing (China); Qiu, Bensheng [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Anhui Computer Application Institute of Traditional Chinese Medicine, Hefei, Anhui (China)

2017-11-15

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

International Nuclear Information System (INIS)

Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan; Li, Ruili; Li, Hongjun; Qiu, Bensheng

2017-01-01

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

HIV stigma and social capital in women living with HIV

OpenAIRE

Cuca, Yvette P.; Asher, Alice; Okonsky, Jennifer; Kaihura, Alphoncina; Dawson-Rose, Carol; Webel, Allison

2016-01-01

Women living with HIV (WLWH) continue to experience HIV-related stigma. Social capital is one resource that could mitigate HIV stigma. Our cross-sectional study examined associations between social capital and HIV-related stigma in 135 WLWH in the San Francisco Bay Area. The mean age of study participants was 48 years; 60% were African American; 29% had less than a high school education; and 19% were employed. Age was significantly associated with perceived HIV stigma (p = .001), but total so...

Incidence and risk factors of herpes zoster among hiv-positive patients in the german competence network for HIV/AIDS (KompNet): a cohort study analysis.

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Jansen, Klaus; Haastert, Burkhard; Michalik, Claudia; Guignard, Adrienne; Esser, Stefan; Dupke, Stephan; Plettenberg, Andreas; Skaletz-Rorowski, Adriane; Brockmeyer, Norbert H

2013-08-10

HIV infection is a risk factor for the development of Herpes zoster (HZ) and its complications. Prior to antiretroviral therapy (ART), HZ incidence in HIV-infected individuals ranged from 2.9-5.1/100 person-years. There is limited evidence for the impact of ART on HZ occurrence among HIV-infected adults. We analysed the incidence of, and risk factors for, HZ in a large cohort of German HIV-positive patients. The study population was taken from the German KompNet cohort, a nationwide multicenter HIV cohort study. The study population was defined by age (≥ 18 years), year of first positive HIV diagnosis, CD4 values ± 6 months from HIV diagnosis (t0), and month of HZ diagnosis. Incidences were estimated using a Poisson distribution, and uni- and multivariate Cox proportional Hazard ratio (HR) regression models were fitted to identify risk factors for developing an initial HZ episode. Independent variables were sex, age at HIV diagnosis, route of HIV transmission, ART status, CD4 count before HZ episode, immunosuppressive medication, and mode of data documentation (retrospective or prospective). HZ incidence in the overall study population was 1.2/100 person-years. In a subset of patients for that we were able to examine risk factors the following was observed: We examined 3,757 individuals whose mean age at t0 was 38 years. Of those individuals, 96% were diagnosed with HIV in 1996 or later, with a mean observation time of 5.8 years. HZ episodes (n = 362) were recorded in 326 patients (8.7%), resulting in annual HZ incidences of 1.7/100 person-years overall, and 1.6/100 person-years for initial HZ cases. The main risk factors associated with an initial HZ episode were: not partaking in ART compared with an ART regimen containing a non-nucleoside reverse-transcriptase inhibitor (HR 0.530, p study HZ incidences were lower than in previous studies relating to HIV-positive patients. We showed that ART is an important protective factor for HZ episodes.

High-dose vitamin D3 reduces deficiency caused by low UVB exposure and limits HIV-1 replication in urban Southern Africans

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Coussens, Anna K.; Naude, Celeste E.; Goliath, Rene; Chaplin, George; Wilkinson, Robert J.; Jablonski, Nina G.

2015-06-01

Cape Town, South Africa, has a seasonal pattern of UVB radiation and a predominantly dark-skinned urban population who suffer high HIV-1 prevalence. This coexistent environmental and phenotypic scenario puts residents at risk for vitamin D deficiency, which may potentiate HIV-1 disease progression. We conducted a longitudinal study in two ethnically distinct groups of healthy young adults in Cape Town, supplemented with vitamin D3 in winter, to determine whether vitamin D status modifies the response to HIV-1 infection and to identify the major determinants of vitamin D status (UVB exposure, diet, pigmentation, and genetics). Vitamin D deficiency was observed in the majority of subjects in winter and in a proportion of individuals in summer, was highly correlated with UVB exposure, and was associated with greater HIV-1 replication in peripheral blood cells. High-dosage oral vitamin D3 supplementation attenuated HIV-1 replication, increased circulating leukocytes, and reversed winter-associated anemia. Vitamin D3 therefore presents as a low-cost supplementation to improve HIV-associated immunity.

A Randomized Study of Incentivizing HIV Testing for Parolees in Community Aftercare.

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Saxena, Preeta; Hall, Elizabeth A; Prendergast, Michael

2016-04-01

HIV risk-behaviors are high in criminal justice populations and more efforts are necessary to address them among criminal justice-involved substance abusers. This study examines the role of incentives in promoting HIV testing among parolees. Participants were randomly assigned to either an incentive (n = 104) or education group (control; n = 98), where the incentive group received a voucher for testing for HIV. Bivariate comparisons showed that a larger proportion of those in the incentive group received HIV testing (59% versus 47%), but this was not statistically significant (p = .09). However, in a multivariate logistic regression model controlling for covariates likely to influence HIV-testing behavior, those in the incentive group had increased odds of HIV testing in comparison to those in the education group (OR = 1.99, p testing and other healthy behaviors in criminal justice populations.

Biological characterization of HIV type 1 envelope V3 regions from mothers and infants associated with perinatal transmission.

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Matala, E; Hahn, T; Yedavalli, V R; Ahmad, N

2001-12-10

Our previous study has shown that the human immunodeficiency virus type 1 (HIV-1) envelope V3 region minor genotypes of infected mothers were transmitted to their infants and predominated initially as a homogeneous virus population in the infants (Ahmad N, Baroudy BM, Baker RC, et al.: J Virol 1995;69:1001-1012). Here we have characterized the biological properties, including cellular tropism, replication efficiency, cytopathic effects, and coreceptor utilization, of these V3 region isolates from mothers and infants. Nineteen V3 region sequences from three mother-infant pairs, including the minor variants of mothers and the major variants of infants as characterized in our previous study, were reciprocally inserted into an HIV-1 infectious molecular clone, pNL4-3, and chimeric viruses were generated by DNA transfections into HeLa cells. Equal amounts of chimeric viruses were then used to infect T lymphocyte cell lines (A3.01 and MT-2), primary blood lymphocytes (PBLs), primary monocyte-derived macrophages (MDMs), and coreceptor cell lines. We found that the V3 region chimeras failed to replicate in T lymphocyte cell lines but replicated in MDMs and PBLs, albeit at reduced levels compared with R5 laboratory HIV-1 strains. In addition, the V3 region chimeras were able to infect the HOS-CD4(+)CCR5(+) cell line, suggesting CCR5 coreceptor utilization. Moreover, the V3 region chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium-inducing (NSI) phenotypes. In conclusion, the HIV-1 minor genotypes of infected mothers with macrophage-tropic and NSI or R5 phenotypes are transmitted to their infants and are initially maintained with the same properties.

a study of nevirapine toxicity in hiv infected pregnant women

African Journals Online (AJOL)

Esem

HIV infected women commenced on nevirapine-based regimen in the current pregnancy with CD4 counts up to. 3. 350 cells/mm at the University Teaching Hospital,. Lusaka, Zambia. Design: Longitudinal observational study with 2 arms. Group 1 (low CD4 count arm): HIV infected pregnant. 3 women with CD4 counts less ...

Is the risk of HIV acquisition increased during and immediately after pregnancy? A secondary analysis of pooled HIV community-based studies from the ALPHA network.

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Milly Marston

Full Text Available Previous studies of HIV acquisition in pregnancy have been in specific population groups, such as sero-discordant couples which have shown an increased risk of HIV acquisition during pregnancy and studies of sexually active women where the results have been ambiguous. However these studies are unable to tell us what the overall impact of pregnancy is on HIV acquisition in the general population.Data from six community-based HIV cohorts were pooled to give 2,628 sero-conversions and a total of 178,000 person years of observation. Multiple imputation was used to allow for the uncertainty of exact sero-conversion date in surveillance intervals greater than the length of a pregnancy. Results were combined using Rubin's rules to give appropriate error bounds. The analysis was stratified into two periods: pre- and post- widespread availability of prevention of mother-to-child HIV transmission services. This allows us to assess whether there is reporting bias relating to a person's knowledge of their own HIV status which would become more widespread in the latter time period.Results suggest that women while pregnant have a lower risk of acquiring HIV infection over all periods (HRR 0.79, 95%CI 0.70-0.89 than women who were not pregnant. There is no evidence for a difference in the rate of HIV acquisition between postpartum and non-pregnant women (HRR 0.92 95%CI 0.84-1.03.Although there may be immunological reasons for increased risk of HIV acquisition during pregnancy, at a population level this study indicates a lower risk of HIV acquisition for pregnant women. Pregnant women may be more likely to be concordant with their current sexual partner than non-pregnant women, i.e. either already HIV positive prior to the pregnancy or if negative at the time of becoming pregnant more likely to have a negative partner.

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.

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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.

Phenotype, genotype, and antibiotic susceptibility of Swedish and Thai oral isolates of Staphylococcus aureus

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Susanne Blomqvist

2015-04-01

Full Text Available Objective: The present study investigated phenotypes, virulence genotypes, and antibiotic susceptibility of oral Staphylococcus aureus strains in order to get more information on whether oral infections with this bacterium are associated with certain subtypes or related to an over-growth of the S. aureus variants normally found in the oral cavity of healthy carriers. Materials and methods: A total number of 157 S. aureus strains were investigated. Sixty-two strains were isolated from Swedish adults with oral infections, 25 strains were from saliva of healthy Swedish dental students, and 45 strains were from tongue scrapings of HIV-positive subjects in Thailand, and 25 Thai strains from non-HIV controls. The isolates were tested for coagulase, nitrate, arginine, and hemolysin, and for the presence of the virulence genes: hlg, clfA, can, sdrC, sdrD, sdrE, map/eap (adhesins and sea, seb, sec, tst, eta, etb, pvl (toxins. MIC90 and MIC50 were determined by E-test against penicillin V, oxacillin, amoxicillin, clindamycin, vancomycin, fusidic acid, and cefoxitin. Results: While the hemolytic phenotype was significantly (p<0.001 more common among the Thai strains compared to Swedish strains, the virulence genes were found in a similar frequency in the S. aureus strains isolated from all four subject groups. The Panton-Valentine leukocidin (PVL genotype was found in 73–100% of the strains. More than 10% of the strains from Swedish oral infections and from Thai HIV-positives showed low antibiotic susceptibility, most commonly for clindamycin. Only three methicillin-resistant S. aureus (MRSA strains were identified, two from oral infections and one from a Thai HIV patient. Conclusions: S. aureus is occasionally occurring in the oral cavity in both health and disease in Sweden and Thailand. It is therefore most likely that S. aureus in opportunistic oral infections originate from the oral microbiota. S. aureus should be considered in case of oral

Promotion of exclusive breastfeeding among HIV-positive mothers: an exploratory qualitative study.

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Hazemba, Alice N; Ncama, Busisiwe P; Sithole, Sello L

2016-01-01

Exclusive breastfeeding has the potential to reduce infant and under-five mortality, but research shows the practice is not widespread in resource-poor settings of sub-Saharan Africa. We explored factors influencing the decision to exclusively breastfeed among HIV-positive mothers accessing interventions for prevention of mother-to-child transmission of HIV in selected sites of Zambia. This exploratory qualitative study was embedded in research conducted on: HIV and infant feeding; choices and decision-outcomes in the context of prevention of mother-to-child transmission among HIV-positive mothers in Zambia. Thirty HIV-positive mothers and six key informants were recruited from two health facilities providing mother-to-child HIV transmission prevention services. A semi-structured guide was used to conduct interviews, which were digitally recorded and simultaneously transcribed. Data coding and analysis was done with the support of QRS Nvivo 10 version software. Despite the known benefits of exclusive breastfeeding, gaps in understanding and potential for behaviour change remained. We found that information promoting exclusive breastfeeding may have been understood by mothers as instructions from the health care workers indicating how to feed their HIV-exposed babies rather than as an option for the mothers' own informed-decision. This understanding influenced a mother's perceptions of breast milk safety while on antiretroviral medicine, of the formula feeding option, and of the baby crying after breastfeeding. The meanings mothers attached to exclusive breastfeeding thus influenced their understanding of breast milk insufficiency, abrupt weaning and mixed feeding in the context of preventing mother-to-child transmission of HIV. In order to enhance feeding practices for HIV-exposed infants, our study suggests a broader health campaign supporting all mothers to exclusively breastfeed.

Natural Plant Alkaloid (Emetine Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity

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Ana Luiza Chaves Valadão

2015-06-01

Full Text Available Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V. Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.

Comparative brain pathology of HIV-seronegative and HIV-infected drug addicts.

Science.gov (United States)

Makrigeorgi-Butera, M; Hagel, C; Laas, R; Puschel, K; Stavrou, D

1996-01-01

Early stages of infection with human immunodeficiency virus (HIV) were studied in HIV-seropositive drug addicts. Since heroin users are immunocompromized even in the absence of HIV infection, the aim of the present study was to compare the morphological alterations present in HIV-seronegative and HIV-seropositive drug addicts. A total of 60 cases (32 HIV-seronegative subjects, 21 HIV-seropositive patients without signs of acquired immunodeficiency syndrome (AIDS), and 7 HIV-seropositive patients with signs of AIDS) were investigated macroscopically, histologically, and immunohistochemically HIV-seronegative patients presented more frequently with acute drug intoxication, died at a significantly younger age than HIV-seropositive patients, and were found to suffer more frequently from alcohol-related changes. These results indicated that HIV-seronegative and HIV-seropositive patients differed possibly in their drug consumption and also in their general conditions of life. In accordance with previous reports activated microglia and a diffuse astrogliosis in the white matter were detected at a significantly higher frequency and found to be more severe in HIV-seropositive subjects than in HIV-seronegative addicts. A lymphocytic meningitis was present in 6 of 21 HIV-seropositive patients but in none of the HIV-seronegative patients. Perivascular infiltrates consisting of lymphocytes and macrophages were detected at similar frequencies in HIV-seronegative and HIV-seropositive patients but were significantly more severe in patients suffering from lymphocytic meningitis or purulent encephalitis. Opportunistic infections were only demonstrated in 2 AIDS cases. In 10 of the HIV-seronegative patients and in 3 of the HIV-seropositive patients CD68-and Ham56-positive multinucleated cells were detected scattered in the subarachnoidal space exclusively over the frontal cortex.

Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

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Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

2015-01-01

Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESNHIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

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Rekosh David

2008-05-01

Full Text Available Abstract AIDS-associated, CCR5-tropic (R5 HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

Altered brain functions in HIV positive patients free of HIV- associated neurocognitive disorders: A MRI study during unilateral hand movements

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Jing Zhao

2015-03-01

Full Text Available This paper aimed to investigate the brain activity of human immunodeficiency virus (HIV positive patients with normal cognition during unilateral hand movement and whether highly active antiretroviral therapy (HAART could affect the brain function. Functional magnetic resonance imaging (fMRI was performed for 60 HIV positive (HIV+ subjects and −42 healthy age-matched right-handed control subjects. Each subject was evaluated by the neuropsychological test and examined with fMRI during left and right hand movement tasks. HIV+ subjects showed greater activation in anterior cingulum, precuneus, occipital lobes, ipsilateral postcentral gyrus and contralateral cerebellum compared with control group during right hand movement task. However, during left hand movement no statistically significant difference was detected between these two groups. HAART medication for HIV+ subjects lowered the increased activity to normal level. Meanwhile patients receiving the regimen of zidovudine, lamivudine and efavirenz showed lower activity at bilateral caudate and ipsilateral inferior frontal gyrus in comparison with subjects receiving other HAART regimens. Therefore, HIV+ subjects demonstrated brain asymmetry in motor cortex, with increased activity present during right hand movement but absent during left hand movement. HAART proves effective in HIV+ subjects even with normal cognition and the specific regimen of HAART could prevent cerebral abnormal functions. Meanwhile, this study validates that during motor tasks, fMRI can detect the brain signal changes prior to the occurrences of other HIV- associated dysfunctions.

HIV Prevention After Discontinuing Pre-Exposure Prophylaxis: Conclusions From a Case Study

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Kai J. Jonas

2018-05-01

Full Text Available Pre-exposure prophylaxis (PrEP with tenofovir disoproxil fumarate in combination with emtricitabine (FTC is a highly effective form of HIV prevention. Endeavors of health-care providers and activists in many countries over the world are directed at making access to PrEP possible, or increasing PrEP use among men-who-have-sex-with-men (MSM. We argue while this effort is necessary, we also need to consider modes of HIV prevention after a period of PrEP use. PrEP uptake is not a one-way street, meaning that individuals may discontinue PrEP use, either voluntarily and involuntarily. Voluntary discontinued PrEP use in conjunction with decreased or no HIV risk exposure is unproblematic, but involuntary discontinuations with continuous high level of HIV risk exposure calls for tailored post-PrEP use HIV prevention. We present a case study of an MSM individual who discontinued PrEP for medical reasons (renal function and seroconverted soon afterward, to illustrate the need for tailored HIV prevention post-PrEP. Furthermore, we provide additional contexts of PrEP discontinuation leading to populations that are in need for post-PrEP types of HIV prevention. Subsequently, we present suggestions for modes of post-PrEP HIV prevention based on knowledge–communication–choice model. Community organization and health-care providers should consider and prepare their HIV prevention consulting protocols for such types of clients and add post-PrEP HIV prevention measures to their consulting offer.

HIV Persistence in Adipose Tissue Reservoirs.

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Couturier, Jacob; Lewis, Dorothy E

2018-02-01

The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue. However, based on viral outgrowth assays, adipose-resident CD4 T cells are latently infected with virus that is replication-competent and infectious. Additionally, adipocytes interact with CD4 T cells and macrophages to promote immune cell activation and inflammation which may be supportive for HIV persistence. Antiviral effector cells, such as CD8 T cells and NK/NKT cells, are abundant in adipose tissue during HIV/SIV infection and typically exceed CD4 T cells, whereas B cells are largely absent from adipose tissue of humans and monkeys. Additionally, CD8 T cells in adipose tissue of HIV patients are activated and have a late differentiated phenotype, with unique TCR clonotypes of less diversity relative to blood CD8 T cells. With respect to the distribution of antiretroviral drugs in adipose tissue, data is limited, but there may be class-specific penetration of fat depots. The trafficking of infected immune cells within adipose tissues is a common event during HIV/SIV infection of humans and monkeys, but the virus may be mostly transcriptionally dormant. Viral replication may occur less in adipose tissue compared to other major reservoirs, such as lymphoid tissue, but replication competence and infectiousness of adipose latent virus are comparable to other tissues. Due to the ubiquitous nature of adipose tissue, inflammatory interactions among adipocytes and CD4 T cells and macrophages, and

HIV, gender, race, sexual orientation, and sex work: a qualitative study of intersectional stigma experienced by HIV-positive women in Ontario, Canada.

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Logie, Carmen H; James, Llana; Tharao, Wangari; Loutfy, Mona R

2011-11-01

HIV infection rates are increasing among marginalized women in Ontario, Canada. HIV-related stigma, a principal factor contributing to the global HIV epidemic, interacts with structural inequities such as racism, sexism, and homophobia. The study objective was to explore experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada. We conducted a community-based qualitative investigation using focus groups to understand experiences of stigma and discrimination and coping methods among HIV-positive women from marginalized communities. We conducted 15 focus groups with HIV-positive women in five cities across Ontario, Canada. Data were analyzed using thematic analysis to enhance understanding of the lived experiences of diverse HIV-positive women. Focus group participants (n = 104; mean age = 38 years; 69% ethnic minority; 23% lesbian/bisexual; 22% transgender) described stigma/discrimination and coping across micro (intra/interpersonal), meso (social/community), and macro (organizational/political) realms. Participants across focus groups attributed experiences of stigma and discrimination to: HIV-related stigma, sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work. Coping strategies included resilience (micro), social networks and support groups (meso), and challenging stigma (macro). HIV-positive women described interdependent and mutually constitutive relationships between marginalized social identities and inequities such as HIV-related stigma, sexism, racism, and homo/transphobia. These overlapping, multilevel forms of stigma and discrimination are representative of an intersectional model of stigma and discrimination. The present findings also suggest that micro, meso, and macro level factors simultaneously present barriers to health and well being--as well as opportunities for coping--in HIV-positive women's lives. Understanding the deleterious effects of stigma and discrimination

HIV, gender, race, sexual orientation, and sex work: a qualitative study of intersectional stigma experienced by HIV-positive women in Ontario, Canada.

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Carmen H Logie

2011-11-01

Full Text Available HIV infection rates are increasing among marginalized women in Ontario, Canada. HIV-related stigma, a principal factor contributing to the global HIV epidemic, interacts with structural inequities such as racism, sexism, and homophobia. The study objective was to explore experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada.We conducted a community-based qualitative investigation using focus groups to understand experiences of stigma and discrimination and coping methods among HIV-positive women from marginalized communities. We conducted 15 focus groups with HIV-positive women in five cities across Ontario, Canada. Data were analyzed using thematic analysis to enhance understanding of the lived experiences of diverse HIV-positive women. Focus group participants (n = 104; mean age = 38 years; 69% ethnic minority; 23% lesbian/bisexual; 22% transgender described stigma/discrimination and coping across micro (intra/interpersonal, meso (social/community, and macro (organizational/political realms. Participants across focus groups attributed experiences of stigma and discrimination to: HIV-related stigma, sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work. Coping strategies included resilience (micro, social networks and support groups (meso, and challenging stigma (macro.HIV-positive women described interdependent and mutually constitutive relationships between marginalized social identities and inequities such as HIV-related stigma, sexism, racism, and homo/transphobia. These overlapping, multilevel forms of stigma and discrimination are representative of an intersectional model of stigma and discrimination. The present findings also suggest that micro, meso, and macro level factors simultaneously present barriers to health and well being--as well as opportunities for coping--in HIV-positive women's lives. Understanding the deleterious effects of stigma and

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study

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Malaba Lucie C

2006-01-01

Full Text Available Abstract Background Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy. Methods We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO, serum transferrin receptor (TfR and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth. Results At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P Conclusion HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.

Linking women who test HIV-positive in pregnancy-related services to HIV care and treatment services in Kenya: a mixed methods prospective cohort study.

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Laura Ferguson

Full Text Available There has been insufficient attention to long-term care and treatment for pregnant women diagnosed with HIV.This prospective cohort study of 100 HIV-positive women recruited within pregnancy-related services in a district hospital in Kenya employed quantitative methods to assess attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services. Qualitative methods were used to explore barriers and facilitators to navigating these services. Structured questionnaires were administered to cohort participants at enrolment and 90+ days later. Participants' medical records were monitored prospectively. Semi-structured qualitative interviews were carried out with a sub-set of 19 participants.Only 53/100 (53% women registered at an HIV clinic within 90 days of HIV diagnosis, of whom 27/53 (51% had a CD4 count result in their file. 11/27 (41% women were eligible for immediate antiretroviral therapy (ART; only 6/11 (55% started ART during study follow-up. In multivariable logistic regression analysis, factors associated with registration at the HIV clinic within 90 days of HIV diagnosis were: having cared for someone with HIV (aOR:3.67(95%CI:1.22, 11.09, not having to pay for transport to the hospital (aOR:2.73(95%CI:1.09, 6.84, and having received enough information to decide to have an HIV test (aOR:3.61(95%CI:0.83, 15.71. Qualitative data revealed multiple factors underlying high patient drop-out related to women's social support networks (e.g. partner's attitude to HIV status, interactions with health workers (e.g. being given unclear/incorrect HIV-related information and health services characteristics (e.g. restricted opening hours, long waiting times.HIV testing within pregnancy-related services is an important entry point to HIV care and treatment services, but few women successfully completed the steps needed for assessment of their treatment needs within three months of diagnosis

Depression in perinatally HIV-infected pregnant women compared to non-perinatally HIV-infected and HIV-uninfected pregnant women.

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Angrand, Ruth C; Sperling, Rhoda; Roccobono, Kinga; Osborne, Lauren M; Jao, Jennifer

2018-05-18

"Depression (as noted in chart by a physician)" was compared between HIV infected pregnant women and controls. Perinatally HIV-infected (PHIV), non-perinatally HIV-infected (NPHIV), and HIV-uninfected (HIV-U) pregnant women were all compared using a logistic regression model. Overall, HIV-infected women had higher rates of depression than HIV-U, with PHIV women demonstrating a clinically and statistically significant increased risk compared to HIV-U women [adjusted OR: 15.9, 95% CI = 1.8-143.8]. Future studies in larger populations are warranted to confirm these findings and further elucidate mental health outcomes of PHIV and NPHIV pregnant women.

Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.

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Lawrence J Tartaglia

2016-02-01

Full Text Available Simian-human immunodeficiency virus (SHIV challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

HIV awareness of outgoing female migrant workers of Bangladesh: a pilot study.

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Islam, M Mofizul; Conigrave, Katherine M; Miah, Md Shahjahan; Kalam, Kazi Abul

2010-12-01

Female migrant workers face a growing scale of unsafe migration, which increases their risk of HIV. Despite this, increasing numbers of women are migrating from Bangladesh to other countries as contractual workers. The aim of the study is to establish a baseline for the socio-demographic status of female migrant workers and the extent of their HIV/AIDS awareness along with the factors that determine it, and to discuss the need for effective HIV awareness programmes. During June-July 2008 data were collected by a questionnaire from 123 participants by approaching a cross section of women at the airport who were ready to fly to take up an overseas job. A total of 87% had heard of HIV/AIDS. Participants who had completed an education level of year ≥8 were more likely to have been informed about HIV than others. The average score in correct identification of modes of HIV infection was 1.6 (out of 4) and for preventive measures 1.8 (out of 5). Television and health workers were the major sources of HIV related knowledge. HIV-knowledge among the potential female migrant workers seems to be poor. As growing numbers of female workers are moving overseas for work, government and other concerned agencies must take a pro-active role to raise their awareness of HIV/AIDS infection and of effective preventive measures.

A cohort pilot study on HIV-associated neuropsychological impairments in haemophilia patients

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Silvia eRiva

2015-06-01

Full Text Available Despite advances in the management of HIV infection with the introduction of combination antiretroviral therapy (cART, it is well known that HIV can directly infect the central nervous system (CNS and, as a result of such infection, neuropsychological impairments can be manifested. In this study we tried to determine whether seropositivity was associated with a poor neuropsychological performance in patients with hemophilia and HIV. Such a cohort of patients is very often underrepresented and understudied in the HIV literature. To amend such a gap, we carried out an extensive neuropsychological evaluation on these patients, and compared their performance with that of a group of seronegative hemophilia patients. The results revealed that HIV infection in HIV seropositive (HIV+ hemophilia patients was associated with deficits in attention, short-term memory, abstraction and visual recognition. Such results are still preliminary and explorative due to the small cohort of patients enrolled. However, the results do seem to have some important implications for day-to-day functioning, as the level of impairment detected may cause difficulties in completing common everyday tasks such as maintaining adherence to complex medication regimens, or maintaining social life activities. Continued research into the mechanisms related to HIV and neurocognitive dysfunction may provide targets for interventions that could have meaningful consequences in the real world for HIV hemophilia patients.

Predicting Bevirimat resistance of HIV-1 from genotype

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Hoffmann Daniel

2010-01-01

Full Text Available Abstract Background Maturation inhibitors are a new class of antiretroviral drugs. Bevirimat (BVM was the first substance in this class of inhibitors entering clinical trials. While the inhibitory function of BVM is well established, the molecular mechanisms of action and resistance are not well understood. It is known that mutations in the regions CS p24/p2 and p2 can cause phenotypic resistance to BVM. We have investigated a set of p24/p2 sequences of HIV-1 of known phenotypic resistance to BVM to test whether BVM resistance can be predicted from sequence, and to identify possible molecular mechanisms of BVM resistance in HIV-1. Results We used artificial neural networks and random forests with different descriptors for the prediction of BVM resistance. Random forests with hydrophobicity as descriptor performed best and classified the sequences with an area under the Receiver Operating Characteristics (ROC curve of 0.93 ± 0.001. For the collected data we find that p2 sequence positions 369 to 376 have the highest impact on resistance, with positions 370 and 372 being particularly important. These findings are in partial agreement with other recent studies. Apart from the complex machine learning models we derived a number of simple rules that predict BVM resistance from sequence with surprising accuracy. According to computational predictions based on the data set used, cleavage sites are usually not shifted by resistance mutations. However, we found that resistance mutations could shorten and weaken the α-helix in p2, which hints at a possible resistance mechanism. Conclusions We found that BVM resistance of HIV-1 can be predicted well from the sequence of the p2 peptide, which may prove useful for personalized therapy if maturation inhibitors reach clinical practice. Results of secondary structure analysis are compatible with a possible route to BVM resistance in which mutations weaken a six-helix bundle discovered in recent experiments

Predictors of HIV, HIV Risk Perception, and HIV Worry Among Adolescent Girls and Young Women in Lilongwe, Malawi.

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Price, Joan T; Rosenberg, Nora E; Vansia, Dhrutika; Phanga, Twambilile; Bhushan, Nivedita L; Maseko, Bertha; Brar, Savvy K; Hosseinipour, Mina C; Tang, Jennifer H; Bekker, Linda-Gail; Pettifor, Audrey

2018-01-01

Adolescent girls and young women (AGYW) in sub-Saharan Africa have high HIV prevalence and incidence. We sought to understand which HIV risk factors individually and in combination contribute to risk, and whether these factors are associated with HIV worry and risk perception. This study is ongoing at 4 public health centers in Lilongwe, Malawi (2016-2017). AGYW of 15-24 years old were recruited to participate in a study assessing 4 models of service delivery. At each health center, participants completed a baseline survey assessing socioeconomic, behavioral, biomedical, and partnership characteristics; self-reported HIV status; and, if HIV-uninfected, HIV risk perception (high versus low or none) and HIV worry (any versus none). We analyzed associations between baseline characteristics and HIV prevalence, risk perception, and worry. Among 1000 AGYW, median age was 19 years (IQR: 17-21). Thirty-three participants reported being HIV-infected. Fifteen characteristics were associated with HIV infection. Having more risk factors was associated with higher HIV prevalence (≤4 factors, 0.5%; 5-8 factors, 6%; >8 factors, 21%). Having more risk factors was also associated with higher risk perception (P risk factors, 52% did not consider themselves to be at high risk and 21% did not report any HIV worry. Most AGYW perceive little risk of HIV acquisition, even those at highest risk. As a critical gap in the HIV prevention cascade, accurate risk perception is needed to tailor effective and sustained combination prevention strategies for this vulnerable population.

HIV infection in male adolescents: a qualitative study.

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Taquette, Stella Regina; Rodrigues, Adriana de Oliveira; Bortolotti, Livia Rocha

2015-07-01

`The gradual reduction in the incidence of AIDS among men who have sex with men has not occurred in the youngest age group; on the contrary, it is growing. This paper examines the vulnerabilities of adolescent males at risk of HIV infection. This is a qualitative study conducted through interviews with HIV positive young men undergoing treatment, whose diagnosis was made during adolescence. The interviews were recorded and transcribed in full. They were analyzed by intensive reading, classified by issues, and interpreted from a hermeneutic-dialectic perspective in dialogue with the literature. We interviewed 16 young men whose diagnosis occurred between the ages of 11 and 19 and for all of them the method of HIV transmission was sexual; 12 of the men were homosexual and 4 were heterosexual. It was evident that vulnerable situations included disbelief in the possibility of contamination, subjection to sex, homophobia and commercial sexual exploitation. This study demonstrates the importance of the formulation of public policies on sexual and reproductive health, which include adolescents and young men. These policies should embody the perspective of masculinity in all its widest aspects, as well as actions in favor of sexual diversity.

The HIV-Brazil cohort study: design, methods and participant characteristics.

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Alexandre Grangeiro

Full Text Available BACKGROUND: The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART and the impact of this treatment on morbidity, quality of life (QOL and mortality. The study design, patients' profiles and characteristics of cART initiation between 2003 and 2010 were described. METHODOLOGY/PRINCIPAL FINDINGS: Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2-5.9 years with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1, with a mean age of 36.9 years (SD 9.9 years; 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4% initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7% and lopinavir/ritonavir (18.2%. The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1-78.6. Nearly half (45.4% of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years. CONCLUSIONS/SIGNIFICANCE: Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient

Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV-negative gay and bisexual men in serodiscordant relationships: a mixed methods study.

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Brooks, Ronald A; Landovitz, Raphael J; Kaplan, Rachel L; Lieber, Eli; Lee, Sung-Jae; Barkley, Thomas W

2012-02-01

The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.

Comparative genomics of Cryptococcus neoformans var. grubii associated with meningitis in HIV infected and uninfected patients in Vietnam.

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Day, Jeremy N; Qihui, Seet; Thanh, Lam Tuan; Trieu, Phan Hai; Van, Anh Duong; Thu, Nha Hoang; Chau, Tran Thi Hong; Lan, Nguyen P H; Chau, Nguyen Van Vinh; Ashton, Philip M; Thwaites, Guy E; Boni, Maciej F; Wolbers, Marcel; Nagarajan, Niranjan; Tan, Patrick B O; Baker, Stephen

2017-06-01

The vast burden of cryptococcal meningitis occurs in immunosuppressed patients, driven by HIV, and is caused by Cryptococcus neoformans var. grubii. We previously reported cryptococcal meningitis in Vietnam arising atypically in HIV uninfected, apparently immunocompetent patients, caused by a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans var. grubii (VNIγ). This variant was less common in HIV infected individuals; it remains unclear why this lineage is associated with apparently immunocompetent patients. To study this host tropism we aimed to further our understanding of clinical phenotype and genomic variation within Vietnamese C. neoformans var. grubii. After performing MLST on C. neoformans clinical isolates we identified 14 sequence types (STs); ST5 correlated with the VNIγ cluster. We next compared clinical phenotype by lineage and found HIV infected patients with cryptococcal meningitis caused by ST5 organisms were significantly more likely to have lymphadenopathy (11% vs. 4%, p = 0.05 Fisher's exact test) and higher blood lymphocyte count (median 0.76 versus 0.55 X109 cells/L, p = 0.001, Kruskal-Wallis test). Furthermore, survivors of ST5 infections had evidence of worse disability outcomes at 70 days (72.7% (40/55) in ST5 infections versus 57.1% (52/91) non-ST5 infections (OR 2.11, 95%CI 1.01 to 4.41), p = 0.046). To further investigate the relationship between strain and disease phenotype we performed genome sequencing on eight Vietnamese C. neoformans var. grubii. Eight genome assemblies exhibited >99% nucleotide sequence identity and we identified 165 kbp of lineage specific to Vietnamese isolates. ST5 genomes harbored several strain specific regions, incorporating 19 annotated coding sequences and eight hypothetical proteins. These regions included a phenolic acid decarboxylase, a DEAD-box ATP-dependent RNA helicase 26, oxoprolinases, a taurine catabolism dioxygenase, a zinc finger protein, membrane transport proteins

The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

DEFF Research Database (Denmark)

Demant, Dyveke T; Lund, Karen; Vollert, Jan

2014-01-01

In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo...... patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment....... The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined...

Asthma phenotypes in childhood.

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Reddy, Monica B; Covar, Ronina A

2016-04-01

This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

Tuberculosis and HIV/AIDS dual infection: A Case study for ...

African Journals Online (AJOL)

A total of 479 (99%) cases had their HIV test results recorded. The HIV positive cases were 244 (51%). Dual infection: The proportion of TB cases also having HIV/AIDS infection was 51%. The cure rate of smear positive, HIV positive cases was 71%; the cure rate of smear positive, HIV negative case was 85%.The mortality ...

Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study

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Ahmed, Ausman; Mekonnen, Desalew; Shiferaw, Atsede M; Belayneh, Fanuel

2018-01-01

Objective This study assessed the incidence of tuberculosis (TB) and its predictors among adults living with HIV/AIDS in government health facilities in north-east Ethiopia. Setting A 5-year retrospective cohort study was conducted from May to June 2015 on 451 adult HIV/AIDS-infected individuals who enrolled in the HIV care clinics of government health facilities in north-east Ethiopia. Participants A total of 451 HIV-infected adults who newly enrolled in the adult HIV care clinic from 1 July 2010 with complete information were followed until May 2015. Primary outcome measure The primary outcome was the proportion of patients diagnosed with TB or the TB incidence rate. Secondary outcome measure The incidence of TB was investigated in relation to years of follow-up. Results A total of 451 charts with complete information were followed for 1377.41 person-years (PY) of observation. The overall incidence density of TB was 8.6 per 100 PYof observation. Previous TB disease (adjusted HR (AHR) 3.65, 95% CI 1.97 to 6.73), being bedridden (AHR 5.45, 95% CI 1.16 to 25.49), being underweight (body mass index (BMI) bedridden condition were the determinants of the incidence of TB. Therefore, addressing the significant predictors and improving TB/HIV collaborative activities should be strengthened in the study setting. PMID:29437750

Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy

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Healy, Michael; Singh, Ravesh; Roider, Julia; Groll, Andreas; Kindra, Chirjeev; Sibaya, Thobekile; Moonsamy, Angeline; McGregor, Callum; Phan, Michelle Q.; Palma, Alejandro; Kloverpris, Henrik; Leslie, Alasdair; Bobat, Raziya; LaRussa, Philip; Ndung'u, Thumbi; Goulder, Philip; Sobieszczyk, Magdalena E.; Archary, Mohendran

2018-01-01

Abstract This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM. We then prospectively measured these markers and correlated them to treatment outcomes in the HIV-infected children at 48 weeks following initiation of ART. Plasma levels of 16sDNA, iFABP and sCD14 were measured by quantitative real time PCR, ELISA and Luminex, respectively. T cell phenotype markers were measured by flow cytometry. Multiple regression analysis was performed using generalized linear models (GLMs) and the least absolute shrinkage and selection operator (LASSO) approach for variable selection. Microbial translocation, T cell activation and exhaustion were increased in HIV-uninfected children with SAM compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial translocation, monocyte, and CD8 T cell activation were independently associated with decreased rates of CD4% immune recovery after 48 weeks of ART. SAM is associated with increased microbial translocation, immune activation, and immune exhaustion in HIV-uninfected children and with worse prognosis and impaired immune recovery in HIV-infected children on ART. PMID:28670966

Cross-sectional study assessing HIV-related knowledge, attitudes and behavior in the Namibian truck transport sector: Readjusting HIV prevention programs in the workplace

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Til R. Kiderlen

2015-07-01

Full Text Available Summary: The objectives of this study were to assess the current status of HIV-related knowledge, attitudes, and behavior (KAB of employees in the private transport sector in Namibia and to compare companies with established HIV workplace program (WPPs with those that have recently initiated the implementation of such programs. The study was designed as a cross-sectional questionnaire-based survey. Between January and March 2011, the survey was conducted in the Namibian truck transport sector in six companies of different sizes. The participants were selected randomly from the workforce. Data collection was based on a KAB questionnaire.The range of correct answers to the survey concerning the knowledge of HIV transmission was 67–95%. Twenty percent of the employees had never been tested for HIV. Additionally, risky sexual behaviors were quite prevalent and included having multiple concurrent partners and the use of sex for incentives. This study revealed that drivers and laborers were especially at risk for such behaviors. The employees of companies with established WPPs were tested for HIV more often than those of companies with new WPPs; however, aside from this difference, only minor differences were observed between the two groups. The findings of this study highlight the need for on-going HIV information and prevention campaigns that focus on the special needs of mobile and low-income workers. WPPs should be tailored accordingly and shift their focus to more practical approaches, such as voluntary counseling and testing (VCT, to increase their effectiveness. Keywords: HIV, Knowledge, Attitudes, Behavior, Namibia, Transport sector

"I never thought that it would happen … " Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya.

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Ngure, Kenneth; Vusha, Sophie; Mugo, Nelly; Emmanuel-Fabula, Mira; Ngutu, Mariah; Celum, Connie; Baeten, Jared M; Heffron, Renee

2016-12-01

In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples' needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples' communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples' counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms.

Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

DEFF Research Database (Denmark)

De Wit, Stephane; Sabin, Caroline A; Weber, Rainer

2008-01-01

OBJECTIVE: The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated...... with the onset of diabetes, and to identify possible mechanisms for any relationships found. RESEARCH DESIGN AND METHODS: D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes...

Time to complete wound healing in HIV-positive and HIV-negative men following medical male circumcision in Kisumu, Kenya: a prospective cohort study.

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John H Rogers

Full Text Available While voluntary medical male circumcision (VMMC has been shown to be protective against HIV-acquisition, the procedure may place men and their partners at risk of HIV infection in the period following circumcision if sex is resumed before the wound is healed. This prospective cohort study evaluates post-circumcision wound healing to determine whether the 42-day post-circumcision abstinence period, recommended by the World Health Organization and adopted by VMMC programs, is optimal.Men were circumcised by forceps-guided method and their post-circumcision wounds examined weekly for seven weeks and at 12 weeks. Time to complete healing was recorded in completed weeks since circumcision, and its associations with baseline covariates were assessed by Kaplan-Meier methods and Cox Proportional Hazard Models. A total of 215 HIV-negative and 108 HIV-positive men aged 18-35 years (median 26, IQR 23-30 were enrolled. 97.1% of scheduled follow-up visits were completed. At week 4, 59.3% of HIV-positive men and 70.4% of age-matched HIV-negative men were healed. At week 6, these percentages rose to 93.4% in HIV-positive men and 92.6% in age-matched HIV-negative men. There was no difference in the hazard of healing between 108 HIV-positive and 108 age-matched HIV-negative men (HR 0.91 95% CI 0.70-1.20. Early post-operative infection was associated with delayed healing in both HIV-positive and HIV-negative men (HR 0.48 95% CI 0.23-1.00.Our results indicate that the WHO recommendation for 42-days post-circumcision sexual abstinence should be maintained for both HIV-positive and HIV-negative men. It is important to stress condom use upon resumption of sex in all men undergoing circumcision.

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.

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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.

Psychiatric morbidity in HIV/AIDS: a 5-year retrospective study in Jos ...

African Journals Online (AJOL)

Background Most studies of psychiatric disorders associated with HIV/AIDS have been carried out in the USA and Europe in patients on anti-retroviral drugs. Few studies have looked at psychiatric disorders and substance use in Africa and a dearth of literature exists on HIV/AIDS and psychiatric morbidity in Nigeria.

Experiences of HIV stigma: the role of visible symptoms, HIV centrality and community attachment for people living with HIV.

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Brener, Loren; Callander, Denton; Slavin, Sean; de Wit, John

2013-01-01

For many people living with HIV (PLHIV), disclosure or concealment of their HIV status may be under their personal control; however, for PLHIV with visible symptoms of their illness, disclosure may no longer be a choice. Previous research suggests that those with visible HIV symptoms have poorer mental and physical health than those without visible HIV symptoms. This study aimed to extend these findings and assess the role of perceived centrality of HIV in the lives of PLHIV as well as the role of attachment to an HIV-positive community in understanding the negative effects on health and well-being for PLHIV with visible HIV symptoms. Participants were 697 PLHIV who completed an online survey that assessed symptom visibility, HIV-status disclosure, perceived stigma, health and well-being, how central HIV was to identity and HIV community attachment. Results indicate that those with visible symptoms experienced more HIV-related stigma and had poorer outcomes on a range of psychological and mental health measures than those who were able to conceal their stigma. These effects remained after controlling for length of time since diagnosis, time on HIV treatment, perceived health satisfaction and age. PLHIV with visible symptoms also reported that HIV was more central to their identity and reported greater attachment to an HIV-positive community. Furthermore, findings suggest that while HIV centrality appears to increase the negative effects of having visible symptoms associated with HIV, greater community attachment seems to ameliorate these effects. This suggests the need for a nuanced understanding of the implications of visible HIV symptoms for PLHIV. The study also highlights the potential benefits of HIV-positive community attachment in buffering PLHIV from the negative effect of visible HIV symptoms on their health and well-being.

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

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

2016-03-01

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

Metabolic complications associated with HIV protease inhibitor therapy.

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Nolan, David

2003-01-01

HIV protease inhibitors were introduced into clinical practice over 7 years ago as an important component of combination antiretroviral drug regimens which in many ways revolutionised the treatment of HIV infection. The significant improvements in prognosis that have resulted from the use of these regimens, combined with the need for lifelong treatment, have increasingly focused attention on the adverse effects of antiretroviral drugs and on the metabolic complications of HIV protease inhibitors in particular. In this review, the cluster of metabolic abnormalities characterised by triglyceride-rich dyslipidaemia and insulin resistance associated with HIV protease inhibitor therapy are considered, along with implications for cardiovascular risk in patients affected by these complications. Toxicity profiles of individual drugs within the HIV protease inhibitor class are examined, as there is an increased recognition of significant intra-class differences both in terms of absolute risk of metabolic complications as well as the particular metabolic phenotype associated with these drugs. Guidelines for clinical assessment and treatment are emphasised, along with pathophysiological mechanisms that may provide a rational basis for the treatment of metabolic complications. Finally, these drug-specific effects are considered within the context of HIV-specific effects on lipid metabolism as well as lifestyle factors that have contributed to a rapidly increasing incidence of similar metabolic syndromes in the general population. These data highlight the importance of individualising patient management in terms of choice of antiretroviral regimen, assessment of metabolic outcomes and use of therapeutic interventions, based on the assessment of baseline (pre-treatment) metabolic status as well as the presence of potentially modifiable cardiovascular risk factors.

Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study

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Ying Zhou

2016-01-01

Full Text Available Antiretroviral therapy (ART has been shown to improve survival of patients with Human Immunodeficiency Virus (HIV infection and to reduce HIV-1 transmission. Therefore, the Chinese central government initiated a national program to provide ART free of charge to HIV-1 patients. We conducted a cross-sectional survey in Jiangsu province to determine the level of drug resistance (DR in HIV-1 infected patients and the correlates of DR in virological failures in 2012. Approximately 10.4% of the HIV-1 patients in the study experienced virological failure after one year of ART and were divided into drug sensitive and drug resistant groups based on genotype determination. The viral loads (VLs in the drug resistant group were significantly lower than the drug sensitive group. There were two independent predictors of virological failure: male gender and increasing duration of treatment. The primary mutations observed in the study were against nucleoside reverse transcriptase inhibitors (NRTIs which were M184V (79.45% and K103N (33.70% in nonnucleoside reverse transcriptase inhibitors (NNRTIs. The overall rate of DR in Jiangsu province is still relatively low among treated patients. However, close monitoring of drug resistance in male patients in the early stages of treatment is vital to maintaining and increasing the benefits of HIV ART achieved to date.

A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru

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Oberhelman, Richard A.; Soto-Castellares, Giselle; Gilman, Robert H.; Castillo, Maria E.; Kolevic, Lenka; Delpino, Trinidad; Saito, Mayuko; Salazar-Lindo, Eduardo; Negron, Eduardo; Montenegro, Sonia; Laguna-Torres, V. Alberto; Maurtua-Neumann, Paola; Datta, Sumona; Evans, Carlton A.

2015-01-01

Background Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis in 525 children with and without HIV-infection. Methods and Findings ‘Cases’ were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81 HIV-positive) and asymptomatic ‘well-control’ children (n = 200 HIV-negative; n = 35 HIV-positive). Specimens (n = 2422) were gastric aspirates, nasopharyngeal aspirates and stools analyzed by a total of 9688 tests. All specimens were tested with an in-house hemi-nested IS6110 PCR that took 0.2) for HIV-positive versus HIV-negative cases. All specimens were also tested with auramine acid-fast microscopy, microscopic-observation drug-susceptibility (MODS) liquid culture, and Lowenstein-Jensen solid culture that took ≤6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 well-controls were negative). Microscopy-positivity was rare (0.21%, 5/2422 specimens) and all microscopy-positive specimens were culture-positive. Culture-positivity was less frequent (P≤0.01) in HIV-infection: 1.2% (1/81) HIV-positive cases versus 11% (22/209) HIV-negative cases; caused by 0.42% (2/481) versus 4.7% (58/1235) of their specimens, respectively. Conclusions In HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458 microscopy and culture tests were done per case confirmed and even in children with culture-proven tuberculosis most tests and specimens were false-negative; whereas PCR was so prone to false-positives that PCR-positivity was as likely in specimens from well-controls as suspected-tuberculosis cases. This demonstrates the importance of control participants in diagnostic test evaluation and that even extensive laboratory testing only rarely contributed to the care of

Mother to child transmission of HIV in Brazil: Data from the "Birth in Brazil study", a national hospital-based study.

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

2018-01-01

to estimate the mother to child transmission (MTCT) of HIV among infected pregnant women identified in the "Birth in Brazil" study and to evaluate care practices provided in order to identify missed opportunities at preventing the MTCT of HIV infection in the country. Descriptive study using data obtained from the consultation of different databases: the "Birth in Brazil" study database and the Brazilian National Information Systems (NIS) databases. We used cases of pregnant women infected with HIV identified in the "Birth in Brazil" study, and cases of AIDS in children under 5 years old identified in the NIS, to estimate the MTCT of HIV infection in the country, with a 95% confidence interval. We also estimated the HIV cascade (HIV diagnosis; use of antiretroviral treatment (ART) during pregnancy, labour, and for the newborn; adequate care during childbirth considering viral load at birth; and no breastfeeding) using data from the same sources. MTCT of HIV of 2.0% (95% CI 0.3%-13.8%). At birth, 84.0% of HIV infected woman showed a positive HIV diagnosis, 74.9% received combined ART during pregnancy, 80.7% received ART during childbirth, 77.1% received adequate care during childbirth, 86.8% of newborns received ART within the first 24 hours after birth, and 2.8% of newborns were breastfed. Considering all steps, 61.3% of the women (95% CI 48.3%-72.8%) received all available medical interventions. In the analysis restricted to women identified in the NIS, 65.3% (95% CI 48.0%-79.3%) of HIV infected women received all available medical interventions. Brazil has healthcare policies that guarantee free access to tests, ART and substitutes for maternal milk. However, missed opportunities to prevent MTCT of HIV were identified in at least one-third of women and may be making it difficult to reach HIV-elimination targets especially in the less developed country regions.

Mother to child transmission of HIV in Brazil: Data from the "Birth in Brazil study", a national hospital-based study.

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Rosa Maria Soares Madeira Domingues

Full Text Available to estimate the mother to child transmission (MTCT of HIV among infected pregnant women identified in the "Birth in Brazil" study and to evaluate care practices provided in order to identify missed opportunities at preventing the MTCT of HIV infection in the country.Descriptive study using data obtained from the consultation of different databases: the "Birth in Brazil" study database and the Brazilian National Information Systems (NIS databases. We used cases of pregnant women infected with HIV identified in the "Birth in Brazil" study, and cases of AIDS in children under 5 years old identified in the NIS, to estimate the MTCT of HIV infection in the country, with a 95% confidence interval. We also estimated the HIV cascade (HIV diagnosis; use of antiretroviral treatment (ART during pregnancy, labour, and for the newborn; adequate care during childbirth considering viral load at birth; and no breastfeeding using data from the same sources.MTCT of HIV of 2.0% (95% CI 0.3%-13.8%. At birth, 84.0% of HIV infected woman showed a positive HIV diagnosis, 74.9% received combined ART during pregnancy, 80.7% received ART during childbirth, 77.1% received adequate care during childbirth, 86.8% of newborns received ART within the first 24 hours after birth, and 2.8% of newborns were breastfed. Considering all steps, 61.3% of the women (95% CI 48.3%-72.8% received all available medical interventions. In the analysis restricted to women identified in the NIS, 65.3% (95% CI 48.0%-79.3% of HIV infected women received all available medical interventions.Brazil has healthcare policies that guarantee free access to tests, ART and substitutes for maternal milk. However, missed opportunities to prevent MTCT of HIV were identified in at least one-third of women and may be making it difficult to reach HIV-elimination targets especially in the less developed country regions.

Barriers to communication between HIV care providers (HCPs) and women living with HIV about child bearing: A qualitative study.

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Ddumba-Nyanzi, Ismael; Kaawa-Mafigiri, David; Johannessen, Helle

2016-05-01

In the context of HIV clinical care, open discussion regarding sexual health and reproductive plans has become increasingly relevant. The aim of this paper is to explore barriers to communication between providers and women living with HIV regarding childbearing. In-depth interviews (IDIs) were conducted with 48 HIV infected women receiving ART at 7 different HIV clinics providing comprehensive HIV care services in four districts in Uganda, between July and August 2012. All women were aware of their HIV diagnosis prior to pregnancy or had given birth while living with HIV. Four themes emerged describing barriers to communication, from the HIV-positive women's point of view: (i) provider indifference or opposition to childbearing post HIV diagnosis, (ii) anticipation of negative response from provider, (iii) provider's emphasis on 'scientific' facts, (iv) 'accidental pregnancy'. Existing evidence regarding effective provider-patient communication should be considered for its application for reproductive counseling among HIV infected women. These data demonstrate the need for current counseling guidelines to explore approaches that encourage open, non-judgmental, non-directive discussions with HIV positive individuals around their reproductive desires and intentions in a health care setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

HIV stigma and social capital in women living with HIV

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Cuca, Yvette P.; Asher, Alice; Okonsky, Jennifer; Kaihura, Alphoncina; Dawson-Rose, Carol; Webel, Allison

2016-01-01

Women living with HIV (WLWH) continue to experience HIV-related stigma. Social capital is one resource that could mitigate HIV stigma. Our cross-sectional study examined associations between social capital and HIV-related stigma in 135 WLWH in the San Francisco Bay Area. The mean age of study participants was 48 years; 60% were African American; 29% had less than a high school education; and 19% were employed. Age was significantly associated with perceived HIV stigma (p = .001), but total social capital was not. Women with lower Value of Life social capital scores had significantly higher total stigma scores (p = .010) and higher Negative Self-image stigma scores (p = .001). Women who felt less valued in their social worlds may have been more likely to perceive HIV stigma, which could have negative health consequences. This work begins to elucidate the possible relationships between social capital and perceived HIV stigma. PMID:27697368

Variations in KIR Genes: A Study in HIV-1 Serodiscordant Couples

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Vijay R. Chavan

2014-01-01

Full Text Available Background. NK cells have anti-HIV activity mediated through killer cell immunoglobulin-like receptors (KIRs. The current prospective cohort study evaluated whether variation in KIR genes is associated with HIV infection in discordant couples (DCs, where one spouse remains seronegative (HSN despite repeated exposure to the HIV. Methods. KIR was genotyped using PCR SSP. Viral load and CD4 counts were estimated using commercially available reagents. Data were analyzed using SPSS software. Results. Among the 47 DCs, HSN spouses had significantly (P=0.006 higher frequencies of KIR3DS1. Regression analysis revealed significant (P=0.009 association of KIR2DS1 with low viral load. KIR2DS4 variant was associated (P=0.032 with high viral load. Three pairs of KIR genes were in strong LD in HSNs and two pairs in HSPs. There were 60 KIR genotypes, and 16 are reported the first time in the Indian population. Exclusive genotypes were present either in HSPs (N=22, 11 unique genotypes or in HSNs (n=27, 9 unique genotypes. Conclusions. This study highlights for the first time in the Indian population an association of KIR genes in HIV infection where presence of exclusive and unique genotypes indicates possible association with either HIV infection or with protection.

Determinants of Human Immunodeficiency Virus (HIV prevalence in homosexual and bisexual men screened for admission to a cohort study of HIV negatives in Belo Horizonte, Brazil: Project Horizonte

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Carneiro Mariângela

2003-01-01

Full Text Available Project Horizonte, an open cohort of homosexual and bisexual human immunodeficiency virus (HIV-1 negative men, is a component of the AIDS Vaccine Program, in Belo Horizonte, Minas Gerais, Brazil. The objective of this study was to compare volunteers testing HIV positive at cohort entry with a sample of those who tested HIV negative in order to identify risk factors for prevalent HIV infection, in a population being screened for enrollment at Project Horizonte. A nested case-control study was conducted. HIV positive volunteers at entry (cases were matched by age and admission date to three HIV negative controls each. Selected variables used for the current analysis included demographic factors, sexual behavior and other risk factors for HIV infection. During the study period (1994-2001, among the 621 volunteers screened, 61 tested positive for HIV. Cases were matched to 183 HIV negative control subjects. After adjustments, the main risk factors associated with HIV infection were unprotected sex with an occasional partners, OR = 3.7 (CI 95% 1.3-10.6, receptive anal intercourse with an occasional partner, OR = 2.8 (95% CI 0.9-8.9 and belonging to the negro racial group, OR = 3.4 (CI 95% 1.1-11.9. These variables were associated with an increase in the risk of HIV infection among men who have sex with men at the screening for admission to an open HIV negative cohort.

A histological autopsy study of the thyroid gland in HIV infected ...

African Journals Online (AJOL)

It is therefore postulated the thyroid gland would be involved in AIDS patients. This study focused on the histologic appearances of the thyroid gland in HIV and AIDS patients on post mortem. The findings will provide evidence based recommendations on the management of thyroid diseases in the HIV infected in Zambia.

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.

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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

Unintended pregnancy, contraceptive use, and childbearing desires among HIV-infected and HIV-uninfected women in Botswana: across-sectional study.

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Mayondi, Gloria K; Wirth, Kathleen; Morroni, Chelsea; Moyo, Sikhulile; Ajibola, Gbolahan; Diseko, Modiegi; Sakoi, Maureen; Magetse, Jane Dipuo; Moabi, Kebaiphe; Leidner, Jean; Makhema, Joseph; Kammerer, Betsy; Lockman, Shahin

2016-01-16

Little is known about the impact of knowledge of HIV serostatus on pregnancy intention and contraceptive use in high-HIV-burden southern African settings in the era of widespread antiretroviral treatment availability. We analyzed interview data collected among 473 HIV-uninfected and 468 HIV-infected pregnant and recently postpartum women at two sites in southern Botswana. Participants were interviewed about their knowledge of their HIV status prior to pregnancy, intendedness of the pregnancy, contraceptive use, and future childbearing desires. The median age of the 941 women was 27 years, median lifetime pregnancies was 2, and 416 (44%) of pregnancies were unintended. Among women reporting unintended pregnancy, 36% were not using a contraceptive method prior to conception. Among contraception users, 81% used condoms, 13% oral contraceptives and 5% an injectable contraceptive. In univariable analysis, women with unintended pregnancy had a higher number of previous pregnancies (P = HIV-infected, 48% reported knowing they were HIV-uninfected, and 22% reported not knowing their HIV status prior to conception. In multivariable analysis, women who did not know their HIV status pre-conception were more likely to report their pregnancy as unintended compared to women who knew that they were HIV-uninfected (aOR = 1.7; 95%CI: 1.2-2.5). After controlling for other factors, unintended pregnancy was not associated with knowing one's HIV positive status prior to conception (compared with knowing one's negative HIV status prior to conception). Among women with unintended pregnancy, there was no association between knowing their HIV status and contraceptive use prior to pregnancy in adjusted analyses. Sixty-one percent of women reported not wanting any more children after this pregnancy, with HIV-infected women significantly more likely to report not wanting any more children compared to HIV-uninfected women (aOR = 3.9; 95%CI: 2.6-5.8). The high rates of reported unintended

Venues for Meeting Sex Partners and Partner HIV Risk Characteristics: HIV Prevention Trials Network (HPTN064) Women's HIV Seroincidence Study (ISIS).

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Roman Isler, M; Golin, C; Wang, J; Hughes, J; Justman, J; Haley, D; Kuo, I; Adimora, A; Chege, W; Hodder, S

2016-06-01

Identifying venues where women meet sexual partners, particular partners who increase women's risk of acquiring HIV, could inform prevention efforts. We categorized venues where women enrolled in HPTN 064 reported meeting their last three sex partners as: (1) Formal, (2) Public, (3) Private, and (4) Virtual spaces. We used multinomial logistic regression to assess the association between these venues and women's individual characteristics and reports of their partners' HIV risk characteristics. The 2099 women reported meeting 3991 partners, 51 % at Public, 30 % Private, 17 % Formal and 3 % at Virtual venues. Women meeting partners at Formal venues reported more education and condom use than women meeting partners at other venues. Fewer partners met through Formal venues had "high" risk characteristics for HIV than through other venues and hence may pose less risk of HIV transmission. HIV prevention interventions can help women choose partners with fewer risk characteristics across all venue types.

HIV, Gender, Race, Sexual Orientation, and Sex Work: A Qualitative Study of Intersectional Stigma Experienced by HIV-Positive Women in Ontario, Canada

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Logie, Carmen H.; James, LLana; Tharao, Wangari; Loutfy, Mona R.

2011-01-01

Background HIV infection rates are increasing among marginalized women in Ontario, Canada. HIV-related stigma, a principal factor contributing to the global HIV epidemic, interacts with structural inequities such as racism, sexism, and homophobia. The study objective was to explore experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada. Methods and Findings We conducted a community-based qualitative investigation using focus groups to understand experiences of stigma and discrimination and coping methods among HIV-positive women from marginalized communities. We conducted 15 focus groups with HIV-positive women in five cities across Ontario, Canada. Data were analyzed using thematic analysis to enhance understanding of the lived experiences of diverse HIV-positive women. Focus group participants (n = 104; mean age = 38 years; 69% ethnic minority; 23% lesbian/bisexual; 22% transgender) described stigma/discrimination and coping across micro (intra/interpersonal), meso (social/community), and macro (organizational/political) realms. Participants across focus groups attributed experiences of stigma and discrimination to: HIV-related stigma, sexism and gender discrimination, racism, homophobia and transphobia, and involvement in sex work. Coping strategies included resilience (micro), social networks and support groups (meso), and challenging stigma (macro). Conclusions HIV-positive women described interdependent and mutually constitutive relationships between marginalized social identities and inequities such as HIV-related stigma, sexism, racism, and homo/transphobia. These overlapping, multilevel forms of stigma and discrimination are representative of an intersectional model of stigma and discrimination. The present findings also suggest that micro, meso, and macro level factors simultaneously present barriers to health and well being—as well as opportunities for coping—in HIV-positive women's lives. Understanding the

24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study.

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Gill, Michelle M; Hoffman, Heather J; Ndatimana, Dieudonne; Mugwaneza, Placidie; Guay, Laura; Ndayisaba, Gilles F; Bobrow, Emily A; Asiimwe, Anita; Mofenson, Lynne M

2017-12-01

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother-child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 and 24 months. The Kaplan-Meier method was used to estimate HIV transmission, survival, and HIV-free survival through 24 months. We enrolled 608 HIV-positive women in 2013-2014; birth outcome data were available for 600 women and 597 live-born infants. By 6 weeks, 11 infants had died and 3 infants had confirmed HIV infection (0.5% transmission; 95% confidence interval [CI] 0.2-1.6). At 9 months, there were 9 additional deaths and 2 new infections (cumulative transmission 0.9%, 95% CI 0.4-2.2). At 18 months, there were 6 additional deaths and no new infant infections. At 24 months, there were no additional child deaths and 1 new infection (cumulative 2.2%, 95% CI 0.7-7.0), for an overall 24-month HIV-free survival of 93.2% (95% CI 89.5-95.6). Low transmission rates and high HIV-free survival at 24 months were achieved in breastfeeding infants of HIV-positive mothers receiving universal ART in urban health facilities in Rwanda, though vigilance on maintaining viral suppression for ART-experienced women is needed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study

DEFF Research Database (Denmark)

Obel, N; Thomsen, Henrik F.; Kronborg, G

2007-01-01

BACKGROUND: There are concerns about highly active antiretroviral therapy (HAART) causing a progressive increase in the risk of ischemic heart disease. We examined this issue in a nationwide cohort study of patients with human immunodeficiency virus (HIV) infection and a population-based control...... group. METHODS: We determined the rate of first hospitalization for ischemic heart disease in all Danish patients with HIV infection (3953 patients) from 1 January 1995 through 31 December 2004 and compared this rate with that for 373,856 subjects in a population-based control group. Data on first...... hospitalization for ischemic heart disease and comorbidity were obtained from the Danish National Hospital Registry for all study participants. We used Cox's regression to compute the hospitalization rate ratio as an estimate of relative risk, adjusting for comorbidity. RESULTS: Although the difference...

Testing the hypothesis that treatment can eliminate HIV: a nationwide, population-based study of the Danish HIV epidemic in men who have sex with men.

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Okano, Justin T; Robbins, Danielle; Palk, Laurence; Gerstoft, Jan; Obel, Niels; Blower, Sally

2016-07-01

Worldwide, approximately 35 million individuals are infected with HIV; about 25 million of these live in sub-Saharan Africa. WHO proposes using treatment as prevention (TasP) to eliminate HIV. Treatment suppresses viral load, decreasing the probability an individual transmits HIV. The elimination threshold is one new HIV infection per 1000 individuals. Here, we test the hypothesis that TasP can substantially reduce epidemics and eliminate HIV. We estimate the impact of TasP, between 1996 and 2013, on the Danish HIV epidemic in men who have sex with men (MSM), an epidemic UNAIDS has identified as a priority for elimination. We use a CD4-staged Bayesian back-calculation approach to estimate incidence, and the hidden epidemic (the number of HIV-infected undiagnosed MSM). To develop the back-calculation model, we use data from an ongoing nationwide population-based study: the Danish HIV Cohort Study. Incidence, and the hidden epidemic, decreased substantially after treatment was introduced in 1996. By 2013, incidence was close to the elimination threshold: 1·4 (median, 95% Bayesian credible interval [BCI] 0·4-2·1) new HIV infections per 1000 MSM and there were only 617 (264-858) undiagnosed MSM. Decreasing incidence and increasing treatment coverage were highly correlated; a treatment threshold effect was apparent. Our study is the first to show that TasP can substantially reduce a country's HIV epidemic, and bring it close to elimination. However, we have shown the effectiveness of TasP under optimal conditions: very high treatment coverage, and exceptionally high (98%) viral suppression rate. Unless these extremely challenging conditions can be met in sub-Saharan Africa, the WHO's global elimination strategy is unlikely to succeed. National Institute of Allergy and Infectious Diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

The second molecular epidemiological study of HIV infection in Mongolia between 2010 and 2016.

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Davaalkham Jagdagsuren

Full Text Available Our previous 2005-2009 molecular epidemiological study in Mongolia identified a hot spot of HIV-1 transmission in men who have sex with men (MSM. To control the infection, we collaborated with NGOs to promote safer sex and HIV testing since mid-2010. In this study, we carried out the second molecular epidemiological survey between 2010 and 2016 to determine the status of HIV-1 infection in Mongolia.The study included 143 new cases of HIV-1 infection. Viral RNA was extracted from stocked plasma samples and sequenced for the pol and the env regions using the Sanger method. Near-full length sequencing using MiSeq was performed in 3 patients who were suspected to be infected with recombinant HIV-1. Phylogenetic analysis was performed using the neighbor-joining method and Bayesian Markov chain Monte Carlo method.MSM was the main transmission route in the previous and current studies. However, heterosexual route showed a significant increase in recent years. Phylogenetic analysis documented three taxa; Mongolian B, Korean B, and CRF51_01B, though the former two were also observed in the previous study. CRF51_01B, which originated from Singapore and Malaysia, was confirmed by near-full length sequencing. Although these strains were mainly detected in MSM, they were also found in increasing numbers of heterosexual males and females. Bayesian phylogenetic analysis estimated transmission of CRF51_01B into Mongolia around early 2000s. An extended Bayesian skyline plot showed a rapid increase in the effective population size of Mongolian B cluster around 2004 and that of CRF51_01B cluster around 2011.HIV-1 infection might expand to the general population in Mongolia. Our study documented a new cluster of HIV-1 transmission, enhancing our understanding of the epidemiological status of HIV-1 in Mongolia.

The second molecular epidemiological study of HIV infection in Mongolia between 2010 and 2016.

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Jagdagsuren, Davaalkham; Hayashida, Tsunefusa; Takano, Misao; Gombo, Erdenetuya; Zayasaikhan, Setsen; Kanayama, Naomi; Tsuchiya, Kiyoto; Oka, Shinichi

2017-01-01

Our previous 2005-2009 molecular epidemiological study in Mongolia identified a hot spot of HIV-1 transmission in men who have sex with men (MSM). To control the infection, we collaborated with NGOs to promote safer sex and HIV testing since mid-2010. In this study, we carried out the second molecular epidemiological survey between 2010 and 2016 to determine the status of HIV-1 infection in Mongolia. The study included 143 new cases of HIV-1 infection. Viral RNA was extracted from stocked plasma samples and sequenced for the pol and the env regions using the Sanger method. Near-full length sequencing using MiSeq was performed in 3 patients who were suspected to be infected with recombinant HIV-1. Phylogenetic analysis was performed using the neighbor-joining method and Bayesian Markov chain Monte Carlo method. MSM was the main transmission route in the previous and current studies. However, heterosexual route showed a significant increase in recent years. Phylogenetic analysis documented three taxa; Mongolian B, Korean B, and CRF51_01B, though the former two were also observed in the previous study. CRF51_01B, which originated from Singapore and Malaysia, was confirmed by near-full length sequencing. Although these strains were mainly detected in MSM, they were also found in increasing numbers of heterosexual males and females. Bayesian phylogenetic analysis estimated transmission of CRF51_01B into Mongolia around early 2000s. An extended Bayesian skyline plot showed a rapid increase in the effective population size of Mongolian B cluster around 2004 and that of CRF51_01B cluster around 2011. HIV-1 infection might expand to the general population in Mongolia. Our study documented a new cluster of HIV-1 transmission, enhancing our understanding of the epidemiological status of HIV-1 in Mongolia.

HIV, appendectomy and postoperative complications at a reference hospital in Northwest Tanzania: cross-sectional study

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Heukelbach Jorg

2010-12-01

Full Text Available Abstract Background Appendicitis is a frequent surgical emergency worldwide. The present study was conducted to determine the prevalence of HIV, and the association of infection with clinical, intraoperative and histological findings and outcome, among patients with appendicitis. Methods We performed a cross sectional study at Weill-Bugando Medical Centre in northwest Tanzania. In total, 199 patients undergoing appendectomy were included. Demographic characteristics of patients, clinical features, laboratory, intraoperative and histopathological findings, and HIV serostatus were recorded. Results In total, 26/199 (13.1% were HIV-seropositive. The HIV-positive population was significantly older (mean age: 38.4 years than the HIV-negative population (25.3 years; p Conclusion HIV infections are common among patients with appendicitis in Tanzania, and are associated with severe morbidity, postoperative complications and longer hospital stays. Early diagnosis of appendicitis and prompt appendectomy are crucial in areas with high prevalence of HIV infection. Routine pre-test counseling and HIV screening for appendicitis patients is recommended to detect early cases who may benefit from HAART.

Let's talk about sex: A qualitative study exploring the experiences of HIV nurses when discussing sexual risk behaviours with HIV-positive men who have sex with men.

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de Munnik, S; den Daas, C; Ammerlaan, H S M; Kok, G; Raethke, M S; Vervoort, S C J M

2017-11-01

Despite prevention efforts, the incidence of sexually transmitted infection among HIV-positive men who have sex with men remains high, which is indicative of unchanged sexual risk behaviour. Discussing sexual risk behaviour has been shown to help prevent sexually transmitted infections among HIV-positive men who have sex with men. The aim of this study was to identify factors that influence whether - and how - specialised HIV nurses discuss sexual risk behaviour with HIV-positive men who have sex with men. Identifying these factors could indicate how best to improve the frequency and quality of discussions about sexual risk behaviour, thereby reducing sexual risk behaviour and sexually transmitted infections. Qualitative study, focus groups among HIV nurses. Dutch HIV treatment centres. A purposive sample was taken of 25 out of 87 HIV nurses working in one of the 26 specialised HIV treatment centres in the Netherlands. Of the 25 HIV nurses we approached, 22 participate in our study. Three semi-structured focus group interviews were held with 22 HIV nurses from 17 hospitals. Interviews were transcribed verbatim, and thematic analysis was performed. HIV nurses agreed that discussing sexual risk behaviour is important, but barriers were experienced in relation to doing so. In accordance with the theory of planned behaviour, attitudes, perceived norms and perceived behavioural control were all found to be relevant variables. Barriers to discussing sexual risk behaviour were identified as: dealing with embarrassment, the changing professional role of an HIV nurse, time constraints, and the structure of the consultation. To improve the frequency and quality of discussions about sexual risk behaviour with HIV-positive men who have sex with men, our data suggests it would be beneficial to support HIV nurses by developing tools and guidelines addressing what to discuss and how. Using a related topic as a conversational 'bridge' may help nurses to broach this subject with

Exploring How Substance Use Impedes Engagement along the HIV Care Continuum: A Qualitative Study

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Gwadz, Marya; de Guzman, Rebecca; Freeman, Robert; Kutnick, Alexandra; Silverman, Elizabeth; Leonard, Noelle R.; Ritchie, Amanda Spring; Muñoz-Plaza, Corinne; Salomon, Nadim; Wolfe, Hannah; Hilliard, Christopher; Cleland, Charles M.; Honig, Sylvie

2016-01-01

Drug use is associated with low uptake of HIV antiretroviral therapy (ART), an under-studied step in the HIV care continuum, and insufficient engagement in HIV primary care. However, the specific underlying mechanisms by which drug use impedes these HIV health outcomes are poorly understood. The present qualitative study addresses this gap in the literature, focusing on African-American/Black and Hispanic persons living with HIV (PLWH) who had delayed, declined, or discontinued ART and who also were generally poorly engaged in health care. Participants (N = 37) were purposively sampled from a larger study for maximum variation on HIV indices. They engaged in 1–2 h audio-recorded in-depth semi-structured interviews on HIV histories guided by a multilevel social-cognitive theory. Transcripts were analyzed using a systematic content analysis approach. Consistent with the existing literature, heavy substance use, but not casual or social use, impeded ART uptake, mainly by undermining confidence in medication management abilities and triggering depression. The confluence of African-American/Black or Hispanic race/ethnicity, poverty, and drug use was associated with high levels of perceived stigma and inferior treatment in health-care settings compared to their peers. Furthermore, providers were described as frequently assuming participants were selling their medications to buy drugs, which strained provider–patient relationships. High levels of medical distrust, common in this population, created fears of ART and of negative interactions between street drugs and ART, but participants could not easily discuss this concern with health-care providers. Barriers to ART initiation and HIV care were embedded in other structural- and social-level challenges, which disproportionately affect low-income African-American/Black and Hispanic PLWH (e.g., homelessness, violence). Yet, HIV management was cyclical. In collaboration with trusted providers and ancillary staff

Predictors of HIV Testing among Youth in Sub-Saharan Africa: A Cross-Sectional Study.

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Ibitola O Asaolu

Full Text Available In spite of a high prevalence of HIV infection among adolescents and young adults in sub-Saharan Africa, uptake of HIV testing and counseling among youth in the region remains sub-optimal. The objective of this study was to assess factors that influence uptake of HIV testing and counseling among youth aged 15-24 years in sub-Saharan Africa.This study used the Demographic and Health Survey (DHS data from countries that represent four geographic regions of sub-Saharan Africa: Congo (Brazzaville, representing central Africa (DHS 2011-2012; Mozambique, representing southern Africa (DHS 2011; Nigeria, representing western Africa (DHS 2013; and Uganda, representing eastern Africa (DHS 2011. Analyses were restricted to 23,367 male and female respondents aged 15-24 years with complete data on the variables of interest. Chi-square tests and logistic regression models were used to assess predictors of HIV testing. Statistical significance was set at p< 0.01.The analysis revealed that a majority of the respondents were female (78.1% and aged 20-24-years (60.7%. Only a limited proportion of respondents (36.5% had ever tested for HIV and even fewer (25.7% demonstrated comprehensive knowledge of HIV/AIDS. There was a significant association between HIV testing and respondents' gender, age, age at sexual debut, and comprehensive knowledge of HIV in the pooled sample. Older youth (adjusted OR (aOR = 2.19; 99% CI = 1.99-2.40 and those with comprehensive knowledge of HIV (aOR = 1.98; 1.76-2.22 had significantly higher odds of ever being tested for HIV than younger respondents and those with limited HIV/AIDS knowledge respectively. Furthermore, men had lower odds of HIV testing than women (aOR = 0.32; 0.28-0.37.Reaching youth in sub-Saharan Africa for HIV testing continues to be a challenge. Public health programs that seek to increase HIV counseling and testing among youth should pay particular attention to efforts that target high-risk subpopulations of youth

Stigmatization among people living with HIV in Hong Kong: A qualitative study.

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Mo, Phoenix K H; Ng, Charlson T Y

2017-10-01

HIV/AIDS is one of the most stigmatized medical conditions across the world. Self-stigma is prevalent among people living with HIV (PLHIV) and a major obstacle to HIV prevention and care. This study aimed to describe the experiences of stigmatization and explore the possible factors that might be associated with stigmatization among PLHIV in Hong Kong. Qualitative in-depth interviews were conducted. 15 PLHIV were recruited from two local non-governmental organizations on HIV prevention. Participants were interviewed about their views and feelings towards oneself as a PLHIV and contributing factors, experiences of discriminations, stigmatizing behaviours, issues about disclosure, social relationships and potential impact of HIV. Thematic analyses revealed three levels of factors which might be associated with stigmatization: (i) intrapersonal level (misconceptions about HIV, attribution of self-responsibility, severe state of illness, side-effects of medication), (ii) interpersonal level (discrimination, social rejection) and (iii) social level (mass media, public stereotypes). Findings provide important insights into which interventions to reduce stigmatization of PLHIV could be designed. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Using High-Impact HIV Prevention to Achieve the National HIV/AIDS Strategic Goals in Miami-Dade County, Florida: A Case Study.

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Carey, James W; LaLota, Marlene; Villamizar, Kira; McElroy, Tamara; Wilson, M Maximillion; Garcia, Jersey; Sandrock, Robert; Taveras, Janelle; Candio, Darline; Flores, Stephen A

2015-01-01

: In response to the release of the National HIV/AIDS Strategy, the Centers for Disease Control and Prevention developed the "Enhanced Comprehensive HIV Prevention Planning" project, which provided support to health departments in 12 Metropolitan Statistical Areas with the highest AIDS prevalence to strengthen local HIV programs. We describe a case study of how 1 Metropolitan Statistical Area, Miami-Dade County, developed and implemented a locally tailored plan. Examples include actions to reinforce local partnerships and identify neighborhoods with highest unmet needs, an improved condom distribution system to assist local HIV care providers, collaboration with local stakeholders to establish a new walk-in center for transgender client needs, and overcoming incompatibilities in health department and Ryan White Program computer record systems to facilitate faster and more efficient patient services. These examples show how jurisdictions both within Florida and elsewhere can create low-cost and sustainable activities tailored to improve local HIV prevention needs.

Sexual Behaviors and HIV Status: A Population-Based Study Among Older Adults in Rural South Africa

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Gómez-Olivé, Francesc X.; Rohr, Julia K.; Houle, Brian C.; Kabudula, Chodziwadziwa W.; Wagner, Ryan G.; Salomon, Joshua A.; Kahn, Kathleen; Berkman, Lisa F.; Tollman, Stephen M.; Bärnighausen, Till

2017-01-01

Objective: To identify the unmet needs for HIV prevention among older adults in rural South Africa. Methods: We analyzed data from a population-based sample of 5059 men and women aged 40 years and older from the study Health and Aging in Africa: Longitudinal Studies of INDEPTH Communities (HAALSI), which was carried out in the Agincourt health and sociodemographic surveillance system in the Mpumalanga province of South Africa. We estimated the prevalence of HIV (laboratory-confirmed and self-reported) and key sexual behaviors by age and sex. We compared sexual behavior profiles across HIV status categories with and without age–sex standardization. Results: HIV prevalence was very high among HAALSI participants (23%, 95% confidence interval [CI]: 21 to 24), with no sex differences. Recent sexual activity was common (56%, 95% CI: 55 to 58) across all HIV status categories. Condom use was low among HIV-negative adults (15%, 95% CI: 14 to 17), higher among HIV-positive adults who were unaware of their HIV status (27%, 95% CI: 22 to 33), and dramatically higher among HIV-positive adults who were aware of their status (75%, 95% CI: 70 to 80). Casual sex and multiple partnerships were reported at moderate levels, with slightly higher estimates among HIV-positive compared to HIV-negative adults. Differences by HIV status remained after age–sex standardization. Conclusions: Older HIV-positive adults in an HIV hyperendemic community of rural South Africa report sexual behaviors consistent with high HIV transmission risk. Older HIV-negative adults report sexual behaviors consistent with high HIV acquisition risk. Prevention initiatives tailored to the particular prevention needs of older adults are urgently needed to reduce HIV risk in this and similar communities in sub-Saharan Africa. PMID:27926667

Sexual Behaviors and HIV Status: A Population-Based Study Among Older Adults in Rural South Africa.

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Rosenberg, Molly S; Gómez-Olivé, Francesc X; Rohr, Julia K; Houle, Brian C; Kabudula, Chodziwadziwa W; Wagner, Ryan G; Salomon, Joshua A; Kahn, Kathleen; Berkman, Lisa F; Tollman, Stephen M; Bärnighausen, Till

2017-01-01

To identify the unmet needs for HIV prevention among older adults in rural South Africa. We analyzed data from a population-based sample of 5059 men and women aged 40 years and older from the study Health and Aging in Africa: Longitudinal Studies of INDEPTH Communities (HAALSI), which was carried out in the Agincourt health and sociodemographic surveillance system in the Mpumalanga province of South Africa. We estimated the prevalence of HIV (laboratory-confirmed and self-reported) and key sexual behaviors by age and sex. We compared sexual behavior profiles across HIV status categories with and without age-sex standardization. HIV prevalence was very high among HAALSI participants (23%, 95% confidence interval [CI]: 21 to 24), with no sex differences. Recent sexual activity was common (56%, 95% CI: 55 to 58) across all HIV status categories. Condom use was low among HIV-negative adults (15%, 95% CI: 14 to 17), higher among HIV-positive adults who were unaware of their HIV status (27%, 95% CI: 22 to 33), and dramatically higher among HIV-positive adults who were aware of their status (75%, 95% CI: 70 to 80). Casual sex and multiple partnerships were reported at moderate levels, with slightly higher estimates among HIV-positive compared to HIV-negative adults. Differences by HIV status remained after age-sex standardization. Older HIV-positive adults in an HIV hyperendemic community of rural South Africa report sexual behaviors consistent with high HIV transmission risk. Older HIV-negative adults report sexual behaviors consistent with high HIV acquisition risk. Prevention initiatives tailored to the particular prevention needs of older adults are urgently needed to reduce HIV risk in this and similar communities in sub-Saharan Africa.

Phenotypic plasticity, costs of phenotypes, and costs of plasticity

DEFF Research Database (Denmark)

Callahan, Hilary S; Maughan, Heather; Steiner, Uli

2008-01-01

Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

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

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

2017-07-01

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

HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A 1H MRS Study

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Cysique, Lucette A.; Moffat, Kirsten; Moore, Danielle M.; Lane, Tammy A.; Davies, Nicholas W. S.; Carr, Andrew; Brew, Bruce J.; Rae, Caroline

2013-01-01

Background Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear. Methods 92 HIV− infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV−) subjects underwent 1H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals. Results Relative to HIV− individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (pHIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter. Conclusions In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by

HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier, and microbial translocation.

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Wang, Hongyin; Kotler, Donald P

2014-07-01

Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

AWARENESS AND SOCIAL STIGMA ASSOCIATED WITH HIV/AIDS AND TUBERCULOSIS AMONG STUDENTS: A COMPARATIVE STUDY

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Leyanna Susan

2015-11-01

Full Text Available INTRODUCTION Human immunodeficiency virus (HIV and Tuberculosis (TB are two major public health problems that are often seen as co-infections, but are spread via different routes having different treatment strategies and outcomes with one being curable and the other not. However, both these diseases have stigma in common. OBJECTIVES (i To assess the knowledge and social stigma regarding HIV/AIDS. (ii To assess the knowledge and social stigma regarding TB. (iii To study the association between knowledge & social stigma in HIV/AIDS and TB. (ivTo compare the social stigma associated with HIV/AIDS and TB. METHODOLOGY A cross-sectional study was carried out in an urban Arts & Science college situated in Kochi among students aged between 17-24 years. Those students who were not willing to participate and who have/had TB or HIV/AIDS were excluded from the study. A total of 171 students were included in the study by random sampling and a pretested self-administered questionnaire was used.INTRODUCTION Human immunodeficiency virus (HIV and Tuberculosis (TB are two major public health problems that are often seen as co-infections, but are spread via different routes having different treatment strategies and outcomes with one being curable and the other not. However, both these diseases have stigma in common. OBJECTIVES (i To assess the knowledge and social stigma regarding HIV/AIDS. (ii To assess the knowledge and social stigma regarding TB. (iii To study the association between knowledge & social stigma in HIV/AIDS and TB. (ivTo compare the social stigma associated with HIV/AIDS and TB. METHODOLOGY A cross-sectional study was carried out in an urban Arts & Science college situated in Kochi among students aged between 17-24 years. Those students who were not willing to participate and who have/had TB or HIV/AIDS were excluded from the study. A total of 171 students were included in the study by random sampling and a pretested self

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

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

2018-07-01

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

Social context surrounding HIV diagnosis and construction of masculinity: a qualitative study of stigma experiences of heterosexual HIV positive men in southwest Nigeria

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Titilayo Ainegbesua Okoror

2016-06-01

Full Text Available Abstract Background Though research has documented experiences of stigma and its effects on the lives of women living with HIV/AIDS, there is limited research on heterosexual positive HIV men experience of stigma in Nigeria. This study explored how social context surrounding HIV diagnosis impacts stigma experiences of heterosexual HIV positive men and their construction of masculinity in southwest Nigeria. Methods Using purposive sampling, 17 heterosexual HIV positive men were recruited through community based organization to participate in two hours focus group discussions or 45 min in-depth interviews that were audio-recorded. Without using the word stigma, discussions and interviews were guided by four questions that explored participants’ experiences of living with HIV/AIDS. Interviews and discussions were conducted in three languages: English, Yoruba and Pidgin English. Thematic data analysis approach was in coding transcribed data, while social constructivist thinking guided data analysis. Results Participants ranged in age from 30 to 57 years old, and all were receiving antiretroviral therapy. Findings indicated that participants’ experiences of stigma might be moderated by the social context surrounding their HIV diagnosis, and whether they have met the socio-cultural construction of masculinity. Participants whose diagnosis were preceded by immediate family members’ diagnosis were less likely to report experiencing HIV stigma and more likely to report “not feeling less than a man” and educating others about HIV/AIDS. Contrarily, participants whose diagnosis was preceded by their own sickness were more likely to report isolation, sigma and feeling of being less than a man. All participants reported limiting their sexual intimacy, and those with children reported adjusting how they performed their role as fathers. Conclusions Social context surrounding HIV diagnosis impact how heterosexual HIV positive men experience HIV

Social context surrounding HIV diagnosis and construction of masculinity: a qualitative study of stigma experiences of heterosexual HIV positive men in southwest Nigeria.

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Okoror, Titilayo Ainegbesua; Falade, Catherine Olufunke; Walker, Ebunlomo Mary; Olorunlana, Adetayo; Anaele, Agaptus

2016-06-13

Though research has documented experiences of stigma and its effects on the lives of women living with HIV/AIDS, there is limited research on heterosexual positive HIV men experience of stigma in Nigeria. This study explored how social context surrounding HIV diagnosis impacts stigma experiences of heterosexual HIV positive men and their construction of masculinity in southwest Nigeria. Using purposive sampling, 17 heterosexual HIV positive men were recruited through community based organization to participate in two hours focus group discussions or 45 min in-depth interviews that were audio-recorded. Without using the word stigma, discussions and interviews were guided by four questions that explored participants' experiences of living with HIV/AIDS. Interviews and discussions were conducted in three languages: English, Yoruba and Pidgin English. Thematic data analysis approach was in coding transcribed data, while social constructivist thinking guided data analysis. Participants ranged in age from 30 to 57 years old, and all were receiving antiretroviral therapy. Findings indicated that participants' experiences of stigma might be moderated by the social context surrounding their HIV diagnosis, and whether they have met the socio-cultural construction of masculinity. Participants whose diagnosis were preceded by immediate family members' diagnosis were less likely to report experiencing HIV stigma and more likely to report "not feeling less than a man" and educating others about HIV/AIDS. Contrarily, participants whose diagnosis was preceded by their own sickness were more likely to report isolation, sigma and feeling of being less than a man. All participants reported limiting their sexual intimacy, and those with children reported adjusting how they performed their role as fathers. Social context surrounding HIV diagnosis impact how heterosexual HIV positive men experience HIV related stigma and how they perceive themselves as men, which may influence their

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

Missed opportunities for HIV control: Gaps in HIV testing for partners of people living with HIV in Lima, Peru.

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Ana L Vasquez

Full Text Available Based on the hypothesis that HIV programs struggle to deliver health services that harmonize necessities of treatment and prevention, we described the outcomes of routinely provided HIV testing to partners of people living with HIV (PLWH through a secondary analysis of routine data collected at a public hospital in Lima, Peru.Among PLWH enrolled in the study center's HIV program between 2005 and 2014, we identified index cases (IC: PLWH who reported a unique partner not previously enrolled. We grouped partners according to their HIV status as reported by IC and collected data on HIV testing, clinical characteristics and admissions. The main outcome was the frequency of HIV testing among partners with reported unknown/seronegative HIV status.Out of 1586 PLWH who reported a unique partner at enrollment, 171 had a previously enrolled partner, leaving 1415 (89% IC. HIV status of the partner was reported as unknown in 571 (40%, seronegative in 325 (23% and seropositive in 519 (37%. Out of 896 partners in the unknown/seronegative group, 72 (8% had HIV testing, 42/72 (58% tested within three months of IC enrollment. Among the 49/72 (68% who tested positive for HIV, 33 (67% were enrolled in the HIV program. The proportion in WHO clinical stage IV was lower in enrolled partners compared to IC (37% vs 9%, p = 0.04. Non-tested partners (824 were likely reachable by the hospital, as 297/824 (36% of their IC were admitted in the study center at least once, 51/243 (21% female IC had received pregnancy care at the study center, and 401/692 (64% of IC on antiretroviral therapy had achieved viral suppression, implying frequent visits to the hospital for pill pick-up.In this setting, HIV testing of partners of PLWH was suboptimal, illustrating missed opportunities for HIV control. Integration of HIV strategies in primarily clinical-oriented services is a challenging need.

Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study

Science.gov (United States)

Bayard, Cornelia; Ledergerber, Bruno; Flepp, Markus; Lecompte, Thanh; Moulin, Estelle; Hoffmann, Matthias; Weber, Rainer; Staehelin, Cornelia; Di Benedetto, Caroline; Fux, Christoph A; Tarr, Philip E; Aubert, V; Battegay, M; Bernasconi, E; Böni, J; Braun, DL; Bucher, HC; Calmy, A; Cavassini, M; Ciuffi, A; Dollenmaier, G; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, CA; Günthard, HF; Haerry, D; Hasse, B; Hirsch, HH; Hoffmann, M; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kouyos, RD; Kovari, H; Ledergerber, B; Martinetti, G; Martinez de Tejada, B; Marzolini, C; Metzner, KJ; Müller, N; Nicca, D; Pantaleo, G; Paioni, P; Rauch, A; Rudin, C; Scherrer, AU; Schmid, P; Speck, R; Stöckle, M; Tarr, P; Trkola, A; Vernazza, P; Wandeler, G; Weber, R; Yerly, S

2017-01-01

Abstract Background HIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS). Methods We used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis. Results We compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN. Conclusions In the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed. PMID:29026869

Prevalence and characteristics of HIV/HBV and HIV/HCV coinfections in Tuscany

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Monia Puglia

2016-07-01

Conclusions: We have observed less advanced disease in HIV and HCV-HIV patients compared with HBV–HIV coinfected patients. Moreover, our results show a higher prevalence of HIV/HCV among drug addicts and in the age-group 35–59, corresponding to those born in years considered most at risk for addiction. This study also confirms the finding of a less advanced HIV disease in HIV/HCV coinfected patients.

Psychiatric disorders, HIV infection and HIV/hepatitis co-infection in the correctional setting.

Science.gov (United States)

Baillargeon, J G; Paar, D P; Wu, H; Giordano, T P; Murray, O; Raimer, B G; Avery, E N; Diamond, P M; Pulvino, J S

2008-01-01

Psychiatric disorders such as bipolar disorder, schizophrenia and depression have long been associated with risk behaviors for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). The US prison population is reported to have elevated rates of HIV, hepatitis and most psychiatric disorders. This study examined the association of six major psychiatric disorders with HIV mono-infection, HIV/HCV co-infection and HIV/HBV co-infection in one of the nation's largest prison populations. The study population consisted of 370,511 Texas Department of Criminal Justice inmates who were incarcerated for any duration between January 1, 2003 and July 1, 2006. Information on medical conditions and sociodemographic factors was obtained from an institution-wide electronic medical information system. Offenders diagnosed with HIV mono-infection, HIV/HCV, HIV/HBV and all HIV combined exhibited elevated rates of major depression, bipolar disorder, schizophrenia, schizoaffective disorder, non-schizophrenic psychotic disorder and any psychiatric disorder. In comparison to offenders with HIV mono-infection, those with HIV/HCV co-infection had an elevated prevalence of any psychiatric disorder. This cross-sectional study's finding of positive associations between psychiatric disease and both HIV infection and hepatitis co-infection among Texas prison inmates holds both clinical and public health relevance. It will be important for future investigations to examine the extent to which psychiatric disorders serve as a barrier to medical care, communication with clinicians and adherence to prescribed medical regimens among both HIV-mono-infected and HIV/hepatitis-co-infected inmates.

Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure.

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Khan, Shahzada; Telwatte, Sushama; Trapecar, Martin; Yukl, Steven; Sanjabi, Shomyseh

2017-11-01

The single greatest challenge to an HIV cure is the persistence of latently infected cells containing inducible, replication-competent proviral genomes, which constitute only a small fraction of total or infected cells in the body. Although resting CD4 + T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4 + T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues. The mechanisms by which latency is established and maintained will likely depend on the location and cytokine milieu surrounding the latently infected cells in each compartment. Therefore, successful HIV cure strategies require identification and characterization of the exact cell types that support viral persistence, particularly in the gut. In this review, we describe the seeding of the latent HIV reservoir in the gut mucosa; highlight the evidence for compartmentalization and depletion of T cells; summarize the immunologic consequences of HIV infection within the gut milieu; propose how the damaged gut environment may promote the latent HIV reservoir; and explore several immune cell targets in the gut and their place on the path toward HIV cure.

Measuring HIV- and AIDS-related stigma and discrimination in Nicaragua: results from a community-based study.

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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.

Upper Gastrointestinal Symptoms Predictive of Candida Esophagitis and Erosive Esophagitis in HIV and Non-HIV Patients: An Endoscopy-Based Cross-Sectional Study of 6011 Patients.

Science.gov (United States)

Takahashi, Yuta; Nagata, Naoyoshi; Shimbo, Takuro; Nishijima, Takeshi; Watanabe, Koji; Aoki, Tomonori; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Sakurai, Toshiyuki; Yokoi, Chizu; Mimori, Akio; Oka, Shinichi; Uemura, Naomi; Akiyama, Junichi

2015-11-01

large-scale endoscopy-based study showed that HIV-infected patients have greater GI symptom scores compared with non-HIV-infected patients even after excluding GI-organic diseases. None of the upper GI symptoms predict candida esophagitis in HIV-infected patients, but dysphagia and odynophagia predict candida esophagitis in non-HIV-infected patients. Heartburn and acid regurgitation predict erosive esophagitis in both patient groups.

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

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Wayland Hsiao

2009-01-01

Full Text Available HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs and corresponding 95% confidence intervals (CI. The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5. In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

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Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

2009-01-01

HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

CASE STUDY – HIV AND LUNG DISEASE

African Journals Online (AJOL)

2011-04-02

Apr 2, 2011 ... pathology deep to the paraseptal bullae. An intercostal drain tip is seen in the left lateral pleural space. Fig. 2. Axial computed tomography scan on lung windows. Large bilateral paraseptal bullae are demonstrated with residual antero-medial pneumothorax. 37. CASE STUDY – HIV AND LUNG DISEASE ...

Preventing HIV Transmission Among Partners of HIV-Positive Male Sex Workers in Mexico City: A Modeling Study.

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Monteiro, João Filipe G; Marshall, Brandon D L; Escudero, Daniel; Sosa-Rubí, Sandra G; González, Andrea; Flanigan, Timothy; Operario, Don; Mayer, Kenneth H; Lurie, Mark N; Galárraga, Omar

2015-09-01

Mexico has a concentrated HIV epidemic, with male sex workers constituting a key affected population. We estimated annual HIV cumulative incidence among male sex workers' partners, and then compared incidence under three hypothetical intervention scenarios: improving condom use; and scaling up HIV treatment as prevention, considering current viral suppression rates (CVS, 60.7 %) or full viral suppression among those treated (FVS, 100 %). Clinical and behavioral data to inform model parameterization were derived from a sample (n = 79) of male sex workers recruited from street locations and Clínica Condesa, an HIV clinic in Mexico City. We estimated annual HIV incidence among male sex workers' partners to be 8.0 % (95 % CI: 7.3-8.7). Simulation models demonstrated that increasing condom use by 10 %, and scaling up HIV treatment initiation by 50 % (from baseline values) would decrease the male sex workers-attributable annual incidence to 5.2, 4.4 % (CVS) and 3.2 % (FVS), respectively. Scaling up the number of male sex workers on ART and implementing interventions to ensure adherence is urgently required to decrease HIV incidence among male sex workers' partners in Mexico City.

Family model of HIV care and treatment: a retrospective study in Kenya

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2012-01-01

Background Nyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV-infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal. Methods A family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV-positive members and to prevent new infections. Comprehensive family-centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach. Results Through the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV- positive partners among those tested: 71% and 89%, respectively. Conclusions The family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement. PMID:22353553

HIV transmission patterns among The Netherlands, Suriname, and The Netherlands Antilles: a molecular epidemiological study.

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Kramer, Merlijn A; Cornelissen, Marion; Paraskevis, Dimitrios; Prins, Maria; Coutinho, Roel A; van Sighem, Ard I; Sabajo, Lesley; Duits, Ashley J; Winkel, Cai N; Prins, Jan M; van der Ende, Marchina E; Kauffmann, Robert H; Op de Coul, Eline L

2011-02-01

We aimed to study patterns of HIV transmission among Suriname, The Netherlands Antilles, and The Netherlands. Fragments of env, gag, and pol genes of 55 HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands and 72 HIV-infected heterosexuals living in Suriname and the Antilles were amplified and sequenced. We included 145 pol sequences of HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands from an observational cohort. All sequences were phylogenetically analyzed by neighbor-joining. Additionally, HIV-1 mobility among ethnic groups was estimated. A phylogenetic tree of all pol sequences showed two Surinamese and three Antillean clusters of related strains, but no clustering between ethnic groups. Clusters included sequences of individuals living in Suriname and the Antilles as well as those who have migrated to The Netherlands. Similar clustering patterns were observed in env and gag. Analysis of HIV mobility among ethnic groups showed significantly lower migration between groups than expected under the hypothesis of panmixis, apart from higher HIV migration between Antilleans in The Netherlands and all other groups. Our study shows that HIV transmission mainly occurs within the ethnic group. This suggests that cultural factors could have a larger impact on HIV mobility than geographic distance.

A qualitative study of barriers to enrollment into free HIV care: perspectives of never-in-care HIV-positive patients and providers in Rakai, Uganda.

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Nakigozi, Gertrude; Atuyambe, Lynn; Kamya, Moses; Makumbi, Fredrick E; Chang, Larry W; Nakyanjo, Neema; Kigozi, Godfrey; Nalugoda, Fred; Kiggundu, Valerian; Serwadda, David; Wawer, Maria; Gray, Ronald

2013-01-01

Early entry into HIV care is low in Sub-Saharan Africa. In Rakai, about a third (31.5%) of HIV-positive clients who knew their serostatus did not enroll into free care services. This qualitative study explored barriers to entry into care from HIV-positive clients who had never enrolled in care and HIV care providers. We conducted 48 in-depth interviews among HIV-infected individuals aged 15-49 years, who had not entered care within six months of result receipt and referral for free care. Key-informant interviews were conducted with 12 providers. Interviews were audio-recorded and transcripts subjected to thematic content analysis based on the health belief model. Barriers to using HIV care included fear of stigma and HIV disclosure, women's lack of support from male partners, demanding work schedules, and high transport costs. Programmatic barriers included fear of antiretroviral drug side effects, long waiting and travel times, and inadequate staff respect for patients. Denial of HIV status, belief in spiritual healing, and absence of AIDS symptoms were also barriers. Targeted interventions to combat stigma, strengthen couple counseling and health education programs, address gender inequalities, and implement patient-friendly and flexible clinic service hours are needed to address barriers to HIV care.

Anorectal pathology amongst HIV infected patients attending the Douala General Hospital: a cross-sectional study.

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Luma, Henry Namme; Eloumou, Servais Albert Fiacre Bagnaka; Fualefeh-Morfaw, Ellis Atemlefeh; Malongue, Agnes; Temfack, Elvis; Lekpa, Fernando Kemta; Donfack-Sontsa, Olivier; Ndip, Lucy; Ditah, Ivo Che

2017-03-01

While gastrointestinal disease is common among HIV infected individuals, the prevalence and distribution of ano-rectal pathology has not been well studied in our setting. The objective of this study therefore was to determine the prevalence and determinants of ano-rectal pathology in HIV infected patients attending the Douala General Hospital HIV treatment centre. A hospital-based cross-sectional study was undertaken. We collected socio-demographic, clinical and laboratory data using a structured questionnaire and patients' files. Each study participant had a full physical and ano-rectal examination. We further studied factors associated with having at least one ano-rectal lesion by logistic regression reporting odds ratios (ORs) and their 95% confidence intervals (CI). We included 390 HIV infected patients. The mean age was 41 (SD: 8) years and 48% were men. Median duration since HIV diagnosis was 3 (interquartile range: 2-5) years and median CD4 cell count was 411 (interquartile range: 234-601) cells/mm 3 . Prevalence of ano-rectal pathology was 22.8% (95% CI: 18.7-27.3). Hemorrhoids and proctitis were most common lesions found; each in 10% of patients. From multivariate logistic regression, factors associated with ano-rectal pathology were CD4 HIV infected patients. Care givers should actively investigate and treat them as this will improve the quality of life of people living with HIV/AIDS.

Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

DEFF Research Database (Denmark)

Williams, Frances M K; Carter, Angela M; Kato, Bernet

2009-01-01

OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs as...

Association between Taenia solium infection and HIV/AIDS in northern Tanzania: a matched cross sectional-study.

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Schmidt, Veronika; Kositz, Christian; Herbinger, Karl-Heinz; Carabin, Hélène; Ngowi, Bernard; Naman, Ezra; Wilkins, Patricia P; Noh, John; Matuja, William; Winkler, Andrea Sylvia

2016-12-01

The frequency of Taenia solium, a zoonotic helminth, is increasing in many countries of sub-Saharan Africa, where the prevalence of the human immunodeficiency virus (HIV) is also high. However, little is known about how these two infections interact. The aim of this study was to compare the proportion of HIV positive (+) and negative (-) individuals who are infected with Taenia solium (TSOL) and who present with clinical and neurological manifestations of cysticercosis (CC). In northern Tanzania, 170 HIV+ individuals and 170 HIV- controls matched for gender, age and village of origin were recruited. HIV staging and serological tests for TSOL antibodies (Ab) and antigen (Ag) were performed. Neurocysticercosis (NCC) was determined by computed tomography (CT) using standard diagnostic criteria. Neurological manifestations were confirmed by a standard neurological examination. In addition, demographic, clinical and neuroimaging data were collected. Further, CD4 + cell counts as well as information on highly active antiretroviral treatment (HAART) were noted. No significant differences between HIV+ and HIV- individuals regarding the sero-prevalence of taeniosis-Ab (0.6% vs 1.2%), CC-Ab (2.4% vs 2.4%) and CC-Ag (0.6% vs 0.0%) were detected. A total of six NCC cases (3 HIV+ and 3 HIV-) were detected in the group of matched participants. Two individuals (1 HIV+ and 1 HIV-) presented with headaches as the main symptom for NCC, and four with asymptomatic NCC. Among the HIV+ group, TSOL was not associated with CD4 + cell counts, HAART duration or HIV stage. This study found lower prevalence of taeniosis, CC and NCC than had been reported in the region to date. This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC. Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself.

Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study1234

Science.gov (United States)

Jacobson, Denise L; Patel, Kunjal; Siberry, George K; Van Dyke, Russell B; DiMeglio, Linda A; Geffner, Mitchell E; Chen, Janet S; McFarland, Elizabeth J; Borkowsky, William; Silio, Margarita; Fielding, Roger A; Siminski, Suzanne; Miller, Tracie L

2011-01-01

Background: Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. Objective: Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clinical variables. Design: In a cross-sectional analysis, children aged 7–16 y in the Pediatric HIV/AIDS Cohort Study underwent regionalized measurements of body fat via anthropometric methods and dual-energy X-ray absorptiometry. Multiple linear regression was used to evaluate body fat by HIV, with adjustment for age, Tanner stage, race, sex, and correlates of body fat in HIV-infected children. Percentage total body fat was compared with NHANES data. Results: Males accounted for 47% of the 369 HIV-infected and 51% of the 176 HEU children. Compared with HEU children, HIV-infected children were older, were more frequently non-Hispanic black, more frequently had Tanner stage ≥3, and had lower mean height (−0.32 compared with 0.29), weight (0.13 compared with 0.70), and BMI (0.33 compared with 0.63) z scores. On average, HIV-infected children had a 5% lower percentage total body fat (TotF), a 2.8% lower percentage extremity fat (EF), a 1.4% higher percentage trunk fat (TF), and a 10% higher trunk-to-extremity fat ratio (TEFR) than did the HEU children and a lower TotF compared with NHANES data. Stavudine use was associated with lower EF and higher TF and TEFR. Non-nucleotide reverse transcriptase inhibitor use was associated with higher TotF and EF and lower TEFR. Conclusion: Although BMI and total body fat were significantly lower in the HIV-infected children than in the HEU children, body fat distribution in the HIV-infected children followed a pattern associated with cardiovascular disease risk and possibly related to specific antiretroviral drugs. PMID:22049166

HIV-1 transmission within marriage in rural Uganda: a longitudinal study.

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Samuel Biraro

Full Text Available BACKGROUND: Early initiation of antiretroviral therapy reduces risk of transmission to the uninfected partner in HIV discordant couples, but there are relatively little observational data on HIV transmission within couples from non-trial settings. The aims of this paper are to estimate HIV incidence among HIV discordant couples using longstanding observational data from a rural Ugandan population and to identify factors associated with HIV transmission within couples, including the role of HSV-2 infection. METHODS: Using existing data collected at population-wide annual serological and behavioural surveys in a rural district in southwest Uganda between 1989 and 2007, HIV discordant partners were identified. Stored serum samples were tested for HSV-2 serostatus using the Kalon ELISA test. HIV seroconversion rates and factors association with HIV seroconversion were analysed using Poisson regression. RESULTS: HIV status of both partners was known in 2465 couples and of these 259 (10.5% were HIV serodiscordant. At enrollment, HSV-2 prevalence was 87.3% in HIV positive partners and 71.5% in HIV negative partners. Of the 259 discordant couples, 62 converted to HIV (seroconversion rate 7.11/100 PYAR, 95%CI; 5.54, 9.11 with the rate decreasing from 10.89 in 1990-1994 to 4.32 in 2005-2007. Factors independently associated with HIV seroconversion were female sex, non-Muslim religion, greater age difference (man older than woman by more than 15 years, higher viral load in the positive partner and earlier calendar period. HSV-2 was not independently associated with HIV acquisition (HR 1.62, 95%CI; 0.57, 4.55 or transmission (HR 0.61, 95%CI; 0.24, 1.57. No transmissions occurred in the 29 couples where the index partner was on ART during follow up (872 person-years on ART. DISCUSSION: HIV negative partners in serodiscordant couples have a high incidence of HIV if the index partner is not on antiretroviral therapy and should be provided with interventions