Hales, Gillian; Birch, Chris; Crowe, Suzanne; Workman, Cassy; Hoy, Jennifer F; Law, Matthew G; Kelleher, Anthony D; Lincoln, Douglas; Emery, Sean
The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART). Randomised, open-label trial with 48-week followup. The study was conducted in a network of primary healthcare sites in Australia and New Zealand. Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent. Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen. Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period. Three hundred and twenty seven patients completing >or= one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p = 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm(3), group B: 50 cells/mm(3); p = 0.28). In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection.
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.
陈小平; 陈观今; 肖斌权; 施文钧; 徐惠芳; 高凯
@@ With the advance of research on HIV/AIDS, CD8 T-lymphocyte is believed to be independently an important immune factor of controlling HIV infection not only in its number but also in its function. Multiple studies on phenotypic markers or surface antigens of lymphocytes show that level of expression of CD25 decrease while that of HIA-DR increased on lymphocytes in HIV-infected individuals compared with that in HIV-negative subjects and that levels of expression of these molecules represent a part of function of lymphocytes. But function testing of CD4 cell and CD8 cell is complicated in technique and time spending. In addition, some studies indicate that apoptosis of CD4 cells play an important role in HIV/AIDS pathogenesis. So it is clinically important to compare the lymphocyte subsets and phenotypes in HIV-positive subjects with those in HIV-negative individuals.
陈小平; 陈观今; 肖斌权; 施文钧; 徐惠芳; 高凯
With the advance of research on HIV/AIDS, CD8 T-lymphocyte is believed to be independently an important immune factor of controlling HIV infection not only in its number but also in its func-tion. Multiple studies on phenotypic markers or surface antigens of lymphocytes show that level of expression of CD25 decrease while that of HLA-DR increased on lymphocytes in HIV-infected individuals compared with that in HIV-negative subjects and that levels of expression of these molecules represent a part of function of lymphocytes. But function testing of CD4 cell and CD8 cell is complicated in technique and time spending. In addition, some studies indicate that apoptosis of CD4 cells play an important role in HIV/AIDS pathogenesis. So it is clinically important to compare the lymphocyte subsets and phenotypes in HIV-positive subjects with those in HIV-negative individuals.
Saliou, Adrien; Delobel, Pierre; Dubois, Martine; Nicot, Florence; Raymond, Stéphanie; Calvez, Vincent; Masquelier, Bernard; Izopet, Jacques
There have been few studies on the concordance between phenotypic assays for predicting human immunodeficiency virus type 1 (HIV-1) coreceptor usage. The sensitivity of ultradeep pyrosequencing combined with genotyping tools is similar to that of phenotypic assays for detecting minor CXCR4-using variants. We evaluated the agreement between two phenotypic assays, the Toulouse tropism test (TTT) and the Trofile assay, and ultradeep pyrosequencing for determining the tropism of HIV-1 quasispecies. The concordance between the TTT and Trofile assays was assessed for 181 samples successfully phenotyped by both assays. The TTT was 86% concordant with the standard Trofile assay and 91.7% with its enhanced-sensitivity version. The concordance between phenotypic characterization of HIV-1 tropism and ultradeep pyrosequencing genotypic prediction was further studied in selected samples. The HIV-1 tropism inferred from ultradeep pyrosequencing of 11 samples phenotyped as X4 and dualtropic and 12 phenotyped as R5-tropic agreed closely with the results of phenotyping. However, ultradeep pyrosequencing detected minor CXCR4-using variants in 3 of 12 samples phenotyped as R5-tropic. Ultradeep pyrosequencing also detected minor CXCR4-using variants that had been missed by direct sequencing in 6 of 9 samples phenotyped as X4-tropic but genotyped as R5-tropic by direct sequencing. Ultradeep pyrosequencing was 87% concordant with the Trofile and TTT phenotypic assays and was in the same range of sensitivity (0.4%) than these two phenotypic assays (0.3 to 0.5%) for detecting minor CXCR4-using variants. Ultradeep pyrosequencing provides a new way to improve the performance of genotypic prediction of HIV-1 tropism to match that of the phenotypic assays.
LI Jue; WANG Zhe; WU Hao; LI Jing-yun; LU Jun-feng; DONG Hua-huang; BAO Zuo-yi; LIU Si-yang; LI Han-ping; ZHUANG Dao-min; LIU Yong-jian; LI Hong
Background This study was aim to explore the characteristics of phenotypic resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare the concordance between the phenotypic resistance and genotypic resistance. Methods The genotypic resistance assay for the HIV-1 clinical isolates was performed. One isolate without resistance mutation was chosen as a drug-sensitive reference strain and seven subtype B isolates with resistance mutations were phenotypically tested. Fifty percent inhibitory concentrations (IC50) between resistant and sensitive viruses were compared. The resistance extent was determined by the folds of the increased IC50. The concordance between the phenotypic resistance and genotypic resistance was also analyzed.Results IC50 of resistant isolates were 0.0006-0.1300 μmol/L for zidovudine (AZT), 0.0016-0.0390 μmol/L for lamivudine (3TC), 0.0104-0.4234 μmol/L for nevirapine (NVP), and 0.0163-0.1142 μmol/L for indinavir (IDV), respectively. Genotypic and phenotypic resistance assays indicated that the resistant strains were intermediately and highly resistant to nucleotide analog reverse transcriptase inhibitors and non-nucleotide analog reverse transcriptase inhibitors. The phenotypic assay was consistent with the genotypic assay. For measuring the potential resistance, the genotypic assay was more sensitive than the phenotypic. In evaluating the resistance to protease inhibitors, these two assays were discrepant.Conclusions Both the phenotypic and genotypic assays indicate that the resistant viruses exist in HIV-infected patients in China who have received treatment. Phenotypic and genotypic assays have high concordance, and the genotypic assay could replace the phenotypic assay to predict the HIV-1 resistance.
张颖; 张岩; 王平忠; 王九平; 黄长形; 孙永涛; 白雪帆
To investigate the phenotypic knockout of HIV-1 chemokine coreceptor CXCR4 and CCR5 by intrakines and its inhibitory effect on HIV-1 infection. Primary human PBLs were transduced with the recombinant vector pLNCX-R-K-S-K(△NGFR), followed by anti-NGFR/anti-IgG-magnetic bead method selection and FCM detection. The transduced PBLs were infected with DP1 HIV-1 virus thereafter envelope-mediated syncytium formation and p24 detection were carried out to study the blockage of HIV-1 infection by co-inactivation of CCR5 and CXCR4. pLNCX-R-K-S-K (△NGFR)-transduced PBILs were isolated with an anti-NGFR/anti-IgG-magnetic bead method. After isolation, about 70% of the PBLs were positive for the NGFR marker. When the transduced PBLs were infected with DP1 HIV-1 virus, envelop-mediated syncytium formation was almost completely inhibited by pLNCX-R-K-S-K(△NGFR) transfection. Also, p24 antigen was very low in the cultures of pLNCX-R-K-S-K (△NGFR) transduced PBLs. pLNCX-R-K-S-K(△NGFR) transduction inhibited the production of DP1 p24 antigen by 15%, 43% and 19% on days 4, 7 and 10 respectively. The lymphocytes with the phenotypic knockout of CCR5 and CXCR4 could protect primary human PBLs from DP1 HIV-1 virus infection.
Buggert, Marcus; Frederiksen, Juliet; Lund, Ole; Betts, Michael R.; Biague, Antonio; Nielsen, Morten; Tauriainen, Johanna; Norrgren, Hans; Medstrand, Patrik; Karlsson, Annika C.; Jansson, Marianne
Objective: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain ‘aviremic’ without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. Design: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants 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 programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells. Conclusion: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection. PMID:27525551
Full Text Available Abstract Background Entry of human immunodeficiency virus type 1 (HIV-1 into the host cell involves interactions between the viral envelope glycoproteins (Env and the cellular receptor CD4 as well as a coreceptor molecule (most importantly CCR5 or CXCR4. Viral preference for a specific coreceptor (tropism is in particular determined by the third variable loop (V3 of the Env glycoprotein gp120. The approval and use of a coreceptor antagonist for antiretroviral therapy make detailed understanding of tropism and its accurate prediction from patient derived virus isolates essential. The aim of the present study is the development of an extended description of the HIV entry phenotype reflecting its co-dependence on several key determinants as the basis for a more accurate prediction of HIV-1 entry phenotype from genotypic data. Results Here, we established a new protocol of quantitation and computational analysis of the dependence of HIV entry efficiency on receptor and coreceptor cell surface levels as well as viral V3 loop sequence and the presence of two prototypic coreceptor antagonists in varying concentrations. Based on data collected at the single-cell level, we constructed regression models of the HIV-1 entry phenotype integrating the measured determinants. We developed a multivariate phenotype descriptor, termed phenotype vector, which facilitates a more detailed characterization of HIV entry phenotypes than currently used binary tropism classifications. For some of the tested virus variants, the multivariant phenotype vector revealed substantial divergences from existing tropism predictions. We also developed methods for computational prediction of the entry phenotypes based on the V3 sequence and performed an extrapolating calculation of the effectiveness of this computational procedure. Conclusions Our study of the HIV cell entry phenotype and the novel multivariate representation developed here contributes to a more detailed
Full Text Available While modulation of regulatory T cell (Treg function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region, characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.
Luke C Swenson
Full Text Available BACKGROUND: 'Virtual' or inferred phenotypes (vPhenotypes are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. METHODS: All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277. Change from baseline pVL was determined as a function of Virco vPhenotype, and the "dynamic range" (defined here by the 10th and 90th percentiles for fold-change in IC₅₀ amongst all patients was estimated from the distribution of vPhenotye fold-changes across the cohort. RESULTS: The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC₅₀ of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small "dynamic ranges" with values of 99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine had large dynamic ranges. CONCLUSION: We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.
Bekele, Yonas; Amu, Sylvie; Bobosha, Kidist; Lantto, Rebecka; Nilsson, Anna; Endale, Birtukan; Gebre, Meseret; Aseffa, Abraham; Rethi, Bence; Howe, Rawleigh; Chiodi, Francesca
T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied.The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells.A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children.B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02).Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity.
Full Text Available BACKGROUND: 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. METHOD AND FINDINGS: 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. CONCLUSIONS: 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.
Full Text Available The sequence of a promoter within a genome does not uniquely determine gene expression levels and their variability; rather, promoter sequence can additionally interact with its location in the genome, or genomic context, to shape eukaryotic gene expression. Retroviruses, such as human immunodeficiency virus-1 (HIV, integrate their genomes into those of their host and thereby provide a biomedically-relevant model system to quantitatively explore the relationship between promoter sequence, genomic context, and noise-driven variability on viral gene expression. Using an in vitro model of the HIV Tat-mediated positive-feedback loop, we previously demonstrated that fluctuations in viral Tat-transactivating protein levels generate integration-site-dependent, stochastically-driven phenotypes, in which infected cells randomly 'switch' between high and low expressing states in a manner that may be related to viral latency. Here we extended this model and designed a forward genetic screen to systematically identify genetic elements in the HIV LTR promoter that modulate the fraction of genomic integrations that specify 'Switching' phenotypes. Our screen identified mutations in core promoter regions, including Sp1 and TATA transcription factor binding sites, which increased the Switching fraction several fold. By integrating single-cell experiments with computational modeling, we further investigated the mechanism of Switching-fraction enhancement for a selected Sp1 mutation. Our experimental observations demonstrated that the Sp1 mutation both impaired Tat-transactivated expression and also altered basal expression in the absence of Tat. Computational analysis demonstrated that the observed change in basal expression could contribute significantly to the observed increase in viral integrations that specify a Switching phenotype, provided that the selected mutation affected Tat-mediated noise amplification differentially across genomic contexts. Our study
Wong, E. B.; Xulu, B.; Prakadan, S.
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...... early and irreversible depletion of MAIT cells in the peripheral circulation, but the effect of HIV on MAIT cells in the lungs is unknown. These researchers report, for the first time, that MAIT cells in the lungs are numerically preserved but phenotypically and clonotypically altered by HIV infection....... They confirm previous reports that circulating MAIT cells are depleted in HIV. Their results suggest that peripheral MAIT cell depletions observed in HIV infection may be due to compartment-specific microbial alterations and/or tissue redistribution. The presenters emphasized that further study is needed...
While hepatitis C virus (HCV)-specific immune responses are attenuated in HCV\\/HIV co-infected patients compared to those infected with HCV alone, the reasons for this remain unclear. In this study, the proportions of regulatory, naïve, and memory T cells, along with chemokine receptor expression, were measured in co-infected and mono-infected patients to determine if there is an alteration in the phenotypic profile of lymphocytes in these patients. HCV\\/HIV co-infected patients had increased proportions of CD4(+) naïve cells and decreased proportions of CD4(+) effector cells when compared to HCV mono-infected patients. The proportions of CD4(+) Tregs and CD4(+) CXCR3(+) T cells were also significantly lower in co-infected patients. A decrease in CD4(+) Tregs and subsequent loss of immunosuppressive function may contribute to the accelerated progression to liver disease in co-infected individuals. Dysregulation of immune responses following reduction in the proportions of CD4(+) CXCR3(+) Th-1 cells may contribute to the reduced functional capacity of HCV-specific immune responses in co-infected patients. The findings of this study provide new information on the T-cell immunophenotype in HCV\\/HIV co-infected patients when compared to those infected with HCV alone, and may provide insight into why cell-mediated immune responses are diminished during HCV infection.
Katzenstein, T L; Pedersen, C; Nielsen, C
OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty...... seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral....... Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P RNA. CONCLUSION: Serum HIV RNA is high around the time...
Full Text Available Introduction: A dual split reporter protein system (DSP, recombining Renilla luciferase (RL and green fluorescent protein (GFP split into two different constructs (DSP1–7 and DSP8–11, was adapted to create a novel rapid phenotypic tropism assay (PTA for HIV-1 infection (DSP-Pheno. Methods: DSP1–7 was stably expressed in the glioma-derived NP-2 cell lines, which expressed CD4/CXCR4 (N4X4 or CD4/CCR5 (N4R5, respectively. An expression vector with DSP8–11 (pRE11 was constructed. The HIV-1 envelope genes were subcloned in pRE11 (pRE11-env and transfected into 293FT cells. Transfected 293FT cells were incubated with the indicator cell lines independently. In developing the assay, we selected the DSP1–7-positive clones that showed the highest GFP activity after complementation with DSP8–11. These cell lines, designated N4R5-DSP1–7, N4X4-DSP1–7 were used for subsequent assays. Results: The env gene from the reference strains (BaL for R5 virus, NL4-3 for X4 virus, SF2 for dual tropic virus subcloned in pRE11 and tested, was concordant with the expected co-receptor usage. Assay results were available in two ways (RL or GFP. The assay sensitivity by RL activity was comparable with those of the published phenotypic assays using pseudovirus. The shortest turnaround time was 5 days after obtaining the patient's plasma. All clinical samples gave positive RL signals on R5 indicator cells in the fusion assay. Median RLU value of the low CD4 group was significantly higher on X4 indicator cells and suggested the presence of more dual or X4 tropic viruses in this group of patients. Comparison of representative samples with Geno2Pheno [co-receptor] assay was concordant. Conclusions: A new cell-fusion-based, high-throughput PTA for HIV-1, which would be suitable for in-house studies, was developed. Equipped with two-way reporter system, RL and GFP, DSP-Pheno is a sensitive test with short turnaround time. Although maintenance of cell lines and
Giacoia-Gripp, Carmem Beatriz Wagner; Sales, Anna Maria; Nery, José Augusto da Costa; Santos-Oliveira, Joanna Reis; de Oliveira, Ariane Leite; Sarno, Euzenir Nunes; Morgado, Mariza Gonçalves
Background It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. Methods/Principal Findings Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR. Conclusion/Significance These data suggest CD38 expression in CD8+ T cells interesting tool
Carmem Beatriz Wagner Giacoia-Gripp
Full Text Available BACKGROUND: It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR. However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. METHODS/PRINCIPAL FINDINGS: Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%, dropping significantly (p<0,05 during post-IRIS/RR moments (median: 29,7%. Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR. CONCLUSION/SIGNIFICANCE: These data suggest CD38 expression in CD8+ T cells
Rodriguez-Garcia, M; Barr, F D; Crist, S G; Fahey, J V; Wira, C R
Prevention of sexual acquisition of HIV in women requires a substantial increase in our knowledge about HIV-target cell availability and regulation in the female reproductive tract (FRT). In this study, we analyzed the phenotype and susceptibility to HIV infection of CD4(+) T cell in the endometrium (EM), endocervix (END), and ectocervix (ECT) of the FRT. We found that T helper type 17 (Th17) cells represent a major subset in FRT tissues analyzed and that Th17 cells were the main CD4(+) T-cell population expressing C-C motif chemokine receptor 5 (CCR5) and CD90. In premenopausal women, CD4(+) T cells and Th17 cells, in particular, were significantly lower in EM relative to END and ECT. Th17 cells were elevated in EM from postmenopausal women relative to premenopausal tissues but not changed in END and ECT. Susceptibility of CD4(+) T cells to HIV infection measured as intracellular p24 was lowest in the EM and highest in the ECT. Additionally, we found that Th17 cells co-expressing CCR5 and CD90 were the most susceptible to HIV infection. Our results provide valuable information for designing preventive strategies directed at targeting highly susceptible target cells in the FRT.
Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R
Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.
Watret, K C; Whitelaw, J A; Froebel, K S; Bird, A G
The CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics of the CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1+ remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.
Yukl, Steven A; Shergill, Amandeep K; Girling, Valerie; Li, Qingsheng; Killian, Maudi; Epling, Lorrie; Li, Peilin; Kaiser, Philipp; Haase, Ashley; Havlir, Diane V; McQuaid, Kenneth; Sinclair, Elizabeth; Wong, Joseph K
Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.
Steven A Yukl
Full Text Available Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.
Full Text Available BACKGROUND: Long-term remission of HIV-1 disease can be readily achieved by combinations of highly effective antiretroviral therapy (HAART. However, a residual persistent immune activation caused by circulating non infectious particles or viral proteins is observed under HAART and might contribute to an higher risk of non-AIDS pathologies and death in HIV infected persons. A sustained immune activation supports lipid dysmetabolism and increased risk for development of accelerated atehrosclerosis and ischemic complication in virologically suppressed HIV-infected persons receiving HAART. AIM: While several HIV proteins have been identified and characterized for their ability to maintain immune activation, the role of HIV-p17, a matrix protein involved in the viral replication, is still undefined. RESULTS: Here, we report that exposure of macrophages to recombinant human p17 induces the expression of proinflammatory and proatherogenic genes (MCP-1, ICAM-1, CD40, CD86 and CD36 while downregulating the expression of nuclear receptors (FXR and PPARγ that counter-regulate the proinflammatory response and modulate lipid metabolism in these cells. Exposure of macrophage cell lines to p17 activates a signaling pathway mediated by Rack-1/Jak-1/STAT-1 and causes a promoter-dependent regulation of STAT-1 target genes. These effects are abrogated by sera obtained from HIV-infected persons vaccinated with a p17 peptide. Ligands for FXR and PPARγ counteract the effects of p17. CONCLUSIONS: The results of this study show that HIV p17 highjacks a Rack-1/Jak-1/STAT-1 pathway in macrophages, and that the activation of this pathway leads to a simultaneous dysregulation of immune and metabolic functions. The binding of STAT-1 to specific responsive elements in the promoter of PPARγ and FXR and MCP-1 shifts macrophages toward a pro-atherogenetic phenotype characterized by high levels of expression of the scavenger receptor CD36. The present work identifies p17 as a
Ana Judith Perisé-Barrios
Full Text Available BACKGROUND: Human immunodeficiency virus type 1 (HIV-1 induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. METHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID mRNA that is responsible for class switch recombination (CSR and somatic hypermutation (SHM. Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. CONCLUSION/SIGNIFICANCE: We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.
Rivera-Toledo, Evelyn; Huerta, Leonor; Larralde, Carlos; Lamoyi, Edmundo
Cells infected with the human immunodeficiency virus (HIV) can fuse with CD4(+) cells leading to the formation of multinucleated cells. The presence of multinucleated cells infected with HIV in tissues of patients has been documented, although their cellular composition and role in AIDS pathogenesis is still under study. Here, we present evidence of in vitro heterotypic lymphocyte-monocyte fusion in cocultures of lymphocytic Jurkat T cells expressing the HIV-1 gp120/gp41 glycoproteins (Env) and CD4(+) monocytic THP-1 cells. Using a previously characterized method that involves differential labeling of fusion partners with fluorescent probes and flow cytometry analysis after coculture, up to 20% of double fluorescent cells were detected in 48h. This double fluorescent cell population was produced by heterotypic lymphocyte-monocyte fusion as it was not observed when Jurkat T cells expressing a mutant non-fusogenic Env protein were used. Heterokaryon formation was inhibited by an anti-CD4 monoclonal antibody and the HIV-fusion inhibitor peptide T-20. About 68% of heterokaryons remained alive and non-apoptotic after 2days of coculture. In heterokaryons, CD4 was barely detectable and the expression of the CD3 and CD28 lymphoid markers was greatly reduced, whereas the expression of CD32 and the intracellular antigen CD68, both markers of monocytic cells, remained unchanged. In contrast with unfused T cells, heterokaryons only expressed very low levels of the lymphoid activation marker CD25 following treatment with PMA plus ionomycin. These studies point to the possible generation of lymphocyte-monocyte heterokaryons with a myeloid phenotype during HIV infection, with unknown consequences for AIDS pathogenesis. Copyright © 2010 Elsevier Inc. All rights reserved.
Hygino, Joana; Vieira, Morgana M; Guillermo, Landi V; Silva-Filho, Renato G; Saramago, Carmen; Lima-Silva, Agostinho A; Andrade, Regis M; Andrade, Arnaldao F B; Brindeiro, Rodrigo M; Tanuri, Amilcar; Guimarães, Vander; de Melo Bento, Cleonice Alves
Our objective was to evaluate the in vitro functional profile of T cells from uninfected neonates born from HIV-1-infected pregnant women who controlled (G1) or not (G2) the virus replication. We demonstrated that the lymphoproliferation of T cell to polyclonal activators was higher in the G2 as compared with G1. Nevertheless, no detectable proliferative response was observed in response to HIV-1 antigens in both neonate groups. Cytokine dosage in the supernatants of these polyclonally activated T cell cultures demonstrated that, while IL-10 was the dominant cytokine produced in G1, Th17-related cytokines were significantly higher in G2 neonates. The higher Th17 phenotype tendency in G2 was related to high production of IL-23 by lipopolysaccharide-activated monocyte-derived dendritic cells from these neonates. Our results demonstrated immunological disorders in uninfected neonates born from viremic HIV-1-infected mothers that can help to explain why some of these children have elevated risk of clinical morbidity and mortality due to pathological hypersensitivity.
Camacho-Sandoval, R; Del Río Estrada, P M; Rivero-Arrieta, A; Reyes-Terán, G; Bonifaz, L C
HIV(+) subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV(+) subjects and HIV(+) controllers (CTs). The HIV(+) subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV(-) ). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-α by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-α compared to the cDC from CTs. Interestingly, the percentage of TNF-α(+) cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-α in response to LPS in viraemic HIV(+) subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC.
Buggert, Marcus; Frederiksen, Juliet Wairimu; Lund, Ole;
OBJECTIVE: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+...
Camacho-Sandoval, R; Del Río Estrada, P M; Rivero-Arrieta, A; Reyes-Terán, G; Bonifaz, L C
HIV+ subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV+ subjects and HIV+ controllers (CTs). The HIV+ subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV–). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-α by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-α compared to the cDC from CTs. Interestingly, the percentage of TNF-α+ cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-α in response to LPS in viraemic HIV+ subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC. PMID:25130456
Kenyon, Chris; Colebunders, Robert; Voeten, Helene; Lurie, Mark
A key question for ecological studies with HIV as the outcome variable is what measure of HIV prevalence to use. In this study we compared the strengths and weaknesses of a variety of measures of HIV prevalence, focusing on peak HIV prevalence and HIV prevalence measured at the same time as the expo
Sullivan John S
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.
Billoir, Elise; Navratil, Vincent; Blaise, Benjamin J
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: email@example.com.
Amu, Sylvie; Lantto Graham, Rebecka; Bekele, Yonas; Nasi, Aikaterini; Bengtsson, Carina; Rethi, Bence; Sorial, Sam; Meini, Genny; Zazzi, Maurizio; Hejdeman, Bo; Chiodi, Francesca
Early initiation of antiretroviral therapy (ART) is becoming a common clinical practice according to current guidelines recommending treatment to all HIV-1-infected patients. However, it is not known whether ART initiated during the early phase of infection prevents the establishment of abnormal phenotypic features previously reported in CD4+ and CD8+T cells during chronic HIV-1 infection. In this cross-sectional study, blood specimens were obtained from 17 HIV-1-infected patients who began ART treatment shortly after infection (early ART [EA]), 17 age-matched HIV-1-infected patients who started ART during chronic phase of infection (late ART [LA]), and 25 age-matched non-HIV-1-infected controls. At collection of specimens, patients in EA and LA groups had received ART for comparable periods of time. Total HIV-1 DNA was measured in white blood cells by quantitative PCR. The concentration of 9 inflammatory parameters and 1 marker of fibrosis, including sCD14 and β-2 microglobulin, was measured in plasma. Furthermore, expression of markers of abnormal immune activation (human leukocyte antigen - antigen D related [HLA-DR] and CD38), exhaustion (programmed death 1, CD28, CD57) and terminal differentiation (CD127) was measured on CD4+ and CD8+T cells. T-cell proliferation was measured through Ki67 expression. The copies of total HIV-1 DNA in blood were significantly lower (P = 0.009) in EA compared with that in LA group. Only the expression of HLA-DR on naïve CD4+ T cells distinguished EA from LA, whereas expression of 3 surface markers distinguished T-cell populations of HIV-1-infected patients from controls. These included HLA-DR distinguishing CD4+ T cells from EA compared with controls, and also CD38 and CD127 on CD4+ and CD8+ T cells, respectively, distinguishing both groups of patients from controls. The sCD14 levels were significantly higher in EA patients, and β-2 microglobulin levels were higher in LA group compared with that in controls. Our results
Full Text Available To date, the majority of HIV-1 phenotypic resistance testing has been performed with subtype B virus backbones (e.g. HXB2. However, the relevance of using this backbone to determine resistance in non-subtype B HIV-1 viruses still needs to be assessed. From 114 HIV-1 subtype C clinical samples (36 ARV-naïve, 78 ARV-exposed, pol amplicons were produced and analyzed for phenotypic resistance using both a subtype B- and C-backbone in which the pol fragment was deleted. Phenotypic resistance was assessed in resulting recombinant virus stocks (RVS for a series of antiretroviral drugs (ARV's and expressed as fold change (FC, yielding 1660 FC comparisons. These Antivirogram® derived FC values were categorized as having resistant or sensitive susceptibility based on biological cut-off values (BCOs. The concordance between resistance calls obtained for the same clinical sample but derived from two different backbones (i.e. B and C accounted for 86.1% (1429/1660 of the FC comparisons. However, when taking the assay variability into account, 95.8% (1590/1660 of the phenotypic data could be considered as being concordant with respect to their resistance call. No difference in the capacity to detect resistance associated with M184V, K103N and V106M mutations was noted between the two backbones. The following was concluded: (i A high level of concordance was shown between the two backbone phenotypic resistance profiles; (ii Assay variability is largely responsible for discordant results (i.e. for FC values close to BCO; (iii Confidence intervals should be given around the BCO's, when assessing resistance in HIV-1 subtype C; (iv No systematic resistance under- or overcalling of subtype C amplicons in the B-backbone was observed; (v Virus backbone subtype sequence variability outside the pol region does not contribute to phenotypic FC values. In conclusion the HXB2 virus backbone remains an acceptable vector for phenotyping HIV-1 subtype C pol amplicons.
van Manen Daniëlle
Full Text Available Abstract Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection. This review gives an overview of findings from the GWAS performed on HIV infection, within different cohorts, with variable patient and phenotype selection. Furthermore, novel techniques and strategies in research that might contribute to the complete understanding of virus-host interactions and its role on the pathogenesis of HIV infection are discussed.
Gonzalez, Sandra M; Taborda, Natalia A; Correa, Luis A; Castro, Gustavo A; Hernandez, Juan C; Montoya, Carlos J; Rugeles, Maria T
The spontaneous control of HIV replication in HIV-controllers underlines the importance of these subjects for exploring factors related to delayed progression. Several studies have revealed fewer immune alterations and effector mechanisms related to viral control, mainly in peripheral blood, in these individuals compared to normal progressors. However, immune characterization of gut-associated lymphoid tissue (GALT), the major target of infection, has not been thoroughly explored in these subjects. We evaluated the following parameters in GALT samples from 11 HIV-controllers and 15 HIV-progressors: (i) frequency and activation phenotype of T cells; (ii) expression of transcription factors associated with immune response profiles; and (iii) frequency of apoptotic cells. Interestingly, HIV-controllers exhibited a particular activation phenotype, with predominance of T cells expressing HLA-DR but not CD38 in GALT. This phenotype, previously associated with better control of infection, was correlated with low viral load and higher CD4(+) T cell count. Furthermore, a positive correlation of this activation phenotype with higher expression of Foxp3 and RORγT transcription factors suggested a key role for Treg and Th17 cells in the control of the immune activation and in the maintenance of gut mucosal integrity. Although we evaluated apoptosis by measuring expression of cleaved caspase-3 in GALT, we did not find differences between HIV-controllers and HIV-progressors. Taken together, our findings suggest that predominance of HLA-DR(+) T cells, along with lower immune activation and higher expression of transcription factors required for the development of Treg and Th17 cells, is associated with better viral control and delayed progression to AIDS.
N Lance Hepler
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.
Hepler, N Lance; Scheffler, Konrad; Weaver, Steven; Murrell, Ben; Richman, Douglas D; Burton, Dennis R; Poignard, Pascal; Smith, Davey M; Kosakovsky Pond, Sergei L
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.
Ndumbi, Patricia; Falutz, Julian; Pant Pai, Nitika; Tsoukas, Christos M.
Background Successful combination antiretroviral therapy (cART) increases levels of CD4+ T-cells, however this increase may not accurately reflect long-term immune recovery since T-cell dysregulation and loss of T-cell homeostasis often persist. We therefore assessed the impact of a decade of effective cART on immune regulation, T-cell homeostasis, and overall T-cell phenotype. Methods We conducted a retrospective study of 288 HIV+ cART-naïve patients initiating therapy. We identified 86 individuals who received cART for at least a decade, of which 44 consistently maintained undetectable plasma HIV-RNA levels throughout therapy. At baseline, participants were classified into three groups according to pre-treatment CD4+ T-cell counts: Group I (CD4350 cells/mm3). Outcomes of interest were: (1) CD4+ T-cell count restoration (CD4>532 cells/mm3); (2) normalization of CD4:CD8 T-cell ratio (1.2–3.3); (3) maintenance of CD3+ T-cell homeostasis (CD3: 65%–85% of peripheral lymphocytes); (4) normalization of the complete T-cell phenotype (TCP). Results Despite a decade of sustained successful cART, complete T-cell phenotype normalization only occurred in 16% of patients, most of whom had initiated therapy at high CD4+ T-cell counts (>350 cells/mm3). The TCP parameter that was the least restored among patients was the CD4:CD8 T-cell ratio. Conclusions Failure to normalize the complete T-cell phenotype was most apparent in patients who initiated cART with a CD4+ T-cell count <200 cells/mm3. The impact of this impaired T-cell phenotype on life-long immune function and potential comorbidities remains to be elucidated. PMID:24710051
Full Text Available BACKGROUND: Successful combination antiretroviral therapy (cART increases levels of CD4+ T-cells, however this increase may not accurately reflect long-term immune recovery since T-cell dysregulation and loss of T-cell homeostasis often persist. We therefore assessed the impact of a decade of effective cART on immune regulation, T-cell homeostasis, and overall T-cell phenotype. METHODS: We conducted a retrospective study of 288 HIV+ cART-naïve patients initiating therapy. We identified 86 individuals who received cART for at least a decade, of which 44 consistently maintained undetectable plasma HIV-RNA levels throughout therapy. At baseline, participants were classified into three groups according to pre-treatment CD4+ T-cell counts: Group I (CD4350 cells/mm3. Outcomes of interest were: (1 CD4+ T-cell count restoration (CD4>532 cells/mm3; (2 normalization of CD4:CD8 T-cell ratio (1.2-3.3; (3 maintenance of CD3+ T-cell homeostasis (CD3: 65%-85% of peripheral lymphocytes; (4 normalization of the complete T-cell phenotype (TCP. RESULTS: Despite a decade of sustained successful cART, complete T-cell phenotype normalization only occurred in 16% of patients, most of whom had initiated therapy at high CD4+ T-cell counts (>350 cells/mm3. The TCP parameter that was the least restored among patients was the CD4:CD8 T-cell ratio. CONCLUSIONS: Failure to normalize the complete T-cell phenotype was most apparent in patients who initiated cART with a CD4+ T-cell count <200 cells/mm3. The impact of this impaired T-cell phenotype on life-long immune function and potential comorbidities remains to be elucidated.
Du Plessis, Nelita; Jacobs, Ruschca; Gutschmidt, Andrea; Fang, Zhuo; van Helden, Paul D; Lutz, Manfred B; Hesseling, Anneke C; Walzl, Gerhard
Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T-cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV-infected and -uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV-exposed, -infected and -uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric- and fluorescence arrays. Peripheral frequencies of cells phenotypically resembling MDSCs were significantly increased in HIV-exposed uninfected (HEU) and M.tb-infected children, but peaked in children with TB disease and remained high following treatment. MDSC in HIV-infected (HI) children were similar to unexposed uninfected controls; however, HAART-mediated MDSC restoration to control levels could not be disregarded. Increased MDSC frequencies in HHC coincided with enhanced indoleamine-pyrrole-2,3-dioxygenase (IDO), whereas increased MDSC in TB cases were linked to heightened IDO and arginase-1. Increased MDSC were paralleled by reduced plasma IP-10 and thrombospondin-2 levels in HEU and significantly increased plasma IL-6 in HI HHC. Current investigations into MDSC-targeted treatment strategies, together with functional analyses of MDSCs, could endorse these cells as novel innate immune regulatory mechanism of infant HIV/TB susceptibility. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Seu, Lillian; Sabbaj, Steffanie; Duverger, Alexandra; Wagner, Frederic; Anderson, Joshua C; Davies, Elizabeth; Wolschendorf, Frank; Willey, Christopher D; Saag, Michael S; Goepfert, Paul; Kutsch, Olaf
The extreme stability of the latent HIV-1 reservoir in the CD4(+) memory T cell population prevents viral eradication with current antiretroviral therapy. It has been demonstrated that homeostatic T cell proliferation and clonal expansion of latently infected T cells due to viral integration into specific genes contribute to this extraordinary reservoir stability. Nevertheless, given the constant exposure of the memory T cell population to specific antigen or bystander activation, this reservoir stability seems remarkable, unless it is assumed that latent HIV-1 resides exclusively in memory T cells that recognize rare antigens. Another explanation for the stability of the reservoir could be that the latent HIV-1 reservoir is associated with an unresponsive T cell phenotype. We demonstrate here that host cells of latent HIV-1 infection events were functionally altered in ways that are consistent with the idea of an anergic, unresponsive T cell phenotype. Manipulations that induced or mimicked an anergic T cell state promoted latent HIV-1 infection. Kinome analysis data reflected this altered host cell phenotype at a system-wide level and revealed how the stable kinase activity changes networked to stabilize latent HIV-1 infection. Protein-protein interaction networks generated from kinome data could further be used to guide targeted genetic or pharmacological manipulations that alter the stability of latent HIV-1 infection. In summary, our data demonstrate that stable changes to the signal transduction and transcription factor network of latently HIV-1 infected host cells are essential to the ability of HIV-1 to establish and maintain latent HIV-1 infection status. The extreme stability of the latent HIV-1 reservoir allows the infection to persist for the lifetime of a patient, despite completely suppressive antiretroviral therapy. This extreme reservoir stability is somewhat surprising, since the latently HIV-1 infected CD4(+) memory T cells that form the
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.
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
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.
Schwartz, Janice B; Moore, Kelly L; Yin, Michael; Sharma, Anjali; Merenstein, Dan; Islam, Talat; Golub, Elizabeth T; Tien, Phyllis C; Adeyemi, Oluwatoyin M
Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±antiretroviral therapy [ART]) were investigated with Women's Interagency HIV Study data (n = 1758 middle-aged women) using multivariable regression. Sixty-three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25-OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART-treated HIV-infected women and unrelated to cholesterol.
Hays Ron D
Full Text Available Abstract The purposewas to compare and comment on use of the SF-36 and MOS-HIV instrumentsin studies of persons with HIV disease. Three medical informationdatabases were searched to identify examples of HIV studies thatincluded the MOS-HIV or SF-36. Thirty-nine and 14 published articleswere identified for illustration in comparing the use of the MOS-HIVand SF-36 in HIV disease, respectively. Support for the reliabilityand construct validity of the MOS-HIV and SF-36 was found. Ceilingand floor effects were reported for both the MOS-HIV and SF-36;however, ceiling effects were more common for the MOS-HIV, in partdue to fewer items in the physical, social, and role functioningdomains. The MOS-HIV measures three domains hypothesized to be associatedwith the health deterioration of HIV disease not measured by theSF-36; however, these domains may not assess aspects of HIV diseasethat typify the majority of the persons with HIV disease today.National norms for the U.S. adult population (and other nationsare available for the SF-36. In addition, the SF-36 has been usedin a wide variety of patient populations, enabling comparisons ofHIV-infected persons with persons with other health conditions.No national norms for the MOS-HIV are available. We conclude thatthere is currently insufficient evidence in the literature to recommendthe use of the MOS-HIV over the SF-36 in HIV-infected persons. Althoughthe SF-36 is not targeted at HIV, it may be preferable to use theSF-36 over the MOS-HIV due to fewer ceiling effects, availabilityof national norms, and the vast amount of data for other populationsin the U.S. and around the world. Head-to-head comparisons demonstratingthe unique value of the MOS-HIV over the SF-36 are clearly needed.More importantly, additional work needs to be directed at comparingthe MOS-HIV and other putatively HIV-targeted instruments to oneanother to help demarcate aspects of HRQOL that are truly genericversus specific to HIV disease
Naylor Melissa G
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.
Ronit, Andreas; Haissman, Judith Melchior; Kirkegaard-Klitbo, Ditte Marie
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...
Kate Buchacz; Carl Armon; Palella, Frank J.; Rose K. Baker; Ellen Tedaldi; Durham, Marcus D.; Brooks, John T.
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
Ronit, Andreas; Haissman, Judith M; Kirkegaard-Klitbo, Ditte Marie
elastography of the liver, computed tomography (CT) angiography of the heart, unenhanced CT of the chest and upper abdomen, and a number of routine biochemical analysis are uniformly collected in participants from the COCOMO study and the CGPS. Plasma, serum, buffy coat, peripheral blood mononuclear cells...... (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...... to a more personalized HIV care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02382822 ....
Doms Robert W
Full Text Available Abstract Background HIV envelope glycoprotein (Env-mediated fusion is driven by the concerted coalescence of the HIV gp41 N-helical and C-helical regions, which results in the formation of 6 helix bundles. Kinetics of HIV Env-mediated fusion is an important determinant of sensitivity to entry inhibitors and antibodies. However, the parameters that govern the HIV Env fusion cascade have yet to be fully elucidated. We address this issue by comparing the kinetics HIV-1IIIB Env with those mediated by HIV-2 from two strains with different affinities for CD4 and CXCR4. Results HIV-1 and HIV-2 Env-mediated cell fusion occurred with half times of about 60 and 30 min, respectively. Binding experiments of soluble HIV gp120 proteins to CD4 and co-receptor did not correlate with the differences in kinetics of fusion mediated by the three different HIV Envs. However, escape from inhibition by reagents that block gp120-CD4 binding, CD4-induced CXCR4 binding and 6-helix bundle formation, respectively, indicated large difference between HIV-1 and HIV-2 envelope glycoproteins in their CD4-induced rates of engagement with CXCR4. Conclusion The HIV-2 Env proteins studied here exhibited a significantly reduced window of time between the engagement of gp120 with CD4 and exposure of the CXCR4 binding site on gp120 as compared with HIV-1IIIB Env. The efficiency with which HIV-2 Env undergoes this CD4-induced conformational change is the major cause of the relatively rapid rate of HIV-2 Env mediated-fusion.
Full Text Available OBJECTIVE: We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART. DESIGN: We studied 163 patients receiving virologically suppressive cART. METHODS: We measured IMT (carotid ultrasound; CD4+/CD8+ T-cell activation (CD38, CD45R0, differentiation (CD127, apoptosis (CD95, and senescence (CD28, CD57 (flow cytometry; plasma sCD14, IL-6, TNF- α, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA; LPS (LAL. The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression. RESULTS: Of 163 patients, 112 demonstrated normal IMT (nIMT, whereas 51 (31.3% had pathological IMT (pIMT: ≥1 mm. Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT, and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p = .95, pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p = .038 and apoptotic CD4+CD95+ (p = .01 and CD8+CD95+ cells (p = .003. In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57- memory CD4+ (p = .048 and CD28-CD57-CD8+ cells (p = .006, both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p = .046. No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors. CONCLUSIONS: Despite the provision of full
Full Text Available OBJECTIVES: To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials. METHODS: HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months. RESULTS: 495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO. The overall HIV incidence rate [95% confidence interval (CI] was 4.3 [3.1-6]; and 4.3 [2.8-6.4] and 4.4 [2.5-8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18-24 (aRR = 4.1, 95% CI 1.6-10.8 and 25-34 (aRR = 2.7, 95% CI 1.2-5.8 years]; alcohol use (aRR = 2.6, 95% CI 1.1-6; and reported genital discharge (aRR = 3.4, 95% CI 1.6-7.2 in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2-0.8; always (aRR = 0.1, 95% CI 0.02-0.9]. In the follow-up risk analysis, young age [18-24 (aRR = 6.2, 95% CI 2.2-17.3 and 25-34 (aRR = 2.3, 95% CI 1.1-5.0 years], reported genital discharge (aRR = 2.5, 95% CI 1.1-5.5, serological syphilis (aRR 3.2, 95% CI 1.3-7.7 and the partner being ART naïve (aRR = 4.8, 95% CI 1.4-16.0 were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study. CONCLUSIONS: The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that
Seng, R; Gustafson, P; Gomes, VF
709) in Bissau, capital of Guinea-Bissau, with the highest known seroprevalence of HIV-2 infection in the world. From May 1996 to June 1998, tuberculosis surveillance and active case finding among contacts was conducted. Patients were HIV-tested, given specific tuberculosis treatment for 8 months......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...... and followed regarding mortality. Simultaneously, an HIV sero-survey was performed in a random sample of 1748 permanent residents. RESULTS: During a 25-month period, 366 tuberculosis cases were identified. After excluding cases among visitors to the area, and adjusting for age, the incidence of tuberculosis...
Ren, L; Wang, H W; Xu, Y; Feng, Y; Zhang, H F; Wang, K H
HIV genotyping has led to conflicting results between laboratories. Therefore, identifying the most accurate gene combinations to sequence remains a priority. Datasets of Chinese HIV subtypes based on several markers and deposited in PubMed, Metstr, CNKI, and VIP databases between 2000 and 2015 were studied. In total, 9177 cases of amplification-positive samples from 26 provinces of China were collected and used to classify HIV subtypes based on eight individual genes or a combination thereof. CRF01_AE, CRF07_BC, CRF08_BC and B were the prevalent HIV subtypes in China, accounting for 84.07% of all genotypes. Gag/Env sequencing classified a greater number of HIV subtypes compared to other genes or combination of gene fragments. The geographical distribution of Gag and Gag/Env genotypes was similar to that observed with all genetic markers. Further principal component analysis showed a significantly different geographical distribution pattern of HIV in China for HIV genotypes detected with Gag/Env, which was in line with the distribution of all HIV genotypes in China. Gag/Env sequences had the highest diversity of the eight markers studied, followed by Gag and Gag/Pol/Env; Pol/Env polymorphisms were the least divergent. Gag/Env can serve as a high-resolution marker for HIV genotyping.
Reutter, L I; Northcott, H C
The findings reported in this paper are part of a larger study that explored how nurses cope with the risk of acquiring HIV infection while caring for persons with AIDS (PWAs). The data were collected through in-depth interviews with 13 nurses who cared for PWAs in a large Western Canadian hospital. Seven of these nurses perceived that they had been exposed to HIV-infected blood or body fluids. This paper describes how these seven nurses coped with actual exposures to HIV-infected blood or body fluids. Data were analyzed using the methodology of grounded theory. Nurses' coping efforts after exposure were grouped into four categories: minimizing the effect of exposures, reducing a sense of vulnerability, selective disclosure to others, and assigning meaning. Nurses minimized the physical effects of exposure through measures such as 'bleeding' the needlestick injury and immersing the affected area in bleach solution. Nurses reduced their sense of vulnerability by assessing the possibility of harm, avoiding situations that aroused fear, and confronting the decision for HIV testing. Nurses limited their disclosures to co-workers to avoid rejection and to preserve professional self-esteem. Disclousre to significant others was influenced primarily by the support nurses perceived they would receive. Finally, nurses attempted to assign meaning to the exposure by determining why the event occurred and by evaluating the implications it has had on their lives. The article concludes with implications for nursing practice.
Yang, Qiong; Wang, Yuanjia
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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.
Greenspan, D; Komaroff, E; Redford, M; Phelan, J A; Navazesh, M; Alves, M E; Kamrath, H; Mulligan, R; Barr, C E; Greenspan, J S
The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.
Amoroso, Antonio; Savoldi, Silvana
Thirty years after the discovery of the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS), no effective vaccines are available and there is no cure for the disease. The susceptibility to HIV infection shows a considerable degree of individual heterogeneity, which may be largely due to the genetic variability of the host. In an effort to find the host factors required for viral replication, to identify the crucial pathogenetic pathways, and reveal the full armament of host defenses, there has been a shift from candidate-gene studies to unbiased genomewide genetic and functional studies. Nevertheless, the number of established genetic factors involved in the susceptibility to diseases caused by HIV infection remains small, explaining only 15-20% of the observed heterogeneity, most of which is attributable to polymorphisms of human leukocyte antigens (HLA). Genetic studies, however, have allowed to clarify which genetic variations underlie the adverse response to some antiretroviral drugs (such as HLA-B*5701 in the treatment with abacavir) or the occurrence of renal complications as the disease progresses. The results of these studies already have a possible impact on healthcare practice.
Papi, Alberto; Magnoni, Maria Sandra; Muzzio, Carmelo Caio; Benso, Gianmarco; Rizzi, Andrea
The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational multicentre international study aimed at defining COPD phenotypes and identifying biomarkers and/or genetic parameters that help to predict disease progression. The study has contributed to a better understanding of COPD heterogeneity, with the characterization of clinically important subtypes/phenotypes of patients, such as the frequent exacerbators or patient with persistent systemic inflammation, who may have different prognosis or treatment requirements. Because of the big amount of information that is starting to be produced from metabolomic, proteomic and genomic approaches, one of the biggest challenges is the integration of data in a biological prospective such as clinical prognosis and response to medicinal products. In this article we highlight some of the progress in phenotyping the heterogeneity of the disease that have been made thanks to the analyses of this longitudinal study.
José R Lapa e Silva
Full Text Available Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demostrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12 or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9 or normal healthy volunteers (n = 3 served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1 and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1 and epithelioid cell marker (RFD9. These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis.
Full Text Available Abstract Background Accurate interpretation of HIV drug resistance (HIVDR testing is challenging, yet important for patient care. We compared genotyping interpretation, based on the Stanford University HIV Drug Resistance Database (Stanford HIVdb, and virtual phenotyping, based on the Janssen Diagnostics BVBA’s vircoTYPE™ HIV-1, and investigated their level of agreement in antiretroviral (ARV naive patients in Asia, where non-B subtypes predominate. Methods Sequences from 1301 ARV-naive patients enrolled in the TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M were analysed by both interpreting systems. Interpretations from both Stanford HIVdb and vircoTYPE™ HIV-1 were initially grouped into 2 levels: susceptible and non-susceptible. Discrepancy was defined as a discordant result between the susceptible and non-susceptible interpretations from the two systems for the same ARV. Further analysis was performed when interpretations from both systems were categorised into 3 levels: susceptible, intermediate and resistant; whereby discrepancies could be categorised as major discrepancies and minor discrepancies. Major discrepancy was defined as having a susceptible result from one system and resistant from the other. Minor discrepancy corresponded to having an intermediate interpretation in one system, with a susceptible or resistant result in the other. The level of agreement was analysed using the prevalence adjusted bias adjusted kappa (PABAK. Results Overall, the agreement was high, with each ARV being in “almost perfect agreement”, using Landis and Koch’s categorisation. Highest discordance was observed for efavirenz (75/1301, 5.8%, all arising from susceptible Stanford HIVdb versus non-susceptible vircoTYPE™ HIV-1 predictions. Protease Inhibitors had highest level of concordance with PABAKs all above 0.99, followed by Nucleoside Reverse Transcriptase Inhibitors with PABAKs above 0.97 and non-NRTIs with the
Trevor A Crowell
Full Text Available Introduction: HIV controllers (HICs experience relatively low-level viraemia and CD4 preservation without antiretroviral therapy (ART, but also immune activation that may predispose to adverse clinical events such as cardiovascular disease and hospitalization. The objective of this study was to characterize the rates and reasons for hospitalization among HICs and persons with medically controlled HIV. Methods: Subjects with consistently well-controlled HIV were identified in the U.S. Military HIV Natural History Study. ART prescription and HIV-1 RNA data were used to categorize subjects as HICs or medically controlled as defined by ≥3 HIV-1 RNA measurements ≤2000 or ≤400 copies/mL, respectively, representing the majority of measurements spanning ≥12 months. Hospitalizations were tallied and assigned diagnostic categories. All-cause hospitalization rates were compared between groups using negative binomial regression. Results and discussion: Of 3106 subjects followed from 2000 to 2013, 221 were HICs, including 33 elite (1.1% and 188 viraemic (6.0% controllers, who contributed 882 person-years (PY of observation time. An additional 870 subjects with medically controlled HIV contributed 4217 PY. Mean hospitalization rates were 9.4/100 PY among HICs and 8.8/100 PY among medically controlled subjects. Non-AIDS-defining infections were the most common reason for hospitalization (2.95/100 PY and 2.70/100 PY, respectively and rates of cardiovascular hospitalization were similar in both groups (0.45/100 PY and 0.76/100 PY. There was no difference in hospitalization rate for HICs compared with subjects with medically controlled HIV (adjusted incidence rate ratio 1.15 [95% confidence interval 0.80 to 1.65]. Conclusions: All-cause and cardiovascular hospitalization rates did not differ between HICs and persons with medically controlled HIV. Non-AIDS defining infections were common in this young, healthy, predominantly male cohort of military
Full Text Available A number of factors have been identified that are related to sexual and injecting HIV transmission. We developed a probabilistic mathematical model to put these factors together and interpret risks in the context of individual behavior among injecting drug-using (IDU couples in St. Petersburg, Russia. Some HIV-discordant couples have unprotected sex and sometimes inject drugs together but stay discordant for a long time, while some individuals acquire HIV on the first encounter. We considered existing estimates of HIV transmission risks through injecting and sexual contacts to develop a predictive survival model for an individual who is exposed to HIV through intimate relationships. We computed simulated survival curves for a number of behavioral scenarios and discussed sources of simulated uncertainty. We then applied the model to a longitudinal study of HIV-discordant couples and validated the model's forecast. Although individual prediction of seroconversion time appeared impossible, the ability to rank behavioral patterns in terms of HIV risk and to estimate the probability of survival HIV-free will be important to educators and counselors.
Rahaman, Md. Matiur; Chen, Dijun; Gillani, Zeeshan; Klukas, Christian; Chen, Ming
Due to an increase in the consumption of food, feed, fuel and to meet global food security needs for the rapidly growing human population, there is a necessity to breed high yielding crops that can adapt to the future climate changes, particularly in developing countries. To solve these global challenges, novel approaches are required to identify quantitative phenotypes and to explain the genetic basis of agriculturally important traits. These advances will facilitate the screening of germplasm with high performance characteristics in resource-limited environments. Recently, plant phenomics has offered and integrated a suite of new technologies, and we are on a path to improve the description of complex plant phenotypes. High-throughput phenotyping platforms have also been developed that capture phenotype data from plants in a non-destructive manner. In this review, we discuss recent developments of high-throughput plant phenotyping infrastructure including imaging techniques and corresponding principles for phenotype data analysis. PMID:26322060
Panidis, Dimitrios; Tziomalos, Konstantinos; Misichronis, Georgios; Papadakis, Efstathios; Betsas, George; Katsikis, Ilias; Macut, Djuro
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by oligo- or anovulation (ANOV), biochemical or clinical manifestations of hyperandrogenemia (HA) and PCOs. Four phenotypes of PCOS exist [phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO) and phenotype 4 (ANOV + PCO)] but the differences between them are not well studied. We compared markers of insulin resistance (IR) and endocrine characteristics between the different PCOS phenotypes. We prospectively studied 1212 consecutive women with PCOS and 254 BMI-matched healthy women. Phenotypes 1-4 were present in 48.2, 30.7, 9.7 and 11.4% of patients, respectively. BMI did not differ between the four phenotypes and controls. Both normal weight and overweight/obese women with phenotypes 1 and 2 were more insulin resistant than controls. Overweight/obese, but not normal weight, women with phenotype 4 were more insulin resistant than controls, while IR in women with phenotype 3 did not differ from controls regardless of obesity. In normal weight subjects, women with phenotypes 1 and 2 were more insulin resistant than women with phenotype 4. In overweight/obese subjects, women with phenotype 1 were more insulin resistant than women with phenotypes 2 and 3 and women with phenotype 4 were more insulin resistant than those with phenotype 3. Circulating androgens were higher in normal weight and overweight/obese PCOS patients with phenotypes 1-3 compared with those with phenotype 4, and higher in normal weight PCOS patients with phenotype 1 than in those with phenotype 2. Phenotype 1 is associated with more IR and more pronounced HA than phenotype 2. Phenotypes 2 and 4 with obesity, are also characterized by IR. In contrast, phenotype 3 is not associated with IR.
Sharma, Shimpa; Gulbake, Arvind
Introduction Ano-Genital Warts (AGW) like other Sexually Transmitted Diseases (STD) is associated with Human Immunodeficiency Virus (HIV) infection. This study of AGW was done in HIV positive and HIV negative patients. Aim To study the risk factors and clinical presentations of ano-genital warts in HIV positive and negative patients. Materials and Methods A comparative, cross-sectional, descriptive study of 25 HIV positive and 25 HIV negative (n=50) AGW patients between 15-60 years of both sex was conducted in Dr. D. Y. Patil Hospital and Research Centre from July 2014 to July 2016. Results Significant association of HIV positivity (phomosexuality (p0.05). No patient presented with changes of malignancy. Four were adolescents below 19 years. Two patients had atypical presentations of giant condylomata i.e., Buschke-Lowenstein Tumour (BLT). Conclusion HIV positivity was significantly associated with the risk factors of age below 30 years, homo sexuality and multiple sexual partners. Anal warts were significantly common in HIV positive patients. Four adolescents with AGW underline the need for high risk behaviour counselling. No patient had malignant ano-genital warts. Follow up of these patients with Human Papilloma Virus (HPV) sub-typing is necessary. PMID:28274028
Harrer, Thomas; Plettenberg, Andreas; Arastéh, Keikawus; Van Lunzen, Jan; Fätkenheuer, Gerd; Jaeger, Hans; Janssens, Michel; Burny, Wivine; Collard, Alix; Roman, François; Loeliger, Alfred; Koutsoukos, Marguerite; Bourguignon, Patricia; Lavreys, Ludo; Voss, Gerald
The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4(+) T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4(+) and CD8(+) T-cell responses, absolute CD4(+) T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4(+) T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (pVaccine-induced HIV-1-specific CD4(+) T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8(+) T-cells or change in CD8(+) T-cell activation marker expression profile was detected. Absolute CD4(+) T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4(+) T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4(+) T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Turan, Janet M.; Bukusi, Elizabeth A.; Onono, Maricianah; Holzemer, William L.; Miller, Suellen; Cohen, Craig R.
HIV/AIDS stigma is a common thread in the narratives of pregnant women affected by HIV/AIDS globally and may be associated with refusal of HIV testing. We conducted a cross-sectional study of women attending antenatal clinics in Kenya (N = 1525). Women completed an interview with measures of HIV/AIDS stigma and subsequently information on their acceptance of HIV testing was obtained from medical records. Associations of stigma measures with HIV testing refusal were examined using multivariate...
Horvath, Denis, E-mail: firstname.lastname@example.org [Centre of Interdisciplinary Biosciences, Institute of Physics, Faculty of Science, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia); Brutovsky, Branislav, E-mail: email@example.com [Department of Biophysics, Institute of Physics, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia)
Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.
Valle, Adrian; Treviño,Ana Cecilia; Zambrano, Farith Francisco; Urriola, Karla Elizabeth; Sánchez, Luis Antonio; Elizondo,Jesus Eduardo
Objectives To assess the internal consistency and factor structure of the abridged Spanish version of the Berger HIV Stigma Scale (HSS-21), to provide evidence for its convergent and discriminant validity, and to 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 abbreviate...
Adrian eValle; Ana Cecilia Treviño; Farith Francisco Zambrano; Karla Elizabeth Urriola; Luis Antonio Sánchez; Jesus Eduardo Elizondo
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 ve...
Ferreira, D F; Fernandes, S B; Bruzi, A T; Ramalho, M A P
The aim of this study was to undertake the theoretical derivations of non-parametric methods, which use linear regressions based on rank order, for stability analyses. These methods were extension different parametric methods used for stability analyses and the result was compared with a standard non-parametric method. Intensive computational methods (e.g., bootstrap and permutation) were applied, and data from the plant-breeding program of the Biology Department of UFLA (Minas Gerais, Brazil) were used to illustrate and compare the tests. The non-parametric stability methods were effective for the evaluation of phenotypic stability. In the presence of variance heterogeneity, the non-parametric methods exhibited greater power of discrimination when determining the phenotypic stability of genotypes.
Apr 2, 2011 ... The mechanisms behind accelerated emphysema in adults with HIV infection and the HIV-infected smoking population are both ... HI virus itself is a predisposing factor in the pathogenesis of bullous lung disease.1-3. In 1989 ...
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.
Md. Matiur eRahaman
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.
Lohse, Nicolai; Hansen, Ann-Brit Eg; Jensen-Fangel, Søren; Kronborg, Gitte; Kvinesdal, Birgit; Pedersen, Court; Larsen, Carsten S; Møller, Axel; Willumsen, Lars; Obel, Niels
We used a population-based cohort study design to describe the demographic characteristics of the HIV-infected population in Denmark and their variation over time. HIV treatment in Denmark is restricted to 9 centres, and all 3941 HIV-1 infected patients more than 15 y old seen at these centres in 1995-2003 were included. We found an estimated HIV prevalence of 70 per 100,000, and a mean annual incidence rate of 5.1 per 100,000 persons. The number of newly infected individuals was stable with a median of 231 per y (period 1995-2002), whereas the number of deaths decreased from 166 in 1995 to 50 in 2000 (p=0.000) and remained stable thereafter. Of the enrolled patients, 75% were males, 80% were Caucasian, 13% were black African, and the primary risk behaviour was male-to-male sexual contact (44%), heterosexual contact (36%), and injection drug use (11%). During the y 1995-2003 we found an increase in age at diagnosis (p=0.000), and no major changes in gender, race, mode of infection, or baseline CD4+ cell count and viral load, neither overall not within subgroups of patients. In this period 14.5% had AIDS at the time of HIV diagnosis. Our data do not confirm concerns about unmonitored evolution in the HIV epidemic in Denmark.
Begum, Ferdouse; Chowdhury, Reshmi; Cheung, Vivian G.; Sherman, Stephanie L.; Feingold, Eleanor
Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated. In this study, using new datasets, we characterized additional recombination phenotypes to uncover novel candidates and further dissect the role of already known loci. We used three datasets totaling 1562 two-generation families, including 3108 parents with 4304 children. We estimated five different recombination phenotypes including two novel phenotypes (average recombination counts within recombination hotspots and outside of hotspots) using dense SNP array genotype data. We then performed gender-specific and combined-sex genome-wide association studies (GWAS) meta-analyses. We replicated associations for several previously reported recombination genes, including RNF212 and PRDM9. By looking specifically at recombination events outside of hotspots, we showed for the first time that PRDM9 has different effects in males and females. We identified several new candidate loci, particularly for recombination events outside of hotspots. These include regions near the genes SPINK6, EVC2, ARHGAP25, and DLGAP2. This study expands our understanding of human meiotic recombination by characterizing additional features that vary across individuals, and identifying regulatory variants influencing the numbers and locations of recombination events. PMID:27733454
Full Text Available Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor genetic variants influence disease progression and early viral load. We performed a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters for detection of novel genetic factors that influence plasma HIV-RNA and cellular HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were localised in the 6p21 major histocompatibility complex (MHC region and were in the vicinity of class I and III genes. Moreover, protective alleles for four disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and rs3093662 were strikingly over-represented among forty-five Long Term HIV controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV reservoir are associated with the same four SNPs, but also with two additional SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and YPEL2 genes and chromosome 8 (rs2575735; within the Syndecan 2 gene. Our data provide evidence that the MHC controls both HIV replication and HIV reservoir. They also indicate that two additional genomic loci may influence the HIV reservoir.
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.
Valle, Adrian; Treviño, Ana Cecilia; Zambrano, Farith Francisco; Urriola, Karla Elizabeth; Sánchez, Luis Antonio; Elizondo, Jesus Eduardo
To assess the internal consistency and factor structure of the abridged Spanish version of the Berger HIV Stigma Scale (HSS-21), to provide evidence for its convergent and discriminant validity, and to describe perceived stigma in an urban population from northeast Mexico. 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. 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. 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. 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.
Acosta, Lisiane M W; Gonçalves, Tonantzin Ribeiro; Barcellos, Nêmora Tregnago
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.
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
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
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
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 wh
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
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 wh
Schizophrenias are diagnosed purely clinically. The biological basis for this clinical entity is still fully unknown. Genetic studies have revealed some interesting hints but have not led to the identification of actual disease genotypes. On the contrary, it has become more and more probable that widely differing genotype constellations together with manifold environmental factors can trigger schizophrenia according to the motto "many roads lead to Rome...". Thus, new strategies that allow a better insight into complex genotype-phenotype relationships, e. g. PGAS (phenotype-based genetic associations studies) are urgently needed. PGAS became possible on the basis of the GRAS data collection, the as yet largest worldwide phenotypical databank of schizophrenic patients. First PGAS proof-of-concept results on cognition or development-relevant genes are already available.
Durgesh Kumar; Mukesh V. Singh; Dinesh Kumar; K. M. Shukla; Singh, D. K.; Singh, Dharmendra K.
Background: The clinical manifestations of HIV infection vary widely among infants, children, and adolescent. So there is a need to study the mode of transmission, clinical presentations, WHO and immunological staging among HIV infected children. Methods: Observational analytic cross sectional study. The children who were HIV positive (confirmed by ELISA for HIV-1 and HIV-2), and attending the OPD of ART Centre and SN Children Hospital, Allahabad during period of one year. The study popula...
Sondag, K. Ann; Strike, Carrie
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.…
Jairam R Lingappa
Full Text Available BACKGROUND: Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use. METHODS: We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403 of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations. RESULTS: After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations. CONCLUSION: This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition.
Bisgaard, Hans Flinker; Vissing, Nadja Hawwa; Carson, C. G.
pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. Pregnant women from eastern Denmark were invited during 2008–2010 to a novel unselected ‘COPSAC2010’ cohort. The women visited the clinic during pregnancy weeks 24 and 36....... Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high‐dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin...... for acute lung symptoms was conducted in the children with recurrent wheeze. Seven hundred and thirty‐eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over‐representation of atopic parents. The participant satisfaction...
Full Text Available Tubular aggregates (TAs are inclusions described in skeletal muscle in a variety of disorders. In a retrospective analysis, TAs were found in 18 (0.24% cases and involved a spectrum of clinical phenotypes. Ultrastructurally, four distinct types of aggregates were noted. There was no correlation between the clinical phenotypes, duration of illness and types of TAs.
J.M. Kerkhof (Hanneke); I. Meulenbelt (Ingrid); T. Akune (Toru); N.K. Arden (Nigel); A. Aromaa (Arpo); S.M. Bierma-Zeinstra (Sita); C. Cooper (Charles); J. Dai; M. Doherty (Michael); S. Doherty (Sally); D. Felson; A. Gonzalez (Antonio); A. Gordon; A. Harilainen (Arsi); D.J. Hart; V.B. Hauksson (Valdimar); M. Heliovaara (Markku); A. Hofman (Albert); S. Ikegawa; T. Ingvarsson (Torvaldur); Q. Jiang; H. Jonsson; I. Jonsdottir (Ingileif); H. Kawaguchi; M. Kloppenburg (Margreet); U.M. Kujala (Urho); N.E. Lane; P. Leino-Arjas (Päivi I.); L.S. Lohmander (Stefan); F.P. Luyten (Frank); K.N. Malizos (Konstantinos); M. Nakajima; M.C. Nevitt (Michael); H.A.P. Pols (Huib); F. Rivadeneira Ramirez (Fernando); D. Shi; E. Slagboom (Eline); T.D. Spector (Timothy); K. Stefansson (Kari); A. Sudo (Akihiro); A. Tamm; A.E. Tamm (Aile); A. Tsezou (Aspasia); A. Uchida; A.G. Uitterlinden (André); J.M. Wilkinson (Mark); N. Yoshimura; A.M. Valdes (Ana Maria); J.B.J. van Meurs (Joyce); A.J. Carr (Andrew Jonathan)
textabstractObjective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consor
Evangeli, Michael; Pady, Kirsten; Wroe, Abigail L
Deciding to test for HIV is necessary for receiving HIV treatment and care among those who are HIV-positive. This article presents a systematic review of quantitative studies on relationships between psychological (cognitive and affective) variables and HIV testing. Sixty two studies were included (fifty six cross sectional). Most measured lifetime testing. HIV knowledge, risk perception and stigma were the most commonly measured psychological variables. Meta-analysis was carried out on the relationships between HIV knowledge and testing, and HIV risk perception and testing. Both relationships were positive and significant, representing small effects (HIV knowledge, d = 0.22, 95 % CI 0.14-0.31, p testing included: perceived testing benefits, testing fear, perceived behavioural control/self-efficacy, knowledge of testing sites, prejudiced attitudes towards people living with HIV, and knowing someone with HIV. Research and practice implications are outlined.
Full Text Available The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1 expression of the CD8+ T-cell subset found in primary HIV infection (PHI was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM cells over fully differentiated terminal effector CD8+ T (TTE cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the
Power, Robert A.; Davaniah, Siva; Derache, Anne; Wilkinson, Eduan; Tanser, Frank; Pillay, Deenan; de Oliveira, Tulio
Background Genome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics. Method We performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naïve to the respective treatment. Results GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting GWAS’s ability to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR. Conclusions These results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS. PMID:27677172
Full Text Available Introduction: HIV-infected pregnant women are very likely to engage in HIV medical care to prevent transmission of HIV to their newborn. After delivery, however, childcare and competing commitments might lead to disengagement from HIV care. The aim of this study was to quantify loss to follow-up (LTFU from HIV care after delivery and to identify risk factors for LTFU. Methods: We used data on 719 pregnancies within the Swiss HIV Cohort Study from 1996 to 2012 and with information on follow-up visits available. Two LTFU events were defined: no clinical visit for >180 days and no visit for >360 days in the year after delivery. Logistic regression analysis was used to identify risk factors for a LTFU event after delivery. Results: Median maternal age at delivery was 32 years (IQR 28–36, 357 (49% women were black, 280 (39% white, 56 (8% Asian and 4% other ethnicities. One hundred and seven (15% women reported any history of IDU. The majority (524, 73% of women received their HIV diagnosis before pregnancy, most of those (413, 79% had lived with diagnosed HIV longer than three years and two-thirds (342, 65% were already on antiretroviral therapy (ART at time of conception. Of the 181 women diagnosed during pregnancy by a screening test, 80 (44% were diagnosed in the first trimester, 67 (37% in the second and 34 (19% in the third trimester. Of 357 (69% women who had been seen in HIV medical care during three months before conception, 93% achieved an undetectable HIV viral load (VL at delivery. Of 62 (12% women with the last medical visit more than six months before conception, only 72% achieved an undetectable VL (p=0.001. Overall, 247 (34% women were LTFU over 180 days in the year after delivery and 86 (12% women were LTFU over 360 days with 43 (50% of those women returning. Being LTFU for 180 days was significantly associated with history of intravenous drug use (aOR 1.73, 95% CI 1.09–2.77, p=0.021 and not achieving an undetectable VL at
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.
Hart, Anna B; Samuels, David C; Hulgan, Todd
Mitochondrial toxicity is implicated in some treatment-limiting antiretroviral therapy complications, and reports of mitochondrial dysfunction in untreated HIV infection suggest antiretroviral therapy independent effects of HIV. Several studies have explored associations between mtDNA haplogroups (patterns of mtDNA polymorphisms) and outcomes of HIV infection and/or antiretroviral therapy, but findings have been inconsistent. We systematically reviewed published studies examining mtDNA haplogroups in HIV-infected persons to summarize reported outcome associations, and to highlight potential future research directions. We identified 21 articles published from 2005-2013. Multiple different phenotypes were studied; most were antiretroviral therapy associated metabolic outcomes (e.g. lipodystrophy, insulin resistance, and dyslipidemia). Haplogroup H was associated with the most outcomes, including AIDS progression, CD4 T-cell recovery, cirrhosis (in hepatitis C coinfection), and metabolic outcomes. This review is the first to focus on the emerging area of mtDNA haplogroups in HIV, and summarizes the published literature on associations between mtDNA haplogroups and clinical outcomes in populations of European and African descent. Several reported associations require replication and ideally biological verification before definitive conclusions can be drawn, but research in this area has the potential to explain outcome disparities and impact clinical management of patients.
The Multispot rapid HIV-1/HIV-2 differentiation assay is comparable with the Western blot and an immunofluorescence assay at confirming HIV infection in a prospective study in three regions of the United States.
Pandori, Mark W; Westheimer, Emily; Gay, Cindy; Moss, Nicholas; Fu, Jie; Hightow-Weidman, Lisa B; Craw, Jason; Hall, Laura; Giancotti, Francesca R; Mak, Mae Ling; Madayag, Carmela; Tsoi, Benjamin; Louie, Brian; Patel, Pragna; Owen, S Michele; Peters, Philip J
A new HIV diagnostic algorithm has been proposed which replaces the use of the HIV-1 Western blot and HIV-1 immunofluorescence assays (IFA) as the supplemental test with an HIV-1/HIV-2 antibody differentiation assay. To compare an FDA-approved HIV-1/HIV-2 antibody differentiation test (Multispot) as a confirmatory test with the HIV-1 Western blot and IFA. Participants were screened with an HIV-1/HIV-2 combination Antigen/Antibody (Ag/Ab) screening assay. Specimens with repeatedly reactive results were tested with Multispot and either Western blot or IFA. Specimens with discordant screening and confirmatory results were resolved with HIV-1 RNA testing. Individuals (37,876) were screened for HIV infection and 654 (1.7%) had a repeatedly reactive Ag/Ab assay result. On Multispot, 554 (84.7%) were HIV-1 reactive, 0 (0%) were HIV-2 reactive, 1 (0.2%) was reactive for both HIV-1 and HIV-2 (undifferentiated), 9 (1.4%) were HIV-1 indeterminate, and 90 (13.8%) were non-reactive. HIV-1 RNA was detected in 47/90 Multispot non-reactive (52.2%) specimens. Among specimens confirmed to have HIV infection (true positives), Multispot and Western blot detected HIV-1 antibody in a similar proportion of cases (93.7% vs. 94.4% respectively) while Multispot and IFA also detected HIV-1 antibody in a similar proportion of cases (84.5% vs. 83.4% respectively). In this study, Multispot confirmed HIV infections at a similar proportion to Western blot and IFA. Multispot, Western blot, and IFA, however, did not confirm all of the reactive Ag/Ab assay results and underscores the importance of HIV NAT testing to resolve discordant screening and confirmatory results. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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; Østergaard, 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
Background 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). Methods 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. Results 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/mm3, IQR (83–247) among HIV-2 infected patients and 146 cells/mm3, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm3 after 24 months on ART for HIV-2 patients and 169 cells/mm3 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). Conclusions 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. PMID:23824279
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.
Alcaide, Maria L; Rodriguez, Violeta J; Fischl, Margaret A; Jones, Deborah L; Weiss, Stephen M
Intravaginal practices (IVPs), include intravaginal cleansing (cleansing the inside of the vagina) or intravaginal insertion of products for hygiene, health or sexuality reasons. IVPs are associated with adverse female health outcomes, development of bacterial vaginosis, HIV acquisition and transmission. A mixed methods approach was used in this study to examine the prevalence of IVP, assess reasons for engagement, and perceptions of IVP among a sample of minority (African-American and Hispanic) women infected, or at-risk, for HIV in Miami, USA, a city with increasing numbers of sexually transmitted infections (STIs) and HIV. Three focus groups (total n=20) and quantitative assessments (n=72) were conducted with women infected or uninfected with HIV. In the qualitative assessments, most women reported engaging in both intravaginal cleansing and intravaginal insertion, and stated the main motivation for IVP was hygiene. The quantitative assessments confirmed that cleansing with water alone, soap with water or using commercial douches was common, as well as intravaginal insertion using a cloth or a rag in both HIV-infected and uninfected women. Women with HIV infection reported less use of water and water and soap for IVPs, and reported learning about the potential harm of IVP from their HIV health care providers. Despite their health risks, IVP appeared common in both HIV-infected and at-risk minority women, and interventions to decrease IVP could have important health implications among populations with high rates of IVP, STIs and HIV. PMID:28280394
Fabio, G; Scorza, R; Lazzarin, A; Marchini, M; Zarantonello, M; D'Arminio, A; Marchisio, P; Plebani, A; Luzzati, R; Costigliola, P
We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups. PMID:1733633
Riou, Catherine; Tanko, Ramla F; Soares, Andreia P; Masson, Lindi; Werner, Lise; Garrett, Nigel J; Samsunder, Natasha; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Burgers, Wendy A
Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4(+) T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4(+) T cells specific for common copathogens is still unclear. To better understand the dynamics of Ag-specific CD4(+) T cells during ART, we assessed the frequency, functional capacity, and memory profile of CD4(+) T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation. After ART initiation, the frequency of M. tuberculosis-specific CD4(+) T cells showed little change, whereas CMV-specific CD4(+) T cells were significantly lower (p = 0.003). There was no difference in the polyfunctional or memory profile of Ag-specific CD4(+) T cells before and after ART. The replenishment of Ag-specific CD4(+) T cells correlated with the memory differentiation profile of these cells prior to ART. Pathogen-specific CD4(+) T cells exhibiting a late differentiated profile (CD45RO(+)CD27(-)) had a lower capacity to replenish (p = 0.019; r = -0.5) compared with cells with an early differentiated profile (CD45RO(+)CD27(+); p = 0.04; r = 0.45). In conclusion, restoration of copathogen-specific memory CD4(+) T cells during treated HIV infection is related to their memory phenotype, in which early differentiated cells (such as most M. tuberculosis-specific cells) have a higher replenishment capacity compared with late differentiated cells (such as most CMV-specific cells). These data identify an important, hitherto unrecognized, factor that may limit restoration of copathogen immunity in HIV-infected individuals on ART.
Full Text Available Background: Tuberculosis (TB and the HIV epidemics have been well known previously but now these are emerging as a combined epidemic to pose new public health challenges. TB is the most common opportunistic infection found among HIV positive individuals. Aims & Objective: To find the prevalence of HIV infection among the TB patients diagnosed and put on treatment under RNTCP. 2. To assess their treatment outcomes in Chandigarh. Material & Methods: The present study was designed as a retrospective cohort study among the adult population (>18 years in Chandigarh from April 2012 - March 2014. All the TB patients registered for treatment at the 17 DMCs of Chandigarh, during this period were taken as the study population. The treatment outcome among TB-HIV co-infected patients was compared with those having only Tuberculosis. Results: From 1st April 2012 - 31st March 2013, a total of 3,551 patients were registered under RNTCP for treatment of tuberculosis. Among the total patients put on DOTS (3,551, 63.2% (2,246 were males and 36.7% (1,305 were females. A total of 3,516 TB patients had their blood tested for HIV. Out of these patients, 88 (2.47% were tested positive for HIV. HIV positive status was also found to be significantly associated with occurrence of extra pulmonary tuberculosis (X2= 17.42; df 2; p 0.0001. Category – II treatment was found to be slightly more among the HIV positive TB patients as compared to the HIV negative patients. From the total sample, 2.19% (78 patients were later diagnosed as having drug resistant tuberculosis with only one (01 patient being co-infected with HIV. Out of all the TB-HIV co-infected patients, 29.55% were declared cured at the end of the treatment. A total of 63.64% of co-infected patients had completed their treatment. Death as an outcome was significantly associated with HIV positive status (1.14% as compared to HIV negative patients. Conclusion: Integration of TB-HIV collaborative activities at
d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Serafino, Sara; Giustini, Noemi; Cavallari, Eugenio Nelson; Bianchi, Luigi; Pavone, Paolo; Bellelli, Valeria; Turriziani, Ombretta; Antonelli, Guido; Stroffolini, Tommaso; Vullo, Vincenzo
HIV infection may enhance immune-activation, while little is known regarding the role of HCV infection. This study investigates the impact of HCV in HIV coinfected patients with undetectable viraemia under HAART on the levels of peripheral T cell's immune-activation. We determined T lymphocytes subsets to characterize immune-activation defined as CD38 and/or HLA-DR expression in chronic monoinfected HCV, HIV, and HIV/HCV coinfected subjects. One hundred and fifty six patients were divided into three groups: (i) 77 HIV+ patients; (ii) 50 HCV+ patients; and (iii) 29 coinfected HIV/HCV patients. The level of CD4(+) was significantly higher in HCV+ than in HIV+ or in coinfected HIV/HCV subjects. The frequencies of CD4(+) CD38(+) /HLA-DR(-) , CD4(+) CD38(-) /HLA-DR(+) and CD4(+) CD38(+) /HLA-DR(+) in HIV+ patients were comparable to those measured in coinfected patients, but statistically higher than those observed in HCV+ subjects. The percentage of CD8(+) was comparable in HIV-1+ patients and coinfected HIV/HCV but the results obtained in both groups were significantly higher compared to the results obtained in HCV patients. The level of CD8(+) CD38(+) /HLA-DR(-) showed values lower in HIV+ patients than in that monoinfected HCV and coinfected HIV/HCV patients. The frequencies of CD8(+) CD38(-) /HLA-DR(+) were higher in HIV+ patients compared to HCV+ and coinfected HIV/HCV patients. HIV/HCV coinfected group showed highest levels of CD8(+) CD38(+) /HLA-DR(+) . HIV plays a pivotal role to determine the immune activation in the host. The role of HCV needs of further investigations but our data show that HCV mainly influences the immune-activation of the pool of CD8, but also probably plays a supporting additive effect on CD4 immune-activation. J. Med. Virol. 88:1347-1356, 2016. © 2016 Wiley Periodicals, Inc.
Full Text Available Background: Human immunodeficiency virus (HIV infection primarily affects women during their reproductive years, and the coexistence of reproductive tract infections (RTIs is not surprising given the fact that HIV is mainly acquired via heterosexual contact. Aim: The aim of the study was to compare the occurrence of RTIs among infected and noninfected women. Materials and Methods: A case control study of 83 HIV positive women, tested by two enzyme linked immunosorbent assay (ELISA and a matched control of 87 HIV negative women were screened for RTIs. They were submitted to gynecological examination and cervical cytology. Results: The mean age for HIV positive women was 30 years and that for HIV negative women was 27 years. 18% HIV positive women had menstrual irregularities compared to 6% in seronegative group ( P = 0.024. Vaginal infections including sexually transmitted infections (STIs were found in 47 (57% HIV positive women and 30 (34% HIV negative women ( P = 0.0037. Vaginal candidiasis was the most common infection (34% in HIV positive women, followed by trichomoniasis (12%. Human papilloma virus (HPV infection was seen in nine HIV positive women versus none in HIV negative women. Cervical cytology showed inflammation in 53 (64% HIV positive women compared to 27 (31% HIV negative women ( P = 0.000023. Genital neoplasia, including carcinoma in situ was observed in 2 (2.5% HIV positive women and in none of the HIV negative women. Conclusion: It is seen that reproductive tract morbidities are common in HIV positive women. So it is imperative that HIV positive women have a complete gynecological evaluation including a Papanicolaou (PAP smear with aggressive screening of STIs.
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.
Boarts, Jessica M; Bogart, Laura M; Tabak, Melanie A; Armelie, Aaron P; Delahanty, Douglas L
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.
Barmania, Sima; Aljunid, Syed Mohamed
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
Full Text Available To examine mechanisms underlying the increased inflammatory state of HIV-infected patients, by investigating the association of HIV-related factors, demography, lifestyle, and body composition with the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR.suPAR was measured in EDTA-plasma and associated with HIV-related factors (HIV-duration, combination antiretroviral treatment (cART, nadir CD4+ cell count, CD4+ cell count, and HIV RNA; demography; lifestyle; and body composition determined by Dual energy X-ray Absorptiometry (DXA scan, in multiple linear regression analyses adjusted for biological relevant covariates, in a cross-sectional study of 1142 HIV-infected patients.Increased suPAR levels were significantly associated with age, female sex, daily smoking, metabolic syndrome and waist circumference. cART was associated with 17% lower suPAR levels. In cART-treated patients 10-fold higher HIV RNA was associated with 15% higher suPAR, whereas there was no association in untreated patients. Patients with CD4+ cell count <350 cells/µL had higher suPAR levels than patients with CD4+ cell count ≥350 cells/µL , though not significantly. We found no association with nadir CD4+ cell count or with duration of HIV-infection [corrected]. Finally, suPAR was not associated with adipose tissue distribution, but strongly associated with low leg muscle mass [corrected].In patients infected through intravenous drug use (IDU, CD4+ cell counts ≥350 cells/µL were associated with 27% lower suPAR (p = 0.03, andsuPAR was 4% lower pr. year during treatment (p = 0.05; however, there was no association with HIV RNA, duration of HIV-infection, nor cART [corrected].We found elevated suPAR levels in untreated patients compared to patients on cART. Moreover, we observed a significant positive association between suPAR and HIV RNA levels in cART-treated patients. Age, HIV-transmission through IDU, metabolic syndrome, smoking, and low leg
Laufer, M.K.; Oosterhout, J.J. van; Perez, M.A.; Kanyanganlika, J.; Taylor, T.E.; Plowe, C.V.; Graham, S.M.
BACKGROUND: Most information about children living with HIV is based on follow up from children identified through mother-to-child transmission studies. Children identified through voluntary counseling and testing (VCT) represent a unique cohort that has not been previously described in the literatu
van der Helm, J.J.
This thesis comprises international epidemiological studies on HIV, Hepatitis C (HCV) and sexually transmitted infections (STI) and the evaluation of STI diagnostic tests with the ultimate goal to decrease spread and disease burden of these infections. The main conclusions are: 1. Without the use of
Berhan, Zelalem; Abebe, Fantu; Gedefaw, Molla; Tesfa, Mulugeta; Assefa, Muluken; Tafere, Yilkal
The estimated HIV prevalence among pregnant women in Ethiopia is 1.2 percent and unfortunately one of every 3 children born to these women gets infected with HIV. Elimination of these mother-to-child transmissions (MTCT) of HIV is possible through HIV testing during pregnancy and taking antiretroviral medications. However, only 24 percent of the pregnant women living with HIV have yet received the medication needed to prevent the transmission of HIV. Hence, there exists a concern that the rate of HIV infection among infants born to HIV positive mothers is increasing. This study assessed the prevalence of HIV infection and associated factors among infants born to women living with HIV, in South Gondar zone, Amhara region, Ethiopia. Facility based document review was conducted upon 434 charts. The study participants were HIV exposed infants enrolled from January to December 2012. The data were reviewed from all the 17 health facilities which were providing PMTCT services in the zone. The study included 434 HIV exposed infants having an HIV Deoxyribonucleic Acid (DNA) Polymerase Chain Reaction (PCR) test result. The data were collected using structured data extraction tool. Binary logistic regression analysis was employed to assess the putative association of independent variables with the outcome variable. Significance was taken at a P valueinstrumental to curb the devastating consequences of HIV on pregnant women and their newborns.
Baptiste, Donna R.; Kapungu, Chisina; Miller, Steve; Crown, Laurel; Henry, David; Da Costa Martinez, Dona; Jo-Bennett, Karen
This article presents preliminary findings of a randomized HIV prevention study in Trinidad and Tobago in the Caribbean. The study centers on a family HIV workshop aimed at strengthening parenting skills that are empirically linked to reducing adolescent HIV exposure and other sexual risks. These skills include parental monitoring; educating youth…
Full Text Available BACKGROUND AND OBJECTIVES: Mucocutaneous manifestations are extremely common and varied in HIV infected patients. The present study was done to know the overall prevalence of mucocutaneous manifestations in HIV infected patients and to know the frequency of individual manifestations. METHODS: A total of 150 HIV seropositive patients from voluntary counseling and testing center were included in the study. Detailed history, thorough physical examination and relevant investigations were done to confirm the mucocutaneous manifestations when present. RESULTS: Ninety two percent (92% of 150 positives had mucocutaneous manifestations at presentation. Majority (75.34% of the patients belonged to the age group 25 – 49 years and male to female ratio was 1.08:1. Oral candidiasis was the most common (33.33% manifestation. Other common infectious conditions seen were HSV (16.67% dermatophytosis (12.67%, genital candidiasis (9.33%, herpes genitalis (10%. Common non-infectious disorders included generalized xerosis and ichthyosis (14.66%, generalized hyperpigmentation (11.33% and seborrheic dermatitis (6.67%. Hair and nail changes included diffuse alopecia (18%, trichomegaly (6.67% and melanonychia (32%.Pruritic papular dermatitis was seen in 16%. INTERPRETATION AND CONCLUSION: This study thus emphasizes the need for dermatological evaluation of all patients with HIV infection for early management and improved quality of life.
Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza; Brígido, Luis Fernando de Macedo
Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications.
Natasha A Karp
Full Text Available A significant challenge facing high-throughput phenotyping of in-vivo knockout mice is ensuring phenotype calls are robust and reliable. Central to this problem is selecting an appropriate statistical analysis that models both the experimental design (the workflow and the way control mice are selected for comparison with knockout animals and the sources of variation. Recently we proposed a mixed model suitable for small batch-oriented studies, where controls are not phenotyped concurrently with mutants. Here we evaluate this method both for its sensitivity to detect phenotypic effects and to control false positives, across a range of workflows used at mouse phenotyping centers. We found the sensitivity and control of false positives depend on the workflow. We show that the phenotypes in control mice fluctuate unexpectedly between batches and this can cause the false positive rate of phenotype calls to be inflated when only a small number of batches are tested, when the effect of knockout becomes confounded with temporal fluctuations in control mice. This effect was observed in both behavioural and physiological assays. Based on this analysis, we recommend two approaches (workflow and accompanying control strategy and associated analyses, which would be robust, for use in high-throughput phenotyping pipelines. Our results show the importance in modelling all sources of variability in high-throughput phenotyping studies.
Karp, Natasha A; Speak, Anneliese O; White, Jacqueline K; Adams, David J; Hrabé de Angelis, Martin; Hérault, Yann; Mott, Richard F
A significant challenge facing high-throughput phenotyping of in-vivo knockout mice is ensuring phenotype calls are robust and reliable. Central to this problem is selecting an appropriate statistical analysis that models both the experimental design (the workflow and the way control mice are selected for comparison with knockout animals) and the sources of variation. Recently we proposed a mixed model suitable for small batch-oriented studies, where controls are not phenotyped concurrently with mutants. Here we evaluate this method both for its sensitivity to detect phenotypic effects and to control false positives, across a range of workflows used at mouse phenotyping centers. We found the sensitivity and control of false positives depend on the workflow. We show that the phenotypes in control mice fluctuate unexpectedly between batches and this can cause the false positive rate of phenotype calls to be inflated when only a small number of batches are tested, when the effect of knockout becomes confounded with temporal fluctuations in control mice. This effect was observed in both behavioural and physiological assays. Based on this analysis, we recommend two approaches (workflow and accompanying control strategy) and associated analyses, which would be robust, for use in high-throughput phenotyping pipelines. Our results show the importance in modelling all sources of variability in high-throughput phenotyping studies.
Brumme Zabrina L
Full Text Available Abstract Background Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q Conclusion Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic backgrounds in different HIV-infected populations may influence HIV evolution in a particular direction as particular HLA-HIV codon associations are determined by specific HLA frequency distributions. Our analysis also suggests a dynamic HLA-associated evolution in HIV with fewer HLA-HIV codon associations observed in the proviral compartment, which is likely enriched in early archived HIV sequences, compared to the plasma virus compartment. These results highlight the importance of comparative HIV evolutionary studies in immunologically different populations worldwide.
Bill, Pierre L.A.
Objective: To investigate differences in clinical presentation, electrodiagnostic measures, CSF changes, and treatment outcome measures in HIV-infected and HIV-uninfected patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: A retrospective analysis of medical records of all patients meeting the European Federation of Neurology diagnostic criteria for idiopathic CIDP was performed in 2 neuromuscular units in Kwa-Zulu Natal between 2003 and 2015. Results: Eighty-four patients were included in the study; 39 were HIV-infected and 45 were HIV-uninfected. Among the HIV-infected patients, the majority were younger, were female, and had a monophasic progressive illness. Eighty-six percent (86%) were corticosteroid-responsive and 76% were in remission within 6–12 months requiring no further treatment. Among the HIV- uninfected patients, the majority were older, were male, and had a relapsing-remitting course. Twenty-seven percent (27%) were corticosteroid-responsive, 95% required combination therapy, and 33% were not in remission by 18 months on therapy. Conclusion: This study shows that HIV-infected patients with CIDP were younger, were more often female, displayed a monophasic progressive course, were highly steroid-responsive, and went into remission within 12 months of corticosteroid initiation. PMID:28054000
C. Kenyon (Chris); R. Colebunders (Robert); H.A.C.M. Voeten (Hélène); M.N. Lurie (Mark N.)
textabstractBackground: Correctly identifying the determinants of generalized HIV epidemics is crucial to bringing down ongoing high HIV incidence in these countries. High rates of migration are believed to be an important determinant of HIV prevalence. This study has two aims. Firstly, it evaluates
Devendra, A; Makawa, A; Kazembe, PN; Calles, NR; Kuper, H. (Harm)
BACKGROUND: As paediatric antiretroviral therapy (ART) is rapidly scaled up in Southern Africa, Human Immunodeficiency Virus (HIV) infection is becoming a chronic illness. Children growing up with HIV may begin to encounter disabilities. The relationship between HIV, disability and the need for rehabilitation has added an additional element that needs to be addressed by paediatric HIV treatment programmes. STUDY OBJECTIVES: 1) Estimate the prevalence of disabilities in HIV-infected and HIV-un...
Goosen, Simone; Hoebe, Christian J P A; Waldhober, Quita; Kunst, Anton E
Asylum seekers are considered to be a particularly vulnerable group with respect to HIV. Data on the HIV prevalence among asylum seekers, however, are scarce. The aim of this study is to map the HIV prevalence among asylum seekers who gave birth in The Netherlands. We used a nationwide electronic medical records database from the community health services for asylum seekers (MOA). The study population consisted of 4,854 women and girls who delivered in asylum reception between 2000 and 2008. A unique electronic health data base was used and case allocation was based on ICPC-codes. The number of women and girls that was HIV positive during their last pregnancy was 80, of which 79 originated from sub-Saharan Africa. The prevalence for women from this region of origin (3.4%) was high compared to women from all other regions of origin (0.04%; OR = 90.2; 95%CI 12.5-648.8). The highest HIV prevalence rates were found for women from Rwanda (17.0%) and Cameroon (13.2%). HIV prevalence rates were higher among women who arrived in reception without partner (OR = 1.82; 95%CI 0.75-4.44) and unaccompanied minors (OR = 2.59; 95%CI 0.79-8.49), compared to women who arrived in reception with partner. We conclude that, among asylum-seeking women from sub-Saharan Africa giving birth in The Netherlands, the HIV prevalence is high compared to the host population. For women from other regions of origin, the prevalence is at the same level as in the host population. The high HIV prevalence underlines the importance of preventive interventions and voluntary HIV testing for sub-Saharan African asylum seekers as from shortly after arrival.
Full Text Available Introduction: HIV infection is difficult to diagnose in infants, as most infected babies appear healthy and exhibit no signs and symptoms at birth. The present study was conducted to study the clinical profile & morbidity pattern of infants born to HIV positive mothers, their nutritional status and growth pattern and compare them with HIV non exposed infants. Methodology: This observational longitudinal study was conducted in Dec 2009 – Dec 2010 where all HIV exposed baby born in the hospital (n=44 were compared with suitable sample of HIV non exposed babies (n=140 in context of clinical profile & morbidity pattern. Results: In maternal weight <50 Kg category, mean weight, length and head circumference of HIV exposed infants is significantly lower than HIV non exposed infants. However, pattern of weight gain remain similar in both group. Grade 1 and grade 2 malnutrition was more in HIV exposed group at 3 month & 6 month. HIV exposed baby reported higher episodes of diarrhea (28.57% as compared to non exposed group (15.33% with statistically significant difference (p value<0.05. Conclusion: HIV exposure does not adversely affect growth potential of infants but because of their lower baseline values they seem to lag behind. Moreover maternal HIV status does not lead to severe degree of malnutrition if these babies were not themselves affected with HIV. [Natl J of Med Res 2012; 2(4.000: 512-517
This study presents the findings of a Knowledge, Attitude, and Practice Survey about sexually transmitted diseases (STDs) and HIV/AIDS in Rajasthan, India. Data were obtained from 153 truck drivers covering "Dhabas" at different highways. Truck operators (TOs), commercial sex workers (CSWs), and iv drug users are the primary at risk populations for HIV/AIDS. In 1997, 73.3% of the 3188 HIV-infected persons were infected through heterosexual intercourse. Findings from TOs indicate a high level of knowledge about STDs, which are prevalent among TOs. Many TOs rely on cleanliness (68.9%) as a safety measure, followed by use of condoms with multiple partners (56.8%). About 50% go for regular check-ups at clinics to avoid the problem of STDs. About 75% of 132 TOs had had at least one problem with STDs during the prior year. About 46.2% consulted a doctor for treatment, 26.5% ignored the problem, and 18.2% received no treatment. 72.7% of 132 TOs had accurate knowledge about AIDS, 62.1% were aware of transmission routes, and 50% knew about prevention. About 85% visited CSWs. Only 14.3% of 112 TOs who visited CSWs used condoms during sexual relations. 10.7% used condoms most of the time, 47.3% used condoms irregularly, and 27.7% never used condoms. Condom availability was an issue. Most TOs learned about HIV/AIDS from mass media, especially posters and banners, followed by the radio. Only 28% of all TOs had complete knowledge of STDs; 13.6% had misconceptions. 37.1% had complete knowledge of HIV/AIDS; 10.6% had misconceptions.
Li, Shuxia; Pang, Zengchang; Zhang, Dongfeng
Aims: The genetic and environmental influences on metabolic phenotypes have been intensively studied by twin modeling in different populations. However, twin studies on secular change in metabolic phenotypes have been rare due to high expenses, losses of follow up, and long waiting time...... in prospective investigations. Based on Chinese twin data collected from Danish-Chinese collaboration research, we perform twin modeling on 13 metabolic phenotypes (total cholesterol; triglyceride; high density lipoprotein (HDL); low density lipoprotein (LDL); urine acid (UA); glucose; weight; body mass index...... environmental factors. Secular changes in all phenotypes are under moderate to high (e2: 0.45 - 0.79) control by unique environmental factors. Conclusions: Variations in secular change in the 13 metabolic phenotypes show limited genetic control. Our results emphasize the special importance of unique environment...
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
Bennett, Siiri N.; Caporaso, Neil; Fitzpatrick, Annette L.; Agrawal, Arpana; Barnes, Kathleen; Boyd, Heather A.; Cornelis, Marilyn C.; Hansel, Nadia N.; Heiss, Gerardo; Heit, John A.; Kang, Jae Hee; Kittner, Steven J.; Kraft, Peter; Lowe, William; Marazita, Mary L.; Monroe, Kristine R.; Pasquale, Louis R.; Ramos, Erin M.; van Dam, Rob M.; Udren, Jenna; Williams, Kayleen
Genome-wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene-environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi-site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross-study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia. PMID:21284036
Bennett, Siiri N; Caporaso, Neil; Fitzpatrick, Annette L; Agrawal, Arpana; Barnes, Kathleen; Boyd, Heather A; Cornelis, Marilyn C; Hansel, Nadia N; Heiss, Gerardo; Heit, John A; Kang, Jae Hee; Kittner, Steven J; Kraft, Peter; Lowe, William; Marazita, Mary L; Monroe, Kristine R; Pasquale, Louis R; Ramos, Erin M; van Dam, Rob M; Udren, Jenna; Williams, Kayleen
Genome-wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene-environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi-site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross-study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia.
Full Text Available Objective. The aim of the study was to determine the prevalence of HIV-associated oral mucosal melanin hyperpigmentation (HIV-OMH in a specific population of HIV-seropositive South Africans and to analyse the associations between HIV-OMH clinical features and the demographic and immunological characteristics of the study cohort. Material and Methods. This cross-sectional study included 200 HIV-seropositive Black subjects. The collected data comprised age, gender, CD4+ T cell count, viral load, systemic disease, medications, oral site affected by HIV-OMH, extent (localized or generalized, intensity of the pigmentation (dark or light, and smoking and snuff use. Results. Overall, 18.5% of the study cohort had HIV-OMH. Twenty-two and a half percent had OMH that could not with confidence be attributed to HIV infection, and 59% did not have any OMH. There was a significant but weak association between smoking and the presence of HIV-OMH. Conclusions. The prevalence of HIV-OMH in the study population was 18.5%, the gingiva being the most commonly affected site. It appears that the CD4+ T cell count does not play any role in the biopathology of HIV-OMH.
Jackson, B S; Mokoena, T
Background People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. Methods A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups. Results 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups—HIV-uninfected and HIV-infected patients not on ARVs. Conclusions There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients. PMID:28179414
Nadya M Belenky
Full Text Available Depressive symptoms have been shown to independently affect both antiretroviral therapy (ART adherence and HIV clinical outcomes in high-income countries. We examined the prospective relationship between depressive symptoms and adherence, virologic failure, and suppressed immune function in people living with HIV/AIDS in Tanzania. Data from 403 study participants who were on stable ART and engaged in HIV clinical care were analyzed. We assessed crude and adjusted associations of depressive symptoms and ART adherence, both at baseline and at 12 months, using logistic regression. We used logistic generalized estimating equations to assess the association and 95% confidence intervals (CI between depressive symptoms and both virologic failure and suppressed immune function. Ten percent of participants reported moderate or severe depressive symptoms at baseline and 31% of participants experienced virologic failure (>150 copies/ml over two years. Depressive symptoms were associated with greater odds of reported medication nonadherence at both baseline (Odds Ratio [OR] per 1-unit increase = 1.18, 95% CI [1.12, 1.24] and 12 months (OR = 1.08, 95% CI [1.03, 1.14]. By contrast, increases in depressive symptom score were inversely related to both virologic failure (OR = 0.93, 95% CI [0.87, 1.00] and immune system suppression (OR = 0.88, 95% CI [0.79, 0.99], though the association between depressive symptoms and clinical outcomes was less precise than for the association with nonadherence. Findings indicate a positive association between depressive symptoms and nonadherence, and also an inverse relationship between depressive symptoms and clinical outcomes, possibly due to informative loss to follow-up.
Full Text Available In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART. We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.
Full Text Available This study was undertaken to examine the association between the immunological impact of HIV (measured by CD4 count and global self-assessed quality of life (QOL (measured with QOL1 for people suffering from HIV, to see if the connection was large and statistically strong enough to support our hypothesis of a strong QOL-immunological connection through the nonspecific, nonreceptor-mediated immune system, and thus to give a rationale for a holistic cure for HIV. This cross-sectional population study in Uganda included 20 HIV infected persons with no symptoms of AIDS and a CD4 count above 200 mill./liter. The main outcome measures were CD4 count, global QOL measured with the validated questionnaire QOL1, translated to Luganda and translated back to English. We found a large, clinically significant correlation between the number of T-helper cells (CD4 and global self-assessed quality of life (QOL1 (r = 0.57, p = 0.021, when controlled for age, gender, and years of infection. Together with other studies and holistic medicine theory, the results have given rationale for a holistic cure for HIV. We suggest, based on our findings and theoretical considerations, that HIV patients who improve their global QOL, also will improve their CD4 counts. Using the technique of holistic medicine based on the life mission theory and the holistic process theory of healing, we hypothesize that the improvement of QOL can have sufficient biological effect on the CD4, which could avoid or postpone the development of AIDS. A holistic HIV/AIDS cure improving the QOL draws on hidden resources in the person and is thus affordable for everybody. Improving global QOL also means a higher consciousness and a more ethical attitude, making it more difficult for the HIV-infected person to pass on the infection.
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.
Full Text Available Background: Itchy folliculitis are pruritic, folliculo-papular lesions seen in human immunodeficiency virus (HIV-infected patients. Previous studies have shown that it was impossible to clinically differentiate between eosinophilic folliculitis (EF and infective folliculitis (IF. Also, attempts to suppress the intense itch of EF were ineffective. Aims: The present study is aimed at correlating clinical, histopathological and immunological features of itchy folliculitis in HIV patients along with their treatment. Methods: The present prospective study lasted for 36 months (September, 2005 to August, 2008 after informed consent, data on skin disorders, HIV status and CD4 count were obtained by physical examination, histopathological examination and laboratory methods. Results: Of 51 HIV-positive patients with itchy folliculitis, the predominant lesion was EF in 23 (45.1% followed by bacterial folliculitis in 21 (41.2%, Pityrosporum folliculitis in five (9.8% and Demodex folliculitis in two (3.9% patients. The diagnosis was based on characteristic histopathological features and was also associated with microbiology confirmation wherever required. EF was associated with a lower mean CD4 count (180.58 ± 48.07 cells/mm 3 , P-value < 0.05, higher mean CD8 count (1675.42 ± 407.62 cells/mm3 and CD8/CD4 ratio of 9.27:1. There was significant reduction in lesions following specific treatment for the specific lesion identified. Conclusion: Clinically, it is impossible to differentiate itchy folliculitis and therefore it requires histopathological confirmation. Appropriate antimicrobial treatment for IF can be rapidly beneficial. The highly active antiretroviral therapy along with Isotretinoin therapy has shown marked reduction in the lesions of EF. Familiarity with these lesions may help in improving the quality of lives of the patients.
P Anitha Krishnan
Full Text Available Objective: This study was designed to compare the microbiological features of angular cheilitis (AC in human immunodeficiency virus (HIV seropositive and HIV seronegative individuals, in a group of south Indians. Materials and Methods: Swabs from oral commissures of 46 patients were obtained and inoculated on to Sabouraud′s dextrose agar (SDA supplemented with chloramphenicol, blood agar (BA and MacConkey′s agar (MCA plates and cultured. α-hemolytic Streptococci, Staphylococcus albus, Staphylococcus aureus, Candida species, Klebsiella species and Pseudomonas species were cultured. Candidal colonies were further speciated by the conventional biotyping technique. Results: In AC of HIV seropositive patients Candida albicans and Staphylococcus aureus were more prevalent than that in HIV seronegative patients. Incidentally in patients with CD4 cell count less than 200 there was an increase in the incidence of Candidal and Staphylococcus aureus colonization when compared to patients with CD4 cell count higher than 200. Conclusion: The present study suggests a definite difference in the microbial flora of AC in HIV seropositive patients than that of HIV seronegative population.
Amit Govind Kamat
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
Gekonge, Bethsebah; Raymond, Andrea D; Yin, Xiangfan; Kostman, Jay; Mounzer, Karam; Collman, Ronald G; Showe, Louise; Montaner, Luis J
We have previously described an antiapoptotic steady-state gene expression profile in circulating human monocytes from asymptomatic viremic HIV(+) donors, but the mechanism associated with this apoptosis resistance remains to be fully elucidated. Here, we show that Rb1 activation is a dominant feature of apoptosis resistance in monocytes exposed to HIV-1 in vivo (as measured ex vivo) and in vitro. Monocytes from asymptomatic viremic HIV(+) individuals show a positive correlation between levels of hypophosphorylated (active) Rb1 and VL in conjunction with increases in other p53-inducible proteins associated with antiapoptosis regulation, such as p21 and PAI-1 (SERPINE1), when compared with circulating monocytes from uninfected donors. Monocytes exposed in vitro to HIV-1 R5 isolates but not X4 isolates showed lower caspase-3 activation after apoptosis induction, indicating a role for the CCR5 signaling pathway. Moreover, monocytes exposed to R5 HIV-1 or MIP-1 β induced Rb1 and p21 expression and an accumulation of autophagy markers, LC3 and Beclin. The inhibition of Rb1 activity in HIV-1 R5 viral-exposed monocytes using siRNA led to increased apoptosis sensitivity, thereby confirming a central role for Rb1 in the antiapoptotic phenotype. Our data identify Rb1 induction in chronic asymptomatic HIV-1 infection as a mediator of apoptosis resistance in monocytes in association with protective autophagy and contributing to monocyte survival during immune activation and/or HIV-1 viremia.
Zheng, Xiangbin; Lin, Min; Xie, Dong-De; Li, Jian; Chen, Jiang-Tao; Eyi, Urbano Monsuy; Monte-Nguba, Santiago-M; Ehapo, Juan Carlos Sala; Yang, Hui; Yang, Hui-Tian; Yang, Li-Ye
Malaria and HIV are two of the most severe public health problems in Africa. However, epidemiological data on Bioko Island is scarce. To investigate the prevalence of malaria and HIV infections and assess association of malaria and HIV infections and possible confounding factors, we performed a cross-sectional survey of people of malaria-endemic Bioko Island, Equatorial Guinea. A cross-sectional study of 1 526 subjects was carried out to determine the prevalence of malaria and HIV infection in Malabo region hospital on Bioko Island. Questionnaires were administered and venous blood samples were drawn for malaria parasites and HIV detection. The prevalence of participants infected with malaria and HIV in this area were 13.8% and 6.6% respectively. The average prevalence of co-infection for malaria and HIV was 0.92%. HIV-infection was significantly associated with the age and gender. Malaria infections were significantly associated with the age. This study showed that the prevalence of HIV and malaria on Bioko Island was higher than expected, although the co-infection prevalence of malaria and HIV was low. The results also indicated that malaria and HIV infections lead to more public health risk to youngsters and women.
Full Text Available Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS approach using principle component analysis(PCA. In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.
AftabAhmad; SadiaAshraf; Abraisham Fatima; Aamina Shah; Samia Saleem; Sheharbano; AneelaYasmeen
Objective: To know the awareness level of Pakistani population about AIDS. Methods: An online survey was conducted in Pakistan with the help of a questionnaire formulated by experts to record the awareness level of common people about HIV infection. The responses were collected and screened by the team of National Academy of Young Scientists, Pakistan. Results: Among the 580 participants of the survey, majorities were male, in the age group of 20–30 years and were living in urban areas. More than 80% of responders did not ever screen themselves for HIV and close to 40% were not aware that where to go for screening. Although, majority of the respondents knew about the nature of disease, they were not fully aware about different tests, treatment, duration of infection and vaccination. According to participants, television and internet were major source of information about AIDS and this disease can be prevented in Pakistan through public awareness. Conclusions: Since majority of the respondents were not fully aware about the disease and its mode of transmission, there should be print and electronic media campaigns as well as workshops and seminars to educate the common public. In addition, a national level prevalence study will be very helpful to know the exact prevalence of HIV in Pakistan and its major routes of transmission.
Nguyen, Nam T; Keithly, Sarah C
Understanding HIV-related behaviours and the factors that influence these behaviours among people living with HIV (PLHIV) is critical to the design of effective HIV-prevention strategies; however, this subject has yet to receive the attention it deserves in Vietnam. Given that greater proportions of new HIV infections in the country stem from heterosexual transmission, it is essential to examine the sexual behaviours of Vietnamese PLHIV. The purpose of this qualitative study was to explore the sexual behaviour of individuals following HIV diagnosis and to gain insight into how and why HIV diagnosis affects sexual practices and relationships. Seventy PLHIV in Thaibinh province participated in semi-structured, in-depth interviews. Qualitative data were supported by a quantitative questionnaire on demographics and sexual and drug use history. Nearly all of the participants reported adopting safer sexual practices following HIV diagnosis by using condoms consistently and reducing the number of sex partners. This was true for injecting drug users, female sex workers, unmarried individuals and participants in both HIV serodiscordant and seroconcordant marriages. Motivations for adopting these preventive measures included avoiding HIV transmission, reinfection or cross-resistance as well as preservation of one's own health. Due to stigma, depression, fear of transmission, health status and/or drug addiction, HIV diagnosis dramatically impacted the sexual health of most participants by reducing sexual desire, pleasure and frequency. Implications for HIV prevention and care programmes and policies in Vietnam are discussed.
Geoffrey S Gottlieb
Full Text Available BACKGROUND: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. METHODS: We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. RESULTS: No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155. Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. CONCLUSION: Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.
Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C
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.
Frischknecht, Friedrich; Fackler, Oliver T
Coinfections with Human Immunodeficiency Virus (HIV) and Plasmodium, the causative agents of AIDS and malaria, respectively, are frequent and their comorbidity especially in sub-Saharan Africa is high. While clinical studies suggest an influence of the two pathogens on the outcome of the respective infections, experimental studies on the molecular and immunological impact of coinfections are rare. This reflects the limited availability of suitable model systems that reproduce key properties of both pathologies. Here, we discuss key aspects of coinfection with a focus on currently established experimental systems, their limitations for coinfection studies and potential strategies for their improvement.
Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.
Full Text Available Background: HIV virus infection was detected first time in India in Tamil Nadu in April 1986; India has the third largest HIV epidemic in the world. In 2013, HIV prevalence in India was an estimated 0.3 percent. The pregnant women and her unborn child who are HIV reactive are mostly innocent bearers of the brunt of the infection. Mother-to-child transmission of HIV is a major route of new infections in children. Without any intervention, the risk of transmission of HIV from infected pregnant women to her child is estimated to be around 20- 45%.Early diagnosis of children born to HIV positive mother using HIV DNA PCR and treating children who are diagnosed HIV-positive with antiretroviral drugs within their first 12 weeks of life reduces mortality by 75%. Methods: This retrospective data analytic study of HIV positive pregnant women who attended antenatal clinic and delivered at M.Y. Hospital, Indore from January 2011 to December 2013 .For screening of ANC patients ELISA method was used. For the children, HIV DNA was done by sending the dried blood smear on blot paper and was sent to the reference laboratory Kasturba Hospital, Mumbai and used for diagnosis at 6 week and 6 month. Results: Only 50% of HIV positive children were started on ART, 20% died, 20% loss to follow up and 10% were not willing for follow up. Also 30% mothers practiced mixed feeding. Neonatal mortality rate was 54.87 per thousand live births which is more than the seronegative mothers. Conclusions: First HIV DNA testing can be done at 72 hours to detect antenatal HIV transmission. Early testing can pick up these cases early and ensure treatment. Mixed feeding should be strongly discouraged by counseling and modern methods of communication.
Hirshfield, Sabina; Grov, Christian; Parsons, Jeffrey T; Anderson, Ian; Chiasson, Mary Ann
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 anal sex (CAS) (AOR 2.70, p gay men. Efficacy trials of technology-based HIV prevention interventions targeting high-risk minority HIV-positive MSM are warranted.
Zhang, Jiaoping; Naik, Hsiang Sing; Assefa, Teshale; Sarkar, Soumik; Reddy, R. V. Chowda; Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh K.
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. PMID:28272456
Zhang, Jiaoping; Naik, Hsiang Sing; Assefa, Teshale; Sarkar, Soumik; Reddy, R V Chowda; Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh K
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.
Jia, Zhongwei; Huang, Xiaojie; Wu, Hao; Zhang, Tong; Li, Ning; Ding, Peipei; Sun, Yixuan; Liu, Zhiying; Wei, Feili; Zhang, Hongwei; Jiao, Yanmei; Ji, Yunxia; Zhang, Yonghong; Guo, Caiping; Li, Wei; Mou, Danlei; Xia, Wei; Li, Zhen; Chen, Dexi; Yan, Huiping; Chen, Xinyue; Zhao, Jinkou; Meyers, Kathrine; Cohen, Ted; Mayer, Kenneth; Salomon, Joshua A.; Lu, Zuhong; Dye, Christopher
We conducted a prospective cohort study among HIV-negative MSM aged 18 years or older between 2007 and 2012 in Beijing, China to measure the rates of incident HIV and identify risk factors for infection. Among 5,800 participants evaluated at enrollment, we identified 486 prevalent cases of HIV (8.4%). Among the 3,625 enrollees who were HIV-negative at enrollment and completed at least one follow-up interview, we identified 440 incident cases of HIV in the follow up period: this constituted an HIV incidence rate of 7.1 per 100 person-years (95% CI: 6.4-7.7). Early treatment of syphilis may have significantly reduced risk of HIV infection (RR: 1.45, 95% CI: 1.11-1.93), while MSM presenting perfect compliance in the cohort did not show reduction in HIV infection. Our study suggested that HIV incidence has been remained high in this sample of Chinese MSM during the intensive preventive intervention, suggesting that we need to find new strategies to prevent HIV infection in this population.
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.
Full Text Available Abstract Background A large proportion of the 2.5 million new adult HIV infections that occurred worldwide in 2007 were in stable couples. Feasible and acceptable strategies to improve HIV prevention in a conjugal context are scarce. In the preparatory phase of the ANRS 12127 Prenahtest multi-site HIV prevention trial, we assessed the acceptability of couple-oriented post-test HIV counseling (COC and men's involvement within prenatal care services, among pregnant women, male partners and health care workers in Cameroon, Dominican Republic, Georgia and India. Methods Quantitative and qualitative research methods were used: direct observations of health services; in-depth interviews with women, men and health care workers; monitoring of the COC intervention and exit interviews with COC participants. Results In-depth interviews conducted with 92 key informants across the four sites indicated that men rarely participated in antenatal care (ANC services, mainly because these are traditionally and programmatically a woman's domain. However men's involvement was reported to be acceptable and needed in order to improve ANC and HIV prevention services. COC was considered by the respondents to be a feasible and acceptable strategy to actively encourage men to participate in prenatal HIV counseling and testing and overall in reproductive health services. Conclusions One of the keys to men's involvement within prenatal HIV counseling and testing is the better understanding of couple relationships, attitudes and communication patterns between men and women, in terms of HIV and sexual and reproductive health; this conjugal context should be taken into account in the provision of quality prenatal HIV counseling, which aims at integrated PMTCT and primary prevention of HIV.
Satchell, Claudette S
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.
Memory CD8(+) T cells elicited by HIV-1 lipopeptide vaccines display similar phenotypic profiles but differences in term of magnitude and multifunctionality compared with FLU- or EBV-specific memory T cells in humans.
Figueiredo, Suzanne; Charmeteau, Benedicte; Surenaud, Mathieu; Salmon, Dominique; Launay, Odile; Guillet, Jean-Gérard; Hosmalin, Anne; Gahery, Hanne
Differentiation marker, multifunctionality and magnitude analyses of specific-CD8(+) memory T cells are crucial to improve development of HIV vaccines designed to generate cell-mediated immunity. Therefore, we fully characterized the HIV-specific CD8(+) T cell responses induced in volunteers vaccinated with HIV lipopeptide vaccines for phenotypic markers, tetramer staining, cytokine secretion, and cytotoxic activities. The frequency of ex vivo CD8(+) T cells elicited by lipopeptide vaccines is very rare and central-memory phenotype and functions of these cells were been shown to be important in AIDS immunity. So, we expanded them using specific peptides to compare the memory T cell responses induced in volunteers by HIV vaccines with responses to influenza (FLU) or Epstein Barr virus (EBV). By analyzing the differentiation state of IFN-γ-secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile (>85%) belonging to a subset of intermediate-differentiated effector T cells for HIV, FLU, and EBV. We then assessed the quality of the response by measuring various T cell functions. The percentage of single IFN-γ T cell producers in response to HIV was 62% of the total of secreting T cells compared with 35% for FLU and EBV, dual and triple (IFN-γ/IL-2/CD107a) T cell producers could also be detected but at lower levels (8% compared with 37%). Finally, HIV-specific T cells secreted IFN-γ and TNF-α, but not the dual combination like FLU- and EBV-specific T cells. Thus, we found that the functional profile and magnitude of expanded HIV-specific CD8(+) T precursors were more limited than those of to FLU- and EBV-specific CD8(+) T cells. These data show that CD8(+) T cells induced by these HIV vaccines have a similar differentiation profile to FLU and EBV CD8(+) T cells, but that the vaccine potency to induce multifunctional T cells needs to be increased in order to improve vaccination strategies.
Jairam R Lingappa
Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519.
Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associat
Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associat
Subhash Chandra Parija
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
Hernando, Victoria; Alejos, Belen; Montero, Marta; Pérez-Elias, MJesús; Blanco, José Ramón; Giner, Livia; Gómez-Sirvent, Juan Luis; Iribarren, Jose Antonio; Bernal, Enrique; Bolumar, Francisco
The aim of this study is to examine the reproductive history of human immunodeficiency virus (HIV)-positive women, before and after HIV diagnosis, to describe the characteristics of women with pregnancies after HIV diagnosis, and to assess the prevalence of mother-to-child transmission.A cross-sectional study was performed among women within reproductive ages (18-49) selected from the cohort in the Spanish AIDS Research Network (CoRIS). A descriptive analysis of the pregnancy outcomes was made according to women's serostatus at the moment of pregnancy and association of women's characteristics with having pregnancy after HIV diagnosis was evaluated using logistic regression models.Overall, 161 women were interviewed; of them, 86% had been pregnant at least once and 39% after HIV diagnosis. There were 347 pregnancies, 29% of them occurred after HIV diagnosis and in these, 20% were miscarriages and 29% were voluntary termination of pregnancy. There were 3 cases of mother-to-child transmission among the 56 children born from HIV-positive mothers; in these cases, women were diagnosed during delivery. Having a pregnancy after HIV diagnosis was more likely when the younger women were at the time of diagnosis: odds ratio (OR) = 1.29 (95% confidence interval 0.40-4.17) for 25 to 29 years old, OR = 0.59 (0.15-2.29) for 30 to 34 years old, OR = 0.14 (0.03-0.74) for ≥35 years old, compared with those diagnosis, who were diagnosed for ≥5 years (OR = 5.27 [1.71-16.18]), who received antiretroviral treatment at some point (OR = 9.38 [1.09-80.45]), and who received information on reproductive health (OR = 4.32 [1.52-12.26]).An important number of pregnancies occurred after HIV diagnosis, reflecting a desire for motherhood in these women. Reproductive and sexual health should be tackled in medical follow-ups.
Lindbom, Sigrid J A; Larsson, Markus; Agardh, Anette
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.
Naicker, Saraladevi; Rahmanian, Sadaf; Kopp, Jeffrey B
Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV
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.
Atkinson, J Hampton; Higgins, Jenny A; Vigil, Ofilio; Dubrow, Robert; Remien, Robert H; Steward, Wayne T; Casey, Corinna Young; Sikkema, Kathleen J; Correale, Jackie; Ake, Chris; McCutchan, J Allen; Kerndt, Peter R; Morin, Stephen F; Grant, Igor
Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six US cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected.
Yeganeh, Nava; Watts, Heather D; Camarca, Margaret; Soares, Gabriel; Joao, Esau; Pilotto, Jose Henrique; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa; Ceriotto, Mariana; Machado, Daisy Maria; Grinzstejn, Beatriz; Grinsztejn, Beatriz; Veloso, Valdilea G; Morgado, Mariza G; Bryson, Yvonne; Mofenson, Lynne M; Nielsen-Saines, Karin
Untreated syphilis during pregnancy is associated with spontaneous abortion, stillbirth, prematurity and infant mortality. Syphilis may facilitate HIV transmission, which is especially concerning in low- and middle-income countries where both diseases are common. We performed an analysis of data available from NICHD/HPTN 040 (P1043), a study focused on the prevention of intrapartum HIV transmission to 1684 infants born to 1664 untreated HIV-infected women. This analysis evaluates risk factors and outcomes associated with a syphilis diagnosis in this cohort of HIV-infected women and their infants. Approximately, 10% of women (n=171) enrolled had serological evidence of syphilis without adequate treatment documented and 1.4% infants (n=24) were dually HIV and syphilis infected. Multivariate logistic analysis showed that compared with HIV-infected women, co-infected women were significantly more likely to self-identify as non-white (adjusted odds ratio [AOR] 2.5, 95% CI: 1.5-4.2), to consume alcohol during pregnancy (AOR 1.5, 95% CI: 1.1-2.1) and to transmit HIV to their infants (AOR 2.1, 95% CI: 1.3-3.4), with 88% of HIV infections being acquired in utero. As compared with HIV-infected or HIV-exposed infants, co-infected infants were significantly more likely to be born to mothers with venereal disease research laboratory titers≥1:16 (AOR 3, 95% CI: 1.1-8.2) and higher viral loads (AOR 1.5, 95% CI: 1.1-1.9). Of 6 newborns with symptomatic syphilis, 2 expired shortly after birth, and 2 were HIV-infected. Syphilis continues to be a common co-infection in HIV-infected women and can facilitate in utero transmission of HIV to infants. Most infants are asymptomatic at birth, but those with symptoms have high mortality rates.
Yeganeh, Nava; Watts, Heather D.; Camarca, Margaret; Soares, Gabriel; Joao, Esau; Pilotto, Jose Henrique; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa; Ceriotto, Mariana; Machado, Daisy Maria; Veloso, Valdilea G.; Grinzstejn, Beatriz; Morgado, Mariza G; Bryson, Yvonne; Mofenson, Lynne M.; Nielsen-Saines, Karin
Background Untreated syphilis during pregnancy is associated with spontaneous abortion, stillbirth, prematurity and infant mortality. Syphilis may facilitate HIV transmission, which is especially concerning in low and middle income countries where both diseases are common. Methods We performed an analysis of data available from NICHD/HPTN 040 (P1043), a study focused on the prevention of intrapartum HIV transmission to 1684 infants born to 1664 untreated HIV-infected women. The present analysis evaluates risk factors and outcomes associated with a syphilis diagnosis in this cohort of HIV-infected women and their infants. Results Approximately 10% (n=171) of women enrolled had serological evidence of syphilis without adequate treatment documented and 1.4% (n=24) infants were dually HIV and syphilis infected. Multivariate logistic analysis showed that compared to HIV-infected women, co-infected women were significantly more likely to self-identify as non-white (AOR 2.5, 95% CI 1.5-4.2), to consume alcohol during pregnancy (AOR 1.5, 95% CI 1.1-2.1) and to transmit HIV to their infants (AOR 2.1, 95% CI 1.3-3.4), with 88% of HIV infections being acquired in-utero. As compared to HIV infected or HIV exposed infants, co-infected infants were significantly more likely to be born to mothers with VDRL titers ≥1:16 (AOR 3, 95% CI 1.1-8.2) and higher viral loads (AOR 1.5 95% CI 1.1-1.9). Of 6 newborns with symptomatic syphilis, 2 expired shortly after birth, and 2 were HIV-infected. Conclusion Syphilis continues to be a common co-infection in HIV-infected women and can facilitate in utero transmission of HIV to infants. Most infants are asymptomatic at birth, but those with symptoms have high mortality rates. PMID:25742089
Marron, Megan M; Singh, Jatinder; Boudreau, Robert M; Christensen, Kaare; Cosentino, Stephanie; Feitosa, Mary F; Minster, Ryan L; Perls, Thomas; Schupf, Nicole; Sebastiani, Paola; Ukraintseva, Svetlana; Wojczynski, Mary K; Newman, Anne B
Hypertension tends to run in families and has both genetic and environmental determinants. We assessed the hypothesis that a novel healthy blood pressure (BP) phenotype is also familial and sought to identify its associated factors. We developed a healthy BP phenotype in the Long Life Family Study, a cohort of two-generation families selected for longevity. Participants from the offspring generation (n = 2211, ages 32-88) were classified as having healthy BP if their age-adjusted and sex-adjusted SBP z-score was between -1.5 and -0.5. Offspring on antihypertensive medications were classified as not having healthy BP. Families with at least two offspring (n = 419 families) were defined as meeting the healthy BP phenotype if at least two and at least 50% of their offspring had healthy BP. Among 2211 offspring, 476 (21.5%) met the healthy BP phenotype. When examining the 419 families, only 44 (10.5%) families met the criteria for the healthy BP phenotype. Both offspring and probands from families with healthy BP performed better on neuropsychological tests that place demands on complex attention and executive function when compared with offspring and probands from remaining families. Among families with the healthy BP phenotype compared with families without, a higher proportion of offspring met the American Heart Association definition of ideal cardiovascular health (10.8 versus 3.8%, respectively; driven by BP, smoking status, and BMI components). In this cohort of familial longevity, few families had a novel healthy BP phenotype in multiple members. Families with this healthy BP phenotype may represent a specific pathway to familial longevity.
Sophie van der Sluis
Full Text Available To date, the genome-wide association study (GWAS is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in loss of statistical power to detect causal variants. Multivariate genotype-phenotype methods do exist but attain maximal power only in special circumstances. Here, we present a new multivariate method that we refer to as TATES (Trait-based Association Test that uses Extended Simes procedure, inspired by the GATES procedure proposed by Li et al (2011. For each component of a multivariate trait, TATES combines p-values obtained in standard univariate GWAS to acquire one trait-based p-value, while correcting for correlations between components. Extensive simulations, probing a wide variety of genotype-phenotype models, show that TATES's false positive rate is correct, and that TATES's statistical power to detect causal variants explaining 0.5% of the variance can be 2.5-9 times higher than the power of univariate tests based on composite scores and 1.5-2 times higher than the power of the standard MANOVA. Unlike other multivariate methods, TATES detects both genetic variants that are common to multiple phenotypes and genetic variants that are specific to a single phenotype, i.e. TATES provides a more complete view of the genetic architecture of complex traits. As the actual causal genotype-phenotype model is usually unknown and probably phenotypically and genetically complex, TATES, available as an open source program, constitutes a powerful new multivariate strategy that allows researchers to identify novel causal variants, while the complexity of traits is no longer a limiting factor.
Okoror, Titilayo Ainegbesua; Falade, Catherine Olufunke; Walker, Ebunlomo Mary; Olorunlana, Adetayo; Anaele, Agaptus
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
Eliud Wekesa; Ernestina Coast
Objectives: To characterise the experiences of heterosexual men and women living with HIV post-diagnosis and explain these experiences in relation to their identity and sexuality. Design: Qualitative study using in-depth interviews and theoretically informed biographic disruption theory. Setting: Interviews were conducted in two Nairobi slums (Kenya). Participants: 41 HIV-infected heterosexual men and women aged 18 years or older Results: People living with HIV have divergent experiences surr...
Wekesa, Eliud; Coast, Ernestina
Objectives To characterise the experiences of heterosexual men and women living with HIV postdiagnosis and explain these experiences in relation to their identity and sexuality. Design Qualitative study using in-depth interviews and a theoretically informed biographic disruption theory. Setting Interviews were conducted in two Nairobi slums (Kenya). Participants 41 HIV-infected heterosexual men and women aged 18?years or older. Results People living with HIV have divergent experiences surroun...
Greenhalgh, Clare; Evangeli, Michael; Frize, Graham; Foster, Caroline; Fidler, Sarah
An increasing number of children born with perinatally acquired HIV (PAH) are surviving into late adolescence and early adulthood. At this developmental stage, forming and sustaining intimate relationships is important. Young adults with PAH face both normative challenges and additional, HIV-related, relationship stressors. One key issue is the decision about whether and how to share their HIV status with others. Being able to disclose one's HIV status to sexual partners may reduce the risk of onward HIV transmission but is associated with the fear of rejection. There has been little research on how young people with PAH manage such disclosure-related stressors in intimate relationships. This study examined how disclosure challenges are managed by young adults with PAH in the UK within their intimate relationships. Seven participants (five females and two males) currently or previously in an intimate relationship, aged 18-23 years, were recruited from a UK hospital clinic. The majority of participants were of sub-Saharan African origins. They took part in in-depth interviews, with data analysed according to the principles of interpretative phenomenological analysis. Four themes were elicited: (1) decisions about starting, continuing or resuming relationships shaped by disclosure, (2) disclosing early to avoid the pain of future rejection, (3) using condoms to avoid disclosure and (4) testing likely partner reactions to disclosure. The study revealed the significant extent to which HIV disclosure affected the experience of relationships in this population. Interventions to support adolescents and young adults with PAH to disclose to their partners should be developed alongside guidance for professionals. Future research should include older samples of adults with PAH and studies in sub-Saharan African settings.
Full Text Available Background: Onychomycosis is one of the early manifestations of HIV infection with a prevalence of 15-40%. Multiple nail involvement, isolation of both common and rare species, and resistance to treatment are the characteristics of onychomycosis in HIV. Aim: To study the epidemiology, clinical manifestations of onychomycosis in HIV-infected individuals and to identify the various causative fungi microbiologically. Methods: A total of 250 HIV infected patients, diagnosed by ELISA, were screened for nail involvement; of which 60 patients i.e., 40 males and 20 females, who had clinically suspected untreated fungal infection were included in this study. Results: Of the 60 respondents, 34 (56.66% were from the 31-40 years age group. Amongst the 40 males, there were 20 manual laborers and 14 farmers; while 18 of 20 females were housewives. Toenail involvement was seen in 38 patients (63.33%, fingernail in 12 patients (20% while 10 (16.66% patients had involvement of both. Twenty eight (46.66% patients gave history of some trauma, 6 (10% had diabetes mellitus, and only 1 patient (1.66% had history of peripheral vascular disease. Nineteen (31.66% patients had associated tinea pedis, 5 (8.33% had tinea manuum, 10 (16.66% had tinea corporis and 7 (11.66% had tinea cruris. Twenty one (35% respondents had distal and lateral superficial onychomycosis (DLSO, 5 (8.33% had proximal subungual onychomycosis (PSO, 1 (1.66% had superficial white onychomycosis (SWO, while 33 (55% had total dystrophic onychomycosis (TDO. Fungal elements were demonstrated by KOH mount in 49 patients (81.66% and growth was seen in 32 (53.33% cultures. Dermatophytes were isolated in 13 (21.66% and nondermatophytic molds (NDM in 19 (31.66%. Out of the 13 positive dermatophyte cultures, Trichophyton rubrum was isolated on 11 and Trichophyton mentagrophytes on 2 cultures. Of the 19 non-dermatophytic cultures, Aspergillus niger was isolated on 3 and Candida spp. on 12 while Cladosporium spp
Full Text Available Studies from Sub-Saharan Africa have shown that a substantial number of HIV patients eligible for antiretroviral therapy (ART do not start treatment. However, data from other low- or middle-income countries are scarce. In this study, we describe the outcomes of 4105 HIV patients who became ART eligible from January 2007 to November 2011 in an HIV cohort study in India. After three years of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3% were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4 count, longer duration of pre-ART care, belonging to a disadvantaged community, being widowed, and not living near a town were associated with delayed ART initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and age >45 years were associated with mortality. Being homeless, being single, not living near a town, having a CD4 count <150 cells/μL, and shorter duration of pre-ART care were associated with loss to followup. These results highlight the need to improve the timely initiation of ART in HIV programmes in India, especially in ART eligible patients with tuberculosis, low CD4 counts, living in rural areas, or having a low socioeconomic status.
Schramm, Birgit; Penn, Michael L.; Palacios, Emil H.; Grant, Robert M.; Kirchhoff, Frank; Goldsmith, Mark A.
Epidemiological studies have shown that human immunodeficiency virus type 2 (HIV-2) is markedly less pathogenic than HIV-1 in vivo. Individuals infected with HIV-2 exhibit a remarkably slow rate of disease development, and these clinical properties have been attributed presumptively to an “attenuated” phenotype of HIV-2 itself. Here, we investigated the impact of coreceptor usage on the cytopathicity of HIV-2 and compared its pathogenic potential with that of HIV-1 in a unique human lymphoid histoculture model. We found that HIV-2 strains, as well as closely related simian immunodeficiency viruses (SIV), displayed mildly or highly aggressive cytopathic phenotypes depending on their abilities to use the coreceptor CCR5 or CXCR4, respectively. A side-by-side comparison of primary X4 HIV-1 and HIV-2 strains revealed similar, high degrees of cytopathicity induced by both HIV types. Furthermore, we found that HIV-2 coreceptor specificity for CCR5 and CXCR4 determined the target cell population for T-cell depletion in lymphoid tissue. Finally, utilization of the alternate coreceptors BOB and Bonzo did not significantly increase the cytopathic properties of HIV-2. These findings demonstrate that coreceptor preference is a key regulator of target cell specificity and the cytopathic potential of HIV-2, with indistinguishable rules compared with HIV-1. Moreover, HIV-2 strains are not characterized by an intrinsically lower cytopathicity than HIV-1 strains. Therefore, direct cytopathic potential per se does not explain the unique behavior of HIV-2 in people, highlighting that other unknown factors need to be elucidated as the basis for their lesser virulence in vivo. PMID:11000231
Leyva-Moral, Juan Manuel; Feijoo-Cid, Maria
Background When conducting qualitative research, participants usually share lots of personal and private information with the researcher. As researchers, we must preserve participants' identity and confidentiality of the data. Objective To critically analyze an ethical conflict encountered regarding confidentiality when doing qualitative research. Research design Case study. Findings and discussion one of the participants in a study aiming to explain the meaning of living with HIV verbalized his imminent intention to commit suicide because of stigma of other social problems arising from living with HIV. Given the life-threatening situation, the commitment related to not disclosing the participant's identity and/or the content of the interview had to be broken. To avoid or prevent suicide, the therapist in charge of the case was properly informed about the participant's intentions. One important question arises from this case: was it ethically appropriate to break the confidentiality commitment? Conclusion confidentiality could be broken if a life-threatening event is identified during data collection and participants must know that. This has to be clearly stated in the informed consent form.
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
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.
Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie
It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.
Rouhani, Shada A; O'Laughlin, Kelli N; Faustin, Zikama M; Tsai, Alexander C; Kasozi, Julius; Ware, Norma C
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.
Madu, Ikenna G; Li, Shirley; Li, Baozong; Li, Haitang; Chang, Tammy; Li, Yi-Jia; Vega, Ramir; Rossi, John; Yee, Jiing-Kuan; Zaia, John; Chen, Yuan
We have recently identified a chemotype of small ubiquitin-like modifier (SUMO)-specific protease (SENP) inhibitors. Prior to the discovery of their SENP inhibitory activity, these compounds were found to inhibit HIV replication, but with an unknown mechanism. In this study, we investigated the mechanism of how these compounds inhibit HIV-1. We found that they do not affect HIV-1 viral production, but significantly inhibited the infectivity of the virus. Interestingly, virions produced from cells treated with these compounds could gain entry and carry out reverse transcription, but could not efficiently integrate into the host genome. This phenotype is different from the virus produced from cells treated with the class of anti-HIV-1 agents that inhibit HIV protease. Upon removal of the SUMO modification sites in the HIV-1 integrase, the compound no longer alters viral infectivity, indicating that the effect is related to SUMOylation of the HIV integrase. This study identifies a novel mechanism for inhibiting HIV-1 integration and a new class of small molecules that inhibits HIV-1 via such mechanism that may contribute a new strategy for cure of HIV-1 by inhibiting the production of infectious virions upon activation from latency.
Full Text Available Abstract Background Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. Methods Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital. Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. Results Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location. Conclusion These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may
Full Text Available Abstract Background The aberrant cell-cycle progression of HIV-1-infected kidney cells plays a major role in the pathogenesis of HIV-associated nephropathy, however the mechanisms whereby HIV-1 induces infected glomerular podocytes or infected tubular epithelium to exit quiescence are largely unknown. Here, we ask whether the expression of HIV-1 genes in infected podocytes induces cyclin D1 and phospho-pRb (Ser780 expression, hallmarks of cyclin D1-mediated G1 → S phase progression. Results We assessed cyclin D1 and phospho-pRb (Ser780 expression in two well-characterized models of HIV-associated nephropathy pathogenesis: HIV-1 infection of cultured podocytes and HIV-1 transgenic mice (Tg26. Compared to controls, cultured podocytes expressing HIV-1 genes, and podocytes and tubular epithelium from hyperplastic nephrons in Tg26 kidneys, had increased levels of phospho-pRb (Ser780, a target of active cyclin D1/cyclin-dependent kinase-4/6 known to promote G1 → S phase progression. HIV-1-infected podocytes showed markedly elevated cyclin D1 mRNA and cyclin D1 protein, the latter of which did not down-regulate during cell-cell contact or differentiation, suggesting post-transcriptional stabilization of cyclin D1 protein levels by HIV-1. The selective suppression of HIV-1 transcription by the cyclin-dependent kinase inhibitor, flavopiridol, abrogated cyclin D1 expression, underlying the requirement for HIV-1 encoded products to induce cyclin D1. Indeed, HIV-1 virus deleted of nef failed to induce cyclin D1 mRNA to the level of other single gene mutant viruses. Conclusions HIV-1 expression induces cyclin D1 and phospho-pRb (Ser780 expression in infected podocytes, suggesting that HIV-1 activates cyclin D1-dependent cell-cycle mechanisms to promote proliferation of infected renal epithelium.
Carmen H Logie
Full Text Available 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
Barbiano di Belgiojoso, G; Trezzi, M; Scorza, D; Barone, M T; Landriani, N; Genderini, A; Bertoli, S
The prevalence of HIV infection in dialysis populations varies according to different countries and geographic areas. We performed a nationwide epidemiological study by means of a questionnaire in the period from January 1990 to December 1995. Questions were about whether and which HIV tests were performed and which preventive measures were adopted. A separate survey evaluated the data the HIV-positive patients. Only 62% of the centers responded to the questionnaire, corresponding to 21,500 dialysis patients in 1990 and 27,000 in 1995. The prevalence of HIV-positive subjects was 0,13% for 1995. A total of 48 patients with HIV infection were identified: risk factors were drug abuse in 16 cases, homosexuality in 9, heterosexual contact in 8, transfusion in 7, renal transplant in 3 and unknown cause in 5. Forty-five patients were on hemodialysis, and 3 were receiving peritoneal dialysis. At follow-up, 19 patients died: infection and malnutrition were the most frequent causes of death. The death rate of patients who were already HIV positive when dialysis was started (group 1, 29 cases) was 19.36 deaths/1,000 patient/month. The correlations, performed only for group 1, showed a significantly worse prognosis for patients with CD4 HIV infection in the dialysis population is low, and the outcome of HIV-positive patients in dialysis was found to be better than earlier literature reports. The use of chronic dialysis for HIV patients with uremia should not be discouraged.
Conclusions: On most behavioral measures, MPS IIIB patients did not differ substantially from MPS IIIA patients over age six, demonstrating autistic features and a Klüver Bucy-like syndrome including lack of fear and poor attention. Delay in onset of behavioral symptoms was associated with later diagnosis in two patients. Lack of fear, poor attention, and autistic-like symptomatology are as characteristic of MPS IIIB as they are of MPS IIIA. A possible difference is that the some behavioral abnormalities develop more quickly in MPS IIIB. If this is so, these patients may become at risk for harm and present a challenge for parenting even earlier than do those with MPS IIIA. In future clinical trials of new treatments, especially with respect to quality of life and patient management, improvement of these behaviors will be an essential goal. Because very young patients were not studied, prospective natural history documentation of the early development of abnormal behaviors in MPS IIIB is needed.
Gwadz, Marya; Cleland, Charles M; Hagan, Holly; Jenness, Samuel; Kutnick, Alexandra; Leonard, Noelle R; Applegate, Elizabeth; Ritchie, Amanda S; Banfield, Angela; Belkin, Mindy; Cross, Bridget; Del Olmo, Montserrat; Ha, Katharine; Martinez, Belkis Y; McCright-Gill, Talaya; Swain, Quentin L; Perlman, David C; Kurth, Ann E
Over 50,000 individuals become infected with HIV annually in the U.S., and over a quarter of HIV infected individuals are heterosexuals. Undiagnosed HIV infection, as well as a lack of retention in care among those diagnosed, are both primary factors contributing to ongoing HIV incidence. Further, there are racial/ethnic disparities in undiagnosed HIV and engagement in care, with African Americans/Blacks and Latinos remaining undiagnosed longer and less engaged in care than Whites, signaling the need for culturally targeted intervention approaches to seek and test those with undiagnosed HIV infection, and link them to care with high retention. The study has two components: one to seek out and test heterosexuals at high risk for HIV infection, and another to link those found infected to HIV care with high retention. We will recruit sexually active African American/Black and Latino adults who have opposite sex partners, negative or unknown HIV status, and reside in locations with high poverty and HIV prevalence. The "Seek and Test" component will compare the efficacy and cost effectiveness of two strategies to uncover undiagnosed HIV infection: venue-based sampling and respondent-driven sampling (RDS). Among those recruited by RDS and found to have HIV infection, a "Treat and Retain" component will assess the efficacy of a peer-driven intervention compared to a control arm with respect to time to an HIV care appointment and health indicators using a cluster randomized controlled trial design to minimize contamination. RDS initial seeds will be randomly assigned to the intervention or control arm at a 1:1 ratio and all recruits will be assigned to the same arm as the recruiter. Participants will be followed for 12 months with outcomes assessed using medical records and biomarkers, such as HIV viral load. Heterosexuals do not test for HIV as frequently as and are diagnosed later than other risk groups. The study has the potential to contribute an efficient, innovative
Full Text Available OBJECTIVES: To get an insight into: 1. Perceived health needs and demands of positive mothers. 2. Constraints and barriers in accessing health services. 3. Impact of positive status on social and economic entitlements.4. Role of positive network in educating and empowering mothers. METHODOLOGY: Type of study; Qualitative research using focus group discussions (FGD. Study Setting; “AnandaJoythi Network of People Living with HIV/AIDS®”- A positive network at Mysore. Period of study; September- October, 2008. Study participants: positive mothers from in and around Mysore city attending AnandaJoythi Network of People Living with HIV/AIDS. Inclusion Criteria; Mother of at least one child irrespective of: Her age. Duration of the positive status/ stage of disease. Age of the child-live/dead. On ART or not. And were willing to participate in the study. EXCLUSION CRITERIA: Those not willing to participate in the study. RESULTS: Health Needs and Demands: The positive women felt the need for regular screening tests for side effects of ART free of cost, nutrition supplementation programmes, more health centres and health education. Barriers to treatment: Poverty is the main barrier to accessing treatment. This is the amount of money required by clients for the government health services before being put on the ART programme and individuals have to pay for a CD4 count, a full hemogram and a liver function test. Poverty also means that people experience difficulty in paying for transport to get to services, especially when travelling from rural areas where distances to the nearest clinic or hospital are further and infrastructure poorer. Social and economic impact of positive status: It becomes difficult to look after their children when they are thrown out of their house. Even though they are mentally harassed by their family members they find it difficult to come out of their house because of their children are too young and need a family support
Rooij, I.A.L.M. van; Zanden, L.F.M. van der; Brouwers, M.M.; Knoers, N.V.A.M.; Feitz, W.F.J.; Roeleveld, N.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The various phenotypes of hypospadias may result from disturbances of dissimilar embryonic processes in different time windows, suggesting aetiological heterogeneity; however, only a few studies have investigated the risk factors for the dif
Demant, Dyveke T; Lund, Karen; Vollert, Jan; Maier, Christoph; Segerdahl, Märtha; Finnerup, Nanna B; Jensen, Troels S; Sindrup, Søren H
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. 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 by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 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 and phenotype of 0.7 (95% CI 0.01-1.4, P=0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-∞) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Peonim, Vichan; Sujirachato, Kanchana; Srisont, Smith; Udnoon, Jitta
To retrospectively study the pathology of HIV seropositive in forensic autopsies. Three hundred thirty five HIV seropositive cases, selected from 7,387 forensic postmortem inquests by law, were studied in Ramathibodi hospital between 2000 and 2010. The study topics were sex, age, cause of death, manner of death, and pathological features. Autopsies were done in 67 cases. The pathological features were classified into five groups, (a) HIV disease with infectious and parasitic diseases, (b) HIV disease with malignant neoplasms, (c) HIV disease with other specified diseases, (d) HIV disease with other conditions, and (e) HIV disease with unspecified pathology. The average prevalence of HIV seropositive cases was 4.5%. The peak was 10.0% in 2001 and gradually decreased until 1.8% in 2010. The ratio of male:female was 4:1. The most manner of death was natural death (83.6%). In unnatural death cases, the most frequently method was suicide by hanging. The prevalence of HIV group (a) to group (e) were 56.7%, 6.0%, 3.0%, 17.9%, and 16.4%, respectively. Pulmonary tuberculosis is the most common found in group (a) with frequency of 28.4%. Kaposi's sarcoma of skin, coronary atherosclerosis, and fatty change of liver were frequently observed in HIV group (b) to group (d), respectively. The pathology showed multiple pathological features in each group, i.e., group (a) pulmonary tuberculosis, pneumonia, disseminated fungal infection, brain abscess, and meningitis, group (b) Kaposi's sarcoma of skin and acute lymphoblastic leukemia, group (c) coronary atherosclerosis, chronic pyelonephritis, gastritis, and cirrhosis of the liver, and group (d) cardiomegaly, fatty change of liver; pulmonary edema, and splenomegaly. HIV disease causes pathology of various organs. The severities vary from severe to asymptomatic disease. Five pathological patterns of HIV were established in this study that showed interesting topics, i.e., pulmonary tuberculosis was the most frequent and occurred (28
Beck Eduard J
Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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.
Beck, Eduard J; Mandalia, Sundhiya; Harling, Guy; Santas, Xenophon M; Mosure, Debra; Delay, Paul R
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.
Ethier, Kathleen A.; Ickovics, Jeannette R.; Fernandez, M. Isabel; Wilson, Tracey E.; Royce, Rachel A.; Koenig, Linda J.
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
Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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
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.
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
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.
Miro, J.M.; Montejo, M.; Castells, L.; Rafecas, A.; Moreno, S.; Aguero, F.; Abradelo, M.; Miralles, P.; Torre-Cisneros, J.; Pedreira, J.D.; Cordero, E.; Rosa, G. De; Moyano, B.; Moreno, A.; Perez, I.; Rimola, A.; Barrera, P.
Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to
W.A.J. Norder (Wilma); R.P.H. Peters (Remco); M. Kok (Maarten); S.L. van Elsland (Sabine); H.E. Struthers (Helen); M.A. Tutu (Mpho); A.M. van Furth (Marceline)
markdownabstractReligion has substantial – positive and negative – influence on South Africa’s HIV context. This qualitative study explored possibilities for positive church engagement in paediatric HIV care in a rural district in Limpopo Province, South Africa. Opinions, attitudes and experiences
Sefhedi, Sheila; Montsi, Mercy; Mpofu, Elias
This exploratory study describes the provision of HIV & AIDS counselling services in Botswana junior secondary schools as perceived by teachers. A total of 45 teachers (age range = 20-55; teaching experience range = 0-21 years) from three schools participated. The participants completed a questionnaire on the types of HIV & AIDS-related…
Ganiem, A.R.; Parwati, I.; Wisaksana, R.; Zanden, A. van der; Beek, D. van de; Sturm, P.D.J.; Ven, A.J.A.M. van der; Alisjahbana, B.; Brouwer, A.E.; Kurniani, N.; Gans, J. de; Crevel, R. van
OBJECTIVE: Indonesia has a concentrated but rapidly growing HIV epidemic. We examined the effect of HIV on causative organisms, clinical features and prognosis of adult meningitis. DESIGN: A prospective cohort study. METHODS: All adult patients at a referral hospital who underwent cerebrospinal flui
Cunningham, A L; Dwyer, D E; Dowton, D N
Viral and immune markers are used for monitoring either progression of human immunodeficiency virus (HIV) disease or response to antiviral therapy. Ideal properties of viral markers are that they are present in all HIV-infected persons at all stages of disease, that they are related to disease pathogenesis, that they can be easily quantitated, that this quantitation correlates rapidly and predictably with both disease stage and response to antivirals, and that they can be developed into rapid, reproducible automated tests. Currently available viral markers include HIV p24 antigenemia (after acid glycine dissociation), anti-p24 antibody titres, quantitative DNA and RNA polymerase chain reaction performed on cells and plasma, and HIV isolate phenotype. In Australia, these markers have been studied in acute HIV seroconversion, in neonatal infection, in body fluids other than blood, and in monitoring of response to antiviral drug therapy.
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
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
Reeder, J M; Hamblet, J L; Killen, A R; King, C A; Uruburu, A
The AIDS epidemic is now in its second decade and shows no sign of relenting. Unfortunately, however, the AORN study shows that perioperative nurses' knowledge regarding HIV and AIDS is not adequate to enable them to provide patient care while maintaining safe practices. Focused educational programs should be made available to perioperative nurses to help them apply universal precautions and OSHA standards to everyday practice. Perioperative nurses must become knowledgeable about the disease and sensitive to the needs of patients who have this illness. All nurses have a special obligation to care for all patients; education and management strategies that enable exploration of values, fears, and prejudices will help nurses understand their own beliefs and those of other individuals. Recommendations from this study may be viewed as a starting point for this perioperative education.
Lingen-Stallard, Andrew; Furber, Christine; Lavender, Tina
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
Arab, Kholoud; Spence, Andrea R; Czuzoj-Shulman, Nicholas; Abenhaim, Haim A
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 < 0.001). Upon adjustment for baseline characteristics, 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.
Aheto, Denis Worlanyo; Gbesemete, Kwame Prosper
The paper compares rural perspectives in Thailand and Ghana on the level of condom acceptance in sexual relations, willingness to test oneself for HIV before and in marriage and sources of information on HIV/AIDS. We also compared the policy approaches to combating HIV/AIDS in both countries. The results indicates that in the villages studied in Thailand, all single men and the majority of the single women were in favour of using condoms in sexual relations. This group also showed a positive attitude to HIV/AIDS test before and in marriage. However, married men in rural Thailand disapproved of the use of condoms with their wives but married women in the sample population were open to the possibility of using condoms. Both married men and women were strongly against HIV/AIDS test in marriage. In contrast to Thailand, most single men in the communities studied in Ghana showed a disapproval to the use of condoms in sexual relations. However, they condoned HIV test before marriage. Married men and women in rural Ghana were against the use of condoms in sexual relations as well as HIV/AIDS test in marriage. In order to mitigate mother-to-child transmission, the Thais applied anti-retroviral drug care for HIV positive pregnant women during pregnancy and after delivery. In Ghana on the other hand, pregnant women were subject to HIV test and counselling. The mode of information acquisition on HIV/AIDS in both countries were through the media, campaigns and village volunteers. Finally, we observed that fighting poverty is a sine qua non for the success of any HIV/AIDS eradication programme.
Pais, Viorel; Danaila, Leon; Pais, Emil
Light microscopy and transmission electron microscopy were used to investigate surgical cases in a variety of pathological conditions (thromboses, tumors, cerebrovascular malformations, Moyamoya disease) to identify and characterize different phenotypes belonging to a new interstitial cell recently described ultrastructurally in the brain and here named "cordocyte." Also, this work is an attempt to identify and characterize precursor/stem cells for cordocytic lineage in the perivascular areas, within perivascular nerves and pia mater (now considered a cordocytic-vascular tissue). Unexpected relationships and functions emerge from observations concerning these phenotypes, almost ubiquitous, but not yet fully studied in the brain.
Bhatia, Divya S; Harrison, Abigail D; Kubeka, Muriel; Milford, Cecilia; Kaida, Angela; Bajunirwe, Francis; Wilson, Ira B; Psaros, Christina; Safren, Steven A; Bangsberg, David R; Smit, Jennifer A; Matthews, Lynn T
This qualitative study investigated gender power inequalities as they contribute to relationship dynamics and HIV-serostatus disclosure among men and women living with HIV in Durban, South Africa. HIV serodiscordance among men and women within stable partnerships contributes to high HIV incidence in southern Africa, yet disclosure rates remain low. Given the emphasis on prevention for HIV-serodiscordant couples, this research supports the urgent need to explore how best to support couples to recognize that they are part of this priority population and to access appropriate prevention and treatment. Thirty-five in-depth individual interviews were conducted with 15 HIV-positive men and 20 HIV-positive women (not couples) receiving care at public-sector clinics near Durban. A structured coding scheme was developed to investigate men's and women's attitudes toward HIV-serostatus disclosure and behaviors of sharing (or not sharing) HIV serostatus with a partner. Narratives were analyzed for barriers and facilitators of disclosure through the lens of sociocultural gender inequality, focusing on reasons for non-disclosure. Among 35 participants: median age was 33 years (men) and 30 years (women); average years since HIV diagnosis was 1 (men) and 1.5 (women). Four themes related to gender inequality and HIV-serostatus disclosure emerged: (1) Men and women fear disclosing to partners due to concerns about stigma and relationship dissolution, (2) suspicions and mistrust between partners underlies decisions for non-disclosure, (3) unequal, gendered power in relationships causes differential likelihood and safety of disclosure among men and women, and (4) incomplete or implicit disclosure are strategies to navigate disclosure challenges. Findings illustrate HIV-serostatus disclosure as a complex process evolving over time, rather than a one-time event. Partner communication about HIV serostatus is infrequent and complicated, with gender inequalities contributing to fear
Divya S. Bhatia
Full Text Available BackgroundThis qualitative study investigated gender power inequalities as they contribute to relationship dynamics and HIV-serostatus disclosure among men and women living with HIV in Durban, South Africa. HIV serodiscordance among men and women within stable partnerships contributes to high HIV incidence in southern Africa, yet disclosure rates remain low. Given the emphasis on prevention for HIV-serodiscordant couples, this research supports the urgent need to explore how best to support couples to recognize that they are part of this priority population and to access appropriate prevention and treatment.MethodsThirty-five in-depth individual interviews were conducted with 15 HIV-positive men and 20 HIV-positive women (not couples receiving care at public-sector clinics near Durban. A structured coding scheme was developed to investigate men’s and women’s attitudes toward HIV-serostatus disclosure and behaviors of sharing (or not sharing HIV serostatus with a partner. Narratives were analyzed for barriers and facilitators of disclosure through the lens of sociocultural gender inequality, focusing on reasons for non-disclosure.ResultsAmong 35 participants: median age was 33 years (men and 30 years (women; average years since HIV diagnosis was 1 (men and 1.5 (women. Four themes related to gender inequality and HIV-serostatus disclosure emerged: (1 Men and women fear disclosing to partners due to concerns about stigma and relationship dissolution, (2 suspicions and mistrust between partners underlies decisions for non-disclosure, (3 unequal, gendered power in relationships causes differential likelihood and safety of disclosure among men and women, and (4 incomplete or implicit disclosure are strategies to navigate disclosure challenges. Findings illustrate HIV-serostatus disclosure as a complex process evolving over time, rather than a one-time event.ConclusionPartner communication about HIV serostatus is infrequent and complicated
Reddy, Elizabeth A.; Agala, Chris Bernard; Maro, Venance P.; Ostermann, Jan; Pence, Brian W.; Itemba, Dafrosa K.; Safley, Donna; Yao, Jia; Thielman, Nathan M.; Whetten, Kathryn
Background Linkage to HIV care is crucial to the success of antiretroviral therapy (ART) programs worldwide, loss to follow up at all stages of the care continuum is frequent, and long-term prospective studies of care linkage are currently lacking. Methods Consecutive clients who tested HIV-positive were enrolled from four HIV testing centers (1 health facility and 3 community-based centers) in the Kilimanjaro region of Tanzania as part of the larger Coping with HIV/AIDS in Tanzania (CHAT) pr...
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.
Khine Wut Yee Kyaw; Myo Minn Oo; Nang Thu Thu Kyaw; Khaing Hnin Phyo; Thet Ko Aung; Theingi Mya; Nilar Aung; Htun Nyunt Oo; Petros Isaakidis
... among HIV-exposed babies which includes being HIV positive, death and LTFU. Methods A retrospective cohort study reviewing routinely collected data in an Integrated HIV care program, Mandalay, Myanmar in June 2016...
Full Text Available Abstract Background Valproic acid (VPA is often used to control pain in HIV-related neuropathy. However, the effect of VPA on cognitive functions in advanced HIV-infected individuals is largely unknown. A recent study would suggest that it may have a neuroprotective effect, the doses used were low and the observation period short. Methods We used a well studied HIV-infected cohort assessed for a median of 15 (range 6–27 months to determine whether individuals who were receiving VPA showed any cognitive benefits. Multiple regression procedures allowed us to control for the effects of HAART and HIV disease status as well as numbers of visits and variation in VPA intake over-time. Results We found a negative effect of VPA (mean dose of 850 mg/d for 18 months on average; range 6–27 months on cognitive performance in eight advanced HIV-infected individuals compared to 32 advanced HIV-infected individuals on no VPA who had comparable neuropsychological performance at baseline. Control for plasma HIV viral load provided similar results. Conclusion Our results suggest that further studies of VPA in advanced HIV-infection should cautiously include high doses over prolonged periods of at least 18 months in order to more accurately determine whether the posited neuroprotective benefit of VPA still occurs or whether it is replaced by toxicity.
Full Text Available Orientation: To encourage workers to participate in workplace HIV testing, some SouthAfrican automotive companies use lotteries. However, there is a lack of empirical evidence on how lottery incentives may influence employees’ workplace HIV counselling and testing behaviour.Research purpose: Determine whether workers intend to test for HIV only to win a lottery prize.Motivation for the study: The positive and also negative influences of lotteries on workers’ HIV testing behaviour need to be understood to avoid undue coercion in workplace HIV testing participation.Research design, approach and method: Post-test only quasi-experimental studies were conducted the day HIV testing and lotteries were announced to staff in four companies using a cross-sectional, self-administered survey that measured workers’ workplace HIV testing behaviour intentions. Intention to participate in workplace HIV counselling and testing was used as the main outcome of respondents’ behaviour and investigated via the statement: ‘If the company would organise its on-site Wellness Day tomorrow, I would go testing for HIV tomorrow’. In a first setting, two companies’ workers had to test for HIV to be entered in the lottery (n = 198. In the second setting, two other companies’ workers did not have to test to be entered in the lottery (n = 316. Chi-square tests were conducted to measure significant differences between the two conditions distinguishing between permanent and non-permanent staff.Main findings: No significant association was found between behaviour intention in the two settings for permanent workers’ workplace HIV testing intention ( χ2 = 1.145, p = 0.285, phi = -0.097. However, a significant association with a small effect size was found for non-permanent workers ( χ2 = 8.04, p = 0.005, phi = -0.279.Practical/managerial implications: Results show that lotteries to encourage workplace HIV testing are very likely to help workers ‘do the right
Stephanie N Lewis
Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.
Oostenbrug, L.E.; Nolte, I.M.; Oosterom, E.; Steege, G. van der; Meerman, G.J. te; Dullemen, H.M. van; Drenth, J.P.H.; Jong, D.J. de; Linde, K. van der; Jansen, P.L.M.; Kleibeuker, J.H.
BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated
Williams, Frances M K; Carter, Angela M; Kato, Bernet;
associated with fibrin phenotypes. METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis...
Thon, R.; Vondeling, H.; Lassen, J.; Hansen, A.K.; Ritskes-Hoitinga, M.
An interview study was carried out with the aim of clarifying the reasons for the limited use of phenotypic characterization of genetically-modified mice (GMM) and identifying issues hindering its implementation. A total of 15 users of GMM participated in semi-structured face-to-face interviews, whi
Wekesa, Eliud; Coast, Ernestina
To characterise the experiences of heterosexual men and women living with HIV postdiagnosis and explain these experiences in relation to their identity and sexuality. Qualitative study using in-depth interviews and a theoretically informed biographic disruption theory. Interviews were conducted in two Nairobi slums (Kenya). 41 HIV-infected heterosexual men and women aged 18 years or older. People living with HIV have divergent experiences surrounding HIV diagnosis. Postdiagnosis, there are multiple phases of identity transition, including status (non-)disclosure, and attempts at identity repair and normalcy. For some people, this process involves a transition to a new self-identity, incorporating both HIV and antiretroviral treatment (ART) into their lives. For others, it involves a partial transition, with some aspects of their prediagnosis identity persisting, and for others it involves a rejection of HIV identity. Those people who were able to incorporate HIV/AIDS in their identity, without it being disruptive to their biography, were pursuing safer sexual and reproductive lives. By contrast, those people with a more continuous biography continued to reflect their prediagnosis identity and sexual behaviour. People living with HIV/AIDS (PLWHA) had to rework their sense of identity following diagnosis in the context of living in a slum setting. Men and women living with HIV in slums are poorly supported by health systems and services as they attempt to cope with a diagnosis of HIV. Given the availability of ART, health services and professionals need to support the rights of PLWHA to be sexually active if they want to and achieve their fertility goals, while minimising HIV transmission risk.
Ard van Sighem
Full Text Available BACKGROUND: New HIV infections in men who have sex with men (MSM have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART. The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6% of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4% of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective
Sowell, Richard L; Holtz, Carol S; Velasquez, Gabriela
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.
van Dijk, Marieke G; Wilson, Kate S; Silva, Martha; Contreras, Xipatl; Fukuda, H Dawn; García, Sandra G
Increased access to antiretroviral therapy has enabled Mexican HIV-infected women to resume healthy sexual and reproductive lives and reduce the risk of mother-to-child transmission of HIV infection. However, little information is available on the experiences of HIV-infected women desiring children. In this qualitative study, we conducted in-depth interviews with 31 HIV-infected women in four Mexican cities. The findings indicated that most of the women were given limited information on their pregnancy options. With some exceptions, the women felt they were denied the option to have (or to have more) children and advised to undergo tubal ligations or abortions. The findings of this study indicate that ongoing efforts are needed to promote the reproductive rights of HIV-infected women in Mexico and to ensure that they receive options aligned with their fertility desires.
Slogrove, Amy L.; Esser, Monika M.; Cotton, Mark F.; Speert, David P.; Kollmann, Tobias R.; Singer, Joel
Background: Much evidence of HIV-exposed uninfected (HEU) infant infectious morbidity predates availability of maternal combination antiretroviral therapy and does not control for universal risk factors (preterm birth, low birth weight, suboptimal breastfeeding and poverty). Methods: This prospective cohort study identified HIV-infected and HIV-uninfected mothers and their newborns from South African community midwife unit. The primary outcome, infectious cause hospitalization or death before 6 months of age, was compared between HEU and HIV-unexposed (HU) infants and classified for type and severity using validated study-specific case definitions. Adjusted odds ratios (aORs) were calculated by logistic regression including stratified analyses conditioned on breastfeeding. Results: One hundred and seventy-six (94 HEU and 82 HU) mother–infant pairs were analyzed. HIV-infected mothers were older (median, 27.8 vs. 24.7 years; P < 0.01) and HU infants more often breastfed (81/82 vs. 35/94; P < 0.001). Groups were similar for maternal education, antenatal course, household characteristics, birth weight, gestational age and immunizations. The primary outcome occurred in 17 (18%) HEU and 10 (12%) HU infants [aOR, 1.45; 95% confidence interval (CI): 0.44–4.55]. In stratified analysis restricted to breastfed infants, the aOR for hospitalization due to very severe infection or death was 4.2 (95% CI: 1.00–19.2; P = 0.05) for HEU infants. Hospitalization for diarrhea was more common in HEU than HU infants [8/94 (8.5%) vs. 1/82 (1.2%); P = 0.04]. Conclusion: The difference between HEU and HU infants in the probability of infectious cause hospitalization or death in the first 6 months of life was not significant. However, among breastfed infants, severe infectious morbidity occurred more often in HEU than HU infants. PMID:28081048
Young, Jeremy D; Patel, Mahesh; Badowski, Melissa; Mackesy-Amiti, Mary Ellen; Vaughn, Pyrai; Shicker, Louis; Puisis, Michael; Ouellet, Lawrence J
Correctional populations have an elevated human immunodeficiency virus (HIV) prevalence, yet many individuals lack access to subspecialty care. Our study showed that HIV-infected inmates had significantly greater virologic suppression and higher CD4 T-lymphocyte counts when managed by a multidisciplinary team of subspecialists conducting clinics via telemedicine. In other studies, these outcomes have been associated with reductions on HIV-related morbidity and mortality, as well as HIV transmission.
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, studentsÃ¢Â€Â™ 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.
Avila-Rios, Santiago; Ormsby, Christopher E; Carlson, Jonathan M; Valenzuela-Ponce, Humberto; Blanco-Heredia, Juan; Garrido-Rodriguez, Daniela; Garcia-Morales, Claudia; Heckerman, David; Brumme, Zabrina L; Mallal, Simon; John, Mina; Espinosa, Enrique; Reyes-Teran, Gustavo
backgrounds in different HIV-infected populations may influence HIV evolution in a particular direction as particular HLA-HIV codon associations are determined by specific HLA frequency distributions. Our analysis also suggests a dynamic HLA-associated evolution in HIV with fewer HLA-HIV codon associations observed in the proviral compartment, which is likely enriched in early archived HIV sequences, compared to the plasma virus compartment. These results highlight the importance of comparative HIV evolutionary studies in immunologically different populations worldwide. PMID:19664284
Extra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study.
Rezaeian, P.; Miller, PE; Haberlen, SA; Razipour, A; Bahrami, H; Castillo, R.; Witt, MD; Kingsley, L; Palella, FJ; Nakanishi, R; Matsumoto, S.; Alani, A; Jacobson, LP; Post, WS; Budoff, MJ
Previous studies have demonstrated an association between HIV infection and coronary artery disease (CAD); little is known about potential associations between HIV infection and extra-coronary calcification (ECC).We analyzed 621 HIV infected (HIV+) and 384 HIV uninfected (HIV-) men from the Multicenter AIDS Cohort Study who underwent non-contrast computed tomography (CT) from 2010-2013. Agatston scores were calculated for mitral annular calcification (MAC), aortic valve calcification (AVC), a...
Pauline Marie Martin
Full Text Available This paper reports a quantitative genetics and genomic analysis of undesirable coat color patterns in goats. Two undesirable coat colors have routinely been recorded for the past 15 years in French Saanen goats. One fifth of Saanen females have been phenotyped "pink" (8.0% or "pink neck" (11.5% and consequently have not been included in the breeding program as elite animals. Heritability of the binary "pink" and "pink neck" phenotype, estimated from 103,443 females was 0.26 for "pink" and 0.21 for "pink neck". Genome wide association studies (using haplotypes or single SNPs were implemented using a daughter design of 810 Saanen goats sired by 9 Artificial Insemination bucks genotyped with the goatSNP50 chip. A highly significant signal (-log10pvalue = 10.2 was associated with the "pink neck" phenotype on chromosome 11, suggesting the presence of a major gene. Highly significant signals for the "pink" phenotype were found on chromosomes 5 and 13 (-log10p values of 7.2 and, 7.7 respectively. The most significant SNP on chromosome 13 was in the ASIP gene region, well known for its association with coat color phenotypes. Nine significant signals were also found for both traits. The highest signal for each trait was detected by both single SNP and haplotype approaches, whereas the smaller signals were not consistently detected by the two methods. Altogether these results demonstrated a strong genetic control of the "pink" and "pink neck" phenotypes in French Saanen goats suggesting that SNP information could be used to identify and remove undesired colored animals from the breeding program.
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.
Buggert, Marcus; Tauriainen, Johanna; Yamamoto, Takuya
-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...
Bernier, Adeline; Acosta, María Elena; Castro, Daniela Rojas; Bonifaz, Cesar; Jaramillo, Santiago; Henry, Emilie; Otis, Joanne; Préau, Marie
To describe the profile of people living with HIV/AIDS (PLHA) who contact HIV/AIDS associations in Ecuador and to identify the factors related to that contact. In 2011, a cross-sectional community study was conducted in two hospitals in Guayaquil. Based on a 125-question survey administered to 300 adult PLHA, a weighted multivariate regression analysis was performed to identify the factors related to contact with an association Of the 300 participants, 34 (11.3%) were in contact with an association. Being over the age of 35, scoring high on the self-efficacy scale, having suffered serious social consequences after disclosing their HIV status, being able to talk to friends about living with HIV, expressing the need to talk about living with HIV with a health professional, and scoring low on the index of the HIV status disclosure control effort were related to that contact. The characteristics of the PLHA in contact with an association were: being over the age of 35, having suffered serious social consequences following disclosure of seropositivity, and feeling that their psychosocial needs were not being met by the health system in terms of the services provided. These people more easily managed their HIV status in their social milieu and displayed a greater ability to talk to friends about their seropositivity. This information is useful for community actors to maintain and support mobilization on HIV in Ecuador.
Full Text Available BACKGROUND Mucocutaneous manifestations occur in more than 90% of HIV infected patients. These manifestations are an early indicator of the presence of HIV infection and also aids in the clinical staging and prognosis as it reflects the underlying immune status. AIM To determine the prevalence and pattern of various mucocutaneous manifestations occurring in people living with HIV (PLHIV. MATERIALS AND METHODS A retrospective chart review of the data collected from the clinical records of all HIV seropositive patients, who had attended the Sexually Transmitted Infection (STI Clinic of Chengalpattu Medical College Hospital, Chengalpattu, Tamil Nadu, during the 3 years period from 2012 to 2015 was carried out. Demographic and clinical data were analysed. RESULTS The total number of HIV seropositive patients attended the STI Clinic were 176 during the study period of 3 years from 2012 to 2015. Among that males were 104 (59.1% and females were 72 (40.9%. The common age group was 35-49 (87 patients, 49.4%. Mucocutaneous manifestations were seen in 117 (66.4% patients. The most common manifestation seen was candidiasis among infections and seborrheic dermatitis among non-infectious dermatoses. CONCLUSION Mucocutaneous manifestations can arouse suspicion of HIV infection in otherwise healthy patients. They can serve as a dependable clinical marker of HIV infection. Awareness of the varied pattern of these manifestations would help in the early diagnosis and management of HIV infection, thereby decreasing the morbidity and improve the quality of life in them
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.
Ciepluch, Karol, E-mail: firstname.lastname@example.org [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Ionov, Maksim [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland); Majoral, Jean-Pierre [Laboratoire de Chimie de Coordination du CNRS (LCC), 205 Route de Narbonne, F-31077 Toulouse cedex 4 (France); Muñoz-Fernández, Maria Angeles [Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Bryszewska, Maria [Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Street 141/143, 90-236 Lodz (Poland)
In this study, dendrimers emerge as an alternative approach for delivery of HIV peptides to dendritic cells. Gp160, NH-EIDNYTNTIYTLLEE-COOH; P24, NH-DTINEEAAEW-COOH and Nef, NHGMDDPEREVLEWRFDSRLAF-COOH peptides were complexed with two types of positively charged phosphorus-containing dendrimers (CPD). Fluorescence polarization, dynamic light scattering, transmission and electron microscopy (TEM) techniques were chosen to evaluate the dendriplexes stability. We were able to show that complexes were stable in time and temperature. This is crucial for using these peptide/dendrimer nano-complexes in a new vaccine against HIV-1 infection. -- Highlights: • The phosphorus dendrimers as nanocarriers of HIV-peptides are proposed. • The complexes of dendrimers and HIV-peptides were stable in time, temperature. • The results convince that phosphorus dendrimers could be consider as anti-HIV vaccine candidates.
Bonaglia, Maria Clara; Ciccone, Roberto; Gimelli, Giorgio; Gimelli, Stefania; Marelli, Susan; Verheij, Joke; Giorda, Roberto; Grasso, Rita; Borgatti, Renato; Pagone, Filomena; Rodriguez, Laura; Martinez-Frias, Maria-Luisa; van Ravenswaaij, Conny; Zuffardi, Orsetta
Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome
Williams, Frances MK; Carter, Angela M; Kato, Bernet; Falchi, Mario; Bathum, Lise; Surdulescu, Gabriela; Kyvik, Kirsten Ohm; Palotie, Aarno; Spector, Tim D; Grant, Peter J
Objectives 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 associated with fibrin phenotypes. Methods 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK Caucasian female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Results Estimates of heritability for d-dimer and turbidometric variables were in the range 17 - 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD>3 on 5 chromosomes (5, 6, 9, 16 and 17). Conclusions The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischaemic cardiovascular disorders and their therapy. PMID:19150881
Mapingure Munyaradzi P
Full Text Available Abstract Background Substantial heterogeneity in HIV prevalence has been observed within sub-Saharan Africa. It is not clear which factors can explain these differences. Our aim was to identify risk factors that could explain the large differences in HIV-1 prevalence among pregnant women in Harare, Zimbabwe, and Moshi, Tanzania. Methods Cross-sectional data from a two-centre study that enrolled pregnant women in Harare (N = 691 and Moshi (N = 2654 was used. Consenting women were interviewed about their socio-demographic background and sexual behaviour, and tested for presence of sexually transmitted infections and reproductive tract infections. Prevalence distribution of risk factors for HIV acquisition and spread were compared between the two areas. Results The prevalence of HIV-1 among pregnant women was 26% in Zimbabwe and 7% in Tanzania. The HIV prevalence in both countries rises constantly with age up to the 25-30 year age group. After that, it continues to rise among Zimbabwean women, while it drops for Tanzanian women. Risky sexual behaviour was more prominent among Tanzanians than Zimbabweans. Mobility and such infections as HSV-2, trichomoniasis and bacterial vaginosis were more prevalent among Zimbabweans than Tanzanians. Reported male partner circumcision rates between the two countries were widely different, but the effect of male circumcision on HIV prevalence was not apparent within the populations. Conclusions The higher HIV-1 prevalence among pregnant women in Zimbabwe compared with Tanzania cannot be explained by differences in risky sexual behaviour: all risk factors tested for in our study were higher for Tanzania than Zimbabwe. Non-sexual transmission of HIV might have played an important role in variation of HIV prevalence. Male circumcision rates and mobility could contribute to the rate and extent of spread of HIV in the two countries.
Chinouya, Martha; Hildreth, Anthony; Goodall, Deborah; Aspinall, Peter; Hudson, Alistair
This paper is based on data collected in 2009 for the international Stigma Index Study which measured the experiences of stigma among participants living with HIV in the UK. Data were collected using a self-completed survey questionnaire and focus group discussions. Quantitative data were analysed using SPSS, while qualitative data were subjected to thematic analysis. The Stigma Index attempts to establish a baseline for documenting the experience of stigma and discrimination by people living with HIV while also acting as an advocacy tool whose power lay in the involvement of people living with HIV in the design of study instruments and data collection. Participants were recruited through collaborations with a broad range of UK HIV support organisations. The ethics protocols used were those described in the Stigma Index guidebook. A total of 867 people living with HIV took part, of whom 276 described themselves as 'immigrants'. Most of this 'migrant' subsample (70%) was women. Nearly, all (91%) identified as heterosexual, while 9% were attracted to someone of the same sex as them. Socioeconomic deprivation was a key theme and they reported other stigmatised chronic conditions in addition to HIV. It is not possible to ascertain from the questionnaire, the migrants' countries of origin and length of stay in the UK. Control of information about HIV was critically managed, with respect to family and partners. Felt stigma increased anxieties about personal safety, particularly among men. Strategies for safeguarding against the negative impact of stigma included avoiding social gatherings, intimacy, and clinical and HIV social care settings. Most participants were unaware of policies and declarations that protected them as persons living with HIV. Specific recommendations include creating awareness about rights as enshrined in various legal frameworks that protect the right of people living with HIV, which has been reconfigured as a 'disability'. © 2014 John Wiley
Jaiantilal, Prafulta; Gutin, Sarah A; Cummings, Beverley; Mbofana, Francisco; Rose, Carol Dawson
Despite the Mozambique government's efforts to curb human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), national prevalence is 11.5% and support is needed to expand HIV-related services and improve program quality. Positive prevention (PP) programs, which prioritize HIV prevention with people living with HIV and AIDS (PLHIV), have been recognized as an important intervention for preventing new HIV infections. To address this, an evidence-based PP training intervention was implemented with HIV healthcare providers in Mozambique. This study focuses on the acceptability and feasibility of a PP intervention in HIV clinics from the healthcare provider perspective. In-depth interviews were conducted with 31 healthcare providers from three provinces who participated in PP trainings in Mozambique. Interview data were coded using content analysis. Study data suggest that healthcare providers found PP acceptable, feasible to implement in their HIV work in clinic settings, and valued this strategy to improve HIV prevention. The PP training also led providers to feel more comfortable counseling their patients about prevention, with a more holistic approach that included HIV testing, treatment and encouraging PLHIV to live positively. While overall acceptance of the PP training was positive, several barriers to feasibility surfaced in the data. Patient-level barriers included resistance to disclosing HIV status due to fear of stigma and discrimination, difficulty negotiating for condom use, difficulty engaging men in testing and treatment, and the effects of poverty on accessing care. Providers also identified work environment barriers including high patient load, time constraints, and frequent staff turnover. Recognizing PP as an important intervention, healthcare providers should be trained to provide comprehensive prevention, care and treatment for PLHIV. Further work is needed to explore the complex social dynamics and cultural challenges such as
Demirkaya, Nazli; Wit, Ferdinand W N M; van Den Berg, Thomas J T P; Kooij, Katherine W; Prins, Maria; Schlingemann, Reinier O; Abramoff, Michael D; Reiss, Peter; Verbraak, Frank D
PURPOSE: Loss of neuroretinal structure and function, ascribed to a 'HIV-associated Neuroretinal Disorder' (HIV-NRD), in the absence of ocular opportunistic infections, has been reported in HIV-infected individuals treated with combination antiretroviral therapy (cART). Whether HIV-infected individu
Full Text Available Introduction: Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+. Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART on the incidence of cardiovascular events (CVE and on the mortality rate are investigated in different HIV+ cohorts. Methods: The HIV HEART (HIVH study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. Results: 1481 HIV+ subjects (mean age: 49.3±10.7 years (y, female: 15.6% were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9% while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%. Advanced clinical and immunological stages were significantly (p<0.001 associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6% and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6% but not with the duration of HIV-infection (per y: Hazard ratio (HR: 0.91 [0.88–0.94] and ART (per y: HR: 0.81 [0.79–0.84] adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%. Median CD4-cells: 286.5 cells/µL (IQR: 168.8–482.8 versus 574 cells/µL (IQR: 406–786. 96.1% of the living HIV+ with CVE had HIV-RNA<50
Esser, Stefan; Eisele, Lewin; Schwarz, Birte; Schulze, Christina; Holzendorf, Volker; Brockmeyer, Nobert H; Hower, Martin; Kwirant, Friedhelm; Rudolph, Roland; Neumann, Till; Reinsch, Nico
Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts. The HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. 1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard ratio (HR): 0.91 [0.88-0.94]) and ART (per y: HR: 0.81 [0.79-0.84]) adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5 cells/µL (IQR: 168.8-482.8) versus 574 cells/µL (IQR: 406-786). 96.1% of the living HIV+ with CVE had HIV-RNA<50 copies/mL and median CD4-cells 542.5 cells
How did the complex metabolic systems we observe today evolve through adaptive evolution? The fitness landscape is the theoretical framework to answer this question. Since experimental data on natural fitness landscapes is scarce, computational models are a valuable tool to predict landscape topologies and evolutionary trajectories. Careful assumptions about the genetic and phenotypic features of the system under study can simplify the design of such models significantly. The analysis of C4 photosynthesis evolution provides an example for accurate predictions based on the phenotypic fitness landscape of a complex metabolic trait. The C4 pathway evolved multiple times from the ancestral C3 pathway and models predict a smooth 'Mount Fuji' landscape accordingly. The modelled phenotypic landscape implies evolutionary trajectories that agree with data on modern intermediate species, indicating that evolution can be predicted based on the phenotypic fitness landscape. Future directions will have to include structural changes of metabolic fitness landscape structure with changing environments. This will not only answer important evolutionary questions about reversibility of metabolic traits, but also suggest strategies to increase crop yields by engineering the C4 pathway into C3 plants.
Full Text Available Abstract Background An exciting application of genetic network is to predict phenotypic consequences for environmental cues or genetic perturbations. However, de novo prediction for quantitative phenotypes based on network topology is always a challenging task. Results Using yeast sporulation as a model system, we have assembled a genetic network from literature and exploited Boolean network to predict sporulation efficiency change upon deleting individual genes. We observe that predictions based on the curated network correlate well with the experimentally measured values. In addition, computational analysis reveals the robustness and hysteresis of the yeast sporulation network and uncovers several patterns of sporulation efficiency change caused by double gene deletion. These discoveries may guide future investigation of underlying mechanisms. We have also shown that a hybridized genetic network reconstructed from both temporal microarray data and literature is able to achieve a satisfactory prediction accuracy of the same quantitative phenotypes. Conclusions This case study illustrates the value of predicting quantitative phenotypes based on genetic network and provides a generic approach.
Obel, Niels; Thomsen, Henrik F; Kronborg, Gitte
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......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...
Full Text Available Abstract Background Previous studies have reported white matter (WM brain alterations in asymptomatic patients with human immunodeficiency virus (HIV. Methods We compared diffusion tensor imaging (DTI derived WM fractional anisotropy (FA between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI. We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. Results Structural MRI revealed no lesions in twelve (HIV-MRN and unspecific mild macrostructural lesions in seven patients (HIV-MRL. Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. Conclusion These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather than a reactive origin of depression in HIV-patients.
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
Prachakul, Worawan; Grant, Joan S; Keltner, Norman L
This cross-sectional exploratory study examined relationships among functional social support, HIV-related stigma, social problem solving, and depressive symptoms in a convenience sample of 30 men and nonpregnant women who sought care at two HIV outpatient clinics in the southeastern United States. Participants completed a set of self-report questionnaires at these clinics during scheduled regular visits. Data were analyzed using descriptive statistics. Consistent with other HIV studies, participants in this sample were at high risk for depression. Depressive symptoms were associated with more perceived HIV-related stigma, less social support provided by others, and dysfunctional social problem solving. These results are preliminary but important in identifying potential components for effective interventions to reduce the risk of depressive symptoms in persons with HIV.
Lohse, Nicolai; Gerstoft, Jan; Kronborg, Gitte
BACKGROUND:: We aimed to estimate the impact of comorbidity acquired before HIV diagnosis on mortality in HIV-infected individuals METHODS:: This cohort study compared two different cohorts. The prospective population-based nationwide observational Danish HIV Cohort Study was used to compare all.......44-2.00) vs 0.27% (0.26-0.28), 4.37% (3.01-6.32) vs 1.36% (1.26-1.47), 8.06% (4.94-13.16) vs 2.44% (2.22-2.68), and 10.15% (5.08-20.30) vs 5.84% (5.19-6.58), respectively. Comorbidity acquired before HIV, HCV, and background mortality accounted for 45% of total mortality in the HIV-infected population...
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.
Lucero, Robert James; Frimpong, Jemima A; Fehlberg, Elizabeth A; Bjarnadottir, Ragnhildur I; Weaver, Michael T; Cook, Christa; Modave, Francois; Rathore, Mobeen H; Morano, Jamie P; Ibanez, Gladys; Cook, Robert L
The human immunodeficiency virus (HIV) continues to be a major health issue in the United States, and an estimated 1.2 million people in the United States are living with HIV. As part of Healthy People 2020, the Office of Disease Prevention and Health Promotion has targeted the persistent demographic and geographic disparities in HIV prevalence and management. Preliminary evidence suggests that mobile health technology (smartphone apps) may be a promising way to support HIV self-management among vulnerable populations of people living with HIV (PLWH) who lack access to appropriate health care services. This study examines the association between individual characteristics of PLWH and level of interest in using a free mobile phone app for HIV self-management. This study was conducted using cross-sectional survey data collected in the Florida Cohort Study between 2014 and 2016 (N=766). Associations between individual characteristics of PLWH and level of interest in using a free mobile phone app for HIV self-management were examined using bivariate analysis and logistic regression. Overall, 85.5% (655/766) of respondents were interested in using a free mobile phone app that supports HIV self-management. Participants expressed the highest interest in app functions that facilitate communication with health care providers (568/740, 76.8%) or help to identify relevant health care services (556/745 74.6%). Age (OR 0.959, 95% CI 0.936-0.982), education (OR 1.281, 95% CI 1.027-1.598) and disability or inability to work (OR 0.296, 95% CI 0.145-0.606) were all significantly associated with being interested in using a free mobile phone app for HIV self-management. This study indicates that a majority of PLWH are interested in using a free mobile phone app to self-manage their condition. The findings can inform the development of mobile phone apps that support effective HIV self-management.
Full Text Available The primary objective was to examine trends in new HIV diagnoses in a UK area of high HIV prevalence between 2000 and 2012 with respect to site of diagnosis and stage of HIV infection.Single-centre observational cohort study.An outpatient HIV department in a secondary care UK hospital.1359 HIV-infected adults.Demographic information (age, gender, ethnicity, and sexual orientation, site of initial HIV diagnosis (Routine settings such as HIV/GUM clinics versus Non-Routine settings such as primary care and community venues, stage of HIV infection, CD4 count and seroconversion symptoms were collated for each participant.There was a significant increase in the proportion of new HIV diagnoses made in Non-Routine settings (from 27.0% in 2000 to 58.8% in 2012; p<0.001. Overall there was a decrease in the rate of late diagnosis from 50.7% to 32.9% (p=0.001. Diagnosis of recent infection increased from 23.0% to 47.1% (p=0.001. Of those with recent infection, significantly more patients were likely to report symptoms consistent with a seroconversion illness over the 13 years (17.6% to 65.0%; p<0.001.This is the first study, we believe, to demonstrate significant improvements in HIV diagnosis and a shift in diagnosis of HIV from HIV/GUM settings to primary practice and community settings due to multiple initiatives.
Elliott, Julian H.; McMahon, James H.; Chang, Christina C.; Lee, Sulggi A.; Hartogensis, Wendy; Bumpus, Namandje; Savic, Rada; Roney, Janine; Hoh, Rebecca; Solomon, Ajantha; Piatak, Michael; Gorelick, Robert J.; Lifson, Jeff; Bacchetti, Peter; Deeks, Steven G.; Lewin, Sharon R.
Background Disulfiram activates HIV transcription in a primary T-cell model of HIV latency and in a pilot clinical study increased plasma HIV RNA in individuals with adequate diulfiram exposure. Methods We conducted a prospective dose escalation study in order to optimise disulfiram exposure. Thirty people with HIV on suppressive antiretroviral therapy (ART) were enrolled, allocated sequentially to one of three dosing cohorts and received disulfiram daily for three days at a dose of 500mg, 1000mg or 2000mg. The primary endpoint was cell-associated unspliced (CA-US) HIV RNA in CD4+ T-cells. The study is registered with ClinicalTrials.gov, number NCT01944371. Findings The estimated fold increases in CA-US HIV RNA during and post-disulfiram for each cohort were: 500mg: 1·7 (95% confidence interval 1·3 – 2·2) and 2·1 (1·5 – 2·9); 1000mg: 1·9 (1·6 – 2·4) and 2·5 (1·9 – 3·3); and 2000mg: 1·6 (1·2 – 2·1) and 2·1 (1·5 – 3·1) respectively (p<0·003 for all). Disulfiram was well tolerated at all doses. Interpretation Short-term administration of disulfiram resulted in increases in CA-US HIV RNA at all doses, consistent with activating HIV latency. Disulfiram may be suited for future studies of combination and prolonged therapy to activate latent HIV. PMID:26614966
Full Text Available Objective: The aim of this study was to investigate the shift in the epidemiological features of HIV/AIDS during the last three decades in Fujian Province, southeastern China, so as to provide evidence for the development of novel HIV/AIDS control strategies. Methods: Data pertaining to the conventional surveillance, sentinel surveillance and epidemiological survey in Fujian Province during the period from 1987 to 2015 were collected. The epidemiological trends were described, and the subtypes of HIV strain were genotyped. In addition, the response to antiretroviral therapy was evaluated, and HIV genotypic resistance was assayed. Results: There was an increasing trend observed in the reported cases of HIV/AIDS in Fujian Province. From 1987 to the end of 2015, a total of 8651 HIV/AIDS cases were reported across the province, with totally 1557 deaths found. Among the total cases, the ratio of male/female cases was 3.7:1, which appeared to be an increasing trend; 77.1% cases were detected in young and middle-aged populations aged 19 to 50 years, however, the new HIV infections recently tended to occur in young people aged 15 to 18 years and in populations aged 50 years and older. Among all infected individuals, 49.3% were married, however, the percentage of unmarried cases increased from 6.67% before 1994 to 40.1% in 2015; 64.8% had junior high school education or lower, however, the proportion of HIV/AIDS cases with junior college education or above gradually increased from 6.5% in 2009 to 21.4% in 2015. The reported HIV/AIDS cases were predominantly found in coastal regions; however, a rapidly increasing trend was seen in the number of HIV/AIDS cases in inland regions, and the geographical variation of the cases gradually reduced. There were multiple routes of HIV transmission found in Fujian Province, and 94.2% infections were sexually transmitted, with a large increase in the percentage of male homosexual transmission. A variety of HIV-1
Yan, Yansheng; Wu, Shouli; Chen, Liang; Yan, Pingping; Qiu, Yuefeng; Xie, Meirong; Wang, Zhenghua; Lin, Xun
Objective: The aim of this study was to investigate the shift in the epidemiological features of HIV/AIDS during the last three decades in Fujian Province, southeastern China, so as to provide evidence for the development of novel HIV/AIDS control strategies. Methods: Data pertaining to the conventional surveillance, sentinel surveillance and epidemiological survey in Fujian Province during the period from 1987 to 2015 were collected. The epidemiological trends were described, and the subtypes of HIV strain were genotyped. In addition, the response to antiretroviral therapy was evaluated, and HIV genotypic resistance was assayed. Results: There was an increasing trend observed in the reported cases of HIV/AIDS in Fujian Province. From 1987 to the end of 2015, a total of 8651 HIV/AIDS cases were reported across the province, with totally 1557 deaths found. Among the total cases, the ratio of male/female cases was 3.7:1, which appeared to be an increasing trend; 77.1% cases were detected in young and middle-aged populations aged 19 to 50 years, however, the new HIV infections recently tended to occur in young people aged 15 to 18 years and in populations aged 50 years and older. Among all infected individuals, 49.3% were married, however, the percentage of unmarried cases increased from 6.67% before 1994 to 40.1% in 2015; 64.8% had junior high school education or lower, however, the proportion of HIV/AIDS cases with junior college education or above gradually increased from 6.5% in 2009 to 21.4% in 2015. The reported HIV/AIDS cases were predominantly found in coastal regions; however, a rapidly increasing trend was seen in the number of HIV/AIDS cases in inland regions, and the geographical variation of the cases gradually reduced. There were multiple routes of HIV transmission found in Fujian Province, and 94.2% infections were sexually transmitted, with a large increase in the percentage of male homosexual transmission. A variety of HIV-1 subtypes were genotyped in
... tube when ARVs are added. Genotypic resistance: The genetic code of HIV has mutations that are linked to ... phenotypic tests are somewhat quicker. GENOTYPIC TESTING The genetic code of the sample virus is compared to the ...
Lee, Yuan-Ti; Nfor, Oswald Ndi; Tantoh, Disline Manli; Huang, Jing-Yang; Ku, Wen-Yuan; Hsu, Shu-Yi; Ko, Pei-Chieh; Hung, Hung-Chang; Jan, Cheng-Feng; Liaw, Yung-Po
This study aimed to investigate the association between herpes zoster (HZ) and human immunodeficiency virus (HIV). Data were retrieved from the Longitudinal Health Insurance Databases (LHID 2005 and 2010), Taiwan. The International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes were used to identify Hz from 2001-2004. Identification of HIV infection was from 2005-2010. The hazard ratios of HIV among herpes zoster infected and non-herpes zoster infected patients were estimated using multiple Cox proportional hazard model. In general, 19685 participants were identified with Hz. The HIV incidence rates (per 104 person-months) in herpes zoster infected and non-infected patients were 0.191(95% CI 0.130-0.280) and 0.079 (95% CI 0.074-0.084), respectively while the hazard ratio (HR) of HIV among infected individuals was 3.518 (95% CI 2.375-5.211). This study concludes that herpes zoster could be considered as a predictor of HIV infection especially among Asian populations, hence it is vital to test herpes zoster infected individuals for HIV antibodies.
Rasmussen, Dlama; da Silva Te, David; Rodkjær, Lotte Ørneborg;
Adherence is a decisive factor in achieving a successful response to antiretroviral therapy (ART) for HIV infection. No previous studies have been conducted regarding HIV treatment adherence in Guinea-Bissau. In this study we assessed barriers and facilitators to patient ART adherence. Semi......-structured interviews were conducted with 20 adult, HIV infected individuals receiving ART at a HIV treatment centre in Bissau, Guinea-Bissau. The grounded theory method was used to gather and analyse data. Results indicated that HIV-related knowledge was a determining factor for optimal adherence. The facilitators...
Malaba Lucie C
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.
Okafor, Chukwuemeka N; Cook, Robert L; Chen, Xinguang; Surkan, Pamela J; Becker, James T; Shoptaw, Steve; Martin, Eileen; Plankey, Michael W
To construct longitudinal trajectories of marijuana use in a sample of men who have sex with men living with or at-risk for HIV infection. We determined factors associated with distinct trajectories of use as well as those that serve to modify the course of the trajectory. Data were from 3658 [1439 HIV-seropositive (HIV+) and 2219 HIV-seronegative (HIV-)] participants of the Multicenter AIDS Cohort Study. Frequency of marijuana use was obtained semiannually over a 29-year period (1984-2013). Group-based trajectory models were used to identify the trajectories and to determine predictors and modifiers of the trajectories over time. Four distinct trajectories of marijuana use were identified: abstainer/infrequent (65 %), decreaser (13 %), increaser (12 %) and chronic high (10 %) use groups. HIV+ status was significantly associated with increased odds of membership in the decreaser, increaser and chronic high use groups. Alcohol, smoking, stimulant and other recreational drug use were associated with increasing marijuana use across all four trajectory groups. Antiretroviral therapy use over time was associated with decreasing marijuana use in the abstainer/infrequent and increaser trajectory groups. Having a detectable HIV viral load was associated with increasing marijuana use in the increaser group only. Future investigations are needed to determine whether long-term patterns of use are associated with adverse consequences especially among HIV+ persons.
Okano, Justin T.; Robbins, Danielle; Palk, Laurence; Gerstoft, Jan; Obel, Niels; Blower, Sally
Summary Background Worldwide, ~35 million individuals are infected with HIV; ~25 million in sub-Saharan Africa (SSA). The 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 1,000 individuals. Here, we test the hypothesis that TasP can substantially reduce epidemics and eliminate HIV. We estimate the impact of TasP, between 1996–2013, on the Danish HIV epidemic in Men-who-have-Sex-with-Men (MSM), an epidemic UNAIDS has identified as a priority for elimination. Methods We use a CD4-staged Bayesian back-calculation approach to estimate incidence, and the “hidden epidemic” (the number of HIV-infected undiagnosed MSM). We use data from an ongoing nationwide population-based study: the Danish HIV Cohort Study. Findings 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 1,000 MSM. There were only 617 (median, 95% BCI: 264–858) undiagnosed MSM. Decreasing incidence and increasing treatment coverage are highly correlated; a threshold effect is apparent. Interpretation 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 SSA, the WHO’s global elimination strategy is unlikely to succeed. Funding NIAID/NIH PMID:27174504
Choi, Stephanie KY; Boyle, Eleanor; Burchell, Ann
Objective Major depression affects up to half of people living with HIV. However, among HIV-positive patients, depression goes unrecognized 60–70% of the time in non-psychiatric settings. We sought to evaluate three screening instruments and their short forms to facilitate the recognition...... of current depression in HIV-positive patients attending HIV specialty care clinics in Ontario. Methods A multi-centre validation study was conducted in Ontario to examine the validity and accuracy of three instruments (the Center for Epidemiologic Depression Scale [CESD20], the Kessler Psychological...... Distress Scale [K10], and the Patient Health Questionnaire depression scale [PHQ9]) and their short forms (CESD10, K6, and PHQ2) in diagnosing current major depression among 190 HIV-positive patients in Ontario. Results from the three instruments and their short forms were compared to results from the gold...
Full Text Available The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.
Full Text Available INTRODUCTION: There has been insufficient attention to long-term care and treatment for pregnant women diagnosed with HIV. OBJECTIVE AND METHODS: 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. FINDINGS: 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. CONCLUSION: 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
Full Text Available Introduction: HIV-positive (HIV+ temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD Temporary Residents Access Study (ATRAS and to determine the short- and long-term outcomes of receiving (subsidized optimal ART and the impact on onwards HIV transmission. Methods: ATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD and the proportion with undetectable (<50 copies/ml HIV viral load are reported at baseline, 6 and 12 months of follow-up. We also estimate the proportion reduction of onward HIV transmission based on the reduction in proportion of people with detectable HIV viral load. Results: A total of 180 patients were recruited to ATRAS by June 2012, and by July 2013 39 patients no longer required ART via ATRAS, 35 of whom became eligible for Medicare-funded medication. At enrolment, 63% of ATRAS patients were receiving ART from alternative sources, 47% had an undetectable HIV viral load (<50 copies/ml and the median CD4 cell count was 343 cells/µl (IQR: 222–479. At 12 months of follow-up, 85% had an undetectable viral load. We estimated a 75% reduction in the risk of onward HIV transmission with the improved rate of undetectable viral load. Conclusions: The
Chulach, Teresa; Gagnon, Marilou; Holmes, Dave
Increasingly HIV-positive refugee women are becoming pregnant. The objective of this qualitative study was to describe and explore the meaning and experience of pregnancy from the perspective of HIV-positive refugee women. The phenomenological analysis revealed 4 core themes. "Making up stories" for privacy and protection emerged as the first theme. The second theme illuminates 2 types of isolation: a double isolation based on refugee and HIV statuses, and isolation endured throughout the pregnancy. Being-in-Between describes the third theme. Finally, the fourth theme sheds light on the experience of disconnection: from baby, culture, body/self, and health care providers.
Melese, Hermela; Wassie, Molla Mesele; Woldie, Haile; Tadesse, Abilo; Mesfin, Nebiyu
Background Anemia is a major public health problem in HIV patients around the world. It has a negative effect on the quality of life of HIV patients and progression of the HIV disease. In the sub-Saharan African setting, including Ethiopia where both HIV infection and under-nutrition are expected to be high, there is a paucity of data on the matter. This study was aimed to reveal the magnitude and factors associated with anemia among adult HIV patients in Debre-Tabor Hospital, northwest Ethiopia. Methods A hospital-based cross-sectional study was used among adult HIV patients in Debre-Tabor Hospital from April 1 to May 30, 2015. The diagnosis of anemia was made following the 2011 World Health Organization recommendation on hemoglobin cut-off points. Univariable and multivariable logistic regression was carried out to assess factors associated with anemia. Results A total of 377 patients’ charts were reviewed. Most of the participants (n=237, 62.9%) were taking antiretroviral treatment (ART). The overall prevalence of anemia was 23% (95% CI: 19.1, 27.6). Being ART-naïve (adjusted odds ratio [AOR]: 3.37; 95% CI: 1.59, 7.14), having treatment history with anti-tuberculosis (TB) drug (AOR: 3.2; 95% CI: 1.19, 8.67), taking zidovudine (ZDV)-containing ART regimen (AOR: 2.14; 95% CI: 1.03, 4.57), and having recent CD4+ T-lymphocytes count of HIV patients. Conclusion and recommendation Anemia continues to be a major co-morbidity among adult HIV patients in Ethiopia. Adult HIV patients who are taking ZDV-containing ART, with a history of TB treatment, have a low CD4+T-lymphocytes count and are ART-naïve should be carefully screened and treated for anemia. PMID:28243151
Roca, V; Pérez-Cecilia, E; Santillana, T; Romero, J; Picazo, J J
A retrospective study of bacteriemias due to S. pneumoniae in adults is performed, from all the cases observed in our hospital during the 1989-1990 period. We compare the clinical characteristics of the disease depending if the affected patients were infected or not by the human immunodeficiency virus (HIV). In the considered period bacteriemia due to S. pneumoniae has been diagnosed in 12 patients with HIV infection and 29 without it. Ten of the twelve patients with HIV infection (83.3%) were in Stage IV (CDC) of the disease, staying the rest in a less developed phase of the disease. Age was significantly higher in non-HIV patients (p < 0.001) and a high percentage of patients in this group (75%) showed some disease considered as predisposing to bacteriemia due to S. pneumoniae. When a respiratory foci was present, VIH positive individuals showed more frequently bilateral radiologic infiltrates and less frequently pleural effusion. Leucocyte count when diagnosis was done were significantly higher in non-HIV group. Sensibility of isolated S. pneumoniae was similar in the two groups, being the immediate mortality related with bacteriemia due to S. pneumoniae higher in the non-HIV group. In our center 29.3% of bacteriemias due to S. pneumoniae are diagnosed in patients with HIV infection. This disease in itself could constitute an added risk factor in the development of bacteriemia due to S. pneumoniae.
Wirth, Kathleen E; Tchetgen Tchetgen, Eric J; Silverman, Jay G; Murray, Megan B
Studies have documented the substantial risk of human immunodeficiency virus (HIV) infection endured by sex-trafficked women, but it remains unclear how exposure to trafficking puts its victims at risk. We assessed whether the association between sex trafficking and HIV could be explained by self-reported forced prostitution or young age at entry into prostitution using cross-sectional data collected from 1,814 adult female sex workers in Karnataka, India, between August 2005 and August 2006. Marginal structural logistic regression was used to estimate adjusted odds ratios for HIV infection. Overall, 372 (21%) women met 1 or both criteria used to define sex trafficking: 278 (16%) began sex work before age 18 years, and 107 (5%) reported being forcibly prostituted. Thirteen (0.7%) met both criteria. Forcibly prostituted women were more likely to be HIV-infected than were women who joined the industry voluntarily, independent of age at entering prostitution (odds ratio = 2.30, 95% confidence interval: 1.08, 4.90). Conversely, after adjustment for forced prostitution and other confounders, no association between age at entry into prostitution and HIV was observed. The association between forced prostitution and HIV infection became stronger in the presence of sexual violence (odds ratio = 11.13, 95% confidence interval: 2.41, 51.40). These findings indicate that forced prostitution coupled with sexual violence probably explains the association between sex trafficking and HIV.
Wirth, Kathleen E.; Tchetgen Tchetgen, Eric J.; Silverman, Jay G.; Murray, Megan B.
Studies have documented the substantial risk of human immunodeficiency virus (HIV) infection endured by sex-trafficked women, but it remains unclear how exposure to trafficking puts its victims at risk. We assessed whether the association between sex trafficking and HIV could be explained by self-reported forced prostitution or young age at entry into prostitution using cross-sectional data collected from 1,814 adult female sex workers in Karnataka, India, between August 2005 and August 2006. Marginal structural logistic regression was used to estimate adjusted odds ratios for HIV infection. Overall, 372 (21%) women met 1 or both criteria used to define sex trafficking: 278 (16%) began sex work before age 18 years, and 107 (5%) reported being forcibly prostituted. Thirteen (0.7%) met both criteria. Forcibly prostituted women were more likely to be HIV-infected than were women who joined the industry voluntarily, independent of age at entering prostitution (odds ratio = 2.30, 95% confidence interval: 1.08, 4.90). Conversely, after adjustment for forced prostitution and other confounders, no association between age at entry into prostitution and HIV was observed. The association between forced prostitution and HIV infection became stronger in the presence of sexual violence (odds ratio = 11.13, 95% confidence interval: 2.41, 51.40). These findings indicate that forced prostitution coupled with sexual violence probably explains the association between sex trafficking and HIV. PMID:23324332
John H Rogers
Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
Nagelkerke, Nico J D; Hontelez, Jan A C; de Vlas, Sake J
The RV144 trial on the ALVAC/AIDSVAX candidate HIV vaccine, carried out in Thailand, showed short-lived protection against infection. Using a deterministic compartmental model we explored the potential impact of this vaccine on heterosexual HIV transmission in Thailand. Both one-off vaccination strategies, as well as strategies with regular boosting, either annually or every two years, were explored. Both targeting the general adult population and prioritizing sex workers were modeled. The impact of risk compensation among high risk groups, as well as whether higher levels of safe sex in high risk groups could be an alternative to vaccination, was studied. One-off vaccination campaigns had only transient effects, and boosting appears to be a key component of successful vaccination campaigns. Intensive vaccination campaigns may reduce HIV incidence by up to 75% after 10 years of vaccination. Targeting only sex workers has a smaller impact but has a more favorable cost-benefit ratio. Risk compensation has the potential of undoing much of the benefits of a vaccination program and may even increase incidence. In contrast, higher levels of safe sex among sex workers would provide a viable alternative to vaccinating this group. The new vaccine holds promise for controlling HIV in Thailand and similar countries. In view of the short lived protection of the vaccine, regular boosting of immunity as well as avoidance of risk compensation are essential. Targeting sex workers would achieve the greatest reduction in incidence per vaccination and may be considered for expensive vaccines but its cost-effectiveness has to be compared to alternatives. Copyright © 2011 Elsevier Ltd. All rights reserved.
Acharya, Sonu; Mandal, Pradip Kumar
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 IgA and deft (r = -0.942, t = 14.32, P IgA deficiency in
Richard A Oberhelman
Full Text Available 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.'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.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 children with suspected TB.This study did not
Danai Tavonga Zhou
Full Text Available HIV infection, together with ART, is associated with changes in biochemical, metabolic parameters and lipid profiles. The aim of this study was to compare changes in lipid profiles among HIV positive outpatients over nine months. 171 patients were investigated, 79% were ART experienced, and 82% of ART experienced patients were on NVP/EFV first line at baseline, but some patients changed ART groups over follow-up and classification was based on intent to treat. More than 60% ART naïve and ART experienced patients had some form of dyslipidemia either at baseline or at follow-up, but mean lipid values for the two groups were within normal limits. At baseline and follow-up, mean levels of TC and HDL were slightly higher in the ART experienced group. Interestingly, there was higher increase in HDL over time in the ART negative group compared to the ART positive group. There was a decrease in TC/HDL ratio in both groups over time, suggesting a reduction in calculated risk of CHD over time. HIV positive patients frequently show various forms of dyslipidemia, but there are no changes in average atherogenic lipid levels and results suggest reduced risk of CHD, mainly due to increases in HDL, after nine months of observation time.
Huntington Susie E
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.
Calvo-Sánchez, M; Perelló, R; Pérez, I; Mateo, M G; Junyent, M; Laguno, M; Blanco, J L; Martínez-Rebollar, M; Sánchez, M; Mallolas, J; Gatell, J M; Domingo, P; Martínez, E
The aim of the study was to assess the separate contributions of smoking, diabetes and hypertension to acute coronary syndrome (ACS) in HIV-infected adults relative to uninfected adults. Two parallel case-control studies were carried out. In the first study, HIV-positive adults diagnosed with ACS between 1997 and 2009 (HIV+/ACS) were matched for age, gender and known duration of HIV infection with HIV-positive adults without ACS (HIV+/noACS), each individual in the HIV+/ACS group being matched with three individuals in the HIV+/noACS group. In the second study, each individual in the HIV+/ACS group in the first study was matched for age, gender and calendar date of ACS diagnosis with three HIV-negative individuals diagnosed with ACS between 1997 and 2009 (HIV-/ACS). Each individual in the HIV-/ACS group was then matched for age and gender with an HIV-negative adult without ACS (HIV-/noACS). After matching, the ratio of numbers of individuals in the HIV+/ACS, HIV+/noACS, HIV-/ACS and HIV-/noACS groups was therefore 1 : 3 : 3 : 3, respectively. We performed logistic regression analyses to identify risk factors for ACS in each case-control study and calculated population attributable risks (PARs) for smoking, diabetes and hypertension in HIV-positive and HIV-negative individuals. There were 57 subjects in the HIV+/ACS group, 173 in the HIV+/noACS group, 168 in the HIV-/ACS group, and 171 in the HIV-/noACS group. Independent risk factors for ACS were smoking [odds ratio (OR) 4.091; 95% confidence interval (CI) 2.086-8.438; P hypertension (OR 6.589; 95% CI 3.554-12.700; P hypertension were 54.35 and 30.58, 6.57 and 17.24, and 9.07 and 38.81% in HIV-positive and HIV-negative individuals, respectively. The contribution of smoking to ACS in HIV-positive adults was generally greater than the contributions of diabetes and hypertension, and was almost twice as high as that in HIV-negative adults. Development of effective smoking cessation strategies should be
Kajubi, Phoebe; Whyte, Susan; Muhumuza, Simon; Kyaddondo, David; Katahoire, Anne R
Knowledge of antiretroviral therapy (ART) among children with HIV depends on open communication with them about their health and medicines. Guidelines assign responsibility for communication to children's home caregivers. Other research suggests that communication is poor and knowledge about ART is low among children on treatment in low-income countries. This study sought to describe communication about medicine for HIV in quantitative terms from the perspectives of both children and caregivers. Thereafter, it established the factors associated with this communication and with children's knowledge about their HIV medicines. We undertook a cross-sectional survey of a random sample of 394 children with HIV on treatment and their caregivers at nine health facilities in Jinja District, Uganda. We assessed reported frequency and content of communication regarding their medicines as well as knowledge of what the medicines were for. Logistic regression analysis was used to determine the factors associated with communication patterns and children's knowledge of HIV medicines. Although 79.6% of the caregivers reported that they explained to the children about the medicines, only half (50.8%) of the children said they knew that they were taking medicines for HIV. Older children aged 15-17 years were less likely to communicate with a caregiver about the HIV medicines in the preceding month (OR 0.5, 95% CI 0.3-0.7, p=0.002). Children aged 11-14 years (OR 6.1, 95% CI 2.8-13.7, pchildren and caregivers was "what the medicines are for" while "the time to take medicines" was by far the most mentioned by children. Communication about, and knowledge of, HIV medicines among children with HIV is low. Young age (less than 15 years) was associated with more frequent communication. Caregivers should be supported to communicate diagnosis and treatment to children with HIV. Age-sensitive guidelines about the nature and content of communication should be developed.
Full Text Available Anemia results in increased morbidity and mortality, underscoring the need to better understand its pathophysiology amongst HIV-exposed and infected children in sub-Saharan Africa, the region where most infant HIV exposure and infections occur.This analysis used samples obtained from children in the Kisumu Breastfeeding Study (KiBS. KiBS was a longitudinal phase IIB, open-label, one-arm clinical trial, designed to investigate the safety, tolerability and effectiveness of a maternal triple-antiretroviral (ARV regimen for prevention of mother-to-child transmission (PMTCT of HIV, during late pregnancy and early infancy while breastfeeding. Blood samples from 482 children were obtained at birth, 2, 6, 10 and 14 weeks and 6, 9, 12, 18 and 24 months. Severity of anemia was graded using the NIH Division of AIDS (DAIDS toxicity tables. We describe the proportion of children with anemia and anomalies in red blood cell parameters at various time points over 24 months and compare rates of anemia between HIV-infected and HIV-uninfected children and by mothers' ARV regimen and infant malaria infection.The proportion of children with anemia significantly increased after the breastfeeding period in both HIV-infected and HIV-uninfected children with higher proportion among HIV-infected children compared to HIV-uninfected children (RR: 1.72; CI: 1.22-2.44, p = 0.002. Maternal triple-antiretroviral regimen was not associated with infant anemia (p = 0.11. There was no significant difference in mean hemoglobin between HIV-uninfected children with and without malaria at each time point except at 24 months.A relatively lower proportion of children with severe anemia during the breastfeeding period suggest that exposure to mother's triple antiretroviral combinations through breast milk, posed minimal risk of hematologic toxicity.
Rosenfeld, Dana; Ridge, Damien; Catalan, Jose; Delpech, Valerie
Studies of disclosure amongst older people living with HIV (PLWH) are uninformed by critical social-gerontological approaches that can help us to appreciate how older PLWH see and treat age as relevant to disclosure of their HIV status. These approaches include an ethnomethodologically-informed social constructionism that explores how 'the' life course (a cultural framework depicting individuals' movement through predictable developmental stages from birth to death) is used as an interpretive resource for determining self and others' characteristics, capacities, and social circumstances: a process Rosenfeld and Gallagher (2002) termed 'lifecoursing'. Applying this approach to our analysis of 74 life-history interviews and three focus groups with older (aged 50+) people living with HIV in the United Kingdom, we uncover the central role that lifecoursing plays in participants' decision-making surrounding disclosure of their HIV to their children and/or older parents. Analysis of participants' accounts uncovered four criteria for disclosure: the relevance of their HIV to the other, the other's knowledge about HIV, the likelihood of the disclosure causing the other emotional distress, and the other's ability to keep the disclosed confidential. To determine if these criteria were met in relation to specific children and/or elders, participants engaged in lifecoursing, evaluating the other's knowledge of HIV, and capacity to appropriately manage the disclosure, by reference to their age. The use of assumptions about age and life-course location in decision-making regarding disclosure of HIV reflects a more nuanced engagement with age in the disclosure decision-making process than has been captured by previous research into HIV disclosure, including on the part of people aging with HIV. Copyright © 2016 Elsevier Inc. All rights reserved.
Warsy, A S; El-Hazmi, M A; Sedrani, S H; Kinhal, M
This study was conducted on 204 plasma samples obtained from Saudis living in the central province of Saudi Arabia, to determine the prevalence of alpha-1-antitrypsin (alpha1AT) phenotypes. The alpha1AT phenotypes were separated by isoelectric focusing on ampholine gels (pH 4-5). The prevalences of PiMM, MS, MZ, SZ, and ZZ were 0.8676, 0.0931, 0.0245, 0.0098, and 0.0049, respectively. The gene frequencies of the alpha1AT variants, i.e.., PiM, PiS, and PiZ, were 0.9265, 0.0515, 0.022, respectively. We describe and compare our results in a Saudi population with those reported for other populations.
Plourde, Vickie; Boivin, Michel; Forget-Dubois, Nadine; Brendgen, Mara; Vitaro, Frank; Marino, Cecilia; Tremblay, Richard T.; Dionne, Ginette
Background: The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and…
Plourde, Vickie; Boivin, Michel; Forget-Dubois, Nadine; Brendgen, Mara; Vitaro, Frank; Marino, Cecilia; Tremblay, Richard T.; Dionne, Ginette
Background: The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and…
Full Text Available Abstract Background Cellulose acetate phthalate (CAP in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH Methods Enzyme linked immunosorbent assays (ELISA were used to (1 study HIV-1 IIIB and BaL binding to micronized CAP; (2 detect virus disintegration; and (3 measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity. Results 1 HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2 The interaction between HIV-1 and micronized CAP led to: (a gp41 six-helix bundle formation; (b virus disintegration and shedding of envelope glycoproteins; and (c rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate, in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL. Conclusions Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.
Castley, Alison; Sawleshwarkar, Shailendra; Varma, Rick; Herring, Belinda; Thapa, Kiran; Dwyer, Dominic; Chibo, Doris; Nguyen, Nam; Hawke, Karen; Ratcliff, Rodney; Garsia, Roger; Kelleher, Anthony; Nolan, David
Rates of new HIV-1 diagnoses are increasing in Australia, with evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing impact of migration and travel. The present study aims to define HIV-1 subtype diversity patterns and investigate possible HIV-1 transmission networks within Australia. The Australian Molecular Epidemiology Network (AMEN) HIV collaborating sites in Western Australia, South Australia, Victoria, Queensland and western Sydney (New South Wales), provided baseline HIV-1 partial pol sequence, age and gender information for 4,873 patients who had genotypes performed during 2005-2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a stringent classification of transmission pairs or clusters (bootstrap ≥98%, genetic distance ≤1.5% from at least one other sequence in the cluster). HIV-1 subtype B represented 74.5% of the 4,873 sequences (WA 59%, SA 68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of sequences, p = 0.3). Significantly more subtype B clusters were comprised of ≥3 sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and significantly more subtype B pairs and clusters were male-only (88% compared to 53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a cluster of any size included; being sequenced in a more recent time period (p3) was associated with being sequenced in a more recent time period (p = 0.05) and being male (p = 0.008). This nationwide HIV-1 study of 4,873 patient sequences highlights the increased diversity of HIV-1 subtypes within the Australian epidemic, as well as differences in transmission networks associated with these HIV-1 subtypes. These findings provide epidemiological insights not readily available using standard surveillance methods and can inform the development of effective public health strategies in the current paradigm of HIV prevention in
Bousquet, Philippe Jean; Devillier, Philippe; Tadmouri, Abir; Mesbah, Kamal; Demoly, Pascal; Bousquet, Jean
Disease stratification, using phenotypic characterization performed either by hypothesis- or data-driven methods, was developed to improve clinical decisions. However, cluster analysis has not been used for allergic rhinitis. To define clusters in allergic rhinitis and to compare them with ARIA (Allergic Rhinitis and Its Impact on Asthma), a hypothesis-driven approach. A French observational prospective multicenter study (EVEIL: Echelle visuelle analogique dans la rhinite allergique) was carried out on 990 patients consulting general practitioners for allergic rhinitis and treated as per clinical practice. In this study, changes in symptom scores, visual analogue scales and quality of life were measured at baseline and after 14 days of treatment. A post hoc analysis was performed to identify clusters of patients with allergic rhinitis – using Ward's hierarchical method – and to define their clinical relevance at baseline and after 14 days of treatment. The cluster approach was compared to the ARIA approach. Patients were clustered into 4 phenotypes which partly followed the ARIA classes. These phenotypes differed in their disease severity including symptoms and quality of life. Physicians in real-life practice prescribed medication regardless of the phenotype and severity, with the exception of patients with ocular symptoms. Prescribed treatments were comparable in hypothesis- and data-driven analyses. The prevalence of uncontrolled patients during treatment was similar in the 4 clusters, but was significantly different according to the ARIA classes. Cluster analysis using demographic and clinical parameters only does not appear to add relevant information for disease stratification in allergic rhinitis. © 2015 S. Karger AG, Basel.
Valenzuela, Carla; Ugarte-Gil, Cesar; Paz, Jorge; Echevarria, Juan; Gotuzzo, Eduardo; Vermund, Sten H.; Kipp, Aaron M.
HIV stigma as a barrier to retention in HIV care has not been well-studied outside the United States. We conducted a case-control study in Lima, Peru to examine this issue. Cases were out-of-care for ≥12 months (n=66) and controls were recruited from patients in active care presenting for a clinic visit (n=110). A previously validated HIV stigma scale with four domains was used. Associations between being out-of-care and each stigma domain were assessed using multivariable logistic regression...
Full Text Available BACKGROUND: Diagnostic disclosure of HIV/AIDS to a child is becoming an increasingly common issue in clinical practice. Nevertheless, some parents and health care professionals are reluctant to inform children about their HIV infection status. The objective of this study was to identify the proportion of children who have knowledge of their serostatus and factors associated with disclosure in HIV-infected children receiving HAART in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18, 2008-April 28, 2008. The study populations were parents/caretakers and children living with HIV/AIDS who were receiving Highly Active Antiretroviral Therapy (HAART in selected hospitals in Addis Ababa. Univariate and multivariate logistic regression analysis were carried out using SPSS 12.0.1 statistical software. RESULTS: A total of 390 children/caretaker pairs were included in the study. Two hundred forty three children (62.3% were between 6-9 years of age. HIV/AIDS status was known by 68 (17.4% children, 93 (29% caretakers reported knowing the child's serostatus two years prior to our survey, 180 (46.2% respondents said that the child should be told about his/her HIV/AIDS status when he/she is older than 14 years of age. Children less than 9 years of age and those living with educated caregivers are less likely to know their results than their counterparts. Children referred from hospital's in-patient ward before attending the HIV clinic and private clinic were more likely to know their results than those from community clinic. CONCLUSION: The proportion of disclosure of HIV/AIDS diagnosis to HIV-infected children is low. Strengthening referral linkage and health education tailored to educated caregivers are recommended to increase the rate of disclosure.
LI Ping; CHEN Xiao; XIE Pei-yan; CHU Ping; LI Dong-liang; LI Qian-qian; SHAO Yi-ming
Background Following the increased human immunodeficiency virus (HIV) notification (infection) rates via sexual transmission and increased abuse of new synthetic drugs instead of heroin in China,a study on HIV infections and risk factors among synthetic drugs and heroin users in Beijing was conducted to provide a cue for further development of targets and strategies of HIV/AIDS control and prevention for different drug populations.Methods A total of 428 subjects including 224 heroin users and 204 new synthetic drug users was recruited from communities in Beijing by convenience sampling.A x2 test was used to compare HIV and syphilis infections between the two subpopulations.Logistic regression models were used to evaluate factors related to HIV,syphilis infections and abuse of synthetic drugs.Results Unbalanced distributions of demographics were detected between the two subpopulations.Compared with heroin users,most users of synthetic drugs were migrants,single and of younger age (age ≤30 years).Ten HIV infections and twenty-four syphilis infections were confirmed among 428 subjects.No significant difference in HIV infection was found between the two subpopulations (crude odds ratio (OR) =0.46,95％ confidence interval (CI):0.07-15.80 and adjusted odds ratio (AOR) =1.26,95％ CI:0.09-18.28) while four times as many syphilis infections were identified among users of synthetics drugs (AOR=3.92,95％ CI:1.06-14.56).HIV and syphilis infections appeared to work synergistically.The migrants who were of Han ethnicity,single and who had stayed in Beijing for more than six months were more likely to abuse synthetics drugs.Conclusions The new synthetic drug users and heroin users are different subpopulations.We optimistically speculate that HIV has not yet been introduced into the former in Beijing,but considering higher syphilis infections in synthetic drug users and the role of syphilis in HIV infection,synthetic drug users,as a possible and important driver of the HIV
Flavone and 95 hydroxyflavones have been studied with ab initio method, and their total energies, atomic charges, dipole moments, multipole moments, molecular orbital compositions, orbital energies etc. were obtained. Among them the relationship between total atomic charges and activities against HIV is basically in accordance with the experimental results. The beneficial references are provided for the extraction and synthesis of strong active anti-HIV medicines.
Suman, Rakesh; Smith, Gabrielle; Hazel, Kathryn E. A.; Kasprowicz, Richard; Coles, Mark; O'Toole, Peter; Chawla, Sangeeta
Time-lapse imaging is a fundamental tool for studying cellular behaviours, however studies of primary cells in complex co-culture environments often requires fluorescent labelling and significant light exposure that can perturb their natural function over time. Here, we describe ptychographic phase imaging that permits prolonged label-free time-lapse imaging of microglia in the presence of neurons and astrocytes, which better resembles in vivo microenvironments. We demonstrate the use of ptychography as an assay to study the phenotypic behaviour of microglial cells in primary neuronal co-cultures through the addition of cyclosporine A, a potent immune-modulator.
Druley, Todd E; Wang, Lihua; Lin, Shiow J
that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). CONCLUSIONS: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants.......BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS...... or as a group across an entire gene for association to aging phenotypes using family based tests. RESULTS: We found significant associations to three genes and nine single variants. Most notably, we found a novel variant significantly associated with exceptional survival in the 3' UTR OBFC1 in 13 individuals...
Yang, Wanneng; Guo, Zilong; Huang, Chenglong; Duan, Lingfeng; Chen, Guoxing; Jiang, Ni; Fang, Wei; Feng, Hui; Xie, Weibo; Lian, Xingming; Wang, Gongwei; Luo, Qingming; Zhang, Qifa; Liu, Qian; Xiong, Lizhong
Even as the study of plant genomics rapidly develops through the use of high-throughput sequencing techniques, traditional plant phenotyping lags far behind. Here we develop a high-throughput rice phenotyping facility (HRPF) to monitor 13 traditional agronomic traits and 2 newly defined traits during the rice growth period. Using genome-wide association studies (GWAS) of the 15 traits, we identify 141 associated loci, 25 of which contain known genes such as the Green Revolution semi-dwarf gene, SD1. Based on a performance evaluation of the HRPF and GWAS results, we demonstrate that high-throughput phenotyping has the potential to replace traditional phenotyping techniques and can provide valuable gene identification information. The combination of the multifunctional phenotyping tools HRPF and GWAS provides deep insights into the genetic architecture of important traits.
Tong, Chunfa; Shen, Lianying; Lv, Yafei; Wang, Zhong; Wang, Xiaoling; Feng, Sisi; Li, Xin; Sui, Yihan; Pang, Xiaoming; Wu, Rongling
Traditional approaches for genetic mapping are to simply associate the genotypes of a quantitative trait locus (QTL) with the phenotypic variation of a complex trait. A more mechanistic strategy has emerged to dissect the trait phenotype into its structural components and map specific QTLs that control the mechanistic and structural formation of a complex trait. We describe and assess such a strategy, called structural mapping, by integrating the internal structural basis of trait formation into a QTL mapping framework. Electrical impedance spectroscopy (EIS) has been instrumental for describing the structural components of a phenotypic trait and their interactions. By building robust mathematical models on circuit EIS data and embedding these models within a mixture model-based likelihood for QTL mapping, structural mapping implements the EM algorithm to obtain maximum likelihood estimates of QTL genotype-specific EIS parameters. The uniqueness of structural mapping is to make it possible to test a number of hypotheses about the pattern of the genetic control of structural components. We validated structural mapping by analyzing an EIS data collected for QTL mapping of frost hardiness in a controlled cross of jujube trees. The statistical properties of parameter estimates were examined by simulation studies. Structural mapping can be a powerful alternative for genetic mapping of complex traits by taking account into the biological and physical mechanisms underlying their formation.
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.
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.
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
Full Text Available Interaction in vitro between cells infected with human immunodeficiency virus (HIV and surrounding, uninfected, target cells often leads to cell fusion and the formation of multinucleated cells, called syncytia. The presence in HIV-infected individuals of virus strains able to induce syncytia in cultures of T cells is associated with disease progression and AIDS. Even in the asymptomatic stage of infection, multinucleated cells have been observed in different organs, indicating that fused cells may be generated and remain viable in the tissues of patients. We used lymphocytic cells transfected for the expression of the HIV-envelope (Env glycoproteins to develop a method for the direct quantification of fusion events by flow cytometry (Huerta et al., 2006, J. Virol. Methods 138, 17–23; López-Balderas et al., 2007, Virus Res. 123, 138–146. The method involves the staining of fusion partners with lipophilic probes and the use of fluorescence resonance energy transfer (FRET to distinguish between fused and aggregated cells. We have shown that such a flow-cytometry assay is appropriate for the screening of compounds that have the potential to modulate HIV-Env–mediated cell fusion. Even those syncytia that are small or few in numbers can be detected. Quantitative analysis of the fusion products was performed with this technique; the results indicated that the time of reaction and initial proportion of fusion partners determine the number, relative size, and average cellular composition of syncytia. Heterogeneity of syncytia generated by HIV-Env–mediated cell-cell fusion may result in a variety of possible outcomes that, in turn, may influence the biological properties of the syncytia and surrounding cells, as well as replication of virus. Given the myriad immune abnormalities leading to AIDS, the full understanding of the extent, diverse composition, and role of fused cells in the pathogenesis of, and immune response to, HIV infection is an
Huerta, Leonor; López-Balderas, Nayali; Rivera-Toledo, Evelyn; Sandoval, Guadalupe; Gómez-Icazbalceta, Guillermo; Villarreal, Carlos; Lamoyi, Edmundo; Larralde, Carlos
Interaction in vitro between cells infected with human immunodeficiency virus (HIV) and surrounding, uninfected, target cells often leads to cell fusion and the formation of multinucleated cells, called syncytia. The presence in HIV-infected individuals of virus strains able to induce syncytia in cultures of T cells is associated with disease progression and AIDS. Even in the asymptomatic stage of infection, multinucleated cells have been observed in different organs, indicating that fused cells may be generated and remain viable in the tissues of patients. We used lymphocytic cells transfected for the expression of the HIV-envelope (Env) glycoproteins to develop a method for the direct quantification of fusion events by flow cytometry (Huerta et al., 2006, J. Virol. Methods 138, 17-23; López-Balderas et al., 2007, Virus Res. 123, 138-146). The method involves the staining of fusion partners with lipophilic probes and the use of fluorescence resonance energy transfer (FRET) to distinguish between fused and aggregated cells. We have shown that such a flow-cytometry assay is appropriate for the screening of compounds that have the potential to modulate HIV-Env-mediated cell fusion. Even those syncytia that are small or few in numbers can be detected. Quantitative analysis of the fusion products was performed with this technique; the results indicated that the time of reaction and initial proportion of fusion partners determine the number, relative size, and average cellular composition of syncytia. Heterogeneity of syncytia generated by HIV-Env-mediated cell-cell fusion may result in a variety of possible outcomes that, in turn, may influence the biological properties of the syncytia and surrounding cells, as well as replication of virus. Given the myriad immune abnormalities leading to AIDS, the full understanding of the extent, diverse composition, and role of fused cells in the pathogenesis of, and immune response to, HIV infection is an important, pending issue.
Ekouevi, Didier K; Coffie, Patrick A.; Eugene Messou; Adrien Sawadogo; Eholie, Serge P.; Djimon Marcel Zannou; Carin Ahouada; Jocelyn Akakpo; Christelle Ahomadegbé; Jules Bashi; Alice Gougounon-Houéto; Angèle Azon-Kouanou; Fabien Houngbé; Sikiratou Koumakpaï; Florence Alihonou
Background 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). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART)...
Full Text Available Abstract Background Despite the availability of antiretroviral therapy (ART, suboptimal treatment outcomes have been observed among HIV-seropositive illicit drug users. As there is an urgent need to improve responses to antiretroviral therapy among this population, we undertook this study to evaluate the role of physician experience on rates of plasma HIV-1 RNA suppression following initiation of ART. Methods Using data from a community-recruited cohort of HIV-positive illicit drug users, we used Cox proportional hazards regression to model the time to plasma viral HIV RNA Results Between May 1996 and December 2008, 267 individuals initiated ART among whom 227 (85% achieved a plasma HIV RNA Conclusions In this setting of universal HIV/AIDS care, illicit drug users with more experienced physicians exhibited faster rates of plasma viral load suppression. These findings argue for specialized services to help optimize HIV treatment outcomes among this population.
Netsanet Fentahun; Ashagre Molla; Beyene Wondafrash
Objective:To determine self-efficacy of HIV sero-status disclosure decisions and safer sex in HIV sero-positive persons in Jimma University Specialized Hospital, south west Ethiopia. Methods:A facility based cross sectional study design was conducted on 601 HIV positive person in Jimma University Specialized Hospital, ART clinic. Data were collected using standard pre-coded interviewer-administered questionnaire. The data were entered into SPSS version 16.0. Descriptive analysis was done to describe the characteristics of the study participants. Logistic regression was used to know the predictor of disclosure. Results:Of the 591 study participants, 564 (95.4%) were disclosed their HIV status. Married HIV patients were 22.4 times more likely practice safe sex than single HIV patients [adjusted odds ratio (AOR), 95%CI:22.4 (8.6, 58.6)]. HIV patients whose educational statuses were secondary school were 0.5 times less likely practice safe sex than HIV patients whose educational statuses were college/university [AOR, 95%CI:0.5 (0.2,0.9)]. HIV patients whose monthly income was in between 901-1 300 ETH Birr was 0.2 times less likely practice safe sex than HIV patients whose monthly income was above 1 300 ETH Birr [AOR, 95%CI: 0.2 (0.1, 0.7)]. A unit increase in total score of self-efficacy on safe sex practice the odds of practicing safe sex was increased by 2.0 [AOR, 95%CI:2.0 (1.1, 3.8)]. Conclusions: The HIV patients had high self-efficacy on disclosure, safe sex and treatment adherence. This good practice should be promoted and enhanced in different part of Ethiopia. The HIV patients had low awareness about their parents’ HIV status. Future effort should be made on awareness level about their parents’ HIV status.
Logie, Carmen H.; James, LLana; Tharao, Wangari; Loutfy, Mona R.
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
Gordon Elisa J
Full Text Available Abstract Background Much attention has been devoted to ethical issues related to randomized controlled trials for HIV treatment and prevention. However, there has been less discussion of ethical issues surrounding families involved in observational studies of HIV transmission. This paper describes the process of ethical deliberation about how best to obtain informed consent from sex partners of injection drug users (IDUs tested for HIV, within a recent HIV study in Eastern Europe. The study aimed to assess the amount of HIV serodiscordance among IDUs and their sexual partners, identify barriers to harm reduction, and explore ways to optimize intervention programs. Including IDUs, either HIV-positive or at high risk for HIV, and their sexual partners would help to gain a more complete understanding of barriers to and opportunities for intervention. Discussion This paper focuses on the ethical dilemma regarding informed recruitment: whether researchers should disclose to sexual partners of IDUs that they were recruited because their partner injects drugs (i.e., their heightened risk for HIV. Disclosing risks to partners upholds the ethical value of respect for persons through informed consent. However, disclosure compromises the IDU's confidentiality, and potentially, the scientific validity of the research. Following a brief literature review, we summarize the researchers' systematic evaluation of this issue from ethical, scientific, and logistical perspectives. While the cultural context may be somewhat unique to Eastern Europe and Central Asia, the issues raised and solutions proposed here inform epidemiological research designs and their underlying ethical tensions. Summary We present ethical arguments in favor of disclosure, discuss how cultural context shapes the ethical issues, and recommend refinement of guidance for couples research of communicable diseases to assist investigators encountering these ethical issues in the future.
Seal, Abhik; Aykkal, Riju; Babu, Rosana O; Ghosh, Mriganka
Natural products are important sources of drug discovery. In this context groups of different set of phytochemicals were taken and docked into the different cavities of the Reverse transcriptase (PDB ID: 1REV) of Human immunodeficiency virus (HIV) and results were discussed. Natural compounds such as Curcumin, Geranin, Gallotannin, Tiliroside, Kaempferol-3-o-glucoside and Trachelogenin were found to very effective according to its binding energy and ligand efficiency score. Those compounds also were found to have no adverse effect as carcinogenicity and mutagenicity and favorable drug likeness score. Hence, considering the facts those compounds could use effectively for HIV-1 drug discovery.
Lebech, Anne-Mette; Kristoffersen, Ulrik Sloth; Mehlsen, Jesper;
BACKGROUND: The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis...... and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction. AIM: To evaluate whether autonomic dysfunction is present in an ART-treated HIV population. METHODS: HIV patients receiving ART for at least 3 years (n = 16) and an age-matched control group...... guidelines and data reported as median (interquartile range). RESULTS: The resting heart rate was higher in HIV patients compared with controls [69 (62-74) versus 57 (52-60); PHIV group compared with the controls...
Harrowing, Jean N; Edwards, Nancy; Richter, Solina; Minnie, Karin; Rae, Tania
Nurses in Jamaica, Kenya, South Africa, and Uganda are at risk for occupational exposure to HIV. Little is known about the experiences and policy supports related to nurses having themselves tested for the virus. This article reports a mixed-methods study about contextual influences on nurses' decision-making about HIV testing. Individual and focus group interviews, as well as a questionnaire on workplace polices and quality assurance and a human resource management assessment tool provided data. Fear of a positive diagnosis and stigma and lack of confidentiality along with gaps in the policy environment contributed to indecision about testing. There were significant differences in policy supports among countries. Institutional support must be addressed if improvements in HIV testing for health care workers are going to be effectively implemented. Future work is required to better understand how HRM policies intersect to create conditions of perceived vulnerability for HIV positive staff.
Friis-Møller, Nina; Thiébaut, Rodolphe; Reiss, Peter;
aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. METHODS AND RESULTS: Prospective multinational cohort study. The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection.......670-0.818) for coronary heart disease and 0.769 (0.695-0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. CONCLUSION: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters...
Yue, Huizhen; Hu, Jian; Guan, Guobo; Tao, Li; Du, Han; Li, Houmin; Huang, Guanghua
Candida dubliniensis is closely related to Candida albicans, a major causative agent of candidiasis, and is primarily associated with oral colonization and infection in human immunodeficiency virus (HIV)-positive patients. Despite the high similarity of genomic and phenotypic features between the 2 species, C. dubliniensis is much less virulent and less prevalent than C. albicans. The ability to change morphological phenotypes is a striking feature of Candida species and is linked to virulence. In this study, we report a novel phenotype, the gray phenotype, in C. dubliniensis. Together with the previously reported white and opaque cell types, the gray phenotype forms a tristable phenotypic switching system in C. dubliniensis that is similar to the white-gray-opaque tristable switching system in C. albicans. Gray cells of C. dubliniensis are similar to their counterparts in C. albicans in terms of several biological aspects including cellular morphology, mating competence, and genetic regulatory mechanisms. However, the gray phenotypes of the 2 species have some distinguishing features. For example, the secreted aspartyl protease (Sap) activity is induced by bovine serum albumin (BSA) in gray cells of C. albicans, but not in gray cells of C. dubliniensis. Taken together, our results demonstrate that the biological features and regulatory mechanisms of white-gray-opaque tristable transitions are largely conserved in the 2 pathogenic Candida species.
Peck, Robert N; Shedafa, Rehema; Kalluvya, Samuel; Downs, Jennifer A; Todd, Jim; Suthanthiran, Manikkam; Fitzgerald, Daniel W; Kataraihya, Johannes B
The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity. In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher's exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding. Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤ 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with
Pedersen, C; Pedersen, B K
, oesophageal candidiasis, meningoencephalitis, rhabdomyolysis and epiglottitis have been reported. The diagnosis of the acute HIV infection syndrome can be established by demonstrating antibodies to HIV or by demonstration of HIV antigen positivity. Detection of virus through culture or PCR may prove......Up to 70% of individuals with primary HIV infection will develop symptoms of an acute illness. The most common symptoms reported are fever, generalized lymphadenopathy, arthralgia and myalgia, headache, pharyngitis, enanthema, skin rash, diarrhoea, and mucocutaneous ulcerations. More rarely...... to be more sensitive, but are not yet used as routine methods. The course of the primary infection has prognostic importance for the subsequent course of HIV infection. This probably reflects the importance of both the viral phenotype and of the initial immune response to HIV. Primary HIV infection should...
Suhadev, Mohanarani; Nyamathi, Adeline M; Swaminathan, Soumya; Venkatesan, P; Raja Sakthivel, M; Shenbagavalli, R; Suresh, Anitha; Fahey, John L
In India, phase-I human clinical trials for a preventive HIV vaccine are being conducted at Pune and Chennai Centres. In order to find out the willingness of populations at risk to participate in future preventive HIV vaccine trials (HIVVTs) and to assess the factors that enhance or deter them from participation, a study was conducted at Chennai and Madurai in Tamil Nadu. This cross-sectional study was conducted among transport workers, people attending sexually transmitted infection clinics, injection drug users, men having sex with men, women in sex industry and a representative sample of monogamous married women, by employing measurement scales. A structured questionnaire on knowledge and attitudes about the HIV vaccine was used to measure the participants' knowledge and attitudes about HIV vaccine and HIVVTs. Of the 112 participants, 67 (60%) were men. Mean age of the respondents was 32 yr; 68 per cent were high school educated. Majority of respondents were willing to participate in a future HIVVT and the reasons were altruism, protection from HIV, and support for the researchers. Major concerns were vaccine efficacy, side effects of the vaccine and the impact of a HIV vaccine on the participants' lives. Majority (85%) agreed that sex without condom would not be safe despite the availability of an HIV vaccine. It is likely that high-risk volunteers will be willing to enroll in HIVVTs. Barriers and concerns should be dealt with carefully by providing correct information. Also there is a need for more education to ensure participants' understanding of key concepts of HIV vaccine trial.
Rai, Tanvi; Lambert, Helen S; Ward, Helen
Migrant workers are designated a bridge population in the spread of HIV and therefore if infected, should be diagnosed and treated early. This study examined pathways to HIV diagnosis and access to care for rural-to-urban circular migrant workers and partners of migrants in northern India, identifying structural, social and individual level factors that shaped their journeys into care. We conducted a qualitative study using in-depth interviews with HIV-positive men (n = 20) and women (n = 13) with a history of circular migration, recruited from an antiretroviral therapy centre in one district of Uttar Pradesh, north India. Migrants and partners of migrants faced a complex series of obstacles to accessing HIV testing and care. Employment insecurity, lack of entitlement to sick pay or subsidised healthcare at destination and the household's economic reliance on their migration-based livelihood led many men to continue working until they became incapacitated by HIV-related morbidity. During periods of deteriorating health they often exhausted their savings on private treatments focused on symptom management, and sought HIV testing and treatment at a public hospital only following a medical or financial emergency. Wives of migrants had generally been diagnosed following their husbands' diagnosis or death, with access to testing and treatment mediated via family members. For some, a delay in disclosure of husband's HIV status led to delays in their own testing. Diagnosing and treating HIV infection early is important in slowing down the spread of the epidemic and targeting those at greatest risk should be a priority. However, despite targeted campaigns, circumstances associated with migration may prevent migrant workers and their partners from accessing testing and treatment until they become sick. The insecurity of migrant work, the dominance of private healthcare and gender differences in health-seeking behaviour delay early diagnosis and treatment initiation.
Heaton, Robert K.; Franklin, Donald R.; Deutsch, Reena; Letendre, Scott; Ellis, Ronald J.; Casaletto, Kaitlin; Marquine, Maria J.; Woods, Steven P.; Vaida, Florin; Atkinson, J. Hampton; Marcotte, Thomas D.; McCutchan, J. Allen; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; Sacktor, Ned; Morgello, Susan; Simpson, David M.; Abramson, Ian; Gamst, Anthony C.; Fennema-Notestine, Christine; Smith, David M.; Grant, Igor; Grant, Igor; McCutchan, J. Allen; Ellis, Ronald J.; Marcotte, Thomas D.; Franklin, Donald; Ellis, Ronald J.; McCutchan, J. Allen; Alexander, Terry; Letendre, Scott; Capparelli, Edmund; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; Dawson, Matthew; Smith, David M.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Marcotte, Thomas D.; Marquie-Beck, Jennifer; McArthur, Justin; Rogalski, Vincent; Morgello, Susan; Simpson, David; Mintz, Letty; McCutchan, J. Allen; Toperoff, Will; Collier, Ann; Marra, Christina; Jones, Trudy; Gelman, Benjamin; Head, Eleanor; Clifford, David; Al-Lozi, Muhammad; Teshome, Mengesha
Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions. PMID:25362201
Full Text Available Hermela Melese,1 Molla Mesele Wassie,2 Haile Woldie,2 Abilo Tadesse,3 Nebiyu Mesfin3 1HIV Follow-up Care Clinic, Debre-Tabor Hospital, Debre‑Tabor, 2Department of Human Nutrition, Institute of Public Health, 3Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Background: Anemia is a major public health problem in HIV patients around the world. It has a negative effect on the quality of life of HIV patients and progression of the HIV disease. In the sub-Saharan African setting, including Ethiopia where both HIV infection and under-nutrition are expected to be high, there is a paucity of data on the matter. This study was aimed to reveal the magnitude and factors associated with anemia among adult HIV patients in Debre-Tabor Hospital, northwest Ethiopia. Methods: A hospital-based cross-sectional study was used among adult HIV patients in Debre-Tabor Hospital from April 1 to May 30, 2015. The diagnosis of anemia was made following the 2011 World Health Organization recommendation on hemoglobin cut-off points. Univariable and multivariable logistic regression was carried out to assess factors associated with anemia. Results: A total of 377 patients’ charts were reviewed. Most of the participants (n=237, 62.9% were taking antiretroviral treatment (ART. The overall prevalence of anemia was 23% (95% CI: 19.1, 27.6. Being ART-naïve (adjusted odds ratio [AOR]: 3.37; 95% CI: 1.59, 7.14, having treatment history with anti-tuberculosis (TB drug (AOR: 3.2; 95% CI: 1.19, 8.67, taking zidovudine (ZDV-containing ART regimen (AOR: 2.14; 95% CI: 1.03, 4.57, and having recent CD4+ T-lymphocytes count of <200 cells/µL (AOR: 2.13; 95% CI: 1.04, 4.36 were associated with occurrence of anemia among adult HIV patients. Conclusion and recommendation: Anemia continues to be a major co-morbidity among adult HIV patients in Ethiopia. Adult HIV patients who are taking ZDV-containing ART
Full Text Available Introduction: Transmission in serodiscordant couples (SDCs accounts for approximately half of all new HIV infections, both in Kenya and the wider sub-Saharan region (1. With evidence to suggest inconsistent condom use within this population (2, the World Health Organization has recommended two new methods of HIV prevention for SDCs: Treatment as Prevention (TasP and Pre-Exposure Prophylaxis (PrEP. However, there has been little research about the attitudes of SDCs towards these strategies (3, 4; knowledge that is paramount for successfully predicting the acceptability and efficacy of each method, as well as for informing decisions regarding HIV policy changes in Kenya. Methods: An exploratory, qualitative study was conducted in the Muhoroni constituency of Nyando district, Kenya from January to March 2013. Purposive sampling was predominately used to recruit 21 HIV-positive and 17 HIV-negative individuals in a serodiscordant relationship from four hospitals and health centres. During face-to-face semi-structured interviews, topic guides were used to elicit information about participants’ attitudes and preferences towards TasP and PrEP. Collected data underwent framework analysis, allowing the development of overarching categories, sub-themes and inductive interpretation. Results: The majority of participants, irrespective of gender and HIV status, found TasP more acceptable than PrEP. A key factor influencing this decision was HIV-negative participants’ limited motivation to take and adhere to antiretrovirals (ARVs, primarily due to a predominantly external health locus of control, a lack of cultural acceptance of prophylactic medication and concerns about side effects. In addition to this, the likely health improvements TasP offers HIV-positive partners, as well as the attitude that the sick individual should be the first to receive HIV medication, also contributed to this conclusion. Issues of risk compensation were raised, with some HIV
Made Asri Budisuari
Full Text Available Background: A policy of service about prevention HIV infection from mother to child integrated with reproduction health care, especially health of mother and baby service at every level of health care. All women who came to reproductive health services at every level of health care information transmission of STIs and HIV prevention during pregnancy and lactation. Policy of prevention of HIV transmission from mother to child through 4 prong. Over 6.5 million women in Indonesia is vulnerable population contracting and transmitting HIV/AIDS, more than 9,000 pregnant women with HIV each year in and more than 30% of them gave birth to babies who are infected when there is no prevention of HIV+ from mother to child/ Prevention Mother To Child Transmission (PMTCT. Methods: The study is a qualitative study, conducted in the month of December 2009 in Surabaya. Data was collected through structured interviews to policy holders, non-governmental organizations (NGOs and providing PMTCT services in health centers on the support and the need for reproductive health services to pregnant women at risk for HIV/AIDS. Result: This analysis showed East Java Provincial Health Office team up PMTCT in the clinic, which consisted of midwives, health center doctors, nurses, and gynecologists, although not all centers have a team of PMTCT. This leads to the possibility of pregnant women with HIV who have not been reached. Dupak health center whose jurisdiction covers the area of localization has a PMTCT program, also conducted Voluntary Counselling Test (VCT, but this time in collaboration with NGOs (Hotline for the implementation of VCT, PMTCT as a team in doubles as an officer pukesmas BP and KIA. PMTCT in the clinic target: pregnant women who perform Antenatal Care (ANC, secondary data obtained from review of documents in Dinkesprov East Java, Surabaya DKK and health centers. Surabaya City Government has sought to implement policies set by the Ministry of Health in
Silvia de Souza Dantas ALCZUK
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.
Full Text Available Abstract The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage.
Yan, Jin; Xiao, Shuiyuan; Zhou, Liang; Tang, Yong; Xu, Guangming; Luo, Dan; Yi, Qifeng
The HIV/AIDS epidemic caused by commercial blood donation in rural Henan Province of China in the early- to mid-1990s is the largest known cohort in the world related to blood donation but is not fully described. The objectives of this study were to describe the epidemic, epidemiology, and social epidemiology of commercial blood donation and HIV/AIDS. Both qualitative and quantitative mixed methods were used. A village was randomly selected from the 38 key HIV/AIDS pandemic villages in Henan Province. "Demographic Data Form" was applied to collect demographic information of each resident. Focus groups were held for the managers, some residents, members of "HIV/AIDS Work-Team" (organized by the Henan Provincial Government) in the village. Every village physician, people living with HIV/AIDS (PLWHA), school header, and other stakeholders were interviewed individually. The social epidemiology of HIV/AIDS was analyzed under three perspectives of the framework: individual, social, and structural perspectives. In this village, there were 2335 residents, 484 (20.3%) were former donors, 107 (4.6%) were PLWHA, and 96.3% of PLWHA were infected through commercial blood donation. Individually, low education and plasma donation were the risky factors of HIV/AIDS infection. Socially, the epidemic was geography-, kinship-, and conformity-related. Structurally, the related macrostructure factor was policy endorsement of national blood products. The microstructure factors were poverty and value belief on male child in passing down generations. It is concluded that commercial blood donation and HIV/AIDS epidemic in the village are symbiotically related. The epidemic is temporary and socially determined.
Barzegar, Abolfazl; Jafari Mousavi, Somaye; Hamidi, Hossein; Sadeghi, Mehdi
The protease of human immunodeficiency virus1 (HIV-PR) is an essential enzyme for antiviral treatments. Carbon nanostructures of fullerene derivatives, have nanoscale dimension with a diameter comparable to the diameter of the active site of HIV-PR which would in turn inhibit HIV. In this research, two dimensional quantitative structure-activity relationships (2D-QSAR) of fullerene derivatives against HIV-PR activity were employed as a powerful tool for elucidation the relationships between structure and experimental observations. QSAR study of 49 fullerene derivatives was performed by employing stepwise-MLR, GAPLS-MLR, and PCA-MLR models for variable (descriptor) selection and model construction. QSAR models were obtained with higher ability to predict the activity of the fullerene derivatives against HIV-PR by a correlation coefficient (R2training) of 0.942, 0.89, and 0.87 as well as R2test values of 0.791, 0.67and 0.674 for stepwise-MLR, GAPLS-MLR, and PCA -MLR models, respectively. Leave-one-out cross-validated correlation coefficient (R2CV) and Y-randomization methods confirmed the models robustness. The descriptors indicated that the HIV-PR inhibition depends on the van der Waals volumes, polarizability, bond order between two atoms and electronegativities of fullerenes derivatives. 2D-QSAR simulation without needing receptor's active site geometry, resulted in useful descriptors mainly denoting ;C60 backbone-functional groups; and ;C60 functional groups; properties. Both properties in fullerene refer to the ligand fitness and improvement van der Waals interactions with HIV-PR active site. Therefore, the QSAR models can be used in the search for novel HIV-PR inhibitors based on fullerene derivatives.
Poignet, J L; Desassis, J F; Chanton, N; Litchinko, M B; Zins, B; Kolko, A; Patte, R; Sobel, A
In order to determine the prevalence of HIV infection in french patients with end-stage renal disease (ESRD) on maintenance dialysis therapy, questionnaire forms were mailed out in february 1997 to the heads of the 260 dialysis facilities. We documented number of patients on maintenance dialysis therapy (hemo and peritoneal dialysis) and for HIV infected dialysis patients: age, gender, cause and duration of ESRD, known duration of HIV infection, risk factors for HIV infection, HBV and/or HCV infection, presence of clinical acquired immunodeficiency syndrome (AIDS), total CD4 count and treatment with antiretroviral agents. Questionnaire forms were returned from 98% of the dialysis facilities. As of february 1997 some 22,707 patients with ESRD were treated by renal replacement therapy, 19,947 by hemodialysis (HD) and 2760 by peritoneal dialysis (PD). 82 patients with ESRD and HIV infection were reported corresponding to 0.36% prevalence rate of all patients undergoing dialysis at the time specified. The 82 study subjects with ESRD and HIV infection received hemodialysis (79 patients) or peritoneal dialysis (3 patients) in 42 facilities. Forty seven patients were treated in Paris and suburbs and 9 in our own center. All 82 patients comprised 63% men and 47% women which included patients coming from Africa (37%), Caribbean and Oceania (28%), Europe (35%) of a mean age of 41.8 years. Modes of transmission were homobisexuals 15%, heterosexuals 31%, intravenous drug abusers 17%, blood transfusion 17% and unknown 20%. The mean duration of HIV infection was 96 months (range 12-168 months) and the mean duration of ESRD was 58 months (range 1-235 months). HIV associated nephropathy was established in 31%. AIDS was diagnosed in 25 patients. Seventy one percent of the patients were receiving an antiretroviral drug (tritherapy in 25% of cases). In conclusion HIV prevalence rate among French dialysis patients is low and focused in Paris and oversea. Sexual transmission is the
Mo, Phoenix K H; Ng, Charlson T Y
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.
Fowler, Nikola; Arkell, Paul; Abouyannis, Michael; James, Catherine; Roberts, Lesley
This qualitative study aims to gain in-depth information about the attitudes of HIV-serodiscordant couples towards two new methods of HIV prevention; Pre-Exposure Prophylaxis and Treatment as Prevention, both of which have been recently recommended by the World Health Organisation. Semi-structured interviews were conducted with 38 individuals in a serodiscordant relationship in Western Kenya. Topic guides were used to elicit information on perceived benefits, concerns, and preferences towards Treatment as Prevention and Pre-Exposure Prophylaxis. Data evaluation and thematic generation were developed using framework analysis. Results suggest that the majority of participants, irrespective of gender and HIV status, found Treatment as Prevention the more acceptable strategy. Key factors influencing this decision were HIV-negative participants' limited motivation to take prophylactic antiretrovirals and the likely health improvements Treatment as Prevention offers HIV-positive partners. However, issues were raised concerning the likelihood of low concurrent condom use and poor medication adherence when using these preventative approaches. It was concluded that the adoption of Treatment as Prevention as a method of HIV control in Kenya is likely to be more readily accepted by serodiscordant couples than Pre-exposure Prophylaxis. However, future implementation of either strategy would require measures to address the possibility of risk compensation and poor adherence.
Rawal, R K; Murugesan, V; Katti, S B
In addition to the nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and integrase inhibitors (INIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) have contributed significantly in the treatment of HIV-1 infections. More than 60 structurally different classes of compounds have been identified as NNRTIs, which are specifically inhibiting HIV-1 reverse transcriptase (RT). Five NNRTIs (nevirapine, delavirdine, efavirenz, etravirine and rilpivirine) have been approved by US Food and Drug Administration (FDA) for clinical use. The NNRTIs bind with a specific 'pocket' site of HIV-1 RT (allosteric site) that is closely associated with the NRTI binding site. Due to mutations of the amino acid residues surrounding the NNRTI-binding site, NNRTIs are notorious for rapidly eliciting resistance. Though, the emergence of resistant HIV strains can be circumvented if the NNRTIs are used either alone or in combination with NRTIs (AZT, 3TC, ddI, ddC, TVD or d4T) and PIs (Indinavir, nelfinavir, saquinavir, ritonavir and lopinavir etc.) as shown by both a decrease in plasma HIV-1 RNA levels and increased CD4 T-cells. Here we are going to discuss recent advances in structure activity relationship studies on nevirapine, delavirdine, efavirenz, etravirine, rilpivirine and 4-thiazolidinones (privileged scaffold) HIV-1 NNRTIs.
Meganck, Vanessa; Goddeeris, Bruno M; Stuyven, Edith; Piepers, Sofie; Cox, Eric; Opsomer, Geert
The present study reports a method for isolating bovine colostrum mononuclear cells (CMC) for phenotyping and functional studies. As well as being an important source of immunoglobulins, colostrum also contains leukocytes that may be of greater importance for passive immunity than has previously been thought. Different protocols have been reported for isolating leukocytes from bovine colostrum, although none of these have been validated, and phenotypic analysis of cell populations has not always been performed. In this study, bovine CMC were isolated by density gradient centrifugation. Cell populations were identified by flow cytometry using antibodies against selected bovine cell surface markers and the proliferative capacity of these cells was determined using a (3)H-thymidine proliferation assay. The mean cell count of isolated CMC was 3 × 10(4) and 1 × 10(5) per mL colostrum for the samples used in the flow cytometric assay and the proliferation assay, respectively. A mean of 25.4 ± 17.1% CMC were identified as T lymphocytes, 2.9 ± 3.0% as B lymphocytes and 32.7 ± 13.7% as macrophages. In terms of proliferation, the mean counts per minute were 4.3 × 10(3) and 1.8 × 10(4) for cells cultured in medium only or in the presence of concanavalin A, respectively, showing that CMC are viable and capable of responding to mitogen stimulation. Isolation of CMC and the subsequent phenotypic analysis of the different subpopulations were repeatable, with agreement indices varying between 0.5 and 1.0. Agreement indices for the proliferation assay were estimated at 0.8.
Roscher, A A; Hoefler, S; Hoefler, G; Paschke, E; Paltauf, F; Moser, A; Moser, H
Disorders of peroxisomal biogenesis include the Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum syndrome, and hyperpipecolic acidemia. These names were assigned before the recognition of the peroxisomal defect and the distinction between phenotypes is uncertain. Recent studies have identified at least four complementation groups, and indicate the presence of at least that number of distinct genotypes. The purpose of the present study was to examine the relationship between genotype and phenotype. We studied cultured skin fibroblasts from 19 patients in whom deficiency of peroxisomes had been established. Complementation analysis was performed with the criterion of complementation being the restoration of the capacity to synthesize plasmalogens when fibroblasts from two patients were fused. Six complementation groups were identified, and consisted of one 13 member group, one two member group, and four groups comprising single cases. The phenotype of each group was examined with respect to age of survival, clinical manifestations, and biochemical alterations. The 13 member group included patients with all of the four currently designated phenotypic entities, while the most common phenotype (Zellweger syndrome) was distributed among five of the six groups. We conclude that the currently used clinical categories do not represent distinct genotypes. Apparently different genes code for a similar phenotype and one defective gene may lead to variant phenotypes. Definitive classification and understanding of these disorders await definition of the specific biochemical defect in each of the genotypes.
Kiderlen, Til R; Conteh, Michael; Roll, Stephanie; Seeling, Stefanie; Weinmann, Stefan
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.
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
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
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
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
Full Text Available Frederik N Engsig1, Jan Gerstoft1, Gitte Kronborg2, Carsten S Larsen3, Gitte Pedersen4, Court Pedersen5, Niels Obel11Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 3Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; 4Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 5Department of Infectious Diseases, Odense University Hospital, Odense, DenmarkBackground: The mechanism for the increased risk of head and neck cancer (HNC observed in HIV patients is controversial. We hypothesized that family-related risk factors increase the risk of HNC why we estimated the risk of this type of cancer in both HIV patients and their parents.Methods: We estimated the cumulative incidence and incidence rate ratios (IRRs of HNC in 1 a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5053 and a cohort of population controls matched on age and gender (n = 50,530 (study period; 1995–2009 and 2 the parents of HIV patients and population controls (study period 1978–2009. To assess the possible impact of human papilloma virus (HPV–associated cancers, the sites of squamous cell HNCs were categorized as HPV related, potentially HPV related, and potentially HPV unrelated.Results: Seventeen (0.3% HIV patients vs 80 (0.2% population controls were diagnosed with HNC cancer in the observation period. HIV patients had an increased risk of HNC (IRR 3.05 [95% CI 1.81–5.15]. The IRR was considerably increased in HIV patients older than 50 years (adjusted IRR; 4.58 [95% CI 2.24–9.35], diagnosed after 1995 (adjusted IRR 6.31 [95% CI 2.82–14.08], previous or current smoker (adjusted IRR 4.51 [95% CI 2.47–8.23], with baseline CD4 count 350 cells/µL (adjusted IRR; 3.89 [95% CI 1.95–7.78], and men heterosexually infected with HIV (adjusted IRR 5
Soerensen, Mette; Nygaard, Marianne; Dato, Serena
-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease......, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture...
Maphanga, Charles; Ombinda-Lemboumba, Saturnin; Manoto, Sello; Maaza, Malik; Mthunzi-Kufa, Patience
Human immunodeficiency virus (HIV-1) infection still remains one amongst the world's most challenging infections since its discovery. Antiretroviral therapy is the recommended treatment of choice for HIV-1 infection taken by patients orally. The highly active antiretroviral therapy (HAART) prevents the replication of HIV-1 and further destruction of the immune system, therefore enabling the body to fight opportunistic life-threatening infections, cancers, and also arrest HIV infection from advancing to AIDS. The major challenge with HAART is the inability to reach the viral reservoirs where the HIV-1 remains latent and persistent, leading to inability to fully eradicate the virus. This study is aimed at initially designing and assembling a fully functional optical translocation setup to optically deliver antiretroviral drugs into HIV-1 infected cells in a targeted manner using Gaussian beam mode femtosecond laser pulses in-vitro. The main objective of our study is to define the in-vitro drug photo-translocation parameters to allow future design of an efficient drug delivery device with potential in-vivo drug delivery applications. In our experiments, HEK 293T cells were used to produce HIV-1 enveloped pseudovirus (ZM53) to infect TZM-bl cells which were later treated with laser pulses emitted by a titanium sapphire laser (800 nm, 1KHz, 113 fs, 6.5 μW) to create sub-microscopic pores on the cell membrane enabling influx of extracellular media. Following laser treatment, changes in cellular responses were analysed using cell morphology studies, cytotoxicity, and luciferase assay studies. Controls included laser untreated cells incubated with the drug for 72 hours. The data in this study was statistically analysed using the SigmaPlot software version 13.
Full Text Available BACKGROUND : Tuberculosis, a major public health problem in most of the developing countries is posing a still bigger threat with the epidemic of HIV and association has been termed as “cursed duet”. There is significant difference in the clinical profile of tuberculosis in HIV infected compared to immunocompetent host. So prompt diagnosis and treatment of tuberculosis in HIV infected will improve the morbidity and mortality associated with dual infection. So the objective of the study was to determine the clinical profile of TB in HIV infected in relation to CD4 counts. MATERIALS AND METHODS : Hundred patients with HIV infection and having symptoms of tuberculosis admitted in the medical wards in Government General Hospital, Guntur were studied. Diagnosis of tuberculosis was based on clinical evaluation, sputum smears, bacteriological and biochemical examination of body fluids, histopathological studies and radiological studies. CD4 T cell counts were done in all patients. RESULTS : 51% had only pulmonary tuberculosis, 43% had only extrapulmonary involvement while 6% had disseminated disease. Sputum positivity was seen in 27.45% of pulmonary tuberculosis. Chest X - ray findings were mixed and varied with infiltrative lesions seen in 83.33% and fibrocavitatory lesions in 11.11%. 55.55% of infiltrative lesions were seen in mid and lower zones. Mean CD4 counts in this study was 133.78 ± 75 cells/μL . Most of the patients with extra pulmonary TB and disseminated TB had CD 200 cells/μL. CONCLUSION : Tuberculosis has a varied clinical presentation in patients with HIV infection. Sputum negative TB, extrapulmonary TB and disseminated TB were common when CD4 < 200 cells/μL and chest X - ray findings were atypical when CD4 < 200 cells/μL. KEYWORDS: Pulmonary Tuberculosis; HIV infection; Clinical profile of tuberculosis .
Kamerman, Peter R.; Veliotes, Demetri G. A.; Phillips, Tudor J.; Asboe, David; Boffito, Marta; Rice, Andrew S. C.
HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-associated Neuropathy Tool) assessing symptoms (pain and numbness) and signs (ankle reflexes and vibration sense) was developed by selecting and combining the most accurate measurands from a deep phenotyping study of HIV positive people (Pain In Neuropathy Study–HIV-PINS). CHANT was alpha-tested in silico against the HIV-PINS dataset and then clinically validated and field-tested in HIV-positive cohorts in London, UK and Johannesburg, South Africa. The Utah Early Neuropathy Score (UENS) was used as the reference standard in both settings. In a second step, neuropathic pain in the presence of HIV-SN was assessed using the Douleur Neuropathique en 4 Questions (DN4)-interview and a body map. CHANT achieved high accuracy on alpha-testing with sensitivity and specificity of 82% and 90%, respectively. In 30 patients in London, CHANT diagnosed 43.3% (13/30) HIV-SN (66.7% with neuropathic pain); sensitivity = 100%, specificity = 85%, and likelihood ratio = 6.7 versus UENS, internal consistency = 0.88 (Cronbach alpha), average item-total correlation = 0.73 (Spearman’s Rho), and inter-tester concordance > 0.93 (Spearman’s Rho). In 50 patients in Johannesburg, CHANT diagnosed 66% (33/50) HIV-SN (78.8% neuropathic pain); sensitivity = 74.4%, specificity = 85.7%, and likelihood ratio = 5.29 versus UENS. A positive CHANT score markedly increased of pre- to post-test clinical certainty of HIV-SN from 43% to 83% in London, and from 66% to 92% in Johannesburg. In conclusion, a combination of four easily and quickly assessed clinical items can be used to accurately diagnose HIV-SN. DN4-interview used in the context of bilateral feet
Full Text Available Zuzana Zbozinkova,1 Adam Barczyk,2 Ruzena Tkacova,3 Arschang Valipour,4 Neven Tudoric,5 Kirill Zykov,6 Attila Somfay,7 Marc Miravitlles,8 Vladimir Koblizek91Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 3Department of Respiratory Medicine, Faculty of Medicine, P.J. Safarik University, Kosice, Slovakia; 4Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Wien, Austria; 5School of Medicine Zagreb, University Hospital Dubrava, Zagreb, Croatia; 6Laboratory of Pulmonology, Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, Russia; 7Department of Pulmonology, University of Szeged, Deszk, Hungary; 8Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 9Department of Pneumology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech RepublicIntroduction: Chronic obstructive pulmonary disease (COPD constitutes a major health challenge in Central and Eastern European (CEE countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE.Methods/design: The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC ,0.7, and absence
Bärnighausen, Till; Hosegood, Victoria; Timaeus, Ian M; Newell, Marie-Louise
Knowledge of the effect of socioeconomic status on HIV infection in Africa stems largely from cross-sectional studies. Cross-sectional studies suffer from two important limitations: two-way causality between socioeconomic status and HIV serostatus and simultaneous effects of socioeconomic status on HIV incidence and HIV-positive survival time. Both problems are avoided in longitudinal cohort studies. We used data from a longitudinal HIV surveillance and a linked demographic surveillance in a poor rural community in KwaZulu-Natal, South Africa, to investigate the effect of three measures of socioeconomic status on HIV incidence: educational attainment, household wealth categories (based on a ranking of households on an assets index scale) and per capita household expenditure. Our sample comprised of 3325 individuals who tested HIV-negative at baseline and either HIV-negative or -positive on a second test (on average 1.3 years later). In multivariable survival analysis, one additional year of education reduced the hazard of acquiring HIV by 7% (P = 0.017) net of sex, age, wealth, household expenditure, rural vs. urban/periurban residence, migration status and partnership status. Holding other factors equal, members of households that fell into the middle 40% of relative wealth had a 72% higher hazard of HIV acquisition than members of the 40% poorest households (P = 0.012). Per capita household expenditure did not significantly affect HIV incidence (P = 0.669). Although poverty reduction is important for obvious reasons, it may not be as effective as anticipated in reducing the spread of HIV in rural South Africa. In contrast, our results suggest that increasing educational attainment in the general population may lower HIV incidence.
Klingenberg, Christian Peter
Developmental mechanisms are usually assumed to evolve by natural selection of the morphological traits they produce. Therefore, information on phenotypic traits is an important component of comparative studies of development. Morphometrics permits the rigorous quantitative analysis of variation in organismal size and shape, and is increasingly being used in developmental contexts. The new methods of morphometrics combine a geometric concept of shape with the procedures of multivariate statistics, and constitute a powerful and flexible set of tools for analyzing morphological variation. This paper briefly reviews these methods and provides examples of their application in studies of genetic variation and developmental modularity. The results of morphometric analyses can be readily interpreted in relation to the geometry and anatomical structure of the parts under study. Genetic studies of shape in the mouse mandible found two recurrent patterns in environmental and genetic variation from different origins, suggesting that the development system 'channels' the phenotypic expression of variation in similar ways. Moreover, by analyzing the correlations of left-right asymmetries of morphometric traits, it is possible to delimit the spatial extent of developmental modules. These methods complement the experimental approaches of developmental biology and genetics, and can be expected to be especially fruitful in combination with them.
Cysique, Lucette A.; Moffat, Kirsten; Moore, Danielle M.; Lane, Tammy A.; Davies, Nicholas W. S.; Carr, Andrew; Brew, Bruce J.; Rae, Caroline
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
Bhatt, Arpan D.; Liehr, Thomas; Bakshi, Sonal R.
CONTEXT: Alterations in the human chromosomal complement are expressed phenotypically ranging from (i) normal, via (ii) frequent fetal loss in otherwise normal person, to (iii) sub-clinical to severe mental retardation and dysmorphism in live births. A subtle and microscopically undetectable chromosomal alteration is uniparental disomy (UPD), which is known to be associated with distinct birth defects as per the chromosome involved and parental origin. UPD can be evident due to imprinted genes and/or activation of recessive mutations. AIMS: The present study comprises of data mining of published UPD cases with a focus on associated phenotypes. The goal was to identify non-random and recurrent associations between UPD and various genetic conditions, which can possibly indicate the presence of new imprinted genes. SETTINGS AND DESIGN: Data mining was carried out using the homepage “http://www.fish.uniklinikum-jena.de/UPD.html.”, an online catalog of published cases with UPD. MATERIALS AND METHODS: The UPD cases having normal karyotype and with or without clinical findings were selected to analyze the associated phenotypes for each chromosome, maternal or paternal involved in UPD. RESULTS: Our results revealed many genetic conditions (other than the known UPD syndromes) to be associated with UPD. Even in cases of bad obstetric history as well as normal individuals chance detection of UPD has been reported. CONCLUSIONS: The role of UPD in human genetic disorders needs to be studied by involving larger cohorts of individuals with birth defects as well as normal population. The genetic conditions were scrutinized in terms of inheritance patterns; majority of these were autosomal recessive indicating the role of UPD as an underlying mechanism. PMID:24339543
De Wit, Stephane; Sabin, Caroline A; Weber, Rainer;
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...
Veronica Varela-Mato; Orlagh O'Shea; James A King; Thomas Yates; David J Stensel; Stuart JH Biddle; Myra A Nimmo; Stacy A Clemes
...) likely contribute to this elevated risk. This study behaviourally phenotyped UK lorry drivers' sedentary and non-sedentary behaviours during workdays and non-workdays and examined markers of drivers cardio-metabolic health...
Simen, Birgitte B; Braverman, Michael S; Abbate, Isabella; Aerssens, Jeroen; Bidet, Yannick; Bouchez, Olivier; Gabriel, Christian; Izopet, Jacques; Kessler, Harald H; Stelzl, Evelyn; Di Giallonardo, Francesca; Schlapbach, Ralph; Radonic, Aleksander; Paredes, Roger; Recordon-Pinson, Patricia; Sakwa, James; St John, Elizabeth P; Schmitz-Agheguian, Gudrun G; Metzner, Karin J; Däumer, Martin P
The detection of mutant spectra within the viral quasispecies is critical for therapeutic management of HIV-1 infections. Routine clinical application of ultrasensitive genotyping requires reproducibility and concordance within and between laboratories. The goal of the study was to evaluate a new protocol on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing (454-UDS) in an international multicenter study. Sixteen blinded HIV-1 subtype B samples were provided for 454-UDS as both RNA and cDNA with viral titers of 88,600-573,000 HIV-1 RNA copies/ml. Eight overlapping amplicons spanning protease (PR) codons 10-99 and reverse transcriptase (RT) codons 1-251 were generated using molecular barcoded primers. 454-UDS was performed using the 454 Life Sciences/Roche GS FLX platform. PR and RT sequences were analyzed using 454 Life Sciences Amplicon Variant Analyzer (AVA) software. Quantified variation data were analyzed for intra-laboratory reproducibility and inter-laboratory concordance. Routine population sequencing was performed using the ViroSeq HIV-1 genotyping system. Eleven laboratories and the reference laboratory 454 Life Sciences sequenced the HIV-1 sample set. Data presented are derived from seven laboratories and the reference laboratory since severe study protocol execution errors occurred in four laboratories leading to exclusion. The median sequencing depth across all sites was 1364 reads per position (IQR=809-2065). 100% of the ViroSeq-reported mutations were also detected by 454-UDS. Minority HIV-1 drug resistance mutations, defined as HIV-1 drug resistance mutations identified at frequencies of 1-25%, were only detected by 454-UDS. Analysis of 10 preselected majority and minority mutations were consistently found across sites. The analysis of drug-resistance mutations detected between 1 and 10% demonstrated high intra- and inter-laboratory consistency in frequency estimates for both RNA and prepared cDNA samples, indicating robustness of the
Full Text Available Purpose. To assess the prevalence and associated factors of unprotected sex with injecting drug users (IDUs among a sample of female sex workers (FSWs in Iran. Methods. This cross-sectional study included 144 FSWs who were interviewed as a part of Unhide HIV Risk Study, a national behavioral survey focusing on various high-risk populations, including IDUs, FSWs, and Men who have Sex with Men (MSMs in 2009. The survey was conducted in eight provinces in Iran using respondent-driven sampling. Participants’ sociodemographic status, HIV knowledge, and HIV attitude were analyzed via logistic regression to determine the predictors of unprotected sex with IDU(s during the past month. Results. Nineteen percent of FSWs reported at least one occasion of unprotected sex with IDU(s in the month preceding the study. Higher educational level (OR=−0.653, 95%CI=-1.192 to −0.115, perceived HIV risk (OR=−1.047, 95%CI=-2.076 to −0.019, and perceived family intimacy during childhood (OR=−1.104, 95%CI=-1.957 to −0.251 were all independently associated with lower odds of having unprotected sex with IDU(s in the month preceding the study. Age, marital status, living condition, HIV knowledge, and perceived behavioral control did not affect the odds of FSWs having sex with IDUs. Conclusion. Perceived HIV risk, which is a modifiable factor, seems to be a promising target for harm reduction interventions amongst Iranian female sex workers. Data presented here may aid in reducing or eliminating the role of sex workers as a bridge for HIV transmission from IDUs to the general population in Iran.
Choi, Stephanie KY; Boyle, Eleanor; Burchell, Ann;
of current depression in HIV-positive patients attending HIV specialty care clinics in Ontario. Methods A multi-centre validation study was conducted in Ontario to examine the validity and accuracy of three instruments (the Center for Epidemiologic Depression Scale [CESD20], the Kessler Psychological...... Distress Scale [K10], and the Patient Health Questionnaire depression scale [PHQ9]) and their short forms (CESD10, K6, and PHQ2) in diagnosing current major depression among 190 HIV-positive patients in Ontario. Results from the three instruments and their short forms were compared to results from the gold...... positive predictive value (0.49–0.58) at their optimal cut-points. Conclusion Among people in HIV care in Ontario, Canada, the three instruments and their short forms performed equally well and accurately. When further in-depth assessments become available, shorter instruments might find greater clinical...
Iyer, Janani; Wang, Qingyu; Le, Thanh; Pizzo, Lucilla; Grönke, Sebastian; Ambegaokar, Surendra S.; Imai, Yuzuru; Srivastava, Ashutosh; Troisí, Beatriz Llamusí; Mardon, Graeme; Artero, Ruben; Jackson, George R.; Isaacs, Adrian M.; Partridge, Linda; Lu, Bingwei; Kumar, Justin P.; Girirajan, Santhosh
About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions. PMID:26994292
Garcia-Gorro, Clara; Camara, Estela; de Diego-Balaguer, Ruth
Huntington's disease is a neurodegenerative disorder characterized by a triad of motor, cognitive and psychiatric disturbances. There is great variability regarding the prominence and evolution of each type of clinical sign. One possible source of phenotypic heterogeneity could be the more prominent degeneration of specific brain circuits. The scope of this review is to highlight the most recent neuroimaging studies that have analysed the relationship between brain changes and motor, cognitive and psychiatric alterations in Huntington's disease. The results from recent neuroimaging studies are heterogeneous. Although there is a great overlap between the different regions associated with each symptomatic domain, there is some degree of differentiation. For example, the motor network is associated with motor impairment, whereas the ventral striatum is especially involved in emotional deficits related with psychiatric problems. Motor, cognitive and psychiatric impairments are associated with structural and functional brain biomarkers. However, the specificity of the regions involved remains unknown, because these studies focused on specific regions and symptoms. In order to tease apart the neural substrates that underlie the phenotypic heterogeneity in Huntington's disease, multivariate approaches combining brain and behavioural measures related to all symptomatic domains should be considered in the future.
Boeckxstaens, G E; Drug, V; Dumitrascu, D; Farmer, A D; Hammer, J; Hausken, T; Niesler, B; Pohl, D; Pojskic, L; Polster, A; Simren, M; Goebel-Stengel, M; Van Oudenhove, L; Vassallo, M; Wensaas, K-A; Aziz, Q; Houghton, L A
Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd.
Frich Jan C
Full Text Available Abstract Background Knowledge about lay beliefs of etiology, transmission and treatment of TB, and lay perceptions of the relationship between TB and HIV is important for understanding patients' health seeking behavior and adherence to treatment. We conducted a study to explore lay beliefs about TB and TB/HIV co-infection in Addis Ababa, Ethiopia. Findings We conducted a qualitative study using in-depth interviews with 15 TB/HIV co-infected patients and 9 health professionals and focus group discussions with 14 co-infected patients in Addis-Ababa, Ethiopia. We found that a predominant lay belief was that TB was caused by exposure to cold. Excessive sun exposure, exposure to mud, smoking, alcohol, khat and inadequate food intake were also reported as causes for TB. Such beliefs initially led to self-treatment. The majority of patients were aware of an association between TB and HIV. Some reported that TB could transform into HIV, while others said that the body could be weakened by HIV and become more susceptible to illnesses such as TB. Some patients classified TB as either HIV-related or non-HIV-related, and weight loss was a hallmark for HIV-related TB. The majority of patients believed that people in the community knew that there was an association between TB and HIV, and some feared that this would predispose them to HIV-related stigma. Conclusion There is a need for culturally sensitive information and educational efforts to address misperceptions about TB and HIV. Health professionals should provide information about causes and treatment of TB and HIV to co-infected patients.
Full Text Available Introduction: Male circumcision (MC reduces the risk of HIV infection. However, the risk reduction effect of MC can be modified by type of circumcision (medical, traditional and religious and sexual risk behaviours post-circumcision. Understanding the risk behaviours associated with HIV infection among circumcised men (regardless of form of circumcision is critical to the design of comprehensive risk reduction interventions. This study assessed risk factors for HIV infection among men circumcised through various circumcision approaches. Methods: This was a case-control study which enrolled 155 cases (HIV-infected and 155 controls (HIV-uninfected, all of whom were men aged 18–35 years presenting at the AIDS Information Center for HIV testing and care. The outcome variable was HIV sero-status. Using SPSS version 17, multivariable logistic regression was performed to identify factors independently associated with HIV infection. Results: Overall, 83.9% among cases and 56.8% among controls were traditionally circumcised; 7.7% of cases and 21.3% of controls were religiously circumcised while 8.4% of cases and 21.9% of controls were medically circumcised. A higher proportion of cases than controls reported resuming sexual intercourse before complete wound healing (36.9% vs. 14.1%; p18 years (AOR: 5.0, CI: 2.4–10.2; resuming sexual intercourse before wound healing (AOR: 3.4, CI: 1.6–7.3; inconsistent use of condoms (AOR: 2.7, CI: 1.5–5.1; and having sexual intercourse under the influence of peers (AOR: 2.9, CI: 1.5–5.5. Men who had religious circumcision were less likely to have HIV infection (AOR: 0.4, 95% CI: 0.2–0.9 than the traditionally circumcised but there was no statistically significant difference between those who were traditionally circumcised and those who were medically circumcised (AOR: 0.40, 95% CI: 0.1–1.1. Conclusions: Being circumcised at adulthood, resumption of sexual intercourse before wound healing, inconsistent
Jennifer Ilo Van Nuil
Full Text Available OBJECTIVE: This qualitative study explored the views and experiences of adolescents with perinatally acquired HIV in Kigali, Rwanda, regarding sex, love, marriage, children and hope for the future. DESIGN: The study enrolled 42 adolescents who had received combination antiretroviral therapy for at least 12 months, and a selection of their primary caregivers. Study methods included 3 multiple day workshops consisting of role-playing and focus group discussions (FGDs with adolescents, 8 in-depth interviews with adolescents, and one FGD with caregivers. RESULTS: The adolescents reported experiencing similar sexual needs and dilemmas as most other adolescents, but with an added layer of complexity due to fears related to HIV transmission and/or rejection by partners. They desired more advice from their parents/caregivers on these topics. Although they struggled with aspects of sex, love, marriage and having children, most agreed that they would find love, be married and have children in the future. The two most discussed HIV-related anxieties were how and when to disclose to a (potential sex/marriage partner and whether to have children. However, most adolescents felt that they had a right to love and be loved, and were aware of prevention-of-mother-to-child-transmission (PMTCT options in Rwanda. Adolescents generally spoke about their future role in society in a positive manner. CONCLUSION: Strengthening the life skills of HIV-positive adolescents, especially around HIV disclosure and reduction of HIV transmission, as well as the support skills of parents/caregivers, may not only reduce onward HIV transmission but also improve quality of life by reducing anxiety.
Lorraine H.C. Fisher
Full Text Available Drought is an important environmental stress limiting the productivity of major crops worldwide. Understanding drought tolerance and possible mechanisms for improving drought resistance is therefore a prerequisite to develop drought-tolerant crops that produce significant yields with reduced amounts of water. Brachypodium distachyon (Brachypodium is a key model species for cereals, forage grasses and energy grasses. In this study, initial screening of a Brachypodium germplasm collection consisting of 138 different ecotypes exposed to progressive drought, highlighted the natural variation in morphology, biomass accumulation and responses to drought stress. A core set of ten ecotypes, classified as being either tolerant, susceptible or intermediate, in response to drought stress, were exposed to mild or severe (respectively 15% and 0% soil water content drought stress and phenomic parameters linked to growth and colour changes were assessed. When exposed to severe drought stress, phenotypic data and metabolite profiling combined with multivariate analysis revealed a remarkable consistency in separating the selected ecotypes into their different pre-defined drought tolerance groups. Increases in several metabolites, including for the phytohormones jasmonic acid and salicylic acid, and TCA-cycle intermediates, were positively correlated with biomass yield and with reduced yellow pixel counts; suggestive of delayed senescence, both key target traits for crop improvement to drought stress. While metabolite analysis also separated ecotypes into the distinct tolerance groupings after exposure to mild drought stress, similar analysis of the phenotypic data failed to do so, confirming the value of metabolomics to investigate early responses to drought stress. The results highlight the potential of combining the analyses of phenotypic and metabolic responses to identify key mechanisms and markers associated with drought tolerance in both the Brachypodium
Katherine I Morley
Full Text Available National electronic health records (EHR are increasingly used for research but identifying disease cases is challenging due to differences in information captured between sources (e.g. primary and secondary care. Our objective was to provide a transparent, reproducible model for integrating these data using atrial fibrillation (AF, a chronic condition diagnosed and managed in multiple ways in different healthcare settings, as a case study.Potentially relevant codes for AF screening, diagnosis, and management were identified in four coding systems: Read (primary care diagnoses and procedures, British National Formulary (BNF; primary care prescriptions, ICD-10 (secondary care diagnoses and OPCS-4 (secondary care procedures. From these we developed a phenotype algorithm via expert review and analysis of linked EHR data from 1998 to 2010 for a cohort of 2.14 million UK patients aged ≥ 30 years. The cohort was also used to evaluate the phenotype by examining associations between incident AF and known risk factors.The phenotype algorithm incorporated 286 codes: 201 Read, 63 BNF, 18 ICD-10, and four OPCS-4. Incident AF diagnoses were recorded for 72,793 patients, but only 39.6% (N = 28,795 were recorded in primary care and secondary care. An additional 7,468 potential cases were inferred from data on treatment and pre-existing conditions. The proportion of cases identified from each source differed by diagnosis age; inferred diagnoses contributed a greater proportion of younger cases (≤ 60 years, while older patients (≥ 80 years were mainly diagnosed in SC. Associations of risk factors (hypertension, myocardial infarction, heart failure with incident AF defined using different EHR sources were comparable in magnitude to those from traditional consented cohorts.A single EHR source is not sufficient to identify all patients, nor will it provide a representative sample. Combining multiple data sources and integrating information on treatment and
Sadraeian, M.; Tsutae, F. M.; Moreira, H. H. T.; Araujo, A. P. U.; Guimarães, F. E. G.; Pincus, S. H.
Pulchellin is a type 2 of ribosome-inactivating proteins isolated from some seeds significantly growing in Brazil. It is a potent agent to inhibit the protein synthesis in cancer cells and also HIV-infected cells. Pulchellin can be conjugated to HIV monoclonal antibodies to specifically target the HIV-infected cells. To analyze the protein synthesis inhibition by Pulchellin, the intracellular localization of the immunoconjugate should be compared to Pulchellin. In this case, the intracellular trafficking of this protein in cells can be determined by confocal microscopy. In our study, we utilized Pulchellin to construct HIV monoclonal antibody-conjugated Pulchellin A chain in order to target HIV-infected lymphocyte cells. Afterward the conjugation was labeled with the superior Alexa Fluor 488 dye. As a subsequent step, we are interested in studying the intracellular trafficking pathway of this novel conjugation in HIV-infected cells by confocal microscopy. Moreover, possible quantitative methods for fluorescent labeling of the immunoconjugate during confocal microscopy will be investigated.
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.
Ngure, Kenneth; Vusha, Sophie; Mugo, Nelly; Emmanuel-Fabula, Mira; Ngutu, Mariah; Celum, Connie; Baeten, Jared M; Heffron, Renee
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.
Duan, Haiping; Pang, Zengchang; Zhang, Dongfeng
Objective: We perform a comprehensive heritability study on multiple phenotypes related to metabolic syndrome using Chinese twins to assess the genetic and environmental effects in determining the variation and covariation of the phenotypes in the Chinese population. Methods: The studied sample...... of the phenotypes. Conclusions: Our results showed significant genetic contributions to the sub-phenotypes of metabolic syndrome. Although pleiotropic genetic control may exist for some physiologically similar phenotypes, our results do not support a common genetic mechanism among the phenotypes covered in our...
Hogg, Robert S; Eyawo, Oghenowede; Collins, Alexandra B; Zhang, Wendy; Jabbari, Shahab; Hull, Mark W; Lima, Viviane Dias; Ahmed, Tareq; Kendall, Claire E; Althoff, Keri N; Justice, Amy C; Barrios, Rolando; Shoveller, Jeannie; Montaner, Julio S G
We sought to understand whether people living with HIV (PLHIV) ever on highly active antiretroviral therapy (ART) follow a pattern where morbidity is compressed into the last years of life or lessened as people age. We aimed to estimate health-adjusted life expectancy (HALE) among adults living with and without HIV, and examine dependency between causes of comorbidities. The Comparative Outcomes and Service Utilization Trends (COAST) study is a retrospective cohort of adults (≥20 years) including all known PLHIV and a 10% random sample of the general population of British Columbia, and with longitudinal data spanning from April 1, 1996, to Dec 31, 2012. We determined the prevalence of select comorbidities (cardiovascular, respiratory, liver, and renal diseases, and non-AIDS defining cancers because of their high prevalence among PLHIV) by age and sex by use of case-finding algorithms. Deaths were obtained from a vital event registry from British Columbia, Canada. Comorbid-specific HALE was estimated from 20 years of age by HIV status and sex. For each comorbidity, a healthy state was defined as the proportion of life expectancy comorbid-free, and was adjusted on the probability of occurrence of other different comorbidities. The sensitivity of HALE estimates was assessed to the sequencing of select comorbidities for the dependent comorbidity adjustments. Our sample consisted of electronic health records from 9310 HIV-infected and 510 313 uninfected adults over the period April 1, 1996, to Dec 31, 2012. These individuals contributed 49 605 deaths and 5 576 841 person-years over the study period. At exactly age 20 years, HALE was about 31 years (SD 0·16) among men living with HIV and 27 years (0·16) among women living with HIV. In the HIV-negative population, HALE was around 58 years (SD 0·02) for men and 63 years (0·02) for women. These results seem independent of ordering. However, PLHIV, particularly women living with HIV, had much shorter overall
Alcaide, Maria L; Chisembele, Maureen; Malupande, Emeria; Arheart, Kristopher; Fischl, Margaret; Jones, Deborah L
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, p<0.001). Neither IVP nor BV were associated with HIV 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/
Fan, Hongmin [Cancer Center, School of Public Health, West Virginia University, Morgantown, WV 265050-9190 (United States); Department of Epidemiology and Statistics, School of Public Health, Hebei United University, Hebei 063000 (China); Ducatman, Alan [Department of Occupational and Environmental Health, School of Public Health, West Virginia University (United States); Department of Medicine, School of Medicine, West Virginia University (United States); Clinical Translational Science Institute, West Virginia University (United States); Zhang, Jianjun [Department of Biostatistics, School Public Health, West Virginia University (United States)
Background: Gilbert syndrome (GS) is an inherited defect of bilirubin conjugation, most commonly caused by a gene mutation for the enzyme UGT1A. GS is known to affect the metabolism and excretion of drugs and xenobiotics. Perfluorocarbon compounds (PFCs) are bio-persistent environmental contaminants that affect metabolic regulation. In this study, we examined the associations of GS phenotype and serum PFCs in the C8 Health Study Population. Materials and methods: Using 2005–2006 data from a large PFC-exposure population survey, we compared serum PFCs concentrations between GS and non GS clinical phenotypes, in a cross sectional design, adjusting for standard risk factors, including age, BMI, smoking status, socioeconomic status and gender. Results: Among 10 PFC compounds considered, only perfluorohexanoic acid (PFHxA) was seen at a significantly higher concentration in GS men and women. Conclusion: PFHxA exposure may be associated with GS. Our findings do not support increased exposure in GS for other PFCs. - Highlights: • Most serum PFCs are not associated with clinically evident Gilbert syndrome. • However, serum perfluorohexanoic acid is positively associated. • The investigation addresses the clinical presentation, not the genetic mutation.
Charles Darwin used domesticated plants and animals as proof of principle for his theory on phenotypic evolution by means of natural selection. Inspired by Darwin's work, we developed an intercross between the wild boar and domestic pigs to study the genetic basis for phenotypic changes during domestication. The difference in coat color is controlled by two major loci. Dominant white color is due to two consecutive mutations in the KIT gene: a 450-kb duplication and a splice mutation. Black spotting is caused by the combined effect of two mutations in MC1R: a missense mutation for dominant black color and a 2-bp insertion leading to a frameshift. A major discovery made using this pedigree is the identification of a single-nucleotide substitution in intron 3 of the gene for insulin-like growth factor 2 (IGF2) that is underlying a quantitative trait locus affecting muscle growth, size of the heart, and fat deposition. The mutation disrupts the interaction with a repressor and leads to threefold increased IGF2 expression in postnatal muscle. In a recent study, we have identified the IGF2 repressor, and this previously unknown protein, named ZBED6, is specific for placental mammals and derived from a domesticated DNA transposon.
Hattori, Toshio; Kobayashi, Nobuyuki; Nagai, Hideaki; Chagan-Yasutan, Haorile; Telan, Elizabeth; Solante, Marietta B
Although the prevalence of pulmonary tuberculosis (TB) and HIV infection in Japan is low, careful monitoring of these two diseases is necessary. We conducted a nationwide survey on multidrug resistant (MDR)-TB (2011-2013) and HIV-TB (2007-2014) to understand the mode of prevention and the effect of therapy. A study on MDR-TB and HIV in San Lazaro Hospital (SLH) in the Philippines was also conducted. These studies introduced an international collaborative study against the global epidemics of HIV-TB/MDR-TB. The nationwide survey of MDR-TB was done in hospitals that treat TB patients in Japan from 2011 to 2013. The HIV-TB survey has been done every year since 2007. Classic information such as chest X-ray (CXR) as well as computed tomography (CT) results for each patient were analyzed. Likewise, the presence of a cavity, involved segments, and patterns of parenchymal lesion were assessed. Finally, tentative diagnosis and disease activity, bronchogenic spread of the lesion with CT, and bronchiectasis were recorded. At SLH, sputa of suspected cases were subjected to GeneXpert testing and HIV testing was performed on all TB patients. In the nationwide MDR survey in Japan, 171 patients were diagnosed as pulmonary MDR-TB (0.2% of total Mycobacterium tuberculosis (MTB) in Japan). Among them, 48 (28%) were foreigners and most were living in big cities. In Tokyo metropolitan areas, 27 out of 53 MDR-TB patients were foreigners: 13 were from China, 4 from the Philippines, and 3 from Myanmar. Thirty nine among 53 MDR-TB patients were cured or treatment was completed with favorable prognosis. Five deaths (9.4%) and six departures from Japan (11.3%) were noted. In the HIV-TB survey in National Hospitals, the HIV-positive rates on MTB were constantly low (0.23-0.46%) from 2007 to 2014. Among the reported 114 HIV-TB patients (0.37% of total MTB in National Hospitals), 17 were foreigners and 3 (2.6%) were MDR-TB cases (2 Chinese, 1 Japanese). Half of the HIV-TB patients have low CD4
Chadwick, D R; Hall, C; Rae, C; Rayment, Ml; Branch, M; Littlewood, J; Sullivan, A
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.
Rogers, Anna Joy; Weke, Elly; Kwena, Zachary; Bukusi, Elizabeth A; Oyaro, Patrick; Cohen, Craig R; Turan, Janet M
Repeat HIV testing in late pregnancy has the potential to decrease rates of mother-to-child transmission of HIV by identifying mothers who seroconvert after having tested negative for HIV in early pregnancy. Despite being national policy in Kenya, the available data suggest that implementation rates are low. We conducted 20 in-depth semi-structured interviews with healthcare providers and managers to explore barriers and enablers to implementation of repeat HIV testing guidelines for pregnant women. Participants were from the Nyanza region of Kenya and were purposively selected to provide variation in socio-demographics and job characteristics. Interview transcripts were coded and analyzed in Dedoose software using a thematic analysis approach. Four themes were identified a priori using Ferlie and Shortell's Framework for Change and additional themes were allowed to emerge from the data. Participants identified barriers and enablers at the client, provider, facility, and health system levels. Key barriers at the client level from the perspective of providers included late initial presentation to antenatal care and low proportions of women completing the recommended four antenatal visits. Barriers to offering repeat HIV testing for providers included heavy workloads, time limitations, and failing to remember to check for retest eligibility. At the facility level, inconsistent volume of clients and lack of space required for confidential HIV retesting were cited as barriers. Finally, at the health system level, there were challenges relating to the HIV test kit supply chain and the design of nationally standardized antenatal patient registers. Enablers to improving the implementation of repeat HIV testing included client dissemination of the benefits of antenatal care through word-of-mouth, provider cooperation and task shifting, and it was suggested that use of an electronic health record system could provide automatic reminders for retest eligibility. This study
Ali, Solomon Ahmed; Mavundla, Thandisizwe R; Fantu, Ribka; Awoke, Tadesse
TB and HIV are the most prevalent communicable diseases of major public health importance in the populations of sub-Saharan African countries, and an estimated 30 % of HIV infected persons have dual infection with TB. TB is the leading cause of death in HIV infected individuals, and HIV co-infected TB patients have multiple individual, disease specific and treatment related factors that can adversely affect their treatment outcomes. There is lack of evidence on the individual patient outcomes of HIV co-infected TB patients who receive anti-TB treatment. It is relevant to understand the differential patient outcomes of HIV co-infected TB patients and identify the factors that are associated with these outcomes. A comparative analysis was done on the data from a random sample of 575 TB patients who were enrolled for TB treatment from January 2013 to December 2013 at eight health facilities in Ethiopia. A descriptive analysis was done on the data, and chi-square test and logistic regression analysis was conducted to compare TB treatment outcomes based on HIV status and to identify factors associated with these outcomes. Out of a total of 575 TB patients enrolled into the study, 360 (62.6 %) were non-HIV infected, 169 (29.4 %) were HIV co-infected, and 46 (8 %) had no documented HIV status. The overall treatment success rate was 91.5 % for all the study participants. HIV co-infected TB patients have a treatment success rate of 88.2 % compared with 93.6 % for non-HIV infected study participants (P = 0.03). HIV co-infected TB patients had a significantly higher rate (11.8 % versus 6.4 %, P = 0.03) of unfavourable outcomes. The cure rate was significantly lower (10.1 % versus 24.2 %, P = 0.001) and the death rate higher in HIV co-infected TB patients (8.3 % versus 2.5 %, P = 0.014). Age and TB classification were significantly associated with treatment outcome. No association was found with starting ART, Cotrimoxazole prophylactic treatment or enrolment in
Lucette A Cysique
Full Text Available 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 (p<.04 and higher myo-inositol (mIo (p<.04; in the caudate: lower NAA (p = .01; and in the posterior cingulate cortex: higher mIo (p<.008- also significant when Holm-Sidak corrected and higher Choline/NAA (p<.04. Regression models showed that an HIV*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
... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ... to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. Some ...
Eliud Wekesa; Ernestina Coast
Objectives Fertility desires require new understanding in a context of expanding access to antiretroviral therapy for people living with HIV/AIDS in Sub-Saharan Africa. This paper studies the fertility desires and their rationales, of slum-dwelling Kenyan men and women living with HIV/AIDS who know their serostatus, but have different antiretroviral therapy treatment statuses. It addresses two research questions: How do people living with HIV/AIDS consider their future fertility? What factors...
Garin, Noe; Zurita, Beatriz; Velasco, Cesar; Feliu, Anna; Gutierrez, Mar; Masip, Montserrat; Mangues, M Antonia
Objectives: Drug interactions, poor adherence to medication and high-risk sexual behaviour may occur in individuals with HIV using recreational drugs. Thus, we aimed to assess the prevalence of recreational drugs use and to explore its clinical impact in HIV patients on treatment. Methods: Observational, cross sectional, study conducted in a 700 bed university hospital, Barcelona, Spain. A total of 208 adults living with HIV on treatment were included. A questionnaire was administered by ...
Thompson Sandra C; Li Jianghong; Nattabi Barbara; Orach Christopher G; Earnest Jaya
Abstract Background Northern Uganda experienced severe civil conflict for over 20 years and is also a region of high HIV prevalence. This study examined knowledge of, access to, and factors associated with use of family planning services among people living with HIV (PLHIV) in this region. Methods Between February and May 2009, a total of 476 HIV clinic attendees from three health facilities in Gulu, Northern Uganda, were interviewed using a structured questionnaire. Semi-structured interview...
Parisi, Maria Rita; Soldini, Laura; Vidoni, Gianmarino; Clemente, Felice; Mabellini, Chiara; Belloni, Teresa; Nozza, Silvia; Brignolo, Livia; Negri, Silvia; Rusconi, Stefano; Schlusnus, Karin; Dorigatti, Fernanda; Lazzarin, Adriano
The submerged portion of undiagnosed HIV infection in Italy is about 30% of subjects found seropositive. This fact represents one of the most important public health problems hindering the control of infection progression. This means we need to fight unawareness and social stigma and promote easy and friendly access to HIV test. We developed a Prevention Program called “EASY test Project”, offering a new rapid HIV test on oral fluid, to evaluate the acceptability of an alternative, free and anonymous test available in different settings (on board a “Motor Home” at public events, Points of Care, STDs outpatient prevention units and GP surgeries). From December 2008 to December 2012 we performed 7,865 HIV saliva tests, with 50 new infections found (0.6% of the total) out of 140,000 informed subjects. From the self-reported characteristics of respondents, the population approaching the EAST test project was represented by males (70%) aged between 20 and 50 years, 61% with a medium-high education level, 62% homosexuals (MSM), 88% reported unsafe sexual behaviours, and 48% had never undergone an HIV screening test. In five years of the Prevention Program, 100% of subjects interviewed gave a general favorable consent in approaching rapid and not invasive screening, immediate return of the result, and a timely specialized approach and treatment of HIV positive subjects. Results from our study confirm that the rapid and alternative test may contribute to HIV prevention strategies and to the control of the spread of infection and HIV disease progression by reaching a larger population, particularly when and where regular screening procedures are difficult to obtain or are not preferred.
Elizabeth F Closson
Full Text Available The success of global treatment as prevention (TasP efforts for individuals living with HIV/AIDS (PLWHA is dependent on successful implementation, and therefore the appropriate contribution of social and behavioral science to these efforts. Understanding the psychosocial context of condomless sex among PLWHA could shed light on effective points of intervention. HPTN 063 was an observational mixed-methods study of sexually active, in-care PLWHA in Thailand, Zambia, and Brazil as a foundation for integrating secondary HIV prevention into HIV treatment. From 2010-2012, 80 qualitative interviews were conducted with PLWHA receiving HIV care and reported recent sexual risk. Thirty men who have sex with women (MSW and 30 women who have sex with men (WSM participated in equal numbers across the sites. Thailand and Brazil also enrolled 20 biologically-born men who have sex with men (MSM. Part of the interview focused on the impact of HIV on sexual practices and relationships. Interviews were recorded, transcribed, translated into English and examined using qualitative descriptive analysis. The mean age was 25 (SD = 3.2. There were numerous similarities in experiences and attitudes between MSM, MSW and WSM across the three settings. Participants had a high degree of HIV transmission risk awareness and practiced some protective sexual behaviors such as reduced sexual activity, increased use of condoms, and external ejaculation. Themes related to risk behavior can be categorized according to struggles for intimacy and fears of isolation, including: fear of infecting a sex partner, guilt about sex, sexual communication difficulty, HIV-stigma, and worry about sexual partnerships. Emphasizing sexual health, intimacy and protective practices as components of nonjudgmental sex-positive secondary HIV prevention interventions is recommended. For in-care PLWHA, this approach has the potential to support TasP. The overlap of themes across groups and countries
Saddiq, Abdullahi; Tolhurst, Rachel; Lalloo, David; Theobald, Sally
Literature on the links between polygamy and HIV and AIDS is limited and the findings inconclusive. Literature to date in Sub-Saharan Africa has relied mainly on case-control studies and surveys. This qualitative study aimed to explore different community members' perceptions of the links between the practice of polygamy and vulnerability or resilience to HIV and AIDS in Maiduguri, north-eastern Nigeria. The study used focus group discussions and in-depth interviews with religious and community leaders and different groups of women and men in the community. Participant views on the links between polygamy and HIV were varied. However, one clear emerging theme was that it is not the practice of polygamy per se that shapes vulnerability to HIV and AIDS but the dynamics of sexual relations and practices both within and beyond the marital union--whether monogamous or polygamous. The ways in which these social relationships are negotiated and experienced are in turn shaped by religious traditions, gender roles and relations, education and socio-economic status. Within the religious environment of north-eastern Nigeria, where asymmetrical gender roles and relations and connotations of morality shape experiences of sexual interactions, windows of opportunity to promote behaviour-change strategies to support women and men's resilience to HIV need to be carefully created. Health practitioners and planners should develop partnerships with religious and community leaders and women's groups to construct and deliver behaviour-changes strategies.
Full Text Available Introduction: Knowledge of antiretroviral therapy (ART among children with HIV depends on open communication with them about their health and medicines. Guidelines assign responsibility for communication to children's home caregivers. Other research suggests that communication is poor and knowledge about ART is low among children on treatment in low-income countries. This study sought to describe communication about medicine for HIV in quantitative terms from the perspectives of both children and caregivers. Thereafter, it established the factors associated with this communication and with children's knowledge about their HIV medicines. Methods: We undertook a cross-sectional survey of a random sample of 394 children with HIV on treatment and their caregivers at nine health facilities in Jinja District, Uganda. We assessed reported frequency and content of communication regarding their medicines as well as knowledge of what the medicines were for. Logistic regression analysis was used to determine the factors associated with communication patterns and children's knowledge of HIV medicines. Results: Although 79.6% of the caregivers reported that they explained to the children about the medicines, only half (50.8% of the children said they knew that they were taking medicines for HIV. Older children aged 15–17 years were less likely to communicate with a caregiver about the HIV medicines in the preceding month (OR 0.5, 95% CI 0.3–0.7, p=0.002. Children aged 11–14 years (OR 6.1, 95% CI 2.8–13.7, p<0.001 and 15–17 years (OR 12.6, 95% CI 4.6–34.3, p<0.001 were more likely to know they were taking medicines for HIV compared to the younger ones. The least common reported topic of discussion between children and caregivers was “what the medicines are for” while “the time to take medicines” was by far the most mentioned by children. Conclusions: Communication about, and knowledge of, HIV medicines among children with HIV is low. Young
Druley, Todd E; Wang, Lihua; Lin, Shiow J;
BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...... that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). CONCLUSIONS: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants....
Moni, Mohammad Ali; Liò, Pietro
Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says "I'd rather have HIV than diabetes" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable
Ellegård, Rada; Crisci, Elisa; Andersson, Jonas; Shankar, Esaki M.; Nyström, Sofia; Hinkula, Jorma
Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNγ and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection. PMID:26157174
Ramírez-Prado, Dolores; Cortés, Ernesto; Aguilar-Segura, María Soledad; Gil-Guillén, Vicente Francisco
In January 2012, a review of the cases of chromosome 15q24 microdeletion syndrome was published. However, this study did not include inferential statistics. The aims of the present study were to update the literature search and calculate confidence intervals for the prevalence of each phenotype using bootstrap methodology. Published case reports of patients with the syndrome that included detailed information about breakpoints and phenotype were sought and 36 were included. Deletions in megabase (Mb) pairs were determined to calculate the size of the interstitial deletion of the phenotypes studied in 2012. To determine confidence intervals for the prevalence of the phenotype and the interstitial loss, we used bootstrap methodology. Using the bootstrap percentiles method, we found wide variability in the prevalence of the different phenotypes (3–100%). The mean interstitial deletion size was 2.72 Mb (95% CI [2.35–3.10 Mb]). In comparison with our work, which expanded the literature search by 45 months, there were differences in the prevalence of 17% of the phenotypes, indicating that more studies are needed to analyze this rare disease. PMID:26925314
Mathew, Mili Mary; Bhat, Jayashree S
Communication is the very essence of life for humans. This is made possible by the highly complex neurophysiological mechanisms governing humans. Any disturbance to this system can result in impairments of communication. HIV infection is one such disease. In India, the management of such individuals is usually restricted to life sustenance. Little importance is given to their communication problems, which play a vital role in day-to-day functioning. It is with this background that this study was conducted. Eight HIV-infected individuals participated in the study. They were subjected to assessment procedures that included the following tests: Western Aphasia Battery, Frenchay Dysarthria Assessment, Standard Articulation test, Fluency test, and subjective assessment of vocal parameters by a speech language pathologist. The results of the study reveal that individuals with HIV-1 infection show a varied picture of affected parameters of voice, swallowing, and oral motor functioning.
Li, Nan; Sando, Mary Mwanyika; Spiegelman, Donna; Hertzmark, Ellen; Liu, Enju; Sando, David; Machumi, Lameck; Chalamilla, Guerino; Fawzi, Wafaie
Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy.
Venizelos, Ioannis; Tamiolakis, Demetrio; Lambropoulou, Maria; Nikolaidou, Sylva; Bolioti, Sophia; Papadopoulos, Hlias; Papadopoulos, Nikolas
Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin's lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/microL). Occasionally, it appears in other immunodepressive states (such as solid organs transplant period) and even, although very rarely, in immunocompetent patients. From a pathogenetic point of view, PEL has been related to Kaposi's sarcoma associated herpes virus (also named human herpesvirus 8, HHV-8), an etiological factor of Kaposi's sarcoma. The relative infrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome support the need of a deeper knowledge. We present here the clinical-biological findings of a patient, HIV seronegative, who was diagnosed with peritoneal PEL of T-cell origin, and not HHV-8-associated, five years after renal transplantation.
Cao, Z K; Huang, Y; Yu, H J; Yuan, S; Tang, B W; Li, Q X; Li, X T; Yang, X H; He, Q Q
To explore the association between obesity phenotype and the risk of hypertension among Chinese adults. A prospective cohort study. Two waves of data were collected in 2009 and 2011 by the China Health Nutrition Survey. According to International Diabetes Federation and Chinese obesity criteria, participants were divided into four groups: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). Logistic regression model was performed to estimate the risk of hypertension with obesity phenotype. Among a total of 4604 adults aged 18-65 years at baseline, 467 developed hypertension during the 2-year follow-up period. After adjusting for several potential confounders, significantly increased risks for hypertension were found for participants in MHO (odd ratio [OR]: 1.78, 95% confidence interval [CI]: 1.39-2.27), MANO (OR: 1.71, 95% CI: 1.02-2.86), and MAO (OR: 3.35, 95% CI: 2.54-4.42) group compared with the MHNO group. Metabolically abnormal individuals, regardless of their body weight status, showed significantly higher risks for hypertension compared with healthy non-overweight/obese group. Furthermore, MHO individuals had significantly increased risk of incident hypertension. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Biobaku Oluwafunmilola, R; Olaleye Atinuke, O; Adefusi Olorunwa, F; Adeyemi Babalola, A; Onipede Anthony, O; Loto Olabisi, M; Imaralu John, O
Group B streptococcus (GBS) is a leading cause of maternal and neonatal infectious morbidity. HIV is prevalent among pregnant women in Nigeria. To determine the rates of anogenital GBS colonization in our institution and compare GBS colonization rates between HIV positive and negative pregnant women. A cross-sectional comparative study was conducted over 6 months. Patients were separated according to their HIV status: positive and negative. GBS colonization was assessed by vaginal and anal swabs collected at 35-37 weeks of gestation and cultured in Todd-Hewitt broth, followed by a confirmatory test. Socio-demographic characteristics and CD4 count were extracted from patient medical records. Secondary outcomes were identification of risk factors for GBS colonization, antibiotic sensitivity, and any association between CD4 count and GBS colonization. Appropriate statistical analysis was done. A total of 200 patients attended the clinic; 67 HIV positive and 133 negative. Analyzed samples were 198; the overall prevalence of GBS was 18.2%. No significant difference in GBS colonization was noted between HIV positive (19.4% ) and negative patients (17.6% [23/131]). Most GBS isolates were susceptible to ampicillin (87%) and penicillin (81%). A high body mass index (BMI) was independently associated with GBS colonization (OR = 1.25, 95% CI: 1.04-1.51). No association was observed between CD4 counts and GBS colonization. A high prevalence of GBS colonization was observed in our institution. Colonization rates were independent of the HIV status but associated with a high BMI in HIV positive women.
Goldberg, D. J.; MacKinnon, H.; Smith, R.; Patel, N. B.; Scrimgeour, J. B.; Inglis, J. M.; Peutherer, J. F.; Urquhart, G. E.; Emslie, J. A.; Covell, R. G.
OBJECTIVE--To determine the prevalence of HIV among pregnant women, in particular those whose behaviour or that of their partners put them at "low risk" of infection. DESIGN--Voluntary named or anonymous HIV testing of pregnant women during 21 months (November 1988 to July 1990). SUBJECTS AND SETTING--All women who planned to continue their pregnancy and attended clinics serving the antenatal populations of Edinburgh and Dundee. All women admitted for termination of pregnancy to gynaecology wards serving the pregnant populations of Dundee and outlying rural areas. MAIN OUTCOME MEASURES--Period prevalence of HIV antibody positivity. RESULTS--91% of antenatal clinic attenders and 97% of women having termination of pregnancy agreed to HIV testing on a named or anonymous basis. HIV period prevalences for antenatal clinic attenders and women having termination of pregnancy tested in Dundee were 0.13% and 0.85% respectively, and for antenatal clinic attenders tested in Edinburgh 0.26%. For those at "low risk" rates for antenatal clinic attenders and women having termination of pregnancy in Dundee were 0.11% and 0.13%, and for antenatal clinic attenders in Edinburgh 0.02%. In Dundee HIV prevalence among women having a termination of pregnancy (0.85%) was significantly greater than that among antenatal clinic attenders (0.13%). CONCLUSIONS--HIV infection is undoubtedly occurring among women at "low risk," and it is clear that a policy of selective testing of those at only "high risk" is inadequate for pregnant women living in areas of high prevalence such as Edinburgh and Dundee. Moreover, when studying pregnant populations in such areas there is the need to include those having a termination of pregnancy. PMID:1586820
Koff, Wayne C; Russell, Nina D; Walport, Mark; Feinberg, Mark B; Shiver, John W; Karim, Salim Abdool; Walker, Bruce D; McGlynn, Margaret G; Nweneka, Chidi Victor; Nabel, Gary J
Human immunodeficiency virus (HIV), the etiologic agent that causes AIDS, is the fourth largest killer in the world today. Despite the remarkable achievements in development of anti-retroviral therapies against HIV, and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. Currently, there is a renaissance in HIV vaccine development, due in large part to the first demonstration of vaccine induced protection, albeit modest, in human efficacy trials, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined targets on HIV for broadly neutralizing antibodies. The main barriers to HIV vaccine development include the global variability of HIV, lack of a validated animal model, lack of correlates of protective immunity, lack of natural protective immune responses against HIV, and the reservoir of infected cells conferred by integration of HIV's genome into the host. Some of these barriers are not unique to HIV, but generic to other variable viral pathogens such as hepatitis C and pandemic influenza. Recommendations to overcome these barriers are presented in this document, including but not limited to expansion of efforts to design immunogens capable of eliciting broadly neutralizing antibodies against HIV, expansion of clinical research capabilities to assess multiple immunogens concurrently with comprehensive immune monitoring, increased support for translational vaccine research, and engaging industry as full partners in vaccine discovery and development.
Abraham, Alison G; Strickler, Howard D; Jing, Yuezhou; Gange, Stephen J; Sterling, Timothy R; Silverberg, Michael; Saag, Michael; Rourke, Sean; Rachlis, Anita; Napravnik, Sonia; Moore, Richard D; Klein, Marina; Kitahata, Mari; Kirk, Greg; Hogg, Robert; Hessol, Nancy A; Goedert, James J; Gill, M John; Gebo, Kelly; Eron, Joseph J; Engels, Eric A; Dubrow, Robert; Crane, Heidi M; Brooks, John T; Bosch, Ronald; D’Souza, Gypsyamber
Objective HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women. Methods Data were obtained from HIV-infected and -uninfected female participants in the NA-ACCORD with no history of ICC at enrollment. Participants were followed from study entry or January, 1996 through ICC, loss-to follow-up or December, 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios (SIR). All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction. Results A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years (pys) of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 pys, respectively). HIV-infected women with baseline CD4+ T-cells of ≥ 350, 200–349 and <200 cells/uL had a 2.3-times, 3.0-times and 7.7-times increase in ICC incidence, respectively, compared with HIV-uninfected women (Ptrend =0.001). Of the 17 HIV-infected cases, medical records for the 5 years prior to diagnosis showed that 6 had no documented screening, 5 had screening with low grade or normal results, and 6 had high-grade results. Conclusions This study found elevated incidence of ICC in HIV-infected compared to -uninfected women, and these rates increased with immunosuppression. PMID:23254153
Rasmussen, Line D; Omland, Lars H; Pedersen, Court
associated with the HIV disease and HAART or whether life-style related or genetic factors also increase the risk in this population. To establish whether the increased risk of myocardial infarction in HIV patients partly reflects an increased risk of MI in their families, we estimated the relative risk...... of MI in parents of HIV-infected individuals METHODS: From the Danish HIV Cohort Study and the Danish Civil Registration System we identified the parents of all HIV-infected patients born in Denmark after 1952 in whom a Danish born mother was identifiable. For each HIV patient, 4 matched population...... controls and their parents were identified. Cumulative incidence functions were constructed to illustrate time to first MI of the parents as registered in the Danish National Hospital Registry. Incidence rate ratios (IRR) were estimated by Cox's regression analyses. Due to the confidential type...
Jones, Jamal; Salazar, Laura F
This review describes the use of social networking sites (SNS) in the context of primary prevention of HIV. A review was conducted to assess the published literature for HIV interventions using SNS. Sixteen articles describing twelve interventions were included. SNS were instrumental in recruiting hard-to-reach populations within a short amount of time; were able to reach wide audiences beyond the targeted population for HIV prevention campaigns; and helped to significantly reduce sexual risk behaviors and increase HIV testing. SNS are a viable option to recruit hidden populations, engage the target audience, and disseminate HIV prevention messages. Researchers should use SNS to generate sampling frames that can be used to select participants. Practitioners should use SNS to post images of preventive behavior within health promotion campaigns. Researchers should use multiple SNS platforms to engage participants. As more studies are published using SNS for HIV prevention, meta-analyses will be needed.
Capoccia, A; Ranieri, R; Busnelli, M; Passaretti, B; Milella, A M; Vecchi, L
Prisoners are considered to be a high risk population for HIV and HBV infection. Aim of this study was to determine the prevalence of HIV, HBV infection and of the VDRL false positivity by performing screening tests in 496 prisoners of Monza in 1987. About a third of prisoners was HIV infected (with a high prevalence in drug addicts) and about a half had a contact with HBV virus. We observed a very common association between HIV and HBV infections. About ten per cent of HIV infected presented a false positivity for VDRL while one per cent of not infected did. Our data show that in Italian prison HIV and HBV infections are spreadly diffused. False positivity for VDRL may be due not only to drug addiction but also to the immunological variations connected with AIDS.
António L. Moreira
Full Text Available Access to free antiretroviral therapy (ART in Sub-Saharan Africa has been steadily increasing over the past decade. However, the success of large-scale ART programmes depends on timely diagnosis and early initiation of HIV care. This study characterizes late presenters to HIV care in Santiago (Cape Verde between 2004 and 2011, and identifies factors associated with late presentation for care. We defined late presentation as persons presenting to HIV care with a CD4 count below 350 cells/mm3. An unmatched case-control study was conducted using socio-demographic and behavioural data of 368 individuals (191 cases and 177 controls collected through an interviewer-administered questionnaire, comparing HIV patients late and early presented to care. Logistic regression was performed to estimate odds ratio and 95% confidence intervals. Results show that 51.9% were late presenters for HIV. No differences were found in gender distribution, marital status, or access to health services between cases and controls. Participants who undertook an HIV test by doctor indication were more likely to present late compared with those who tested for HIV by their own initiative. Also, individuals taking less time to initiate ART are more likely to present late. This study highlights the need to better understand reasons for late presentation to HIV care in Cape Verde. People in older age groups should be targeted in future approaches focused on late presenters to HIV care.
Moreira, António L.; Fronteira, Inês; Augusto, Gonçalo Figueiredo; Martins, Maria Rosario O.
Access to free antiretroviral therapy (ART) in Sub-Saharan Africa has been steadily increasing over the past decade. However, the success of large-scale ART programmes depends on timely diagnosis and early initiation of HIV care. This study characterizes late presenters to HIV care in Santiago (Cape Verde) between 2004 and 2011, and identifies factors associated with late presentation for care. We defined late presentation as persons presenting to HIV care with a CD4 count below 350 cells/mm3. An unmatched case-control study was conducted using socio-demographic and behavioural data of 368 individuals (191 cases and 177 controls) collected through an interviewer-administered questionnaire, comparing HIV patients late and early presented to care. Logistic regression was performed to estimate odds ratio and 95% confidence intervals. Results show that 51.9% were late presenters for HIV. No differences were found in gender distribution, marital status, or access to health services between cases and controls. Participants who undertook an HIV test by doctor indication were more likely to present late compared with those who tested for HIV by their own initiative. Also, individuals taking less time to initiate ART are more likely to present late. This study highlights the need to better understand reasons for late presentation to HIV care in Cape Verde. People in older age groups should be targeted in future approaches focused on late presenters to HIV care. PMID:26999167
Bordoni, V; Casetti, R; Capuano, G; De Stefani, B; Piselli, P; Gioia, C; Agrati, C; Martini, F
Multicolor flow cytometry allows to study the markers differentially expressed during maturation, activation, function and senescence on immune cells. Despite the availability of reagents and technology, scarce agreement has been gained regarding phenotypic markers of HIV disease progression other than CD4 T-cell count. In this work, we present a novel high-throughput global analysis of CD4 and CD8 T-lymphocyte profiles by standardized 8-color combinations of antibodies aimed at analyzing HIV disease course progression. For this purpose, two tubes with lyophilized reagent cocktails (CD4- and CD8-specific tubes) were designed to compare the immunological characteristics of HIV-infected persons (37 "high CD4" HAART-treated and 32 "low CD4" naïve or failed-treatment patients) with healthy donors (HD). In particular, T-cell activation (CD25, CD38, CD69), differentiation (CD45RA, CCR7), apoptosis (CD95) and immune suppression profiles (CD25(high)CD127-) in HIV+ patients were compared with HD. Statistical analysis was performed by identifying the parameters associated with disease progression, namely markers that were found to be significantly different between groups with high CD4 counts (including HD) and low CD4 counts (restricted to HIV patients) but not between the HD and the "high CD4" group. This set of markers, including those identifying different maturation and senescence subtypes of CD4 and CD8 T cells, was found to be associated with therapy failure, and it is in fact evaluated in an ongoing study aimed to verify its prognostic value. This robust assay was found feasible on a semi-routine scale for HIV-infected persons, and allows for broader clinical studies aimed at defining markers associated with treatment outcome, possibly having a high impact on the clinical management of HIV disease.
Atav, A Serdar; Sendir, Merdiye; Darling, Rosa; Acaroglu, Rengin
Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a complex healthcare problem. Research has demonstrated that negative attitudes affect healthcare provision. The purpose of this study was to compare nursing students' attitudes using the AIDS Attitude Scale (AAS). A descriptive, cross-sectional study was conducted in nursing schools in Istanbul, Turkey, and in Upstate New York (NY). Baccalaureate nursing students (n = 613) from both countries completed the questionnaire. Demographic data, overall AAS attitudes, and attitudes within each subscale were compared. Analyses included frequency and percentages of the grouped variables, arithmetic means and standard deviations, t-test for independent samples, and multiple analysis of variance. Upstate NY students' mean total AAS scores were significantly more positive toward HIV+ patients than Turkish students'. Scores for Professional Resistance and Emotions subscales were significantly more positive for the Upstate NY students, but Fear of Contagion was not. Upstate NY students had more negative attitudes in the contexts of job risk and eating in a restaurant where the chef has AIDS; more professional resistance to referring patients and training specialists for HIV/AIDS patients; and lower tender feelings for people with HIV/AIDS (p < .01 for each). Improvement in students' attitudes is beneficial for promoting nonjudgmental, compassionate care for the HIV+ population. © 2014 Wiley Periodicals, Inc.
Full Text Available Although India is in the grip of HIV/AIDS epidemic, not much information is available on clinico-epidemiological and socio-behavioral aspects of people living with HIV/AIDS (PLWHA. This study analyzed these features using standard methodologies in 82 HIV sero-positives, AIDS patients attending ART clinic of three major government hospitals of Delhi. Majority of the patients (73% were found to be young (<40 years and married (79%. As high as 91.5% came from low socio-economic class and more than 95% acquired HIV transmission through heterosexual routes. A large proportion (63% of these patients reported an extremely high level of anxiety, moderate level of stress and a borderline level of clinical depression. While most of the patients (72% were well-adjusted with the ART, the rest of the patients reported difference in making adjustment with the treatment schedules. The study suggests that counseling and supportive therapy could play a pivotal role in controlling anxiety, stress, depression and rehabilitating people with HIV/AIDS.
Full Text Available Background: Living with HIV is of daily concern for many South Africans and poses challenges including adapting to a chronic illness and continuing to achieve and meet social expectations. This study explored experiences of being HIV-positive and how people manage stigma in their daily social interactions. Methods: Using qualitative methods we did repeat interviewed with 42 HIV-positive men and women in Cape Town and Mthatha resulting in 71 interviews. Results: HIV was ubiquitous in our informants’ lives, and almost all participants reported fear of stigma (perceived stigma, but this fear did not disrupt them completely. The most common stigma experiences were gossips and insults where HIV status was used as a tool, but these were often resisted. Many feared the possibility of stigma, but very few had experiences that resulted in discrimination or loss of social status. Stigma experiences were intertwined with other daily conflicts and together created tensions, particularly in gender relations, which interfered with attempts to regain normality. Evidence of support and resistance to stigma was common, and most encouraging was the evidence of how structural interventions such as de-stigmatizing policies impacted on experiences and transference into active resistance. Conclusions: The study showed the complex and shifting nature of stigma experiences. These differences must be considered when we intensify stigma reduction with context- and gender-specific strategies focussing on those not yet on ARV programmes.
Sandra C. Fuchs
Full Text Available Cardiovascular disease has emerged as a crescent problem among HIV-infected population. This study aimed to determine the 10-year risk of coronary heart disease using the Framingham risk score among HIV-infected patients from three regions of Brazil. This is a pooled analysis of three cohort studies, which enrolled 3,829 individuals, 59% were men, 66% had white skin color, and mean age 39.0 ± 9.9 years. Comparisons among regions showed that there were marked differences in demographic, socioeconomic, clinical, and HIV-related characteristics. Prevalence of Framingham score ≥10 was 4.5% in the Southern, 4.2% in the Midwest, and 3.9% in the Northeast of Brazil. The Framingham score ≥10 was similar between regions for males, patients aged ≥60 years, with obesity, central obesity, hypertension, and diabetes mellitus. Women were three times more likely to have coronary heart disease in 10 years than men. Hypertension and diabetes increased more than four times the risk of coronary heart disease, followed by central obesity, obesity, and prehypertension. The use of antiretroviral agents and time since HIV diagnosis were not risk factors for coronary artery disease in 10 years. In conclusion, hypertension and diabetes are the strongest independent predictors of 10-year risk of coronary heart disease among HIV-infected population.
Tene, Larissa; Tagny, Claude T.; Mintya-Ndoumba, Annick; Fossi, Vincent N.; Mbanya, Dora
Bleeding disorders are haematological manifestations that are frequently observed during HIV infection. This study intends to describe the haemostatic trends in HIV-infected patients in Cameroon. This cross-sectional descriptive study was carried out at the haematology unit of the Yaoundé University Teaching Hospital from March to June 2012. It included consenting HIV-positive patients, aged 18 years and above, naive to antiretroviral treatment or not. The coagulation profile was measured with Stago reagents (Stago Diagnostics, Asnières sur Seine, France) using a chronometric technique on a semi-automate (Stago Diagnostics). Platelets count was estimated on a human count automate (Human diagnostic, Wiesbaden, Germany) by flow cytometry. A total of 139 HIV-infected patients were included in this study, out of which 106 were females (76.3%) against 33 (23.7%) males, giving a sex ratio of 0.3 (M/F). Mean age was 38.85 years (range 22–73 years) and median CD4 count was 353 cells/μl (Interquartile range 200–500 cells/μl). Hyperfibrinogenaemia was the most frequent bleeding disorder in the studied population [40 of 139 (28.78%)], followed by low prothrombin time (PT) [22 of 139 (15.83%)], thrombocytopenia [19 of 139 (13.67%)], hypofibrinogenaemia [18 of 139 (12.95)], prolonged activated partial thromboplastin time (7.91) and by thrombocytosis which was less frequent [6 of 139 (4.32%)]. Out of the six haemostatic disorders, only low PT was significantly associated with CD4 count (P=0.02). This study showed that bleeding disorders are very frequent in the HIV-infected patients studied. Low PT was significantly associated with CD4 count, hence it may be recommended to systematic screen for bleeding disorders in severe immune-depressed (CD4 ≤ 200) HIV-infected patients. PMID:24469390
Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene
FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.
Kang, Guolian; Bi, Wenjian; Zhao, Yanlong; Zhang, Ji-Feng; Yang, Jun J; Xu, Heng; Loh, Mignon L; Hunger, Stephen P; Relling, Mary V; Pounds, Stanley; Cheng, Cheng
We propose in this paper a set-valued (SV) system model, which is a generalized form of logistic (LG) and Probit (Probit) regression, to be considered as a method for discovering genetic variants, especially rare genetic variants in next-generation sequencing studies, for a binary phenotype. We propose a new SV system identification method to estimate all underlying key system parameters for the Probit model and compare it with the LG model in the setting of genetic association studies. Across an extensive series of simulation studies, the Probit method maintained type I error control and had similar or greater power than the LG method, which is robust to different distributions of noise: logistic, normal, or t distributions. Additionally, the Probit association parameter estimate was 2.7-46.8-fold less variable than the LG log-odds ratio association parameter estimate. Less variability in the association parameter estimate translates to greater power and robustness across the spectrum of minor allele frequencies (MAFs), and these advantages are the most pronounced for rare variants. For instance, in a simulation that generated data from an additive logistic model with an odds ratio of 7.4 for a rare single nucleotide polymorphism with a MAF of 0.005 and a sample size of 2,300, the Probit method had 60% power whereas the LG method had 25% power at the α = 10(-6) level. Consistent with these simulation results, the set of variants identified by the LG method was a subset of those identified by the Probit method in two example analyses. Thus, we suggest the Probit method may be a competitive alternative to the LG method in genetic association studies such as candidate gene, genome-wide, or next-generation sequencing studies for a binary phenotype.
Kang, Guolian; Bi, Wenjian; Zhao, Yanlong; Zhang, Ji-Feng; Yang, Jun J.; Xu, Heng; Loh, Mignon L.; Hunger, Stephen P.; Relling, Mary V.; Pounds, Stanley; Cheng, Cheng
We propose in this paper a set-valued (SV) system model, which is a generalized form of Logistic (LG) and Probit (Probit) regression, to be considered as a method for discovering genetic variants, especially rare genetic variants in next generation sequencing studies, for a binary phenotype. We propose a new set-valued system identification method to estimate all the underlying key system parameters for the Probit model and compare it with the LG model in the setting of genetic association studies. Across an extensive series of simulation studies, the Probit method maintained Type I error control and had similar or greater power than the LG method which is robust to different distributions of noise: logistic, normal or t distributions. Additionally, the Probit association parameter estimate was 2.7–46.8 fold less variable than the LG log-odds ratio association parameter estimate. Less variability in the association parameter estimate translates to greater power and robustness across the spectrum of minor allele frequencies (MAFs), and these advantages are the most pronounced for rare variants. For instance, in a simulation that generated data from an additive logistic model with odds ratio of 7.4 for a rare single nucleotide polymorphism with a MAF of 0.005 and a sample size of 2300, the Probit method had 60% power whereas the LG method had 25% power at the α=10−6 level. Consistent with these simulation results, the set of variants identified by the LG method was a subset of those identified by the Probit method in two example analyses. Thus, we suggest the Probit method may be a competitive alternative to the LG method in genetic association studies such as candidate gene, genome-wide, or next generation sequencing studies for a binary phenotype. PMID:25096228
Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene
FOXO3Avariation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3Avariation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3Atagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92–93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3Avariation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94–100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed. PMID:25470651
Dʼsouza, Gypsyamber; Matson, Pamela A; Grady, Cynthia D; Nahvi, Shadi; Merenstein, Dan; Weber, Kathleen M; Greenblatt, Ruth; Burian, Pam; Wilson, Tracey E
Despite the major benefits of effective antiretroviral therapy on HIV-related survival, there is an ongoing need to help alleviate medication side effects related to antiretroviral therapy use. Initial studies suggest that marijuana use may reduce HIV-related symptoms, but medical marijuana use among HIV-infected individuals has not been well described. The authors evaluated trends in marijuana use and reported motivations for use among 2776 HIV-infected women in the Women's Interagency HIV Study between October 1994 and March 2010. Predictors of any and daily marijuana use were explored in multivariate logistic regression models clustered by person using generalized estimating equation. In 2009, participants were asked if their marijuana use was medical, "meaning prescribed by a doctor," or recreational, or both. Over the 16 years of this study, the prevalence of current marijuana use decreased significantly from 21% to 14%. In contrast, daily marijuana use almost doubled from 3.3% to 6.1% of all women and from 18% to 51% of current marijuana users. Relaxation, appetite improvement, reduction of HIV-related symptoms, and social use were reported as common reasons for marijuana use. In 2009, most marijuana users reported either purely medicinal use (26%) or both medicinal and recreational usage (29%). Daily marijuana use was associated with higher CD4 cell count, quality of life, and older age. Demographic characteristics and risk behaviors were associated with current marijuana use overall but were not predictors of daily use. This study suggests that both recreational and medicinal marijuana use are relatively common among HIV-infected women in the United States.
Full Text Available Fertility desires require new understanding in a context of expanding access to antiretroviral therapy for people living with HIV/AIDS in Sub-Saharan Africa. This paper studies the fertility desires and their rationales, of slum-dwelling Kenyan men and women living with HIV/AIDS who know their serostatus, but have different antiretroviral therapy treatment statuses. It addresses two research questions: How do people living with HIV/AIDS consider their future fertility? What factors contribute to an explanation of fertility desires among people living with HIV/AIDS.A mixed methods study (survey [n = 513] and in-depth interviews [n = 41] with adults living with HIV/AIDS living in Nairobi slums was conducted in 2010. Regression analyses assess independent relationships between fertility desires and socio-demographic factors. Analyses of in-depth interviews are used to interpret the statistical analyses of fertility desires.Our analyses show that fertility desires are complex and ambivalent, reflecting tensions between familial and societal pressures to have children versus pressures for HIV (re-infection prevention. More than a third (34% of men and women living with HIV expressed future fertility desires; however, this is significantly lower than in the general population. Factors independently associated with desiring a child among people living with HIV/AIDS were age, sex, number of surviving children, social support and household wealth of the respondent.Increasing access to ART is changing the context of future childbearing for people living with HIV/AIDS. Prevailing values mean that, for many people living with HIV/AIDS, having children is seen as necessary for a "normal" and healthy adult life. However, the social rewards of childbearing conflict with moral imperatives of HIV prevention, presenting dilemmas about the "proper" reproductive behaviour of people living with HIV/AIDS. The health policy and service delivery implications of
Wekesa, Eliud; Coast, Ernestina
Fertility desires require new understanding in a context of expanding access to antiretroviral therapy for people living with HIV/AIDS in Sub-Saharan Africa. This paper studies the fertility desires and their rationales, of slum-dwelling Kenyan men and women living with HIV/AIDS who know their serostatus, but have different antiretroviral therapy treatment statuses. It addresses two research questions: How do people living with HIV/AIDS consider their future fertility? What factors contribute to an explanation of fertility desires among people living with HIV/AIDS. A mixed methods study (survey [n = 513] and in-depth interviews [n = 41]) with adults living with HIV/AIDS living in Nairobi slums was conducted in 2010. Regression analyses assess independent relationships between fertility desires and socio-demographic factors. Analyses of in-depth interviews are used to interpret the statistical analyses of fertility desires. Our analyses show that fertility desires are complex and ambivalent, reflecting tensions between familial and societal pressures to have children versus pressures for HIV (re-)infection prevention. More than a third (34%) of men and women living with HIV expressed future fertility desires; however, this is significantly lower than in the general population. Factors independently associated with desiring a child among people living with HIV/AIDS were age, sex, number of surviving children, social support and household wealth of the respondent. Increasing access to ART is changing the context of future childbearing for people living with HIV/AIDS. Prevailing values mean that, for many people living with HIV/AIDS, having children is seen as necessary for a "normal" and healthy adult life. However, the social rewards of childbearing conflict with moral imperatives of HIV prevention, presenting dilemmas about the "proper" reproductive behaviour of people living with HIV/AIDS. The health policy and service delivery implications of these
Wajcman, Henri; Riou, Jean
Phenotype studies still occupy a key position in the diagnosis of hemoglobin (Hb) disorders. An additional dimension to the methods for diagnosis of Hb disorders which are mostly based on difference in charge of the Hb molecules may be brought by studying some properties of the globin chains. Among the methods proposed, reversed-phase liquid-chromatography (RP-LC) reveals differences in hydrophobicity allowing to discriminate between variants displaying identical charges. Thus, abnormal Hbs responsible for hematological disorders, such as chronic hemolytic anemia, erythrocytosis, or thalassemia like presentation, but with a charge similar to HbA or to that of a common variant may be revealed. Also RP-LC, which discriminates between the two types of gamma chains, may be of interest for diagnosis of hereditary persistence of fetal hemoglobin (HPFH) or for suggesting a haplotype in the case of sickle cell anemia.
Golin, C.; Wang, J.; Hughes, J.; Justman, J.; Haley, D.; Kuo, I.; Adimora, A.; Chege, W.; Hodder, S.
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. PMID:25863466
Rodkjaer, L; Laursen, T; Balle, N;
Background International studies suggesting that 20-37% of HIV-positive patients have diagnosable depression may underestimate the prevalence of this condition. The aim of this study was to investigate the prevalence of depression among HIV-positive patients in an out-patient clinic in Denmark an......, loneliness, a difficult financial situation, low adherence and unsafe sex. Screening for depression should be conducted regularly to provide full evaluation and relevant psychiatric treatment. This is particularly important at the time of diagnosis and before initiating HAART....... logistic regression model, self-reported stress, loneliness, constant thoughts about HIV and being in a difficult financial situation were associated with risk of depression. Patients at risk of major depression were nearly six times more likely to have missed at least one dose of highly active...
Full Text Available There has been a drastic rise of tuberculosis (TB infection across the world associated with the pandemic occurrence of HIV/AIDS. There are various determinants factors that increase the chance of TB infection among HIV positives (TB/HIV confection that varies contextually. This study aimed to assess the determinants of TB/HIV coinfection among adult HIV positives attending clinical care at two public health facilities in Nekemte, western Ethiopia. Unmatched case-control study was conducted from December 26, 2011, to February 29, 2012. Cases were 123 TB infected HIV positives, and controls were 246 non-TB infected HIV positives. Being divorced/widowed , 95% CI (1.70, 7.88, not attending formal education , 95% CI (2.20, 14.15, being underweight ( kg/m2 , 95% CI (2.18, 6.87, having history of diabetic mellitus , 95% CI (1.33, 9.94, and being in advanced WHO HIV/AIDS clinical staging , 95% CI (1.32, 3.98, were determinant factors associated with TB/HIV co-infection. Having a separate kitchen , 95% CI (0.28, 0.81 showed protective role. For most of these determinants interventions can be made at individual and institutional levels, whereas, factors like education and nutrition need societal level integrations.
Lohse, Nicolai; Gerstoft, Jan; Kronborg, Gitte
We aimed to estimate the impact of comorbidity acquired before HIV diagnosis on mortality in individuals infected with HIV.......We aimed to estimate the impact of comorbidity acquired before HIV diagnosis on mortality in individuals infected with HIV....
Full Text Available BACKGROUND: The acceptance of HIV testing among patients with tuberculosis (TB is low in Ethiopia. The purpose of this study was to assess predictors of acceptance of HIV testing among patients with TB in North Ethiopia. METHODS: A case control study was conducted in eight randomly selected health facilities in North Ethiopia from February 5 to March 11, 2009. A total of 282 participants (188 controls and 94 cases were included in the study. Cases were TB patients who refused to be tested for HIV. We used quantitative and qualitative methods of data collection. For the quantitative survey, cases and controls were interviewed by trained nurses using a pre-tested and structured questionnaire. In-depth interviews were conducted with 5 nurse counselors and 15 TB patients. Bivariate and multivariate analysis was done using SPSS 16.0 statistical software. RESULTS: The uptake of HIV testing among TB patients in the study health facilities was 70.6%. The rate of TB/HIV co-infection in those who were tested was 36.2%. From the source population, a total of 282 participants were included in the study. TB patients who had formal education [OR = 2.35, (95%CI: 1.33, 4.13], high awareness about the benefits of HIV counseling and testing [OR = 3.14, 95%CI: 1.77, 5.50], and a low stigmatized attitude [OR = 3.16, 95%CI: 1.79, 5.59] were more likely to accept HIV testing. The qualitative study also revealed that low awareness and stigma were the major reasons for non-acceptance of HIV testing. CONCLUSION: "Knowledge and attitude" factors were the major barriers for HIV testing. Tailored training should be given to TB patients and the community concerning the benefits of HIV testing. During counseling sessions, health workers should focus on barriers of uptake of HIV testing such as stigma and discrimination.
Mitchell, Jason W; Torres, Maria Beatriz; Joe, Jennifer; Danh, Thu; Gass, Bobbi; Horvath, Keith J
Although gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV) infection, few test for HIV at regular intervals. Smartphone apps may be an ideal tool to increase regular testing among MSM. However, the success of apps to encourage regular testing among MSM will depend on how frequently the apps are downloaded, whether they continue to be used over months or years, and the degree to which such apps are tailored to the needs of this population. The primary objectives of this study were to answer the following questions. (1) What features and functions of smartphone apps do MSM believe are associated with downloading apps to their mobile phones? (2) What features and functions of smartphone apps are most likely to influence MSM's sustained use of apps over time? (3) What features and functions do MSM prefer in an HIV testing smartphone app? We conducted focus groups (n=7, with a total of 34 participants) with a racially and ethnically diverse group of sexually active HIV