Science.gov

Sample records for early hiv infection

  1. Cognitive function in early HIV infection.

    PubMed

    Prakash, Aanchal; Hou, Jue; Liu, Lei; Gao, Yi; Kettering, Casey; Ragin, Ann B

    2017-04-01

    This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

  2. CMV colitis in early HIV infection.

    PubMed

    Smith, P R; Glynn, M; Sheaff, M; Aitken, C

    2000-11-01

    Cytomegalovirus (CMV) colitis is a well recognized complication of advanced HIV disease and is only rarely diagnosed in patients with normal immune function. A case of CMV colitis occurring in early HIV infection is described. Although CMV infection is normally confined to patients with advanced HIV disease, it is possible that a number of contributing factors may have led to clinical disease in this patient. CMV colitis is an important diagnosis to consider in all patients who present with a diarrhoeal illness associated with systemic features, regardless of underlying immunosuppression.

  3. The stochastic dance of early HIV infection

    NASA Astrophysics Data System (ADS)

    Merrill, Stephen J.

    2005-12-01

    The stochastic nature of early HIV infection is described in a series of models, each of which captures aspects of the dance of HIV during the early stages of infection. It is to this highly variable target that the immune response must respond. The adaptability of the various components of the immune response is an important aspect of the system's operation, as the nature of the pathogens that the response will be required to respond to and the order in which those responses must be made cannot be known beforehand. As HIV infection has direct influence over cells responsible for the immune response, the dance predicts that the immune response will be also in a variable state of readiness and capability for this task of adaptation. The description of the stochastic dance of HIV here will use the tools of stochastic models, and for the most part, simulation. The justification for this approach is that the early stages and the development of HIV diversity require that the model to be able to describe both individual sample path and patient-to-patient variability. In addition, as early viral dynamics are best described using branching processes, the explosive growth of these models both predicts high variability and rapid response of HIV to changes in system parameters.In this paper, a basic viral growth model based on a time dependent continuous-time branching process is used to describe the growth of HIV infected cells in the macrophage and lymphocyte populations. Immigration from the reservoir population is added to the basic model to describe the incubation time distribution. This distribution is deduced directly from the modeling assumptions and the model of viral growth. A system of two branching processes, one in the infected macrophage population and one in the infected lymphocyte population is used to provide a description of the relationship between the development of HIV diversity as it relates to tropism (host cell preference). The role of the immune

  4. HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection.

    PubMed

    Chaillon, Antoine; Smith, Davey M; Vanpouille, Christophe; Lisco, Andrea; Jordan, Parris; Caballero, Gemma; Vargas, Milenka; Gianella, Sara; Mehta, Sanjay R

    2017-01-01

    Understanding the dynamics of HIV across anatomic compartments is important to design effective eradication strategies. In this study, we evaluated viral trafficking between blood and semen during primary HIV infection in 6 antiretroviral-naive men who have sex with men. Deep sequencing data of HIV env were generated from longitudinal blood plasma, peripheral blood mononuclear cells, and seminal plasma samples. The presence or absence of viral compartmentalization was assessed using tree-based Slatkin-Maddison and distance-based Fst methods. Phylogeographic analyses were performed using a discrete Bayesian asymmetric approach of diffusion with Markov jump count estimation to evaluate the gene flow between blood and semen during primary HIV infection. Levels of DNA from human herpesviruses and selected inflammatory cytokines were also measured on genital secretions collected at baseline to evaluate potential correlates of increased viral migration between anatomic compartments. We detected varying degrees of compartmentalization in all 6 individuals evaluated. None of them maintained viral compartmentalization between blood and seminal plasma throughout the analyzed time points. Phylogeographic analyses revealed that the HIV population circulating in blood plasma populated the seminal compartment during the earliest stages of infection. In our limited data set, we found no association between local inflammation or herpesvirus shedding at baseline and viral trafficking between semen and blood. The early spread of virus from blood plasma to genital tract and the complex viral interplay between these compartments suggest that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.

  5. Performances of fourth generation HIV antigen/antibody assays on filter paper for detection of early HIV infections.

    PubMed

    Kania, Dramane; Truong, Tam Nguyen; Montoya, Ana; Nagot, Nicolas; Van de Perre, Philippe; Tuaillon, Edouard

    2015-01-01

    Point-of-care testing and diagnosis of HIV acute infections play important roles in preventing transmission, but HIV rapid diagnosis tests have poor capacity to detect early infections. Filter paper can be used for capillary blood collection and HIV testing using 4th generation immunoassays. Antigen/antibody combined immunoassays were evaluated for their capacity to identify early HIV infections using filter paper in comparison with rapid test. Thirty nine serum samples collected from HIV seroconverters were spotted onto filter paper and tested by the Roche Elecsys(®) HIV Combi PT test and the DiaSorin Liaison XL Murex HIV Ab/Ag assay. Fourth generation immunoassays identified 34 out of 39 HIV early infections using dried serum spot, whereas the Determine™ HIV-1/2 rapid test detected 24 out of 39 HIV positive serum (87.2% vs 61.5% respectively, p = 0.009). p24 antigen was detected by the Liaison XL in 19 dried serum samples (48.7%). In the group characterized by a negative western blot, 7 out of 8 (87.5%) and 6 out of 8 (75.0%) samples were found positive for HIV using the Elecsys and the Liaison XL, respectively. None of these eight samples classified in this group of early acute infections were found positive by the rapid test. Fourth generation Ag/Ab immunoassays performed on dried serum spot had good performance for HIV testing during the early phases of HIV infection. This method may be useful to detect HIV early infections in hard-to-reach populations and individuals living in remote areas before rapid tests become positive. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Early cytoplasmic uncoating is associated with infectivity of HIV-1

    PubMed Central

    Cianci, Gianguido C.; Anderson, Meegan R.; Hope, Thomas J.

    2017-01-01

    After fusion, HIV delivers its conical capsid into the cytoplasm. To release the contained reverse-transcribing viral genome, the capsid must disassemble in a process termed uncoating. Defining the kinetics, dynamics, and cellular location of uncoating of virions leading to infection has been confounded by defective, noninfectious particles and the stochastic minefield blocking access to host DNA. We used live-cell fluorescent imaging of intravirion fluid phase markers to monitor HIV-1 uncoating at the individual particle level. We find that HIV-1 uncoating of particles leading to infection is a cytoplasmic process that occurs ∼30 min postfusion. Most, but not all, of the capsid protein is rapidly shed in tissue culture and primary target cells, independent of entry pathway. Extended time-lapse imaging with less than one virion per cell allows identification of infected cells by Gag-GFP expression and directly links individual particle behavior to infectivity, providing unprecedented insights into the biology of HIV infection. PMID:28784755

  7. Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons

    PubMed Central

    Moore, David J.; Letendre, Scott; Poehlman Roediger, Mollie; Eberly, Lynn; Weintrob, Amy; Ganesan, Anuradha; Johnson, Erica; Del Rosario, Raechel; Agan, Brian K.; Hale, Braden R.

    2013-01-01

    Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls. Methods: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV−) military beneficiaries. HIV+ patients were categorized as earlier (<6 years of HIV, no AIDS-defining conditions, and CD4 nadir >200 cells/mm3) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests. Results: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm3, and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm3). NCI was diagnosed among 38 (19%, 95% confidence interval 14%–25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV− patients. Conclusions: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment. PMID:23303852

  8. HIV Infection: Transmission, Effects on Early Development, and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1997-01-01

    Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

  9. Effects of Perinatal HIV Infection and Early Institutional Rearing on Physical and Cognitive Development of Children in Ukraine

    ERIC Educational Resources Information Center

    Dobrova-Krol, Natasha A.; van IJzendoorn, Marinus H.; Bakermans-Kranenburg, Marian J.; Juffer, Femmie

    2010-01-01

    To study the effects of perinatal HIV-1 infection and early institutional rearing on the physical and cognitive development of children, 64 Ukrainian uninfected and HIV-infected institutionalized and family-reared children were examined (mean age = 50.9 months). Both HIV infection and institutional care were related to delays in physical and…

  10. Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1-Infected Infants.

    PubMed

    Koay, Wei Li A; Lindsey, Jane C; Uprety, Priyanka; Bwakura-Dangarembizi, Mutsa; Weinberg, Adriana; Levin, Myron J; Persaud, Deborah

    2018-05-12

    Biomarkers of intestinal integrity (intestinal fatty acid binding protein (iFABP) and zonulin), were compared in early antiretroviral-treated, HIV-1-infected (HIV+; n=56) African infants and HIV-exposed but uninfected (HEU; n=53) controls. Despite heightened inflammation and immune activation in HIV+ infants, iFABP and zonulin levels at three months of age were not different from those in HEU infants, and largely not correlated with inflammatory and immune activation biomarkers. However, zonulin levels increased, and became significantly higher in HIV+ compared to HEU infants by five months of age despite ART-suppression. These findings have implications for intestinal integrity biomarker profiling in perinatal HIV-1 infection.

  11. ASSOCIATION OF KIDNEY FUNCTION AND EARLY KIDNEY INJURY WITH INCIDENT HYPERTENSION IN HIV-INFECTED WOMEN

    PubMed Central

    Ascher, Simon B.; Scherzer, Rebecca; Peralta, Carmen A.; Tien, Phyllis C.; Grunfeld, Carl; Estrella, Michelle M.; Abraham, Alison; Gustafson, Deborah R.; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H.; Butch, Anthony W.; Young, Mary A.; Bennett, Michael R.; Shlipak, Michael G.

    2016-01-01

    Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected persons. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women’s Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C (eGFR), urine albumin-to-creatinine ratio (ACR), and seven urine biomarkers of tubular injury: alpha-1-microglobulin, interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid binding protein, N-acetyl-beta-D-glucosaminidase (NAG), and alpha1-acid-glycoprotein (AAG). We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as two consecutive visits of anti-hypertensive medication use. Over a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher ACR was independently associated with incident hypertension (RR=1.13 per ACR doubling, 95%CI: 1.07, 1.20), as was lower eGFR (RR=1.10 per 10 ml/min/1.73m2 lower eGFR, CI: 1.04, 1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, ACR was not associated with incident hypertension, whereas higher IL-18, AAG and NAG were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in HIV-infected persons. The associations of the tubular markers with hypertension in HIV-uninfected women should be validated in other studies. PMID:27993956

  12. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

    PubMed

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred; Emery, Sean; Grund, Birgit; Sharma, Shweta; Avihingsanon, Anchalee; Cooper, David A; Fätkenheuer, Gerd; Llibre, Josep M; Molina, Jean-Michel; Munderi, Paula; Schechter, Mauro; Wood, Robin; Klingman, Karin L; Collins, Simon; Lane, H Clifford; Phillips, Andrew N; Neaton, James D

    2015-08-27

    Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. The initiation of

  13. HIV sequence diversity during the early phase of infection is associated with HIV DNA reductions during antiretroviral therapy.

    PubMed

    Wang, Nidan; Li, Yijia; Han, Yang; Xie, Jing; Li, Taisheng

    2017-06-01

    The association between baseline human immunodeficiency virus (HIV) sequence diversity and HIV DNA decay after the initiation of antiretroviral therapy (ART) remains uncharacterized during the early stages of HIV infection. Samples were obtained from a cohort of 17 patients with early HIV infection (<6 months after infection) who initiated ART, and the C2V5 region of the HIV-1 envelope (env) gene was amplified via single genome amplification (SGA) to determine the peripheral plasma HIV quasispecies. We categorized HIV quasispecies into two groups according to baseline viral sequence genetic distance, which was determined by the Poisson-Fitter tool. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), viral load, and T cell subsets were measured prior to and after the initiation of ART. The median SGA sequence number was 17 (range 6-28). At baseline, we identified 7 patients with homogeneous viral populations (designated the Homogeneous group) and 10 patients with heterogeneous viral populations (designated the Heterogeneous group) based on SGA sequences. Both groups exhibited similar HIV DNA decay rates during the first 6 months of ART (P > 0.99), but the Homogenous group experienced more prominent decay than the Heterogeneous group after 6 months (P = 0.037). The Heterogeneous group had higher CD4 cell counts after ART initiation; however, both groups had comparable recovery in terms of CD4/CD8 ratios and CD8 T cell activation levels. Viral population homogeneity upon the initiation of ART is associated with a decrease in HIV DNA levels during ART. J. Med. Virol. 89:982-988, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non infected infants early treated with cART in the ANRS 12140-Pediacam study in Cameroon.

    PubMed

    Kfutwah, Anfumbom K W; Ngoupo, Paul Alain T; Sofeu, Casimir Ledoux; Ndongo, Francis Ateba; Guemkam, Georgette; Ndiang, Suzie Tetang; Owona, Félicité; Penda, Ida Calixte; Tchendjou, Patrice; Rouzioux, Christine; Warszawski, Josiane; Faye, Albert; Tejiokem, Mathurin Cyrille

    2017-03-23

    The outcome of CMV/HIV co-infection in infants treated early with combined antiretroviral therapy (cART) in resource-limited settings has not been described. We aimed to estimate the prevalence and identify factors associated with early CMV infection in HIV-infected and non-infected infants included in a study in Cameroon, and to compare HIV disease progression and survival after 1 year of early cART, following infants' CMV status. HIV-infected infants followed from birth or from HIV diagnosis before 7 months old and HIV-uninfected infants born to HIV-infected or uninfected mothers were tested for CMV at a median age of 4.0 months [Interquartile range (IQR): 3.4-4.9]. Multivariable logistic regression was performed to identify factors associated with CMV infection. Early cART was offered to HIV-infected infants: mortality, immunological and virological outcomes were assessed. Three hundred and sixty-nine infants were tested. The proportion of infants infected with CMV at baseline was significantly higher in HIV-infected than in HIV-uninfected groups (58.9% (86/146) vs 30.0% (67/223), p < 0.001). At baseline, median CMV viral load was higher in HIV-infected (3.7 log copies/ml [IQR; 3.1-4.3]) than in HIV-uninfected infants (2.8 log copies [IQR; 2.1-3.4], p < 0.001). cART was initiated in 90% of HIV-infected infants (132/146) at a median age of 4.0 months (IQR; 3.2-5.9); in this sub-group CMV infection was independently associated with being followed from the time of HIV diagnosis rather than from birth (aOR = 3.1, 95%CI [1.2-8.0]), born to a non-single mother (aOR = 3.4[1.4-8.1]), and breastfeeding (aOR = 7.3 [2.7-19.4]). HIV-infected infants were retested after a median of 7.1 months [4.8-9.5]: CMV was undetectable in 37 of the 61 (60.7%) initially CMV-infected cases and became detectable in 8 of the 38 (21.1%) initially CMV-negative cases. After 1 year of cART, the probability of death (0.185 vs 0.203; p = 0.75), the proportion of

  15. Cost-Effectiveness of Early Infant HIV Diagnosis of HIV-Exposed Infants and Immediate Antiretroviral Therapy in HIV-Infected Children under 24 Months in Thailand

    PubMed Central

    Collins, Intira Jeannie; Cairns, John; Ngo-Giang-Huong, Nicole; Sirirungsi, Wasna; Leechanachai, Pranee; Le Coeur, Sophie; Samleerat, Tanawan; Kamonpakorn, Nareerat; Mekmullica, Jutarat; Jourdain, Gonzague; Lallemant, Marc

    2014-01-01

    Background HIV-infected infants have high risk of death in the first two years of life if untreated. WHO guidelines recommend early infant HIV diagnosis (EID) of all HIV-exposed infants and immediate antiretroviral therapy (ART) in HIV-infected children under 24-months. We assessed the cost-effectiveness of this strategy in HIV-exposed non-breastfed children in Thailand. Methods A decision analytic model of HIV diagnosis and disease progression compared: EID using DNA PCR with immediate ART (Early-Early); or EID with deferred ART based on immune/clinical criteria (Early-Late); vs. clinical/serology based diagnosis and deferred ART (Reference). The model was populated with survival and cost data from a Thai observational cohort and the literature. Incremental cost-effectiveness ratio per life-year gained (LYG) was compared against the Reference strategy. Costs and outcomes were discounted at 3%. Results Mean discounted life expectancy of HIV-infected children increased from 13.3 years in the Reference strategy to 14.3 in the Early-Late and 17.8 years in Early-Early strategies. The mean discounted lifetime cost was $17,335, $22,583 and $29,108, respectively. The cost-effectiveness ratio of Early-Late and Early-Early strategies was $5,149 and $2,615 per LYG, respectively as compared to the Reference strategy. The Early-Early strategy was most cost-effective at approximately half the domestic product per capita per LYG ($4,420 in Thailand 2011). The results were robust in deterministic and probabilistic sensitivity analyses including varying perinatal transmission rates. Conclusion In Thailand, EID and immediate ART would lead to major survival benefits and is cost- effective. These findings strongly support the adoption of WHO recommendations as routine care. PMID:24632750

  16. Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis

    PubMed Central

    Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S. W.; Fortin, Claude; Coutlée, François; Roger, Michel

    2013-01-01

    The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS. PMID:24088852

  17. Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.

    PubMed

    Dumaresq, Jeannot; Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S W; Fortin, Claude; Coutlée, François; Roger, Michel

    2013-12-01

    The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

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

    PubMed Central

    Hatano, Hiroyu; Bacon, Oliver; Rutishauser, Rachel; Kearney, Mary F.; Anderson, Elizabeth M.; Cohen, Stephanie E.; Abdel-Mohsen, Mohamed; Pohlmeyer, Christopher W.; Hoh, Rebecca; McCune, Joseph M.; Spindler, Jonathan; Thanh, Cassandra; Gibson, Erica A.; Kuritzkes, Daniel R.; Siliciano, Robert F.; Price, Richard W.; Liegler, Teri

    2017-01-01

    Background It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART. Methods and findings Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from Pr

  19. Association of Kidney Function and Early Kidney Injury With Incident Hypertension in HIV-Infected Women.

    PubMed

    Ascher, Simon B; Scherzer, Rebecca; Peralta, Carmen A; Tien, Phyllis C; Grunfeld, Carl; Estrella, Michelle M; Abraham, Alison; Gustafson, Deborah R; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H; Butch, Anthony W; Young, Mary A; Bennett, Michael R; Shlipak, Michael G

    2017-02-01

    Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected people. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C, urine albumin-to-creatinine ratio, and 7 urine biomarkers of tubular injury: α-1-microglobulin, interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N-acetyl-β-d-glucosaminidase, and α1-acid-glycoprotein. We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as 2 consecutive visits of antihypertensive medication use. During a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher urine albumin-to-creatinine ratio was independently associated with incident hypertension (relative risk =1.13 per urine albumin-to-creatinine ratio doubling, 95% confidence interval, 1.07-1.20), as was lower estimated glomerular filtration rate (relative risk =1.10 per 10 mL/min/1.73 m 2 lower estimated glomerular filtration rate; 95% confidence interval, 1.04-1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, urine albumin-to-creatinine ratio was not associated with incident hypertension, whereas higher urine interleukin-18, α1-acid-glycoprotein, and N-acetyl-β-d-glucosaminidase levels were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in

  20. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.

    PubMed

    Keele, Brandon F; Giorgi, Elena E; Salazar-Gonzalez, Jesus F; Decker, Julie M; Pham, Kimmy T; Salazar, Maria G; Sun, Chuanxi; Grayson, Truman; Wang, Shuyi; Li, Hui; Wei, Xiping; Jiang, Chunlai; Kirchherr, Jennifer L; Gao, Feng; Anderson, Jeffery A; Ping, Li-Hua; Swanstrom, Ronald; Tomaras, Georgia D; Blattner, William A; Goepfert, Paul A; Kilby, J Michael; Saag, Michael S; Delwart, Eric L; Busch, Michael P; Cohen, Myron S; Montefiori, David C; Haynes, Barton F; Gaschen, Brian; Athreya, Gayathri S; Lee, Ha Y; Wood, Natasha; Seoighe, Cathal; Perelson, Alan S; Bhattacharya, Tanmoy; Korber, Bette T; Hahn, Beatrice H; Shaw, George M

    2008-05-27

    The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.

  1. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection

    PubMed Central

    Keele, Brandon F.; Giorgi, Elena E.; Salazar-Gonzalez, Jesus F.; Decker, Julie M.; Pham, Kimmy T.; Salazar, Maria G.; Sun, Chuanxi; Grayson, Truman; Wang, Shuyi; Li, Hui; Wei, Xiping; Jiang, Chunlai; Kirchherr, Jennifer L.; Gao, Feng; Anderson, Jeffery A.; Ping, Li-Hua; Swanstrom, Ronald; Tomaras, Georgia D.; Blattner, William A.; Goepfert, Paul A.; Kilby, J. Michael; Saag, Michael S.; Delwart, Eric L.; Busch, Michael P.; Cohen, Myron S.; Montefiori, David C.; Haynes, Barton F.; Gaschen, Brian; Athreya, Gayathri S.; Lee, Ha Y.; Wood, Natasha; Seoighe, Cathal; Perelson, Alan S.; Bhattacharya, Tanmoy; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.

    2008-01-01

    The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense. PMID:18490657

  2. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

    PubMed

    Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G; Henry, Keith; Jain, Mamta K; Palfreeman, Adrian; Mugyenyi, Peter; Domingo, Pere; Hoffmann, Christian; Read, Tim R H; Pujari, Sanjay; Meulbroek, Michael; Johnson, Margaret; Wilkin, Timothy; Mitsuyasu, Ronald

    2016-12-15

     In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.  Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights

  3. Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna, Austria

    PubMed Central

    Herout, Sandra; Mandorfer, Mattias; Breitenecker, Florian; Reiberger, Thomas; Grabmeier-Pfistershammer, Katharina; Rieger, Armin; Aichelburg, Maximilian C.

    2016-01-01

    Background It is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART. Methods We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis. Results Among the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004). Conclusions Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits. PMID:27065239

  4. Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

    PubMed Central

    Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

    2014-01-01

    Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

  5. Effects of Antiretroviral Therapy on Autonomic Function in Early HIV Infection: A Preliminary Report

    PubMed Central

    Chow, Dominic; Kocher, Morgan; Shikuma, Cecilia; Parikh, Nisha; Grandinetti, Andrew; Nakamoto, Beau; Seto, Todd; Low, Phillip

    2012-01-01

    Background: A prospective study was conducted in human immunodeficiency virus (HIV)-infected patients as they undergo alterations in their antiretroviral therapy (ART) to determine the effect of ART on autonomic function. Methods: HIV-infected subjects who were either 1) naïve to ART and initiating ART, or 2) receiving ART and in HIV virologic failure for at least 4 months and were about to switch ART were enrolled in this study. Autonomic function assessment (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4 months after initiating the new ART. Changes in clinical autonomic symptoms and virologic assessment were assessed. Results: Twelve subjects completed the study: 92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non-Hispanic. Seventy-five percent were ART naïve while 25% were failing their ART regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm3. All subjects achieved an undetectable HIV viral load by the 4-month follow-up visit. The majority of naïve subjects were started on an ART regimen of tenofovir / emtricitabine / efavirenz. There were no significant differences in autonomic function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests, with regards to ART initiation. Conclusion: This is the first study to examine the effects of initiating ART on autonomic function in early HIV infection. This study found no appreciable differences of ART on the autonomic nervous system when ART is initiated early in the course of HIV disease. ART may not contribute to short-term changes in autonomic function. PMID:22859899

  6. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

    PubMed

    Wall, Kristin M; Rida, Wasima; Haddad, Lisa B; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H; Latka, Mary H; Anzala, Omu; Sanders, Eduard J; Bekker, Linda-Gail; Edward, Vinodh A; Price, Matt A

    2017-03-01

    Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement <200 cells/μl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/μl or a single CD4 ≤350 cells/μl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

  7. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

    PubMed

    Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

    2018-04-01

    While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

  8. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

    PubMed Central

    Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

    2018-01-01

    While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

  9. Herpes zoster in African patients: an early manifestation of HIV infection.

    PubMed

    Van de Perre, P; Bakkers, E; Batungwanayo, J; Kestelyn, P; Lepage, P; Nzaramba, D; Bogaerts, J; Serufilira, A; Rouvroy, D; Uwimana, A

    1988-01-01

    During a 3-month period, 131 cases of herpes zoster were diagnosed in Kigali, Rwanda. There were 46 female and 85 male patients. Mean age was 29 years (range 1-66). An unusually high proportion of patients presented with cranial and sacral nerve localisation of their cutaneous lesions. 55/131 patients (42%) had involvement of more than one dermatome. None of the patients had an underlying condition known to favour herpes zoster. 120/131 (92%) had antibodies to HIV detected by an immunoenzymatic assay (EIA) and indirect immunofluorescence. 92/125 adult patients (74%) had no sign or symptom related to HIV infection other than herpes zoster. This study suggests that herpes zoster in Central Africa is an early and readily detectable manifestation of HIV-induced immunosuppression.

  10. Estimating time since infection in early homogeneous HIV-1 samples using a poisson model

    PubMed Central

    2010-01-01

    Background The occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, i.e., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (e.g., BEAST), which are instead based on the simulation of genealogies. Results We have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (i.e., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection. Conclusions When the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool

  11. HIV Type 1 (HIV-1) Proviral Reservoirs Decay Continuously Under Sustained Virologic Control in HIV-1–Infected Children Who Received Early Treatment

    PubMed Central

    Luzuriaga, Katherine; Tabak, Barbara; Garber, Manuel; Chen, Ya Hui; Ziemniak, Carrie; McManus, Margaret M.; Murray, Danielle; Strain, Matthew C.; Richman, Douglas D.; Chun, Tae-Wook; Cunningham, Coleen K.; Persaud, Deborah

    2014-01-01

    Background. Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)–infected infants controls HIV-1 replication and reduces mortality. Methods. Plasma viremia (lower limit of detection, <2 copies/mL), T-cell activation, HIV-1–specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1–infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth. Results. Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P = .03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P = .03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1–specific immune responses. Conclusions. Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies. PMID:24850788

  12. Developments in early diagnosis and therapy of HIV infection in newborns.

    PubMed

    Canals, Francisco; Masiá, Mar; Gutiérrez, Félix

    2018-01-01

    Infants who acquire HIV have an exceptionally high risk of morbidity and mortality if they do not receive antiretroviral therapy (ART). Areas covered: This review aims to summarize the currently available evidence on ART in HIV-infected neonates. Data were obtained from literature searches from PubMed, abstracts from International Conferences (2000-2017), and authors' files. Expert opinion: Current evidence favors early diagnosis and prompt ART of HIV infection in newborns. The precise timing of initiation of ART remains undetermined. Very early (close to birth) ART appears to limit the size of the viral reservoir and may restrict replication-competent virus, but the clinical benefit remains unproven. Among the current options for initial therapy, in full term neonates from 2 weeks of life onwards, a lopinavir/ritonavir-based three-drug regimen is preferred. In term infants, younger than 2 weeks a nevirapine-based regimen is recommended, although there are no clinical trial data supporting that initiating treatment before 2 weeks improves outcome compared to starting afterwards. Existing safety information is insufficient to recommend ART in preterm infants, with pharmacokinetic data available for zidovudine only. If ART is considered in this setting, an individual case assessment of the risk/benefit ratio of treatment should be made.

  13. Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

    PubMed Central

    Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

    2016-01-01

    The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

  14. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries

    PubMed Central

    Rida, Wasima; Haddad, Lisa B.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H.; Latka, Mary H.; Anzala, Omu; Sanders, Eduard J.; Bekker, Linda-Gail; Edward, Vinodh A.; Price, Matt A.

    2017-01-01

    Background: Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. Methods: From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement <200 cells/μl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/μl or a single CD4 ≤350 cells/μl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. Results: Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. Conclusions: In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted. PMID:27893488

  15. Impact of early cART on HIV blood and semen compartments at the time of primary infection.

    PubMed

    Chéret, Antoine; Durier, Christine; Mélard, Adeline; Ploquin, Mickaël; Heitzmann, Julia; Lécuroux, Camille; Avettand-Fenoël, Véronique; David, Ludivine; Pialoux, Gilles; Chennebault, Jean-Marie; Müller-Trutwin, Michaela; Goujard, Cécile; Rouzioux, Christine; Meyer, Laurence

    2017-01-01

    HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART. Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment. At enrollment, HIV-RNA load was higher in blood than in semen (median 5.66 vs 4.22 log10 cp/mL, p<0.0001). Semen HIV-RNA load correlated strongly with blood HIV-RNA load (r = 0.81, p = 0.02, the CD4 cell count (r = -0.98, p<0.0001), and the CD4/CD8 ratio (r = -0.85, p<0.01) in acute infection but not in later stages of PHI. Median blood and seminal cellular HIV-DNA levels were 3.59 and 0.31 log10cp/106 cells, respectively. HIV-DNA load peaked in semen later than in blood and then correlated with blood IP10 level (r = 0.62, p = 0.04). HIV-RNA was undetectable in blood and semen after two years of effective cART. Semen HIV-DNA load declined similarly, except in one patient who had persistently high IP-10 and IL-6 levels and used recreational drugs. HIV reservoir cells are found in semen during PHI, with gradual compartmentalization. Its size was linked to the plasma IP-10 level. Early treatment purges both the virus and infected cells, reducing the high risk of transmission during PHI. NCT01033760.

  16. Early HIV Infections Among Men Who Have Sex with Men in Five Cities in the United States

    PubMed Central

    Smith, A.; Masciotra, S.; Zhang, W.; Bingham, T.; Flynn, C.; German, D.; Al-Tayyib, A.; Magnus, M.; LaLota, M.; Rose, C. E.; Owen, S. M.

    2016-01-01

    We tested blood samples from men who have sex with men (MSM) to detect early HIV infection. Early HIV included both acute (infected past 30 days) and recent (estimated recency past 240 days). Acute infections were defined as screen immunoassay (IA) negative/NAAT-positive or IA-positive/Multispot-negative/NAAT-positive. Recent infections were defined as avidity index cutoff <30 % on an avidity-based IA and, (1) not reporting antiretroviral therapy use or, (2) HIV RNA >150 copies/mL. Of 937 samples, 26 % (244) were HIV-infected and of these 5 % (12) were early. Of early infections, 2 were acute and 10 recent; most (8/12) were among black MSM. Early infection was associated with last partner of black race [adjusted relative risk (ARR) = 4.6, confidence intervals (CI) 1.2–17.3], receptive anal sex at last sex (ARR = 4.3, CI 1.2–15.0), and daily Internet use to meet partners/ friends (ARR = 3.3, CI 1.1–9.7). Expanding prevention and treatment for black MSM will be necessary for reducing incidence in the United States. PMID:25680518

  17. Live-Cell Imaging of Early Steps of Single HIV-1 Infection.

    PubMed

    Francis, Ashwanth C; Melikyan, Gregory B

    2018-05-19

    Live-cell imaging of single HIV-1 entry offers a unique opportunity to delineate the spatio-temporal regulation of infection. Novel virus labeling and imaging approaches enable the visualization of key steps of HIV-1 entry leading to nuclear import, integration into the host genome, and viral protein expression. Here, we discuss single virus imaging strategies, focusing on live-cell imaging of single virus fusion and productive uncoating that culminates in HIV-1 infection.

  18. Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs.

    PubMed

    Alaoui, Lamine; Palomino, Gustavo; Zurawski, Sandy; Zurawski, Gerard; Coindre, Sixtine; Dereuddre-Bosquet, Nathalie; Lecuroux, Camille; Goujard, Cecile; Vaslin, Bruno; Bourgeois, Christine; Roques, Pierre; Le Grand, Roger; Lambotte, Olivier; Favier, Benoit

    2018-05-01

    Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.

  19. Asymptomatic HIV infection

    MedlinePlus

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

  20. Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

    PubMed Central

    Koenig, Serena P.; Bang, Heejung; Severe, Patrice; Jean Juste, Marc Antoine; Ambroise, Alex; Edwards, Alison; Hippolyte, Jessica; Fitzgerald, Daniel W.; McGreevy, Jolion; Riviere, Cynthia; Marcelin, Serge; Secours, Rode; Johnson, Warren D.; Pape, Jean W.; Schackman, Bruce R.

    2011-01-01

    Background In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. Methods and Findings Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS). Conclusions Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests. Trial registration ClinicalTrials.gov NCT00120510 Please see

  1. Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection

    PubMed Central

    Anderson, Christy M.; Var, Susanna R.; Oliveira, Michelli F.; Lada, Steven M.; Vargas, Milenka V.; Little, Susan J.; Richman, Douglas D.; Strain, Matthew C.; Pérez-Santiago, Josué; Smith, Davey M.

    2016-01-01

    replication is associated with higher levels of immune activation and HIV disease progression. We hypothesized that HHV-associated activation of HIV-infected CD4+ T cells might lead to increased HIV DNA. This study found that detectable CMV in blood cells of HIV-infected men was associated with slower decay of HIV DNA even during antiretroviral therapy (ART) that was started during early HIV infection. Similarly, levels of EBV DNA were associated with higher levels of HIV DNA during ART. If this observation points to a causal pathway, interventions that control CMV and EBV replication may be able to reduce the HIV reservoir, which might be relevant to current HIV cure efforts. PMID:26842469

  2. Plasma Viral Loads During Early HIV-1 Infection Are Similar in Subtype C– and Non-Subtype C–Infected African Seroconverters

    PubMed Central

    Campbell, Mary S.; Kahle, Erin M.; Celum, Connie; Lingappa, Jairam R.; Kapiga, Saidi; Mujugira, Andrew; Mugo, Nelly R.; Fife, Kenneth H.; Mullins, James I.; Baeten, Jared M.; Celum, Connie; Wald, Anna; Lingappa, Jairam; Baeten, Jared M.; Campbell, Mary S.; Corey, Lawrence; Coombs, Robert W.; Hughes, James P.; Magaret, Amalia; McElrath, M. Juliana; Morrow, Rhoda; Mullins, James I.; Coetzee, David; Fife, Kenneth; Were, Edwin; Essex, Max; Makhema, Joseph; Katabira, Elly; Ronald, Allan; Allen, Susan; Kayitenkore, Kayitesi; Karita, Etienne; Bukusi, Elizabeth; Cohen, Craig; Allen, Susan; Kanweka, William; Allen, Susan; Vwalika, Bellington; Kapiga, Saidi; Manongi, Rachel; Farquhar, Carey; John-Stewart, Grace; Kiarie, James; Allen, Susan; Inambao, Mubiana; Farm, Orange; Delany-Moretlwe, Sinead; Rees, Helen; de Bruyn, Guy; Gray, Glenda; McIntyre, James; Mugo, Nelly Rwamba

    2013-01-01

    Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C–infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa. PMID:23315322

  3. HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis

    DOE PAGES

    Volz, Erik M.; Ionides, Edward; Romero-Severson, Ethan O.; ...

    2013-12-10

    Conventional epidemiological surveillance of infectious diseases is focused on characterization of incident infections and estimation of the number of prevalent infections. Advances in methods for the analysis of the population-level genetic variation of viruses can potentially provide information about donors, not just recipients, of infection. Genetic sequences from many viruses are increasingly abundant, especially HIV, which is routinely sequenced for surveillance of drug resistance mutations. In this study, we conducted a phylodynamic analysis of HIV genetic sequence data and surveillance data from a US population of men who have sex with men (MSM) and estimated incidence and transmission rates bymore » stage of infection.« less

  4. HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis

    SciT

    Volz, Erik M.; Ionides, Edward; Romero-Severson, Ethan O.

    Conventional epidemiological surveillance of infectious diseases is focused on characterization of incident infections and estimation of the number of prevalent infections. Advances in methods for the analysis of the population-level genetic variation of viruses can potentially provide information about donors, not just recipients, of infection. Genetic sequences from many viruses are increasingly abundant, especially HIV, which is routinely sequenced for surveillance of drug resistance mutations. In this study, we conducted a phylodynamic analysis of HIV genetic sequence data and surveillance data from a US population of men who have sex with men (MSM) and estimated incidence and transmission rates bymore » stage of infection.« less

  5. Five year neurodevelopment outcomes of perinatally HIV-infected children on early limited or deferred continuous antiretroviral therapy.

    PubMed

    Laughton, Barbara; Cornell, Morna; Kidd, Martin; Springer, Priscilla Estelle; Dobbels, Els Françoise Marie-Thérèse; Rensburg, Anita Janse Van; Otwombe, Kennedy; Babiker, Abdel; Gibb, Diana M; Violari, Avy; Kruger, Mariana; Cotton, Mark Fredric

    2018-05-01

    Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV-infected (HIV-positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long-term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV-infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART-Def); immediate time-limited ART for 40 weeks (ART-40W) or 96 weeks (ART-96W). ART was restarted in the time-limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants. A prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery-Buktenica developmental tests for visual motor integration at 60 months. HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms. In this study, 28 ART-Def, 35 ART-40W, 33 ART-96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART-Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV-infected children (mean standard scores: 75.8 ART-Def, 79.8 ART-40W, 75.9 ART-96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)). Early locomotor delay in the ART-Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV-infected children on early time-limited ART were

  6. Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression ▿

    PubMed Central

    Mlotshwa, Mandla; Riou, Catherine; Chopera, Denis; de Assis Rosa, Debra; Ntale, Roman; Treunicht, Florette; Woodman, Zenda; Werner, Lise; van Loggerenberg, Francois; Mlisana, Koleka; Abdool Karim, Salim; Williamson, Carolyn; Gray, Clive M.

    2010-01-01

    Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection. PMID:20826686

  7. HIV antibodies for treatment of HIV infection

    PubMed Central

    Margolis, David M.; Koup, Richard A.; Ferrari, Guido

    2016-01-01

    Summary The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Further, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. PMID:28133794

  8. HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians

    PubMed Central

    Cook, R.; Jones, D. L.; Nehra, R.; Kumar, A. M.; Prabhakar, S.; Waldrop-Valverde, D.; Sharma, S.; Kumar, M.

    2017-01-01

    HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm3) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. PMID:23722088

  9. HIV Clade-C Infection and Cognitive Impairment, Fatigue, Depression, and Quality of Life in Early-Stage Infection in Northern Indians.

    PubMed

    Cook, R; Jones, D L; Nehra, R; Kumar, A M; Prabhakar, S; Waldrop-Valverde, D; Sharma, S; Kumar, M

    2016-07-01

    HIV disease progression is associated with declining quality of life and overall health status, although most research in this domain has been conducted among Western populations where B is the infecting clade. This study sought to determine the effects of early-stage clade-C HIV infection (CD4 count ≥400 cells/mm(3)) on neurocognitive functioning, cognitive depression, and fatigue by comparing a matched sample of HIV-positive and HIV-negative Northern Indians. This study also examined the impact of these factors on quality of life within the HIV-positive individuals. HIV-positive participants demonstrated reduced cognitive functioning, increased fatigue, and lower quality of life. Fatigue and cognitive impairment interacted to negatively impact quality of life. Results suggest that early-stage HIV clade-C-infected individuals may experience subclinical symptoms, and further research is needed to explore the benefit of therapeutic interventions to ensure optimal clinical outcomes and maintain quality of life in this vulnerable population. © The Author(s) 2013.

  10. Hepatocellular Carcinoma in HIV-Infected Patients: Check Early, Treat Hard

    PubMed Central

    Garlassi, Elisa; Cacopardo, Bruno; Cappellani, Alessandro; Guaraldi, Giovanni; Cocchi, Stefania; De Paoli, Paolo; Lleshi, Arben; Izzi, Immacolata; Torresin, Augusta; Di Gangi, Pietro; Pietrangelo, Antonello; Ferrari, Mariachiara; Bearz, Alessandra; Berretta, Salvatore; Nasti, Guglielmo; Di Benedetto, Fabrizio; Balestreri, Luca; Tirelli, Umberto; Ventura, Paolo

    2011-01-01

    Purpose. Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era. The aims of this study were to describe HCC tumor characteristics and different therapeutic approaches, to evaluate patient survival time from HCC diagnosis, and to identify clinical prognostic predictors in patients with and without HIV infection. Patients and Methods. A multicenter observational retrospective comparison of 104 HIV-infected patients and 484 uninfected patients was performed in four Italian centers. HCC was staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria. Results. Tumor characteristics of patients with and without HIV were significantly different for age, Eastern Cooperative Oncology Group performance status (PS) score ≤1, and etiology of chronic liver disease. Despite the similar potentially curative option rate and better BCLC stage at diagnosis, the median survival time was significantly shorter in HIV+ patients. HIV+ patients were less frequently retreated at relapse. Independent predictors of survival were: BCLC stage, potentially effective HCC therapy, tumor dimension ≤3 cm, HCC diagnosis under a screening program, HCC recurrence, and portal vein thrombosis. Restricting the analysis to HIV+ patients only, all positive prognostic factors were confirmed together with HAART exposure. Conclusion. This study confirms a significantly shorter survival time in HIV+ HCC patients. The less aggressive retreatment at recurrence approach does not balance the benefit of younger age and better BCLC stage and PS score of HIV+ patients. Thus, considering the prognosis of HIV+ HCC patients, effective screening techniques, programs, and specific management guidelines are urgently needed. PMID:21868692

  11. MHC-driven HIV-1 control on the long run is not systematically determined at early times post-HIV-1 infection.

    PubMed

    Antoni, Guillemette; Guergnon, Julien; Meaudre, Céline; Samri, Assia; Boufassa, Faroudy; Goujard, Cécile; Lambotte, Olivier; Autran, Brigitte; Rouzioux, Christine; Costagliola, Dominique; Meyer, Laurence; Theodorou, Ioannis

    2013-07-17

    Human leukocyte antigen (HLA) class I-driven long-term protection against HIV-1 is mainly associated with HLA-B*27 and HLA-B*57. This effect is observed early after infection. Clarification needs to be established concerning the moment of action for the other HLA-B or HLA-C alleles. HLA-B and HLA-C alleles from 111 individuals that control HIV-1 disease for over 8 years and from 747 seroconverters frequencies were compared. Also, HLA-B and HLA-C influence on early levels of plasma HIV-RNA, cellular HIV-DNA, CD4, CD8 and CD4/CD8 ratio was evaluated among the seroconverters. We performed univariate, multivariate and haplotypic analyses in order to disentangle the respective contribution of the HLA-B and HLA-C genes. The haplotypes analysis shows three patterns of protective effects of HLA-B and HLA-C alleles or haplotypes. First, the HLA B*57, HLA-B*27, HLA-B*13 and HLA-C*14 alleles, which have a strong effect on long-term disease control, also influence at least one of the early infection phenotypes. Second, HLA-B*52 has a strong effect during early time points on HIV-RNA without significant effect on the long-term control of HIV-1. Finally, the HLA-B*14-C*08 haplotype has a strong effect on the long-term protection, without influencing early viral control. Our study highlighted independent effects of HLA-B and HLA-C alleles on HIV-disease progression. Furthermore, some alleles appeared to be specifically associated with either long-term control or early virological parameters, suggesting different immunological mechanisms according to the disease stages.

  12. Risk Behavior and Sexually Transmitted Infections Among Transgender Women and Men Undergoing Community-Based Screening for Acute and Early HIV Infection in San Diego.

    PubMed

    Green, Nella; Hoenigl, Martin; Morris, Sheldon; Little, Susan J

    2015-10-01

    The transgender community represents an understudied population in the literature. The objective of this study was to compare risk behavior, and HIV and sexually transmitted infection (STI) rates between transgender women and transgender men undergoing community-based HIV testing.With this retrospective analysis of a cohort study, we characterize HIV infection rates as well as reported risk behaviors and reported STI in 151 individual transgender women and 30 individual transgender men undergoing community based, voluntary screening for acute and early HIV infection (AEH) in San Diego, California between April 2008 and July 2014.HIV positivity rate was low for both, transgender women and transgender men undergoing AEH screening (2% and 3%, respectively), and the self-reported STI rate for the prior 12 months was 13% for both. Although transgender women appeared to engage in higher rates of risk behavior overall, with 69% engaged in condomless receptive anal intercourse (CRAI) and 11% engaged in sex work, it is important to note that 91% of transgender women reported recent sexual intercourse, 73% had more than 1 sexual partner, 63% reported intercourse with males, 37% intercourse with males and females, and 30% had CRAI.Our results indicate that in some settings rates of HIV infection, as well as rates of reported STIs and sexual risk behavior in transgender men may resemble those found in transgender women. Our findings support the need for comprehensive HIV prevention in both, transgender women and men.

  13. A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection

    PubMed Central

    Avettand-Fenoël, Véronique; Nembot, Georges; Mélard, Adeline; Blanc, Catherine; Lascoux-Combe, Caroline; Slama, Laurence; Allegre, Thierry; Allavena, Clotilde; Yazdanpanah, Yazdan; Duvivier, Claudine; Katlama, Christine; Goujard, Cécile; Seksik, Bao Chau Phung; Leplatois, Anne; Molina, Jean-Michel; Meyer, Laurence; Autran, Brigitte; Rouzioux, Christine

    2013-01-01

    Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3−CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that

  14. Clinical Impact and Cost-effectiveness of Diagnosing HIV Infection During Early Infancy in South Africa: Test Timing and Frequency.

    PubMed

    Francke, Jordan A; Penazzato, Martina; Hou, Taige; Abrams, Elaine J; MacLean, Rachel L; Myer, Landon; Walensky, Rochelle P; Leroy, Valériane; Weinstein, Milton C; Parker, Robert A; Freedberg, Kenneth A; Ciaranello, Andrea

    2016-11-01

     Diagnosis of human immunodeficiency virus (HIV) infection during early infancy (commonly known as "early infant HIV diagnosis" [EID]) followed by prompt initiation of antiretroviral therapy dramatically reduces mortality. EID testing is recommended at 6 weeks of age, but many infant infections are missed.  We simulated 4 EID testing strategies for HIV-exposed infants in South Africa: no EID (diagnosis only after illness; hereafter, "no EID"), testing once (at birth alone or at 6 weeks of age alone; hereafter, "birth alone" and "6 weeks alone," respectively), and testing twice (at birth and 6 weeks of age; hereafter "birth and 6 weeks"). We calculated incremental cost-effectiveness ratios (ICERs), using discounted costs and life expectancies for all HIV-exposed (infected and uninfected) infants.  In the base case (guideline-concordant care), the no EID strategy produced a life expectancy of 21.1 years (in the HIV-infected group) and 61.1 years (in the HIV-exposed group); lifetime cost averaged $1430/HIV-exposed infant. The birth and 6 weeks strategy maximized life expectancy (26.5 years in the HIV-infected group and 61.4 years in the HIV-exposed group), costing $1840/infant tested. The ICER of the 6 weeks alone strategy versus the no EID strategy was $1250/year of life saved (19% of South Africa's per capita gross domestic product); the ICER for the birth and 6 weeks strategy versus the 6 weeks alone strategy was $2900/year of life saved (45% of South Africa's per capita gross domestic product). Increasing the proportion of caregivers who receive test results and the linkage of HIV-positive infants to antiretroviral therapy with the 6 weeks alone strategy improved survival more than adding a second test.  EID at birth and 6 weeks improves outcomes and is cost-effective, compared with EID at 6 weeks alone. If scale-up costs are comparable, programs should add birth testing after strengthening 6-week testing programs. © The Author 2016. Published by Oxford

  15. Prevention of HIV-1 Infection with Early Antiretroviral Therapy: Treatment as -

    NASA Astrophysics Data System (ADS)

    Gilada, Ishwar; Gilada, T.

    2014-07-01

    There are 34.2 million living with HIV/AIDS globally according to the UNAIDS. The incidence is 2.5 million new infections every year. Out of the 24.8 million patients eligible for antiretroviral treatment, only 8 million are actually receiving it. Nearly 1.7 million people (4658 per day) die of the disease every year i.e., 4658/day, making HIV/AIDS a planetary emergency. The most disturbing fact is that more than 50% of the infected people do not reveal their HIV status to their sexual partners. The UN Sec-Gen Ban Ki-moon suggested "3 Zeros"--Zero Infection, Zero Stigma, Zero AIDS-deaths in 2008...

  16. Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

    PubMed

    Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

    2015-07-31

    HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Linkage and retention in HCV care for HIV-infected populations: early data from the DAA era.

    PubMed

    Sacks-Davis, Rachel; Doyle, Joseph S; Rauch, Andri; Beguelin, Charles; Pedrana, Alisa E; Matthews, Gail V; Prins, Maria; van der Valk, Marc; Klein, Marina B; Saeed, Sahar; Lacombe, Karine; Chkhartishvili, Nikoloz; Altice, Frederick L; Hellard, Margaret E

    2018-04-01

    There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV-infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co-infected populations in the context of implementation science theory. HCV elimination initiatives and studies in HIV co-infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. Seven HCV elimination initiatives and studies were identified in HIV co-infected populations, mainly operating in high-income countries. Four were focused mainly on HCV elimination in HIV-infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV-infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV-infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). Early results from emerging research on HCV elimination in HIV-infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have

  18. Early age at start of antiretroviral therapy associated with better virologic control after initial suppression in HIV-infected infants.

    PubMed

    Shiau, Stephanie; Strehlau, Renate; Technau, Karl-Günter; Patel, Faeezah; Arpadi, Stephen M; Coovadia, Ashraf; Abrams, Elaine J; Kuhn, Louise

    2017-01-28

    The report of the 'Mississippi baby' who was initiated on antiretroviral therapy (ART) within 30 h of birth and maintained viral suppression off ART for 27 months has increased interest in the timing of ART initiation early in life. We examined associations between age at ART initiation and virologic outcomes in five cohorts of HIV-infected infants and young children who initiated ART before 2 years of age in Johannesburg, South Africa. We compared those who initiated ART early (<6 months of age) and those who started ART late (6-24 months of age). Two primary outcomes were examined: initial response to ART in three cohorts and later sustained virologic control after achieving suppression on ART in two cohorts. We did not observe consistent differences in initial viral suppression rates by age at ART initiation. Overall, initial viral suppression rates were low. Only 31, 40.1, and 26.5% of early-treated infants (<6 months of age) in the three cohorts, respectively, were suppressed less than 50 copies/ml of HIV RNA 6 months after starting ART. We did observe better sustained virologic control after achieving suppression on ART among infants starting ART early compared with late. Children who started ART early were less likely to experience viral rebound (>50 copies/ml or >1000 copies/ml) than children who started late in both cohorts. These findings provide additional support for early initiation of ART in HIV-infected infants.

  19. Development and validation of the San Diego Early Test Score to predict acute and early HIV infection risk in men who have sex with men.

    PubMed

    Hoenigl, Martin; Weibel, Nadir; Mehta, Sanjay R; Anderson, Christy M; Jenks, Jeffrey; Green, Nella; Gianella, Sara; Smith, Davey M; Little, Susan J

    2015-08-01

    Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency virus (HIV), the risk of HIV infection within this population is not uniform. The objective of this study was to develop and validate a score to estimate incident HIV infection risk. Adult MSM who were tested for acute and early HIV (AEH) between 2008 and 2014 were retrospectively randomized 2:1 to a derivation and validation dataset, respectively. Using the derivation dataset, each predictor associated with an AEH outcome in the multivariate prediction model was assigned a point value that corresponded to its odds ratio. The score was validated on the validation dataset using C-statistics. Data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%). Four risk behavior variables were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable analysis and were used to derive the San Diego Early Test (SDET) score: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus ≥5 male partners (3 points), ≥10 male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points)-all as reported for the prior 12 months. The C-statistic for this risk score was >0.7 in both data sets. The SDET risk score may help to prioritize resources and target interventions, such as preexposure prophylaxis, to MSM at greatest risk of acquiring HIV infection. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Paediatric HIV infection.

    PubMed

    Scarlatti, G

    1996-09-28

    By the year 2000 there will be six million pregnant women and five to ten million children infected with HIV-1. Intervention strategies have been planned and in some instances already started. A timely and cost-effective strategy needs to take into account that most HIV-1 infected individuals reside in developing countries. Further studies are needed on immunological and virological factors affecting HIV-1 transmission from mother to child, on differential disease progression in affected children, and on transient infection.

  1. Changes in cognitive function in women with HIV infection and early life stress.

    PubMed

    Spies, Georgina; Fennema-Notestine, Christine; Cherner, Mariana; Seedat, Soraya

    2017-01-01

    HIV is frequently associated with deficits in brain function, including memory, psychomotor speed, executive function and attention. Early life stress (ELS) has also been shown to have a direct influence on neurocognitive performance. However, little is known about the combined impact of ELS and HIV on neurocognitive function over time. The aim of the present study was to follow a cohort of affected women, allowing us to assess the effects of HIV and childhood trauma on cognition and the change in cognition over time. A battery of neurocognitive tests was administered to 117 women at baseline and then a year later. The sample included a total of 67 HIV + and 50 HIV - women, 71 with ELS and 46 without ELS. Controlling for age, education and antiretroviral therapy (ART) at baseline and 12-month follow-up, raw scores were compared across groups using a repeated-measures analysis of covariance. More women were on ART at follow-up compared to baseline. Results revealed a significant combined HIV and childhood trauma effect over time on the Wisconsin Card Sorting Test (p = .003) and Category Fluency Test (p = .006). A significant individual HIV effect over time was evident on the WAIS-III Digit Symbol Test (p = .03) and the Controlled Oral Word Association Test (p = .003). Findings suggest better performance in abstract reasoning, speed of information processing and verbal fluency over time. While all groups showed improvements that may correspond to practice effects, effects of HIV and childhood trauma remained evident at 12-month follow-up despite greater ART uptake and improved HIV disease status. This is the first study to assess the combined impact of HIV and trauma on neurocognitive function over time in an all-female cohort with more advanced disease.

  2. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

    PubMed

    Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

    2012-07-31

    For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

  3. High Viremia and Wasting Before Antiretroviral Therapy Are Associated With Pneumonia in Early-Treated HIV-Infected Kenyan Infants.

    PubMed

    Sridharan, Geetha; Wamalwa, Dalton; John-Stewart, Grace; Tapia, Kenneth; Langat, Agnes; Moraa Okinyi, Helen; Adhiambo, Judith; Chebet, Daisy; Maleche-Obimbo, Elizabeth; Karr, Catherine J; Benki-Nugent, Sarah

    2017-09-01

    Human immunodeficiency virus (HIV)-infected children are particularly susceptible to acute respiratory infections (ARIs). We determined incidence and cofactors for ARIs in HIV-infected infants receiving antiretroviral therapy (ART). Human immunodeficiency virus-infected infants initiated ART at ≤12 months of age and were observed monthly for 2 years in Nairobi. Acute respiratory infection rates and cofactors were determined using Andersen-Gill models, allowing for multiple events per infant. Among 111 HIV-infected infants, median age at ART initiation was 4.5 months. Pre-ART median CD4% was 19%, and 29% had wasting. During 24-months follow-up while on ART, upper respiratory infection (URI) and pneumonia rates were 122.6 and 34.7 per 100 person-years (py), respectively. Infants with higher pre-ART viral load (VL) (plasma HIV ribonucleic acid [RNA] ≥7 log10 copies/mL) had 4.12-fold increased risk of pneumonia (95% confidence interval [CI], 2.17-7.80), and infants with wasting (weight-for-height z-score < -2) had 2.87-fold increased risk (95% CI, 1.56-5.28). Infants with both high pre-ART VL and wasting had a higher pneumonia rate (166.8 per 100 py) than those with only 1 of these risk factors (44.4 per 100 py) or neither (17.0 per 100 py). Infants with exposure to wood fuel had significantly higher risk of URI (hazard ratio [HR] = 1.82; 95% CI, 1.44-2.28) and pneumonia (HR = 3.31; 95% CI, 1.76-6.21). In early ART-treated HIV-infected infants, higher HIV RNA and wasting before ART were independent risk factors for pneumonia. Wood fuel use was associated with URI and pneumonia. Additional data on air pollution and respiratory outcomes in HIV-infected children may help optimize interventions to improve their lung health. © The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Real-World Impact of Neurocognitive Deficits in Acute and Early HIV Infection

    PubMed Central

    Doyle, Katie L.; Morgan, Erin E.; Morris, Sheldon; Smith, Davey M.; Little, Susan; Iudicello, Jennifer E.; Blackstone, Kaitlin; Moore, David J.; Grant, Igor; Letendre, Scott L.; Woods, Steven Paul

    2013-01-01

    The acute and early period of HIV-1 infection (AEH) is characterized by neuroinflammatory and immunopathogenic processes that can alter the integrity of neural systems and neurocognitive functions. However, the extent to which central nervous system changes in AEH confer increased risk of real-world functioning (RWF) problems is not known. In the present study, 34 individuals with AEH and 39 seronegative comparison participants completed standardized neuromedical, psychiatric, and neurocognitive research evaluations, alongside a comprehensive assessment of RWF that included cognitive symptoms in daily life, basic and instrumental activities of daily living, clinician-rated global functioning, and employment. Results showed that AEH was associated with a significantly increased risk of dependence in RWF, which was particularly elevated among AEH persons with global neurocognitive impairment (NCI). Among those with AEH, NCI (i.e., deficits in learning and information processing speed), mood disorders (i.e., Bipolar Disorder), and substance dependence (e.g., methamphetamine dependence) were all independently predictive of RWF dependence. Findings suggest that neurocognitively impaired individuals with AEH are at notably elevated risk of clinically significant challenges in normal daily functioning. Screening for neurocognitive, mood, and substance use disorders in AEH may facilitate identification of individuals at high risk of functional dependence who may benefit from psychological and medical strategies to manage their neuropsychiatric conditions. PMID:24277439

  5. Lung Cancer in HIV Infection

    PubMed Central

    Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

    2011-01-01

    Lung cancer is the most prevalent non-AIDS-defining malignancy in the HAART era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is 2–4 times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the commonest histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Since pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies for this population frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. PMID:21802373

  6. Lung cancer in HIV Infection.

    PubMed

    Mani, Deepthi; Haigentz, Missak; Aboulafia, David M

    2012-01-01

    Lung cancer is the most prevalent non-AIDS-defining malignancy in the highly active antiretroviral therapy era. Smoking plays a significant role in the development of HIV-associated lung cancer, but the cancer risk is two to four times greater in HIV-infected persons than in the general population, even after adjusting for smoking intensity and duration. Lung cancer is typically diagnosed a decade or more earlier among HIV-infected persons (mean age, 46 years) compared to those without HIV infection. Adenocarcinoma is the most common histological subtype, and the majority of patients are diagnosed with locally advanced or metastatic carcinoma. Because pulmonary infections are common among HIV-infected individuals, clinicians may not suspect lung cancer in this younger patient population. Surgery with curative intent remains the treatment of choice for early-stage disease. Although there is increasing experience in using radiation and chemotherapy for HIV-infected patients who do not have surgical options, there is a need for prospective studies because this population is frequently excluded from participating in cancer trials. Evidence-based treatments for smoking-cessation with demonstrated efficacy in the general population must be routinely incorporated into the care of HIV-positive smokers. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Substance Use is a Risk Factor for Neurocognitive Deficits and Neuropsychiatric Distress in Acute and Early HIV Infection

    PubMed Central

    Weber, Erica; Morgan, Erin E.; Iudicello, Jennifer E.; Blackstone, Kaitlin; Grant, Igor; Ellis, Ronald J.; Letendre, Scott L.; Little, Susan; Morris, Sheldon; Smith, Davey M.; Moore, David J.; Woods, Steven Paul

    2012-01-01

    The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naïve adults with median duration of infection of 75 days, relative to sample a of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States (POMS), a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly five-fold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use. PMID:23250704

  8. Impact of maternal HIV infection on obstetrical and early neonatal outcome.

    PubMed

    Braddick, M R; Kreiss, J K; Embree, J B; Datta, P; Ndinya-Achola, J O; Pamba, H; Maitha, G; Roberts, P L; Quinn, T C; Holmes, K K

    1990-10-01

    In a case-control study of 177 HIV-seropositive and 326 seronegative women and their newborns in Nairobi, Kenya, maternal HIV infection at term was independently associated with travel to other African countries [odds ratio (OR) 4.9, P less than 0.0001], history of a blood transfusion since 1980 (OR 3.5, P = 0.01), history of more than one sexual partner in the previous 5 years (OR 1.8, P = 0.02) and unmarried status (OR 1.8, P = 0.02). Neonates of HIV-positive and HIV-negative women differed little with respect to occurrence of congenital malformations, stillbirths, in-hospital mortality, sex, APGAR score, or gestational age. However, the mean birth weight of singleton neonates of HIV-positive women was significantly lower than that of controls (3090 versus 3220 g, P = 0.005), and birth weight was less than 2500 g in 9% of cases and 3% of controls (OR 3.0, P = 0.007). Among neonates of HIV-seropositive women, birth weight was less than 2500 g in 17% if mothers were symptomatic and 6% if mothers were asymptomatic (OR 3.4, P = 0.08).

  9. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection.

    PubMed

    Peluso, Michael J; Meyerhoff, Dieter J; Price, Richard W; Peterson, Julia; Lee, Evelyn; Young, Andrew C; Walter, Rudy; Fuchs, Dietmar; Brew, Bruce J; Cinque, Paola; Robertson, Kevin; Hagberg, Lars; Zetterberg, Henrik; Gisslén, Magnus; Spudich, Serena

    2013-06-01

    Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited. We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)-based metabolites. Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = -0.35, P = .02; r = -0.40, P = .009, respectively), frontal white matter (r = -0.43, P = .003; r = -0.30, P = .048, respectively), and parietal gray matter (r = -0.43, P = .003; r = -0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups. Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation.

  10. Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection

    PubMed Central

    Peluso, Michael J.; Meyerhoff, Dieter J.; Price, Richard W.; Peterson, Julia; Lee, Evelyn; Young, Andrew C.; Walter, Rudy; Fuchs, Dietmar; Brew, Bruce J.; Cinque, Paola; Robertson, Kevin; Hagberg, Lars; Zetterberg, Henrik; Gisslén, Magnus; Spudich, Serena

    2013-01-01

    Background. Cerebrospinal fluid (CSF) and neuroimaging abnormalities demonstrate neuronal injury during chronic AIDS, but data on these biomarkers during primary human immunodeficiency virus (HIV) infection is limited. Methods. We compared CSF concentrations of neurofilament light chain, t-tau, p-tau, amyloid precursor proteins, and amyloid-beta 42 in 92 subjects with primary HIV infection and 25 controls. We examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic resonance spectroscopy (MRS)–based metabolites. Results. Neurofilament light chain was elevated in primary HIV infection compared with controls (P = .0004) and correlated with CSF neopterin (r = 0.38; P = .0005), interferon gamma-induced protein 10 (r = 0.39; P = .002), white blood cells (r = 0.32; P = .004), protein (r = 0.59; P < .0001), and CSF/plasma albumin ratio (r = 0.60; P < .0001). Neurofilament light chain correlated with decreased N-acteylaspartate/creatine and glutamate/creatine in the anterior cingulate (r = −0.35, P = .02; r = −0.40, P = .009, respectively), frontal white matter (r = −0.43, P = .003; r = −0.30, P = .048, respectively), and parietal gray matter (r = −0.43, P = .003; r = −0.47, P = .001, respectively). Beta-amyloid was elevated in the primary infection group (P = .0005) and correlated with time infected (r = 0.34; P = .003). Neither marker correlated with neuropsychological abnormalities. T-tau and soluble amyloid precursor proteins did not differ between groups. Conclusions. Elevated neurofilament light chain and its correlation with MRS-based metabolites suggest early neuronal injury in a subset of participants with primary HIV infection through mechanisms involving central nervous system inflammation. PMID:23460748

  11. Early diagnosis is critical to ensure good outcomes in HIV-infected children: outlining barriers to care.

    PubMed

    Feucht, Ute D; Meyer, Anell; Thomas, Winifred N; Forsyth, Brian W C; Kruger, Mariana

    2016-01-01

    HIV-infected children require early initiation of antiretroviral therapy (ART) to ensure good outcomes. The aim was to investigate missed opportunities in childhood HIV diagnosis leading to delayed ART initiation. Baseline data were reviewed of all children aged <15 years referred over a 1-year period for ART initiation to the Kalafong Hospital HIV services in Gauteng, South Africa. Of the 250 children, one-quarter (24.5%) was of school-going age, 34.5% in the preschool group, 18% between 6 and 12 months old and 23% below 6 months of age (median age = 1.5 years [interquartile range 0.5-4.8]). Most children (82%) presented with advanced/severe HIV disease, particularly those aged 6-12 months (95%). Malnutrition was prominent and referrals were mostly from hospital inpatient services (61%). A structured caregiver interview was conducted in a subgroup, with detailed review of medical records and HIV results. The majority (≥89%) of the 65 interviewed caregivers reported good access to routine healthcare, except for postnatal care (26%). Maternal HIV-testing was mostly done during the second and third pregnancy trimesters (69%). Maternal non-disclosure of HIV status was common (63%) and 83% of mothers reported a lack of psychosocial support. Routine infant HIV-testing was not done in 66%, and inadequate reporting on patient-held records (Road-to-Health Cards/Booklets) occurred frequently (74%). Children with symptomatic HIV disease were not investigated at primary healthcare in 53%, and in 68% of families the siblings were not tested. One-third of children (35%) had a previous HIV diagnosis, with 77% of caregivers aware of these prior results, while 50% acknowledged failing to attend ART services despite referral. In conclusion, a clear strategy on paediatric HIV case finding, especially at primary healthcare, is vital. Multiple barriers need to be overcome in the HIV care pathway to reach high uptake of services, of which especially maternal reasons for not

  12. Lessons from acute HIV infection.

    PubMed

    Robb, Merlin L; Ananworanich, Jintanat

    2016-11-01

    Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection. Robust HIV-specific CD8 T-cell responses lower viral set points. Phylogenetic analyses of founder viruses demonstrated unique bottleneck selections and specific genetic signatures to optimize for high-fitness variants and successful transmission events. HIV clades, route of transmission and the presence of minor variants may affect vaccine protection. Antiretroviral treatment in AHI results in smaller HIV reservoir size, better CD4 T-cell recovery and fewer virus escapes. The knowledge of untreated and treated AHI informs the development of vaccines, in that preventive vaccines will require broad coverage for multiple clades and antigenic variants associated with unique bottleneck selections. Vaccines that help the host to control viremia could minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission should be studied in early-treated individuals who have few or no viral escape mutants and a more preserved immune system.

  13. Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    Law, Matthew G; Achhra, Amit; Deeks, Steven G; Gazzard, Brian; Migueles, Stephen A; Novak, Richard M; Ristola, Matti

    2014-01-01

    Objectives A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined. Methods We assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomisation. The key covariables considered for this analysis were race, hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤50 and ≤400 copies/mL using logistic regression. Because of the strong association between region of randomisation and baseline low HIV RNA, analyses were stratified by region. Results We found that of 4676 eligible participants randomised in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher HDL levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA. Conclusion In a modern cohort of early untreated HIV infection we found that HIV exposure routes other than male homosexual contact and higher HDL were associated with increased odds of low HIV RNA. PMID:25711322

  14. Human Papillomavirus Positivity in the Anal Canal in HIV-Infected and HIV-Uninfected Men Who Have Anal Sex with Men in Guangzhou, China: Implication for Anal Exams and Early Vaccination.

    PubMed

    Ren, Xuqi; Ke, Wujian; Zheng, Heping; Yang, Ligang; Huang, Shujie; Qin, Xiaolin; Yang, Bin; Zou, Huachun

    2017-01-01

    Background. The epidemiology of HPV in men who have sex with men (MSM) in Guangzhou, China, had not been reported previously. Methods . HIV-infected and HIV-uninfected MSM were recruited from a Guangzhou-based MSM clinic in 2013. Sociodemographic characteristics and sexual behaviors were collected. An anal cytological sample was taken for HPV testing. Results. We recruited 79 HIV-infected and 85 HIV-uninfected MSM. The median age was 26 years in both groups. The positivities of anal HPV of any type (81.0% versus 48.2%), any high risk type (50.6% versus 27.1%), any low risk type (55.7% versus 31.8%), and any 9-valent vaccine type (74.7% versus 36.5%) were all significantly higher among HIV-infected compared to that among HIV-negative MSM ( p for all < 0.05). The great majority of HPV-infected MSM were infected with 9-valent vaccine types (59 out of 64 HIV-infected and 31 out of 41 HIV-uninfected). Anal bacterial infections were associated with higher anal HPV positivity and greater number of anal HPV types. Conclusion. Sexually active MSM in Guangzhou, especially those infected with HIV, had high and multiple HPV detections. The majority of these cases were potentially preventable by HPV vaccine. Regular anal exams and early HPV vaccination are warranted in this population.

  15. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC.

    PubMed

    Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F; McMichael, Andrew; Shaw, George M; Hahn, Beatrice H; Korber, Bette; Seoighe, Cathal

    2009-05-01

    The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide

  16. HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC

    PubMed Central

    Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F.; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F.; McMichael, Andrew; Shaw, George M.; Hahn, Beatrice H.; Korber, Bette; Seoighe, Cathal

    2009-01-01

    The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide

  17. Risk Factors for Early and Late Transmission of HIV via Breast-Feeding among Infants Born to HIV-Infected Women in a Randomized Clinical Trial in Botswana

    PubMed Central

    Shapiro, Roger L.; Smeaton, Laura; Lockman, Shahin; Thior, lbou; Rossenkhan, Raabya; Wester, Carolyn; Stevens, Lisa; Moffat, Claire; Arimi, Peter; Ndase, Patrick; Asmelash, Aida; Leidner, Jean; Novitsky, Vladimir; Makhema, Joseph; Essex, Max

    2009-01-01

    Risk factors for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breast-feeding were evaluated in a randomized trial. HIV-infected women and their infants received zidovudine as well as single-dose nevirapine or placebo. Infants were randomized to formula-feed (FF) or breast-feed (BF) in combination with zidovudine prophylaxis. Of 1116 at-risk infants, 6 (1.1%) in the FF group and 7 (1.3%) in the BF group were infected between birth and 1 month)P = .99). Maternal receipt of nevirapine did not predict early MTCT in the BF group (P = .45). Of 547 infants in the BF group at risk for late MTCT, 24 (4.4%) were infected. Maternal HIV-1 RNA levels in plasma (P<.001) and breast milk (P<.001) predicted late MTCT. These findings support the safety of 1 month of breast-feeding in combination with maternal and infant antiretroviral prophylaxis. PMID:19090775

  18. The effect of micronutrient supplementation on active TB incidence early in HIV infection in Botswana

    PubMed Central

    Campa, Adriana; Baum, Marianna K; Bussmann, Hermann; Martinez, Sabrina Sales; Farahani, Mansour; van Widenfelt, Erik; Moyo, Sikhulile; Makhema, Joseph; Essex, Max; Marlink, Richard

    2017-01-01

    Background Coinfection with active tuberculosis (TB) is one of the leading causes of death in people living with HIV (PLWH) in Africa. This investigation explores the role of micronutrient supplementation in preventing active TB in PLWH. Methods A randomized trial of nutritional supplementation was conducted among antiretroviral- naïve (without previous antiretroviral treatment [ART]) HIV-infected people in Botswana between 2004 and 2009. The study had a factorial design with four arms: the selenium (Se) alone arm, the multivitamins (MVT) alone arm that contained vitamin B complex and vitamins C and E, the combined Se+MVT group and the placebo group. Those participants with prior or current active TB were excluded, as were participants with advanced HIV disease (CD4 <250 cells/μL) or who had already qualified for ART. HIV-positive adults (N=878) were followed monthly for study pill dispensation, every 3 months for CD4 cell count and every 6 months for viral load during 24 months or until they were started on ART. Results The participants' characteristics were not significantly different among the four groups at baseline. Supplementation with Se alone (hazard ratio =0.20, 95% confidence interval: 0.04, 0.95, P=0.043) and the two combined SE groups (Se and Se+MVT) had significantly lower risk of developing incident TB disease compared with placebo in multivariate adjusted models (hazard ratio=0.32, 95% confidence interval: 0.11, 0.93, P=0.036). Multivitamins alone did not affect the incidence of TB. Isoniazid preventive therapy was received by 12.2% of participants, a rate that was not significantly different among the four study arms (P=0.122) and the newly diagnosed cases. Conclusion Se supplementation, alone and with MVT, decreased the incidence of TB disease in PLWH who were ART-naïve. Supplementation with these micronutrients should be considered in HIV infection, prior to ART, in areas where TB and malnutrition are endemic. PMID:29187783

  19. Mass Cytometry Analysis Reveals the Landscape and Dynamics of CD32a+ CD4+ T Cells From Early HIV Infection to Effective cART.

    PubMed

    Coindre, Sixtine; Tchitchek, Nicolas; Alaoui, Lamine; Vaslin, Bruno; Bourgeois, Christine; Goujard, Cecile; Avettand-Fenoel, Veronique; Lecuroux, Camille; Bruhns, Pierre; Le Grand, Roger; Beignon, Anne-Sophie; Lambotte, Olivier; Favier, Benoit

    2018-01-01

    CD32a has been proposed as a specific marker of latently HIV-infected CD4 + T cells. However, CD32a was recently found to be expressed on CD4 + T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a + CD4 + T cells during HIV infection. To this end, we analyzed CD32a + CD4 + T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors. We found that CD32a + CD4 + T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive ( N ), central memory ( CM ), and effector/memory ( Eff/Mem ) CD32a + CD4 + T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2 - CD32a + CD4 + T-cell clusters of either the T N , T CM , or T Eff/Mem phenotype were more abundant in healthy individuals. Finally, an activated CD32a + CD4 + T Eff/Mem cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a + CD4 + T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4 + T cells during HIV infection.

  20. Pharmacotherapy of Pediatric HIV Infection

    PubMed Central

    Rakhmanina, Natella; Phelps, Ryan

    2012-01-01

    SYNOPSIS With the ongoing epidemic of human immune deficiency virus (HIV) infections in the pediatric age group, the delivery of safe and effective antiretroviral therapy to children and adolescents is crucial to save the lives of millions of children worldwide. Antiretroviral drugs have been demonstrated to significantly decrease HIV-associated morbidity and mortality, assure normal growth and development, and improve survival and quality of life in children and adolescents. The immunologic response to HIV infection is closely related to the child’s development and creates age specific parameters for the evaluation of therapeutic response to antiretroviral therapy in pediatric HIV disease. In addition to the changes in immunological response to HIV infection, the development and maturation of organ systems involved in drug absorption, distribution, metabolism, and elimination determines significant changes in the pharmacokinetics of antiretroviral drugs throughout the childhood. Multiple factors including age-specific adherence barriers, changes in social and economical surroundings, and psychological and sexual maturation affect the choices and outcomes of the treatment of pediatric HIV disease. In this chapter we will review the evolution of antiretroviral treatment from early infancy through adolescence. PMID:23036246

  1. Assessment of biomarkers of cardiovascular risk among HIV type 1-infected adolescents: role of soluble vascular cell adhesion molecule as an early indicator of endothelial inflammation.

    PubMed

    Syed, Salma S; Balluz, Rula S; Kabagambe, Edmond K; Meyer, William A; Lukas, Susan; Wilson, Craig M; Kapogiannis, Bill G; Nachman, Sharon A; Sleasman, John W

    2013-03-01

    Cardiovascular disease (CVD) biomarkers were examined in a cohort of HIV-infected and HIV-uninfected adolescents who participated in Adolescent Trials Network study 083 utilizing samples from the Reaching for Excellence in Adolescent Care cohort, a longitudinal study of youth infected through adult risk behavior. Nonfasting blood samples from 97 HIV-infected and 81 HIV-uninfected adolescents infected by adult risk behaviors were analyzed for total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglycerides, apolipoprotein A-I, high-sensitivity C-reactive protein (hsCRP), soluble vascular adhesion molecule-1 (sVCAM-1), myeloperoxidase, and neopterin at baseline and 18 months later. Results were analyzed using ANOVA, Wilcoxon signed-rank, and paired t tests. Among infected subjects 67 received antiretroviral therapy and 30 were treatment naive. The HIV-infected and HIV-uninfected subjects were similar in gender, ethnicity, and cardiovascular risk factors such as smoking and obesity. In all groups lipid parameters were within accepted guidelines for cardiovascular risk. Among HIV-infected youth on antiretroviral therapy (ART), HDL and apoprotein A-I were significantly lower when compared to uninfected youth. hsCRP was not elevated and thus not predictive for risk in any group. sVCAM-1 levels were significantly elevated in both HIV-infected groups: 1,435 ng/ml and 1,492 ng/ml in untreated and treated subjects, respectively, and 1,064 ng/ml in the uninfected group (p<0.0001). Across all groups neopterin correlated with sVCAM at 18 months (Spearman correlation coefficient 0.58, p<0.0001). Only 9% of ART-treated subjects fully suppressed virus. Lipid profiles and hsCRP, traditional markers of cardiovascular disease, are not abnormal among HIV-infected youth but elevated sVCAM may be an early marker of atherosclerosis.

  2. HIV infection in children.

    PubMed

    Canosa, C A

    1991-01-01

    Various studies have reported rates of human immunodeficiency virus (HIV) transmission from mother to child of 13-40%. Vertical transmission occurs in utero, during delivery, or, in a small number of cases, through breast milk. Whether mothers at various stages of HIV infection experience different rates of transmission remains unknown. Maternal antibodies cross the placenta and are present from birth up to 18 months of age. The offspring of HIV-positive mothers tend to be low birthweight, under 37 weeks' gestation, and at high risk of perinatal mortality. It is likely, however, that this profile is indicative of the low socioeconomic status of most women with HIV rather than a result of infection. Also emerging is a psychosocial profile of the HIV child. These children are isolated, neglected, battered, frequently abandoned, and exhibit various degrees of mental retardation. Also common are delayed psychomotor development, loss of developmental milestones, limited attention span, poor language development, and abnormal reflexes. These features result from the interaction of low socioeconomic status, a lack of psychosocial stimulation, nutritional deficiencies, and central nervous system infections. Since HIV-infected children tend to be the offspring of drug addicts, bisexuals, and prostitutes, they are not awarded the same compassion as children afflicted with other terminal illnesses. Moreover, these children are generally neglected by groups formed to provide support to AIDS patients. Thus, it is up to the general public, the mass media, and the health care system to advocate for the needs of these neglected children.

  3. Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?

    PubMed Central

    Ghiglione, Yanina; Hormanstorfer, Macarena; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D.; Pando, María de los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Sued, Omar

    2018-01-01

    Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied. PMID:29342870

  4. Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting.

    PubMed

    Goldenberg, Shira M; Chettiar, Jill; Simo, Annick; Silverman, Jay G; Strathdee, Steffanie A; Montaner, Julio S G; Shannon, Kate

    2014-01-01

    To explore factors associated with early sex work initiation and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Baseline data (2010-2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. SWs completed a questionnaire and HIV/sexually transmitted infection testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs. Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian born [adjusted odds ratio (AOR): 6.8, 95% confidence interval (CI): 2.42 to 19.02], inject drugs (AOR: 1.6, 95% CI: 1.0 to 2.5), and to have worked for a manager (AOR: 2.22, 95% CI: 1.3 to 3.6) or been coerced into sex work (AOR: 2.3, 95% CI: 1.14 to 4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3 to 3.2) and prostitution arrests (AOR: 2.0, 95% CI: 1.3 to 3.2). Adolescent sex work initiation is concentrated among marginalized, drug, and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs.

  5. Risk Factors for Acute and Early HIV Infection Among Men Who Have Sex With Men (MSM) in San Diego, 2008 to 2014: A Cohort Study.

    PubMed

    Hoenigl, Martin; Green, Nella; Mehta, Sanjay R; Little, Susan J

    2015-07-01

    The objectives of this study were to identify risk factors associated with acute and early HIV infection (AEH) among men who have sex with men (MSM) undergoing community HIV testing and to compare demographics in those diagnosed with AEH with those diagnosed at chronic stage of HIV infection.In this retrospective cohort study, we analyzed risk factors associated with AEH among 8925 unique MSM (including 200 with AEH [2.2%] and 219 [2.5%] with newly diagnosed chronic HIV infection) undergoing community-based, confidential AEH screening in San Diego, California.The combination of condomless receptive anal intercourse (CRAI) plus ≥5 male partners, CRAI with an HIV-positive male, CRAI with a person who injects drugs, and prior syphilis diagnosis were significant predictors of AEH in the multivariable Cox regression model. Individuals reporting ≥1 of these 4 risk factors had a hazard ratio of 4.6 for AEH. MSM diagnosed with AEH differed in race (P = 0.005; more reported white race [P = 0.001], less black race [P = 0.030], trend toward less Native American race [P = 0.061]), when compared to those diagnosed with chronic HIV infection, while there was no difference observed regarding age.We established a multivariate model for the predicting risk of AEH infection in a cohort of MSM undergoing community HIV screening, which could be potentially used to discern those in need of further HIV nucleic acid amplification testing for community screening programs that do not test routinely for AEH. In addition, we found that race differed between those diagnosed with AEH and those diagnosed at chronic stage of HIV infection underlining the need for interventions that reduce stigma and promote the uptake of HIV testing for black MSM.

  6. High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS.

    PubMed

    Pizzolo, G; Vinante, F; Morosato, L; Nadali, G; Chilosi, M; Gandini, G; Sinicco, A; Raiteri, R; Semenzato, G; Stein, H

    1994-06-01

    To determine the serum levels of the soluble form of the CD30 (sCD30) activation molecule in the early phase of HIV-1 infection, and to investigate the possible correlation with evolution to AIDS. sCD30 values were determined by an enzyme-linked immunosorbent assay (ELISA) on serum samples collected at the time of the first evidence of HIV-1 infection in 110 individuals with a median follow-up of 56 months (range, 12-88 months), at the A1 (74 cases) or A2 (36 cases) stages of the 1993 revised Centers for Disease Control and Prevention classification. The data were evaluated using established clinical and immunological parameters, including circulating CD4+ T-cell count. The controls were 110 blood donors and 51 HIV-1-negative subjects belonging to groups at risk for HIV-1 infection. Elevated sCD30 levels (> 20 U/ml) were found in 83.6% of HIV-1-infected cases and in 47% of at-risk seronegatives. Data analysis revealed that HIV-1-infected patients with higher sCD30 levels (> 35 U/ml) experienced faster disease progression (P = 0.0002). This was also the case in patients at the earliest stage (A1) of HIV infection (P = 0.0027). In these latter cases the predictive value of sCD30 was independent of the initial absolute number of circulating CD4+ lymphocytes. Serum levels of sCD30 are increased in the large majority of patients in the early phase of HIV-1 infection and represent an indicator of progression to AIDS independent of other prognostic parameters.

  7. Early infant diagnosis of HIV infection using DNA-PCR at a referral center: an 8 years retrospective analysis.

    PubMed

    Olana, Tolessa; Bacha, Tigist; Worku, Walelign; Tadesse, Birkneh Tilahun

    2016-01-01

    Over the last decade, Ethiopia adopted different strategies of prevention of mother to child transmission of HIV (PMTCT). Prior to implementation of Option A in 2011, there was no provision of prophylaxis for PMTCT. With 'Option A', PMTCT interventions relied on maternal CD4 count. In early 2013, ''Option B+'' has been started; with this option, antiretroviral therapy is started and continued for life to any HIV positive pregnant mother irrespective of CD4 count with an enhanced treatment for the baby. Though there are a number of studies which evaluated the effectiveness of PMTCT interventions, the current study assessed the real-world effectiveness of PMTCT options in a setting where there is limitation of resources. This study tried to address three questions: what proportion of babies tested by DNA-PCR are HIV infected in the first 2 months of life? How does the type of PMTCT intervention affect presence of HIV infection at this age? What are the factors affecting HIV transmission, after controlling for type of PMCT-HIV intervention? We assessed records of 624 registered HIV exposed infants and 412 mothers who were delivered at Bishoftu Hospital from May 2006 to August 2014. Presence of HIV infection at 6-8 weeks of age was assessed from the records. Maternal and infant risk factors for infection at this age were analyzed. Data were collected using standard data abstraction format and were analyzed using SPSS version 20. Among all the infants who were delivered at the hospital during the study period, 624/936 (66.7 %) had undergone early infant diagnosis at 6-8 weeks. Twenty-seven (4.3 %) were positive for HIV DNA PCR at the age of 6-8 weeks. None of the infants who received ''Option B+'' had a positive HIV DNA PCR result. HIV infection rate was highest among those who took either no prophylaxis or single dose Nevirapine (11.5 and 11.1 % respectively). Those who took single dose Nevirapine and Zidovudine had HIV positivity rate of 3.9 %. Many of the

  8. Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting

    PubMed Central

    GOLDENBERG, Shira M.; CHETTIAR, Jill; SIMO, Annick; SILVERMAN, Jay G.; STRATHDEE, Steffanie A.; MONTANER, Julio; SHANNON, Kate

    2014-01-01

    Objectives To explore factors associated with early sex work initiation, and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Design Baseline data (2010–2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time-location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. Methods SWs completed a questionnaire and HIV/STI testing. Using multivariate logistic regression, we identified associations with early sex work initiation (<18 years old) and constructed confounder models examining the independent effect of early initiation on HIV and prostitution arrests among adult SWs. Results Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian-born (Adjusted Odds Ratio (AOR): 6.8, 95% Confidence Interval (CI): 2.42–19.02), inject drugs (AOR: 1.6, 95%CI: 1.0–2.5), and to have worked for a manager (AOR: 2.22, 95%CI: 1.3–3.6) or been coerced into sex work (AOR: 2.3, 95%CI: 1.14–4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3–3.2) and prostitution arrests (AOR: 2.0, 95%CI: 1.3–3.2). Conclusions Adolescent sex work initiation is concentrated among marginalized, drug and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs. PMID:23982660

  9. Effects of Inner Nuclear Membrane Proteins SUN1/UNC-84A and SUN2/UNC-84B on the Early Steps of HIV-1 Infection.

    PubMed

    Schaller, Torsten; Bulli, Lorenzo; Pollpeter, Darja; Betancor, Gilberto; Kutzner, Juliane; Apolonia, Luis; Herold, Nikolas; Burk, Robin; Malim, Michael H

    2017-10-01

    leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis. Copyright © 2017 Schaller et al.

  10. Identification of early HIV infections using the fourth generation Abbott ARCHITECT HIV Ag/Ab Combo chemiluminescent microparticle immunoassay (CIA) in San Diego County.

    PubMed

    Manlutac, Anna Liza M; Giesick, Jill S; McVay, Patricia A

    2013-12-01

    HIV screening assays have gone through several generations of development in an effort to narrow the "window period" of detection. Utilizing a fourth generation HIV screening assay has the potential to detect earlier HIV infection, thus reducing HIV-1 transmission. To identify acute infections to decrease HIV transmission in San Diego County. Serum specimens were collected from clients seen by multiple submitters in San Diego County. All acceptable specimens were screened using the 4th Gen Combo Assay. Initially reactive specimens were repeated in duplicate and if repeatedly reactive, were confirmed by HIV-1 Immunofluorescent Antibody Assay (IFA). IFA negative/inconclusive specimens were sent for HIV-1 NAT and HIV-2 antibody testing to referral laboratories. BioRad Multispot HIV-1/HIV-2 Rapid Test was also performed on a subset of specimens. Of 14,559 specimens received in 20 months, 14,517 specimens were tested. Of the 14,517 specimens that were tested, a total of 279 (1.9%) specimens were CIA repeatedly reactive and 240 of the 279 confirmed by HIV-1 IFA. Thirty-nine gave IFA negative/inconclusive result and 30 were further tested for HIV-1 NAT and 36 for HIV-2 antibody. Thirteen specimens were considered false positives by CIA and 17 specimens were classified as acute infections. Eleven of 39 IFA negative/inconclusive specimens were further tested by Multispot. Five of the 11 were positive by Multispot. The fourth generation Abbott ARCHITECT HIV Ag/Ab Combo Assay identified 17 patients who may have been missed by the prior HIV-1 screening assay used at San Diego County Public Health Laboratory. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Investigating the Consequences of Interference between Multiple CD8+ T Cell Escape Mutations in Early HIV Infection

    PubMed Central

    Garcia, Victor; Feldman, Marcus W.; Regoes, Roland R.

    2016-01-01

    During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV’s genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains –an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction– could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by

  12. Elevated NT-Pro-Brain Natriuretic Peptide Level Is Independently Associated with All-Cause Mortality in HIV-Infected Women in the Early and Recent HAART Eras in the Women’s Interagency HIV Study Cohort

    PubMed Central

    Gingo, Matthew R.; Zhang, Yingze; Ghebrehawariat, Kidane B.; Jeong, Jong-Hyeon; Chu, Yanxia; Yang, Quanwei; Lucht, Lorrie; Hanna, David B.; Lazar, Jason M.; Gladwin, Mark T.; Morris, Alison

    2015-01-01

    Background HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women. Design Prospective cohort study. Methods and Results We measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women’s Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3–2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4–5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women. Conclusion NT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women. PMID:25811188

  13. Comparison of developmental milestone attainment in early treated HIV-infected infants versus HIV-unexposed infants: a prospective cohort study.

    PubMed

    Benki-Nugent, Sarah; Wamalwa, Dalton; Langat, Agnes; Tapia, Kenneth; Adhiambo, Judith; Chebet, Daisy; Okinyi, Helen Moraa; John-Stewart, Grace

    2017-01-17

    Infant HIV infection is associated with delayed milestone attainment. The extent to which effective antiretroviral therapy (ART) prevents these delays is not well defined. Ages at attainment of milestones were compared between HIV-infected (initiated ART by age <5 months), and HIV-unexposed uninfected (HUU) infants. Kaplan Meier analyses were used to estimate and compare (log-rank tests) ages at milestones between groups. Adjusted analyses were performed using Cox proportional hazards models. Seventy-three HIV-infected on ART (median enrollment age 3.7 months) and 92 HUU infants (median enrollment age 1.6 months) were followed prospectively. HIV-infected infants on ART had delays in developmental milestone attainment compared to HUU: median age at attainment of sitting with support, sitting unsupported, walking with support, walking unsupported, monosyllabic speech and throwing toys were each delayed (all p-values <0.0005). Compared with HUU, the subset of HIV-infected infants with both virologic suppression and immune recovery at 6 months had delays for speech (delay: 2.0 months; P = 0.0002) and trend to later walking unsupported. Among HIV-infected infants with poor 6-month post-ART responses (lacking viral suppression and immune recovery) there were greater delays versus HUU for: walking unsupported (delay: 4.0 months; P = 0.0001) and speech (delay: 5.0 months; P < 0.0001). HIV infected infants with viral suppression on ART had better recovery of developmental milestones than those without suppression, however, deficits persisted compared to uninfected infants. Earlier ART may be required for optimized cognitive outcomes in perinatally HIV-infected infants. NCT00428116 ; January 22, 2007.

  14. APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus-1 infection.

    PubMed

    Gourraud, P A; Karaouni, A; Woo, J M; Schmidt, T; Oksenberg, J R; Hecht, F M; Liegler, T J; Barbour, J D

    2011-03-01

    We examined single nucleotide polymorphisms (SNP) in the APOBEC3 locus on chromosome 22, paired with population sequences of pro-viral human immunodeficiency virus-1 (HIV-1) vif from peripheral blood mononuclear cells, from 96 recently HIV-1-infected treatment-naive adults. We found evidence for the existence of an APOBEC3H linkage disequilibrium (LD) block associated with variation in GA → AA, or APOBEC3F/H signature, sequence changes in pro-viral HIV-1 vif sequence (top 10 significant SNPs with a significant p = 4.8 × 10(-3)). We identified a common five position risk haplotype distal to APOBEC3H (A3Hrh). These markers were in high LD (D' = 1; r(2) = 0.98) to a previously described A3H "RED" haplotype containing a variant (E121) with enhanced susceptibility to HIV-1 Vif. This association was confirmed by a haplotype analysis. Homozygote carriers of the A3Hrh had lower GA->AA (A3F/H) sequence editing upon pro-viral HIV-1 vif sequence (p = 0.01), and lower HIV-1 RNA levels over time during early, untreated HIV-1 infection, (p = 0.015 mixed effects model). This effect may be due to enhanced susceptibility of A3H forms to HIV-1 Vif mediated viral suppression of sequence editing activity, slowing viral diversification and escape from immune responses. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Talaromyces (Penicillium) marneffei infection in non-HIV-infected patients

    PubMed Central

    Chan, Jasper FW; Lau, Susanna KP; Yuen, Kwok-Yung; Woo, Patrick CY

    2016-01-01

    Talaromyces (Penicillium) marneffei is an important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia. The clinical significance of T. marneffei became evident when the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome epidemic arrived in Southeast Asia in 1988. Subsequently, a decline in the incidence of T. marneffei infection among HIV-infected patients was seen in regions with access to highly active antiretroviral therapy and other control measures for HIV. Since the 1990s, an increasing number of T. marneffei infections have been reported among non-HIV-infected patients with impaired cell-mediated immunity. Their comorbidities included primary adult-onset immunodeficiency due to anti-interferon-gamma autoantibodies and secondary immunosuppressive conditions including other autoimmune diseases, solid organ and hematopoietic stem cell transplantations, T-lymphocyte-depleting immunsuppressive drugs and novel anti-cancer targeted therapies such as anti-CD20 monoclonal antibodies and kinase inhibitors. Moreover, improved immunological diagnostics identified more primary immunodeficiency syndromes associated with T. marneffei infection in children. The higher case-fatality rate of T. marneffei infection in non-HIV-infected than HIV-infected patients might be related to delayed diagnosis due to the lack of clinical suspicion. Correction of the underlying immune defects and early use of antifungals are important treatment strategies. Clinicians should be familiar with the changing epidemiology and clinical management of T. marneffei infection among non-HIV-infected patients. PMID:26956447

  16. Adipose Tissue in HIV Infection.

    PubMed

    Koethe, John R

    2017-09-12

    HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling. HIV viral proteins persist in circulation and locally within adipose tissue despite suppression of plasma viremia on ART, and exposure to these proteins impairs preadipocyte maturation and reduces adipocyte expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and other genes involved in cell regulation. Several early nucleoside reverse transcriptase inhibitor and protease inhibitor antiretroviral drugs demonstrated substantial adipocyte toxicity, including reduced mitochondrial DNA content and respiratory chain enzymes, reduced PPAR-γ and other regulatory gene expression, and increased proinflammatory cytokine production. Newer-generation agents, such as integrase inhibitors, appear to have fewer adverse effects. HIV infection also alters the balance of CD4+ and CD8+ T cells in adipose tissue, with effects on macrophage activation and local inflammation, while the presence of latently infected CD4+ T cells in adipose tissue may constitute a protected viral reservoir. This review provides a synthesis of the literature on how HIV virus, ART treatment, and host characteristics interact to affect adipose tissue distribution, immunology, and contribution to metabolic health, and adipocyte maturation, cellular regulation, and energy storage. © 2017 American Physiological Society. Compr Physiol 7:1339-1357, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  17. Socio-economic status and time trends associated with early ART initiation following primary HIV infection in Montreal, Canada: 1996 to 2015.

    PubMed

    Mehraj, Vikram; Cox, Joseph; Lebouché, Bertrand; Costiniuk, Cecilia; Cao, Wei; Li, Taisheng; Ponte, Rosalie; Thomas, Réjean; Szabo, Jason; Baril, Jean-Guy; Trottier, Benoit; Côté, Pierre; LeBlanc, Roger; Bruneau, Julie; Tremblay, Cécile; Routy, Jean-Pierre

    2018-02-01

    Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study. The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs). Recently diagnosed HIV-infected adults were categorized as receiving early (vs. delayed) ART if ART was initiated within 180 days of the baseline visit. Associations between early ART initiation and socio-demographic, socio-economic and behavioural information were examined. Independent associations of factors linked with early ART initiation were determined using multivariable binary logistic regression analysis. A total of 348 participants had a documented date of HIV acquisition of <180 days. The median interquartile range (IQR) age of participants was 35 (28; 42) years and the majority were male (96%), having paid employment (63%), men who have sex with men (MSM) (78%) and one to four sexual partners in the last three months (70%). Participants presented with a median IQR HIV plasma viral load of 4.6 (3.7; 5.3) log 10 copies/ml, CD4 count of 510 (387; 660) cells/μl and were recruited in CMCs (52%) or UMCs (48%). Early ART initiation was observed in 47% of the participants and the trend followed a V-shaped curve with peaks in 1996 to 1997 (89%) and 2013 to 2015 (88%) with a dip in 2007 to 2009 (22%). Multivariable analyses showed that having a paid employment adjusted odds ratio (aOR: 2.43; 95% CI: 1.19, 4.95), lower CD4 count (aOR per 50 cell increase: 0.93; 95% CI: 0.87, 0.99) and care at UMCs (aOR: 2.03; 95% CI: 1.06 to 3.90) were independently associated with early ART

  18. CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients.

    PubMed

    Ghosh, Gopal Chandra; Sharma, Brijesh; Gupta, B B

    2016-01-01

    Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients.

  19. [HIV infection and immigration].

    PubMed

    Monge, Susana; Pérez-Molina, José A

    2016-01-01

    Migrants represent around one third of patients newly diagnosed with HIV in Spain and they constitute a population with higher vulnerability to its negative consequences due to the socio-cultural, economical, working, administrative and legal contexts. Migrants are diagnosed later, which worsens their individual prognosis and facilitates the maintenance of the HIV epidemic. In spite of the different barriers they experience to access healthcare in general, and HIV-related services in particular, access to antiretroviral treatment has been similar to that of the autochthonous population. However, benefits of treatment have been not, with women in general and men from Sub-Saharan Africa exhibiting the worse response to treatment. We need to proactively promote earlier diagnosis of HIV infection, the adoption of preventive measures to avoid new infections, and to deliver accessible, adapted and high-quality health-care. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Travel medicine and HIV infection.

    PubMed

    Igreja, Ricardo

    2008-09-01

    The number of HIV-infected persons who travel is increasing. This increase arises from those who have benefited from advances in antiretroviral therapy. The key to successful travel is careful pre-trip planning although many patients do not obtain advice before travelling. Travel advice for HIV patients is becoming increasingly specialized, and includes travel vaccination and highly active antiretroviral therapy-related issues. A closer collaboration between HIV and travel health clinics could provide better care for HIV-infected individuals.

  1. The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection

    PubMed Central

    Mehraj, Vikram; Jenabian, Mohammad-Ali; Ponte, Rosalie; Lebouché, Bertrand; Costiniuk, Cecilia; Thomas, Réjean; Baril, Jean-Guy; LeBlanc, Roger; Cox, Joseph; Tremblay, Cécile; Routy, Jean-Pierre

    2016-01-01

    Objective: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Design: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. Methods: IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Results: Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. Conclusion: As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis. PMID:27045377

  2. Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

    PubMed Central

    Ghiglione, Yanina; Falivene, Juliana; Socias, María Eugenia; Laufer, Natalia; Coloccini, Romina Soledad; Rodriguez, Ana María; Ruiz, María Julia; Pando, María Ángeles; Giavedoni, Luis David; Cahn, Pedro; Sued, Omar; Salomon, Horacio; Gherardi, María Magdalena

    2013-01-01

    The important role of the CD8+ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8+ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8+ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4+ T-cell set points were observed in PHI subjects with higher HIV-specific CD8+ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8+ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection. PMID:23616666

  3. Improved Survival of HIV-1-Infected Patients with Progressive Multifocal Leukoencephalopathy Receiving Early 5-Drug Combination Antiretroviral Therapy

    PubMed Central

    Hendel-Chavez, Houria; Dulioust, Anne; Pakianather, Sophie; Mazet, Anne-Aurélie; de Goer de Herve, Marie-Ghislaine; Lancar, Rémi; Lascaux, Anne-Sophie; Porte, Lydie; Delfraissy, Jean-François; Taoufik, Yassine

    2011-01-01

    Background Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery. Methods and Findings All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008). Conclusions The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death. Trial Registration ClinicalTrials.gov NCT00120367 PMID:21738597

  4. Immunology of Pediatric HIV Infection

    PubMed Central

    Tobin, Nicole H.; Aldrovandi, Grace M.

    2013-01-01

    Summary Most infants born to human immunodeficiency virus (HIV)-infected women escape HIV infection. Infants evade infection despite an immature immune system and, in the case of breastfeeding, prolonged repetitive, exposure. If infants become infected, the course of their infection and response to treatment differs dramatically depending upon the timing (in utero, intrapartum, or during breastfeeding) and potentially the route of their infection. Perinatally acquired HIV infection occurs during a critical window of immune development. HIV’s perturbation of this dynamic process may account for the striking age-dependent differences in HIV disease progression. HIV infection also profoundly disrupts the maternal immune system upon which infants rely for protection and immune instruction. Therefore, it is not surprising that infants who escape HIV infection still suffer adverse effects. In this review, we highlight the unique aspects of pediatric HIV transmission and pathogenesis with a focus on mechanisms by which HIV infection during immune ontogeny may allow discovery of key elements for protection and control from HIV. PMID:23772619

  5. Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection.

    PubMed

    Rossenkhan, Raabya; MacLeod, Iain J; Brumme, Zabrina L; Magaret, Craig A; Sebunya, Theresa K; Musonda, Rosemary; Gashe, Berhanu A; Edlefsen, Paul T; Novitsky, Vlad; Essex, M

    Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.

  6. Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

    PubMed Central

    Rossenkhan, Raabya; MacLeod, Iain J.; Brumme, Zabrina L.; Magaret, Craig A.; Sebunya, Theresa K.; Musonda, Rosemary; Gashe, Berhanu A.; Edlefsen, Paul T.; Novitsky, Vlad

    2016-01-01

    Abstract Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission. PMID:27349335

  7. Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study.

    PubMed

    Puthanakit, Thanyawee; Ananworanich, Jintanat; Vonthanak, Saphonn; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; van der Lugt, Jasper; Kerr, Stephen J; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vibol, Ung; Pruksakaew, Kanchana; Suwarnlerk, Tulathip; Apornpong, Tanakorn; Ratanadilok, Kattiya; Paul, Robert; Mofenson, Lynne M; Fox, Lawrence; Valcour, Victor; Brouwers, Pim; Ruxrungtham, Kiat

    2013-05-01

    We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes. Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319). At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist. In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.

  8. Early life traumatic stressors and the mediating role of PTSD in incident HIV infection among US men, comparisons by sexual orientation and race/ethnicity: results from the NESARC, 2004-2005.

    PubMed

    Reisner, Sari L; Falb, Kathryn L; Mimiaga, Matthew J

    2011-08-01

    Stressful life events in childhood during critical periods of development have long-term psychological and neurobiological sequelae, which may affect risk for HIV infection across the life course. Data were from a nationally representative sample of 13,274 US men (National Epidemiologic Survey on Alcohol and Related Conditions, 2004-2005). Weighted multivariable logistic regression models examined (1) the association of childhood violent events before age 18 on 12-month incident HIV infection and (2) whether posttraumatic stress disorder (PTSD) diagnosis (clinical interview) mediated the association between early life events and HIV. Overall, the 12-month HIV incidence was <1% (0.35%); 44% of new infections were among racial/ethnic minorities and 31% among men who have sex with men). One-third of the sample (33.5%) reported one or more early life stressors (physical abuse, sexual abuse, neglect, verbal violence, or witnessed violence). In a weighted multivariable logistic regression model adjusted for age, education, family's socioeconomic position, and sexual behaviors, each additional early life violent event was associated with an elevated odds of HIV infection [adjusted odds ratio (aOR) = 1.32; 95% confidence interval (CI): 1.16 to 1.50]. Adding PTSD to this adjusted model, PTSD was highly associated with incident HIV infection (aOR = 5.75; 95% CI: 4.76 to 6.95). There was evidence that PTSD partially mediated the relationship between early life events and HIV (aOR = 1.14; 95% CI: 1.02 to 1.28). Experiencing early life violent family stressors was associated with HIV infection among men. Early life events and HIV infection were mediated by PTSD, which has implications for understanding disparities in HIV infection. Interventions are urgently needed that address the long-term sequelae of childhood violence.

  9. Preventing HIV infection in women.

    PubMed

    Adimora, Adaora A; Ramirez, Catalina; Auerbach, Judith D; Aral, Sevgi O; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth A

    2013-07-01

    Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral, and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be performed to implement scientific advancements and to resolve many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities.

  10. Preventing HIV Infection in Women

    PubMed Central

    Adimora, Adaora A.; Ramirez, Catalina; Auerbach, Judith D.; Aral, Sevgi O.; Hodder, Sally; Wingood, Gina; El-Sadr, Wafaa; Bukusi, Elizabeth Anne

    2014-01-01

    Although the number of new infections has declined recently, women still constitute almost half of the world's 34 million people with HIV infection, and HIV remains the leading cause of death among women of reproductive age. Prevention research has made considerable progress during the past few years in addressing the biological, behavioral and social factors that influence women's vulnerability to HIV infection. Nevertheless, substantial work still must be done in order to implement scientific advancements and to resolve the many questions that remain. This article highlights some of the recent advances and persistent gaps in HIV prevention research for women and outlines key research and policy priorities. PMID:23764631

  11. HIV Infection and Bone Abnormalities.

    PubMed

    Ahmad, Aamir N; Ahmad, Shahid N; Ahmad, Nafees

    2017-01-01

    More than 36 million people are living with human immunodeficiency virus (HIV) infection worldwide and 50% of them have access to antiretroviral therapy (ART). While recent advances in HIV therapy have reduced the viral load, restored CD4 T cell counts and decreased opportunistic infections, several bone-related abnormalities such as low bone mineral density (BMD), osteoporosis, osteopenia, osteomalacia and fractures have emerged in HIV-infected individuals. Of all classes of antiretroviral agents, HIV protease inhibitors used in ART combination showed a higher frequency of osteopenia, osteoporosis and low BMD in HIV-infected patients. Although the mechanisms of HIV and/or ART associated bone abnormalities are not known, it is believed that the damage is caused by a complex interaction of T lymphocytes with osteoclasts and osteoblasts, likely influenced by both HIV and ART. In addition, infection of osteoclasts and bone marrow stromal cells by HIV, including HIV Gp120 induced apoptosis of osteoblasts and release of proinflammatory cytokines have been implicated in impairment of bone development and maturation. Several of the newer antiretroviral agents currently used in ART combination, including the widely used tenofovir in different formulations show relative adverse effects on BMD. In this context, switching the HIV-regimen from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) showed improvement in BMD of HIV-infected patients. In addition, inclusion of integrase inhibitor in ART combination is associated with improved BMD in patients. Furthermore, supplementation of vitamin D and calcium with the initiation of ART may mitigate bone loss. Therefore, levels of vitamin D and calcium should be part of the evaluation of HIV-infected patients.

  12. Aging, inflammation, and HIV infection.

    PubMed

    Aberg, Judith A

    2012-01-01

    Prolonged survival in HIV infection is accompanied by an increased frequency of non-HIV-related comorbidities. A number of age-related comorbidities occur earlier in HIV-infected patients than in individuals without HIV infection. This "accelerated aging" appears to be largely related to chronic inflammation, chronic immune activation, and immunosenescence in HIV infection. Levels of markers of inflammation and coagulopathy are elevated in HIV-infected patients, and elevations in markers such as high-sensitivity C-reactive protein, D-dimer, and interleukin 6 (IL-6) have been associated with increased risk for cardiovascular disease, opportunistic conditions, or all-cause mortality. In both HIV infection and aging, immunosenescence is marked by an increased proportion of CD28-, CD57+ memory CD8+ T cells with reduced capacity to produce interleukin 2 (IL-2), increased production of IL-6, resistance to apoptosis, and shortened telomeres. A number of AIDS Clinical Trials Group studies are under way to examine treatment aimed at reducing chronic inflammation and immune activation in HIV infection. This article summarizes a presentation by Judith A. Aberg, MD, at the IAS-USA live continuing medical education course held in New York City in October 2011.

  13. Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child.

    PubMed

    Palma, Paolo; Zangari, Paola; Alteri, Claudia; Tchidjou, Hyppolite K; Manno, Emma Concetta; Liuzzi, Giuseppina; Perno, Carlo Federico; Rossi, Paolo; Bertoli, Ada; Bernardi, Stefania

    2016-12-09

    HIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child. A perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL <40copies/ml. After 116 weeks on ART we were able to perform amplification and sequencing assay on the plasma virus. At this time VL was <40 copies/ml and CD4 percentage was 40%. Again the genotypic resistance test revealed a wild-type virus. The phylogenetic analysis performed on the HIV-1 pol sequences of the mother and the child revealed that sequences clustered with C subtype reference strains and formed a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%). Any major evolutionary divergence was detected. eART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission.

  14. Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants.

    PubMed Central

    Pollack, H; Zhan, M X; Ilmet-Moore, T; Ajuang-Simbiri, K; Krasinski, K; Borkowsky, W

    1993-01-01

    The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1. PMID:8460144

  15. Transmitted Drug Resistance and Phylogenetic Relationships among Acute and Early HIV-1 Infected Individuals in New York City

    PubMed Central

    Castor, Delivette; Low, Andrea; Evering, Teresa; Karmon, Sharon; Davis, Brandi; Figueroa, Amir; LaMar, Melissa; Garmon, Donald; Mehandru, Saurabh; Markowitz, Martin

    2012-01-01

    Background Transmitted drug resistance (TDR) is critical to managing HIV-1 infected individuals as well as being a public health concern. Here we report on TDR prevalence and include analyses of phylogenetic clustering of HIV-1 in a predominantly MSM cohort diagnosed during acute/recent HIV-1 infection (AHI) in New York City. Methods Genotypic resistance testing was conducted on plasma samples of 600 individuals with AHI (1995–2010). Sequences were used for resistance and phylogenetic analyses. Demographic and clinical data were abstracted from medical records. TDR was defined according to IAS USA and Stanford HIV database guidelines. Phylogenetic and other analyses were conducted using PAUP*4.0 and SAS, respectively. Results The mean duration since HIV-1 infection was 66.5 days. TDR prevalence was 14.3%, and stably ranged between 10.8% and 21.6% (Ptrend=0.42). NRTI resistance declined from 15.5% to 2.7% over the study period (Ptrend=0.005). M41L (3.7%), T215Y (4.0%), and K103N/S (4.7%) were the most common mutations. K103N/S prevalence increased from 1.9% to 8.0% between 1995 and 2010 (Ptrend=0.04). Using a rigorous definition of clustering, 19.3% (112/581) of subtype B viral sequences co-segregated into transmission clusters, and clusters increased over time. There were fewer and smaller transmission clusters than had been reported in a similar cohort in Montreal, but similar to reports from elsewhere. Conclusions TDR is stable in this cohort and remains a significant concern to both individual patient management and the public health. PMID:22592583

  16. Cognitive Function and Neurodevelopmental Outcomes in HIV-Infected Children Older than 1 Year of Age Randomized to Early Versus Deferred Antiretroviral Therapy: The PREDICT Neurodevelopmental Study

    PubMed Central

    Puthanakit, Thanyawee; Ananworanich, Jintanat; Vonthanak, Saphonn; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; van der Lugt, Jasper; Kerr, Stephen J.; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vibol, Ung; Pruksakaew, Kanchana; Suwarnlerk, Tulathip; Apornpong, Tanakorn; Ratanadilok, Kattiya; Paul, Robert; Mofenson, Lynne M.; Fox, Lawrence; Valcour, Victor; Brouwers, Pim; Ruxrungtham, Kiat

    2013-01-01

    Background We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early vs. deferred ART in the PREDICT Study. We now report neurodevelopmental outcomes. Methods 284 HIV-infected Thai and Cambodian children aged 1–12 years with CD4 counts between 15–24% and no AIDS-defining illness were randomized to initiate ART at enrollment (“early”, n=139) or when CD4 count became <15% or a CDC C event developed (“deferred”, n=145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration (VMI), Purdue Pegboard, Color Trails and Child Behavioral Checklist (CBCL). Thai children (n=170) also completed Wechsler Intelligence Scale (IQ) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n=319). Results At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% vs. 24%, p<0.001) and a greater percentage of children with viral suppression (91% vs. 40%, p<0.001). Neurodevelopmental scores did not differ by arm and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on IQ, Beery VMI, Binet memory and CBCL Conclusions In HIV-infected children surviving beyond one year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15–24% vs. < 15%; but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy. PMID:23263176

  17. Pediatric HIV Infection and Developmental Disabilities.

    ERIC Educational Resources Information Center

    Seidel, John F.

    This paper presents an overview of the developmental disabilities associated with pediatric Human Immunodeficiency Virus (HIV) infection, and examines efficacious practices for assessment and intervention programming. The focus population is early childhood into school age. The paper describes the complex array of challenges presented by these…

  18. Toxoplasmosis in HIV infection: An overview

    PubMed Central

    Basavaraju, Anuradha

    2016-01-01

    Toxoplasma gondii is an obligate intracellular protozoan parasite presenting as a zoonotic infection distributed worldwide. In HIV-positive individuals, it causes severe opportunistic infections, which is of major public health concern as it results in physical and psychological disabilities. In healthy immunocompetent individuals, it causes asymptomatic chronic persistent infections, but in immunosuppressed patients, there is reactivation of the parasite if the CD4 counts fall below 200 cells/μl. The seroprevalence rates are variable in different geographic areas. The tissue cyst or oocyst is the infective form which enters by ingestion of contaminated meat and transform into tachyzoites and disseminate into blood stream. In immunocompetent persons due to cell-mediated immunity the parasite is transformed into tissue cyst resulting in life long chronic infection. In HIV-infected people opportunistic infection by T. gondii occurs due to depletion of CD4 cells, decreased production of cytokines and interferon gamma and impaired cytotoxic T-lymphocyte activity resulting in reactivation of latent infection. The diagnosis can be done by clinical, serological, radiological, histological or molecular methods, or by the combination of these. There is various treatment regimen including acute treatment, maintenance therapy should be given as the current anti T. gondii therapy cannot eradicate tissue cysts. In HIV patients, CD4 counts <100; cotrimoxazole, alternately dapsone + pyrimethamine can be given for 6 months. Hence, early diagnosis of T. gondii antibodies is important in all HIV-positive individuals to prevent complications of cerebral toxoplasmosis. PMID:27722101

  19. Post-treatment control of HIV infection

    SciT

    Conway, Jessica M.; Perelson, Alan S.

    Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infectedmore » cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. As a result, using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for non-controllers consistent with observations.« less

  20. Post-treatment control of HIV infection

    DOE PAGES

    Conway, Jessica M.; Perelson, Alan S.

    2015-04-13

    Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infectedmore » cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. As a result, using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for non-controllers consistent with observations.« less

  1. HIV Infection and Adult Vaccination

    MedlinePlus

    ... not gotten this vaccine or do not have immunity to these diseases Varicella vaccine to protect against ... doses of this vaccine or do not have immunity to this disease If you have HIV infection ...

  2. Mucosal immunology of HIV infection.

    PubMed

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S

    2013-07-01

    Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection, but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of 'symbiotic' intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high-level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4(+) T-cell responses, binding anti-bodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Furthermore, immune therapies specifically directed toward boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Mucosal Immunology of HIV Infection

    PubMed Central

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

    2013-01-01

    Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

  4. Early limited antiretroviral therapy is superior to deferred therapy in HIV-infected South African infants: results from the CHER (Children with HIV Early antiRetroviral) Randomized Trial

    PubMed Central

    Cotton, Mark F; Violari, Avy; Otwombe, Kennedy; Panchia, Ravindre; Dobbels, Els; Rabie, Helena; Josipovic, Deirdre; Liberty, Afaff; Lazarus, Erica; Innes, Steve; van Rensburg, Anita Janse; Pelser, Wilma; Truter, Handre; Madhi, Shabir A; Handelsman, Edward; Jean-Philippe, Patrick; McIntyre, James A; Gibb, Diana M; Babiker, Abdel G

    2014-01-01

    Background Interim results from the CHER trial showed that early antiretroviral therapy (ART) was life-saving for HIV-infected infants. Given limited options and potential for toxicity with life-long ART, CHER compared early limited ART with deferred ART. Methods CHER was an open 3-arm trial in HIV-infected asymptomatic infants aged <12 weeks with CD4% ≥25%. Infants were randomized to deferred (ART-Def) or immediate ART for 40weeks (ART-40W) or 96weeks (ART-96W), followed by interruption. Criteria for ART initiation in ART-Def and re-initiation after interruption were CD4% <25% in infancy; otherwise <20% or CDC severe stage B or stage C disease. Lopinavir-ritonavir, zidovudine, lamivudine was the first-line regimen at ART initiation and re-initiation. The primary endpoint was time-to-failure of first-line ART (immunological/clinical/virological) or death. Comparisons were by intent-to-treat, using time-to-event methods. Findings 377 infants were enrolled: median age 7.4weeks; CD4% 35% and HIV RNA log 5.7copies/ml. Median follow-up was 4.8 years; 34 (9%) were lost-to-follow-up. Median time to ART initiation in ART-Def was 20 (IQR 16–25) weeks. Time to restarting ART after interruption was 33 (26–45) weeks in ART-40W and 70 (35–109) weeks in ART-96W; at trial end 19% and 32% respectively, remained off ART. Proportions of follow-up time spent on ART were 81%, 70% and 69% in ART-Def, ART-40W and ART-96W arms. 48/125(38%), 32/126(25%) and 26/126(21%) children reached the primary endpoint; hazard ratio (95%CI), relative to ART-Def, was 0.59(0.38-0.93, p=0.02) for ART-40W and 0.47(0.27-0.76, p=0.002) for ART-96W. Seven children (3 ART-Def, 3 ART-40W, 1 ART-96W) switched to second-line ART. Interpretation Early limited ART had superior clinical/immunological outcome with no evidence of excess disease progression during subsequent interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption with

  5. Early morning urine collection to improve urinary lateral flow LAM assay sensitivity in hospitalised patients with HIV-TB co-infection.

    PubMed

    Gina, Phindile; Randall, Philippa J; Muchinga, Tapuwa E; Pooran, Anil; Meldau, Richard; Peter, Jonny G; Dheda, Keertan

    2017-05-12

    Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.

  6. HIV and co-infections

    PubMed Central

    Chang, Christina C; Crane, Megan; Zhou, JingLing; Mina, Michael; Post, Jeffrey J; Cameron, Barbara A; Lloyd, Andrew R; Jaworowski, Anthony; French, Martyn A; Lewin, Sharon R

    2013-01-01

    Summary Despite significant reductions in morbidity and mortality secondary to availability of effective combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub-Saharan Africa where rates of opportunistic co-infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV-infected patients globally. These include co-infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus (HBV), hepatitis C virus (HCV), and Plasmodium falciparum. Specifically, we review the natural history of each co-infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co-infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co-infection via vaccination. Finally, we discuss the opportunities and gaps for future research. PMID:23772618

  7. US hospital care for patients with HIV infection and pneumonia: the role of public, private, and Veterans Affairs hospitals in the early highly active antiretroviral therapy era.

    PubMed

    Uphold, Constance R; Deloria-Knoll, Maria; Palella, Frank J; Parada, Jorge P; Chmiel, Joan S; Phan, Laura; Bennett, Charles L

    2004-02-01

    We evaluated differences in processes and outcomes of HIV-related pneumonia care among patients in Veterans Affairs (VA), public, and for-profit and not-for-profit private hospitals in the United States. We compared the results of our current study (1995 to 1997) with those of our previous study that included a sample of patients receiving care during the years 1987 to 1990 to determine how HIV-related pneumonia care had evolved over the last decade. The sample consisted of 1,231 patients with HIV infection who received care for Pneumocystis carinii pneumonia (PCP) and 750 patients with HIV infection who received care for community-acquired pneumonia (CAP) during the years 1995 to 1997. We conducted a retrospective medical record review and evaluated patient and hospital characteristics, HIV-related processes of care (timely use of anti-PCP medications, adjunctive corticosteroids), non-HIV-related processes of care (timely use of CAP treatment medications, diagnostic testing, ICU utilization, rates of endotracheal ventilation, placement on respiratory isolation), length of inpatient hospital stay, and inpatient mortality. Rates of timely use of antibiotics and adjunctive corticosteroids for treating PCP were high and improved dramatically from the prior decade. However, compliance with consensus guidelines that recommend < 8 h as the optimal time window for initiation of antibiotics to treat CAP was lower. For both PCP and CAP, variations in processes of care and lengths of in-hospital stays, but not mortality rates, were noted at VA, public, private not-for-profit hospitals, and for-profit hospitals. This study provides the first overview of HIV-related pneumonia care in the early highly active antiretroviral therapy era, and contrasts current findings with those of a similarly conducted study from a decade earlier. Quality of care for patients with PCP improved, but further efforts are needed to facilitate the appropriate management of CAP. In the third decade of

  8. Saquinavir inhibits early events associated with establishment of HIV-1 infection: potential role for protease inhibitors in prevention.

    PubMed

    Stefanidou, Martha; Herrera, Carolina; Armanasco, Naomi; Shattock, Robin J

    2012-08-01

    The maturation of newly formed human immunodeficiency virus type 1 (HIV-1) virions is a critical step for the establishment of productive infection. We investigated the potential of saquinavir (SQV), a protease inhibitor (PI) used in highly active antiretroviral therapy (HAART), as a candidate microbicide. SQV inhibited replication of clade B and clade C isolates in a dose-dependent manner in all cellular models tested: PM-1 CD4 T cells, peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells (iMDDCs). SQV also inhibited production of infectious virus in cervical, penile, and colorectal explants cocultured with T cells. Moreover, SQV demonstrated inhibitory potency against trans infection of T cells by in vitro-derived dendritic cells and by primary dendritic cells that emigrate from penile and cervical tissue explants. No cellular or tissue toxicity was detected in the presence of SQV, suggesting that this drug could be considered for development as a component of an effective microbicide, capable of blocking viral maturation and transmission of HIV-1 at mucosal surfaces.

  9. Early evolution of HLA-associated escape mutations in variable Gag proteins predicts CD4+ decline in HIV-1 subtype C infected women

    PubMed Central

    Chopera, Denis R.; Ntale, Roman; Ndabambi, Nonkululeko; Garrett, Nigel; Gray, Clive M.; Matten, David; Karim, Quarraisha Abdool; Karim, Salim Abdool; Williamson, Carolyn

    2016-01-01

    Objective HIV-1 escape from cytotoxic T-lymphocytes (CTL) results in the accumulation of HLA-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of CTL escape in a cohort followed from infection for five years. Methods Viral loads and CD4+ counts were monitored in 78 subtype C infected individuals from onset of infection until CD4+ decline to <350 cells/μl or five years post-infection. The gag gene was sequenced and HLA-associated changes between enrolment and 12 months post-infection were mapped. Results HLA-associated escape mutations were identified in 48 (62%) of the participants and were associated with CD4+ decline to <350 copies/ml (p=0.05). Escape mutations in variable Gag proteins (p17 and p7p6) had a greater impact on disease progression than escape in more conserved regions (p24) (p=0.03). The association between HLA-associated escape mutations and CD4+ decline was independent of protective HLA allele (B*57, B*58:01, B*81) expression. Conclusion The high frequency of escape contributed to rapid disease progression in this cohort. While HLA-adaption in both conserved and variable Gag domains in the first year of infection was detrimental to long term clinical outcome, escape in variable domains had greater impact. PMID:27755110

  10. [Microbiological diagnosis of HIV infection].

    PubMed

    López-Bernaldo de Quirós, Juan Carlos; Delgado, Rafael; García, Federico; Eiros, José M; Ortiz de Lejarazu, Raúl

    2007-12-01

    Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

  11. Neurodevelopment in children born to HIV-infected mothers by infection and treatment status.

    PubMed

    Le Doaré, Kirsty; Bland, Ruth; Newell, Marie-Louise

    2012-11-01

    We reviewed the impact of HIV, HIV exposure, and antiretroviral therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV-exposed-uninfected infants and children. A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990-March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if results were reported in children <16 years of age who were exposed to HIV and antiretrovirals in fetal/early life, and excluded if children did not acquire HIV from their mothers or were not exposed to antiretrovirals in fetal/early life. Infants who acquired HIV during fetal and early life tended to display poorer mean developmental scores than HIV-unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs below the population mean. Mean scores improved if the infant received treatment before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected children treated with highly active antiretroviral therapy demonstrated near normal global mean neurocognitive scores; subtle differences in language, memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech and language delay, although not universally. In comparison with resource-rich settings, HIV-infected and HIV-exposed-uninfected infants/children in resource-poor settings demonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from an early age and HIV-exposed-uninfected children particularly in resource-poor settings remain unclear.

  12. Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

    PubMed

    Turk, Gabriela; Ghiglione, Yanina; Hormanstorfer, Macarena; Laufer, Natalia; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Holgado, María Pía; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D; Pando, María de Los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Pury, Pedro A; Sued, Omar

    2018-01-13

    Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4⁺ T-cell activation ( p < 0.05). However, none of these cytokines had good predictive values to distinguish "progressors" from "non-progressors". Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

  13. HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report.

    PubMed

    Frange, Pierre; Faye, Albert; Avettand-Fenoël, Véronique; Bellaton, Erianna; Descamps, Diane; Angin, Mathieu; David, Annie; Caillat-Zucman, Sophie; Peytavin, Gilles; Dollfus, Catherine; Le Chenadec, Jerome; Warszawski, Josiane; Rouzioux, Christine; Sáez-Cirión, Asier

    2016-01-01

    from this case suggest that long-term HIV-1 remission is possible in perinatally infected children who receive treatment early, with characteristics similar to those reported in adult HIV post-treatment controllers. Further studies are needed to understand the mechanisms associated with HIV remission and whether early treatment of infected children might favour the conditions needed to achieve HIV control after treatment discontinuation. Agence de recherche ANRS (France Recherche Nord & Sud Sida-HIV Hépatites). Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Feasibility of Routinely Offering Early Combined Antiretroviral Therapy to HIV-infected Infants in a Resource-limited Country: The ANRS-PediaCAM Study in Cameroon.

    PubMed

    Tejiokem, Mathurin Cyrille; Warszawski, Josiane; Ateba Ndongo, Francis; Tetang Ndiang, Suzie; Ndongo, Jean Audrey; Owona, Félicité; Ngoupo, Paul Alain; Tchendjou, Patrice; Kfutwah, Anfumbom; Penda, Ida Calixte; Faye, Albert

    2015-10-01

    Early diagnosis of HIV is increasingly available for infants in resource-limited settings. We assessed the timing of events until combined antiretroviral therapy (cART) initiation in infants diagnosed before 7 months of age in Cameroon. The ANRS-PediaCAM cohort included HIV-infected infants followed from birth associated with prevention of mother-to-child transmission activities (group 1) or diagnosed for any other reason before 7 months of age (group 2). All infants were offered free cART early after diagnosis. Frequency and factors associated with no or delayed cART initiation, were studied using univariable and multivariable logistic regressions. Between 2007 and 2011, 210 HIV-infected infants (group 1: 69; group 2: 141) were included. Fewer group 1 (14.3%) than group 2 (59.1%) infants were symptomatic (World Health Organization stage 3 or 4). Overall, 5.7% (n = 12) died before receiving any cART. Of the remaining 198 infants, 3.0% (n = 6) were not treated. The median age at initiating cART was 4.1 months [interquartile range (IQR): 3.2-5.6]. The median time until cART initiation after HIV testing was 6.2 weeks (IQR: 4.4-9.4) in group 1 and 5.1 weeks (IQR: 2.9-9.4) in group 2. No or delayed cART, observed for 37.9% (75 of 198) of the infants, was associated with clinical site [adjusted odds ratio (aOR): 4.8; 95% confidence interval: (2.1-11.2)], late diagnosis [aOR: 2.0 (0.9-4.1)], and delayed pretherapeutic biological assessment [aOR: 3.7 (1.4-10.0)]. Although most children included were treated before age 7 months, the initiation of therapy was delayed for more than 1 in 3. The period around HIV diagnosis is critical and should be better managed to reduce delays before cART initiation.

  15. Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV Infection Among Men Who Have Sex With Men and Transgender Women in Lima, Peru, 2013-2017.

    PubMed

    Lama, Javier R; Brezak, Audrey; Dobbins, James G; Sanchez, Hugo; Cabello, Robinson; Rios, Jessica; Bain, Carolyn; Ulrich, Angela; De la Grecca, Robert; Sanchez, Jorge; Duerr, Ann

    2018-03-07

    The Sabes study evaluates a treatment-as-prevention intervention in cis-gender men who have sex with men and transgender women in Lima, Peru, populations disproportionately affected by the HIV epidemic. The intervention is designed to prevent onward transmission of HIV by identifying HIV-negative, high-risk individuals, testing them monthly for the presence of HIV, and then rapidly treating those who become HIV positive. The main outcome of interest is the development of a model predicting the population-level impact of early detection of HIV infection and immediate initiation of antiretroviral therapy (ART) in this population From July 2013 to September 2015, 3,336 subjects were screened for HIV; 2,682 (80.4%) were negative and 2,084 began monthly testing. We identified 248 individuals shortly after HIV acquisition, 215 of whom were enrolled in the treatment phase of our study. All participants were followed for 48 weeks and then were referred to the Peruvian Ministry of Health to continue free HIV care and treatment. This intervention demonstrates that it is possible to recruit high-risk individuals, screen them for HIV, continue to test those who are initially HIV negative in order to identify incident cases shortly after acquisition, and then rapidly link them to care.

  16. Implementation and new insights in molecular diagnostics for HIV infection.

    PubMed

    Tsang, Hin-Fung; Chan, Lawrence Wing-Chi; Tong, Jennifer Chiu-Hung; Wong, Heong-Ting; Lai, Christopher Koon-Chi; Au, Thomas Chi-Chuen; Chan, Amanda Kit-Ching; Ng, Lawrence Po-Wah; Cho, William Chi-Shing; Wong, Sze-Chuen Cesar

    2018-05-01

    Acquired immunodeficiency syndrome (AIDS) is a kind of acquired disease that breaks down the immune system. Human immunodeficiency virus (HIV) is the causative agent of AIDS. By the end of 2016, there were 36.7 million people living with HIV worldwide. Early diagnosis can alert infected individuals to risk behaviors in order to control HIV transmission. Infected individuals are also benefited from proper treatment and management upon early diagnosis. Thanks to the public awareness of the disease, the annual increase of new HIV infections has been slowly declining over the past decades. The advent of molecular diagnostics has allowed early detection and better management of HIV infected patients. Areas covered: In this review, the authors summarized and discussed the current and future technologies in molecular diagnosis as well as the biomarkers developed for HIV infection. Expert Commentary: A simple and rapid detection of viral load is important for patients and doctors to monitor HIV progression and antiretroviral treatment efficiency. In the near future, it is expected that new technologies such as digital PCR and CRISPR-based technology will play more important role in HIV detection and patient management.

  17. Troubled Adolescents and HIV Infection.

    ERIC Educational Resources Information Center

    Woodruff, John O., Ed.; And Others

    This report on adolescents, Acquired Immune Deficiency Syndrome (AIDS), and Human Immune Virus (HIV) infection had its beginning in the Knowledge Development Workshop "Issues in the Prevention and Treatment of AIDS Among Adolescents with Serious Emotional Disturbance," held June 9-10, 1988 in the District of Columbia. These papers are included:…

  18. Vitamin D in HIV-Infected Patients

    PubMed Central

    JE, Lake; JS, Adams

    2013-01-01

    Observational studies have noted very high rates of low 25(OH)D (vitamin D) levels in both the general and HIV-infected populations. In HIV-infected patients, low 25(OH)D levels are likely a combination of both traditional risk factors and HIV- and antiretroviral therapy-specific contributors. Because of this unique risk profile, HIV-infected persons may be at greater risk for low 25(OH)D levels and frank deficiency and/or may respond to standard repletion regimens differently than HIV-uninfected patients. Currently, the optimal repletion and maintenance dosing regimens for HIV-infected patients remain unknown, as do potential benefits of supplementation that may be unique to the HIV-infected population. This paper reviews data published on HIV infection and vitamin D health in adults over the last year. PMID:21647555

  19. Correlates of age at attainment of developmental milestones in HIV-infected infants receiving early antiretroviral therapy.

    PubMed

    Benki-Nugent, Sarah; Eshelman, Christal; Wamalwa, Dalton; Langat, Agnes; Tapia, Ken; Okinyi, Helen Moraa; John-Stewart, Grace

    2015-01-01

    Infant HIV-1 infection is associated with impaired neurologic and motor development. Antiretroviral therapy (ART) has the potential to improve developmental outcomes but the relative contributions of pre-ART disease status, growth, treatment regimen and ART response during infancy are unknown. Kenyan ART-naive infants <5-months old initiated ART and had monthly assessment of age of full neck control, unsupported walking and monosyllabic speech during 24 months of follow-up. Pre-ART and post-ART correlates of age at milestone attainment were evaluated using t tests or multivariate linear regression. Among 99 infants, pre-ART correlates of later milestone attainment included: underweight and stunted (neck control, walking and speech, all P values <0.05), missed prevention of mother-to-child transmission (P = 0.04) (neck control), previous hospitalization, World Health Organization (WHO) Stage III/IV, low CD4 count, and wasting (speech and walking, all P values <0.05), and low maternal CD4 (speech, P = 0.04). Infants initiated ART at a median of 14 days following enrollment. Infants receiving nevirapinevs lopinavir/ritonavir-based ART attained later speech (18.1 vs. 15.5 months, P = 0.003) [corrected]. Adjusting for pre-ART level, lower 6-month gain in CD4% was associated with later walking (0.18 months earlier per unit increase in CD4%; P = 0.004) and speech (0.12 months earlier per unit increase in CD4%; P = 0.05), and lower 6-month gains in weight-for-age (P = 0.009), height-for-age (P = 0.03) and weight-for-height (P = 0.02) were associated with later walking. In HIV-infected infants, compromised pre-ART immune and growth status, poor post-ART immune and growth responses, and use of nevirapine- vs. lopinavir/ritonavir-based ART were each associated with later milestone attainment [corrected]. The long-term consequences of these delays are unknown.

  20. [Tuberculosis in HIV-infected and AIDS patients].

    PubMed

    Rakhmanova, A G; Stepanova, E V; Romanova, E I; Evseeva, I D

    2003-01-01

    The course of the combined infection (tuberculosis plus HIV-infection) has been analysed in 41 patients. Of them, 24 patients developed tuberculosis in the presence of HIV-infection (group 1) and 17 were infected with HIV when they already had tuberculosis running up to 5 years. HIV-infection in group 1 ran a more severe course, the patients developed generalized, disseminated and complicated forms of tuberculosis with more frequent lethal outcome. 39 patients of both groups received specific antituberculous therapy including 1-5 drugs. A response to treatment was achieved in 23 (60%) patients (52 and 47.8% at early and late HIV-infection stages, respectively). Treatment failure was explained by development of severe opportunistic infections and secondary diseases (generalized cytomegalovirus infection, advanced candidiasis, toxoplasmosis), poor compliance, asocial life style, advanced tuberculosis process, late diagnosis, inadequate treatment. It is shown that in late HIV-infection positive results of treatment can be expected only in early detection of tuberculosis and active long-term treatment.

  1. [HIV infection in the Stavropol' region].

    PubMed

    Filonenko, N G; Isaev, V P; Pelikh, N L

    2001-01-01

    The data on the dynamics of HIV infection in the Stavropol Territory beginning with 1987 are given. The situation became aggravated after 1996, and its sharp deterioration occurred in 2000 when 138 cases of HIV infection were detected and the area of this infection increased. In most cases patients became infected beyond the borders of the territory. About a half of the new cases of HIV infection registered in 2000 were detected in Ingushetia and Chechnya. The leading factor in the spread of HIV infection was the use of drugs by injection. The main trends of the prophylactic work are presented.

  2. Innate immunity and HIV-1 infection.

    PubMed

    Lehner, T; Wang, Y; Whittall, T; Seidl, T

    2011-04-01

    HIV-1 is predominantly transmitted through mucosal tissues, targeting CD4(+)CCR5(+) T cells, 50% of which are destroyed within 2 weeks of infection. Conventional vaccination strategies have so far failed to prevent HIV-1 infection. Neither antibodies nor cytotoxic lymphocytes are capable of mounting a sufficiently rapid immune response to prevent early destruction of these cells. However, innate immunity is an early-response system, largely independent of prior encounter with a pathogen. Innate immunity can be classified into cellular, extracellular, and intracellular components, each of which is exemplified in this review by γδ T cells, CC chemokines, and APOBEC3G, respectively. First, γδ T cells are found predominantly in mucosal tissues and produce cytokines, CC chemokines, and antiviral factors. Second, the CC chemokines CCL-3, CCL-4, and CCL-5 can be upregulated by immunization of macaques with SIVgp120 and gag p27, and these can bind and downmodulate CCR5, thereby inhibiting HIV-1 entry into the host cells. Third, APOBEC3G is generated and maintained following rectal mucosal immunization in rhesus macaques for over 17 weeks, and the innate anti-SIV factor is generated by CD4(+)CD95(+)CCR7(-) effector memory T cells. Thus, innate anti-HIV-1 or SIV immunity can be linked with immune memory, mediated by CD4(+) T cells generating APOBEC3G. The multiple innate functions may mount an early anti-HIV-1 response and either prevent viral transmission or contain the virus until an effective adaptive immune response develops.

  3. Predictors of early mortality in a cohort of HIV-infected children receiving high active antiretroviral treatment in public hospitals in Ethiopia.

    PubMed

    Ebissa, Getachew; Deyessa, Negusse; Biadgilign, Sibhatu

    2015-01-01

    Highly active antiretroviral therapy (HAART) is the breakthrough in care and treatment of people living with HIV, leading to a reduction in mortality and an improvement in the quality of life. Without antiretroviral treatment, most HIV-infected children die before their fifth birthday. So the objective of this study is to determine the mortality and associated factors in a cohort of HIV-infected children receiving ART in Ethiopia. A multicentre facility-based retrospective cohort study was done in selected pediatric ART units in hospitals found in Addis Ababa, Ethiopia. The probability of survival was estimated using the Kaplan-Meier method, and multivariate analysis by Cox proportional hazards regression models was conducted to determine the independent predictor of survival. A total of 556 children were included in this study. Of the total children, 10.4% were died in the overall cohort. More deaths (70%) occurred in the first 6 months of ART initiation, and the remaining others were still on follow-up at different hospitals. Underweight (moderate and severe; HR: 10.10; 95% CI: 2.08, 28.00; P = 0.004; and HR: 46.69; 95% CI: 9.26, 200.45; P < 0.01, respectively), advanced disease stage (WHO clinical stages III and IV; HR: 10.13: 95% CI: 2.25, 45.58; P = 0.003), poor ART adherence (HR: 11.72; 95% CI: 1.60, 48.44; P = 0.015), and hemoglobin level less than 7 g/dl (HR: 4.08: 95% CI: 1.33, 12.56; P = 0.014) were confirmed as significant independent predictors of death after controlling for other factors. Underweight, advanced disease stage, poor adherence to ART, and anemia appear to be independent predictor of survival in HIV-infected children receiving HAART at the pediatric units of public hospitals in Ethiopia. Nutritional supplementations, early initiation of HAART, close supervision, and monitoring of patients during the first 6 months, the follow up period is recommended.

  4. Maternal HIV Infection Influences the Microbiome of HIV Uninfected Infants

    PubMed Central

    Bender, Jeffrey M.; Li, Fan; Martelly, Shoria; Byrt, Erin; Rouzier, Vanessa; Leo, Marguerithe; Tobin, Nicole; Pannaraj, Pia S.; Adisetiyo, Helty; Rollie, Adrienne; Santiskulvong, Chintda; Wang, Shuang; Autran, Chloe; Bode, Lars; Fitzgerald, Daniel; Kuhn, Louise; Aldrovandi, Grace M.

    2017-01-01

    More than one million HIV-exposed, uninfected infants are born annually to HIV-positive mothers worldwide. This growing population of infants experiences twice the mortality of HIV-unexposed infants. We found that although there were very few differences seen in the microbiomes of mothers with and without HIV infection, maternal HIV infection was associated with changes in the microbiome of HIV-exposed, uninfected infants. Furthermore, we observed that human breast milk oligosaccharides were associated with the bacterial species in the infant microbiome. The disruption of the infant’s microbiome associated with maternal HIV infection may contribute to the increased morbidity and mortality of HIV-exposed, uninfected infants. PMID:27464748

  5. Concurrency and HIV transmission network characteristics among MSM with recent HIV infection.

    PubMed

    Pines, Heather A; Wertheim, Joel O; Liu, Lin; Garfein, Richard S; Little, Susan J; Karris, Maile Y

    2016-11-28

    Sexual partner concurrency is common among MSM and may increase the probability of HIV transmission during recent (acute or early) infection. We examined the relationship between concurrency and HIV transmission network characteristics (proxies for HIV transmission) among MSM with recent HIV infection. Observational study integrating behavioral, clinical, and molecular epidemiology. We inferred a partial HIV transmission network using 986 HIV-1 pol sequences obtained from HIV-infected individuals in San Diego, California (1996-2015). We further analyzed data from 285 recently HIV-infected MSM in the network who provided information on up to three sexual partners in the past 3 months, including the timing of intercourse with each partner. Concurrency was defined as sexual partners overlapping in time. Logistic and negative binomial regressions were used to investigate the link between concurrency and HIV transmission network characteristics (i.e. clustering and degree or number of connections to others in the network) among these MSM. Of recently HIV-infected MSM (n = 285), 54% reported concurrent partnerships and 54% were connected by at least one putative transmission link to others (i.e. clustered) in the network (median degree = 1.0; interquartile range: 0.0-3.0). Concurrency was positively associated with HIV transmission network clustering (adjusted odds ratio = 1.83, 95% confidence interval: 1.08, 3.10) and degree (adjusted incidence rate ratio = 1.48, 95% confidence interval: 1.02, 2.15). Our findings provide empirical evidence consistent with the hypothesis that concurrency facilitates HIV transmission during recent infection. Interventions to mitigate the impact of concurrency on HIV transmission may help curb the HIV epidemic among MSM.

  6. A Hypereosinophilic Syndrome Associated with HIV Infection

    DTIC Science & Technology

    1992-01-01

    et al, however, were very similar to that of ours and suggests a relationship (6). Eosinophilic folliculitis is a papular eruption which occurs in HIV...patients with moderate to advanced HIV infection (14). The dermatopathology of eosinophilic folliculitis is primarily characterized by follicular...Berger TG. HIV-associated eosinophilic folliculitis : A unique dermatosis associated with advanced HIV infection. Arch Derm 1991; 127: 206 15. Ray TL

  7. Chest Low-Dose Computed Tomography for Early Lung Cancer Diagnosis as an Opportunity to Diagnose Vertebral Fractures in HIV-Infected Smokers, an ANRS EP48 HIV CHEST Substudy.

    PubMed

    Thouvenin, Yann; Makinson, Alain; Cournil, Amandine; Eymard-Duvernay, Sabrina; Lentz, Pierre; Delemazure, Anne-Sophie; Corneloup, Olivier; Fabre, Sylvie; Quesnoy, Mylène; Poire, Sylvain; Brillet, Pierre-Yves; Cyteval, Catherine; Reynes, Jacques; Le Moing, Vincent

    2015-07-01

    To estimate the prevalence of vertebral fractures on chest low-dose computed tomography (LDCT) in HIV-infected smokers. Cross-sectional study of vertebral fractures visualized on chest LDCT from a multicenter prospective cohort evaluating feasibility of chest LDCT for early lung cancer diagnosis in HIV-infected subjects. Subjects were included if 40 years or older, had been active smokers within the last 3 years of at least 20 pack-years, and had a CD4 T-lymphocyte nadir cell count <350 per microliter and an actual CD4 T-cell count >100 cells per microliter. Spinal reconstructed sagittal planes obtained from chest axial native acquisitions were blindly read by a musculoskeletal imaging specialist. Assessment of the fractured vertebra used Genant semiquantitative method. The study end point was the prevalence of at least 1 vertebral fracture. Three hundred ninety-seven subjects were included. Median age was 49.5 years, median smoking history was 30 pack-years, median last CD4 count was 584 cells per microliter, and median CD4 nadir count was 168 cells per microliter; 90% of subjects had a viral load below 50 copies per milliliter. At least 1 fracture was visible in 46 (11.6%) subjects. In multivariate analysis, smoking ≥40 packs-years [OR = 2.5; 95% CI: (1.2 to 5.0)] was associated with an increased risk of vertebral fracture, while HIV viral load <200 copies per milliliter [OR = 0.3; 95% CI: (0.1 to 0.9)] was protective. Prevalence of vertebral fractures on chest LDCT was 11.6% in this high-risk population. Smoking cessation and early introduction of antiretroviral therapy for prevention of vertebral fractures could be beneficial. Chest LDCT is an opportunity to diagnose vertebral fractures.

  8. HIV Infection: The Clinical Picture.

    ERIC Educational Resources Information Center

    Redfield, Robert R.; Burke, Donald S.

    1988-01-01

    Reports on the human immunodeficiency virus which causes disease that culminates in the Acquired Immunodeficiency Syndrome (AIDS). States that the key to prolonging life and health is early detection of the infection which usually occurs years before symptoms emerge. (RT)

  9. Survival of HIV-1 vertically infected children

    PubMed Central

    Davies, Mary-Ann; Gibb, Diana; Turkova, Anna

    2017-01-01

    Purpose of review It is 20 years since the start of the combination antiretroviral therapy (cART) era and >10 years since cART scale-up began in resource-limited settings. We examined survival of vertically HIV-infected infants and children in the cART era. Recent findings Good survival has been achieved on cART in all settings with up to ten-fold mortality reductions compared to before cART availability. Although mortality risk remains high in the first few months after cART initiation in young children with severe disease, it drops rapidly thereafter even for those who started with advanced disease, and longer term mortality risk is low. However, suboptimal retention on cART in routine programs threatens good survival outcomes and even on treatment children continue to experience high comorbidity risk; infections remain the major cause of death. Interventions to address infection risk include co-trimoxazole prophylaxis, isoniazid preventive therapy, routine childhood and influenza immunization and improving maternal survival. Summary Pediatric survival has improved substantially with cART and HIV-infected children are aging into adulthood. It is important to ensure access to diagnosis and early cART, good program retention and optimal co-morbidity prophylaxis and treatment to achieve the best possible long-term survival and health outcomes for vertically infected children. PMID:27716730

  10. HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders.

    PubMed

    Janes, Holly; Herbeck, Joshua T; Tovanabutra, Sodsai; Thomas, Rasmi; Frahm, Nicole; Duerr, Ann; Hural, John; Corey, Lawrence; Self, Steve G; Buchbinder, Susan P; McElrath, M Juliana; O'Connell, Robert J; Paris, Robert M; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttihum, Punnee; Kaewkungwal, Jaranit; Robb, Merlin L; Michael, Nelson L; Mullins, James I; Kim, Jerome H; Gilbert, Peter B; Rolland, Morgane

    2015-10-01

    Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically linked HIV-1 founder variants represent a minority of HIV-1 infections, we found--n two different cohorts--hat more diverse HIV-1 populations in early infection were associated with significantly higher VL 1 year after HIV-1 diagnosis.

  11. Could Early Antiretroviral Therapy Entail More Risks than Benefits in sub-Saharan African HIV-Infected Adults? A Model-Based Analysis

    PubMed Central

    Anglaret, Xavier; Scott, Callie A.; Walensky, Rochelle P.; Ouattara, Eric; Losina, Elena; Moh, Raoul; Becker, Jessica E.; Uhler, Lauren; Danel, Christine; Messou, Eugene; Eholié, Serge; Freedberg, Kenneth A.

    2013-01-01

    Background Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4 counts. Methods We used a simulation model to compare ART initiation upon entry to care (“immediate ART”) to initiation at CD4 ≤350 cells/μL (“WHO 2010 ART”) in African adults with CD4 counts >500 cells/μL. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. Results Fifteen-year mortality was 56.7% for WHO 2010 and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was >1.0/100PY, the rate of withdrawal from care was >1.2-fold higher or the rate of ART failure due to poor adherence was >4.3-fold higher on immediate ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100PY) were combined with rates of withdrawal from care >1.1-fold higher and rates of treatment failure >2.1-fold higher on immediate ART than on WHO 2010 ART. Conclusions In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4 counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be critical. PMID:22809695

  12. Early diagnosis of tuberculosis using an INF-gamma assay in a child with HIV-1 infection and a very low CD4 count.

    PubMed

    Spyridis, Nikos; Chakraborty, Rana; Sharland, Mike; Heath, Paul T

    2007-01-01

    An 11-y-old girl diagnosed with HIV-1, presented with prolonged pyrexia and a non-reactive tuberculin skin test. An INF-gamma assay (ELISpot) was positive and led to administration of tuberculosis treatment. Positive cultures for Mycobacterium tuberculosis followed 6 weeks later. INF-gamma assays should be considered as first line investigations in HIV-1 infected subjects when TB is a diagnostic possibility.

  13. Molecular epidemiology of early and acute HIV type 1 infections in the United States Navy and Marine Corps, 2005-2010.

    PubMed

    Heipertz, Richard A; Sanders-Buell, Eric; Kijak, Gustavo; Howell, Shana; Lazzaro, Michelle; Jagodzinski, Linda L; Eggleston, John; Peel, Sheila; Malia, Jennifer; Armstrong, Adam; Michael, Nelson L; Kim, Jerome H; O'Connell, Robert J; Scott, Paul T; Brett-Major, David M; Tovanabutra, Sodsai

    2013-10-01

    The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and calculate the most recent common ancestor for the related sequences. We identified 39 individuals infected with subtype B and one infected with CRF01_AE. Comparison of the pairwise genetic distance of Sea Service sequences and reference sequences in the env and pro/rt regions showed that five samples were part of molecular clusters, a group of two and a group of three, confirmed by single genome amplification. Real-time molecular monitoring of new HIV-1 acquisitions in the Sea Services may have a role in facilitating public health interventions at sites where related HIV-1 infections are identified.

  14. Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America

    PubMed Central

    Lau, Bryan; Justice, Amy C.; Engels, Eric; Gill, M. John; Goedert, James J.; Kirk, Gregory D.; D’Souza, Gypsyamber; Bosch, Ronald J.; Brooks, John T.; Napravnik, Sonia; Hessol, Nancy A.; Jacobson, Lisa P.; Kitahata, Mari M.; Klein, Marina B.; Moore, Richard D.; Rodriguez, Benigno; Rourke, Sean B.; Saag, Michael S.; Sterling, Timothy R.; Gebo, Kelly A.; Press, Natasha; Martin, Jeffrey N.; Dubrow, Robert

    2012-01-01

    Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7–151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5–61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8–6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5–2.2). In comparison with the period 2000–2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3–.9) in 1996–1999 and 0.9 (95% CI, .6–1.2) in 2004–2007. Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued. PMID:22291097

  15. Bone health in HIV-infected children and adolescents.

    PubMed

    Eckard, Allison R; Mora, Stefano

    2016-05-01

    Chronic HIV infection and exposure to antiretroviral therapy compromises bone health in children and adolescents, potentially impacting their long-term quality of life. Thus, the purpose of this article is to review the most recent literature on this topic in HIV-infected children and adolescents. Recent studies continue to demonstrate bone abnormalities in HIV-infected children and adolescents, whether HIV is acquired perinatally or during adolescence. Researchers have employed new modalities, both high tech and those that can be utilized in resource-limited settings, to better assess bone health. New data suggest that this population may also be experiencing an increase incidence of fractures, and they may not acquire the same peak bone mass as their HIV-uninfected counterparts. Reassuringly, however, in-utero tenofovir exposure does not appear to have a significant impact on bone health in HIV-exposed, uninfected infants. HIV-infected children and adolescents are exposed to HIV and antiretroviral therapy for many decades starting early in life and during the most critical time for skeletal growth and bone mass accrual. Recent findings underscore the need for further research on bone in this population. Longitudinal studies are especially needed to evaluate long-term risk of osteoporosis and fracture.

  16. The role of polymorphonuclear neutrophils during HIV-1 infection.

    PubMed

    Yaseen, Mahmoud Mohammad; Abuharfeil, Nizar Mohammad; Yaseen, Mohammad Mahmoud; Shabsoug, Barakat Mohammad

    2018-01-01

    It is well-recognized that human immunodeficiency virus type-1 (HIV-1) mainly targets CD4 + T cells and macrophages. Nonetheless, during the past three decades, a huge number of studies have reported that HIV-1 can directly or indirectly target other cellular components of the immune system including CD8 + T cells, B cells, dendritic cells, natural killer cells, and polymorphonuclear neutrophils (PMNs), among others. PMNs are the most abundant leukocytes in the human circulation, and are known to play principal roles in the elimination of invading pathogens, regulating different immune responses, healing of injured tissues, and maintaining mucosal homeostasis. Until recently, little was known about the impact of HIV-1 infection on PMNs as well as the impact of PMNs on HIV-1 disease progression. This is because early studies focused on neutropenia and recurrent microbial infections, particularly, during advanced disease. However, recent studies have extended the investigation area to cover new aspects of the interactions between HIV-1 and PMNs. This review aims to summarize these advances and address the impact of HIV-1 infection on PMNs as well as the impact of PMNs on HIV-1 disease progression to better understand the pathophysiology of HIV-1 infection.

  17. Primary Human Immunodeficiency Virus Type 1 (HIV-1) Infection during HIV-1 Gag Vaccination▿

    PubMed Central

    Balamurugan, Arumugam; Lewis, Martha J.; Kitchen, Christina M. R.; Robertson, Michael N.; Shiver, John W.; Daar, Eric S.; Pitt, Jacqueline; Ali, Ayub; Ng, Hwee L.; Currier, Judith S.; Yang, Otto O.

    2008-01-01

    Vaccination for human immunodeficiency virus type 1 (HIV-1) remains an elusive goal. Whether an unsuccessful vaccine might not only fail to provoke detectable immune responses but also could actually interfere with subsequent natural immunity upon HIV-1 infection is unknown. We performed detailed assessment of an HIV-1 gag DNA vaccine recipient (subject 00015) who was previously uninfected but sustained HIV-1 infection before completing a vaccination trial and another contemporaneously acutely infected individual (subject 00016) with the same strain of HIV-1. Subject 00015 received the vaccine at weeks 0, 4, and 8 and was found to have been acutely HIV-1 infected around the time of the third vaccination. Subject 00016 was a previously HIV-1-seronegative sexual contact who had symptoms of acute HIV-1 infection approximately 2 weeks earlier than subject 00015 and demonstrated subsequent seroconversion. Both individuals reached an unusually low level of chronic viremia (<1,000 copies/ml) without treatment. Subject 00015 had no detectable HIV-1-specific cytotoxic T-lymphocyte (CTL) responses until a borderline response was noted at the time of the third vaccination. The magnitude and breadth of Gag-specific CTL responses in subject 00015 were similar to those of subject 00016 during early chronic infection. Viral sequences from gag, pol, and nef confirmed the common source of HIV-1 between these individuals. The diversity and divergence of sequences in subjects 00015 and 00016 were similar, indicating similar immune pressure on these proteins (including Gag). As a whole, the data suggested that while the gag DNA vaccine did not prime detectable early CTL responses in subject 00015, vaccination did not appreciably impair his ability to contain viremia at levels similar to those in subject 00016. PMID:18199650

  18. [Is it possible to cure HIV infection?].

    PubMed

    Gutiérrez, Carolina; Madrid, Nadia P; Moreno, Santiago

    2015-09-01

    Antiretroviral therapy has significantly improved the life expectancy in HIV-infected people, but it cannot cure the disease by itself. Several barriers have been identified for the cure of HIV infection, including a reservoir of latently infected cells, persistent viral replication in tissues, and anatomical sanctuaries. The main strategy proposed for the cure of HIV consists on the administration of drugs that, through the reactivation of latent HIV, would eliminate the cell reservoir. Ongoing clinical trials have shown the proof of concept, but the efficacy of these drugs in decreasing the reservoir size has not been proved so far.

  19. HIV infection in females dependent on drugs.

    PubMed

    Wai, B H; Singh, S; Varma, S L

    1996-03-01

    One hundred and seventy-one drug-dependent females in a drug rehabilitation centre were studied to estimate the prevalence of HIV infection among them. Twenty-four (14%) were positive on the Western Blot test. The presence of HIV infection was significantly correlated with syphilis (p < 0.03) and age (p < 0.001); 83% of those who were HIV positive were intravenous drug users. The need for harm reduction programmes to prevent spread of HIV infection among injecting drug users is stressed.

  20. Unresolved antiretroviral treatment management issues in HIV-infected children.

    PubMed

    Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

    2012-02-01

    Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

  1. The Dilemmas of Childhood HIV Infection.

    ERIC Educational Resources Information Center

    Rudigier, Anne F.; And Others

    1990-01-01

    Increase in number of children infected with human immunodeficiency virus (HIV), and consequential developmental disabilities of these children are discussed. Families caring for HIV-infected children express four recurrent themes: psychological stress, grief and mourning, guilt and self-blame, and isolation and fear of discrimination. Flexible…

  2. Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

    PubMed

    Sarr, Abdoulaye Dieng; Eisen, Geoffrey; Guèye-Ndiaye, Aissatou; Mullins, Christopher; Traoré, Ibrahima; Dia, Mamadou Ciré; Sankalé, Jean-Louis; Faye, Diegane; Mboup, Souleymane; Kanki, Phyllis

    2005-05-01

    Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

  3. Emmonsia helica Infection in HIV-Infected Man, California, USA.

    PubMed

    Rofael, Martin; Schwartz, Ilan S; Sigler, Lynne; Kong, Li K; Nelson, Nicholas

    2018-01-01

    Emmonsia-like fungi have rarely been reported from North America. We report a fatal case of E. helica infection in a man with advanced HIV infection from California, USA, who had progressive respiratory failure and a brain abscess.

  4. Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

    PubMed Central

    Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Goujard, Cécile; Deveau, Christiane; Meyer, Laurence; Ngo, Nicole; Rouzioux, Christine; Guillet, Jean-Gérard; Delfraissy, Jean-François; Sinet, Martine; Venet, Alain

    1999-01-01

    HIV-specific CD8+ T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8+ T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0–6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1–13). The frequency of HIV-specific CD8+ T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8+CD28– terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination. J. Clin. Invest. 104:1431–1439 (1999). PMID:10562305

  5. Cancer screening in patients infected with HIV.

    PubMed

    Sigel, Keith; Dubrow, Robert; Silverberg, Michael; Crothers, Kristina; Braithwaite, Scott; Justice, Amy

    2011-09-01

    Non-AIDS-defining cancers are a rising health concern among HIV-infected patients. Cancer screening is now an important component of health maintenance in HIV clinical practice. The decision to screen an HIV-infected patient for cancer should include an assessment of individualized risk for the particular cancer, life expectancy, and the harms and benefits associated with the screening test and its potential outcome. HIV-infected patients are at enhanced risk of several cancers compared to the general population; anal cancer, hepatocellular carcinoma, Hodgkin's lymphoma, and lung cancer all have good evidence demonstrating an enhanced risk in HIV-infected persons. A number of cancer screening interventions have shown benefit for specific cancers in the general population, but data on the application of these tests to HIV-infected persons are limited. Here we review the epidemiology and background literature relating to cancer screening interventions in HIV-infected persons. We then use these data to inform a conceptual model for evaluating HIV-infected patients for cancer screening.

  6. The Importance of Quality of Care: Effects of Perinatal HIV Infection and Early Institutional Rearing on Preschoolers' Attachment and Indiscriminate Friendliness

    ERIC Educational Resources Information Center

    Dobrova-Krol, Natasha A.; Bakermans-Kranenburg, Marian J.; Van IJzendoorn, Marinus H.; Juffer, Femmie

    2010-01-01

    Background: The rearing environment of human immunodeficiency virus (HIV)-infected children is often compromised, putting these children at additional risks. Positive caregiving may ameliorate the impact of adverse circumstances and promote attachment security. The goal of the present study was to examine the attachment relationships of…

  7. Hepatitis C virus infection in HIV-infected patients.

    PubMed

    Sulkowski, Mark S

    2007-10-01

    The hepatitis C virus (HCV) is a spherical enveloped RNA virus of the Flaviviridae family, classified within the Hepacivirus genus. Since its discovery in 1989, HCV has been recognized as a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to cirrhosis and hepatocellular carcinoma. In the United States, approximately 4 million people have been infected with HCV, and 10,000 HCVrelated deaths occur each year. Due to shared routes of transmission, HCV and HIV co-infection are common, affecting approximately one third of all HIV-infected persons in the United States. In addition, HIV co-infection is associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease, leading to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons because the incidence of infection is increased and the natural history of HCV infection is accelerated in co-infected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed among HIV/HCV co-infected individuals.

  8. Contraception and HIV infection in women.

    PubMed

    Heikinheimo, Oskari; Lähteenmäki, Pekka

    2009-01-01

    More than 15 million women, many of reproductive age, were infected with human immunodeficiency virus (HIV) at the end of 2007. As the HIV epidemic evolves, heterosexual intercourse is increasingly risky: the risk of infection in exposed young women is 4- to 7-fold higher than in young men and nearly half a million newborns annually have HIV. This review aims to show the effect of contraceptive choices on risk of HIV and on the course of disease in women with HIV. Relevant citations were selected by agreement between the authors after a search of MEDLINE using the terms HIV/AIDS and contraception. Risk of transmission of HIV varies from 1 in 200 to 1 in 10 000 coital incidents, depending in part on the integrity of the vaginal epithelium. Consistent use of male condoms has been proven to reduce horizontal transmission of HIV by 80% among HIV-serodiscordant couples. Hormonal contraception may increase the risk of HIV acquisition in high-risk women such as commercial sex workers, but not in women at low risk of HIV. While hormonal contraception did not affect progression of disease in two cohort studies involving 370 women, in a randomized trial among women not receiving antiretroviral medication, clinical disease accelerated in the oral contraception group (13.2/100 woman-years) compared with the copper intrauterine devices group (8.6/100 woman-years; hazard ratio, 1.5; 95% confidence interval, 1.04-2.1). Hormonal contraception does not interfere with antiviral drug effectiveness. All the available reversible contraceptive methods can generally be used by women at risk of HIV infection and by HIV-infected women. Further studies are needed to investigate the safety and efficiency of hormonal contraception in women living with HIV/AIDS.

  9. Shifting the Paradigm: Using HIV Surveillance Data as a Foundation for Improving HIV Care and Preventing HIV Infection

    PubMed Central

    Sweeney, Patricia; Gardner, Lytt I; Buchacz, Kate; Garland, Pamela Morse; Mugavero, Michael J; Bosshart, Jeffrey T; Shouse, R Luke; Bertolli, Jeanne

    2013-01-01

    Context Reducing HIV incidence in the United States and improving health outcomes for people living with HIV hinge on improving access to highly effective treatment and overcoming barriers to continuous treatment. Using laboratory tests routinely reported for HIV surveillance to monitor individuals’ receipt of HIV care and contacting them to facilitate optimal care could help achieve these objectives. Historically, surveillance-based public health intervention with individuals for HIV control has been controversial because of concerns that risks to privacy and autonomy could outweigh benefits. But with the availability of lifesaving, transmission-interrupting treatment for HIV infection, some health departments have begun surveillance-based outreach to facilitate HIV medical care. Methods Guided by ethics frameworks, we explored the ethical arguments for changing the uses of HIV surveillance data. To identify ethical, procedural, and strategic considerations, we reviewed the activities of health departments that are using HIV surveillance data to contact persons identified as needing assistance with initiating or returning to care. Findings Although privacy concerns surrounding the uses of HIV surveillance data still exist, there are ethical concerns associated with not using HIV surveillance to maximize the benefits from HIV medical care and treatment. Early efforts to use surveillance data to facilitate optimal HIV medical care illustrate how the ethical burdens may vary depending on the local context and the specifics of implementation. Health departments laid the foundation for these activities by engaging stakeholders to gain their trust in sharing sensitive information; establishing or strengthening legal, policy and governance infrastructure; and developing communication and follow-up protocols that protect privacy. Conclusions We describe a shift toward using HIV surveillance to facilitate optimal HIV care. Health departments should review the

  10. Cyclophilin B enhances HIV-1 infection

    SciT

    DeBoer, Jason; Madson, Christian J.; Belshan, Michael, E-mail: michaelbelshan@creighton.edu

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

  11. Innate immunity in resistance to HIV infection.

    PubMed

    Biasin, Mara; Clerici, Mario; Piacentini, Luca

    2010-11-01

    Resistance to human immunodeficiency virus (HIV) infection in subjects who do not seroconvert despite multiple exposures to the virus and to the progression to AIDS in HIVinfected individuals depends on multiple factors involving both the innate and the adaptive immune system. The contribution of natural immunity in preventing HIV infection has so far received little attention, but many recently published articles suggest a key role for Toll‐like receptors, natural killer cells, interleukin‐22, acute‐phase amyloid A protein, and APOBEC3G in conferring resistance to HIV infection. The study of these factors will shed light on HIV pathogenesis and contribute to the development of new therapeutic approaches to this elusive disease.

  12. Cancer Prevention in HIV-Infected Populations

    PubMed Central

    Goncalves, Priscila H.; Montezuma-Rusca, Jairo M.; Yarchoan, Robert; Uldrick, Thomas S.

    2016-01-01

    People living with human immunodeficiency virus (HIV) are living longer since the advent of effective combined antiretroviral therapy (cART). While cART substantially decreases the risk of developing some cancers, HIV-infected individuals remain at high risk for Kaposi sarcoma, lymphoma and several solid tumors. Currently HIV-infected patients represent an aging group, and malignancies have become a leading cause of morbidity and mortality. Tailored cancer-prevention strategies are needed for this population. In this review we describe the etiologic agents and pathogenesis of common malignancies in the setting of HIV, as well as current evidence for cancer prevention strategies and screening programs. PMID:26970136

  13. Heroin dependence and HIV infection in Malaysia.

    PubMed

    Chawarski, Marek C; Mazlan, Mahmud; Schottenfeld, Richard S

    2006-04-01

    Malaysia is experiencing severe problems with heroin dependence and HIV infection. This, study evaluated drug use and other HIV risk behaviors and their association with HIV and other infectious diseases in heroin-dependent subjects enrolled in a clinical trial of drug abuse treatment in Muar, Malaysia. Baseline assessment of treatment-seeking subjects (n=177) included the Addiction Severity Index; AIDS Risk Inventory; serological tests for HIV, hepatitis B, and hepatitis C; and chest X-ray. All of the subjects were male; 67.8% were Malays, 28.8% Chinese, and 2.3%. Indian. Subjects had a mean (SD) age of 37.2 (9.1) years and 14.4 (8.5) years of using heroin; 76.3% reported lifetime injection drug use (IDU), and 41.5% reported current IDU; 30 of 156 (19.2%) tested HIV positive, 143 of 159 (89.9%) tested hepatitis C positive, and 25 of 159 (15.7%) had radiological evidence of pulmonary tuberbulosis. Malay subjects had a significantly higher prevalence of current IDU, needle sharing (p<0.01), and HIV infection (p<0.05) compared with Chinese subjects. Lifetime IDU, needle sharing, lack of consistent condom use, and Malay ethnicity were significantly associated with HIV infection. The high prevalence of HIV infection among heroin-dependent individuals, in Malaysia supports the important of interventions to reduce the major risk factors for HIV, including IDU, needle sharing, and unprotected sex.

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

    PubMed

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

    2008-01-01

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

  15. What Can We Learn From Measles? No New HIV Infections.

    PubMed

    Smith, Davey M

    2015-01-01

    Reducing the incidence of HIV infection until there are no new infections depends on driving the number of secondary infections produced by a typical source infection in a completely susceptible population (basic reproduction number; R0) down to less than 1. Components of R0 that must be addressed are the number of sexual contacts the infectious person makes per unit of time (C), the probability of transmission per single sexual contact with the infectious person (P), and the duration that the infected person is infectious to others (D) (R0 = C × P × D). Numerous strategies may contribute to driving transmission of HIV infection down to zero, including early initiation of antiretroviral treatment and pre- or postexposure prophylaxis. This article summarizes a presentation by Davey M. Smith, MD, at the IAS-USA continuing education program held in San Francisco, California, in March 2015.

  16. [Genital warts in HIV-infected individuals].

    PubMed

    Wieland, U; Kreuter, A

    2017-03-01

    Anogenital warts (condylomata acuminata) are much more frequent in human immunodeficiency (HIV)-positive patients compared to HIV-negative individuals. Anogenital warts of HIV-infected patients differ from those of HIV-negative individuals with respect to their spread, occurrence on more unusual anatomical sites, human papillomavirus (HPV)-type spectrum, tendency to recur, and risk of malignant transformation. Between 18 and 56% of anogenital warts of HIV-positive patients harbor high-grade dysplasia. Therefore, anogenital warts of HIV-infected patients should be preferentially treated with ablative methods and should be evaluated histopathologically. Gender-neutral prophylactic HPV vaccination of HPV-naive boys and girls could also lead to a significant reduction of anogenital warts in this patient group in the future.

  17. Women at greater risk of HIV infection.

    PubMed

    Mahathir, M

    1997-04-01

    Although many people believe that mainly men get infected with HIV/AIDS, women are actually getting infected at a faster rate than men, especially in developing countries, and suffer more from the adverse impact of AIDS. As of mid-1996, the Joint UN Program on AIDS estimated that more than 10 million of the 25 million adults infected with HIV since the beginning of the epidemic are women. The proportion of HIV-positive women is growing, with almost half of the 7500 new infections daily occurring among women. 90% of HIV-positive women live in a developing country. In Asia-Pacific, 1.4 million women have been infected with HIV out of an estimated total 3.08 million adults from the late 1970s until late 1994. Biologically, women are more vulnerable than men to infection because of the greater mucus area exposed to HIV during penile penetration. Women under age 17 years are at even greater risk because they have an underdeveloped cervix and low vaginal mucus production. Concurrent sexually transmitted diseases increase the risk of HIV transmission. Women's risk is also related to their exposure to gender inequalities in society. The social and economic pressures of poverty exacerbate women's risk. Prevention programs are discussed.

  18. FRAILTY AND CONSTELLATIONS OF FACTORS IN AGING HIV-INFECTED AND UNINFECTED WOMEN - THE WOMEN'S INTERAGENCY HIV STUDY

    PubMed Central

    GUSTAFSON, D.R.; SHI, Q.; THURN, M.; HOLMAN, S.A.; MINKOFF, H.; COHEN, M.; PLANKEY, M.W.; HAVLIK, R.; SHARMA, A.; GANGE, S.; GANDHI, M.; MILAM, J.; HOOVER, D.

    2016-01-01

    Background Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. Objectives We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV− women. Design Cross-sectional. Setting The Women's Interagency HIV Study (WIHS). Participants 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV−). Measurements The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. Results Overall frailty prevalence was 15.2% (HIV+, 17%; HIV−, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. Conclusions Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger `at risk' populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death. PMID:26980368

  19. In–Depth Characterization of Viral Isolates from Plasma and Cells Compared with Plasma Circulating Quasispecies in Early HIV-1 Infection

    PubMed Central

    Erkizia, Itziar; Pino, Maria; Pou, Christian; Paredes, Roger; Clotet, Bonaventura; Martinez-Picado, Javier; Prado, Julia G.

    2012-01-01

    Background The use of in vitro models to unravel the phenotypic characteristics of circulating viral variants is key to understanding HIV-1 pathogenesis but limited by the availability of primary viral isolates from biological samples. However, overall in vivo genetic variability of HIV-1 within a subject may not be reflected in the viable viral population obtained after isolation. Although several studies have tried to determine whether viral populations expanded in vitro are representative of in vivo findings, the answer remains unclear due to the reduced number of clonal sequences analyzed or samples compared. In order to overcome previous experimental limitations, here we applied Deep Pyrosequencing (DPS) technology in combination with phenotypic experiments to analyze and compare with unprecedented detail the composition of viral isolates and in vivo quasispecies. Methodology/Principal Findings We amplified by DPS HIV-1 genomic regions covering gag, protease, integrase and env-V3 to characterize paired isolates from plasma and peripheral blood mononuclear cells and compare them with total plasma viral RNA in four recently HIV-1 infected subjects. Our study demonstrated the presence of unique haplotypes scattered between sample types with conservation of major variants. In addition, no differences in intra- and inter-population encoded protein variability were found between the different types of isolates or when these were compared to plasma viral RNA within subjects. Additionally, in vitro experiments demonstrated phenotypic similarities in terms of replicative capacity and co-receptor usage between viral isolates and plasma viral RNA. Conclusion This study is the first in-depth comparison and characterization of viral isolates from different sources and plasma circulating quasispecies using DPS in recently HIV-1 infected subjects. Our data supports the use of primary isolates regardless of their plasma or cellular origin to define genetic variability and

  20. Neuromuscular Diseases Associated with HIV-1 Infection

    PubMed Central

    Robinson-Papp, Jessica; Simpson, David M.

    2010-01-01

    Neuromuscular disorders are common in HIV, occurring at all stages of disease and affecting all parts of the peripheral nervous system. These disorders have diverse etiologies including HIV itself, immune suppression and dysregulation, co-morbid illnesses and infections, and side effects of medications. In this article, we review the following HIV-associated conditions: distal symmetric polyneuropathy, inflammatory demyelinating polyneuropathy, mononeuropathy, mononeuropathy multiplex, autonomic neuropathy, progressive polyradiculopathy due to cytomegalovirus, herpes zoster, myopathy and other rarer disorders. PMID:19771594

  1. Measles infection in HIV-infected African infants.

    PubMed

    Perry, R T; Mmiro, F; Ndugwa, C; Semba, R D

    2000-11-01

    Measles infection remains a serious threat to child survival in the developing world despite vaccination and treatment with vitamin A. This report reviews the epidemiology of measles in HIV-infected children in Africa. In hospitalized infants, the rate of malnutrition before measles and the rate of death after measles are both higher in HIV-positive than in HIV-negative infants. However, the rates of pneumonia and diarrhea in infants hospitalized with measles are the same in HIV-positive as in HIV-negative infants. In an autopsy study, measles was associated with death in HIV-positive children, only for those over 15 months of age. A cohort study found that infants of HIV-positive women were more likely than infants of HIV-negative women to have measles before 9 months of age, although the rates of complications did not differ between the two groups. The HIV status of the infants and the measles serology were too incomplete to draw firm conclusions, though only 1 of 54 infants tested was seropositive for measles at 6 months of age. In the context of the HIV epidemic, further work is needed to determine the risk of measles and its complications in HIV-positive infants and the optimal age of measles immunization.

  2. Computational analysis of antibody dynamics identifies recent HIV-1 infection.

    PubMed

    Seaton, Kelly E; Vandergrift, Nathan A; Deal, Aaron W; Rountree, Wes; Bainbridge, John; Grebe, Eduard; Anderson, David A; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L; Denny, Thomas N; Liao, Hua-Xin; Haynes, Barton F; Robb, Merlin L; Parkin, Neil; Santos, Breno R; Garrett, Nigel; Price, Matthew A; Naniche, Denise; Duerr, Ann C; Keating, Sheila; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D; Cohen, Myron S; Tomaras, Georgia D

    2017-12-21

    Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.

  3. Computational analysis of antibody dynamics identifies recent HIV-1 infection

    PubMed Central

    Seaton, Kelly E.; Vandergrift, Nathan A.; Deal, Aaron W.; Rountree, Wes; Anderson, David A.; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L.; Denny, Thomas N.; Haynes, Barton F.; Robb, Merlin L.; Parkin, Neil; Santos, Breno R.; Price, Matthew A.; Naniche, Denise; Duerr, Ann C.; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D.; Cohen, Myron S.

    2017-01-01

    Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1–infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation. PMID:29263306

  4. Major depressive disorder and suicidality in early HIV infection and its association with risk factors and negative outcomes as seen in semi-urban and rural Uganda.

    PubMed

    Kinyanda, Eugene; Nakasujja, Noeline; Levin, Jonathan; Birabwa, Harriet; Mpango, Richard; Grosskurth, Heiner; Seedat, Soraya; Patel, Vikram

    2017-04-01

    There is a paucity of research into the psychiatric problems associated with early stage HIV clinical disease in sub-Saharan Africa. A cross sectional study was undertaken among 899 adult ART naïve persons in early stage HIV clinical disease (participants with CD4≥250 and who were at WHO clinical Stage I or II) attending a semi-urban and a rural clinic in Uganda. The prevalence of major depressive disorder in this study was 14.0% [95% CI 11.7-6.3%] while that of 'moderate to high risk for suicidality' was 2.8% [95% CI 1.7%; 3.9%]. Multivariable analyses found that factors in the socio-demographic, vulnerability/protective and stress (only for major depressive disorder) domains were significantly associated with both major depressive disorder and 'moderate to high risk for suicidality'. Major depressive disorder but not 'moderate to high risk for suicidality' was significantly associated with impaired psychosocial functioning, greater utilisation of health services and non-adherence to septrin/dasone. Neither major depressive disorder nor 'moderate to high risk for suicidality' was associated with CD4 counts, risky sexual behaviour nor with non-utilisation of condoms. The bidirectional nature of some of the relationships between the investigated psychiatric problems, risk factors and outcomes in this cross sectional study makes it difficult to elucidate the actual direction of causality. Early stage HIV clinical disease is associated with considerable major depressive disorder and 'moderate to high risk for suicidality'. Therefore there is a need to integrate mental health into HIV interventions that target early stage HIV disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Male circumcision and HIV infection risk.

    PubMed

    Krieger, John N

    2012-02-01

    Male circumcision is being promoted to reduce human immunodeficiency virus type 1 (HIV) infection rates. This review evaluates the scientific evidence suggesting that male circumcision reduces HIV infection risk in high-risk heterosexual populations. We followed the updated International Consultation on Urological Diseases evidence-based medicine recommendations to critically review the scientific evidence on male circumcision and HIV infection risk. Level 1 evidence supports the concept that male circumcision substantially reduces the risk of HIV infection. Three major lines of evidence support this conclusion: biological data suggesting that this concept is plausible, data from observational studies supported by high-quality meta-analyses, and three randomized clinical trials supported by high-quality meta-analyses. The evidence from these biological studies, observational studies, randomized controlled clinical trials, meta-analyses, and cost-effectiveness studies is conclusive. The challenges to implementation of male circumcision as a public health measure in high-risk populations must now be faced.

  6. Low CD1c + myeloid dendritic cell counts correlated with a high risk of rapid disease progression during early HIV-1 infection.

    PubMed

    Diao, Yingying; Geng, Wenqing; Fan, Xuejie; Cui, Hualu; Sun, Hong; Jiang, Yongjun; Wang, Yanan; Sun, Amy; Shang, Hong

    2015-08-19

    During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.

  7. The VUKA Family Program: Piloting a family-based psychosocial intervention to promote health and mental health among HIV infected early adolescents in South Africa

    PubMed Central

    Bhana, Arvin; Mellins, Claude Ann; Petersen, Inge; Alicea, Stacey; Myeza, Nonhlahla; Holst, Helga; Abrams, Elaine; John, Sally; Chhagan, Meera; Nestadt, Danielle F; Leu, Cheng-Shiun; McKay, Mary

    2013-01-01

    An increasing number of adolescents born with HIV in South Africa are on antiretroviral treatment and have to confront complex issues related to coping with a chronic, stigmatizing and transmittable illness. Very few evidence-based mental health and health promotion programs for this population exist in South Africa. This study builds on a previous collaboratively designed and developmentally-timed family-based intervention for early adolescents (CHAMP). The study uses community-based participatory approach as part of formative research to evaluate a pilot randomized control trial at two hospitals. The paper reports on the development, feasibility and acceptability of the VUKA family-based program and its short-term impact on a range of psychosocial variables for HIV+ pre-adolescents and their caregivers. A ten session intervention of approximately 3 months duration was delivered to 65 pre-adolescents aged 10-13 years and their families. VUKA participants were noted to improve on all dimensions, including mental health, youth behaviour, HIV treatment knowledge, stigma, communication and adherence to medication. VUKA shows promise as a family-based mental and HIV prevention program for HIV+ pre-adolescents and which could be delivered by trained lay staff. PMID:23767772

  8. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

    SciT

    Di Nunzio, Francesca, E-mail: francesca.di-nunzio@pasteur.fr; Fricke, Thomas; Miccio, Annarita

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants formore » the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites.« less

  9. CCD Camera Detection of HIV Infection.

    PubMed

    Day, John R

    2017-01-01

    Rapid and precise quantification of the infectivity of HIV is important for molecular virologic studies, as well as for measuring the activities of antiviral drugs and neutralizing antibodies. An indicator cell line, a CCD camera, and image-analysis software are used to quantify HIV infectivity. The cells of the P4R5 line, which express the receptors for HIV infection as well as β-galactosidase under the control of the HIV-1 long terminal repeat, are infected with HIV and then incubated 2 days later with X-gal to stain the infected cells blue. Digital images of monolayers of the infected cells are captured using a high resolution CCD video camera and a macro video zoom lens. A software program is developed to process the images and to count the blue-stained foci of infection. The described method allows for the rapid quantification of the infected cells over a wide range of viral inocula with reproducibility, accuracy and at relatively low cost.

  10. New Antiretroviral Therapies for Pediatric HIV Infection

    PubMed Central

    Morris, Jennifer L.; Kraus, Donna M.

    2005-01-01

    Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

  11. Factors Associated with Recent HIV Testing among Heterosexuals at High Risk for HIV Infection in New York City.

    PubMed

    Gwadz, Marya; Cleland, Charles M; Kutnick, Alexandra; Leonard, Noelle R; Ritchie, Amanda S; Lynch, Laura; Banfield, Angela; McCright-Gill, Talaya; Del Olmo, Montserrat; Martinez, Belkis

    2016-01-01

    The Centers for Disease Control and Prevention recommends persons at high risk for HIV infection in the United States receive annual HIV testing to foster early HIV diagnosis and timely linkage to health care. Heterosexuals make up a significant proportion of incident HIV infections (>25%) but test for HIV less frequently than those in other risk categories. Yet factors that promote or impede annual HIV testing among heterosexuals are poorly understood. The present study examines individual/attitudinal-, social-, and structural-level factors associated with past-year HIV testing among heterosexuals at high risk for HIV. Participants were African-American/Black and Hispanic heterosexual adults (N = 2307) residing in an urban area with both high poverty and HIV prevalence rates. Participants were recruited by respondent-driven sampling in 2012-2015 and completed a computerized structured assessment battery covering background factors, multi-level putative facilitators of HIV testing, and HIV testing history. Separate logistic regression analysis for males and females identified factors associated with past-year HIV testing. Participants were mostly male (58%), African-American/Black (75%), and 39 years old on average (SD = 12.06 years). Lifetime homelessness (54%) and incarceration (62%) were common. Half reported past-year HIV testing (50%) and 37% engaged in regular, annual HIV testing. Facilitators of HIV testing common to both genders included sexually transmitted infection (STI) testing or STI diagnosis, peer norms supporting HIV testing, and HIV testing access. Among women, access to general medical care and extreme poverty further predicted HIV testing, while recent drug use reduced the odds of past-year HIV testing. Among men, past-year HIV testing was also associated with lifetime incarceration and substance use treatment. The present study identified gaps in rates of HIV testing among heterosexuals at high risk for HIV, and both common and

  12. Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

    PubMed

    Luetkemeyer, Annie; Hare, C Bradley; Stansell, John; Tien, Phyllis C; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion

    2006-01-01

    Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

  13. Retinitis due to opportunistic infections in Iranian HIV infected patients.

    PubMed

    Abdollahi, Ali; Mohraz, Minoo; Rasoulinejad, Mehrnaz; Shariati, Mona; Kheirandish, Parastou; Abdollahi, Maryam; Soori, Tahereh

    2013-01-01

    We tried to evaluate prevalence and characteristics of Iranian HIV infected patients with retinitis due to opportunistic infections. In this cross sectional study, we evaluated 106 HIV infected patients via indirect ophthalmoscopy and slit lamp examination by 90 lens to find retinitis cases. General information and results of ophthalmologic examination were analyzed. Prevalence of retinitis due to opportunistic infections was 6.6%: cytomegalovirus (CMV) retinitis 1.88%, toxoplasmosis retinochoroiditis 1.88% and tuberculosis chorioretinitis 2.83%. CD4 count was higher than 50 cell/µlit in both cases with CMV retinitis. Along with increasing survival in the HIV infected patients, the prevalence of complications such as ocular manifestation due to opportunistic infections are increasing and must be more considered.

  14. B cell responses to HIV infection

    PubMed Central

    Moir, Susan; Fauci, Anthony S.

    2016-01-01

    Summary The induction of neutralizing antibodies directed against the human immunodeficiency virus (HIV) has received considerable attention in recent years, in part driven by renewed interest and opportunities for antibody-based strategies for prevention such as passive transfer of antibodies and the development of preventive vaccines, as well as immune-based therapeutic interventions. Advances in the ability to screen, isolate and characterize HIV-specific antibodies have led to the identification of a new generation of potent broadly neutralizing antibodies (bNAbs). The majority of these antibodies have been isolated from B cells of chronically HIV-infected individuals with detectable viremia. In this review, we provide insight into the phenotypic and functional attributes of human B cells, with a focus on HIV-specific memory B cells and plasmablasts/cells that are responsible for sustaining humoral immune responses against HIV. We discuss the abnormalities in B cells that occur in HIV infection both in the peripheral blood and lymphoid tissues, especially in the setting of persisting viremia. Finally, we consider the opportunities and drawbacks of intensively interrogating antibodies isolated from HIV-infected individuals to guide strategies aimed at developing effective antibody-based vaccine and therapeutic interventions for HIV. PMID:28133792

  15. B-cell responses to HIV infection.

    PubMed

    Moir, Susan; Fauci, Anthony S

    2017-01-01

    The induction of neutralizing antibodies directed against the human immunodeficiency virus (HIV) has received considerable attention in recent years, in part driven by renewed interest and opportunities for antibody-based strategies for prevention such as passive transfer of antibodies and the development of preventive vaccines, as well as immune-based therapeutic interventions. Advances in the ability to screen, isolate, and characterize HIV-specific antibodies have led to the identification of a new generation of potent broadly neutralizing antibodies (bNAbs). The majority of these antibodies have been isolated from B cells of chronically HIV-infected individuals with detectable viremia. In this review, we provide insight into the phenotypic and functional attributes of human B cells, with a focus on HIV-specific memory B cells and plasmablasts/cells that are responsible for sustaining humoral immune responses against HIV. We discuss the abnormalities in B cells that occur in HIV infection both in the peripheral blood and lymphoid tissues, especially in the setting of persisting viremia. Finally, we consider the opportunities and drawbacks of intensively interrogating antibodies isolated from HIV-infected individuals to guide strategies aimed at developing effective antibody-based vaccine and therapeutic interventions for HIV. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  16. HIV infection among pregnant women in Nigeria.

    PubMed

    Sagay, A S; Kapiga, S H; Imade, G E; Sankale, J L; Idoko, J; Kanki, P

    2005-07-01

    To determine risk factors for HIV among pregnant women (N = 2657) receiving antenatal services in Jos, Plateau state, Nigeria. Information about potential risk factors was obtained at interview. Biological samples were collected for detection of HIV and other sexually transmitted infections (STIs). The prevalence of HIV was 8.2%. Women aged 20-29 years had more than 4-fold increased risk of HIV. Women of Catholic (adjusted odds ratio (AOR) = 1.72, 95% CI = 1.01-2.95) and Pentecostal (AOR = 2.57, 95% CI = 1.46-4.52) denominations were more likely to be HIV-infected when compared to Moslem women. The risk of HIV was also increased among women with multiple marriages and in women married to a banker/accountant. Other predictors of HIV were having a husband with other partners, perceived risk of HIV, STIs, candidiasis and bacterial vaginosis. Development of effective interventions, including behavioral change, expansion of perinatal HIV prevention services and STI control, should be given the highest priority.

  17. Early childhood transmission of hepatitis B prior to the first hepatitis B vaccine dose is rare among babies born to HIV-infected and non-HIV infected mothers in Gulu, Uganda

    PubMed Central

    Van Geertruyden, J.P.; Ssenyonga, R.; Opio, C.K.; Kaducu, J.M.; Sempa, J.B.; Colebunders, R.; Ocama, P.

    2017-01-01

    Background Hepatitis B (HBV) in sub-Saharan Africa is believed to be horizontally acquired. However, because of the high HBV prevalence in northern Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin, we hypothesize that vertical transmission also could also play an important role. We therefore investigated the incidence of HBV among babies presenting for their first HBV vaccine dose in Gulu, Uganda. Methods We recruited mothers and their babies (at least 6-week old) presenting for their postnatal care and first HBV vaccine dose respectively. Socio-demographic and risk factors for HBV transmission were recorded. Mothers were tested for Hepatitis B core antibody (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were tested for HBsAg at presentation and at the last immunization visit. A sample of HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests were utilized to investigate associations and t-tests or Wilcoxon rank-sum test for continuous differences. Results We recruited 612 mothers, median age 23 years (IQR 20–28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG-positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6–7.0) IU/mL with 9 (17.6%) having levels ≥105 IU/mL. Eighty (13.3%) mothers were HIV-infected of whom 9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive. Conclusion Vertical transmission does not seem to contribute substantially to the high HBV endemicity in northern Uganda. The current practice of administering the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in control of HBV transmission. PMID:28434689

  18. First UK case report of kidney transplantation from an HIV-infected deceased donor to two HIV-infected recipients.

    PubMed

    Nolan, Eileen; Karydis, Nikolaos; Drage, Martin; Hilton, Rachel

    2018-04-01

    Kidney transplantation is now considered the treatment of choice for many human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Graft survival rates using HIV-negative donors and carefully selected HIV-positive ESRD patients are similar to those observed in HIV-uninfected kidney transplant recipients. To address the relative shortfall in donated organs it has been proposed that organs from HIV-infected deceased donors might be allocated to HIV-infected patients on the transplant waiting list. Preliminary experience in South Africa reports promising short-term outcomes in a small number of HIV-infected recipients of kidney transplants from HIV-infected donors. We sought to replicate this experience in the UK by accepting kidney offers from HIV infected deceased donors for patients with HIV-infection on the kidney transplant waiting list. Here we report the UK's first cases of kidney transplantation between HIV-positive donors and recipients.

  19. Family physicians and HIV infection.

    PubMed

    Hall, N; Crochette, N; Blanchi, S; Lavoix, A; Billaud, E; Baron, C; Abgueguen, P; Perré, P; Rabier, V

    2015-01-01

    We aimed to describe the current and desired involvement of family physicians (FPs) in the treatment of HIV patients (screening practices, potential training and patient follow-up) to reduce the duration and frequency of their hospital treatment. We conducted a descriptive cross-sectional survey between 2011 and 2012 with the support of COREVIH (Regional Coordinating Committee on HIV). We sent a self-assessment questionnaire to all FPs of the Pays de la Loire region to enquire about their HIV screening practices and expectations for the management of HIV patients. A total of 871 FPs completed the questionnaire (response rate: 30.4%). A total of 54.2% said to provide care to HIV patients; the mean number of HIV patients per FP was estimated at 1.4. With regard to HIV screening, 12.2% systematically suggest an HIV serology to their patients and 72.7% always suggest it to pregnant women. About 45.4% of responding FPs said to be willing to manage HIV patients (clinical and biological monitoring, compliance checks and prescription renewal). FPs mainly reported the lack of training and the low number of HIV patients as a barrier to their further involvement in the management of HIV patients. The responding FPs provide care to very few HIV patients. They are, however, willing to be more involved in the routine care of these patients. Medical training provided by COREVIH would help improve HIV screening. The management of HIV patients could thus be handed over to willing FPs. Copyright © 2015. Published by Elsevier SAS.

  20. Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure

    PubMed Central

    Treurnicht, F.K.; Seoighe, C.; Martin, D.P.; Wood, N.; Abrahams, M-R.; de Assis Rosa, D.; Bredell, H.; Woodman, Z.; Hide, W.; Mlisana, K.; Karim, S Abdool; Gray, C.M.; Williamson, C.

    2009-01-01

    It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential “transmission signatures”, we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission. PMID:19913270

  1. Domestic violence and childhood sexual abuse in HIV-infected women and women at risk for HIV.

    PubMed Central

    Cohen, M; Deamant, C; Barkan, S; Richardson, J; Young, M; Holman, S; Anastos, K; Cohen, J; Melnick, S

    2000-01-01

    OBJECTIVES: The purpose of this study was to determine the prevalence and effect of domestic violence and childhood sexual abuse in women with HIV or at risk for HIV infection. METHODS: Participants with HIV or at risk for HIV infection enrolled in the Women's Interagency HIV Study. Childhood sexual abuse; all physical, sexual, and coercive violence by a partner; HIV serostatus; demographic data; and substance use and sexual habits were assessed. RESULTS: The lifetime prevalence of domestic violence was 66% and 67%, respectively, in 1288 women with HIV and 357 uninfected women. One quarter of the women reported recent abuse, and 31% of the HIV-seropositive women and 27% of the HIV-seronegative women reported childhood sexual abuse. Childhood sexual abuse was strongly associated with a lifetime history of domestic violence and high-risk behaviors, including using drugs, having more than 10 male sexual partners and having male partners at risk for HIV infection, and exchanging sex for drugs, money, or shelter. CONCLUSIONS: Our data support the hypothesis of a continuum of risk, with early childhood abuse leading to later domestic violence, which may increase the risk of behaviors leading to HIV infection. PMID:10754970

  2. Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

    PubMed Central

    Kardava, Lela; Moir, Susan; Shah, Naisha; Wang, Wei; Wilson, Richard; Buckner, Clarisa M.; Santich, Brian H.; Kim, Leo J.Y.; Spurlin, Emily E.; Nelson, Amy K.; Wheatley, Adam K.; Harvey, Christopher J.; McDermott, Adrian B.; Wucherpfennig, Kai W.; Chun, Tae-Wook; Tsang, John S.; Li, Yuxing; Fauci, Anthony S.

    2014-01-01

    Recently, several neutralizing anti-HIV antibodies have been isolated from memory B cells of HIV-infected individuals. Despite extensive evidence of B cell dysfunction in HIV disease, little is known about the cells from which these rare HIV-specific antibodies originate. Accordingly, we used HIV envelope gp140 and CD4 or coreceptor (CoR) binding site (bs) mutant probes to evaluate HIV-specific responses in peripheral blood B cells of HIV-infected individuals at various stages of infection. In contrast to non-HIV responses, HIV-specific responses against gp140 were enriched within abnormal B cells, namely activated and exhausted memory subsets, which are largely absent in the blood of uninfected individuals. Responses against the CoRbs, which is a poorly neutralizing epitope, arose early, whereas those against the well-characterized neutralizing epitope CD4bs were delayed and infrequent. Enrichment of the HIV-specific response within resting memory B cells, the predominant subset in uninfected individuals, did occur in certain infected individuals who maintained low levels of plasma viremia and immune activation with or without antiretroviral therapy. The distribution of HIV-specific responses among memory B cell subsets was corroborated by transcriptional analyses. Taken together, our findings provide valuable insight into virus-specific B cell responses in HIV infection and demonstrate that memory B cell abnormalities may contribute to the ineffectiveness of the antibody response in infected individuals. PMID:24892810

  3. Immune pathogenesis of pediatric HIV-1 infection

    PubMed Central

    TIEMESSEN, CAROLINE T.; KUHN, LOUISE

    2008-01-01

    Vertical exposure to HIV occurs at a time when functional capacity of the infant’s immune system is attenuated through immaturity. Immune response capability is rooted in host genetic makeup, and the broad and fine specificity of innate and adaptive immune responses, respectively, shape the outcomes of HIV encounter in some instances and imprint viral changes through selective immune pressure in others. Findings from recent studies have profound implications for understanding immune pathogenesis of pediatric HIV infection, and in particular highlight the importance of host genetics of both mother and child in determining whether an exposed child acquires HIV infection or not, and if infected, the rate of disease progression. This review focuses on the key host molecules, the CC chemokine CCL3 and HLA, which have taken center stage in these new developments. PMID:16522254

  4. Cumulative HIV viremia and non-AIDS-defining malignancies among a sample of HIV-infected male veterans.

    PubMed

    Kowalkowski, Marc A; Day, Rena S; Du, Xianglin L; Chan, Wenyaw; Chiao, Elizabeth Y

    2014-10-01

    Research suggests that cumulative measurement of HIV exposure is associated with mortality, AIDS, and AIDS-defining malignancies. However, the relationship between cumulative HIV and non-AIDS-defining malignancies (NADMs) remains unclear. The aim of this study was to evaluate the effect of different HIV measures on NADM hazard among HIV-infected male veterans. We performed a retrospective cohort study using Veterans Affairs HIV Clinical Case Registry data from 1985 to 2010. We analyzed the relationship between HIV exposure (recent HIV RNA, % undetectable HIV RNA, and HIV copy-years viremia) and NADM. To evaluate the effect of HIV, we calculated hazard ratios for 3 common virally associated NADM [ie, hepatocarcinoma (HCC), Hodgkin lymphoma (HL), and squamous cell carcinoma of the anus (SCCA)] in multivariable Cox regression models. Among 31,576 HIV-infected male veterans, 383 HCC, 211 HL, and 373 SCCA cases were identified. In multivariable regression models, cross-sectional HIV measurement was not associated with NADM. However, compared with <20% undetectable HIV, individuals with ≥80% had decreased HL [adjusted hazard ratio (aHR) = 0.62; 95% confidence interval (CI): 0.37 to 1.02] and SCCA (aHR = 0.64; 95% CI: 0.44 to 0.93). Conversely, each log10 increase in HIV copy-years was associated with elevated HL (aHR = 1.22; 95% CI: 1.06 to 1.40) and SCCA (aHR = 1.36; 95% CI: 1.21 to 1.52). Model fit was best with HIV copy-years. Cumulative HIV was not associated with HCC. Cumulative HIV was associated with certain virally associated NADM (ie, HL and SCCA), independent of measured covariates. Findings underline the importance of early treatment initiation and durable medication adherence to reduce cumulative HIV burden. Future research should prioritize how to best apply cumulative HIV measures in screening for these cancers.

  5. [Renal transplantation in HIV-infected patients in Spain].

    PubMed

    Mazuecos, A; Pascual, J; Gómez, E; Sola, E; Cofán, F; López, F; Puig-Hooper, C E; Baltar, J M; González-Molina, M; Oppenheimer, F; Marcén, R; Rivero, M

    2006-01-01

    HIV infection has experienced dramatic improvement in morbidity and mortality with the highly active antiretroviral therapy (HAART). This prompted a reevaluation of organ-solid transplantation as a treatment option for HIV-infected patients. Some trials in the United States have shown that one- and 2-year graft and patient survival is comparable to HIV-negative transplant population. In Europe the experience is still scarce. The aim of this study is to analyse the outcome and the clinical characteristics of HIV-infected patients who received kidney transplantation in Spain in the HAART era. Ten patients were transplanted in our country since 2001. Only one patient was black. The main cause of end-stage renal disease reported was glomerulonephritis. Six of the recipients were coinfected by hepatitis C virus. Inclusion criteria included undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46) months, respectively. One recipient lost his graft because of early renal venous thrombosis. The remaining patients are functioning graft with mean serum creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was diagnosed in 4 recipients and was reversed in all cases with antirejection treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have been stable in excess of 200 cell/microL. None of patients have developed AIDS complications. Recipients receiving protease inhibitor-based HAART regimens required significant dosing modification to maintain appropriate tacrolimus levels. Our results show that renal transplantation can be a safe and effective treatment in select HIV-infected patients. Like other series, the acute rejection rate was higher than in non-HIV recipients. The reasons of this rejection incidence remain unknown.

  6. Malignancies in HIV-Infected and AIDS Patients.

    PubMed

    Ji, Yongjia; Lu, Hongzhou

    2017-01-01

    Currently, HIV infection and AIDS are still one of the most important epidemic diseases around the world. As early in the initial stage of HIV epidemic, the high incidence of ADCs including Kaposi sarcoma and non-Hodgkin's lymphoma was the substantial amount of disease burden of HIV infection and AIDS. With the increasing accessibility of HAART and improving medical care for HIV infection and AIDS, AIDS-related illness including ADCs has dramatically decreased. Meanwhile, the incidence of NADCs rises in PLWH. Compared with the general population, most of cancers are more likely to attack PLWH, and NADCs in PLWH were characterized as earlier onset and more aggressive. However, the understanding for cancer development in PLWH is still dimness. Herein, we reviewed the current knowledge of epidemiology and pathogenesis for malignancies in PLWH summarized from recent studies. On the basis of that, we discussed the special considerations for cancer treatment in PLWH. As those malignancies could be the major issue for HIV infection or AIDS in the future, we expect enhanced investigations, surveillances, and clinical trial for improving the understanding and management for cancers developed in PLWH.

  7. Reduction in undiagnosed HIV infection in the European Union/European Economic Area, 2012 to 2016.

    PubMed

    van Sighem, Ard; Pharris, Anastasia; Quinten, Chantal; Noori, Teymur; Amato-Gauci, Andrew J

    2017-11-01

    It is well-documented that early HIV diagnosis and linkage to care reduces morbidity and mortality as well as HIV transmission. We estimated the median time from HIV infection to diagnosis in the European Union/European Economic Area (EU/EEA) at 2.9 years in 2016, with regional variation. Despite evidence of a decline in the number of people living with undiagnosed HIV in the EU/EEA, many remain undiagnosed, including 33% with more advanced HIV infection (CD4 < 350 cells/mm3).

  8. Reduction in undiagnosed HIV infection in the European Union/European Economic Area, 2012 to 2016

    PubMed Central

    van Sighem, Ard; Pharris, Anastasia; Quinten, Chantal; Noori, Teymur; Amato-Gauci, Andrew J

    2017-01-01

    It is well-documented that early HIV diagnosis and linkage to care reduces morbidity and mortality as well as HIV transmission. We estimated the median time from HIV infection to diagnosis in the European Union/European Economic Area (EU/EEA) at 2.9 years in 2016, with regional variation. Despite evidence of a decline in the number of people living with undiagnosed HIV in the EU/EEA, many remain undiagnosed, including 33% with more advanced HIV infection (CD4 < 350 cells/mm3). PMID:29208159

  9. [Heterosexual transmission of HIV infection

    PubMed

    Coulaud, J P

    1993-02-01

    The AIDS epidemic has spread rapidly in Africa among the urban impoverished where multiple sexual partners and sexually transmitted diseases are common. Over 80% of the 9 million Africans who will develop AIDS before the year 2000 will have been contaminated sexually. Poverty, multiple sexual partners in the framework of prostitution, and drug addiction are responsible for rapid spread of HIV infection in Southeast Asia, the West India, and Brazil. Drug addiction has played a major role in diffusion of HIV into the general population of Europe and the US. Prevalence rates are much higher in sexually transmitted disease centers in France and the US than among blood donors or pregnant women. Sexually transmitted diseases and heterosexual transmission have been studied in Africas since diagnostic tests became available. Several studies, the majority conducted among prostitutes in Nairobi or Kinshasa and their clients, allow establishment of a list of sexually transmitted diseases associated with increased risk of seroconversion. Genital ulcers within the past 6 months presented a relative risk of 2-4 depending on the series. Urethral or cervical gonorrhea has a lower relative risk of 1.2 in most studies. Absence of circumcision was also a risk factor. Studies were subsequently conducted in Europe on factors favoring sexual transmission. 513 heterosexual couples together for a minimum duration of 18 months and an average of 38 months were included in the Multicenter European Study conducted in 10 centers in 9 countries. The "index" subject was male in 400 cases and female in 113. At entry into the study, 73 of 400 males (18.2%) and 10 of 113 females (8.8%) had already infected their partners. Duration of union, frequency of intercourse, mode of transmission of the index subject, and oral contraceptive use had no effect on risk of transmission. Factors increasing risk of infection included the severity of immunosuppression of the index subject, whether judged by

  10. Early infant HIV diagnosis and entry to HIV care cascade in Thailand: an observational study.

    PubMed

    Sirirungsi, Wasna; Khamduang, Woottichai; Collins, Intira Jeannie; Pusamang, Artit; Leechanachai, Pranee; Chaivooth, Suchada; Ngo-Giang-Huong, Nicole; Samleerat, Tanawan

    2016-06-01

    Early infant diagnosis of HIV is crucial for timely initiation of antiretroviral therapy (ART) in infected children who are at high risk of mortality. Early infant diagnosis with dried blood spot testing was provided by the National AIDS Programme in Thailand from 2007. We report ART initiation and vital status in children with HIV after 7 years of rollout in Thailand. Dried blood spot samples were collected from HIV-exposed children in hospitals in Thailand and mailed to the Faculty of Associated Medical Sciences, Chiang Mai University, where HIV DNA was assessed with real-time PCR to establish HIV infection. We linked data from children with an HIV infection to the National AIDS Programme database to ascertain ART and vital status. Between April 5, 2007, and Oct 1, 2014, 16 046 dried blood spot samples were sent from 8859 children in 364 hospitals in Thailand. Median age at first dried blood spot test was 2·1 (IQR 1·8-2·5) months. Of 7174 (81%) children with two or more samples, 223 (3%) were HIV positive (including five unconfirmed). Of 1685 (19%) children with one sample, 70 (4%) were unconfirmed positive. Of 293 (3%) children who were HIV positive, 220 (75%) registered for HIV care and 170 (58%) initiated ART. Median age at ART initiation decreased from 14·2 months (IQR 10·2-25·6) in 2007 to 6·1 months (4·2-9·2) in 2013, and the number of children initiating ART aged younger than 1 year increased from five (33%) of 15 children initiating ART in 2007 to ten (83%) of 12 initiating ART in 2013. 15 (9%) of 170 children who initiated ART died and 16 (32%) of 50 who had no ART record died. Early infant diagnosis with dried blood spot testing had high uptake in primary care settings. Further improvement of linkage to HIV care is needed to ensure timely treatment of all children with an HIV infection. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Innate immunity against HIV-1 infection.

    PubMed

    Altfeld, Marcus; Gale, Michael

    2015-06-01

    During acute HIV-1 infection, viral pathogen-associated molecular patterns are recognized by pathogen-recognition receptors (PRRs) of infected cells, which triggers a signaling cascade that initiates innate intracellular antiviral defenses aimed at restricting the replication and spread of the virus. This cell-intrinsic response propagates outward via the action of secreted factors such as cytokines and chemokines that activate innate immune cells and attract them to the site of infection and to local lymphatic tissue. Antiviral innate effector cells can subsequently contribute to the control of viremia and modulate the quality of the adaptive immune response to HIV-1. The concerted actions of PRR signaling, specific viral-restriction factors, innate immune cells, innate-adaptive immune crosstalk and viral evasion strategies determine the outcome of HIV-1 infection and immune responses.

  12. Evolving character of chronic central nervous system HIV infection.

    PubMed

    Price, Richard W; Spudich, Serena S; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

    2014-02-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Evolving Character of Chronic Central Nervous System HIV Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena S.; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

    2014-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. PMID:24715483

  14. Micronutrient supplementation in adults with HIV infection

    PubMed Central

    Visser, Marianne E; Durao, Solange; Sinclair, David; Irlam, James H; Siegfried, Nandi

    2017-01-01

    additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrients None of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient. Authors' conclusions The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects. These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals. Micronutrient supplements for non-pregnant adults with HIV infection Cochrane researchers conducted a review of the effects of micronutrient supplements for people living with HIV. This is an update of a Cochrane Review previously published in 2010. After searching for relevant

  15. Parasitic infections in HIV infected individuals: Diagnostic & therapeutic challenges

    PubMed Central

    Nissapatorn, Veeranoot; Sawangjaroen, Nongyao

    2011-01-01

    After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leismaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection. PMID:22310820

  16. Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naive HIV-1-infected patients: the ANRS COPANA cohort.

    PubMed

    Boufassa, Faroudy; Goujard, Cécile; Viard, Jean-Paul; Carlier, Robert; Lefebvre, Bénédicte; Yeni, Patrick; Bouchaud, Olivier; Capeau, Jacqueline; Meyer, Laurence; Vigouroux, Corinne

    2012-01-01

    The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naive HIV-1-infected patients. We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4(+) T-cell counts (≤200/mm(3)). Patients with low CD4(+) T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4(+) T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4(+) T-cell count >500/mm(3) as the reference), in addition to older age (β: +0.26 for a 10-year increase; P=0.01) and higher BMI (β: +0.07 for a 1-kg/m(2) increase; P=0.003). In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for

  17. Pregnancy wastage among HIV infected women in a high HIV prevalence district of India.

    PubMed

    Halli, Shiva S; Khan, C G Hussain; Shah, Iqbal; Washington, Reynold; Isac, Shajy; Moses, Stephen; Blanchard, James F

    2015-07-02

    Bagalkot district in Karnataka state is one of the highest HIV prevalence districts in India. A large proportion of the girls also marry at early age in the district and negative pregnancy outcomes among the HIV positive women likely to have large pregnancy wastages. Therefore, this study examined the pregnancy wastages and the associated factors among HIV positive women in a high prevalent district in India. We used data from a cross-sectional survey conducted recently among randomly selected currently married HIV positive women, 15-29 years of age, in one of the high HIV prevalence districts in India. The study used the experience of reported pregnancy wastage as an outcome variable, and both bi-variate and multivariate logistic regression analyses were carried out to understand the factors associated with the pregnancy wastage among HIV infected women. Overall, 17% of the respondents reported pregnancy wastage, of which 81% were due to spontaneous abortions. Respondents who became pregnant since testing HIV positive reported significantly higher level of pregnancy wastage as compared to those were pregnant before they were tested for HIV. (AOR = 1.9; p = 0.00). While a positive association between duration of marriage and pregnancy wastage was noticed (AOR = 7.4; p = 0.01), there was a negative association between number of living children and pregnancy wastage (AOR = 0.24; p = 0.00). Living in a joint family was associated with increased reporting of pregnancy wastage as compared to those living in nuclear families (AOR = 1.7; p = 0.03). HIV prevention and care programs need to consider the reproductive health needs of HIV infected married women as a priority area since large proportion of these women reported negative pregnancy outcomes. There is also a need to explore ways to raise the age at marriage in order to stop women getting married before the legal age at marriage.

  18. Preexposure prophylaxis for HIV infection among African women.

    PubMed

    Van Damme, Lut; Corneli, Amy; Ahmed, Khatija; Agot, Kawango; Lombaard, Johan; Kapiga, Saidi; Malahleha, Mookho; Owino, Fredrick; Manongi, Rachel; Onyango, Jacob; Temu, Lucky; Monedi, Modie Constance; Mak'Oketch, Paul; Makanda, Mankalimeng; Reblin, Ilse; Makatu, Shumani Elsie; Saylor, Lisa; Kiernan, Haddie; Kirkendale, Stella; Wong, Christina; Grant, Robert; Kashuba, Angela; Nanda, Kavita; Mandala, Justin; Fransen, Katrien; Deese, Jennifer; Crucitti, Tania; Mastro, Timothy D; Taylor, Douglas

    2012-08-02

    Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety. HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).

  19. Virology, Immunology, and Clinical Course of HIV Infection.

    ERIC Educational Resources Information Center

    McCutchan, J. Allen

    1990-01-01

    Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

  20. Performance of an Early Infant Diagnostic Test, AmpliSens DNA-HIV-FRT, Using Dried Blood Spots Collected from Children Born to Human Immunodeficiency Virus-Infected Mothers in Ukraine

    PubMed Central

    Shanmugam, Vedapuri; Azarskova, Marianna; Nguyen, Shon; Hurlston, Mackenzie; Sabatier, Jennifer; Zhang, Guoqing; Osmanov, Saladin; Ellenberger, Dennis; Yang, Chunfu; Vitek, Charles; Liulchuk, Maria; Nizova, Natalya

    2015-01-01

    An accurate accessible test for early infant diagnosis (EID) is crucial for identifying HIV-infected infants and linking them to treatment. To improve EID services in Ukraine, dried blood spot (DBS) samples obtained from 237 HIV-exposed children (≤18 months of age) in six regions in Ukraine in 2012 to 2013 were tested with the AmpliSens DNA-HIV-FRT assay, the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 Qual test, and the Abbott RealTime HIV-1 Qualitative assay. In comparison with the paired whole-blood results generated from AmpliSens testing at the oblast HIV reference laboratories in Ukraine, the sensitivity was 0.99 (95% confidence interval [CI], 0.95 to 1.00) for the AmpliSens and Roche CAP/CTM Qual assays and 0.96 (95% CI, 0.90 to 0.98) for the Abbott Qualitative assay. The specificity was 1.00 (95% CI, 0.97 to 1.00) for the AmpliSens and Abbott Qualitative assays and 0.99 (95% CI, 0.96 to 1.00) for the Roche CAP/CTM Qual assay. McNemar analysis indicated that the proportions of positive results for the tests were not significantly different (P > 0.05). Cohen's kappa (0.97 to 0.99) indicated almost perfect agreement among the three tests. These results indicated that the AmpliSens DBS and whole-blood tests performed equally well and were comparable to the two commercially available EID tests. More importantly, the performance characteristics of the AmpliSens DBS test meets the World Health Organization EID test requirements; implementing AmpliSens DBS testing might improve EID services in resource-limited settings. PMID:26447114

  1. Performance of an Early Infant Diagnostic Test, AmpliSens DNA-HIV-FRT, Using Dried Blood Spots Collected from Children Born to Human Immunodeficiency Virus-Infected Mothers in Ukraine.

    PubMed

    Chang, Joy; Tarasova, Tetyana; Shanmugam, Vedapuri; Azarskova, Marianna; Nguyen, Shon; Hurlston, Mackenzie; Sabatier, Jennifer; Zhang, Guoqing; Osmanov, Saladin; Ellenberger, Dennis; Yang, Chunfu; Vitek, Charles; Liulchuk, Maria; Nizova, Natalya

    2015-12-01

    An accurate accessible test for early infant diagnosis (EID) is crucial for identifying HIV-infected infants and linking them to treatment. To improve EID services in Ukraine, dried blood spot (DBS) samples obtained from 237 HIV-exposed children (≤18 months of age) in six regions in Ukraine in 2012 to 2013 were tested with the AmpliSens DNA-HIV-FRT assay, the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 Qual test, and the Abbott RealTime HIV-1 Qualitative assay. In comparison with the paired whole-blood results generated from AmpliSens testing at the oblast HIV reference laboratories in Ukraine, the sensitivity was 0.99 (95% confidence interval [CI], 0.95 to 1.00) for the AmpliSens and Roche CAP/CTM Qual assays and 0.96 (95% CI, 0.90 to 0.98) for the Abbott Qualitative assay. The specificity was 1.00 (95% CI, 0.97 to 1.00) for the AmpliSens and Abbott Qualitative assays and 0.99 (95% CI, 0.96 to 1.00) for the Roche CAP/CTM Qual assay. McNemar analysis indicated that the proportions of positive results for the tests were not significantly different (P > 0.05). Cohen's kappa (0.97 to 0.99) indicated almost perfect agreement among the three tests. These results indicated that the AmpliSens DBS and whole-blood tests performed equally well and were comparable to the two commercially available EID tests. More importantly, the performance characteristics of the AmpliSens DBS test meets the World Health Organization EID test requirements; implementing AmpliSens DBS testing might improve EID services in resource-limited settings. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Cyclophilin B enhances HIV-1 Infection

    PubMed Central

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

    2016-01-01

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. PMID:26774171

  3. Cyclophilin B enhances HIV-1 infection.

    PubMed

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

    2016-02-01

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

  4. Plasma membrane signaling in HIV-1 infection.

    PubMed

    Abbas, Wasim; Herbein, Georges

    2014-04-01

    Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4+ T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. [Mechanisms of lymphopenia in HIV infection].

    PubMed

    Roger, P M; Pradier, C; Dellamonica, P

    1994-01-22

    Blood counts of CD4 cells remain the best prognostic factor in patients infected with human immunodeficiency virus (HIV). However, the small number of infected cells contrasts with the importance of lymphocyte depletion. Several mechanisms might explain this depletion including: antibody-dependent cytotoxicity. Twenty to 50% of the antibodies produced in vitro by B lymphocytes are directed against HIV antigens, especially the gp120 and gp41 viral envelope antigen. If this cytotoxicity effect occurs in vivo, it could reduce of lymphocytes carrying the viral genome and partially explain the major lymphopenia in HIV-infected patients. It is not yet known whether the long-term effect of these antibodies is immunoprotective or deleterious, but they may play a protective role at least in the initial stages of the disease. autoimmunity. Sequence homology between the HLA II molecules and the glycoproteins of the viral envelope has been clinically and biologically documented in many manifestations of HIV infection. It has been suggested that alloreactivity, similar to the graft-versus-host reaction could be involved. In addition, programmed cell-death of the CD4 lymphocytes appears to be overactivated in HIV-positive subjects, possibly because the gp120 viral antigen perturbs the CD4-dependent signal for cell death. deleterious effects of cytokines. Tumour necrosis factor, for example, is known to play a role in the regulation of viral replication; it may favour the destruction of contaminated cells but also the initiation of provirus replication and integration into the cell genome. supra-antigens and/or infectious factors. Supra-antigenes, which can link with HLA molecules, are capable of oligoclonal activation without being "processed" in the cell presenting the antigen. This activation might affect cell death. Certain germ toxins could also play a role as cofactors. Cohort studies of asymptomatic HIV patients are needed to improve our understanding of these mechanisms

  6. Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.

    PubMed

    Leitman, Ellen M; Thobakgale, Christina F; Adland, Emily; Ansari, M Azim; Raghwani, Jayna; Prendergast, Andrew J; Tudor-Williams, Gareth; Kiepiela, Photini; Hemelaar, Joris; Brener, Jacqui; Tsai, Ming-Han; Mori, Masahiko; Riddell, Lynn; Luzzi, Graz; Jooste, Pieter; Ndung'u, Thumbi; Walker, Bruce D; Pybus, Oliver G; Kellam, Paul; Naranbhai, Vivek; Matthews, Philippa C; Gall, Astrid; Goulder, Philip J R

    2017-11-06

    Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. © 2017 Leitman et al.

  7. Complementary feeding adequacy in relation to nutritional status among early weaned breastfed children who are born to HIV-infected mothers: ANRS 1201/1202 Ditrame Plus, Abidjan, Cote d'Ivoire.

    PubMed

    Becquet, Renaud; Leroy, Valériane; Ekouevi, Didier K; Viho, Ida; Castetbon, Katia; Fassinou, Patricia; Dabis, François; Timite-Konan, Marguerite

    2006-04-01

    In high HIV prevalence resource-constrained settings, exclusive breastfeeding with early cessation is one of the conceivable interventions aimed at the prevention of HIV through breast milk. Nevertheless, this intervention has potential adverse effects, such as the inappropriateness of complementary feeding to take over breast milk. The purpose of our study first was to describe the nature and the ages of introduction of complementary feeding among early weaned breastfed infants up to their first birthday and second was to assess the nutritional adequacy of these complementary foods by creating a child feeding index and to investigate its association with child nutritional status. A prospective cohort study in Abidjan, Côte d'Ivoire, was conducted in HIV-infected pregnant women who were willing to breastfeed and had received a perinatal antiretroviral prophylaxis. They were requested to practice exclusive breastfeeding and initiate early cessation of breastfeeding from the fourth month to reduce breast milk HIV transmission. Nature and ages of introductory complementary feeding were described in infants up to their first birthday by longitudinal compilation of 24-hour and 7-day recall histories. These recalls were done weekly until 6 weeks of age, monthly until 9 months of age, and then quarterly. We created an index to synthesize the nutritional adequacy of infant feeding practices (in terms of quality of the source of milk, dietary diversity, food, and meal frequencies) ranging from 0 to 12. The association of this feeding index with growth outcomes in children was investigated. Among the 262 breastfed children included, complete cessation of breastfeeding occurred in 77% by their first birthday, with a median duration of 4 months. Most of the complementary foods were introduced within the seventh month of life, except for infant food and infant formula that were introduced at age 4 months. The feeding index was relatively low (5 of 12) at age 6 months, mainly

  8. Global oral inequalities in HIV infection.

    PubMed

    Challacombe, S J

    2016-04-01

    Analysis of the prevalence and incidence of HIV infection globally reveal striking variances with regard to continent, country, region and gender. Of the global total of 33 million people infected with HIV, approximately 65% are in sub-Saharan African countries and 15% in South and South-East Asia with the remaining 20% spread over the rest of the world. As a percentage of the population, the Caribbean at 1.1% is second only to sub-Saharan Africa (5.5%). The majority of the world's HIV is in women. Deaths from HIV are twenty-fold greater in Africa than in Europe or the USA. Individual countries in sub-Saharan Africa show huge variances in the HIV+ prevalence with most West African countries having a rate of less than 2% whilst southern African countries including Swaziland and Botswana have rates of around 25%. Environment, education and social habits all contribute to the HIV infection rates. Similar variations between countries are seen in SE Asia with Cambodia and Papua New Guinea having rates three times greater than Pakistan. One of the most striking examples of inequality is in life years added to HIV populations as a result of antiretroviral therapy. UN AIDS figures over 1996-2008 suggest an average of 2.88 added years in the USA and Europe, but only 0.1 in sub-Saharan Africa, a thirty-fold difference largely due to accessibility to ART. ART leads to a reduction in oral lesions but it is estimated that some 10 million HIV+ subjects do not have access to oral care. Thus, inequalities exist both for HIV infection and for the associated oral lesions, mainly related to ART access. HIV infection and oral mucosal lesions both appear to be related to general social determinants of health. Oral HCW must be part of mainstream healthcare teams to address these inequalities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Moyamoya Syndrome in a Child With HIV-1 Infection.

    PubMed

    Jindal, Ankur Kumar; Bhattad, Sagar; Suri, Deepti; Singhal, Manphool; Gupta, Aman; Singh, Paramjeet

    2018-06-01

    Neurologic manifestations of HIV infection are not uncommon. However, stroke secondary to Moyamoya syndrome has rarely been described in children with HIV infection. We report a 10-year-old boy with perinatally acquired HIV-1 infection, who presented with recurrent strokes while on antiretroviral therapy.

  10. Survival Outcomes and Effect of Early vs. Deferred cART Among HIV-Infected Patients Diagnosed at the Time of an AIDS-Defining Event: A Cohort Analysis

    PubMed Central

    Mussini, Cristina; Johnson, Margaret; d'Arminio Monforte, Antonella; Antinori, Andrea; Gill, M. John; Sighinolfi, Laura; Uberti-Foppa, Caterina; Borghi, Vanni; Sabin, Caroline

    2011-01-01

    Objectives We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997–2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30–270 days after AIDS event) cART. Results The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/µL and 5.2 (4.5, 5.7) log10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). Conclusions Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting. PMID:22043301

  11. Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

    PubMed Central

    Xu, Jiahong; Yeganeh, Nava; Camarca, Margaret; Morgado, Mariza G.; Watts, D. Heather; Mofenson, Lynne M.; Veloso, Valdilea G.; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J.; Grinsztejn, Beatriz; Moye, Jack; Klausner, Jeffrey D.; Bristow, Claire C.; Dickover, Ruth; Mirochnick, Mark; Nielsen-Saines, Karin

    2018-01-01

    Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1–3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5–7.7). Individually, maternal CMV (aOR 4.4 1.5–13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2–7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT. Trial registration NCT00099359. PMID:29304083

  12. Changing risk factors for HIV infection.

    PubMed

    Volkow, Patricia; Mohar, Alejandro; Terrazas, José-Juan; Pérez-Padilla, José-Rogelio; Vilar-Compte, Diana; Carranza, Dora; Sierra-Madero, Juan

    2002-01-01

    HIV infection in women is a growing problem in developing countries. Risk factors for HIV infection vary from country to country and may change with time. We describe a retrospective review of the epidemiologic characteristics and associated gynecologic diseases of all HIV-infected women seen at two tertiary-care hospitals in Mexico City. One hundred thirty consecutive patients were included in the study from March 1985 to January 1996. Mean age at HIV diagnosis was 36.2 years (range: 16-76). Of the 75 women diagnosed with AIDS prior to 1992, 58 (69%) were infected through blood transfusion and 17 (20%) through sexual contact. After January 1992, 11 (23%) acquired infection through blood transfusion and 28 (60%) through sexual contact; these differences were statistically significant (p <0.0001). Prior to 1992, 66 (90%) women presented in stage IV, whereas after that year only 29 (51%) (p <0.001) presented in stage IV. Of 92 patients on whom a cervico-vaginal smear was carried out, human papillomavirus infection was identified in 22 (24%) women, nine (9.8%) had morphologic evidence of a cervical intraepithelial neoplasia (four with mild or moderate dysplasia and five with in situ cervical carcinoma). Four patients had invasive cervical carcinoma. The main risk factor for HIV infection in Mexican women with AIDS changed from transfusion acquired to sexually acquired in 1992. As a country, we were successful in providing safe blood but failed to prevent sexual transmission. Our patients had a high frequency of cervical carcinoma and precursor lesions associated with human papilloma virus.

  13. 42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

  14. 42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

  15. 42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

  16. 42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

  17. 42 CFR Appendix A to Part 130 - Definition of HIV Infection or HIV

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Definition of HIV Infection or HIV A Appendix A to... PAYMENTS RICKY RAY HEMOPHILIA RELIEF FUND PROGRAM Pt. 130, App. A Appendix A to Part 130—Definition of HIV Infection or HIV ER31MY00.000 ER31MY00.001 ...

  18. Knowledge and perceptions of sexual and reproductive health and HIV among perinatally HIV-infected adolescents in rural China.

    PubMed

    Mu, Weiwei; Zhao, Yan; Khoshnood, Kaveh; Cheng, Yuewu; Sun, Xin; Liu, Xia; Xu, Wenqing; Wang, Shuiwang; Ma, Ye; Zhang, Fujie

    2015-01-01

    Due to the success of highly active antiretroviral therapy, more children infected with HIV perinatally are living to adolescence. This brings new challenges on sexual and reproductive health (SRH) needs and psychosocial support specific to adolescents. To improve such efforts on long-term care of this vulnerable population, we assessed SRH and HIV knowledge and perceptions among perinatally HIV-infected adolescents (PHIVA). This descriptive cross-sectional study was conducted between July and September 2013 in a rural HIV clinic. A structured questionnaire focusing on SRH and HIV was administered to 124 PHIVA attending quarterly medical visit. Multivariable logistic regression was used to detect associated factors with knowledge acquisition. Among participants, 79% had never discussed puberty development or sexuality with parents. Over 50% had never heard of condoms and 20% reported not having any informational source of SRH and HIV knowledge. Only 5% correctly answered all questions regarding HIV knowledge and pregnancy, with 18% correctly answered questions regarding contraception. Adolescents older than age of 15 and who had been disclosed of HIV status were more likely to acquire correct knowledge of SRH and HIV. Most PHIVA did not report having access to comprehensive information on SRH and HIV, in part because of the early death of caretakers or unfavorable family status. Further integration of SRH services with HIV treatment programs is needed to provide comprehensive care for adolescents and prepare them for the transition to adult care.

  19. Herpes zoster and HIV infection in Tanzania.

    PubMed

    Naburi, A E; Leppard, B

    2000-04-01

    Two hundred consecutive patients with herpes zoster attending the skin clinic at the Kilimanjaro Christian Medical Centre (KCMC) were examined and checked for HIV infection. They ranged in age from 10 months to 86 years with the majority in their 20s and 30s. The dermatomes involved were thoracic (97), trigeminal (50), cervical (37), lumbar (19) and sacral (3). Six (3%) had more than one dermatome involved and 2 (1%) had disseminated disease. Only 2 (1%) had severe ulceration of the skin and all healed in less than 4 weeks. In children under the age of 10 years and in adults between the ages of 20 and 49 years virtually 100% were HIV positive; even in the age group 50-59 more than three-quarters were HIV positive. We conclude that the presence of herpes zoster at any site is a good indication that the patient is HIV positive except in the teens and the very elderly.

  20. Early loss to follow-up of recently diagnosed HIV-infected adults from routine pre-ART care in a rural district hospital in Kenya: a cohort study.

    PubMed

    Hassan, Amin S; Fielding, Katherine L; Thuo, Nahashon M; Nabwera, Helen M; Sanders, Eduard J; Berkley, James A

    2012-01-01

    To determine the rate and predictors of early loss to follow-up (LTFU) for recently diagnosed HIV-infected, antiretroviral therapy (ART)-ineligible adults in rural Kenya. Prospective cohort study. Clients registering for HIV care between July 2008 and August 2009 were followed up for 6 months. Baseline data were used to assess predictors of pre-ART LTFU (not returning for care within 2 months of a scheduled appointment), LTFU before the second visit and LTFU after the second visit. Logistic regression was used to determine factors associated with LTFU before the second visit, while Cox regression was used to assess predictors of time to LTFU and LTFU after the second visit. Of 530 eligible clients, 178 (33.6%) were LTFU from pre-ART care (11.1/100 person-months). Of these, 96 (53.9%) were LTFU before the second visit. Distance (>5 km vs. <1 km: adjusted hazard ratio 2.6 [1.9-3.7], P < 0.01) and marital status (married vs. single: 0.5 [0.3-0.6], P < 0.01) independently predicted pre-ART LTFU. Distance and marital status were independently associated with LTFU before the second visit, while distance, education status and seasonality showed weak evidence of predicting LTFU after the second visit. HIV disease severity did not predict pre-ART LTFU. A third of recently diagnosed HIV-infected, ART-ineligible clients were LTFU within 6 months of registration. Predictors of LTFU among ART-ineligible clients are different from those among clients on ART. These findings warrant consideration of an enhanced pre-ART care package aimed at improving retention and timely ART initiation. © 2011 Blackwell Publishing Ltd.

  1. Developmental Services for Children with HIV Infection.

    ERIC Educational Resources Information Center

    Crocker, Allen C.

    1989-01-01

    The special developmental needs of young children with congenital HIV (Human Immunodeficiency Virus) infection require evaluation, training, therapy, and other supports. Such services should be guided by developmentalists in a child study center in close alliance with medical, educational, and community service providers. Concerns about the…

  2. Fosamprenavir calcium plus ritonavir for HIV infection.

    PubMed

    Torres, Harrys A; Arduino, Roberto C

    2007-06-01

    Fosamprenavir is a protease inhibitor (PI) approved for the treatment of HIV-1 infection. Fosamprenavir is a prodrug of amprenavir developed to reduce the pill burden yet maintain the unique resistance pattern and efficacy associated with amprenavir. In a head-to-head, noninferiority trial in antiretroviral treatment-naive HIV-infected patients, the antiviral efficacy and tolerability of ritonavir-boosted fosamprenavir was not inferior to ritonavir-boosted lopinavir, when the PIs were combined with two other nucleoside reverse transcriptase inhibitors. There are fewer studies published about fosamprenavir use in antiretroviral treatment-experienced HIV-infected patients. The high genetic barrier to the development of resistance to fosamprenavir and the low level of cross-resistance between ritonavir-boosted fosamprenavir and other PI regimens are notable. As with amprenavir, gastrointestinal disturbance and rash are the most frequent short-term treatment-limiting events with fosamprenavir. Treatment with ritonavir-boosted fosamprenavir can produce a durable response. To date, fosamprenavir is one of the recommended preferred PI components for the treatment of antiretroviral-naive HIV-infected patients.

  3. HIV Infection in the Etiology of Lung Cancer

    PubMed Central

    Kirk, Gregory D.; Merlo, Christian A.

    2011-01-01

    Persons infected with HIV have an elevated risk of lung cancer, but whether the increase simply reflects a higher smoking prevalence continues to be debated. This review summarizes existing data on the association of HIV infection and lung cancer, with particular attention to study design and adjustment for cigarette smoking. Potential mechanisms by which HIV infection may lead to lung cancer are discussed. Finally, irrespective of causality and mechanisms, lung cancer represents an important and growing problem confronting HIV-infected patients and their providers. Substantial efforts are needed to promote smoking cessation and to control lung cancer among HIV-infected populations. PMID:21653536

  4. Opportunistic infection of HIV/AIDS patients in West Papua

    NASA Astrophysics Data System (ADS)

    Witaningrum, A. M.; Khairunisa, S. Q.; Yunifiar, M. Q.; Bramanthi, R.; Rachman, B. E.; Nasronudin

    2018-03-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) had a major impact on health problemin Indonesia. HIV type 1 (HIV-1) epidemic is currently infected with HIV viruses developing rapidly in Indonesia.Papua provinces have the highest prevalence rate of human immunodeficiency virus type 1 (HIV-1) infection in Indonesia; however, data on opportunistic infection of HIV-1 are limited. The study using medical records as a research sample was conducted among HIV patients from January 2013 - December 2014 in Sele be Solu hospital among 49 patients. Opportunistic infections commonly occur in HIV-infected patients. The aim of the study was to know theprevalence of opportunistic infection among HIV positive patients in West Papua. Forty-nine HIV-1 patients were collected in Sele be Solu Hospital, West Papua.Opportunistic infection was identified such as tuberculosis, tuberculosis Pulmo, tuberculosis and candidiasis, candidiasis and diarrhea. The clinical sign appeared in HIV infected patients such as itchy, cough and loss weight. The prevalence of opportunistic infection indicated the necessity of monitoring the opportunistic infection of HIV/AIDS patients in Indonesia.

  5. HIV Infection and Health Policy.

    ERIC Educational Resources Information Center

    Weiss, Robin; Hardy, Leslie M.

    1990-01-01

    Describes issues facing policymakers dealing with the human immunodeficiency virus (HIV) epidemic. Addresses six challenges for policymakers: (1) protecting people from discrimination; (2) designing testing and screening programs; (3) developing safe and effective antiviral drugs; (4) planning for future vaccine trials; (5) organizing and…

  6. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria

    PubMed Central

    Dillon, Stephanie M.; Phang, Tzu; Lee, Eric J.; Helm, Karen; Kappes, John C.; McCarter, Martin D.

    2017-01-01

    Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF) HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a molecular blueprint

  7. Risk of HIV infection among men having sex with men in Kathmandu Valley, Nepal.

    PubMed

    Deuba, Keshab; Karki, Deepak Kumar; Shrestha, Rachana; Aryal, Umesh Raj; Bhatta, Laxmi; Rai, Krishna Kumar

    2014-03-01

    Despite extensive distribution of free condoms and lubricants to prevent HIV transmission among men having sex with men (MSM) in Nepal, the prevalence of HIV and risky sexual behaviors remain high. The influence of individual-level, social-capital, and social-structural factors on HIV risk has been insufficiently explored in MSM. The authors assessed association of these factors with HIV risk among 150 MSM enrolled using snowball sampling in the Kathmandu Valley. HIV risk was calculated on the basis of number and type of sexual partners and condom use during anal sex. Multivariate analysis showed a high risk of HIV infection was significantly associated with being involved in sex work, having no knowledge of male sexually transmitted infection (STI) symptoms, and having a history of STI symptoms. HIV prevention could be made more effective by targeting MSM who are involved in sex work and by improving their knowledge of male STI symptoms and early diagnosis and treatment.

  8. Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia.

    PubMed

    Fox, Matthew P; Brooks, Daniel; Kuhn, Louise; Aldrovandi, Grace; Sinkala, Moses; Kankasa, Chipepo; Mwiya, Mwiya; Horsburgh, Robert; Thea, Donald M

    2008-05-01

    In developing countries, where mother-to-child transmission of HIV through breast-feeding is common, little is known about the impact of postpartum transmission on child survival. This study assessed whether children infected postpartum have longer survival from time of infection versus those infected during gestation or delivery. We used a prospective cohort study to analyze data from 213 HIV-infected children enrolled in a breast-feeding intervention trial in Lusaka, Zambia (2001 to 2004). We compared mortality 1 year after HIV infection in children stratified by age of infection: 0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum [IP/EPP] group), and >40 days (postpartum [PP] group). A total of 61, 71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively. Children with intrauterine or intrapartum/early postpartum transmission had higher mortality over the first 12 months after infection than children with postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences were detected between children with intrauterine and intrapartum/early postpartum transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after infection, whereas nearly 10% of the PP group had died by this time. After adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal death, children infected postpartum had one quarter the mortality rate (hazard ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected in utero. Stopping breast-feeding increased mortality in infected children (HR = 3.1, 95% CI: 1.8 to 5.3). This study demonstrates a survival benefit among children infected postpartum versus children infected during pregnancy or delivery and a benefit to increased breast-feeding duration among infected children. Testing children for HIV early may provide a means to allow for earlier intervention.

  9. Trends in Epidemiology of COPD in HIV-Infected Patients in Spain (1997–2012)

    PubMed Central

    de Miguel-Díez, Javier; López-de-Andrés, Ana; Jiménez-García, Rodrigo; Puente-Maestu, Luis; Jiménez-Trujillo, Isabel; Hernández-Barrera, Valentín

    2016-01-01

    Purpose The aim of this study was to estimate trends of incidence of hospital admissions and in-hospital mortality (IHM) in HIV-infected patients with COPD in the combination antiretroviral therapy (cART) era in Spain (1997–2012). Methods A retrospective study with data from nationwide population-based COPD diagnoses in the Spanish Minimum Basic Data Set (MBDS) was performed. We established groups according to their HIV and HCV infections: 1) HIV-uninfected patients; 2) HIV-infected patients (with or without HCV coinfection). Results 1,580,207 patients discharge with a COPD diagnosis were included in the study, 8902 of them were HIV-infected patients (5000 HIV-monoinfected patients and 3902 HIV/HCV-coinfected patients). The HIV-infected patients had higher incidence rates of hospital admissions for COPD than the HIV-uninfected patients during the study period. The HIV-monoinfected patients had higher rates of hospitalizations for COPD than the HIV/HCV-coinfected patients in the early-period cART (1997–1999), but these rates decreased in the first group and increased in the second, being even similar in both groups in the late-period cART (2004–2011). On the other hand, the HIV-infected patients with COPD had higher IHM than the HIV-uninfected patients with COPD. The mortality rates were higher in the HIV-monoinfected patients with COPD than in the HIV/HCV-coinfected patients with COPD in the early-period cART; however, in the late-period cART, the mortality rates trends seems higher in the HIV/HCV group. The likelihood of death in HIV/HCV-coinfected patients with COPD was similar to than in HIV-monoinfected patients with COPD. Conclusions Incidence of hospital admissions for COPD and IHM have decreased among HIV-monoinfected individuals but have increased steadily among HIV/HCV-coinfected individuals in the cART era. PMID:27846297

  10. Strategies for the cure of HIV infection.

    PubMed

    Rodríguez-Muñoz, Jesús; Moreno, Santiago

    2018-03-03

    The disadvantages of the long-term administration of antiretroviral therapy as well as the huge number of affected persons have placed the cure of HIV as a primary goal of Public Health. HIV may persist in the organism by at least four mechanisms: a latently infected cellular reservoir, the persistent replication of HIV in spite of ART, anatomic sanctuaries, and the immune dysfunction. Several strategies directed against these mechanisms have been developed. With all this, a complete eradication of HIV has been achieved in a patient using the transplantation of haemopoietic stem cells that were resistant to HIV-infection, and there are examples of functional cure either spontaneously (elite controllers) or after antiretroviral therapy (post-treatment controllers). However, no strategies have been successful in reducing the reservoir size, nor in achieving constant, uniform remissions. The failure of isolated strategies makes it likely that the combination of several of them may be the future solution. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Sacral myeloradiculitis complicating genital herpes in a HIV-infected patient.

    PubMed

    Corral, I; Quereda, C; Navas, E; Pérez-Elias, M J; Jover, F; Moreno, S

    2005-02-01

    Myeloradiculitis is a rare neurological complication of herpes simplex type 2 (HSV-2) infection, frequently associated with a fatal outcome. Among patients with HIV infection, HSV-2 myeloradiculitis has occasionally been reported, always associated with advanced immunosuppression and AIDS. We report a patient with HIV infection but no history of previous opportunistic infections, who developed sacral myeloradiculitis immediately after an episode of genital herpes. Magnetic resonance imaging with gadolinium showed necrotizing myelitis in the conus medullaris and enhancement of sacral roots. CD4 lymphocyte count was 530/mm3. Other possible causes of myeloradiculitis in HIV-infected patients were appropriately excluded. Acyclovir therapy resulted in partial clinical improvement. This report shows that myeloradiculitis as a complication of genital herpes may occur in the early stages of HIV infection and may have a favourable outcome with antiviral treatment.

  12. Performance of the fourth-generation Bio-Rad GS HIV Combo Ag/Ab enzyme immunoassay for diagnosis of HIV infection in Southern Africa

    PubMed Central

    Piwowar-Manning, Estelle; Fogel, Jessica M.; Richardson, Paul; Wolf, Shauna; Clarke, William; Marzinke, Mark A.; Fiamma, Agnès; Donnell, Deborah; Kulich, Michal; Mbwambo, Jessie K.K.; Richter, Linda; Gray, Glenda; Sweat, Michael; Coates, Thomas J.; Eshleman, Susan H.

    2015-01-01

    Background Fourth-generation HIV assays detect both antigen and antibody, facilitating detection of acute/early HIV infection. The Bio-Rad GS HIV Combo Ag/Ab assay (Bio-Rad Combo) is an enzyme immunoassay that simultaneously detects HIV p24 antigen and antibodies to HIV-1 and HIV-2 in serum or plasma. Objective To evaluate the performance of the Bio-Rad Combo assay for detection of HIV infection in adults from Southern Africa. Study design Samples were obtained from adults in Soweto and Vulindlela, South Africa and Dar es Salaam, Tanzania (300 HIV-positive samples; 300 HIV-negative samples; 12 samples from individuals previously classified as having acute/early HIV infection). The samples were tested with the Bio-Rad Combo assay. Additional testing was performed to characterize the 12 acute/early samples. Results All 300 HIV-positive samples were reactive using the Bio-Rad Combo assay; false positive test results were obtained for 10 (3.3%) of the HIV-negative samples (sensitivity: 100%, 95% confidence interval [CI]: 98.8–100%); specificity: 96.7%, 95% CI: 94.0–98.4%). The assay detected 10 of the 12 infections classified as acute/early. The two infections that were not detected had viral loads < 400 copies/mL; one of those samples contained antiretroviral drugs consistent with antiretroviral therapy. Conclusions The Bio-Rad Combo assay correctly classified the majority of study specimens. The specificity reported here may be higher than that seen in other settings, since HIV-negative samples were pre-screened using a different fourth-generation test. The assay also had high sensitivity for detection of acute/early infection. False-negative test results may be obtained in individuals who are virally suppressed. PMID:25542477

  13. IFN-ε protects primary macrophages against HIV infection.

    PubMed

    Tasker, Carley; Subbian, Selvakumar; Gao, Pan; Couret, Jennifer; Levine, Carly; Ghanny, Saleena; Soteropoulos, Patricia; Zhao, Xilin; Landau, Nathaniel; Lu, Wuyuan; Chang, Theresa L

    2016-12-08

    IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4 + T cells or transformed cell lines unless activated CD4 + T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-ε-stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-α in macrophages. IFN-ε induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-ε induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-α. Understanding the mechanism of IFN-ε-mediated HIV inhibition through immune modulation has implications for prevention.

  14. IFN-ε protects primary macrophages against HIV infection

    PubMed Central

    Tasker, Carley; Subbian, Selvakumar; Gao, Pan; Couret, Jennifer; Levine, Carly; Ghanny, Saleena; Soteropoulos, Patricia; Zhao, Xilin; Landau, Nathaniel; Lu, Wuyuan

    2016-01-01

    IFN-ε is a unique type I IFN that is not induced by pattern recognition response elements. IFN-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-ε was thought to be weak compared with IFN-α, IFN-ε controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-ε induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-ε had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-ε acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-ε–stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-α in macrophages. IFN-ε induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-ε induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-α. Understanding the mechanism of IFN-ε–mediated HIV inhibition through immune modulation has implications for prevention. PMID:27942584

  15. HIV/AIDS and Early Childhood.

    ERIC Educational Resources Information Center

    Hanssen, Elizabeth, Ed.; Zimanyi, Louise, Ed.

    2002-01-01

    The Consultative Group on Early Childhood Care and Development is increasingly concerned with the lack of attention to children affected by the HIV/AIDS pandemic. This theme issue of "Coordinators' Notebook" examines issues related to ensuring that orphans and vulnerable children under 5 years receive attention in the international,…

  16. HIV Infection: The Cellular Picture.

    ERIC Educational Resources Information Center

    Weber, Jonathan N.; Weiss, Robin A.

    1988-01-01

    Explains a key finding of the research which revealed that initial infection resulted from the binding of the human immunodeficiency virus to a molecule known as the CD4 antigen. Describes various assays used to determine the affect of antibodies on the ability of the virus to infect the cells. (RT)

  17. Late HIV Testing in a Cohort of HIV-Infected Patients in Puerto Rico.

    PubMed

    Tossas-Milligan, Katherine Y; Hunter-Mellado, Robert F; Mayor, Angel M; Fernández-Santos, Diana M; Dworkin, Mark S

    2015-09-01

    Late HIV testing (LT), defined as receiving an AIDS diagnosis within a year of one's first positive HIV test, is associated with higher HIV transmission, lower HAART effectiveness, and worse outcomes. Latinos represent 36% of LT in the US, yet research concerning LT among HIV cases in Puerto Rico is scarce. Multivariable logistic regression analysis was used to identify factors associated with LT, and a Cochran‒Armitage test was used to determine LT trends in an HIV-infected cohort followed at a clinic in Puerto Rico specialized in the management and treatment of HIV. From 2000 to 2011, 47% of eligible patients were late testers, with lower median CD4 counts (54 vs. 420 cells/mm3) and higher median HIV viral load counts (253,680 vs. 23,700 copies/mL) than non-LT patients. LT prevalence decreased significantly, from 47% in 2000 to 37% in 2011. In a mutually adjusted logistic regression model, males, older age at enrollment and past history of IDU significantly increased LT odds, whereas having a history of amphetamine use decreased LT odds. When the data were stratified by mode of transmission, it became apparent that only the category men who have sex with men (MSM) saw a significant reduction in the proportion of LT, falling from 67% in 2000 to 33% in 2011. These results suggest a gap in early HIV detection in Puerto Rico, a gap that decreased only among MSM. An evaluation of the manner in which current HIV-testing guidelines are implemented on the island is needed.

  18. Human Papilloma Virus-Associated Lips Verrucous Carcinoma in HIV-Infected Male.

    PubMed

    De Socio, Giuseppe Vittorio; Bidovanets, Olena; Tomassini, Gian Marco; Fanelli, Luca; Simonetti, Stefano

    Human papillomavirus (HPV) infection, widely known as the necessary cause of cervical cancer, has been established as a major etiologic factor for head and neck cancer (HNC). HIV-infected individuals are at higher risk of HPV-associated cancers than the general population. We describe a 45-year-old man with HIV and HPV coinfection, who presented progressively enlarging verrucous neoformations of the lips. The final diagnosis of verrucous carcinoma was delayed. Early detection of HPV lesions in oral mucosa and HPV screening activities could be important in improving the diagnostic sensitivity for the HIV-infected patients with oral cancer.

  19. Aging with HIV infection: a journey to the center of inflammAIDS, immunosenescence and neuroHIV.

    PubMed

    Nasi, Milena; Pinti, Marcello; De Biasi, Sara; Gibellini, Lara; Ferraro, Diana; Mussini, Cristina; Cossarizza, Andrea

    2014-11-01

    In the last years, a significant improvement in life expectancy of HIV+ patients has been observed in Western countries. The parallel increase in the mean age of these patients causes a parallel increase in the frequency of non-AIDS related complications (i.e., neurocognitive, cardiovascular, liver and kidney diseases, metabolic syndrome, osteoporosis, non-HIV associated cancers, among others), even when antiviral treatment is successful. Immune activation and persistent inflammation characterizes both HIV infection and physiological aging, and both conditions share common detrimental pathways that lead to early immunosenescence. Furthermore, HIV-associated neurocognitive disorders represent important consequences of the infection. The persistent systemic immune activation, the continuous migration of activated monocytes to the central nervous system and progressive patients' aging contribute to develop neuronal injuries, that are in turn linked to HIV-associated neurocognitive disorders, which can persist despite successful antiretroviral treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. [Structured treatment interruption in HIV-infected adolescents].

    PubMed

    Vidal, P; Lalande, M; Rodiere, M

    2009-07-01

    Structured treatment interruption in HIV is now being debated. There are 2 cases in which it may be discussed: when the initial treatment was started early and when there is no compliance to treatment [Yeni P, et al. Les nouvelles recommandations de prise en charge des personnes infectées par le VIH 2006. Paris: Flammarion médecine-sciences; 2006]. Noncompliant behavior is one of the characteristics of chronic illness during adolescence. In HIV infection, however, the prognosis is negatively influenced because the resulting resistance to the antiretroviral therapy can further reduce therapeutic options. Therefore, it is important in such a critical period to consider both what is consciously and unconsciously at stake and what responsible action could be taken when a specialist is faced with spontaneous (unplanned) treatment interruption. We report here examples of follow-up care, interruption, and resumption of treatment in 4 female adolescents.

  1. Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays.

    PubMed

    Fogel, Jessica M; Piwowar-Manning, Estelle; Debevec, Barbara; Walsky, Tamara; Schlusser, Katherine; Laeyendecker, Oliver; Wilson, Ethan A; McCauley, Marybeth; Gamble, Theresa; Tegha, Gerald; Soko, Dean; Kumwenda, Johnstone; Hosseinipour, Mina C; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2017-08-01

    Antiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays. Samples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or <250 cells/mm or an AIDS-defining illness (delayed ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result). Ten (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection. False-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

  2. HIV-1 early and late diagnosis in the Emilia Romagna Region (Italy): a three year study.

    PubMed

    Musumeci, Giuseppina; Magnani, Giacomo; Bon, Isabella; Longo, Serena; Bertoldi, Alessia; Degli Antoni, Anna Maria; Rossi, Maria Rita; Ruggeri, Alessandro; Sambri, Vittorio; Semprini, Simona; Sighinolfi, Laura; Ursitti, Maria Alessandra; Zerbini, Alessandro; Colangeli, Vincenzo; Calza, Leonardo; Finarelli, Alba Carola; Massimiliani, Erika; Re, Maria Carla

    2016-10-01

    It is crucial to establish the timing of infection and distinguish between early and long-lasting HIV-1 infections not only for partner notification and epidemiological surveillance, but also to offer early drug treatment and contain the spread of infection. This study analyzed serum and/or plasma samples with a first positive HIV antibody/antigen result coming from different Medical Centers in the Emilia Romagna Region, North East Italy, using the avidity assay, Western Blotting, RNA viral load, CD4 cell counts and genotyping assay. From May 2013 to May 2016, we certified 845 new HIV-1 infections, 18.7% of which were classified on the basis of avidity index as recent infections and 81.3% as long-lasting infections, with an estimated conversion time exceeding six months at the time of study. Western Blotting showed reactivity to only one or two HIV-1 proteins in recently infected patients (RIPs), while a complete pattern to gag, env and pol proteins was observed in most long-lasting infected patients (LLIPs). The median age, gender, nationality and risk transmission factors were comparable in RIPs and LLIPs. Phylogenetic analysis performed in available plasma disclosed B strains, non-B subtypes and circulating recombinant forms (CRFs) in both groups of patients, with a major presence of CRFs in non-Italian HIV subjects. The large number of patients unaware of their HIV status makes it crucial to discover hidden epidemics and implement appropriate targeted public health interventions.

  3. Ascending paralysis associated with HIV infection

    PubMed Central

    Afzal, Aasim; Benjamin, Mina; Gummelt, Kyle L.; Afzal, Sadaf; Tribble, Marc

    2015-01-01

    We present two patients with a high viral load of HIV-1 who developed symptoms of ascending paralysis leading to respiratory failure and autonomic instability. One patient had symptom improvement with highly active antiretroviral therapy (HAART) and a subsequent decrease in viral load. The other patient improved with intravenous immunoglobulin therapy and did not show much improvement on HAART alone. There are several proposed mechanisms for peripheral neuropathies seen in HIV-infected patients, including a direct action of HIV on the nerve by neurotropic strains or formation of autoantibodies against nerve elements. The comparison of the response to different therapies in these two cases highlights the importance of understanding different pathophysiologies, as the treatment modality may differ. PMID:25552790

  4. HIV heterosexual transmission to stable sexual partners of HIV-infected Brazilian hemophiliacs.

    PubMed

    Nicolau, J E; Benard, G; Fonseca, L A; Casseb, J S; Sato, M N; Cianga, M; Tanji, M M; Lorenzi, T F; Duarte, A J

    1996-01-01

    Nineteen Brazilian HIV-infected hemophiliacs and their stable heterosexual sexual partners were studied with the aim of assessing the rate of HIV transmission in this at risk group. The mean length of relationship between couples was 7.4 years. The hemophiliac men were Class II (n = 6), III (n = 11) and IVa (n = 2) of the CDC classification. They had decreased CD4+ and elevated CD8+ cell numbers; five had p24 antigenemia. We found 3 HIV-infected women (15.8 percent) by routine and confirmatory tests, a prevalence similar to that seen in other countries. They were asymptomatic and had no detectable p24 antigenemia. The 3 seropositive women's partners were Class II and III-CDC, and had normal CD4+ and CD8+ values and no p24 antigenemia. All seronegative women also had normal CD4+ and CD8+ numbers, except for elevated CD8+ cells in three of them, but immune abnormalities had already been seen in some seronegative partners at high risk for HIV infection. Our results reinforce previous suggestions that heterosexual transmission to stable female partners occurs preferentially early after initiation of sexual exposure, and possibly when the transmitter had high levels of viremia and regular sexual activity.

  5. Fertility intentions among HIV-infected, sero-concordant Kenyan couples in Nyanza Province, Kenya

    PubMed Central

    Dworkin, Shari; Harrington, Elizabeth; Kwena, Zachary; Onono, Maricianah; Bukusi, Elizabeth; Cohen, Craig R.; Grossma, Daniel; Newmann, Sara J.

    2013-01-01

    Research in sub-Saharan Africa has shown significant diversity in how HIV influences infected couples’ fertility intentions. Supporting HIV-infected, sero-concordant couples in sub-Saharan Africa to make informed choices about their fertility options has not received sufficient attention. In-depth interviews were conducted among 23 HIV-positive, sero-concordant married couples in Kenya, to better understand how HIV impacted fertility intentions. HIV compelled many to reconsider fertility plans, sometimes promoting childbearing intentions in some individuals but often reducing fertility plans among most, largely due to fears of early death, health concerns, stigma, perinatal HIV transmission and financial difficulties (particularly in men). Preferences for sons and large families influenced some couples’ intentions to continue childbearing, although none had discussed their intentions with health care providers. Additional support and services for HIV-infected, sero-concordant couples are needed. Family planning counselling should be tailored to the unique concerns of HIV-infected couples, addressing perinatal transmission but also individual, couple-level, and socio-cultural fertility expectations. Community-level programmes are needed to reduce stigma and make HIV-infected couples more comfortable in discussing fertility intentions with health care providers. PMID:23885924

  6. HIV infection among intravenous drug users: epidemiology and risk reduction.

    PubMed

    Des Jarlais, D C; Friedman, S R

    1987-07-01

    Research on the epidemiology of HIV infection among IV drug users is still at a relatively early stage. Multilocation studies that would permit better geographic comparisons are greatly needed. Multi-method studies within single geographic areas are also needed to assess possible biases with respect to sample recruitment and data collection procedures. The continuation of the epidemic provides a changing historical context that complicates any comparisons. Despite these problems, there are some consistencies that can be seen across studies. Studies of HIV seroprevalence among IV drug users show wide variation among cities in the United States and Europe. The time that the virus was introduced into the IV drug using group within the city is one factor in explaining these differences; other cross-city factors have yet to be identified. Once HIV has been introduced into the IV drug use group within a particular geographic area, there is the possibility of rapid spread up to seroprevalence levels of 50% or greater. Thus, a currently low seroprevalence rate should not be seen as a stable situation. Frequency of injection and sharing of equipment with multiple other drug users (particularly at shooting galleries) have been frequently associated with HIV exposure. Being female, ethnicity (in the USA) and engaging in prostitution also may be associated with increased risk for HIV exposure, suggesting that prevention programs should include special consideration of sex and ethnic differences. Studies of AIDS risk reduction show that substantial proportions of IV drug users are changing their behavior to avoid exposure to HIV. This risk reduction is probably more advanced in New York, with its high seroprevalence and incidence of cases, but is also occurring in cities with lower seroprevalence and limited numbers of cases. The primary forms of risk reduction are increasing the use of sterile equipment, reducing the number of needle sharing partners, and reducing the

  7. Using HIV Sequence and Epidemiologic Data to Assess the Effect of Self-referral Testing for Acute HIV Infection on Incident Diagnoses in San Diego, California

    PubMed Central

    Mehta, Sanjay R.; Murrell, Ben; Anderson, Christy M.; Kosakovsky Pond, Sergei L.; Wertheim, Joel O.; Young, Jason A.; Freitas, Lorri; Richman, Douglas D.; Mathews, W. Chris; Scheffler, Konrad; Little, Susan J.; Smith, Davey M.

    2016-01-01

    Background. Because recently infected individuals disproportionately contribute to the spread of human immunodeficiency virus (HIV), we evaluated the impact of a primary HIV screening program (the Early Test) implemented in San Diego. Methods. The Early Test program used combined nucleic acid and serology testing to screen for primary infection targeting local high-risk individuals. Epidemiologic, HIV sequence, and geographic data were obtained from the San Diego County Department of Public Health and the Early Test program. Poisson regression analysis was performed to determine whether the Early Test program was temporally and geographically associated with changes in incident HIV diagnoses. Transmission chains were inferred by phylogenetic analysis of sequence data. Results. Over time, a decrease in incident HIV diagnoses was observed proportional to the number primary HIV infections diagnosed in each San Diego region (P < .001). Molecular network analyses also showed that transmission chains were more likely to terminate in regions where the program was marketed (P = .002). Although, individuals in these zip codes had infection diagnosed earlier (P = .08), they were not treated earlier (P = .83). Conclusions. These findings suggests that early HIV diagnoses by this primary infection screening program probably contributed to the observed decrease in new HIV diagnoses in San Diego, and they support the expansion and evaluation of similar programs. PMID:27174704

  8. Using HIV Sequence and Epidemiologic Data to Assess the Effect of Self-referral Testing for Acute HIV Infection on Incident Diagnoses in San Diego, California.

    PubMed

    Mehta, Sanjay R; Murrell, Ben; Anderson, Christy M; Kosakovsky Pond, Sergei L; Wertheim, Joel O; Young, Jason A; Freitas, Lorri; Richman, Douglas D; Mathews, W Chris; Scheffler, Konrad; Little, Susan J; Smith, Davey M

    2016-07-01

    Because recently infected individuals disproportionately contribute to the spread of human immunodeficiency virus (HIV), we evaluated the impact of a primary HIV screening program (the Early Test) implemented in San Diego. The Early Test program used combined nucleic acid and serology testing to screen for primary infection targeting local high-risk individuals. Epidemiologic, HIV sequence, and geographic data were obtained from the San Diego County Department of Public Health and the Early Test program. Poisson regression analysis was performed to determine whether the Early Test program was temporally and geographically associated with changes in incident HIV diagnoses. Transmission chains were inferred by phylogenetic analysis of sequence data. Over time, a decrease in incident HIV diagnoses was observed proportional to the number primary HIV infections diagnosed in each San Diego region (P < .001). Molecular network analyses also showed that transmission chains were more likely to terminate in regions where the program was marketed (P = .002). Although, individuals in these zip codes had infection diagnosed earlier (P = .08), they were not treated earlier (P = .83). These findings suggests that early HIV diagnoses by this primary infection screening program probably contributed to the observed decrease in new HIV diagnoses in San Diego, and they support the expansion and evaluation of similar programs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  9. Opportunistic and other intestinal parasitic infections in AIDS patients, HIV seropositive healthy carriers and HIV seronegative individuals in southwest Ethiopia.

    PubMed

    Mariam, Zelalem T; Abebe, Gemeda; Mulu, Andargachew

    2008-12-01

    Human Immunodeficiency Virus (HIV) infection leads to acquired immunodeficiency syndrome (AIDS) and major causes of morbidity and mortality of such patients are opportunistic infections caused by viral, bacterial, fungal and parasitic pathogens. To determine the magnitude of opportunistic and non-opportunistic intestinal parasitic infections among AIDS patients and HIV positive carrier individuals. Cross-sectional study was conducted among AIDS patients, HIV positive healthy carriers and HIV negative individuals in Jimma University Hospital, Mother Theresa Missionary Charity Centre, Medan Acts Projects and Mekdim HIV positive persons and AIDS orphans' national association from January to May, 2004. Convenient sampling technique was employed to identify the study subjects and hence a total of 160 subjects were included. A pre-tested structured questionnaire was used to collect socio-demographic data of the patients. Stool samples were examined by direct saline, iodine wet mount, formol-ether sedimentation concentration, oocyst concentration and modified Ziehl-Neelsen staining technique. Out of 160 persons enrolled in this study 100 (62.5%) (i.e. 65 male and 35 female) were infected with one or more intestinal parasites. The highest rate 36 (69.2%) of intestinal parasites were observed among HIV/AIDS patients, followed by HIV positive healthy carriers 35 (61.4%) of and HIV negative individuals (29 (56.9%). Isospora belli 2 (3.9%), Cryptosporidum parvum 8 (15.4%), Strongyloides stercoralis 6 (11.5%) and Blastocystis 2 (3.9%) were found only in HIV/AIDS groups I. belli, C. parvum, S. stercoralis and Blastocystis are the major opportunistic intestinal parasites observed in HIV/AIDS patients. Therefore, early detection and treatment of these parasites are important to improve the quality of life of HIV/AIDS patients with diarrhoea.

  10. Predictors of human immunodeficiency virus (HIV) infection in primary care: a systematic review protocol.

    PubMed

    Rumbwere Dube, Benhildah N; Marshall, Tom P; Ryan, Ronan P

    2016-09-20

    Antiretroviral therapies for human immunodeficiency virus are more effective if infected individuals are diagnosed early, before they have irreversible immunologic damage. A large proportion of patients that are diagnosed with HIV, in United Kingdom, would have seen a general practitioner (GP) within the previous year. Determining the demographic and clinical characteristics of HIV-infected patients prior to diagnosis of HIV may be useful in identifying patients likely to be HIV positive in primary care. This could help inform a strategy of early HIV testing in primary care. This systematic review aims to identify characteristics of HIV-infected adults prior to diagnosis that could be used in a prediction model for early detection of HIV in primary care. The systematic review will search for literature, mainly observational (cohort and case-control) studies, with human participants aged 18 years and over. The exposures are demographic, socio-economic or clinical risk factors or characteristics associated with HIV infection. The comparison group will be patients with no risk factors or no comparison group. The outcome is laboratory-confirmed HIV/AIDS infection. Evidence will be identified from electronic searches of online databases of EMBASE, MEDLINE, The Cochrane Library and grey literature search engines of Open Grey, Web of Science Conference Proceedings Citation Index and examination of reference lists from selected studies (reference searching). Two reviewers will be involved in quality assessment and data extraction of the review. A data extraction form will be developed to collate data from selected studies. A checklist for quality assessment will be adapted from the Scottish Intercollegiate Guidelines Network (SIGN). This systematic review will identify and consolidate existing scientific evidence on characteristics of HIV infected individuals that could be used to inform decision-making in prognostic model development. PROSPERO CRD42016042427.

  11. Psychiatric symptoms, risky behavior, and HIV infection.

    PubMed

    Woody, G E; Metzger, D; Navaline, H; McLellan, T; O'Brien, C P

    1997-01-01

    These data are internally consistent and lead to several conclusions, as follows: Elevated levels of psychiatric symptoms were found among IDUs in methadone treatment as compared to their counterparts who were out of treatment. IVDUs who entered treatment had higher symptom levels than those who did not enter treatment. Higher symptom levels were found among injectors than noninjectors, and needle sharers had especially high psychiatric symptom levels. Higher symptom levels were found among those who seroconverted in the 6 months following notification, but not thereafter. Symptom levels did not distinguish between HIV-positive and HIV-negative individuals 24 months following notification of seropositivity. Taken together, these findings indicate that elevated psychiatric symptoms are risk factors for continued high risk behavior, as well as for seroconversion. The data add to those of Brooner and colleagues (1993), who demonstrated that ASPD serves as a risk factor for HIV infection. The fact that antisocial personality disorder and psychiatric severity are associated with risky behavior and with actual HIV infection further expands earlier findings showing that these two factors are associated with poorer treatment outcome. Other axis II disorders (e.g., borderline or narcissistic), as well as other axis I disorders with high symptom levels that were not well represented in these studies (schizophrenia, manic depressive illness), may also show similar elevated rates of risky behavior and seroconversion, although there is a scarcity of data currently available to assess the risk behavior of these patients. The evidence from treatment studies that psychiatrically focused therapies, when combined with substance abuse treatment, can improve overall outcome for patients with clinically significant levels of psychiatric symptoms may be relevant in the design of future risk reduction efforts. That is, these treatment outcome studies may serve as a starting point for

  12. Neutropenia during HIV Infection: Adverse Consequences and Remedies

    PubMed Central

    Shi, Xin; Sims, Matthew D; Hanna, Michel M; Xie, Ming; Gulick, Peter G; Zheng, Yong-Hui; Basson, Marc D; Zhang, Ping

    2016-01-01

    Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient’s association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients. PMID:24654626

  13. Nanotechnology and the Treatment of HIV Infection

    PubMed Central

    Parboosing, Raveen; Maguire, Glenn E. M.; Govender, Patrick; Kruger, Hendrik G.

    2012-01-01

    Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the lifelong treatment of HIV infection challenging. The emerging field of nanotechnology may play an important role in addressing these challenges by creating drugs that possess pharmacological advantages arising out of unique phenomena that occur at the “nano” scale. At these dimensions, particles have physicochemical properties that are distinct from those of bulk materials or single molecules or atoms. In this review, basic concepts and terms in nanotechnology are defined, and examples are provided of how nanopharmaceuticals such as nanocrystals, nanocapsules, nanoparticles, solid lipid nanoparticles, nanocarriers, micelles, liposomes and dendrimers have been investigated as potential anti-HIV therapies. Such drugs may, for example, be used to optimize the pharmacological characteristics of known antiretrovirals, deliver anti-HIV nucleic acids into infected cells or achieve targeted delivery of antivirals to the immune system, brain or latent reservoirs. Also, nanopharmaceuticals themselves may possess anti-HIV activity. However several hurdles remain, including toxicity, unwanted biological interactions and the difficulty and cost of large-scale synthesis of nanopharmaceuticals. PMID:22590683

  14. [Epidemiology of HIV infection in 2005].

    PubMed

    Arvieux, Cédric

    2005-06-04

    Various concomitant epidemics of HIV infection currently exist and have created a worldwide pandemic. In Eastern Europe, in France and in industrialized countries, the prevalence of HIV infection is on the rise due to the increased life expectancy of seropositive patients and the persistently "high" incidence rate. In Western Europe, the proportion of new cases among women and people from endemic countries is growing. The role of drug use in HIV transmission is decreasing. The opposite situation is encountered in Eastern Europe, where intravenous drug abuse remains the major risk factor, although heterosexual contamination is also rising. In sub-Saharan Africa, the situation is alarming: decreased life expectancy, increased infant mortality, and a prevalence approaching 50% in prenatal consultations in some countries. Minor improvements have been noted (decline in the prevalence in Uganda). Major deficits in the healthcare systems thwart antiHIV campaigns. In southern and eastern Asia, the epidemic is expanding, notably in countries in which it is recent (China, Indonesia). It is difficult today to envisage a global answer to the epidemic, in view of the wide variety of situations.

  15. Sex-based differences in neurocognitive functioning in HIV-infected young adults.

    PubMed

    Burlacu, Ruxandra; Umlauf, Anya; Luca, Anca; Gianella, Sara; Radoi, Roxana; Ruta, Simona M; Marcotte, Thomas D; Ene, Luminita; Achim, Cristian L

    2018-01-14

    Sex differences in cognition of HIV positive (HIV) patients are controversial. We aimed to investigate the relationship between cognition, HIV status, and sex, in a highly homogenous cohort of young Romanians parenterally infected during early childhood. In total, 250 HIV participants were compared with age-matched HIV negative (HIV) controls (n = 72) in a cross-sectional study. After standardized neurocognitive, psychological testing and medical evaluation, linear regression was used to assess the effect of sex and HIV on neurocognitive outcomes. Study participants were on average 23 years old with balanced sex distribution (% women = 52% vs. 43%). HIV were more educated (12.7 vs. 11.6 years, P = 0.002).HIV status was associated with a lower global performance (β = -0.22, P < 0.001), after controlling for age and education. HIV women had better previous and current HIV-associated markers. The effect of HIV on global cognition did not differ between sexes in most cognitive domains (β = 0.07, P = 0.14). An interaction between sex, HIV status, and cognitive functioning was found in the psychomotor domain. HIV women had worse motor skills than HIV women (β = -0.32, P < 0.001) suggesting a specific effect of HIV on motor functioning in women only. Moreover, current CD4 less than 200 cells/μl (P = 0.013) and longer time lived with CD4 less than 200 cells/μl (P = 0.023) were negatively correlated with the motor scaled score in women (β = -0.22, P = 0.034). Despite less advanced disease in women, long-term HIV infection has an equally detrimental effect on cognitive performances of both sexes, in all cognitive domains, except the psychomotor domain where women are preferentially affected.

  16. Redefining Aging in HIV Infection Using Phenotypes.

    PubMed

    Stoff, David M; Goodkin, Karl; Jeste, Dilip; Marquine, Maria

    2017-10-01

    This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

  17. Buddy programs for people infected with HIV.

    PubMed

    Burrage, Joe; Demi, Alice

    2003-01-01

    The purposes of this correlational study were to describe and compare clients' and volunteers' perceptions of a buddy program for people infected with HIV and to identify relationships between social support and clients' quality of life. Clients' social support was assessed with the Interpersonal Support Evaluation List(ISEL), and their quality of life was assessed with the Medical Outcomes Study-HIV (MOS-HIV) Scale. Clients' and volunteers' perceptions of satisfaction and assistance with activities were assessed with researcher-developed instruments. A convenience sample of 46 client-volunteer dyads was recruited from five AIDS service organizations. Clients perceived adequate levels of social support, moderate amounts of assistance, high levels of satisfaction with client-volunteer relationships, and moderate to low quality of life. A positive relationship was found between clients' and volunteers' perceptions of satisfaction. Relationships were found between ISEL subscales and the Health Transition and Mental Health subscales of the MOS-HIV and the MOS-HIV total scale scores. The findings of the study provide support for the continuation of buddy programs.

  18. Immunization of HIV-infected adult patients — French recommendations

    PubMed Central

    Frésard, Anne; Gagneux-Brunon, Amandine; Lucht, Frédéric; Botelho-Nevers, Elisabeth; Launay, Odile

    2016-01-01

    ABSTRACT Human immunodeficiency virus (HIV)-infected patients remain at increased risk of infection including vaccine-preventable diseases. Vaccines are therefore critical components in the protection of HIV-infected patients from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected patients persist and vaccine coverage in this population could be improved. This article presents the French recommendations regarding immunization of HIV-infected adults in the light of the evidence-based literature on the benefits and the potential risks of vaccines among this vulnerable population. PMID:27409293

  19. Transmitted drug resistance in patients with acute/recent HIV infection in Brazil.

    PubMed

    Ferreira, Ana Cristina G; Coelho, Lara E; Grinsztejn, Eduarda; Jesus, Carlos S de; Guimarães, Monick L; Veloso, Valdiléa G; Grinsztejn, Beatriz; Cardoso, Sandra W

    The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are

  20. Simple Epidemiological Dynamics Explain Phylogenetic Clustering of HIV from Patients with Recent Infection

    PubMed Central

    Volz, Erik M.; Koopman, James S.; Ward, Melissa J.; Brown, Andrew Leigh; Frost, Simon D. W.

    2012-01-01

    Phylogenies of highly genetically variable viruses such as HIV-1 are potentially informative of epidemiological dynamics. Several studies have demonstrated the presence of clusters of highly related HIV-1 sequences, particularly among recently HIV-infected individuals, which have been used to argue for a high transmission rate during acute infection. Using a large set of HIV-1 subtype B pol sequences collected from men who have sex with men, we demonstrate that virus from recent infections tend to be phylogenetically clustered at a greater rate than virus from patients with chronic infection (‘excess clustering’) and also tend to cluster with other recent HIV infections rather than chronic, established infections (‘excess co-clustering’), consistent with previous reports. To determine the role that a higher infectivity during acute infection may play in excess clustering and co-clustering, we developed a simple model of HIV infection that incorporates an early period of intensified transmission, and explicitly considers the dynamics of phylogenetic clusters alongside the dynamics of acute and chronic infected cases. We explored the potential for clustering statistics to be used for inference of acute stage transmission rates and found that no single statistic explains very much variance in parameters controlling acute stage transmission rates. We demonstrate that high transmission rates during the acute stage is not the main cause of excess clustering of virus from patients with early/acute infection compared to chronic infection, which may simply reflect the shorter time since transmission in acute infection. Higher transmission during acute infection can result in excess co-clustering of sequences, while the extent of clustering observed is most sensitive to the fraction of infections sampled. PMID:22761556

  1. High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV Infection: the PrEP Brasil demonstration project.

    PubMed

    Hoagland, Brenda; Moreira, Ronaldo I; De Boni, Raquel B; Kallas, Esper G; Madruga, José Valdez; Vasconcelos, Ricardo; Goulart, Silvia; Torres, Thiago S; Marins, Luana M S; Anderson, Peter L; Luz, Paula M; Costa Leite, Iuri da; Liu, Albert Y; Veloso, Valdilea G; Grinsztejn, Beatriz

    2017-04-06

    The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and São Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (<350 fmol/punch, ≥350-699 fmol/punch and ≥700 fmol/punch). 1,270 individuals were assessed for participation; n = 738 were potentially eligible and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled individuals were younger, had lower HIV risk perception and had lower PrEP awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP concentrations, 94.1% in the protective range (≥350 fmol/punch, consistent with ≥2 pills per week), and 78% were in the highly protective range (≥700 fmol/punch, ≥4 pills per week). Participants with ≥12 years of schooling had 1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than participants with <12 years of schooling. Condomless receptive anal intercourse in the prior 3 months was also associated with higher drug levels (adjusted OR = 1.78; 95% CI 1.08-2.94). The high uptake and early adherence indicate that PrEP for high-risk MSM and TGW can be successfully delivered in the context of the Brazilian Public Health System. Interventions to

  2. Surveillance of recent HIV infections among newly diagnosed HIV cases in Germany between 2008 and 2014.

    PubMed

    Hofmann, Alexandra; Hauser, Andrea; Zimmermann, Ruth; Santos-Hövener, Claudia; Bätzing-Feigenbaum, Jörg; Wildner, Stephan; Kücherer, Claudia; Bannert, Norbert; Hamouda, Osamah; Bremer, Viviane; Bartmeyer, Barbara

    2017-07-11

    The HIV surveillance system in Germany is based on mandatory, anonymous notification of newly diagnosed HIV cases by laboratories. Because the time between HIV infection and the diagnosis of HIV varies widely between persons, it is difficult to determine the number of cases of recent HIV infection among newly diagnosed cases of HIV. In Germany, the BED-capture-enzyme immunoassay (BED-CEIA) has been used to distinguish between recent and long-standing HIV infection. The aim of this analysis is to report the proportion of cases of recent HIV infection among newly diagnosed cases in Germany between 2008 and 2014 and to identify factors associated with recent infections. A sample of voluntary laboratories among all HIV diagnostic laboratories was recruited. Residual blood from HIV diagnostic tests was spotted on filter paper as dried serum or dried plasma spots and was sent along with the notification form of the HIV cases. The BED-CEIA test was performed. A case was defined as recent HIV infection with a BED-CEIA test result of less than 0.8 normalized optical density, with the exclusion of CDC stage C. The proportion of recent newly diagnosed HIV infections among different groups (such as transmission groups, gender or age groups) was calculated. We used logistic regression to identify factors associated with recent HIV infection and to identify subpopulations with high proportions of recent HIV infections. Approximately 10,257 newly diagnosed cases were tested for recency using the BED-CEIA. In total, 3084 (30.4%) of those were recently infected with HIV. The highest proportion of recent HIV infections was found among men who had sex with men (MSM) (35%) and persons between 18 and 25 years of age (43.0%). Logistic regression revealed that female German intravenous drug users with a recent HIV infection had a higher chance of being detected than German MSM (OR 2.27). Surveillance of recent HIV infection is a useful additional tool to monitor the HIV epidemic in

  3. Exploring the benefits of antibody immune response in HIV-1 infection using a discrete model.

    PubMed

    Showa, S P; Nyabadza, F; Hove-Musekwa, S D; Magombedze, G

    2016-06-01

    The role of antibodies in HIV-1 infection is investigated using a discrete-time mathematical model that considers cell-free and cell-associated transmission of the virus. Model analysis shows that the effect of each type of antibody is dependent on the stage of the infection. Neutralizing antibodies are efficient in controlling the viral levels in the early days after seroconversion and antibodies that coat HIV-1-infected cells and recruit effector cells to either kill the HIV-1-infected cells or inhibit viral replication are efficient when the infection becomes established. Model simulations show that antibodies that inhibit viral replication are more effective in controlling the infection than those that recruit Natural Killer T cells after infection establishment. The model was fitted to subjects of the Tsedimoso study conducted in Botswana and conclusions similar to elasticity analysis results were obtained. Model fitting results predicted that neutralizing antibodies are more efficient in controlling the viral levels than antibodies that coat HIV-1-infected cells and recruit effector cells to either kill the HIV-1-infected cells or inhibit viral replication in the early days after seroconversion. © The Authors 2015. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  4. Mitochondrial function and apoptosis of peripheral mononuclear cells (PBMCs) in the HIV infected patients.

    PubMed

    Bociąga-Jasik, Monika; Góralska, Joanna; Polus, Anna; Śliwa, Agnieszka; Gruca, Anna; Raźny, Urszula; Zdzienicka, Anna; Garlicki, Aleksander; Mach, Tomasz; Dembińska-Kieć, Aldona

    2013-06-01

    HIV infection results in the development of immunodeficiency mainly due to the apoptosis of infected and by stander CD4 cells. The aim of the study was to follow the mitochondrial dependent pathway of apoptosis, one of the suggested mechanisms of above process. The inner mitochondrial membrane potential (MMP), Adenosine-5'-triphosphate (ATP) generation, apoptosis and necrosis markers of peripheral mononuclear cells (PBMCs) were compared in HIV infected patients and HIV negative control group. The correlation of blood viral load, TNFα concentration, CD4 cells count and duration of ARV therapy was considered. Additionally, group of HIV infected ARV-naive patients was involved for the follow-up study and the effects of one year of ARV therapy on measured parameters were studied. PBMCs of HIV infected individuals (especially without ARV therapy) demonstrated lower MMP and ATP generation and higher percentage of apoptotic/necrotic PBMCs. Correlation between blood TNFα level and mitochondrial dysfunction was observed. The first months of ARV therapy resulted in most significant restoration of mitochondrial function and living PBMCs count. HIV infection and ARV therapy have significant impact on mitochondrial function and apoptosis of PBMCs. They are driven by abnormal mitochondrial function apoptosis of immune cells which seems to be the key element leading to immunosuppression, thus an early intervention in this process by therapy can be beneficial for symptomatology of HIV infected patients.

  5. [Visceral leishmaniasis in patient with HIV infection].

    PubMed

    Olea, Pilar; Pinilla, Jorge

    2013-04-01

    Leishmaniasis is a parasitic disease caused by the protozoa of the genus Leishmania transmitted by sandfly bites. It causes subclinical infection and diverse clinical manifestations with cutaneous, mucosal or visceral involvement. The last one, called visceral leishmaniasis, is usually fatal without treatment and in VIH patients with deep immunosuppression, has been recognized as an opportunistic infection with a high degree of difficulty in diagnosis and treatment. We present the case of a patient with HIV infection and visceral leishmaniasis. The clinical presentation was a prolonged febril syndrome with hepatosplenomegaly, lymphadenopathy and pancytopenia. The differential diagnosis was made with lymphoma and other opportunistic infections, as mycobacteriosis. The bone marrow aspirate reveled parasite amastigotes. The patient received treatment with amphotericin B deoxycholate for 14 days and 2 months after he relapsed. Then he was treated with the same drug for 21 days and after that he has been in prophylaxis for 29 months with good outcome, without any other relapse.

  6. Persistent inflammation in HIV infection: established concepts, new perspectives.

    PubMed

    Nasi, Milena; Pinti, Marcello; Mussini, Cristina; Cossarizza, Andrea

    2014-10-01

    Immune activation is now considered a main driving force for the progressive immune failure in HIV infection. During the early phases of infection, a rapid depletion of gastrointestinal CD4+ T cells occurs that is followed by a deterioration of the gut epithelium and by the subsequent translocation of microbial products into the blood. Activation of innate immunity results in massive production of proinflammatory cytokines, which can trigger activation induced cell death phenomena among T lymphocytes. Moreover, persistent antigenic stimulation and inflammatory status causes immune exhaustion. The chronic immune activation also damages lymphoid tissue architecture, so contributing to the impairment of immune reconstitution. Recently, new mechanisms were identified, so opening new perspective on the innate immune sensing in HIV-1 infection. Cell death is followed by the release of molecules containing "damage-associated molecular patterns", that trigger a potent innate immune response through the engagement of Toll-like receptors. Then, also different types of HIV-related nucleic acids can act as potent stimulators of innate immunity. All these events contribute to the loss of T cell homeostatic regulation and to the failure of adaptive immunity. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Listeria monocytogenes empyema in an HIV infected patient

    PubMed Central

    Marron, A.; Roson, B.; Mascaro, J.; Carratala, J.

    1997-01-01

    Listeriosis in HIV infected patients is uncommon and usually presents as meningitis or bacteraemia. Pleural fluid infections caused by this organism are extremely rare. A case is described of empyema caused by Listeria monocytogenes in an HIV infected patient that was successfully treated with medical treatment only. 




 PMID:9337838

  8. College Students' Attitudes Toward People Infected with HIV

    ERIC Educational Resources Information Center

    Popova, N. V.

    2007-01-01

    According to data of the World Health Organization, 34-46 million people are infected with the human immunodeficiency virus (HIV). In 2003 alone, the number of newly infected people in all countries came to about 5 million. By January 2001, more than 80,000 HIV-infected people were registered in Russia, of whom over 90 percent were drug users.…

  9. Preexposure Prophylaxis for HIV Infection among African Women

    PubMed Central

    Van Damme, Lut; Corneli, Amy; Ahmed, Khatija; Agot, Kawango; Lombaard, Johan; Kapiga, Saidi; Malahleha, Mookho; Owino, Fredrick; Manongi, Rachel; Onyango, Jacob; Temu, Lucky; Monedi, Modie Constance; Mak’Oketch, Paul; Makanda, Mankalimeng; Reblin, Ilse; Makatu, Shumani Elsie; Saylor, Lisa; Kiernan, Haddie; Kirkendale, Stella; Wong, Christina; Grant, Robert; Kashuba, Angela; Nanda, Kavita; Mandala, Justin; Fransen, Katrien; Deese, Jennifer; Crucitti, Tania; Mastro, Timothy D.; Taylor, Douglas

    2013-01-01

    BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. METHODS In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF–FTC in preventing HIV acquisition and to evaluate safety. RESULTS HIV infections occurred in 33 women in the TDF–FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P = 0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF–FTC group (P = 0.04, P<0.001, and P = 0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF–FTC group (4.7%) than in the placebo group (3.0%, P = 0.051). Less than 40% of the HIV-uninfected women in the TDF–FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. CONCLUSIONS Prophylaxis with TDF–FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.) PMID:22784040

  10. Nosocomial infections in HIV infected patients. Gruppo HIV e Infezioni Ospedaliere.

    PubMed

    Petrosillo, N; Pugliese, G; Girardi, E; Pallavicini, F; Carosi, G; Moro, M L; Ippolito, G

    1999-04-01

    To determine the incidence of nosocomial infections (NI) in HIV-infected patients and to analyse some of the associated risk factors. Multicentre prospective study on consecutive HIV-infected patients admitted to 19 Italian acute-care infectious disease wards. All patients admitted during a 1-year period were followed-up for NI until their discharge. Univariate and multivariate analyses were performed for NI risk factors. As of June 1998 a total of 344 NI occurred in 4330 admissions, with at least one NI in 273 admissions (6.3%). The incidence rate of NI was 3.6 per 1000 patient days [95% confidence interval (CI), 3.2-4.1]. Overall distribution by site was 36.6% bloodstream infections (BSI), 30.5% urinary tract infections, 18.4% pneumonia, 5.2% skin/soft tissue infections, 2.0% surgical wound infections and 7.3% others. Fifty-five out of the 126 BSI were related to a central venous catheter (CVC); the rate of CVC-associated infections was eight infections per 1000 devices. At multivariate analysis, variables independently associated with NI included CD4 T-lymphocyte count < 200 x 10(6)/l [odds ratio (OR), 2.21; 95% CI, 1.35-3.62], Karnofsky Performance Status < 40 (OR, 1.89; 95% CI, 1.28-2.78), therapy with corticosteroids (OR, 1.78; 95% CI, 1.29-2.45), CVC (OR, 3.24; 95% CI, 2.41-4.35), urinary catheter (OR, 6.53; 95% CI, 4.81-8.86) and surgery (OR, 3.13; 95% CI, 1.90-5.15). Results suggest that NI occur commonly in HIV-infected patients. As the number of cases of HIV continues to increase, the number of HIV-infected patients requiring hospitalization may also increase. Clinicians need to be aware of the risk factors for NI and must consider these infections in the overall management of HIV-infected, hospitalized patients.

  11. B-cell development and pneumococcal immunity in vertically acquired HIV infection.

    PubMed

    Eisen, Sarah; Hayden, Clare; Young, Carmel J; Gilson, Richard; Jungmann, Eva; Jacobsen, Marianne C; Poulsom, Hannah; Goldblatt, David; Klein, Nigel J; Baxendale, Helen E

    2016-07-31

    Many children with HIV infection now survive into adulthood. This study explored the impact of vertically acquired HIV in the era of antiretroviral therapy on the development of humoral immunity. Natural and vaccine-related immunity to pneumococcus and B-cell phenotype was characterized and compared in three groups of young adults: those with vertically-acquired infection, those with horizontally acquired infection and healthy controls. Serotype-specific pneumococcal (Pnc) immunoglobulin M and G concentrations before and up to 1 year post-Pnc polysaccharide (Pneumovax) immunization were determined, and opsonophagocytic activity was analysed. B-cell subpopulations and dynamic markers of B-cell signalling, turnover and susceptibility to apoptosis were evaluated by flow cytometry. HIV-infected patients showed impaired natural Pnc immunity and reduced humoral responses to immunization with Pneumovax; this was greatest in those viraemic at time of the study. Early-life viral control before the age of 10 years diminished these changes. Expanded populations of abnormally activated and immature B-cells were seen in both HIV-infected cohorts. Vertically infected patients were particularly vulnerable to reductions in marginal zone and switched memory populations. These aberrations were reduced in patients with early-life viral control. In children with HIV, damage to B-cell memory populations and impaired natural and vaccine immunity to pneumococcus is evident in early adult life. Sustained viral control from early childhood may help to limit this effect and optimize humoral immunity in adult life.

  12. A mathematical approach to HIV infection dynamics

    NASA Astrophysics Data System (ADS)

    Ida, A.; Oharu, S.; Oharu, Y.

    2007-07-01

    In order to obtain a comprehensive form of mathematical models describing nonlinear phenomena such as HIV infection process and AIDS disease progression, it is efficient to introduce a general class of time-dependent evolution equations in such a way that the associated nonlinear operator is decomposed into the sum of a differential operator and a perturbation which is nonlinear in general and also satisfies no global continuity condition. An attempt is then made to combine the implicit approach (usually adapted for convective diffusion operators) and explicit approach (more suited to treat continuous-type operators representing various physiological interactions), resulting in a semi-implicit product formula. Decomposing the operators in this way and considering their individual properties, it is seen that approximation-solvability of the original model is verified under suitable conditions. Once appropriate terms are formulated to describe treatment by antiretroviral therapy, the time-dependence of the reaction terms appears, and such product formula is useful for generating approximate numerical solutions to the governing equations. With this knowledge, a continuous model for HIV disease progression is formulated and physiological interpretations are provided. The abstract theory is then applied to show existence of unique solutions to the continuous model describing the behavior of the HIV virus in the human body and its reaction to treatment by antiretroviral therapy. The product formula suggests appropriate discrete models describing the dynamics of host pathogen interactions with HIV1 and is applied to perform numerical simulations based on the model of the HIV infection process and disease progression. Finally, the results of our numerical simulations are visualized and it is observed that our results agree with medical and physiological aspects.

  13. Suppression of HIV-1 Infectivity by Human Glioma Cells

    PubMed Central

    Hoque, Sheikh Ariful; Tanaka, Atsushi; Islam, Salequl; Ahsan, Gias Uddin; Jinno-Oue, Atsushi

    2016-01-01

    Abstract HIV-1 infection to the central nervous system (CNS) is very common in AIDS patients. The predominant cell types infected in the brain are monocytes and macrophages, which are surrounded by several HIV-1–resistant cell types, such as astrocytes, oligodendrocytes, neurons, and microvascular cells. The effect of these HIV-1–resistant cells on HIV-1 infection is largely unknown. In this study, we examined the stability of HIV-1 cultured with several human glioblastoma cell lines, for example, NP-2, U87MG, T98G, and A172, to determine whether these HIV-1–resistant brain cells could enhance or suppress HIV-1 infection and thus modulate HIV-1 infection in the CNS. The HIV-1 titer was determined using the MAGIC-5A indicator cell line as well as naturally occurring CD4+ T cells. We found that the stability of HIV-1 incubated with NP-2 or U87MG cells at 37°C was significantly shorter (half-life, 2.5–4 h) compared to that of HIV-1 incubated with T98G or A172 cells or in culture medium without cells (half-life, 8–18 h). The spent culture media (SCM) of NP-2 and U87MG cells had the ability to suppress both R5- and X4-HIV-1 infection by inhibiting HIV-1 attachment to target cells. This inhibitory effect was eliminated by the treatment of the SCM with chondroitinase ABC but not heparinase, suggesting that the inhibitory factor(s) secreted by NP-2 and U87MG cells was chiefly mediated by chondroitin sulfate (CS) or CS-like moiety. Thus, this study reveals that some but not all glioma cells secrete inhibitory molecules to HIV-1 infection that may contribute in lowering HIV-1 infection in the CNS in vivo. PMID:26650729

  14. The investigation of CD4+T-cell functions in primary HIV infection with antiretroviral therapy

    PubMed Central

    Sun, Yu; Fu, Yajing; Zhang, Zining; Tang, Tian; Liu, Jing; Ding, Haibo; Han, Xiaoxu; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun

    2017-01-01

    Abstract Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function. PMID:28700479

  15. Cardiovagal Autonomic Function in HIV-Infected Patients with Unsuppressed HIV Viremia

    PubMed Central

    Chow, Dominic C.; Wood, Robert; Choi, Julia; Grandinetti, Andrew; Gerschenson, Mariana; Sriratanaviriyakul, Narin; Nakamoto, Beau; Shikuma, Cecilia; Low, Phillip

    2011-01-01

    Purpose HIV infection has been implicated in dysregulation of the autonomic nervous system. Method Cross-sectional study examining the relationship between the presence of persistent detectable HIV viral load with autonomic function, measured by heart rate variability (HRV). Non-virologic suppression (NVS) was defined as having a detectable viral load for at least 3 months prior to autonomic function testing. HRV was measured during the following 4 maneuvers: resting and paced respirations and sustained handgrip and tilt. Inferences on parasympathetic and sympathetic modulations were determined by analyzing time and frequency domains of HRV. Results 57 participants were enrolled in 3 groups: 22 were HIV-infected participants with HIV virologic suppression (VS; undetectable HIV viral load), 9 were HIV-infected participants who had NVS, and 26 were HIV seronegative controls. There were lower time domain parameters in the HIV-infected group as a whole compared to controls. There were no significant differences in time domain parameters among HIV-infected participants. There were no differences in frequency domain parameters during any of the maneuvers between controls and all HIV-infected participants, nor between the NVS and VS groups. Conclusion There were differences in autonomic function between HIV-infected individuals and HIV seronegative controls, but not between the NVS and VS groups. PMID:21684854

  16. Demographic processes affect HIV-1 evolution in primary infection before the onset of selective processes.

    PubMed

    Herbeck, Joshua T; Rolland, Morgane; Liu, Yi; McLaughlin, Sherry; McNevin, John; Zhao, Hong; Wong, Kim; Stoddard, Julia N; Raugi, Dana; Sorensen, Stephanie; Genowati, Indira; Birditt, Brian; McKay, Angela; Diem, Kurt; Maust, Brandon S; Deng, Wenjie; Collier, Ann C; Stekler, Joanne D; McElrath, M Juliana; Mullins, James I

    2011-08-01

    HIV-1 transmission and viral evolution in the first year of infection were studied in 11 individuals representing four transmitter-recipient pairs and three independent seroconverters. Nine of these individuals were enrolled during acute infection; all were men who have sex with men (MSM) infected with HIV-1 subtype B. A total of 475 nearly full-length HIV-1 genome sequences were generated, representing on average 10 genomes per specimen at 2 to 12 visits over the first year of infection. Single founding variants with nearly homogeneous viral populations were detected in eight of the nine individuals who were enrolled during acute HIV-1 infection. Restriction to a single founder variant was not due to a lack of diversity in the transmitter as homogeneous populations were found in recipients from transmitters with chronic infection. Mutational patterns indicative of rapid viral population growth dominated during the first 5 weeks of infection and included a slight contraction of viral genetic diversity over the first 20 to 40 days. Subsequently, selection dominated, most markedly in env and nef. Mutants were detected in the first week and became consensus as early as day 21 after the onset of symptoms of primary HIV infection. We found multiple indications of cytotoxic T lymphocyte (CTL) escape mutations while reversions appeared limited. Putative escape mutations were often rapidly replaced with mutually exclusive mutations nearby, indicating the existence of a maturational escape process, possibly in adaptation to viral fitness constraints or to immune responses against new variants. We showed that establishment of HIV-1 infection is likely due to a biological mechanism that restricts transmission rather than to early adaptive evolution during acute infection. Furthermore, the diversity of HIV strains coupled with complex and individual-specific patterns of CTL escape did not reveal shared sequence characteristics of acute infection that could be harnessed for

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

    ClinicalTrials.gov

    2010-05-07

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

  18. The state of science: violence and HIV infection in women.

    PubMed

    Manfrin-Ledet, Linda; Porche, Demetrius J

    2003-01-01

    Violence and human immunodeficiency virus (HIV) are two critical public health problems affecting the lives of millions of women today. The purpose of this article is to review the state of science that exists in linking the phenomena of violence and HIV infection in women. The history and scope of violence and HIV infection is presented. Theoretical models for the phenomena of violence and abuse against women and HIV risk behavior reduction are explored. The literature review consists of 44 research articles that examine risk factors for violence and HIV, violence associated with HIV/AIDS disclosure, history of violence and HIV/AIDS, forced or coercive sex and HIV/AIDS, and violence associated with HIV self-protection conduct. Implications for nursing practice and nursing research are presented.

  19. The involvement of plasmacytoid cells in HIV infection and pathogenesis.

    PubMed

    Aiello, Alessandra; Giannessi, Flavia; Percario, Zulema A; Affabris, Elisabetta

    2018-04-01

    Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that are specialized in type I interferon (IFN) production. pDCs are key players in the antiviral immune response and serve as bridge between innate and adaptive immunity. Although pDCs do not represent the main reservoir of the Human Immunodeficiency Virus (HIV), they are a crucial subset in HIV infection as they influence viral transmission, target cell infection and antigen presentation. pDCs act as inflammatory and immunosuppressive cells, thus contributing to HIV disease progression. This review provides a state of art analysis of the interactions between HIV and pDCs and their potential roles in HIV transmission, chronic immune activation and immunosuppression. A thorough understanding of the roles of pDCs in HIV infection will help to improve therapeutic strategies to fight HIV infection, and will further increase our knowledge on this important immune cell subset. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Solid Organ Transplants in HIV-infected Patients

    PubMed Central

    Harbell, Jack; Terrault, Norah A.; Stock, Peter

    2018-01-01

    There is a growing need for kidney and liver transplants in persons living with HIV. Fortunately, with the significant advances in antiretroviral therapy and management of opportunistic infections, HIV infection is no longer an absolute contraindication for solid organ transplantation. Data from several large prospective multi-center cohort studies have shown that solid organ transplantation in carefully selected HIV-infected individuals is safe. However, significant challenges have been identified including prevention of acute rejection, management of drug-drug interactions and treatment of recurrent viral hepatitis. This article reviews the selection criteria, outcomes, and special management considerations for HIV-infected patients undergoing liver or kidney transplantation. PMID:23893004

  1. First UK case report of kidney transplantation from an HIV-infected deceased donor to two HIV-infected recipients

    PubMed Central

    Nolan, Eileen; Karydis, Nikolaos; Drage, Martin

    2018-01-01

    Abstract Kidney transplantation is now considered the treatment of choice for many human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Graft survival rates using HIV-negative donors and carefully selected HIV-positive ESRD patients are similar to those observed in HIV-uninfected kidney transplant recipients. To address the relative shortfall in donated organs it has been proposed that organs from HIV-infected deceased donors might be allocated to HIV-infected patients on the transplant waiting list. Preliminary experience in South Africa reports promising short-term outcomes in a small number of HIV-infected recipients of kidney transplants from HIV-infected donors. We sought to replicate this experience in the UK by accepting kidney offers from HIV infected deceased donors for patients with HIV-infection on the kidney transplant waiting list. Here we report the UK’s first cases of kidney transplantation between HIV-positive donors and recipients. PMID:29644073

  2. Early loss to follow-up and mortality of HIV-infected patients diagnosed after the era of antiretroviral treatment scale up: a call for re-invigorating the response in Iran.

    PubMed

    Badie, Banafsheh Moradmand; Nabaei, Ghaemeh; Rasoolinejad, Mehrnaz; Mirzazadeh, Ali; McFarland, Willi

    2013-12-01

    In Iran, the HIV/AIDS epidemic is growing during an era of scaling up the national surveillance system and antiretroviral therapy programs. We examined the early loss to follow-up and mortality rates in a retrospective cohort of 1495 HIV-infected patients by survival proportional hazard Cox model. We also conducted a data abstraction sub-study in a systematic random sample of 147 patients to assess the association between mortality and predictor factors. Overall, 17.3% patients were not seen after their first visit and 17.4% more were lost by 6 months. The overall mortality rate was 7.0 (95% CI 6.1-8.1) per 100 person-years. Moreover, crude mortality rate was higher in men (8.6) than in women (1.7), with an age-adjusted hazard ratio for men compared to women of 4.55 (95% CI 2.31-8.93). Lastly, history of tuberculosis and not being on antiretroviral therapy were significantly associated with higher mortality in the patient sub-sample.

  3. Revised surveillance case definition for HIV infection--United States, 2014.

    PubMed

    2014-04-11

    Following extensive consultation and peer review, CDC and the Council of State and Territorial Epidemiologists have revised and combined the surveillance case definitions for human immunodeficiency virus (HIV) infection into a single case definition for persons of all ages (i.e., adults and adolescents aged ≥13 years and children aged <13 years). The revisions were made to address multiple issues, the most important of which was the need to adapt to recent changes in diagnostic criteria. Laboratory criteria for defining a confirmed case now accommodate new multitest algorithms, including criteria for differentiating between HIV-1 and HIV-2 infection and for recognizing early HIV infection. A confirmed case can be classified in one of five HIV infection stages (0, 1, 2, 3, or unknown); early infection, recognized by a negative HIV test within 6 months of HIV diagnosis, is classified as stage 0, and acquired immunodeficiency syndrome (AIDS) is classified as stage 3. Criteria for stage 3 have been simplified by eliminating the need to differentiate between definitive and presumptive diagnoses of opportunistic illnesses. Clinical (nonlaboratory) criteria for defining a case for surveillance purposes have been made more practical by eliminating the requirement for information about laboratory tests. The surveillance case definition is intended primarily for monitoring the HIV infection burden and planning for prevention and care on a population level, not as a basis for clinical decisions for individual patients. CDC and the Council of State and Territorial Epidemiologists recommend that all states and territories conduct case surveillance of HIV infection using this revised surveillance case definition.

  4. Neoplasms-associated deaths in HIV-1 infected and non-infected patients in Bahia, Brazil.

    PubMed

    Marques, Marinho; Luz, Estela; Leal, Mateus; Oliveira, João Vitor; Patrício, Rejane; Netto, Eduardo Martins; Brites, Carlos

    2018-05-01

    HIV-infected patients are at a higher risk to develop malignancies than general population. Although AIDS-related malignancies are a common feature of late-stage disease, patients under successful antiretroviral therapy also have an increased risk for development of non-AIDS malignancies. To compare the frequency and characteristics of adults HIV-infected patients and general population who died of malignancies in Bahia, Brazil from January 2000 to December 2010. National Information System on Mortality (SIM) was searched to identify all deaths in the study period caused by malignancies in general population and in HIV patients. The frequency of malignancies in these two groups was compared. For HIV patients we also recorded the last HIV-1 RNA plasma viral load and CD4+ cells count, retrieved from oficial databases on laboratory monitoring for HIV patients. In the study period 733,645 deaths were reported, 677,427 (92.3%) of them in individual older than 13 years. Malignancies were the cause of death in 77,174 (11.4%) of them, and 5156 (0.8%) were associated to HIV/Aids. Among deaths of HIV/Aids patients, Kaposi´s sarcoma was the most prevalent malignancy (OR: 309.7; 95% CI: 177-544), followed by non-Hodgkin lymphoma (OR: 10.1; 95% CI: 5.3-19.3), Hodgkin´s lymphoma (OR: 4.3; 95% CI: 2.2-8.4), and cranial nervous malignancies (OR: 3.3; 95% CI:1.6-7.0). HIV patients died at a significantly lower age (43.7 years), than general population (64.5 years, p < 0.0001). Patients who had a diagnosis of Aids-related malignancies had lower CD4+ cells count than those with non-AIDS relates malignancies (p = 0.04). HIV infection is a clear risk fator for development of some malignancies, and is associated with early mortality, compared to general population. The level of CD4+ cells count predicts the type of malignancies causing death in this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. CD4 T Follicular Helper Cells and HIV Infection: Friends or Enemies?

    PubMed

    Moukambi, Félicien; Rodrigues, Vasco; Fortier, Yasmina; Rabezanahary, Henintsoa; Borde, Chloé; Krust, Bernard; Andreani, Guadalupe; Silvestre, Ricardo; Petrovas, Constantinos; Laforge, Mireille; Estaquier, Jérôme

    2017-01-01

    Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation. Our recent observations indicated an early and profound loss of splenic Tfh cells. The role of transcriptional activator and repressor factors that control Tfh differentiation is also discussed in the context of HIV/SIV infection. Because Tfh cells are important for B cell differentiation and antibody production, accelerating the Tfh responses early during HIV/SIV infection could be promising as novel immunotherapeutic approach or alternative vaccine strategies. However, because Tfh cells are infected during the HIV/SIV infection and represent a reservoir, this may interfere with HIV vaccine strategy. Thus, Tfh represent the good and bad guys during HIV infection.

  6. CD4 T Follicular Helper Cells and HIV Infection: Friends or Enemies?

    PubMed Central

    Moukambi, Félicien; Rodrigues, Vasco; Fortier, Yasmina; Rabezanahary, Henintsoa; Borde, Chloé; Krust, Bernard; Andreani, Guadalupe; Silvestre, Ricardo; Petrovas, Constantinos; Laforge, Mireille; Estaquier, Jérôme

    2017-01-01

    Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation. Our recent observations indicated an early and profound loss of splenic Tfh cells. The role of transcriptional activator and repressor factors that control Tfh differentiation is also discussed in the context of HIV/SIV infection. Because Tfh cells are important for B cell differentiation and antibody production, accelerating the Tfh responses early during HIV/SIV infection could be promising as novel immunotherapeutic approach or alternative vaccine strategies. However, because Tfh cells are infected during the HIV/SIV infection and represent a reservoir, this may interfere with HIV vaccine strategy. Thus, Tfh represent the good and bad guys during HIV infection. PMID:28265271

  7. HIV Infection Affects Streptococcus mutans Levels, but Not Genotypes

    PubMed Central

    Liu, G.; Saxena, D.; Chen, Z.; Norman, R.G.; Phelan, J.A.; Laverty, M.; Fisch, G.S.; Corby, P.M.; Abrams, W.; Malamud, D.; Li, Y.

    2012-01-01

    We report a clinical study that examines whether HIV infection affects Streptococcus mutans colonization in the oral cavity. Whole stimulated saliva samples were collected from 46 HIV-seropositive individuals and 69 HIV-seronegative control individuals. The level of S. mutans colonization was determined by conventional culture methods. The genotype of S. mutans was compared between 10 HIV-positive individuals before and after highly active antiretroviral therapy (HAART) and 10 non-HIV-infected control individuals. The results were analyzed against viral load, CD4+ and CD8+ T-cell counts, salivary flow rate, and caries status. We observed that S. mutans levels were higher in HIV-infected individuals than in the non-HIV-infected control individuals (p = 0.013). No significant differences in S. mutans genotypes were found between the two groups over the six-month study period, even after HAART. There was a bivariate linear relationship between S. mutans levels and CD8+ counts (r = 0.412; p = 0.007), but not between S. mutans levels and either CD4+ counts or viral load. Furthermore, compared with non-HIV-infected control individuals, HIV-infected individuals experienced lower salivary secretion (p = 0.009) and a positive trend toward more decayed tooth surfaces (p = 0.027). These findings suggest that HIV infection can have a significant effect on the level of S. mutans, but not genotypes. PMID:22821240

  8. Decision tree for accurate infection timing in individuals newly diagnosed with HIV-1 infection.

    PubMed

    Verhofstede, Chris; Fransen, Katrien; Van Den Heuvel, Annelies; Van Laethem, Kristel; Ruelle, Jean; Vancutsem, Ellen; Stoffels, Karolien; Van den Wijngaert, Sigi; Delforge, Marie-Luce; Vaira, Dolores; Hebberecht, Laura; Schauvliege, Marlies; Mortier, Virginie; Dauwe, Kenny; Callens, Steven

    2017-11-29

    There is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives. Three methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed. Clear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5 days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample. A step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important

  9. Applying the HIV-associated neurocognitive disorder diagnostic criteria to HIV-infected youth

    PubMed Central

    Phillips, Nicole; Joska, John A.; Paul, Robert; Donald, Kirsten A.; Stein, Dan J.; Thomas, Kevin G.F.

    2016-01-01

    Objective: The aim of this study was to apply the HIV-associated neurocognitive disorders (HAND) criteria for diagnosing HAND in HIV-infected adults, in a cohort of HIV-infected youth to thus establish whether this system is able to detect a spectrum of neurocognitive disorders (ND) in HIV-infected youth. Methods: We used a comprehensive pediatric neurocognitive battery, an assessment of functional competence, and the American Academy of Neurology system for diagnosing ND in a cross-sectional study of HIV-infected youth (n = 86) and HIV-negative controls (n = 34) to establish whether this system could detect a spectrum of ND in HIV-infected youth (6–16 years). Results: Compared to a well-matched control group of HIV-negative youth, HIV-infected youth performed significantly more poorly on tests of Verbal IQ, Full Scale IQ, processing speed, finger tapping, verbal memory, expressive language, cognitive flexibility, and inhibition. HIV-infected youth were also more likely to have impaired total competence on the Child Behavior Checklist. Using the criteria for HAND, we found that 45.35% of the 86 HIV-infected youth could be diagnosed with an ND. Furthermore, youth with HIV encephalopathy (HIVE) were 9.4 times more likely to have a diagnosis of a major ND compared to HIV-infected youth without HIVE. Conclusions: The HAND criterion designed for adults was able to identify youth with important functional cognitive impairments who do not fit criteria for HIVE and would therefore not have been identified otherwise. This has major clinical implications regarding the importance of managing HIV-infected youth. PMID:27206720

  10. Infective endocarditis in drug addicts: role of HIV infection and the diagnostic accuracy of Duke criteria.

    PubMed

    Cecchi, Enrico; Imazio, Massimo; Tidu, Massimo; Forno, Davide; De Rosa, Francesco Giuseppe; Dal Conte, Ivano; Preziosi, Costantina; Lipani, Filippo; Trinchero, Rita

    2007-03-01

    Intravenous drug users (IVDUs) are at increased risk of infective endocarditis. Moreover, HIV infection is common in IVDUs, with a reported prevalence of 40-90%. The clinical features of IVDUs with infective endocarditis and HIV infection may be peculiar. Few data have been reported on the diagnostic accuracy of Duke criteria in IVDUs with or without HIV infection, and a comparison of these two populations is lacking. The present study aimed to compare prospectively the clinical features of patients with infective endocarditis with or without HIV infection and to evaluate the diagnostic accuracy of Duke criteria in these patients. The study population consisted of 201 consecutive adult IVDUs with a suspected infective endocarditis (102 patients with HIV infection and 99 patients without HIV infection). Infective endocarditis was the final diagnosis in 40 of 102 patients (38.2%) with HIV infection and in 55 of 99 HIV-negative patients (55.6%). Despite similar baseline features, longer vegetations were recorded in infective endocarditis without HIV infection (23.7 +/- 7.1 mm versus 13.6 +/- 6.8 mm; P = 0.001). Patients with infective endocarditis and HIV infection had a higher total mortality at 2 months (respectively 12.5% versus 1.8%; P = 0.09); almost all the deaths were recorded in patients with AIDS or a CD4 cell count below 200 per microl, and no deaths were recorded in patients with HIV infection and a CD4 cell count > 500 per microl. Despite no identical clinical features, Duke criteria had a similar sensitivity, specificity and diagnostic accuracy in IVDUs with and without HIV infection.

  11. Yellow fever vaccine for patients with HIV infection.

    PubMed

    Barte, Hilary; Horvath, Tara H; Rutherford, George W

    2014-01-23

    Yellow fever (YF) is an acute viral haemorrhagic disease prevalent in tropical Africa and Latin America. The World Health Organization (WHO) estimates that there are 200,000 cases of YF and 30,000 deaths worldwide annually. Treatment for YF is supportive, but a live attenuated virus vaccine is effective for preventing infection. WHO recommends immunisation for all individuals > 9 months living in countries or areas at risk. However, the United States Advisory Committee on Immunization Practices (ACIP) advises that YF vaccine is contraindicated in individuals with HIV. Given the large populations of HIV-infected individuals living in tropical areas where YF is endemic, YF vaccine may be an important intervention for preventing YF in immunocompromised populations. To assess the risk and benefits of YF immunisation for people infected with HIV. We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Randomised controlled trials and cohort studies of individuals with HIV infection who received YF vaccine (17DD or 17D-204). Two authors screened abstracts of references identified by electronic or bibliographic searches according to inclusion and exclusion criteria as detailed in the protocol. We identified 199 references and examined 19 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Three cohort studies were included in the review. They examined 484 patients with HIV infection who received YF immunisation. Patients with HIV infection developed significantly lower concentrations of neutralising antibodies in the first year post immunisation compared to uninfected patients, though decay patterns were similar for recipients regardless of HIV infection. No study patient with HIV infection suffered serious adverse events as a result of YF vaccination. YF vaccination can produce protective levels of neutralising antibodies in

  12. Neurological disorders in HIV-infected children in India.

    PubMed

    Gupta, S; Shah, D M; Shah, I

    2009-09-01

    There are few studies of HIV-related neurological disorders from centres in low-income countries where facilities are available for detailed investigation. Records of all patients attending the paediatric HIV outpatient department at B. J. Wadia Hospital for Children, Mumbai between April 2000 and March 2008 were reviewed. Of 668 HIV-infected patients, 48 (7.2%) had neurological manifestations and are included in this study. Twenty-six (54.2%) children had HIV encephalopathy. Other causes of neurological manifestations include febrile convulsion in five (10.4%), bacterial meningitis in three (6.3%), epilepsy in two (4.2%), tuberculous meningitis and progressive multi-focal encephalopathy in two (4.2%) each and toxoplasmosis, vasculitis, acute demyelinating encephalomyelitis, anti-phospholipid antibody syndrome, Down's syndrome, birth asphyxia, herpes simplex encephalopathy and mitochondrial encephalopathy in one (2.1%) each. Mean (SD) age at presentation was 4.36 (3.38) years with a range of 2 months to 15 years. The common subtle neurological manifestations were abnormal deep tendon reflexes and extensor plantar reflexes. The common symptomatic manifestations were delayed milestones in 21 children (43.8%) and seizures in 19 (39.6%). Seizures were more common in males (54%) than in females (25%) (p=0.038). In children <5 years, delayed milestones was the most common manifestation while focal neurological deficits were more common in older children. Of the 13 children who received HAART, nine (60.23%) improved. Early diagnosis of neurological disorders in HIV-infected children is important for appropriate investigation and management, especially the introduction of HAART.

  13. Syphilis and HIV co-infection. Epidemiology, treatment and molecular typing of Treponema pallidum.

    PubMed

    Salado-Rasmussen, Kirsten

    2015-12-01

    The studies included in this PhD thesis examined the interactions of syphilis, which is caused by Treponema pallidum, and HIV. Syphilis reemerged worldwide in the late 1990s and hereafter increasing rates of early syphilis were also reported in Denmark. The proportion of patients with concurrent HIV has been substantial, ranging from one third to almost two thirds of patients diagnosed with syphilis some years. Given that syphilis facilitates transmission and acquisition of HIV the two sexually transmitted diseases are of major public health concern. Further, syphilis has a negative impact on HIV infection, resulting in increasing viral loads and decreasing CD4 cell counts during syphilis infection. Likewise, HIV has an impact on the clinical course of syphilis; patients with concurrent HIV are thought to be at increased risk of neurological complications and treatment failure. Almost ten per cent of Danish men with syphilis acquired HIV infection within five years after they were diagnosed with syphilis during an 11-year study period. Interestingly, the risk of HIV declined during the later part of the period. Moreover, HIV-infected men had a substantial increased risk of re-infection with syphilis compared to HIV-uninfected men. As one third of the HIV-infected patients had viral loads >1,000 copies/ml, our conclusion supported the initiation of cART in more HIV-infected MSM to reduce HIV transmission. During a five-year study period, including the majority of HIV-infected patients from the Copenhagen area, we observed that syphilis was diagnosed in the primary, secondary, early and late latent stage. These patients were treated with either doxycycline or penicillin and the rate of treatment failure was similar in the two groups, indicating that doxycycline can be used as a treatment alternative - at least in an HIV-infected population. During a four-year study period, the T. pallidum strain type distribution was investigated among patients diagnosed by PCR

  14. Effects of Early, Abrupt Weaning on HIV-free Survival of Children in Zambia

    PubMed Central

    Kuhn, Louise; Aldrovandi, Grace M.; Sinkala, Moses; Kankasa, Chipepo; Semrau, Katherine; Mwiya, Mwiya; Kasonde, Prisca; Scott, Nancy; Vwalika, Cheswa; Walter, Jan; Bulterys, Marc; Tsai, Wei-Yann; Thea, Donald M.

    2008-01-01

    Background In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. Methods We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. Results In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P = 0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P = 0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P = 0.007). Conclusions Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants

  15. Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.

    PubMed

    Bi, Xiuqiong; Ishizaki, Azumi; Nguyen, Lam Van; Matsuda, Kazunori; Pham, Hung Viet; Phan, Chung Thi Thu; Ogata, Kiyohito; Giang, Thuy Thi Thanh; Phung, Thuy Thi Bich; Nguyen, Tuyen Thi; Tokoro, Masaharu; Pham, An Nhat; Khu, Dung Thi Khanh; Ichimura, Hiroshi

    2016-08-02

    CD4⁺ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(-)) aged 2-12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4⁺-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38⁺HLA (human leukocyte antigen)-DR⁺CD8⁺- (activated CD8⁺) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(-) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8⁺-cell activation status. Among the ART(+) children, the total CD4⁺-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8-8.3 years, whereas Th1 counts and the CD8⁺-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8⁺ cells and monocytes, and ART induced rapid Th1 recovery and early CD8⁺-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring.

  16. Recent advances targeting innate immunity-mediated therapies against HIV-1 infection.

    PubMed

    Shankar, Esaki Muthu; Velu, Vijayakumar; Vignesh, Ramachandran; Vijayaraghavalu, Sivakumar; Rukumani, Devi Velayuthan; Sabet, Negar Shafiei

    2012-08-01

    Early defence mechanisms of innate immunity respond rapidly to infection against HIV-1 in the genital mucosa. Additionally, innate immunity optimises effective adaptive immune responses against persistent HIV infection. Recent research has highlighted the intrinsic roles of apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G, tripartite motif-containing protein 5, tetherin, sterile α-motif and histidine/aspartic acid domain-containing protein 1 in restricting HIV-1 replication. Likewise, certain endogenously secreted antimicrobial peptides, namely α/β/θ-defensins, lactoferrins, secretory leukocyte protease inhibitor, trappin-2/elafin and macrophage inflammatory protein-3α are reportedly protective. Whilst certain factors directly inhibit HIV, others can be permissive. Interferon-λ3 exerts an anti-HIV function by activating Janus kinase-signal transducer and activator of transcription-mediated innate responses. Morphine has been found to impair intracellular innate immunity, contributing to HIV establishment in macrophages. Interestingly, protegrin-1 could be used therapeutically to inhibit early HIV-1 establishment. Moreover, chloroquine inhibits plasmacytoid dendritic cell activation and improves effective T-cell responses. This minireview summarizes the recently identified targets for innate immunity-mediated therapies and outlines the challenges that lie ahead in improving treatment of HIV infection. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

  17. Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

    PubMed

    Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L

    2010-11-01

    To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.

  18. Pediatric HIV Infection: A Neuropsychological and Educational Challenge.

    ERIC Educational Resources Information Center

    Armstrong, F. Daniel; And Others

    1993-01-01

    This article reviews the effects of human immunodeficiency virus (HIV) on the central nervous system and the educational implications of increasing numbers of students with perinatal HIV infection and pediatric acquired immunodeficiency syndrome (AIDS). Studies on the relationship between HIV and child development are urged. (Author/DB)

  19. Taking Antiretroviral Therapy for HIV Infection

    PubMed Central

    Laws, M Barton; Wilson, Ira B; Bowser, Diana M; Kerr, Sarah E

    2000-01-01

    OBJECTIVE To describe how people with HIV understand and experience the problem of adhering to antiretroviral medication regimens. DESIGN We performed a qualitative study based on interviews with HIV-infected patients, including 46 clients of AIDS service organizations, who were sampled according to age, ethnicity, and injection drug use history, and a convenience sample of 15 patients. Interviews were conducted in English or Spanish and were audiotaped and transcribed. PARTICIPANTS Of 52 respondents who had prescriptions for antiretroviral therapy, 25 were randomly selected for in-depth analysis. Of these, 5 reported having an AIDS diagnosis, 15 reported symptoms they attributed to HIV, and 5 reported having no symptoms of HIV disease. MEASUREMENTS AND MAIN RESULTS Investigators prepared structured abstracts of interviews to extract adherence-related data. One investigator compared the abstracts with the original transcripts to confirm the interpretations, and used the abstracts to organize and classify the findings. Most subjects (84%) reported recent nonadherent behavior, including ceasing treatment, medication “holidays,” sleeping through doses, forgetting doses, skipping doses due to side effects, and following highly asymmetric schedules. Initially, most reported that they were not significantly nonadherent, and many did not consider their behavior nonadherent. Only a minority clearly understood the possible consequences of missing doses. Most said they had not discussed their nonadherence with their physicians. CONCLUSIONS Many people rationalize their difficulty in adhering to HIV treatment by deciding that the standard of adherence they can readily achieve is appropriate. Physicians should inquire about adherence-related behavior in specific detail, and ensure that patients understand the consequences of not meeting an appropriate standard. PMID:11119181

  20. HIV Infection and Older Americans: The Public Health Perspective

    PubMed Central

    Buchacz, Kate; Gebo, Kelly A.; Mermin, Jonathan

    2012-01-01

    HIV disease is often perceived as a condition affecting young adults. However, approximately 11% of new infections occur in adults aged 50 years or older. Among persons living with HIV disease, it is estimated that more than half will be aged 50 years or older in the near future. In this review, we highlight issues related to HIV prevention and treatment for HIV-uninfected and HIV-infected older Americans, and outline unique considerations and emerging challenges for public health and patient management in these 2 populations. PMID:22698038

  1. [Impact of HIV/HBV infection and HIV/HBV co-infection on outcomes of pregnancy].

    PubMed

    Yang, Y; Cheng, W T; Zhou, Y B; Jiang, Q W

    2017-06-10

    Both HIV and HBV infection have become major health problems, of global concern, due to the high prevalence in the past few decades. Data from cumulated epidemiological surveys have shown the links between maternal HIV or HBV infection and adverse outcomes on pregnancy. Maternal HIV or HBV infection may also increase the mother-to-child (MTCT) transmission of the two diseases. However, association between HIV-HBV co-infection and adverse pregnancy is still inconclusive. Does maternal HIV-HBV co-infection have an impact on mother-to-child transmission on either HIV or HBV? Study on effective precautionary measures to promote both maternal and child's health is deemed necessary.

  2. [Neuromeningeal cryptococcosis in patients infected with HIV at Agadir regional hospital, (Souss-Massa, Morocco)].

    PubMed

    Chadli, S; Aghrouch, M; Taqarort, N; Malmoussi, M; Ouagari, Z; Moustaoui, F; Bourouache, M; Oulkheir, S

    2018-03-01

    Neuromeningeal cryptococcosis (NMC) is a severe and fatal opportunistic infection. Lethality is frequent in the absence of treatment, especially in the presence of HIV co-infection. To determine the prevalence, epidemiological, clinical, biological and therapeutic aspects as well as the evolution of NMC for patients infected with HIV. This is a retrospective study of 40 cases of neuromeningeal cryptococcosis diagnosed in HIV-infected patients. Data are collected for 7 years (from January 2010 to December 2016) in the registers of the parasitology laboratory and the infectious diseases department at the regional hospital center in Agadir. A reduction in the prevalence of neuromeningeal cryptococcosis in HIV-infected patients was noted from 2010 to 2016 (3.66% to 0.83%). The overall prevalence of NMC was 1.53%. The mean age was 37±10 years old, with 90% of patients aged less than 45 years. The main clinical symptomatology was headache (75%). The main cytochemical abnormalities of cerebrospinal fluid analysis were hyperproteinorachy (60%), hypoglycorachy (63%) and lymphocytosis (50%). The mean CD4 cell count was 47/mm 3 . Patients were initially treated with amphotericin B, relayed with fluconazole. The overall lethality was 35%. Neuromeningeal cryptococcosis is a serious opportunistic infection in patients HIV-infected, and the lethality rate remains unacceptable. Fighting NMC in HIV+ patients requires early diagnosis, increased access to antiretrovirals, rapid introduction of appropriate treatment and the prescription of effective systemic antifungals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. The immunology of Leishmania/HIV co-infection.

    PubMed

    Okwor, Ifeoma; Uzonna, Jude Eze

    2013-05-01

    Leishmaniases are emerging as an important disease in human immunodeficiency virus (HIV)-infected persons living in several sub-tropical and tropical regions around the world, including the Mediterranean. The HIV/AIDS pandemic is spreading at an alarming rate in Africa and the Indian subcontinent, areas with very high prevalence of leishmaniases. The spread of HIV into rural areas and the concomitant spread of leishmaniases to suburban/urban areas have helped maintain the occurrence of Leishmania/HIV co-infection in many parts of the world. The number of cases of Leishmania/HIV co-infection is expected to rise owing to the overlapping geographical distribution of the two infections. In Southwestern Europe, there is also an increasing incidence of Leishmania/HIV co-infection (particularly visceral leishmaniasis) in such countries as France, Italy, Spain and Portugal. Studies suggest that in humans, very complex mechanisms involving dysregulation of host immune responses contribute to Leishmania-mediated immune activation and pathogenesis of HIV. In addition, both HIV-1 and Leishmania infect and multiply within cells of myeloid or lymphoid origin, thereby presenting a perfect recipe for reciprocal modulation of Leishmania and HIV-1-related disease pathogenesis. Importantly, because recovery from leishmaniases is associated with long-term persistence of parasites at the primary infection sites and their draining lymph nodes, there is very real possibility that HIV-mediated immunosuppression (due to CD4(+) T cell depletion) could lead to reactivation of latent infections (reactivation leishmaniasis) in immunocompromised patients. Here, we present an overview of the immunopathogenesis of Leishmania/HIV co-infection and the implications of this interaction on Leishmania and HIV disease outcome.

  4. HIV dynamics with multiple infections of target cells.

    PubMed

    Dixit, Narendra M; Perelson, Alan S

    2005-06-07

    The high incidence of multiple infections of cells by HIV sets the stage for rapid HIV evolution by means of recombination. Yet how HIV dynamics proceeds with multiple infections remains poorly understood. Here, we present a mathematical model that describes the dynamics of viral, target cell, and multiply infected cell subpopulations during HIV infection. Model calculations reproduce several experimental observations and provide key insights into the influence of multiple infections on HIV dynamics. We find that the experimentally observed scaling law, that the number of cells coinfected with two distinctly labeled viruses is proportional to the square of the total number of infected cells, can be generalized so that the number of triply infected cells is proportional to the cube of the number of infected cells, etc. Despite the expectation from Poisson statistics, we find that this scaling relationship only holds under certain conditions, which we predict. We also find that multiple infections do not influence viral dynamics when the rate of viral production from infected cells is independent of the number of times the cells are infected, a regime expected when viral production is limited by cellular rather than viral factors. This result may explain why extant models, which ignore multiple infections, successfully describe viral dynamics in HIV patients. Inhibiting CD4 down-modulation increases the average number of infections per cell. Consequently, altering CD4 down-modulation may allow for an experimental determination of whether viral or cellular factors limit viral production.

  5. HIV dynamics with multiple infections of target cells

    PubMed Central

    Dixit, Narendra M.; Perelson, Alan S.

    2005-01-01

    The high incidence of multiple infections of cells by HIV sets the stage for rapid HIV evolution by means of recombination. Yet how HIV dynamics proceeds with multiple infections remains poorly understood. Here, we present a mathematical model that describes the dynamics of viral, target cell, and multiply infected cell subpopulations during HIV infection. Model calculations reproduce several experimental observations and provide key insights into the influence of multiple infections on HIV dynamics. We find that the experimentally observed scaling law, that the number of cells coinfected with two distinctly labeled viruses is proportional to the square of the total number of infected cells, can be generalized so that the number of triply infected cells is proportional to the cube of the number of infected cells, etc. Despite the expectation from Poisson statistics, we find that this scaling relationship only holds under certain conditions, which we predict. We also find that multiple infections do not influence viral dynamics when the rate of viral production from infected cells is independent of the number of times the cells are infected, a regime expected when viral production is limited by cellular rather than viral factors. This result may explain why extant models, which ignore multiple infections, successfully describe viral dynamics in HIV patients. Inhibiting CD4 down-modulation increases the average number of infections per cell. Consequently, altering CD4 down-modulation may allow for an experimental determination of whether viral or cellular factors limit viral production. PMID:15928092

  6. Stem cell transplantation in the context of HIV--how can we cure HIV infection?

    PubMed

    Bauer, Gerhard; Anderson, Joseph S

    2014-01-01

    All HIV target cells are derived from hematopoietic stem cells. More than two decades ago, a hypothesis was postulated that a cure for HIV may be possible by performing a transplant with HIV-resistant hematopoietic stem cells that would allow for an HIV-resistant immune system to arise. HIV-resistant stem cells could be generated by genetically modifying them with gene therapy vectors transferring anti-HIV genes. First attempts of stem cell gene therapy for HIV were carried out in the USA in the 1990s demonstrating safety, but also little efficacy at that time. The first demonstration that the postulated hypothesis was correct was the cure of an HIV-infected individual in Berlin in 2009 who received an allogeneic bone marrow transplant from a donor who lacked the CCR5 chemokine receptor, a naturally arising mutation rendering HIV target cells resistant to infection with macrophage tropic strains of HIV. In 2013, reports were published about a possible cure of HIV-infected individuals who received allogeneic bone marrow transplants with cells not resistant to HIV. We will review these stem cell transplant procedures and discuss their utility to provide a cure for HIV infection, including efficacious future stem cell gene therapy applications.

  7. Cloning of a long HIV-1 readthrough transcript and detection of an increased level of early growth response protein-1 (Egr-1) mRNA in chronically infected U937 cells.

    PubMed

    Dron, M; Hameau, L; Benboudjema, L; Guymarho, J; Cajean-Feroldi, C; Rizza, P; Godard, C; Jasmin, C; Tovey, M G; Lang, M C

    1999-01-01

    To identify the pathways involved in HIV-1 modification of cellular gene expression, chronically infected U937 cells were screened by mRNA differential display. A chimeric transcript consisting of the 3' end of the LTR of a HIV-1 provirus, followed by 3.7 kb of cellular RNA was identified suggesting that long readthrough transcription might be one of the mechanisms by which gene expression could be modified in individual infected cells. Such a phenomenon may also be the first step towards the potential transduction of cellular sequences. Furthermore, the mRNA encoding for the transcription factor Egr-1 was detected as an over-represented transcript in infected cells. Northern blot analysis confirmed the increase of Egr-1 mRNA content in both HIV-1 infected promonocytic U937 cells and T cell lines such as Jurkat and CEM. Interestingly a similar increase of Egr-1 mRNA has previously been reported to occur in HTLV-1 and HTLV-2 infected T cell lines. Despite the consistent increase in the level of Egr-1 mRNA, the amount of the encoded protein did not appear to be modified in HIV-1 infected cells, suggesting an increased turn over of the protein in chronically infected cells.

  8. Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America

    PubMed Central

    Cesar, Carina; Shepherd, Bryan E.; Krolewiecki, Alejandro J.; Fink, Valeria I.; Schechter, Mauro; Tuboi, Suely H.; Wolff, Marcelo; Pape, Jean W.; Leger, Paul; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; Sued, Omar; McGowan, Catherine C.; Masys, Daniel R.; Cahn, Pedro E.

    2010-01-01

    Background HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%–70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. Methodology Antiretroviral-naïve patients > = 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. Principal Findings Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31–44), and median CD4 count was 105 cells/uL (IQR, 38–200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15–17%) and 28% (95% CI 27–29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1–2.6) and 2.1 (95% CI 1.7–2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1–1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. Conclusions Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed

  9. The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial.

    PubMed

    Menezes, C N; Duarte, R; Dickens, C; Dix-Peek, T; Van Amsterdam, D; John, M-A; Ive, P; Maskew, M; Macphail, P; Fox, M P; Raal, F; Sanne, I; Crowther, N J

    2013-04-01

    Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients. Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism. These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF. © 2012 British HIV Association.

  10. Serious Non-AIDS Conditions in HIV: Benefit of Early ART.

    PubMed

    Lundgren, Jens D; Borges, Alvaro H; Neaton, James D

    2018-04-01

    Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function. HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.

  11. Impact of early treatment programs on HIV epidemics: An immunity-based mathematical model.

    PubMed

    Rahman, S M Ashrafur; Vaidya, Naveen K; Zou, Xingfu

    2016-10-01

    While studies on pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) have demonstrated substantial advantages in controlling HIV transmission, the overall benefits of the programs with early initiation of antiretroviral therapy (ART) have not been fully understood and are still on debate. Here, we develop an immunity-based (CD4+ T cell count based) mathematical model to study the impacts of early treatment programs on HIV epidemics and the overall community-level immunity. The model is parametrized using the HIV prevalence data from South Africa and fully analyzed for stability of equilibria and infection persistence criteria. Using our model, we evaluate the effects of early treatment on the new infection transmission, disease death, basic reproduction number, HIV prevalence, and the community-level immunity. Our model predicts that the programs with early treatments significantly reduce the new infection transmission and increase the community-level immunity, but the treatments alone may not be enough to eliminate HIV epidemics. These findings, including the community-level immunity, might provide helpful information for proper implementation of HIV treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Foster care history and HIV infection among drug-using African American female sex workers.

    PubMed

    Surratt, Hilary L; Kurtz, Steven P

    2012-05-01

    Foster care has been associated with increased HIV risk behaviors among youth, yet long-term association with HIV infection has not been examined. This study explored the associations between foster placement, victimization, mental health, onset of sex work and HIV infection among highly vulnerable female sex workers. 562 drug-involved African American women were enrolled into an intervention study to increase health services utilization and reduce HIV risk. Seventeen percent reported a history of foster placement. Foster history was associated with significantly lower educational attainment, higher victimization, and more severe mental health problems. Women with foster histories reported significantly earlier entry into paid sex work, with some 62% active in the sex trade before age 18. Multivariate analyses found that foster care was independently associated with HIV seropositivity, and that early sex work partially mediated this association. The potential long-term health vulnerabilities associated with foster placement are understudied and warrant additional research.

  13. T cells establish and maintain CNS viral infection in HIV-infected humanized mice.

    PubMed

    Honeycutt, Jenna B; Liao, Baolin; Nixon, Christopher C; Cleary, Rachel A; Thayer, William O; Birath, Shayla L; Swanson, Michael D; Sheridan, Patricia; Zakharova, Oksana; Prince, Francesca; Kuruc, JoAnn; Gay, Cynthia L; Evans, Chris; Eron, Joseph J; Wahl, Angela; Garcia, J Victor

    2018-06-04

    The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell-only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state.

  14. Management of bone mineral density in HIV-infected patients.

    PubMed

    Negredo, Eugenia; Bonjoch, Anna; Clotet, Bonaventura

    2016-01-01

    Loss of bone mineral density is an emerging problem in persons living with HIV infection. Earlier and more rapid bone demineralization has been attributed not only to the high prevalence of traditional risk factors, but also to specific HIV-related factors. The aim of this guidance is to stimulate an appropriate management of osteoporosis in this population, to identify patients at risk and to better manage them. Appropriate screening of HIV-infected subjects to identify those at risk for bone fractures is described, as well as the recommended interventions. American and European recommendations in HIV-infected and non-infected populations were considered. As the etiology of bone loss is multifactorial, many factors have to be addressed. Overall, recommendations on traditional risk factors are the same for HIV-infected and non-HIV-infected subjects. However, we should consider some specific factors in the HIV-infected population, including an appropriate antiretroviral therapy in patients with low bone mineral density, and probably novel strategies that could provide an additional benefit, such as anti-inflammatory drugs, although data supporting this approach are scant. Some personal opinions are highlighted on the management of bone health in HIV-infected subjects, mainly on the use of FRAX(®) score and DXA scans. In addition, the need to implement new strategies to delay demineralization is remarked upon.

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

    PubMed

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

    2018-05-18

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

  16. Gut Microbiota Linked to Sexual Preference and HIV Infection

    PubMed Central

    Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

    2016-01-01

    The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

  17. Gut Microbiota Linked to Sexual Preference and HIV Infection.

    PubMed

    Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

    2016-03-01

    The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.

  18. Treatment of HIV infection: Swedish recommendations 2009.

    PubMed

    Josephson, Filip; Albert, Jan; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Moberg, Lars; Navér, Lars; Svedhem, Veronica; Svennerholm, Bo; Sönnerborg, Anders

    2009-01-01

    On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/microl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.

  19. Platelet activation suppresses HIV-1 infection of T cells

    PubMed Central

    2013-01-01

    Background Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. Results We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Conclusions Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens. PMID:23634812

  20. Platelet activation suppresses HIV-1 infection of T cells.

    PubMed

    Solomon Tsegaye, Theodros; Gnirß, Kerstin; Rahe-Meyer, Niels; Kiene, Miriam; Krämer-Kühl, Annika; Behrens, Georg; Münch, Jan; Pöhlmann, Stefan

    2013-05-01

    Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.

  1. Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

    PubMed Central

    Cele, Sandile; Ferreira, Isabella Markham; Young, Andrew C; Karim, Farina; Madansein, Rajhmun; Dullabh, Kaylesh J; Chen, Chih-Yuan; Buckels, Noel J; Ganga, Yashica; Khan, Khadija; Boulle, Mikael; Lustig, Gila; Neher, Richard A

    2018-01-01

    HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high. PMID:29555018

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

    PubMed

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

    2000-10-20

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

  3. Intestinal Parasitic Infections in HIV Infected and Non-Infected Patients in a Low HIV Prevalence Region, West-Cameroon

    PubMed Central

    Nkenfou, Céline Nguefeu; Nana, Christelle Tafou; Payne, Vincent Khan

    2013-01-01

    The magnitude of intestinal parasitic infection in acquired immunodeficiency syndrome patients requires careful consideration in the developing world where poor nutrition is associated with poor hygiene and several tropical diseases. However, there have been very few studies addressing this issue in Cameroon. This study was conducted to determine the prevalence of intestinal parasitosis in HIV/AIDS patients in Dschang -Cameroon. Stool and blood specimens from HIV/AIDS patients and control group were screened respectively for intestinal parasites and for HIV antibodies. Intestinal parasites were identified using direct microscopy, formalin-ether concentration and Ziehl Neelsen methods. Out of 396 participants recruited among patients consulting at hospital, 42 (10.6%) were HIV positive, thirty of them treatment naïve. The overall prevalence of intestinal parasites was 14.64%. Out of 42 HIV/AIDS patients, 59.5% (25/42) were infected with intestinal parasites, while only 9.32% (33/354) of the HIV negative patients were infected with intestinal parasites. The parasites detected in our study population included Crystosporidium parvum (2.53%), Entamoeba histolytica (7.52%), Entamoeba coli (4.04%), Giardia lamblia (0.25%), Trichuris trichura (0.25%), Strongyloides stercoralis (0.25%) and Taenia spp. (0.25%). In the HIV infected group, Crystosporidium parvum (19.04%), Entamoeba histolytica (19.04%), Entamoeba coli (21.42%), Giardia lamblia (2.38%), Strongyloides stercoralis (0.25%) and Taenia spp. (0.25%) were found. Crystosporidium parvum was found to be significantly higher in HIV/AIDS patients than in controls (P<0.05). Multivariate analysis showed that the HIV status and the quality of water were the major risk factors for intestinal parasitosis. Routine examinations of stool samples for parasites would significantly benefit the HIV patients by contributing in reducing morbidity and improving the efficiency of antiretroviral treatment. Even after the introduction of

  4. Ocular surface squamous neoplasia in HIV-infected patients: current perspectives.

    PubMed

    Rathi, Shweta Gupta; Ganguly Kapoor, Anasua; Kaliki, Swathi

    2018-01-01

    Ocular surface squamous neoplasia (OSSN) refers to a spectrum of conjunctival and corneal epithelial tumors including dysplasia, carcinoma in situ, and invasive carcinoma. In this article, we discuss the current perspectives of OSSN associated with HIV infection, focusing mainly on the epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of these tumors in patients with HIV. Upsurge in the incidence of OSSN with the HIV pandemic most severely affected sub-Saharan Africa, due to associated risk factors, such as human papilloma virus and solar ultraviolet exposure. OSSN has been reported as the first presenting sign of HIV/AIDS in 26%-86% cases, and seropositivity is noted in 38%-92% OSSN patients. Mean age at presentation of OSSN has dropped to the third to fourth decade in HIV-positive patients in developing countries. HIV-infected patients reveal large aggressive tumors, higher-grade malignancy, higher incidence of corneal, scleral, and orbital invasion, advanced-stage T4 tumors, higher need for extended enucleation/exenteration, and increased risk of tumor recurrence. Current management of OSSN in HIV-positive individuals is based on standard treatment guidelines described for OSSN in the general population, as there is little information available about various treatment modalities or their outcomes in patients with HIV. OSSN can occur at any time in the disease course of HIV/AIDS, and no significant trend has been discovered between CD4 count and grade of OSSN. Furthermore, the effect of highly active antiretroviral therapy on OSSN is controversial. The current recommendation is to conduct HIV screening in all cases presenting with OSSN to rule out undiagnosed HIV infection. Patient counseling is crucial, with emphasis on regular follow-up to address high recurrence rates and early presentation to an ophthalmologist for of any symptoms in the unaffected eye. Effective evidence-based interventions are needed to allow early diagnosis

  5. Live attenuated herpes zoster vaccine for HIV-infected adults.

    PubMed

    Shafran, S D

    2016-04-01

    Multiple guidelines exist for the use of live viral vaccines for measles-mumps-rubella (MMR), varicella and yellow fever in people with HIV infections, but these guidelines do not make recommendations regarding live attenuated herpes zoster vaccine (LAHZV), which is approved for people over 50 years in the general population. LAHZV is made with the same virus used in varicella vaccine. The incidence of herpes zoster remains increased in people with HIV infection, even when on suppressive antiretroviral therapy, and a growing proportion of HIV-infected patients are over 50 years of age. The purpose of this article is to review the use of varicella vaccine and LAHZV in people with HIV infection and to make recommendations about the use of LAHZV in adults with HIV infection. A PubMed search was undertaken using the terms 'herpes zoster AND HIV' and 'varicella AND HIV'. Reference lists were also reviewed for pertinent citations. Varicella vaccine is recommended in varicella-susceptible adults, as long as they have a CD4 count > 200 cells/μL, the same CD4 threshold used for MMR and yellow fever vaccines. No transmission of vaccine strain Varicella zoster virus has been documented in people with HIV infections with a CD4 count above this threshold. LAHZV was administered to 295 HIV-infected adults with a CD4 count > 200 cells/μL, and was safe and immunogenic with no cases of vaccine strain infection. It is recommended that LAHZV be administered to HIV-infected adults with a CD4 count above 200 cells/μL, the same CD4 threshold used for other live attenuated viral vaccines. © 2015 British HIV Association.

  6. CD4 mimetics sensitize HIV-1-infected cells to ADCC.

    PubMed

    Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B; Park, Jongwoo; Jones, David M; Courter, Joel R; Melillo, Bruno N; Kaufmann, Daniel E; Hahn, Beatrice H; Permar, Sallie R; Haynes, Barton F; Madani, Navid; Sodroski, Joseph G; Finzi, Andrés

    2015-05-19

    HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.

  7. CD4 mimetics sensitize HIV-1-infected cells to ADCC

    PubMed Central

    Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie; Iyer, Shilpa S.; Roger, Michel; Martin, Loïc; Pazgier, Marzena; Schön, Arne; Freire, Ernesto; Routy, Jean-Pierre; Smith, Amos B.; Park, Jongwoo; Jones, David M.; Courter, Joel R.; Melillo, Bruno N.; Kaufmann, Daniel E.; Hahn, Beatrice H.; Permar, Sallie R.; Haynes, Barton F.; Madani, Navid; Sodroski, Joseph G.; Finzi, Andrés

    2015-01-01

    HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection. PMID:25941367

  8. Prevalence and mortality of cancer among HIV-infected inpatients in Beijing, China.

    PubMed

    Yang, Jun; Su, Shu; Zhao, Hongxin; Wang, Dennis; Wang, Jiali; Zhang, Fujie; Zhao, Yan

    2016-02-16

    Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer. Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p < 0.001). For patients diagnosed with cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p < 0.001]. The prevalence of cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients.

  9. Genital infections and syndromic diagnosis among HIV-infected women in HIV care programs in Kenya

    PubMed Central

    Djomand, Gaston; Gao, Hongjiang; Singa, Benson; Hornston, Sureyya; Bennett, Eddas; Odek, James; McClelland, R. Scott; John-Stewart, Grace; Bock, Naomi

    2015-01-01

    Background Control of genital infections remains challenging in most regions. Despite advocacy by the World Health Organization (WHO) for syndromic case management, there are limited data on the syndromic approach, especially in HIV care settings. This study compared the syndromic approach against laboratory diagnosis among women in HIV care in Kenya. Methods A mobile team visited 39 large HIV care programs in Kenya and enrolled participants using population-proportionate sampling. Participants provided behavioral and clinical data with genital and blood specimens for lab testing. Results Among 1,063 women, 68.4% had been on antiretroviral therapy >1 year; 58.9% were using cotrimoxazole prophylaxis; 51 % had CD4+T-lymphocytes < 350 cells/mL. Most women (63.1%) reported at least one genital symptom. Clinical signs were found in 63% of women; and 30.8% had an etiological diagnosis. Bacterial vaginosis (17.4%), vaginal candidiasis (10.6%) and trichomoniasis (10.5%) were the most common diagnoses. Using laboratory diagnoses as gold standard, sensitivity and positive predictive value of the syndromic diagnosis for vaginal discharge were 47.6% and 52.7%, respectively, indicating a substantial amount of overtreatment. A systematic physical examination increased by 9.3% the positive predictive value for genital ulcer disease. Conclusions Women attending HIV care programs in Kenya have high rates of vaginal infections. Syndromic diagnosis was a poor predictor of those infections. PMID:25614522

  10. Genital infections and syndromic diagnosis among HIV-infected women in HIV care programmes in Kenya.

    PubMed

    Djomand, Gaston; Gao, Hongjiang; Singa, Benson; Hornston, Sureyya; Bennett, Eddas; Odek, James; McClelland, R Scott; John-Stewart, Grace; Bock, Naomi

    2016-01-01

    Control of genital infections remains challenging in most regions. Despite advocacy by the World Health Organization for syndromic case management, there are limited data on the syndromic approach, especially in HIV care settings. This study compared the syndromic approach with laboratory diagnosis among women in HIV care in Kenya. A mobile team visited 39 large HIV care programmes in Kenya and enrolled participants using population-proportionate sampling. Participants provided behavioural and clinical data with genital and blood specimens for lab testing. Among 1063 women, 68.4% had been on antiretroviral therapy >1 year; 58.9% were using cotrimoxazole prophylaxis; 51 % had CD4+T-lymphocytes < 350 cells/µL. Most women (63.1%) reported at least one genital symptom. Clinical signs were found in 63% of women; and 30.8% had an aetiological diagnosis. Bacterial vaginosis (17.4%), vaginal candidiasis (10.6%) and trichomoniasis (10.5%) were the most common diagnoses. Using laboratory diagnoses as gold standard, sensitivity and positive predictive value of the syndromic diagnosis for vaginal discharge were 47.6% and 52.7%, respectively, indicating a substantial amount of overtreatment. A systematic physical examination increased by 9.3% the positive predictive value for genital ulcer disease. Women attending HIV care programmes in Kenya have high rates of vaginal infections. Syndromic diagnosis was a poor predictor of those infections. © The Author(s) 2015.

  11. Early physiological abnormalities after simian immunodeficiency virus infection.

    PubMed

    Horn, T F; Huitron-Resendiz, S; Weed, M R; Henriksen, S J; Fox, H S

    1998-12-08

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

  12. Early physiological abnormalities after simian immunodeficiency virus infection

    PubMed Central

    Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

    1998-01-01

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

  13. Transitioning HIV-infected youth into adult health care.

    PubMed

    2013-07-01

    With advances in antiretroviral therapy, most HIV-infected children survive into adulthood. Optimal health care for these youth includes a formal plan for the transition of care from primary and/or subspecialty pediatric/adolescent/family medicine health care providers (medical home) to adult health care provider(s). Successful transition involves the early engagement and participation of the youth and his or her family with the pediatric medical home and adult health care teams in developing a formal plan. Referring providers should have a written policy for the transfer of HIV-infected youth to adult care, which will guide in the development of an individualized plan for each youth. The plan should be introduced to the youth in early adolescence and modified as the youth approaches transition. Assessment of developmental milestones is important to define the readiness of the youth in assuming responsibility for his or her own care before initiating the transfer. Communication among all providers is essential and should include both personal contact and a written medical summary. Progress toward the transition should be tracked and,once completed, should be documented and assessed.

  14. ALS syndrome in patients with HIV-1 infection.

    PubMed

    Verma, Ashok; Berger, Joseph R

    2006-01-15

    A viral etiology of amyotrophic lateral sclerosis (ALS) has been proposed because of the selective vulnerability of motor neurons to certain viruses. During the last 20 years, at least 19 cases of ALS or ALS-like disease have been reported in HIV-1 (HIV) seropositive individuals. To describe two cases of clinically definite ALS in patients with HIV infection and to review the previously reported cases of HIV-associated ALS syndrome. A multidisciplinary ALS center and Neuro-AIDS clinic at a tertiary care university hospital. We investigated and prospectively monitored two patients who had developed clinically definite ALS by El Escorial criteria several years after acquiring the HIV infection. The previously reported cases of ALS or ALS-like disease in patients with HIV infection were reviewed for comparison and contrast with the characteristics of sporadic ALS. The clinical course of ALS in our two HIV seropositive individuals mirrored that of classical sporadic ALS. A review of previously described 19 patients with ALS syndrome revealed clinically definite ALS in 4 cases and clinically probable or possible ALS in 15. ALS commenced at different stages of the HIV disease; in 7 patients, HIV infection was discovered contemporaneously with diagnosis of ALS. CD4+ T cell count ranged from 2 to 560 cells/mm3. Three (1 definite ALS) of the fatal cases were studied at autopsy and all exhibited pathology outside the motor neuron pool. Unlike our patients, 7 of 8 patients with HIV-associated ALS syndrome receiving HAART demonstrated at least partial recovery of their motor deficit. ALS-like syndrome can occur in association with HIV infection; however, the causal relationship remains uncertain. Patients with ALS syndrome related to HIV infection are generally younger in age and often demonstrate pathology outside the motor neuron system. Patients with HIV-associated ALS syndrome may improve following antiretroviral therapy. An aggressive HAART regimen to reduce viral load

  15. Outcomes of cervical cancer among HIV-infected and HIV-uninfected women treated at the Brazilian National Institute of Cancer.

    PubMed

    Ferreira, Mariana P; Coghill, Anna E; Chaves, Claudia B; Bergmann, Anke; Thuler, Luiz C; Soares, Esmeralda A; Pfeiffer, Ruth M; Engels, Eric A; Soares, Marcelo A

    2017-02-20

    We assessed mortality, treatment response, and relapse among HIV-infected and HIV-uninfected women with cervical cancer in Rio de Janeiro, Brazil. Cohort study of 87 HIV-infected and 336 HIV-uninfected women with cervical cancer. Patients at the Brazilian National Institute of Cancer (2001-2013) were matched on age, calendar year of diagnosis, clinical stage, and tumor histology. Staging and treatment with surgery, radiotherapy, and/or chemotherapy followed international guidelines. We used a Markov model to assess responses to initial therapy, and Cox models for mortality and relapse after complete response (CR). Among 234 deaths, most were from cancer (82% in HIV-infected vs. 93% in HIV-uninfected women); only 9% of HIV-infected women died from AIDS. HIV was not associated with mortality during initial follow-up but was associated more than 1-2 years after diagnosis [overall mortality: stage-adjusted hazard ratio 2.02, 95% confidence interval (CI) 1.27-3.22; cancer-specific mortality: 4.35, 1.86-10.2]. Among 222 patients treated with radiotherapy, HIV-infected had similar response rates to initial cancer therapy as HIV-uninfected women (hazard ratio 0.98, 95% CI 0.58-1.66). However, among women who were treated and had a CR, HIV was associated with elevated risk of subsequent relapse (hazard ratio 3.60, 95% CI 1.86-6.98, adjusted for clinical stage). Among women with cervical cancer, HIV infection was not associated with initial treatment response or early mortality, but relapse after attaining a CR and late mortality were increased in those with HIV. These results point to a role for an intact immune system in control of residual tumor burden among treated cervical cancer patients.

  16. Molecular clock of HIV-1 envelope genes under early immune selection

    DOE PAGES

    Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.; ...

    2016-06-01

    Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

  17. Molecular clock of HIV-1 envelope genes under early immune selection

    SciT

    Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.

    Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

  18. Exploring Factors Associated with Recent HIV Testing among Heterosexuals at High Risk for HIV Infection Recruited with Venue-based Sampling.

    PubMed

    Gwadz, Marya; Cleland, Charles M; Jenness, Samuel M; Silverman, Elizabeth; Hagan, Holly; Ritchie, Amanda S; Leonard, Noelle R; McCright-Gill, Talaya; Martinez, Belkis; Swain, Quentin; Kutnick, Alexandra; Sherpa, Dawa

    2016-02-01

    Annual HIV testing is recommended for high-risk populations in the United States, to identify HIV infections early and provide timely linkage to treatment. However, heterosexuals at high risk for HIV, due to their residence in urban areas of high poverty and elevated HIV prevalence, test for HIV less frequently than other risk groups, and late diagnosis of HIV is common. Yet the factors impeding HIV testing in this group, which is predominantly African American/Black and Latino/Hispanic, are poorly understood. The present study addresses this gap. Using a systematic community-based sampling method, venue-based sampling (VBS), we estimate rates of lifetime and recent (past year) HIV testing among high-risk heterosexuals (HRH), and explore a set of putative multi-level barriers to and facilitators of recent testing, by gender. Participants were 338 HRH African American/Black and Latino/Hispanic adults recruited using VBS, who completed a computerized structured assessment battery guided by the Theory of Triadic Influence, comprised of reliable/valid measures on socio-demographic characteristics, HIV testing history, and multi-level barriers to HIV testing. Logistic regression analysis was used to identify factors associated with HIV testing within the past year. Most HRH had tested at least once (94%), and more than half had tested within the past year (58%), but only 37% tested annually. In both men and women, the odds of recent testing were similar and associated with structural factors (better access to testing) and sexually transmitted infection (STI) testing and diagnosis. Thus VBS identified serious gaps in rates of annual HIV testing among HRH. Improvements in access to high-quality HIV testing and leveraging of STI testing are needed to increase the proportion of HRH testing annually for HIV. Such improvements could increase early detection of HIV, improve the long-term health of individuals, and reduce HIV transmission by increasing rates of viral

  19. Innate Lymphoid Cells in HIV/SIV Infections.

    PubMed

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  20. Innate Lymphoid Cells in HIV/SIV Infections

    PubMed Central

    Shah, Spandan V.; Manickam, Cordelia; Ram, Daniel R.; Reeves, R. Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections. PMID:29326704

  1. Perinatal HIV Infection and Exposure and Their Association With Dental Caries in Nigerian Children.

    PubMed

    Coker, Modupe; El-Kamary, Samer S; Enwonwu, Cyril; Blattner, William; Langenberg, Patricia; Mongodin, Emmanuel; Akhigbe, Paul; Obuekwe, Ozo; Omoigberale, Austin; Charurat, Manhattan

    2018-01-01

    Although HIV infection is associated with well-known oral pathologies, there remains a dearth of comparative studies aimed at determining the association between HIV infection/exposure and early childhood caries. This is a cross-sectional study using a convenience sample of 3 groups of children receiving care at a tertiary care hospital in Nigeria. The groups include HIV infected (HI), HIV exposed but uninfected and HIV-unexposed and -uninfected children 6 through 72 months of age. Medical records were reviewed, and caregivers were interviewed for sociodemographic, maternal and birth factors as well as early feeding and dietary information. Oral examinations were performed by trained dentist examiners. Of 335 children enrolled, 33 (9.9%) presented with caries. In an adjusted analysis, compared with HIV-unexposed and -uninfected children, HI children had significantly greater odds of having caries (odds ratio = 2.58; 95% confidence interval: 1.04-6.40; P = 0.04), but there was no statistically significant difference in HIV exposed but uninfected children (odds ratio = 2.01; 95% confidence interval: 0.56-7.23; P = 0.28). Factors significantly associated with higher caries prevalence include low CD4 counts and percentage, older age, longer duration of breastfeeding and spontaneous membrane rupture during delivery. Caries was more prevalent in HI children. These findings support the need to target HI children for oral health prevention and treatment services particularly in Nigeria and other developing countries.

  2. HIV Infection Legal Issues: An Introduction for Developmental Services. Technical Report on Developmental Disabilities and HIV Infection, Number 2.

    ERIC Educational Resources Information Center

    Harvey, David C.; Decker, Curtis L.

    As agencies and programs serving individuals with developmental disabilities are called upon to serve a new population of individuals with human immunodeficiency virus (HIV) infection, they will be forced to confront complex legal questions. This paper discusses the legal frameworks in which individuals with HIV infection are considered eligible…

  3. HIV-1 infection depletes human CD34+CD38- hematopoietic progenitor cells via pDC-dependent mechanisms.

    PubMed

    Li, Guangming; Zhao, Juanjuan; Cheng, Liang; Jiang, Qi; Kan, Sheng; Qin, Enqiang; Tu, Bo; Zhang, Xin; Zhang, Liguo; Su, Lishan; Zhang, Zheng

    2017-07-01

    Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to multi-lineage hematopoietic abnormalities or pancytopenia. The deficiency in hematopoietic progenitor cells (HPCs) induced by HIV-1 infection has been proposed, but the relevant mechanisms are poorly understood. We report here that both human CD34+CD38- early and CD34+CD38+ intermediate HPCs were maintained in the bone marrow (BM) of humanized mice. Chronic HIV-1 infection preferentially depleted CD34+CD38- early HPCs in the BM and reduced their proliferation potential in vivo in both HIV-1-infected patients and humanized mice, while CD34+CD38+ intermediate HSCs were relatively unaffected. Strikingly, depletion of plasmacytoid dendritic cells (pDCs) prevented human CD34+CD38- early HPCs from HIV-1 infection-induced depletion and functional impairment and restored the gene expression profile of purified CD34+ HPCs in humanized mice. These findings suggest that pDCs contribute to the early hematopoietic suppression induced by chronic HIV-1 infection and provide a novel therapeutic target for the hematopoiesis suppression in HIV-1 patients.

  4. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2)

    ClinicalTrials.gov

    2016-04-13

    Acquired Immunodeficiency Syndrome; Lung Diseases; Cardiovascular Diseases; Heart Diseases; Heart Failure; HIV Infections; Cytomegalovirus Infections; Pneumocystis Carinii Infections; Ebstein-Barr Virus Infections

  5. Assessment of the HBV vaccine response in a group of HIV-infected children in Morocco.

    PubMed

    Haban, Houda; Benchekroun, Soumia; Sadeq, Mina; Benjouad, Abdelaziz; Amzazi, Said; Oumzil, Hicham; Elharti, Elmir

    2017-09-29

    Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, and since then all infants, including vertically HIV-infected infants, have been following the vaccination schedule, implemented by the Moroccan ministry of health. An assessment of the immunization of these children is important to optimize efforts aimed at tackling Hepatitis B coinfection, within the country. Forty-nine HIV-infected children (HIV group) and 112 HIV uninfected children (control group) were enrolled in this study. Samples were tested by Elisa (Monolisa Anti-HBs, Biorad) to quantify the anti-HBs antibodies. The % of lymphocyte subsets i.e. CD4+ T cells, CD8+ T cells, B cells, and NK, was determined by flow cytometry, using CellQuest Pro software (Becton-Dickinson), and for HIV group, HIV viral load was measured by real time PCR assay (Abbott). All variables were statistically compared in the two groups. The median age was 51 ± 35 months for the HIV group and 50 ± 36 months (p > 0.05) for the control group. Female represented 63% and 41% (p = 0.01), among the HIV group and the control group, respectively. Among HIV-infected children, 71.4% (35/49) were under HAART therapy at the enrollment in the study. Seroprotection titer i.e. anti-HBs ≥10mUI/ml among control group was 76% (85/112), and only 29% (14/49) among the perinatally HIV-infected children (p < 0.0001). Lower % of CD4 + T cells was observed in HIV-infected children with a poor anti-HBs response. In this studied group, we have shown that despite the vaccination of HIV-children with HBV vaccine, 71% did not show any seroprotective response. These findings support the need for monitoring HBV vaccine response among HIV-infected children in Morocco, in order to revaccinate non-immunized children.

  6. Impact of childhood trauma on functionality and quality of life in HIV-infected women.

    PubMed

    Troeman, Zyrhea C E; Spies, Georgina; Cherner, Mariana; Archibald, Sarah L; Fennema-Notestine, Christine; Theilmann, Rebecca J; Spottiswoode, Bruce; Stein, Dan J; Seedat, Soraya

    2011-09-30

    While there are many published studies on HIV and functional limitations, there are few in the context of early abuse and its impact on functionality and Quality of Life (QoL) in HIV. The present study focused on HIV in the context of childhood trauma and its impact on functionality and Quality of Life (QoL) by evaluating 85 HIV-positive (48 with childhood trauma and 37 without) and 52 HIV-negative (21 with childhood trauma and 31 without) South African women infected with Clade C HIV. QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Patient's Assessment of Own Functioning Inventory (PAOFI), the Activities of Daily Living (ADL) scale and the Sheehan Disability Scale (SDS). Furthermore, participants were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Childhood Trauma Questionnaire (CTQ). Subjects had a mean age of 30.1 years. After controlling for age, level of education and CES-D scores, analysis of covariance (ANCOVA) demonstrated significant individual effects of HIV status and childhood trauma on self-reported QoL. No significant interactional effects were evident. Functional limitation was, however, negatively correlated with CD4 lymphocyte count. In assessing QoL in HIV-infected women, we were able to demonstrate the impact of childhood trauma on functional limitations in HIV.

  7. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

    PubMed Central

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

    2016-01-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  8. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.

    PubMed

    Gisslén, Magnus; Krut, Jan; Andreasson, Ulf; Blennow, Kaj; Cinque, Paola; Brew, Bruce J; Spudich, Serena; Hagberg, Lars; Rosengren, Lars; Price, Richard W; Zetterberg, Henrik

    2009-12-22

    Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.

  9. Helicobacter pylori gastritis in HIV-infected patients: a review.

    PubMed

    Nevin, Daniel T; Morgan, Christopher J; Graham, David Y; Genta, Robert M

    2014-10-01

    The risk factors for acquiring Helicobacter pylori and Human Immunodeficiency Virus (HIV) infections are different: H. pylori is transmitted by gastro- or fecal-oral routes and is associated with low socioeconomic conditions, while HIV is transmitted through sexual intercourse, infected body fluids, and transplacentally. If the host responses to these infections were independent, the prevalence of H. pylori should be similar in HIV-infected and non-infected patients. Yet, several studies have detected a lower prevalence of H. pylori in patients with HIV infection, whereas other studies found either no differences or greater rates of H. pylori infection in HIV-positive subjects. To review studies that addressed the issue of these two simultaneous infections and attempt to determine whether reliable conclusions can be drawn from this corpus of often contrasting evidence. Electronic literature search for relevant publications, followed by manual search of additional citations from extracted articles. The initial search yielded 44 publications; after excluding case reports, reviews, narrowly focused articles, and duplicate reports, there remained 29 articles, which are the corpus of this review. With one exception, all studies reported higher rates of H. pylori infection in HIV-negative subjects. Five studies also examined the CD4 lymphocyte counts and found an inverse correlation between the degree of immunosuppression and the prevalence of active H. pylori infection. Current evidence suggests that it is likely that H. pylori needs a functional immune system to successfully and persistently colonize the human gastric mucosa. © 2014 John Wiley & Sons Ltd.

  10. Preventing secondary infections among HIV-positive persons.

    PubMed Central

    Filice, G A; Pomeroy, C

    1991-01-01

    Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children. PMID:1910184

  11. Association of subclinical atherosclerosis with lipid levels amongst antiretroviral-treated and untreated HIV-infected women in the Women’s Interagency HIV Study

    PubMed Central

    Parrinello, Christina M; Landay, Alan L; Hodis, Howard N; Gange, Stephen J.; Norris, Philip J; Young, Mary; Anastos, Kathryn; Tien, Phyllis C; Xue, Xiaonan; Lazar, Jason; Benning, Lorie; Tracy, Russell P; Kaplan, Robert C

    2013-01-01

    Objective We examined serum lipids in association with carotid artery intima-media thickness (CIMT) in HIV-infected and HIV-uninfected women. Methods In 2003–4, among 1827 Women’s Interagency HIV Study participants, we measured CIMT and lipids (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], total cholesterol [TC], non-HDL-c). A subset of 520 treated HIV-infected women had pre-1997 lipid measures. We used multivariable linear regression to examine associations between lipids and CIMT. Results In HIV-uninfected women, higher TC, LDL-c and non-HDL-c were associated with increased CIMT. Among HIV-infected women, associations of lipids with CIMT were observed in treated but not untreated women. Among the HIV-infected women treated in 2003–4, CIMT was associated both with lipids measured a decade earlier in infection, and with late lipid measurements. Conclusion Among HIV-infected women, hyperlipidemia is most strongly associated with subclinical atherosclerosis in treated women. Among treated women, the association appeared strongest early in the disease course. PMID:23089369

  12. Genital mycoplasma & Chlamydia trachomatis infections in treatment naïve HIV-1 infected adults

    PubMed Central

    Ghosh, Arnab; Dhawan, Benu; Chaudhry, Rama; Vajpayee, Madhu; Sreenivas, Vishnubhatla

    2011-01-01

    Background & objectives: Sexually transmitted infections (STIs) enhance the transmission of human immunodeficiency virus (HIV). Thus, screening for STIs is a routine component of primary HIV care. There are limited data for selective screening guidelines for genital mycoplasmas and Chlamydia trachomatis in HIV-infected adults. The aim of the present study was to determine the frequency of genital infections with Ureaplasma spp., Mycoplasma hominis, M. genitalium and C. trachomatis in treatment naïve asymptomatic HIV-1 - infected adults and study their association with CD4+ T-cell count. Methods: First-void urine samples were collected from 100 treatment-naïve HIV-1-infected adults and 50 healthy volunteers. C. trachomatis and M. genitalium were detected by polymerase chain reaction (PCR). Ureaplasma spp. and M. hominis were detected by both culture and PCR. Circulating CD4+ cell counts of HIV-1-infected patients were determined from peripheral blood by flow-cytometry. Results: C. trachomatis was detected in 7 per cent of HIV-1-infected adults compared to none in control population. Ureaplasma spp. and M. hominis showed infection rates of 6 and 1 per cent in the HIV group and 2 and 0 per cent in the control group, respectively. None of the individuals from the patient and control groups was tested positive for M. genitalium. A significant association was found between CD4 cell count and detection of C. trachomatis in HIV-infected adults (P = 0.01). Interpretation & conclusions: Screening of HIV-infected individuals for C. trachomatis infection could be recommended as a routine component of HIV care. The role of mycoplasmas as co-pathogens of the genitourinary tract in HIV-1 infected patients seems to be unlikely. Further longitudinal studies need to be done to confirm these findings. PMID:22310829

  13. Metabolic health across the BMI spectrum in HIV-infected and HIV-uninfected men.

    PubMed

    Lake, Jordan E; Li, Xiuhong; Palella, Frank J; Erlandson, Kristine M; Wiley, Dorothy; Kingsley, Lawrence; Jacobson, Lisa P; Brown, Todd T

    2018-01-02

    In the general population, metabolic health often declines as BMI increases. However, some obese individuals maintain metabolic health. HIV and antiretroviral therapy have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV) men on suppressive antiretroviral therapy experience less metabolic health than HIV-uninfected (HIV) men across all BMI categories. In a cross-sectional analysis of 1018 HIV and 1092 HIV men enrolled in the multicenter AIDS cohort study, Poisson regression with robust variance determined associations between HIV serostatus and metabolic health prevalence (defined as meeting ≤2 of 5 National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking, and hepatitis C virus infection status. HIV men were younger (54 vs. 59 years) and had lower median BMI (25 vs. 27 kg/m). Nonobese HIV men had lower metabolic health prevalence than HIV men (BMI ≤25 kg/m: 80 vs. 94%, P < 0.001; BMI 25-29 kg/m: 64 vs. 71%, P = 0.05), but metabolic health prevalence among obese men did not differ by HIV serostatus (BMI 30-34 kg/m: 35 vs. 39%, P = 0.48; BMI ≥35 kg/m: 27 vs. 25%, P = 0.79). In the adjusted model, nonobese HIV men were less likely to demonstrate metabolic health than nonobese HIV men. Among HIV men, per year darunavir, zidovudine, and stavudine use were associated with lower metabolic health likelihood. Metabolically healthy obesity prevalence does not differ by HIV serostatus. However, among nonobese men, HIV infection is associated with lower metabolic health prevalence, with associations between lack of metabolic health and darunavir and thymidine analog nucleoside reverse transcriptase inhibitor exposure observed.

  14. HIV Infection and Survival Among Women With Cervical Cancer

    PubMed Central

    Bvochora-Nsingo, Memory; Suneja, Gita; Efstathiou, Jason A.; Grover, Surbhi; Chiyapo, Sebathu; Ramogola-Masire, Doreen; Kebabonye-Pusoentsi, Malebogo; Clayman, Rebecca; Mapes, Abigail C.; Tapela, Neo; Asmelash, Aida; Medhin, Heluf; Viswanathan, Akila N.; Russell, Anthony H.; Lin, Lilie L.; Kayembe, Mukendi K.A.; Mmalane, Mompati; Randall, Thomas C.; Chabner, Bruce; Lockman, Shahin

    2016-01-01

    Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer (P = .035), those treated with curative intent (P = .003), and those with a lower CD4 cell count (P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival. PMID:27573661

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

    PubMed

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

    2012-01-01

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

  16. Identifying Recent HIV Infections: From Serological Assays to Genomics.

    PubMed

    Moyo, Sikhulile; Wilkinson, Eduan; Novitsky, Vladimir; Vandormael, Alain; Gaseitsiwe, Simani; Essex, Max; Engelbrecht, Susan; de Oliveira, Tulio

    2015-10-23

    In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV negative individuals over time are the current gold standard approach, but they are logistically challenging, time consuming and an expensive enterprise. Methods that utilize cross-sectional testing and biomarker information have become an affordable alternative to the longitudinal approach. These methods use well-characterized biological makers to differentiate between recent and established HIV infections. However, recent results have identified a number of limitations in serological based assays that are sensitive to the variability in immune responses modulated by HIV subtypes, viral load and antiretroviral therapy. Molecular methods that explore the dynamics between the timing of infection and viral evolution are now emerging as a promising approach. The combination of serological and molecular methods may provide a good solution to identify recent HIV infection in cross-sectional data. As part of this review, we present the advantages and limitations of serological and molecular based methods and their potential complementary role for the identification of HIV infection recency.

  17. Newly diagnosed HIV-1 infections in pregnancy: evidences from a cohort study in south-eastern Italy.

    PubMed

    Favia, Anna; Fiore, Josè Ramon; Pastore, Giuseppe

    2004-01-01

    The authors report and discuss the characteristics of 22 women who discovered their HIV seropositivity while pregnant. Most of the women had never been tested for HIV and this occurred not only for 'not at risk' women but also for sexual partners of HIV-infected men. Several infections were diagnosed late in pregnancy when most women were already immunodeficient. An implementation of HIV prenatal testing as an early standard clinical practice, should be promoted in all women, regardless of the presence of risk factors.

  18. Infection of KSHV and Interaction with HIV: The Bad Romance.

    PubMed

    Qin, Jie; Lu, Chun

    2017-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), namely, human herpesvirus 8 (HHV-8), is considered as the pathogen of Kaposi's sarcoma (KS), the most frequent cancer in untreated HIV-infected individuals. Patients infected with HIV have a much higher possibility developing KS than average individual. Researchers have found that HIV, which functions as a cofactor of KS, contributes a lot to the development of KS. In this article, we will give a brief introduction of KS and KSHV and how the interaction between KSHV and HIV contributes to the development of KS. Also we will take a glance at the development of treatment in KS, especially AIDS-KS.

  19. Intimate partner violence and HIV infection among married Indian women.

    PubMed

    Silverman, Jay G; Decker, Michele R; Saggurti, Niranjan; Balaiah, Donta; Raj, Anita

    2008-08-13

    Despite reductions in prevalence of human immunodeficiency virus (HIV) infection among the general population of India, women account for a rising percentage of all HIV cases with husbands' risk behavior described as the major source of women's infection. Intimate partner violence (IPV) has been described as being associated with heterosexual transmission of HIV to women in India and elsewhere. To assess the relationship between experiencing IPV and the occurrence of HIV infection in a nationally representative sample of married Indian women tested for HIV. The Indian National Family Health Survey 3 was conducted across all Indian states in 2005 through 2006. The nationally representative sample included 124,385 married women; analyses conducted in 2007 and 2008 were limited to 28,139 married women who provided IPV data and HIV test results via systematic selection into respective subsamples. Prevalence estimates of lifetime IPV and HIV infection were calculated and demographic differences assessed. Intimate partner violence was conceptualized as physical violence with or without sexual violence and then was further categorized as physical violence only vs physical and sexual violence. Regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for HIV infection among Indian women based on experiences of IPV after adjusting for demographics and women's HIV risk behaviors. One-third of married Indian women (35.49%) reported experiencing physical IPV with or without sexual violence from their husbands; 7.68% reported both physical and sexual IPV, and 27.80% reported experiencing physical IPV in the absence of sexual violence. Approximately 1 in 450 women (0.22%) tested positive for HIV. In adjusted models, married Indian women experiencing both physical and sexual violence from husbands demonstrated elevated HIV infection prevalence vs those not experiencing IPV (0.73% vs 0.19%; adjusted OR, 3.92; 95% CI, 1.41-10.94; P = .01

  20. Caregiver Perceptions and Motivation for Disclosing or Concealing the Diagnosis of HIV Infection to Children Receiving HIV Care in Mbarara, Uganda: A Qualitative Study

    PubMed Central

    Kiwanuka, Julius; Mulogo, Edgar; Haberer, Jessica E.

    2014-01-01

    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 process deserves further

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

    PubMed

    Kiwanuka, Julius; Mulogo, Edgar; Haberer, Jessica E

    2014-01-01

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

  2. [Lymphogranuloma venereum proctocolitis in men with HIV-1 infection].

    PubMed

    Heras, Eva; Llibre, Josep M; Martró, Elisa; Casabona, Jordi; Martin-Iguacel, Raquel; Martín, Raquel; Sirera, Guillem

    2011-02-01

    We present a series of 15 cases with lymphogranuloma venereum (LGV) with the aim of evaluating the response to a 21-day oral course of doxycycline (100mg twice daily). It is an observational study where we describe a series of cases with LGV diagnosed in the Hospital Germans Trias i Pujol's HIV Unit between March 2008 and April 2009. All our patients were HIV infected men who had sex with men with proctitis in 80% of the cases. In all of them Chlamydia trachomatis was determined by PCR on rectal swab specimens, with a negative result after 21 days of treatment with doxycycline. Serovar L2 was confirmed in all the specimens with the reverse hybridization technique. A high index of clinical suspicion is the mainstay to the early diagnosis of LGV since the clinical presentation remains unspecific. The treatment with doxycycline eradicates C. trachomatis in HIV patients with LGV. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  3. Trends of HIV and sexually transmitted infections, estimated HIV incidence, and risky sexual behaviors among gay bathhouse attendees in Taiwan: 2004-2008.

    PubMed

    Ko, Nai-Ying; Lee, Hsin-Chun; Hung, Chien-Ching; Tseng, Fan-Chen; Chang, Jui-Ling; Lee, Nan-Yao; Chang, Chia-Ming; Lee, Meng-Ping; Chen, Bo-Jie; Wang, Shainn-Wei; Ko, Wen-Chien

    2011-02-01

    Five serial cross-sectional surveys were done at eight gay bathhouses in Taiwan to investigate the trends of HIV and sexually transmitted infections (STIs) and estimated HIV incidence between 2004 and 2008. Bathhouse attendees completed a questionnaire and tests for HIV, syphilis, hepatitis C virus, and amoebiasis. Twenty-nine (38.6%) were identified as having recent HIV-1 infections. There was a significant increase in HIV incidence, from 7.8% in 2004 to 15% in 2007 (χ(2) = 17.59, P-trend <0.001). Recreational drug use is the primary risk behavior. Comprehensive screening programs in gay bathhouses for early detection of HIV and STIs are important.

  4. Prevalence of Pulmonary tuberculosis and immunological profile of HIV co-infected patients in Northwest Ethiopia

    PubMed Central

    2012-01-01

    Background In sub-Saharan Africa, as high as 2/3 of tuberculosis patients are HIV/AIDS co-infected and tuberculosis is the most common cause of death among HIV/AIDS patients worldwide. Tuberculosis and HIV co-infections are associated with special diagnostic and therapeutic challenges and constitute an immense burden on healthcare systems of heavily infected countries like Ethiopia. The aim of the study was to determine the prevalence of pulmonary tuberculosis and their immunologic profiles among HIV positive patients. Methods A cross sectional study was conducted among adult HIV-positive patients attending HIV/AIDS clinic of Gondar University Hospital. Clinical and laboratory investigations including chest x-ray and acid fast staining were used to identify tuberculosis cases. Blood samples were collected to determine CD4+ lymphocyte count. A structured questionnaire was used to collect socio-demographic characteristics of study subjects. The data was entered and analyzed using SPSS version 16 software. Results A total of 400 HIV positive study participants were enrolled. Thirty (7.5%, 95%CI: 5.2-10.6%) of the study participants were found to have pulmonary tuberculosis. In multivariate analysis, only CD4+ lymphocyte count (AOR = 2.9; 95% CI: 1.002-8.368) was found to be independently associated with tuberculosis-HIV co-infection. Individuals who had advanced WHO clinical stage were also statistically significant for co-infection. The mean CD4+ lymphocyte count of HIV mono-infected participants were 296 ± 192 Cells/mm3 and tuberculosis-HIV co-infected patients had mean CD4+ lymphocyte count of 199 ± 149 Cells/mm3 with p value of 0.007. Conclusions We found high prevalence of tuberculosis-HIV co-infection. Lower CD4+ lymphocyte count was found to be the only predicting factor for co-infection. Early detection of co-infection is very necessary to prolong their ART initiation time and by then strengthening their immune status. PMID:22738361

  5. Hematologic abnormalities associated with Simian Immunodeficieny Virus (SIV) Infection mimic those in HIV infection

    PubMed Central

    Gill, Amy F.; Ahsan, Muhammad H.; Lackner, Andrew A.; Veazey, Ronald S.

    2012-01-01

    Studies of hematologic abnormalities in HIV infected patients are confounded by a multitude of factors. A retrospective data analysis of SIV infected Rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from rhesus macaques inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared to non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggest that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. PMID:22620272

  6. PRESCRIPTION LONG-TERM OPIOID USE IN HIV-INFECTED PATIENTS

    PubMed Central

    Silverberg, Michael J.; Ray, G. Thomas; Saunders, Kathleen; Rutter, Carolyn M.; Campbell, Cynthia I.; Merrill, Joseph O.; Sullivan, Mark D.; Banta-Green, Caleb; Von Korff, Michael; Weisner, Constance

    2011-01-01

    Objectives To examine changes in use of prescription opioids for the management of chronic non-cancer pain in HIV-infected patients and to identify patient characteristics associated with long-term use. Methods Long-term prescription opioid use (i.e. 120+ days supply or 10+ prescriptions during a year) was assessed between 1997 and 2005 among 6,939 HIV-infected Kaiser Permanente members and HIV-uninfected persons in the general health plan memberships. Results In 2005, 8% of HIV+ individuals had prevalent long-term opioid use, more than double the prevalence among HIV-uninfected individuals. However, the large increases in use from 1997 to 2005 in the general population were not observed for HIV-infected individuals. The strongest associations with prevalent use among HIV-infected individuals were female gender with a prevalence ratio [PR] of 1.8 (95% CI=1.3, 2.5); Charlson comorbidity score of 2 or more (compared with a score of 0) with a PR of 1.9 (95% CI=1.4, 2.8); injection drug use history with a PR of 1.8 (95% CI=1.3, 2.6); substance use disorders with a PR of 1.8 (95% CI=1.3, 2.5). CD4, HIV RNA, and AIDS diagnoses were associated with prevalent opioid use early in the antiretroviral therapy era (1997), but not in 2005. Conclusions Long-term opioid use for chronic pain has remained stable over time for HIV patients, while use increased in the general population. The prevalence of prescribed opioids in HIV patients was highest for certain subgroups, including women, and those with a comorbidity and substance abuse history. PMID:21677568

  7. Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells.

    PubMed

    Jiang, Ai-Ping; Jiang, Jin-Feng; Wei, Ji-Fu; Guo, Ming-Gao; Qin, Yan; Guo, Qian-Qian; Ma, Li; Liu, Bao-Chi; Wang, Xiaolei; Veazey, Ronald S; Ding, Yong-Bing; Wang, Jian-Hua

    2015-12-30

    The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection. In this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1 trans-infection of CD4(+) T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination. Copyright © 2016, American Society

  8. Cancer clinical trials in persons with HIV infection.

    PubMed

    Little, Richard F

    2017-01-01

    The era of modern HIV therapeutics is well underway. The cancer and infectious disease epidemiology of HIV disease has markedly altered as populations are availed to the benefits of antiretroviral therapy (ARV). The types of cancers occurring among those with HIV infection has broadened but the case burden in absolute numbers is very low relative to the background population. There are fewer incident cases of the AIDS-defining cancers (aggressive B-cell lymphomas, Kaposi's sarcoma, and cervical cancer). There is an increased risk for certain non-AIDS-defining cancers, but these occur somewhat sporadically relative to clinical trial enrollment. The changing epidemiology of cancer in HIV poses challenges as well as opportunities for participation of persons with HIV in cancer therapy clinical trials. There are excellent examples of cancer trials that inform cancer therapy for patients with HIV infection. Examples include those from HIV-specific trials and from trials mainly focused on the background population that included patients with HIV infection. Interpretation of clinical trials to guide therapy for those with HIV infection and cancer largely depends on data that does not include HIV-infected patients. The ability to extend clinical trial findings to populations not included in clinical trials remains problematic for a variety of populations, including those with HIV or AIDS. Careful prioritization of studies designed to bridge this gap is needed. However, there are published studies that serve as excellent examples bridging these gaps and the portfolio of cancer therapy trials underway will inform HIV and cancer better than at any time in the past.

  9. Morbidity and Mortality of a Cohort of Peruvian HIV-infected Children 2003-2012.

    PubMed

    Baker, Amira N; Bayer, Angela M; Viani, Rolando M; Kolevic, Lenka; Sim, Myung-Shin; Deville, Jaime G

    2018-06-01

    Data on pediatric HIV in Peru are limited. The National Institute of Child Health (Instituto Nacional de Salud del Niño: INSN) cares for the most HIV-infected children under the age of 18 years in the country. We describe the outcomes of children seen at INSN's HIV clinic over the 10 years when antiretroviral therapy and prevention of mother-to-child transmission (PMTCT) interventions became available in 2004. We conducted a retrospective review of INSN HIV clinic patients between 2003 and 2012. Deidentified data were collected and analyzed. A total of 280 children were included: 50.0% (140/280) were male; 80.0% (224/280) lived in metropolitan Lima. Perinatal transmission was the mode of HIV infection in 91.4% (256/280) of children. Only 17% (32/191) of mothers were known to be HIV-infected at delivery; of these mothers, 41% (13/32) were receiving antiretroviral therapy at delivery, 72% (23/32) delivered by Cesarean section and 47% (15/32) of their infants received antiretroviral prophylaxis. Median age at HIV diagnosis for all children was 35.7 months (interquartile range 14.5-76.8 months), and 67% (143/213) had advanced disease (clinical stage C). After HIV diagnosis, the most frequent hospitalization discharge diagnoses were bacterial pneumonia, chronic malnutrition, diarrhea, anemia and tuberculosis. Twenty-four patients (8.6%) died at a median age of 77.4 months. Most cases of pediatric HIV were acquired via perinatal transmission; few mothers were diagnosed before delivery; and among mothers with known HIV status, PMTCT was suboptimal even after national PMTCT policy was implemented. Most children were diagnosed with advanced disease. These findings underscore the need for improving early pediatric HIV diagnosis and treatment, as well as PMTCT strategies.

  10. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

  11. Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.

    PubMed

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H; Valcour, Victor

    2012-01-01

    Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

  12. Rethinking the Heterosexual Infectivity of HIV-1: A Systematic Review and Meta-analysis

    PubMed Central

    Powers, Kimberly A.; Poole, Charles; Pettifor, Audrey E.; Cohen, Myron S.

    2009-01-01

    Background Studies of cumulative HIV incidence suggest that co-factors such as genital ulcer disease (GUD), HIV disease stage, and circumcision influence HIV transmission; however, the heterosexual infectivity of HIV-1 is commonly cited as a fixed value (∼0·001, or 1 transmission per thousand contacts). We sought to estimate transmission co-factor effects on the heterosexual infectivity of HIV-1 and to quantify the extent to which study methods have affected infectivity estimates. Methods We conducted a systematic search (through April 2008) of PubMed, Web of Science, and relevant bibliographies to identify articles estimating the heterosexual infectivity of HIV-1. We used meta-regression and stratified random-effects meta-analysis to assess differences in infectivity by co-factors and study methods. Findings Infectivity estimates were extremely heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some sero-discordant couples to one transmission for every 3·1 episodes of heterosexual anal intercourse. Estimates were only weakly associated with study methods. Infectivity differences (95% confidence intervals), expressed as number of transmissions per 1000 contacts, were 8 (0-16) comparing uncircumcised to circumcised male susceptibles, 6 (3-9) comparing susceptible individuals with and without GUD, 2 (1-3) comparing late-stage to mid-stage index cases, and 3 (0-5) comparing early-stage to mid-stage index cases. Interpretation A single value for the heterosexual infectivity of HIV-1 fails to reflect the variation associated with important co-factors. The commonly cited value of ∼0·001 was estimated among stable couples with low prevalences of high-risk co-factors, and represents a lower bound. Co-factor effects are important to include in epidemic models, policy considerations, and prevention messages. PMID:18684670

  13. The health of HIV-exposed children after early weaning.

    PubMed

    Parker, Megan E; Tembo, Martin; Adair, Linda; Chasela, Charles; Piwoz, Ellen G; Jamieson, Denise J; Ellington, Sascha; Kayira, Dumbani; Soko, Alice; Mkhomawanthu, Chimwemwe; Martinson, Francis; van der Horst, Charles M; Bentley, Margaret E

    2013-04-01

    There are potential health risks associated with the use of early weaning to prevent mother-to-child transmission of human immunodeficiency virus (HIV) in resource-poor settings. Our objective was to examine growth and nutrient inadequacies among a cohort of children weaned early. Children participating in the Breastfeeding Antiretrovirals and Nutrition (BAN) Study in Lilongwe, Malawi, had HIV-infected mothers, were weaned at 6 months and fed LNS until 12 months. 40 HIV-negative, BAN-exited children were compared with 40 HIV-negative, community children matched on age, gender and local health clinic. Nutrient intake was calculated from 24-h dietary recalls collected from BAN-exited children. Anthropometric measurements were collected from BAN-exited and matched community children at 15-16 months, and 2 months later. Longitudinal random effects sex-stratified models were used to evaluate anthropometric differences between the two groups. BAN-exited children consumed adequate energy, protein and carbohydrates but inadequate amounts of fat. The prevalence of inadequate micronutrient intakes were: 46% for vitamin A; 20% for vitamin B6; 69% for folate; 13% for vitamin C; 19% for iron; 23% for zinc. Regarding growth, BAN-exited girls gained weight at a significantly lower rate {0.02 g kg(-1) per day [95% confidence interval (CI): 0.01, 0.03]} than their matched comparison [0.05 g kg(-1) per day (95% CI: 0.03, 0.07)]; BAN girls grew significantly slower [0.73 cm month(-1) (95% CI: 0.40,1.06)] than their matched comparison (1.55 cm month(-1) [95% CI: 0.98, 2.12]). Among this sample of BAN-exited children, early weaning was associated with dietary deficiencies and girls experienced reduced growth velocity. In resource-poor settings, HIV prevention programmes must ensure that breastfeeding stop only once a nutritionally adequate and safe diet without breast milk can be provided. © 2011 Blackwell Publishing Ltd.

  14. Alterations in the gut microbiota associated with HIV-1 infection.

    PubMed

    Lozupone, Catherine A; Li, Marcella; Campbell, Thomas B; Flores, Sonia C; Linderman, Derek; Gebert, Matthew J; Knight, Rob; Fontenot, Andrew P; Palmer, Brent E

    2013-09-11

    Understanding gut microbiota alterations associated with HIV infection and factors that drive these alterations may help explain gut-linked diseases prevalent with HIV. 16S rRNA sequencing of feces from HIV-infected individuals revealed that HIV infection is associated with highly characteristic gut community changes, and antiretroviral therapy does not consistently restore the microbiota to an HIV-negative state. Despite the chronic gut inflammation characteristic of HIV infection, the associated microbiota showed limited similarity with other inflammatory states and instead showed increased, rather than decreased, diversity. Meta-analysis revealed that the microbiota of HIV-infected individuals in the U.S. was most similar to a Prevotella-rich community composition typically observed in healthy individuals in agrarian cultures of Malawi and Venezuela and related to that of U.S. individuals with carbohydrate-rich, protein- and fat-poor diets. By evaluating innate and adaptive immune responses to lysates from bacteria that differ with HIV, we explore the functional drivers of these compositional differences. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Inhibition of HIV infection by caerin 1 antimicrobial peptides.

    PubMed

    VanCompernolle, Scott; Smith, Patricia B; Bowie, John H; Tyler, Michael J; Unutmaz, Derya; Rollins-Smith, Louise A

    2015-09-01

    The major mode of transmission of the human immunodeficiency virus (HIV) is by sexual intercourse. In the effort to halt the spread of HIV, one measure that holds great promise is the development of effective microbicides that can prevent transmission. Previously we showed that several amphibian antimicrobial peptides (AMPs) completely inhibit HIV infection of T cells while maintaining good viability of the T cell targets. These peptides also inhibited the transfer of HIV by dendritic cells (DCs) to T cells when added up to 8h after virus exposure. Here we report on the anti-HIV activity of 18 additional structurally related caerin 1 family peptides in comparison with our previous best candidate caerin 1.9. Nine peptides were equally effective or more effective in the inhibition of T cell infection and disruption of the HIV envelope as caerin 1.9. Of those nine peptides, three peptides (caerin 1.2, caerin 1.10, and caerin 1.20) exhibited excellent inhibition of HIV infectivity at low concentrations (12-25μM) and limited toxicity against target T cells and endocervical epithelial cells. There was a direct correlation between the effectiveness of the peptides in disruption of the viral envelope and their capacity to inhibit infection. Thus, several additional caerin 1 family peptides inhibit HIV infection have limited toxicity for vaginal epithelial cells, and would be good candidates for inclusion in microbicide formulations. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Tuberculosis and HIV co-infection in Vietnam.

    PubMed

    Trinh, Q M; Nguyen, H L; Do, T N; Nguyen, V N; Nguyen, B H; Nguyen, T V A; Sintchenko, V; Marais, B J

    2016-05-01

    Tuberculosis (TB) and human immunodeficiency virus (HIV) infection are leading causes of disease and death in Vietnam, but TB/HIV disease trends and the profile of co-infected patients are poorly described. We examined national TB and HIV notification data to provide a geographic overview and describe relevant disease trends within Vietnam. We also compared the demographic and clinical profiles of TB patients with and without HIV infection. During the past 10 years (2005-2014) cumulative HIV case numbers and deaths increased to 298,151 and 71,332 respectively, but access to antiretroviral therapy (ART) improved and new infections and deaths declined. From 2011-2014 routine HIV testing of TB patients increased from 58.9% to 72.5% and of all TB patients diagnosed with HIV in 2014, 2,803 (72.4%) received ART. The number of multidrug resistant (MDR)-TB cases enrolled for treatment increased almost 3-fold (578 to 1,532) from 2011-2014. The rate of HIV co-infection in MDR and non-MDR TB cases (51/1,532; 3.3% vs 3,774/100,555; 3.8%; OR 0.77, 95% CI 0.7-1.2) was similar in 2014. The care of TB/HIV co-infected patients have shown sustained improvement in Vietnam. Rising numbers of MDR-TB cases is a concern, but this is not "driven" by HIV co-infection. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Clinical, nutritional and immunological characteristics of HIV-infected children in an area of high HIV prevalence.

    PubMed

    Pedrini, Maura; Moraleda, Cinta; Macete, Eusebio; Gondo, Kizito; Brabin, Bernard J; Menéndez, Clara

    2015-08-01

    To evaluate the clinical, nutritional and neurodevelopment status of HIV-infected children in a high HIV prevalence area. All HIV-infected children under 15 years of age attending an outpatient clinic of Mozambique between April and May 2010 were recruited. Clinical data were collected and physical examination was performed. In all, 140 children were recruited. The median age at HIV diagnosis was 2.1 years. Fifty-one percent of the children were classified in WHO clinical Stages 3 or 4. Median age of antiretroviral treatment commencement was 3.9 years. Overall, 68% were undernourished, mainly stunted. Forty-four percent failed to pass the national psychomotor developmental test. The pathways for early HIV diagnosis and start of antiretrovirals in children should be improved in Mozambique. Malnutrition, especially stunting, and developmental delay were highly prevalent. Further research focused on early diagnosis of neurocognitive disorders and on the indications of antiretroviral treatment commencement based on chronic malnutrition is required. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Mice chronically infected with chimeric HIV resist peripheral and brain superinfection: a model of protective immunity to HIV.

    PubMed

    Kelschenbach, Jennifer L; Saini, Manisha; Hadas, Eran; Gu, Chao-Jiang; Chao, Wei; Bentsman, Galina; Hong, Jessie P; Hanke, Tomas; Sharer, Leroy R; Potash, Mary Jane; Volsky, David J

    2012-06-01

    Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

  19. Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia.

    PubMed

    Vinikoor, Michael J; Mulenga, Lloyd; Siyunda, Alice; Musukuma, Kalo; Chilengi, Roma; Moore, Carolyn Bolton; Chi, Benjamin H; Davies, Mary-Ann; Egger, Matthias; Wandeler, Gilles

    2016-11-01

    To describe liver disease epidemiology among HIV-infected individuals in Zambia. We recruited HIV-infected adults (≥18 years) at antiretroviral therapy initiation at two facilities in Lusaka. Using vibration controlled transient elastography, we assessed liver stiffness, a surrogate for fibrosis/cirrhosis, and analysed liver stiffness measurements (LSM) according to established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for cirrhosis). All participants underwent standardised screening for potential causes of liver disease including chronic hepatitis B (HBV) and C virus co-infection, herbal medicine, and alcohol use. We used multivariable logistic regression to identify factors associated with elevated liver stiffness. Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53% female). HBV co-infection (12%) and alcohol use disorders (41%) were common and hepatitis C virus co-infection (<1%) was rare. According to LSM, 75 (12%) had significant fibrosis and 13 (2%) had cirrhosis. In multivariable analysis, HBV co-infection as well as male sex, increased age and WHO clinical stage 3 or 4 were independently associated with LSM >7.0 kPa (all P < 0.05). HBV co-infection was the only independent risk factor for LSM >11.0 kPa. Among HIV-HBV patients, those with elevated ALT and HBV viral load were more likely to have significant liver fibrosis than patients with normal markers of HBV activity. HBV co-infection was the most important risk factor for liver fibrosis and cirrhosis and should be diagnosed early in HIV care to optimise treatment outcomes. © 2016 John Wiley & Sons Ltd.

  20. Neuropsychological performance in patients with asymptomatic HIV-1 infection.

    PubMed

    Martínez-Banfi, Martha; Vélez, Jorge I; Perea, M Victoria; García, Ricardo; Puentes-Rozo, Pedro J; Mebarak Chams, Moises; Ladera, Valentina

    2018-05-01

    Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.

  1. Women and HIV Infection: The Makings of a Midlife Crisis

    PubMed Central

    Santoro, Nanette; Fan, Maria; Maslow, BatSheva; Schoenbaum, Ellie

    2009-01-01

    With the advent of highly active antiretroviral agents, women with HIV infection can expect to live longer than ever before. This increased survival has led to concerns about the long-term implications of HIV disease and its treatment. Women with HIV infection appear to lose ovarian function earlier in life than women without HIV infection. They also have evidence of reduced bone mineral density and increased cardiovascular risk. Moreover, many of these increases in risk factors are present even prior to the menopausal transition. All of these risks, present at mid-life, augur poorly for future health and describe a substantially increased burden of disease likely to accrue to HIV infected women as they enter older age groups. Further compounding the adversity faced by the HIV infected, the demographics of women most vulnerable to this disease include adverse social and economic influences, both of which worsen their long term prognosis. For example, drug use and poverty are related to more severe menopausal symptoms and chronic stress is related to worse psychological and cardiovascular risk. An understanding of how menopause interacts with HIV infection is therefore most important to alert the clinician to perform surveillance for common health problems in postmenopausal women, and to address directly and appropriately symptomatology during the menopausal transition. PMID:19783389

  2. Drug-resistant herpes simplex virus in HIV infected patients.

    PubMed

    Lolis, Margarita S; González, Lenis; Cohen, Philip J; Schwartz, Robert A

    2008-01-01

    Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in human immunodeficiency virus (HIV)-infected patients, since reactivations - whether symptomatic or asymptomatic - are associated with increased HIV viral load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated for the treatment of HSV2 in HIV patients. This class of drugs has been shown to enhance survival in HIV-infected individuals. However, with the emergence of drug-resistant strains of HSV2, the rates of resistance among HIV patients are almost ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2 infections tend to be more severe and to recur. More ominously, disease progression of HIV is promoted by concurrent infection with HSV2. Intravenous foscarnet and cidofovir may be used for acyclovir-resistant HSV; however, resistance to these drugs has been documented. Newer therapies such as the toll-like receptor agonist imiquimod and immunomodulating dipeptides offer promise for the treatment of HSV2 in HIV-infected individuals.

  3. Effect of Advanced HIV Infection on the Respiratory Microbiome.

    PubMed

    Twigg, Homer L; Knox, Kenneth S; Zhou, Jin; Crothers, Kristina A; Nelson, David E; Toh, Evelyn; Day, Richard B; Lin, Huaiying; Gao, Xiang; Dong, Qunfeng; Mi, Deming; Katz, Barry P; Sodergren, Erica; Weinstock, George M

    2016-07-15

    Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. To measure the lung microbiome in an HIV-infected population with advanced disease. 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 subjects infected with HIV with advanced disease (baseline mean CD4 count, 262 cells/mm(3)) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relative abundance of some bacteria between the two groups at baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era.

  4. Metabolic complications and selected cytokines in HIV-infected individuals.

    PubMed

    Bociąga-Jasik, Monika; Polus, Anna; Góralska, Joanna; Śliwa, Agnieszka; Raźny, Urszula; Zdzienicka, Anna; Garlicki, Aleksander; Mach, Tomasz; Dembińska-Kieć, Aldona

    2014-01-01

    Human immunodeficiency virus (HIV)-infected individuals are at a higher risk of developing metabolic disturbances. The pathogenesis of these complications is complex and not fully explored. The aim of the study was to investigate the effect of HIV infection and antiretroviral (ARV) therapy on the development of metabolic changes and adipocytokine concentrations. The analysis of the differences in the investigated parameters among lipodystrophic and nonlipodystrophic patients was also performed. A total of 42 HIV‑infected patients on ARV therapy (HIV[+]ARV[+]), 13 HIV‑infected ARV naive patients (HIV[+]ARV[-]), and 20 healthy controls were included in the study. A lipid profile, fasting free fatty acids (FFAs), glucose, insulin, and insulin resistance (homeostasis model assessment of insulin resistance--HOMA‑IR) were tested. Serum concentrations of tumor necrosis factor α (TNF‑α), interleukin 6 (IL‑6), adiponectin, leptin, and fatty acid-binding protein 4 (FABP4) were determined. Increased FFA levels were observed in HIV(+)ARV(-) patients. HIV(+)ARV(+) patients had significantly higher triglycerides and insulin level compared with controls. HOMA‑IR showed a tendency to be higher in HIV(+)ARV(+) patients compared with the other study groups. The ARV therapy longer than 2 years resulted in more pronounced metabolic abnormalities. HIV infection itself had a significant effect on inflammation expressed by elevated TNF‑α and IL‑6 levels. We did not observe differences in adiponectin and FABP4 concentrations among the study groups, while the leptin concentration was significantly lower in HIV‑infected lipodystrophic than in nonlipodystrophic patients. HIV infection induces lipid disorders, especially associated with fatty acid turnover augmented by ARV therapy. Compared with FABP4, leptin is a better biological marker of metabolic complications in HIV‑infected patients.

  5. [Overweight, obesity and underweight in HIV infected patients].

    PubMed

    Kwiatkowska, Wiesława; Knysz, Brygida; Drelichowska-Durawa, Justyna; Czarnecki, Marcin; Gasiorowski, Jacek; Biłyk, Ewa; Karczewski, Maciej; Witkiewicz, Wojciech

    2013-01-01

    The history of HIV infection has always been associated with patient nutritional problems, initially in the form of wasting syndrome, and since the introduction of highly active antiretroviral therapy such metabolic disorders as lipodystrophy, obesity, insulin resistance, dyslipidemia that are risk factors for cardiovascular diseases have been observed. evaluation of nutritional disorders in HIV infected patients using anthropometric parameters: waist circumference, BMI (body mass index) and WHR (waist-hip ratio). the study included 72 HIV infected patients (48 men, 24 women, average age 39.4). The control group comprised 27 not infected subjects, matched for age and sex. Physical examination with measurements of body mass, height, waist and hip circumference was performed and the values of two anthropometric parameters--body mass index and waist/hip ratio were calculated. BMI in the group of HIV infected patients was significantly lower than in the control group (23.6 vs. 25.6 kg/m2, p = 0.01). These BMI values are normal, but significantly lower in HIV-infected men compared with not infected, and no differences were found between women. Infected men are less likely to be overweight and obese than not infected ones. Underweight was noted in 6.8% of patients from the study group (6% of men and 4% of women). WHR was significantly higher in the study group comparing with the healthy subjects (0.92 vs. 0.86 p = 0.002), which resulted from significantly lower hip circumference among the infected patients (93.0 vs. 98.3, p = 0.002). Waist circumference was similar in both groups (85.1 vs. 84.0). The WHR value in the infected women was a result of insignificantly higher waist circumference and lower hip circumference. HIV infected women have significantly more often too large waist circumference comparing with not infected ones (46% vs 0%, p = 0.01). In the group of infected men, the WHR value was significantly affected only by low hip circumference, and larger waist

  6. Multifarious immunotherapeutic approaches to cure HIV-1 infection.

    PubMed

    Imami, Nesrina; Herasimtschuk, Anna A

    2015-01-01

    Immunotherapy in the context of treated HIV-1 infection aims to improve immune responses to achieve better control of the virus. To date, multifaceted immunotherapeutic approaches have been shown to reduce immune activation and increase CD4 T-lymphocyte counts, further to the effects of antiretroviral therapy alone, in addition to improving HIV-1-specific T-cell responses. While sterilizing cure of HIV-1 would involve elimination of all replication-competent virus, a functional cure in which the host has long-lasting control of viral replication may be more feasible. In this commentary, we discuss novel strategies aimed at targeting the latent viral reservoir with cure of HIV-1 infection being the ultimate goal, an achievement that would have considerable impact on worldwide HIV-1 infection.

  7. Computer service not liable for customer's HIV infection.

    PubMed

    1996-12-27

    A U.S. District judge ruled that Prodigy Services Co. cannot be held liable for damages because one of its employees infected a customer with HIV. The customer, [name removed], claimed that the employee, [name removed], granted her unlimited access to his online account and repeatedly denied he was HIV-positive. The judge ruled that [name removed]' conduct, failing to disclose his HIV status and having unprotected sex, was outside the scope of his employment with Prodigy.

  8. HIV infection and specific mucosal immunity: workshop 4B.

    PubMed

    Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M

    2011-04-01

    Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

  9. Placental pathology in HIV infection at term: a comparison with HIV-uninfected women.

    PubMed

    Kalk, Emma; Schubert, Pawel; Bettinger, Julie A; Cotton, Mark F; Esser, Monika; Slogrove, Amy; Wright, Colleen A

    2017-05-01

    To describe and correlate placental characteristics from pregnancies in HIV-infected and HIV-negative women with maternal and infant clinical and immunological data. Prospective descriptive study of placentas from term, uncomplicated vaginal births in a cohort of HIV-infected (n = 120) and HIV-negative (n = 103) women in Cape Town, South Africa. Microscopic and macroscopic features were used to dete