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Sample records for hiv-1-infected pregnant women

  1. Enhanced Th17 phenotype in uninfected neonates born from viremic HIV-1-infected pregnant women.

    PubMed

    Hygino, Joana; Vieira, Morgana M; Guillermo, Landi V; Silva-Filho, Renato G; Saramago, Carmen; Lima-Silva, Agostinho A; Andrade, Regis M; Andrade, Arnaldao F B; Brindeiro, Rodrigo M; Tanuri, Amilcar; Guimarães, Vander; de Melo Bento, Cleonice Alves

    2011-04-01

    Our objective was to evaluate the in vitro functional profile of T cells from uninfected neonates born from HIV-1-infected pregnant women who controlled (G1) or not (G2) the virus replication. We demonstrated that the lymphoproliferation of T cell to polyclonal activators was higher in the G2 as compared with G1. Nevertheless, no detectable proliferative response was observed in response to HIV-1 antigens in both neonate groups. Cytokine dosage in the supernatants of these polyclonally activated T cell cultures demonstrated that, while IL-10 was the dominant cytokine produced in G1, Th17-related cytokines were significantly higher in G2 neonates. The higher Th17 phenotype tendency in G2 was related to high production of IL-23 by lipopolysaccharide-activated monocyte-derived dendritic cells from these neonates. Our results demonstrated immunological disorders in uninfected neonates born from viremic HIV-1-infected mothers that can help to explain why some of these children have elevated risk of clinical morbidity and mortality due to pathological hypersensitivity.

  2. Population Pharmacokinetics of Nevirapine in HIV-1-Infected Pregnant Women and Their Neonates ▿

    PubMed Central

    Benaboud, Sihem; Ekouévi, Didier K.; Urien, Saik; Rey, Elisabeth; Arrivé, Elise; Blanche, Stéphane; Gray, Glenda; Sim, Kruy Leang; Avit, Divine; McIntyre, James; Nerrienet, Eric; Dabis, François; Tréluyer, Jean-Marc; Hirt, Déborah

    2011-01-01

    The aim of the present study was to describe the nevirapine (NVP) pharmacokinetics (PK) in pregnant women and their neonates and to evaluate the transplacental drug transfer and administration scheme for the prevention of mother-to-child transmission. Thirty-eight HIV-1-infected pregnant women were administered one tablet of NVP (200 mg) and two tablets of tenofovir-emtricitabine (Truvada) at the initiation of labor. Children were given NVP syrup (2 mg/kg of body weight) as a single dose (sdNVP) on the first day of life. By pair, NVP concentrations were measured in 11 maternal, 1 cord blood, and 2 neonatal plasma samples and analyzed by a population approach. A one-compartment model was used for mothers and neonates; the absorption rate constants for mothers and neonates were 0.95 h−1 (intersubject variability, 111%) and 0.39 h−1, respectively; the apparent elimination clearances were 1.42 liter·h−1 (intersubject variability, 22%) and 0.035 liter·h−1, respectively; and apparent volumes of distribution were 87.3 liters (intersubject variability, 25%) and 5.65 liters, respectively. An effect compartment was linked to maternal circulation by mother-to-cord and cord-to-mother rate constants of 1.10 h−1 and 1.43 h−1, respectively. Placental transfer, expressed as the fetal-to-maternal area under the curve ratio, was 75%. Neonates had a very long half-lives (110 h) compared to adults. In the 38 mothers, the simulated median individual predicted time during which the NVP concentration remained above the half-maximal inhibitory concentration (IC50) was 13.2 days (range, 12 to 19.2 days). Thus, the administration of tenofovir-emtricitabine for at least 3 weeks after delivery should be considered to prevent the emergence of resistant viruses. The neonate must receive sdNVP immediately after birth when the infant is born less than 30 min after maternal drug intake to keep NVP concentrations above the IC50. PMID:20956588

  3. Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA

    PubMed Central

    Newell, Marie-Louise; Huang, Sharon; Fiore, Simona; Thorne, Claire; Mandelbrot, Laurent; Sullivan, John L; Maupin, Robert; Delke, Isaac; Watts, D Heather; Gelber, Richard D; Cunningham, Coleen K

    2007-01-01

    Background Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT. Methods In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression. Results In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections. More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery. Conclusion These findings confirm that there are important

  4. Association of Body Mass Index of HIV-1-Infected Pregnant Women and Infant Weight, Body Mass Index, Length, and Head Circumference: The NISDI Perinatal Study

    PubMed Central

    Cruz, Maria Letícia S.; Harris, D. Robert; Read, Jennifer S.; Mussi-Pinhata, Marisa M.; Succi, Regina C.M.

    2008-01-01

    This study assessed the relationship between the body mass index (BMI) of HIV-1-infected women and their infants’ perinatal outcomes. The study population consisted of women enrolled in the NICHD International Site Development Initiative (NISDI) Perinatal Study with data allowing calculation of the BMI adjusted for length of gestation (adjBMI), who delivered singleton infants. Outcome variables included infant growth parameters at birth (weight, BMI, length and head circumference) and gestational age. Of 697 women from Argentina, the Bahamas, Brazil and Mexico who were included in the analysis, the adjBMI was classified as underweight for 109 (15.6%), normal for 418 (60.0%), overweight for 88 (12.6%) and obese for 82 (11.8%). Median infant birth weight, BMI, birth length and head circumference differed significantly according to maternal adjBMI (P≤0.0002). Underweight mothers gave birth to infants with lower weight, lower BMI, shorter length and smaller head circumference, while infants born to normal, overweight and obese mothers were of similar size. PMID:19081829

  5. Pharmacokinetics and Safety of Single-Dose Tenofovir Disoproxil Fumarate and Emtricitabine in HIV-1-Infected Pregnant Women and Their Infants▿

    PubMed Central

    Flynn, Patricia M.; Mirochnick, Mark; Shapiro, David E.; Bardeguez, Arlene; Rodman, John; Robbins, Brian; Huang, Sharon; Fiscus, Susan A.; Van Rompay, Koen K. A.; Rooney, James F.; Kearney, Brian; Mofenson, Lynne M.; Watts, D. Heather; Jean-Philippe, Patrick; Heckman, Barbara; Thorpe, Edwin; Cotter, Amanda; Purswani, Murli

    2011-01-01

    Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (C24) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (Cmax) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (P = 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression. PMID:21896911

  6. Universal antiretroviral therapy for pregnant and breast-feeding HIV-1-infected women: towards the elimination of mother-to-child transmission of HIV-1 in resource-limited settings.

    PubMed

    Becquet, Renaud; Ekouevi, Didier K; Arrive, Elise; Stringer, Jeffrey S A; Meda, Nicolas; Chaix, Marie-Laure; Treluyer, Jean-Marc; Leroy, Valériane; Rouzioux, Christine; Blanche, Stéphane; Dabis, François

    2009-12-15

    Prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) remains a challenge in most resource-limited settings, particularly in Africa. Single-dose and short-course antiretroviral (ARV) regimens are only partially effective and have failed to achieve wide coverage despite their apparent simplicity. More potent ARV combinations are restricted to pregnant women who need treatment for themselves and are also infrequently used. Furthermore, postnatal transmission via breast-feeding is a serious additional threat. Modifications of infant feeding practices aim to reduce HIV-1 transmission through breast milk; replacement feeding is neither affordable nor safe for the majority of African women, and early breast-feeding cessation (eg, prior to 6 months of life) requires substantial care and nutritional counseling to be practiced safely. The recent roll out of ARV treatment has changed the paradigm of prevention of MTCT. To date, postnatal ARV interventions that have been evaluated target either maternal ARV treatment to selected breast-feeding women, with good efficacy, or single-drug postexposure prophylaxis for short periods of time to their neonates, with a partial efficacy and at the expense of acquisition of drug-related viral resistance. We hypothesize that a viable solution to eliminate pediatric AIDS lies in the universal provision of fully suppressive ARV regimens to all HIV-1-infected women through pregnancy, delivery, and the entire breast-feeding period. On the basis of available evidence, we suggest translating into practice the recently available evidence on this matter without any further delay.

  7. Tetanus and diphtheria antibodies and response to a booster dose in Brazilian HIV-1-infected women.

    PubMed

    Bonetti, Tatiana C S; Succi, Regina C M; Weckx, Lily Y; Tavares-Lopes, L; de Moraes-Pinto, M Isabel

    2004-09-09

    Tetanus and diphtheria (Td) antibodies were studied in HIV-1-infected women during puerperium. HIV group (n=61) was compared with Control group (n=101). Twenty-one women from HIV and 13 from Control group who had antibody levels lower than 0.1 IU/mL received a booster with Td vaccine. Antibodies were assessed by double antigen ELISA. Mean tetanus and diphtheria antibody levels from HIV group were lower than those from Control group. Multiple linear regression analysis showed that tetanus and diphtheria antibody levels were decreased by HIV-1-infection, and that was independent of the reduction due to the time interval between last booster and antibody assessment. After a booster dose, both groups had an increase in mean tetanus and diphtheria antibody levels, but in Control group the levels were higher than in HIV group.

  8. Universal antiretroviral therapy for pregnant and breast-feeding HIV-1-infected women: towards the elimination of mother-to-child transmission of HIV-1 in resource-limited settings

    PubMed Central

    Becquet, Renaud; Ekouevi, Didier Koumavi; Arrivé, Elise; Stringer, Jeffrey Sa; Meda, Nicolas; Chaix, Marie Laure; Tréluyer, Jean-Marc; Leroy, Valériane; Rouzioux, Christine; Blanche, Stéphane; Dabis, François

    2009-01-01

    Prevention of mother-to-child transmission of HIV-1 (MTCT) remains a challenge in most resource-limited settings, particularly in Africa. Single-dose and short-course antiretroviral (ARV) regimens are only partially effective and have failed to achieve wide coverage despite their apparent simplicity. More potent ARV combinations are restricted to pregnant women who need treatment for themselves but are also infrequently used. Furthermore, postnatal transmission via breastfeeding is a serious additional threat. Modifications of infant feeding practices aim to reduce breast-milk HIV transmission: replacement feeding is neither affordable nor safe for the majority of African women, and early breastfeeding cessation (e.g. prior to 6 months of life) requires substantial care and nutritional counselling to be practised safely. The recent roll out of ARV treatment has changed the paradigm of prevention of MTCT. To date, postnatal ARV interventions that have been evaluated target either maternal ARV treatment to selected breastfeeding women, with good efficacy, or single-drug post-exposure prophylaxis for short periods of time to their neonates, with a partial efficacy and at the expense of acquisition of drug-related viral resistance. We hypothesize that a viable solution to eliminate paediatric AIDS lies in the universal provision of fully suppressive ARV regimens to all HIV-infected women through pregnancy, delivery, and covering the entire breastfeeding period. Based on the available evidence, we suggest translating into practice the recently available evidence on this matter without any further delay. PMID:19916796

  9. Human Papillomavirus Infection in HIV-1 Infected Women in Catalonia (Spain): Implications for Prevention of Cervical Cancer

    PubMed Central

    Stuardo, Valeria; Agustí, Cristina; Godinez, José Manuel; Montoliu, Alexandra; Torné, Aureli; Tarrats, Antoni; Alcalde, Carmen; Martín, Dolores; Fernández-Montoli, Eulalia; Vanrell, Cristina; Solé, Josefa; Canet, Yolanda; Marqueta, José Manuel; Mohamed, Jadiyettu; Cuenca, Isabel; Lonca, Montserrat; Sirera, Guillem; Ferrer, Elena; Domingo, Pere; Lloveras, Belen; Miro, Josep María; De Sanjosé, Silvia; Casabona, Jordi

    2012-01-01

    Background High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women. Methods We enrolled 479 HIV-1–infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis. Results Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1–5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200cells/mm3 versus >500cells/mm3 (OR,8.4; 95%CI,3.7–19.2), HIV-1 viral load >10,000copies/mL versus <400copies/mL (OR,2.1; 95%CI,1.0–4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0–3.9). Sixty percent of HIV-1–infected women had had one Pap smear within the last 2 years. Conclusions The high prevalence of HPV infection and cervical lesions in the HIV-1–infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and

  10. Effectiveness of highly active antiretroviral therapy among HIV-1 infected women

    PubMed Central

    Gange, S; Barron, Y; Greenblatt, R; Anastos, K; Minkoff, H; Young, M; Kovacs, A; Cohen, M; Meyer, W; Munoz, A

    2002-01-01

    Design: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. Setting: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). Participants: A total of 1691 HIV seropositive women with a study visit after April 1996. Main results: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. Conclusions: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality. PMID:11812817

  11. DEFB1 5'UTR polymorphisms modulate the risk of HIV-1 infection in Mexican women.

    PubMed

    Estrada-Aguirre, J A; Osuna-Ramírez, I; Prado Montes de Oca, E; Ochoa-Ramirez, L A; Ramirez, M; Magallon-Zazueta, L G; Gonzalez-Beltran, M S; Cazarez-Salazar, S G; Rangel-Villalobos, H; Velarde-Felix, J S

    2014-01-01

    Immunologic and genetic factors are involved in HIV-1/AIDS pathogenesis. Defensins are key molecules in innate immunity that participate in the control and/or development of infection and disease. Using PCR-RFLPs, we determined the association between HIV-1/AIDS and human β-defensin 1 (DEFB1) 5'UTR -52 G/A (rs1799946), -44 C/G (rs1800972), and -20 G/A (rs11362) polymorphisms in three groups of women from the state of Sinaloa, located in the Northwest region of Mexico: i) healthy blood donors; ii) sex-workers; and iii) HIV-1 patients. The -52GG genotype was more frequent in blood donors than in patients (p= 0.023; Odds Ratio, OR= 0.49; 95% CI= 0.25-0.95), whereas the - 52GA genotype was significantly higher in patients (p= 0.013; OR= 2.03; 95% CI= 1.11-3.79, statistical power SP= 98.8%), as well as the frequencies of -20A allele (p= 0.017; OR= 1.60; 95% CI= 1.06-2.40), -20AA genotype (p= 0.047; OR = 2.02; 95% CI= 0.93-4.33) and the ACA haplotype with respect to healthy blood donors (p= 0.000012; OR= 5.82; 95% CI= 2.33-16.43, SP= 99.89%) and sex-workers (p= 0.019; OR= 2.18; 95% CI= 1.07-4.46). Conversely, the ACG haplotype was higher in healthy blood donors than in patients (p= 0.009; OR= 0.55; 95% CI= 0.34-0.89). In addition, the -44CC genotype was associated with a low plasma viral load (p= 0.015), whereas AGA, AGG and GGA haplotypes were more prevalent in individuals with high CD4 counts (p= 0.004, 0.046, and 0.029, respectively). These findings associate DEFB1 5'UTR polymorphisms with HIV-1/AIDS in Mexican women for the first time.

  12. Amino- and Carboxyl-Terminal CCR5 Mutations in Brazilian HIV-1-Infected Women and Homology Model of p.L55Q CCR5 Mutant.

    PubMed

    Costa, Giselle Calasans de Souza; Nunes, Marcio Roberto T; Jesus, Jaqueline Goes; Novaes, Thiago; Cardoso, Jedson Ferreira; Sousa Júnior, Edivaldo Costa; Santos, Edson de Souza; Galvão-Castro, Bernardo; Zanette, Dalila Luciola; Gonçalves, Marilda de Souza; Alcantara, Luiz Carlos Junior

    2015-07-01

    Genetic factors from an HIV-1 host can affect the rate of progression to AIDS and HIV infection. To investigate the frequency of mutations in the CCR5 gene, HIV-1 samples from infected women and uninfected individuals were selected for sequencing of the CCR5 gene regions encoding the N- and C-terminal protein domains. Physicochemical CCR5 modeling and potential protein domain analysis were performed in order to evaluate the impact of the mutations found in the properties and structure of CCR5. The p.L55Q mutation in the N-terminal protein domain was observed only in uninfected individuals, with an allelic frequency of 1.8%. Physicochemical analysis revealed that the p.L55Q mutation magnified the flexibility and accessibility profiles and the modeling of CCR5 structures showed resulting in a small deviation to the right, as well as a hydrophobic to hydrophilic property alteration. The p.L55Q mutation also resulted in a slight modification of the electrostatic load of this region. Additionally, three novel silent mutations were found at the C-terminal coding region among HIV-1-infected women. The results suggest that the p.L55Q mutation might alter CCR5 conformation. Further studies should be conducted to verify the role of this mutation in HIV-1 susceptibility.

  13. Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women

    PubMed Central

    2010-01-01

    Background Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution. Methods We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log10VL to assess the combined effect of these variables. Results In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels). Conclusions Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication. PMID:20822522

  14. Longitudinal Trends in Sexual Behaviors with Advancing Age and Menopause Among Women With and Without HIV-1 Infection

    PubMed Central

    Weedon, Jeremy; Golub, Elizabeth T.; Karpiak, Stephen E.; Gandhi, Monica; Cohen, Mardge H.; Levine, Alexandra M.; Minkoff, Howard L.; Adedimeji, Adebola A.; Goparaju, Lakshmi; Holman, Susan; Wilson, Tracey E.

    2014-01-01

    We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women’s Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62–64 % per decade of age. The odds of SA in a 6-month interval for women aged 40–57 declined by 18–22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions. PMID:25245474

  15. Differences in Clinical Manifestations of Acute and Early HIV-1 Infection between HIV-1 Subtypes in African Women

    PubMed Central

    Watkins, Richard R.; Morrison, Charles S.; Kwok, Cynthia; Chipato, Tsungai; Musoke, Robert; Arts, Eric J.; Nankya, Immaculate; Salata, Robert A.

    2015-01-01

    Little is known about the differences in clinical manifestations between women with various HIV-1 subtypes during acute (AI) and early (EI) HIV infection. In a longitudinal cohort study, clinical signs and symptoms among Uganda and Zimbabwe women with AI and EI were compared with HIV-negative controls; symptoms were assessed quarterly for 15 to 24 months. Early HIV infection was defined as the first visit during which a woman tested HIV antibody positive. Women who were HIV negative serologically but DNA polymerase chain reaction positive were considered AI. In all, 26 women were classified AI and 192 EI, with 654 HIV-negative controls. Primary HIV infection (AI and EI) was associated with unexplained fever (P <.01), weight loss (P <.01), fatigue (P <.01), inguinal adenopathy (P <.01), and cervical friability (P =.01). More women with subtype C infection had unexplained fever, fatigue, and abnormal vaginal discharge compared to subtype A or D infection. Inguinal adenopathy occurred less often in women with subtype A infection than those with subtype C or D infection. PMID:24106054

  16. Differences in Clinical Manifestations of Acute and Early HIV-1 Infection between HIV-1 Subtypes in African Women.

    PubMed

    Lemonovich, Tracy L; Watkins, Richard R; Morrison, Charles S; Kwok, Cynthia; Chipato, Tsungai; Musoke, Robert; Arts, Eric J; Nankya, Immaculate; Salata, Robert A

    2015-01-01

    Little is known about the differences in clinical manifestations between women with various HIV-1 subtypes during acute (AI) and early (EI) HIV infection. In a longitudinal cohort study, clinical signs and symptoms among Uganda and Zimbabwe women with AI and EI were compared with HIV-negative controls; symptoms were assessed quarterly for 15 to 24 months. Early HIV infection was defined as the first visit during which a woman tested HIV antibody positive. Women who were HIV negative serologically but DNA polymerase chain reaction positive were considered AI. In all, 26 women were classified AI and 192 EI, with 654 HIV-negative controls. Primary HIV infection (AI and EI) was associated with unexplained fever (P <.01), weight loss (P <.01), fatigue (P <.01), inguinal adenopathy (P <.01), and cervical friability (P =.01). More women with subtype C infection had unexplained fever, fatigue, and abnormal vaginal discharge compared to subtype A or D infection. Inguinal adenopathy occurred less often in women with subtype A infection than those with subtype C or D infection.

  17. Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women.

    PubMed

    Shen, Ruizhong; Achenbach, Jenna; Shen, Yue; Palaia, Jana; Rahkola, Jeremy T; Nick, Heidi J; Smythies, Lesley E; McConnell, Michelle; Fowler, Mary G; Smith, Phillip D; Janoff, Edward N

    2015-01-01

    Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT). Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs) and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

  18. Reasons for poor adherence to antiretroviral therapy postnatally in HIV-1 infected women treated for their own health: experiences from the Mitra Plus study in Tanzania

    PubMed Central

    2013-01-01

    Background In a study of prevention of mother-to-child transmission of HIV (PMTCT) by triple antiretroviral therapy (ART) in Dar es Salaam, Tanzania (the Mitra Plus study), retrospective viral load testing revealed a high and increasing frequency of detectable viral load during follow-up for two years postnatally in women given continuous ART for their own health suggesting poor adherence. This study explored women’s own perceived barriers to adherence to ART post-delivery so as to identify ways to facilitate better drug adherence among women in need of ART for their own health. Methods Semi-structured interviews were conducted with 23 of the 48 women who had detectable viral load at 24 months postnatally. Content analysis was used to analyze the data. Results Most women in the study did not acknowledge poor adherence until confronted with the viral load figures. Then, however, they revealed multiple reasons for failing to adhere. They said that their motivation to take ART decreased once they had protected their children from becoming infected and successfully weaned them. Feeling well for some, and a feeling of hopelessness for others, also decreased motivation to continue ART. The overwhelming demands of everyday life, poverty and lack of empowerment also posed significant barriers to long-term adherence. The need to keep their HIV status a secret and not let anyone see them taking the drugs was another steep barrier. Conclusion Reasons for postnatal failure to adhere by mothers put on ART for life during pregnancy included lack of motivation to continue ART after weaning the child, poverty and stigma. Projects that simultaneously address stigma, poverty and women’s lack of empowerment may be necessary for PMTCT and ART to reach their full potential. Our results indicate that the new WHO proposal to start all HIV-infected pregnant women on lifelong ART regardless of CD4 cell count needs to address the challenging realities of women in resource-poor contexts

  19. Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

    PubMed Central

    Delaugerre, Constance; Chaix, Marie-Laure; Blanche, Stephane; Warszawski, Josiane; Cornet, Dorine; Dollfus, Catherine; Schneider, Veronique; Burgard, Marianne; Faye, Albert; Mandelbrot, Laurent; Tubiana, Roland; Rouzioux, Christine

    2009-01-01

    Background Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns. Patients and Methods We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing. Results Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%): drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10) and neonatal lymphocytes (2/8) suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped. Conclusion This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%), drug resistance was archived in

  20. Epidemiology and detection of HIV-1 among pregnant women in the United Kingdom: results from national surveillance 1988-96.

    PubMed Central

    Nicoll, A.; McGarrigle, C.; Brady, A. R.; Ades, A. E.; Tookey, P.; Duong, T.; Mortimer, J.; Cliffe, S.; Goldberg, D.; Tappin, D.; Hudson, C.; Peckham, C.

    1998-01-01

    OBJECTIVE: To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom. DESIGN: Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists. SETTING: United Kingdom, 1988-96. SUBJECTS: Pregnant women proceeding to live births and their children. MAIN OUTCOME MEASURES: Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics. RESULTS: HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers' infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy. CONCLUSIONS: HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children. PMID:9472504

  1. High-risk oncogenic HPV genotype infection associates with increased immune activation and T cell exhaustion in ART-suppressed HIV-1-infected women

    PubMed Central

    Papasavvas, Emmanouil; Surrey, Lea F.; Glencross, Deborah K.; Azzoni, Livio; Joseph, Jocelin; Omar, Tanvier; Feldman, Michael D.; Williamson, Anna-Lise; Siminya, Maureen; Swarts, Avril; Yin, Xiangfan; Liu, Qin; Firnhaber, Cynthia; Montaner, Luis J.

    2016-01-01

    ABSTRACT Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV+ women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24). Sampling included endocervical brushing (HPV DNA genotyping), Pap smear (cytology), colposcopic punch biopsy (histopathology, histochemical evaluation of immune cells), and peripheral blood (clinical assessment, flow cytometry-based immune subset characterization). Statistics were done using R2.5.1. Irrespective of the presence of CIN, HR (+) HPV women had higher circulating levels of T cells expressing markers of activation/exhaustion (CD38, PD1, CTLA-4, BTLA, CD160), Tregs, and myeloid subsets expressing corresponding ligands (PDL1, PDL2, CD86, CD40, HVEM) than HR (-) HPV women. A decrease in circulating NK cells was associated with CIN grade. CD4+ T cell count associated negatively with T cell exhaustion and expression of negative regulators on myeloid cells. Women with CIN when compared to HR (-) HPV women, had higher cervical cell density in stroma and epithelium for CD4+, CD68+, and CD11c+ cells, and only in stroma for CD8+ cells. We conclude that in ART-suppressed HIV-infected women with HPV co-infection the levels of T and myeloid cell activation/exhaustion are associated with the presence of HR HPV genotypes. PMID:27467943

  2. Relationship Between Genital Drug Concentrations and Cervical Cellular Immune Activation and Reconstitution in HIV-1-Infected Women on a Raltegravir Versus a Boosted Atazanavir Regimen

    PubMed Central

    Palmer, Claire; Predhomme, Julie; Searls, Kristina; Kerr, Becky; Seifert, Sharon; Caraway, Patricia; Gardner, Edward M.; MaWhinney, Samantha; Anderson, Peter L.

    2015-01-01

    Abstract Determinants of HIV-infected women's genital tract mucosal immune health are not well understood. Because raltegravir (RAL) achieves relatively higher genital tract concentrations than ritonavir-boosted atazanavir (ATV), we examined whether an RAL-based regimen is associated with improved cervical immune reconstitution and less activation in HIV+ women compared to an ATV-based regimen. Peripheral blood, cervical brushings, cervical–vaginal lavage (CVL), and cervical biopsies were collected from HIV+ women on tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and either RAL (n=14) or ATV (n=19) with CD4+ T cells>300 cells/mm3 and HIV RNA<48 copies/ml. HLA-DR+CD38+ T cells were measured in blood and cervical cells using flow cytometry, CD4+ and CD8+ T cells were quantified in cervical biopsies by immunofluorescent analysis, and HIV RNA (VL), ATV, and RAL concentrations were measured in CVL. In a linear regression model of log(CVL concentration) versus both log(plasma concentration) and treatment group, the RAL CVL level was 519% (95% CI: 133, 1,525%) higher than for ATV (p<0.001). Genital tract VL was undetectable in 90% of subjects and did not differ by regimen. There were no significant differences between groups in terms of cervical %HLA-DR+CD38+CD4+ or CD8+ T cells, CD4+ or CD8+ T cells/mm2, or CD4:CD8 ratio. After adjusting for treatment time and group, the CVL:plasma drug ratio was not associated with the cervical CD4:CD8 ratio or immune activation (p>0.6). Despite significantly higher genital tract penetration of RAL compared to ATV, there were no significant differences in cervical immune activation or reconstitution between women on these regimens, suggesting both drug regimens achieve adequate genital tract levels to suppress virus replication. PMID:26059647

  3. Mortality during the first 24 months after delivery in relation to CD4 T-lymphocyte levels and viral load in a cohort of breast-feeding HIV-1-infected women in Dar es Salaam, Tanzania.

    PubMed

    Kilewo, Charles; Karlsson, Katarina; Swai, Andrew; Massawe, Augustine; Lyamuya, Eligius; Mhalu, Fred; Biberfeld, Gunnel

    2005-04-15

    resource-limited settings in HIV-1-infected adults with CD4 cell counts <200/mm and show that this is appropriate also among perinatal women.

  4. Vaccinations for pregnant women.

    PubMed

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources.

  5. Macrophage polarization and HIV-1 infection.

    PubMed

    Cassol, Edana; Cassetta, Luca; Alfano, Massimo; Poli, Guido

    2010-04-01

    Polarization of MP into classically activated (M1) and alternatively activated (M2a, M2b, and M2c) macrophages is critical in mediating an effective immune response against invading pathogens. However, several pathogens use these activation pathways to facilitate dissemination and pathogenesis. Viruses generally induce an M1-like phenotype during the acute phase of infection. In addition to promoting the development of Th1 responses and IFN production, M1 macrophages often produce cytokines that drive viral replication and tissue damage. As shown for HIV-1, polarization can also alter macrophage susceptibility to infection. In vitro polarization into M1 cells prevents HIV-1 infection, and M2a polarization inhibits viral replication at a post-integration level. M2a cells also express high levels of C-type lectins that can facilitate macrophage-mediated transmission of HIV-1 to CD4(+) T cells. Macrophages are particularly abundant in mucosal membranes and unlike DCs, do not usually migrate to distal tissues. As a result, macrophages are likely to contribute to HIV-1 pathogenesis in mucosal rather than lymphatic tissues. In vivo polarization of MP is likely to span a spectrum of activation phenotypes that may change the permissivity to and alter the outcome of HIV-1 and other viral infections.

  6. Cyclophilin B enhances HIV-1 infection

    SciTech Connect

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

    2016-02-15

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

  7. Lymph drainage in pregnant women.

    PubMed

    Cataldo Oportus, Sylvia; de Paiva Rodrigues, Lilian; Pereira de Godoy, José Maria; Guerreiro Godoy, Maria de Fátima

    2013-01-01

    Aim. The aim of this study was to evaluate the efficacy of lymph drainage to reduce edema of pregnant women. Method. Pregnant women (30 limbs) from the Obstetrics Outpatient Clinic of the Medical School of Santa Casa in São Paulo in the period December 2009 to May 2010 were enrolled in this quantitative, prospective study. The patients, in the 5th to 8th months of gestation, were submitted to one hour of manual lymph drainage of the legs. The volume of the legs was measured by water displacement volumetry before and after one hour of drainage using the Godoy & Godoy manual lymph drainage technique. The paired t-test was used for statistical analysis with an alpha error of 5% being considered significant. Results. Manual lymph drainage significantly reduced swelling of the legs of pregnant women during the day (P = 0.04). Conclusion. Manual lymph drainage helps to reduce limb size during the day of pregnant women.

  8. Antithrombotic therapy for pregnant women.

    PubMed

    Toyoda, Kazunori

    2013-01-01

    Coagulability increases during pregnancy, and thromboembolism can easily occur. Venous thromboembolism is a cause of death in pregnant women, but arterial thrombosis such as ischemic stroke in pregnancy is also not uncommon. In pharmacotherapy for thromboembolism in pregnant women, fetal toxicity and teratogenicity must be carefully considered. As anticoagulants in pregnant women, unfractionated heparin and low-molecular-weight heparin are recommended, but warfarin is not recommended since it has a low molecular weight and crosses the placenta. Various types of new oral anticoagulant drugs have been available in Japan since 2011. However, the Japanese package inserts for these anticoagulants advise quite cautious administration in pregnant women. The guidelines on pregnant women include less information about antiplatelet drugs than anticoagulant drugs. Aspirin may cause teratogenicity and fetal toxicity, and perinatal mortality is increased. However, when low doses of aspirin are administered as antiplatelet therapy, the US Food and Drug Administration has assigned pregnancy category C, and treatment is relatively safe. Neurosurgeons and neurologists commonly encounter pregnant women with thromboembolism, such as ischemic stroke. Up-to-date information and correct selection of drugs are necessary in consultation with specialists in perinatal care.

  9. Serum IgD behaviour in HIV-1 infected patients.

    PubMed

    Raiteri, R; Albonico, M; Deiana, R; Marietti, G; Sinicco, A

    1991-01-01

    From September 1987 to February 1990, repeated tests were performed in 325 HIV-1 infected subjects at different clinical stages using a radial immunodiffusion method to determine serum IgD behaviour in HIV-1 infection. Four patients had acute HIV-1 infection, 72 asymptomatic infection, 163 PGL, 49 ARC and 37 AIDS. During the study, 57 seropositive patients developed AIDS. The correlation between serum IgD and the clinical stage of HIV-1 infection, CD4+ and CD8+ lymphocyte levels, CD4+/CD8+ ratio, HIV-1 (p24) antigenemia and reactivity to core proteins, IgG, IgA, IgM isotypes and serum beta 2-microglobulin concentration. A significant correlation was noted between HIV-1 (p24) antigenemia, the disappearance of the antibodies reactivity to core proteins and IgD levels in ARC patients. A progressive increase of serum IgD before the occurrence of the symptomatic stage of HIV-1 infection was observed in HIV-1 infected patients who developed AIDS.

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

    PubMed

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

    2016-05-01

    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.

  11. Eradicating HIV-1 infection: seeking to clear a persistent pathogen

    PubMed Central

    Archin, Nancie M.; Sung, Julia Marsh; Garrido, Carolina; Soriano-Sarabia, Natalia; Margolis, David M.

    2015-01-01

    Effective antiretroviral therapy (ART) blunts viraemia, which enables HIV-1-infected individuals to control infection and live long, productive lives. However, HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbours integrated provirus within host cellular DNA. This latent infection is unaffected by ART and hidden from the immune system. Recent studies have focused on the development of therapies to disrupt latency. These efforts unmasked residual viral genomes and highlighted the need to enable the clearance of latently infected cells, perhaps via old and new strategies that improve the HIV-1-specific immune response. In this Review, we explore new approaches to eradicate established HIV-1 infection and avoid the burden of lifelong ART. PMID:25402363

  12. Broadly neutralizing antibodies: An approach to control HIV-1 infection.

    PubMed

    Yaseen, Mahmoud Mohammad; Yaseen, Mohammad Mahmoud; Alqudah, Mohammad Ali

    2017-01-02

    Although available antiretroviral therapy (ART) has changed human immunodeficiency virus (HIV)-1 infection to a non-fatal chronic disease, the economic burden of lifelong therapy, severe adverse ART effects, daily ART adherence, and emergence of ART-resistant HIV-1 mutants require prospecting for alternative therapeutic modalities. Indeed, a growing body of evidence suggests that broadly neutralizing anti-HIV-1 antibodies (BNAbs) may offer one such feasible alternative. To evaluate their therapeutic potential in established HIV-1 infection, we sought to address recent advances in pre-clinical and clinical investigations in this area of HIV-1 research. In addition, we addressed the obstacles that may impede the success of such immunotherapeutic approach, suggested strategic solutions, and briefly compared this approach with the currently used ART to open new insights for potential future passive immunotherapy for HIV-1 infection.

  13. Immune reconstitution and vaccination outcome in HIV-1 infected children

    PubMed Central

    Cagigi, Alberto; Cotugno, Nicola; Giaquinto, Carlo; Nicolosi, Luciana; Bernardi, Stefania; Rossi, Paolo; Douagi, Iyadh; Palma, Paolo

    2012-01-01

    Current evidence on routine immunization of HIV-1 infected children point out the need for a special vaccine schedule in this population. However, optimal strategies for identifying individuals susceptible to infections, and then offering them sustained protection through appropriate immunization schedule, both in terms of timing and number of vaccine doses, still remain to be elucidated. Understanding the degree of immune recovery after HAART initiation is important in guiding administration of routine vaccination in HIV-1 infected children. Although quantitative measures (e.g., CD4+ T-cell counts and immunoglobulin levels) are frequently performed to evaluate immune parameters, these measures do not fully mirror functional immune recovery. Here, we will review the status of single mandatory and recommended vaccines for HIV-1 infected children in relation to immune recovery after HAART initiation with the aim of identifying new means to help design personalized vaccine schedules for this population. PMID:22906931

  14. 42 CFR 435.116 - Pregnant women.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... waiver of the State plan covering pregnant women, as of March 23, 2010 or December 31, 2013, if higher... 42 Public Health 4 2014-10-01 2014-10-01 false Pregnant women. 435.116 Section 435.116 Public..., AND AMERICAN SAMOA Mandatory Coverage Mandatory Coverage of Pregnant Women, Children Under 19,...

  15. 42 CFR 435.116 - Pregnant women.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... waiver of the State plan covering pregnant women, as of March 23, 2010 or December 31, 2013, if higher... 42 Public Health 4 2013-10-01 2013-10-01 false Pregnant women. 435.116 Section 435.116 Public..., AND AMERICAN SAMOA Mandatory Coverage Mandatory Coverage of Pregnant Women, Children Under 19,...

  16. Constructing the Average Natural History of HIV-1 Infection

    NASA Astrophysics Data System (ADS)

    Diambra, L.; Capurro, A.; Malta, C. P.

    2007-05-01

    Many aspects of the natural course of the HIV-1 infection remains unclear, despite important efforts towards understanding its long-term dynamics. Using a scaling approach that places progression markers (viral load, CD4+, CD8+) of many individuals on a single average natural course of disease progression, we introduce the concept of inter-individual scaling and time scaling. Our quantitative assessment of the natural course of HIV-1 infection indicates that the dynamics of the evolution for the individual that developed AIDS (opportunistic infections) is different from that of the individual that did not develop AIDS. This means that the rate of progression is not relevant for the infection evolution.

  17. Prevalence of mutant CCR5 allele in Slovenian HIV-1-infected and non-infected individuals.

    PubMed

    Poljak, M; Tomazic, J; Seme, K; Maticic, M; Vidmar, L

    1998-02-01

    A 32 bp deletion in the CCR5 gene designated CCR5 delta 32 has been identified recently as the cellular basis for resistance to human immunodeficiency virus type 1 (HIV-1) in some individuals which remained non-infected despite a repeated exposure to this virus. The prevalence of this deletion was examined by polymerase chain reaction (PCR) on 51 HIV-1-infected and 385 non-infected individuals from all parts of Slovenia. 84.4% of the the HIV-1-infected and 83.2% of the non-infected individuals were homozygous for wild type CCR5, and 19.6% and 16.3%, respectively, were heterozygous. No homozygous mutant genotype was observed among the HIV-1-infected patients. Of the non-infected individuals, 2 women (0.5%) were found to harbour the CCR5 delta 32/CCR5 delta 32 genotype only, which is, to the best of our knowledge, the lowest prevalence of this particular genotype found among Caucasians to date.

  18. Callosal Degradation in HIV-1 Infection Predicts Hierarchical Perception: A DTI study

    PubMed Central

    Müller-Oehring, Eva M.; Schulte, Tilman; Rosenbloom, Margaret J.; Pfefferbaum, Adolf; Sullivan, Edith V.

    2010-01-01

    HIV-1 infection affects white matter circuits linking frontal, parietal, and subcortical regions that subserve visuospatial attention processes. Normal perception requires the integration of details, preferentially processed in the left hemisphere, and the global composition of an object or scene, preferentially processed in the right hemisphere. We tested whether HIV-related callosal white matter degradation contributes to disruption of selective lateralized visuospatial and attention processes. A hierarchical letter target detection paradigm was devised, where large (global) letters were composed of small (local) letters. Participants were required to identify target letters among distractors presented at global, local, both or neither level. Attention was directed to one (global or local) or both levels. Participants were 21 HIV-1 infected and 19 healthy control men and women who also underwent Diffusion Tensor Imaging (DTI). HIV-1 participants showed impaired hierarchical perception owing to abnormally enhanced global facilitation effects but no impairment in attentional control on local-global feature selection. DTI metrics revealed poorer fiber integrity of the corpus callosum in HIV-1 than controls that was more pronounced in posterior than anterior regions. Analysis revealed a double dissociation of anterior and posterior callosal compromise in HIV-1 infection: Compromise in anterior but not posterior callosal fiber integrity predicted response conflict elicited by global targets, whereas compromise in posterior but not anterior callosal fiber integrity predicted response facilitation elicited by global targets. We conclude that component processes of visuospatial perception are compromised in HIV-1 infection attributable, at least in part, to degraded callosal microstructural integrity relevant for local-global feature integration. PMID:20018201

  19. Short Communication Phylogenetic Characterization of HIV Type 1 CRF01_AE V3 Envelope Sequences in Pregnant Women in Northern Vietnam

    PubMed Central

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca

    2012-01-01

    Abstract Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005–2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology. PMID:21936713

  20. Short communication: phylogenetic characterization of HIV type 1 CRF01_AE V3 envelope sequences in pregnant women in Northern Vietnam.

    PubMed

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca; Ehrnst, Anneka

    2012-08-01

    Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005-2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology.

  1. Impairment of B-cell functions during HIV-1 infection.

    PubMed

    Amu, Sylvie; Ruffin, Nicolas; Rethi, Bence; Chiodi, Francesca

    2013-09-24

    A variety of B-cell dysfunctions are manifested during HIV-1 infection, as reported early during the HIV-1 epidemic. It is not unusual that the pathogenic mechanisms presented to elucidate impairment of B-cell responses during HIV-1 infection focus on the impact of reduced T-cell numbers and functions, and lack of germinal center formation in lymphoid tissues. To our understanding, however, perturbation of B-cell phenotype and function during HIV-1 infection may begin at several different B-cell developmental stages. These impairments can be mediated by intrinsic B-cell defects as well as by the lack of proper T-cell help. In this review, we will highlight some of the pathways and molecular interactions leading to B-cell impairment prior to germinal center formation and B-cell activation mediated through the B-cell receptor in response to HIV-1 antigens. Recent studies indicate a regulatory role for B cells on T-cell biology and immune responses. We will discuss some of these novel findings and how these regulatory mechanisms could potentially be affected by the intrinsic defects of B cells taking place during HIV-1 infection.

  2. Low seroprevalence of herpes simplex virus type 2 among pregnant women in Senegal.

    PubMed

    Diawara, Silman; Toure Kane, Coumba; Legoff, Jérôme; Gaye, Astou Gueye; Mboup, Souleymane; Bélec, Laurent

    2008-03-01

    Herpes simplex virus type 2 (HSV-2) is considered as a major co-factor of both sexual transmission and acquisition of the human immunodeficiency virus (HIV). The HIV epidemic in Senegal is characterized by a remarkable and stable low prevalence. Whether HSV-2 may also constitute a possible co-factor favouring the spreading of HIV epidemic in Senegal is yet unknown. This prompted us to evaluate the HSV-2 seroprevalence in the sentinel population of pregnant women in Senegal. Two hundred and sixty pregnant women attending Roi Baudouin maternity in the capital city Dakar (n = 14; 135) and the antenatal clinic in Kaolack (n = 125), the third city of Senegal, were prospectively recruited between March and August 2003. Fifty-six women (22%) were positive for HSV-2 serology. The prevalence of HSV-2 seropositivity was higher in women living in Dakar (26%) than in those living in Kaolack (16%) (P < 0.01). Only two women from Dakar and two other from Kaolack were found to be HIV-1-infected. Our observations suggest a seemingly low seroprevalence of HSV-2 infection in adult women Senegal, comparable with those usually reported in Western countries. Further, epidemiological surveys are needed to confirm these results in the general population.

  3. Sedentary behavior patterns in non-pregnant and pregnant women.

    PubMed

    Hawkins, Marquis; Kim, Youngdeok; Gabriel, Kelley Pettee; Rockette-Wagner, Bonny Jane; Chasan-Taber, Lisa

    2017-06-01

    Sedentary behavior has been associated with adverse health outcomes among pregnant women; however, few studies have characterized sedentary behavior patterns in this population. We described patterns of accelerometer-determined indicators of sedentary behavior among a national sample of US pregnant (n = 234) women and non-pregnant (n = 1146) women participating in the NHANES 2003-06 cycles. We included women with ≥ 4 days of accelerometer wear of ≥ 10 h/day. A count threshold of < 100 cpm was used to describe sedentary behavior as: 1) total accumulated sedentary time by bout length categories; 2) accumulated sedentary time within discrete bout length categories; 3) mean, median, and usual bout length; and 4) and bout frequency. Both non-pregnant and pregnant women spent up to 60% of their accelerometer wear time in sedentary behavior depending on the minimum bout threshold applied. Sedentary time was higher among pregnant women compared to non-pregnant women when lower bout thresholds (i.e. 10 min or less) were applied. The majority of total sedentary time was accumulated in bouts lasting < 10 min. The women averaged less than two prolonged sedentary bouts (i.e., ≥ 30 min) per day, which accounted for nearly 20% of total accumulated sedentary time. When applying a minimum threshold of at least 15 min, sedentary time increased across pregnancy trimesters, while sedentary time was similar across trimesters when using lower thresholds. These findings provide the first characterization of accelerometer-determined indicators of sedentary behavior in pregnant women. The minimum bout threshold applied influenced estimates of sedentary time and patterns sedentary time accumulation across pregnancy trimesters.

  4. Altered sialylation of alveolar macrophages in HIV-1-infected individuals

    PubMed Central

    PERRIN, C; GIORDANENGO, V; BANNWARTH, S; BLAIVE, B; LEFEBVRE, J-C

    1997-01-01

    In previous studies, we have demonstrated that O-glycans at the surface of HIV-1-infected cell lines were hyposialylated. Moreover, we and others have shown that HIV+ individuals produced autoantibodies that react with hyposialylated CD43, on T cell lines. Since the autoantigen responsible for this abnormal immune response was not easily found in the peripheral blood cells of corresponding patients, we searched for its possible presence in other sites. Using fluorescence staining of alveolar macrophages with various lectins, we show that the binding of the PNA lectin specific for asialo O-glycans is much more efficient on cells from HIV-1-infected individuals. Moreover, the degree of reactivity of PNA is correlated with the clinical stage of the illness. PMID:9353144

  5. Altered sialylation of alveolar macrophages in HIV-1-infected individuals.

    PubMed

    Perrin, C; Giordanengo, V; Bannwarth, S; Blaive, B; Lefebvre, J C

    1997-10-01

    In previous studies, we have demonstrated that O-glycans at the surface of HIV-1-infected cell lines were hyposialylated. Moreover, we and others have shown that HIV+ individuals produced autoantibodies that react with hyposialylated CD43, on T cell lines. Since the autoantigen responsible for this abnormal immune response was not easily found in the peripheral blood cells of corresponding patients, we searched for its possible presence in other sites. Using fluorescence staining of alveolar macrophages with various lectins, we show that the binding of the PNA lectin specific for asialo O-glycans is much more efficient on cells from HIV-1-infected individuals. Moreover, the degree of reactivity of PNA is correlated with the clinical stage of the illness.

  6. Treating HIV-1 Infection: What Might the Future Hold?

    PubMed Central

    Lichterfeld, Mathias; Zachary, Kimon C.

    2011-01-01

    Advances in antiretroviral combination therapy lasting the past two decades have transformed HIV-1 infection from a fatal disease into a chronic medical condition that in many cases does not compromise life quality. There are 25 different antiretroviral agents available currently, allowing for patient-centered, individualized management of HIV-1 infection, and ongoing progress in HIV-1 virology and antiretroviral pharmacology is likely to expand treatment options further in the future. Nevertheless, antiretroviral therapy continues to have limitations, including insufficient immunological reconstitution, selection of drug resistance, ongoing abnormal immune activation despite effective suppression of HIV-1 viremia, and the inability to target latently infected cells that are responsible for long-term viral persistence. Owing to these shortcomings, the theoretical ability of antiretroviral therapy to extend life expectancy to normal levels is not realized in many cases. Strategies to address these limitations are a matter of active ongoing research and will be summarized in this article. PMID:23251756

  7. Differentially-Expressed Pseudogenes in HIV-1 Infection

    PubMed Central

    Gupta, Aditi; Brown, C. Titus; Zheng, Yong-Hui; Adami, Christoph

    2015-01-01

    Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these “functional” pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit. PMID:26426037

  8. Defective proviruses rapidly accumulate during acute HIV-1 infection.

    PubMed

    Bruner, Katherine M; Murray, Alexandra J; Pollack, Ross A; Soliman, Mary G; Laskey, Sarah B; Capoferri, Adam A; Lai, Jun; Strain, Matthew C; Lada, Steven M; Hoh, Rebecca; Ho, Ya-Chi; Richman, Douglas D; Deeks, Steven G; Siliciano, Janet D; Siliciano, Robert F

    2016-09-01

    Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies.

  9. The macrophage in HIV-1 infection: from activation to deactivation?

    PubMed

    Herbein, Georges; Varin, Audrey

    2010-04-09

    Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-gamma display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease.

  10. The epidemiology of HIV-1 infection in urban areas, roadside settlements and rural villages in Mwanza Region, Tanzania.

    PubMed

    Barongo, L R; Borgdorff, M W; Mosha, F F; Nicoll, A; Grosskurth, H; Senkoro, K P; Newell, J N; Changalucha, J; Klokke, A H; Killewo, J Z

    1992-12-01

    Between August 1990 and February 1991, health workers took blood samples from, and trained interviewers spoke to, 5145 15-to-54-year-old adults living in either an urban area (1554), in a rural village (2434), or in a roadside settlement (1157) in the Mwanza Region of Tanzania to determine the prevalence of HIV-1 infection and its most significant risk factors. The prevalence rate of HIV-1 infection was highest in urban areas, lower in roadside settlements, and lowest in rural areas (11.8%, 7.3%, and 2.5%, respectively), suggesting that HIV-1 had spread along main roads. Yet, there were as many people infected with HIV-1 in rural areas of the Mwanza Region as there were in Mwanza town. Women were 1.2 (rural) to 1.7 (urban) times more likely to be infected with HIV-1 than were men, indicating greater efficiency of HIV-1 transmission from men to women than from women to men. HIV-1 infection peaked in the 15-to-34-year-old group in women and in the 25-to-44-year-old group in men. Separated, divorced, or widowed men and women were at increased risk of being HIV-1 infected, even when controlled for numerous factors (odds ratio (OR) = 3.4 and 1.6, respectively). This may have been an indication of multiple partners, since the question concerning multiple partners was vague. Other important risk factors for women and men were syphilis antibodies (OR = 1.7 and 1.85), history of genital discharge or chancroid (OR = 2, 1.6 and 2.7, 1.6), travel to Mwanza town (OR = 2.1 and 1.7), and receiving injections during the previous 12 months (OR = 1.5 and 1.9). There was no link between male circumcision and HIV-1 infection. In fact, there seemed to be a moderate protective effect (OR = 0.8). This effect may be even more likely since urban men, who were at greatest risk of HIV-1 infection (8.7% vs. 5.4% [roadside] and 2.4% [rural]), had the highest rate of circumcision (61% vs. 29% and 17%, respectively).

  11. Gelsolin activity controls efficient early HIV-1 infection

    PubMed Central

    2013-01-01

    Background HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-receptor interactions and that generates the tension at the plasma membrane necessary to potentiate fusion pore formation, thereby favouring early HIV-1 infection. However, it remains unclear whether the dynamic processing of F-actin and the amount of cortical actin available during the initial virus-cell contact are required to such events. Results Here we show that gelsolin restructures cortical F-actin during HIV-1 Env-gp120-mediated signalling, without affecting cell-surface expression of receptors or viral co-receptor signalling. Remarkably, efficient HIV-1 Env-mediated membrane fusion and infection of permissive lymphocytes were impaired when gelsolin was either overexpressed or silenced, which led to a loss or gain of cortical actin, respectively. Indeed, HIV-1 Env-gp120-induced F-actin reorganization and viral receptor capping were impaired under these experimental conditions. Moreover, gelsolin knockdown promoted HIV-1 Env-gp120-mediated aberrant pseudopodia formation. These perturbed-actin events are responsible for the inhibition of early HIV-1 infection. Conclusions For the first time we provide evidence that through its severing of cortical actin, and by controlling the amount of actin available for reorganization during HIV-1 Env-mediated viral fusion, entry and infection, gelsolin can constitute a barrier that restricts HIV-1 infection of CD4+ lymphocytes in a pre-fusion step. These findings provide important insights into the complex molecular and actin-associated dynamics events that underlie early viral infection. Thus, we propose that gelsolin is a new factor that can limit HIV-1 infection acting at a pre-fusion step

  12. Medroxyprogesterone acetate increases HIV-1 infection of unstimulated peripheral blood mononuclear cells in vitro

    PubMed Central

    Sampah, Maame Efua S.; Laird, Gregory M.; Blankson, Joel N.; Siliciano, Robert F.; Coleman, Jenell S.

    2015-01-01

    Objective Several observational studies suggest that medroxyprogesterone acetate (MPA) injectable contraception may increase a woman’s risk of sexual HIV-1 acquisition. In vitro studies are conflicting, mainly due to differences in the type of progestin studied or activation status of the primary cells. We sought to determine if MPA increases infection of unstimulated peripheral blood mononuclear cells (PBMC). Methods Freshly isolated PBMC from normal blood donors were treated with physiologic MPA concentrations ranging from 0.003 ng/mL to 5 ng/mL and infected with GFP-tagged R5-tropic or X4-tropic HIV-1 pseudoviruses by spinoculation. The infection was limited to a single cycle. Cells were stained with CD3, CD8, and CD14. Infection was quantified as the percentage of GFP+ cells by flow cytometry. Results Absolute infection was greater among unstimulated MPA-treated CD3+CD8− T cells versus untreated cells across MPA concentrations of 0.003 to 3 ng/mL using R5 (P <0.003) and 0.03 to 0.3 ng/mL using X4 pseudovirus (P < 0.005). There was increased relative infection of CD3+CD8− T cells in MPA-treated whole PBMC cultures but not after monocytes were depleted (P<0.02). HIV-1 infection of stimulated PBMC showed no differences in R5 or X4 infection across all MPA concentrations (P > 0.5). Conclusions CD3+CD8− T cell population of MPA-treated unstimulated PBMC were more susceptible to HIV-1 infection than untreated cells. The increased infection was partly due to monocytes and was lost when PBMC were exogenously stimulated. These data provide confirmation of a biological association between MPA exposure and increased susceptibility to HIV-1 infection, particularly among women who inject drugs. PMID:26035316

  13. The impact of pregnancy on the HIV-1-specific T cell function in infected pregnant women.

    PubMed

    Hygino, Joana; Vieira, Morgana M; Kasahara, Taissa M; Xavier, Luciana F; Blanco, Bernardo; Guillermo, Landi V C; Filho, Renato G S; Saramago, Carmen S M; Lima-Silva, Agostinho A; Oliveira, Ariane L; Guimarães, Vander; Andrade, Arnaldo F B; Bento, Cleonice A M

    2012-12-01

    Evidences indicate that pregnancy can alter the Ag-specific T-cell responses. This work aims to evaluate the impact of pregnancy on the in vitro HIV-1-specific immune response. As compared with non-pregnant patients, lower T-cell proliferation and higher IL-10 production were observed in T-cell cultures from pregnant patients following addition of either mitogens or HIV-1 antigens. In our system, the main T lymphocyte subset involved in producing IL-10 was CD4(+)FoxP3(-). Depletion of CD4(+) cells elevated TNF-α and IFN-γ production. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was inversely related to IL-10 production. In these cultures, the neutralization of IL-10 by anti-IL-10 mAb elevated TNF-α release and HIV-1 replication. In conclusion, our results reveal that pregnancy-related events should favor the expansion of HIV-1-specific IL-10-secreting CD4(+) T-cells in HIV-1-infected women, which should, in the scenario of pregnancy, help to reduce the risk of vertical HIV-1 transmission.

  14. Exercise and Human Immunodeficiency Virus (HIV-1) Infection

    NASA Technical Reports Server (NTRS)

    Lawless, DeSales; Jackson, Catherine G. R.; Greenleaf, John E.

    1995-01-01

    The human immune system is highly efficient and remarkably protective when functioning properly. Similar to other physiological systems, it functions best when the body is maintained with a balanced diet, sufficient rest and a moderately stress-free lifestyle. It can be disrupted by inappropriate drug use and extreme emotion or exertion. The functioning of normal or compromised immune systems can be enhanced by properly prescribed moderate exercise conditioning regimens in healthy people, and in some human immunodeficiency virus (HIV-1)-infected patients but not in others who unable to complete an interval training program. Regular exercise conditioning in healthy people reduces cardiovascular risk factors, increases stamina, facilitates bodyweight control, and reduces stress by engendering positive feelings of well-being. Certain types of cancer may also be suppressed by appropriate exercise conditioning. Various exercise regimens are being evaluated as adjunct treatments for medicated patients with the HIV-1 syndrome. Limited anecdotal evidence from patients suggests that moderate exercise conditioning is per se responsible for their survival well beyond expectancy. HIV-1-infected patients respond positively, both physiologically and psychologically, to moderate exercise conditioning. However, the effectiveness of any exercise treatment programme depends on its mode, frequency, intensity and duration when prescribed o complement the pathological condition of the patient. The effectiveness of exercise conditioning regimens in patients with HIV-1 infection is reviewed in this article. In addition, we discuss mechanisms and pathways, involving the interplay of psychological and physiological factors, through which the suppressed immune system can be enhanced. The immune modulators discussed are endogenous opioids, cytokines, neurotransmitters and other hormones. Exercise conditioning treatment appears to be more effective when combined with other stress management

  15. Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine

    PubMed Central

    2010-01-01

    Background Ukraine has the highest HIV prevalence (1.6%) and is facing the fastest growing epidemic in Europe. Our objective was to describe the clinical, immunological and virological characteristics, treatment and response in vertically HIV-infected children living in Ukraine and followed from birth. Methods The European Collaborative Study (ECS) is an ongoing cohort study, in which HIV-1 infected pregnant women are enrolled and followed in pregnancy, and their children prospectively followed from birth. ECS enrolment in Ukraine started in 2000 initially with three sites, increasing to seven sites by 2009. Results A total of 245 infected children were included in the cohort by April 2009, with a median age of 23 months at most recent follow-up; 33% (n = 77) had injecting drug using mothers and 85% (n = 209) were infected despite some use of antiretroviral prophylaxis for prevention of mother-to-child transmission. Fifty-five (22%) children had developed AIDS, at a median age of 10 months (IQR = 6-19). The most prevalent AIDS indicator disease was Pneumocystis jiroveci pneumonia (PCP). Twenty-seven (11%) children had died (median age, 6.2 months). Overall, 108 (44%) children had started highly active antiretroviral treatment (HAART), at a median 18 months of age; median HAART duration was 6.6 months to date. No child discontinued HAART and 92% (100/108) remained on their first-line HAART regimen to date. Among children with moderate/severe immunosuppression, 36% had not yet started HAART. Among children on HAART, 71% (69/97) had no evidence of immunosuppression at their most recent visit; the median reduction in HIV RNA was 4.69 log10 copies/mL over a median of 10 months treatment. From survival analysis, an estimated 94%, 84% and 81% of children will be alive and AIDS-free at 6, 12 and 18 months of age, respectively. However, survival increased significantly over time: estimated survival rates to 12 months of age were 87% for children born in 2000/03 versus 96

  16. Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

    PubMed Central

    Wang, Tong; Gong, Nan; Liu, Jianuo; Kadiu, Irena; Kraft-Terry, Stephanie D.; Mosley, R. Lee; Volsky, David J.; Ciborowski, Pawel; Gendelman, Howard E.

    2008-01-01

    Background HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system's microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions These observations provide unique insights into glial crosstalk during disease by supporting astrocyte-mediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery and therapeutics that may influence the course of HIV-1-mediated neurodegeneration. PMID:18575609

  17. HIV-1 infected astrocytes and the microglial proteome

    PubMed Central

    Wang, Tong; Gong, Nan; Liu, Jianuo; Kadiu, Irena; Kraft-Terry, Stephanie D; Schlautman, Joshua D; Ciborowski, Pawel; Volsky, David J; Gendelman, Howard E

    2008-01-01

    The human immunodeficiency virus (HIV) invades the central nervous system early after viral exposure but causes progressive cognitive, behavior, and motor impairments years later with the onset of immune deficiency. Although in the brain, HIV preferentially replicates productively in cells of mononuclear phagocyte (MP; blood borne macrophage and microglia), astrocytes also can be infected, at low and variable frequency, particularly in patients with encephalitis. Among their many functions, astrocytes network with microglia to provide the first line of defense against microbial infection; however, very little is known about its consequences on MP. Here, we addressed this question using co-culture systems of HIV infected mouse astrocytes and microglia. Pseudotyped vesicular stomatis virus/HIV was used to circumvent absence of viral receptors and ensure cell genotypic uniformity for studies of intercellular communication. The study demonstrated that infected astrocytes show modest changes in protein elements as compared to uninfected cells. In contrast, infected astrocytes induce robust changes in the proteome of HIV-1 infected microglia. Accelerated cell death and redox proteins, amongst others, were produced in abundance. The observations confirmed the potential of astrocytes to influence the neuropathogenesis of HIV-1 infection by specifically altering the neurotoxic potential of infected microglia and in this manner, disease progression. PMID:18587649

  18. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects

    PubMed Central

    Ortiz, Gabriel M.; Wellons, Melissa; Brancato, Jason; Vo, Ha T. T.; Zinn, Rebekah L.; Clarkson, Daniel E.; Van Loon, Katherine; Bonhoeffer, Sebastian; Miralles, G. Diego; Montefiori, David; Bartlett, John A.; Nixon, Douglas F.

    2001-01-01

    The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4+ T cells >400 per μl. CD4+ T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-γ-producing HIV-1-specific CD8+ and CD4+ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8+ T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4+ T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4+ T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4+ T cell counts, and showed no enhancement of antiviral CD8+ T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution. PMID:11687611

  19. Defective proviruses rapidly accumulate during acute HIV-1 infection

    PubMed Central

    Bruner, Katherine M.; Murray, Alexandra J.; Pollack, Ross A.; Soliman, Mary G.; Laskey, Sarah B.; Capoferri, Adam A.; Lai, Jun; Strain, Matthew C.; Lada, Steven M.; Hoh, Rebecca; Ho, Ya-Chi; Richman, Douglas D.; Deeks, Steven G.; Siliciano, Janet D.; Siliciano, Robert F.

    2016-01-01

    Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, HIV-1 persists in CD4+ T cells in a latent form not targeted by the immune system or ART1–5. This latent reservoir is a major barrier to cure. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective6. However, the dynamics of the accumulation and persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. Using an unbiased method to amplify near full-length proviral genomes from HIV-1 infected adults treated at different stages of infection, we demonstrate that early ART initiation limits the size of the reservoir but does not profoundly impact the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals treated early vs. late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies. PMID:27500724

  20. Care and management of the infant of the HIV-1-infected mother.

    PubMed

    Paintsil, Elijah; Andiman, Warren A

    2007-04-01

    Mother-to-child transmission of the human immunodeficiency virus continues to be a major global health problem. The pediatric HIV-1 epidemic is fueled by HIV-1 infection in women of childbearing age with vertical transmission in utero or at the time of birth. In resource-rich countries, the birth of an infected child is a sentinel health event signaling a chain of missed opportunities and barriers to prevention. Because the fate and ultimate HIV-infection status of the baby is inextricably linked to the infection status of the mother and her general state of well-being, we provide in this review: 1) background and state-of-the-art management guidelines for optimum maternal care; 2) strategies to minimize the risk of vertical transmission of HIV; and 3) recommendations for managing infants born to HIV-infected women. These are discussed under four case scenarios that obstetric and pediatric providers frequently encounter in their practices.

  1. Seasonal Flu Vaccine Safety and Pregnant Women

    MedlinePlus

    ... Submit What's this? Submit Button Past Newsletters Flu Vaccine Safety and Pregnancy Questions & Answers Language: English Españ ... allergic conditions. How is the safety of flu vaccines in pregnant women monitored? CDC and FDA conduct ...

  2. Zika Virus: Protecting Pregnant Women and Babies

    MedlinePlus

    ... Digital Press Kit Read the MMWR Science Clips Zika Virus Protecting Pregnant Women and Babies Language: English ... Pregnancy Registry (50 US states and DC) Problem Zika infection during pregnancy can cause serious birth defects ...

  3. Chemokines and Chemokine Receptors in Susceptibility to HIV-1 Infection and Progression to AIDS

    PubMed Central

    Chatterjee, Animesh; Rathore, Anurag; Vidyant, Sanjukta; Kakkar, Kavita; Dhole, Tapan N.

    2012-01-01

    A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals. PMID:22377730

  4. Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women.

    PubMed

    Sacha, C R; Vandergrift, N; Jeffries, T L; McGuire, E; Fouda, G G; Liebl, B; Marshall, D J; Gurley, T C; Stiegel, L; Whitesides, J F; Friedman, J; Badiabo, A; Foulger, A; Yates, N L; Tomaras, G D; Kepler, T B; Liao, H X; Haynes, B F; Moody, M A; Permar, S R

    2015-03-01

    A successful HIV-1 vaccine must elicit immune responses that impede mucosal virus transmission, though functional roles of protective HIV-1 Envelope (Env)-specific mucosal antibodies remain unclear. Colostrum is a rich source of readily accessible mucosal B cells that may help define the mucosal antibody response contributing to prevention of postnatal HIV-1 transmission. To examine the HIV-1 Env-specific colostrum B-cell repertoire, single B cells were isolated from 17 chronically HIV-infected, lactating women, producing 51 blood and 39 colostrum HIV-1 Env-specific B-cell antibodies. All HIV-1 Env-specific colostrum-derived antibodies were immunoglobulin (Ig)G1 isotype and had mean heavy chain complementarity-determining region 3 (CDR3) lengths and mutation frequencies similar to those isolated from blood. However, variable heavy chain (VH) gene subfamily 1(∼)69 usage was higher among colostrum than blood HIV-1 Env-reactive antibodies (49% vs. 20%, P=0.006, Fisher's exact test). Additionally, more HIV-1 Env-specific colostrum antibodies were gp120 specific than those isolated from blood (44% vs. 16%, P=0.005, Fisher's exact test). One cross-compartment HIV-1 Env-specific clonal B-cell lineage was identified. These unique characteristics of colostrum B-cell antibodies suggest selective homing of HIV-1-specific IgG1-secreting memory B cells to the mammary gland and have implications for targeting mucosal B-cell populations by vaccination.

  5. [Cartography of healthcare for pregnant women].

    PubMed

    Silva, Raimunda Magalhães da; Costa, Milena Silva; Matsue, Regina Yoshie; Sousa, Girliani Silva de; Catrib, Ana Maria Fontenelle; Vieira, Luiza Jane Eyre de Souza

    2012-03-01

    This work uses cartography as a method for mapping the trajectory of primary healthcare provided to pregnant women. The scope of the study comprises 9 Basic Healthcare Units located in the city of Juazeiro do Norte in the State of Ceará. In all, fifteen women in the 37th to 39th week of pregnancy were selected. Interviews were conducted with these women during the period from January to June 2010. The cartographic findings were depicted in stages in the flowchart, which exposed lacunas in prenatal healthcare, such as the low number of oncotic cytology exams conducted and the lack of educational counseling. Nevertheless, in the interviews, a significant number of pregnant women expressed satisfaction with the prenatal care provided. The good relationships developed between the healthcare professionals and the pregnant women were the main reason that led them to continue the treatment. This fact reinforces the importance of dialogue between these two actors for the success of prenatal healthcare.

  6. Sentinel surveillance of HIV-1 infection in Tamilnadu, India.

    PubMed

    Solomon, S; Anuradha, S; Ganapathy, M; Jagadeeswari

    1994-01-01

    The objective was to determine the time trends in the prevalence of HIV infection and to evaluate appropriate preventive intervention in different population groups. Sentinel surveillance of HIV-1 infection by anonymous unlinked technique was carried out in Tamilnadu from December 1989 to March 1993. The sentinel population monitored were attendees of STD clinics, blood donors and antenatal mothers. The results of HIV seropositivity were compared for each 6-month period. During the study period there was 10-fold rise of HIV seropositivity among STD patients (1% to 10%), 2-fold rise among antenatal attendees (0.37% to 0.76%), and 3-fold rise in blood donors (0.24% to 0.72%). There was a steady increase in the incidence of HIV infection among those with high risk behaviour (STD attendees) as well as in the general population. This information is of value in planning and evaluation of preventive and control programmes in India.

  7. Designing Drug Trials: Considerations for Pregnant Women

    PubMed Central

    Sheffield, Jeanne S.; Siegel, David; Mirochnick, Mark; Heine, R. Phillips; Nguyen, Christine; Bergman, Kimberly L.; Savic, Rada M.; Long, Jill; Dooley, Kelly E.; Nesin, Mirjana

    2014-01-01

    Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate. PMID:25425722

  8. Therapeutic targets for HIV-1 infection in the host proteome

    PubMed Central

    Liang, Winnie S; Maddukuri, Anil; Teslovich, Tanya M; de la Fuente, Cynthia; Agbottah, Emmanuel; Dadgar, Shabnam; Kehn, Kylene; Hautaniemi, Sampsa; Pumfery, Anne; Stephan, Dietrich A; Kashanchi, Fatah

    2005-01-01

    Background Despite the success of HAART, patients often stop treatment due to the inception of side effects. Furthermore, viral resistance often develops, making one or more of the drugs ineffective. Identification of novel targets for therapy that may not develop resistance is sorely needed. Therefore, to identify cellular proteins that may be up-regulated in HIV infection and play a role in infection, we analyzed the effects of Tat on cellular gene expression during various phases of the cell cycle. Results SOM and k-means clustering analyses revealed a dramatic alteration in transcriptional activity at the G1/S checkpoint. Tat regulates the expression of a variety of gene ontologies, including DNA-binding proteins, receptors, and membrane proteins. Using siRNA to knock down expression of several gene targets, we show that an Oct1/2 binding protein, an HIV Rev binding protein, cyclin A, and PPGB, a cathepsin that binds NA, are important for viral replication following induction from latency and de novo infection of PBMCs. Conclusion Based on exhaustive and stringent data analysis, we have compiled a list of gene products that may serve as potential therapeutic targets for the inhibition of HIV-1 replication. Several genes have been established as important for HIV-1 infection and replication, including Pou2AF1 (OBF-1), complement factor H related 3, CD4 receptor, ICAM-1, NA, and cyclin A1. There were also several genes whose role in relation to HIV-1 infection have not been established and may also be novel and efficacious therapeutic targets and thus necessitate further study. Importantly, targeting certain cellular protein kinases, receptors, membrane proteins, and/or cytokines/chemokines may result in adverse effects. If there is the presence of two or more proteins with similar functions, where only one protein is critical for HIV-1 transcription, and thus, targeted, we may decrease the chance of developing treatments with negative side effects. PMID:15780141

  9. HIV-1 Variants and Drug Resistance in Pregnant Women from Bata (Equatorial Guinea): 2012-2013

    PubMed Central

    Alvarez, Patricia; Fernández McPhee, Carolina; Prieto, Luis; Martín, Leticia; Obiang, Jacinta; Avedillo, Pedro; Vargas, Antonio; Rojo, Pablo; Benito, Agustín; Ramos, José Tomás; Holguín, África

    2016-01-01

    Objectives This is the first study describing drug resistance mutations (DRM) and HIV-1 variants among infected pregnant women in Equatorial Guinea (GQ), a country with high (6.2%) and increasing HIV prevalence. Methods Dried blood spots (DBS) were collected from November 2012 to December 2013 from 69 HIV-1 infected women participating in a prevention of mother-to-child transmission program in the Hospital Regional of Bata and Primary Health Care Centre María Rafols, Bata, GQ. The transmitted (TDR) or acquired (ADR) antiretroviral drug resistance mutations at partial pol sequence among naive or antiretroviral therapy (ART)-exposed women were defined following WHO or IAS USA 2015 lists, respectively. HIV-1 variants were identified by phylogenetic analyses. Results A total of 38 of 69 HIV-1 specimens were successfully amplified and sequenced. Thirty (79%) belonged to ART-experienced women: 15 exposed to nucleoside reverse transcriptase inhibitors (NRTI) monotherapy, and 15 to combined ART (cART) as first regimen including two NRTI and one non-NRTI (NNRTI) or one protease inhibitor (PI). The TDR rate was only found for PI (3.4%). The ADR rate was 37.5% for NNRTI, 8.7% for NRTI and absent for PI or NRTI+NNRTI. HIV-1 group M non-B variants caused most (97.4%) infections, mainly (78.9%) recombinants: CRF02_AG (55.2%), CRF22_A101 (10.5%), subtype C (10.5%), unique recombinants (5.3%), and A3, D, F2, G, CRF06_cpx and CRF11_cpx (2.6% each). Conclusions The high rate of ADR to retrotranscriptase inhibitors (mainly to NNRTIs) observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in GQ to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present. PMID:27798676

  10. Population pharmacokinetics of abacavir in pregnant women.

    PubMed

    Fauchet, Floris; Treluyer, Jean-Marc; Préta, Laure-Helene; Valade, Elodie; Pannier, Emmanuelle; Urien, Saik; Hirt, Déborah

    2014-10-01

    For the first time, a population approach was used to describe abacavir (ABC) pharmacokinetics in HIV-infected pregnant and nonpregnant women. A total of 266 samples from 150 women were obtained. No covariate effect (from age, body weight, pregnancy, or gestational age) on ABC pharmacokinetics was found. Thus, it seems unnecessary to adapt the ABC dosing regimen during pregnancy.

  11. Dynamics of a stochastic HIV-1 infection model with logistic growth

    NASA Astrophysics Data System (ADS)

    Jiang, Daqing; Liu, Qun; Shi, Ningzhong; Hayat, Tasawar; Alsaedi, Ahmed; Xia, Peiyan

    2017-03-01

    This paper is concerned with a stochastic HIV-1 infection model with logistic growth. Firstly, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HIV-1 infection model. Then we obtain sufficient conditions for extinction of the infection. The stationary distribution shows that the infection can become persistent in vivo.

  12. Assisting pregnant women to prepare for disaster.

    PubMed

    Ewing, Bonnie; Buchholtz, Susan; Rotanz, Richard

    2008-01-01

    Disasters are natural or man-made life-altering events that require preplanning to save lives. Pregnant women are a particularly vulnerable population in such events, because they have special physical and psychosocial needs. Preparations made for labor and birth might have to be drastically altered in the event of an emergency, especially if a woman is separated from her familiar healthcare providers and facilities. The issue of breastfeeding also must be considered in disaster planning for pregnant women, along with occurrences such as food shortages and outbreak of illnesses caused by overcrowding of displaced persons. Recent events such as hurricane Katrina have demonstrated that maternal/child nurses need to become more aware of disaster planning and help to empower pregnant women with knowledge of how to handle their special needs in times of crisis.

  13. The molecular mechanism of human resistance to HIV-1 infection in persistently infected individuals--a review, hypothesis and implications.

    PubMed

    Becker, Yechiel

    2005-08-01

    Resistance to HIV-1 infection in Europeans is associated with a mutation in the gene that codes for the CCR5 protein that is present in Th2 cells and serves as a coreceptor for HIV-1 R5 strain. A deletion of 32 amino acids from the cytokine receptor prevents infection. This mutation prevails in Europeans and is absent in Africans. However, duplication of a gene that codes for a chemokine that binds to the CCR5 was discovered in Africans (mean gene copy 6 while in non-Africans the mean gene copy is 3). Higher expression of these genes protects T cells against HIV-1 infection in vitro. It should be noted that resistance to HIV-1 R5 variant does not protect against HIV-1 R4 variant. It was reported that a minority of highly HIV-1 exposed African professional sex workers (APSW) were resistant to the virus infection during a 10 years period. Recently, the analysis of the cytokines in the serum of the persistently infected seronegative women revealed that the latter hypo-expresses the cytokine IL-4. Since the molecular events during HIV-1 infection are associated with a marked increase in the levels of IL-4 and IgE in the sera of the infected individuals, it suggests that AIDS is an allergy. Thus, a very low level of IL-4 production may abrogate the virus infection. Studies on the human IL-4 gene revealed that together with the IL-4 mRNA a spliced variant with a deletion of exon 2 is synthesized. The latter is a natural antagonist of IL-4 and when expressed in an individual at a level higher than IL-4, the person will resist a microbial infection (e.g. Mycobacterium tuberculosis) or asthma. The present hypothesis suggests that the HIV-1 resistant APSWs produce more IL-4 delta 2 molecules than IL-4 molecules. The binding of IL-4 delta 2 to IL-4 receptors on T and B cells prevents their functions and the infection by HIV-1. The implications of these studies are that treatment of HIV-1 infected people with drugs that will block the IL-4 receptors will stop HIV-1 infections

  14. Anesthetic management of pregnant women with stroke.

    PubMed

    Yoshitani, Kenji; Inatomi, Yuzuru; Kuwajima, Ken; Ohnishi, Yoshihiko

    2013-01-01

    Stroke during pregnancy is rare, but after occurring, most patients develop serious neurological conditions. Hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, often requires emergency surgical intervention. In addition to significant maternal physiological changes, the potential for fetal harm should be considered during anesthetic management of these patients. Whether cesarean section or neurosurgical intervention should be prioritized or performed simultaneously in pregnant women with stroke is an important issue. Whether the patients receive general or spinal and epidural anesthesia is another clinically significant issue. Finally neurosurgeons, anesthesiologists, and obstetricians should cooperate to manage pregnant women with stroke.

  15. Multivitamin supplements for pregnant women. New insights.

    PubMed Central

    Ahn, Eric; Nava-Ocampo, Alejandro A.; Koren, Gideon

    2004-01-01

    QUESTION: One of my patients is planning pregnancy and has started taking multivitamin supplements. She is experiencing gastric discomfort. What are the alternatives? ANSWER: Gastric discomfort is usually related to iron intake; pregnant women could use supplements with less iron. Pregnant women need 0.4 to 1.0 mg of folic acid daily. If they have a family history of neural tube defects (NTDs), insulin-dependent diabetes mellitus, or epilepsy, or are currently taking valproic acid, carbamazepine, or antifolates (eg, sulfonamides), they are at intermediate-to-high risk of having babies with NTDs and need 4.0 to 5.0 mg of folic acid daily. PMID:15171671

  16. Pharmacokinetics of fenoterol in pregnant women.

    PubMed

    von Mandach, U; Böni, R; Danko, J; Huch, R; Huch, A

    1995-02-01

    The beta 2-sympathomimetic drug fenoterol (fenoterol hydrobromide, CAS 1944-12-3, Partusisten) is routinely used to inhibit uterine contractions (tocolysis). Investigations of plasma concentrations of those receiving i.v. or oral tocolysis often show different results, both within particular groups of pregnant women and in comparison with non-pregnant persons. The aim of this study was to determine the pharmacokinetics of fenoterol in pregnant women, an important factor which so far had not been known. Four healthy pregnant women with similar weight and gestational age and all with premature labor were administered a continuous intravenous infusion of 4 micrograms fenoterol/min. During and up to 24 hours after the end of the infusion, venous blood samples were taken in order to determine the fenoterol plasma concentrations by radioimmunoassay. From a steady state concentration (css) of 2242 +/- 391 pg/ml (x +/- S.E.), a non-linear two-phased plasma elimination was seen with half-lives t1/2 of 11.40 min and 4.87 h. The area under the plasma concentration-time curve (AUC0-12h) was 6.27 ng/ml x h. The total clearance (Cltot) was 114.8 l/h. These data are nearly the same as the data already known for healthy non-pregnant (male) volunteers. The deviations which are seen in the plasma concentrations in pregnant women in comparison to non-pregnant persons during or after continuous i.v. infusion can therefore not be caused by differences in the pharmacokinetics. Other factors, however, such as body weight and/or gestational age, might influence the results.

  17. Elimination of HIV-1-infected cells by broadly neutralizing antibodies

    PubMed Central

    Bruel, Timothée; Guivel-Benhassine, Florence; Amraoui, Sonia; Malbec, Marine; Richard, Léa; Bourdic, Katia; Donahue, Daniel Aaron; Lorin, Valérie; Casartelli, Nicoletta; Noël, Nicolas; Lambotte, Olivier; Mouquet, Hugo; Schwartz, Olivier

    2016-01-01

    The Fc region of HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) is required for suppressing viraemia, through mechanisms which remain poorly understood. Here, we identify bNAbs that exert antibody-dependent cellular cytotoxicity (ADCC) in cell culture and kill HIV-1-infected lymphocytes through natural killer (NK) engagement. These antibodies target the CD4-binding site, the glycans/V3 and V1/V2 loops on gp120, or the gp41 moiety. The landscape of Env epitope exposure at the surface and the sensitivity of infected cells to ADCC vary considerably between viral strains. Efficient ADCC requires sustained cell surface binding of bNAbs to Env, and combining bNAbs allows a potent killing activity. Furthermore, reactivated infected cells from HIV-positive individuals expose heterogeneous Env epitope patterns, with levels that are often but not always sufficient to trigger killing by bNAbs. Our study delineates the parameters controlling ADCC activity of bNAbs, and supports the use of the most potent antibodies to clear the viral reservoir. PMID:26936020

  18. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

    PubMed Central

    Hoehn, Kenneth B.; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S. J.; Kaye, S.; Weber, J. N.; McClure, M. O.; Kellam, Paul; Pybus, Oliver G.

    2015-01-01

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. PMID:26194755

  19. Genomic architecture of HIV-1 infection: current status & challenges.

    PubMed

    Kaur, Gurvinder; Sharma, Gaurav; Kumar, Neeraj; Kaul, Mrinali H; Bansal, Rhea A; Vajpayee, Madhu; Wig, Naveet; Sharma, Surender K; Mehra, Narinder K

    2013-11-01

    Studies on host genomics have revealed the existence of identifiable HIV-1 specific protective factors among infected individuals who remain naturally resistant viraemia controllers with little or no evidence of virus replication. These factors are broadly grouped into those that are immune associated (MHC, chemokines, cytokines, CTLs and others), linked to viral entry (chemokine co-receptors and ligands), act as post-entry restriction elements (TRIM5a, APOBEC3) and those associated with viral replication (cytokines and others). These features have been identified through multiple experimental approaches ranging from candidate gene approaches, genome wide association studies (GWAS), expression analysis in conjunction with functional assays in humans to primate based models. Several studies have highlighted the individual and population level gross differences both in the viral clade sequences as well as host determined genetic associations. This review collates current information on studies involving major histocompatibility complex (MHC) as well as non MHC genes in the context of HIV-1 infection and AIDS involving varied ethnic groups. Special focus of the review is on the genetic studies carried out on the Indian population. Further challenges with regard to therapeutic interventions based on current knowledge have been discussed along with discussion on documented cases of stem cell therapy and very early highly active antiretroviral therapy (HAART) interventions.

  20. Analysis of HIV type 1 diversity in pregnant women from four Latin American and Caribbean countries.

    PubMed

    Gomez-Carrillo, Manuel; Pampuro, Sandra; Duran, Adriana; Losso, Marcelo; Harris, D Robert; Read, Jennifer S; Duarte, Geraldo; De Souza, Ricardo; Soto-Ramirez, Luis; Salomón, Horacio

    2006-11-01

    Worldwide, the distribution of HIV-1 subtypes and intersubtype recombinants is not homogeneous. In Latin America and the Caribbean, HIV-1 subtype B predominates. However, in the south of Brazil and in countries of the Southern cone (Argentina, Chile, Paraguay, and Uruguay) there is a different distribution of viral subtypes and intersubtype recombinants. The aim of this work was to analyze HIV-1 diversity in a cohort of pregnant women (with primarily heterosexual acquisition of the infection) who were diagnosed with HIV-1 infection during their current pregnancy and who received ARVs during pregnancy for perinatal transmission prophylaxis. Analysis of 121 partial pol sequences from subjects enrolled in Argentina, Brazil, the Bahamas, and Mexico was performed by phylogenetic and recombinant characterization. Different prevalences of subtype B were observed (100% for specimens from Mexico and the Bahamas, 61% for Brazil, and 30% for Argentina). Subtypes C and F were found, along with BC, BF, FC, and CBF recombinants in specimens from Brazilians. A high prevalence of BF recombinants was found (70%) in specimens from Argentina. The different patterns of HIV- 1 subtypes and intersubtype recombinants in South America (Argentina and Brazil) compared to those in Central and North America should be considered in the design of future HIV-1 vaccine trials.

  1. Pregnant Women Need a Flu Shot

    MedlinePlus

    ... have not been shown to cause harm to pregnant women or their developing babies. If you have your baby before getting your flu shot, you still need to get vaccinated. The flu is spread from person to person. You, or others who care for ...

  2. HIV among Pregnant Women, Infants, and Children

    MedlinePlus

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Pregnant Women, Infants, and Children Format: Select ...

  3. Sympathetic baroreflex gain in normotensive pregnant women

    PubMed Central

    Usselman, Charlotte W.; Skow, Rachel J.; Matenchuk, Brittany A.; Chari, Radha S.; Julian, Colleen G.; Stickland, Michael K.; Davenport, Margie H.

    2015-01-01

    Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m2) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m2). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (−3.7 ± 0.5 vs. −5.4 ± 0.5 bursts·100 heart beats−1·mmHg−1, P = 0.03), as was baroreflex gain calculated with total sympathetic activity (−294 ± 24 vs. −210 ± 24 au·100 heart beats−1·mmHg−1; P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = −0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure

  4. Underestimated Amoebic Appendicitis among HIV-1-Infected Individuals in Japan

    PubMed Central

    Kobayashi, Taiichiro; Yano, Hideaki; Murata, Yukinori; Igari, Toru; Nakada-Tsukui, Kumiko; Yagita, Kenji; Nozaki, Tomoyoshi; Kaku, Mitsuo; Tsukada, Kunihisa; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Oka, Shinichi

    2016-01-01

    ABSTRACT Entamoeba histolytica is not a common causative agent of acute appendicitis. However, amoebic appendicitis can sometimes be severe and life threatening, mainly due to a lack of awareness. Also, its frequency, clinical features, and pathogenesis remain unclear. The study subjects were HIV-1-infected individuals who presented with acute appendicitis and later underwent appendectomy at our hospital between 1996 and 2014. Formalin-fixed paraffin-embedded preserved appendix specimens were reexamined by periodic acid-Schiff (PAS) staining and PCR to identify undiagnosed amoebic appendicitis. Appendectomies were performed in 57 patients with acute appendicitis. The seroprevalence of E. histolytica was 33% (14/43) from the available stored sera. Based on the medical records, only 3 cases were clinically diagnosed as amoebic appendicitis, including 2 diagnosed at the time of appendectomy and 1 case diagnosed by rereview of the appendix after the development of postoperative complications. Retrospective analyses using PAS staining and PCR identified 3 and 3 more cases, respectively. Thus, E. histolytica infection was confirmed in 9 cases (15.8%) in the present study. Apart from a significantly higher leukocyte count in E. histolytica-positive patients than in negative patients (median, 13,760 versus 10,385 cells/μl, respectively, P = 0.02), there were no other differences in the clinical features of the PCR-positive and -negative groups. In conclusion, E. histolytica infection was confirmed in 9 (15.8%) of the appendicitis cases. However, only 3, including one diagnosed after intestinal perforation, were diagnosed before the present analyses. These results strongly suggest there is frequently a failure to detect trophozoites in routine examination, resulting in an underestimation of the incidence of amoebic appendicitis. PMID:27847377

  5. Sexual behaviour among youths at high risk for HIV-1 infection in Dar es Salaam, Tanzania

    PubMed Central

    Mwakagile, D; Mmari, E; Makwaya, C; Mbwana, J; Biberfeld, G; Mhalu, F; Sandstrom, E

    2001-01-01

    Objectives: To investigate sex specific sexual behaviour in youths visiting a youth clinic for sexual and reproductive health in Dar es Saalam. Methods: A questionnaire was administered to a random sample of youths between 10 and 24 years of age attending the youth health clinic in Dar es Saalam. The clinical investigation included testing for syphilis and HIV-1 antibodies Results: 1423 youths attended the clinic between September 1997 and August 1998. The study population comprised 213 (53.5%) males and 185 (46.5%) females. 97 (24.4%) were below 20 years. The mean age at coitarche was 16.5 and 17.0 years of age for males and females, respectively. The coitarche was involuntary in 15 females (8.6%). 49.5% males reported more than five lifetime partners compared with 14.1% for females (p<0.0001). Males reported recent partners to be 2.5 years younger, while females reported them to be 5.0 years older. No contraceptive use was reported by 29.7% of the males and 40.3% of females. 52.7% females had been pregnant and 26 (14.1%) reported induced abortions. Genital discharge was found in 69.5% and 73.9% and GUD in 36.6% and 27.1% of males and females respectively. 12 males (5.9%) and 43 females (24.6%) were found to be HIV-1 infected. 13.8% of the females with only one lifetime partner were HIV-1 infected compared with 40.9% with more than five partners (p = 0.028). Conclusions: Many youths in Dar es Salaam engage in sexual behaviours that put them at risk of unwanted pregnancies and STIs including HIV infection. Female youths were more likely to contract HIV infection than males. In African urban areas youth oriented clinics can have a pivotal role in HIV/STI prevention and control Key Words: youth; sexual behaviour; HIV PMID:11463924

  6. Thiolated pyrimidine nucleotides may interfere thiol groups concentrated at lipid rafts of HIV-1 infected cells.

    PubMed

    Kanizsai, Szilvia; Ongrádi, Joseph; Aradi, János; Nagy, Károly

    2014-12-01

    Upon HIV infection, cells become activated and cell surface thiols are present in increased number. Earlier we demonstrated in vitro anti-HIV effect of thiolated pyrimidine nucleotide UD29, which interferes thiol function. To further analyse the redox processes required for HIV-1 entry and infection, toxicity assays were performed using HIV-1 infected monolayer HeLaCD4-LTR/ β-gal cells and suspension H9 T cells treated with several thiolated nucleotide derivatives of UD29. Selective cytotoxicity of thiolated pyrimidines on HIV-1 infected cells were observed. Results indicate that thiolated pyrimidine derivates may interfere with -SH (thiol) groups concentrated in lipid rafts of cell membrane and interacts HIV-1 infected (activated) cells resulting in a selective cytotoxicity of HIV-1 infected cells, and reducing HIV-1 entry.

  7. Galectin-3 promotes caspase-independent cell death of HIV-1-infected macrophages.

    PubMed

    Xue, Jing; Fu, Chunyan; Cong, Zhe; Peng, Lingjuan; Peng, Zhuoying; Chen, Ting; Wang, Wei; Jiang, Hong; Wei, Qiang; Qin, Chuan

    2017-01-01

    HIV-1-infected macrophages are a key contributor to the formation of a viral reservoir and new treatment strategies focus on eliminating this pool of virus. Galectin-3 is a potent apoptosis-inducing protein that regulates diverse cellular activities. In the present study, we investigated whether galectin-3 could induce cell death in HIV-1-infected macrophages using HIV-1-infected THP1 monocytes (THP1-MNs) and THP1-derived macrophages (THP1-MΦs) as in vitro cellular models. We found that THP1-MΦs were more resistant than the THP1-MNs to HIV-1 infection-induced death, and that HIV-1 infection of the THP1-MΦs increased expression of the anti-apoptotic proteins Mcl-1, Bcl-2 and Bcl-xL. Additionally, galectin-3 but not FasL, tumor necrosis factor (TNF)-related apoptosis-inducing ligand or TNF-α, could induce cell death in HIV-1-infected THP1-MΦs. A similar result was shown for primary human monocyte-derived macrophages. Galectin-3-induced cell death was also significantly increased in macrophages obtained from SIVmac251-infected macaques compared to that of macrophages from healthy macaques. Furthermore, galectin-3-induced cell death in HIV-1-infected THP1-MΦs was caspase independent. Interestingly, endonuclease G (Endo G) was increased in the nucleus and decreased in the cytoplasm of galectin-3-treated cells; thus, galectin-3-induced cell death in HIV-1-infected THP1-MΦs is most likely related to the translocation of Endo G from the cytoplasm to the nucleus. These findings suggest that galectin-3 may potentially aid in the eradication of HIV-1/SIV-infected macrophages.

  8. Wanted: better care for pregnant women.

    PubMed

    Kestler, E

    1993-01-01

    In three prenatal clinics in Latin America the average attendance time by pregnant women was 129 minutes but the average time spent with a doctor was only 8-10 minutes. In order to improve prenatal care, providers should analyse what happens during visits. Assessments should be made of the usefulness of the services offered and some thought should be given as to who might best provide them.

  9. [Children and pregnant women at high altitude].

    PubMed

    Rehakova, P; Rexhaj, E; Farron, F; Duplain, H

    2014-05-07

    Nowadays, high altitude resorts have become popular destinations for family vacations. Based on a limited number of publications and international guidelines, this article summarizes the effects of high altitude on children and pregnant women. Children also suffer from high altitude-related diseases, however their presentation and clinical significance are different from their adult counterparts. Careful planning of the itinerary with respect to altitude of the overnight stays, access to medical services and potential evacuation routes is the cornerstone of a successful vacation.

  10. [Low back pain in pregnant women].

    PubMed

    Majchrzycki, Marian; Mrozikiewicz, Przemysław M; Kocur, Piotr; Bartkowiak-Wieczorek, Joanna; Hoffmann, Marcin; Stryła, Wanda; Seremak-Mrozikiewicz, Agnieszka; Grześkowiak, Edmund

    2010-11-01

    Pain of lumbosacral segment of the vertebral column and the pelvis concerns about 45% of all pregnant women. The change of the body posture during pregnancy is the result of gravity centre relocation, which affects the musculosceletal system. Development of the joint, ligament and myofascial dysfunctions, as well as the pain in the lumbosacral segment and the pelvis, are the most common reasons of spine pain. The aim of this review is to present the current state of knowledge about lumbar spine pain in pregnant women with special focus on the pain connected with muscular, joint and ligament disorders. Pregnancy is a serious burden for the female osteo-skeletal system. Lumbar pain with different location and intensification is the negative consequence of the position changes during pregnancy. Pharmacotherapy could be useful only in cases of intensive low back pain, with possible application of small spectrum of drugs that are safe during pregnancy. Physical therapy including manual therapy exercises, massage and techniques of local anesthesia are alternative methods in case of low back pain in pregnant women.

  11. Multiple T-cell responses are associated with better control of acute HIV-1 infection

    PubMed Central

    Sun, Jianping; Zhao, Yan; Peng, Yanchun; Han, Zhen; Liu, Guihai; Qin, Ling; Liu, Sai; Sun, Huanhuan; Wu, Hao; Dong, Tao; Zhang, Yonghong

    2016-01-01

    Abstract Cytotoxic T lymphocyte (CTL) responses play pivotal roles in controlling the replication of human immunodeficiency virus type 1 (HIV-1), but the correlation between CTL responses and the progression of HIV-1 infection are controversial on account of HIV immune escape mutations driven by CTL pressure were reported. The acute HIV-1-infected patients from Beijing were incorporated into our study to investigate the effects of CTL response on the progression of HIV-1 infection. A longitudinal study was performed on acute HIV-1-infected patients to clarify the kinetic of T-cell responses, the dynamic of escape mutations, as well as the correlation between effective T-cell response and the progression of HIV infection. Seven human leukocyte antigen-B51+ (HLA-B51+) individuals were screened from 105 acute HIV-1 infectors. The detailed kinetic of HLA-B51-restricted CTL responses was described through blood sampling time points including seroconversion, 3 and 6 months after HIV-1 infection in the 7 HLA-B51+ individuals, by using 16 known HLA-B51 restricted epitopes. Pol743–751 (LPPVVAKEI, LI9), Pol283–289 (TAFTIPSI, TI8), and Gag327–3459 (NANPDCKTI, NI9) were identified as 3 dominant epitopes, and ranked as starting with LI9, followed by TI8 and NI9 in the ability to induce T-cell responses. The dynamics of escape mutations in the 3 epitopes were also found with the same order as T-cell response, by using sequencing for viral clones on blood sampling at seroconversion, 3 and 6 months after HIV-1 infection. We use solid evidence to demonstrate the correlation between T-cell response and HIV-1 mutation, and postulate that multiple T-cell responses might benefit the control of HIV-1 infection, especially in acute infection phase. PMID:27472741

  12. Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease

    PubMed Central

    Maubert, Monique E.; Pirrone, Vanessa; Rivera, Nina T.; Wigdahl, Brian; Nonnemacher, Michael R.

    2016-01-01

    In many individuals, drug abuse is intimately linked with HIV-1 infection. In addition to being associated with one-third of all HIV-1 infections in the United States, drug abuse also plays a role in disease progression and severity in HIV-1-infected patients, including adverse effects on the central nervous system (CNS). Specific systems within the brain are known to be damaged in HIV-1-infected individuals and this damage is similar to that observed in drug abuse. Even in the era of anti-retroviral therapy (ART), CNS pathogenesis occurs with HIV-1 infection, with a broad range of cognitive impairment observed, collectively referred to as HIV-1-associated neurocognitive disorders (HAND). A number of HIV-1 proteins (Tat, gp120, Nef, Vpr) have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each of the proteins in a number of tissues, including the CNS, even in ART-suppressed patients. In this review, we have made Tat the center of attention for a number of reasons. First, it has been shown to be synthesized and secreted by HIV-1-infected cells in the CNS, despite the most effective suppression therapies available to date. Second, Tat has been shown to alter the functions of several host factors, disrupting the molecular and biochemical balance of numerous pathways contributing to cellular toxicity, dysfunction, and death. In addition, the advantages and disadvantages of ART suppression with regard to controlling the genesis and progression of neurocognitive impairment are currently under debate in the field and are yet to be fully determined. In this review, we discuss the individual and concerted contributions of HIV-1 Tat, drug abuse, and ART with respect to damage in the CNS, and how these factors contribute to the development of HAND in HIV-1-infected patients. PMID:26793168

  13. Impact of gender on response to highly active antiretroviral therapy in HIV-1 infected patients: a nationwide population-based cohort study

    PubMed Central

    2012-01-01

    Background Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial. Methods From a nationwide cohort of Danish HIV infected individuals we identified all heterosexually infected women (N=587) and heterosexually infected men (N=583) with no record of Hepatitis C infection diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%) and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We used Cox regression to calculate hazard ratio (HR) for time to initiation of HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of treatment modification the first year, logistic regression to estimate differences in the proportion with an undetectable viral load, and linear regression to detect differences in CD4 count at year 1, 3 and 6 after start of HAART. Results At initiation of HAART, women were younger, predominantly of Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders. Conclusions In a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART. Differences observed between genders are mainly attributable to initiation of HAART in pregnant women. PMID:23140254

  14. [Psychotherapy for pregnant women with psychiatric disorders].

    PubMed

    Müldner-Nieckowski, Łukasz; Cyranka, Katarzyna; Smiatek-Mazgaj, Bogna; Mielimąka, Michał; Sobański, Jerzy; Rutkowski, Krzysztof

    2015-01-01

    Pregnancy is a major life change for many women. The related biological changes, especially complications in its course and in the course of delivery, carry a risk of developing a variety of psychological problems and mental disorders. However, their treatment is challenging due to the teratogenic effects of most psychoactive drugs and specific requirements for entering different psychotherapeutic programs. Mental disorders during pregnancy are undoubtedly an important issue for both gynecology and psychiatry. There is still a discussion considering the question whether psychotherapy during pregnancy is safe, although no scientifically valid data contradicting the safety of psychotherapy during pregnancy has been published so far. Together with psychotherapy - as a treatment of choice - clinicians approve some other relatively safe treatment methods for psychiatric disorders in pregnant women. Light therapy, limited pharmacotherapy, ECT are included. The goal of this paper is to review current opinions of clinicians and researches concerning possibilities, indications and outcome of psychological treatments as a way to help pregnant women who suffer from different psychiatric conditions, and also because this subject is not yet present in Polish psychiatric journals.

  15. Breast cancer in pregnant and lactating women.

    PubMed

    Usmani, K; Moran, E M; Haider, W; Afzal, H; Ahmad, N

    1995-01-01

    Between 1988 and 1991, we treated 595 women with breast cancer in the Breast Disease Section of the Cancer Research Foundation of Pakistan. We report here on 61 patients who were pregnant or lactating. Most patients presented at a late stage of disease because of ignorance, social taboos, or fear of hospitalization and operation. The largest diameter of the breast mass at presentation was 15 cm. Lymph nodes were involved in 70.5% of cases. Multiparity, young marriages, malnutrition, and unhygienic conditions are ripe in the rural environment of Pakistan. No oral contraceptives are used. Modern and conventional methods of treatment did not increase the survival rate of these cancer patients.

  16. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

    PubMed

    Lu, Ching-Lan; Murakowski, Dariusz K; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V; Caskey, Marina; Chakraborty, Arup K; Nussenzweig, Michel C

    2016-05-20

    Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.

  17. Elevated Levels of Microbial Translocation Markers and CCL2 Among Older HIV-1-Infected Men.

    PubMed

    Scully, Eileen; Lockhart, Ainsley; Huang, Lisa; Robles, Yvonne; Becerril, Carlos; Romero-Tejeda, Marisol; Albrecht, Mary A; Palmer, Christine D; Bosch, Ronald J; Altfeld, Marcus; Kuritzkes, Daniel R; Lin, Nina H

    2016-03-01

    The aging of the human immunodeficiency virus type 1 (HIV-1)-infected population obligates a focus on the interaction between aging, comorbid conditions, and HIV-1. We recruited a cohort of HIV-1-infected men aged ≤ 35 years or ≥ 50 years who were receiving fully suppressive antiretroviral therapy (ART). We analyzed plasma markers of inflammation; T-cell activation, exhaustion, proliferation; and innate cellular subsets and functional capacity. Levels of lipopolysaccharide and the plasma marker of chemokine (C-C motif) ligand 2 were significantly elevated in older HIV-infected men despite comparable cellular phenotypes. Compared with similarly age-stratified uninfected subjects, older HIV-1-infected adults were also more frequently in the upper quartile of soluble CD14 expression.

  18. How Metformin Acts in PCOS Pregnant Women

    PubMed Central

    Romualdi, Daniela; De Cicco, Simona; Gagliano, Donatella; Busacca, Matteo; Campagna, Giuseppe; Lanzone, Antonio; Guido, Maurizio

    2013-01-01

    OBJECTIVE Metformin has been reported to reduce the risk of gestational diabetes (GD) in women with polycystic ovarian syndrome (PCOS). However, little is known about the mechanisms of action of this drug during pregnancy. In the attempt to fill this gap, we performed a prospective longitudinal study providing a detailed examination of glucose and insulin metabolism in pregnant women with PCOS undergoing metformin therapy. RESEARCH DESIGN AND METHODS We enrolled 60 women with PCOS who conceived while undergoing metformin treatment. An oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp were performed at each trimester of gestation in 47 ongoing pregnancies. RESULTS Twenty-two of the study subjects had development of GD despite the treatment. At baseline, insulin sensitivity was comparable between women who had development of GD and women who did not. A progressive decline in this parameter occurred in all subjects, independently of the trimester of GD diagnosis. Insulin secretion was significantly higher during the first trimester in patients with an early failure of metformin treatment. Women with third trimester GD and women with no GD exhibited a significant increase in insulin output as gestation proceeded. All newborns were healthy and only one case of macrosomia was observed. CONCLUSIONS Women with PCOS who enter pregnancy in a condition of severe hyperinsulinemia have development of GD earlier, independently of metformin treatment. The physiologic deterioration of insulin sensitivity is not affected by the drug and does not predict the timing and severity of the glycemic imbalance. Despite the high incidence of GD observed, the drug itself or the intensive monitoring probably accounted for the good neonatal outcome. PMID:23315599

  19. Distinct Characteristics of Endometrial and Decidual Macrophages and Regulation of Their Permissivity to HIV-1 Infection by SAMHD1

    PubMed Central

    Quillay, Héloïse; El Costa, Hicham; Marlin, Romain; Duriez, Marion; Cannou, Claude; Chrétien, Fabrice; Fernandez, Hervé; Lebreton, Anne; Ighil, Julien; Schwartz, Olivier; Barré-Sinoussi, Françoise; Nugeyre, Marie-Thérèse

    2014-01-01

    ABSTRACT In order to develop strategies to prevent HIV-1 (human immunodeficiency virus type 1) transmission, it is crucial to better characterize HIV-1 target cells in the female reproductive tract (FRT) mucosae and to identify effective innate responses. Control of HIV-1 infection in the decidua (the uterine mucosa during pregnancy) can serve as a model to study natural mucosal protection. Macrophages are the main HIV-1 target cells in the decidua. Here we report that in vitro, macrophages and T cells are the main HIV-1 targets in the endometrium in nonpregnant women. As reported for decidual macrophages (dM), endometrial macrophages (eM) were found to have an M2-like phenotype (CD68+ CD163+ CD206+ IL-10high). However, eM and dM may belong to different subpopulations, as they differently express certain markers and secrete different amounts of proinflammatory and anti-inflammatory cytokines. We observed strong expression of the SAMHD1 restriction factor and weak expression of its inactive form (pSAMHD1, phosphorylated at residue Thr592) in both eM and dM. Infection of macrophages from both tissues was enhanced in the presence of the viral protein Vpx, suggesting a role for SAMHD1 in the restriction of HIV-1 infection. This study and further comparisons of the decidua with FRT mucosae in nonpregnant women should help to identify mechanisms of mucosal protection against HIV-1 infection. IMPORTANCE The female reproductive tract mucosae are major portals of HIV-1 entry into the body. The decidua (uterine mucosa during pregnancy) can serve as a model for studying natural mucosal protection against HIV-1 transmission. A comparison of target cells and innate responses in the decidua versus the endometrium in nonpregnant women could help to identify protective mechanisms. Here, we report for the first time that macrophages are one of the main HIV-1 target cells in the endometrium and that infection of macrophages from both the endometrium and the decidua is restricted by

  20. Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART

    PubMed Central

    Bekele, Yonas; Amu, Sylvie; Bobosha, Kidist; Lantto, Rebecka; Nilsson, Anna; Endale, Birtukan; Gebre, Meseret; Aseffa, Abraham; Rethi, Bence; Howe, Rawleigh; Chiodi, Francesca

    2015-01-01

    Abstract T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied. The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells. A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children. B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02). Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity. PMID:26166114

  1. Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART.

    PubMed

    Bekele, Yonas; Amu, Sylvie; Bobosha, Kidist; Lantto, Rebecka; Nilsson, Anna; Endale, Birtukan; Gebre, Meseret; Aseffa, Abraham; Rethi, Bence; Howe, Rawleigh; Chiodi, Francesca

    2015-07-01

    T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied.The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells.A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children.B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02).Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity.

  2. Psychological Empowerment Model in Iranian Pregnant Women

    PubMed Central

    Taghipour, Ali; Sadat Borghei, Narjes; Latifnejad Roudsari, Robab; Keramat, Afsaneh; Jabbari Nooghabi, Hadi

    2016-01-01

    ABSTRACT Background: Women’s empowerment programs during pregnancy focus primarily on increasing women’s health goals and psychological empowerment has been considered important in most issues related to pregnant mothers’ mental health. Using path analysis, this study aims to examine the direct and indirect components of psychological empowerment of pregnant mothers. Methods: This model-testing study was conducted in Gorgan, northwest of Iran during three months in spring of 2015. Through random cluster sampling, a total number of 160 pregnant women were selected from 10 urban medical centers and clinics as primary centers. We used Spritzer’s Psychological empowerment scale. Suitable sampling based on Nunally and Bernstein was followed in the model. The relationships between the dependent variables were then examined by means of path analysis using Amos 18. Results: The psychological empowerment of pregnant mothers (PEPW) model is impacted by individual factors, such as marriage age and employment, including some subjectively rated factors such as marital satisfaction and experience of violence. The PEPW model was deemed appropriate as optimum conditions indicators of goodness of fit; low index of χ2/df shows little difference between the conceptual model and observed data, while RMSEA value indicated the goodness of fit. Other indicators such as CMIN=0.957, CMIN/DF=0.957, P-CLOSE=0.418, χ2=0.957 and probability level=0.328 the fact that the model is ideal. The mothers’ employment had the highest coefficient in the PEPW path model .731 (0.443, 0.965) bootstrap confidence intervals by 95%, and with a p-value of less than 0.05. Conclusions: The mothers’ employment is the most important factor in psychological empowerment, but it cannot be addressed quickly. Programming to increase marital satisfaction followed by a decrease in family violence and prevention of early marriage are necessary for promotion of psychological empowerment during pregnancy. PMID

  3. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.

    PubMed

    Palladino, Claudia; Gómez, María Luisa Navarro; Soler-Palacín, Pere; González-Tomé, María Isabel; De Ory, Santiago J; Espiau, María; Hoyos, Santiago Pérez; León-Leal, Juan Antonio; Méndez, María; Moreno-Pérez, David; Guasch, Claudia Fortuny; Sierra, Antoni Mur; Guruceta, Itziar Pocheville; Guillén, Santiago Moreno; Briz, Verónica

    2015-10-23

    Maraviroc (MVC) is not approved for HIV-1-infected paediatric patients. This is the first assessment of the use of MVC-based salvage therapy in vertically HIV-1-infected paediatric patients in clinical settings. The results suggest that MVC-based salvage therapy is useful in children and adolescents with extensive resistance profile leading to maintained virological suppression in up to 88% of the patients with CCR5-tropic virus. The likelihood of treatment success might increase when MVC is combined with other active drugs.

  4. Stochastic modeling for dynamics of HIV-1 infection using cellular automata: A review.

    PubMed

    Precharattana, Monamorn

    2016-02-01

    Recently, the description of immune response by discrete models has emerged to play an important role to study the problems in the area of human immunodeficiency virus type 1 (HIV-1) infection, leading to AIDS. As infection of target immune cells by HIV-1 mainly takes place in the lymphoid tissue, cellular automata (CA) models thus represent a significant step in understanding when the infected population is dispersed. Motivated by these, the studies of the dynamics of HIV-1 infection using CA in memory have been presented to recognize how CA have been developed for HIV-1 dynamics, which issues have been studied already and which issues still are objectives in future studies.

  5. Loss of DNAM-1 contributes to CD8+ T cell exhaustion in chronic HIV-1 infection

    PubMed Central

    Cella, Marina; Presti, Rachel; Vermi, William; Lavender, Kerry; Turnbull, Emma; Ochsenbauer-Jambor, Christina; Kappes, John C.; Ferrari, Guido; Kessels, Lisa; Williams, Ian; McMichael, Andrew J.; Haynes, Barton F.; Borrow, Persephone; Colonna, Marco

    2011-01-01

    Summary The hallmark of chronic viral infections is a progressive exhaustion of antigen specific CD8+ T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8+ T cells that makes them dysfunctional. Here we show that during human chronic HIV-1 infection a CD8+ T cell positive costimulatory pathway mediated by DNAM-1 is also disrupted. Thus, DNAM-1 downregulation on CD8+ T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection. PMID:20201043

  6. The role of micronutrients in the diet of HIV-1-infected individuals.

    PubMed

    Nunnari, Giuseppe; Coco, Christian; Pinzone, Marilia Rita; Pavone, Piero; Berretta, Massimiliano; Di Rosa, Michelino; Schnell, Matthias; Calabrese, Giorgio; Cacopardo, Bruno

    2012-06-01

    Vitamins, zinc and selenium are important micronutrients that play crucial functions at the cellular and molecular level. Immune response of several different cell types can be modulated by these micronutrients. Deficiency in micronutrients has been extensively reported in HIV-1-infected individuals and further correlated with CD4+ T-cell count, HIV-1 plasma viral load, disease progression and mortality. Supplementation by micronutrients has had controversial effects. Thorough future investigations and trials are certainly needed to strategically plan evidence-based interventions. Here, we review the available data on use of micronutrients during the course of HIV-1 infection.

  7. Acute HIV-1 Infection in the Southeastern United States: A Cohort Study

    PubMed Central

    Cope, Anna B.; Gay, Cynthia L.; McGee, Kara S.; Kuruc, JoAnn D.; Kerkau, Melissa G.; Hurt, Christopher B.; Fiscus, Susan A.; Ferrari, Guido; Margolis, David M.; Eron, Joseph J.; Hicks, Charles B.

    2013-01-01

    Abstract In 1998 a collaboration between Duke University and the University of North Carolina, Chapel Hill (UNC) was founded to enhance identification of persons with acute HIV-1 infection (AHI). The Duke-UNC AHI Research Consortium Cohort consists of patients ≥18 years old with a positive nucleic acid amplification test (NAAT) and either a negative enzyme immunoassay (EIA) test or a positive EIA with a negative/indeterminate Western blot. Patients were referred to the cohort from acute care settings and state-funded HIV testing sites that use NAAT testing on pooled HIV-1 antibody-negative samples. Between 1998 and 2010, 155 patients with AHI were enrolled: 81 (52%) African-Americans, 63 (41%) white, non-Hispanics, 137 (88%) males, 108 (70%) men who have sex with men (MSM), and 18 (12%) females. The median age was 27 years (IQR 22–38). Most (n=138/155) reported symptoms with a median duration of 17.5 days. The median nadir CD4 count was 408 cells/mm3 (IQR 289–563); the median observed peak HIV-1 level was 726,859 copies/ml (IQR 167,585–3,565,728). The emergency department was the most frequent site of initial presentation (n=55/152; 3 missing data). AHI diagnosis was made at time of first contact in 62/137 (45%; 18 missing data) patients. This prospectively enrolled cohort is the largest group of patients with AHI reported from the Southeastern United States. The demographics reflect the epidemic of this geographic area with a high proportion of African-Americans, including young black MSM. Highlighting the challenges of diagnosing AHI, less than half of the patients were diagnosed at the first healthcare visit. Women made up a small proportion despite increasing numbers in our clinics. PMID:22839749

  8. Increased incidence of hepatocellular carcinoma (HCC) in HIV-1 infected patients.

    PubMed

    Murillas, Javier; Del Río, Manuel; Riera, Melchor; Vaquer, Pedro; Salas, Ana; Leyes, María; Angeles Ribas, M; Peñaranda Vera, María; Villalonga, Concepcion

    2005-04-01

    BACKGROUND: The likely increased incidence of hepatocarcinoma (HCC) in HIV-1 infected patients has not yet been demonstrated. METHODS: We studied all cases of HCC occurring in HIV-1 infected patients in our hospital during the past 15 years. Incidence and survival time were compared with those of the general population in the same area and the same time of the study. RESULTS: We found 6 cases of HCC in a cohort of 2383 HIV-1 infected patients between 1986 and 2001. This is a higher than expected incidence rate of HCC compared with the general population, with a standardized incidence ratio of 13.95. Chronic hepatitis virus infection and alcohol abuse were present in four and two cases, respectively. In one patient, no liver disease was known before the HCC and the surrounding liver was normal in the necropsy study. CONCLUSION: The improved survival of patients on highly active antiretroviral treatment (HAART) and the increasing incidence of end-stage liver disease in these patients caused by chronic hepatitis virus infection and alcohol abuse may be responsible for an increase in the incidence of HCC in HIV-1 infected patients.

  9. The impact of inflammation and immune activation on B cell differentiation during HIV-1 infection.

    PubMed

    Ruffin, Nicolas; Thang, Pham Hong; Rethi, Bence; Nilsson, Anna; Chiodi, Francesca

    2011-01-01

    One important pathogenic feature of human immunodeficiency virus (HIV)-1 infection is chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells was reported to occur in both children and adults infected with HIV-1; these cells are responsible for maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.

  10. The Impact of Inflammation and Immune Activation on B Cell Differentiation during HIV-1 Infection

    PubMed Central

    Ruffin, Nicolas; Thang, Pham Hong; Rethi, Bence; Nilsson, Anna; Chiodi, Francesca

    2012-01-01

    One important pathogenic feature of human immunodeficiency virus (HIV)-1 infection is chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells was reported to occur in both children and adults infected with HIV-1; these cells are responsible for maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells. PMID:22566879

  11. LINE-1 Retrotransposable Element DNA Accumulates in HIV-1-Infected Cells

    PubMed Central

    Song, Haihan; Xu, Yang; Garrison, Keith E.; Buzdin, Anton A.; Anwar, Naveed; Hunter, Diana V.; Mujib, Shariq; Mihajlovic, Vesna; Martin, Eric; Lee, Erika; Kuciak, Monika; Raposo, Rui André Saraiva; Bozorgzad, Ardalan; Meiklejohn, Duncan A.; Ndhlovu, Lishomwa C.; Nixon, Douglas F.; Ostrowski, Mario A.

    2013-01-01

    Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable elements that retain the potential for activity in the human genome but are suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription of L1 in the cytosol has the potential to activate innate immune sensors. We hypothesized that HIV-1 infection would compromise cellular control of L1 elements, resulting in the induction of retrotransposition events. Here, we show that HIV-1 infection enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent manner. In primary CD4+ cells, HIV-1 infection results in the accumulation of L1 DNA, at least the majority of which is extrachromosomal. These data expose an unrecognized interaction between HIV-1 and endogenous retrotransposable elements, which may have implications for the innate immune response to HIV-1 infection, as well as for HIV-1-induced genomic instability and cytopathicity. PMID:24089548

  12. LINE-1 retrotransposable element DNA accumulates in HIV-1-infected cells.

    PubMed

    Jones, R Brad; Song, Haihan; Xu, Yang; Garrison, Keith E; Buzdin, Anton A; Anwar, Naveed; Hunter, Diana V; Mujib, Shariq; Mihajlovic, Vesna; Martin, Eric; Lee, Erika; Kuciak, Monika; Raposo, Rui André Saraiva; Bozorgzad, Ardalan; Meiklejohn, Duncan A; Ndhlovu, Lishomwa C; Nixon, Douglas F; Ostrowski, Mario A

    2013-12-01

    Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable elements that retain the potential for activity in the human genome but are suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription of L1 in the cytosol has the potential to activate innate immune sensors. We hypothesized that HIV-1 infection would compromise cellular control of L1 elements, resulting in the induction of retrotransposition events. Here, we show that HIV-1 infection enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent manner. In primary CD4(+) cells, HIV-1 infection results in the accumulation of L1 DNA, at least the majority of which is extrachromosomal. These data expose an unrecognized interaction between HIV-1 and endogenous retrotransposable elements, which may have implications for the innate immune response to HIV-1 infection, as well as for HIV-1-induced genomic instability and cytopathicity.

  13. Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection

    SciTech Connect

    Wang, Lin-Xu; Mellon, Michael; Bowder, Dane; Quinn, Meghan; Shea, Danielle; Wood, Charles; Xiang, Shi-Hua

    2015-01-15

    Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from Neisseria gonorrhoeae, which enabled surface display of the antibody molecule. Our results indicate that the scFv-VRC01 antibody molecule was displayed on the surface of the bacteria as demonstrated by flow cytometry and immunofluorescence microscopy. The engineered bacteria can capture HIV-1 particles via surface-binding and inhibit HIV-1 infection in cell culture. - Highlights: • Designed single-chain VRC01 antibody was demonstrated to bind HIV-1 envelope gp120. • Single-chain VRC01 antibody was successfully displayed on the surface of E. coli. • Engineered bacteria can absorb HIV-1 particles and prevent HIV-1 infection in cell culture.

  14. Quantitative proteomic analysis of exosomes from HIV-1 infected lymphocytic cells

    PubMed Central

    Li, Ming; Aliotta, Jason M.; Asara, John M.; Tucker, Lynne; Quesenberry, Peter; Lally, Michelle; Ramratnam, Bharat

    2013-01-01

    HIV-1 infection causes profound effects both inside and outside of cells through multiple mechanisms, including those mediated by exosomes. Using the technique of Stable Isotope Labeling by Amino acids in Cell culture (SILAC), we compared protein expression patterns in the exosomal compartment of HIV-1 infected and uninfected lymphocytic H9 cells. Of 770 proteins identified in two independent sets of exosomal samples, 14 proteins were found to be differentially expressed in the exosomal fraction of HIV-1 infected cells vs. uninfected controls. Gene Ontology survey and DAVID analysis revealed that identified proteins were enriched for functional categories such as binding. Of these 14 proteins, three immunomodulatory molecules were reproducibly identified in both replicates and included ADP-ribosyl cyclase 1 (CD38), L-lactate dehydrogenase B chain (LDHB) and Annexin A5 (ANXA5). In addition to previously reported HIV-1 associations with CD38 and LDHB, new interactions were identified and validated for ANXA5, CD38 and LDHB, which were found to bind to HIV-1 p24 and Tat. In summary, our studies reveal that exosomes released from HIV-1 infected cells are composed of a unique and quantitatively different protein signature and harbor regulatory molecules that impact the processes of cellular apoptosis (ANXA5 and LDHB) and proliferation (CD38). PMID:22807456

  15. [Intracranial arteriovenous malformations in pregnant women].

    PubMed

    Perquin, D A; Kloet, A; Tans, J T; Witte, G N; Dörr, P J

    1999-03-06

    Three women, aged 27, 32 and 30 years, respectively, suffered from headache, nausea and neurological abnormalities and were found to have an intracranial arteriovenous malformation (AVM). One of them after diagnosis had two pregnancies, both ended by caesarean section with good results. Another woman was 32 weeks pregnant when the AVM manifested itself with a haemorrhage; she recovered well and was delivered by caesarean section. After the AVM proved radiologically to have been obliterated, she delivered after her subsequent pregnancy by the vaginal route with vacuum extraction. The third woman was 15 weeks pregnant when major abnormalities developed. There was a large intracerebral haematoma with break-through to the ventricular system; this patient died. Intracranial haemorrhage during pregnancy is rate. It can result in maternal and foetal morbidity and mortality. It appears that pregnancy does not increase the rate of first cerebral haemorrhage from an AVM. The management of AVM rupture during pregnancy should be based primarily on neurosurgical rather than on obstetric considerations. Close collaboration with a team of neurologists, neurosurgeons, obstetricians and anaesthesiologists is mandatory.

  16. [Cardiopulmonary resuscitation in pregnant women: peculiarities].

    PubMed

    Grau Gandía, S; Martínez Ramón, M A

    1998-01-01

    This review main purpose is to show nursing the present knowledge about cardiopulmonary resuscitation (CPR) in pregnant women because of the scarce information published by Spanish Nursing Publications. The bibliographical research was made using both the Medline (from January 1982 to March 1998) and Index de Enfermería databases. There, we can find 32 references from which only 23 were selected (all of them belong to the Medline database) in spite of 3 chapters that had already been selected from other different books. Although maternal cardiac arrest rarely happens during pregnancy, it is very important for sanitary staff to be familiarized with the specifics thecnics and equipment (ultrasound and cardiotocograph monitoring). This review describes the physiological changes that take place during pregnancy and have an incidence into CPR. The article also includes the conclusions about the checked papers and the peculiarities that have to be taken into account in each CPR, such as the fetal viability evaluation, right CPR position, airway and breathing, desfibrillation, external cardiac compression and use of pharmacologic therapy and intravenous fluids. Moreover, there is a special mention of the perimortem cesarean delivery features: antecedents, foetus-maternals consequences and managements, due to the fact that this surgical operation should be included inside the CPR protocols of the pregnant.

  17. Alterations in the Fecal Microbiota of Patients with HIV-1 Infection: An Observational Study in A Chinese Population

    PubMed Central

    Ling, Zongxin; Jin, Changzhong; Xie, Tiansheng; Cheng, Yiwen; Li, Lanjuan; Wu, Nanping

    2016-01-01

    The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients. The ratio of Firmicutes/Bacteroidetes increased significantly in HIV-1-infected patients. Several key bacterial phylotypes, including Prevotella, were prevalent in HIV-1-infected patients; whereas Phascolarctobacterium, Clostridium XIVb, Dialister and Megamonas were significantly correlated with systemic inflammatory cytokines. After short-term, effective HAART, the viral loads of HIV-1 were reduced; however, the diversity and composition of the fecal microbiota were not completely restored. and the dysbiosis remained among HIV-1-infected subjects undergoing HAART. Our detailed analysis demonstrated that dysbiosis of fecal microbiota might play an active role in HIV-1 infection. Thus, new insights may be provided into therapeutics that target the microbiota to attenuate the progression of HIV disease and to reduce the risk of gut-linked disease in HIV-1-infected patients. PMID:27477587

  18. IL-8 Alterations in HIV-1 Infected Children With Disease Progression.

    PubMed

    Pananghat, Ambili Nair; Aggarwal, Heena; Prakash, Somi Sankaran; Makhdoomi, Muzamil Ashraf; Singh, Ravinder; Lodha, Rakesh; Ali, Shakir; Srinivas, Maddur; Das, Bimal Kumar; Pandey, Ravindra Mohan; Kabra, Sushil Kumar; Luthra, Kalpana

    2016-05-01

    Disease progression in HIV-1 infected children is faster than in adults. Less than 5% of the infected children maintain stable CD4 counts beyond 7 years of infection and are termed long-term nonprogressors (LTNPs). Delineating the host immune response in antiretroviral naïve (ART) and treated HIV-1 infected children at different disease stages will help in understanding the immunopathogenesis of the disease.A total of 79 asymptomatic, perinatally HIV-1 infected children (50 ART naïve and 29 ART treated) and 8 seronegative donors were recruited in this study. T- and B-cell activation PCR arrays were performed from the cDNA, using total RNA extracted from the peripheral blood mononuclear cells (PBMCs) of 14 HIV-1 infected children at different stages of the disease. The differentially expressed genes were identified. Quantitative RT-PCR was performed for the (interleukin-8) IL-8 gene and its transcriptional mediators, that is, SHP2, GRB2, and IL-8R (IL-8 receptor/CXCR1). Plasma levels of IL-8 were measured by flow cytometry.Gene array data revealed a higher expression of IL-8 in the ART naïve HIV-1 infected progressors and in ART nonresponders than LTNPs and ART responders, respectively. Quantitative RT-PCR analysis demonstrated a significant higher expression of IL-8 (P < 0.001), its receptor CXCR1 (P = 0.03) and the upstream signaling molecule SHP2 (P = 0.04) in the progressors versus LTNPs. Plasma levels of IL-8 were significantly higher in progressors versus LTNPs (P < 0.001), and ART nonresponders versus ART responders (P < 0.001). A significant negative correlation of plasma levels of IL-8 with CD4 counts (cells/μL) was observed in HIV-1 infected ART naïve subjects (r = -0.488; P < 0.001), while the IL-8 levels positively correlated with viral load in the ART treated children (r = 0.5494; P < 0.001). ART naïve progressors on follow up demonstrated a significant reduction in the mRNA expression (P = 0.05) and plasma

  19. IL-8 Alterations in HIV-1 Infected Children With Disease Progression

    PubMed Central

    Pananghat, Ambili Nair; Aggarwal, Heena; Prakash, Somi Sankaran; Makhdoomi, Muzamil Ashraf; Singh, Ravinder; Lodha, Rakesh; Ali, Shakir; Srinivas, Maddur; Das, Bimal Kumar; Pandey, Ravindra Mohan; Kabra, Sushil Kumar; Luthra, Kalpana

    2016-01-01

    Abstract Disease progression in HIV-1 infected children is faster than in adults. Less than 5% of the infected children maintain stable CD4 counts beyond 7 years of infection and are termed long-term nonprogressors (LTNPs). Delineating the host immune response in antiretroviral naïve (ART) and treated HIV-1 infected children at different disease stages will help in understanding the immunopathogenesis of the disease. A total of 79 asymptomatic, perinatally HIV-1 infected children (50 ART naïve and 29 ART treated) and 8 seronegative donors were recruited in this study. T- and B-cell activation PCR arrays were performed from the cDNA, using total RNA extracted from the peripheral blood mononuclear cells (PBMCs) of 14 HIV-1 infected children at different stages of the disease. The differentially expressed genes were identified. Quantitative RT-PCR was performed for the (interleukin-8) IL-8 gene and its transcriptional mediators, that is, SHP2, GRB2, and IL-8R (IL-8 receptor/CXCR1). Plasma levels of IL-8 were measured by flow cytometry. Gene array data revealed a higher expression of IL-8 in the ART naïve HIV-1 infected progressors and in ART nonresponders than LTNPs and ART responders, respectively. Quantitative RT-PCR analysis demonstrated a significant higher expression of IL-8 (P < 0.001), its receptor CXCR1 (P = 0.03) and the upstream signaling molecule SHP2 (P = 0.04) in the progressors versus LTNPs. Plasma levels of IL-8 were significantly higher in progressors versus LTNPs (P < 0.001), and ART nonresponders versus ART responders (P < 0.001). A significant negative correlation of plasma levels of IL-8 with CD4 counts (cells/μL) was observed in HIV-1 infected ART naïve subjects (r = −0.488; P < 0.001), while the IL-8 levels positively correlated with viral load in the ART treated children (r = 0.5494; P < 0.001). ART naïve progressors on follow up demonstrated a significant reduction in the mRNA expression (P = 0

  20. BST-2 Expression Modulates Small CD4 Mimetic Sensitization of HIV-1-infected cells to ADCC.

    PubMed

    Richard, Jonathan; Prévost, Jérémie; von Bredow, Benjamin; Ding, Shilei; Brassard, Nathalie; Medjahed, Halima; Coutu, Mathieu; Melillo, Bruno; Bibollet-Ruche, Frédéric; Hahn, Beatrice H; Kaufmann, Daniel E; Smith, Amos B; Sodroski, Joseph; Sauter, Daniel; Kirchhoff, Frank; Gee, Katrina; Neil, Stuart J; Evans, David T; Finzi, Andrés

    2017-03-22

    Antibodies recognizing conserved CD4-induced (CD4i) epitopes on HIV-1 Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV+ sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4-mimetics (CD4mc) which are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera. However, HIV-1 developed additional mechanisms to avoid ADCC including Vpu-mediated BST-2 antagonism, which decreases the overall amount of Env present at the cell surface. Accordingly, BST-2 up-regulation in response to IFN-α was shown to increase the susceptibility of HIV-1-infected cells to ADCC despite the activity of Vpu. Here we show that BST-2 upregulation by IFN-β and IL-27 also increases the surface expression of Env and thus boosts the ability of CD4mc to sensitize HIV-1-infected cells to ADCC by sera from HIV-1-infected individuals.IMPORTANCE HIV-1 evolved sophisticated strategies to conceal Env epitopes from ADCC-mediating antibodies present in HIV+ sera. Vpu-mediated BST-2 downregulation was shown to decrease ADCC responses by limiting the amount of Env present at the cell surface. This effect of Vpu was shown to be attenuated by IFN-α treatment. Here we show that in addition to IFN-α, IFN-β and IL-27 also affect Vpu-mediated BST-2 downregulation and greatly enhance ADCC responses against HIV-1-infected cells in the presence of CD4mc. These findings may inform strategies aimed at HIV prevention and eradication.

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

    SciTech Connect

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

    2015-11-15

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

  2. Obstetricians and the rights of pregnant women.

    PubMed

    Minkoff, Howard; Paltrow, Lynn M

    2007-05-01

    At times, obstetricians are called upon to assist pregnant women in making clinical choices between options that may selectively disadvantage either the mother or the fetus. If a mother chooses a therapeutic course that disadvantages the fetus the physician may feel distressed. In this paper we argue that the choices made by mothers are almost always in the interests of the fetus, and supported by physicians. When there is disagreement it is often due to poor communication. While acknowledging that the rare circumstances in which the physician and patient wish to pursue different clinical paths can be stressful for the provider, we explain why obstetricians should accept the judgment of their patient in all instances. Finally, we will maintain that positing a choice between maternal and fetal interests is, in fact, creating a false choice, in as much as options are presented as being exclusive, when in fact that is not the case.

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

    PubMed

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

    2015-11-01

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

  4. Δ(9)-Tetrahydrocannabinol treatment during human monocyte differentiation reduces macrophage susceptibility to HIV-1 infection.

    PubMed

    Williams, Julie C; Appelberg, Sofia; Goldberger, Bruce A; Klein, Thomas W; Sleasman, John W; Goodenow, Maureen M

    2014-06-01

    The major psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation. THC treatment of primary human monocytes during differentiation reduced HIV-1 infection of subsequent macrophages by replication competent or single cycle CCR5 using viruses. In contrast, treatment of macrophages with THC immediately prior to or continuously following HIV-1 exposure failed to alter infection. Specific receptor agonists indicated that the THC effect during monocyte differentiation was mediated primarily through CB2. THC reduced the number of p24 positive cells with little to no effect on virus production per infected cell, while quantitation of intracellular viral gag pinpointed the THC effect to an early event in the viral life cycle. Cells treated during differentiation with THC displayed reduced expression of CD14, CD16, and CD163 and donor dependent increases in mRNA expression of selected viral restriction factors, suggesting a fundamental alteration in phenotype. Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency.

  5. Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection

    PubMed Central

    2013-01-01

    Background HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP). Findings Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint. Conclusions The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function. PMID:24245727

  6. Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission.

    PubMed

    Rousseau, Christine M; Nduati, Ruth W; Richardson, Barbra A; John-Stewart, Grace C; Mbori-Ngacha, Dorothy A; Kreiss, Joan K; Overbaugh, Julie

    2004-11-15

    Understanding how the level of human immunodeficiency virus type 1 (HIV-1)-infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1-infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R=.144; P=.032), levels of cell-free virus in blood plasma (R=.365; P<.001), and the detection of proviral DNA in cervical and vaginal secretions (P<.001 and P = .030, respectively). The number of infected BMCs per million cells was lower in colostrum or early milk than in mature milk (P<.001). Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P<.001). Each log10 increase in infected BMCs per milliliter was associated with a 3.19-fold-increased risk of transmission (P=.002), after adjustment for cell-free virus in plasma (hazard ratio [HR], 2.09; P=.03) and breast milk (HR, 1.01; P=1.00). This suggests that infected BMCs may play a more important role in transmission of HIV via breast-feeding than does cell-free virus.

  7. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    PubMed Central

    Sehl, Mary; Sinsheimer, Janet S.; Hultin, Patricia M.; Hultin, Lance E.; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D.

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x10-200 and 0.47, p<1x10-200. Weighted gene correlation network analysis (WGCNA) identified 17 co-methylation modules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage= 0.007088, p=2.08 x 10-9; βHIV= 0.099574, p=0.0011; Data set 2: βage= 0.008762, p=1.27x 10-5; βHIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to

  8. Correlates of Stress among Pregnant Hispanic Women

    PubMed Central

    Silveira, Marushka Leanne; Pekow, Penelope S.; Dole, Nancy; Markenson, Glenn; Chasan-Taber, Lisa

    2012-01-01

    Objectives Prenatal psychosocial stress has been associated with adverse pregnancy outcomes, even after controlling for known risk factors. This paper aims to evaluate correlates of high perceived stress among Hispanic women, a group with elevated rates of stress during pregnancy. Methods We conducted this analysis among 1426 pregnant Hispanic women using data from Proyecto Buena Salud, a prospective cohort study conducted in Western Massachusetts. Cohen’s Perceived Stress Scale (PSS-14) validated in English and Spanish was administered in early (mean=12.4 wks gestation), mid (mean=21.3 wks gestation) and late (mean=30.8 wks gestation) pregnancy at which time bilingual interviewers collected data on socio-demographic, acculturation, behavioral, and psychosocial factors. High perceived stress was defined as a PSS score>30. Results Young maternal age (odds ratio (OR) =0.6; 95% confidence interval (CI) 0.4-0.9 for <19 vs. 19-23yrs), pre-pregnancy consumption of alcohol (OR=2.2; 95% CI 1.4-3.5 for >12 drinks/mo. vs. none) and smoking (OR=2.2; 95% CI 1.3-3.7 for >10 cigarettes/day vs. none) were associated with high perceived stress during early pregnancy. Furthermore, higher annual household income (OR=0.4; 95% CI 0.1-0.9 for >$30,000 vs. <$15,000), greater number of adults in the household (OR=1.8; 95% CI 1.1-3.0 for ≥3 vs. 1) and language preference (OR=0.6; 95% CI 0.4-0.9 for Spanish vs. English) were associated with high stress during mid-pregnancy. Likewise, annual household income was inversely associated with high stress during late pregnancy. Conclusion Our results have important implications for incorporation of routine screening for psychosocial stress during prenatal visits and implementation of psychosocial counseling services for women at high risk. PMID:23010861

  9. Prenatal Vitamins: OK for Women Who Aren't Pregnant?

    MedlinePlus

    ... and women age 51 and older and all adult men need only 8 mg a day. Getting too much iron can be toxic because it can build up in your body, causing constipation, nausea, vomiting, diarrhea and, in severe cases, possibly death. Calcium. Pregnant adult women and healthy men and women ages 19 ...

  10. Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

    PubMed Central

    Holmes, Derek; Jiang, Qi; Zhang, Liguo

    2014-01-01

    FoxP3+CD4+CD25+ regulatory T (Treg) cells are implicated in a number of pathologic processes including elevated levels in cancers and infectious diseases, and reduced levels in autoimmune diseases. Treg cells are activated to modulate immune responses to avoid over-reactive immunity. However, conflicting findings are reported regarding relative levels of Treg cells during HIV-1 infection and disease progression. The role of Treg cells in HIV-1 diseases (aberrant immune activation) is poorly understood due to lack of a robust model. We summarize here the regulation and function of Foxp3 in Treg cells and in modulating HIV-1 replication. Based on recent findings from SIV/monkey and HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1 infection and immuno-pathogenesis is discussed. PMID:18726715

  11. Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.

    PubMed

    Baxter, Amy E; Russell, Rebecca A; Duncan, Christopher J A; Moore, Michael D; Willberg, Christian B; Pablos, Jose L; Finzi, Andrés; Kaufmann, Daniel E; Ochsenbauer, Christina; Kappes, John C; Groot, Fedde; Sattentau, Quentin J

    2014-12-10

    Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. Macrophages infected by this cell-to-cell route were highly permissive for both CCR5-using macrophage-tropic and otherwise weakly macrophage-tropic transmitted/founder viruses but restrictive for nonmacrophage-tropic CXCR4-using virus. These results have implications for establishment of the macrophage reservoir and HIV-1 dissemination in vivo.

  12. FDA Issues Anesthesia Warning for Pregnant Women, Kids Under 3

    MedlinePlus

    ... gov/news/fullstory_162543.html FDA Issues Anesthesia Warning for Pregnant Women, Kids Under 3 A long ... latest published studies, the agency announced that these warnings need to be added to the labels of ...

  13. Pregnant Women Should Avoid Zika-Hit Texas Town: CDC

    MedlinePlus

    ... news/fullstory_162573.html Pregnant Women Should Avoid Zika-Hit Texas Town: CDC Advisory follows reports of ... border with Mexico, because five cases of local Zika infection have been reported there, U.S. health officials ...

  14. 45 CFR 46.204 - Research involving pregnant women or fetuses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Research involving pregnant women or fetuses. 46... PROTECTION OF HUMAN SUBJECTS Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.204 Research involving pregnant women or fetuses. Pregnant women or fetuses may...

  15. Interleukin 18 and cardiovascular disease in HIV-1 infection: a partner in crime?

    PubMed

    Torre, Donato; Pugliese, Agostino

    2010-01-01

    Cardiovascular disease has been frequent in HIV-infected patients both before and after the advent of antiretroviral therapy (HAART). The pathogenic basis for the increase of cardiovascular disease, in particular myocardial lesions, may involve HIV-1 itself or other mechanisms including endothelial dysfunction, activation of proinflammatory cytokines, and changes in platelets, which lead to atherosclerotic lesions of blood vessels. In the last decade, among the proinflammatory cytokines, interleukin 18 seems to play a central role in the inflammatory cascade, leading to development of atherosclerotic disease and the occurrence of ischemic heart disease in uninfected HIV-1 people. Increased levels of interleukin 18 were observed in HIV-1 infected patients. This review attempts to evaluate the role of interleukin 18 in cardiovascular disease, especially in myocardial infarction, in HIV-1 infection, as well as the relationship between interleukin 18 and atherosclerotic plaque formation. Two other characteristic aspects in HIV-1 infection, metabolic syndrome and lipodystrophy, will be evaluated in light of activity of interleukin 18. Moreover, the role of platelets and interleukin 18 as an important linkage between chronic inflammation, endothelial dysfunction, and atherogenesis will be highlighted. Finally, experimental an animal model of rhesus macaques infected with simian immunodeficiency virus clearly demonstrates the involvement of interleukin 18 in myocardial lesions, and that circulating levels of interleukin 18 are important predictors of coronary heart disease. In conclusion, interleukin 18 may be considered a partner in crime with other factors, including endothelial dysfunction, increased expression and production of adhesion molecules and proinflammatory cytokines in determining cardiovascular disease.

  16. Mitochondrial Haplogroup Influences Motor Function in Long-Term HIV-1-Infected Individuals

    PubMed Central

    Azar, Ashley; Giovannetti, Tania; Pirrone, Vanessa; Nonnemacher, Michael R.; Passic, Shendra; Kercher, Katherine; Williams, Jean W.; Wigdahl, Brian; Dampier, William; Libon, David J.; Sell, Christian

    2016-01-01

    Evolutionary divergence of the mitochondrial genome has given rise to distinct haplogroups. These haplogroups have arisen in specific geographical locations and are responsible for subtle functional changes in the mitochondria that may provide an evolutionary advantage in a given environment. Based on these functional differences, haplogroups could define disease susceptibility in chronic settings. In this study, we undertook a detailed neuropsychological analysis of a cohort of long-term HIV-1-infected individuals in conjunction with sequencing of their mitochondrial genomes. Stepwise regression analysis showed that the best model for predicting both working memory and declarative memory were age and years since diagnosis. In contrast, years since diagnosis and sub-haplogroup were significantly predictive of psychomotor speed. Consistent with this, patients with haplogroup L3e obtained better scores on psychomotor speed and dexterity tasks when compared to the remainder of the cohort, suggesting that this haplogroup provides a protective advantage when faced with the combined stress of HIV-1 infection and long-term antiretroviral therapies. Differential performance on declarative memory tasks was noted for individuals with other sub-L haplogroups, but these differences were not as robust as the association between L3e and psychomotor speed and dexterity tasks. This work provides evidence that mitochondrial haplogroup is related to neuropsychological test performance among patients in chronic disease settings such as HIV-1 infection. PMID:27711166

  17. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells.

    PubMed

    Bonifati, Serena; Daly, Michele B; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A; Shepard, Caitlin; Kennedy, Edward M; Kim, Dong-Hyun; Schinazi, Raymond F; Kim, Baek; Wu, Li

    2016-08-01

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G1/G0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

  18. Inhibition of HIV-1 infection by synthetic peptides derived CCR5 fragments

    SciTech Connect

    Imai, Masaki; Baranyi, Lajos; Okada, Noriko; Okada, Hidechika; E-mail: hiokada@med.nagoya-cu.ac.jp

    2007-02-23

    HIV-1 infection requires interaction of viral envelope protein gp160 with CD4 and a chemokine receptor, CCR5 or CXCR4 as entry coreceptor. We designed HIV-inhibitory peptides targeted to CCR5 using a novel computer program (ANTIS), which searched all possible sense-antisense amino acid pairs between proteins. Seven AHBs were found in CCR5 receptor. All AHB peptides were synthesized and tested for their ability to prevent HIV-1 infection to human T cells. A peptide fragment (LC5) which is a part of the CCR5 receptor corresponding to the loop between the fifth and sixth transmembrane regions (amino acids 222-240) proved to inhibit HIV-1{sub IIIB} infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. LC5 effectively indicated dose-dependent manner, and the suppression was enhanced additively by T20 peptide, which inhibits infection in vitro by disrupting the gp41 conformational changes necessary for membrane fusion. Thus, these results indicate that CCR5-derived AHB peptides could provide a useful tool to define the mechanism(s) of HIV infection, and may provide insight which will contribute to the development of an anti-HIV-1 reagent.

  19. HIV-1-infected macrophages induce astrogliosis by SDF-1{alpha} and matrix metalloproteinases

    SciTech Connect

    Okamoto, Mika; Wang, Xin; Baba, Masanori . E-mail: baba@m.kufm.kagoshima-u.ac.jp

    2005-11-04

    Brain macrophages/microglia and astrocytes are known to be involved in the pathogenesis of HIV-1-associated dementia (HAD). To clarify their interaction and contribution to the pathogenesis, HIV-1-infected or uninfected macrophages were used as a model of brain macrophages/microglia, and their effects on human astrocytes in vitro were examined. The culture supernatants of HIV-1-infected or uninfected macrophages induced significant astrocyte proliferation, which was annihilated with a neutralizing antibody to stromal cell-derived factor (SDF)-1{alpha} or a matrix metalloproteinase (MMP) inhibitor. In these astrocytes, CXCR4, MMP, and tissue inhibitors of matrix metalloproteinase mRNA expression and SDF-1{alpha} production were significantly up-regulated. The supernatants of infected macrophages were always more effective than those of uninfected cells. Moreover, the enhanced production of SDF-1{alpha} was suppressed by the MMP inhibitor. These results indicate that the activated and HIV-1-infected macrophages can indirectly induce astrocyte proliferation through up-regulating SDF-1{alpha} and MMP production, which implies a mechanism of astrogliosis in HAD.

  20. Psoralen/UV inactivation of HIV-1-infected cells for use in cytologic and immunologic procedures

    SciTech Connect

    Watson, A.J.; Klaniecki, J.; Hanson, C.V. )

    1990-04-01

    A rapid procedure for the inactivation of HIV-1-infected cells using psoralen and ultraviolet (UV) light is described. Exposure of HIV-1-infected cells to 5 micrograms/ml psoralen followed by UV irradiation (320-380 nm) for 5 minutes yields cells that are noninfectious as assessed by extended infectivity assays. The psoralen/UV inactivation procedure described is effective with cells chronically or acutely infected with HIV-1 and is unaffected by cell densities up to 12 x 10(6)/ml. At 5 micrograms/ml psoralen does little damage to cellular permeability as shown by the ability of treated cells to exclude trypan blue and propidium iodide. Psoralen/UV treatment of HIV-1-infected cells does not cause a significant decrease in the reactivity of HIV-1 core and envelope antigens or cellular antigens to monoclonal antibodies. Experiments are presented demonstrating the use of these cells for flow cytometry studies and for cell surface labeling using the lactoperoxidase {sup 125}I iodination procedure.

  1. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.

    PubMed

    Caskey, Marina; Schoofs, Till; Gruell, Henning; Settler, Allison; Karagounis, Theodora; Kreider, Edward F; Murrell, Ben; Pfeifer, Nico; Nogueira, Lilian; Oliveira, Thiago Y; Learn, Gerald H; Cohen, Yehuda Z; Lehmann, Clara; Gillor, Daniel; Shimeliovich, Irina; Unson-O'Brien, Cecilia; Weiland, Daniela; Robles, Alexander; Kümmerle, Tim; Wyen, Christoph; Levin, Rebeka; Witmer-Pack, Maggi; Eren, Kemal; Ignacio, Caroline; Kiss, Szilard; West, Anthony P; Mouquet, Hugo; Zingman, Barry S; Gulick, Roy M; Keler, Tibor; Bjorkman, Pamela J; Seaman, Michael S; Hahn, Beatrice H; Fätkenheuer, Gerd; Schlesinger, Sarah J; Nussenzweig, Michel C; Klein, Florian

    2017-02-01

    Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.

  2. Alterations in the nuclear proteome of HIV-1 infected T-cells

    SciTech Connect

    DeBoer, Jason; Jagadish, Teena; Haverland, Nicole A.; Madson, Christian J.; Ciborowski, Pawel; Belshan, Michael

    2014-11-15

    Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines.

  3. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

    SciTech Connect

    Bonifati, Serena; Daly, Michele B.; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A.; Shepard, Caitlin; Kennedy, Edward M.; Kim, Dong-Hyun; Schinazi, Raymond F.; Kim, Baek; Wu, Li

    2016-08-15

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

  4. Choroidal thickness in pregnant women: a cross-sectional study

    PubMed Central

    Liu, Ru; Kuang, Guo-Ping; Luo, Di-Xian; Lu, Xiao-He

    2016-01-01

    AIM To investigate choroidal thickness in pregnant women and compare the measurements with those of normal nonpregnant women. METHODS Using enhanced depth imaging optical coherence tomography (EDI-OCT), choroidal thickness was measured at the fovea and at 1 mm and 3 mm superior, inferior, temporal, and nasal to the fovea in both healthy pregnant women and nonpregnant women. Pearson correlation analysis was performed to evaluate the relationships between subfoveal choroidal thickness (SFCT) and the demographic and ocular parameters. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-effects model when Meta-analyses were conducted. RESULTS Comparison of choroidal thickness between the groups showed that it was significantly greater in healthy pregnant women's eyes than in normal nonpregnant women's eyes at all locations except at 3 mm superior and 3 mm temporal from the fovea (P<0.05). The mean SFCT was 344.13±50.94 µm in healthy pregnant women's eyes and 315.03±60.57 µm in normal nonpregnant women's eyes, with a statistically significant difference (P=0.008). Pearson correlation analysis showed that age and axial length were significantly related to SFCT in healthy pregnant women, normal nonpregnant women, and all subjects. The results of our cross-sectional study were consistent with the results of the further Meta-analysis, with a pooled weighted mean difference (WMD) of 33.66 µm (95% CI: 26.16 to 41.15) for SFCT. CONCLUSION Our results, along with the comprehensive Meta-analysis, suggest that choroidal thickness in healthy pregnant women is greater than that in normal nonpregnant women. PMID:27588276

  5. Dental caries and gingivitis among pregnant and non-pregnant women in Chiang Mai, Thailand.

    PubMed

    Rakchanok, Noochpoung; Amporn, Dejpitak; Yoshida, Yoshitoku; Harun-Or-Rashid, Md; Sakamoto, Junichi

    2010-02-01

    The aims of this study were to identify dental caries and gingivitis among pregnant women, and to compare it with those in non-pregnant women in Chiang Mai, Thailand. Data were collected from 197 women (94 pregnant and 103 non-pregnant) from June to August, 2008. Dental caries and gingivitis was defined clinically according to the World Health Organization (WHO) diagnostic criteria. Over 74.0% of pregnant women had caries, and 86.2% had gingivitis. There were significant differences between pregnant and non-pregnant women with regard to dental caries (p < 0.001) and gingivitis (p = 0.021). The pregnant women were 2.9 times more likely to suffer from dental caries (95% confidence intervals (CI), 1.6-5.4), and 2.2 times more (95% CI, 1.1-4.7) from gingivitis compared to non-pregnant women. Farmers (Odd ratio (OR), 7.0; 95% CI, 1.8-26.3), high school graduation (OR, 3.0; 95% CI, 1.2-7.3), and universal health insurance coverage (OR, 2.1; 95% CI, 1.0-4.3) were significant predictors for gingivitis. Only high school graduates were found to be significant predictors of dental caries with an OR of 2.8 (95% CI, 1.2-6.3). Poor oral hygiene (OR, 2.2; 95% CI, 0.8-6.5), lack of knowledge (OR, 2.0; 95% CI, 0.6-6.3), and poor oral hygiene habits (OR, 3.0; 95% CI, 1.1-8.6) were important risk factors for dental caries. Similarly, inadequate oral hygiene status (OR, 24.8; 95% CI, 5.5-112.2), and poor oral health habits (OR, 5.2; 95% CI, 1.1-25.2) were found to be significant risk factors for gingivitis among pregnant women indicating, that most women should be trained in proper oral hygiene practices. Community awareness programs should be conducted to increase women's awareness of such hygienic practices.

  6. Congenital toxoplasmosis infection in an infant born to an HIV-1-infected mother.

    PubMed

    Cruz, Maria Letícia Santos; Cardoso, Claudete Araújo; Saavedra, Mariza C; Santos, Eliane Dos; Melino, Tatiana

    2007-12-01

    We report the occurrence of congenital toxoplasmosis in an infant born to an HIV infected mother who had high anti-toxoplasma IgG and negative IgM at nine weeks of gestation. We briefly review available literature and discuss the possible mechanisms of transmission of congenital toxoplasmosis among HIV infected pregnant women.

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

    PubMed Central

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

    2015-01-01

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4+ T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. PMID:26184775

  8. Elevated expression of IFN-gamma in the HIV-1 infected brain.

    PubMed

    Shapshak, Paul; Duncan, Robert; Minagar, Alireza; Rodriguez de la Vega, Pura; Stewart, Renée V; Goodkin, Karl

    2004-05-01

    We determined the extent of expression of three cytokines (IFN-gamma, IL-4, and TNF-alpha ) in brain tissue infected with human immunodeficiency virus-1 (HIV-1). The selections were IFN-gamma as a Th1 cytokine, IL- 4 as a Th2 cytokine, and TNF-alpha as a pro-inflammatory cytokine (and because of its prior implication in brain tissue damage due to HIV-1 infection). Based on current models for pathogenesis of HIV-1-associated dementia (HAD), in the periphery, Th1 cytokines are considered to be salutary, whereas Th2 cytokines are regarded as deleterious. However, we hypothesized that in the CNS these roles are reversed. Post-mortem temporal lobe tissue specimens from 16 HIV-1-seropositive patients and 11 HIV-1-seronegative controls were stained for IFN-gamma, IL-4, and TNF-alpha utilizing immunohistochemistry and alkaline phosphatase. HIV-1 infection causes alterations of brain cytokine expression that include increased IFN-gamma expression for HIV-1-seropositive vs. HIV-1-seronegative individuals. There was increased expression of IFN-gamma for HIV-1-seropositive individuals with or without HAD, with or without the broader category of neuropsychiatric impairment (NPI), and with or without opportunistic infections (OIs) compared to HIV-1-seronegatives. A significant inverse correlation between IFN-gamma vs. IL-4 in HIV-1-seropositives with HAD and in seronegative individuals was observed. There was an inverse correlation in seropositives between IFN-gamma vs. TNF-alpha, a positive trend with HAD, significant without HAD, significant with NPI and significant without OIs. Between IL-4 vs. TNF-alpha there was a correlation (trend) in seropositives, a trend with NPI, significant without NPI, and a trend without OI. Due to HIV-1 infection of the brain and neurological disease there is a prominent increased expression of IFN-gamma, an inverse expression of IFN-gamma vs. TNF-alpha, and TNF-alpha vs. IL-4. The inverse correlation between increased IFN-gamma and decreased IL-4

  9. Antiretroviral resistance among HIV type 1-infected women first exposed to antiretrovirals during pregnancy: plasma versus PBMCs.

    PubMed

    Soto-Ramirez, Luis E; Rodriguez-Diaz, Roberto; Durán, Adriana S; Losso, Marcelo H; Salomón, Horacio; Gómez-Carrillo, Manuel; Pampuro, Sandra; Harris, D Robert; Duarte, Geraldo; De Souza, Ricardo S; Read, Jennifer S

    2008-06-01

    Resistance-associated mutations (RAMs) in plasma samples from HIV-1-infected women who received antiretroviral (ARV) prophylaxis during pregnancy was assessed and correlated with the detection of RAMs in peripheral blood mononuclear cells (PMBCs). The study population was composed of HIV-1-infected women enrolled in a prospective cohort study in Latin America and the Caribbean (NISDI Perinatal Study) as of March 1, 2005, who were diagnosed with HIV-1 infection during the current pregnancy, who received ARVs during pregnancy for prevention of mother-to-child transmission of HIV-1, and who were followed through at least the 6-12 week postpartum visit. Plasma samples collected at enrollment during pregnancy and at 6-12 weeks postpartum were assayed for RAMs. Plasma results were compared to previously described PBMC results from the same study population. Of 819 enrolled subjects, 197 met the eligibility criteria. Nucleic acid amplification was accomplished in 123 plasma samples at enrollment or 6-12 weeks postpartum, and RAMs were detected in 22 (17.9%; 95%CI: 11.7-25.9%). Previous analyses had demonstrated detection of RAMs in PBMCs in 19 (16.1%). There was high concordance between RAMs detected in plasma and PBMC samples, with only eight discordant pairs. The prevalence of RAMs among these pregnant, HIV-1-infected women is high (15%). Rates of detection of RAMs in plasma and PBMC samples were similar.

  10. Antiretroviral Resistance among HIV Type 1-Infected Women First Exposed to Antiretrovirals during Pregnancy: Plasma versus PBMCs

    PubMed Central

    Soto-Ramirez, Luis E.; Rodriguez-Diaz, Roberto; Durán, Adriana S.; Losso, Marcelo H.; Salomón, Horacio; Gómez-Carrillo, Manuel; Pampuro, Sandra; Harris, D. Robert; Duarte, Geraldo; De Souza, Ricardo S.

    2008-01-01

    Abstract Resistance-associated mutations (RAMs) in plasma samples from HIV-1-infected women who received antiretroviral (ARV) prophylaxis during pregnancy was assessed and correlated with the detection of RAMs in peripheral blood mononuclear cells (PMBCs). The study population was composed of HIV-1-infected women enrolled in a prospective cohort study in Latin America and the Caribbean (NISDI Perinatal Study) as of March 1, 2005, who were diagnosed with HIV-1 infection during the current pregnancy, who received ARVs during pregnancy for prevention of mother-to-child transmission of HIV-1, and who were followed through at least the 6–12 week postpartum visit. Plasma samples collected at enrollment during pregnancy and at 6–12 weeks postpartum were assayed for RAMs. Plasma results were compared to previously described PBMC results from the same study population. Of 819 enrolled subjects, 197 met the eligibility criteria. Nucleic acid amplification was accomplished in 123 plasma samples at enrollment or 6–12 weeks postpartum, and RAMs were detected in 22 (17.9%; 95%CI: 11.7–25.9%). Previous analyses had demonstrated detection of RAMs in PBMCs in 19 (16.1%). There was high concordance between RAMs detected in plasma and PBMC samples, with only eight discordant pairs. The prevalence of RAMs among these pregnant, HIV-1-infected women is high (>15%). Rates of detection of RAMs in plasma and PBMC samples were similar. PMID:18507526

  11. PLASMA ADIPONECTIN CONCENTRATIONS IN NON PREGNANT, NORMAL PREGNANCY AND OVERWEIGHT PREGNANT WOMEN

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Study design A cross-sectional study was designed to include normal pregnant women (normal weight and overweight; 11–42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant difference in the median adiponectin concentrations between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower adiponectin concentrations than normal weight women. Conclusion Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. Condensation Plasma adiponectin concentrations decrease with advancing gestational age only in nonobese women. PMID:17919116

  12. Relationship Between Quality of Life and Depression in Pregnant Women

    PubMed Central

    Abbaszadeh, Fatemeh; Kafaei Atrian, Mahboobe; Masoudi Alavi, Negin; Bagheri, Azam; Sadat, Zohreh; Karimian, Zahra

    2013-01-01

    Background: Quality of life differs for different people in different situations and is related to one's self-satisfaction with life. Quality of life is affected by health status. Objectives: The current study examined the relationship between quality of life and depression in pregnant women in Kashan city. Patients and Methods: A Case - control study was performed on 112 depressed pregnant women (Case Group) and 353 Non-depressed pregnant women (Control Group) who referred to the prenatal health care centers of Kashan University of Medical Sciences .They completed Short Form 36 Health Survey (SF-36) to assess the quality of life and the Beck Depression Inventory to assess the level of depressive symptoms. T-test, chi-square and Pearson correlation coefficient statistical tests were used for data analysis. Results: The findings showed that there was an inverse relationship between quality of life and depression in pregnancy (P = 0.0001). Average scores in all eight domains of quality of life were significantly lower in depressed pregnant women compared to non- depressed women. The strongest relationship was observed between depression and vitality (r =-0.52, P = 0.0001), mental health (r = -0.50, P = 0.001) and social functioning (r =-0.38, P = 0.001). Conclusion: Depressed pregnant women had a lower quality of life. The proper management of depression during pregnancy can improve the quality of life in women. It is recommended that antenatal services integrate screening for depression into routine antenatal care. PMID:25414858

  13. Dream-associated Behaviors Affecting Pregnant and Postpartum Women

    PubMed Central

    Nielsen, Tore; Paquette, Tyna

    2007-01-01

    Study objectives: Evaluate the prevalence and phenomenology of dream-associated behaviors affecting pregnant and postpartum mothers. Episodes consist of anxious dreams and nightmares about the new infant that are accompanied by complex behaviors (motor activity, speaking, expressing emotion). Design: Three-group design (postpartum, pregnant, null gravida), self-report, and repeated measures. Setting: Pregnancy and postpartum groups: completion of questionnaires in hospital room within 48 hours of giving birth and home telephone interviews; null gravida group: completion of questionnaires and interview in person or by telephone. Participants: Two hundred seventy-three women in 3 groups: postpartum: n = 202 (mean age = 29.7 ± 4.94 years; 95 primiparas, 107 multiparas); pregnant: n = 50 (mean age = 31.1 ± 5.44 years); null gravida: n = 21 (mean age = 28.5 ± 6.34 years). Interventions: Subjects completed questionnaires about pregnancy and birth factors, personality, and sleep and participated in interviews concerning the prevalence of recent infant dreams and nightmares, associated behaviors, anxiety, depression, and other psychopathologic factors. Measurements and Results: Most women in all groups recalled dreams (88%-91%). Postpartum and pregnant women recalled infant dreams and nightmares with equal prevalence, but more postpartum women reported they contained anxiety (75%) and the infant in peril (73%) than did pregnant women (59%, P < 0.05 and 42%, P < 0.0001). More postpartum (63%) than pregnant (40%) women reported dream-associated behaviors (P < 0.01), but neither group differed from null gravida women (56%). This was due to different distributions over groups of the behavior subtypes. Motor activity was present in twice as many postpartum (57%) as pregnant (24%) or null gravida (25%) women (all P < 0.0001). Expressing emotion was more prevalent among null gravida (56%) than postpartum women (27%) (P < 0.05) but was not different from pregnant women (37

  14. Prevalence of Musculoskeletal Dysfunctions among Indian Pregnant Women

    PubMed Central

    Maiya, Arun G.; Kumar, Pratap; Kamath, Asha

    2015-01-01

    Background and Objectives. Pregnancy triggers a wide range of changes in a woman's body leading to various musculoskeletal dysfunctions. Most commonly reported musculoskeletal discomforts by pregnant women are low back pain and symphysis pubis pain. The culture and the environmental factors may influence the discomforts experienced by a pregnant woman. There is a dearth of literature in India, regarding the common musculoskeletal dysfunctions experienced by a pregnant woman, and hence this study. Method. A questionnaire to identify the musculoskeletal dysfunction was developed; content was validated and was translated to local languages through parallel back translation. 261 primiparous pregnant women participated in the study and filled the questionnaire in their native language. Results. Among the musculoskeletal dysfunctions reported by the pregnant women, 64.6% reported calf muscle cramps, 37.1% reported foot pain, and 33.7% experienced low back pain in their third trimester. In the second trimester, common musculoskeletal dysfunctions experienced by the women were that of calf pain (47.8%), low back pain (42%), and pelvic girdle pain (37%). Conclusion. Musculoskeletal dysfunctions and general discomforts very commonly affect the activities of daily living of pregnant women. Understanding the common discomforts during various trimesters of pregnancy will help to develop a comprehensive program for prevention and cure. PMID:25642349

  15. Supporting pregnant Aboriginal and Torres Strait Islander women to quit smoking: views of antenatal care providers and pregnant indigenous women.

    PubMed

    Passey, Megan E; Sanson-Fisher, Rob W; Stirling, Janelle M

    2014-12-01

    To assess support for 12 potential smoking cessation strategies among pregnant Australian Indigenous women and their antenatal care providers. Cross-sectional surveys of staff and women in antenatal services providing care for Indigenous women in the Northern Territory and New South Wales, Australia. Respondents were asked to indicate the extent to which each of a list of possible strategies would be helpful in supporting pregnant Indigenous women to quit smoking. Current smokers (n = 121) were less positive about the potential effectiveness of most of the 12 strategies than the providers (n = 127). For example, family support was considered helpful by 64 % of smokers and 91 % of providers; between 56 and 62 % of smokers considered advice and support from midwives, doctors or Aboriginal Health Workers likely to be helpful, compared to 85-90 % of providers. Rewards for quitting were considered helpful by 63 % of smokers and 56 % of providers, with smokers rating them more highly and providers rating them lower, than most other strategies. Quitline was least popular for both. This study is the first to explore views of pregnant Australian Indigenous women and their antenatal care providers on strategies to support smoking cessation. It has identified strategies which are acceptable to both providers and Indigenous women, and therefore have potential for implementation in routine care. Further research to explore their feasibility in real world settings, uptake by pregnant women and actual impact on smoking outcomes is urgently needed given the high prevalence of smoking among pregnant Indigenous women.

  16. Transcriptional Regulation of CXCL5 in HIV-1-Infected Macrophages and Its Functional Consequences on CNS Pathology.

    PubMed

    Guha, Debjani; Klamar, Cynthia R; Reinhart, Todd; Ayyavoo, Velpandi

    2015-05-01

    Human immunodeficiency virus-1 (HIV-1)-infected monocytes/macrophages and microglia release increased levels of proinflammatory cytokines and chemokines, including ELR+ (containing glutamic acid-leucine-arginine motif) chemokines. To investigate the role of HIV-1 infection on chemokine regulation, monocyte-derived macrophages (MDMs) from normal donors were infected with HIV-1 and the expression of chemokines and their downstream biological functions were evaluated. Among the tested chemokines, CXCL5 was upregulated significantly both at the mRNA and protein level in the HIV-1-infected MDMs compared with mock-infected cultures. Upregulation of CXCL5 in the HIV-1-infected MDMs is, in part, regulated by increased interleukin-1β (IL-1β) production and phosphorylation of ERK1/2. Functional analyses indicate that HIV-1-induced overexpression of CXCL5 has enhanced the ability to attract neutrophils, as observed by chemotaxis assay. However, exposure of NT2, SH-SY5Y cells, and primary neurons to HIV-1-infected MDM supernatants resulted in cell death that was not rescued by anti-CXCL5 antibody suggesting that CXCL5 does not have direct effect on neuronal death. Together, these results suggest that the increased level of CXCL5 in tissue compartments, including the central nervous system of HIV-1-infected individuals might alter the inflammatory response through the infiltration of neutrophils into tissue compartment, thus causing secondary effects on resident cells.

  17. Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection.

    PubMed

    Cagigi, Alberto; Mowafi, Frida; Phuong Dang, Linh V; Tenner-Racz, Klara; Atlas, Ann; Grutzmeier, Sven; Racz, Paul; Chiodi, Francesca; Nilsson, Anna

    2008-12-01

    HIV-1 infection is associated with B-cell abnormalities, such as hypergammaglobulinemia, poor immunization responses, and loss of serologic memory. To determine whether altered expression of chemokine receptors and their ligands may play a role in B-cell dysfunctions during HIV-1 infection, the expression of CXC chemokine receptor 4 (CXCR4), CXCR5, and CC chemokine receptor 7 (CCR7) and their respective ligands on CD19(+) B cells were examined in HIV-1-infected patients and controls. We report a decreased CXCR5 expression on B cells from patients (P < .05), a phenomenon associated with a low CD4 T-cell count (< 350 cells/microL). Interestingly, an increased expression of CXC chemokine ligand 13 (CXCL13), the ligand for CXCR5, was found in peripheral B cells from HIV-1-infected patients. Moreover, on B-cell activation in vitro, CXCL13 was secreted in culture. CXCL13(+) B cells were also found in the lymph nodes of HIV-1-infected patients, but not in control tissue. B-cell migration toward CXCL13, CXCL12, and CC chemokine ligand 21 (CCL21), ligands for CXCR5, CXCR4, and CCR7 was also evaluated. In patients with a low CD4 T-cell count, migration toward all ligands was increased. Our findings indicate that altered expression of the chemokine receptor-ligand pair, CXCR5/CXCL13, may participate in the establishment of B-cell dysfunctions during HIV-1 infection.

  18. Health & Nutrition Information for Pregnant & Breastfeeding Women

    MedlinePlus

    ... Adults Moms/ Moms-to-Be Print Share Health & Nutrition Information When you are pregnant or breastfeeding, you ... Story Last Updated: Feb 9, 2017 RESOURCES FOR NUTRITION AND HEALTH MYPLATE What Is MyPlate? Fruits Vegetables ...

  19. Zika virus and pregnant women: A psychological approach.

    PubMed

    Filgueiras Meireles, Juliana Fernandes; Neves, Clara Mockdece; Morgado, Fabiane Frota da Rocha; Caputo Ferreira, Maria Elisa

    2017-03-27

    Zika virus presents risk of physical harm to pregnant women, but the fear of infection is also affecting women around the world. There is a gap in the research on Zika virus in the areas involving the impact on the psychosocial well-being of pregnant women. Therefore, this study is aimed at the investigation of the psychosocial adjustment of pregnant women to the risks of Zika virus infection during pregnancy. We investigated 14 pregnant women who were classified in three different groups: six in the first trimester, five in the second trimester and three in the third trimester, aged from 28 to 40 years (33.43 ± 3.76 years). Content analysis was used to interpret data. Our results show that the psychosocial adjustment of participants was significantly negative and included five aspects: (1) negative feelings, (2) changes in family planning, (3) adopting new customs (avoiding places of risk, use of specific clothes and use of repellent), (4) changed attitudes regarding body image and (5) feeling of external demand regarding prevention. The fear of Zika virus infection and all its associated risks have a negative biopsychosocial impact on the pregnant women in this study.

  20. Health Care Resources for Children and Pregnant Women.

    ERIC Educational Resources Information Center

    Perloff, Janet D.

    1992-01-01

    Reviews evidence about health care resources currently available to children and pregnant women in the United States. Evidence suggests that the maldistribution of resources remains a serious threat to health care access for women and children at greatest risk of adverse pregnancy outcomes and child morbidity and mortality. (SLD)

  1. School Exclusion and Educational Inclusion of Pregnant Young Women

    ERIC Educational Resources Information Center

    Rudoe, Naomi

    2014-01-01

    This article analyses the school exclusion and subsequent educational inclusion of pregnant young women participating in a course of antenatal and key skills education at an alternative educational setting. It examines the young women's transitions from "failure" in school to "success" in motherhood and re-engagement with…

  2. Immunization of pregnant women: Future of early infant protection

    PubMed Central

    Faucette, Azure N; Pawlitz, Michael D; Pei, Bo; Yao, Fayi; Chen, Kang

    2015-01-01

    Children in early infancy do not mount effective antibody responses to many vaccines against commons infectious pathogens, which results in a window of increased susceptibility or severity infections. In addition, vaccine-preventable infections are among the leading causes of morbidity in pregnant women. Immunization during pregnancy can generate maternal immune protection as well as elicit the production and transfer of antibodies cross the placenta and via breastfeeding to provide early infant protection. Several successful vaccines are now recommended to all pregnant women worldwide. However, significant gaps exist in our understanding of the efficacy and safety of other vaccines and in women with conditions associated with increased susceptible to high-risk pregnancies. Public acceptance of maternal immunization remained to be improved. Broader success of maternal immunization will rely on the integration of advances in basic science in vaccine design and evaluation and carefully planned clinical trials that are inclusive to pregnant women. PMID:26366844

  3. ANTIMICROBIAL SUSCEPTIBILITY OF Streptococcus agalactiae ISOLATED FROM PREGNANT WOMEN

    PubMed Central

    de MELO, Simone Cristina Castanho Sabaini; SANTOS, Nathally Claudiane de Souza; de OLIVEIRA, Marcia; SCODRO, Regiane Bertin de Lima; CARDOSO, Rosilene Fressatti; PÁDUA, Rúbia Andreia Falleiros; SILVA, Flavia Teixeira Ribeiro; COSTA, Aline Balandis; CARVALHO, Maria Dalva de Barros; PELLOSO, Sandra Marisa

    2016-01-01

    SUMMARY Introduction: Group B streptococcus (GBS) or Streptococcus agalactiae can colonize the gastrointestinal and genitourinary tracts and has been considered one of the most important risk factors for the development of neonatal disease. The present study evaluated the antimicrobial susceptibility of GBS isolates from pregnant women who were attended at a public health service in Northern Paraná, Brazil. Methods: A descriptive analytical cross-sectional study was performed with 544 pregnant women, at ≥ 35 weeks of gestation. One hundred and thirty-six GBS isolates from pregnant women were tested for antimicrobial susceptibility. Results: All of the GBS isolates showed susceptibility to the drug that is most frequently used for intrapartum prophylaxis: penicillin. Resistance to clindamycin and erythromycin was detected, thus decreasing the options of prophylaxis in women who are allergic to penicillin. Conclusions: Additional studies should be conducted to increase the knowledge of GBS sensitivity profile to antimicrobials in other health centers. PMID:27828624

  4. Perceived Barriers to Physical Activity among Pregnant Women

    PubMed Central

    Evenson, Kelly R.; Moos, Merry-K; Carrier, Kathryn; Siega-Riz, Anna Maria

    2008-01-01

    Objective Physical activity generally declines during pregnancy, but barriers to activity during this time period are not well understood. The objective was to examine barriers to physical activity in a large cohort of pregnant women and to explore these barriers in more depth with qualitative data derived from a separate focus group study using a socioecologic framework. Method A total of 1535 pregnant women (27–30 weeks’ gestation) enrolled in the Pregnancy, Infection, and Nutrition Study were asked an open-ended question about their primary barrier to physical activity; responses were coded into categories according to the socioecologic framework. To further elucidate, 13 focus groups of a total of 58 pregnant women (20–37 weeks’ gestation) were conducted among Hispanic, African American, and White participants. Results Among the 1535 pregnant women participating in the survey, 85% reported an intrapersonal barrier to physical activity, of which almost two-thirds were health related. Only 2% of the women reported their main barrier to physical activity as interpersonal and 3% reported a neighborhood or environmental barrier. These results were supported by the focus group data, overall and by race/ethnicity and body mass index. Although women discussed barriers to physical activity at a variety of levels, the intrapersonal level was the most frequently cited and discussed factor in both studies. Conclusions Since pregnancy may trigger the development of obesity and since physical activity is recommended for healthy pregnant women, it is imperative to promote physical activity in a more relevant way. These quantitative and qualitative studies revealed many barriers to physical activity among pregnant women and some suggestions for interventions. PMID:18478322

  5. Nutritional status and weight gain in pregnant women.

    PubMed

    Sato, Ana Paula Sayuri; Fujimori, Elizabeth

    2012-01-01

    This study described the nutritional status of 228 pregnant women and the influence of this on birth weight. This is a retrospective study, developed in a health center in the municipality of São Paulo, with data obtained from medical records. Linear regression analysis was carried out. An association was verified between the initial and final nutritional status (p<0.001). The mean of total weight gain in the pregnant women who began the pregnancy underweight was higher compared those who started overweight/obese (p=0.005). Weight gain was insufficient for 43.4% of the pregnant women with adequate initial weight and for 36.4% of all the pregnant women studied. However, 37.1% of those who began the pregnancy overweight/obese finished with excessive weight gain, a condition that ultimately affected almost a quarter of the pregnant women. Anemia and low birth weight were uncommon, however, in the linear regression analysis, birth weight was associated with weight gain (p<0.05). The study highlights the importance of nutritional care before and during pregnancy to promote maternal-infant health.

  6. Intestinal Parasitic Infections among Pregnant Women in Venezuela

    PubMed Central

    Rodríguez-Morales, Alfonso J.; Barbella, Rosa A.; Case, Cynthia; Arria, Melissa; Ravelo, Marisela; Perez, Henry; Urdaneta, Oscar; Gervasio, Gloria; Rubio, Nestor; Maldonado, Andrea; Aguilera, Ymora; Viloria, Anna; Blanco, Juan J.; Colina, Magdary; Hernández, Elizabeth; Araujo, Elianet; Cabaniel, Gilberto; Benitez, Jesús; Rifakis, Pedro

    2006-01-01

    Introduction. Intestinal parasitic infections, especially due to helminths, increase anemia in pregnant women. The results of this are low pregnancy weight gain and IUGR, followed by LBW, with its associated greater risks of infection and higher perinatal mortality rates. For these reasons, in the setting of no large previous studies in Venezuela about this problem, a national multicentric study was conducted. Methods. Pregnant women from nine states were studied, a prenatal evaluation with a coproparasitological study. Univariated and multivariated analyses were made to determine risk factors for intestinal parasitosis and related anemia. Results. During 19 months, 1038 pregnant women were included and evaluated. Intestinal parasitosis was evidenced in 73.9%: A lumbricoides 57.0%, T trichiura 36.0%, G lamblia 14.1%, E hystolitica 12.0%, N americanus 8.1%, E vermicularis 6.3%, S stercoralis 3.3%. Relative risk for anemia in those women with intestinal parasitosis was 2.56 (P < .01). Discussion. Intestinal parasitoses could be associated with conditions for development of anemia at pregnancy. These features reflect the need of routine coproparasitological study among pregnant women in rural and endemic zones for intestinal parasites. Further therapeutic and prophylactic protocols are needed. Additional research on pregnant intestinal parasitic infection impact on newborn health is also considered. PMID:17093349

  7. Special health care needs of homeless pregnant women.

    PubMed

    Killion, C M

    1995-12-01

    As women and families join the ranks of the homeless in increasing numbers, many women find themselves confronting both pregnancy and homelessness. When pregnancy accompanies the precarious state of homelessness, the need for adequate shelter is not being met during one of the most critical periods of a woman's life. This article focuses on the unique health needs of homeless pregnant women. Detailed accounts of the daily life experiences of African American, Anglo, and Latina homeless pregnant women were derived from an ethnographic study conducted in a large metropolitan area in southern California. Their pregnancies were difficult because normal physiological changes of pregnancy often became pathological, signs of potential complications went unnoticed or unattended, and minor discomforts of pregnancy were exacerbated by the women's environment. Nursing therapeutics that support health maintenance and coping strategies of the women while on the streets or in shelters were explicated.

  8. Pregnant Women in Louisiana Are Not Meeting Dietary Seafood Recommendations

    PubMed Central

    Lammi-Keefe, C. J.

    2016-01-01

    Background. The 2015–2020 Dietary Guidelines for Americans recommend that pregnant women and women of childbearing ages consume 8–12 oz. of seafood per week. Fish are the major dietary source of omega-3 long chain polyunsaturated fatty acids, which have benefits for the mother and fetus. Methods. In this observational study, we investigated dietary habits of pregnant women in Baton Rouge, Louisiana, USA, to determine if they achieve recommended seafood intake. A print survey, which included commonly consumed foods from protein sources (beef, chicken, pork, and fish), was completed by pregnant women at a single-day hospital convention for expecting families in October 2015. Women (n = 221) chose from six predefined responses to answer how frequently they were consuming each food. Results. Chicken was consumed most frequently (75% of women), followed by beef (71%), pork (65%), and fish (22%), respectively. Consumption frequency for the most consumed fish (catfish, once per month) was similar to or lower than that of the least consumed beef, chicken, and pork foods. Consumption frequency for the most consumed chicken and beef foods was at least once per week. Conclusion. Our data indicate that pregnant women in Louisiana often consume protein sources other than fish and likely fail to meet dietary seafood recommendations. PMID:27504202

  9. PPARgamma Pro12Ala polymorphism in HIV-1-infected patients with HAART-related lipodystrophy.

    PubMed

    Saumoy, Maria; Veloso, Sergi; Alonso-Villaverde, Carlos; Domingo, Pere; Chacón, Matilde R; Miranda, Merce; Aragonès, Gerard; Gutiérrez, Maria Mar; Viladés, Consuelo; Peraire, Joaquim; Sirvent, Joan-Josep; López-Dupla, Miguel; Aguilar, Carmen; Richart, Cristóbal; Vidal, Francesc

    2009-09-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in obesity and in some components of the metabolic syndrome in unselected population. To determine whether PPARgamma genetic variants are associated with the risk of developing lipodystrophy and its associated metabolic disturbances in HIV-1-infected patients treated with HAART and to assess PPARgamma mRNA expression in subcutaneous adipose tissue (SAT). The study group comprised 278 patients infected with HIV-1 and treated with antiretroviral drugs (139 with lipodystrophy and 139 without) and 105 uninfected controls (UC). The PPARgamma Pro12Ala (C%>G) single nucleotide polymorphism (SNP) was assessed using PCR-RFLPs on white cell DNA. PPARgamma mRNA expression in SAT was assessed in 38 patients (25 with lipodystrophy and 13 without) and in 21 UC by real-time PCR. Statistical analysis was based on Student's T tests, Chi(2) tests, Spearman's correlations tests and logistic regression tests. PPARgamma Pro12Ala genotype distribution and allele frequencies were non-significantly different between both HIV-1-infected categories, lipodystrophy vs non-lipodystrophy (p=0.9 and p=0.87, respectively). Lipodystrophic patients harbouring the rare X/Ala genotype (Ala/Ala plus Pro/Ala) had significantly greater plasma total and LDL cholesterol levels compared with carriers of the common Pro/Pro genotype (p=0.029 and p=0.016, respectively) at univariate analyses. At multivariate analyses these associations were no longer significant. There was a near-significant decreased SAT PPARgamma mRNA expression in patients with lipodystrophy compared to UC (p=0.054). PPARgamma Pro12Ala SNP has no effect on the risk of developing lipodystrophy in HIV-1-infected patients treated with HAART. PPARgamma mRNA SAT expression appears decreased in lipodystrophy.

  10. Risk factors for neonatal conjunctivitis in babies of HIV-1 infected mothers

    PubMed Central

    Gichuhi, Stephen; Bosire, Rose; Mbori-Ngacha, Dorothy; Gichuhi, Christine; Wamalwa, Dalton; Maleche-Obimbo, Elizabeth; Farquhar, Carey; Wariua, Grace; Otieno, Phelgona; John-Stewart, Grace C.

    2011-01-01

    Purpose To determine the prevalence and correlates of neonatal conjunctivitis in infants born to human immunodeficiency virus type 1 (HIV-1) infected mothers. Methods This was a nested case-control study within a perinatal HIV-1 cohort. HIV-1 seropositive mothers were enrolled during pregnancy and mother-infant pairs followed after delivery with assessment for neonatal conjunctivitis at 48 hours and up to 4 weeks after birth. Genital infections (chlamydia, gonorrhea, syphilis, trichomonas, bacterial vaginosis, and candida) were screened for at 32 weeks gestation. Mothers received treatment for genital infections diagnosed during pregnancy and short-course zidovudine. Newborns did not receive ocular prophylaxis at hospital deliveries. Multivariate logistic regression models were used to determine cofactors for neonatal conjunctivitis overall and stratified for infant HIV-1 status. Results Four hundred and fifty-two infants were assessed and 101 (22.3%) had neonatal conjunctivitis during the first month postpartum. In multivariate analyses using odds ratios (OR) and confidence intervals (CI), neonatal conjunctivitis was associated with neonatal sepsis (adjusted OR 21.95, 95% CI 1.76, 274.61), birth before arrival to hospital (adjusted OR 13.91, 95% CI 1.39, 138.78) and birth weight (median 3.4 versus 3.3 kilograms, p=0.016, OR 1.79, 95% CI 1.01, 3.15). Infant HIV-1 infection was not associated with conjunctivitis. Conclusions Despite detection and treatment of genital infections during pregnancy, neonatal conjunctivitis was frequently diagnosed in infants born to HIV-1 infected mothers suggesting a need for increased vigilance and prophylaxis for conjunctivitis in these infants. Neonatal sepsis, birth before arrival to hospital, and higher birthweight are factors that may predict higher risk of neonatal conjunctivitis in this population. PMID:19995198

  11. Reliability of laboratory markers of HIV-1 infection in Argentinian infants at risk of perinatal infection.

    PubMed

    Mangano, A; Pittis, G; Galindez, C; Bologna, R; Sen, L

    1998-09-01

    Early and accurate diagnosis of HIV-1 infection in infants born to HIV-1-seropositive mothers is of great importance. Polymerase chain reaction (PCR), HIV culture, and p24 antigen detection assays were evaluated for their ability to detect the presence of HIV in 195 infants at risk of perinatal infection. Using the Centers for Disease Control and Prevention guidelines for assessing HIV infection status in children younger than 18 months, 70 infants (36%) were diagnosed as HIV-1 infected and 125 (64%) lacked virologic and clinical evidence of infection. PCR and HIV culture were the most sensitive laboratory markers, detecting 100% and 98% of positive samples, respectively, regardless of age at testing. HIV-1 p24 antigen assay was detected in 26 of 38 positive samples but not in negative samples. PCR was performed with three different sets of primers (SK38/SK39-SK19-gag, SK68/SK69-SK70-env, and SK150/SK431-SK102-gag). The sensitivity/specificity of the individual assays were for SK19, 96.1%/94.25%; SK70, 89.6%/100%; and SK102, 100%/100%. A sample was considered HIV-1 positive when two positive PCR results were obtained with two different pairs of primers, and negative if the sample was negative when three sets of primers were used. False-positive results were occasionally obtained with probe SK19 in six seroreverter infants before serologic status was known. This suggested that the infection was caused by nonreplicative strains or were false-positive results probably by nonspecific amplification due to cross-reaction with other microorganisms; contamination was discarded because there was no specific amplification with the other two primers. All the HIV-1-infected infants were correctly identified with PCR; all except one could be identified with coculture and only 68.4% were confirmed with p24 antigen assay. No seroreverter infant was misdiagnosed using the criteria selected.

  12. 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

  13. Exosomes Derived from HIV-1-infected Cells Contain Trans-activation Response Element RNA*

    PubMed Central

    Narayanan, Aarthi; Iordanskiy, Sergey; Das, Ravi; Van Duyne, Rachel; Santos, Steven; Jaworski, Elizabeth; Guendel, Irene; Sampey, Gavin; Dalby, Elizabeth; Iglesias-Ussel, Maria; Popratiloff, Anastas; Hakami, Ramin; Kehn-Hall, Kylene; Young, Mary; Subra, Caroline; Gilbert, Caroline; Bailey, Charles; Romerio, Fabio; Kashanchi, Fatah

    2013-01-01

    Exosomes are nano-sized vesicles produced by healthy and virus-infected cells. Exosomes derived from infected cells have been shown to contain viral microRNAs (miRNAs). HIV-1 encodes its own miRNAs that regulate viral and host gene expression. The most abundant HIV-1-derived miRNA, first reported by us and later by others using deep sequencing, is the trans-activation response element (TAR) miRNA. In this study, we demonstrate the presence of TAR RNA in exosomes from cell culture supernatants of HIV-1-infected cells and patient sera. TAR miRNA was not in Ago2 complexes outside the exosomes but enclosed within the exosomes. We detected the host miRNA machinery proteins Dicer and Drosha in exosomes from infected cells. We report that transport of TAR RNA from the nucleus into exosomes is a CRM1 (chromosome region maintenance 1)-dependent active process. Prior exposure of naive cells to exosomes from infected cells increased susceptibility of the recipient cells to HIV-1 infection. Exosomal TAR RNA down-regulated apoptosis by lowering Bim and Cdk9 proteins in recipient cells. We found 104–106 copies/ml TAR RNA in exosomes derived from infected culture supernatants and 103 copies/ml TAR RNA in the serum exosomes of highly active antiretroviral therapy-treated patients or long term nonprogressors. Taken together, our experiments demonstrated that HIV-1-infected cells produced exosomes that are uniquely characterized by their proteomic and RNA profiles that may contribute to disease pathology in AIDS. PMID:23661700

  14. LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection

    PubMed Central

    Qi, Ying; Apps, Richard; Gao, Xiaojiang; Burke, Patrick S.; Taylor, Craig J.; Rogich, Jerome; Wolinsky, Steven; Bream, Jay H.; Duggal, Priya; Hussain, Shehnaz; Martinson, Jeremy; Weintrob, Amy; Kirk, Gregory D.; Fellay, Jacques; Buchbinder, Susan P.; Goedert, James J.; Deeks, Steven G.; Pereyra, Florencia; Trowsdale, John; Lichterfeld, Mathias; Telenti, Amalio; Walker, Bruce D.; Allen, Rachel L.; Carrington, Mary; Yu, Xu G.

    2014-01-01

    Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10−2). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10−11–10−9) and African (p = 10−5–10−3) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement. PMID:24603468

  15. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA.

    PubMed

    Narayanan, Aarthi; Iordanskiy, Sergey; Das, Ravi; Van Duyne, Rachel; Santos, Steven; Jaworski, Elizabeth; Guendel, Irene; Sampey, Gavin; Dalby, Elizabeth; Iglesias-Ussel, Maria; Popratiloff, Anastas; Hakami, Ramin; Kehn-Hall, Kylene; Young, Mary; Subra, Caroline; Gilbert, Caroline; Bailey, Charles; Romerio, Fabio; Kashanchi, Fatah

    2013-07-05

    Exosomes are nano-sized vesicles produced by healthy and virus-infected cells. Exosomes derived from infected cells have been shown to contain viral microRNAs (miRNAs). HIV-1 encodes its own miRNAs that regulate viral and host gene expression. The most abundant HIV-1-derived miRNA, first reported by us and later by others using deep sequencing, is the trans-activation response element (TAR) miRNA. In this study, we demonstrate the presence of TAR RNA in exosomes from cell culture supernatants of HIV-1-infected cells and patient sera. TAR miRNA was not in Ago2 complexes outside the exosomes but enclosed within the exosomes. We detected the host miRNA machinery proteins Dicer and Drosha in exosomes from infected cells. We report that transport of TAR RNA from the nucleus into exosomes is a CRM1 (chromosome region maintenance 1)-dependent active process. Prior exposure of naive cells to exosomes from infected cells increased susceptibility of the recipient cells to HIV-1 infection. Exosomal TAR RNA down-regulated apoptosis by lowering Bim and Cdk9 proteins in recipient cells. We found 10(4)-10(6) copies/ml TAR RNA in exosomes derived from infected culture supernatants and 10(3) copies/ml TAR RNA in the serum exosomes of highly active antiretroviral therapy-treated patients or long term nonprogressors. Taken together, our experiments demonstrated that HIV-1-infected cells produced exosomes that are uniquely characterized by their proteomic and RNA profiles that may contribute to disease pathology in AIDS.

  16. Heart failure in pregnant women: is it peripartum cardiomyopathy?

    PubMed

    Dennis, Alicia Therese

    2015-03-01

    Peripartum cardiomyopathy is a rare but important cause of maternal morbidity and mortality. Women with peripartum cardiomyopathy often present with symptoms and signs of heart failure. The diagnosis of peripartum cardiomyopathy is made after all other causes of heart failure are excluded. Emphasis is on the immediate recognition of an unwell pregnant or recently pregnant woman, early diagnosis with the use of echocardiography, and the correct treatment of heart failure.

  17. Efficient human immunodeficiency virus (HIV-1) infection of cells lacking PDZD8.

    PubMed

    Zhang, Shijian; Sodroski, Joseph

    2015-07-01

    PDZD8 can bind the capsid proteins of different retroviruses, and transient knockdown of PDZD8 results in a decrease in the efficiency of an early, post-entry event in the retrovirus life cycle. Here we used the CRISPR-CAS9 system to create cell lines in which PDZD8 expression is stably eliminated. The PDZD8-knockout cell lines were infected by human immunodeficiency virus (HIV-1) and murine leukemia virus as efficiently as the parental PDZD8-expressing cells. These results indicate that PDZD8 is not absolutely necessary for HIV-1 infection and diminishes its attractiveness as a potential target for intervention.

  18. Asymptotic behaviors of a cell-to-cell HIV-1 infection model perturbed by white noise

    NASA Astrophysics Data System (ADS)

    Liu, Qun

    2017-02-01

    In this paper, we analyze a mathematical model of cell-to-cell HIV-1 infection to CD4+ T cells perturbed by stochastic perturbations. First of all, we investigate that there exists a unique global positive solution of the system for any positive initial value. Then by using Lyapunov analysis methods, we study the asymptotic property of this solution. Moreover, we discuss whether there is a stationary distribution for this system and if it owns the ergodic property. Numerical simulations are presented to illustrate the theoretical results.

  19. CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection

    PubMed Central

    Cagigi, Alberto; Du, Likun; Dang, Linh Vu Phuong; Grutzmeier, Sven; Atlas, Ann; Chiodi, Francesca

    2009-01-01

    Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27−IgA+ and CD27−IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27− cells from patients. Taken together, these results show that during HIV-1 infection, CD27− B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection. PMID:19412542

  20. Association of DC-SIGNR Expression in Peripheral Blood Mononuclear Cells with DC-SIGNR Genotypes in HIV-1 Infection.

    PubMed

    Chaudhary, Omkar; Kumar, Sanjeev; Bala, Manju; Singh, Jasbir; Hazarika, Anjali; Luthra, Kalpana

    2015-10-01

    Dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin related molecule (DC-SIGNR) is a C-type lectin, calcium-dependent carbohydrate-binding protein, which can act as a cell-adhesion and pathogen recognition receptor. DC-SIGNR is known to be highly expressed on liver sinusoidal cells and in the lymph nodes. However, its expression in peripheral blood mononuclear cells (PBMCs) in HIV-1 infection has not been addressed. Therefore, this study determined the expression of DC-SIGNR in PBMCs of HIV-1-infected patients and healthy seronegative individuals by real-time polymerase chain reaction and assessed its correlation with CD4+ T cell counts and DC-SIGNR genotypes. A significantly higher expression of DC-SIGNR was observed in the PBMCs of HIV-1-infected patients compared with healthy seronegative individuals. Further, there was a negative correlation between DC-SIGNR expression and CD4+ T cell counts and positive with viral load, with higher DC-SIGNR expression in the PBMCs of HIV-1-infected patients with a CD4+ T cell count <200 cells/μL than those with >200 cells/μL. This is the first study to report the expression of DC-SIGNR in PBMCs of HIV-1-infected patients. A salient finding of this study is that the DC-SIGNR expression was higher in HIV-1-infected patients, and its positive correlation with viral load and negative with CD4+ T cells counts suggesting a potential role of DC-SIGNR in HIV-1 infection.

  1. Should all pregnant women be screened for syphilis?

    PubMed

    Buvé, Anne

    2007-09-01

    In industrialized countries, the incidence of syphilis has decreased dramatically since the discovery of penicillin in the 1940s. However, syphilis and congenital syphilis are far from eradicated, especially in low- and middle-income countries. Syphilis in pregnant women is a cause of adverse pregnancy outcomes that can be prevented by screening for syphilis and early treatment in pregnancy. Several studies have found screening of pregnant women for syphilis to be a highly cost-effective intervention, even if the prevalence of syphilis is low. Obstacles to universal screening of pregnant women include low awareness of syphilis and low quality of antenatal care and healthcare in general in many low- and middle-income countries. For these settings, we need simpler and more reliable serological tests for syphilis, but we also need to strengthen health services in general to ensure sustainable antenatal care services to ensure sustainability of syphilis screening programmes.

  2. Bile Acid Determination after Standardized Glucose Load in Pregnant Women

    PubMed Central

    Adams, April; Jacobs, Katherine; Vogel, Rachel Isaksson; Lupo, Virginia

    2015-01-01

    Objective Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disorder, usually manifesting in the third trimester and associated with increased perinatal morbidity and mortality. The hallmark laboratory abnormality in ICP is elevated fasting serum bile acids; however, there are limited data on whether a nonfasting state affects a pregnant woman's total bile acids. This study assesses fasting and nonfasting bile acid levels in 10 healthy pregnant women after a standardized glucose load to provide insight into the effects of a glucose load on bile acid profiles. Study Design Pilot prospective cohort analysis of serum bile acids in pregnant women. A total of 10 healthy pregnant women from 28 to 32 weeks' gestation were recruited for the study before undergoing a glucose tolerance test. Total serum bile acids were collected for each subject in the overnight fasting state, and 1 and 3 hours after the 100-g glucose load. Results There was a statistically significant difference between fasting versus 3-hour values. There was no statistically significant difference between fasting versus 1-hour and 1-hour versus 3-hour values. Conclusion There is a difference between fasting and nonfasting total serum bile acids after a 100-g glucose load in healthy pregnant women. PMID:26495178

  3. [Antiparasitic treatments in pregnant women and in children in 2003].

    PubMed

    Richard-Lenoble, D; Chandenier, J; Duong, T H

    2003-01-01

    Like antibacterial agents, antiparasite drugs for pregnant women and children must be chosen in function of the stage of pregnancy, age of the child, and expected benefit-risk ratio. While no agent is totally safe, there are few absolute contraindications. Most zones of serious endemic parasite disease are located in developing countries where parasite, bacterial, or viral conditions combined with poor nutrition treatment make it necessary to treat disease in a complex pathogenic environment that weakens pregnant women and children with multiple parasite infections. In both temperate and tropical zones, there have been few real therapeutic advances involving release of new products on the market or development of new indications for existing products. Constant appearance and extension of hematozoa resistance to conventional and even more recent antimalarial agents have prompted research to find new active drugs and long-lasting treatment combinations. Real therapeutic breakthroughs have resulted from the need to develop safe drugs without substantial side-effects for single-dose use in control programs against endemic parasite diseases in mass populations including pregnant women and young children in tropical zones. There are several notable examples in the field of major verminous diseases. Ivermectin is a versatile drug that can be used against filariasis as well as for management of intestinal worms or ectoparasitosis in temperate and tropical countries. Praziquantel is an important advance in platyhelminthiasis, especially bilharziais. Triclabendazole, the latest addition to the benzimidazole family, has shown promise as a substitute for bithionol, that is difficult to procure and not recommended in pregnant women, for treatment distomiasis occurring in pregnant women and children. Other examples include albendazole against giardiasis, nitazoxamide against cryptosporidiosis, artemisinine against bilharziasis, and paramomycine, not recommended in pregnant women

  4. [Determinants of urban obstetrical service utilization in rural pregnant women].

    PubMed

    Park, J S

    1991-12-01

    This study examines the decisions of rural pregnant women who sought obstetric care elsewhere, especially in an urban area. The principal data source was the "Patients' Survey of 1988", a nationwide data collection. Among 4091 rural pregnant women, 3090 women left their home counties for obstetric care; 1946 women went to small or medium-sized cities, 645 to large cities. Multivariate techniques were used to examine the factors related to selecting urban obstetric care. The analysis shows that younger, abnormally delivered women were more likely to seek urban obstetrical facilities. In addition, medical insurance, the number of registered cars/1000, the number of general hospitals in the county, and the distance to the nearest large city were positively related to the decision to go to any city. However, distance to the nearest small or medium-sized city had a negatively significant effect on urban obstetrical service utilization. (author's modified)

  5. Need of tetraiodothyronine supplemental therapy in pregnant women

    NASA Astrophysics Data System (ADS)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid hormones are essential for fetal development. Normal thyroid function in pregnant women adjusts by itself in cases of pregnancy, phenomenon that is deficient in cases of previous maternal thyroid disease. The study group was represented by 120 females, with reproductive age, with known thyroid disease, that had a up to delivery pregnancy. Thyroid ultrasound parameters and functional parameters were follow-up during the 9-month of gestation. The study proposes a mathematical model of predicting the need and the amount of tetraiodothyronine treatment in pregnant women with prevalent thyroid disease.

  6. [Seroprevalence of toxoplasmosis in pregnant women in Rabat, Morocco].

    PubMed

    El Mansouri, B; Rhajaoui, M; Sebti, F; Amarir, F; Laboudi, M; Bchitou, R; Hamad, M; Lyagoubi, M

    2007-10-01

    In Morocco, the seroprevalence of toxoplasmosis in pregnant women living in Rabat, was estimated by analyzing antibodies (IgG, IgM) levels using an ELISA test. The analysis of 2456 serums at the Institut National d'Hygiène showed that the seroprevalence of toxoplasmosis is about 50.6%. According to the questionnaire, the lack of knowledge about this disease and soil contact could be the main causes of toxoplasmosis infection. The use of IgG avidity test has excluded a recent infection in 93.5% of pregnant women with IgM positive sera.

  7. [International recommandations on physical exercise for pregnant women].

    PubMed

    Filhol, G; Bernard, P; Quantin, X; Espian-Marcais, C; Ninot, G

    2014-12-01

    Benefits of physical exercise on the physical and psychological health lead to specifics guidelines during pregnancy. For pregnant women, to take part in aerobics exercise (walking, biking) (i.e. 30 minutes, three times per week at 60-90% of the maximal heart rate) and strength training (i.e. one to two times per week) is recommended. Physical exercise programs during pregnancy have shown benefits for preventing and treating complications pregnancy (e.g. gestational diabetes mellitus, overweight). Benefits of exercise and risks associated with sedentary should be widely diffused among pregnant women and prenatal caregivers.

  8. [Asymptomatic bacteriuria in pregnant women with insulin-dependent diabetes].

    PubMed

    Maciołek-Blewniewska, G; Wilczyński, J; Woch, G

    1994-04-01

    Results of studies of the urinary tract of 43 pregnant women with insulin-dependent diabetes have been presented. No clinical symptoms of infection of this system were observed in particular trimesters of pregnancy. It was found that, despite the lack of symptoms of the urinary tract infection, the infection as such did occur-most frequently in the 2nd trimester. The most common bacteria in pregnant women with insulin-dependent diabetes (lasting over 10 years) were Staphylococcus epidermidis and Staphylococcus saprophiticus.

  9. [Impact of nutritional deficiencies on anemia in pregnant women].

    PubMed

    Leke, L; Kremp, D

    1989-12-01

    Dietary deficiency in iron and to a lesser extent folic acid is the principle cause of anemia in the world. Reproductive aged women and growing children are the principle groups at risk of anemia. About half of nonpregnant reproductive aged women in tropical countries have hemoglobin levels lower than 12 g/100 ml, the level used by the World Health Organization to define anemia. Nutritional anemia is even more widespread among pregnant and lactating women because of the increased needs for iron during those periods. Pregnant women need almost 500 mg of iron for their increased red blood cell mass, 220 mg for routine iron loss through the urine, bile, sweat, and other routes; 290 mg for the fetus, and almost 25 mg for the placenta. In all, the pregnant women theoretically requires over 1000 mg of iron through diet or bodily reserves. Healthy, well-nourished women have total iron reserves of 2500 mg, but according to published data almost 2/3 of pregnant women even in favorable circumstances end their pregnancies with no remaining iron reserves. In tropical regions the lack of iron reserves is aggravated by parasites and infections, closely spaced pregnancies that do not allow restoration of reserves, and poor dietary availability of iron. Anemia during pregnancy is associated with elevated risks of maternal morbidity and mortality. Fatigue, dyspnea, palpitations and tachycardia, vertigo, loss of appetite and cravings for soil or other inappropriate substances are frequently observed in anemic women. The risks of prematurity and low weight are increased for infants of anemic women. Fetal malformation may be associated with folic acid deficiency. Nutrition education is needed for pregnant women. Local foods may be enriched with iron, and pregnant women may be given iron and vitamin B12 supplements directly. Iron supplements may rapidly increase iron reserves, but they are poorly tolerated by many women. The supplements should be avoided if possible early in the

  10. Lactoferrin efficacy versus ferrous sulfate in curing iron disorders in pregnant and non-pregnant women.

    PubMed

    Paesano, R; Berlutti, F; Pietropaoli, M; Goolsbee, W; Pacifici, E; Valenti, P

    2010-01-01

    Iron homeostasis in pregnancy compensates for increased iron requirements and in women of child-bearing age for iron loss in menses. Oral administration of ferrous sulfate, prescribed to cure iron deficiency (ID) and ID anemia (IDA), often fails to increase hematological parameters and causes adverse effects. Recently, we demonstrated safety and efficacy of bovine lactoferrin (bLf) in pregnant women suffering from ID/IDA. Two clinical trials were conducted on pregnant and non-pregnant women of child-bearing age suffering from ID/IDA. In both trials, women received oral administration of bLf 100 mg/twice/day (Arm A), or ferrous sulfate 520 mg/day (Arm B). Hematological parameters, serum IL-6 and prohepcidin were assayed before and after therapy. Unlike ferrous sulfate, bLf increased hematological parameters (P less than 0.0001). In pregnant women, bLf decreased serum IL-6 (P less than 0.0001), and increased prohepcidin (P=0.0007). In non-pregnant women bLf did not change the low IL-6 levels while it increased prohepcidin (P less than 0.0001). Ferrous sulfate increased IL-6 (P less than 0.0001) and decreased prohepcidin (P=0.093). bLf established iron homeostasis by modulating serum IL-6 and prohepcidin synthesis, whereas ferrous sulfate increased IL-6 and failed to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA.

  11. Evolutionary analysis identifies an MX2 haplotype associated with natural resistance to HIV-1 infection.

    PubMed

    Sironi, Manuela; Biasin, Mara; Cagliani, Rachele; Gnudi, Federica; Saulle, Irma; Ibba, Salomè; Filippi, Giulia; Yahyaei, Sarah; Tresoldi, Claudia; Riva, Stefania; Trabattoni, Daria; De Gioia, Luca; Lo Caputo, Sergio; Mazzotta, Francesco; Forni, Diego; Pontremoli, Chiara; Pineda, Juan Antonio; Pozzoli, Uberto; Rivero-Juarez, Antonio; Caruz, Antonio; Clerici, Mario

    2014-09-01

    The protein product of the myxovirus resistance 2 (MX2) gene restricts HIV-1 and simian retroviruses. We demonstrate that MX2 evolved adaptively in mammals with distinct sites representing selection targets in distinct branches; selection mainly involved residues in loop 4, previously shown to carry antiviral determinants. Modeling data indicated that positively selected sites form a continuous surface on loop 4, which folds into two antiparallel α-helices protruding from the stalk domain. A population genetics-phylogenetics approach indicated that the coding region of MX2 mainly evolved under negative selection in the human lineage. Nonetheless, population genetic analyses demonstrated that natural selection operated on MX2 during the recent history of human populations: distinct selective events drove the frequency increase of two haplotypes in the populations of Asian and European ancestry. The Asian haplotype carries a susceptibility allele for melanoma; the European haplotype is tagged by rs2074560, an intronic variant. Analyses performed on three independent European cohorts of HIV-1-exposed seronegative individuals with different geographic origin and distinct exposure route showed that the ancestral (G) allele of rs2074560 protects from HIV-1 infection with a recessive effect (combined P = 1.55 × 10(-4)). The same allele is associated with lower in vitro HIV-1 replication and increases MX2 expression levels in response to IFN-α. Data herein exploit evolutionary information to identify a novel host determinant of HIV-1 infection susceptibility.

  12. Toll-interacting protein inhibits HIV-1 infection and regulates viral latency.

    PubMed

    Li, Chuan; Kuang, Wen-Dong; Qu, Di; Wang, Jian-Hua

    2016-06-24

    HIV-1 latency is mainly characterized by a reversible silencing of long-terminal repeat (LTR)-driven transcription of provirus. The existing of repressive factors has been described to contribute to transcription silencing of HIV-1. Toll-interacting protein (Tollip) has been identified as a repressor of Toll like receptors (TLR)-mediated signaling. Our previous study has found that Tollip inhibited NF-κB-dependent HIV-1 promoter LTR-driven transcription, indicating the potential role of Tollip in governing viral latency. In this study, by using HIV-1 latently infected Jurkat T-cell and central memory CD4(+) T-cells, we demonstrate the role of Tollip in regulating HIV-1 latency, as the knock-down of Tollip promoted HIV-1 reactivation from both HIV-1 latently infected Jurkat CD4(+) T cells and primary central memory T cells (TCM). Moreover, we found that the activities of LTRs derived from multiple HIV-1 subtypes could be repressed by Tollip; Knock-down of Tollip promoted HIV-1 transcription and infection in CD4(+) T cells. Our data indicate a key role of Tollip in suppressing HIV-1 infection and regulating viral latency, which provides a potential host target for combating HIV-1 infection and latency.

  13. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.

    PubMed

    Caskey, Marina; Klein, Florian; Lorenzi, Julio C C; Seaman, Michael S; West, Anthony P; Buckley, Noreen; Kremer, Gisela; Nogueira, Lilian; Braunschweig, Malte; Scheid, Johannes F; Horwitz, Joshua A; Shimeliovich, Irina; Ben-Avraham, Sivan; Witmer-Pack, Maggi; Platten, Martin; Lehmann, Clara; Burke, Leah A; Hawthorne, Thomas; Gorelick, Robert J; Walker, Bruce D; Keler, Tibor; Gulick, Roy M; Fätkenheuer, Gerd; Schlesinger, Sarah J; Nussenzweig, Michel C

    2015-06-25

    HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

  14. 3BNC117 a Broadly Neutralizing Antibody Suppresses Viremia in HIV-1-Infected Humans

    PubMed Central

    Caskey, Marina; Klein, Florian; Lorenzi, Julio C. C.; Seaman, Michael S.; West, Anthony P.; Buckley, Noreen; Kremer, Gisela; Nogueira, Lilian; Braunschweig, Malte; Scheid, Johannes F.; Horwitz, Joshua A.; Shimeliovich, Irina; Ben Avraham-Shulman, Sivan; Witmer-Pack, Maggi; Platten, Martin; Lehmann, Clara; Burke, Leah A.; Hawthorne, Thomas; Gorelick, Robert J.; Walker, Bruce D.; Keler, Tibor; Gulick, Roy M.; Fätkenheuer, Gerd; Schlesinger, Sarah J.; Nussenzweig, Michel C.

    2016-01-01

    HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned1–3. However, recently developed single cell based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies (bNAbs) to HIV-14,5. These antibodies can prevent infection and suppress viremia in humanized mice (hu-mice) and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated6–10. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody11, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favorable pharmacokinetics. A single 30 mg/kg infusion of 3BNC117 reduced the viral load (VL) in HIV-1-infected individuals by 0.8 – 2.5 log10 and viremia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that as a single agent 3BNC117 is safe and effective in reducing HIV-1 viremia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy, and cure. PMID:25855300

  15. SEROPREVALENCE OF HTLV IN A POPULATION OF HIV1-INFECTED PATIENTS IN MIDWESTERN BRAZIL

    PubMed Central

    KOZLOWSKI, Aline Garcia; de MATOS, Márcia Alves Dias; CARNEIRO, Megmar Aparecida dos Santos; LOPES, Carmen Luci Rodrigues; TELES, Sheila Araújo; VICENTE, Carolina Paulo; MARTINS, Regina Maria Bringel

    2016-01-01

    SUMMARY Human T-cell lymphotropic virus (HTLV) may affect the clinical course of human immunodeficiency virus 1 (HIV1). Both infections are common in endemic areas because these viruses share similar routes of transmission. The aim of this study was to estimate the seroprevalence of HTLV1/2 in a population of HIV1-infected patients in the state of Goiás, Midwestern Brazil. Of the 505 studied patients, four (0.79%) were positive for anti-HTLV1/2 by enzyme-linked immunosorbent assay (ELISA), with HTLV1 infection confirmed by line immunoassay (LIA) and polymerase chain reaction (PCR) in all of the ELISA-positive samples. No cases of HTLV2 infection were observed. The prevalence of HTLV1/HIV1 coinfection was 0.79% (4/505; 95% CI: 0.25-2.16). All the coinfected patients reported sexual risk behaviors and only one reported intravenous drug use. Sequencing of the viral long terminal repeat (LTR) region and phylogenetic analysis revealed that the four HTLV1 isolates belonged to the Transcontinental a subgroup of the Cosmopolitan (1a) subtype, the most frequent subgroup detected in Brazil. This study shows a low prevalence of HTLV1/2 in HIV1-infected patients in Midwestern Brazil. PMID:27828621

  16. Lack of Detection of XMRV in Seminal Plasma from HIV-1 Infected Men in The Netherlands

    PubMed Central

    Cornelissen, Marion; Zorgdrager, Fokla; Blom, Petra; Jurriaans, Suzanne; Repping, Sjoerd; van Leeuwen, Elisabeth; Bakker, Margreet; Berkhout, Ben; van der Kuyl, Antoinette C.

    2010-01-01

    Background Xenotropic murine leukaemia virus-related virus (XMRV) is a recently discovered human gammaretrovirus with yet unknown prevalence and transmission route(s). Its presence in prostate stromal fibroblasts and prostatic secretions suggests that XMRV might be sexually transmitted. We chose to study a compartment closely connected to the prostate, a location where XMRV was detected in independent studies. Seminal plasma samples from HIV-1 infected men were examined as they have an increased probability of acquiring sexually transmitted pathogens. Methodology/Principal Findings We studied the prevalence of XMRV in 93 seminal plasma samples of 54 HIV-1 infected men living in The Netherlands with a nested PCR amplification specifically targeting the XMRV gag gene. As a control for the presence and integrity of retrovirus particles, HIV-1 was amplified from the same samples with a PCR amplification targeting the env gene of the virus, or HIV-1 was quantified with a real-time PCR amplifying part of the pol gene. Conclusions/Significance Although HIV-1 was amplified from 25% of the seminal plasma samples, no XMRV was detected, suggesting that either the prevalence of XMRV is very low in The Netherlands, or that XMRV is not naturally present in the seminal plasma. PMID:20706581

  17. Bullous impetigo in homosexual men--a risk marker for HIV-1 infection?

    PubMed Central

    Donovan, B; Rohrsheim, R; Bassett, I; Mulhall, B P

    1992-01-01

    OBJECTIVE--To determine the incidence of bullous impetigo in a group of homosexual men at high risk of HIV-1 infection. DESIGN--A longitudinal descriptive study (1984-9). SETTING--A private primary care and STD clinic in Sydney, Australia. SUBJECTS--88 homosexual men documented to seroconvert to HIV-1, and 37 homosexual controls who had practised unprotected anal intercourse with another man known to be HIV-1 positive but who remained HIV-1 negative. MAIN OUTCOME MEASURE--Incidence of bullous impetigo. RESULTS--The crude annual incidence of bullous impetigo was 0.015 in subjects while they remained HIV-1 negative (10 cases) and 0.045 in early HIV-1 positive subjects (2 cases). Overall, 9% of the HIV-1 seroconverters and 9% of the HIV-1 negative controls were documented as suffering bullous impetigo over a mean of 29.2 and 39.3 months, respectively. CONCLUSIONS--Bullous impetigo in an adult could prove to be a clinical indication that a person is either infected with HIV-1 or is in close (possibly sexual) contact with a person with HIV-1 infection. If true, the recognition of bullous impetigo could provide an opportunity for behavioural intervention to limit the spread of HIV-1. Images PMID:1607190

  18. High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART

    PubMed Central

    Ramirez, L. A.; Arango, T. A.; Thompson, E.; Naji, M.; Tebas, P.; Boyer, J. D.

    2014-01-01

    HIV-1-infected subjects, despite control of viral replication with ART, have an altered immune cytokine/chemokine milieu. Changes in systemic cytokines and chemokines can alter immune responses. IP-10, in particular, has been associated with pathogenesis in a number of conditions, and we found that IP-10 is increased in serum in subjects who are HIV-1 infected and on stable ART compared with HIV-1-uninfected individuals. In a series of in vitro studies, we found that PBMCs exposed to IP-10 showed a significant decrease in the number of cells capable of secreting IFN-γ, as well as other cytokines, when stimulated with recall antigens. Furthermore, treatment with IP-10 led to decreased antigen-specific calcium signaling and MAPK38 phosphorylation. Importantly, the cytokines, as well as proliferative responses, could be enhanced with an IP-10 Nab. Our findings suggest that IP-10-modulating drugs may potentially enhance T cell responses to vaccination and HIV-1 in HIV+ subjects on ART. PMID:25157027

  19. Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption

    SciTech Connect

    Mercier, Simon; St-Pierre, Christian; Pelletier, Isabelle; Ouellet, Michel; Tremblay, Michel J. Sato, Sachiko

    2008-02-05

    Following primary infection with human immunodeficiency virus type-1 (HIV-1), macrophages are thought to play an important role, as they are one of the first target cells the virus encounters and can also sustain a significant production of viruses over extended periods of time. While the interaction between the primary cellular receptor CD4 and the virus-encoded external envelope glycoprotein gp120 initiates the infection process, it has been suggested that various host factors are exploited by HIV-1 to facilitate adsorption onto the cell surface. Macrophages and other cells found at the infection site can secrete a soluble mammalian lectin, galectin-1, which binds to {beta}-galactoside residues through its carbohydrate recognition domain. Being a dimer, galectin-1 can cross-link ligands expressed on different constituents to mediate adhesion between cells or between cells and pathogens. We report here that galectin-1, but not galectin-3, increased HIV-1 infectivity in monocyte-derived macrophages (MDMs). This phenomenon was likely due to an enhancement of virus adsorption kinetics, which facilitates HIV-1 entry. The fusion inhibitors T-20 and TAK779 remained effective at reducing infection even in the presence of galectin-1, indicating that the galectin-1-mediated effect is occurring at a step prior to fusion. Together, our data suggest that galectin-1 can facilitate HIV-1 infection in MDMs by promoting early events of the virus replicative cycle (i.e. adsorption)

  20. Thermosensitive Gel Containing Cellulose Acetate Phthalate-Efavirenz Combination Nanoparticles for Prevention of HIV-1 Infection.

    PubMed

    Date, Abhijit A; Shibata, Annemaria; McMullen, Emily; La Bruzzo, Krista; Bruck, Patrick; Belshan, Michael; Zhou, You; Destache, Christopher J

    2015-03-01

    The objective of this investigation was to develop and evaluate a nano-microbicide containing a combination of cellulose acetate phthalate (HIV-1 entry inhibitor) and efavirenz (anti-HIV agent) for HIV prophylaxis. Cellulose acetate phthalate-efavirenz combination nanoparticles (CAP-EFV-NPs) were fabricated by the nanoprecipitation method and were characterized for particle size, zeta potential and encapsulation efficiency of efavirenz. CAP-EFV-NPs were incorporated into a thermosensitive gel (CAP-EFV-NP-Gel). CAP-EFV-NPs, CAP-EFV-NP-Gel and efavirenz solution were evaluated for cytotoxicity to HeLa cells and for in vitro short-term (1-day) and long-term (3-day) prophylaxis against HIV-1 infection in TZM-bl cells. CAP-EFV-NPs had size < 100 nm, negative surface charge and encapsulation efficiency of efavirenz was > 98%. CAP-EFV-NPs and CAP-EFV-NP-Gel were significantly less toxic (P < 0.01) to HeLa cells as compared to efavirenz solution. CAP-EFV-NPs showed significantly higher prophylactic activity (P < 0.01) against HIV-1 infection to TZM-bl cells as compared to efavirenz solution and blank CAP nanoparticles. CAP-EFV-NP-Gel can be a promising nano-microbicide for long-term HIV prophylaxis.

  1. Elemental profile in amniotic fluid of some Nigerian pregnant women.

    PubMed

    Yahaya, M I; Ogunfowokan, A O; Orji, E O

    2011-06-01

    In this study concentration level of calcium, cadmium, copper, iron, magnesium, manganese, nickel, lead and zinc were determined in the amniotic fluid of pregnant women, aged 15 - 45 years enrolled at the Obafemi Awolowo University Teaching Hospitals Complex Ile - Ife. This was with a view to predict the body burden of the metals in the pregnant women and assess the health implications of the toxic elements to the pregnant women and their fetuses. Fifty samples of the amniotic fluid were collected from the pregnant women. The efficiency of extraction of trace metals using conventional wet acid digestion method (CDM) and microwave induced acid digestion method (MWD) was determined by recovery experiments. Levels of trace metals were determined using Atomic Absorption Spectrophotometry. The high percentage recoveries obtained from MWD made it a more efficient method than the CDM and hence its adoption for sample digestion. Statistical analysis of data using descriptive and inferential statistics revealed that age; education and profession have effects on the levels of the trace metals. The mean levels of most of the toxic metals obtained in this study were lower than the recommended limits of trace metals in women whole blood.

  2. Connectivity and HIV-1 infection: role of CD4(+) T-cell counts and HIV-1 RNA copy number.

    PubMed

    Padierna-Olivos, L; Moreno-Altamirano, M M; Sánchez-Colón, S; Massó-Rojas, F; Sánchez-García, F J

    2000-12-01

    Following primary infection with human immunodeficiency virus (HIV)-1, antibodies against specific HIV-1 epitopes are elicited. However, non-HIV-1 specific antibodies, including autoantibodies, also arise. In fact, it has been proposed that such autoantibodies have an important role in the pathogenesis of HIV-1 infection. Because an imbalance in connectivity has been associated with autoimmune processes, we investigated the connectivity status of HIV-1-infected individuals. Moreover, we tested the possible role of viral load and CD4(+) T-cell counts, in connectivity, because these parameters appear to be important in the prognosis of HIV-1 infection. Results show that indeed, there is an alteration in connectivity in these patients, both for immunoglobulin (Ig)G and IgM, which is an immune alteration not previously identified in HIV-1 infection. In addition, our results show that viral load and CD4(+) T-cell counts are both equally important in defining the characteristic pattern of connectivity in HIV-1-infected individuals, and that neither is independently responsible for alterations in patient connectivity status.

  3. Cutting edge: An antibody recognizing ancestral endogenous virus glycoproteins mediates antibody-dependent cellular cytotoxicity on HIV-1-infected cells.

    PubMed

    Michaud, Henri-Alexandre; SenGupta, Devi; de Mulder, Miguel; Deeks, Steven G; Martin, Jeffrey N; Kobie, James J; Sacha, Jonah B; Nixon, Douglas F

    2014-08-15

    The failure of antiviral vaccines is often associated with rapid viral escape from specific immune responses. In the past, conserved epitope or algorithmic epitope selections, such as mosaic vaccines, have been designed to diversify immunity and to circumvent potential viral escape. An alternative approach is to identify conserved stable non-HIV-1 self-epitopes present exclusively in HIV-1-infected cells. We showed previously that human endogenous retroviral (HERV) mRNA transcripts and protein are found in cells of HIV-1-infected patients and that HERV-K (HML-2)-specific T cells can eliminate HIV-1-infected cells in vitro. In this article, we demonstrate that a human anti-HERV-K (HML-2) transmembrane protein Ab binds specifically to HIV-1-infected cells and eliminates them through an Ab-dependent cellular cytotoxicity mechanism in vitro. Thus, Abs directed against epitopes other than HIV-1 proteins may have a role in eliminating HIV-1-infected cells and could be targeted in novel vaccine approaches or immunotherapeutic modalities.

  4. Psychiatric Disorders and Treatment in Low-Income Pregnant Women

    PubMed Central

    Flick, Louise H.; Homan, Sharon M.; Campbell, Claudia; McSweeney, Maryellen; Gallagher, Mary Elizabeth

    2010-01-01

    Abstract Aims This study estimated the prevalence of twenty-two 12-month and lifetime psychiatric disorders in a sample of 744 low-income pregnant women and the frequency that women with psychiatric disorders received treatment. Method To identify psychiatric disorders, the Diagnostic Interview Schedule (DIS) was administered to Medicaid or Medicaid-eligible pregnant women enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). The sample was stratified by the rural or urban location of the WIC sites in southeastern Missouri and the city of St. Louis. Eligible women were enrolled at each site until their numbers were proportional to the racial distribution of African American and Caucasian pregnant women served there. Results The 12-month prevalence of one or more psychiatric disorders was 30.9%. Most common were affective disorders (13.6%), particularly major depressive disorder (8.2%) and bipolar I disorder (5.2%). Only 24.3% of those with a psychiatric disorder reported that they received treatment in the past year. Lifetime prevalence of at least one disorder was 45.6%, with affective disorders being the most frequent (23.5%). Caucasian women were more likely than African Americans to have at least one 12-month disorder, with the difference largely accounted for by nicotine dependence. Higher prevalence of lifetime disorders was also found in Caucasian women, particularly affective disorders and substance use disorders. There were no differences in the prevalence of 12-month or lifetime psychiatric disorders by the urban or rural residence of subjects. Conclusions With nearly one third of pregnant women meeting criteria for a 12-month psychiatric disorder and only one fourth receiving any type of mental health treatment, comprehensive psychiatric screening during pregnancy is needed along with appropriate treatment. PMID:20524895

  5. How Does Heroin Use Affect Pregnant Women

    MedlinePlus

    ... Naloxone Pain Prevention Treatment Trends & Statistics Women and Drugs Publications Funding Funding Opportunities Clinical Research Post-Award Concerns General Information Grant & Contract Application ...

  6. Don't Punish Pregnant Women for Opioid Use, Docs Say

    MedlinePlus

    ... news/fullstory_163680.html Don't Punish Pregnant Women for Opioid Use, Docs Say Better prevention and ... should be the focus when dealing with pregnant women who use opioids, a leading pediatricians' group says. ...

  7. Kinetics of CMV seroconversion in a Swiss pregnant women population.

    PubMed

    Maine, Gregory T; Stricker, René; Stricker, Reto

    2012-07-01

    Retrospective evaluation of the kinetics of cytomegalovirus (CMV) seroconversion with CMV IgM, IgG, and IgG avidity assays, in a Swiss pregnant women population, has shown that the current published CMV serologic diagnostic algorithms were valid and fit for use. In 19% of the cases analyzed, CMV-specific IgM was detected before IgG.

  8. Dilemmas in Managing Pregnant Women With Ebola: 2 Case Reports.

    PubMed

    Caluwaerts, Séverine; Fautsch, Tessy; Lagrou, Daphne; Moreau, Michel; Modet Camara, Alseny; Günther, Stephan; Di Caro, Antonino; Borremans, Benny; Raymond Koundouno, Fara; Akoi Bore, Joseph; Logue, Christopher H; Richter, Martin; Wölfel, Roman; Kuisma, Eeva; Kurth, Andreas; Thomas, Stephen; Burkhardt, Gillian; Erland, Elin; Lionetto, Fanshen; Lledo Weber, Patricia; de la Rosa, Olimpia; Macpherson, Hassan; Van Herp, Michel

    2016-04-01

    We report 2 cases of Ebola viral disease (EVD) in pregnant women who survived, initially with intact pregnancies. Respectively 31-32 days after negativation of the maternal blood EVD-polymerase chain reaction (PCR) both patients delivered a stillborn fetus with persistent EVD-PCR amniotic fluid positivity.

  9. 45 CFR 96.131 - Treatment services for pregnant women.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Substance Abuse Prevention and Treatment Block Grant § 96.131 Treatment services for pregnant women. (a) The... Director for Substance Abuse Services. (f) The State shall develop effective strategies for monitoring.... Programs which serve an injecting drug abuse population and who receive Block Grant funds shall...

  10. 45 CFR 96.131 - Treatment services for pregnant women.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Substance Abuse Prevention and Treatment Block Grant § 96.131 Treatment services for pregnant women. (a) The... Director for Substance Abuse Services. (f) The State shall develop effective strategies for monitoring.... Programs which serve an injecting drug abuse population and who receive Block Grant funds shall...

  11. 45 CFR 96.131 - Treatment services for pregnant women.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Substance Abuse Prevention and Treatment Block Grant § 96.131 Treatment services for pregnant women. (a) The... Director for Substance Abuse Services. (f) The State shall develop effective strategies for monitoring.... Programs which serve an injecting drug abuse population and who receive Block Grant funds shall...

  12. Vitamin D Deficiency in Pregnant Women and Their Neonates

    PubMed Central

    Abbasian, Maryam; Chaman, Reza; Amiri, Mohammad; Ajami, Mohammad Esmaeil; Jafari-Koshki, Tohid; Rohani, Hossein; Taghavi-Shahri, Seyed Mahmood; Sadeghi, Erfan; Raei, Mehdi

    2016-01-01

    Background and Objective: Vitamin D deficiency during pregnancy is a worldwide problem. Studies have reported prevalence ranged 18-84% in pregnant women. Receiving adequate calcium and vitamin D during pregnancy period is necessary for calcium homeostasis, fetal growth and bone mineralization. This study was aimed to determine the prevalence of vitamin D deficiency in pregnant women and their neonates in Shahroud city in the northeast Iran. Methods: In this cross-sectional study, 284 pregnant women and their neonates referred to Fatemiyeh Hospital of Shahroud were included. Blood samples of mothers and umbilical cords were collected during the delivery and were sent to laboratory in order to measure calcium and 25-hydroxy vitamin D. Findings: Amounts of Vitamin D insufficiency (20-30 ng/mL) and deficiency (<20 ng/mL) in (mothers, neonates) were found to be (60.2%, 48.9%) and (1.1%, 2.5%) respectively. Calcium deficiency (<8.5 mg/dL) was present in 33.5% of mothers and 25% of neonates. There was a weak correlation between maternal serum and cord blood 25-hydroxy vitamin D (r=0.12, p=0.053). Conclusion: More than half of the mothers and their neonates had some degrees of vitamin D deficiency. It is recommended to evaluate the nutritional status of vitamin D in pregnant women along with public health interventions to be carried out. PMID:27157170

  13. High Prevalence of Vitamin D Deficiency among Pregnant Saudi Women.

    PubMed

    Al-Faris, Nora A

    2016-02-04

    Vitamin D deficiency has emerged as a public health problem worldwide due to its important role in health and disease. The present work is intended to examine prevalence of vitamin D deficiency among pregnant Saudi women and related risk factors. A cross-sectional study was carried out at King Fahad Medical City in Riyadh, Saudi Arabia. Serum 25-hydroxy vitamin D (25(OH)D) was measured by enzyme-linked immunosorbent assay in 160 pregnant women during the first trimester of pregnancy. Socio-demographic, lifestyle and maternal characteristics were collected and vitamin D intake was assessed using a 24-h dietary recall. Weight and height were measured using standardized methods. Vitamin D deficiency (25(OH)D < 50 nmol/L) and insufficiency (25(OH)D = 50-74 nmol/L) were reported in 50% and 43.8% of the study sample, respectively. Median serum 25(OH)D concentration was 49.9 nmol/L. Adequate vitamin D intake (≥600 IU/day) was reported among only 8.1% of pregnant women. Age group, educational level, sun exposure frequency and daytime and daily practice of exercise were significantly associated with vitamin D status. Overall, vitamin D deficiency was common among pregnant Saudi women in Riyadh. Steps should be taken to address the current situation, including increased sunlight exposure, consumption of fatty fish, and vitamin D supplements.

  14. Seroprevalence of Hepatitis E Among Pregnant Women in Urmia, Iran

    PubMed Central

    Rostamzadeh Khameneh, Zakieh; Sepehrvand, Nariman; Khalkhali, Hamid-Reza

    2013-01-01

    Background While hepatitis E virus (HEV) mostly causes self-limited disease in general population, it is more severe in pregnant women. Objectives This study aimed to investigate the seroprevalence of anti-HEV IgG among a population of pregnant women in West Azerbaijan of Iran . Patients and Methods One hundred thirty six pregnant women referred to urban health centers of Urmia for pursuing pregnancy-related health services were enrolled in a descriptive, cross-sectional study. Anti-HEV IgG antibody was evaluated using enzyme-linked immunosorbent assay (enzyme-linked immunosorbent assay, ELISA; Dia.Pro; Diagnostic Bioprobes). Results Only five (3.6%) of 136 cases had positive results for anti-HEV IgG. There was no significant difference between age (P=0.88), and income level (P = 0.19) of the two seropositive and seronegative groups. All seropositive cases were from urban areas. Conclusions The seroprevalence of anti-HEV IgG is low in the population of pregnant women in , similar to the rates reported from developed countries. Effective health services and provision of safe water supplies in Urmia may take role in this low prevalence rate. PMID:24348644

  15. Current Concepts in Nutrition--Pregnant Women and Premature Infants.

    ERIC Educational Resources Information Center

    King, Janet C.; Charlet, Sara

    1978-01-01

    Discusses energy and nutrient requirements of pregnant women with respect to kcal needs and vitamins B-6, folacin, vitamin E, and intake of certain trace elements. Also discusses nutritional needs of the premature infant and the ways of supplying these nutrients. (MA)

  16. Utilization of Pregnant Enlisted Women Transferred Off Ships

    DTIC Science & Technology

    1994-01-01

    pregnant women in their division worked until 2 weeks before delivery. 12 Afterconvalmesew leave, wome geeamly returned to their work center. according...by circling the number In front of your choice. You may write In an answer If you feel that none of the answers is right for you. Please be honest in

  17. Factors Associated with Periodontal Disease in Pregnant Diabetic Women.

    PubMed

    Anwar, N; Zaman, N; Nimmi, N; Chowdhury, T A; Khan, M H

    2016-04-01

    There have been an association between systemic diseases and hormonal changes particularly diabetes which has been cited as a risk factor in the progression of periodontitis in pregnant women. The incidence and severity of periodontal diseases are increasing at a higher rate and a common condition in pregnant diabetic women among Bangladeshi population. This cross sectional study included 200 pregnant women who were selected from gynecological department and examined at the dental unit. The clinical parameters used were the Silness and Loe plaque index (PI), gingival scores and periodontal status and any relationship to socio demographic variables (age, occupation, level of education and urban or rural residence) and clinical variables (gestation period, previous pregnancy, type of diabetes and periodontal maintenance) were evaluated. The results showed that these clinical parameters increased concomitantly with an increase in the stage of pregnancy and in women with multiple pregnancies. Increased age, lower level of education, unemployment and patients residing in rural areas were associated with significantly higher gingival scores and periodontal measures. Women with increased age and multiple pregnancies usually have less interest to frequent periodontal maintenance showing a significant statistical relation between an increased age and changes in gingival and periodontal status; however no significant association was found between increased age and plaque index. It is concluded that gingival inflammatory symptoms are aggravated during pregnancy in diabetic women and are related to different clinical and demographic variables.

  18. Seroprevalence of Toxoplasma gondii infection among pregnant women in Cameroon

    PubMed Central

    Njunda, Anna L.; Assob, Jules C.N.; Nsagha, Dickson S.; Kamga, Henri L.; Nde, Peter F.; Yugah, Vuchas C.

    2011-01-01

    Toxoplasmosis is caused by an intracellular protozoan, Toxoplasma gondii, which has a wide geographical distribution. The congenital form results in a gestational form that can present a temporary parasiteamia that will infect the fetus. For this reason early diagnosis in pregnancy is highly desirable, allowing prompt intervention in cases of infection. The aim of this study was to determine the seroprevalence of Toxoplasma gondii antibodies among pregnant women attending the Douala General Hospital. The study was carried out between March and July 2009, whereby 110 pregnant women were tested for IgG and IgM antibodies and information about eating habits and hygienic conditions was collected using a questionnaire. These women's ages ranged from 20–44 years old with an average of 29.9 years; the overall IgG and IgM seroprevalence was 70% and 2.73 % respectively. Seroprevalence was significantly high amongst women who ate raw vegetables (76.39%, P<0.05) and there was a significant trend towards a higher seroprevalence in women who did not have a good source of water (75.58%, P<0.05). This research showed that consumption of raw vegetables and poor quality drinking water are two risk factors associated with Toxoplasma gondii infection amongst pregnant women attending the Douala General Hospital in Cameroon. PMID:28299065

  19. Ambient air pollution and annoyance responses from pregnant women

    NASA Astrophysics Data System (ADS)

    Llop, Sabrina; Ballester, Ferran; Estarlich, Marisa; Esplugues, Ana; Fernández-Patier, Rosalia; Ramón, Rosa; Marco, Alfredo; Aguirre, Amelia; Sunyer, Jordi; Iñiguez, Carmen; INMA-Valencia cohort

    ObjectivesTo describe the degree of annoyance caused by air pollution and noise in pregnant women in a birth cohort; to determine the modifying factors and their relation with exposure to ambient nitrogen dioxide (NO 2). MethodsThe study population was 855 pregnant women in Valencia, Spain. Annoyance caused by air pollution and noise, and explanatory factors were obtained from 786 pregnant women through a questionnaire. NO 2 levels were determined combining measurements at 93 points within the area of study and using geostatistical techniques (kriging). ResultsIn all 7.9% of the women reported high annoyance caused by air pollution and 13.1% high annoyance caused by noise. There was a significant difference in the degree of annoyance due to both air pollution and noise depending on the area where the women lived and their working status. The degree of annoyance correlated better with measured NO 2 at the municipality level (air pollution: r=0.53; noise: r=0.44) than at the individual level (air pollution and noise: r=0.21). On multivariate analysis, being a housewife, higher NO 2 levels and high traffic density were associated with higher degrees of annoyance. ConclusionsThere was a high percentage of women who perceived medium-high annoyance due to noise and air pollution. Annoyance caused by environmental pollutants could lead to some psychological effects, which impair the quality of life, or even physiological ones, which affect prenatal development.

  20. [The expectancy-stress factor in pregnant refugee women].

    PubMed

    Gogol', K N; Gotsiridze, E G; Guruli, Z V; Kintraia, N P; Tsaava, F D

    2006-09-01

    Our study revealed that refugee status increases the risks and worsens the outcome of pregnancy among Georgian refugees. 125 Georgian refugee women participated in this study. The study included examinations of the psychological status of expecting mothers, clinical development of pregnancy, complications of labor, functional status of the fetus, and EEG and neuro-ultrasound data of newborns. The control group comprised 125 pregnant women who experienced no stress during pregnancy. An examination of the psycho-emotional status of pregnant refugee women revealed high percentage indicators (82%) for hypochondria, depression, psychopathy, hysteria and psychoastenia in contrast to the control group. The deterioration of psycho-emotional status and biochemical indicators in pregnant refugee women was directly proportional to the worsening of functional and clinical conditions in fetuses. Prolonged stress is the cause of increased morbidity and mortality during pregnancy and child birth in refugee women. Infants born to refugee women also faced increased risks and belong to the group of special premature care and observation.

  1. Enhanced clearance of HIV-1-infected cells by anti-HIV-1 broadly neutralizing antibodies in vivo

    PubMed Central

    Lu, Ching-Lan; Murakowski, Dariusz K.; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A.; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V.; Caskey, Marina; Chakraborty, Arup K.; Nussenzweig, Michel C.

    2016-01-01

    Anti-retroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life-cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1 infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody (bNAb), suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection, but also include acceleration of infected cell clearance. Consistent with these observations, we find that bNAbs can target CD4+ T cells infected with patient viruses and decrease their in vivo half-lives by a mechanism that requires FcγR engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1 infected cells. PMID:27199430

  2. Issues and concerns of healthy pregnant women.

    PubMed Central

    Burst, H V

    1987-01-01

    The issues and concerns of the 85 percent of essentially healthy women who have normal pregnancies and births are reviewed. The importance of their issues in relation to their health care and outcomes is discussed. PMID:3120221

  3. High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections.

    PubMed

    Sukasem, Chonlaphat; Chamnanphon, Montri; Koomdee, Napatrupron; Puangpetch, Apichaya; Santon, Siwalee; Jantararoungtong, Thawinee; Prommas, Santirat; Chantratita, Wasun; Manosuthi, Weerawat

    2013-01-01

      Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavirenz) in 100 Thai adults with HIV-1 infection using high-performance liquid chromatography. Candidate CYP2B6 polymorphisms (c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T) were conducted by real-time PCR-based allelic discrimination. The most frequent polymorphisms among this cohort were the CYP2B6 c.785A>G and c.516G>T, which had a frequency of 0.36 and 0.32, respectively. From the cases observed, two single nucleotide polymorphisms (SNPs) (c.516G>T and c.785A>G) were significantly associated with high efavirenz plasma levels (p < 0.05). The most frequent haplotypic combinations were *1/*6, *1/*1, *1/*2 and *6/*6 at a frequency of 42.0%, 32.0%, 8.0% and 7.0%, respectively. Increased plasma concentrations of efavirenz were present in individuals with CYP2B6 *6/*6 [7.210 mg/L; interquartile range (IQR), 5.020-9.260] when compared to those with CYP2B6*1/*1 (1.570 mg/L; IQR, 1.295-2.670), p < 0.001. In our study, the impact of SNPs which are correlated with a high level of efavirenz plasma concentrations was found. The genetic configuration of SNPs which are associated with high plasma efavirenz levels may be useful in optimizing the efavirenz dose that is used in HIV-1 infected patients.

  4. Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection.

    PubMed

    Hoffmann, Matthias; Pantazis, Nikos; Martin, Genevieve E; Hickling, Stephen; Hurst, Jacob; Meyerowitz, Jodi; Willberg, Christian B; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Babiker, Abdel; Weber, Jonathan; Nwokolo, Nneka; Fox, Julie; Fidler, Sarah; Phillips, Rodney; Frater, John

    2016-07-01

    The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of 'exhaustion' or 'immune checkpoint' markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches.

  5. Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection

    PubMed Central

    Hickling, Stephen; Hurst, Jacob; Meyerowitz, Jodi; Willberg, Christian B.; Robinson, Nicola; Brown, Helen; Kinloch, Sabine; Babiker, Abdel; Nwokolo, Nneka; Fox, Julie; Fidler, Sarah; Phillips, Rodney; Frater, John

    2016-01-01

    The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches. PMID:27415828

  6. Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

    PubMed Central

    Fabra-Garcia, A.; Gonzalez, N.; Nicolas, D.; Merino-Mansilla, A.; Manzardo, C.; Ambrosioni, J.; Schultz, A.; Meyerhans, A.; Mascola, J. R.; Gatell, J. M.; Alcami, J.; Miro, J. M.; Yuste, E.

    2016-01-01

    ABSTRACT A fraction of HIV-1 patients are able to generate broadly neutralizing antibodies (bNAbs) after 2 to 4 years of infection. In rare occasions such antibodies are observed close to the first year of HIV-1 infection but never within the first 6 months. In this study, we analyzed the neutralization breadth of sera from 157 antiretroviral-naive individuals who were infected for less than 1 year. A range of neutralizing activities was observed with a previously described panel of six recombinant viruses from five different subtypes (M. Medina-Ramirez et al., J Virol 85:5804–5813, 2011, http://dx.doi.org/10.1128/JVI.02482-10). Some sera were broadly reactive, predominantly targeting envelope epitopes within the V2 glycan-dependent region. The neutralization breadth was positively associated with time postinfection (P = 0.0001), but contrary to what has been reported for chronic infections, no association with the viral load was observed. Notably, five individuals within the first 6 months of infection (two as early as 77 and 96 days postinfection) showed substantial cross-neutralization. This was confirmed with an extended panel of 20 Env pseudoviruses from four different subtypes (two in tier 3, 14 in tier 2, and four in tier 1). Sera from these individuals were capable of neutralizing viruses from four different subtypes with a geometric mean 50% infective dose (ID50) between 100 and 800. These results indicate that induction of cross-neutralizing responses, albeit rare, is achievable even within 6 months of HIV-1 infection. These observations encourage the search for immunogens able to elicit this kind of response in preventive HIV-1 vaccine approaches. IMPORTANCE There are very few individuals able to mount broadly neutralizing activity (bNA) close to the first year postinfection. It is not known how early in the infection cross-neutralizing responses can be induced. In the present study, we show that bNAbs, despite being rare, can be induced much earlier

  7. Tailored enrichment strategy detects low abundant small noncoding RNAs in HIV-1 infected cells

    PubMed Central

    2012-01-01

    Background The various classes of small noncoding RNAs (sncRNAs) are important regulators of gene expression across divergent types of organisms. While a rapidly increasing number of sncRNAs has been identified over recent years, the isolation of sncRNAs of low abundance remains challenging. Virally encoded sncRNAs, particularly those of RNA viruses, can be expressed at very low levels. This is best illustrated by HIV-1 where virus encoded sncRNAs represent approximately 0.1-1.0% of all sncRNAs in HIV-1 infected cells or were found to be undetected. Thus, we applied a novel, sequence targeted enrichment strategy to capture HIV-1 derived sncRNAs in HIV-1 infected primary CD4+ T-lymphocytes and macrophages that allows a greater than 100-fold enrichment of low abundant sncRNAs. Results Eight hundred and ninety-two individual HIV-1 sncRNAs were cloned and sequenced from nine different sncRNA libraries derived from five independent experiments. These clones represent up to 90% of all sncRNA clones in the generated libraries. Two hundred and sixteen HIV-1 sncRNAs were distinguishable as unique clones. They are spread throughout the HIV-1 genome, however, forming certain clusters, and almost 10% show an antisense orientation. The length of HIV-1 sncRNAs varies between 16 and 89 nucleotides with an unexpected peak at 31 to 50 nucleotides, thus, longer than cellular microRNAs or short-interfering RNAs (siRNAs). Exemplary HIV-1 sncRNAs were also generated in cells infected with different primary HIV-1 isolates and can inhibit HIV-1 replication. Conclusions HIV-1 infected cells generate virally encoded sncRNAs, which might play a role in the HIV-1 life cycle. Furthermore, the enormous capacity to enrich low abundance sncRNAs in a sequence specific manner highly recommends our selection strategy for any type of investigation where origin or target sequences of the sought-after sncRNAs are known. PMID:22458358

  8. 42 CFR 435.116 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Qualified pregnant women and children who are not... Categorically Needy Mandatory Coverage of Pregnant Women, Children Under 8, and Newborn Children § 435.116 Qualified pregnant women and children who are not qualified family members. (a) The agency must...

  9. 42 CFR 435.170 - Pregnant women eligible for extended coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Pregnant women eligible for extended coverage. 435... Mandatory Coverage of Special Groups § 435.170 Pregnant women eligible for extended coverage. (a) The agency... pregnancy to women who, while pregnant, applied for, were eligible for, and received Medicaid services...

  10. 42 CFR 435.116 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Qualified pregnant women and children who are not... Categorically Needy Mandatory Coverage of Pregnant Women, Children Under 8, and Newborn Children § 435.116 Qualified pregnant women and children who are not qualified family members. (a) The agency must...

  11. 42 CFR 436.122 - Pregnant women eligible for extended coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Pregnant women eligible for extended coverage. 436... ISLANDS Mandatory Coverage of the Categorically Needy § 436.122 Pregnant women eligible for extended... period following termination of pregnancy to women who, while pregnant, applied for, were eligible...

  12. Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions.

    PubMed

    Li, Xuelin; Price, Matthew A; He, Dongning; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Sanders, Eduard J; Anzala, Omu; Amornkul, Pauli N; Allen, Susan; Hunter, Eric; Kaslow, Richard A; Gilmour, Jill; Tang, Jianming

    2014-09-01

    Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of "missing heritability" in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

  13. Global stability for an HIV-1 infection model with Beddington-DeAngelis incidence rate and CTL immune response

    NASA Astrophysics Data System (ADS)

    Lv, Cuifang; Huang, Lihong; Yuan, Zhaohui

    2014-01-01

    In this paper, an HIV-1 infection model with Beddington-DeAngelis incidence rate and CTL immune response is investigated. One main feature of this model is that an eclipse stage for the infected cells is included and a portion of these cells is reverted to uninfected cells. We derive the basic reproduction number R1 and the immune response reproduction number R2 for the HIV-1 infection model. By constructing Lyapunov functions, the global stabilities for the equilibria have been analyzed.

  14. Substance Use among Pregnant Women: The Report of the Task Force for the Prevention of Substance Use among Pregnant Women.

    ERIC Educational Resources Information Center

    Kayye, Paul T.; Relos, Ruth

    This document contains a report from the North Carolina Task Force for the Prevention of Substance Use Among Pregnant Women, a task force established to develop a long-range plan to decrease infant death and disability due to exposure to toxic substances in utero. The executive summary identifies four major problem areas which negatively affect…

  15. Acute HIV infection among pregnant women in Malawi.

    PubMed

    Gay, Cynthia L; Mwapasa, Victor; Murdoch, David M; Kwiek, Jesse J; Fiscus, Susan A; Meshnick, Steven R; Cohen, Myron S

    2010-04-01

    There are limited data on acute HIV infection (AHI) prevalence during pregnancy. Malawian pregnant women admitted in the third trimester and meeting eligibility criteria underwent dual HIV rapid antibody testing. AHI prevalence was retrospectively detected through HIV RNA pooling of seronegative plasma. Among 3,825 pregnant women screened, dual HIV rapid testing indicated that 30.2% were HIV positive, 69.7% were HIV negative, and 0.1% were indeterminate. Sensitivity and specificity of dual rapid testing was 99.0% and 98.7%, respectively. Of 2,666 seronegative specimens, 2,327 had samples available for HIV RNA pooling; 5 women (0.21%) (95% confidence interval, 0.03-0.40%) had AHI with a median peripartum viral load of 1,324,766 copies/mL. Pregnant women are at risk for AHI, warranting counseling of all women and their sexual partners about incident HIV during pregnancy. Dual HIV rapid tests have high sensitivity and specificity. HIV testing should be repeated in the third trimester and/or at delivery.

  16. Acute HIV Infection among Pregnant Women in Malawi

    PubMed Central

    Gay, Cynthia L.; Mwapasa, Victor; Murdoch, David M.; Kwiek, Jesse J.; Fiscus, Susan A.; Meshnick, Steven R.; Cohen, Myron S.

    2009-01-01

    Introduction There are limited data on acute HIV infection (AHI) prevalence during pregnancy. Methods Malawian pregnant women admitted in the third trimester and meeting eligibility criteria underwent dual HIV rapid antibody testing. AHI prevalence was retrospectively detected through HIV RNA pooling of seronegative plasma. Results Among 3825 pregnant women screened, dual HIV rapid testing indicated that 30.2% were HIV positive, 69.7% were HIV negative and 0.1% were indeterminate. Sensitivity and specificity of dual rapid testing was 99.0% and 98.7%, respectively. Of 2666 seronegative specimens, 2327 had samples available for HIV RNA pooling; 5 women (0.21%) (95% CI: 0.03, 0.40%) had AHI with a median peripartum viral load of 1,324,766 copies/mL. Discussion Pregnant women are at risk for AHI, warranting counseling of all women and their sexual partners about incident HIV during pregnancy. Dual HIV rapid tests have high sensitivity and specificity. HIV testing should be repeated in the third trimester and/or at delivery. PMID:20226326

  17. New therapy to revert dysfunctional antibody responses during HIV-1 infection

    PubMed Central

    Chiodi, Francesca

    2010-01-01

    Individuals infected with HIV-1 progress to AIDS at different rates. Rapid progressors develop AIDS within 2–5 years of initial infection, compared with approximately 10 years in typical progressors. Progression to AIDS is associated with impaired humoral and cellular immunity. In this issue of the JCI, Titanji and colleagues report that activated memory B (mBAct) cells are depleted in SIV-infected macaques defined as rapid progressors. Depletion was mediated by programmed death-1 (PD-1) and resulted in reduction of antibody titers specific for SIV and bacterial antigens. Interestingly, blockade of PD-1 in infected animals protected B cells from apoptosis and increased levels of SIV-specific antibodies in blood. These findings pave the way for a new therapeutic strategy aimed at improving humoral immunity in HIV-1 infection. PMID:20972328

  18. Pharmacodynamics of folic acid-receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice

    PubMed Central

    Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana; Mosley, R. Lee; Gorantla, Santhi; Poluektova, Larisa; McMillan, JoEllyn; Gendelman, Howard E.

    2015-01-01

    Long acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, if such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407 coated-ritonavir boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three every other week 100 mg/kg FA-nanoATV/r intramuscular injection administered to infected animals viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold from what was reported for untargeted nanoATV/r. We posit that these nanoformulations have potential for translation to human use. PMID:26026666

  19. Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection.

    PubMed

    Séror, Claire; Melki, Marie-Thérèse; Subra, Frédéric; Raza, Syed Qasim; Bras, Marlène; Saïdi, Héla; Nardacci, Roberta; Voisin, Laurent; Paoletti, Audrey; Law, Frédéric; Martins, Isabelle; Amendola, Alessandra; Abdul-Sater, Ali A; Ciccosanti, Fabiola; Delelis, Olivier; Niedergang, Florence; Thierry, Sylvain; Said-Sadier, Najwane; Lamaze, Christophe; Métivier, Didier; Estaquier, Jérome; Fimia, Gian Maria; Falasca, Laura; Casetti, Rita; Modjtahedi, Nazanine; Kanellopoulos, Jean; Mouscadet, Jean-François; Ojcius, David M; Piacentini, Mauro; Gougeon, Marie-Lise; Kroemer, Guido; Perfettini, Jean-Luc

    2011-08-29

    Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches.

  20. Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

    PubMed Central

    Séror, Claire; Melki, Marie-Thérèse; Subra, Frédéric; Raza, Syed Qasim; Bras, Marlène; Saïdi, Héla; Nardacci, Roberta; Voisin, Laurent; Paoletti, Audrey; Law, Frédéric; Martins, Isabelle; Amendola, Alessandra; Abdul-Sater, Ali A.; Ciccosanti, Fabiola; Delelis, Olivier; Niedergang, Florence; Thierry, Sylvain; Said-Sadier, Najwane; Lamaze, Christophe; Métivier, Didier; Estaquier, Jérome; Fimia, Gian Maria; Falasca, Laura; Casetti, Rita; Modjtahedi, Nazanine; Kanellopoulos, Jean; Mouscadet, Jean-François; Ojcius, David M.; Piacentini, Mauro; Gougeon, Marie-Lise

    2011-01-01

    Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches. PMID:21859844

  1. Noninvasive micromanipulation of live HIV-1 infected cells via laser light

    NASA Astrophysics Data System (ADS)

    Mthunzi, Patience

    2015-12-01

    Live mammalian cells from various tissues of origin can be aseptically and noninvasively micromanipulated via lasers of different regimes. Laser-driven techniques are therefore paving a path toward the advancement of human immuno-deficiency virus (HIV-1) investigations. Studies aimed at the interaction of laser light, nanomaterials, and biological materials can also lead to an understanding of a wealth of disease conditions and result in photonics-based therapies and diagnostic tools. Thus, in our research, both continuous wave and pulsed lasers operated at varying wavelengths are employed, as they possess special properties that allow classical biomedical applications. This paper discusses photo-translocation of antiretroviral drugs into HIV-1 permissive cells and preliminary results of low-level laser therapy (LLLT) in HIV-1 infected cells.

  2. Noninvasive micromanipulation of live HIV-1 infected cells via laser light

    SciTech Connect

    Mthunzi, Patience

    2015-12-31

    Live mammalian cells from various tissues of origin can be aseptically and noninvasively micromanipulated via lasers of different regimes. Laser-driven techniques are therefore paving a path toward the advancement of human immuno-deficiency virus (HIV-1) investigations. Studies aimed at the interaction of laser light, nanomaterials, and biological materials can also lead to an understanding of a wealth of disease conditions and result in photonics-based therapies and diagnostic tools. Thus, in our research, both continuous wave and pulsed lasers operated at varying wavelengths are employed, as they possess special properties that allow classical biomedical applications. This paper discusses photo-translocation of antiretroviral drugs into HIV-1 permissive cells and preliminary results of low-level laser therapy (LLLT) in HIV-1 infected cells.

  3. A Therapeutic Dendritic Cell-Based Vaccine for HIV-1 Infection

    PubMed Central

    Climent, Núria; Assoumou, Lambert; Gil, Cristina; González, Nuria; Alcamí, José; León, Agathe; Romeu, Joan; Dalmau, Judith; Martínez-Picado, Javier; Lifson, Jeff; Autran, Brigitte; Costagliola, Dominique; Clotet, Bonaventura; Gatell, Josep M; Plana, Montserrat; Gallart, Teresa

    2011-01-01

    A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects. Clinical trial.gov NCT00402142 PMID:21233310

  4. Birth planning--is it beneficial to pregnant women?

    PubMed

    Peart, Kerry

    2004-03-01

    The aim of this study was to investigate the experience of birth planning for pregnant women. Research in Australia and overseas has suggested that there are a number of conflicting issues with women's preparation and participation in childbirth. The researcher interviewed forty-two first time mothers in a variety of maternity settings around Victoria to ascertain the importance of birth planning in their approach to childbirth and the ways they went about making their plan and negotiating their needs with health professionals. The data from those interviews demonstrated that the means women used to negotiate their needs for childbirth with health professionals had little influence on their overall pregnancy and birth experience.

  5. [HIV infection in pregnant women in Dakar (Senegal)].

    PubMed

    Diouf, A; Kebe, F; Faye, E O; Diallo, D; Ndour Sarr, A; Mboup, S; Diadhiou, F

    1996-01-01

    The epidemiologic and sociodemographic characteristics of human deficiency virus (HIV) infection vary from one country to another. The objective of this study was to determine the prevalence of HIV infection in pregnant women in Dakar and associated factors. Systematic anonymous screening was performed in pregnant women admitted to the maternity ward. Women whose seropositivity was confirmed by Western blot retroviral serology were included. One woman out of four was assigned by simple random selection to the case control group. Over a 24 month period, 12,498 women were tested. 104 were seropositive (44 HIV1, 58HIV2, and 2 HIV1-HIV2 giving a prevalence of 0.8%. Factors associated with HIV1 and HIV2 were different: mean age 21.7 years for HIV1 versus 30.6 for HIV 2 (p = 0.05); origin in Guinea-Bissau for HIV2 (p = 0.001); mean number of pregnancies 2.6 for HIV1 versus 5.9 for HIV2 (p = 0.001); mean parity 1.5 for HIV1 versus 4.5 for HIV2 (p < 0.01); vitality of the conception product in 85.1% for HIV2 versus 67.5% for HIV1 (p = 0.0001). These data confirm the low prevalence of HIV infection in pregnant women, with a predominance for HIV2. The factors identified in associated with virus type suggest a different mode of transmission and/or reduced virulence or HIV2 compared with HIV1. Knowledge of these factors helps orient management strategies, especially in pregnant women.

  6. Listeriosis Prevention Knowledge Among Pregnant Women in the USA

    DOE PAGES

    Ogunmodede, Folashade; Jones, Jeffery L.; Scheftel, Joni; ...

    2005-01-01

    Background: Listeriosis is a food-borne disease often associated with ready-to-eat foods. It usually causes mild febrile gastrointestinal illness in immunocompetent persons. In pregnant women, it may cause more severe infection and often crosses the placenta to infect the fetus, resulting in miscarriage, fetal death or neonatal morbidity. Simple precautions during pregnancy can prevent listeriosis. However, many women are unaware of these precautions and listeriosis education is often omitted from prenatal care. Methods: Volunteer pregnant women were recruited to complete a questionnaire to assess their knowledge of listeriosis and its prevention, in two separate studies. One study was a nationalmore » survey of 403 women from throughout the USA, and the other survey was limited to 286 Minnesota residents. Results: In the multi-state survey, 74 of 403 respondents (18%) had some knowledge of listeriosis, compared with 43 of 286 (15%) respondents to the Minnesota survey. The majority of respondents reported hearing about listeriosis from a medical professional. In the multi-state survey, 33% of respondents knew listeriosis could be prevented by not eating delicatessen meats, compared with 17% in the Minnesota survey ( p = 0.01). Similarly, 31% of respondents to the multi-state survey compared with 19% of Minnesota survey respondents knew listeriosis could be prevented by avoiding unpasteurized dairy products (p = 0.05). As for preventive behaviors, 18% of US and 23% of Minnesota respondents reported avoiding delicatessen meats and ready-to-eat foods during pregnancy, whereas 86% and 88%, respectively, avoided unpasteurized dairy products. Conclusions: Most pregnant women have limited knowledge of listeriosis prevention. Even though most respondents avoided eating unpasteurized dairy products, they were unaware of the risk associated with ready-to-eat foods. Improved education of pregnant women regarding the risk and sources of listeriosis in pregnancy is needed.« less

  7. Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease

    PubMed Central

    Kumari, Namita; Ammosova, Tatiana; Diaz, Sharmin; Lin, Xionghao; Niu, Xiaomei; Ivanov, Andrey; Jerebtsova, Marina; Dhawan, Subhash; Oneal, Patricia; Nekhai, Sergei

    2017-01-01

    The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1). HIV-1 inhibition was less pronounced in hepcidin-treated SCD PBMCs and more pronounced in the iron or iron chelators treated, suggesting a key role of iron metabolism. In SCD PBMCs, labile iron levels were reduced and protein levels of ferroportin, HIF-1α, IKBα, and HO-1 were increased. Hemin treatment induced ferroportin expression and inhibited HIV-1 in THP-1 cells, mimicking the HIV-1 inhibition in SCD PBMCs, especially as hepcidin similarly prevented HIV-1 inhibition. In THP-1 cells with knocked down ferroportin, IKBα, or HO-1 genes but not HIF-1α or p21, HIV-1 was not inhibited by hemin. Activity of SAMHD1-regulatory CDK2 was decreased, and SAMHD1 phosphorylation was reduced in SCD PBMCs and hemin-treated THP-1 cells, suggesting SAMHD1-mediated HIV-1 restriction in SCD. Our findings point to ferroportin as a trigger of HIV-1 restriction in SCD settings, linking reduced intracellular iron levels to the inhibition of CDK2 activity, reduction of SAMHD1 phosphorylation, increased IKBα expression, and inhibition of HIV-1 RT and transcription. PMID:28203649

  8. Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L.

    PubMed Central

    2011-01-01

    Background The mint family (Lamiaceae) produces a wide variety of constituents with medicinal properties. Several family members have been reported to have antiviral activity, including lemon balm (Melissa officinalis L.), sage (Salvia spp.), peppermint (Mentha × piperita L.), hyssop (Hyssopus officinalis L.), basil (Ocimum spp.) and self-heal (Prunella vulgaris L.). To further characterize the anti-lentiviral activities of Prunella vulgaris, water and ethanol extracts were tested for their ability to inhibit HIV-1 infection. Results Aqueous extracts contained more anti-viral activity than did ethanol extracts, displaying potent antiviral activity against HIV-1 at sub μg/mL concentrations with little to no cellular cytotoxicity at concentrations more than 100-fold higher. Time-of-addition studies demonstrated that aqueous extracts were effective when added during the first five hours following initiation of infection, suggesting that the botanical constituents were targeting entry events. Further analysis revealed that extracts inhibited both virus/cell interactions and post-binding events. While only 40% inhibition was maximally achieved in our virus/cell interaction studies, extract effectively blocked post-binding events at concentrations similar to those that blocked infection, suggesting that it was targeting of these latter steps that was most important for mediating inhibition of virus infectivity. Conclusions We demonstrate that aqueous P. vulgaris extracts inhibited HIV-1 infectivity. Our studies suggest that inhibition occurs primarily by interference of early, post-virion binding events. The ability of aqueous extracts to inhibit early events within the HIV life cycle suggests that these extracts, or purified constituents responsible for the antiviral activity, are promising microbicides and/or antivirals against HIV-1. PMID:21513560

  9. Increased immunoglobulin G, but not M, binding to endogenous retroviral antigens in HIV-1 infected persons.

    PubMed

    Lawoko, A; Johansson, B; Rabinayaran, D; Pipkorn, R; Blomberg, J

    2000-12-01

    The modes of interaction between products of human endogenous retroviral (HERV) sequences and the immune system are largely unknown. In HIV infected persons, an exogenous retrovirus adds further complexity to the situation. Therefore, 14 synthetic peptides with sequences derived from conserved regions of various endogenous retroviruses (ERVs) and from related exogenous retroviruses were used to search for IgG and IgM antibodies that bind to such antigens in 15 HIV-1 seropositive and 17 seronegative immunosuppressed patients. IgG binding to three peptides, namely, the C-terminal half of murine leukemia virus (MLV) capsid protein, the conserved portion of HERV-H transmembrane protein, and the Pol region of human mouse mammary tumor virus (MMTV)-like (HML3) sequence, was observed in both groups. Binding was, however, more frequent and more firm in HIV-1 positive samples (P<0.0001, Wilcoxon rank sum test). IgM binding to the same peptides showed no significant differentiation between the two groups of patients. Binding to both immunoglobulin isotypes was sometimes variable over time in both groups. No correlation of either IgG or IgM peptide binding with progression to AIDS in HIV-1 infected individuals was observed. Inhibition studies using analogous endogenous and exogenous retroviral peptides, including HIV-1, demonstrated specificity of the IgG antibodies for a narrow range of MLV- and MMTV-like retroviral antigens, and excluded cross-reactivity of antibodies to HIV-1 as a cause of these observations. Thus, unlike IgG, IgM binding to retroviral antigens was ubiquitous. It is suggested that anti-HERV IgM belong to a class of natural antibodies and might serve as primers in the mediation of humoral immune responses to more or less related exogenous retroviruses. Increased IgG binding in HIV-1 infected individuals could result from such priming, or reflect higher HERV antigen expression.

  10. Emotional state and dreams in pregnant women.

    PubMed

    Mancuso, Alfredo; De Vivo, Antonio; Fanara, Giusi; Settineri, Salvatore; Giacobbe, Annamaria; Pizzo, Alfonsa

    2008-09-30

    The aim of this study was to investigate the frequency of recall and the content of dreams during pregnancy, as well as their correlation with socio-demographic, obstetric and physician-patients relationship variables, emotional state and duration of labour. A questionnaire, designed to analyse background characteristics, was given to 290 women in the third trimester of gestation. The psychiatric analysis of anxiety and depression was performed using the Hamilton Rating Scale for Anxiety and the Montgomery-Asberg Depression Rating Scale, while dreams were divided into masochistic and pleasant according to Beck's criteria. Oneiric activity was found to be associated with age >or= 35 years, higher family income, higher educational level, and a "satisfactory" physician-patient relationship. Masochistic content was associated with age<35 years, quality of information and frequent thoughts of delivery. Concerning the emotional state, depression levels were higher in women reporting masochistic dreams, while no difference in anxiety levels was found. Labour duration was shorter in the dreamer group and in patients with masochistic dream content. These findings may indicate that, also in pregnancy, the number and the content of dreams are influenced by women's mood and that the evaluation of the oneiric activity might represent a useful tool for clinicians either to investigate the women's emotional state or to predict its repercussions on the course of labour.

  11. [Pregnant women's sick leave is behind the increased sick leave among women of fertile age. A study of pregnant women's sick leave 1978-1997].

    PubMed

    Sydsjö, A; Sydsjö, G

    2001-08-08

    Sick leave rates among pregnant women have been found to vary substantially over time. 8,884 woman delivered at Linköping and Värnamo Women's Clinics in 1978, 1986, 1988, 1992, 1995 and 1997 were studied. Sick leave nearly doubled between 1978 and 1986, and dropped back to the 1978 level in 1997. The somewhat paradoxical findings in our surveys indicate that attitudes, especially as observed in the youngest age groups, together with a sensible adaptation to the prevailing terms of the social security system, may well be the most plausible explanation. Studies on sick leave among women of fertile age should preferably also contain information on the proportion of sick-listed pregnant women, as a small proportion of pregnant women may have a profound impact on sick leave statistics among all insured women of fertile age.

  12. Attitudes of pregnant women towards participation in perinatal epidemiological research.

    PubMed

    Nechuta, Sarah; Mudd, Lanay M; Biery, Lynette; Elliott, Michael R; Lepkowski, James M; Paneth, Nigel

    2009-09-01

    We assessed attitudes of a multi-ethnic sample of pregnant women in regard to participation in five data collection procedures planned for use in the National Children's Study. A cross-sectional survey was conducted in nine prenatal clinics in Kent County, Michigan between April and October 2006. Women were approached in clinic waiting rooms at the time of their first prenatal visit and 311 (91.0%) participated. Women were asked about their willingness to participate, and the smallest amount of compensation required for participation in a 45-min in-person interview, a 15-min telephone interview, maternal and infant medical record abstraction, and an infant physical examination. Percentages for willingness to participate were highest for telephone interview (83%), followed by in-person interview (60%), infant examination (57%), and maternal (56%) and infant medical records (54%). About 34-48% of women reported that no compensation would be required for participation by data procedure. Some women reported unwillingness to participate in telephone (9%) or personal (17%) interview, record abstraction (34%) or infant examination (26%), even with compensation. Education greater than high school was associated with increased odds of refusal for infant physical examination, adjusted odds ratio 2.44 [95% confidence interval 1.41, 4.23]. In conclusion, 9-34% of pregnant women, depending on procedure, stated they would not participate in non-invasive research procedures such as medical record abstraction and infant examination, even with compensation. Resistance to these research procedures was especially noted among more highly educated women. Planning for the National Children's Study will have to address potential resistance to research among pregnant women.

  13. Rural pregnant women's stressors and priorities for stress reduction.

    PubMed

    Bloom, Tina L; Bullock, Linda F C; Parsons, Lindsay

    2012-12-01

    Rural residence and maternal stress are risk factors for adverse maternal-child health outcomes across the globe, but rural women have been largely overlooked in maternal stress research. We recruited low-income, rural pregnant women for qualitative interviews to explore their stress exposures during pregnancy, reactions to stress, and priorities for stress reduction. We also used quantitative measures (Perceived Stress Scale, Center for Epidemiologic Studies of Depression Scale-Revised, Posttraumatic Stress Disorder Checklist-Civilian, Lifetime Exposure to Violence Scale) to describe stress exposures and reactions. We interviewed 24 pregnant rural women from a Midwestern US state, who were primarily young, white, partnered, and unemployed. Women's predominant stressor was financial stress, compounded by a lack of employment, transportation, and affordable housing options; extended family interdependence; small-town gossip; isolation/loneliness; and boredom. Quantitative measures revealed high levels of global perceived stress, violence exposure, and symptoms of depression and posttraumatic stress disorder among the sample. Women most commonly reported that employment and interventions to increase their employability would most effectively decrease their stress, but faced numerous barriers to education or job training. Tested maternal stress interventions to date include nurse-case management, teaching women stress management techniques, and mind-body interventions. Pregnant women's own priorities for stress-reduction intervention may differ, depending on the population under study. Our findings suggest that rural clinicians should address maternal stress, violence exposure, and mental health symptoms in prenatal care visits and that clinicians and researchers should include the voices of rural women in the conceptualization, design, implementation, and evaluation of maternal stress-reduction interventions.

  14. Prevalence of various antiphospholipid antibodies in pregnant women.

    PubMed

    Fialová, L; Mikulíková, L; Matous-Malbohan, I; Benesová, O; Zwinger, A

    2000-01-01

    Antiphospholipid antibodies (APAs) are characterized as a heterogeneous population of autoantibodies directed against different target antigens, predominantly anionic phospholipids or phospholipid-containing structures. The presence of APAs has been strongly associated with a variety of clinical disorders including adverse pregnancy complications such as spontaneous abortions, pregnancy-induced hypertension, preeclampsia and intrauterine growth retardation. The purpose of this study was to compare the prevalence of anticardiolipin antibodies (ACAs), which are routinely examined, with APAs directed against phosphatidylserine (APS), phosphatidylinositol (API), phosphatidylethanolamine (APE) and phosphatidylcholine (APC) in the sera of pregnant women. We examined 410 serum samples of pregnant women hospitalized in the department for pathological pregnancies. They underwent prenatal biochemical screening of fetal congenital abnormalities in the first and the second trimester of gravidity. Anticardiolipin IgG and IgM were measured using commercial ELISA kits (ImmuLisa Anti-Cardiolipin Antibody), whereas APS, APE, API and APC were determined by our modified ELISA kit. Among 410 pregnant women we found 21 patients (5.1%) positive for ACA IgG (>20 GPL) and 30 patients (7.3%) positive for ACA IgM (>10 MPL). It was found that 7.8% of pregnant women had at least one high-titer APA IgG and 9.8% high-titer APA IgM. One third of ACA IgG or IgM positive sera contained polyspecific autoantibodies reactive to at least two various phospholipids. In the group of IgG ACA positive women, 28.6% patients were positive for APS, 28.6% were positive or moderately positive for API, 23.8% for APC and 19% for APE. In the group of IgM ACA positive women, 33.3% were also positive for APS, 26.7% for APE, 26.7% for API and 23.3% for APC were present. IgG and IgM ACA negative patients exhibited a significantly lower incidence of other APA than the group of ACA positive pregnant women. It still

  15. Bacterial sensitivity to fosfomycin in pregnant women with urinary infection.

    PubMed

    Souza, Rodrigo Batista; Trevisol, Daisson José; Schuelter-Trevisol, Fabiana

    2015-01-01

    The aim this study was to determine the in vitro susceptibility to fosfomycin of bacteria isolated from urine samples of pregnant women with urinary tract infection. Samples of urine culture with bacterial growth of pregnant women were collected from clinical laboratories in Tubarão, state of Santa Catarina, Brazil, between September 2012 and May 2013. In the experimental stage, the colonies were tested for sensitivity to fosfomycin by using the Kirby-Bauer method. The following information relating to the samples was also collected: patients' age, colony count, type(s) of identified bacterial(s) and result of the antimicrobial sensitivity test. Student's t-test was used for mean comparison. A total of 134 samples were selected for the study. The age of the subjects ranged from 15 to 40 years (mean 26.7). Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) were the most commonly identified species. In 89% of cases, the microorganisms were sensitive to fosfomycin. E. coli and S. aureus were the main species of bacteria responsible for urinary tract infections in women in the study area. The most prevalent microorganisms in pregnant women with urinary tract infection were susceptible to fosfomycin.

  16. [Correlativity of subtype B viral transmission among elderly HIV-1 infected individuals in Yongding district, Zhangjiajie city, Hunan province].

    PubMed

    Wu, Y Q; Zou, X B; Qin, R; He, J M; Zhang, P F; Jiang, Y; Chen, G M; Yang, Y J; Chen, X

    2016-12-10

    Objective: To investigate the characteristics of transmission correlativity regarding subtype B among elderly HIV-1 infected individuals in Yongding district, Zhangjiajie city, Hunan province and to explore a method on its traceability. Methods: A total of 43 newly diagnosed elderly HIV-1 Infected individuals in Yongding district were enrolled in this study. Pol area genes were amplified and sequenced by 'In house' method. Methods used to analyze the relationship related to HIV individuals transmission would include Bayesian phylogenetic tree and other epidemiological ones. Results: A total of 42 valid sequences were successfully obtained, with predominant strain as subtype B (80.95%, 34/42). All the 42 sequences were gathered into eight clusters. In each cluster, the genetic distance was significantly shorter than the average from the 34 subtype B strains (0.058 3). The HIV-1 infected individuals in one cluster had the same high-risk behaviors and the significantly patchy distributions were identified at the sites where the high-risk behaviors existed. Our results indicated that the local elderly HIV-infected individuals had high level of homology between geographical position and related behaviors. Conclusions: The patchy distribution between geographical position and behavior was associated among the elderly HIV-1 infected individuals. Guidance related to epidemic precise positioning and effective interventions was provided through the findings of this study.

  17. [Application progress of CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection].

    PubMed

    Han, Yinglun; Li, Qingwei

    2016-01-01

    The goal of gene therapy is to introduce foreign genes into human target cells in a certain way to correct or compensate diseases caused by defective or abnormal genes. Therefore, gene therapy has great practical significance in studying the treatment of persistent or latent HIV-1 infection. At present, the existing methods of gene therapy have some major defects such as limited target site recognition and high frequency of off-targets. The latest research showed that the clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR-associated nuclease 9 (Cas9) system from bacteria and archaea has been successfully reformed to a targeted genome editing tool. Thus, how to achieve the goal of treating HIV-1 infection by modifying targeted HIV-1 virus genome effectively using the CRISPR/Cas9 system has become a current research focus. Here we review the latest achievements worldwide and briefly introduce applications of the CRISPR/Cas9 genome editing technology in the treatment of HIV-1 infection, including CCR5 gene editing, removal of HIV-1 virus and activation of HIV-1 virus, in order to provide reference for the prevention and treatment of HIV-1 infection.

  18. Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

    PubMed Central

    Carryl, Heather; Swang, Melanie; Lawrence, Jerome; Curtis, Kimberly; Kamboj, Herman; Van Rompay, Koen K. A.; De Paris, Kristina; Burke, Mark W.

    2015-01-01

    Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1, neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems. PMID:26034832

  19. Knowledge and beliefs regarding oral health among pregnant women

    PubMed Central

    Boggess, Kim A.; Urlaub, Diana M.; Moos, Merry-K; Polinkovsky, Margaret; El-Khorazaty, Jill; Lorenz, Carol

    2015-01-01

    Background Racial or ethnic and economic disparities exist in terms of oral diseases among pregnant women and children. The authors hypothesized that women of a racial or ethnic minority have less oral health knowledge than do women not of a racial or ethnic minority. Therefore, the authors conducted a study to assess and compare maternal oral health knowledge and beliefs and to determine if maternal race and ethnicity or other maternal factors contributed to women’s knowledge or beliefs. Methods The authors administered a written oral health questionnaire to pregnant women. The authors calculated the participants’ knowledge and belief scores on the basis of correct answers or answers supporting positive oral health behaviors. They conducted multivariable analysis of variance to assess associations between oral health knowledge and belief scores and characteristics. Results The authors enrolled 615 women in the study, and 599 (97.4 percent) completed the questionnaire. Of 599 participants, 573 (95.7 percent) knew that sugar intake is associated with caries. Almost one-half (295 participants [49.2 percent]) did not know that caries and periodontal disease are oral infections. Median (interquartile range) knowledge and belief scores were 6.0 (5.5–7.0) and 6.0 (5.0–7.0), respectively. Hispanic women had median (interquartile range) knowledge and belief scores significantly lower than those of white or African American women (6.0 [4.0–7.0] versus 7.0 [6.0–7.0] versus 7.0 [6.0–7.0], respectively [P < .001]; and 5.0 [4.0–6.0] versus 6.0 [5.0–7.0] versus 6.0 [5.0–7.0], respectively [P < .001]). Multivariable analysis of variance results showed that being of His-panic ethnicity was associated significantly with a lower knowledge score, and that an education level of eighth grade or less was associated significantly with a lower belief score. Conclusions Pregnant women have some oral health knowledge. Knowledge varied according to maternal race or

  20. Urinary excretion of parabens in pregnant Japanese women.

    PubMed

    Shirai, Sayaka; Suzuki, Yayoi; Yoshinaga, Jun; Shiraishi, Hiroaki; Mizumoto, Yoshifumi

    2013-01-01

    Urinary excretion of free and total (free plus conjugated) forms of methyl, ethyl, n-propyl and n-butyl parabens (MP, EP, PP and BP, respectively) and their metabolite p-hydroxybenzoic acid were measured for 111 pregnant Japanese women. Frequent detection of parabens and their metabolite indicated that exposure takes place daily for pregnant Japanese women. The estrogenic potency of PP was 20 times higher than those of the other 3 parabens for the present subjects when both abundance in the urine and the relative estrogenic activity of each compound was considered. Detection of free parabens suggested dermal exposure, probably from their inclusion in personal care products. No statistical association was found between the anogenital index (birth weight-adjusted AGD) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects.

  1. Inhaled beclomethasone in pregnant asthmatic women--a systematic review.

    PubMed

    de Aguiar, M M; da Silva, H J; Rizzo, J Â; Leite, D F B; Silva Lima, M E P L; Sarinho, E S C

    2014-01-01

    The aim of this study was to systematically review the safety and efficacy of inhaled beclomethasone for asthma treatment in pregnant women. We performed a systematic review in Medline, LILACS and SciELO electronic databases in December 2012. A total of 3433 articles were found by using the keywords asthma, pregnancy and beclomethasone. Among these, 1666 were from Medline, via PubMed, and 1767 were from LILACS and SciELO. Nine of these articles were selected. Only one paper suggested an increased foetal risk for congenital malformations, and one other for offspring endocrine and metabolic disturbances. Data are mostly reassuring, supporting the use of glucocorticoid inhalants during pregnancy, and we found no evidence of inferiority in relation to efficacy and safety of beclomethasone compared to other drugs used in pregnant asthmatic women.

  2. Serum metabolic profiles of pregnant women with burdened obstetrical history.

    PubMed

    Khaustova, S A; Senyavina, N V; Tonevitsky, A G; Eremina, O V; Pavlovich, S V

    2013-11-01

    The content of low-molecular-weight components in blood serum was studied by tandem mass-spectrometry in pregnant women. Serum metabolic profiles of patients with a grave obstetrical history were detected. The most significant changes were observed for the concentrations of low-molecular-weight substances involved in glucogenesis and β-oxidation processes and in metabolic chains involving carbohydrates, carnitines, amino acids, and lipids.

  3. [Magnesium orotate in treatment of chronic hypertension in pregnant women].

    PubMed

    Gaĭsin, I R; Valeeva, R M; Maksimov, N I; Iskhakova, A S; Khodyrev, L A; Shilina, L V

    2013-01-01

    We examined 150 pregnant women with essential hypertension (EHT), EHT and connective tissue dysplasia (CTD), and healthy. Presence of CTD aggravated clinical picture of EHT and was associated with pronounced cardialgic, neurological, asthenic, vertebrogenic, visceral, and other syndromes. The use of antihypertensive, metabolic (magnesium orotate) drugs, sedative and uroseptic phytotherapy, application of other nondrug measures in conditions of multidisciplinary dynamic support of the gestational period facilitated regress of clinical symptoms of EHT and EHT+CTD, favorable course of pregnancy and successful delivery.

  4. Oxidative Profile and δ-Aminolevulinate Dehydratase Activity in Healthy Pregnant Women with Iron Supplementation

    PubMed Central

    De Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B.; Neme, Walter S.; Gallarreta, Francisco M. P.; Gonçalves, Thissiane L.

    2016-01-01

    An oxidative burst occurs during pregnancy due to the large consumption of oxygen in the tissues and an increase in metabolic demands in response to maternal physiological changes and fetal growth. This study aimed to determine the oxidative profile and activity of δ-aminolevulinate dehydratase (δ-ALA-D) in pregnant women who received iron supplementation. Oxidative stress parameters were evaluated in 25 pregnant women with iron supplementation, 25 pregnant women without supplementation and 25 non-pregnant women. The following oxidative stress parameters were evaluated: thiobarbituric acid reactive substances (TBARS), protein thiol groups (P-SH), non-protein thiol levels (NP-SH), vitamin C levels, catalase and δ-ALA-D activity. Markers of oxidative stress and cell damage, such as TBARS in plasma were significantly higher in pregnant women without supplementation. Levels of P-SH, NP-SH and δ-ALA-D activity were significantly lower in pregnant women without supplementation compared to non-pregnant and pregnant women with supplementation, while vitamin C levels were significantly lower in pregnant women without supplementation when compared to non-pregnant women. The increase in the generation of oxidative species and decrease of antioxidants suggest the loss of physiological oxidative balance during normal pregnancy, which was not observed in pregnant women with iron supplementation, suggesting a protective effect of iron against oxidative damage. PMID:27153075

  5. Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4(+) T Cells.

    PubMed

    St Gelais, Corine; Roger, Jonathan; Wu, Li

    2015-08-01

    HIV-1 interacts with numerous cellular proteins during viral replication. Identifying such host proteins and characterizing their roles in HIV-1 infection can deepen our understanding of the dynamic interplay between host and pathogen. We previously identified non-POU domain-containing octamer-binding protein (NonO or p54nrb) as one of host factors associated with catalytically active preintegration complexes (PIC) of HIV-1 in infected CD4(+) T cells. NonO is involved in nuclear processes including transcriptional regulation and RNA splicing. Although NonO has been identified as an HIV-1 interactant in several recent studies, its role in HIV-1 replication has not been characterized. We investigated the effect of NonO on the HIV-1 life cycle in CD4(+) T cell lines and primary CD4(+) T cells using single-cycle and replication-competent HIV-1 infection assays. We observed that short hairpin RNA (shRNA)-mediated stable NonO knockdown in a CD4(+) Jurkat T cell line and primary CD4(+) T cells did not affect cell viability or proliferation, but enhanced HIV-1 infection. The enhancement of HIV-1 infection in Jurkat T cells correlated with increased viral reverse transcription and gene expression. Knockdown of NonO expression in Jurkat T cells modestly enhanced HIV-1 gag mRNA expression and Gag protein synthesis, suggesting that viral gene expression and RNA regulation are the predominantly affected events causing enhanced HIV-1 replication in NonO knockdown (KD) cells. Furthermore, overexpression of NonO in Jurkat T cells reduced HIV-1 single-cycle infection by 41% compared to control cells. Our data suggest that NonO negatively regulates HIV-1 infection in CD4(+) T cells, albeit it has modest effects on early and late stages of the viral life cycle, highlighting the importance of host proteins associated with HIV-1 PIC in regulating viral replication.

  6. Altered T cell surface glycosylation in HIV-1 infection results in increased susceptibility to galectin-1-induced cell death.

    PubMed

    Lantéri, Marion; Giordanengo, Valérie; Hiraoka, Nobuyoshi; Fuzibet, Jean-Gabriel; Auberger, Patrick; Fukuda, Minoru; Baum, Linda G; Lefebvre, Jean-Claude

    2003-12-01

    The massive T cell death that occurs in HIV type 1 (HIV-1) infection contributes profoundly to the pathophysiology associated with AIDS. The mechanisms controlling cell death of both infected and uninfected T cells ("bystander" death) are not completely understood. We have shown that HIV-1 infection of T cells results in altered glycosylation of cell surface glycoproteins; specifically, it decreased sialylation and increased expression of core 2 O-glycans. Galectin-1 is an endogenous human lectin that recognizes these types of glycosylation changes and induces cell death of activated lymphocytes. Therefore we studied the possible contribution of galectin-1 in the pathophysiology of AIDS. O-glycan modifications were investigated on peripheral lymphocytes from AIDS patients. Oligosaccharides from CD43 and CD45 of CEM cells latently infected with HIV-1 were chemically analyzed. Consistent with our previous results, we show that HIV-1 infection results in accumulation of exposed lactosamine residues, oligosaccharides recognized by galectin-1 on cell surface glycoproteins. Both latently HIV-1-infected T cell lines and peripheral CD4 and CD8 T cells from AIDS patients exhibited exposed lactosamine residues and demonstrated marked susceptibility to galectin-1-induced cell death, in contrast to control cultures or cells from uninfected donors. The fraction of cells that died in response to galectin-1 exceeded the fraction of infected cells, indicating that death of uninfected cells occurred. Altered cell surface glycosylation of T cells during HIV-1 infection increases the susceptibility to galectin-1-induced cell death, and this death pathway can contribute to loss of both infected and uninfected T cells in AIDS.

  7. Kinetics of human immunodeficiency virus type 1 (HIV-1) DNA and RNA synthesis during primary HIV-1 infection.

    PubMed Central

    Graziosi, C; Pantaleo, G; Butini, L; Demarest, J F; Saag, M S; Shaw, G M; Fauci, A S

    1993-01-01

    HIV-1 replication and viral burden in peripheral blood mononuclear cells (PBMC) have been reported to be high in primary infection but generally very low during the prolonged period of clinical latency. It is uncertain precisely when this transition occurs during the HIV-1 infection and what the relationship is between the changes in HIV-1 replication versus the clearance of infected cells in the overall control of viral replication. In the present study, the kinetics of viral burden (i.e., frequency of HIV-1-infected cells) and replication during primary and early-chronic infection were analyzed in PBMC of four acutely infected individuals. High frequencies of HIV-1-infected cells and high levels of virus replication were observed in PBMC after primary HIV-1 infection. Down-regulation of virus replication in PBMC was observed in all four patients coincident with the emergence of HIV-1-specific immune responses. Other parameters of virus replication, such as circulating plasma p24 antigen and plasma viremia showed similar kinetics. In contrast, a significant decline in viral burden in PBMC was observed in only one of four patients. These results indicate that the down-regulation in the levels of virus replication associated with the clinical transition from acute to chronic infection does not necessarily reflect a reduction in viral burden, thus suggesting the involvement of additional factors. Identification of these factors will be important in elucidating the host mechanisms involved in the early control of HIV-1 infection and disease. Images Fig. 1 Fig. 2 Fig. 3 PMID:8341646

  8. Nef Neutralizes the Ability of Exosomes from CD4+ T Cells to Act as Decoys during HIV-1 Infection

    PubMed Central

    da Silva, Elaine Z. M.; Silveira, Paola P.; da Silva-Januário, Mara E.; Arruda, Eurico; Jamur, Maria C.; Oliver, Constance; Aguiar, Renato S.; daSilva, Luis L. P.

    2014-01-01

    Nef is an HIV-1 accessory protein that promotes viral replication and pathogenesis. A key function of Nef is to ensure sustained depletion of CD4 and MHC-I molecules in infected cells by inducing targeting of these proteins to multivesicular bodies (MVBs), and ultimately to lysosomes for degradation. Nef also affects cellular secretory routes promoting its own secretion via exosomes. To better understand the effects of Nef on the exocytic pathway, we investigated whether this viral factor modifies the composition of exosomes released by T lymphocytes. We showed that both CD4 and MHC-I molecules are secreted in exosomes from T cells and that the expression of Nef reduces the amount of these proteins in exosomes. To investigate the functional role for this novel activity of Nef, we performed in vitro HIV-1 infection assays in the presence of distinct populations of exosomes. We demonstrated that exosomes released by CD4+ T cells, but not CD4− T cells, efficiently inhibit HIV-1 infection in vitro. Because CD4 is the main receptor for HIV-1 infection, these results suggest that CD4 molecules displayed on the surface of exosomes can bind to envelope proteins of HIV-1 hindering virus interaction with target cells and infection. Importantly, CD4-depleted exosomes released by CD4+ T cells expressing Nef have a reduced capacity to inhibit HIV-1 infection in vitro. These results provide evidence that Nef promotes HIV-1 infection by reducing the expression of CD4 in exosomes from infected cells, besides the original role of Nef in reducing the CD4 levels at the cell surface. PMID:25423108

  9. Perturbations of Monocyte Subsets and Their Association with T Helper Cell Differentiation in Acute and Chronic HIV-1-Infected Patients

    PubMed Central

    Chen, Peng; Su, Bin; Zhang, Tong; Zhu, Xiaojing; Xia, Wei; Fu, Yan; Zhao, Guoxian; Xia, Huan; Dai, Lili; Sun, Lijun; Liu, Lifeng; Wu, Hao

    2017-01-01

    Monocytes have been recently subdivided into three subsets: classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) subsets, but phenotypic and functional abnormalities of the three monocyte subsets in HIV-1 infection have not been fully characterized, especially in acute HIV-1 infection (AHI). In the study, we explored the dynamic changes of monocyte subsets and their surface markers, and the association between monocyte subsets and the IFN-γ, interleukin (IL)-4, IL-17, and TNF-α producing CD4+ T cells in acute and chronic HIV-1-infected patients. We found that, in the acute HIV-1-infected individuals, the frequency of the intermediate CD14++CD16+ monocyte subsets, the CD163 density and HLA-DR density on intermediate CD14++CD16+ monocytes, and plasma soluble form of CD163 (sCD163) were significantly higher than that in healthy controls. Intermediate CD14++CD16+ monocyte subsets and their HLA-DR expression levels were inversely correlated with the CD4+ T cell counts, and the intermediate CD14++CD16+ monocytes were positively correlated with plasma sCD163. In contrast to the non-classical CD14+CD16++ and classical CD14++CD16− monocyte subsets, the frequency of the intermediate CD14++CD16+ monocytes was positively associated with the frequency of IFN-γ and IL-4 producing CD4+ T cells in HIV-1-infected patients. Taken together, our observations provide new insight into the roles of the monocyte subsets in HIV pathogenesis, particularly during AHI, and our findings may be helpful for the treatment of HIV-related immune activation. PMID:28348563

  10. No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

    PubMed Central

    Jones, Aksana Kaefer; Santini-Oliveira, Marilia; Taylor, Graham P.; Patterson, Kristine B.; Nilius, Angela M.; Klein, Cheri Enders

    2015-01-01

    Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC0–12) and concentration prior to dosing (Cpredose) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC0–12 or Cpredose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy

  11. Violence and Pregnancy: Are Pregnant Women at Greater Risk of Abuse?

    ERIC Educational Resources Information Center

    Gelles, Richard J.

    1988-01-01

    Examined data from Second National Family Violence Survey. Found women under age 25 to be more likely than older women to be both pregnant and to be hit and abused by husbands and partners. Although pregnant women were not particularly vulnerable group, pregnancy did not insulate them from high rates of violence experienced by young women.…

  12. Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells

    PubMed Central

    Jimenez-Moyano, Esther; Ruiz, Alba; Kløverpris, Henrik N.; Rodriguez-Plata, Maria T.; Peña, Ruth; Blondeau, Caroline; Selwood, David L.; Izquierdo-Useros, Nuria; Moris, Arnaud; Clotet, Bonaventura; Goulder, Philip; Towers, Greg J.

    2016-01-01

    ABSTRACT Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type 1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two nonhuman TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T-cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the nonimmunosuppressive analog of cyclosporine (CsA), sarcosine-3(4-methylbenzoate)–CsA (SmBz-CsA), we found a significant reduction in CD107a/MIP-1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for nonhuman TRIM5 variants in cellular immunity. We hypothesize that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The nonhuman TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM

  13. Virtual traumatology of pregnant women: the PRegnant car Occupant Model for Impact Simulations (PROMIS).

    PubMed

    Auriault, F; Thollon, L; Peres, J; Delotte, J; Kayvantash, K; Brunet, C; Behr, M

    2014-01-03

    This study report documents the development of a finite element (FE) model for analyzing trauma in pregnant women involved in road accidents and help the design of a specific safety device. The model is representative of a 50th percentile pregnant woman at 26 weeks of pregnancy in sitting position. To achieve this, the HUMOS 2 model, which has been validated in a wide range of dynamic tests, was scaled to the morphology of a woman in the 50th percentile and coupled with a model of gravid uterus. During scaling, special attention was paid to the pelvic region which is known to differ considerably in morphological terms between men and women. The gravid uterus model includes a placenta, a fetus, uterosacral ligaments and the amniotic fluid by means of fluid structure interaction formulation. The uterus and the female model were coupled using an original method whereby the growth of an uterus was simulated to compress the abdominal organs in a realistic manner. The model was validated based on experimental tests described in the literature. Additional tests based on abdominal loadings with a seatbelt on Post Mortem Human Surrogates (PMHS) coupled to silicone uterus were also performed. Results highlighted the role of the possible interaction of the fetus in the pregnant woman abdominal response. Experimental corridors taking into account the presence of this fetus could therefore be proposed.

  14. Predictors of Prenatal Empowerment Among Iranian Pregnant Women

    PubMed Central

    Borghei, Narjes Sadat; Taghipour, Ali; Roudsari, Robab Latifnejad; Keramat, Afsaneh; Noghabi, Hadi Jabbari

    2016-01-01

    Introduction Considering that empowering expectant mothers is an important issue to maintain a healthy pregnancy, this study was conducted to evaluate the predictors of empowerment among Iranian pregnant women. Methods This cross sectional study was conducted in Golestan, North of Iran in 2015. A total number of 161 pregnant women were selected through random cluster sampling from urban health centers, using PASS software. The socio-political, educational, and mental-financial predictors of empowerment were measured using a self-structured questionnaire during pregnancy and was analyzed by a linear regression model using SPSS version 16. Results The findings of linear regression showed that educational dimension of empowerment had the highest coefficient in the regression model, on total empowerment (βeta standardized coefficient [β]=0.696 with DW=1.830 and means error=0). The total empowerment score of pregnant women was controlled by individual factors such as the age of marriage (β-0.228), employment (β-0.210), and educational factors such as participation in prenatal education classes (β-0.246), and moral issues such as sense of spiritual support (β-0.217). Conclusion By recognizing and observing predictors of empowerment during pregnancy, health care providers can increase women’s power over their pregnancy. Educational predictors of empowerment were the most important factors to empower women during pregnancy. The objective of childbirth education classes, therefore, should shift from simply giving information to women, towards giving them appropriate knowledge in order to provide them with empowerment during pregnancy. PMID:27790351

  15. Assessment of Recent HIV-1 Infection by a Line Immunoassay for HIV-1/2 Confirmation

    PubMed Central

    Schüpbach, Jörg; Gebhardt, Martin D; Tomasik, Zuzana; Niederhauser, Christoph; Yerly, Sabine; Bürgisser, Philippe; Matter, Lukas; Gorgievski, Meri; Dubs, Rolf; Schultze, Detlev; Steffen, Ingrid; Andreutti, Corinne; Martinetti, Gladys; Güntert, Bruno; Staub, Roger; Daneel, Synove; Vernazza, Pietro

    2007-01-01

    Background Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this “recency” information can also be gained from an HIV confirmatory assay. Methods and Findings The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (≤ 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two

  16. Notwithstanding Circumstantial Alibis, Cytotoxic T Cells Can Be Major Killers of HIV-1-Infected Cells

    PubMed Central

    Gadhamsetty, Saikrishna; Coorens, Tim

    2016-01-01

    ABSTRACT Several experiments suggest that in the chronic phase of human immunodeficiency virus type 1 (HIV-1) infection, CD8+ cytotoxic T lymphocytes (CTL) contribute very little to the death of productively infected cells. First, the expected life span of productively infected cells is fairly long, i.e., about 1 day. Second, this life span is hardly affected by the depletion of CD8+ T cells. Third, the rate at which mutants escaping a CTL response take over the viral population tends to be slow. Our main result is that all these observations are perfectly compatible with killing rates that are much faster than one per day once we invoke the fact that infected cells proceed through an eclipse phase of about 1 day before they start producing virus. Assuming that the major protective effect of CTL is cytolytic, we demonstrate that mathematical models with an eclipse phase account for the data when the killing is fast and when it varies over the life cycle of infected cells. Considering the steady state corresponding to the chronic phase of the infection, we find that the rate of immune escape and the rate at which the viral load increases following CD8+ T cell depletion should reflect the viral replication rate, ρ. A meta-analysis of previous data shows that viral replication rates during chronic infection vary between 0.5 ≤ ρ ≤ 1 day−1. Balancing such fast viral replication requires killing rates that are several times larger than ρ, implying that most productively infected cells would die by cytolytic effects. IMPORTANCE Most current data suggest that cytotoxic T cells (CTL) mediate their control of human immunodeficiency virus type 1 (HIV-1) infection by nonlytic mechanisms; i.e., the data suggest that CTL hardly kill. This interpretation of these data has been based upon the general mathematical model for HIV infection. Because this model ignores the eclipse phase between the infection of a target cell and the start of viral production by that cell, we

  17. Seroprevalence and vaccination coverage of vaccine-preventable diseases in perinatally HIV-1-infected patients

    PubMed Central

    Sticchi, Laura; Bruzzone, Bianca; Caligiuri, Patrizia; Rappazzo, Emanuela; Lo Casto, Michele; De Hoffer, Laura; Gustinetti, Giulia; Viscoli, Claudio; Di Biagio, Antonio

    2014-01-01

    Background Even in the era of highly active antiretroviral therapy (HAART), HIV-infected subjects are at higher risk of complications from vaccine-preventable diseases than those uninfected. The current international guidelines strongly recommend that these patients should receive all the routine childhood vaccinations. Although these children represent an appropriate target for immunization, the available data indicate suboptimal coverage rates. Methods To evaluate seroprotection/seropositivity rates and vaccination coverage against the common vaccine-preventable diseases, all patients with vertically transmitted HIV-1 infection who attended San Martino Hospital were enrolled. Blood samples were collected for testing antibodies against diphtheria, tetanus, hepatitis A and B viruses by Enzyme-Linked ImmunoSorbent Assay and polioviruses by microneutralization test. In order to assess immunization coverage, retrospectively was recorded the vaccination history collecting data from Regional Immunization Database. Results A total of 39 perinatally HIV-1 infected patients were included in the study. At the time of serum was obtained, the mean age was 18,1 years (range: 6–28). The median CD4+ T-lymphocyte count was 702 cells/mm3 (2–1476 cells/mm3). Twenty-nine (74.4%) patients were found with HIV RNA load < 50 copies/mL. The proportion of subjects with protective anti-tetanus and anti-HBs were 43.6% and 30.8%, respectively. Seroprotection rates about 20% against rubella and measles were found, less than 20% against all the other antigens investigated. In particular, all patients resulted susceptible to mumps. High immunization rates were observed for polio and HBV (100% and 92.3%, respectively) and suboptimal for diphtheria-tetanus (84.6%). For the other recommended vaccines the rates were generally low. None of the patients received varicella vaccine doses. Conclusions As in the HAART era the vertically acquired HIV infection has become a chronic treatable disease

  18. Stressors, Resources, and Stress Responses in Pregnant African American Women

    PubMed Central

    Giurgescu, Carmen; Kavanaugh, Karen; Norr, Kathleen F.; Dancy, Barbara L.; Twigg, Naomi; McFarlin, Barbara L.; Engeland, Christopher G.; Hennessy, Mary Dawn; White-Traut, Rosemary C.

    2013-01-01

    This research aimed to develop an initial understanding of the stressors, stress responses, and personal resources that impact African American women during pregnancy, potentially leading to preterm birth. Guided by the ecological model, a prospective, mixed-methods, complementarity design was used with 11 pregnant women and 8 of their significant others. Our integrated analysis of quantitative and qualitative data revealed 2 types of stress responses: high stress responses (7 women) and low stress responses (4 women). Patterns of stress responses were seen in psychological stress and cervical remodeling (attenuation or cervical length). All women in the high stress responses group had high depression and/or low psychological well-being and abnormal cervical remodeling at one or both data collection times. All but 1 woman had at least 3 sources of stress (racial, neighborhood, financial, or network). In contrast, 3 of the 4 women in the low stress responses group had only 2 sources of stress (racial, neighborhood, financial, or network) and 1 had none; these women also reported higher perceived support. The findings demonstrate the importance of periodically assessing stress in African American women during pregnancy, particularly related to their support network as well as the positive supports they receive. PMID:23360946

  19. Collagen Fiber Orientation and Dispersion in the Upper Cervix of Non-Pregnant and Pregnant Women

    PubMed Central

    Myers, Kristin M.; Vink, Joy Y.; Wapner, Ronald J.; Hendon, Christine P.

    2016-01-01

    The structural integrity of the cervix in pregnancy is necessary for carrying a pregnancy until term, and the organization of human cervical tissue collagen likely plays an important role in the tissue’s structural function. Collagen fibers in the cervical extracellular matrix exhibit preferential directionality, and this collagen network ultrastructure is hypothesized to reorient and remodel during cervical softening and dilation at time of parturition. Within the cervix, the upper half is substantially loaded during pregnancy and is where the premature funneling starts to happen. To characterize the cervical collagen ultrastructure for the upper half of the human cervix, we imaged whole axial tissue slices from non-pregnant and pregnant women undergoing hysterectomy or cesarean hysterectomy respectively using optical coherence tomography (OCT) and implemented a pixel-wise fiber orientation tracking method to measure the distribution of fiber orientation. The collagen fiber orientation maps show that there are two radial zones and the preferential fiber direction is circumferential in a dominant outer radial zone. The OCT data also reveal that there are two anatomic regions with distinct fiber orientation and dispersion properties. These regions are labeled: Region 1—the posterior and anterior quadrants in the outer radial zone and Region 2—the left and right quadrants in the outer radial zone and all quadrants in the inner radial zone. When comparing samples from nulliparous vs multiparous women, no differences in these fiber properties were noted. Pregnant tissue samples exhibit an overall higher fiber dispersion and more heterogeneous fiber properties within the sample than non-pregnant tissue. Collectively, these OCT data suggest that collagen fiber dispersion and directionality may play a role in cervical remodeling during pregnancy, where distinct remodeling properties exist according to anatomical quadrant. PMID:27898677

  20. Physiological reactivity of pregnant women to evoked fetal startle

    PubMed Central

    DiPietro, Janet A.; Voegtline, Kristin M.; Costigan, Kathleen A.; Aguirre, Frank; Kivlighan, Katie; Chen, Ping

    2013-01-01

    Objective The bidirectional nature of mother-child interaction is widely acknowledged during infancy and childhood. Prevailing models during pregnancy focus on unidirectional influences exerted by the pregnant woman on the developing fetus. Prior work has indicated that the fetus also affects the pregnant woman. Our objective was to determine whether a maternal psychophysiological response to stimulation of the fetus could be isolated. Methods Using a longitudinal design, an airborne auditory stimulus was used to elicit a fetal heart rate and motor response at 24 (n = 47) and 36 weeks (n = 45) gestation. Women were blind to condition (stimulus versus sham). Maternal parameters included cardiac (heart rate) and electrodermal (skin conductance) responses. Multilevel modeling of repeated measures with 5 data points per second was used to examine fetal and maternal responses. Results As expected, compared to a sham condition, the stimulus generated a fetal motor response at both gestational ages, consistent with a mild fetal startle. Fetal stimulation was associated with significant, transient slowing of maternal heart rate coupled with increased skin conductance within 10 s of the stimulus at both gestational ages. Nulliparous women showed greater electrodermal responsiveness. The magnitude of the fetal motor response significantly corresponded to the maternal skin conductance response at 5, 10, 15, and 30 s following stimulation. Conclusion Elicited fetal movement exerts an independent influence on the maternal autonomic nervous system. This finding contributes to current models of the dyadic relationship during pregnancy between fetus and pregnant woman. PMID:24119937

  1. Hybrid spreading mechanisms and T cell activation shape the dynamics of HIV-1 infection.

    PubMed

    Zhang, Changwang; Zhou, Shi; Groppelli, Elisabetta; Pellegrino, Pierre; Williams, Ian; Borrow, Persephone; Chain, Benjamin M; Jolly, Clare

    2015-04-01

    HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts. The contribution of this hybrid spreading mechanism, which is also a characteristic of some important computer worm outbreaks, to HIV-1 progression in vivo remains unknown. Here we present a new mathematical model that explicitly incorporates the ability of HIV-1 to use hybrid spreading mechanisms and evaluate the consequences for HIV-1 pathogenenesis. The model captures the major phases of the HIV-1 infection course of a cohort of treatment naive patients and also accurately predicts the results of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) trial. Using this model we find that hybrid spreading is critical to seed and establish infection, and that cell-to-cell spread and increased CD4+ T cell activation are important for HIV-1 progression. Notably, the model predicts that cell-to-cell spread becomes increasingly effective as infection progresses and thus may present a considerable treatment barrier. Deriving predictions of various treatments' influence on HIV-1 progression highlights the importance of earlier intervention and suggests that treatments effectively targeting cell-to-cell HIV-1 spread can delay progression to AIDS. This study suggests that hybrid spreading is a fundamental feature of HIV infection, and provides the mathematical framework incorporating this feature with which to evaluate future therapeutic strategies.

  2. Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

    PubMed Central

    Garcia-Knight, Miguel A.; Slyker, Jennifer; Payne, Barbara Lohman; Pond, Sergei L. Kosakovsky; de Silva, Thushan I.; Chohan, Bhavna; Khasimwa, Brian; Mbori-Ngacha, Dorothy; John-Stewart, Grace; Rowland-Jones, Sarah L.; Esbjörnsson, Joakim

    2016-01-01

    Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines. PMID:27403940

  3. Biophysical characterization of V3-lipopeptide liposomes influencing HIV-1 infectivity

    SciTech Connect

    Rizos, Apostolos K. . E-mail: Rizos@iesl.forth.gr; Baritaki, Stavroula; Tsikalas, Ioannis; Doetschman, David C.; Spandidos, Demetrios A.; Krambovitis, Elias; E-mail: krambo@imbb.forth.gr

    2007-04-20

    The V3-loop of the HIV-1 gp120 alters host cell immune function and modulates infectivity. We investigated biophysical parameters of liposome constructs with embedded lipopeptides from the principle neutralizing domain of the V3-loop and their influence on viral infectivity. Dynamic light scattering measurements showed liposome supramolecular structures with hydrodynamic radius of the order of 900 and 1300 nm for plain and V3-lipopeptide liposomes. Electron paramagnetic resonance measurements showed almost identical local microenvironment. The difference in liposome hydrodynamic radius was attributed to the fluctuating ionic environment of the V3-lipopeptide liposomes. In vitro HIV-1 infectivity assays showed that plain liposomes reduced virus production in all cell cultures, probably due to the hydrophobic nature of the aggregates. Liposomes carrying V3-lipopeptides with different cationic potentials restored and even enhanced infectivity (p < 0.05). These results highlight the need for elucidation of the involvement of lipid bilayers as dynamic components in supramolecular structures and in HIV-1 fusion mechanisms.

  4. Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease-Sensitive Toxin Nanocapsules

    PubMed Central

    Wen, Jing; Yan, Ming; Liu, Yang; Li, Jie; Xie, Yiming; Lu, Yunfeng; Kamata, Masakazu; Chen, Irvin S. Y.

    2016-01-01

    Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels; however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The silent provirus can be activated through the use of drugs, including protein kinase C activators and histone deacetylase inhibitors. This “shock” approach is then followed by “kill” of the producing cells either through direct HIV-1-induced cell death or natural immune mechanisms. However, these mechanisms are relatively slow and effectiveness is unclear. Here, we develop an approach to specifically target and kill cells that are activated early in the process of virus production. We utilize a novel nanocapsule technology whereby the ricin A chain is encapsulated in an inactive form within a polymer shell. Specificity for release of the ricin A toxin is conferred by peptide crosslinkers that are sensitive to cleavage by HIV-1 protease. By using well-established latent infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1-producing cell expressing functional HIV-1 protease will the nanocapsule release its ricin A cargo, shutting down viral and cellular protein synthesis, and ultimately leading to rapid death of the producer cell. Thus, we provide proof of principle for a novel technology to kill HIV-1-producing cells without effects on non-target cells. PMID:27049645

  5. Antiviral activity of derivatized dextrans on HIV-1 infection of primary macrophages and blood lymphocytes.

    PubMed

    Seddiki, N; Mbemba, E; Letourneur, D; Ylisastigui, L; Benjouad, A; Saffar, L; Gluckman, J C; Jozefonvicz, J; Gattegno, L

    1997-11-28

    The present study demonstrates at the molecular level that dextran derivatives carboxymethyl dextran benzylamine (CMDB) and carboxymethyl dextran benzylamine sulfonate (CMDBS), characterized by a statistical distribution of anionic carboxylic groups, hydrophobic benzylamide units, and/or sulfonate moieties, interact with HIV-1 LAI gp120 and V3 consensus clades B domain. Only limited interaction was observed with carboxy-methyl dextran (CMD) or dextran (D) under the same conditions. CMDBS and CMDB (1 microM) strongly inhibited HIV-1 infection of primary macrophages and primary CD4+ lymphocytes by macrophage-tropic and T lymphocyte-tropic strains, respectively, while D or CMD had more limited effects on M-tropic infection of primary macrophages and exert no inhibitory effect on M- or T-tropic infection of primary lymphocytes. CMDBS and CMDB (1 microM) had limited but significant effect on oligomerized soluble recombinant gp120 binding to primary macrophages while they clearly inhibit (> 50%) such binding to primary lymphocytes. In conclusion, the inhibitory effect of CMDB and the CMDBS, is observed for HIV M- and T-tropic strain infections of primary lymphocytes and macrophages which indicates that these compounds interfere with steps of HIV replicative cycle which neither depend on the virus nor on the cell.

  6. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection.

    PubMed

    Hu, Wenhui; Kaminski, Rafal; Yang, Fan; Zhang, Yonggang; Cosentino, Laura; Li, Fang; Luo, Biao; Alvarez-Carbonell, David; Garcia-Mesa, Yoelvis; Karn, Jonathan; Mo, Xianming; Khalili, Kamel

    2014-08-05

    AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide RNA (gRNA) system, in single and multiplex configurations. We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither genotoxicity nor off-target editing to the host cells, and completely excised a 9,709-bp fragment of integrated proviral DNA that spanned from its 5' to 3' LTRs. Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered to provide a specific, efficacious prophylactic and therapeutic approach against AIDS.

  7. High incidence and prevalence of HIV-1 infection in high risk population in Calcutta, India.

    PubMed

    Gupta, Phalguni; Kingsley, Lawrence; Sheppard, Haynes W; Harrison, Lee H; Chatterjee, Ramdas; Ghosh, Adhir; Roy, Pratima; Neogi, Dhruba K

    2003-07-01

    HIV-1 infection in India has been increasing steadily over the last decade. In the absence of potent antiviral therapy, estimates of HIV infection are needed to monitor the epidemic, institute prevention strategies in target populations and determine the suitable populations for vaccine studies. In this report we present the HIV-1 seroprevalence and annual estimates of seroincidence in a high risk population from Calcutta, the most populous city in the eastern part of India. In 1206 high risk subjects tested over two years between February of 1999 and December 2000, we have determined an overall seroprevalence of 40.1% using enzyme-linked immunosorbent assay followed by a confirmatory Western blot testing. Furthermore, using a newly described Standardized Testing Algorithm for Recent HIV-1 Seroconversion (STARHS), we have estimated an annual seroincidence rate of about 7% in this population during this two-year study. Such a high annual seroincidence rate makes this population well suited for studies of HIV-1 prevention, including vaccine trials.

  8. Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase.

    PubMed Central

    Jacqué, J M; Mann, A; Enslen, H; Sharova, N; Brichacek, B; Davis, R J; Stevenson, M

    1998-01-01

    Infection of a cell by human immunodeficiency virus type 1 (HIV-1) results in the formation of a reverse transcription complex in which viral nucleic acids are synthesized. Efficient disengagement of the reverse transcription complex from the cell membrane and subsequent nuclear translocation require phosphorylation of reverse transcription complex components by a virion-associated kinase. In this study, we identify the virion-associated kinase as mitogen-activated protein kinase (ERK/MAPK). Upon density gradient fractionation, MAPK, but not its activating kinase MEK, co-sedimented with viral particles. Expression of a constitutively active, but not kinase-inactive, MEK1 in virus producer cells was able to activate virion-associated MAPK in trans. Stimulation of virion-associated MAPK activity in trans by the mitogen phorbol myristate acetate (PMA) increased viral infectivity. Conversely, suppression of virion-associated MAPK by specific inhibitors of the MAPK cascade markedly impaired viral infectivity. These studies demonstrate regulation of an early step in HIV-1 infection by the host cell MAPK signal transduction pathway. PMID:9564043

  9. What do mathematical models tell us about killing rates during HIV-1 infection?

    PubMed

    Gadhamsetty, Saikrishna; Beltman, Joost B; de Boer, Rob J

    2015-11-01

    Over the past few decades the extent to which cytotoxic T lymphocytes (CTLs) control human immunodeficiency virus (HIV) replication has been studied extensively, yet their role and mode of action remain controversial. In some studies, CTLs were found to kill a large fraction of the productively infected cells relative to the viral cytopathicity, whereas in others CTLs were suggested to kill only a small fraction of infected cells. In this review, we compile published estimates of CTL-mediated death rates, and examine whether these studies permit determining the rate at which CTLs kill HIV-1 infected cells. We highlight potential misinterpretations of the CTL-killing rates from the escape rates of mutants, and from perturbations of the steady state viral load during chronic infection. Our major conclusion is that CTL-mediated killing rates remain unknown. But contrary to current consensus, we argue that killing rates higher than one per day are perfectly consistent with the experimental data, which would imply that the majority of the productively infected cells could still die from CTL-mediated killing rather than from viral cytopathicity.

  10. Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection.

    PubMed

    Bruno, Christopher J; Jacobson, Jeffrey M

    2010-09-01

    The majority of currently available agents for the treatment of HIV-1 infection act by targeting one of several intracellular steps in the viral life cycle. Despite improvements in efficacy and tolerability, the development of viral resistance to these agents is common and significant toxicity and adherence issues still occur. For this reason the development of safe, well tolerated antiviral agents that target a novel step in the viral life cycle remains important. Viral entry into host cells affords several potential extracellular targets for antiretroviral therapy. Ibalizumab, a humanized monoclonal antibody to CD4, the primary host cellular receptor for HIV-1 entry, has been shown to block HIV-1 entry in vitro. Early clinical trials have demonstrated significant antiviral efficacy with a >1 log(10) reduction in viral load when given as monotherapy. Its long half-life, which allows weekly dosing, and its administration as an intravenous infusion differentiate it from other currently available antiretroviral agents. These properties may prove useful in allowing improved drug delivery to patients who have had difficulty adhering to daily oral regimens. Its unique mode of action reduces the risk of cross-resistance with currently available antiretroviral agents, with the potential to expand the choices available to treat drug-resistant HIV-1.

  11. Evaluation of Dried Blood Spots with a Multiplex Assay for Measuring Recent HIV-1 Infection

    PubMed Central

    Curtis, Kelly A.; Ambrose, Krystin M.; Kennedy, M. Susan; Owen, S. Michele

    2014-01-01

    Laboratory-based HIV tests for recent infection (TRIs), which primarily measure a specific serological biomarker(s) that distinguishes recent from long-term HIV infection, have facilitated the estimation of population-based incidence. Dried blood spots (DBS) on filter paper are an attractive sample source for HIV surveillance, given the simplified and cost-effective methods of specimen collection, storage, and shipment. Here, we evaluated the use of DBS in conjunction with an in-house multiplex TRI, the HIV-1-specific Bio-Plex assay, which measures direct antibody binding and avidity to multiple HIV-1 analytes. The assay performance was comparable between matched plasma and DBS samples from HIV-1 infected individuals obtained from diverse sources. The coefficients of variation, comparing the median antibody reactivity for each analyte between plasma and DBS, ranged from 2.78% to 9.40% and the correlation coefficients between the two sample types ranged from 0.89 to 0.97, depending on the analyte. The correlation in antibody reactivity between laboratory and site-prepared DBS for each analyte ranged from 0.87 to 0.98 and from 0.90 to 0.97 between site-prepared DBS and plasma. The correlation in assay measures between plasma and DBS indicate that the sample types can be used interchangeably with the Bio-Plex format, without negatively impacting the misclassification rate of the assay. PMID:25232736

  12. Nef enhances HIV-1 infectivity via association with the virus assembly complex

    SciTech Connect

    Qi Mingli; Aiken, Christopher

    2008-04-10

    The HIV-1 accessory protein Nef enhances virus infectivity by facilitating an early post-entry step of infection. Nef acts in the virus producer cell, leading to a beneficial modification to HIV-1 particles. Nef itself is incorporated into HIV-1 particles, where it is cleaved by the viral protease during virion maturation. To probe the role of virion-associated Nef in HIV-1 infection, we generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle assembly. Pharmacologic or genetic inhibition of CypA-Nef binding to Gag prevented incorporation of CypA-Nef into virions and inhibited infectivity enhancement. Our results indicate that infectivity enhancement by Nef requires its association with a component of the assembling HIV-1 particle.

  13. Specific Elimination of Latently HIV-1 Infected Cells Using HIV-1 Protease-Sensitive Toxin Nanocapsules.

    PubMed

    Wen, Jing; Yan, Ming; Liu, Yang; Li, Jie; Xie, Yiming; Lu, Yunfeng; Kamata, Masakazu; Chen, Irvin S Y

    2016-01-01

    Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels; however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The silent provirus can be activated through the use of drugs, including protein kinase C activators and histone deacetylase inhibitors. This "shock" approach is then followed by "kill" of the producing cells either through direct HIV-1-induced cell death or natural immune mechanisms. However, these mechanisms are relatively slow and effectiveness is unclear. Here, we develop an approach to specifically target and kill cells that are activated early in the process of virus production. We utilize a novel nanocapsule technology whereby the ricin A chain is encapsulated in an inactive form within a polymer shell. Specificity for release of the ricin A toxin is conferred by peptide crosslinkers that are sensitive to cleavage by HIV-1 protease. By using well-established latent infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1-producing cell expressing functional HIV-1 protease will the nanocapsule release its ricin A cargo, shutting down viral and cellular protein synthesis, and ultimately leading to rapid death of the producer cell. Thus, we provide proof of principle for a novel technology to kill HIV-1-producing cells without effects on non-target cells.

  14. IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection

    PubMed Central

    Younes, Souheil-Antoine; Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Reynaldi, Arnold; Estes, Jacob D.; Deleage, Claire; Lucero, Carissa; Anderson, Jodi; Schacker, Timothy W.; Davenport, Miles P.; McCune, Joseph M.; Hunt, Peter W.; Lee, Sulggi A.; Debernardo, Robert L.; Jacobson, Jeffrey M.; Canaday, David H.; Sekaly, Rafick-Pierre; Sieg, Scott F.; Lederman, Michael M.

    2016-01-01

    In HIV-1–infected patients, increased numbers of circulating CD8+ T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1–infected patients. Compared with healthy controls, untreated HIV-1–infected patients have an increased population of proliferating, granzyme B+, CD8+ T cells in circulation. Vβ expression and deep sequencing of CDR3 revealed that in untreated HIV-1 infection, cycling memory CD8 T cells possess a broad T cell repertoire that reflects the repertoire of the resting population. This suggests that cycling is driven by bystander activation, rather than specific antigen exposure. Treatment of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B+ phenotype in CD8+ T cells. Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1–infected patients correlated with circulating CD8+ T cell counts and was normalized in these patients following antiretroviral therapy. Together, these results suggest that IL-15 drives bystander activation of CD8+ T cells, which predicts disease progression in untreated HIV-1–infected patients and suggests that elevated IL-15 may also drive CD8+ T cell expansion that is linked to increased morbidity and mortality in treated patients. PMID:27322062

  15. Raltegravir for HIV-1 infected children and adolescents: efficacy, safety, and pharmacokinetics

    PubMed Central

    Larson, Kajal B; King, Jennifer R; Acosta, Edward P

    2013-01-01

    Raltegravir was the first HIV integrase strand-transfer inhibitor to be approved by the US FDA, in October 2007, for the treatment of HIV-1 infection in combination with other antiretroviral agents. Raltegravir can be used in treatment-naïve and -experienced patients, as well as for the treatment of multidrug-resistant infection. Raltegravir exists in two formulations: a film-coated tablet administered orally at 400 mg twice daily, and a chewable tablet administered orally at 300 mg twice daily. In 2011, raltegravir was also approved for the treatment of children and adolescents, ages 2–18 years. For adolescents (ages 12–18 years), the recommended dose is 400 mg twice daily (film-coated tablet). If children (ages 6–12 years) weigh at least 25 kg, the film-coated tablet is recommended at 400 mg twice daily. Otherwise, patients receive the chewable tablet according to weight-based dosing at approximately 6 mg/kg/dose. Studies are ongoing for children ages 4 weeks to 2 years, and preliminary efficacy and safety data are promising. This article reviews current studies on the efficacy, safety, and pharmacokinetics of raltegravir in the pediatric population and the challenges of treating HIV in children and adolescents. PMID:24600298

  16. Inhibition of ecto-ATPase activities impairs HIV-1 infection of macrophages.

    PubMed

    Schachter, Julieta; Delgado, Kelly Valcárcel; Barreto-de-Souza, Victor; Bou-Habib, Dumith Chequer; Persechini, Pedro Muanis; Meyer-Fernandes, José Roberto

    2015-05-01

    Nucleotides and nucleosides are secreted into extracellular media at different concentrations as a consequence of different physiologic and pathological conditions. Ecto-nucleotidases, enzymes present on the surface of most cells, hydrolyze these extracellular nucleotides and reduce the concentration of them, thus affecting the activation of different nucleotide and nucleoside receptors. Also, ecto-nucleotidases are present in a number of microorganisms and play important roles in host-pathogen interactions. Here, we characterized the ecto-ATPase activities present on the surface of HIV-1 particle and human macrophages as well. We found that the kinetic properties of HIV-1 and macrophage ecto-ATPases are similar, suggesting that the enzyme is the same. This ecto-ATPase activity was increased in macrophages infected in vitro with HIV-1. Using three different non-related ecto-ATPase inhibitors-POM-1, ARL67156 and BG0-we showed that the inhibition of these macrophage and viral ecto-ATPase activities impairs HIV-1 infection. In addition, we also found that elevated extracellular concentrations of ATP inhibit HIV-1 production by infected macrophages.

  17. [Poor, propertyless and pregnant: classification of women's status by country].

    PubMed

    1988-12-01

    A new study called "Poor, propertyless, and pregnant" that classified the condition of women in 99 countries found women in Sweden, Finland, and the US to enjoy the best legal and social conditions and the greatest degree of equality with men. The worst discrimination against women occurred in Bangladesh, Mali, Afghanistan, North Yemen, Pakistan, Nigeria, and Saudi Arabia. Women do not have complete equality with men in any country. But over 60% of the world's female population lives in countries where extensive poverty and sexual discrimination have created conditions of deprivation. One of the principal mechanisms that negatively influences the condition of women is early procreation; early and frequent childbirth obliterates women's chances for education and paid employment. Feminization of poverty is becoming universal, largely because a growing proportion of households are headed by women with dependent children. In developed and developing countries alike, working women with families work a double day. Although the struggle for legal and social equality for women takes different forms in different countries, certain basic measures can be applied by all governments. Reforms are needed to give women access to more remunerative jobs, equal property rights, and access to credit. Greater investments are needed in reproductive health and in education and training for women. Governments, employers, and husbands should recognize the social value of childbirth and child rearing. The study is divided into 5 sections, each of which has 4 series of data, so that each country is evaluated on 20 variables. The 5 sections are health, nuptiality and children, education, economic participation, and social equality. In most developed countries women live an average of 7 years longer than men, but in developing countries the difference is only 2 years. Complications of pregnancy and childbirth cause the deaths of over 500,000 women each year and affect another 5 million, mostly

  18. High prevalence of human papillomaviruses in Ghanaian pregnant women.

    PubMed

    Schulze, Marco H; Völker, Fabian M; Lugert, Raimond; Cooper, Paul; Hasenclever, Kai; Groß, Uwe; Pfister, Herbert; Silling, Steffi

    2016-12-01

    Data about the prevalence of human papillomaviruses (HPV) in African women with normal and abnormal cervical cytology are still scarce. Current HPV vaccines contain HPV types, which mainly represent the HPV epidemiology of industrial countries. As further developments of HPV vaccines are going on, it is necessary to regard regional differences in HPV type prevalence to ensure optimal protection by the vaccine. Vaginal swabs of Ghanaian pregnant women, routinely collected before delivery to rule out bacterial infections causing early onset sepsis, were screened for 12 high-risk (HR), 13 probably/possibly (pHR), and 18 low-risk (LR) HPV types. Most pregnant women come for delivery to the hospital. This was considered as appropriate possibility to have an unselected group of women. HPV DNA were detected in 55/165 women (33.3, 95 % CI 26.3-41.1 %). Thirty-four out of fifty-five (61.8, 95 % CI 47.7-74.3 %) of HPV-positive women were infected with HR and/or pHR HPV types. The five most prevalent HR or pHR HPV types were HPV-52 and HPV-67 (7 women each, 4.2, 95 % CI 1.9-8.9 %), HPV-53 (six women, 3.6, 95 % CI 1.5-8.1 %), HPV-45 (five women, 3.0, 95 % CI 1.1-7.3 %), and HPV-18 (four women, 2.4, 95 % CI 0.8-6.5 %), respectively. HPV-16 was found in two women only (1.2, 95 % CI 0.2-4.8 %). Future HPV vaccine research may devote special interest to HPV-67 and HPV-53 provided further studies confirm their high prevalence in the general population of Sub-Saharan African countries. The true carcinogenic potential of HPV-67, which is a member of species alpha9 including HPV-16, and so far categorized as pHR, should be clarified.

  19. Zika Virus Infection in Pregnant Women in Rio de Janeiro.

    PubMed

    Brasil, Patrícia; Pereira, José P; Moreira, M Elisabeth; Ribeiro Nogueira, Rita M; Damasceno, Luana; Wakimoto, Mayumi; Rabello, Renata S; Valderramos, Stephanie G; Halai, Umme-Aiman; Salles, Tania S; Zin, Andrea A; Horovitz, Dafne; Daltro, Pedro; Boechat, Marcia; Raja Gabaglia, Claudia; Carvalho de Sequeira, Patrícia; Pilotto, José H; Medialdea-Carrera, Raquel; Cotrim da Cunha, Denise; Abreu de Carvalho, Liege M; Pone, Marcos; Machado Siqueira, André; Calvet, Guilherme A; Rodrigues Baião, Ana E; Neves, Elizabeth S; Nassar de Carvalho, Paulo R; Hasue, Renata H; Marschik, Peter B; Einspieler, Christa; Janzen, Carla; Cherry, James D; Bispo de Filippis, Ana M; Nielsen-Saines, Karin

    2016-12-15

    Background Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. Methods We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. Results A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester

  20. Cadmium, lead and mercury exposure in non smoking pregnant women

    SciTech Connect

    Hinwood, A.L.; Callan, A.C.; Ramalingam, M.; Boyce, M.; Heyworth, J.; McCafferty, P.; Odland, J.Ø.

    2013-10-15

    Recent literature suggests that exposure to low concentrations of heavy metals may affect both maternal and child health. This study aimed to determine the biological heavy metals concentrations of pregnant women as well as environmental and dietary factors that may influence exposure concentrations. One hundred and seventy three pregnant women were recruited from Western Australia, each providing a sample of blood, first morning void urine, residential soil, dust and drinking water samples. Participants also completed a questionnaire which included a food frequency component. All biological and environmental samples were analysed for heavy metals using ICP-MS. Biological and environmental concentrations of lead and mercury were generally low (Median Pb Drinking Water (DW) 0.04 µg/L; Pb soil <3.0 µg/g; Pb dust 16.5 µg/g; Pb blood 3.67 µg/L; Pb urine 0.55; µg/L Hg DW <0.03; Hg soil <1.0 µg/g; Hg dust <1.0 µg/g; Hg blood 0.46 µg/L; Hg urine <0.40 µg/L). Cadmium concentrations were low in environmental samples (Median CdDW 0.02 µg/L; Cdsoil <0.30 ug/g; Cddust <0.30) but elevated in urine samples (Median 0.55 µg/L, creatinine corrected 0.70 µg/g (range <0.2–7.06 µg/g creatinine) compared with other studies of pregnant women. Predictors of increased biological metals concentrations in regression models for blood cadmium were residing in the Great Southern region of Western Australia and not using iron/folic acid supplements and for urinary cadmium was having lower household annual income. However, these factors explained little of the variation in respective biological metals concentrations. The importance of establishing factors that influence low human exposure concentrations is becoming critical in efforts to reduce exposures and hence the potential for adverse health effects. -- Highlights: • Biological heavy metals concentrations in women in their 3rd trimester of pregnancy. • Exposure assessment including environmental, lifestyle and activity

  1. The expectations of pregnant women regarding antenatal care.

    PubMed

    Mathibe-Neke, J M

    2008-09-01

    From a feminist perspective, research on childbirth and women's health is a means to a positive change that is conducted in partnership with women for their benefit. A patient-led National Health System (NHS) (Hillan, 1999) also calls for consultation with patients and the wider public for shaping the current and future health services. This study was aimed at exploring and describing the expectations that pregnant women have regarding antenatal care service by the midwife practitioner. In-depth interviews were conducted in an antenatal unit of an Academic Hospital in Gauteng Povince. Data saturation was reached with a sample of eighteen pregnant women who were conveniently selected. Data analysis ran concurrently with data collection. A manual content analysis as described by Tesch was used. Lincoln and Guba's method of ensuring trustworthiness was adopted (Lincoln & Guba, 1985:328) Literature was undertaken to compare the findings of this study with those of other previous studies. Women displayed several common expectations that led to the saturation of data. It also became apparent from the findings that each woman had varied expectations. There were also some commonalities within the women's expectations. Health care, as the major expectation and a basic human right, appeared to be basically fulfilled, with the exception of interactional characteristics such as the communication of information, guidance, involvement, the understanding and explanation of aspects, freedom of choice, punctuality, individualized care and continuity of care. The conclusions that were reached let to recommendations for nursing practice, education, research and the formulation of guidelines for the midwife practitioner for the implementation of effective antenatal care, based on the identified expectations.

  2. Process of construction of an educational booklet for health promotion of pregnant women.

    PubMed

    Reberte, Luciana Magnoni; Hoga, Luiza Akiko Komura; Gomes, Ana Luisa Zaniboni

    2012-01-01

    This study aimed to describe the production process of an educational booklet focusing on health promotion of pregnant women. The action research method was used in this process composed of the following steps: choice of the content based on the needs of pregnant women, creation of illustrations, content preparation based on scientific literature, validation of the material by experts and pregnant women. This work resulted in the final version of the booklet, which was entitled "Celebrating life: our commitment with the health promotion of pregnant women". Active participation of health professionals and pregnant women through dialogue and collective strategy permeated the process of development of the booklet. The opinions of pregnant women and experts who considered the booklet enriching and enlightening justify the use of it as an additional resource of educational activities carried out during the prenatal care.

  3. 40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... women and fetuses involved in observational research. 26.304 Section 26.304 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in...

  4. 40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... women and fetuses involved in observational research. 26.304 Section 26.304 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in...

  5. 40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... women and fetuses involved in observational research. 26.304 Section 26.304 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in...

  6. 40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... women and fetuses involved in observational research. 26.304 Section 26.304 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in...

  7. 40 CFR 26.304 - Additional protections for pregnant women and fetuses involved in observational research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... women and fetuses involved in observational research. 26.304 Section 26.304 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.304 Additional protections for pregnant women and fetuses involved in...

  8. [Serum homocysteine levels in pregnant women with preeclampsia].

    PubMed

    Stoĭkova, V; Ivanov, S; Mazneĭkova, V; Tsoncheva, A

    2005-01-01

    Preeclampsia is one of the most common and severe pregnancy complications, which ethiology remains unclear. It is certain that endothelial dysfunction plays a key role in the development of preeclampsia. Homocysteine is an important independent cardiovascular risk factor, which might induce the endothelial dysfunction observed in preeclampsia. 26 pregnant women--14 with preeclampsia (group 1) and 12 healthy term pregnant controls (group 2) were enrolled in the study between December 2003 and August 2004. Six of the women in this group had a superimposed preeclampsia. The mean homocysteine level in the first group was 11,04 mol/l, while in the control group it was 6,24 micromol/l (p < 0.05). The women with a severe preeclampsia had a significantly higher serum homocysteine levels than those with mild form (F = 0.025). Seven of the patients (50%) gave birth before 34th weeks of gestation. The study finds a link between the serum homocysteine as an endothelial dysfunction marker and the development of preeclampsia and a relation between the severity of preeclampsia and the degree of the elevation of the serum homocysteine levels.

  9. Amniocentesis in HIV pregnant women: 16 years of experience.

    PubMed

    Simões, Mafalda; Marques, Catarina; Gonçalves, Ana; Pereira, Ana Paula; Correia, Joaquim; Castela, João; Guerreiro, Cristina

    2013-01-01

    The iatrogenic risk of HIV vertical transmission, calculated in initial epidemiologic studies, seemed to counterindicate invasive prenatal diagnosis (PND) procedures. The implementation of highly active antiretroviral therapy (HAART) represented a turning point in PND management, owing to a rapid and effective reduction of maternal viral load (VL). In the present study, we identified cases of vertical transmission in HIV-infected pregnant women who did amniocentesis in the second trimester of pregnancy (n = 27), from 1996 to 2011. We divided our sample into Group A--women under HAART when submitted to amniocentesis (n = 20) and Group B--women without antiretroviral therapy before amniocentesis (n = 7). We had 1 case of vertical transmission in Group B. Preconceptional or early first trimester HIV serology is essential to avoid performing an amniocentesis without antiretroviral therapy or viral suppression. When there is an indication for amniocentesis in an HIV-infected pregnant woman, it should be done if the patient is on HAART and, if possible, when VL is undetectable. Nowadays, with combined first trimester screening test to select pregnancies with high risk of aneuploidies, advanced maternal age is a less frequent indication to perform PND invasive procedures, representing an outstanding gain in prenatal diagnosis of this population.

  10. Periodontitis-associated risk factors in pregnant women

    PubMed Central

    de Vasconcellos Piscoya, Maria Dilma Bezerra; de Alencar Ximenes, Ricardo Arraes; da Silva, Genivaldo Moura; Jamelli, Sílvia Regina; Coutinho, Sônia Bechara

    2012-01-01

    OBJECTIVE: The main objective of this study was to investigate the risk factors associated with periodontitis in pregnant women. METHODS: This study was conducted in two stages. In Stage 1, a cross-sectional study was conducted to determine the prevalence of periodontitis among 810 women treated at the maternity ward of a university hospital. In Stage 2, the factors associated with periodontitis were investigated in two groups of pregnant women: 90 with periodontitis and 720 without. A hierarchized approach to the evaluation of the risk factors was used in the analysis, and the independent variables related to periodontitis were grouped into two levels: 1) socio-demographic variables; 2a) variables related to nutritional status, smoking, and number of pregnancies; and 2b) variables related to oral hygiene. Periodontitis was defined as a probing depth ≥4 mm and an attachment loss ≥3 mm at the same site in four or more teeth. A logistic regression analysis was also performed. RESULTS: The prevalence of periodontitis in this sample was 11%. The variables that remained in the final multivariate model with the hierarchized approach were schooling, family income, smoking, body mass index, and bacterial plaque. CONCLUSION: The factors identified underscore the social nature of the disease, as periodontitis was associated with socioeconomic, demographic status, and poor oral hygiene. PMID:22249477

  11. Influenza Vaccination in Pregnant Women: A Systematic Review

    PubMed Central

    Galvao, Tais F.; Silva, Marcus T.; Zimmermann, Ivan R.; Lopes, Luiz Antonio B.; Bernardo, Eneida F.; Pereira, Mauricio G.

    2013-01-01

    Objective. To assess the effects of the inactivated influenza virus vaccine on influenza outcomes in pregnant women and their infants. Methods. We performed a systematic review of the literature. We searched for randomized controlled trials and cohort studies in the MEDLINE, Embase, and other relevant databases (inception to September 2013). Two researchers selected studies and extracted the data independently. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the quality of the evidence. Results. We included eight studies out of 1,967 retrieved records. Influenza vaccination in pregnant women significantly reduced the incidence of influenza-like illness in mothers and their infants when compared with control groups (high-quality evidence) and reduced the incidence of laboratory-confirmed influenza in infants (moderate-quality evidence). No difference was found with regard to influenza-like illness with fever higher than 38°C (moderate-quality evidence) or upper respiratory infection (very-low-quality evidence) in mothers and infants. Conclusions. Maternal vaccination against influenza was shown to prevent influenza-like illness in women and infants; no differences were found for other outcomes. As the quality of evidence was not high overall, further research is needed to increase confidence and could possibly change these estimates. PMID:24971194

  12. Daily versus intermittent iron supplementation in pregnant women

    PubMed Central

    2011-01-01

    Background The purpose of this study was compare of daily iron supplementation in three time frames- daily, weekly and three time weekly supplementation in preventing anemia in healthy pregnant women. Method The present study was a prospective simply randomized clinical trial. During January 2006- January 2008, 150 healthy pregnant women without anemia, in their 16th week of pregnancy were randomly allocated into three equal groups. The first group (n = 50) received a 50 mg-ferrous sulfate tablet daily, second group (n = 50) received a 50 mg-ferrous sulfate tablet three times a week, and the third group (n = 50) received two 50 mg-ferrous sulfate tablets (100 mg) weekly, respectively for 12 consecutive weeks. Serum hemoglobin, ferritin, and iron were measured before and after the supplementation. Paired t and ANOVA tests were used as appropriated. Results There were no significant differences between the pre- and post-treatment hemoglobin levels with iron supplementation in the three group (P = 0.518, P = 0.276, respectively). The mean serum iron level before and after treatment with iron supplementation in the three groups was not statistically significant (P = 0.962, P = 0.970, respectively). Although the mean serum ferritin level before and after treatment with iron supplementation was statistically significant in the three groups, no significant differences were found comparing the three groups (P = 0.827, P = 0.635 respectively). Conclusions This results suggested, three times a week or weekly iron supplementation is as effective as daily supplementation for healthy pregnant women without anemia. Trial Registration ISRCTN: IRCT201101093820N1 PMID:22026956

  13. Antiretroviral Therapy Fails to Restore Levels of HIV-1 Restriction miRNAs in PBMCs of HIV-1-infected MSM.

    PubMed

    Liu, Man-Qing; Zhao, Min; Kong, Wen-Hua; Peng, Jin-Song; Wang, Fang; Qiu, Hong-Yan; Zhu, Ze-Rong; Tang, Li; Sang, Ming; Wu, Jian-Guo; Ho, Wen-Zhe; Zhou, Wang

    2015-11-01

    A number of cellular microRNAs (miRNAs) have been identified to have the ability to inhibit HIV-1 replication. In this study, we examined the impact of combination antiretroviral therapy (cART) on the expression of HIV-1 restriction miRNAs in peripheral blood mononuclear cells of HIV-1-infected men who have sex with men (MSM). Compared with male healthy donors, HIV-infected MSM had significantly lower levels of 9 HIV-1 restriction miRNAs. The treatment of HIV-1-infected MSM with cART, however, failed to restore the levels of these miRNAs in peripheral blood mononuclear cells. These observations suggest that the suppression of the cellular restriction miRNAs by HIV-1 may attribute to the virus latency during cART.

  14. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection.

    PubMed

    Hou, Panpan; Chen, Shuliang; Wang, Shilei; Yu, Xiao; Chen, Yu; Jiang, Meng; Zhuang, Ke; Ho, Wenzhe; Hou, Wei; Huang, Jian; Guo, Deyin

    2015-10-20

    Genome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4(+) cells by binding to envelope protein, gp120. Here, we show that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to HIV-1 resistance of human primary CD4(+) T cells. We also show that the Cas9-mediated ablation of CXCR4 demonstrated high specificity and negligible off-target effects without affecting cell division and propagation. The precise and efficient genome editing of CXCR4 will provide a new strategy for therapeutic application against HIV-1 infection.

  15. BRAIN ABSCESS DUE TO Staphylococcus aureus OF CRYPTOGENIC SOURCE IN AN HIV-1 INFECTED PATIENT IN USE OF ANTIRETROVIRAL THERAPY

    PubMed Central

    de OLIVEIRA, Anna Paula Romero; PAPPALARDO, Mara Cristina; DANTAS, Daniel; LINS, Diogo; VIDAL, José Ernesto

    2016-01-01

    The spectrum of neurological complications associated with human immunodeficiency virus type 1 (HIV-1) infection is broad. The most frequent etiologies include primary diseases (caused by HIV itself) or secondary diseases (opportunistic infections or neoplasms). Despite these conditions, HIV-infected patients are susceptible to other infections observed in patients without HIV infection. Here we report a rare case of a brain abscess caused by Staphylococcus aureus in an HIV-infected patient. After drainage of the abscess and treatment with oxacilin, the patient had a favorable outcome. This case reinforces the importance of a timely neurosurgical procedure that supported adequate management of an unusual cause of expansive brain lesions in HIV-1 infected patients. PMID:27074328

  16. Antibodies against oxidized low density lipoproteins in pregnant women.

    PubMed

    Fialová, L; Mikulíková, L; Malbohan, I; Benesová, O; Stípek, S; Zima, T; Zwinger, A

    2002-01-01

    Oxidized low density lipoproteins (oxLDL) formed in vivo induce a humoral immune response. Oxidative modification of LDL renders it immunogenic and a heterogeneous population of specific anti-oxLDL antibodies is produced. These antibodies could represent a biological marker of oxidative stress and serve as markers of atherosclerosis. Autoantibodies against oxLDL (oLAb) have been detected in human subjects practically of every age. oLAb also appear in the blood of pregnant women. Some studies have shown that the levels of antibodies to oxLDL were elevated in women with established preeclampsia. The present study was aimed to estimate the oLAb IgG levels in the first and second trimester of pregnancy. Furthermore, we estimated the correlation between maternal serum (MS) levels of oLAb and alpha-1-fetoprotein (MS AFP), human chorionic gonadotrophin (MS HCG) and trophoblast-specific-beta-1-glycoprotein (MS SP1), because these proteins are determined as a part of prenatal biochemical screening for fetal congenital abnormalities. Our study deals with the oLAb changes in women with pregnancy-induced hypertension. We also investigated the correlation between oLAb IgG and anticardiolipin antibodies IgG (ACA) in the serum of pregnant women. We examined 40 pregnant women attending Institute for Mother and Child Care for their antenatal care as outpatients. Routine blood samplings between the 9-13th week of pregnancy and 16-18th week of pregnancy were performed as a part of biochemical prenatal screening for fetal congenital abnormalities (Group 1). Their mean age was 27 +/- 4.1 years. Furthermore, we examined 26 women in the second or third trimester with pregnancy-induced hypertension (Group 2). Group 2 was compared with 49 pregnant women in the second or third trimester who were normotensive (Group 3). We used commercial standardized ELISA kits for determination of oLAb IgG, ACA IgG, MS AFP and MS HCG, MS SP1 was analyzed by single radial immunodiffusion. We did not find

  17. Smoking habits of pregnant women in Brisbane, Australia.

    PubMed

    Counsilman, J J; Mackay, E V

    1985-11-01

    A survey of postpartum women in Brisbane revealed that many gave up smoking just before or shortly after becoming pregnant, and that many of the remainder reduced their rate of consumption. Husbands who smoked showed no comparable changes in behaviour. Thus apparently many couples were aware of the dangers to the fetus of active smoking by the woman, but not of the dangers of her passive inhalation of smoke. Other significant findings included (i) increasing rates of consumption during successive pregnancies, (ii) high degrees of conformity for most habits (e.g. use of filters), and (iii) stronger addiction and earlier starting ages among heavy smokers than light smokers.

  18. Interleukin-10 (IL-10) Pathway: Genetic Variants and Outcomes of HIV-1 Infection in African American Adolescents

    PubMed Central

    Shrestha, Sadeep; Wiener, Howard W.; Aissani, Brahim; Song, Wei; Shendre, Aditi; Wilson, Craig M.; Kaslow, Richard A.; Tang, Jianming

    2010-01-01

    Background Immunological and clinical outcomes can vary considerably at the individual and population levels during both treated and untreated HIV-1 infection. Cytokines encoded by the interleukin-10 gene (IL10) family have broad immunomodulatory function in viral persistence, and several SNPs in the IL10 promoter sequence have been reported to influence pathogenesis or acquisition of HIV-1 infection. Methodology/Principal Findings We examined 104 informative SNPs in IL10, IL19, IL20, IL24, IL10RA and IL10RB among 250 HIV-1 seropositive and 106 high-risk seronegative African American adolescents in the REACH cohort. In subsequent evaluation of five different immunological and virological outcomes related to HIV-1 infection, 25 SNPs were associated with a single outcome and three were associated with two different outcomes. One SNP, rs2243191 in the IL19 open reading frame (Ser to Phe substitution) was associated with CD4+ T-cell increase during treatment. Another SNP rs2244305 in IL10RB (in strong linkage disequilibrium with rs443498) was associated with an initial decrease in CD4+ T-cell by 23±9% and 29±9% every 3 months (for AA and AG genotypes, respectively, compared with GG) during ART-free period. These associations were reversed during treatment, as CD4+ T-cell increased by 31±0.9% and 17±8% every 3 months for AA and AG genotype, respectively. Conclusions/Significance In African Americans, variants in IL10 and related genes might influence multiple outcomes of HIV-1 infection, especially immunological response to HAART. Fine mapping coupled with analysis of gene expression and function should help reveal the immunological importance of the IL10 gene family to HIV-1/AIDS. PMID:20976276

  19. Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection

    PubMed Central

    Dagenais-Lussier, Xavier; Aounallah, Mouna; Mehraj, Vikram; El-Far, Mohamed; Tremblay, Cecile; Sekaly, Rafick-Pierre; Routy, Jean-Pierre

    2016-01-01

    ABSTRACT Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss. Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. We further show that IL-2 signaling in memory CD4 T cells is improved by the antioxidant N-acetylcysteine. Early initiation of antiretroviral therapy restored the IL-2 response in memory CD4 T cells by reducing reactive oxygen species and kynurenine production. The study findings provide a kynurenine-dependent mechanism through IL-2 signaling for reduced CD4 T-cell survival, which can be reversed by early treatment initiation in HIV-1 infection. IMPORTANCE The persistence of functional memory CD4 T cells represents the basis for long-lasting immune protection in individuals after exposure to HIV-1. Unfortunately, primary HIV-1 infection results in the massive loss of these cells within weeks of infection, which is mainly driven by inflammation and massive infection by the virus. These new findings show that the enhanced production of kynurenine, a metabolite related to tryptophan catabolism, also impairs memory CD4 T-cell survival and interferes with IL-2 signaling early during HIV-1 infection. PMID:27356894

  20. Prevalence of hepatitis B virus infection in pregnant Turkish women and their families.

    PubMed

    Kuru, U; Turan, O; Kuru, N; Saglam, Z; Ceylan, Y; Nurluoglu, M; Agacfidan, A

    1996-03-01

    A total of 5,366 pregnant Turkish women were screened for hepatitis B surface antigen (HBsAg) and 225 (4.2%) of them were found to be positive. Hepatitis B e antigen (HBeAg) was detected in 6.2% of HBsAg-positive pregnant women. the overall prevalence of HBsAg and antibody to HBsAg (anti-HBs) among the spouses, previous children, mothers and first degree relatives of the HBsAg-positive pregnant women was 56%, 49%, 79% and 74% respectively. The prevalence of HBsAg is thus high in pregnant Turkish women with familial clustering of hepatitis B virus infection.

  1. FlowCytomix analysis for Toxoplasma gondii infection in pregnant women in central Taiwan.

    PubMed

    Chou, C S; Lin, L Y; Chen, K M; Lai, S C

    2011-07-01

    The study was to determine the seroprevalence of toxoplasmosis in the sera of pregnant women in central Taiwan and to investigate the levels of cytokine in the sera of pregnant women with Toxoplasma gondii infection. The 220 blood samples were collected from pregnant women. The haematological parameters of peripheral blood were analysed by a haematology analyser. Serum samples of the pregnant women were analysed by a commercially available anti-T. gondii IgM/IgG antibody enzyme-linked immunosorbent assay (ELISA) kit and FlowCytomix assays. Six (2.7%) of the sera samples had IgM anti-T. gondii antibodies, and twenty (9.1%) had T. gondii IgG seropositive. All six IgM seropositive samples had low IgG avidity, indicative of acute infection. Total white blood cells and eosinophils were statistically significantly increased (p<0.05) in pregnant women with T. gondii infection, as compared with healthy pregnant women. Th1 cytokines IFN-γ, IL-1β, IL-2 and IL-12 p70, and Th2 cytokines IL-10 in pregnant women with T. gondii IgM/IgG seropositive were significantly increased (p<0.05), as compared with healthy pregnant women. These results showed that both of Th1 and Th2 cytokines play an important role in the toxoplasmosis of pregnant women.

  2. [Retrospective study of infection by the human immunodeficiency virus in pregnant women. Future of the child and the mother].

    PubMed

    Makuwa, M; Taty, E; Beuzit, Y; Loemba, H; Miehakanda, J

    1992-01-01

    5.4% (108 of 2,000) women have been confirmed for HIV 1 infection in Brazzaville in 1987. 1,172 deliveries have been registered by study, 7.76% have been occurred in HIV+ women. The prevalence of miscarriages was significantly, higher in HIV+ women than in HIV- ones (p less than 0.001). The birth-weight of new-borns was not significantly different among the children born to HIV+ and HIV- mothers. There were the various probable reasons of death of children born to HIV+ mothers. More frequently the respiratory affections with persistent hyperthermia were noticed. During the follow-up, in all groups of age, the fever with failure of thrive were the most frequent signs (50%) with pneumopathy. The clinical picture was completed by diarrhoea after six months of live.

  3. The effects of low level laser therapy on both HIV-1 infected and uninfected TZM-bl cells.

    PubMed

    Lugongolo, Masixole Yvonne; Manoto, Sello Lebohang; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

    2017-01-27

    Human immunodeficiency virus (HIV-1) infection remains a major health problem despite the use of highly active antiretroviral therapy (HAART), which has greatly reduced mortality rates. Due to the unavailability of an effective vaccine and treatment that would completely eradicate the virus in infected individuals, the quest for new therapies continues. Low level laser therapy (LLLT) involves the exposure of cells to low levels of red or infrared light. LLLT has been widely used in different medical conditions, but not in HIV-1 infection. This study aimed to determine the effects of LLLT on HIV-1 infected and uninfected TZM-bl cells. Both infected and uninfected cells were irradiated at a wavelength of 660 nm with different fluences from 2 J/cm(2) to 10 J/cm(2) . Changes in cellular responses were assessed using cell morphology, viability, proliferation, cytotoxicity and luciferase activity assays. Upon data analysis, uninfected irradiated cells showed no changes in cell morphology, viability, proliferation and cytotoxicity, while the infected irradiated cells did. In addition, laser irradiation reduced luciferase activity in infected cells. Finally, laser irradiation had no inhibitory effect in uninfected cells, whereas it induced cell damage in a dose dependent manner in infected cells.

  4. Rapid selection of escape mutants by the first CD8 T cell responses in acute HIV-1 infection

    SciTech Connect

    Korber, Bette Tina Marie

    2008-01-01

    The recent failure of a vaccine that primes T cell responses to control primary HIV-1 infection has raised doubts about the role of CD8+ T cells in early HIV-1 infection. We studied four patients who were identified shortly after HIV-1 infection and before seroconversion. In each patient there was very rapid selection of multiple HIV-1 escape mutants in the transmitted virus by CD8 T cells, including examples of complete fixation of non-synonymous substitutions within 2 weeks. Sequencing by single genome amplification suggested that the high rate of virus replication in acute infection gave a selective advantage to virus molecules that contained simultaneous and gained sequential T cell escape mutations. These observations show that whilst early HIV-1 specific CD8 T cells can act against virus, rapid escape means that these T cell responses are unlikely to benefit the patient and may in part explain why current HIV-1 T cell vaccines may not be protective.

  5. Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo

    PubMed Central

    Lavender, Kerry J.; Gibbert, Kathrin; Peterson, Karin E.; Van Dis, Erik; Francois, Sandra; Woods, Tyson; Messer, Ronald J.; Gawanbacht, Ali; Müller, Janis A.; Münch, Jan; Phillips, Katie; Race, Brent; Harper, Michael S.; Guo, Kejun; Lee, Eric J.; Trilling, Mirko; Hengel, Hartmut; Piehler, Jacob; Verheyen, Jens; Wilson, Cara C.; Santiago, Mario L.

    2016-01-01

    ABSTRACT Although all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in the control of different viral infections. The IFN-α2 subtype is currently in HIV-1 clinical trials, but it has not consistently reduced viral loads in HIV-1 patients and is not the most effective subtype against HIV-1 in vitro. We now demonstrate in humanized mice that, when delivered at the same high clinical dose, the human IFN-α14 subtype has very potent anti-HIV-1 activity whereas IFN-α2 does not. In both postexposure prophylaxis and treatment of acute infections, IFN-α14, but not IFN-α2, significantly suppressed HIV-1 replication and proviral loads. Furthermore, HIV-1-induced immune hyperactivation, which is a prognosticator of disease progression, was reduced by IFN-α14 but not IFN-α2. Whereas ineffective IFN-α2 therapy was associated with CD8+ T cell activation, successful IFN-α14 therapy was associated with increased intrinsic and innate immunity, including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations in HIV-1 proviral DNA, and higher frequencies of TRAIL+ NK cells. These results identify IFN-α14 as a potent new therapeutic that operates via mechanisms distinct from those of antiretroviral drugs. The ability of IFN-α14 to reduce both viremia and proviral loads in vivo suggests that it has strong potential as a component of a cure strategy for HIV-1 infections. The broad implication of these results is that the antiviral efficacy of each individual IFN-α subtype should be evaluated against the specific virus being treated. IMPORTANCE The naturally occurring antiviral protein IFN-α2 is used to treat hepatitis viruses but has proven rather ineffective against HIV in comparison to triple therapy with the antiretroviral (ARV) drugs. Although ARVs suppress the replication of HIV, they fail to completely

  6. Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization

    PubMed Central

    2010-01-01

    Background HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells. Results We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates' activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5). Conclusion These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucosa. PMID:20546571

  7. Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients.

    PubMed

    Shirasaka, Takuma; Tadokoro, Taketsugu; Yamamoto, Yasuyuki; Fukutake, Katsuyuki; Kato, Yukihiko; Odawara, Takashi; Nakamura, Tetsuya; Ajisawa, Atsushi; Negishi, Masayoshi

    2011-10-01

    Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.

  8. Epigenetic alterations in the brain associated with HIV-1 infection and methamphetamine dependence.

    PubMed

    Desplats, Paula; Dumaop, Wilmar; Cronin, Peter; Gianella, Sara; Woods, Steven; Letendre, Scott; Smith, David; Masliah, Eliezer; Grant, Igor

    2014-01-01

    HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions.

  9. Immunotherapy with Canarypox Vaccine and Interleukin-2 for HIV-1 Infection: Termination of a Randomized Trial

    PubMed Central

    Smith, Kendall A; Andjelic, Sofija; Popmihajlov, Zoran; Kelly-Rossini, Liza; Sass, Aquanette; Lesser, Martin; Benkert, Steven; Waters, Cory; Ruitenberg, Joyce; Bellman, Paul

    2007-01-01

    Objectives: To determine whether immunotherapy of chronic HIV-1 infection can prevent or attenuate viremia upon antiviral discontinuation. Design: This was a Phase II randomized, partially double blinded, 2×2 factorial study of three steps of 12 wk/step. Step I involved four groups: (1) vaccine placebo, (2) vaccine (ALVAC, vCP1452), (3) placebo + interleukin 2 (IL-2), and (4) vaccine + IL-2. Step II involved a 12-wk diagnostic treatment interruption (DTI). Step III involved an extension of the DTI for an additional 12 wk. Setting: The Weill-Cornell General Clinical Research Center. Participants: Chronically infected HIV-1 positive adults with undetectable HIV-1 levels and > 400 CD4+ T cells/μl. Interventions An HIV canarypox vaccine (vCP1452) and vaccine placebo, administered every 4 wk for four doses, and low-dose IL-2 administered daily for 12–24 wk. Outcome measures: Primary endpoints: (1) Proportion of participants with undetectable plasma HIV RNA during trial Step II, (2) mean log10 HIV RNA copies/ml ([HIV]) from weeks 21–25, and (3) proportion of individuals eligible for trial Step III. Results: 44 participants were randomized, but 16 withdrew or were withdrawn before completing Step II. As all participants underwent viral relapse in Step II, the study was terminated after 28 participants completed Step II. Among the four groups, there was no difference in mean [HIV] or the proportion of individuals with < log10 4.48 HIV; no difference between the mean [HIV] of the two groups that received ALVAC (n = 17) versus placebo (n = 11); and no significant difference between the mean [HIV] of the two groups that received IL-2 (n = 11) versus placebo (n = 17). Conclusions: Neither ALVAC (vCP1452) nor low-dose daily IL-2 nor their combination prevented the relapse of viremia upon discontinuation of antiviral therapy. PMID:17260026

  10. A Generalized Entropy Measure of Within-Host Viral Diversity for Identifying Recent HIV-1 Infections

    PubMed Central

    Wu, Julia Wei; Patterson-Lomba, Oscar; Novitsky, Vladimir; Pagano, Marcello

    2015-01-01

    improving accuracy when identifying recent HIV-1 infections. PMID:26496342

  11. Resilience and Life Expectations of Perinatally HIV-1 Infected Adolescents in France

    PubMed Central

    Funck-Brentano, Isabelle; Assoumou, Lambert; Veber, Florence; Moshous, Despina; Frange, Pierre; Blanche, Stéphane

    2016-01-01

    Background: Resilience of perinatally HIV-infected youth in European countries is poorly studied. Life satisfaction and expectations for adulthood are rarely examined. Objective: This cross-sectional, descriptive study of a French cohort of 54 perinatally HIV-infected adolescents raised in France (age 14-20 years) aimed to (1) evaluate their psychosocial adjustment, (2) identify their expectations for adulthood and (3) delineate risk and protective factors associated with mental health, life satisfaction, and HIV-1 viral load level. Method: Medical evaluation, psychological semi-structured interview, and self-report questionnaires were used. Results: All the adolescents had been receiving Highly Active Anti-Retroviral Therapy (HAART) for 9 to 11 years and 2/3 were healthy with controlled viral load (<50 copies/mL). The majority had medium to high levels of life satisfaction. They viewed HIV as having only minor impact on their current daily life and had positive expectations for adulthood. However, 46% exhibited psychiatric symptomatology. Multivariable analysis showed that having a deceased parent and current worries about HIV were substantial risk factors for psychiatric symptoms. Having two living parents and being satisfied with life were protective factors for mental health. Good quality of caregiver-adolescent relationships and high life satisfaction were significant protective factors for controlled viral load. Conclusion: These data indicate psychosocial resilience among perinatally HIV-1 infected adolescents with 10 years of HAART treatment. These findings demonstrate the influence of life satisfaction, parent’s life status and quality of caregiver-adolescent relationships on resilience and health outcomes in these patients. We conclude that healthcare providers should attend to these factors. PMID:27990195

  12. A Generalized Entropy Measure of Within-Host Viral Diversity for Identifying Recent HIV-1 Infections.

    PubMed

    Wu, Julia Wei; Patterson-Lomba, Oscar; Novitsky, Vladimir; Pagano, Marcello

    2015-10-01

    accuracy when identifying recent HIV-1 infections.

  13. Molecular and pathologic insights from latent HIV-1 infection in the human brain

    PubMed Central

    Desplats, Paula; Dumaop, Wilmar; Smith, David; Adame, Anthony; Everall, Ian; Letendre, Scott; Ellis, Ronald; Cherner, Mariana; Grant, Igor

    2013-01-01

    Objective: We aimed to investigate whether HIV latency in the CNS might have adverse molecular, pathologic, and clinical consequences. Methods: This was a case-control comparison of HIV-1 seropositive (HIV+) patients with clinical and neuropathologic examination. Based on the levels of HIV-1 DNA, RNA, and p24 in the brain, cases were classified as controls, latent HIV CNS infection, and HIV encephalitis (HIVE). Analysis of epigenetic markers including BCL11B, neurodegeneration, and neuroinflammation was performed utilizing immunoblot, confocal microscopy, immunochemistry/image analysis, and qPCR. Detailed antemortem neurocognitive data were available for 23 out of the 32 cases. Results: HIV+ controls (n = 12) had no detectable HIV-1 DNA, RNA, or p24 in the CNS; latent HIV+ cases (n = 10) showed high levels of HIV-1 DNA but no HIV RNA or p24; and HIVE cases (n = 10) had high levels of HIV-1 DNA, RNA, and p24. Compared to HIV+ controls, the HIV+ latent cases displayed moderate cognitive impairment with neurodegenerative and neuroinflammatory alterations, although to a lesser extent than HIVE cases. Remarkably, HIV+ latent cases showed higher levels of BCL11B and other chromatin modifiers involved in silencing. Increased BCL11B was associated with deregulation of proinflammatory genes like interleukin-6, tumor necrosis factor–α, and CD74. Conclusion: Persistence of latent HIV-1 infection in the CNS was associated with increased levels of chromatin modifiers, including BCL11B. Alteration of these epigenetic factors might result in abnormal transcriptomes, leading to inflammation, neurodegeneration, and neurocognitive impairment. BCL11B and other epigenetic factors involved in silencing might represent potential targets for HIV-1 involvement of the CNS. PMID:23486877

  14. Characteristics of pregnant women who report previous induced abortions*

    PubMed Central

    Harlap, Susan; Davies, A. Michael

    1975-01-01

    Associations between previous induced abortion and demographic and health factors in pregnancy were measured in 9 874 women who gave birth and who had been interviewed during pregnancy. Previous abortion was most rare among women having their first baby and increased with increasing birth order up to the fourth, thereafter decreasing. It was positively correlated with maternal age and negatively with age at marriage. There was no effect of years of schooling, when other variables were taken into account, but there were significant differences between ethnic groups, abortion being commonest among Jewish women from North African countries and more prevalent in those from western and Asian countries than in the second-generation Israel-born or in Arab women. Women who reported abortions were less likely to be strict as regards religious observance and less likely to have had a previous stillbirth or child death, other variables being equal. They were more likely to be smokers or former smokers and to be delivered of their babies in certain obstetric units. They more often reported vomiting, bleeding, and medication in early pregnancy. On the other hand, there was no significant association with diabetes, anaemia, blood groups, or season of birth. The findings show that women reporting previous induced abortions differ significantly from other pregnant women in a wide range of demographic and health characteristics. Such women may also be biased for complications of pregnancy and outcome, particularly if selected from a clinic population. Observations that indicate a deleterious effect of induced abortions on subsequent pregnancy outcomes must therefore be interpreted with considerable caution. PMID:1083303

  15. Breastfeeding intention among pregnant Hong Kong Chinese women.

    PubMed

    Lau, Ying

    2010-09-01

    This study set out to (1) estimate the prevalence of three forms of feeding intention among 2,178 pregnant women in six of Hong Kong's regional hospitals and (2) identify the associated demographic, socioeconomic, obstetric and relational correlates. The research design was exploratory, cross-sectional, and quantitative. The Chinese version of a self-administered questionnaire was used to collect the demographic, socio-economic, and obstetric characteristics of the women. Couples' relationships were investigated using the Dyadic Adjustment Scale. All women in the second trimester of their pregnancies who attended the target antenatal clinics within the data collection period of December 2004 to December 2006 were recruited. The prevalence rates of breastfeeding, mixed feeding and artificial feeding were 53.9%, 14.8%, and 31.3%, respectively. Women who had been born in Hong Kong, lived in accommodation that was > or = 300 feet(2) (approximately 30 m(2)), had made an early antenatal booking, had a planned pregnancy, were experiencing their first pregnancy, and had a lower level of conflict with their partners were significantly more likely to opt for breastfeeding. Women who had been born in Hong Kong and already had children were significantly more likely to choose mixed feeding, compared with the artificial group in a multinomial logistic regression model. These findings suggest that effective promotion of breastfeeding during the prenatal period must target the correlates of feeding intention.

  16. Women's autonomy and unintended pregnancy among currently pregnant women in Bangladesh.

    PubMed

    Rahman, Mosfequr

    2012-08-01

    This paper examines the net effect of women's autonomy on their pregnancy intention status among currently pregnant Bangladeshi women. This study is based on data from the Bangladesh Demographic Health Survey, 2007 (BDHS). A subset of interviews from currently pregnant women (718) were extracted from 10,146 married women of reproductive age. The BDHS 2007 used a pre-tested, structured questionnaire to collect sociodemographic, women's empowerment, and pregnancy information. Associations between unintended pregnancy and explanatory variables were assessed using bivariate analysis. Logistic regression was used to assess the net effect of women's autonomy on current pregnancy intention status after controlling for other variables. Results indicate that women's autonomy is a significant predictor of unintended pregnancy after adjusting for other factors. A unit increase in the autonomy scale decreases the odds of unintended pregnancy by 16%. Besides autonomy, our results also indicate that current age, number of children ever born, age at marriage, religion, media access, and contraceptive use exert strong influences over unintended pregnancy. Women who have ever used contraceptives are 82% more likely to classify their current pregnancies as unintended compared with women who are non-users of contraceptives. Improvement in women's autonomy and effective and efficient use of contraceptives may reduce unintended pregnancies as well as improve reproductive health outcomes.

  17. Morning sickness and vitamin B6 status of pregnant women.

    PubMed

    Schuster, K; Bailey, L B; Dimperio, D; Mahan, C S

    1985-01-01

    The relationship between the vitamin B6 status of 180 pregnant women and the incidence and degree of morning sickness experienced during the first trimester was investigated. There were no significant differences in plasma pyridoxal 5'-phosphate (PLP), erythrocyte aspartate aminotransferase (AspAT) activity, and stimulation of erythrocyte AspAT activity by exogenous PLP between subjects who experienced morning sickness and those who did not. No relationship was found between these indicators of vitamin B6 status and the degree of morning sickness experienced by this group during early pregnancy. There were no differences in the number of women who experienced morning sickness or in the number with different degrees of sickness when plasma levels of PLP, erythrocyte AspAT activity or stimulation by PLP were divided into upper and lower 50th percentile groups and compared. Therefore these data show no relationship between vitamin B6 status and the incidence or degree of morning sickness.

  18. Plasma immunoreactive relaxin levels in pregnant and nonpregnant women.

    PubMed

    O'Byrne, E M; Carriere, B T; Sorensen, L; Segaloff, A; Schwabe, C; Steinetz, B G

    1978-11-01

    Immunoreactive relaxin was measured in plasma samples obtained from human volunteers utilizing the RIA procedure of Sherwood et al., as modified by O'Byrne and Steinetz for heterologous plasma samples. Immunoreactive hormone was not detected in samples obtained from men, and only rarely in plasma of nonpregnant women. Immunoreactive relaxin was present as early as the fourth week of pregnancy and was detectable throughout the course of gestation. Immunoreactive relaxin tended to be higher early in pregnancy, and there was no peak just before parturition as occurs in many other species. Our results are at variance with those of Bryant and coworkers, who reported high levels of immunoreactive relaxin in men and nonpregnant as well as pregnant women. The possible reasons for this discrepancy are presented.

  19. Smoking cessation support for pregnant women: role of mobile technology

    PubMed Central

    Heminger, Christina L; Schindler-Ruwisch, Jennifer M; Abroms, Lorien C

    2016-01-01

    Background Smoking during pregnancy has deleterious health effects for the fetus and mother. Given the high risks associated with smoking in pregnancy, smoking cessation programs that are designed specifically for pregnant smokers are needed. This paper summarizes the current landscape of mHealth cessation programs aimed at pregnant smokers and where available reviews evidence to support their use. Methods A search strategy was conducted in June–August 2015 to identify mHealth programs with at least one component or activity that was explicitly directed at smoking cessation assistance for pregnant women. The search for text messaging programs and applications included keyword searches within public health and medical databases of peer-reviewed literature, Google Play/iTunes stores, and gray literature via Google. Results Five unique short message service programs and two mobile applications were identified and reviewed. Little evidence was identified to support their use. Common tools and features identified included the ability to set your quit date, ability to track smoking status, ability to get help during cravings, referral to quitline, and tailored content for the individual participant. The theoretical approach utilized was varied, and approximately half of the programs included pregnancy-related content, in addition to cessation content. With one exception, the mHealth programs identified were found to have low enrollment. Conclusion Globally, there are a handful of applications and text-based mHealth programs available for pregnant smokers. Future studies are needed that examine the efficacy of such programs, as well as strategies to best promote enrollment. PMID:27110146

  20. Safety of Tdap vaccine in pregnant women: an observational study

    PubMed Central

    Petousis-Harris, Helen; Walls, Tony; Watson, Donna; Paynter, Janine; Graham, Patricia; Turner, Nikki

    2016-01-01

    Objectives Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. Design and settings A prospective observational study conducted in 2 New Zealand regions. Participants Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. Main outcomes measures Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. Results 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. Conclusions Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Trial registration number ACTRN12613001045707. PMID:27091823

  1. Breastfeeding, pregnant, and non-breastfeeding nor pregnant women's food consumption: A matched within-household analysis in India

    PubMed Central

    Fledderjohann, Jasmine; Vellakkal, Sukumar; Stuckler, David

    2016-01-01

    Objective Promoting breastfeeding is major maternal and child health goal in India. It is unclear whether mothers receive additional food needed to support healthy breastfeeding. Methods Using the latest National Family and Health Survey (2005–2006), we applied multilevel linear regression models to document correlates of nutrition for (n = 20,764) breastfeeding women. We then compared consumption of pulses, eggs, meat, fish, dairy, fruit, and vegetables across a sample of breastfeeding, non-breastfeeding/pregnant (NBP), and pregnant women (n = 3,409) matched within households and five-year age bands. We tested whether breastfeeding women had greater advantages in the 18 high-focus states of India's National Rural Health Mission (NRHM). Results Vegetarianism, caste, and religion were the strongest predictors of breastfeeding women's nutrition. Breastfeeding women had no nutritional advantage compared to NBP women, and were disadvantaged in their consumption of milk (b = −0.14) in low-focus states. Pregnant women were similarly disadvantaged in their consumption of milk in low-focus states (b = −0.32), but consumed vegetables more frequently (b = 0.12) than NBP women in high-focus states. Conclusions Breastfeeding women do not receive nutritional advantages compared to NBP women. Targeted effort is needed to assess and improve nutritional adequacy for breastfeeding Indian women. PMID:26826049

  2. Imported malaria in pregnant women: a retrospective pooled analysis

    PubMed Central

    Käser, Annina K.; Arguin, Paul M.; Chiodini, Peter L.; Smith, Valerie; Delmont, Jean; Jiménez, Beatriz C.; Färnert, Anna; Kimura, Mikio; Ramharter, Michael; Grobusch, Martin P.; Schlagenhauf, Patricia

    2015-01-01

    Summary Background Data on imported malaria in pregnant women are scarce. Method A retrospective, descriptive study of pooled data on imported malaria in pregnancy was done, using data from 1977 to 2014 from 8 different collaborators in Europe, the United States and Japan. Most cases were from the period 1991–2014. National malaria reference centresas well as specialists on this topic were asked to search their archives for cases of imported malaria in pregnancy. A total of 632 cases were collated, providing information on Plasmodium species, region of acquisition, nationality, country of residence, reason for travel, age, gestational age, prophylactic measures and treatment used, as well as on complications and outcomes in mother and child. Results Datasets from some sources were incomplete. The predominant Plasmodium species was P. falciparum in 72% of cases. Among the 543 cases where information on the use of chemoprophylaxis was known, 471 (74.5%) did not use chemoprophylaxis or used incorrect or incomplete chemoprophylaxis. The main reason for travelling was “visiting friends and relatives” VFR (48.6%) and overall, most cases of malaria were imported from West Africa (85.9%). Severe anaemia was the most frequent complication in the mother. Data on offspring outcome was limited, but spontaneous abortion was a frequently reported foetal outcome (n = 14). A total of 50 different variants of malaria treatment regimens were reported. Conclusion Imported cases of malaria in pregnancy are mainly P. falciparum acquired in sub-Saharan Africa. Malaria prevention and treatment in pregnant travellers is a challenge for travel medicine due to few data on medication safety and maternal and foetal outcomes. International, collaborative efforts are needed to capture standardized data on imported malaria cases in pregnant women. PMID:26227740

  3. Effectiveness of the Gold Standard Programmes (GSP) for Smoking Cessation in Pregnant and Non-Pregnant Women

    PubMed Central

    Rasmussen, Mette; Heitmann, Berit Lilienthal; Tønnesen, Hanne

    2013-01-01

    Background: Smoking is considered the most important preventable risk factor in relation to the development of complications during pregnancy and delivery. The aim of this study was to evaluate the effectiveness of an intensive 6-week gold standard programme (GSP) on pregnant women in real life. Methods: This was a prospective cohort study based on data from a national Danish registry on smoking cessation interventions. The study population included 10,682 women of a fertile age. The pregnancy status of the study population was identified using the National Patient Registry. Results: The response rate to follow up was 76%. The continuous abstinence rate for both pregnant and non-pregnant smokers was 24–32%. The following prognostic factors for continuous abstinence were identified: programme format (individual/group), older age, heavy smoking, compliance with the programme, health professional recommendation, and being a disadvantaged smoker. Conclusions: The GSP seems to be as effective among pregnant smokers as among non-pregnant smoking women. Due to the relatively high effect and clinical significance, the GSP would be an attractive element in smoking cessation intervention among pregnant women. PMID:23959083

  4. Perinatal Outcomes in Pregnant Women Users of Illegal Drugs.

    PubMed

    Oliveira, Tenilson Amaral; Bersusa, Ana Aparecida Sanches; Santos, Tatiana Fiorelli Dos; Aquino, Márcia Maria Auxiliadora de; Mariani Neto, Corintio

    2016-04-01

    Objective The purpose of this study was to evaluate the perinatal outcomes in pregnant women who use illicit drugs. Methods A retrospective observational study of patients who, at the time of delivery, were sent to or who spontaneously sought a public maternity hospital in the eastern area of São Paulo city. We compared the perinatal outcomes of two distinct groups of pregnant women - illicit drugs users and non-users - that gave birth in the same period and analyzed the obstetric and neonatal variables. We used Student's t-test to calculate the averages among the groups, and the Chi-square test or Fisher's exact test to compare categorical data from each group. Results We analyzed 166 women (83 users and 83 non-users) in both groups with a mean of age of 26 years. Ninety-five percent of the drug users would use crack or pure cocaine alone or associated with other psychoactive substances during pregnancy. Approximately half of the users group made no prenatal visit, compared with 2.4% in the non-users group (p < 0.001). Low birth weight (2,620 g versus 3,333 g on average, p < 0.001) and maternal syphilis (15.7% versus 0%, p < 0.001) were associated with the use of these illicit drugs. Conclusions The use of illicit drugs, mainly crack cocaine, represents an important perinatal risk. Any medical intervention in this population should combine adherence to prenatal care with strategies for reducing maternal exposure to illicit drugs.

  5. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    PubMed Central

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    “Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  6. Are pregnant and postpartum women: at increased risk for violent death? Suicide and homicide findings from North Carolina.

    PubMed

    Samandari, Ghazaleh; Martin, Sandra L; Kupper, Lawrence L; Schiro, Sharon; Norwood, Tammy; Avery, Matt

    2011-07-01

    The purpose of this study is to estimate rates of suicide and homicide death among pregnant, postpartum and non-pregnant/non-postpartum women ages 14-44, and to determine comparative rates of violent death for pregnant and/or postpartum women compared to non-pregnant/non-postpartum women. North Carolina surveillance and vital statistics data from 2004 to 2006 were used to examine whether pregnant or postpartum women have higher (or lower) rates of suicide and homicide compared to other reproductive-aged women. The suicide rate for pregnant women was 27% of the rate for non-pregnant/non-postpartum women (rate ratio= 0.27, 95% CI = 0.11-0.66), and the suicide rate for postpartum women was 54% of the rate for non-pregnant/non-postpartum women (rate ratio = 0.54, 95% CI = 0.31-0.95). Homicide rates also were lower for pregnant and postpartum women, with the homicide rate for pregnant women being 73% of the rate for non-pregnant/non-postpartum women (rate ratio = 0.73, 95% CI = 0.39-1.37), and the homicide rate for postpartum women being half the rate for non-pregnant/non-postpartum women (rate ratio = 0.50, 95% CI = 0.26-0.98). Although pregnant and postpartum women are at risk for homicide and suicide death, the highest risk group is non-pregnant/non-postpartum women. Violence prevention efforts should target all women of reproductive age, and pay particular attention to non-pregnant/non-postpartum women, who may have less access to health care services than pregnant and postpartum women.

  7. Determining rubella immunity in pregnant Alberta women 2009-2012.

    PubMed

    Lai, Florence Y; Dover, Douglas C; Lee, Bonita; Fonseca, Kevin; Solomon, Natalia; Plitt, Sabrina S; Jaipaul, Joy; Tipples, Graham A; Charlton, Carmen L

    2015-01-29

    Rubella IgG levels for 157,763 pregnant women residing in Alberta between 2009 and 2012 were analyzed. As there have been no reported cases of indigenous rubella infection in Canada since 2005, there has been a lack of naturally acquired immunity, and the current prenatal population depends almost entirely on vaccine induced immunity for protection. Rubella antibody levels are significantly lower in younger maternal cohorts with 16.8% of those born prior to universal vaccination programs (1971-1980), and 33.8% of those born after (1981-1990) having IgG levels that are not considered protective (<15 IU/mL). Analysis across pregnancies showed only 35.0% of women responded with a 4-fold increase in antibody levels following post-natal vaccination. Additionally, 41.2% of women with antibody levels <15 IU/mL had previously received 2 doses of rubella containing vaccine. These discordant interpretations generate a great deal of confusion for laboratorians and physicians alike, and result in significant patient follow-up by Public Health teams. To assess the current antibody levels in the prenatal population, latent class modeling was employed to generate a two class fit model representing women with an antibody response to rubella, and women without an antibody response. The declining level of vaccine-induced antibodies in our population is disconcerting, and a combined approach from the laboratory and Public Health may be required to provide appropriate follow up for women who are truly susceptible to rubella infection.

  8. Psychometric Evaluation of the Multidimensional Assessment of Fatigue Scale for Use with Pregnant and Postpartum Women

    ERIC Educational Resources Information Center

    Fairbrother, Nichole; Hutton, Eileen K.; Stoll, Kathrin; Hall, Wendy; Kluka, Sandy

    2008-01-01

    Although fatigue is a common experience for pregnant women and new mothers, few measures of fatigue have been validated for use with this population. To address this gap, the authors assessed psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale, which was used in 2 independent samples of pregnant women. Results…

  9. Sources of Malaria Information among Pregnant Women in Ebonyi State and Implications for Malaria Health Education

    ERIC Educational Resources Information Center

    Amari-Omaka, Lois Nnenna; Obande-Ogbuinya, Nkiru Edith

    2016-01-01

    The purpose of this study was to determine sources of malaria information among pregnant women in Ebonyi state and implications for malaria education. The cross sectional research design was adopted and stratified sampling technique was used to select a total of five hundred and four (504) pregnant women from 12 hospitals in the state. A self…

  10. Zika Virus Knowledge among Pregnant Women Who Were in Areas with Active Transmission

    PubMed Central

    Whittemore, Kate; Tate, Anna; Illescas, Alex; Saffa, Alhaji; Collins, Austin; Varma, Jay K.

    2017-01-01

    We surveyed women in New York, New York, USA, who were in areas with active Zika virus transmission while pregnant. Of 99 women who were US residents, 30 were unaware of the government travel advisory to areas with active Zika virus transmission while pregnant, and 37 were unaware of their pregnancies during travel. PMID:27855041

  11. Zika Virus Knowledge among Pregnant Women Who Were in Areas with Active Transmission.

    PubMed

    Whittemore, Kate; Tate, Anna; Illescas, Alex; Saffa, Alhaji; Collins, Austin; Varma, Jay K; Vora, Neil M

    2017-01-01

    We surveyed women in New York, New York, USA, who were in areas with active Zika virus transmission while pregnant. Of 99 women who were US residents, 30 were unaware of the government travel advisory to areas with active Zika virus transmission while pregnant, and 37 were unaware of their pregnancies during travel.

  12. 42 CFR 436.120 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Qualified pregnant women and children who are not... women and children who are not qualified family members. (a) The Medicaid agency must provide Medicaid to a pregnant woman whose pregnancy has been medically verified and who— (1) Would be eligible for...

  13. Assessment of Anemia Knowledge, Attitudes and Behaviors among Pregnant Women in Sierra Leone

    ERIC Educational Resources Information Center

    M'Cormack, Fredanna A. D.; Drolet, Judy C.

    2012-01-01

    Introduction: Iron deficiency anemia prevalence of pregnant Sierra Leone women currently is reported to be 59.7%. Anemia is considered to be a direct cause of 3-7% of maternal deaths and an indirect cause of 20-40% of maternal deaths. This study explores knowledge, attitudes, and behaviors of urban pregnant Sierra Leone women regarding anemia.…

  14. 42 CFR 436.120 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Qualified pregnant women and children who are not... women and children who are not qualified family members. (a) The Medicaid agency must provide Medicaid to a pregnant woman whose pregnancy has been medically verified and who— (1) Would be eligible for...

  15. Prevention of supine hypotensive syndrome in pregnant women treated with transcranial magnetic stimulation.

    PubMed

    Kim, Deborah Rubin; Wang, Eileen

    2014-08-15

    In our studies of transcranial magnetic stimulation in pregnant women with major depressive disorder, two subjects had an episode of supine hypotensive syndrome and one subject had an episode of dizziness without hypotension. Prevention of the supine hypotensive syndrome in pregnant women receiving transcranial magnetic stimulation is described.

  16. Recruitment and Retention of Substance-Using Pregnant and Parenting Women: Lessons Learned.

    ERIC Educational Resources Information Center

    Laken, Marilyn Poland; Hutchins, Ellen

    According to current estimates, approximately 5.5 percent of all American pregnant women use an illicit drug during pregnancy. National concern for drug-exposed infants prompted interest in the needs of substance using pregnant women and in the development of drug treatment programs for them. A total of 147 comprehensive programs have been funded…

  17. 42 CFR 436.120 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Qualified pregnant women and children who are not... women and children who are not qualified family members. (a) The Medicaid agency must provide Medicaid to a pregnant woman whose pregnancy has been medically verified and who— (1) Would be eligible for...

  18. 42 CFR 436.120 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Qualified pregnant women and children who are not... women and children who are not qualified family members. (a) The Medicaid agency must provide Medicaid to a pregnant woman whose pregnancy has been medically verified and who— (1) Would be eligible for...

  19. 42 CFR 436.120 - Qualified pregnant women and children who are not qualified family members.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Qualified pregnant women and children who are not... women and children who are not qualified family members. (a) The Medicaid agency must provide Medicaid to a pregnant woman whose pregnancy has been medically verified and who— (1) Would be eligible for...

  20. Deoxynivalenol Exposure Assessment for Pregnant Women in Bangladesh.

    PubMed

    Ali, Nurshad; Blaszkewicz, Meinolf; Al Nahid, Abdullah; Rahman, Mustafizur; Degen, Gisela H

    2015-09-24

    The trichothecene mycotoxin deoxynivalenol (DON) is a contaminant of crops worldwide and known to cause adverse health effects in exposed animals and humans. A small survey reported the presence of DON in maize samples in Bangladesh, but these data are insufficient to assess human exposure, and also, biomonitoring data are still scarce. The present study applied biomarker analysis to investigate the DON exposure of pregnant women in Bangladesh. Urine samples were collected from pregnant women living in a rural (n = 32) and in a suburban (n = 22) area of the country. Urines were subjected to enzymatic hydrolysis of glucuronic acid conjugates and to immunoaffinity column clean-up prior to LC-MS/MS analysis of DON and its de-epoxy metabolite DOM-1. The limits of detection (LOD) for DON and DOM-1 in urine were 0.16 ng/mL and 0.10 ng/mL, respectively. DOM-1 was not detected in any of the urines, whilst DON was detectable in 52% of the samples at levels ranging from 0.18-7.16 ng/mL and a mean DON concentration of 0.86 ± 1.57 ng/mL or 2.14 ± 4.74 ng/mg creatinine. A significant difference in mean urinary DON levels was found between the rural (0.47 ± 0.73 ng/mL) and suburban (1.44 ± 2.20 ng/mL) cohort, which may be related to different food habits in the two cohorts. Analysis of food consumption data for the participants did not show significant correlations between their intake of typical staple foods and DON levels in urine. The biomarker concentrations found and published urinary excretion rates for DON were used to estimate daily mycotoxin intake in the cohort: the mean DON intake was 0.05 µg/kg b.w., and the maximum intake was 0.46 µg/kg b.w., values lower than the tolerable daily intake of 1 µg/kg b.w. These first results indicate a low dietary exposure of pregnant women in Bangladesh to DON. Nonetheless, further biomonitoring studies in children and in adult cohorts from other parts of the country are of interest to gain more insight into DON exposure in the

  1. Preparedness of pregnant women for childbirth and the postpartum period: their knowledge and fear.

    PubMed

    Tugut, N; Tirkes, D; Demirel, G

    2015-05-01

    The aim of the study was to identify knowledge and fear related to childbirth and the postpartum period in pregnant women. The sample consisted of 114 pregnant women. It was determined that pregnant women had insufficient levels of knowledge related to childbirth and the postpartum period. The Fear of Childbirth and Postpartum Anxiety Scale score for childbirth and the postpartum period related to 'fear regarding the action of childbirth', was found to be the highest. The highest causes for concern were determined to be 'infant-related anxiety' and 'fear regarding infant and puerperal health'. No statistically significant correlation was observed between the perceived sufficiency of the knowledge of pregnant women in terms of maintaining their own health and care, and their mean childbirth and postpartum period concern score. These findings indicate that the level of concern among pregnant women with relation to the postpartum period and childbirth is rather high.

  2. 16S rRNA gene-based metagenomic analysis reveals differences in bacteria-derived extracellular vesicles in the urine of pregnant and non-pregnant women

    PubMed Central

    Yoo, Jae Young; Rho, Mina; You, Young-Ah; Kwon, Eun Jin; Kim, Min-Hye; Kym, Sungmin; Jee, Young-Koo; Kim, Yoon-Keun; Kim, Young Ju

    2016-01-01

    Recent evidence has indicated that bacteria-derived extracellular vesicles (EVs) are important for host–microbe communication. The aims of the present study were to evaluate whether bacteria-derived EVs are excreted via the urinary tract and to compare the composition of bacteria-derived EVs in the urine of pregnant and non-pregnant women. Seventy-three non-pregnant and seventy-four pregnant women were enrolled from Dankook University and Ewha Womans University hospitals. DNA was extracted from urine EVs after EV isolation using the differential centrifugation method. 16S ribosomal RNA (16S rRNA) gene sequencing was performed using high-throughput 454 pyrosequencing after amplification of the V1–V3 region of the 16S rDNA. The composition of 13 taxa differed significantly between the pregnant and non-pregnant women. At the genus level, Bacillus spp. EVs were more significantly enriched in the urine of the pregnant women than in that of the non-pregnant women (45.61% vs 0.12%, respectively). However, Pseudomonas spp. EVs were more dominant in non-pregnant women than in pregnant women (13.2% vs 4.09%, respectively). Regarding the compositional difference between pregnant women with normal and preterm delivery, EVs derived from Ureaplasma spp. and the family Veillonellaceae (including Megasphaera spp.) were more abundant in the urine of preterm-delivered women than in that of women with normal deliveries. Taken together, these data showed that Bacillus spp. EVs predominate in the urine of pregnant women, whereas Pseudomonas spp. EVs predominate in the urine of non-pregnant women; this suggests that Bacillus spp. EVs might have an important role in the maintenance of pregnancy. PMID:26846451

  3. 16S rRNA gene-based metagenomic analysis reveals differences in bacteria-derived extracellular vesicles in the urine of pregnant and non-pregnant women.

    PubMed

    Yoo, Jae Young; Rho, Mina; You, Young-Ah; Kwon, Eun Jin; Kim, Min-Hye; Kym, Sungmin; Jee, Young-Koo; Kim, Yoon-Keun; Kim, Young Ju

    2016-02-05

    Recent evidence has indicated that bacteria-derived extracellular vesicles (EVs) are important for host-microbe communication. The aims of the present study were to evaluate whether bacteria-derived EVs are excreted via the urinary tract and to compare the composition of bacteria-derived EVs in the urine of pregnant and non-pregnant women. Seventy-three non-pregnant and seventy-four pregnant women were enrolled from Dankook University and Ewha Womans University hospitals. DNA was extracted from urine EVs after EV isolation using the differential centrifugation method. 16S ribosomal RNA (16S rRNA) gene sequencing was performed using high-throughput 454 pyrosequencing after amplification of the V1-V3 region of the 16S rDNA. The composition of 13 taxa differed significantly between the pregnant and non-pregnant women. At the genus level, Bacillus spp. EVs were more significantly enriched in the urine of the pregnant women than in that of the non-pregnant women (45.61% vs 0.12%, respectively). However, Pseudomonas spp. EVs were more dominant in non-pregnant women than in pregnant women (13.2% vs 4.09%, respectively). Regarding the compositional difference between pregnant women with normal and preterm delivery, EVs derived from Ureaplasma spp. and the family Veillonellaceae (including Megasphaera spp.) were more abundant in the urine of preterm-delivered women than in that of women with normal deliveries. Taken together, these data showed that Bacillus spp. EVs predominate in the urine of pregnant women, whereas Pseudomonas spp. EVs predominate in the urine of non-pregnant women; this suggests that Bacillus spp. EVs might have an important role in the maintenance of pregnancy.

  4. Maraviroc Pharmacokinetics in HIV-1–Infected Pregnant Women

    PubMed Central

    Colbers, Angela; Best, Brookie; Schalkwijk, Stein; Wang, Jiajia; Stek, Alice; Hidalgo Tenorio, Carmen; Hawkins, David; Taylor, Graham; Kreitchmann, Regis; Burchett, Sandra; Haberl, Annette; Kabeya, Kabamba; van Kasteren, Marjo; Smith, Elizabeth; Capparelli, Edmund; Burger, David; Mirochnick, Mark

    2015-01-01

    Objective. To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)–infected women during pregnancy and post partum. Methods. HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. Results. Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60–.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58–0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03–0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing. Conclusions. Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy. Clinical Trials Registration. NCT00825929 and NCT000422890. PMID:26202768

  5. Intimate partner violence and suicidal ideation in pregnant women.

    PubMed

    Alhusen, Jeanne L; Frohman, N; Purcell, Genevieve

    2015-08-01

    Intimate partner violence (IPV) during pregnancy is a major public health issue with significant implications for maternal mental health. Less studied is the association between IPV during pregnancy and suicidal ideation. This study reports the prevalence and correlates of suicidal ideation among low-income pregnant women receiving prenatal care at a university obstetrical clinic from February 2009 to March 2010. We performed a cross-sectional analysis of 166 women surveyed between 24 and 28 weeks of gestation using the Edinburgh Postnatal Depression Scale (EPDS) and the Abuse Assessment Screen (AAS). Multiple logistic regression identified factors associated with antenatal suicidal ideation. The prevalence of suicidal ideation was 22.89 %. In the fully adjusted model, antenatal depressive symptomatology (OR = 17.04; 95 % CI 2.10-38.27) and experiencing IPV (OR = 9.37; 95 % CI 3.41-25.75) were significantly associated with an increased risk of antenatal suicidal ideation. The prevalence of antenatal suicidal ideation in the current study was higher than other population-based samples though this sample was predominantly single, low-income, and 19 % experienced IPV during pregnancy. Given the strong association of antenatal suicidal ideation, depressive symptomatology, and IPV, health care providers are urged to identify those women at risk so that antenatal care can be tailored to best support optimal maternal and neonatal outcomes.

  6. Epidemiology of anaemia among pregnant women in Geizera, central Sudan.

    PubMed

    Abdelgadir, M A; Khalid, A R; Ashmaig, A L; Ibrahim, A R M; Ahmed, A-Aziz M; Adam, I

    2012-01-01

    A cross-sectional study was conducted between August and September 2010 at the antenatal care clinic of the Araba Waeshreen Hospital (Geizera), central Sudan. Sociodemographic, medical, obstetric and use of pica information were gathered. Body mass index (BMI) was calculated. Haemoglobin levels were measured and blood films and stools were examined for malaria and schistosomiasis. Out of the 292 women, 119 (40.8%) had anaemia (HB < 11 g/dl); eight (2.7%) had severe anaemia (HB < 7 g/dl). One patient had a positive blood film for malaria. A total of 38 (13.0%) out of the 292 pregnant women had S. mansoni infections. While age, parity, gestational age, education, occupation, interpregnancy interval and BMI were not associated with anaemia, pica (OR = 1.7, 95% CI = 1.0-2.9, p = 0.02) and S. mansoni infections (OR = 2.8, 95% CI = 1.2-6.7, p = 0.01) were significantly associated with anaemia using univariate and multivariate analyses. The high prevalence of anaemia among these women needs to be controlled through preventive measurement of S. mansoni infections and health education to prevent practising pica.

  7. Abnormal vaginal flora in symptomatic non-pregnant and pregnant women in a Greek hospital: a prospective study.

    PubMed

    Tansarli, G S; Skalidis, T; Legakis, N J; Falagas, M E

    2017-02-01

    Bacterial vaginosis (BV), candidiasis, and trichomoniasis were the three established types of vaginal conditions until aerobic vaginitis (AV) was defined in the early 2000s. We sought to study the prevalence of abnormal vaginal flora (AVF) with inflammation in our hospital and to correlate it with AV. We prospectively collected vaginal smear specimens originated from symptomatic women who were examined at Iaso Obstetrics, Gynecology and Children's Hospital of Athens from April 2014 until September 2015. Amsel's criteria were used for the diagnosis of BV. The presence of leukocytes and lactobacillary grade were evaluated to classify a condition as AVF with inflammation; subsequently, bacterial cultures were performed. A total of 761 women were included. Five hundred and seventy-nine women were diagnosed with candidiasis, BV, trichomoniasis, or other types of vaginitis in which no pathogenic bacterial growth occurred in cultures. One hundred and eighty-two women (23.9 %) were diagnosed with AVF with inflammation (116 non-pregnant, 66 pregnant). Escherichia coli was the most common pathogen among these women (non-pregnant: 45.7 %, pregnant: 34.8 %). Other common pathogens were Group-B-Streptococcus (non-pregnant: 20.7 %, pregnant: 22.7 % respectively), Enterococcus faecalis (14.7 %, 18.2 %), and Klebsiella pneumoniae (6.9 %, 12.1 %). The prevalence of AVF with inflammation may be high. Since inflammation criteria were applied, most cases of BV were eliminated and the majority of cases of AVF are AV. Therefore, clinicians should include AV in the differential diagnosis of vaginitis, while microbiologists should take into account the growth of aerobic bacteria in vaginal cultures originating from women with microscopic findings of AV.

  8. [Radiation effects on pregnant women, fetuses, and children].

    PubMed

    Neriishi, Kazuo; Monzen, Yoshio; Okamoto, Naomasa

    2012-03-01

    We conducted a review of literature related to radiation effects on pregnant women, fetuses, and children from the perspective of epidemiology, pathology, and radiobiology. During 8-25 weeks post-conception the central nervous system is particularly sensitive to radiation. Fetal doses in excess of 100 mGy can result in some reduction of IQ (intelligence quotient). Fetal doses in the range of 1000 mGy can lead to severe mental retardation and microcephaly, particularly during 8-15 weeks and to a lesser extent 16-25 weeks after conception. Recent studies of cancers and chromosome aberrations indicated less radiosensitivity in prenatally exposed A-bomb survivors compared with postnatally exposed survivors, for which we provide possible hypotheses as an explanation.

  9. Attitudes, Intentions, and Barriers Toward Influenza Vaccination Among Pregnant Korean Women.

    PubMed

    Kang, Hee Sun; De Gagne, Jennie C; Kim, Jung-Hee

    2015-09-01

    Following our study of attitudes, barriers, and intentions concerning the influenza vaccination among pregnant women in South Korea, we discovered that women displaying a more positive attitude toward the influenza vaccination were more likely to receive it during their pregnancy. We also found that attitudes toward vaccination were more positive among vaccinated pregnant women than among those who were unvaccinated. Furthermore, women showed a greater intention to get vaccinated if a clinician, rather than friends, recommended it. The major perceived barriers to receiving an influenza vaccination were being pregnant, fearing harm to the baby, feeling healthy, and thinking it is unnecessary.

  10. A Pilot Study of the Nutritional Status of Opiate Abusing Pregnant Women on Methadone Maintenance Therapy

    PubMed Central

    Tomedi, Laura E.; Bogen, Debra; Hanusa, Barbara H.; Wisner, Katherine L.; Bodnar, Lisa M.

    2011-01-01

    Pregnant women in methadone maintenance therapy may have poor nutrition during pregnancy. In 2006–2008, methadone treated pregnant women (n = 22) were recruited at an urban academic medical center and compared with non-drug using pregnant women (n = 119) at 20–35 weeks gestation. We measured adiposity using pre-pregnancy body mass index (BMI), dietary intake using a food frequency questionnaire, and micronutrient and essential fatty acid status using biomarkers. Methadone treated women had lower BMI, consumed more calories, had lower serum carotenoid concentrations and higher plasma homocysteine concentrations than controls. The study’s limitations and implications for future research are discussed. PMID:22217127

  11. Broadly Neutralizing Antibodies Display Potential for Prevention of HIV-1 Infection of Mucosal Tissue Superior to That of Nonneutralizing Antibodies.

    PubMed

    Cheeseman, Hannah M; Olejniczak, Natalia J; Rogers, Paul M; Evans, Abbey B; King, Deborah F L; Ziprin, Paul; Liao, Hua-Xin; Haynes, Barton F; Shattock, Robin J

    2017-01-01

    Definition of the key parameters mediating effective antibody blocking of HIV-1 acquisition within mucosal tissue may prove critical to effective vaccine development and the prophylactic use of monoclonal antibodies. Although direct antibody-mediated neutralization is highly effective against cell-free virus, antibodies targeting different sites of envelope vulnerability may display differential activity against mucosal infection. Nonneutralizing antibodies (nnAbs) may also impact mucosal transmission events through Fc-gamma receptor (FcγR)-mediated inhibition. In this study, a panel of broadly neutralizing antibodies (bnAbs) and nnAbs, including those associated with protection in the RV144 vaccine trial, were screened for the ability to block HIV-1 acquisition and replication across a range of cellular and mucosal tissue models. Neutralization potency, as determined by the TZM-bl infection assay, did not fully predict activity in mucosal tissue. CD4-binding site (CD4bs)-specific bnAbs, in particular VRC01, were consistent in blocking HIV-1 infection across all cellular and tissue models. Membrane-proximal external region (MPER) (2F5) and outer domain glycan (2G12) bnAbs were also efficient in preventing infection of mucosal tissues, while the protective efficacy of bnAbs targeting V1-V2 glycans (PG9 and PG16) was more variable. In contrast, nnAbs alone and in combinations, while active in a range of cellular assays, were poorly protective against HIV-1 infection of mucosal tissues. These data suggest that tissue resident effector cell numbers and low FcγR expression may limit the potential of nnAbs to prevent establishment of the initial foci of infection. The solid protection provided by specific bnAbs clearly demonstrates their superior potential over that of nonneutralizing antibodies for preventing HIV-1 infection at the mucosal portals of infection.

  12. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms

    PubMed Central

    Harper, Michael S.; Guo, Kejun; Gibbert, Kathrin; Lee, Eric J.; Dillon, Stephanie M.; Barrett, Bradley S.; McCarter, Martin D.; Hasenkrug, Kim J.; Dittmer, Ulf; Wilson, Cara C.; Santiago, Mario L.

    2015-01-01

    HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs) likely serve as a first line of defense, but the relative expression and antiviral properties of the 12 IFNα subtypes against HIV-1 infection of mucosal tissues remain unknown. Here, we evaluated the expression of all IFNα subtypes in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined the relative antiviral potency of each IFNα subtype ex vivo using the human intestinal Lamina Propria Aggregate Culture model. IFNα subtype transcripts from the centromeric half of the IFNA gene complex were highly expressed in pDCs following HIV-1 exposure. There was an inverse relationship between IFNA subtype expression and potency. IFNα8, IFNα6 and IFNα14 were the most potent in restricting HIV-1 infection. IFNα2, the clinically-approved subtype, and IFNα1 were both highly expressed but exhibited relatively weak antiviral activity. The relative potencies correlated with binding affinity to the type I IFN receptor and the induction levels of HIV-1 restriction factors Mx2 and Tetherin/BST-2 but not APOBEC3G, F and D. However, despite the lack of APOBEC3 transcriptional induction, the higher relative potency of IFNα8 and IFNα14 correlated with stronger inhibition of virion infectivity, which is linked to deaminase-independent APOBEC3 restriction activity. By contrast, both potent (IFNα8) and weak (IFNα1) subtypes significantly induced HIV-1 GG-to-AG hypermutation. The results unravel non-redundant functions of the IFNα subtypes against HIV-1 infection, with strong implications for HIV-1 mucosal immunity, viral evolution and IFNα-based functional cure strategies. PMID:26529416

  13. Dyslipidemia and Cardiovascular Disease Risk Factor Management in HIV-1-Infected Subjects Treated with HAART in the Spanish VACH Cohort

    PubMed Central

    Domingo, Pere; Suarez-Lozano, Ignacio; Teira, Ramón; Lozano, Fernando; Terrón, Alberto; Viciana, Pompeyo; González, Juan; Galindo, Mª José; Geijo, Paloma; Vergara, Antonio; Cosín, Jaime; Ribera, Esteban; Roca, Bernardino; Garcia-Alcalde, Mª Luisa; Sánchez, Trinitario; Torres, Ferran; Lacalle, Juan Ramón; Garrido, Myriam

    2008-01-01

    Background: There is increasing evidence that metabolic adverse effects associated with antiretroviral therapy may translate into an increased cardiovascular risk in HIV-1-infected patients. Objectives: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-1-infected persons, and to investigate any association between them, stage of HIV-1 disease, and use of antiretroviral therapies. Methods: Multicentric, cross-sectional analysis of CVD risk factors of treated patients in the VACH cohort. The data collected includes: demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidemia, body mass index, stage of HIV-1 infection, and antiretroviral therapy. Results: The analysis included 2358 patients. More than 18% of the study population was at an age of appreciable risk of CVD. 1.7% had previous CVD and 59.2% were smokers. Increased prevalence of elevated total cholesterol was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 3.34; 95% confidence interval (CI), 1.77–6.31], PI but no NNRTI (OR, 4.04; 95% CI, 2.12–7.71), or NNRTI + PI (OR, 17.77; 95% CI, 7.24–43.59) compared to patients treated only with nucleoside reverse transcriptase inhibitors (NRTI). Higher CD4 cell count, lower plasma HIV-1 RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated cholesterol levels. The use of lipid lowering agents was very low among our patients. Conclusion: Patients in the VACH cohort present multiple known risk factors for CVD, and a very low rate of lipid lowering therapy use. NNRTI and/or PI-based antiretroviral therapies are associated with the worst lipid profile. This is more frequent in older subjects with greater CD4 counts and controlled HIV-1 replication. PMID:18923695

  14. Viremic Control and Viral Coreceptor Usage in Two HIV-1-Infected Persons Homozygous for CCR5 Δ32

    PubMed Central

    Henrich, Timothy J.; Hanhauser, Emily; Hu, Zixin; Stellbrink, Hans-Jürgen; Noah, Christian; Martin, Jeffrey N.; Deeks, Steven G.; Kuritzkes, Daniel R.; Pereyra, Florencia

    2015-01-01

    Objectives To determine viral and immune factors involved in transmission and control of HIV-1 infection in persons without functional CCR5 Design Understanding transmission and control of HIV-1 in persons homozygous for CCR5Δ32 is important given efforts to develop HIV-1 curative therapies aimed at modifying or disrupting CCR5 expression. Methods We identified two HIV-infected CCR5Δ32/Δ32 individuals among a cohort of patients with spontaneous control of HIV-1 infection without antiretroviral therapy and determined co-receptor usage of the infecting viruses. We assessed genetic evolution of full-length HIV-1 envelope sequences by single-genome analysis from one participant and his sexual partner, and explored HIV-1 immune responses and HIV-1 mutations following virologic escape and disease progression. Results Both participants experienced viremia of less than 4,000 RNA copies/ml with preserved CD4+ T cell counts off ART for at least 3.3 and 4.6 years after diagnosis, respectively. One participant had phenotypic evidence of X4 virus, had no known favorable HLA alleles, and appeared to be infected by minority X4 virus from a pool that predominately used CCR5 for entry. The second participant had virus that was unable to use CXCR4 for entry in phenotypic assay but was able to engage alternative viral coreceptors (e.g. CXCR6) in vitro. Conclusions Our study demonstrates that individuals may be infected by minority X4 viruses from a population that predominately uses CCR5 for entry, and that viruses may bypass traditional HIV-1 coreceptors (CCR5 and CXCR4) completely by engaging alternative coreceptors to establish and propagate HIV-1 infection. PMID:25730507

  15. Adjustment Disorder in Pregnant Women: Prevalence and Correlates in a Northern Mexican City

    PubMed Central

    Alvarado-Esquivel, Cosme; Sifuentes-Alvarez, Antonio; Salas-Martinez, Carlos

    2015-01-01

    Background The epidemiology of adjustment disorder in pregnant women is largely unknown. We sought to determine the prevalence and correlates of adjustment disorder in pregnant women in Durango City, Mexico. Methods Pregnant women (n = 300) attending in a public hospital in Durango City, Mexico were studied. All enrolled pregnant women had a psychiatric interview to evaluate the presence of adjustment disorder using the DSM-IV criteria. A questionnaire was submitted to obtain general epidemiological data of the pregnant women studied. Bivariate and multivariate analyses were used to assess the association of adjustment disorder with the epidemiological data of the women studied. Results Fifteen (5.0%) of the 300 women studied had adjustment disorder according to the DSM-IV criteria. Adjustment disorder was not associated with age, occupation, marital status, or education of pregnant women. In contrast, multivariate analysis of socio-demographic, clinical and psychosocial variables showed that adjustment disorder was associated with the variables lack of support from her couple (odds ratio (OR) = 3.83; 95% confidence interval (CI): 1.00 - 14.63; P = 0.04) and couple living abroad (OR = 10.12; 95% CI: 1.56 - 65.50; P = 0.01). Conclusions This is the first report about the epidemiology of adjustment disorder in pregnant women in Mexico. Results provide evidence of the presence of adjustment disorder and contributing psychosocial factors associated with this disorder in pregnant women in Mexico. Results point towards further clinical and research attention should be given to this neglected disorder in pregnant women. PMID:26346070

  16. Implications of Nutritional Beliefs and Taboos--Hausa and Yoruba Pregnant Women in Lagos, Nigeria.

    ERIC Educational Resources Information Center

    Abidoye, R. O.; Akinpelumi, O. B.

    1997-01-01

    Investigated taboos and beliefs about the nutritional value of foods among pregnant women from Nigeria's Hausa and Yoruba tribes. Found that Hausa women had greater nutritional anemia than Yoruba women; their babies had greater incidence of low birth weights and smaller chest and head measurements. Hausa women learned food-related beliefs from…

  17. Acne vulgaris and acne rosacea as part of immune reconstitution disease in HIV-1 infected patients starting antiretroviral therapy.

    PubMed

    Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David

    2008-07-01

    Immune reconstitution disease (IRD) has been widely reported following the commencement of antiretrovirals. We report a case series from a cohort of HIV-1-infected patients of whom four developed acne vulgaris and one developed acne rosacea after the initiation of antiretroviral therapy. Acne vulgaris, as part of IRD, has been reported only once in the literature, whereas acne rosacea has not, to our knowledge, previously been described. This serves as a reminder not to overlook dermatological manifestations of disease in patients with HIV infection after starting antiretrovirals.

  18. 34 CFR 403.81 - How must funds be used under the Single Parents, Displaced Homemakers, and Single Pregnant Women...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., Displaced Homemakers, and Single Pregnant Women Program? 403.81 Section 403.81 Education Regulations of the... Secretary Assist Under the Basic Programs? Single Parents, Displaced Homemakers, and Single Pregnant Women... Pregnant Women Program? A State shall use funds reserved in accordance with § 403.180(b)(2)(i)...

  19. 45 CFR 46.203 - Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... involving pregnant women, fetuses, and neonates. 46.203 Section 46.203 Public Welfare DEPARTMENT OF HEALTH... Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.203 Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates. In addition to other responsibilities assigned...

  20. 45 CFR 46.203 - Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... involving pregnant women, fetuses, and neonates. 46.203 Section 46.203 Public Welfare DEPARTMENT OF HEALTH... Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.203 Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates. In addition to other responsibilities assigned...

  1. 45 CFR 46.203 - Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... involving pregnant women, fetuses, and neonates. 46.203 Section 46.203 Public Welfare DEPARTMENT OF HEALTH... Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.203 Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates. In addition to other responsibilities assigned...

  2. 45 CFR 46.203 - Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... involving pregnant women, fetuses, and neonates. 46.203 Section 46.203 Public Welfare Department of Health... Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.203 Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates. In addition to other responsibilities assigned...

  3. 45 CFR 46.203 - Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... involving pregnant women, fetuses, and neonates. 46.203 Section 46.203 Public Welfare DEPARTMENT OF HEALTH... Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.203 Duties of IRBs in connection with research involving pregnant women, fetuses, and neonates. In addition to other responsibilities assigned...

  4. Effect of betel chewing on the frequency of sister chromatid exchanges in pregnant women and women using oral contraceptives.

    PubMed

    Ghosh, P K; Ghosh, R

    1988-06-01

    The incidence of sister chromatid exchange (SCE) was investigated in the lymphocyte chromosomes of betel chewing and non-chewing normal women, pregnant women, and women using oral contraceptives. The frequency of SCE was found to be 7.82 +/- 0.24 and 8.27 +/- 0.27 in non-chewing pregnant women and women using oral contraceptives respectively, which were significantly higher than the mean value of 5.21 +/- 0.18 observed in non-chewing normal women. Betel chewing induced higher SCE in pregnant women and women using oral contraceptives, the frequencies being 11.79 +/- 0.38 and 12.51 +/- 0.44, respectively, which were significantly higher than the SCE frequency of 6.28 +/- 0.21 found in normal betel chewing females.

  5. Economic Evaluation of Health Services Costs During Pandemic Influenza A (H1N1) Pdm09 Infection in Pregnant and Non-Pregnant Women in Spain

    PubMed Central

    MORALES-SUÁREZ-VARELA, María; LLOPIS-GONZÁLEZ, Agustín; GONZÁLEZ-CANDELA, Fernando; ASTRAY, Jenaro; ALONSO, Jordi; GARIN, Olatz; CASTRO, Ady; GALAN, Juan Carlos; SOLDEVILA, Nuria; CASTILLA, Jesús; GODOY, Pere; DELGADO-RODRÍGUEZ, Miguel; MARTIN, Vicente; MAYORAL, Jose María; PUMAROLA, Tomas; QUINTANA, José Maria; TAMAMES, Sonia; RUBIO-LÓPEZ, Nuria; DOMINGUEZ, Angela

    2016-01-01

    Background: The healthcare and socio-economic burden resulting from influenza A (H1N1) pdm09 in Spain was considerable. Our aim was to estimate and compare the management (resource utilization) and economic healthcare impact in an at-risk group of unvaccinated pregnant women with an unvaccinated group of non-pregnant woman of childbearing age (15–44 yr old). Methods: We addressed this question with a longitudinal, observational, multicentre study. Inputs were the requirements in managing both groups of women. Outcome measures were healthcare costs. Direct healthcare (including medical utilisation, prescriptions of antivirals, medication, diagnostic tests, and hospitalisation) costs and indirect (productivity loss) costs were considered. Unit of cost was attributed to the frequency of health service resources utilisation. The mean cost per patient was calculated in this group of women. Results: We found that the influenza clinical pattern was worse in non-pregnant women as they had a high medical risk of 20.4% versus 6.1% of pregnant women. Non-pregnant required more antipyretics and antibiotics, and needed more health service resource utilisation (338 medical visits in non-pregnant women vs. 42 in pregnant women). The total cost of non-pregnant women was higher (€4,689.4/non-pregnant and €2,945.07/pregnant). Conclusions: Cost per (H1N1) pdm09 was lower for pregnant women, probably due to more preventive measures adopted for their protection in Spain. The highest costs were incurred by hospitalisations/day and work absenteeism for non-pregnant than for pregnant women. These data will allow better future pandemic influenza planning. PMID:27252911

  6. Brazilian pregnant and lactating women do not change their food intake to meet nutritional goals

    PubMed Central

    2014-01-01

    Background Nutritional requirements are increased during pregnancy and lactation. The aim of this study was to compare the food intake and prevalence of inadequate nutrient intake among pregnant, lactating and reproductive-age women. Methods Two-day dietary records of 322 pregnant and 751 lactating women were compared to those of 6837 non-pregnant and non-lactating women aged 19 to 40 years from a nationwide representative sample. The usual nutrient intake was estimated using the National Cancer Institute method, and compared to nutritional goals to estimate prevalence of inadequate intake. Results Pregnant, lactating and reproductive-age women did not differ in their average consumption of 18 food groups, except for rice, with greatest intake among lactating women. The prevalence of nutrient inadequacy in pregnant women was higher than in reproductive-age women for folate (78% versus 40%) and vitamin B6 (59% versus 33%). In lactating women, prevalence was higher than in reproductive-age women for vitamin A (95% versus 72%), vitamin C (56% versus 37%), vitamin B6 (75% vs. 33%), folate (72% versus 40%) and zinc (64% versus 20%). The percentage of sodium intake above the upper limit was greater than 70% in the three groups. Conclusions Inadequate intake is frequent in women and increases during pregnancy and lactation, because women do not change their food intake. Guidelines should stimulate healthy food intake for women across the lifespan. PMID:24890188

  7. Rubella Immune Status in Pregnant Women in a Northern Mexican City

    PubMed Central

    Alvarado-Esquivel, Cosme; Hernandez-Tinoco, Jesus; Sanchez-Anguiano, Luis Francisco; Ramos-Nevarez, Agar; Cerrillo-Soto, Sandra Margarita; Salas-Pacheco, Jose Manuel; Sandoval-Carrillo, Ada Agustina; Martinez-Ramirez, Lucio; Antuna-Salcido, Elizabeth Irasema; Guido-Arreola, Carlos Alberto

    2016-01-01

    Background The seroepidemiology of rubella virus infection in pregnant women in northern Mexico is largely unknown. We sought to determine the seroprevalence of rubella virus infection in pregnant women in the northern Mexican city of Durango, Mexico. Seroprevalence association with the socio-demographic, clinical and behavioral characteristics of the pregnant women was also investigated. Methods Through a cross-sectional study, we determined the seroprevalence of IgG and IgM anti-rubella virus in 279 pregnant women (mean age 29.17 ± 5.96 years; range 15 - 43 years) attending in a clinic of family medicine using enzyme-linked fluorescent assays. A questionnaire was used to obtain the socio-demographic, clinical and behavioral characteristics of the pregnant women. The association of rubella seropositivity and characteristics of the women was assessed by bivariate and multivariate analyses. Results Anti-rubella IgG antibodies (≥ 15 IU/mL) were found in 271 (97.1%) of the 279 pregnant women examined. None of the 279 pregnant women were positive for anti-rubella IgM antibodies. Multivariate analysis of socio-demographic, clinical and behavioral variables showed that seroreactivity to rubella virus was positively associated with national trips (OR = 7.39; 95% CI: 1.41 - 38.78; P = 0.01), and negatively associated with age (OR = 0.26; 95% CI: 0.06 - 0.99; P = 0.04). Conclusions Rate of rubella immunity in pregnant women in the northern Mexican city of Durango is high. However, nearly 3% of pregnant women are susceptible to rubella in our setting. Risk factors associated with rubella seropositivity found in this study may be useful for optimal design of preventive measures against rubella and its sequelae. PMID:27540439

  8. Head and Neck Squamous Cell Carcinoma in Pregnant Women

    PubMed Central

    Eliassen, Anna M.; Hauff, Samantha J.; Tang, Alice L.; Thomas, Dafydd H.; McHugh, Jonathan B.; Walline, Heather M.; Stoerker, Jay; Maxwell, Jessica H.; Worden, Francis P.; Eisbruch, Avraham; Czerwinski, Michael J.; Papagerakis, Silvana M.; Chepeha, Douglas B.; Bradford, Carol R.; Hanauer, David A.; Carey, Thomas E.; Prince, Mark E.

    2012-01-01

    Objective To investigate oral cancer in pregnant women, a rare but therapeutically challenging patient subset. Methods After IRB approval, an EMERSE search was used to identify all women treated at the University of Michigan from 1998–2010 with head and neck squamous cell carcinoma (HNSCC) during pregnancy. This identified four patients with tongue cancer. Biomarkers and HPV were assessed by immunohistochemistry and multiplex PCR/Mass spectrometry, respectively. Results Two patients responded well to therapy and are alive more than 10 years after diagnosis; two died of disease. All tumors overexpressed EGFR and Bcl-xL, three of four overexpressed c-Met, both tumors that progressed overexpressed p53. All tumors were negative for HPV, p16, ER, PR, and HER-2. Conclusions Biomarkers of aggressive tumors (high EGFR, Bcl-xL, c-Met; low p53) did not correlate with outcome. Additional studies are needed to determine whether perineural invasion, delay in diagnosis, and p53 overexpression are factors related to poorer survival. PMID:22422571

  9. Etravirine Pharmacokinetics in HIV-Infected Pregnant Women

    PubMed Central

    Mulligan, Nikki; Schalkwijk, Stein; Best, Brookie M.; Colbers, Angela; Wang, Jiajia; Capparelli, Edmund V.; Moltó, José; Stek, Alice M.; Taylor, Graham; Smith, Elizabeth; Hidalgo Tenorio, Carmen; Chakhtoura, Nahida; van Kasteren, Marjo; Fletcher, Courtney V.; Mirochnick, Mark; Burger, David

    2016-01-01

    Background: The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. Methods: IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). Results: Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0–12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19–4.25) and no perinatal transmission occurred. Conclusion: Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. Clinical Trial registration: The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929. PMID:27540363

  10. Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals

    SciTech Connect

    Gorny, Miroslaw K.; Pan, Ruimin; Williams, Constance; Wang, Xiao-Hong; Volsky, Barbara; O; Neal, Timothy; Spurrier, Brett; Sampson, Jared M.; Li, Liuzhe; Seaman, Michael S.; Kong, Xiang-Peng; Zolla-Pazner, Susan

    2012-05-18

    The recent analysis of the first successful RV144 vaccine trial revealed that a high titer of plasma anti-V2 antibodies (Abs) correlated with a decreased risk of HIV-1 infection in vaccine recipients. To understand the mechanism of immune correlates, we studied seven anti-V2 monoclonal Abs (mAbs) developed from HIV-1 infected individuals. The V2 mAbs target conserved epitopes, including the binding site for {alpha}4{beta}7 integrin, and are broadly cross-reactive with various gp120 proteins. Preferential usage of the VH1-69 gene by V2 mAbs may depend on selection by the same antigenic structure. Six of seven V2 mAbs weakly neutralized four to eight of the 41 pseudoviruses tested and resistance to neutralization was correlated with longer V2 domains. The data suggest the presence of shared, conserved structural elements in the V2 loop, and these can be used in the design of vaccine immunogens inducing broadly reactive Abs with anti-viral activities.

  11. Dolutegravir: a review of its use in the management of HIV-1 infection in adolescents and adults.

    PubMed

    McCormack, Paul L

    2014-07-01

    Dolutegravir (Tivicay(®)) is a new-generation HIV-1 integrase strand transfer inhibitor recently approved in the EU and Japan for the treatment of HIV-1 infection in adolescents and adults in combination with other antiretroviral drugs. It is suitable for once-daily administration and achieves therapeutic concentrations without the need for pharmacokinetic boosting. It has a high barrier to resistance and is generally active against viral strains resistant to first-generation integrase inhibitors. In well-designed clinical trials in treatment-naive or treatment-experienced, integrase inhibitor-naive patients, dolutegravir-based combinations were shown to be noninferior or superior to raltegravir-based combinations, an efavirenz-based combination and ritonavir-boosted darunavir-based combinations with respect to virological suppression (plasma HIV-1 RNA <50 copies/mL) at week 48. Dolutegravir was also effective in a high proportion of patients failing on raltegravir- or elvitegravir-based therapy as a result of integrase resistance mutations. Dolutegravir was generally well tolerated, with the vast majority of adverse events being mild or moderate in intensity; serious adverse events were uncommon. Therefore, dolutegravir is an important new addition to the expanding list of antiretroviral drugs for treating HIV-1 infection in adults and adolescents.

  12. Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection

    SciTech Connect

    Thangavelu, Pulari U.; Gupta, Vipul; Dixit, Narendra M.

    2014-01-20

    The contest between the host factor APOBEC3G (A3G) and the HIV-1 protein Vif presents an attractive target of intervention. The extent to which the A3G–Vif interaction must be suppressed to tilt the balance in favor of A3G remains unknown. We employed stochastic simulations and mathematical modeling of the within-host dynamics and evolution of HIV-1 to estimate the fraction of progeny virions that must incorporate A3G to render productive infection unsustainable. Using three different approaches, we found consistently that a transition from sustained infection to suppression of productive infection occurred when the latter fraction exceeded ∼0.8. The transition was triggered by A3G-induced hypermutations that led to premature stop codons compromising viral production and was consistent with driving the basic reproductive number, R{sub 0}, below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G–Vif axis. - Highlights: • We perform simulations and mathematical modeling of the role of APOBEC3G in suppressing HIV-1 infection. • In three distinct ways, we estimate that when over 80% of progeny virions carry APOBEC3G, productive HIV-1 infection would be suppressed. • Our estimate of this critical fraction presents quantitative guidelines for strategies targeting the APOBEC3G–Vif axis.

  13. Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles

    SciTech Connect

    Peretti, Silvia; Schiavoni, Ilaria; Pugliese, Katherina; Federico, Maurizio . E-mail: federico@iss.it

    2006-02-05

    We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies.

  14. The second wave: Toward responsible inclusion of pregnant women in research

    PubMed Central

    Lyerly, Anne Drapkin; Little, Margaret Olivia; Faden, Ruth

    2009-01-01

    Though much progress has been made on inclusion of non-pregnant women in research, thoughtful discussion about including pregnant women has lagged behind. We outline resulting knowledge gaps and their costs and then highlight four reasons why ethically we are obliged to confront the challenges of including pregnant women in clinical research. These are: the need for effective treatment for women during pregnancy, fetal safety, harm from the reticence to prescribe potentially beneficial medication, and the broader issues of justice and access to benefits of research participation. Going forward requires shifting the burden of justification from inclusion to exclusion and developing an adequate ethical framework that specifies suitable justifications for excluding pregnant women from research. PMID:19774226

  15. IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation.

    PubMed

    Dai, Lue; Lidie, Kristy B; Chen, Qian; Adelsberger, Joseph W; Zheng, Xin; Huang, DaWei; Yang, Jun; Lempicki, Richard A; Rehman, Tauseef; Dewar, Robin L; Wang, Yanmei; Hornung, Ronald L; Canizales, Kelsey A; Lockett, Stephen J; Lane, H Clifford; Imamichi, Tomozumi

    2013-03-11

    The susceptibility of macrophages to HIV-1 infection is modulated during monocyte differentiation. IL-27 is an anti-HIV cytokine that also modulates monocyte activation. In this study, we present new evidence that IL-27 promotes monocyte differentiation into macrophages that are nonpermissive for HIV-1 infection. Although IL-27 treatment does not affect expression of macrophage differentiation markers or macrophage biological functions, it confers HIV resistance by down-regulating spectrin β nonerythrocyte 1 (SPTBN1), a required host factor for HIV-1 infection. IL-27 down-regulates SPTBN1 through a TAK-1-mediated MAPK signaling pathway. Knockdown of SPTBN1 strongly inhibits HIV-1 infection of macrophages; conversely, overexpression of SPTBN1 markedly increases HIV susceptibility of IL-27-treated macrophages. Moreover, we demonstrate that SPTBN1 associates with HIV-1 gag proteins. Collectively, our results underscore the ability of IL-27 to protect macrophages from HIV-1 infection by down-regulating SPTBN1, thus indicating that SPTBN1 is an important host target to reduce HIV-1 replication in one major element of the viral reservoir.

  16. Do pregnant women have a higher risk for venous thromboembolism following air travel?

    PubMed Central

    Izadi, Morteza; Alemzadeh-Ansari, Mohammad Javad; Kazemisaleh, Davood; Moshkani-Farahani, Maryam; Shafiee, Akbar

    2015-01-01

    International travel has become increasingly common and accessible, and it is part of everyday life in pregnant women. Venous thromboembolism (VTE) is a serious public health disorder that occurs following long-haul travel, especially after air travel. The normal pregnancy is accompanied by a state of hypercoagulability and hypofibrinolysis. Thus, it seems that pregnant women are at a higher risk of VTE following air travel, and, if they have preexisting risk factors, this risk would increase. There is limited data about travel-related VTE in pregnant women; therefore, in the present study, we tried to evaluate the pathogenesis of thrombosis, association of thrombosis and air travel, risk factors and prevention of VTE in pregnant women based on available evidences. Pregnancy is associated with a five- to 10-fold increased risk of VTE compared with nonpregnant women; however, during the postpartum period, this risk would increase to 20–80-fold. Furthermore, the risk of thrombosis is higher in individuals with preexisting risk factors, and the most common risk factor for VTE during pregnancy is a previous history of VTE. Pregnant women are at a higher risk for thrombosis compared with other women. Thus, the prevention of VTE and additional risk factors should be considered for all pregnant women who travel by plane. PMID:25802829

  17. [Characteristics of pregnant women, labor, and the newborn at the Skopje Clinic from 1978 to 1979].

    PubMed

    Antonovski, L; Curciev, K

    1979-01-01

    An analysis was made of the first computer data received from the IFRP (International Fertility Research Program) within the framework of the International Study "Maternity Record" -- "Maternity Monitoring Care'. The main findings are the following: The women who were confined at the Skopje University Hospital during 1978--1979 were young, in their twenties. Women over thirty were confined very rarely. Most of the women surveyed had about 12 years of education. Pregnant women had artificial abortions very rarely (1:5.7 in favor of terminating pregnancy). Preventive work on contraception should include women at the time of delivery. Pregnant women in Skopje come to the Consulting Centers for a check-up mostly five times. The higher the parity, the less frequent the visits. More than half of pregnant women during the antenatal period had no complaints. Younger pregnant women had fewer difficulties and complications. The values of haemoglobin under 10 g% were very often in primiparas and over 12 g% in multiparas. The birthweight of women smoker's babies proved lower than that of women non-smokers' babies. In two thirds of women the delivery was induced by drugs and amniotomy. The delivery mostly lasted between 7--12 h, regardless of parity. Prolonged deliveries were the more frequent the younger the women. Primiparas gave birth to babies with a lower birthweight than multiparas. Almost all women (92.4%) were previously using no contraceptive devices. The main method of protection was coitus interruptus.

  18. Novel pandemic A (H1N1) influenza vaccination among pregnant women: motivators and barriers.

    PubMed

    Steelfisher, Gillian K; Blendon, Robert J; Bekheit, Mark M; Mitchell, Elizabeth W; Williams, Jennifer; Lubell, Keri; Peugh, Jordon; DiSogra, Charles A

    2011-06-01

    We sought to examine motivators and barriers related to monovalent 2009 influenza A (H1N1) vaccination among pregnant women. We conducted a national poll of pregnant women using a random online sample (237) and opt-in supplement (277). In all, 42% of pregnant women reported getting the vaccine. Vaccination was positively associated with attitudinal factors including believing the vaccine is very safe or benefits the baby, and with provider recommendations. Women in racial/ethnic minority groups, women with less education, and women <35 years were less likely to get the vaccine and had differing views and experiences. Despite H1N1 vaccination rates that are higher than past seasonal influenza rates, barriers like safety concerns may persist in a pandemic. Messaging from providers that encourages women to believe the vaccine is very safe and benefits their baby may be compelling. Messaging and outreach during future pandemics may require customization to increase vaccination among high-risk groups.

  19. [The structure of extragenital pathology in pregnant women with diabetes in endemic by iodine region].

    PubMed

    Bobyk, Iu Iu; Lemish, N Iu

    2014-01-01

    We have conducted a complex clinical and paraclinical study of 108 women, 78 of which had diabetes and 30 healthy women that made a control group. In 60.3% of the pregnant patients type 1 diabetes was diagnosed, in 11.5%--type 2. Gestational diabetes was found in 28.2% of pregnant women. The vast number of the surveyed pregnant women (52.6%) was diagnosed with moderate and severe (38.5%) degree of the disease. In 12.5% of them the disease was compensated, in 82.1% subcompensated, while in 5.1%--decompensated. In pregnant women with diabetes a high incidence of extragenital diseases was revealed, the most common of which was iron deficiency anemia, which complicated the pregnancy of more than half of the pregnant of the basic group (57.7%), while in the control--in 13.3% of women (p < 0.05). Thyroid diseases in the study group were more than three times more common compared to the control group (47.4% and 13.3%, p < 0.05), while in pregnant women with type 1 diabetes in 55.3% of the patients. Herewith in 29.4% of cases were diagnosed with hypothyroidism, in 52.9--subclinical hypothyroidism, in 25.5% of pregnant women were found autoimmune thyroiditis. These data indicate the need of screening of the pregnant women with diabetes to identify the pathology of the thyroid gland even if the clinical symptom are absent, particularly in the areas of iodine deficiency.

  20. Immediate Needs and Concerns among Pregnant Women During and after Typhoon Haiyan (Yolanda)

    PubMed Central

    Sato, Mari; Nakamura, Yasuka; Atogami, Fumi; Horiguchi, Ribeka; Tamaki, Raita; Yoshizawa, Toyoko; Oshitani, Hitoshi

    2016-01-01

    Introduction: Pregnant and postpartum women are especially vulnerable to natural disasters. These women suffer from increased risk of physical and mental issues including pregnant related problems. Typhoon Haiyan (Yolanda), which hit the Philippines affected a large number of people and caused devastating damages. During and after the typhoon, pregnant women were forced to live in particularly difficult circumstances. The purpose of this study was to determine concerns and problems regarding public health needs and coping mechanisms among pregnant women during and shortly after the typhoon. Methods: This study employed a cross-sectional design utilizing focus group discussions (FGDs). Participants were 53 women (mean age: 26.6 years old; 42 had children) from four affected communities who were pregnant at the time of the typhoon. FGDs were conducted 4 months after the typhoon, from March 19 to 28, 2014, using semi-structured interviews. Data were analyzed using the qualitative content analysis. Result: Three themes were identified regarding problems and concerns during and after the typhoon: 1) having no ideas what is going to happen during the evacuation, 2) lacking essentials to survive, and 3) being unsure of how to deal with health concerns. Two themes were identified as means of solving issues: 1) finding food for survival and 2) avoiding diseases to save my family. As the pregnant women already had several typhoon experiences without any major problems, they underestimated the catastrophic nature of this typhoon. During the typhoon, the women could not ensure their safety and did not have a strong sense of crisis management. They suffered from hunger, food shortage, and poor sanitation. Moreover, though the women had fear and anxiety regarding their pregnancy, they had no way to resolve these concerns. Pregnant women and their families also suffered from common health problems for which they would usually seek medical services. Under such conditions, the

  1. [Vegetarian diets in the nutrition of pregnant and breastfeeding women].

    PubMed

    Brzezińska, Małgorzata; Kucharska, Alicja; Sińska, Beata

    2016-04-01

    Pregnant and breastfeeding women who eat vegetarian are a source of much controversy. This is the result of concern that eliminating some or all animal produce may lead to nutritional deficiencies and thus adversely affect the mother's and child's health. The American Dietetic Association's position is that appropriately planned vegan, lacto-vegetarian and lacto-ovo-vegetarian diets ensure a normal course of pregnancy and lactation. However, in practice the balancing of such a diet can pose certain difficulties, especially for individuals without the necessary experience or knowledge about nutrition. Nutrients to which particular attention needs to be paid to ensure their sufficient supply include: protein (essential amino acids), Omega-3 essential fatty acids, iron and calcium as well as vitamins D and B(12). The proper adherence to recommendations can be attained with a varied diet containing suitable plant products compensating for the nutritional value of the eliminated animal products. Supplementation with vitamin D and vitamin B(12) is also necessary. Research shows that infants born to vegetarian mothers are born at term and have normal birth weight. There is an increased risk of hypospadias in boys. The main difference in the composition of vegetarian mothers' milk compared to non-vegetarians' is lower content of docosahexaenoic acid and higher content of Linoleic and α-Linolenic acid.

  2. Calcium and magnesium status is not impaired in pregnant women.

    PubMed

    Rocha, Vivianne S; Lavanda, Ivana; Nakano, Eduardo Y; Ruano, Rodrigo; Zugaib, Marcelo; Colli, Célia

    2012-07-01

    Deficiencies in calcium (Ca) and magnesium (Mg) are associated with various complications during pregnancy. To test the hypothesis that the status of these minerals is inadequate in pregnancy, a cross-sectional study was conducted of the dietary intake and status of Ca and Mg in pregnant women (n = 50) attending a general public university hospital in Brazil. Dietary intake was assessed from 4-day food records; levels of plasma Mg, erythrocyte Mg, and urinary Ca and Mg excretion were determined by flame atomic absorption spectroscopy; and type I collagen C-telopeptides were evaluated by enzyme-linked immunosorbent assay. Probabilities of inadequate Ca and Mg intake were exhibited by 58 and 98% of the study population, respectively. The mean levels of urinary Ca and Mg excretion were 8.55 and 3.77 mmol/L, respectively. Plasma C-telopeptides, plasma Mg, and erythrocyte Mg were within normal levels. Multiple linear regression analysis revealed positive relationships among urinary Ca excretion, Ca intake (P = .002) and urinary Mg excretion (P < .001) and between erythrocyte Mg and Mg intake (P = .023). It is concluded that the Ca and Mg status of participants was adequate even though the intake of Ca and Mg was lower than the recommended level.

  3. Eye care services utilisation among pregnant women in Nigeria.

    PubMed

    Ibraheem, Waheed A; Ibraheem, Anifat B; Owonikoko, Musliudeen; Tijani, Aramide; Olamoyegun, Michael Adeyemi; AbdSalam, Soliu

    2016-07-01

    One hundred and sixty-five pregnant Nigerian women attending the antenatal clinic of LAUTECH teaching hospital, Ogbomoso, Nigeria between January and April 2014 were interviewed using a structured questionnaire. Socio-demographic characteristics of the respondents were obtained. Respondents were also asked: if they had had their eye examined by an eye specialist during the index pregnancy, frequencies of visit to eye care centers and indications for their visitation. A history of previous eye examination by eye care specialist/visit to eye clinic was considered as eye care utilisation. Selection of eligible subjects who consented to participate in the study was done using simple random technique. Logistic regression model was used to control sociodemographic and obstetric factors in order to determine independent covariate factor influencing the use of eye care services. Among the population studied, only 46 (32%) had eye examination during the index pregnancy. Level of education and occupational status of the respondents were found to be statistically significant factors (p = 0.001 and 0.008, respectively). There is a need for a policy that will encourage regular eye care services usage during pregnancy.

  4. Systemic alterations and their oral manifestations in pregnant women.

    PubMed

    Silva de Araujo Figueiredo, Camilla; Gonçalves Carvalho Rosalem, Cíntia; Costa Cantanhede, Andre Luis; Abreu Fonseca Thomaz, Érika Bárbara; Fontoura Nogueira da Cruz, Maria Carmen

    2017-01-01

    The aims of this literature review are: to depict the main oral diseases that are related to pregnancy; to clarify some of the possible systemic mechanisms that are associated with these changes; and to address issues about oral care during pregnancy. A woman's organs undergo various physiological, neurological, and hormonal changes during pregnancy. Such changes occur gradually and are essential for the development of the fetus, providing what is needed for tissue formation and establishment of reserves for uterine and fetal life. In turn, the oral cavity shows some events during this period. Among the changes most frequently cited in the literature are pyogenic granuloma, gingivitis, and periodontitis. The inflammation of the periodontal tissues due to the formation of the biofilm increases dramatically in size and severity during the course of a normal pregnancy, even without changes in the amount of biofilm present. In addition, a decrease in salivary pH is observed in pregnant women and may lead to an increased incidence of dental caries in this period.

  5. Fetal Biometry of Head Circumference for Malaysian Pregnant Women

    NASA Astrophysics Data System (ADS)

    Ramli, Remsen Maizan; Jaafar, M. S.; Ismail, N. E.; Saltani, Hend A. A.; Ahmad, A. L.; Bermakai, M. Yahaya

    2010-07-01

    The purpose of this research is to study the fetal head circumference (HC) biometry for local population. Retrospective study was selected, done at Hospital Pulau Pinang and 5551 files of pregnant women were collected. The HC mean values of this study (HCmean) was compared with other published studies to see whether there was any difference between the various populations in the world. Comparison of means, regression analysis and paired sample t-test in SPSS software version 11.5 were used in the analysis. A total of 9874 HC data (mm) were recorded for gestational age (GA) of 12 to 41 weeks. The HC growth rate in second trimester (11.32 mm/week) has decreased to nearly half than in third trimester (5.53 mm/week). The HCmean was found to be highly significant difference (SD) than other 9 studies and only lower than HC values of USA, UK and Zimbabwe populations. The HC values of German show close similarity with HCmean. From 45 comparisons done, more than three-quarter of the comparisons resulted as SD (37) compared to insignificant differences (8). Consequently, each country should have their own standard HC of fetus biometry of the various gestations for their own population.

  6. Depression and Rural Environment are Associated With Poor Oral Health Among Pregnant Women in Northern Appalachia.

    PubMed

    McNeil, Daniel W; Hayes, Sarah E; Randall, Cameron L; Polk, Deborah E; Neiswanger, Kathy; Shaffer, John R; Weyant, Robert J; Foxman, Betsy; Kao, Elizabeth; Crout, Richard J; Chapman, Stella; Brown, Linda J; Maurer, Jennifer L; Marazita, Mary L

    2016-01-01

    Both oral health problems and depression among pregnant women contribute to maternal-infant health outcomes. Little is known, however, about the potential effects of clinically significant depression on the oral health status of pregnant women. The purpose of the present study was to determine the influence of clinically significant depression and rural- or urban-dwelling status on oral health outcomes among pregnant women. Pregnant women (N = 685) in rural (i.e., West Virginia) and urban (i.e., Pittsburgh, PA) areas of northern Appalachia were assessed by calibrated examiners regarding gingivitis, oral hygiene, and DMFT (decayed, missing, and filled teeth), completed the Center for Epidemiologic Studies-Depression Scale (CES-D) and provided demographics. Participants were categorized based on clinically significant depressive symptoms (CES-D ≥ 16) and rural/urban domicile. Women with depression and those living in rural areas had worse oral health on all three indices than their non-depressed and urban counterparts. Depression, particularly among women in rural areas, affects certain oral health indices and represents a modifiable target for intervention. Moreover, treatments designed specifically for rural populations may be of particular utility. Women who are pregnant or planning to become pregnant may benefit from regular depression screenings from their dental and medical health care providers.

  7. The use of hormones indicators in human saliva in diagnosing parodontitis in pregnant women

    PubMed Central

    Dolomatov, S. I.; Zukow, W.; Atmazhov, I. D.; Muszkieta, R.; Skaliy, A.

    2012-01-01

    AIMS: The purpose of this work– was to study the dynamics of biochemical parameters of human saliva and analyze the features of the chemical composition of the saliva of women with abnormal pregnancy and in periodontitis against pregnancy. MATERIALS AND METHODS: The study included four groups of women: a control group of nonpregnant women of childbearing age (10), pregnant women with physiological pregnancy (24-28 weeks) without any signs of periodontal disease (10), pregnant with a generalized periodontitis I--II degrees in remission (10), women with pathological pregnancy with no signs of periodontal inflammation (10). In each of the groups over two samples of saliva were collected, the first collection of saliva in the morning on an empty stomach. Then mouthwash 0.9% sodium chloride solution was assigned and after 30 minutes the second portion of saliva. By enzyme immunoassay in samples of saliva of control groups of nonpregnant and pregnant women, as well as women with signs of a pathological course of pregnancy, the content of estriol, testosterone, and dehydroepiandrosterone sulfate was determined. STATISTICAL ANALYSIS USED: Statistical data analysis was performed by the standard technique using Student's t-test. RESULTS: The results of biochemical analysis of saliva samples collected before rinsing the mouth with saline in groups of healthy nonpregnant and pregnant women were compared. It was established that during pregnancy the concentration of salivary estriol increases, but in pregnant women with periodontitis, the amount of this hormone in the saliva was significantly reduced. The highest content of testosterone in saliva samples, observed in healthy pregnant women, was significantly higher than nonpregnant women. In pregnant women with periodontitis concentration of testosterone in saliva is reduced, while remaining significantly higher than its level in the saliva of nonpregnant women. The highest concentration of testosterone is observed in the

  8. Pregnant women in vehicles: Driving habits, position and risk of injury.

    PubMed

    Auriault, F; Brandt, C; Chopin, A; Gadegbeku, B; Ndiaye, A; Balzing, M-P; Thollon, L; Behr, M

    2016-04-01

    This study proposed to broadly examine vehicle use by pregnant women in order to improve realism of accident simulations involving these particular occupants. Three research pathways were developed: the first consisted in a questionnaire survey examining the driving habits of 135 pregnant women, the second obtained measurements of 15 pregnant women driving position in their own vehicle from the 6th to the 9th month of pregnancy by measuring distances between body parts and vehicle parts, and the third examined car accidents involving pregnant occupants. Results obtained indicate that between 90% and 100% of pregnant women wore their seat belts whatever their stage of pregnancy, although nearly one third of subjects considered the seat belt was dangerous for their unborn child. The measurements obtained also showed that the position of the pregnant woman in her vehicle, in relation to the various elements of the passenger compartment, changed significantly during pregnancy. In the studied accidents, no correlation was found between the conditions of the accident and the resulting fetal injury. Results reveal that pregnant women do not modify significantly the seat setting as a function of pregnancy stage. Only the distance between maternal abdomen and steering wheel change significantly, from 16 cm to 12 cm at 6 and 9 month respectively. Pregnant women are mainly drivers before 8 months of pregnancy, passengers after that. Car use frequency falls down rapidly from 6 to 9 months of pregnancy. Real crashes investigations indicate a low rate of casualties, i.e. 342 car accidents involving pregnant women for a period of 9 years in an approximately 1.7 million inhabitants area. No specific injury was found as a function of stage of pregnancy.

  9. Serodiscordance and disclosure among HIV-positive pregnant women in the Southwestern United States.

    PubMed

    Nacius, Lori A; Levison, Judy; Minard, Charles G; Fasser, Carl; Davila, Jessica A

    2013-04-01

    The prevalence of HIV-positive pregnant women in relationships with HIV-negative men in the United States is unclear. The purpose of this study was to calculate the prevalence of HIV-positive pregnant women with a serodiscordant (HIV-negative) partner within a single clinic population, assess disclosure of their HIV status, and examine factors associated with disclosure. All HIV-positive pregnant women who received prenatal care at the Harris County Hospital District Women's Program at Northwest Health Center in Houston TX between 1/1/2006 and 4/1/2011 were identified. Data were obtained from electronic medical records. Prevalence of serodiscordance and disclosure was calculated, and predictors of disclosure were evaluated. We identified 212 HIV-positive pregnant women. About 40% had a serodiscordant partner, and 34% had a partner with an unknown HIV status. Disclosure occurred in over 90% of women with a serodiscordant partner and in 68% of women with partners whose HIV status was unknown. Among pregnant women who knew their HIV status prior to the current pregnancy and had a serodiscordant partner, 92% reported disclosing their status prior to conception. Our data indicated that serodiscordant relationships are common in our clinic population. Suboptimal disclosure rates were observed, especially among women who have a partner with an unknown HIV status. Further research is needed to evaluate the prevalence of serodiscordance and disclosure in other United States populations.

  10. Activity of histidine in peripheral blood erythrocytes of pregnant women during exacerbation of cytomegalovirus infection.

    PubMed

    Lutsenko, M T; Andrievskaya, I A

    2014-10-01

    We studied the effect of active cytomegalovirus infection on histidine content in peripheral blood erythrocytes of pregnant women at gestation weeks 20-22 and its involvement into hemoglobin oxygenation. Using the histochemical technique developed by us, we studied the distribution of products of specific reaction for histidine in peripheral blood erythrocytes of pregnant women. The percentage of histidine-positive erythrocytes and their area were evaluated. The relationship between the distribution of the products of the reaction for histidine in peripheral blood erythrocytes of pregnant women and the titer of anti-cytomegalovirus IgG was revealed. The histidine content in peripheral blood erythrocytes of pregnant women with active cytomegalovirus infection was reduced, which impaired heme binding to globin and decreased the formation of oxyhemoglobin.

  11. Webinar Presentation: The Contribution of Diet to Pesticide Exposure in Pregnant Women and Children

    EPA Pesticide Factsheets

    This presentation, The Contribution of Diet to Pesticide Exposure in Pregnant Women and Children, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Food and Children's Health held on Dec. 9, 2015.

  12. Social Factors Determining the Experience of Blindness among Pregnant Women in Developing Countries: The Case of India

    ERIC Educational Resources Information Center

    Pandey, Shanta; Lin, Yuan; Collier-Tenison, Shannon; Bodden, Jamie

    2012-01-01

    Approximately 10 million pregnant women around the world develop night blindness annually. In India, one in 11 pregnant women suffers from night blindness. This study used a nationally representative sample of 35,248 women from India between the ages of 15 and 49 who had given birth in the past five years to understand the effect of women's…

  13. Examining pica in NYC pregnant women with elevated blood lead levels.

    PubMed

    Thihalolipavan, Sayone; Candalla, Barbara M; Ehrlich, Jacqueline

    2013-01-01

    We sought to describe the impact of pica, the craving for and intentional ingestion of substances not defined as food, as a risk factor for lead poisoning in New York City (NYC) pregnant women. In order to describe pregnant women with elevated blood lead levels (BLLs) who report pica, NYC health department data from 491 cases of lead-poisoned pregnant women from January 2001 to June 2009 were reviewed. Descriptive frequencies were obtained for women reporting pica. Data were compared between women reporting and not reporting pica. In NYC, of the 43 (9%) lead-poisoned pregnant women reporting pica, 42 (97.7%) were immigrants and 28 (64.6%) had consumed soil. Compared to lead-poisoned pregnant women not reporting pica, women reporting pica had higher peak BLLs (29.5 vs. 23.8 μg/dL, P = 0.0001), were more likely to have had a BLL ≥ 45 μg/dL (OR = 3.3, 95% CI, 1.25, 8.68) and receive chelation (OR = 10.88, 95% CI, 1.49, 79.25), more likely to have emigrated from Mexico (OR = 3.05, 95% CI, 1.38–6.72), and less likely to have completed high school (OR = indeterminate; 0 vs. 34%; P = 0.003). Among NYC lead-poisoned pregnant women, pica was associated with higher peak BLLs. Providers in NYC, and possibly other urban settings, should be vigilant and question pregnant women, especially immigrants, about pica and strongly consider testing this at-risk population for lead poisoning.

  14. Off-label use of rilpivirine in combination with emtricitabine and tenofovir in HIV-1-infected pediatric patients

    PubMed Central

    Falcon-Neyra, Lola; Palladino, Claudia; Navarro Gómez, María Luisa; Soler-Palacín, Pere; González-Tomé, María Isabel; De Ory, Santiago J.; Frick, Marie Antoinette; Fortuny, Clàudia; Noguera-Julian, Antoni; Moreno, Elena Bermúdez; Santos, Juan Luis; Olbrich, Peter; López-Cortés, Luis F.; Briz, Verónica; Neth, Olaf

    2016-01-01

    Abstract To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA < 20 copies/mL on stable combined antiretroviral therapy (cART), and detectable viral load (dVL) group, HIV-1 RNA ≥ 20 copies/mL at RPV/FTC/TDF initiation. Patients were monitored from the date of RPV/FTC/TDF initiation until June 30, 2015, RPV/FTC/TDF discontinuation or failure to follow-up. Seventeen patients (8 in uVL and 9 in dVL group) with age between 11.6 and 17.6 were included. Reasons for switching were toxicity (n = 4) and simplification (n = 4) in uVL; viral failure (n = 8) and cART initiation (n = 1) in the dVL group. After a median follow-up of 90 (uVL) and 40 weeks (dVL), 7/8 (86%) patients maintained and 8/9 (89%) achieved and maintained HIV-1 suppression. Median CD4 count increased from 542 to 780/μL (uVL, P = 0.069) and 480 to 830/μL (dVL, P = 0.051). Five patients (2 in uVL and 3 in dVL) improved their immunological status from moderate to no immunosuppression. Serum lipid profiles improved in both groups; cholesterol dropped significantly in the dVL group (P = 0.008). Grade 1 laboratory adverse events (AEs) were observed in 3 patients. No clinical AEs occurred. Adherence was complete in 9 patients (5 in uVL and 4 in dVL); 1 adolescent interrupted treatment. Once-daily STR with RPV/FTC/TDF may be a safe and effective choice in selected HIV-1-infected adolescents and children. PMID:27310962

  15. Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling

    PubMed Central

    Sachdeva, Meenakshi; Sharma, Aman; Arora, Sunil K.

    2015-01-01

    Introduction Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs). The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART). Methods Phenotypic and functional characteristics of circulating myeloid DCs (mDCs) in 56 ART-naive patients (23 in early and 33 in advanced stage of disease), 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs) were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS)-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR. Results The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase(SHP)-1 and a reduced expression of positive regulators like Janus kinase(JAK)2 and Nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells. Conclusions Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral

  16. Molecular Epidemiology of HIV-1 Infection among Men who Have Sex with Men in Taiwan in 2012

    PubMed Central

    Huang, Szu-Wei; Wang, Sheng-Fan; Cowó, Ángel E.; Chen, Marcelo; Lin, Yu-Ting; Hung, Chun-Po; Chen, Yi-Hsien; Yang, Jyh-Yuan; Tang, Hung-Jen; Chen, Yi-Ming Arthur

    2015-01-01

    The number of men who have sex with men (MSM) infected with HIV-1 in Taiwan has increased rapidly in the past few years. The goal of this study was to conduct a molecular epidemiological study of HIV-1 infection among MSM in Taiwan to identify risk factors for intervention. Voluntary counseling program and anonymous testing were provided to patrons at 1 gay bar, 7 night clubs and 3 gay saunas in Taipei and New Taipei Cities in 2012. HIV-1 subtypes were determined using gag subtype-specific PCR and phylogenetic analysis by env sequences. Recent HIV-1 infection was determined using LAg-Avidity EIA. In-depth interviews and questionnaires were used to identify risk factors. The prevalence and incidence of HIV-1 among MSM in Taiwan were 4.38% (53/1,208) and 3.29 per 100 person-years, respectively. Of 49 cases genotyped, 48 (97.9%) were infected with subtype B and 1 with CRF01_AE (2%). Phylogenetic analysis of 46 HIV-1 strains showed that 25 (54.4%) subtype B strains formed 9 clusters with each other or with other local strains. The CRF01_AE case clustered with a reference strain from a Thai blood donor with bootstrap value of 99. Multivariate logistic regression analysis showed that risk factors associated with HIV-1 infection included use of oil-based solution as lubricant (vs. saliva or water-based lubricants, OR= 4.23; p <0.001); exclusively receptive role (vs. insertive role, OR= 9.69; p <0.001); versatile role (vs. insertive role, OR= 6.45; p= 0.003); oral sex (vs. insertive role, OR= 11.93; p= 0.044); times of sexual contact per week (2-3 vs. zero per week, OR= 3.41; p= 0.021); illegal drug use (OR= 4.12; p <0.001); and history of sexually transmitted diseases (OR= 3.65; p= 0.002). In conclusion, there was no new HIV-1 subtype or circulating recombinant form responsible for the increase of HIV-1 among MSM in Taiwan in 2012. Misuse of oil-based solution as lubricant is a new risk factor identified among MSM in Taiwan. The Taiwan’s Centers for Disease Control has

  17. 34 CFR 403.82 - In what settings may the Single Parents, Displaced Homemakers, and Single Pregnant Women Program...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pregnant women. (Authority: 20 U.S.C. 2335(b)) Sex Equity Program ... Homemakers, and Single Pregnant Women Program be offered? 403.82 Section 403.82 Education Regulations of the... Secretary Assist Under the Basic Programs? Single Parents, Displaced Homemakers, and Single Pregnant...

  18. 40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant...

  19. 40 CFR 26.303 - Duties of IRBs in connection with observational research involving pregnant women and fetuses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... observational research involving pregnant women and fetuses. 26.303 Section 26.303 Protection of Environment... Protections for Pregnant Women and Fetuses Involved as Subjects in Observational Research Conducted or Supported by EPA § 26.303 Duties of IRBs in connection with observational research involving pregnant...

  20. [Effect of respiratory and aqua-gymnastics on the adaptive potential of pregnant women].

    PubMed

    Krivonogova, T S; Gerget, O M; Agarkova, L A

    2010-01-01

    This paper deals with one of the most promising methods for the assessment of the health status of pregnant women and their children based on information criteria in the framework of an intelligent system. Inter-relations between the revealed adaptation strategies and functional disturbances in the organism are considered with special reference to various types of adaptive reactions in pregnant women and adaptational capacities of their children.

  1. Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

    SciTech Connect

    Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

    1986-11-01

    RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

  2. Interim Guidelines for Pregnant Women During a Zika Virus Outbreak--United States, 2016.

    PubMed

    Petersen, Emily E; Staples, J Erin; Meaney-Delman, Dana; Fischer, Marc; Ellington, Sascha R; Callaghan, William M; Jamieson, Denise J

    2016-01-22

    CDC has developed interim guidelines for health care providers in the United States caring for pregnant women during a Zika virus outbreak. These guidelines include recommendations for pregnant women considering travel to an area with Zika virus transmission and recommendations for screening, testing, and management of pregnant returning travelers. Updates on areas with ongoing Zika virus transmission are available online (http://wwwnc.cdc.gov/travel/notices/). Health care providers should ask all pregnant women about recent travel. Pregnant women with a history of travel to an area with Zika virus transmission and who report two or more symptoms consistent with Zika virus disease (acute onset of fever, maculopapular rash, arthralgia, or conjunctivitis) during or within 2 weeks of travel, or who have ultrasound findings of fetal microcephaly or intracranial calcifications, should be tested for Zika virus infection in consultation with their state or local health department. Testing is not indicated for women without a travel history to an area with Zika virus transmission. In pregnant women with laboratory evidence of Zika virus infection, serial ultrasound examination should be considered to monitor fetal growth and anatomy and referral to a maternal-fetal medicine or infectious disease specialist with expertise in pregnancy management is recommended. There is no specific antiviral treatment for Zika virus; supportive care is recommended.

  3. Views of pregnant women and clinicians regarding discussion of exposure to phthalate plasticizers

    PubMed Central

    2014-01-01

    Objective This study explores the views of pregnant women and clinicians regarding discussion of exposure to phthalate plasticizers during pregnancy, subsequent to the 2011 Health Canada ban of certain phthalates at a concentration greater than 1000 mg/kg in baby toys. This occurred with no regulation of products to which pregnant women are exposed, such as food packaging and cosmetics. Methods Pregnant women, physicians and midwives were recruited through posters and pamphlets in prenatal clinics in Southwestern Ontario for a semi-structured interview. All interviews were audiotaped, transcribed, and subjected to rigorous qualitative analysis through a grounded theory approach, supported by NVIVO™ software. Themes emerged from line by line, open, and axial coding in an iterative manner. Results Theoretical sufficiency was reached after 23 pregnant women and 11 clinicians had been interviewed. The themes (and subthemes from which they arose) were: Theme I-Information Provision (IA-Sources of Information, IB-Standardization, IC-Constraints, ID-Role of Government); Theme II-Risk (IIA-Significant Risk, IIB-Perceived Relevance, IIC-Reconciliation); and Theme III- Factors Influencing Level of Concern (IIIA-Current Knowledge, IIIB-Demographic Factors). Conclusion To respond to the increasing media and research attention regarding risk of phthalates to women, and pregnant women in particular, national professional organizations should provide patient information. This could include pamphlets on what a pregnant woman should know about phthalates and how they can be avoided, as well as information to clinicians to facilitate this discussion. PMID:24952638

  4. Use of Herbal Medicine Among Pregnant Women on Antenatal Care at Nekemte Hospital, Western Ethiopia

    PubMed Central

    Bayisa, Bodena; Tatiparthi, Ramanjireddy; Mulisa, Eshetu

    2014-01-01

    Background: Investigations across the world confirm dramatic increment in the use of complementary and alternative medicine in pregnant women. The most important aspect is lack of awareness of pregnant women about potential effects of using traditional medicine on fetus; some herbal products may be teratogenic in human and animal models. In this area, so far, no research has been conducted in Ethiopia to assess traditional medicine use in pregnant women. Objectives: Therefore, the main objective of this study was to investigate the prevalence and use of herbal drugs among pregnant women attending Nekemte Hospital to provide baseline information for future studies. Patients and Methods: A cross-sectional descriptive study was conducted by quantitative and qualitative approaches to identify the prevalence of using herbal medicines among pregnant women. About 50.4% of study participants used herbal drugs during their pregnancy. The proportion of herbal drug usage was gradually decreased along with the first, second and third trimesters of pregnancy. The most and least commonly used herbs were ginger (44.36%) and tenaadam (9.15 %), respectively. The common indications of herbal remedies use during pregnancy were nausea (23.90%) and morning sickness (21.05%). Results: The result of the present study confirmed wide use of herbal drugs use during pregnancy that need to report the safety concerns of these drugs during pregnancy. Conclusions: To achieve the requirements of pregnant women, it is vital for health care workers to be familiar with the effect of herbal medicine in pregnancy. PMID:25625049

  5. [Syphilis in addicted pregnant women: better care through more awareness and contract between organizations involved].

    PubMed

    Schneider, A J; Bosman, A

    1999-11-13

    Three women, aged 21, 20 and 30 years, were cocaine users and pregnant. There had been no prenatal monitoring until they reported with uterine contractions. Blood of the first two women was then tested; serology revealed active syphilis infections: their children had died in utero. The blood of the third woman had been tested as part of a street project; it revealed an active syphilitic infection but she could not be found for treatment. After delivery, the child showed withdrawal symptoms. The first and third women and the child of the third woman were treated with benzylpenicillin. The system for screening and treating drug-addicted pregnant women should be intensified.

  6. Omega-3 Fatty Acid Intake of Pregnant Women and Women of Childbearing Age in the United States: Potential for Deficiency?

    PubMed Central

    Nordgren, Tara M.; Lyden, Elizabeth; Anderson-Berry, Ann; Hanson, Corrine

    2017-01-01

    Omega-3 fatty acids play critical roles during fetal growth and development with increased intakes associated with improved maternal-fetal outcomes. Omega-3 fatty acid intake in Western diets is low, and the impact of socioeconomic factors on omega-3 fatty acid intake in pregnant women and women of childbearing age has not been reported. We used the National Health and Nutrition Examination Survey (NHANES) cycles 2003–2012 to assess the relationship between omega-3 fatty acid intake and socioeconomic factors in women of childbearing age. Out of 7266 eligible participants, 6478 were women of childbearing age, while 788 were identified as pregnant at the time of the survey. Mean EPA+DHA intake of the population was 89.0 mg with no significant difference between pregnant and non-pregnant women. By univariate and multivariate analyses adjusting for confounders, omega-3 fatty acid intake was significantly associated with poverty-to-income ratio, race, and educational attainment. Our results demonstrate that omega-3 fatty acid intake is a concern in pregnant women and women of childbearing age in the United States, and that socioeconomically disadvantaged populations are more susceptible to potential deficiencies. Strategies to increase omega-3 fatty acid intake in these populations could have the potential to improve maternal and infant health outcomes. PMID:28245632

  7. Omega-3 Fatty Acid Intake of Pregnant Women and Women of Childbearing Age in the United States: Potential for Deficiency?

    PubMed

    Nordgren, Tara M; Lyden, Elizabeth; Anderson-Berry, Ann; Hanson, Corrine

    2017-02-26

    Omega-3 fatty acids play critical roles during fetal growth and development with increased intakes associated with improved maternal-fetal outcomes. Omega-3 fatty acid intake in Western diets is low, and the impact of socioeconomic factors on omega-3 fatty acid intake in pregnant women and women of childbearing age has not been reported. We used the National Health and Nutrition Examination Survey (NHANES) cycles 2003-2012 to assess the relationship between omega-3 fatty acid intake and socioeconomic factors in women of childbearing age. Out of 7266 eligible participants, 6478 were women of childbearing age, while 788 were identified as pregnant at the time of the survey. Mean EPA+DHA intake of the population was 89.0 mg with no significant difference between pregnant and non-pregnant women. By univariate and multivariate analyses adjusting for confounders, omega-3 fatty acid intake was significantly associated with poverty-to-income ratio, race, and educational attainment. Our results demonstrate that omega-3 fatty acid intake is a concern in pregnant women and women of childbearing age in the United States, and that socioeconomically disadvantaged populations are more susceptible to potential deficiencies. Strategies to increase omega-3 fatty acid intake in these populations could have the potential to improve maternal and infant health outcomes.

  8. 45 CFR 96.131 - Treatment services for pregnant women.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... Programs which serve an injecting drug abuse population and who receive Block Grant funds shall give preference to treatment as follows: (1) Pregnant injecting drug users; (2) Pregnant substance abusers; (3) Injecting drug users; and (4) All others. (b) The State will, in carrying out this provision publicize...

  9. Knowledge and practice on Toxoplasma infection in pregnant women from Malaysia, Philippines, and Thailand.

    PubMed

    Andiappan, Hemah; Nissapatorn, Veeranoot; Sawangjaroen, Nongyao; Khaing, Si-Lay; Salibay, Cristina C; Cheung, Mary Mae M; Dungca, Julieta Z; Chemoh, Waenurama; Xiao Teng, Ching; Lau, Yee-Ling; Mat Adenan, Noor A

    2014-01-01

    Toxoplasma gondii, is one of the infectious agents of congenital TORCH infections, causes severe clinical outcomes in fetus and newborns. Nevertheless this life-threatening parasitic disease is preventable by simple preventive measures related to lifestyle during pregnancy. We aim to study on the knowledge about toxoplasmosis and practices that prevents this infection among the pregnant women. Total of 2598 pregnant women from Malaysia, Philippines, and Thailand were randomly surveyed to determine the knowledge and their practices on Toxoplasma infection. The questionnaire covered respondents' general information and knowledge on plausible risks factors, symptoms, timing of infection, prevention knowledge, and preventive behavior regarding Toxoplasma infection. Majority of these pregnant women were in their age group of 20-29 years (50.9%), completed secondary level of education (51.7%), in their second trimester of pregnancies (38.1%), non-parous (36.6%), and had no history of abortion (90.4%). Based on this survey, only 11% of these pregnant women had read, heard, or seen information regarding toxoplasmosis and 3.5% of them were aware of being tested for the infection. A small percentage of these pregnant women knew that T. gondii were shed in the feces of infected cats (19.4%) and sometimes found in the raw or undercooked meat (11.0%). There was 16.1% of responding women knew that toxoplasmosis is caused by an infection. Demographic profiles such as age group, level of education, pregnancy term, and number of children of the pregnant women showed significant association with their responses toward prevention knowledge and preventive behavior related questions (P < 0.05). Thus, it is suggested that health education on toxoplasmosis and primary behavioral practices should be consistently offered to reproductive age women in general and pregnant women in particular. This information could help to reduce vertical transmission of Toxoplasma infection during pregnancy.

  10. Salivary flow rate, pH, and concentrations of calcium, phosphate, and sIgA in Brazilian pregnant and non-pregnant women

    PubMed Central

    Rockenbach, Maria I; Marinho, Sandra A; Veeck, Elaine B; Lindemann, Laura; Shinkai, Rosemary S

    2006-01-01

    Background Studies on salivary variables and pregnancy in Latin America are scarce. This study aimed to compare salivary flow rate, pH, and concentrations of calcium, phosphate, and sIgA of unstimulated whole saliva in pregnant and non-pregnant Brazilians. Methods Cross-sectional study. Sample was composed by 22 pregnant and 22 non-pregnant women attending the Obstetrics and Gynecology Clinics, São Lucas Hospital, in Porto Alegre city, South region of Brazil. Unstimulated whole saliva was collected to determine salivary flow rate, pH, and biochemical composition. Data were analyzed by Student t test and ANCOVA (two-tailed α = 0.05). Results No difference was found for salivary flow rates and concentrations of total calcium and phosphate between pregnant and non-pregnant women (p > 0.05). Pregnant women had lower pH (6.7) than non-pregnant women (7.5) (p < 0.001), but higher sIgA level (118.9 mg/L) than the latter (90.1 mg/L) (p = 0.026). Conclusion Some of the tested variables of unstimulated whole saliva were different between pregnant and non-pregnant Brazilians in this sample. Overall, the values of the tested salivary parameters were within the range of international references of normality. PMID:17132167

  11. Effects of Microtubule Modulators on HIV-1 Infection of Transformed and Resting CD4 T Cells ▿

    PubMed Central

    Yoder, Alyson; Guo, Jia; Yu, Dongyang; Cui, Zongqiang; Zhang, Xian-En; Wu, Yuntao

    2011-01-01

    Previous studies have observed fluorescently labeled HIV particles tracking along microtubule networks for nuclear localization. To provide direct evidence for the involvement of microtubules in early steps of HIV infection of human CD4 T cells, we used multiple microtubule modulators such as paclitaxel (originally called taxol; 1 μM), vinblastine (1 and 10 μM), colchicine (10 and 100 μM), and nocodazole (10 and 100 μM) to disturb microtubule networks in transformed and resting CD4 T cells. Although these drugs disrupted microtubule integrity, almost no inhibition of HIV-1 infection was observed. Our results do not appear to support an essential role for microtubules in the initiation of HIV infection of CD4 T cells. PMID:21209111

  12. Antiviral molecules correlate with vitamin D pathway genes and are associated with natural resistance to HIV-1 infection.

    PubMed

    Aguilar-Jimenez, Wbeimar; Zapata, Wildeman; Rugeles, María T

    2016-01-01

    The relationship between the immunomodulatory effects of Vitamin D (VitD) and the expression of anti-HIV-1 molecules has not been explored in HIV-1-exposed seronegative individuals (HESNs). Higher mRNA levels of cathelicidin and HAD-4 in oral-mucosa and peripheral-blood, along with higher CYP24A1 mRNA in vaginal-mucosa and lower TLR2 mRNA in endocervical-mucosa were found in HESNs compared to non-exposed controls. Furthermore, the mRNA of anti-HIV molecules Elafin, TRIM5, Cathelicidin, HAD-4 and RNase7, previously associated with natural resistance to HIV-1 infection, positively correlated with the mRNA expression of VDR in HESNs, suggesting the potential participation of VitD in natural resistance to HIV-1.

  13. Dutrebis (lamivudine and raltegravir) for use in combination with other antiretroviral products for the treatment of HIV-1 infection.

    PubMed

    Casado, José Luis; Bañón, Sara

    2015-01-01

    Raltegravir and lamivudine have been part of highly active therapy regimens throughout the past years of antiretroviral therapy. A fixed-dose, single-tablet regimen comprising a non-poloxamer formulation of the integrase inhibitor raltegravir and the transcriptase inhibitor lamivudine (raltegravir/lamivudine; Dutrebis(®)) has been recently licensed for the treatment of HIV-1 infection. In several Phase I pharmacokinetic studies, one Dutrebis (150 mg lamivudine/300 mg raltegravir) fixed-dose combination tablet showed a higher bioavailability but comparable lamivudine and 400 mg raltegravir poloxamer exposures. Thus, the co-administration of raltegravir together with lamivudine created a potent, effective, well-tolerated antiretroviral combination, which could be more convenient for the patient. However, the disadvantage of twice a day administration, and the existence of other fixed-dose combinations limit its widespread clinical use. This article reviews pharmacokinetics data and appraises their potential use in current and future HIV therapy.

  14. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection.

    PubMed

    Wu, Xueling; Zhang, Zhenhai; Schramm, Chaim A; Joyce, M Gordon; Kwon, Young Do; Zhou, Tongqing; Sheng, Zizhang; Zhang, Baoshan; O'Dell, Sijy; McKee, Krisha; Georgiev, Ivelin S; Chuang, Gwo-Yu; Longo, Nancy S; Lynch, Rebecca M; Saunders, Kevin O; Soto, Cinque; Srivatsan, Sanjay; Yang, Yongping; Bailer, Robert T; Louder, Mark K; Mullikin, James C; Connors, Mark; Kwong, Peter D; Mascola, John R; Shapiro, Lawrence

    2015-04-23

    HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ∼2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.

  15. Iron Supplementation Alters Heme and Heme Oxygenase 1 (HO-1) Levels In Pregnant Women in Ghana

    PubMed Central

    Salifu, Hassana; Wilson, Nana O.; Liu, Mingli; Dickinson-Copeland, Carmen; Yatich, Nelly; Keenan, John; Turpin, Cornelius; Jolly, Pauline; Gyasi, Richard; Adjei, Andrew A.; Stiles, Jonathan K.

    2016-01-01

    Background Iron supplementation is recommended for pregnant women to meet their iron requirement for a healthy pregnancy. The benefits and risks of universal iron supplementation during pregnancy in malaria endemic countries are currently being debated. As part of a broader study that focused on the effect of heme/HO-1 on pregnancy outcomes in malaria in pregnancy, we determined the association between iron supplementation and free heme levels in blood of pregnant women with and without malaria in Ghana. We hypothesized that pregnant women with malaria who took iron supplements will have higher levels of Heme/HO-1 than those who did not take iron supplements. Methods A total of 337 women were recruited for this study. Blood samples were collected for malaria diagnosis and heme/HO-1 measurement. Quantification of heme was done using a heme colorimetric assay kit and HO-1 levels were performed using Enzyme-Linked Immunosorbent Assay (ELISA) on plasma samples. Results Malaria positive iron supplemented women, in their third trimester, had significantly higher median levels of heme 59.3(43.1 – 60.4) than non-malaria iron supplemented women 35.7(33.0 – 62.2), p = 0.026. Also, malaria positive iron supplemented women had significant higher median levels of HO-16.2(IQR 4.9 – 8.1) than pregnant women who did not take iron supplements 2.9 (IQR 2.1 – 3.8), p = <0.001 Conclusion Although iron supplementation may be highly beneficial and improve pregnancy outcomes for iron deficient or anemic mothers, it is also likely that iron supplementation for pregnant women who are not iron deficient may put this group of women at risk for adverse pregnancy outcomes. Findings from this study sheds light on the effect of iron supplementation on malaria derived heme in pregnancy, which may inform how iron supplementation is recommended for pregnant women who are not iron deficient. PMID:28124024

  16. Abacavir/dolutegravir/lamivudine single-tablet regimen: a review of its use in HIV-1 infection.

    PubMed

    Greig, Sarah L; Deeks, Emma D

    2015-04-01

    A fixed-dose, single-tablet regimen comprising the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine (abacavir/dolutegravir/lamivudine; Triumeq®) is now available for the treatment of HIV-1 infection. In a randomized, double-blind, phase III trial in antiretroviral therapy (ART)-naive adults (SINGLE), once-daily dolutegravir plus abacavir/lamivudine had noninferior efficacy to once-daily efavirenz/tenofovir disoproxil fumarate (tenofovir DF)/emtricitabine with regard to establishing and sustaining virological suppression over 144 weeks, and subsequent superiority testing significantly favoured dolutegravir plus abacavir/lamivudine. This outcome was predominantly driven by more favourable rates of discontinuation due to adverse events versus the efavirenz/tenofovir DF/emtricitabine group. These data were generally supported by findings from other phase III trials in ART-naive adults receiving dolutegravir plus either abacavir/lamivudine or tenofovir DF/emtricitabine (SPRING-2 and FLAMINGO). Dolutegravir plus abacavir/lamivudine is generally well tolerated, with a tolerability profile that appears to be more favourable than efavirenz/tenofovir DF/emtricitabine. In the SINGLE trial, there were no major treatment-emergent INSTI or NRTI resistance-associated mutations in dolutegravir plus abacavir/lamivudine recipients with protocol-defined virological failure, indicating a high genetic barrier to resistance. Thus, triple combination therapy with abacavir, dolutegravir and lamivudine is an effective, generally well tolerated option for the management of HIV-1 infection, with the convenient once-daily fixed-dose tablet providing the first single-tablet regimen option without tenofovir DF.

  17. Prevalence and Clinical Impact of Human Pegivirus-1 Infection in HIV-1-Infected Individuals in Yunnan, China

    PubMed Central

    Miao, Zhijiang; Gao, Li; Song, Yindi; Yang, Ming; Zhang, Mi; Lou, Jincheng; Zhao, Yue; Wang, Xicheng; Feng, Yue; Dong, Xingqi; Xia, Xueshan

    2017-01-01

    Human Pegivirus-1 (HPgV-1) may have a beneficial impact on disease progression in human immunodeficiency virus-1 (HIV-1) infection. However, analysis of the genotypic diversity of HPgV-1 and its relevance to the progression of HIV-1 disease remains limited. A total of 1062 HIV-1-infected individuals were recruited in all sixteen prefectures of Yunnan province, China. The reverse transcription nested polymerase chain reaction (RT-nPCR), phylogenetic analyses, and clinical data analyses were used to detect HPgV-1 infection, determine genotype, and analyze HPgV-1 genotype impact on HIV-1 disease progression. The overall positive rate of HPgV-1 RNA was 23.4% (248/1062), and the frequency of HPgV-1 infection in injecting drug users (IDUs) (28.5%, 131/460) was significantly higher than in heterosexuals (19.4%, 117/602). Multiple genotypes were identified in 212 subjects with successful sequencing for the E2 gene, including genotype 7 (55.7%), genotype 3 (34.9%), genotype 4 (4.7%), genotype 2 (3.3%), and an unclassified group (1.4%). Moreover, genotype 7 predominated in IDUs, whereas genotype 3 was the most common in heterosexuals. Our results revealed that HPgV-1 genotype 7 groups exhibited significantly lower HIV-1 viral load and higher CD4+ cell counts. This finding suggests that HPgV-1 genotype 7 may be associated with a better progression of HIV-1 disease. PMID:28212298

  18. HIV-1-Infected and/or Immune Activated Macrophages Regulate Astrocyte SDF-1 Production Through IL-1β

    PubMed Central

    PENG, HUI; ERDMANN, NATHAN; WHITNEY, NICHOLAS; DOU, HUANGYU; GORANTLA, SANTHI; GENDELMAN, HOWARD E.; GHORPADE, ANUJA; ZHENG, JIALIN

    2007-01-01

    Stromal cell-derived factor 1 alpha (SDF-1α) and its receptor CXCR4 play important roles in the pathogenesis of human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) by serving as a HIV-1 co-receptor and affecting cell migration, virus-mediated neurotoxicity, and neurodegeneration. However, the underlying mechanisms regulating SDF-1 production during disease are not completely understood. In this report we investigated the role of HIV-1 infected and immune competent macrophage, the principal target cell and mediator of neuronal injury and death in HAD, in regulating SDF-1 production by astrocytes. Our data demonstrated that astrocytes are the primary cell type expressing SDF-1 in the brain. Immune-activated or HTV-1-infected human monocyte-derived-macrophage (MDM) conditioned media (MCM) induced a substantial increase in SDF-1 production by human astrocytes. This SDF-1 production was directly dependent on MDM IL-1β following both viral and immune activation. The MCM-induced production of SDF-1 was prevented by IL-1β receptor antagonist (IL-1Ra) and IL-1β siRNA treatment of human MDM. These laboratory observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HIVE). In these HIVE mice, reactive astrocytes showed a significant increase in SDF-1 expression, as observed by immunocytochemical staining. Similarly, SDF-1 mRNA levels were increased in the encephalitic region as measured by real time RT-PCR, and correlated with IL-1β mRNA expression. These observations provide direct evidence that IL-1β, produced from HIV-1-infected and/or immune competent macrophage, induces production of SDF-1 by astrocytes, and as such contribute to ongoing SDF-1 mediated CNS regulation during HAD. PMID:16944452

  19. Stimulation of the primary anti-HIV antibody response by IFN-{alpha} in patients with acute HIV-1 infection

    PubMed Central

    Adalid-Peralta, Laura; Godot, Véronique; Colin, Céline; Krzysiek, Roman; Tran, Thi; Poignard, Pascal; Venet, Alain; Hosmalin, Anne; Lebon, Pierre; Rouzioux, Christine; Chêne, Geneviève; Emilie, Dominique

    2008-01-01

    Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-α2b. Patients with acute HIV-1 infection were randomized to receive anti-retroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-α2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-α2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-α2b administration, there were 8.5 (6.5–10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0–10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-α2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies. PMID:18182457

  20. Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans.

    PubMed

    McLaren, Paul J; Ripke, Stephan; Pelak, Kimberly; Weintrob, Amy C; Patsopoulos, Nikolaos A; Jia, Xiaoming; Erlich, Rachel L; Lennon, Niall J; Kadie, Carl M; Heckerman, David; Gupta, Namrata; Haas, David W; Deeks, Steven G; Pereyra, Florencia; Walker, Bruce D; de Bakker, Paul I W

    2012-10-01

    A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; P= 3.4 × 10(-18)] and B*81:01 (OR = 4.8; P= 1.3 × 10(-9)). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P = 1.2 × 10(-21)) and explains the signal of several HLA-B alleles, including B*57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus P= 2.8 × 10(-15)) in the canonical F pocket, position 63 in the B pocket (P= 1.5 × 10(-3)) and the non-pocket position 245 (P= 8.8 × 10(-10)), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of HLA-B in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control.

  1. Role of CCR5, CCR2 and SDF-1 gene polymorphisms in a population of HIV-1 infected individuals.

    PubMed

    Mazzucchelli, R; Corvasce, S; Violin, M; Riva, C; Bianchi, R; Dehò, L; Velleca, R; Cibella, J; Bada, M; Moroni, M; Galli, M; Balotta, C

    2001-01-01

    The finding that in addition to CD4 molecule HIV-1 uses, CCR5 or CXCR4 receptors to enter target cells prompted the research to identify polymorphisms in coreceptor genes affecting disease progression. In this study we analyzed the prevalence of CCR5-delta32, CCR2-641 and SDF1-3'A alleles in a highly selected group of 42 Long-Term Nonprogressors (LTNPs) compared to 112 subjects with a typical course of HIV-1 infection (TPs) and 117 healthy controls (HCs). In addition, we correlated CCR5, CCR2 and SDF-1 genotypes with molecular indexes of HIV-1 replication, cell-free RNA and both unspliced (US) and multiply spliced (MS) intracellular transcripts, to investigate the role of the mutant alleles in determining a long-term nonprogressive course of HIV-1 disease. Our results indicate a significantly higher prevalence of CCR5-delta32 allele in LTNPs compared to TPs (p=0.0434), while the proportions of CCR2-64I and SDF1-3'A alleles were comparable between the two groups. However, SDF-1 wild type LTNP subjects showed significantly lower levels of HIV-1 genomic RNA, US and MS transcripts than SDF1-3'A heterozygous ones (p=0.0021, 0.016, 0.0031, respectively), whereas both CCR5 and CCR2 wild type individuals had similar rates of viral replication compared to CCR5-delta32 and CCR2-64I heterozygous ones. CCR5, CCR2 and SDF-1 combined genotypes were also studied and this analysis did not identify a specific protective cluster of alleles in LTNPs. Taken together, our results indicate that genetic background involving CCR5, CCR2 and SDF-1 alleles may play a limited role in the natural history of HIV-1 infection.

  2. Different Expression of Interferon Stimulated Genes in Response to HIV-1 Infection in Dendritic Cells According to Their Maturation State.

    PubMed

    Calonge, Esther; Bermejo, Mercedes; Diez-Fuertes, Francisco; Mangeot, Isabelle; Gonzalez, Nuria; Coiras, Mayte; Jimenez Tormo, Laura; García-Perez, Javier; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Alcamí, José

    2017-02-01

    Dendritic cells (DCs) are professional antigen presenting cells whose functions are dependent on their degree of differentiation. In their immature state, DCs, capture pathogens and migrate to the lymph nodes. During this process DCs become resident mature cells specialized in antigen presentation. DCs are characterized by a highly limiting environment to HIV-1 replication due to the expression of restriction factors as SAMHD1 and APOBEC3G. However, uninfected DCs capture and transfer viral particles to CD4 lymphocytes through a trans-enhancement mechanism in which chemokines are involved. We analyzed changes in gene expression with whole-genome-microarray when immature (IDCs) or mature (MDCs) dendritic cells were productively infected using Vpx-loaded HIV-1 particles. Whereas productive HIV infection of IDCs induced expression of interferon stimulated genes (ISGs), such induction was not produced in MDCs in which a sharp decrease in ISG and CXCR3-binding chemokines was observed lessening trans-infection of CD4 lymphocytes. Similar patterns of gene expression were found when DCs were infected with HIV-2 that naturally express Vpx. Differences were also observed in conditions of restrictive HIV-1 infection, in the absence of Vpx. ISGs expression was not modified in IDCs whereas an increase of ISG and CXCR3-binding chemokines was observed in MDCs. Overall these results suggest that sensing and restriction of HIV-1 infection are different between IDCs and MDCs. We propose that restrictive infection results in increased virulence through different mechanisms. In IDC avoiding sensing and induction of ISGs whereas in MDC increased production of CXCR3-binding chemokines would result in lymphocyte attraction and enhanced infection at the immune synapse.

  3. High levels of anti-Nef antibodies may prevent AIDS disease progression in vertically HIV-1-infected infants

    PubMed Central

    Corró, Guillermo; Crudeli, Cintia Milena; Rocco, Carlos Alberto; Marino, Silvia Alejandra; Sen, Luisa

    2014-01-01

    Introduction HIV-1-associated CD4+ T-cell depletion is a consequence of uninfected cell death. Nef is one of the viral factors that trigger apoptosis on bystander cells, though the plasma Nef levels do not correlate with Th lymphocytes counts. The aim of our study was to evaluate whether anti-Nef antibodies were involved in paediatric AIDS development and whether they can prevent the CD4+ T-cell depletion in vertically infected children. Methods Two hundred and seventy three HIV-1 vertically infected children seen at Garrahan Paediatric Hospital were randomly included in the study, adding 13 selected cases: seven LTNP (long-term non-progressors) and six RP (rapid progressors) children (n total=286). Specific anti-HIV-1-Nef antibodies were titrated by indirect ELISA and compared between groups. The plasma blocking effect on Nef-dependent cytotoxicity was evaluated in Jurkat cells using recombinant Nef as apoptotic stimulus and patient plasmas as blockers, measuring the apoptotic levels using Annexin-V stain and flow cytometry. Results Only 63.4% of the patients had specific anti-Nef antibodies, and the levels of anti-Nef antibodies found in the selected LTNPs plasmas were always significantly higher (p=1.55×10−4) than those in RPs or general HIV-1+ paediatric populations. The LTNPs’ plasma had a strong inhibitory effect on Nef-dependent cytotoxicity even at high dilutions, while RP plasmas had little or no effect on Nef-induced apoptosis. Discussion and conclusions High anti-Nef antibody levels are associated and predict slow or non-progression to AIDS in vertically HIV-1-infected children. They could be an efficient tool in preventing Nef-associated bystander effect, preserving CD4+ T-cells and the immune function in the context of paediatric HIV-1 infection. PMID:24560340

  4. Prevalence and persistence of antibody titers to recombinant HIV-1 core and matrix proteins in HIV-1 infection.

    PubMed

    Janvier, B; Mallet, F; Cheynet, V; Dalbon, P; Vernet, G; Besnier, J M; Choutet, P; Goudeau, A; Mandrand, B; Barin, F

    1993-08-01

    Numerous studies have established the correlation between antibodies to the core protein p24 of HIV-1 and the progression of the acquired immunodeficiency syndrome. In this study, we analyzed the immune response to two recombinant gag proteins, p24 and p17, in order to evaluate their diagnostic or prognostic significance. Immune response to the immunodominant domain of the transmembrane glycoprotein gp41 was used as a reference. Sera collected from individuals from France and Burundi (Central Africa) at various CDC stages of HIV-1 infection were tested using three sandwich enzyme-linked immunoassays developed with a synthetic peptide corresponding to the immunodominant domain of gp41, SP gp41, or recombinant p24 and p17 cloned and expressed in Escherichia coli. These assays allowed detection of titer antibodies to the three cited antigens. Antibodies to SP gp41 were detected in every HIV-1-positive patient from France and Burundi, generally at a high and stable level. Results obtained with p24 confirmed the value of antibodies to p24 as a prognostic marker only in European and North American populations, since the African population had very high levels of these antibodies even at an advanced stage of the disease. They also confirmed that initial antibody response to p24 is more predictive of outcome than antibody titer change over time. Although antibodies to p17 decline during progression to AIDS, they are frequently absent in French patients at early, asymptomatic stages and therefore could not be used as a prognostic marker. In contrast, antibodies to p17 are significantly less common in African patients with AIDS when compared with symptomless HIV-1-infected African individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Nanogel-Conjugated Reverse Transcriptase Inhibitors and Their Combinations as Novel Antiviral Agents with Increased Efficacy against HIV-1 Infection.

    PubMed

    Senanayake, T H; Gorantla, S; Makarov, E; Lu, Y; Warren, G; Vinogradov, S V

    2015-12-07

    Nucleoside reverse transcriptase inhibitors (NRTIs) are an integral part of the current antiretroviral therapy (ART), which dramatically reduced the mortality from AIDS and turned the disease from lethal to chronic. The further steps in curing the HIV-1 infection must include more effective targeting of infected cells and virus sanctuaries inside the body and modification of drugs and treatment schedules to reduce common complications of the long-term treatment and increase patient compliancy. Here, we describe novel NRTI prodrugs synthesized from cholesteryl-ε-polylysine (CEPL) nanogels by conjugation with NRTI 5'-succinate derivatives (sNRTI). Biodegradability, small particle size, and high NRTI loading (30% by weight) of these conjugates; extended drug release, which would allow a weekly administration schedule; high therapeutic index (>1000) with a lower toxicity compared to NRTIs; and efficient accumulation in macrophages known as carriers for HIV-1 infection are among the most attractive properties of new nanodrugs. Nanogel conjugates of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) have been investigated individually and in formulations similar to clinical NRTI cocktails. Nanodrug formulations demonstrated 10-fold suppression of reverse transcriptase activity (EC90) in HIV-infected macrophages at 2-10, 2-4, and 1-2 μM drug levels, respectively, for single nanodrugs and dual and triple nanodrug cocktails. Nanogel conjugate of lamivudine was the most effective single nanodrug (EC90 2 μM). Nanodrugs showed a more favorable pharmacokinetics compared to free NRTIs. Infrequent iv injections of PEGylated CEPL-sAZT alone could efficiently suppress HIV-1 RT activity to background level in humanized mouse (hu-PBL) HIV model.

  6. Establishment and Replenishment of the Viral Reservoir in Perinatally HIV-1-infected Children Initiating Very Early Antiretroviral Therapy

    PubMed Central

    Martínez-Bonet, Marta; Puertas, Maria Carmen; Fortuny, Claudia; Ouchi, Dan; Mellado, Maria José; Rojo, Pablo; Noguera-Julian, Antoni; Muñoz-Fernández, Ma Angeles; Martinez-Picado, Javier

    2015-01-01

    Background. Combination antiretroviral therapy (cART) generally suppresses the replication of the human immunodeficiency virus type 1 (HIV-1) but does not cure the infection, because proviruses persist in stable latent reservoirs. It has been proposed that low-level proviral reservoirs might predict longer virologic control after discontinuation of treatment. Our objective was to evaluate the impact of very early initiation of cART and temporary treatment interruption on the size of the latent HIV-1 reservoir in vertically infected children. Methods. This retrospective study included 23 perinatally HIV-1-infected children who initiated very early treatment within 12 weeks after birth (n = 14), or early treatment between week 12 and 1 year (n = 9). We measured the proviral reservoir (CD4+ T-cell–associated HIV-1 DNA) in blood samples collected beyond the first year of sustained virologic suppression. Results. There is a strong positive correlation between the time to initiation of cART and the size of the proviral reservoir. Children who initiated cART within the first 12 weeks of life showed a proviral reservoir 6-fold smaller than children initiating cART beyond this time (P < .01). Rapid virologic control after initiation of cART also limits the size of the viral reservoir. However, patients who underwent transient treatment interruptions showed a dramatic increase in the size of the viral reservoir after discontinuation. Conclusions. Initiation of cART during the first 12 weeks of life in perinatally HIV-1-infected children limits the size of the viral reservoir. Treatment interruptions should be undertaken with caution, as they might lead to fast and irreversible replenishment of the viral reservoir. PMID:26063721

  7. Phenotypical and functional evaluation of CD8+/S6F1+ T lymphocytes in haemophiliac individuals with HIV-1 infection.

    PubMed Central

    Cavallin, F; Traldi, A; Zambello, R

    1993-01-01

    In this study we investigated the distribution of the S6F1 antigen, an epitope of the lymphocyte function-associated antigen, on CD8+ T lymphocytes in a series of 15 HIV-1+ and 20 HIV-1- haemophiliac patients. MoAbs recognizing the S6F1 antigen have been claimed to distinguish between killer effectors (brightly S6F1+ stained) and suppressor cells (dimly S6F1+ stained) within the CD8+ lymphoid population. In addition, we tried to find a correlation between the spontaneous in vitro immunoglobulin synthesis from patients' peripheral blood lymphocytes and the pattern of S6F1 expression. Although the total number of double-positive CD8+/S6F1+ cells was similar in both HIV-1+ and HIV-1- haemophiliac patients, a significant increase in the CD8+/S6F1+ population bright versus dim was documented in HIV-1-infected with respect to HIV-1- haemophiliacs (bright/dim ratio 3.97 +/- 0.61 versus 0.75 +/- 0.1, respectively, P < 0.005). This finding was correlated to a significant increase in spontaneous in vitro immunoglobulin production in HIV-1+ subjects compared with control haemophiliacs (P < 0.005). Purified CD8+ lymphocytes from HIV-1+ subjects showed a reduced suppressor activity on mitogen-induced immunoglobulin production. Taken together, these data suggest that HIV-1 infection favours the generation of CD8+/S6F1+ bright cells with putative cytotoxic-associated function, leading to a progressive reduction in the number of CD8+/S6F1+ dim suppressor lymphocytes. This phenomenon may contribute to the polyclonal hypergammaglobulinaemia present in HIV-1+ haemophiliac patients. PMID:8324903

  8. Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans

    PubMed Central

    McLaren, Paul J.; Ripke, Stephan; Pelak, Kimberly; Weintrob, Amy C.; Patsopoulos, Nikolaos A.; Jia, Xiaoming; Erlich, Rachel L.; Lennon, Niall J.; Kadie, Carl M.; Heckerman, David; Gupta, Namrata; Haas, David W.; Deeks, Steven G.; Pereyra, Florencia; Walker, Bruce D.; de Bakker, Paul I. W.

    2012-01-01

    A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; P= 3.4 × 10–18] and B*81:01 (OR = 4.8; P= 1.3 × 10−9). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P = 1.2 × 10−21) and explains the signal of several HLA-B alleles, including B*57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus P= 2.8 × 10−15) in the canonical F pocket, position 63 in the B pocket (P= 1.5 × 10−3) and the non-pocket position 245 (P= 8.8 × 10−10), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of HLA-B in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control. PMID:22718199

  9. Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection.

    PubMed

    Adalid-Peralta, Laura; Godot, Véronique; Colin, Céline; Krzysiek, Roman; Tran, Thi; Poignard, Pascal; Venet, Alain; Hosmalin, Anne; Lebon, Pierre; Rouzioux, Christine; Chene, Genevieve; Emilie, Dominique

    2008-04-01

    Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-alpha2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-alpha2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha2b administration, there were 8.5 (6.5-10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0-10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-alpha2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.

  10. Early type I Interferon response induces upregulation of human β-defensin 1 during acute HIV-1 infection

    PubMed Central

    Lisanti, Antonella C.; Körner, Christian; Schiff, Abigail E.; Rosenberg, Eric S.; Allen, Todd M.; Altfeld, Marcus; Kwon, Douglas S.

    2017-01-01

    HIV-1 is able to evade innate antiviral responses during acute infection to establish a chronic systemic infection which, in the absence of antiretroviral therapy (ART), typically progresses to severe immunodeficiency. Understanding these early innate immune responses against HIV-1 and their mechanisms of failure is relevant to the development of interventions to better prevent HIV-1 transmission. Human beta defensins (HBDs) are antibacterial peptides but have recently also been associated with control of viral replication. HBD1 and 2 are expressed in PBMCs as well as intestinal tissue, but their expression in vivo during HIV-1 infection has not been characterized. We demonstrate that during acute HIV-1 infection, HBD1 but not HBD2 is highly upregulated in circulating monocytes but returns to baseline levels during chronic infection. HBD1 expression in monocytes can be induced by HIV-1 in vitro, although direct infection may not entirely account for the increase in HBD1 during acute infection. We provide evidence that HIV-1 triggers antiviral IFN-α responses, which act as a potent inducer of HBD1. Our results show the first characterization of induction of an HBD during acute and chronic viral infection in humans. HBD1 has been reported to have low activity against HIV-1 compared to other defensins, suggesting that in vivo induced defensins may not significantly contribute to the robust early antiviral response against HIV-1. These data provide important insight into the in vivo kinetics of HBD expression, the mechanism of HBD1 induction by HIV-1, and the role of HBDs in the early innate response to HIV-1 during acute infection. PMID:28253319

  11. Obesity and periodontal disease in diabetic pregnant women.

    PubMed<