Publications by authors named "Debra Adams"

34 Publications

Durable protection against repeated penile exposures to simian-human immunodeficiency virus by broadly neutralizing antibodies.

Nat Commun 2020 06 24;11(1):3195. Epub 2020 Jun 24.

Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIV). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIV exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 μg ml correlated with ≥99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.
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http://dx.doi.org/10.1038/s41467-020-16928-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314794PMC
June 2020

Development of a repeat-exposure penile SHIV infection model in macaques to evaluate biomedical preventions against HIV.

PLoS One 2018 27;13(3):e0194837. Epub 2018 Mar 27.

Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

Penile acquisition of HIV infection contributes substantially to the global epidemic. Our goal was to establish a preclinical macaque model of penile HIV infection for evaluating the efficacy of new HIV prevention modalities. Rhesus macaques were challenged once or twice weekly with consistent doses of SHIVsf162P3 (a chimeric simian-human immunodeficiency virus containing HIV env) ranging from 4-600 TCID50 (50% tissue culture infective dose), via two penile routes, until systemic SHIV infection was confirmed. One route exposed the inner foreskin, glans and urethral os to virus following deposition into the prepuce (foreskin) pouch. The second route introduced the virus non-traumatically into the distal urethra only. Single-route challenges resulted in dose-dependent rates of SHIV acquisition informing selection of optimal SHIV dosing. Concurrent SHIV challenges via the prepuce pouch (200 TCID50) and urethra (16 TCID50) resulted in infection of 100% (10/10) animals following a median of 2.5 virus exposures (range, 1-12). We describe the first rhesus macaque repeat-exposure SHIV challenge model of penile HIV acquisition. Utilization of the model should further our understanding of penile HIV infection and facilitate the development of new HIV prevention strategies for men.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194837PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870976PMC
July 2018

Quality improvement collaborative: A novel approach to improve infection prevention and control. Perceptions of lead infection prevention nurses who participated.

J Infect Prev 2018 Mar 19;19(2):64-71. Epub 2017 Sep 19.

The Royal Wolverhampton NHS Trust, UK.

Background: In response to the ongoing infection prevention (IP) challenges in England, a 90-day quality improvement (QI) collaborative programme was developed. The paper discusses the approach, benefits, challenges and evaluation of the programme.

Objective: The objective of the collaborative was to develop new approaches to enable sustainable and effective IP.

Methodology: Six trusts in the region participated in the collaborative. Each defined their bespoke IP focus. There was no expectation that statistically significant measurable improvements would be identified during the short time frame. The experiences of the participants were sought both during the programme to facilitate its constant review and at the end of the programme to evaluate its effectiveness. The feedback focused on achievements, barriers to change and benefits of participating in a QI collaborative. To measure the potential success of the projects, participants completed the Model for Understanding Success in Quality framework. (MUSIQ; Kaplan et al., 2012).

Results: Since each trusts IP focus was bespoke commonalities of success were not evaluated. Participants identified a positive outcome from their QI interventions. The MUSIQ score identified the projects had the potential for success.

Discussion: The feedback from the participants demonstrated that it is worthy of further development.
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http://dx.doi.org/10.1177/1757177417726154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846978PMC
March 2018

SHIV susceptibility changes during the menstrual cycle of pigtail macaques.

J Med Primatol 2014 Oct 29;43(5):310-6. Epub 2014 Apr 29.

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Hormonal changes during menstrual cycling may affect susceptibility to HIV.

Methods: We determined the simian human immunodeficiency virus (SHIV) acquisition time point in 43 cycling pigtail macaques infected by repeated vaginal virus exposures initiated randomly in the cycle.

Results: SHIV infection was first detected in the follicular phase in 38 macaques (88%), and in the luteal phase in five macaques (12%), indicating a statistically significant timing difference. Assuming a 7-day eclipse phase, most infections occurred during or following a high-progesterone period associated with menstruation, vaginal epithelium thinning, and suppressed mucosal immunity.

Conclusions: This raises questions whether other high-progesterone conditions (pregnancy, hormonal contraception) similarly affect HIV risk.
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http://dx.doi.org/10.1111/jmp.12124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175065PMC
October 2014

The sharps end of the law.

Authors:
Debra Adams

Nurs Stand 2014 Mar 19-25;28(29):65

NHS Trust Development Authority.

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http://dx.doi.org/10.7748/ns2014.03.28.29.65.s52DOI Listing
June 2014

FIT4Safety: recommendations in the diabetes care setting.

Br J Nurs 2013 Sep 12-25;22(17):997-1000

Independent Consultant Advisor/Head of Infection Prevention and Control (Midlands and East) at NHS Trust Development Authority.

Sharps injuries pose a serious threat to health professionals, patients, and downstream workers. FIT4Safety is an initiative that seeks to promote safety and best practice in the diabetes setting. An Introduction to FIT4Safety and its Recommendations for the Safety of Sharps in the Diabetes Care Setting explains how and why the FIT4Safety initiative was formed, what it aims to achieve, and the importance of ensuring safety in the diabetes care setting. Outputs from FIT4Safety include Injection Safety in UK and Ireland: Safety of Sharps in Diabetes Recommendations. These recommendations were developed to provide a resource for all those directly involved in, or overseeing, diabetes care. The main topics and guidance detailed within the recommendations are discussed, as well as EU Directive 2010/32 on sharps injury prevention and the UK's Health and Safety (Sharp Instruments in Healthcare) Regulations 2013.
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http://dx.doi.org/10.12968/bjon.2013.22.17.997DOI Listing
January 2014

Susceptibility to repeated, low-dose, rectal SHIVSF162P3 challenge is independent of TRIM5 genotype in rhesus macaques.

AIDS Res Hum Retroviruses 2013 Jul 29;29(7):1091-4. Epub 2013 Mar 29.

Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Infections following repeated, low-dose (RLD), mucal S(H)IV exposures of macaques are used to model sexual HIV exposures for biomedical prevention testing. Different susceptibilities among animals can complicate study designs. In rhesus macaques, TRIM5 alleles Q, CypA, and TFP are resistance factors for infection with some S(H)IV strains, but not for SIVmac239 due to its capsid properties. SIVmac239-derived SHIVSF162P3 has been demonstrated to reproducibly infect mucosally in vaginal and rectal RLD models. To further test the suitability of SHIVSF162P3 for RLD models, we studied the influence of the TRIM5 genotype on susceptibility to rectal RLD infection and on plasma viremia by analyzing 43 male Indian rhesus macaques from control arms of completed studies. The median number of exposures required for infection was three (Q/Q, n=4) (TRIM5 alleles, number of macaques, respectively), four (Q/CypA, n=7), three (TFP/Q, n=15), three (TFP/TFP, n=15), and two (TFP/CypA, n=2); TRIM5(CypA/CypA) was not represented in our study. Median peak viremia (log10 viral copies/ml) in infected animals was 7.4 (Q/Q, n=4), 7.2 (Q/CypA, n=6), 7.3 (TFP/Q, n=13), 7.1 (TFP/TFP, n=15), and 6.5 (TFP/CypA; n=2). Neither susceptibility nor peak viremia was significantly different (log rank test, Kruskal-Wallis test, respectively). Rhesus macaques' susceptibility to RLD SHIVSF162P3 is independent of the TRIM5 TFP, CypA, and Q alleles, with the limitation that the power to detect any impact of CypA/CypA and TFP/CypA genotypes was nonexistent or low, due to absence or infrequency, respectively. The finding that TRIM5 alleles do not restrict mucosal infection or ensuing replication rates suggests that SHIVSF162P3 is indeed suitable for RLD experimentation.
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http://dx.doi.org/10.1089/aid.2012.0383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685693PMC
July 2013

Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues.

J Med Primatol 2013 Apr 12;42(2):89-100. Epub 2013 Jan 12.

Division of Scientific Resources, NCEZID, CDC, Atlanta, GA 30333, USA.

Background: FTY720 is an immunomodulatory agent that reduces lymphocytes in peripheral tissues and circulation. Such agents may be effective as vaginal microbicides for HIV prevention. Systemic or vaginal application of FTY720 may reduce lymphocyte concentrations in genital tissues, reducing HIV target cell numbers.

Methods: Five female pigtail macaques received topical vaginal gel FTY720 (n = 2), intravenous (i.v.) FTY720 (n = 2), or placebo gel (n = 1) in this pilot study. Circulating and mucosal lymphocytes and genital mucosa, cytokines, and tissue histology were analyzed to document topical and i.v. FTY720 effects.

Results: Topical and i.v. FTY720 appeared to decrease the levels of cervicovaginal IL-8, IL-1ra, and genital inflammatory cells. Small sample size precluded statistical analysis. Topical administration had no overt adverse effects.

Conclusions: This study introduces FTY720 as an immunomodulatory agent for the vaginal mucosa, compares topical effects to those of i.v. administration, and provides the basis for future studies involving FTY720 for HIV prevention.
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http://dx.doi.org/10.1111/jmp.12033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594332PMC
April 2013

Needlestick and sharps injuries: practice update.

Authors:
Debra Adams

Nurs Stand 2012 May 16-22;26(37):49-57; quiz 58

NHS Midlands and East, Birmingham.

Member states of the European Union have until May 112013 to implement the Council Directive 2010/32/EU Implementing the Framework Agreement on Prevention from Sharps Injuries in the Hospital and Healthcare Sector. The aim of this legislation is to achieve a safe working environment and prevent injuries to healthcare professionals caused by all medical sharps, including needlesticks. This article examines the issues surrounding needlestick and sharps injuries, including risk assessment and prevention, information provision, raising awareness, use of safety devices, training and reporting procedures.
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http://dx.doi.org/10.7748/ns2012.05.26.37.49.c9107DOI Listing
July 2012

Reduced inflammation and CD4 loss in acute SHIV infection during oral pre-exposure prophylaxis.

J Infect Dis 2012 Sep 27;206(5):770-9. Epub 2012 Jun 27.

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: The impact of pre-exposure prophylaxis (PrEP) with antiretrovirals on breakthrough HIV or SHIV infection is not fully documented. We addressed the hypothesis that SHIV(SF162P3) infection despite active PrEP results in altered early immune parameters, compared with untreated infection.

Methods: Eleven rhesus macaques were infected during repeated, rectal, low-dose SHIV(SF162P3) exposures while receiving concurrent oral PrEP (Truvada [n = 2] or GS7340 [n = 4]) or as untreated controls (n = 5). We measured SHIV RNA, inflammatory cytokines, CD4 cells, and SHIV-specific and memory T cells until 20 weeks after peak viremia.

Results: SHIV infection during PrEP resulted in 100-fold lower peak viremia and lower IL-15, IL-18, and IL-1Ra levels, compared with controls (P < .05; Wilcoxon rank-sum test). Unlike controls, PrEP-treated macaques showed no significant CD4 cell count reduction during acute infection and developed more SHIV-specific central memory T cells, relative to controls. After in vivo CD8 cell depletion, viral load increased to similar levels, indicating that CD8 cells were critical for viral control in both groups.

Conclusions: PrEP with antiretrovirals has beneficial effects on early SHIV infection even when infection is not prevented. Although long-term immune control could not be examined in this SHIV infection model, our results suggest that PrEP results in improved early disease parameters in breakthrough infections.
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http://dx.doi.org/10.1093/infdis/jis422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491742PMC
September 2012

Needle stick and sharps injuries: practice update.

Authors:
Debra Adams

Nurs Stand 2012 May;26(37):49-58

NHS Midlands and East, Birmingham.

Member states of the European Union have until May 11 2013 to implement the Council Directive 2010/32/EU Implementing the Framework Agreement on Prevention from Sharps Injuries in the Hospital and Healthcare Sector. The aim of this legislation is to achieve a safe working environment and prevent injuries to healthcare professionals caused by all medical sharps, including needlesticks. This article examines the issues surrounding needlestick and sharps injuries, including risk assessment and prevention, information provision, raising awareness, use of safety devices, training and reporting procedures.
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http://dx.doi.org/10.7748/ns.26.37.49.s54DOI Listing
May 2012

A comparative study to evaluate surface microbial contamination associated with copper-containing and stainless steel pens used by nurses in the critical care unit.

Am J Infect Control 2011 Oct 12;39(8):e52-e54. Epub 2011 Jun 12.

University Hospitals Birmingham, National Health Service Foundation Trust, The Queen Elizabeth Hospital,. Electronic address:

A clinical study was undertaken to compare the surface microbial contamination associated with pens constructed of either a copper alloy or stainless steel used by nurses on intensive care units. A significantly lower level of microbial contamination was found on the copper alloy pens.
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http://dx.doi.org/10.1016/j.ajic.2010.12.012DOI Listing
October 2011

High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques.

J Acquir Immune Defic Syndr 2011 Aug;57(4):261-4

Division of HIV/AIDS Prevention, CDC, Atlanta, GA 30329, USA.

Fluctuations in susceptibility to HIV or SHIV during the menstrual cycle are currently not fully documented. To address this, the time point of infection was determined in 19 adult female pigtail macaques vaginally challenged during their undisturbed menstrual cycles with repeated, low-dose SHIV(SF162P3) exposures. Eighteen macaques (95%) first displayed viremia in the follicular phase, as compared with 1 macaque (5%) in the luteal phase (P < 0.0001). Due to a viral eclipse phase, we estimated a window of most frequent virus transmission between days 24 and 31 of the menstrual cycle, in the late luteal phase. Thus, susceptibility to vaginal SHIV infection is significantly elevated in the second half of the menstrual cycle when progesterone levels are high and when local immunity may be low. Such susceptibility windows have been postulated before but not definitively documented. Our data support the findings of higher susceptibility to HIV in women during progesterone-dominated periods including pregnancy and contraceptive use.
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http://dx.doi.org/10.1097/QAI.0b013e318220ebd3DOI Listing
August 2011

T cell chemo-vaccination effects after repeated mucosal SHIV exposures and oral pre-exposure prophylaxis.

PLoS One 2011 Apr 26;6(4):e19295. Epub 2011 Apr 26.

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

Pre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a "chemo-vaccination" effect, could contribute to PrEP efficacy. To study possible chemo-vaccination, we monitored humoral and cellular immune responses in nine rhesus macaques undergoing up to 14 weekly, low-dose SHIV(SF162P3) rectal exposures. Six macaques concurrently received PrEP with intermittent, oral Truvada; three were no-PrEP controls. PrEP protected 4 macaques from infection. Two of the four showed evidence of chemo-vaccination, because they developed anti-SHIV CD4(+) and CD8(+) T cells; SHIV-specific antibodies were not detected. Control macaques showed no anti-SHIV immune responses before infection. Chemo-vaccination-induced T cell responses were robust (up to 3,940 SFU/10(6) PBMCs), predominantly central memory cells, short-lived (≤22 weeks), and appeared intermittently and with changing specificities. The two chemo-vaccinated macaques were virus-challenged again after 28 weeks of rest, after T cell responses had waned. One macaque was not protected from infection. The other macaque concurrently received additional PrEP. It remained uninfected and T cell responses were boosted during the additional virus exposures. In summary, we document and characterize PrEP-induced T cell chemo-vaccination. Although not protective after subsiding in one macaque, chemo-vaccination-induced T cells warrant more comprehensive analysis during peak responses for their ability to prevent or to control infections after additional exposures. Our findings highlight the importance of monitoring these responses in clinical PrEP trials and suggest that a combination of vaccines and PrEP potentially might enhance efficacy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019295PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082568PMC
April 2011

Investigation and management of an A. Baumannii outbreak in ICU.

Br J Nurs 2011 Feb 10-23;20(3):140, 142,144-7

Infection Prevention and Control.

Acinetobacter baumannii infection is responsible for a wide range of infections, including pneumonia, bacteraemia, meningitis, wound infections, and urinary tract infections. During June 2010, two patients on an intensive care unit in an acute hospital in the UK had multi-resistant A. baumannii identified in samples obtained from a variety of specimens. A further case was identified 31 days following confirmation of the first outbreak. The investigation and management of this outbreak included the introduction of enhanced infection prevention and control precautions; the establishment of an Outbreak Control Team; epidemiological investigations; and the decontamination of equipment and the environment. Isolate typing by the Health Protection Agency Centre for Infections laboratory confirmed the three cases had identical A. baumannii strains: European clone II lineage encoded with an OXA-51-type carbapenemase. This suggests that there was a patient-to-patient spread of multi-resistant A. baumannii.
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http://dx.doi.org/10.12968/bjon.2011.20.3.140DOI Listing
March 2011

Resistance to Simian HIV infection is associated with high plasma interleukin-8, RANTES and Eotaxin in a macaque model of repeated virus challenges.

J Acquir Immune Defic Syndr 2010 Apr;53(5):574-81

From the Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Animal models for research on susceptibility to HIV are currently not available. Here we explore whether a macaque model of repeated low-dose rectal or vaginal virus challenges could be employed. We tested the hypothesis that susceptibility to Simian HIV is not merely stochastic in this model but rather is associated with identifiable host factors. Forty macaques required a median of 3.5 SHIVSF162P3 challenges for infection. We studied the association of their susceptibility with 13 predisposing plasma cytokines/chemokines (RANTES, Eotaxin, monocyte chemoattractant protein (MCP)-1, IL-7, MIP-1beta, TNF-alpha, MIP-1alpha, granulocyte colony-stimulating factor, IL-8, interferon-gamma, IL-17, IL-1beta, IL-6). Higher plasma RANTES, IL-8, and Eotaxin were associated with lower susceptibility, that is, higher resistance to infection. In a group of macaques with low IL-8 and RANTES, a median 3 exposures were required to infect; whereas, when either IL-8 or RANTES were high, a median 12 exposures were required. Thus, susceptibility was associated with identifiable discrete host factors and was not stochastic. In addition, the macaque model identified key human resistance factors (RANTES, Eotaxin), but also revealed a novel association with resistance (IL-8). Future direct evaluation of these or other factors in the animal model may be beneficial for developing new immunomodulation strategies for HIV prevention.
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http://dx.doi.org/10.1097/QAI.0b013e3181d3521fDOI Listing
April 2010

Repeated rectal SHIVSF162P3 exposures do not consistently induce sustained T cell responses prior to systemic infection in the repeat-low dose preclinical macaque model.

AIDS Res Hum Retroviruses 2009 Sep;25(9):905-17

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

The macaque model of repeated SHIV exposures is increasingly used as a preclinical tool to evaluate biomedical HIV intervention strategies. It is unclear whether multiple virus exposures induce immune responses in macaques, as documented in uninfected individuals repeatedly exposed to HIV. We here address whether repeated, rectal SHIV(SF162P3) exposures lead to systemic T cell activation in 12 rhesus macaques, and whether this is associated with increased infection resistance. Eight macaques became systemically infected after 2-7 exposures, three macaques were less susceptible (infection after 10-12 exposures), and one macaque remained uninfected after 14 exposures. PBMCs were retrospectively monitored for increases in T cell activation by analyzing the proportion of CD8(+) T cells, recently activated or proliferated T cells (markers CD38, Ki67), a marker for cytotoxicity (granzyme B), or T cell-produced plasma cytokines (IFN-gamma, RANTES, IL-2). Repeated virus exposures did not induce sustained, potent, or diverse T cell responses prior to systemic infection. Some changes occurred in the analyzed parameters during repeated virus exposures, but similar T cell activities were also observed in five SHIV-unexposed control macaques. Thus, we found no evidence that delayed infection or resistance to infection was associated with systemic, long-lasting, protective T cell responses to repeated rectal virus exposures. Our results provide further insights into the repeat exposure macaque model. We find that this model can be used for testing biomedical prevention strategies without concern of eliciting a systemic vaccination effect.
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http://dx.doi.org/10.1089/aid.2008.0287DOI Listing
September 2009

Evaluation of the lymphocyte trafficking drug FTY720 in SHIVSF162P3-infected rhesus macaques.

J Antimicrob Chemother 2009 Apr 13;63(4):758-62. Epub 2009 Feb 13.

Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Objectives: FTY720 causes retention of lymphocytes in lymphatic tissues. Previous studies revealed that FTY720 can decrease or eliminate chronic viral infections of mice. We address here whether therapeutic use of FTY720 in simian human immunodeficiency virus (SHIV)-infected rhesus macaques could also decrease viraemia.

Methods: FTY720 was administered intravenously to three SHIV(SF162P3)-infected macaques at 39, 7 or 6 weeks of infection; three control macaques (47, 48 or 6 weeks of infection) did not receive drug. FTY720 was given at 0.004 mg/kg on days 0, 1, 2, 14, 15 and 16, followed by 0.1 mg/kg on days 28, 29, 30, 42, 43 and 44. Blood was collected seven times throughout and four times during 47 days of follow-up.

Results: Only the 0.1 mg/kg dose resulted in a reduction in mean blood CD4+ T cells and B cells (to 33% and 27% of pre-drug levels, P=0.0024 and 0.003, respectively). FTY720 treatment did not lead to significant deviations from the natural pattern of viral control. Plasma viraemia progressed from a range of 10(4)-10(2) copies/mL before treatment to 10(4)-temporarily undetectable levels on the last day of treatment. SHIV(SF162P3) was not eliminated, however, as plasma viraemia and proviral DNA persisted during the follow-up. No significant alterations in T cell activity were noted throughout the drug course.

Conclusions: FTY720 administration had no detectable therapeutic effect at the doses and schedules outlined here, although blood CD4+ T cells and B cells were effectively reduced. Future work might reveal whether FTY720 could be beneficial in more pathogenic SHIV, simian immunodeficiency virus or HIV infections.
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http://dx.doi.org/10.1093/jac/dkp008DOI Listing
April 2009

Efficacy of adding 2% (w/v) chlorhexidine gluconate to 70% (v/v) isopropyl alcohol for skin disinfection prior to peripheral venous cannulation.

Infect Control Hosp Epidemiol 2008 Oct;29(10):963-5

Department of Clinical Microbiology and Infection Control, University Hospital Birmingham NHS Foundation Trust, The Queen Elizabeth Hospital, Edgbaston, England.

We undertook a clinical trial to compare the efficacy of 2% (w/v) chlorhexidine gluconate in 70% (v/v) isopropyl alcohol with the efficacy of 70% (v/v) isopropyl alcohol alone for skin disinfection to prevent peripheral venous catheter colonization and contamination. We found that the addition of 2% chlorhexidine gluconate reduced the number of peripheral venous catheters that were colonized or contaminated.
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http://dx.doi.org/10.1086/590664DOI Listing
October 2008

Short communication: no evidence of occult SHIV infection as demonstrated by CD8+ cell depletion after chemoprophylaxis-induced protection from mucosal infection in rhesus macaques.

AIDS Res Hum Retroviruses 2008 Apr;24(4):543-6

Division of HIV/AIDS prevention, NCHHSTP, CCID, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

Preexposure prophylaxis (PrEP) with antiretroviral drugs constitutes a promising strategy for HIV prevention. Potent PrEP regimens with reverse transcriptase inhibitors can prevent detectable SHIV infection in a repeated low-dose macaque model that resembles human transmission, supporting plans to quickly move this approach into human trials. However, the possibility remains that extremely low levels of virus replication could nonetheless occur during PrEP and seed viral reservoirs in tissues. Therefore, seemingly protected macaques may harbor occult virus that may be initially contained by cytotoxic T cells, but could emerge later. To explore this possibility, we studied whether CD8(+) cells suppress viremia in four rhesus macaques apparently protected by daily or intermittent Truvada (FTC and tenofovir) during 14 low-dose, rectal SHIV(SF162P3) challenges and during a subsequent drug washout period. CD8(+) cells were efficiently ablated with antibodies in these and two additional control macaques that were previously infected but had reached undetectable virus set points. During 4 weeks of follow-up, all four macaques remained free of plasma viremia and provirus in blood lymphocytes. In contrast, plasma viremia resurged to 10(6) to 10(7) copies per milliliter within 2 weeks in both control macaques. Thus, these results indicate that the undetectable viremia in the PrEP-protected macaques was not due to CD8(+) cells that were containing a low-level infection. Rather, the PrEP treatment created conditions in which infection was prevented, eliminated, or controlled by unknown mechanisms. These data provide important information for PrEP usage to prevent HIV transmission, and fully support the continued pursuit of PrEP prevention measures in humans.
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http://dx.doi.org/10.1089/aid.2007.0222DOI Listing
April 2008

Systemic and mucosal immunological responses during repeated mucosal SHIV(162P3) challenges prior to and following infection in pigtailed macaques.

Virology 2008 Jun 19;375(2):492-503. Epub 2008 Mar 19.

Laboratory Branch, Division of HIV and AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Local and systemic immunological changes following vaginal HIV-1 exposures are poorly characterized and may influence susceptibility to infection. Therefore, we examined longitudinal mucosal, plasma cytokine profiles and viral-specific T-cell responses (vSTRs) before and during weekly repeated low-dose SHIV(SF162P3) viral challenges in six female pigtailed macaques, even in the absence of overt systemic infection. Following a single viral challenge, induction of several cytokines was detected consistently in cervico-vaginal lavages (CVL). With additional exposure and documented systemic infection, a hallmark of response profile was defined as peak levels in both CVL (MCP-1, MIP-1alpha, TNF-alpha, IL-1beta, IL-1RA and IL-8) and plasma cytokines (MCP-1, eotaxin and IL-1RA) in the macaques. In the periphery, vSTRs were observed within the first one or two viral challenges, but prior to the detection of systemic infection in 5/6 exposed pigtailed macaques. These findings provide valuable information regarding mucosal HIV-1 infection that may benefit microbicide research and development.
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http://dx.doi.org/10.1016/j.virol.2008.01.040DOI Listing
June 2008

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

PLoS Med 2008 Feb;5(2):e28

Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.

Methods And Findings: We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.

Conclusions: This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.
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http://dx.doi.org/10.1371/journal.pmed.0050028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225435PMC
February 2008

Hypnosis for childbirth: a retrospective comparative analysis of outcomes in one obstetrician's practice.

Am J Clin Hypn 2007 Oct;50(2):109-19

Marquette University College of Nursing, Milwaukee, WI 53201-1881, USA.

This exploratory, descriptive study, done retrospectively from perinatal medical records, compared childbirth outcomes in one obstetrician's caseload between 50 women who elected antepartal hypnosis preparation (usually a 5-class series) and 51 who did not. The groups were demographically similar. To achieve similar numbers to the hypnosis group, the control group was randomly selected from the women in the caseload who opted not to take hypnosis preparation, based on characteristics of parity and delivery mode. Prenatal hypnosis preparation resulted in significantly less use of sedatives, analgesia, and regional anesthesia during labor and in higher 1-minute neonatal Apgar scores. Other physiologic and outcome measures did not reveal statistical significance, although some trends were of clinical interest. Well-controlled studies are warranted for clinicians to offer hypnosis more frequently as a pain relief option for childbirth. Additional information provided includes pragmatic, clinical, and cost information about incorporating hypnosis into a physician's practice.
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http://dx.doi.org/10.1080/00029157.2007.10401608DOI Listing
October 2007

Direct stringency comparison of two macaque models (single-high vs. repeat-low) for mucosal HIV transmission using an identical anti-HIV chemoprophylaxis intervention.

J Med Primatol 2007 Aug;36(4-5):238-43

Laboratory Branch, Division of HIV/AIDS Prevention, NCHHSTP, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Background: In our previous work, oral chemoprophylaxis with tenofovir disoproxil fumarate (TDF) provided partial protection in rhesus macaques against repeated low-dose (RL) intrarectal SHIV162p3 exposure.

Methods: Here, we make a direct comparison of these previous findings with data generated using a single high (SH)-dose challenge strategy.

Results: All 5 (100%) control macaques were infected after a SH challenge and only three of five (60%) TDF-treated macaques became infected. The remaining two TDF-treated macaques remained virus-negative and were susceptible to virus infection upon re-challenge in the absence of oral TDF. Thus, two of five (40%) TDF-treated macaques were protected by the pre-exposure chemoprophylaxis regimen. By comparison with the RL challenge system, only one of four (25%) of TDF-treated macaques were protected from infection, whereas four of four (100%) control macaques became infected using RL challenges.

Conclusion: Taken together, these findings indicate that the stringency of the RL challenge model for testing antiretroviral interventions is not lower and possibly greater than that of the SH challenge model.
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http://dx.doi.org/10.1111/j.1600-0684.2007.00241.xDOI Listing
August 2007

Needlestick injuries: is it time for a new approach?

Br J Nurs 2007 Mar 22-Apr 11;16(6):334

Microbiology Research and Developmental Group, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital.

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http://dx.doi.org/10.12968/bjon.2007.16.6.23001DOI Listing
July 2007

Skin antiseptics used prior to intravascular catheter insertion.

Br J Nurs 2007 Mar 8-21;16(5):278-80

Microbiology Research and Development Group, University Hospital Birmingham NHS Foundation Trust, The Queen Elizabeth Hospital, Edgbaston, Birmingham.

The recent epic2 publication (Pratt et al, 2007) provides evidence-based guidelines for the prevention of healthcare-associated infections. One of the new recommendations related to the prevention of central venous catheter (CVC) associated infection states that 2% chlorhexidine gluconate (CHG) in 70% isopropyl alcohol (IPA) should be used for cutaneous antisepsis prior to device insertion. This article reviews cutaneous antisepsis prior to intravascular catheter placement.
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http://dx.doi.org/10.12968/bjon.2007.16.5.22997DOI Listing
May 2007

Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection against infection with simian human immunodeficiency virus in macaques given multiple virus challenges.

J Infect Dis 2006 Oct 29;194(7):904-11. Epub 2006 Aug 29.

Division of HIV/AIDS Prevention, National Center for HIV, STD, & TB Prevention, National Center for Infectious Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

We examined the efficacy of tenofovir disoproxil fumarate (TDF) in blocking simian human immunodeficiency virus (SHIV) infection in Chinese rhesus macaques. Once weekly for 14 weeks or until a macaque became infected, 12 male macaques were inoculated intrarectally with amounts of SHIV(SF162P3) (10 median tissue culture infective doses; 3.8 x 10(5) virus particles) that were approximately 5-fold higher than the human immunodeficiency virus type 1 RNA levels noted in human semen during an acute infection. Of the 12 macaques, 4 received oral TDF daily, 4 received oral TDF once weekly, and 4 (control animals) received no TDF. The control animals became infected after receiving a median of 1.5 virus inoculations; macaques receiving TDF daily (1 macaque remained uninfected after 14 inoculations) and those receiving TDF weekly became infected after a median duration of 6.0 and 7.0 weeks, respectively. Although infection was delayed in treated macaques, compared with control macaques, the differences were not statistically significant (P=.315); however, the study was limited by the small numbers of animals evaluated and the variability in blood levels of TDF that resulted from oral dosing. These data demonstrate that treatment with oral TDF provided partial protection against SHIV infection but ultimately did not protect all TDF treated animals against multiple virus challenges.
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http://dx.doi.org/10.1086/507306DOI Listing
October 2006

Repetitive exposures with simian/human immunodeficiency viruses: strategy to study HIV pre-clinical interventions in non-human primates.

J Med Primatol 2006 Aug;35(4-5):210-6

Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD, TB Prevention, CCID, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

Background: Non-human primate models for human immunodeficiency virus (HIV) infection represent a valuable pre-clinical tool to evaluate interventions (e.g., topical microbicides, vaccines, and chemoprophylaxis) designed to prevent transmission or slow disease progression after infection. Standard transmission models use a single-dose exposure with high, non-physiologic levels of virus to approach 100% infection rates of control animals. These single-exposure models do not represent the circumstances of mucosal HIV transmission in humans and may result in misleading data with regard to intervention efficacy. Therefore, we have developed a repetitive mucosal exposure model using doses of virus that better reflects human exposures.

Methods: The virus used for these evaluations was simian-human immunodeficiency virus [SHIVSF162P3 (R5-using, subtype B HIV-1 envelope)] and the virus dose used (approximately 10(5)-10(6) viral particle equivalents or approximately 10 tissue culture infectious doses per exposure) approximates viral loads observed in the semen during acute HIV-1 infection. Using the repeated mucosal exposure approach, we have evaluated a candidate vaginal microbicide (cellulose acetate phthalate, CAP) given 15 minutes prior to each weekly virus exposure. Pig-tailed macaques were exposed weekly by vaginal inoculations with and without microbicide until systemic viral RNA was detected.

Results: Groups of naïve control monkeys were infected after an average of three to four exposures for the vaginal route of inoculation. Data from the first application of this monkey model to evaluate the topical microbicide CAP suggested that protection from SHIV infection was possible with three of four CAP-treated monkeys remaining uninfected after 12 exposures (P = 0.015). CAP efficacy was markedly improved from 66% in a previous single-dose virus exposure study to 92% in this repeated exposure system.

Conclusions: Our experience with using repetitive virus exposures to study topical microbicides and the findings to date from this study provides a basis to refine monkey models to more closely resemble human exposure during HIV transmission. This model may be highly relevant to pre-clinical evaluation for a variety of therapeutic interventions which is discussed here.
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http://dx.doi.org/10.1111/j.1600-0684.2006.00169.xDOI Listing
August 2006

Multiple vaginal exposures to low doses of R5 simian-human immunodeficiency virus: strategy to study HIV preclinical interventions in nonhuman primates.

J Infect Dis 2005 Jan 9;191(2):164-73. Epub 2004 Dec 9.

HIV/AIDS and Retrovirology Branch, Mailstop G-19, DASTLR, NCHSTP, CDC, 1600 Clifton Rd., Atlanta, GA 30333, USA.

A nonhuman-primate model of human immunodeficiency virus type 1 (HIV-1) infection that more closely emulates human heterosexual transmission by use of multiple exposures to low doses of virus is critical to better evaluate intervention strategies that include microbicides or vaccines. In this report, we describe such a system that uses female pig-tailed macaques exposed vaginally to a CCR5-using simian-human immunodeficiency virus (SHIV(SF162P3)) at weekly intervals. Results of dose-titration experiments indicated that 3 once-weekly exposures to 10 tissue culture infectious doses of SHIV(SF162P3) resulted in consistent transmission of virus and establishment of systemic infection. The efficacy of cellulose acetate phthalate (CAP) as a vaginal microbicide was evaluated by applying it to the vaginal vault of macaques (n = 4) 15 min before each weekly exposure to SHIV(SF162P3). One conclusion that can be drawn from the data derived from multiple exposures to virus is that CAP prevented infection in 12 of 13 possible chances for infection, over the course of 39 total exposures. Our findings provide a basis to refine monkey models for transmission of HIV-1, which may be relevant to preclinical evaluation for therapeutic interventions.
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http://dx.doi.org/10.1086/426452DOI Listing
January 2005