Total Solutions

Atlanta, GA, United States

Total Solutions

Atlanta, GA, United States

Time filter

Source Type

Henning T.R.,1600 Clifton Rd NE | Butler K.,1600 Clifton Rd NE | Hanson D.,1600 Clifton Rd NE | Sturdevant G.,National Institute of Allergy and Infectious Diseases | And 9 more authors.
Journal of Infectious Diseases | Year: 2014

Background: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood. Methods: Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy. Results: Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P =.04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P =.01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤.05, by the Wilcoxon test). Conclusions: C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological assocations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.


PubMed | National Institute of Allergy and Infectious Diseases, Total Solutions, University of Washington and Centers for Disease Control and Prevention
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2014

Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood.Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy.Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon , interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P .05, by the Wilcoxon test).C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological associations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.


Dobard C.W.,Centers for Disease Control and Prevention | Taylor A.,Total Solutions | Sharma S.,Centers for Disease Control and Prevention | Anderson P.L.,Aurora Pharmaceutical | And 9 more authors.
Journal of Infectious Diseases | Year: 2015

Background. Rectal human immunodeficiency virus (HIV) transmission is an important driver of the HIV epidemic. Optimally formulated gels of antiretroviral drugs are under development for preventing rectally acquired HIV. We investigated in a macaque model the pharmacokinetics and efficacy of 3 rectal gel formulations Methods. Single-dose pharmacokinetics of low-osmolar 1% maraviroc (MVC), 1% tenofovir (TFV), or 1% MVC/1% TFV combination gel were evaluated in blood, rectal fluids, colorectal biopsy specimens, and rectal lymphocytes. Efficacy was evaluated over 10 twice-weekly rectal SHIV162p3 challenges in rhesus macaques that received either placebo (n = 7), MVC (n = 6), TFV (n = 6), or MVC/TFV (n = 6) gel 30 minutes before each challenge. Results. MVC and TFV were detected in plasma 30 minutes after gel application and remained above 95% inhibitory concentrations in rectal fluids at 24 hours. MVC, TFV, and TFV diphosphate (TFV-DP) concentrations in colorectal tissues collected up to 30 cm from the anal margin were all high at 2 hours, demonstrating rapid and extended tissue dosing. TFV-DP concentrations in tissue homogenates and rectal lymphocytes were highly correlated (r2 = 0.82). All 3 gel formulations were highly protective (82% efficacy; P. ≤02 by the log-rank test). Conclusions. Desirable pharmacokinetic profiles and high efficacy in this macaque model support the clinical development of these gel formulations for preventing rectal HIV infection. © 2015 The Author.


PubMed | Total Solutions, Emory University and Centers for Disease Control and Prevention
Type: Journal Article | Journal: Journal of medical primatology | Year: 2015

Varying susceptibility during menstrual cycling could be a factor for S(H)IV infection risk in female rhesus macaques. We retrospectively determined vaginal SIV infection time points relative to the menstrual cycle in a group of rhesus macaques (n=11) enrolled in an HIV transmission trial. Eight of nine rhesus macaques became infected around menstruation time.


PubMed | Centers for Disease Control and Prevention, University of Pittsburgh, Aurora Pharmaceutical and Total Solutions
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2015

Rectal human immunodeficiency virus (HIV) transmission is an important driver of the HIV epidemic. Optimally formulated gels of antiretroviral drugs are under development for preventing rectally acquired HIV. We investigated in a macaque model the pharmacokinetics and efficacy of 3 rectal gel formulationsSingle-dose pharmacokinetics of low-osmolar 1% maraviroc (MVC), 1% tenofovir (TFV), or 1% MVC/1% TFV combination gel were evaluated in blood, rectal fluids, colorectal biopsy specimens, and rectal lymphocytes. Efficacy was evaluated over 10 twice-weekly rectal SHIV162p3 challenges in rhesus macaques that received either placebo (n = 7), MVC (n = 6), TFV (n = 6), or MVC/TFV (n = 6) gel 30 minutes before each challenge.MVC and TFV were detected in plasma 30 minutes after gel application and remained above 95% inhibitory concentrations in rectal fluids at 24 hours. MVC, TFV, and TFV diphosphate (TFV-DP) concentrations in colorectal tissues collected up to 30 cm from the anal margin were all high at 2 hours, demonstrating rapid and extended tissue dosing. TFV-DP concentrations in tissue homogenates and rectal lymphocytes were highly correlated (r(2) = 0.82). All 3 gel formulations were highly protective (82% efficacy; P .02 by the log-rank test).Desirable pharmacokinetic profiles and high efficacy in this macaque model support the clinical development of these gel formulations for preventing rectal HIV infection.


Butler K.,Centers for Disease Control and Prevention | Ritter J.M.,Centers for Disease Control and Prevention | Ellis S.,Total Solutions | Morris M.R.,Total Solutions | And 3 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2016

Introduction: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). Methods: Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. Results: It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P 0.03, t test using the Satterthwaite degrees-of-freedom approximation). Conclusions: SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition. © 2016 Wolters Kluwer Health, Inc.


News Article | December 8, 2016
Site: www.prweb.com

Total Solutions has announced today the promotion of Nick Freling to Chief Revenue Officer. In this position, Mr. Freling is responsible for the strategy, process, and execution of revenue growth at Total Solutions. He will oversee all marketing, business development, and sales activity. Mr. Freling joins the Executive Team at Total Solutions from his previous position as Vice President of Sales. “Nick has consistently demonstrated commitment above and beyond the normal call of duty,” said Matt Fleszar, CEO at Total Solutions. “He never quits, and his focus is on efficient, predictable growth in revenue. Nick's impressive results since joining our team make him a perfect fit to lead us into our full growth potential." Mr. Freling started at Total Solutions in 2009, working as a sales representative. Quickly scaling the ladder, Mr. Freling moved into a role as a sales manager and eventually Vice President of Business Development. Through his contributions and leadership, Total Solutions has achieved double digit growth each of the past 5 years. Mr. Freling is a graduate of Michigan State University and has an active passion for the resurgence of the City of Detroit. “I’m humbled by the opportunity to contribute to Total Solutions in this new role,” said Freling. “I believe our future is to strengthen and streamline our alignment and workflow with strategic partners. The key is to maintain our reputation as a top-quality solutions provider and expand that brand beyond our current customer base.” Total Solutions is an IT consulting and development firm based out of Brighton, MI with 25 on-staff IT professionals. Total Solutions provides Business Productivity Consulting for Microsoft products and also develops Custom Applications. In particular, Total Solutions offers a robust array of solutions to help architect, implement, customize, and administer SharePoint systems. Learn more about TSI at http://www.totalsol.com


Tsuiki A.,Scientific-Atlanta | Luo W.,NCHHSTP | Henning T.,NCHHSTP | Vishwanathan S.,NCHHSTP | And 10 more authors.
Journal of Medical Primatology | Year: 2013

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 (IV) 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 IV FTY720 effects. Results: Topical and IV 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 IV administration, and provides the basis for future studies involving FTY720 for HIV prevention. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.


Butler K.,National Center for HIV AIDS | Ritter J.,National Center for Emerging and Zoonotic Infectious Diseases | Ellis S.,Total Solutions | Henning T.R.,National Center for HIV AIDS | And 5 more authors.
Journal of Medical Primatology | Year: 2015

Background: Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility. Methods: Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks. Results: All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 μm in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 μm for the descending doses, respectively. Conclusions: All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections. © 2015 John Wiley & Sons A/S.


PubMed | Total Solutions, National Center for Emerging and Zoonotic Infectious Diseases and National Center for HIV AIDS
Type: Journal Article | Journal: Journal of medical primatology | Year: 2015

Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility.Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks.All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 m in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 m for the descending doses, respectively.All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections.

Loading Total Solutions collaborators
Loading Total Solutions collaborators