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1.  HIV outcomes in Hepatitis B virus coinfected individuals on HAART 
Understanding the impact of hepatitis B virus (HBV) coinfection on HIV outcomes in the HAART era continues to be a critical priority given the high prevalence of coinfection and the potential for impaired immunologic, virologic and clinical recovery.
Participants from the U.S. Military HIV Natural History Study with an HIV diagnosis, on HAART and serologically confirmed HBV infection status at HAART initiation (HI) were classified into four HBV infection (HB) groups. HIV virologic, immunologic, and clinical outcomes were evaluated by HB status.
Of 2536 HIV positive HAART recipients, with HBV testing results available to determine HB status in the HI window, HB status at HI was classified as HB negative (n=1505; 66%), resolved HB (n=518; 23%); isolated HBcAb (n=139; 6%) or; chronic HB (n=131; 6%). HIV virologic suppression and failure at 6 months or 1 year were not significantly different by HB status. A significantly faster rate of increase in CD4 cell count during the period between 4 and 12 years was observed for chronic HB relative to HB negative.
Chronic and resolved HB were associated with an increased risk of AIDS/death compared to HB negative individuals (chronic HB; HR=1.68; 95% CI 1.05–2.68, resolved HB; HR=1.61; 95% CI 1.15–2.25).
HB status did not have a significant impact on HIV virologic outcomes, however, CD4 cell count reconstitution post HI and the risk of an AIDS event or death post HI may be associated with HB status.
PMCID: PMC4034265  PMID: 24694929
Hepatitis B virus; chronic hepatitis B; human immunodeficiency virus; highly active antiretroviral therapy
2.  Epidemiology of HIV among US Air Force Military Personnel, 1996–2011 
PLoS ONE  2015;10(5):e0126700.
The objectives of this study were to describe the epidemiology of HIV in the United States Air Force (USAF) from 1996 through 2011 and to assess whether socio-demographic characteristics and service-related mobility, including military deployments, were associated with HIV infection.
We conducted a retrospective cohort analysis of USAF personnel who were HIV-infected during the study period January 1, 1996 through December 31, 2011 and a matched case-control study. Cases were USAF personnel newly-diagnosed with HIV during the study period. Five randomly-selected HIV-uninfected controls were matched to each case by age, length of service, sex, race, service, component, and HIV test collection date. Socio-demographic and service-related mobility factors and HIV diagnosis were assessed using conditional logistic regression.
During the study period, the USAF had 541 newly diagnosed HIV-infected cases. HIV incidence rate (per 100,000 person-years) among 473 active duty members was highest in 2007 (16.78), among black/ African-American USAF members (26.60) and those aged 25 to 29 years (10.84). In unadjusted analysis restricted to personnel on active duty, 10 characteristics were identified and considered for final multivariate analysis. Of these single (adjusted odds ratio [aOR], 8.15, 95% confidence interval [CI] 5.71–11.6) or other marital status (aOR 4.60, 95% CI 2.72–7.75), communications/ intelligence (aOR 2.57, 95% CI 1.84–3.60) or healthcare (aOR 2.07, 95% CI 1.28–3.35) occupations, and having no deployment in the past 2 years before diagnosis (aOR 2.02, 95% CI 1.47–2.78) conferred higher odds of HIV infection in adjusted analysis.
The highest risk of HIV infection in the USAF was among young unmarried deployment-naïve males, especially those in higher risk occupation groups. In an era when worldwide military operations have increased, these analyses identified potential areas where targeted HIV prevention efforts may be beneficial in reducing HIV incidence in the USAF military population.
PMCID: PMC4427109  PMID: 25961564
3.  Prevalence of HIV, Syphilis, and Other Sexually Transmitted Infections among MSM from Three Cities in Panama 
Respondent-driven sampling (RDS) was used to conduct a biobehavioral survey among men who have sex with men (MSM) in three cities in the Republic of Panama. We estimated the prevalence of HIV, syphilis, and other sexually transmitted infections (STIs), sociodemographic characteristics, and sexual risk behaviors. Among 603 MSM recruited, RDS-adjusted seroprevalences (95 % confidence intervals) were: HIV—David 6.6 % (2.2–11.4 %), Panama 29.4 % (19.7–39.7 %), and Colon 32.6 % (18.0–47.8 %); active syphilis—David 16.0 % (8.9–24.2 %), Panama 24.7 % (16.7–32.9 %), Colon 31.6 % (14.8–47.5 %); resolved HBV infection—David 10.0 % (4.8–16.8 %), Panama 29.4 % (20.0–38.3 %), and Colon 40.6 % (21.9–54.4 %); herpes simplex virus type 2—David 38.4 % (27.9–48.9 %), Panama 62.6 % (52.8–71.0 %), and Colon 72.9 % (57.4–85.8 %). At least a third of MSM in each city self-identified as heterosexual or bisexual. HIV prevalence is concentrated among MSM. Preventive interventions should focus on increasing HIV and syphilis testing, and increasing promotion of condom awareness and use.
PMCID: PMC4134449  PMID: 24927712
HIV; Syphilis; Sexually transmitted diseases; Sexual behavior; Respondent-driven sampling; Sampling hidden populations; Panama
4.  Discrepant Amplification Results during the Development of an Assay Leads to Reclassification of Two AIDS Reagent Repository HIV-2 Isolates as HIV-1 
PLoS ONE  2014;9(5):e96554.
The development and verification of HIV-2 assays depends in part on the availability of well-characterized samples, including those from reagent repositories. During the development of an HIV-2 RNA quantification assay, two HIV-2 viral isolates (CDC 301340 and CDC 301342) obtained from the NIAID AIDS Reagent and Reference Repository were not detected leading to an investigation. Two HIV-2 primers/probe sets of known performance in real-time viral RNA quantification assays, targeting different regions of the virus, also failed to generate RT-PCR products for these two isolates. These isolates were tested in the HIV-1 specific COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0 (Roche Molecular Diagnostics) and were quantified at high copy number. Other HIV-2 isolates tested were not amplified in the COBAS HIV-1 TaqMan assay. Furthermore, the discrepant isolates were highly reactive in an HIV-1 p24 antigen test while the other HIV-2 isolates showed very weak, if any, cross-reactivity with the HIV-1 p24 assay. Phylogenetic tree analysis of sequences from the protease-reverse transcriptase regions of the discrepant HIV-2 isolates mapped with HIV-1 Group M, Subtype CRF02_AG confirming these isolates were of HIV-1 origin and had been misclassified as HIV-2. The use of misclassified isolates in the verification of molecular and immunological assays can lead to misinterpretation of test results, misdirection of efforts into assay redesign and increased development costs. The results of this study were shared with the NIAID AIDS Reagent Program, leading to the reclassification of the two discrepant isolates as HIV-1.
PMCID: PMC4010467  PMID: 24797800
5.  Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity 
The continued global spread and evolution of HIV diversity pose significant challenges to diagnostics and vaccine strategies. NIAID partnered with the FDA, WRAIR, academia, and industry to form a Viral Panel Working Group to design and prepare a panel of well-characterized current and diverse HIV isolates. Plasma samples that had screened positive for HIV infection and had evidence of recently acquired infection were donated by blood centers in North and South America, Europe, and Africa. A total of 80 plasma samples were tested by quantitative nucleic acid tests, p24 antigen, EIA, and Western blot to assign a Fiebig stage indicative of approximate time from initial infection. Evaluation of viral load using FDA-cleared assays showed excellent concordance when subtype B virus was tested, but lower correlations for subtype C. Plasma samples were cocultivated with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from normal donors to generate 30 viral isolates (50–80% success rate for samples with viral load >10,000 copies/ml), which were then expanded to 107–109 virus copies per ml. Analysis of env sequences showed that sequences derived from cultured PBMCs were not distinguishable from those obtained from the original plasma. The pilot collection includes 30 isolates representing subtypes B, C, B/F, CRF04_cpx, and CRF02_AG. These studies will serve as a basis for the development of a comprehensive panel of highly characterized viral isolates that reflects the current dynamic and complex HIV epidemic, and will be made available through the External Quality Assurance Program Oversight Laboratory (EQAPOL).
PMCID: PMC3358106  PMID: 22149143
6.  DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial 
PLoS ONE  2013;8(4):e59340.
DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.
Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 1010 or 1011 particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody.
120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.
DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.
Trial Registration NCT00109629
PMCID: PMC3620125  PMID: 23577062
7.  Efficient Quantification of HIV-1 in Heparin Plasma Spiked with Cultured HIV-1 by the Roche Cobas TaqMan and Abbott RealTime HIV-1 Tests 
Journal of Clinical Microbiology  2012;50(8):2804-2806.
The current automated real-time HIV-1 viral load assays, the Roche Cobas AmpliPrep/Cobas TaqMan test and the Abbott RealTime test, are FDA cleared for use with EDTA plasma. We show that both real-time reverse transcription-PCR (RT-PCR) tests reliably quantify HIV-1 RNA in heparin plasma specimens spiked with HIV-1 isolate MN.
PMCID: PMC3421498  PMID: 22675128
8.  Hepatitis B Virus Coinfection Negatively Impacts HIV Outcomes in HIV Seroconverters 
The Journal of Infectious Diseases  2011;205(2):185-193.
(See the editorial commentary by Peters and Marston, on pages 166–8.)
Background. Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.
Methods. Participants with HIV diagnosis seroconversion window of ≤3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.
Results. Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15–2.71); 3.27 (2.71–3.84); 3.75 (2.25–5.25); and 5.41 (3.41–7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20–2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94–1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75–1.75).
Conclusions. HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.
PMCID: PMC3244364  PMID: 22147794
9.  Short Communication: Investigation of Incident HIV Infections Among U.S. Army Soldiers Deployed to Afghanistan and Iraq, 2001–2007 
AIDS Research and Human Retroviruses  2012;28(10):1308-1312.
The U.S. Army initiated an investigation in response to observations of a possible increase in HIV incidence among soldiers deployed to combat. Human immunodeficiency virus (HIV)-infected U.S. Army soldiers are not eligible to deploy. Combat presents a health hazard to HIV-infected soldiers and they pose a threat to the safety of the battlefield blood supply and their contacts. All soldiers are routinely screened for HIV every 2 years and those who deploy are also screened both prior to and after deployment. Seroconversion rates were estimated for all soldiers who deployed to Afghanistan or Iraq in the period 2001–2007 and all active duty soldiers who did not. Seroconverters with an estimated date of infection, based on calculation of the midpoint between the last seronegative and first seropositive test date, that was either before or during deployment were eligible for inclusion. Confidential interviews and medical record reviews were conducted to determine the most likely time, geographic location, and mode of infection. Reposed predeployment samples were tested for HIV ribonucleic acid. The HIV seroconversion rate among all soldiers who deployed was less than the rate among those who did not deploy: 1.04 and 1.42 per 10,000 person-years, respectively. Among 48 cases, most were determined to have been infected in the United States or Germany and prior to deployment (n=20, 42%) or during rest and relaxation leave (n=13, 27%). Seven seronegative acute infections were identified in the predeployment period. Subtype was determined for 40 individuals; all were subtype B infections. All were acquired through sexual contact. These findings can inform development of preventive interventions and refinement of existing screening policy to further reduce HIV-infected deployed soldier person time.
PMCID: PMC3448093  PMID: 22280248
10.  Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection 
PLoS ONE  2012;7(3):e33948.
Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.
Methods and Findings
We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24.
At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm3. HIV RNA was 5.5 log10 copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/106 PBMC) vs. Fiebig I (8 copy/106 PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008).
After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).
Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.
PMCID: PMC3316511  PMID: 22479485
11.  A Double-Blind Randomized Phase I Clinical Trial Targeting ALVAC-HIV Vaccine to Human Dendritic Cells 
PLoS ONE  2011;6(9):e24254.
We conducted a novel pilot study comparing different delivery routes of ALVAC-HIV (vCP205), a canarypox vaccine containing HIV gene inserts: env, gag and pol. We explored the concept that direct ex vivo targeting of human dendritic cells (DC) would enhance the immune response compared to either conventional intramuscular or intradermal injections of the vaccine alone.
Methodology/Principal Findings
Healthy HIV-1 uninfected volunteers were administered ALVAC-HIV or placebo by intramuscular injection (IM), intradermal injection (ID) or subcutaneous injection (SQ) of autologous ex vivo transfected DC at months 0, 1, 3 and 6. All vaccine delivery routes were well tolerated. Binding antibodies were observed to both the ALVAC vector and HIV-1 gp160 proteins. Modest cellular responses were observed in 2/7 individuals in the DC arm and 1/8 in the IM arm as determined by IFN-γ ELISPOT. Proliferative responses were most frequent in the DC arm where 4/7 individuals had measurable responses to multiple HIV-1 antigens. Loading DC after maturation resulted in lower gene expression, but overall better responses to both HIV-1 and control antigens, and were associated with better IL-2, TNF-α and IFN-γ production.
ALVAC-HIV delivered IM, ID or SQ with autologous ex vivo transfected DC proved to be safe. The DC arm was most immunogenic. Proliferative immune responses were readily detected with only modest cytotoxic CD8 T cell responses. Loading mature DC with the live viral vaccine induced stronger immune responses than loading immature DC, despite increased transgene expression with the latter approach. Volunteers who received the autologous vaccine loaded mature DC developed a broader and durable immune response compared to those vaccinated by conventional routes.
Trial Registration NCT00013572
PMCID: PMC3174939  PMID: 21949699
12.  Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic, Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate 
PLoS ONE  2010;5(11):e13983.
We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand.
Methodology/Principal Findings
MVA-CMDR or placebo was administered intra-muscularly (IM; 107 or 108 pfu) or intradermally (ID; 106 or 107 pfu) at months 0, 1 and 3, to 48 healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each dosage group were randomized to receive MVA-CMDR or placebo (10∶2). Volunteers were actively monitored for local and systemic reactogenicity and adverse events post vaccination. Cellular immunogenicity was assessed by a validated IFNγ Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation and a 51Cr-release assay. Humoral immunogenicity was assessed by ADCC for gp120 and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well tolerated with no vaccine related serious adverse events. Cell-mediated immune responses were: (i) moderate in magnitude (median IFNγ Elispot of 78 SFC/106 PBMC at 108 pfu IM), but high in response rate (70% 51Cr-release positive; 90% Elispot positive; 100% ICS positive, at 108 pfu IM); (ii) predominantly HIV Env-specific CD4+ T cells, with a high proliferative capacity and durable for at least 6 months (100% LPA response rate by the IM route); (iv) dose- and route-dependent with 108 pfu IM being the most immunogenic treatment. Binding antibodies against gp120 and p24 were detectable in all vaccination groups with ADCC capacity detectable at the highest dose (40% positive at 108 pfu IM).
MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses.
Trial Registration NCT00376090
PMCID: PMC2981570  PMID: 21085591
13.  Hepatitis B Vaccine Responses in a Large U.S. Military Cohort of HIV-Infected Individuals: Another Benefit of HAART in Those with Preserved CD4 Count 
Vaccine  2009;27(34):4731-4738.
The influence of highly active antiretroviral therapy (HAART) upon hepatitis B virus (HBV) vaccine responses in HIV-infected individuals is unclear. After classification of vaccinees as non-responders (HBsAb <10 IU/L) or responders (HBsAb ≥10 IU/L) in our HIV cohort, multivariate logistic regression was used to assess factors associated with subsequent vaccine response. Of 626 participants vaccinated from 1988–2005, 217 (35%) were vaccine responders. Receipt of ≥3 doses of vaccine (OR 1.83, 95% CI 1.24–2.70), higher CD4 count at vaccination (OR 1.09, 95% CI 1.05–1.13 per 50 cells/μl increase), and use of HAART (OR 2.37, 95% CI 1.56–3.62) were all associated with increased likelihood of developing a response. However, only 49% of those on HAART at last vaccination responded, and 62% of those on HAART, with CD4 count ≥350, and HIV RNA <400 copies/mL responded. Compared to those on HAART with CD4 count ≥350, those not on HAART with CD4 count ≥350 had significantly reduced odds of developing a vaccine response (OR 0.47, 95% CI 0.30–0.70). While HAART use concurrent with HBV immunization was associated with increased probability of responding to the vaccine, the response rate was low for those on HAART. These data provide additional evidence of HAART benefits, even in those with higher CD4 counts, but also highlight the need for improving HBV vaccine immunogenicity.
PMCID: PMC2707509  PMID: 19540026
Hepatitis B vaccine; Hepatitis B virus; Human Immunodeficiency Virus; Highly active antiretroviral therapy; immunization
14.  Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells 
Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.
To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.
We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.
Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.
PMCID: PMC2542375  PMID: 18667072
15.  Large-Scale Human Immunodeficiency Virus Rapid Test Evaluation in a Low-Prevalence Ugandan Blood Bank Population▿  
Journal of Clinical Microbiology  2007;45(10):3281-3285.
The use of rapid tests for human immunodeficiency virus (HIV) has become standard in HIV testing algorithms employed in resource-limited settings. We report an extensive HIV rapid test validation study conducted among Ugandan blood bank donors at low risk for HIV infection. The operational characteristics of four readily available commercial HIV rapid test kits were first determined with 940 donor samples and were used to select a serial testing algorithm. Uni-Gold Recombigen HIV was used as the screening test, followed by HIV-1/2 STAT-PAK for reactive samples. OraQuick HIV-1 testing was performed if the first two test results were discordant. This algorithm was then tested with 5,252 blood donor samples, and the results were compared to those of enzyme immunoassays (EIAs) and Western blotting. The unadjusted algorithm sensitivity and specificity were 98.6 and 99.9%, respectively. The adjusted sensitivity and specificity were 100 and 99.96%, respectively. This HIV testing algorithm is a suitable alternative to EIAs and Western blotting for Ugandan blood donors.
PMCID: PMC2045340  PMID: 17699650
16.  Blood genomic profiles of exposures to Venezuelan equine encephalitis in Cynomolgus macaques (Macaca fascicularis) 
Virology Journal  2007;4:82.
Lymphocytes provide invaluable whistle blowers of changes due to infections. We use the information registered by these cells using their mRNAs as they encounter the pathogen to develop patterns of expression that correspond to that specific pathogen.
Venezuelan equine encephalitis (VEE) is a mosquito-borne viral disease characterized by fever and one or more of the following: severe headache, back pain, myalgias, prostration, chills, nausea, vomiting, weakness and other flu-like symptoms.
Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.
We have been carrying out gene expression analysis of PBMC exposed to VEEV to extract signatures and diagnostic markers of early exposure to be used in non invasive blood analysis methods.
In this study, we used high throughput gene expression analysis to identify markers of early and late exposures to VEEV in vivo in Cynomolgus macaques (Macaca fascicularis). We carried out cDNA microarrays and real time PCR on blood samples obtained from the NHP model resulting in a panel of host genes that are altered in response to VEEV.
Screening for host mRNA obtained from blood samples after exposure to VEEV may provide the means for early detection of surrogate markers of the impending illness and provide appropriate strategies for treatment.
PMCID: PMC2042503  PMID: 17727720
17.  Prevalence of HIV and other sexually transmitted infections and factors associated with syphilis among female sex workers in Panama 
Sexually Transmitted Infections  2012;89(2):156-164.
Biological and behavioural surveillance of HIV and sexually transmitted infections (STIs) among populations at highest risk have been used to monitor trends in prevalence and in risk behaviours. Sex work in Panama is regulated through registration with the Social Hygiene Programme, Ministry of Health. We estimated prevalence of HIV and STIs, and factors associated with active syphilis among female sex workers (FSWs).
A cross-sectional study using venue-based, time-space sampling was conducted among FSWs in Panama from 2009 to 2010. FSWs were interviewed about sociodemographic characteristics, sexual risk behaviour, health history and drug use using an anonymous structured questionnaire. Blood was collected for serological testing of HIV and other STIs. Factors associated with active syphilis were studied using logistic regression analysis.
The overall HIV-1 prevalence of 0.7% varied by FSW category; 1.6% in 379 unregistered, and 0.2% in 620 registered FSWs. Overall prevalence (and 95% CI) of STIs were: syphilis antibody, 3.8% (2.7% to 5.2%); herpes simplex virus type 2 antibody (anti-HSV-2), 74.2% (71.4% to 76.9%); hepatitis B surface antigen, 0.6% (0.2% to 1.3%); hepatitis B core antibody, 8.7% (7.0% to 10.6%); and hepatitis C antibody, 0.2% (0.0% to 0.7%). In multivariate analysis, registration (adjusted OR (AOR)=0.35; 95% CI 0.16 to 0.74), having a history of STI (AOR=2.37; 95% CI 1.01 to 5.58), forced sex (AOR=2.47; 95% CI 1.11 to 5.48), and anti-HSV-2 (AOR=10.05; 95% CI 1.36 to 74.38) were associated with active syphilis.
Although HIV prevalence is low among FSWs in Panama, unregistered FSWs bear a higher burden of HIV and STIs than registered FSWs. Programmes aimed at overcoming obstacles to registration, and HIV, STI and harm reduction among unregistered FSWs is warranted to prevent HIV transmission, and to improve their sexual and reproductive health.
PMCID: PMC3595153  PMID: 23002191
Surveillance; Commercial Sex; HIV; Seroprevalence; Syphilis

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