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author:("romano, Anne")
1.  Point-of-care tests for sexually transmissible infections: what do ‘end users’ want? 
Sexual health  2013;10(6):541-545.
Background
Clinicians and developers identify sensitivity as an important quality in a point-of-care test (POCT) for sexually transmissible infections (STIs). Little information exists regarding what patients want for STI POCTs.
Methods
A qualitative study, encompassing five focus groups among attendees of STI and adolescent health centres in Baltimore, Maryland, and Cincinnati, Ohio, were conducted between March 2008 and April 2009. Discussion topics included advantages and disadvantages of having a POCT, perceived barriers to using POCTs in the clinic setting and at home, priorities for the development of new POCTs for STIs, and envisioned characteristics of an ideal POCT. All discussions were recorded and transcribed. A qualitative content analysis was performed to examine frequencies or patterns of recurring codes, which were regrouped and indexed to identify salient themes.
Results
Patients attending STI and adolescent outpatient clinics are in favour of diagnostic tests that are rapid, easy to read and simple to use. Home testing options for POCTs were acceptable and provided better confidentiality, privacy and convenience, but clinic-based POCTs were also acceptable because they offer definitive results and ensure immediate treatment. Barriers to home POCTs centred on cost and the ability to read and perform the test correctly at home. Opinions did not differ by patient ethnicity, except that Hispanic participants questioned the reliability of home test results, wanted high sensitivity and desired bilingual instructions.
Conclusions
Patients attending STI and adolescent medical centres are in favour of STI POCTs if they are affordable, rapid, easy to read and simple to use.
doi:10.1071/SH13047
PMCID: PMC4061493  PMID: 24160838
acceptability; clinic-based test; diagnostics; home-based test
2.  Dense Genotyping of Immune-Related Loci Identifies Variants Associated with Clearance of HPV among HIV-Positive Women in the HIV Epidemiology Research Study (HERS) 
PLoS ONE  2014;9(6):e99109.
Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance (p<10−6). A variant (rs1633038) in HLA-G were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes.
doi:10.1371/journal.pone.0099109
PMCID: PMC4053382  PMID: 24918582
3.  HIV Acquisition Among Women From Selected Areas of the United States 
Annals of internal medicine  2013;158(1):10-18.
Background
Women account for 23% of newly diagnosed HIV infections in the United States, but there are few recent, well-characterized cohorts of U.S. women in whom behavior characteristics and HIV acquisition have been well-described.
Objective
To evaluate HIV incidence and describe behaviors among U.S. women residing in areas of high HIV prevalence.
Design
Multisite, longitudinal cohort of women who had HIV rapid testing and audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months. (ClinicalTrials.gov: NCT00995176)
Setting
10 urban and periurban communities with high HIV prevalence and poverty rates, located in the northeastern and southeastern United States.
Patients
Venue-based sampling was used to recruit women aged 18 to 44 years who recently had unprotected sex and had 1 or more additional personal or partner risk factors and no self-reported previous HIV diagnosis.
Measurements
HIV prevalence and incidence, frequency of HIV risk behaviors, and health status perceptions.
Results
Among 2099 high-risk women (85.9% black and 11.7% of Hispanic ethnicity), 32 (1.5%) were diagnosed with HIV infection at enrollment. Annual HIV incidence was 0.32% (95% CI, 0.14% to 0.74%). Older age, substance use, and knowing a partner had HIV were associated with HIV prevalence. Ten women died during the study (0.61% per year).
Limitations
Longitudinal assessment of risk behaviors was limited to a maximum of 12 months. There were few incident HIV infections, precluding identification of characteristics predictive of HIV acquisition.
Conclusion
This study enrolled a cohort of women with HIV incidence substantially higher than the Centers for Disease Control and Prevention national estimate in the general population of U.S. black women. Concerted efforts to improve preventive health care strategies for HIV and overall health status are needed for similar populations.
doi:10.7326/0003-4819-158-1-201301010-00004
PMCID: PMC4033695  PMID: 23277896
5.  THE INFLUENCE OF HLA CLASS I ALLELES AND THEIR POPULATION FREQUENCIES ON HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 CONTROL AMONG AFRICAN AMERICANS 
Human immunology  2011;72(4):312-318.
Populations of African ancestry continue to account for a disproportionate burden of human immunodeficiency virus type 1 (HIV-1) epidemic in the US. We investigated the effects of human leukocyte antigen (HLA) class I markers in association with virologic and immunologic control of HIV-1 infection among 338 HIV-1 subtype B-infected African Americans in two cohorts: REACH (Reaching for Excellence in Adolescent Care and Health) and HERS (HIV Epidemiology Research Study). One-year treatment-free interval measurements of HIV-1 RNA viral loads and CD4+ T-cells were examined both separately and combined to represent three categories of HIV-1 disease control (76 “controllers,” 169 “intermediates,” and 93 “non-controllers”). Certain previously or newly implicated HLA class I alleles (A*32, A*36, A*74, B*14, B*1510, B*3501, B*45, B*53, B*57, Cw*04, Cw*08, Cw*12, and Cw*18) were associated with one or more of the endpoints in univariate analyses. After multivariable adjustments for other genetic and non-genetic risk factors of HIV-1 progression, the subset of alleles more strongly or consistently associated with HIV-1 disease control included A*32, A*74, B*14, B*45, B*53, B*57, and Cw*08. Carriage of infrequent HLA-B but not HLA-A alleles was associated with more favorable disease outcomes. Certain HLA class I associations with control of HIV-1 infection span the boundaries of race and viral subtype; while others appear confined within one or the other of those boundaries.
doi:10.1016/j.humimm.2011.01.003
PMCID: PMC3778654  PMID: 21262311
HLA class I; Allele frequency; HIV-1 control; African American
6.  The Value of Clinical Needs Assessments for Point-of-Care Diagnostics 
Point of care  2012;11(2):108-113.
Most entrepreneurial ventures fail long before the core technology can be brought to the marketplace because of disconnects in performance and usability measures such as accuracy, cost, complexity, assay stability, and time requirements between technology developers’ specifications and needs of the end-users. By going through a clinical needs assessment (CNA) process, developers will gain vital information and a clear focus that will help minimize the risks associated with the development of new technologies available for use within the health care system.
This article summarizes best practices of the principal investigators of the National Institute of Biomedical Imaging and Bioengineering point-of-care (POC) centers within the National Institute of Biomedical Imaging and Bioengineering POC Technologies Research Network. Clinical needs assessments are particularly important for product development areas that do not sufficiently benefit from traditional market research, such as grant-funded research and development, new product lines using cutting-edge technologies developed in start-up companies, and products developed through product development partnerships for low-resource settings. The objectives of this article were to (1) highlight the importance of CNAs for development of POC devices, (2) discuss methods applied by POC Technologies Research Network for assessing clinical needs, and (3) provide a road map for future CNAs.
doi:10.1097/POC.0b013e31825a241e
PMCID: PMC3737000  PMID: 23935405
user needs assessment; brain trauma; sexually transmitted infections; disaster medicine; global health
7.  Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis Infections in Men With Nongonococcal Urethritis: Predictors and Persistence After Therapy 
The Journal of Infectious Diseases  2012;206(3):357-365.
Background. Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated with nongonococcal urethritis (NGU). We assessed their predictors and persistence after treatment.
Methods. We analyzed data from an NGU treatment trial among symptomatic heterosexual men aged 16–45 years from STI clinics. Nucleic acid amplification tests detected CT, MG, and TV at baseline and at 1 and 4 weeks after therapy. Associations between variables and STI detection were investigated.
Results. Among 293 participants, 44% had CT, 31% had MG, and 13% had TV at baseline. In multivariate analysis, CT infection was associated with young age and STI contact. Young age was also associated with MG, and having ≥1 new partner was negatively associated with TV. We detected persistent CT in 12% and MG in 44% of participants at 4 weeks after therapy, which were associated with signs and symptoms of NGU. Persistent CT was detected in 23% of participants after azithromycin treatment vs 5% after doxycycline treatment (P = .011); persistent MG was detected in 68% of participants after doxycycline vs 33% after azithromycin (P = .001). All but 1 TV infection cleared after tinidazole.
Conclusions. Persistent CT and MG after treatment of NGU are common, and were associated with clinical findings and drug regimen.
doi:10.1093/infdis/jis356
PMCID: PMC3490700  PMID: 22615318
8.  Perceptions on Point-of-Care Tests for Sexually Transmitted Infections – Comparison between Frontline Clinicians and Professionals in Industry 
Point of care  2012;11(2):126-129.
Objectives
To determine if a gap exists between sexually transmitted infection (STI) clinicians and industry professionals regarding perceptions of the ideal types and characteristics of STI point-of-care tests (POCTs).
Methods
Our online survey design contained sections on demographics; barriers of use for available STI POCTs; characteristics of an ideal POCT, including prioritizing pathogens for targets; and “building your own POCT”. Practicing clinicians and academic experts from two venues, STI-related international conference attendees and U.S. STD clinic clinicians, were invited to participate in the clinician survey. Professionals from industry in the STI diagnostic field were invited to participate in the industry survey. Chi-square test and conditional logistical regression were used for data analysis.
Results
Clinician survey participants (n=218) identified “the time frame required” (39.9%), “complexity” (31.2%), and “interruption of work flow” (30.3%) as the top three barriers making it difficult to use STI POCTs, while the industry survey participants (n=107) identified “complexity” (65.4%), “unreliability” (53.3%), and “difficulty in reading results” (34.6%) as the top three barriers (all p values <0.05). Sensitivity was always the most important attribute to be considered for a new STI POCT by both participant groups. Participants of the clinician group chose cost as the second priority attribute, while those of the industry group chose specificity as the second priority.
Conclusion
We identified differences in the perceptions regarding barriers and ideal attributes for STI POCTs between frontline clinical providers and industry personnel. Tailored training is warranted to inform scientists, biomedical engineers, and other industry experts about characteristics that clinicians desire for STI POCTs.
doi:10.1097/POC.0b013e31825a25e8
PMCID: PMC3404836  PMID: 22844231
point-of-care test; sexually transmitted infections; perceptions; discrete choice experiment
9.  Minding the Gap: An approach to determine critical drivers in the development of Point of Care diagnostics 
Point of care  2012;11(2):130-139.
Introduction
A point of care test (POCT) for Chlamydia trachomatis detection is an urgent public health need. Technology advances in diagnostics have made solutions possible. Yet no reliable POCT exist. Our goal was to address the gap between chlamydia POCT needs and successful POCT development by determining which characteristics of POCT tests are most critical and if any flexibility in the attributes assigned those characteristics exist between technology developer and end user.
Methods
We employed a process known as WALEX (Warfare Analysis Laboratory Exercise) in combination with Design of Experiment (DOE) methodology using discrete choice experiments (DCE), to describe the attributes of the most realistic, rather than the most ideal POCT. The WALEX was conducted as interactive oral and simultaneous electronic discussion among experts with differing expertise, but linked by a common interest in development of a chlamydia POCT.
Results
Our studies demonstrated which features of the ideal chlamydia POCT were considered critical to test acceptance by users and which were open to negotiation. In particular, end users were more lenient on the requirement for the fastest ideal test and the lowest one time instrument costs, if the requirement for higher throughput, lowest cost and vaginal sample source collection were preserved. DOE methods used in forced choice question design provided confirmation of opinions derived from oral and electronic WALEX comments
Conclusions
The WALEX in combination with DCE helped us achieve our goal in identifying the gaps in the chlamydia POCT and determining the most realistic solutions to bridge those gaps.
doi:10.1097/POC.0b013e31825a25fc
PMCID: PMC3423323  PMID: 22919287
Point of Care Test; sexually transmitted infection; chlamydia trachomatis; Design of Experiments; Discrete Choice Experiment
10.  Lack of Association of Herpes Simplex Virus Type 2 Seropositivity With the Progression of HIV Infection in the HERS Cohort 
American Journal of Epidemiology  2011;173(7):837-844.
Many studies have chronicled the “epidemiologic synergy” between human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). HIV adversely affects the natural history of HSV-2 and results in more frequent and severe HSV-2 reactivation. Few longitudinal studies, however, have examined whether HSV-2 is associated with increased HIV plasma viral loads or decreased CD4 counts. The authors estimated the effect of HSV-2 seropositivity on HIV RNA viral load and on CD4 count over time among 777 HIV-seropositive US women not receiving suppressive HSV-2 therapy in the HIV Epidemiology Research Study (1993–2000). Linear mixed models were used to assess the effect of HSV-2 on log HIV viral load and CD4 count/mm3 prior to widespread initiation of highly active antiretroviral therapy. Coinfection with HSV-2 was not associated with HIV RNA plasma viral loads during study follow-up. There was a statistically significant association between HSV-2 seropositivity and CD4 count over time, but this difference was small and counterintuitive at an increase of 8 cells/mm3 (95% confidence interval: 2, 14) per year among HSV-2-seropositive women compared with HSV-2-seronegative women. These data do not support a clinically meaningful effect of baseline HSV-2 seropositivity on the trajectories of HIV plasma viral loads or CD4 counts.
doi:10.1093/aje/kwq432
PMCID: PMC3105280  PMID: 21372062
CD4 lymphocyte count; herpes simplex; herpesvirus 2, human; HIV; viral load
11.  Preventing sexually transmitted infections: back to basics 
The Journal of Clinical Investigation  2011;121(12):4580-4583.
Sexually transmitted infections (STIs) have plagued humans for millennia and can result in chronic disease, pregnancy complications, infertility, and even death. Recent technological advances have led to a better understanding of the causative agents for these infections as well as aspects of their pathogenesis that might represent novel therapeutic targets. The articles in this Review Series provide excellent updates on the recent advances in understanding of the pathogenesis of some very important and persistent STIs and discuss the importance of considering each pathogen in the broader context of the environment of the individual who it infects.
doi:10.1172/JCI61592
PMCID: PMC3226012  PMID: 22133882
12.  Association between Semen Exposure and Incident Bacterial Vaginosis 
Objective. To identify correlates of incident bacterial vaginosis (BV) diagnosed with Nugent scoring among high-risk women. Study Design. We conducted both cohort and case-crossover analyses, stratified by HIV infection status, based on 871 HIV-infected and 439 HIV-uninfected participants in the HIV Epidemiology Research Study, conducted in 4 US sites in 1993–2000. Results. BV incidence was 21% and 19% among HIV-infected and -uninfected women, respectively. Fewer correlates of BV were found with case-crossover than with cohort design. Reporting frequent coitus (regardless of consistency of condom use) was correlated with BV in cohort analyses but not in case-crossover analyses. The sole correlate of BV in both types of analyses was the detection of spermatozoa on Gram stain, which is a marker of semen exposure. Conclusion. The inconsistent association between condom use and BV in prior studies could be from reporting bias. We found evidence of a relationship between semen exposure and incident BV.
doi:10.1155/2011/842652
PMCID: PMC3235572  PMID: 22190844
13.  What has Changed about Vaginal Douching among African American Mothers and Daughters? 
Objectives
To explore African American mothers’ and daughters’ practices and influences related to vaginal douching.
Design and Sample
Our overall study used a sequential mixed-method design with 3 phases. Phase 1, the focus of this report, used grounded theory methods and in-depth, semistructured individual interviews. Two generations of African American girls and women: 24 girls (“daughters”) aged 14–18 and 17 women (“mothers” or “mother figures”) aged 22–43, recruited from 1 adolescent health clinic in Baltimore, MD.
Measures
In-depth interviews were taped and transcribed and data analysis used the constant comparison method.
Results
Daughters were much less likely to douche or to have been exposed to douching information than mothers. Many mothers and daughters were influenced by health care providers and/or family members to not initiate, to decrease, or to stop douching. Women who currently douche often do so because of the perception of improved smell and cleanliness around menstruation and sexual intercourse.
Conclusions
These data indicate that although some women continue to believe that vaginal douching has therapeutic value, others have been influenced to stop or not start douching by family and health care providers. Health care providers should continue efforts to educate patients on the risks of vaginal douching.
doi:10.1111/j.1525-1446.2010.00874.x
PMCID: PMC3012353  PMID: 20840711
African Americans; vaginal douching; women’s health
14.  Bacterial Vaginosis and the Natural History of Human Papillomavirus 
Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV). Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.
doi:10.1155/2011/319460
PMCID: PMC3159014  PMID: 21869857
15.  Enhanced Molecular Typing of Treponema pallidum: Geographical Distribution of Strain Types and Association with Neurosyphilis 
The Journal of infectious diseases  2010;202(9):1380-1388.
Background
Strain typing is a tool for determining diversity and epidemiology of infections.
Methods
T. pallidum DNA was isolated from 158 syphilis patients from the US, China, Ireland, and Madagascar and from 15 T. pallidum isolates. Six typing targets were assessed: 1) number of 60 bp repeats in acidic repeat protein gene; 2) restriction fragment length polymorphism (RFLP) analysis of T. pallidum repeat (tpr) subfamily II genes; 3) RFLP analysis of tprC gene; 4) determination of tprD allele in tprD gene locus; 5) presence of 51 bp insertion between tp0126/tp0127; 6) sequence analysis of 84 bp region of tp0548. The combination of #1 and #2 comprises the CDC T. pallidum subtyping method.
Results
Adding sequence analysis of tp0548 to the CDC method yielded the most discriminating typing system. Twenty-four strain types were identified and designated as CDC subtype/tp0548 sequence. Type 14d/f was seen in 5 of 6 locations. In Seattle, strain types changed from 1999– 2008 (p<0.001). Twenty-two (50%) of 44 patients infected with type 14d/f had neurosyphilis compared to 9 (23%) of 39 infected with the other types combined (p=0.01).
Conclusion
We describe an enhanced T. pallidum strain typing system that shows biological and clinical relevance.
doi:10.1086/656533
PMCID: PMC3114648  PMID: 20868271
syphilis; molecular typing; neurosyphilis; Treponema pallidum
16.  What Qualities Are Most Important to Making a Point of Care Test Desirable for Clinicians and Others Offering Sexually Transmitted Infection Testing? 
PLoS ONE  2011;6(4):e19263.
Background
To investigate the possible effects of different levels of attributes of a point-of-care test (POCT) on sexually transmitted infection (STI) professionals' decisions regarding an ideal POCT for STI(s).
Methods
An online survey was designed based on a large-scale in-depth focus discussion study among STI experts and professionals. The last section of the survey “build your own POCT” was designed by employing the discrete choice experiment approach. Practicing clinicians from two venues, STI-related international conference attendees and U.S. STD clinic clinicians were invited to participate in the survey. Conditional logistical regression modeling was used for data analysis.
Results
Overall, 256 subjects took the online survey with 218 (85%) completing it. Most of the participants were STD clinic clinicians who already used some POCTs in their practice. “The time frame required” was identified as a major barrier that currently made it difficult to use STI POCTs. Chlamydia trachomatis was the organism chosen as the top priority for a new POCT, followed by a test that would diagnose early seroconversion for HIV, and a syphilis POCT. Without regard to organism type selected, sensitivity of 90–99% was always the most important attribute to be considered, followed by a cost of $20. However, when the test platform was prioritized for early HIV seroconversion or syphilis, sensitivity was still ranked as most important, but specificity was rated second most important.
Conclusions
STI professionals preferred C. trachomatis as the top priority for a new POCT with sensitivity over 90%, low cost, and a very short completion time.
doi:10.1371/journal.pone.0019263
PMCID: PMC3084795  PMID: 21559435
17.  Perceptions of an Ideal Point-of-Care Test for Sexually Transmitted Infections – A Qualitative Study of Focus Group Discussions with Medical Providers 
PLoS ONE  2010;5(11):e14144.
Background
A point-of-care test (POCT) for sexually transmitted infections (STIs), which offers immediate diagnosis resulting in patients receiving diagnosis and treatment in a single visit, has the ability to address some of the STI control needs. However, needs assessment from STI experts and end users about currently available STI POCTs and their future new development has not been evaluated since World Health Organization Sexually Transmitted Diseases Diagnostics Initiative was formed over 15 years ago. Therefore, our objective was to explore the perceptions of the ideal types of STI POCT for use in health care settings.
Methodology/Principal Findings
A qualitative study, encompassing eight focus groups, was conducted from March 2008 through April 2009. Participants included 6 STD clinic directors, 63 clinicians, and 7 public health/laboratory/epidemiology professionals in the STI field. Discussion topics included currently available POCT, perceived barriers to using POCT in clinics, priority STI for the development of new POCT, and characteristics of the ideal POCT. All discussions were recorded and transcribed verbatim. Themes raised as barriers for current POCT included complexity, long time frames of the so-called “rapid” test, multiple time-driven steps, requiring laboratory technician, difficulty in reading result, interruption of workflow, unreliability, and invasiveness. Chlamydia trachomatis was identified as the priority organism for development of a new STI POCT. Themes indicated for the ideal POCT included rapid turnaround (up to 20 minutes), ease of use, non-invasive, accurate (preferred sensitivity and specificity in the range of high 90s), Clinical Laboratory Improvement Amendments (CLIA)-waived, user-friendly (for both patients and staff), compact, durable, and sturdy.
Conclusions/Significance
Focus group discussions with STI experts and professionals highlighted chlamydia as the top priority pathogen for POCT development, and identified the qualities of new POCT for STIs. Participants endorsed ease of use, rapid turnaround and high accuracy as essential characteristics of an ideal POCT.
doi:10.1371/journal.pone.0014144
PMCID: PMC2994750  PMID: 21152386
18.  Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans▿  
Journal of Virology  2009;84(5):2610-2617.
The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson's r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.
doi:10.1128/JVI.01962-09
PMCID: PMC2820922  PMID: 20032191
19.  Serologic Screening for Herpes Simplex Virus Among University Students: A Pilot Study 
Objective
The authors examined the feasibility of conducting serologic testing for the herpes simplex virus 2 (HSV-2) among university students and assessed the psychosocial impact of an HSV-2 diagnosis.
Methods
The authors recruited a convenience sample of 100 students (aged 18–39 years) without a history of genital herpes from 1 university between September 2004 and March 2006. Participants received HSV-2 antibody testing by Focus ELISA and Western Blot assays and completed a questionnaire that addressed psychological functioning. Twenty-eight participants completed the questionnaire again at a 3-month follow-up visit.
Results
The study revealed (1) low test-reliability in the student population, (2) that positive test results may cause a decline in psychological well-being, and (3) that substantial resources are required to support students with positive HSV-2 results.
Conclusions
Test performance, psychological impact, and availability of resources for counseling students with positive diagnoses should be considered before implementing HSV testing programs.
doi:10.3200/JACH.57.3.291-296
PMCID: PMC2774724  PMID: 18980884
clinical medicine; mental health; sexually transmitted disease
20.  Lumbar Puncture in HIV-Infected Patients with Syphilis and No Neurologic Symptoms 
Background
The decision to perform lumbar puncture in patients with asymptomatic human immunodeficiency virus (HIV) infection and syphilis is controversial. The Centers for Disease Control and Prevention recommend certain criteria that warrant lumbar puncture. Here, we assess the performance of these criteria for detecting asymptomatic neurosyphilis (ANS).
Methods
Eligible subjects consisted of all patients with concurrent HIV infection and syphilis in a prospective clinical cohort who had no neurologic symptoms at the time of lumbar puncture. We retrospectively applied different stratification criteria to calculate the performance of lumbar puncture in detecting ANS: (1) lumbar puncture in patients with late latent syphilis or syphilis of an unknown duration, regardless of the CD4 cell count or rapid plasma reagin titer; (2) lumbar puncture if the CD4 cell count was ≤350 cells/mL and/or the rapid plasma reagin titer was ≥1:32, regardless of the syphilis stage; and (3) lumbar puncture in the context of serologic nonresponse to syphilis therapy.
Results
Two hundred two of 231 patients with syphilis did not have neurologic symptoms. Immediate lumbar puncture was performed for 46 patients, and 10 cases (22%) of ANS were detected. With use of the first criterion, 2 (14%) of 10 cases of ANS in patients with early-stage syphilis would have been missed (sensitivity, 80% [95% confidence interval {CI}, 44%–97%]; specificity, 76% [95% CI, 60%–89%]). Criterion 2 would not have missed any cases of ANS (sensitivity, 100% [95% CI, 70%–100%]; specificity, 87% [95% CI, 72%–96%]) but would have required that a lumbar puncture be performed for 88% of patients. Performance of lumbar puncture performed in 13 cases based on serologic nonresponse to syphilis therapy yielded 4 cases (31%) of ANS.
Conclusions
In patients with concurrent HIV infection and syphilis, the use of criteria based on rapid plasma reagin titer and CD4 cell count, instead of stage-based criteria, improved the ability to identify ANS.
doi:10.1086/597096
PMCID: PMC2716000  PMID: 19187028
21.  Performance of Focus ELISA Tests for HSV-1 and HSV-2 Antibodies Among University Students With No History of Genital Herpes 
Sexually transmitted diseases  2007;34(9):681-685.
Objectives
To define the performance characteristics of the Focus ELISA HSV-1 and HSV-2 assay among 100 university students.
Study Design
HSV-1 and HSV-2 Focus ELISA and Western Blot assays were performed on sera from university students who reported no history of genital herpes.
Results
HSV-2 and HSV-1 seroprevalence by Western Blot were 3.4% and 48%, respectively. In this population, the positive predictive value of the Focus HSV-2 ELISA was 37.5%, the sensitivity was 100%, and specificity was 94.1%. The PPV of the Focus HSV-1 ELISA was 96.7%, the sensitivity was 69.0%, and the specificity was 97.8%.
Conclusions
In this low-prevalence population, the positive predictive value of the Focus HSV-2 ELISA test was low. This finding, together with those reported elsewhere, indicates that caution is warranted when recommending HSV screening in low-prevalence or heterogeneous populations. Consideration should be given to raising the cutoff index value for defining a positive test result.
doi:10.1097/01.olq.0000258307.18831.f0
PMCID: PMC2648390  PMID: 17457239
22.  Antiretroviral Therapy Is Associated with Reduced Serologic Failure Rates for Syphilis among HIV-Infected Patients 
Background
Syphilis and human immunodeficiency virus (HIV) frequently coexist in patients, but the effects of immunosuppression on the course of syphilis are unknown. Our goal was to determine whether the degree of HIV-mediated immunosuppression and the use of highly active antiretroviral therapy impact syphilis serologic responses.
Methods
We assessed all cases of syphilis with positive serologic test results from 1990 through 2006 in a prospective, observational clinical cohort of HIV-infected patients. We defined seroreversion as the loss of reactivity in a patient who previously had a serologic test result positive for syphilis. We defined serologic failure as the lack of a 4-fold decrease in rapid plasma reagin titers 270–365 days after therapy or a 4-fold increase in titers ⩾30 days after therapy. We used Cox proportional hazards models with statistical adjustments for multiple failure instances.
Results
One hundred eighty subjects experienced 231 cases of syphilis. The median follow-up time was 5.3 years. A total of 71 episodes of serologic failure were documented. A CD4 cell count of <200 cells/mL at the time of syphilis diagnosis was associated with an increased risk of serologic failure (adjusted hazard ratio, 2.48; 95% confidence interval, 1.26–4.88). The receipt of highly active antiretroviral therapy was associated with a 60% reduction in the rate of serologic failure (adjusted hazard ratio, 0.40; 95% confidence interval, 0.21–0.75), independent of concomitant CD4 cell response. Rapid plasma reagin seroreversion was infrequent (16.1%) and inconsistent, and it was more likely to occur among patients who received macrolides.
Conclusion
The use of highly active antiretroviral therapy to reverse immunosuppression and the routine use of macrolides for the prevention of opportunistic infections may reduce syphilis serologic failure rates among HIV-infected patients who have syphilis.
doi:10.1086/589295
PMCID: PMC2562285  PMID: 18532887
23.  Neurosyphilis in a clinical cohort of HIV-1-infected patients 
AIDS (London, England)  2008;22(10):1145-1151.
Objectives
To describe the risk factors, clinical presentation, and long-term follow up of patients enrolled in a clinical cohort of HIV-infected patients who were diagnosed and treated for neurosyphilis.
Methods
Comprehensive demographic, clinical, and therapeutic data were collected prospectively on all patients between 1990 and 2006. Patients were diagnosed with neurosyphilis if they had positive syphilis serologies and any of the following: (a) one or more cerebrospinal fluid abnormalities on lumbar puncture [white blood cells >10/μl; protein >50 mg/dl; reactive venereal diseases research laboratory], (b) an otherwise unexplained neurological finding.
Results
Of 231 newly diagnosed syphilis cases, 41 neurosyphilis cases met entry criteria (median age 38.6 years, 79.1% male). Risk factors for neurosyphilis included a CD4 cell count of less than 350 cells/ml at the time of syphilis diagnosis (odds ratio: 2.87; 95% confidence interval: 1.18–7.02), a rapid plasma regain titer >1:128 (2.83; 1.11–7.26), and male sex (2.46; 1.06–5.70). Use of any highly active antiretroviral therapy before syphilis infection reduced the odds of neurosyphilis by 65% (0.35; 0.14–0.91). Sixty-three percent of cases presented with early neurosyphilis and the median time to neurosyphilis diagnosis was 9 months. Symptomatic patients had more cerebrospinal fluid abnormalities on initial lumbar puncture than asymptomatic patients (P =0.01). Follow-up lumbar puncture within 12 months revealed that only 38% had resolution of all cerebrospinal fluid abnormalities. At 1 year, 38% had persistence of their major symptom despite adequate treatment for neurosyphilis. Twelve of 41 (29%) patients were retreated for syphilis.
Conclusion
Early neurosyphilis was common in this cohort. Highly active antiretroviral therapy to reverse immunosuppression may help mitigate neurological complications of syphilis.
doi:10.1097/QAD.0b013e32830184df
PMCID: PMC2553365  PMID: 18525260
highly active antiretroviral therapy; HIV; immunosuppression; neurosyphilis; syphilis
24.  Vaginal flora morphotypic profiles and assessment of bacterial vaginosis in women at risk for HIV infection. 
Specific morphotypic profiles of normal and abnormal vaginal flora, including bacterial vaginosis (BV), were characterized. A prospective study of 350 women yielded concurrent Gram-stain data and clinical assessment (n = 3455 visits). Microbiological profiles were constructed by Gram stain. Eight profile definitions were based on dichotomizing the levels of Lactobacillus, Gardnerella, and curved, Gram-negative bacillus (Mobiluncus) morphotypes. Of these, two were rare, and the other six demonstrated a graded association with the clinical components of BV. The proposed profiles from the Gram stain reflect the morphotypic categories describing vaginal flora that may enable clearer elucidation of gynecologic and obstetric outcomes in various populations.
doi:10.1080/10647440400020711
PMCID: PMC1784599  PMID: 15763911
25.  Sequence Diversity of Treponema pallidum subsp. pallidum tprK in Human Syphilis Lesions and Rabbit-Propagated Isolates 
Journal of Bacteriology  2003;185(21):6262-6268.
The tprK gene of Treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, belongs to a 12-member gene family and encodes a protein with a predicted cleavable signal sequence and predicted transmembrane domains. Except for the Nichols type strain, all rabbit-propagated isolates of T. pallidum examined thus far are comprised of mixed populations of organisms with heterogeneous tprK sequences. We show that tprK sequences in treponemes obtained directly from syphilis patients are also heterogeneous. Clustering analysis demonstrates that primary chancre tprK sequences are more likely to cluster within a sample than among samples and that tighter clustering is seen within chancre samples than within rabbit-propagated isolates. Closer analysis of tprK sequences from a rabbit-propagated isolate reveals that individual variable regions have different levels of diversity, suggesting that variable regions may have different intrinsic rates of sequence change or may be under different levels of selection. Most variable regions show increased sequence diversity upon passage. We speculate that the diversification of tprK during infection allows organisms to evade the host immune response, contributing to reinfection and persistent infection.
doi:10.1128/JB.185.21.6262-6268.2003
PMCID: PMC219401  PMID: 14563860

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