Faculty Bibliography

BACKGROUND: Commercial sex venues (e.g., bathhouses) that cater to men who have sex with men (MSM) continue to function in most urban areas. These venues present a challenge to developing strategies to prevent the spread of the human immunodeficiency virus (HIV), but they also provide opportunities for interventions to reduce the risk and rate of disease transmission. Several cities in the United States have developed programs that offer HIV testing in these venues. Similar programs have not existed before in New York City. METHODS: A pilot HIV testing program was implemented at 2 New York City bathhouses. Testing included rapid HIV testing, the use of the serologic testing algorithm for recent HIV seroconversion, and pooled plasma HIV viral load to detect and date incident and acute HIV infections. In addition to HIV tests, behavioral and demographic data were collected from 493 presumed HIV-negative participants. RESULTS: The pilot program recruited MSM who were at high risk for HIV infection. Of the 493 men tested, 20 (4%) were found to be positive for HIV, and 8 (40%) of these 20 men demonstrated evidence of acute or recent HIV infection. The program tested men often not tested in more traditional medical settings. Significant disparities were demonstrated in the testing habits of MSM who reported having sex with women and had not disclosed same-sex activities to their caregivers. CONCLUSIONS: Bathhouse-based testing for HIV infection can be implemented in New York City and would include a population of MSM who are at high risk for HIV infection. Because of the high rate of recent HIV infection, expanded testing in these venues may be a good strategy to reduce the forward transmission of HIV in this highly sexually active population

OBJECTIVE: To describe physical symptoms in those local residents, local workers, and cleanup workers who were enrolled in a treatment program and had reported symptoms and exposure to the dust, gas, and fumes released with the destruction of the World Trade Center (WTC) on September 11, 2001. METHODS: Symptomatic individuals underwent standardized evaluation and subsequent treatment. RESULTS: One thousand eight hundred ninety-eight individuals participated in the WTC Environmental Health Center between September 2005 and May 2008. Upper and lower respiratory symptoms that began after September 11, 2001 and persisted at the time of examination were common in each exposure population. Many (31%) had spirometry measurements below the lower limit of normal. CONCLUSIONS: Residents and local workers as well as those with work-associated exposure to WTC dust have new and persistent respiratory symptoms with lung function abnormalities 5 or more years after the WTC destruction

BACKGROUND: Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels. METHODS: We undertook a double-blind, phase II, test-of-concept study at 34 sites in North America, the Caribbean, South America, and Australia. We randomly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine (n=1494) or placebo (n=1506). Randomisation was prestratified by sex, adenovirus type 5 (Ad5) antibody titre at baseline, and study site. Primary objective was a reduction in HIV-1 acquisition rates (tested every 6 months) or a decrease in HIV-1 viral-load setpoint (early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis). Analyses were per protocol and modified intention to treat. The study was stopped early because it unexpectedly met the prespecified futility boundaries at the first interim analysis. This study is registered with ClinicalTrials.gov, number NCT00095576. FINDINGS: In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less, 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio [HR] 1.2 [95% CI 0.6-2.2]). All but one infection occurred in men. The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients (4.61 vs 4.41 log(10) copies per mL, one tailed p value for potential benefit 0.66). The vaccine elicited interferon-gamma ELISPOT responses in 75% (267) of the 25% random sample of all vaccine recipients (including both low and high Ad5 antibody titres) on whose specimens this testing was done (n=354). In exploratory analyses of all study volunteers, irrespective of baseline Ad5 antibody titre, the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (HR 2.3 [95% CI 1.2-4.3]) and uncircumcised men (3.8 [1.5-9.3]), but was not increased in Ad5 seronegative (1.0 [0.5-1.9]) or circumcised (1.0 [0.6-1.7]) men. INTERPRETATION: This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level. Mechanisms for insufficient efficacy of the vaccine and the increased HIV-1 infection rates in subgroups of vaccine recipients are being explored

BACKGROUND: The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5-vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial. METHODS: Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5 human immunodeficiency virus type 1 vaccine containing from 3 x 10(6) to 1 x 10(11) viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-gamma enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose. RESULTS: Of 259 randomized individuals, 257 (99%) received > or = 1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of > or = 3 x 10(9) viral particles elicited positive enzyme-linked immunosorbent spot responses to > or = 1 vaccine component in > 60% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzyme-linked immunosorbent spot responses at all doses except the 3 x 10(10) viral particle dose. CONCLUSIONS: The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy

PURPOSE: To study the role of the Pentacam (Oculus), Orbscan II (Bausch & Lomb), and WaveScan (Visx) in evaluating topographic features identified as risk factors for ectasia after laser in situ keratomileusis to identify parameters that may be important in interpreting elevation topography and wavefront data when screening refractive surgery candidates. SETTING: Private practice, New York, New York, USA. METHODS: One hundred forty-five eyes of 75 consecutive patients were evaluated for refractive surgery by ultrasound pachymetry (Humphrey Atlas), videokeratography, WaveScan, Orbscan II, and Pentacam. Eyes were classified as normal or suspect based on the Rabinowitz criteria for keratoconus suspect on Placido disk-based videokeratography. Forty-six parameters were evaluated in a comparison of topographically normal eyes and eyes that met the criteria for keratoconus suspect. RESULTS: The suspect group had thinner pachymetry, multiple distinguishing characteristics on the anterior and posterior corneal surfaces by elevation topography, and larger amounts of coma by wavefront analysis. Multivariable regression analysis identified the following as the strongest predictors of a suspect Placido topography: Pentacam, thinner pachymetry and larger differences between the highest and lowest points on the posterior elevation; Orbscan II, higher anterior maximum elevation, horizontal location of the thinnest point on the pachymetry map, and larger differences between the highest and lowest points on the posterior elevation. CONCLUSION: Several parameters provided by the Pentacam, Orbscan II, WaveScan, and pachymetry were statistically correlated with keratoconus suspect, defined by higher asymmetry and steeper curvature on Placido topography

BACKGROUND: Microbial exposures have been suggested to confer protection from allergic disorders and reduced exposures to gastrointestinal microbiota have been proposed as an explanation for the increase in asthma prevalence. Since the general prevalence of Helicobacter pylori has been decreasing, we hypothesized that H. pylori serostatus would be inversely related to the presence of asthma. METHODS: Adults were recruited to participate in the New York University (NYU)/Bellevue Asthma Registry in New York City. Adult asthma cases (N = 318) and controls (N = 208) were identified and serum IgG antibodies to H. pylori whole cell antigens or the immunodominant CagA antigen were measured. RESULTS: As expected, the asthma cases and controls differed with respect to atopy and lung function. Seropositivity to H. pylori or CagA antigen was present in 47.1% of the total case and control study population. Asthma was inversely associated with CagA seropositivity (OR = 0.57, 95% CI = 0.36-0.89). Median age of onset of asthma (doctor's diagnosis) was older (21 years) among individuals with CagA+ strains than among H. pylori- individuals (11 years) (p = 0.006). CONCLUSION: These data are consistent with the hypothesis that colonization with CagA+ H. pylori strains is inversely associated with asthma and is associated with an older age of asthma onset in an urban population. The data suggest H. pylori as a marker for protection

OBJECTIVES:: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS:: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS:: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS:: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection