OBJECTIVES/SPECIFIC AIMS: In the first aim, we will evaluate the proportion of highly HIV-susceptible memory CD4+ T cells present in the rectal mucosa, based on the proliferation status and ...expression of the HIV susceptibility markers, CCR5 and α4β7, between HIV-negative adolescent MSM and adult MSM engaging in RAI. The second aim will assess differences between the two study groups in the ratio of Th17 cells (CD4+ IL17+) to Treg cells (CD4+ FoxP3+ CD25+) in the rectal mucosa as a determinant of mucosal inflammation. Finally, in the third aim, we will utilize ex vivo rectal biopsy explant challenge experiments to examine whether HIV target cell availability and the Th17/Treg ratio influence rectal mucosal HIV susceptibility. METHODS/STUDY POPULATION: Rectal biopsy specimens are being collected from healthy, HIV-negative men that comprise the two study groups: 40 adolescent MSM 18-21 years of age who have engaged in RAI at least once previously in their lifetime and 40 adult MSM ≥35 years of age who have engaged in RAI for the previous 5 consecutive years with a minimum of 12 episodes annually. To identify CD4+ subsets of interest for aims 1 and 2, rectal mucosal mononuclear cells are isolated and phenotyped with CD45, CD3, CD4, CD45RA, CCR7, CD69, CCR5, α4β7, Ki67, FOXP3, and CD25 antibodies. To identify the Th17 cell subtype, the cells are stimulated with PMA/Ionamycin and stained with an antibody specific to IL-17A. Using cross-sectional analyses, we will compare the frequencies of mucosal CD4+ T cells that express certain phenotypic characteristics and evaluate differences in the Th17/Treg ratio between adolescent and adult MSM. For aim 3, rectal biopsy specimens are inoculated with HIV virus and the culture supernatant is assayed for p24 concentration on days 3, 7, 10 14, and 18. Longitudinal analyses will be performed to detect differences in p24 concentration at each time point and assess associations with mucosal target cell availability and with the Th17/Treg ratio. RESULTS/ANTICIPATED RESULTS: We hypothesize that younger age will be associated with enhanced memory CD4+ T cell proliferation and increased expression of HIV susceptibility markers (CCR5 and/or α4β7). In addition, we expect that the rectal mucosa of adolescent MSM will demonstrate a higher Th17/Treg ratio as compared to adult MSM, which could facilitate HIV transmission. It is also anticipated that rectal mucosal immune phenotypes characterized by increased HIV target cell availability and high Th17/Treg ratios will be associated with enhanced mucosal HIV susceptibility in the explant challenge model. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a paucity of information regarding the mechanisms of rectal HIV transmission, and no studies to date investigate the immunologic effects of aging on transmission in the rectal mucosa. The results from this study will provide important information regarding age-related differences in the immune cell composition of the rectal mucosa as a critical step in better understanding immunologic factors that influence rectal HIV transmission.
Forty-three Spanish populations of hairy fleabane, sampled from perennial crop locations, were studied under controlled and field conditions to confirm and characterize glyphosate resistance. In the ...initial screening, under controlled conditions, significant differences in glyphosate response between locations and among plant progenies within location were observed. From the initial screening, six populations (five potentially resistant R and one susceptible S) were selected, and a dose–response experiment was conducted to determine the resistance factor. The resistance factor was close to 10× for the most resistant population. In addition, the glyphosate response of R and S populations was dependant on phenological stages: the glyphosate rate required for control increased as a function of plant age. Finally, the resistance was confirmed with field trials conducted in five locations (one S and four R previously studied under controlled conditions). The field trials were also used to find alternative solutions for Spanish farmers to control resistant hairy fleabane populations. Nomenclature: Flazasulfuron; fluroxypyr; glyphosate; glufosinate; hairy fleabane, Conyza bonariensis (L.) Cronq. ERIBO.
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We tested a couples HIV testing and counseling (CHTC) intervention with male couples in Atlanta by randomizing eligible couples to receive either CHTC or separate individual voluntary HIV counseling ...and testing (iVCT). To evaluate the acceptability and safety of CHTC, main outcomes were satisfaction with the intervention and the proportions of couples reporting intimate partner violence (IPV) and relationship dissolution after the service. The results indicated that the service was very acceptable to men (median 7-item index of satisfaction was 34 for CHTC and 35 for iVCT, P = .4). There was no difference in either incident IPV (22% versus 17% for CHTC and iVCT, respectively, P = .6) or relationship dissolution (42% versus 51% for CHTC and iVCT, respectively, P = .5). Based on the preliminary data, CHTC is safe for male couples, and it is equally acceptable to iVCT for men who have main partners.
To respond to the need for new HIV prevention services for men who have sex with men (MSM) in the United States, and to respond to new data on the key role of main partnerships in US MSM epidemics, ...we sought to develop a new service for joint HIV testing of male couples. We used the ADAPT-ITT framework to guide our work. From May 2009 to July 2013, a multiphase process was undertaken to identify an appropriate service as the basis for adaptation, collect data to inform the adaptation, adapt the testing service, develop training materials, test the adapted service, and scale up and evaluate the initial version of the service. We chose to base our adaptation on an African couples HIV testing service that was developed in the 1980s and has been widely disseminated in low- and middle-income countries. Our adaptation was informed by qualitative data collections from MSM and HIV counselors, multiple online surveys of MSM, information gathering from key stakeholders, and theater testing of the adapted service with MSM and HIV counselors. Results of initial testing indicate that the adapted service is highly acceptable to MSM and to HIV counselors, that there are no evident harms (e.g., intimate partner violence, relationship dissolution) associated with the service, and that the service identifies a substantial number of HIV serodiscordant male couples. The story of the development and scale-up of the adapted service illustrates how multiple public and foundation funding sources can collaborate to bring a prevention adaptation from concept to public health application, touching on research, program evaluation, implementation science, and public health program delivery. The result of this process is an adapted couples HIV testing approach, with training materials and handoff from academic partners to public health for assessment of effectiveness and consideration of the potential benefits of implementation; further work is needed to optimally adapt the African couples testing service for use with male–female couples in the United States.
We tested a couples HIV testing and counseling (CHTC) intervention with male couples in Atlanta by randomizing eligible couples to receive either CHTC or separate individual voluntary HIV counseling ...and testing (iVCT). To evaluate the acceptability and safety of CHTC, main outcomes were satisfaction with the intervention and the proportions of couples reporting intimate partner violence (IPV) and relationship dissolution after the service. The results indicated that the service was very acceptable to men (median 7-item index of satisfaction was 34 for CHTC and 35 for iVCT, P = .4). There was no difference in either incident IPV (22% versus 17% for CHTC and iVCT, respectively, P = .6) or relationship dissolution (42% versus 51% for CHTC and iVCT, respectively, P = .5). Based on the preliminary data, CHTC is safe for male couples, and it is equally acceptable to iVCT for men who have main partners.
In the United States, a substantial proportion of HIV transmissions among men who have sex with men (MSM) arise from main sex partners. Couples voluntary HIV testing and counseling (CHTC) is used in ...many parts of the world with male–female couples, but CHTC has historically not been available in the U.S. and few data exist about the extent of HIV serodiscordance among U.S. male couples. We tested partners in 95 Atlanta male couples (190 men) for HIV. Eligible men were in a relationship for ≥3 months and were not known to be HIV-positive. We calculated the prevalence of couples that were seroconcordant HIV-negative, seroconcordant HIV-positive, or HIV serodiscordant. We evaluated differences in the prevalence of HIV serodiscordance by several dyadic characteristics (e.g., duration of relationship, sexual agreements, and history of anal intercourse in the relationship). Overall, among 190 men tested for HIV, 11 % (
n
= 20) were newly identified as HIV-positive. Among the 95 couples, 81 % (
n
= 77) were concordant HIV-negative, 17 % (
n
= 16) were HIV serodiscordant, and 2 % (
n
= 2) were concordant HIV-positive. Serodiscordance was not significantly associated with any evaluated dyadic characteristic. The prevalence of undiagnosed HIV serodiscordance among male couples in Atlanta is high. Offering testing to male couples may attract men with a high HIV seropositivity rate to utilize testing services. Based on the global evidence base for CHTC with heterosexual couples and the current evidence of substantial undiagnosed HIV serodiscordance among U.S. MSM, we recommend scale-up of CHTC services for MSM, with ongoing evaluation of acceptability and couples’ serostatus outcomes.
Thesis (Ph. D.)--University of Chicago, 1911.
"Published as no. 93 of the Psychological monographs." Includes bibliographical references (p. 50) Also available on the Internet.
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