Browsing by Author "Wilson, Craig M."

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    Evaluating Testing Strategies for Identifying Youths With HIV Infection and Linking Youths to Biomedical and Other Prevention Services
    (American Medical Association, 2017-06-01) Miller, Robin Lin; Boyer, Cherrie B.; Chiaramonte, Danielle; Lindeman, Peter; Chutuape, Kate; Cooper-Walker, Bendu; Kapogiannis, Bill G.; Wilson, Craig M.; Fortenberry, J. Dennis; Pediatrics, School of Medicine
    Importance: Most human immunodeficiency virus (HIV)-infected youths are unaware of their serostatus (approximately 60%) and therefore not linked to HIV medical or prevention services. The need to identify promising and scalable approaches to promote uptake of HIV testing among youths at risk is critical. Objective: To evaluate a multisite HIV testing program designed to encourage localized HIV testing programs focused on self-identified sexual minority males and to link youths to appropriate prevention services after receipt of their test results. Design, Setting, and Participants: Testing strategies were evaluated using an observational design during a 9-month period (June 1, 2015, through February 28, 2016). Testing strategies were implemented by 12 adolescent medicine HIV primary care programs and included targeted testing, universal testing, or a combination. Data were collected from local youth at high risk of HIV infection and, specifically, sexual minority males of color. Main Outcomes and Measures: Proportion of sexual minority males and sexual minority males of color tested, proportion of previously undiagnosed HIV-positive youths identified, and rates of linkage to prevention services. Results: A total of 3301 youths underwent HIV testing. Overall, 35 (3.6%) of those who underwent universal testing in primary care clinical settings, such as emergency departments and community health centers, were sexual minority males (35 [3.6%] were males of color) compared with 236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted testing and 693 (37.8%) (503 [27.4%] were males of color) through combination efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%) via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%) through targeted testing. However, when targeted tests were separated from universal testing results for sites using a combined strategy, the rate of newly identified HIV-positive cases identified through universal testing decreased to 1 (0.1%). Rates of new HIV-positive cases identified through targeted testing increased to 49 (6.3%). Youths who tested through targeted testing (416 [85.1%]) were more likely to link successfully to local HIV prevention services, including preexposure prophylaxis, compared with those who underwent universal testing (328 [34.1%]). Conclusions and Relevance: The findings suggest that community-based targeted approaches to HIV testing are more effective than universal screening for reaching young sexual minority males (especially males of color), identifying previously undiagnosed HIV-positive youths, and linking HIV-negative youths to relevant prevention services. Targeted, community-based HIV testing strategies hold promise as a scalable and effective means to identify high-risk youths who are unaware of their HIV status.
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    HIV Continuum of Care for Youth in the United States
    (Wolters Kluwer, 2018-01-01) Lally, Michelle A.; van den Berg, Jacob J.; Westfall, Andrew O.; Rudy, Bret J.; Hosek, Sybil G.; Fortenberry, J. Dennis; Monte, Dina; Tanney, Mary R.; McFarland, Elizabeth J.; Xu, Jiahong; Kapogiannis, Bill G.; Wilson, Craig M.; Pediatrics, School of Medicine
    BACKGROUND: Beneficial HIV treatment outcomes require success at multiple steps along the HIV Continuum of Care. Youth living with HIV are a key population, and sites in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) are known for modeling optimum HIV adolescent care. METHODS: A longitudinal cohort study conducted at 14 network sites across the United States assessed how the later steps of the Continuum of Care were achieved among the youth: engagement, treatment, and viral load (VL) suppression. Youth aged 13-24 who were behaviorally infected with HIV and linked to care at an ATN-affiliated site were eligible to participate. RESULTS: A total of 467 youth were enrolled and had 1 year of available data. Most were aged 22-24 (57%), male (79%), and black/non-Hispanic (71%). Most used alcohol (81%) and marijuana (61%) in the 3 months before enrollment, and 40% had a history of incarceration. Among this cohort of youth, 86% met criteria for care engagement; among these, 98% were prescribed antiretroviral therapy and 89% achieved VL suppression. Sustained VL suppression at all measured time points was found among 59% with initial suppression. Site characteristics were notable for the prevalence of adherence counseling (100%), case management (100%), clinic-based mental health (93%), and substance use (64%) treatment. CONCLUSIONS: Youth living with HIV in the United States can be successfully treated at health care sites with experience, excellence, and important resources and services. Sustained VL suppression may be an important step to add to the Continuum of Care for youth.
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    Implementation of an Integrated Approach to the National HIV/AIDS Strategy for Improving Human Immunodeficiency Virus Care for Youths
    (AMA, 2017-07) Fortenberry, J. Dennis; Koenig, Linda J.; Kapogiannis, Bill G.; Ellen, Jonathan M.; Wilson, Craig M.; Pediatrics, School of Medicine
    Importance Youths aged 13 to 24 years old living with human immunodeficiency virus (HIV) are less likely than adults to receive the health and prevention benefits of HIV treatments, with only a small proportion having achieved sustained viral suppression. These age-related disparities in HIV continuum of care are owing in part to the unique developmental issues of adolescents and young adults as well as the complexity and fragmentation of HIV care and related services. This article summarizes a national, multiagency, and multilevel approach to HIV care for newly diagnosed youths designed to bridge some of these fragmentations by addressing National HIV/AIDS Strategy goals for people living with HIV. Design, Setting, and Participants Three federal agencies developed memoranda of understanding to sequentially implement 3 protocols addressing key National HIV/AIDS Strategy goals. The goals were addressed in the Adolescent Trials Network, with protocols implemented in 12 to 15 sites across the United States. Outcome data were collected from recently diagnosed youth referred to the program. Main Outcomes and Measures Cross-agency collaboration, youth-friendly linkage to care services, community mobilization to address structural barriers to care, cooperation among services, proportion of all men who have sex with men who tested, and rates of linkage to prevention services. Results The program addressed National HIV/AIDS Strategy goals 2 through 4 including steps within each goal. A total of 3986 HIV-positive youths were referred for care, with more than 75% linked to care within 6 weeks of referral, with almost 90% of those youths engaged in subsequent HIV care. Community mobilization efforts implemented and completed structural change objectives to address local barriers to care. Age and racial/ethnic group disparities were addressed through targeted training for culturally competent, youth-friendly care, and intensive motivational interviewing training. Conclusions and Relevance A national program to address the National HIV/AIDS Strategy specifically for youths can improve coordination of federal resources as well as implement best-practice models that are adapted to decrease service fragmentation and systemic barriers at local jurisdictions.
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    Insertional tagging of at least two loci associated with resistance to adenine arabinoside in Toxoplasma gondii, and cloning of the adenosine kinase locus
    (Elsevier, 1999) Sullivan, William J., Jr.; Chiang, Chi-Wu; Wilson, Craig M.; Naguib, Fardos N. M.; el Kouni, Mahmoud H.; Donald, Robert G. K.; Roos, David S.
    A genetic approach has been exploited to investigate adenylate salvage pathways in the protozoan parasite Toxoplasma gondii, a purine auxotroph. Using a new insertional mutagenesis vector designed to facilitate the rescue of tagged loci even when multiple plasmids integrate as a tandem array, 15 independent clonal lines resistant to the toxic nucleoside analog adenine arabinoside (AraA) were generated. Approximately two-thirds of these clones lack adenosine kinase (AK) activity. Parallel studies identified an expressed sequence tag (EST) exhibiting a small region of weak similarity to human AK, and this locus was tagged in several AK-deficient insertional mutants. Library screening yielded full-length cDNA and genomic clones. The T. gondii AK gene contains five exons spanning a approximately 3 kb locus, and the predicted coding sequence was employed to identify additional AK genes and cDNAs in the GenBank and dbEST databases. A genomic construct lacking essential coding sequence was used to create defined genetic knock-outs at the T. gondii AK locus, and AK activity was restored using a cDNA-derived minigene. Hybridization analysis of DNA from 13 AraA-resistant insertional mutants reveals three distinct classes: (i) AK-mutants tagged at the AK locus; (ii) AK- mutants not tagged at the AK locus, suggesting the possibility that another locus may be involved in regulating AK expression; and (iii) mutants with normal AK activity (potential transport mutants).
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    The adenosine transporter of Toxoplasma gondii: Identification by insertional mutagenesis, cloning, and recombinant expression
    (Elsevier, 1999) Chiang, Chi-Wu; Carter, Nicola; Sullivan, William J., Jr.; Donald, Robert G. K.; Roos, David S.; Naguib, Fardos N. M.; el Kouni, Mahmoud H.; Ullman, Buddy; Wilson, Craig M.
    Purine transport into the protozoan parasite Toxoplasma gondii plays an indispensable nutritional function for this pathogen. To facilitate genetic and biochemical characterization of the adenosine transporter of the parasite, T. gondii tachyzoites were transfected with an insertional mutagenesis vector, and clonal mutants were selected for resistance to the cytotoxic adenosine analog adenine arabinoside (Ara-A). Whereas some Ara-A-resistant clones exhibited disruption of the adenosine kinase (AK) locus, others displayed normal AK activity, suggesting that a second locus had been tagged by the insertional mutagenesis plasmid. These Ara-A(r) AK+ mutants displayed reduced adenosine uptake capability, implying a defect in adenosine transport. Sequences flanking the transgene integration point in one mutant were rescued from a genomic library of Ara-A(r) AK+ DNA, and Southern blot analysis revealed that all Ara-A(r) AK+ mutants were disrupted at the same locus. Probes derived from this locus, designated TgAT, were employed to isolate genomic and cDNA clones from wild-type libraries. Conceptual translation of the TgAT cDNA open reading frame predicts a 462 amino acid protein containing 11 transmembrane domains, a primary structure and membrane topology similar to members of the mammalian equilibrative nucleoside transporter family. Expression of TgAT cRNA in Xenopus laevis oocytes increased adenosine uptake capacity in a saturable manner, with an apparent K(m) value of 114 microM. Uptake was inhibited by various nucleosides, nucleoside analogs, hypoxanthine, guanine, and dipyridamole. The combination of genetic and biochemical studies demonstrates that TgAT is the sole functional adenosine transporter in T. gondii and a rational target for therapeutic intervention.
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    Transmission Risk among Youth Living with HIV in the United States
    (Elsevier, 2020-07) van den Berg, Jacob J.; Gamarel, Kristi E.; Westfall, Andrew O.; Fortenberry, J. Dennis; Hosek, Sybil G.; Wilson, Craig M.; Lally, Michelle A.; Medicine, School of Medicine
    Purpose: HIV treatment as prevention is effective for reducing the risk of HIV transmission and the messaging campaign, undetectable = untransmittable, is gaining recognition. As youth living with HIV (YLWH) who have condomless sex may acquire and potentially transmit other sexually transmitted infections (STIs), the purpose of this study was to assess potential differences in transmission risk of HIV and other STIs among YLWH to inform subsequent HIV and STI prevention efforts. Methods: A cohort of 600 HIV behaviorally infected youth aged 13-24 years who were engaged in medical care completed an audio computer-assisted self-interview including questions about demographics, HIV disclosure, mental health, substance use, and sexual behaviors and beliefs. HIV viral loads and the presence of other STIs were abstracted from medical records. A viral load <200 copies/mL was considered undetectable. Univariate and bivariate analyses were conducted to examine differences by viral load and STIs. Results: Participants were categorized into four groups: (1) undetectable without STIs (55.2%); (2) undetectable with STIs (14.2%); (3) detectable without STIs (22.8%); and (4) detectable with STIs (7.8%). In comparison to the other three groups, youth in the undetectable group with STIs reported more favorable sexual risk reduction attitudes and beliefs, internet use for finding sex partners, anal sex with male partners, and condomless anal sex with male partners. Conclusions: YLWH with undetectable viral loads and other STIs engaged in higher risk behaviors. To realize the promise of the messaging campaign, undetectable = untransmittable, efforts must focus on sustained viral suppression and prevention of STIs among YLWH.