RESUMEN
T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 1010 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 109 PU of rAd5 Gag/Pol. CD4+ T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8+ T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4+ T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.
Asunto(s)
Vacunas contra el SIDA/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígenos VIH/inmunología , Adolescente , Adulto , Linfocitos T CD8-positivos/inmunología , Método Doble Ciego , Epítopos/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vacunación , Adulto Joven , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/inmunologíaRESUMEN
BACKGROUND: HIV disproportionately impacts transgender populations globally, creating challenges to inclusion in trials requiring low HIV risk profiles (LHRP) for acquisition. Our knowledge of transgender individuals with LHRP is limited. We conducted an analysis of transgender and cisgender individuals in HVTN trials enrolling individuals with LHRP. METHODS: We analyzed data from 694 participants enrolled in the phase 1-2a HVTN trials in the US and Peru from 2009 to 2014 that included individuals who reported gender identity (GI) differing from assigned birth sex (transgender [TG]), and compared them with those who reported a congruent GI (cisgender [CG]). RESULTS: 681 participants (98%) were CG and 13 (2%) were TG. Mean age was 25â¯years. 16% were Hispanic and most (69%) were White. Reasons for enrolling included to help find an effective vaccine (TG 100%; CG 98%) and help their community (TG 100%; CG 96%). Significant differences by GI were observed in reported pre-existing conditions (pâ¯=â¯0.004); however, approximately 10% of pre-existing conditions reported by TG were GI-related (e.g., gender dysphoria). Significant differences were observed in hormone therapy use (pâ¯<â¯0.001) and mental health medications (pâ¯=â¯0.007). Retention was excellent with 2.1% missed visits and no discontinuations of vaccination for TG and 3% missed visits and 7.1% discontinuations among CG. There was no statistically significant difference in HIV incidence. CONCLUSIONS: Primary reasons for participation were altruistic for all participants. Comparable to CG counterparts, TG participants maintained LHRP, followed trial procedures, and had high retention, facilitating meaningful early phase HIV preventive vaccine trial contributions.
Asunto(s)
Vacunas contra el SIDA/administración & dosificación , Infecciones por VIH/prevención & control , Selección de Paciente , Personas Transgénero/estadística & datos numéricos , Adolescente , Adulto , Demografía , Femenino , Identidad de Género , Infecciones por VIH/epidemiología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Perú/epidemiología , Factores de Riesgo , Conducta Sexual , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
CONTEXT: Partner services are a broad array of services that should be offered to persons with human immunodeficiency virus (HIV) and that are based on a process through which HIV-infected persons are interviewed to elicit information about their sex and needle-sharing partners. Human immunodeficiency virus testing of partners can result in a high yield of newly diagnosed HIV positivity, but despite this yield and the benefits of partners knowing their exposures and HIV status, partner services are often not conducted. OBJECTIVE: We sought to determine the newly diagnosed HIV positivity and benefits to 2 health departments that conducted demonstration projects that focused on statewide HIV partner services. DESIGN: The main sources of information used for this case study analysis included the health department funding applications, progress reports and final reports submitted to the Centers for Disease Control and Prevention, and records of communications between Centers for Disease Control and Prevention and the health departments. Required quantitative reporting included the number of partners tested and the number of partners with newly diagnosed confirmed HIV infection. Required qualitative reporting included how health departments benefited from their demonstration project activities. SETTING: Hawaii and New Mexico. PARTICIPANTS: Sex and needle-sharing partners of persons who were newly diagnosed with HIV infection. INTERVENTION: The use of HIV surveillance data to initiate statewide HIV partner services. MAIN OUTCOME MEASURE: Newly diagnosed HIV positivity. RESULTS: During 2012-2015, the newly diagnosed HIV positivity among partners was 18% (78/427): 16% (17/108) in Hawaii and 19% (61/319) in New Mexico. The health departments benefited from improved collaborations among HIV prevention program and surveillance staff and among the health departments, providers, and AIDS service organizations. CONCLUSIONS: Hawaii and New Mexico each achieved a high newly diagnosed HIV positivity and benefited from improved local collaborations. As a result of the success of these projects, both health departments have continued the activities since the end of category C funding by securing alternative funding sources.
Asunto(s)
Infecciones por VIH/diagnóstico , Vigilancia de la Población/métodos , Asociación entre el Sector Público-Privado/tendencias , Minería de Datos/métodos , Infecciones por VIH/epidemiología , Hawaii/epidemiología , Humanos , Compartición de Agujas/estadística & datos numéricos , New Mexico/epidemiología , Conducta Sexual/estadística & datos numéricos , Gobierno EstatalRESUMEN
BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials. METHODS: Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA). RESULTS: Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos. CONCLUSIONS: The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies.