The extraordinarily high level of genetic variation of HIV-1 env genes poses a challenge to obtain antibodies that cross-react with multiple subtype Env glycoproteins. To determine if cross-reactive monoclonal antibodies (mAbs) to highly conserved epitopes in HIV-1 envelope glycoproteins can be induced, we immunized mice with wild-type or consensus HIV-1 Env proteins and characterized a panel of ten mAbs that reacted with varying breadth to subtypes A, B, C, D, F, G, CRF01_AE and a highly divergent SIVcpzUS Env proteins by ELISA and Western blot analysis. Two mAbs (3B3 and 16H3) cross–reacted with all tested Env proteins, including SIVcpzUS Env. Surface plasmon resonance analyses showed both 3B3 and 16H3 bound Env proteins with high affinity. However, neither neutralized primary HIV-1 pseudoviruses. These data indicate that broadly-reactive non-neutralizing monoclonal antibodies can be elicited, but that the conserved epitopes that they recognize are not present on functional virion trimers. Nonetheless, such mAbs represent valuable reagents to study the biochemistry and structural biology of Env protein oligomers.
Expanding PrEP access necessitates training that supports healthcare providers’ progression along the PrEP implementation cascade, moving from PrEP awareness to prescription. We surveyed 359 USA providers about PrEP training content and format recommendations. We examined the association between cascade location and training recommendations. Most providers were aware of PrEP (100%), willing to prescribe PrEP (97.2%), had discussed PrEP with patients (92.2%), and had prescribed PrEP (79.9%). Latent class regression analysis revealed that cascade location was associated with training recommendations. Although all providers recommended PrEP-specific content (e.g., patient eligibility), providers who were located further along the cascade also recommended more comprehensive content, including sexual history-taking and sexual and gender minority competence training. Providers further along the cascade were also more likely to recommend interactive training formats (e.g., role-playing). These insights from providers furthest along the cascade indicate the importance of including comprehensive content and interactive formats in future PrEP training initiatives. Supplementary Information The online version contains supplementary material available at 10.1007/s10461-021-03375-w.
Depression among persons with HIV is associated with antiretroviral therapy (ART) interruption and discontinuation, virological failure, and poor clinical and survival outcomes. Case management services can address needs for emotional counseling and other supportive services to facilitate HIV care engagement. Using 2009-2013 North Carolina Medical Monitoring Project data from 910 persons engaged in HIV care, we estimated associations of case management utilization with "probable current depression" and with 100% ART dose adherence. After weighting, 53.2% of patients reported receiving case management, 21.7% reported depression, and 87.0% reported ART adherence. Depression prevalence was higher among those reporting case management (24.9%) than among other patients (17.6%) (p < 0.01). Case management was associated with depression among patients living above the poverty level [adjusted prevalence ratio (aPR), 2.05; 95% confidence interval (CI) 1.25-3.36], and not among other patients (aPR, 1.01; 95% CI 0.72-1.43). Receipt of case management was not associated with ART adherence (aPR, 1.00; 95% CI 0.95-1.05). Our analysis indicates a need for more effective depression treatment, even among persons receiving case management services. Self-reported ART adherence was high overall, though lower among persons experiencing depression (unadjusted prevalence ratio, 0.92; 95% CI 0.86-0.99). Optimal HIV clinical and prevention outcomes require addressing psychological wellbeing, monitoring of ART adherence, and effective case management services. KeywordsSupportive services • Quality care • Unmet need • Patient adherence • HIV care ResumenLa depresión en personas con VIH está asociada con la interrupción y descontinuación de terapia antirretroviral (TAR), fallo virológico, y resultados clínicos y de sobrevivencia deficientes. Los servicios de atención individualizada pueden abordar las necesidades de consejería emocional y otros servicios de apoyo para facilitar el enlace y cuidado del VIH. Con el uso datos del North Carolina Medical Monitoring Project (Proyecto del Monitoreo Médico de Carolina del Norte, MMP -por sus siglas en inglés) de 2009-2013, de 910 personas recibiendo cuidado para el VIH, estimamos asociaciones entre el uso de atención individualizada y "depresión actual probable" con 100% de cumplimiento de TAR. Después de ponderación, 53.2% de pacientes reportaron recibir atención individualizada, 21.7% reportaron depresión, y 87.0% reportaron cumplimiento con TAR. La prevalencia de depresión resultó ser más alta en aquellos reportando atención individualizada (24.9%) que en otros pacientes (17.6%) (p < 0.01). Hubo una asociación entre la atención individualizada y depresión en pacientes viviendo arriba del nivel de pobreza [tasa de prevalencia ajustada (aPR, 1.01; 95% intervalo de confianza (IC), 1.25-3.36], y no en otros pacientes (aPR, 1.01; 95% IC 0.72-1.43). No hubo asociación entre la recepción de atención individualizada y cumplimiento con TAR (aPR, 1.00; 95% IC 0.95-1.05). Nuestro análisis indica una necesi...
Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported 10 murine monoclonal antibodies induced by group M consensus Env, CON-6 immunization. Each demonstrated broad cross-reactivity to recombinant Envs. Here we characterized the Env epitopes to which they bind. Seven mapped to linear epitopes in gp120, five at the Env N-terminus, and two at the Env C-terminus. One antibody, 13D7, bound at the gp120 N-terminus (aa 30-42), reacted with HIV-1-infected CD4 T cells, and when expressed in a human IgG1 backbone, mediated antibody-dependent cellular cytotoxicity. Antibody 18F11 bound at the gp120 C-terminus (aa 445-459) and reactivity was glycan dependent. Antibodies 13D7, 3B3, and 16H3 bound to 100 percent of HIV-1 Envs tested in ELISA and sodium dodecyl sulfate/polyacrylamide gel electrophoresis/western blot analysis. These data define the epitopes of monoclonal antibody reagents for characterization of recombinant Envs, one epitope of which is also expressed on the surface of HIV-1-infected CD4 T cells.
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