Problem-Based Learning Could Tackle the Issue of Insufficient Education and Adherence in People Living With HIV/AIDS.

Background: Poor medication adherence is still the main cause of antiretroviral therapy (ART) failure among people living with HIV/AIDS (PLWHA). Effective behavioral interventions are needed to improve HIV awareness and medication adherence. Methods: In this retrospective cohort study, we assessed the effect of problem-based learning (PBL) approaches to HIV-related education and adherence outcomes among PLWHA and a college student sample. In our study, compared with 309 demography-matched control participants using conventional counseling methods (109 PLWHA and 200 college students), 321 subjects (111 PLWHA and 210 college students) chose to learn HIV-related knowledge via PBL-integrated methods. Co-primary outcomes were self-administered questionnaire after HIV-related education by all participants and self-reported medication adherence by newly diagnosed PLWHA, measured in terms of the number of missed doses in the past week at each of the seven visits during a 1-year period. Multivariate regression models adjusting different covariates were used to test the robustness of HIV awareness and adherence association. Mediation model was used to investigate the relationship among PBL training, awareness of HIV, and ART adherence. Results: The knowledge scores of participants in the PBL group were higher than those in the controls (P = 0.001), especially the subgroup of newly diagnosed PLWHA in the PBL group (P = 0.001). The HIV-related health scores of the PBL college students were also higher than those of subjects exposed to conventional education (P < 0.001). There was no significant difference between the two by newly diagnosed PLWHA groups in the number of missed doses during the past week at each visit except at the first follow-up visit (P = 0.018). The indirect effect of PBL-integrated education on ART adherence at the 2-week visit through HIV awareness had a point estimate of 0.0349 and a 95% bias-corrected bootstrap confidence interval of 0.0061∼0.0874 in newly diagnosed PLWHA. Conclusions: PLWHA and college students using PBL showed improved awareness of HIV and higher levels of recent ART adherence; however, there was no change in long-term ART adherence in newly diagnosed PLWHA.

Distinct HIV-1 Neutralization Potency Profiles of Ibalizumab-Based Bispecific Antibodies.

BACKGROUND: Preexposure prophylaxis using antiretroviral agents has been shown to effectively prevent human immunodeficiency virus type 1 (HIV-1) acquisition in high-risk populations. However, the efficacy of these regimens is highly variable, which is thought to be largely due to the varying degrees of adherence to a daily intervention in the populations. Passive immunization using broadly neutralizing antibodies (bNAbs) against HIV-1, with their relatively long half-life and favorable safety profile, could provide an alternative to daily preexposure prophylaxis. However, most bNAbs have a limited breadth, only neutralizing 70%-90% of all HIV-1 strains. METHODS: To overcome the problem of limited antiviral breadth, we proposed that targeting human CD4 and HIV-1 envelope proteins simultaneously may improve virus-neutralization breadth and potency. Therefore, we constructed bispecific antibodies (biAbs) using single-chain variable fragments of anti-gp120 bNAbs fused to ibalizumab (iMab), a humanized monoclonal antibody that binds human CD4, the primary receptor for HIV-1. RESULTS: Some of our biAbs neutralized 100% of HIV-1 strains tested in vitro at clinically achievable concentrations. Distinct neutralization patterns were observed in this panel of biAbs. Those biAbs with specificity for the CD4-binding site on gp120 demonstrated 100% breadth, as well as slightly improved potency compared with iMab. In contrast, biAbs with specificity for the V1-V2 apex epitope or the V3-glycan epitope on gp120 demonstrated dramatically improved potency; some showed limited gain in neutralization breadth, whereas others (eg, PGT128-LM52 and 123-iMab) improved to 100% breadth. CONCLUSION: Our data suggest that this panel of iMab-based biAbs could be used to probe the parameters for potent HIV-1 neutralization. Moreover, a few of these biAbs warrant further studies and possibly clinical development.