A Rapid Qualitative Assessment of the Impact of the COVID-19 Pandemic on a Racially/Ethnically Diverse Sample of Gay, Bisexual, and Other Men who Have Sex with Men Living with HIV in the US South.

Persons living with HIV (PLWH) may be at increased risk for severe COVID-19-related illness. Our community-based participatory research partnership collected and analyzed semi-structured interview data to understand the early impact of the COVID-19 pandemic on a sample of racially/ethnically diverse gay, bisexual, and other men who have sex with men living with HIV. Fifteen cisgender men participated; their mean age was 28. Six participants were Black/African American, five were Spanish-speaking Latinx, and four were White. Seventeen themes emerged that were categorized into six domains: knowledge and perceptions of COVID-19; COVID-19 information sources and perceptions of trustworthiness; impact of COVID-19 on behaviors, health, and social determinants of health; and general COVID-19-related concerns. Interventions are needed to ensure that PLWH have updated information and adhere to medication regimens, and to reduce the impact of COVID-19 on social isolation, economic stability, healthcare access, and other social determinants of health within this vulnerable population.

RESUMEN: Las personas que viven con VIH (PLWH por sus siglas en inglés) pueden tener mayor riesgo de contraer serias enfermedades relacionadas con el COVID-19. Nuestra investigación participativa basada en la comunidad recopiló y analizó datos de entrevistas semiestructuradas para entender el impacto inicial de la pandemia COVID-19 en una muestra de hombres gay, bisexuales y otros hombres que tienen sexo con hombres de diversos grupos étnicos y raciales que viven con VIH. Participaron quince hombres cisgénero con un promedio de edad de 28 años. Seis participantes fueron negros/afroamericanos, cinco latinx hispanohablantes y cuatro blancos. Emergieron diecisiete temas que fueron categorizados en seis ámbitos: conocimiento y percepciones de COVID-19; fuentes de información sobre COVID-19 y percepciones de confiabilidad; impacto de COVID-19 en comportamientos, salud y determinantes sociales de la salud e inquietudes generales relacionadas con COVID-19. Se necesitan intervenciones para garantizar que las personas que viven con VIH tengan información actualizada y cumplan con adherirse a su régimen de tratamiento y reducir el impacto de COVID-19 en lo que respecta a aislamiento social, estabilidad económica, acceso a los servicios de atención médica y otros determinantes sociales de la salud en estas poblaciones vulnerables.

Maintenance of Viral Suppression in Human Immunodeficiency Virus Controllers Despite Waning T-Cell Responses During Antiretroviral Therapy.

AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) controllers start antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Before ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. During ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

Antiretroviral Therapy Reduces T-cell Activation and Immune Exhaustion Markers in Human Immunodeficiency Virus Controllers.

BACKGROUND: Despite low plasma human immunodeficiency virus (HIV) RNA, HIV controllers have evidence of viral replication and elevated inflammation. We assessed the effect of antiretroviral therapy (ART) on HIV suppression, immune activation, and quality of life (QoL). METHODS: A5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in ART-naive HIV controllers (N = 35), defined as having HIV RNA <500 copies/mL for ≥12 months. The primary outcome measured change in %CD38+HLA-DR+ CD8+ T cells. Residual plasma viremia was measured using the integrase single-copy assay. QoL was measured using the EQ-5D questionnaire. Outcomes were evaluated using repeated measures general estimating equations models. RESULTS: Before ART, HIV controllers with undetectable residual viremia <0.6 HIV-1 RNA copies/mL had higher CD4+ counts and lower levels of T-cell activation than those with detectable residual viremia. ART use was effective in further increasing the proportion of individuals with undetectable residual viremia (pre-ART vs after 24-48 weeks of ART: 19% vs 94%, P < .001). Significant declines were observed in the %CD38+HLA-DR+CD8+ T cells at 24-48 (-4.0%, P = .001) and 72-96 (-7.2%, P < .001) weeks after ART initiation. ART use resulted in decreases of several cellular markers of immune exhaustion and in a modest but significant improvement in self-reported QoL. There were no significant changes in CD4+ counts or HIV DNA. CONCLUSIONS: ART in HIV controllers reduces T-cell activation and improves markers of immune exhaustion. These results support the possible clinical benefits of ART in this population.

Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353.

BACKGROUND: The AIDS Clinical Trials Group study A5353 demonstrated the efficacy and safety of dolutegravir and lamivudine for initial treatment of HIV-1 infection at week 24 in individuals with HIV-1 RNA 1000-500 000 copies/mL. Optimal ART for treatment-naive individuals must be durable. OBJECTIVES: The aim of this study was to estimate the efficacy and safety of dolutegravir plus lamivudine at week 48 and compare the efficacy in participants with baseline HIV-1 RNA ≤100 000 copies/mL versus >100 000 copies/mL. METHODS: Virological success was defined as HIV-1 RNA <50 copies/mL by FDA Snapshot criteria. Definition of virological failure included confirmed HIV-1 RNA >200 copies/mL at week 24 or later. The proportion of participants with virological success was estimated using two-sided exact Clopper-Pearson 95% CI. Comparison between screening HIV-1 RNA (≤100 000 versus >100 000 copies/mL) strata was carried out by Fisher's exact test. The study was registered with ClinicalTrials.gov, number NCT02582684. RESULTS: A total of 120 enrolled eligible participants were included in the analysis. At week 48, 102 of the 120 participants (85%; 95% CI 77%-91%) had virological success. Virological success was similar between screening HIV-1 RNA groups. Six (5%) participants had virological non-success and one additional participant experienced virological failure while on study but off study treatment. No new drug resistance mutations were observed. Six (5%) participants had study-related grade 3 or higher adverse events and none discontinued study treatment. CONCLUSIONS: These results add to the evidence that dolutegravir plus lamivudine is a safe and effective option for initial ART in individuals with HIV-1 RNA <500 000 copies/mL.

A rapid qualitative assessment of the impact of the COVID-19 pandemic on a racially/ethnically diverse sample of gay, bisexual, and other men who have sex with men living with HIV in the US South.

Persons living with HIV (PLWH) may be at increased risk for severe COVID-19-related illness. Our community-based participatory research partnership collected and analyzed semi-structured interview data to understand the early impact of the COVID-19 pandemic on a sample of racially/ethnically diverse gay, bisexual, and other men who have sex with men living with HIV. Fifteen cisgender men participated; their mean age was 28. Six participants were Black/African American, five were Spanish-speaking Latinx, and four were White. Seventeen themes emerged that were categorized into six domains: knowledge and perceptions of COVID-19; COVID-19 information sources and perceptions of trustworthiness; impact of COVID-19 on behaviors, health, and social determinants of health; and general COVID-19-related concerns. Interventions are needed to ensure that PLWH have updated information and adhere to medication regimens, and to reduce the impact of COVID-19 on social isolation, economic stability, healthcare access, and other social determinants of health within this vulnerable population.

Las personas que viven con VIH (PLWH por sus siglas en inglés) pueden tener mayor riesgo de contraer serias enfermedades relacionadas con el COVID-19. Nuestra investigación participativa basada en la comunidad recopiló y analizó datos de entrevistas semiestructuradas para entender el impacto inicial de la pandemia COVID-19 en una muestra de hombres gay, bisexuales y otros hombres que tienen sexo con hombres de diversos grupos étnicos y raciales que viven con VIH. Participaron quince hombres cisgénero con un promedio de edad de 28 años. Seis participantes fueron negros/afroamericanos, cinco latinx hispanohablantes y cuatro blancos. Emergieron diecisiete temas que fueron categorizados en seis ámbitos: conocimiento y percepciones de COVID-19; fuentes de información sobre COVID-19 y percepciones de confiabilidad; impacto de COVID-19 en comportamientos, salud y determinantes sociales de la salud e inquietudes generales relacionadas con COVID-19. Se necesitan intervenciones para garantizar que las personas que viven con VIH tengan información actualizada y cumplan con adherirse a su régimen de tratamiento y reducir el impacto de COVID-19 en lo que respecta a aislamiento social, estabilidad económica, acceso a los servicios de atención médica y otros determinantes sociales de la salud en estas poblaciones vulnerables.

Severe postvaccinia encephalitis with acute disseminated encephalomyelitis: recovery with early intravenous immunoglobulin, high-dose steroids, and vaccinia immunoglobulin.

We report the second case of severe postvaccinial encephalitis with acute disseminated encephalomyelitis since smallpox vaccination was reintroduced in 2002. Both affected patients responded dramatically with early intervention of intravenous immunoglobulin. Our patient, who also received concurrent vaccinia immunoglobulin and corticosteroids, demonstrated full recovery.

Barriers to HIV Testing Within a Sample of Spanish-speaking Latinx Gay, Bisexual, and Other Men Who Have Sex with Men: Implications for HIV Prevention and Care.

Gay, bisexual, and other men who have sex with men (GBMSM) have higher rates of HIV infection compared to the general population in the United States, and the infection rate is growing among Latinx GBMSM, compared to a decline in most other demographic subgroups. Uptake of pre-exposure prophylaxis (PrEP), a biomedical strategy designed to reduce HIV transmission, is very low among Latinx GBMSM. HIV testing is a critical first step in the HIV prevention and care continua. We analyzed data from a community-based sample of Latinx GBMSM in the southeastern United States to identify the most common HIV testing barriers and the factors associated with barriers. The five most commonly reported HIV testing barriers included not knowing where to get tested, not having health insurance, fear of being HIV positive, practicing safer sex and perceiving not needing to be tested, and not being recommended to get tested. Using multivariable logistic regression modeling, speaking only Spanish, being unemployed, and adhering to traditional notions of masculinity were associated with increased barriers to HIV testing. We recommend that interventions to increase HIV testing among Latinx GBMSM be in Spanish and use culturally congruent messaging, be accessible to those who are unemployed, and incorporate positive risk-reducing aspects of masculinity.

Community-Engaged Research as an Approach to Expedite Advances in HIV Prevention, Care, and Treatment: A Call to Action.

Throughout the world, we continue to face profound challenges to reducing the impact of the HIV epidemic. Community-engaged research has emerged as an approach to increase our understanding of HIV and reduce health disparities, increase health equity, and promote community and population health. Our partnership has conducted more than 25 community-engaged research studies in the U.S. and Guatemala, and members have identified nine themes to facilitate community-engaged research and expedite advances in HIV prevention, care, and treatment. These themes include the inclusion of multisectoral partners, trust building and maintenance, the alignment of partner priorities, a can-do attitude, capacity and desire to move beyond service and conduct research, flexibility, power sharing, empowerment, an assets orientation, the shared and timely use of findings, and a stepwise approach. To reduce HIV disparities, community-engaged research is as critical now as ever, and we desperately need to reinvigorate our commitment to and support of it.

Preliminary Impact of the weCare Social Media Intervention to Support Health for Young Men Who Have Sex with Men and Transgender Women with HIV.

Young racial/ethnic minority men who have sex with men (MSM) and transgender women with HIV often have poor health outcomes. They also utilize a wide array of social media. Accordingly, we developed and implemented weCare, a social media intervention utilizing Facebook, texting, and GPS-based mobile social and sexual networking applications to improve HIV-related care engagement and health outcomes. We compared viral load suppression and clinic appointment attendance among 91 participants during the 12-month period before and after weCare implementation. McNemar's chi-square test analyses were conducted comparing the pre- and postintervention difference using paired data. Since February 2016, intervention staff and 91 intervention participants (79.1% African American and 13.2% Latino, mean age = 25) exchanged 13,830 messages during 3,758 conversations (average: 41.3 conversations per participant) across a variety of topics, including appointment reminders, medication adherence, problem solving, and reducing barriers. There were significant reductions in missed HIV care appointments (68.0% vs. 53.3%, p = 0.04) and increases in viral load suppression (61.3% vs. 88.8%, p < 0.0001) 12 months postimplementation. Our results highlight the initial success of weCare in improving care engagement and viral suppression. Social media is an important tool, especially for young MSM and transgender women, to support individual- (e.g., viral suppression) and community- (e.g., reduced transmission efficiency) level health. It may also be a useful tool for improving engagement with biomedical HIV prevention tools (e.g., PrEP use).

Vaccination of mice with gonococcal TbpB expressed in vivo from Venezuelan equine encephalitis viral replicon particles.

We investigated the immunogenicity of gonococcal transferrin binding protein B (TbpB) expressed with and without a eukaryotic secretion signal from a nonpropagating Venezuelan equine encephalitis virus replicon particle (VRP) delivery system. TbpB was successfully expressed in baby hamster kidney (BHK) cells, and the presence of the eukaryotic secretion signal not only apparently increased the protein's expression but also allowed for extracellular localization and glycosylation. Mice immunized with VRPs produced significant amounts of serum antibody although less than the amounts produced by mice immunized with recombinant protein. The response of mice immunized with VRPs encoding TbpB was consistently more Th1 biased than the response of mice immunized with recombinant protein alone. Boosting with recombinant protein following immunization with TbpB VRPs resulted in higher specific-antibody levels without altering the Th1/Th2 bias. Most of the immunization groups produced significant specific antibody binding to the intact surface of the homologous Neisseria gonorrhoeae strain. Immunization with TbpB VRPs without a eukaryotic secretion signal generated no measurable specific antibodies on the genital mucosal surface, but inclusion of a eukaryotic secretion signal or boosting with recombinant protein resulted in specific immunoglobulin G (IgG) and IgA in mucosal secretions after TbpB VRP immunization. The TbpB VRP system has potential for an N. gonorrhoeae vaccine.

Comparison of immune responses to gonococcal PorB delivered as outer membrane vesicles, recombinant protein, or Venezuelan equine encephalitis virus replicon particles.

Porin (PorB) is a major outer membrane protein produced by all Neisseria gonorrhoeae strains and has been a focus of intense interest as a vaccine candidate. In this study, the immunogenicity of PorB in mice was investigated after several immunization regimens. Outer membrane vesicles (OMV), recombinant renatured PorB (rrPorB), and PorB-expressing Venezuelan equine encephalitis (VEE) virus replicon particles (PorB VRP) were delivered intranasally (i.n.) or subcutaneously (s.c.) into the dorsal area or the hind footpad in three-dose schedules; the PorB VRP-immunized mice were given a single additional booster dose of rrPorB in Ribi adjuvant. Different delivery systems and administration routes induced different immune responses. Mice immunized s.c. with rrPorB in Ribi had the highest levels of PorB-specific serum immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Surprisingly, there was an apparent Th1 bias, based on IgG1/IgG2a ratios, after immunization with rrPorB in Ribi in the footpad while the same vaccine given in the dorsal area gave a strongly Th2-biased response. PorB VRP-immunized mice produced a consistent Th1 response with a high gamma interferon response in stimulated splenic lymphocytes and very low IgG1/IgG2a ratios. Immunization by OMV delivered i.n. was the only regimen that resulted in a serum bactericidal response, and it generated an excellent mucosal IgA response. Serum from mice immunized with rrPorB preferentially recognized the surface of whole gonococci expressing a homologous PorB, whereas serum from PorB VRP-immunized mice had relatively low whole-cell binding activity but recognized both heterologous and homologous PorB equally. The data resulting from this direct comparison suggested that important aspects of the immune response can be manipulated by altering the form of the antigen and its delivery. This information coupled with an understanding of protective antigonococcal immune responses will enable the design of the optimal vaccine for N. gonorrhoeae.