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.
Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in ...PWH with low to moderate traditional CVD risk.
To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation.
This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020.
HIV disease.
The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP).
The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% 2.6%-6.8%), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 3%), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 23% and 118 of 743 16%, respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median IQR IL-6 level, 1.71 1.05-3.04 pg/mL vs 1.45 0.96-2.60 pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01).
In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.
Abstract
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.
A5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in antiretroviral therapy (ART)-naive human immunodeficiency virus (HIV) controllers. ART further suppressed low-level viremia with reductions in T-cell activation and markers of immune exhaustion, suggesting possible clinical benefits for HIV controllers.
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).
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.
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.
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.
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.
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.
Abstract
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.
In a large cohort of human immunodeficiency virus (HIV) controllers (AIDS Clinical Trials A5308), HIV-specific T-cell responses were higher in nonviremic than in viremic controllers. Despite decreasing T-cell responses on antiretroviral therapy, controller status was preserved after therapy was stopped.
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.
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.
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.
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