A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN® vaccine in healthy adults.

Since vaccination remains the only effective protection against orthopox virus-induced diseases such as smallpox or monkeypox, the strategic use and stockpiling of these vaccines remains of significant public health importance. The approved liquid-frozen formulation of Bavarian Nordic's Modified Vaccinia Ankara (MVA-BN) smallpox vaccine has specific cold-chain requirements, while the freeze-dried (FD) formulation of this vaccine provides more flexibility in terms of storage conditions and shelf life. In this randomized phase 3 trial, the immunogenicity and safety of 3 consecutively manufactured lots of the FD MVA-BN vaccine was evaluated.

Parents' Acceptance of COVID-19 Compared to Human Papillomavirus Vaccines.

Purpose: The first vaccine against SARS-CoV-2 (COVID-19) for adolescents 16 years and older in the United States received Emergency Use Authorization in December 2020. Soon after its approval, parents expressed concerns about vaccine safety for adolescents. Similar concerns about vaccine safety partially explain suboptimal human papillomavirus (HPV) vaccine uptake.

Chlamydia Vaccination: Parent Opinions and Implications for Future Promotion Programs.

Background: Chlamydia vaccines are currently under development and have the potential to lower the incidence of infection and disease, which are highest among adolescents and young adults. Ideally, a chlamydia vaccine would be administered to adolescents before sexual debut, a time when parents are the primary vaccine decision makers. This study explores parent opinions about an adolescent chlamydia vaccine to understand barriers and facilitators to uptake.

Risk Factors for Incident Hypertension Within 1 Year of Initiating Antiretroviral Therapy Among People with HIV.

Hypertension (HTN) is a common comorbidity among people with HIV and associated with an increased risk for atherosclerotic cardiovascular disease and chronic kidney disease. The relationship of antiretroviral therapy (ART) initiation to incident HTN remains a clinical question. We determined HTN incidence at 48 weeks of follow-up among ART-naive participants without HTN and not taking antihypertensive medications at ART initiation through randomized clinical trials through the AIDS Clinical Trial Group between 1999 and 2011.

Perceived Need and Acceptance of a Future Chlamydia Vaccine Among Health Care Providers.

Background: Chlamydia vaccination is a potentially important strategy to prevent infections and reduce the global burden of disease. Ideally, chlamydia immunization programs would require vaccinating adolescents before they engage in sexual activity. Communication by health care providers (HCPs) has been shown to have an impact on vaccine acceptance.

Hepatitis C Among High-Risk Alabamians: Disease Burden and Screening Effectiveness.

Background: The effectiveness of hepatitis C testing and linkage-to-care (LTC) is poorly characterized in low-resource jurisdictions facing gaps in harm reduction, including illegality of syringe exchange services. Effectiveness of a community-based test/LTC program was evaluated in Alabama.

Methods: In 2016-2018, shelters, drug treatment centers (DTCs), AIDS organizations, and Federally Qualified Health Centers (FQHCs) engaged in screening/LTC.

A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS.

Traditional replicating smallpox vaccines are associated with serious safety concerns in the general population and are contraindicated in immunocompromised individuals. However, this very population remains at greatest risk for severe complications following viral infections, making vaccine prevention particularly relevant. MVA-BN was developed as a non-replicating smallpox vaccine that is potentially safer for people who are immunocompromised.

Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).

Background: Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk.

Rationale and design of the Mechanistic Substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE): Effects of pitavastatin on coronary artery disease and inflammatory biomarkers.

Background: People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown.

Methods: REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs.

Rapid Boosting of HIV-1 Neutralizing Antibody Responses in Humans Following a Prolonged Immunologic Rest Period.

Background: The durability and breadth of human immunodeficiency virus type 1 (HIV-1)-specific immune responses elicited through vaccination are important considerations in the development of an effective HIV-1 vaccine. Responses to HIV-1 envelope subunit protein (Env) immunization in humans are often described as short-lived.

Methods: We enrolled 16 healthy volunteers who had received priming with an HIV-1 subtype B Env vaccine given with MF59 adjuvant 5-17 years previously and 20 healthy unprimed volunteers.

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial.

Background: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.

Methods: The trial was conducted at 34 sites in the US.

Vitamin D Supplementation Does Not Affect Metabolic Changes Seen With ART Initiation.

Background: Insulin resistance and lipid changes are common after antiretroviral therapy (ART) initiation. Observational studies suggest that vitamin D supplementation reduces the risk of developing diabetes and improves lipid profiles.

Methods: This 48-week prospective, randomized, double-blind, placebo-controlled study evaluated high-dose vitamin D3 (4000 IU daily) plus calcium supplementation (1000 mg calcium carbonate daily) in HIV-infected participants initiating ART with efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF).

The Impact of Statin and Angiotensin-Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Therapy on Cognitive Function in Adults With Human Immunodeficiency Virus Infection.

Background: Although statins, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are generally well tolerated, the impact of these therapies individually or in combination on the change in neurocognitive function in persons with human immunodeficiency virus infection is unknown.

Methods: The study included participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort participants not receiving a statin or ACEI/ARB within 30 days of first neurologic assessment (baseline), with assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit symbol test [DST]) from ≥2 measurements. Marginal structural models estimated the causal effect of statin or ACEI/ARB initiation on neurocognitive function; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter.

The hidden risk: Incorporating inflammation and HIV serostatus into coronary artery disease screening.

CAD is a well-established comorbidity associated with HIV infection. This association is in large part due to ongoing inflammation propagated by viremia and dysregulation of the immune system. Despite this knowledge, evidence to guide clinical management and screening for CAD among HIV-infected patients is lacking.

Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence.

HIV infection and antiretroviral therapy (ART) use are associated with perturbations in glucose and lipid metabolism. Increasing incidence of diabetes, cardiovascular disease, and obesity highlights the need for early identification and treatment of metabolic dysfunction. Newer ART regimens are less toxic for cellular function and metabolism but have failed to completely eliminate metabolic dysfunction with HIV infection.

Effects of once-daily darunavir/ritonavir versus atazanavir/ritonavir on insulin sensitivity in HIV-infected persons over 48 weeks: results of an exploratory substudy of METABOLIK, a phase 4, randomized trial.

Background: The phase 4, METABOLIK trial demonstrated that changes in metabolic parameters with darunavir with low-dose ritonavir (DRV/r) were comparable to those observed with atazanavir with low-dose ritonavir (ATV/r). A comprehensive assessment of the effects of these agents on insulin sensitivity will provide additional, relevant clinical information.

Methods: In this substudy of METABOLIK, HIV-1-infected, antiretroviral agent-naïve male subjects aged ≥18 years with a viral load of >1,000 copies/mL were randomized to receive DRV/r 800/100 mg once daily (qd) or ATV/r 300/100 mg qd, both with a fixed dose of tenofovir disoproxil fumarate/emtricitabine 300/200 mg qd.

Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.

Background.  First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness.

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

Background: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1).

Methods: This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1.

Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial.

Background: Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD).

Objective: To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation.

Design: 48-week prospective, randomized, double-blind, placebo-controlled study.

Effects of atorvastatin and pravastatin on immune activation and T-cell function in antiretroviral therapy-suppressed HIV-1-infected patients.

This retrospective study was designed to assess statin effects on T-cell activation from HIV-infected individuals. Peripheral blood mononuclear cells from antiretroviral therapy suppressed HIV-infected individuals receiving atorvastatin or pravastatin were evaluated for T-cell activation, exhaustion and function. Atorvastatin was associated with a significant reduction in CD8 T-cell activation (HLA-DR, CD38/HLA-DR) and exhaustion (TIM-3, TIM-3/PD-1) whereas pravastatin had no effect.

Impact of Poor Retention in HIV Medical Care on Hepatitis B Vaccination.

Background: We identified factors associated with complete hepatitis B vaccination of patients with HIV.

Methods: Retrospective analysis of patients undergoing HIV clinic orientation from 2000 to 2010. Vaccine-eligible patients had negative hepatitis B serologies at baseline.

HIV-related metabolic comorbidities in the current ART era.

Despite effective antiretroviral therapy (ART), HIV-infected individuals have residual chronic immune activation that contributes to the pathogenesis of HIV infection. This immune system dysregulation is a pathogenic state manifested by very low naïve T-cell numbers and increased terminally differentiated effector cells that generate excessive proinflammatory cytokines with limited functionality. Immune exhaustion leaves an individual at risk for accelerated aging-related diseases, including renal dysfunction, atherosclerosis, diabetes mellitus, and osteoporosis.

Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans.

The intranasal use of rintatolimod, a specific TLR-3 agonist, combined with trivalent seasonal influenza vaccine generated cross-protection against highly pathogenic H5N1 avian influenza in mice. The purpose of this clinical trial is to assess the safety and impact of rintatolimod on intranasal influenza vaccine in healthy adults. During Stage I of this Phase I/II clinical trial, 12 volunteers were immunized intranasally with 3 doses of FluMist seasonal influenza vaccine on Days 0, 28, and 56 followed by intranasal rintatolimod (50 μg, 200 μg, or 500 μg) 3 days later.