Limited antiretrovirals are currently available for the management of multidrug-resistant (MDR) HIV-1 infection. Ibalizumab, a recombinant humanized monoclonal antibody, represents the first novel agent for HIV-1 management in over a decade and is the first monoclonal antibody for the treatment of MDR HIV-1 infection in combination with other forms of antiretroviral therapy in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Ibalizumab demonstrates a novel mechanism of action as a CD4-directed postattachment inhibitor and has a favorable pharmacokinetic profile that allows for a dosing interval of every 14 days after an initial loading dose. Clinical studies have demonstrated reasonably substantial antiretroviral activity with ibalizumab among a complex patient population with advanced HIV-1 infection who are receiving an optimized background regimen, where limited therapeutic options exist. Ibalizumab was well tolerated in clinical trials, and the most common adverse effects included diarrhea, nausea, dizziness, fatigue, pyrexia, and rash. Resistance to ibalizumab has also been observed via reduced expression or loss of the potential N-linked glycosylation sites in the V5 loop of the envelope glycoprotein 120. The mechanism of action, pharmacokinetic parameters, efficacy, and safety of ibalizumab present an advance in the management of MDR HIV-1 infection. Future studies and postmarketing experience will further determine longer-term clinical efficacy, safety, and resistance data for ibalizumab.
Kaposi sarcoma (KS) is a vascular tumor initiated by infection of endothelial cells (ECs) with KS-associated herpesvirus (KSHV). KS is dependent on sustained proinflammatory signals provided by intralesional leukocytes and continued infection of new ECs. However, the sources of these cytokines and infectious virus within lesions are not fully understood. Here, mast cells (MCs) are identified as proinflammatory cells within KS lesions that are permissive for, and activated by, infection with KSHV. Three validated MC lines were used to assess permissivity of MCs to infection with KSHV and to evaluate MCs activation following infection. Biopsies from 31 AIDS-KS cases and 11 AIDS controls were evaluated by IHC for the presence of MCs in KS lesions and assessment of MC activation state and infection with KSHV. Plasma samples from 26 AIDS-KS, 13 classic KS, and 13 healthy adults were evaluated for levels of MC granule contents tryptase and histamine. In culture, MCs supported latent and lytic KSHV infection, and infection-induced MC degranulation. Within KS lesions, MCs were closely associated with spindle cells. Furthermore, MC activation was extensive within patients with KS, reflected by elevated circulating levels of tryptase and a histamine metabolite. One patient with clinical signs of extensive MC activation was treated with antagonists of MC proinflammatory mediators, which resulted in a rapid and durable regression of AIDS-KS lesions. Using complimentary and studies we identify MCs as a potential long-lived reservoir for KSHV and a source of proinflammatory mediators within the KS lesional microenvironment. In addition, we identify MC antagonists as a promising novel therapeutic approach for KS. .
The SARS-CoV-2 pandemic exposed the inadequacy of infectious disease surveillance throughout the US and other countries. Isolation and contact tracing to identify all infected people are key public health interventions necessary to control infectious disease outbreaks. However, these activities are dependent upon the surveillance platform to identify infections quickly. A robust surveillance platform can also reinforce community adherence to behavioral interventions such as social distancing. In situations where contact tracing is feasible, all suspected cases and contacts of confirmed cases must be tested for a SARS-CoV-2 infection and effectively isolated. At the community level wastewater surveillance can identify areas where transmission is or is not occurring, and genetic sequencing of SARS-CoV-2 can help to elucidate the intensity of transmission independent of the number of known cases and hospitalizations. State and county public health departments should improve the infectious disease surveillance platform whilst the public is practicing social distancing. These enhanced surveillance activities are necessary to contain the epidemic once the curve has been sufficiently flattened in highly burdened areas, and to prevent escalation in areas where transmission is minimal.
Alcohol use among people living with HIV (PWH) has been increasingly recognized as an important component of HIV care. Transdiagnostic treatments, such as Acceptance and Commitment Therapy (ACT), that target core processes common to multiple mental health and substance-related problems, may be ideal in HIV treatment settings where psychological and behavioral health comorbidities are high. In advance of a randomized clinical trial (RCT), the overall objective of this study was to systematically adapt an ACT-based intervention originally developed for smoking cessation, into an ACT intervention for PWH who drink at hazardous levels. Consistent with the ADAPT-ITT model, the adaptation progressed systematically in several phases, which included structured team meetings, three focus group discussions with PWH (N = 13), and in-depth interviews with HIV providers (N = 10), and development of standardized operating procedures for interventionist training, supervision, and eventual RCT implementation. The procedures described here offer a template for transparent reporting on early phase behavioral RCTs.
Bacillus Calmette-Guerin (BCG) is derived from attenuated Mycobacterium bovis. It is the most common intravesical immunotherapy for treating early stage bladder cancer. Pott's disease is a form of mycobacterial infection that involves the vertebrae. This case highlights an unusual presentation of epidural abscess infection with M. bovis following BCG therapy for bladder cancer.
Young Men who have Sex with Men (MSM) continue to face disproportionate HIV risk. Despite its well accepted role in HIV prevention, pre-exposure prophylaxis (PrEP) uptake remains below desired goals. Systemic barriers to PrEP access, including insurance complexity, cost, and wait times to start PrEP may contribute to low PrEP engagement. We conducted in-depth interviews and designed a discrete choice experiment (DCE) to assess preferences for and barriers to PrEP access in the United States. Methods: We conducted in-depth interviews with 18 MSM aged 18–30 years old who were not on PrEP and created a DCE based on the results. For the DCE, a convenience sample of young MSM in the United States who reported recent condomless anal sex was recruited through social media applications. Consenting participants provided sociodemographic information and responded to a series of 10 choice tasks about PrEP access. Preferences were analyzed utilizing marginal willingness-to-pay (mWTP) methods. Results: In-depth interviews revealed preferences for highly effective PrEP and concerns about barriers to access due to insurance coverage and privacy. The online DCE was completed by 236 eligible MSM aged 18–30. The most-preferred PrEP package—with all elements significantly preferred over other options—was insurance covered, could be maintained confidential from parents and employers, was available immediately, and had an online option. Need to take out new insurance or add a supplemental insurance in order to cover PrEP significantly detracted from willingness to pay for a PrEP program. Attributes most associated with willingness to pay for PrEP were PrEP being covered by an insurance the client already has and insurance coverage that was private. Conclusions: Young MSM at high risk for HIV in the United States who are not currently on PrEP showed strong preferences for PrEP options that were covered by insurance and could be kept confidential from parents and employers. Lack of these options may present major barriers to PrEP access among young MSM who are at particularly high risk. Rapid access to PrEP, as well as the option of receiving some care online, may also enhance PrEP uptake.
Background: The COVID-19 pandemic has exacerbated health inequities in vulnerable populations. Linguistic and sociocultural barriers, misinformation, and mistrust of Western medicine hinder public health outreach to diverse refugee and non-refugee immigrant communities. SUNY Upstate Medical University partnered with local resettlement agencies and health navigators to expand outreach and screening to this hard-to-reach population. Methods: Health navigators engaged participants for enrollment and screening. SARS-CoV2 status was assessed via RT-PCR of saliva swabs. Surveys captured COVID-19-related psychosocial behavioral insights.Results: Over 9 weekly sessions, 603 individuals in 195 refugee/immigrant households from 27 countries of origin were screened. COVID-19 positivity rate was 2% for households and 0.2% amongst individuals. Surveys provided insight into households’ concerns and health behaviors, and a space to reinforce protective behaviors and address misinformation and stigma. Conclusions: During these unprecedented times, our interdisciplinary community-clinical partnership successfully implemented COVID-19 screening, outreach, and support to local refugees and non-refugee immigrants through trusted networks of culturally, socially, linguistically congruent health navigators.
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