Since 1976, each February has been host to a series of events recognizing the achievements and contributions of African Americans throughout U.S. history. It is as much a celebration as it is a time of education and reflection. Accordingly, UNMC has planned multiple events to share and commemorate African American culture. Check out the UNMC Newsroom’s post for full details and see below for an abbreviated summary of this week’s events.
Speakers and Panels
February 6th, 7pm Tiffany Gamble, executive director of Emerging Ladies Academy and CEO of Gamble Tech Firm, along with David Pollock, founder of Code Black, will discuss the need for more African Americans in IT. Presentation via YouTube.
February 7th, 12pm Presentation by Kia Noelle Johnson, PhD, associate director of the Arthur M. Blank Center for Stuttering Education and Research Satellite in Atlanta and chair of the board of directors for the National Black Association for Speech-Language and Hearing. Zoom link here.
February 8th, 1pm Preston Love Jr., former University of Nebraska Cornhusker football player, Nebraska Black Sports Hall of Fame inductee and founder of 4Urban, will present “Recent Attempts to Turn Wine into Water.” Love will discuss the fullness and richness of Black history and the deep waters of racism and politics. RSVP here for RSVP here for Zoom link.
Other Events
February 6th-24th Donate to a campuswide diaper and supply drive. Donations will go to A Mother’s Love and the Nebraska Diaper Bank. A list of donations and drop-off locations can be found here.
Heads up for later this month
February 25th A two-hour guided tour of North Omaha. On this tour, attendees will learn about the rich legacy of the area, the African American community and why North Omaha is a beacon of the past and important for the future. Pre-registration is required.
It is with profound sadness that the university of Nebraska medical center division of infectious diseases announces the passing of Dr. Diana Florescu. She was a mentor to countless trainees and faculty in Transplant ID, and an inspiration to many more. She was recently honored with the UNMC Scientist Laureate Award, the highest recognition given to UNMC faculty researchers for their contributions to advancing the science of healthcare.
Dr. Florescu will be remembered for her tenacity, grit, kindness, determination, and a positive energy that lit up every room, especially the ballroom when she danced.
We were blessed to have her as an esteemed faculty member in our division and are so grateful that she got her flowers while she was still with us. Our division of ID, and department of internal medicine are devastated, heartbroken as we surround her family with the love and support they need during this time.
More details can be found in this remembrance posting from UNMC, and information about her memorial service can be found in her obituary. Please keep her home and work families in your prayers.
The following post exploring a switch from IV to oral antibiotics for treatment of bacteremia was written by Molly Miller, PharmD, ID Pharmacist at Nebraska Medicine.
How do we usually treat bloodstream infections?
Standard management of bloodstream infections (BSIs) due to Gram-negative rods (GNRs) is empiric IV therapy with an active antimicrobial agent (typically a third or fourth generation cephalosporin, piperacillin-tazobactam, a fluoroquinolone, or a carbapenem) followed by eventual narrowing to definitive therapy based on culture results and susceptibilities. In addition to antibiotic therapy, perhaps the most important aspect of management is source control, which is accomplished by eliminating any nidus of infection (i.e., removing infected catheters/devices, draining abscesses or fluid collections). Treatment of GNR bacteremia is generally recommended for a duration of 7-14 days, but this can be extended for longer durations if the infection is complicated and source control is not achieved.
There has been recent interest in using oral therapy for many serious infections which were traditionally treated exclusively with IV therapy. Recent studies include the POET and OVIVA trials for endocarditis and bone and joint infections, respectively.1,2 Current evidence shows that there are several potential benefits to using oral therapy over extended courses of IV therapy, including reduction in catheter-related complications such as infection and thrombosis, reduction in length of stay (LOS), improvement in patient satisfaction and comfort, and reduction in healthcare costs.1-5
What specifically is the evidence for the use of oral antibiotics in this infection?
Though there have been no prospective, randomized, controlled trials published thus far regarding the use of oral therapy for GNR bacteremia (the SOAB trial is in progress), there is a growing body of observational data supporting this approach. In 2019, Tamma and colleagues published a multicenter, propensity-matched, retrospective cohort study comparing outcomes between adults with monomicrobial bacteremia due to Enterobacterales species who received oral step-down therapy versus continued IV therapy.3 Eligible patients had source control, clinical improvement on initial therapy, an active oral agent available to treat the causative organism, and the ability to take and absorb oral medication. Of the patients transitioned to oral therapy, most (84%) received a “highly bioavailable” antibiotic (fluoroquinolone or trimethoprim-sulfamethoxazole). The median time to oral switch was 3 days of IV therapy. There was no difference in all-cause mortality or recurrent bacteremia at 30 days between the oral and IV therapy groups; however, there was a shorter median time to discharge (5 days vs 7 days) in the oral step-down group.3 A number of smaller retrospective studies have shown similar results, with transition to oral therapy resulting in similar clinical outcomes with reductions in hospital LOS and IV line-associated complications.4,5
In 2016, a retrospective study was published by Kutob and colleagues, which included patients with GNR BSI and compared outcomes between patients receiving high, moderate, and low bioavailability agents.6 This study found that high bioavailability oral agents were effective definitive therapy; however, a higher failure rate was observed in patients receiving a moderate to low bioavailability agent compared to a high bioavailability agent (12-14% vs 2%). This poses the question: which oral antibiotics are suitable for use as step-down therapy in GNR BSI? A recent meta-analysis compared outcomes of oral step down to fluoroquinolones (FQs) or trimethoprim-sulfamethoxazole (TMP-SMX) versus oral beta-lactams (OBLs) for Enterobacterales BSI.7 This meta-analysis pooled a population of 2,289 patients, of whom 65% received FQs, 7.7% received TMP-SMX, and 27.2% received OBL therapy. Across the studies, patients were transitioned to oral therapy after a median of 3-5 days of IV therapy. There was no difference in mortality noted between groups receiving FQ or TMP-SMX compared to OBL (5.1% vs 3.5%, p = 0.63); however, patients receiving OBLs had a 2x higher odds of recurrent infection versus FQs. An important thing to note, however, is that bioavailability is only part of the equation, and other pharmacokinetic and pharmacodynamic (PK/PD) principles are important to consider when dosing oral antibiotics to treat serious infections. One specific concern the authors of this meta-analysis had was that 30-50% of patients in the included studies received suboptimal doses of OBLs. Another concern is that OBLs require every 6-8 hour dosing to attain target levels compared to every 12-24 hour dosing for TMP-SMX or FQs, which may introduce adherence issues and therefore increase the risk of treatment failure as well.
Though FQs and TMP-SMX have benefits compared to OBLs for the reasons discussed above, note that these therapies have significant toxicities, and it is important to consider drug- and patient-specific factors when choosing an oral antibiotic. FQs have many boxed warnings for serious adverse events, including tendon rupture, aortic aneurysm rupture, central nervous system effects, QT prolongation, dysglycemias, and increased risk of C. difficileinfection. TMP-SMX may cause blood dyscrasias, severe dermatologic reactions, hyperkalemia, and increased serum creatinine, and it also carries some drug-drug interactions, particularly with warfarin and other agents causing increased serum potassium. In comparison, OBLs are fairly well-tolerated, with rash and gastrointestinal side effects being most common. As always, patient co-morbidities, allergies/intolerances, and drug-drug interactions should be taken into account when choosing appropriate therapy.
In summary…
Patients who have achieved effective source control and are clinically stable (including hemodynamically stable and afebrile) who are able to tolerate and absorb oral antibiotics with no contraindications can be considered for transition to oral therapy if there is assurance of good adherence and close monitoring and follow-up. Oral antibiotics with high bioavailability have the most supportive evidence for use in these circumstances. While most often this is a FQ or potentially TMP-SMX, there is emerging evidence that some OBLs may be acceptable if dosed appropriately. Other considerations include patient-specific factors (allergies, co-morbidities, and drug-drug interactions), antibiotic penetration to the site of infection, and antimicrobial susceptibility. By transitioning patients to oral therapy when possible, we can reduce the risk of IV line-related complications, reduce length of stay, and improve patient satisfaction and comfort.
References:
Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. New Engl J Med. 2019;380(5):415-24.
Li H-K, Rombach I, Zambellas R, et al. Oral versus Intravenous Antibiotics for Bone and Joint Infection. New Engl J Med. 2019;380(5):425-36.
Tamma PD, Conley AT, Cosgrove SE, Harris AD, Lautenbach E, Amoah J, Avdic E, Tolomeo P, Wise J, Subudhi S, Han JH; Antibacterial Resistance Leadership Group. Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia. JAMA Intern Med. 2019 Mar 1;179(3):316-323. doi: 10.1001/jamainternmed.2018.6226. Erratum in: JAMA Intern Med. 2019 Nov 1;179(11):1607. PMID: 30667477; PMCID: PMC6439703.
Rieger KL, Bosso JA, MacVane SH, Temple Z, Wahlquist A, Bohm N. Intravenous-only or intravenous transitioned to oral antimicrobials for Enterobacteriaceae-associated bacteremic urinary tract infection. Pharmacotherapy. 2017;37(11): 1479-1483. doi:10.1002/phar.2024
Thurber KM, Arnold JR, Narayanan PP, Dierkhising RA, Sampathkumar P. Comparison of intravenous and oral definitive antibiotic regimens in hospitalised patients with Gram-negative bacteraemia from a urinary tract infection. J Glob Antimicrob Resist. 2019 Sep;18:243-248. doi: 10.1016/j.jgar.2019.03.013. Epub 2019 Mar 26. PMID: 30926468.
Kutob LF, Justo JA, Bookstaver PB, Kohn J, Albrecht H, Al-Hasan MN. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections. Int J Antimicrob Agents. 2016;48(5):498-503.
Punjabi C, Tien V, Meng L, et al. Oral Fluoroquinolone or Trimethoprim-Sulfamethoxazole vs beta-lactams as step-down therapy for Enterobacteriaceae Bacteremia: Systematic Review and Meta-analysis. Open Forum Infect Dis. 2019; 6(10): ofz364.
Last week Dr. Diana F. Florescu was honored at a celebration recognizing her recent achievement of being named the UNMC Scientist Laureate, the highest award UNMC bestows upon its researchers.
Dr. Florescu is a Professor in the Division of Infectious Diseases here at UNMC. She came to UNMC first in 2009 as a phenomenal clinician with a focus in treating infections in immunocompromised hosts (solid organ transplant recipients and individuals with malignancy), and over the next 14 years would develop a distinguished research career focused on viral infections in solid organ transplant recipients, including treatment and vaccines. This work has been nationally and internationally recognized with nearly 100 peer-reviewed articles, and in 2020, she was a recipient of the UNMC Distinguished Scientist award, recognizing the most productive researchers at UNMC in the previous 5 years. She did not slow this work during the COVID-19 pandemic, in fact, she escalated her clinical research, leading investigation as a top enrolling site for the Novovax (NVX-CoV2373) COVID-19 vaccine clinical trial, as well as other COVID-19 treatment trials and other non-COVID-19 studies in immunocompromised patients.
In addition to her extraordinary contributions to research and clinical care, Dr. Florescu has served as an invaluable mentor to the UNMC ID Faculty, residents, and APPs in the transplant ID service line. Outside of the hospital, she has been an advocate for her immunocompromised patients and patients experiencing homelessness in Omaha, and combines her love (and talent!) for ballroom dancing with this service, competing in and winning many dance competition fundraisers. UNMC ID is immensely proud of Dr. Florescu and excited to celebrate this recognition with her.
Here are some highlights of her outstanding accomplishments and comments made by a few of her mentors, colleagues, mentees, and friends celebrating her recognition. Congratulations, Dr. Florescu!
A #PharmToExamTable question about the evidence for using voriconazole in disseminated Histoplasmosis infection, answered by Molly Kernan, PharmD, a graduate of the UNMC College of Pharmacy and current pharmacy resident at Nebraska Medicine.
(Reviewed by Andrew Watkins, PharmD)
What is Histoplasma?
Histoplasma capsulatum is a dimorphic fungus that is endemic in the Ohio and Mississippi River valleys in the United States. It is primarily found in soil contaminated with bat and bird droppings.1 In immunocompetent patients, infection with H. capsulatum typically produces mild to no symptoms; however, in immunocompromised patients, the infection can spread systemically leading to pneumonia, pericarditis, or meningitis. Most immunocompetent patients will clear the infection without treatment, but more severe manifestations require systemic antifungal treatment.2
How do we treat it?
Current IDSA treatment guidelines stratify treatment by both site and severity of infection. In general, the preferred treatment for moderate to severe histoplasmosis of any body site is one to two weeks of intravenous (IV) amphotericin B followed by maintenance oral itraconazole for at least 12 weeks with the potential for life-long suppression in some patients. The guidelines also recommend voriconazole, among all three other available triazoles, as a second-line agent if itraconazole is not tolerated, failed, or contraindicated.3 There are many reasons itraconazole could be inappropriate for a specific patient. Itraconazole is not appropriate for patients with a history of cardiac or liver disease, chronic obstructive pulmonary disease (COPD), or preexisting hearing loss. There is rather intensive monitoring that is required with itraconazole therapy due to its unpredictable absorption and intrapatient variability. For these reasons, many patients and clinicians have chosen to use voriconazole as a second-line option for oral antifungal therapy, but there is limited evidence regarding its efficacy in treating histoplasmosis.
What evidence does exist?
Freifeld et al. followed nine patients with disseminated histoplasmosis who had failed amphotericin B or itraconazole and were placed on voriconazole as second-line therapy. All nine patients clinically improved during their voriconazole course. Random drug levels obtained ranged from undetectable (<0.125 μg/mL) to 8 μg/mL. While it is impossible to determine if the patients with undetectable blood levels had adequate blood levels of the drug, the fact that all nine patients clinically improved led to the conclusion that voriconazole is a potential treatment for histoplasmosis in some patients, but monitoring of blood levels is essential.5 Accordingly, IDSA guidelines suggest routine monitoring of blood levels if voriconazole is chosen for histoplasmosis treatment.3
In addition to the above PK study, there have been several case reports of patients with histoplasmosis who recovered after treatment with voriconazole. Dhawan et al. followed a three-year-old child diagnosed with disseminated cutaneous histoplasmosis who cleared the infection after treatment with voriconazole was started at a dose of 70 mg by mouth daily following treatment failure with the first-line agents.8 Another case study by Nakamura et al. followed a patient with AIDS who presented with disseminated histoplasmosis and was initially treated with 18 days of amphotericin B; he was then switched to oral itraconazole and started antiretroviral therapy. After two weeks, C-reactive protein and (1,3)-β-D glucan were still elevated, so he was switched to oral voriconazole. He clinically improved and was discharged from the hospital two weeks later. After two and a half years of voriconazole therapy, his (1,3)-β-D glucan was still positive, but he showed no residual symptoms of infection.9
Are there any large studies investigating these different treatment options?
Although there are no prospective studies available comparing itraconazole and voriconazole, the largest available data set comes from a retrospective cohort study performed by Hendrix et al. The study included 194 patients with confirmed histoplasmosis infection, with 40.7% classified as immunocompetent and 59.3% considered immunosuppressed in some manner (including malignancy, transplant recipient, HIV, or receiving chemotherapy, prednisone, a biologic agent or a nonsteroidal immunosuppressive agent). Amphotericin B induction was used in 45.9% of patients before switching to oral azole therapy, 90.2% of whom were placed on itraconazole and 9.8% of whom were placed on voriconazole. The results of this study indicate that voriconazole should not be chosen as a first line option if amphotericin B induction is not used, but that similar outcomes might be expected with maintenance therapy of itraconazole and voriconazole.7
Conclusion
In summary, there is limited data available to justify using voriconazole for the treatment of histoplasmosis infection. While there have been several case reports of patients successfully treated with voriconazole, PK data indicates there may be resistance emerging. In the only retrospective study available, there was a significant increase in mortality with voriconazole vs itraconazole when used as monotherapy with no amphotericin B induction. There was, however, no difference in mortality between voriconazole and itraconazole when amphotericin B induction was used. These data suggest that itraconazole should be used as a first-line option, but voriconazole may be an appropriate alternative option for patients who cannot take or tolerate itraconazole, especially if amphotericin B induction was used.
Wheat LJ, Frreifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45:807-25.
Freifeld A, Arnold S, Ooi W, Chen F, Meyer T, Wheat JL, et al. Relationship of Blood Level and Susceptibility in Voriconazole Treatment of Histoplasmosis. Antimicrob Agents Chemother. 2007 Jul;51(7):2656-57.
Wheat JL, Connolly P, Smedema M, Durkin M, Brizendine E, Mann P, et al. Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who railed fluconazole. J Antimicrob Chemoth. 2006 April 20;57:1235-1239.
Hendrix MJ, Larson L, Rauseo AM, Rutjanawech S, Franklin AD, Powderly WG, et al. Voriconazole Versus Itraconazole for the Initial and Step-down Treatment of Histoplasmosis: A Retrospective Cohort. Clin Infect Dis. 2020 Oct:1-6.
Dhawan J, Verma P, Sharma A, Ramam M, Kabra SK, Gupta S. Disseminated cutaneous histoplasmosis in an immunocompetent child, relepsed with itraconazole, successfully treated with voriconazole. Pediatr Dermatol. Oct 2010;27(5):549-551.
Nakamura A, Tawara I, Ino K, Matsumoto T, Hayashi A, Imai H, et al. Achievement of long-term remission of disseminated histoplasmosis in an AIDS patient. Medical Mycology Case Reports. 2020;27:25-28.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
In our previous post, we reviewed the merits of long-acting HIV treatments as a recent breakthrough in HIV/AIDS medical research. Briefly, these treatments may replace daily oral medication(s), instead offering injectable treatment that lasts for months between doses. This has the promise to ease the burdens of daily pills as well as help contribute to increased compliance, decreased HIV burden in the community, and potentially slow the development of antimicrobial resistance to these crucial drugs.
These same benefits touted for long-acting HIV treatment formulations theoretically can be applied to a host of other infectious diseases which require either short- or long-term antibiotic/antiviral regimens. This is a topic explored in many articles included in the Long-Acting and Extended-Release Formulations for the Treatment and Prevention of Infectious Diseases supplement in the journal Clinical Infectious Diseases. Today, we feature a few of theses articles as we explore how advances in HIV medicine may spill over and benefit all of Infectious Disease.
Tuberculosis is caused by the pathogen Mycobacterium tuberculosis and most commonly involves infection of the lung, among other tissues. Unlike most infections, tuberculosis can manifest acutely with primary tuberculosis as well as go dormant and asymptomatic for a period of years in a manifestation called latent tuberculosis. This latent type of infection can then reactivate, causing secondary tuberculosis. Despite this, it is considered a very treatable disease, but is complicated by high prevalence in developing nations where access to medical care may be suboptimal, a long course of antibiotic treatment needed (sometimes upwards of 6-9 months) for effective clearance, and a significant side effect profile of medications used. These factors make tuberculosis treatments ideal candidates for long-acting formulation. Indeed, this is the idea that is explored in this article, co-authored by Dr. Susan Swindells. Check out the full manuscript for an overview of the specific considerations and current preclinical advancements relevant for the development of long-acting technologies of TB drugs for treatment of latent infection, including attributes of target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies. With more research, this technology could be leveraged to generate a one-shot-cure for latent TB.
Hepatitis B and Hepatitis C are two additional infectious diseases where treatment may be substantially improved with long-acting formulation technology. The considerations of this are explored in two articles included in the supplement (Long-Acting Treatments for Hepatitis B and Prospects for Long-Acting Treatments for Hepatitis C). In the case of HBV, weekly injections of pegylated interferon alpha are already currently in use as a semi-long acting formulation. Even longer acting formulations may, with additional research, further effectively combat this virus and help prevent mother-to-infant transmission, which is the predominant route of transmission worldwide. This is crucially important as there is no current cure for hepatitis B infection, making long-term pharmaceutical treatment our only tool to prevent transmission. HCV, on the other hand, can now be cured in most people with 2-3 months of treatment. Much like in the case of tuberculosis, this requires adherence to consistent dosing of an oral medication. It follows then that the same benefits that long-acting formulations may provide to tuberculosis also extend to HCV infection, with the hope of a one-shot-cure that would benefit those living with HCV in areas without robust access to pharmacies or medical care. Read both articles (here and here) for the full details on the progress and work still needed before these treatments can be utilized to improve care for people living with hepatitis B or C.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
Dr. Susan Swindells, editor of the new Clinical Infectious Diseases supplement on long-acting formulations of infectious disease treatments.
Today, we feature a new supplement in Clinical Infectious Diseases, edited by UNMC ID’s Dr. Susan Swindells. This supplement contains articles chronicling and exploring the use of long-acting formulations in the treatment of infectious diseases. This category of therapy associated with HIV treatment is considered one of the major recent successes in HIV infection treatment, and involves the development of long-acting antiretrovial therapies (LA ARTs) which circumvent the need to take a complicated combination of multiple medications each day to remain HIV undetectable.
Researchers and Clinicians have been working to simplify treatment regimens for HIV for over a decade. With early formulations of antiretroviral treatments, people living with HIV (PWH) were prescribed a complicated combination of medications every day, with little room for error. In some cases, this proved problematic as interruptions in medical care such as shifts in insurance coverage, pharmacy shortages, medication side effects, and misunderstandings of dosing schedule by patients could all interrupt treatment and recovery of PWH. Advancements steadily improved over the years, transitioning from many pills per day to the possibility of just one. This particular advancement has significantly improved medication compliance in PWH. However, treatment adherence remains an important and significant public health aspect of this epidemic.
Now, new advancements are allowing injectable formulations of LA ARTs which can treat HIV for up to 8 weeks at a time, eliminating the need for daily medications and further improving treatment adherence. LA ARTs may have other benefits as well. In the introductory article of this supplement, co-authored by Dr. Swindells, it is noted that LA ARTs may be preferable over daily oral medications due to reduced stigma of taking HIV medication, alleviating some socioeconomic barriers to daily medication, and reducing the selection of antimicrobial resistance due to consistent and complete drug exposure. There are also downsides to long-acting therapies however, such as prolonged side effects due to difficulty of treatment discontinuation after an injection which is designed to last multiple weeks. Other disadvantages noted include fear of injections, costs, and efficacy. Nevertheless, many patients prefer LA ARTs, with some studies citing nearly all patients studied preferred the long-acting injectable over their previous oral treatment regimen (see our previous Research Digesthere).
Stay tuned for our next post, where we will dive into this supplement and explore how these same principles are being proposed to treat additional infectious diseases and may change the future of ID.
If you would like to read Dr. Swindell’s introductory article or the rest of this fascinating supplement, check out the full list of articles here.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
In this month’s research digest, we will cover recent work by UNMC ID faculty uncovering the link between HIV and various comorbidities associated with infection. HIV research is far from a new topic for this installment (see our previous HIV-focused research digests here and here), which speaks to the commitment of UNMC ID faculty to furthering HIV knowledge and research. Read on for a quick summary of two articles focused on HIV comorbidities dealing with brains and bones, namely HIV-associated neurocognitive disorder and bone fractures.
Dr. Swindells, co-author of a recent paper investigating HIV-associated neurocognitive disorder.
The first paper, co-authored by Dr. Susan Swindells, aims to define the functional similarities and differences between Alzheimer’s disease and HIV-associated neurocognitive disorder. The most common form of dementia in the general population is Alzheimers disease, affecting about 10% of adults age 65 or older. However, in those living with HIV, HIV-associated neurocognitive disfunction becomes even more common, affecting 40-70% of this population. Understanding how and where brain dysfunction occurs in these two diseases could help researchers design new treatments for both conditions. Using functional MRI imaging, that is exactly what the authors studied. They uncovered distinct differences in brain dysfunction in these two diseases, which may also lead to better diagnosis of these conditions in the future. Read the full article here for the details on what these differences were and what they may mean in a broader context.
Dr. Bares, co-author on a recent paper assessing the efficacy of hormone therapy for fracture prevention in WLWH.
The second paper spotlighted here is co-authored by Dr. Sara Bares and investigates the effectiveness of hormone therapy for the prevention of fractures in older women living with HIV (WLWH). This population has been reported to experience fractures at a higher rate than those living without HIV, but no data existed previously to suggest whether estrogen treatment could help prevent fractures in WLWH. The study found that smoking as well as certain demographic factors were associated with increased risk of fracture, but they did not find evidence that hormone therapy or HIV status affected fracture rates. They end with a call for further research of hormone therapy in this population, which may have other benefits beyond fracture prevention. For the full findings, read the paper here.
This post is part of an ongoing series on HIV/AIDS in recognition of HIV/AIDS awareness month 2022. In this series, we focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic.
A computer-generated 3D representation of the HIV virus. Source.
Today, we start a new series of posts on the UNMC ID Blog: Microbe Monday. This is a monthly installment introducing the microbiology behind the pathogens routinely encountered in the clinic. While these posts are geared more towards education, recent research advances and interesting historical context should be broadly interesting to all readers. Our first microbe is the human immunodeficiency virus (HIV). Read on to learn more about this important pathogen.
HIV
HIV is what is known as a retrovirus. This class of virus have the unique ability to convert its genetic material into DNA, much like the DNA that exists in human cells. Once this happens during infection, the viral DNA can hide within human DNA and evade detection for a period of months to years. This is also why HIV is so difficult to cure, with only a handful of cases ever reported. Functionally, there is no current cure for HIV, but this is an active field of research and there are many extremely effective treatments which have revolutionized the medicine of HIV care.
Advanced HIV results in an acquired immunodeficiency syndrome (also known as AIDS). In this syndrome, advanced HIV leads to severe immune system damage and increased susceptibility to multiple different cancers and infection by opportunistic pathogens (microbes which normally do not cause disease in healthy people, but thrive in those with compromised immune function). Advanced HIV is defined when a person with HIV has a reduced CD4 T-cell count (a specific type of immune cell), or diagnosis with one of these cancers or opportunistic infections, even without identified immune dysfunction.
Macrophages, T-cells, nooks and crannies
HIV is first thought of as an infection of T lymphocytes (T-cells), as these are the cells that clinicians use to characterize the severity of HIV infection. T-cells are specialized immune cells responsible for controlling many different aspects of your immune system. They come in two flavors: CD4 and CD8. CD4 T-cells are the primary target of HIV, which is important because these cells act as your immune system’s ‘generals’, coordinating the rest of your immune system to fight infections or cancers. It makes sense then that as these cells start to decline, people with HIV (PWH) start to become increasingly susceptible to infections and malignancy.
HIV (green) seen attached to the surface of a macrophage. Source.
However, it has been recently shown that this virus also infects other cell types. The most recognized example of this is HIV infection of macrophages. These cells are essential components of the ‘front lines’ of the immune response and are present in almost every part of the body. More recent research suggests that there may be additional cellular reservoirs where this virus may hide. Some emerging evidence point to certain types of glia, your brain’s supporting cells, which may inadvertently shield this virus from attack from the immune system or certain antiviral drugs (see this paper and others for further reading). But this is far from settled science, and there is much we still do not know about the mechanics of HIV infection.
The symptoms of HIV infection are unique from most viral infections. In the days and weeks following initial infection, 50-90% of infected individuals will experience a strong flu-like illness, with symptoms like fever, swollen lymph nodes, sore throat, rash, muscle and joint aches and pains, and fatigue. This acute infection quickly resolves as your immune system fights off the initial wave of HIV infection. At this point, the virus goes dormant for a period of months to years where is slowly depletes CD4 T-cell levels with few identifiable symptoms. This continues until the disease becomes advanced, meaning CD4 levels are low enough to lead to opportunistic infection or cancer. Clinical outlook for PWH who remain undiagnosed and/or untreated is poor, with most reaching complete T-cell depletion by 5-10 years after initial infection.
Fortunately, we have many very effective tools to fight these infections in the form of antiretroviral drugs. The way these drugs work varies, but all of them impede the ability of HIV to replicate itself. If treatments are taken consistently and life-long, undetectable HIV viral loads are not only possible, but clinically expected. Importantly, PWH who have undetectable HIV viral loads are unable to transmit the virus to others. This knowledge is the basis of the U=U (undetectable = untransmittable) campaign.
While treatment of HIV has been revolutionized since the onset of the epidemic, this infection remains incurable, making prevention the best medicine. Three main approaches are used currently to improve preventive measures in the population. First, public education with science-backed information is of prime importance. There are preventative measures that can be taken by those at risk of HIV that forms an important first barrier to spreading this infection. Second, since someone can be unknowingly infected with HIV for many years before diagnosis, routine testing is a powerful way to support one’s own and the community’s health. Lastly, certain medications can be prescribed for prevention called PrEP (Pre-Exposure Prophylaxis), when taken regularly, can reduce the risk of contracting HIV by 99%, providing an additional layer of protection to those who may be exposed to HIV. Additionally, the U=U campaign means that if we can initiate and maintain every person with HIV on antiretroviral treatment with an undetectable viral load, this can also significantly contribute to the prevention of onward transmission of HIV.
Conclusion
HIV is serious pathogen and an important consideration for public health. It has been just over 40 years since the first case of AIDS was diagnosed in the United States (June 1981). In this short period of time, advancements in research and clinical practice have dramatically changed the outlook for PWH. Proper use of preventive and treatment measures along with continued support for research on HIV/AIDS has the promise to continue to accelerate our ability to fight this infection.
Beginning with World AIDS Day on December 1st, the month of December is a time to raise awareness and reflect on the impact this epidemic has had on our communities and the world. There has been considerable progress made in the last 40 years on the treatment and support of people living with HIV infection (PWH), including much work conducted here at UNMC. But every inch of progress has been hard-fought, and there is still plenty of work to be done.
This month, in recognition of HIV/AIDS Awareness month, we will focus our posts on education, research, achievements, and medicine pertaining to the HIV/AIDS epidemic. We have many successes to celebrate, and hopefully many more to look forward to in the future of PWH care.
Keep an eye out for upcoming HIV/AIDS awareness posts, and please share what you learn. Together, we can raise awareness and help reach the U.S. Department of Health and Human Service’s goal, Ending the HIV Epidemic in the U.S.
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