HIV

First Cases of HIV Transmitted Through Cosmetic Needles Identified: CDC

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Patients received facials at a spa.

First Cases of HIV Transmitted Through Cosmetic Needles Identified: CDC
An ampule with Botox, with the European name “Vistabel,” at a cosmetic treatment center in Berlin in this Jan. 29, 2007

Multiple people contracted human immunodeficiency virus (HIV) through cosmetic needles after receiving facials at an unlicensed spa in New Mexico, according to the Centers for Disease Control and Prevention (CDC).

Three women who received platelet-rich plasma (PRP) microneedling facials, also known as vampire facials, at the spa contracted HIV and an investigation pointed to the facials as the method of transmission, a new paper from CDC scientists states.

The spa in question, the since-shuttered VIP Salon, was dubbed spa A in the paper.

“This investigation is the first to associate HIV transmission with nonsterile cosmetic injection services. A common exposure to spa A among clients without behaviors associated with HIV acquisition helped identify a possible cluster association, and analysis of additional data suggested that HIV transmission likely occurred via receipt of PRP with microneedling facial procedures,” said the scientists, who worked with New Mexico health officials.

The source of the contamination remains unknown, they said.

PRP microneedling facials involve taking blood from a person and separating out PRP. Then, a microneedle makes holes in the person’s skin, and the PRP is applied to the holes.

COVID-19 Vaccine Protection Among Children Plummets Within Months: CDC Study

The procedure is said to help treat acne and have other health benefits.

New Mexico authorities announced in 2019 that they were investigating the VIP Spa after people contracted HIV following visits to the spa. Officials were providing free testing of any people who received treatments, including the microneedling facials, at the spa.

An inspection by authorities led to the closure of VIP Spa after the identification of unsafe practices

Maria de Lourdes Ramos de Ruiz, former owner of the spa, was later hit with felony charges, including practicing medicine without a license. She pleaded guilty in 2022 to five counts.

“This is a warning to those who place profit over the health and safety of New Mexico consumers, and I remain highly concerned that these procedures are not being regulated at the state and federal level,” New Mexico Attorney General Hector Balderas said at the time.

Investigation

New Mexico officials described two HIV cases among spa visitors previously. A wider investigation identified additional patients, scientists with the state and the CDC said in the new paper.

Through calls, surveys, and other methods, authorities found five people with HIV, four of whom received microneedling at the spa in 2018. The fifth was in a sexual relationship with a spa client. Analysis of the patients’ blood showed that their cases were all related to the facility.

The cases involving the man and woman in a sexual relationship were stage 3 or chronic HIV, which suggests “that their infections were likely attributed to exposures before receipt of cosmetic injection services,” according to the scientists.

But no alternative explanations for the infections among the other three female patients were discovered.

“The other three patients in this cluster had no known social contact with one another, and no specific mechanism for transmission among these patients was confirmed,” scientists said. “Evidence suggests that contamination from an undetermined source at the spa during spring and summer 2018 resulted in HIV-1 transmission to these three patients.”

HIV is a virus that attacks immune systems and can lead to acquired immunodeficiency syndrome (AIDS) if not treated. Symptoms include sore throat, fatigue, and ulcers in the mouth. Most people who contract the illness are gay or bisexual. While there is no cure for HIV, it can be controlled through available treatments.

Nearly 200 other spa clients and their sexual partners were tested through 2023 as part of the investigation but none tested positive for HIV, hepatitis B, or hepatitis C, according to the paper.

The findings highlight the importance of looking at “novel sources of HIV transmission among persons with no known HIV risk factors,” the scientists said.

They also encouraged facilities to implement practices to control infections to try to prevent the transmission of bloodborne pathogens.

Inspection Results

When the spa was inspected in 2018, authorities saw troubling practices.

Lying on a kitchen counter, for instance, were a centrifuge, a heating dry bath, and a rack of unlabeled tubes containing blood.

In a refrigerator, stored with food, authorities found tubes of blood without labels, as well as medical injectables such as Botox.

Unwrapped syringes were located in multiple places, including in drawers.

No steam sterilizer was present and certain items designed to be disposable were cleaned and reused by staffers at the spa, authorities said.

The investigation was hindered by disorganized records, including the lack of a system for scheduling appointments, according to the paper. Such systems usually include contact information for clients. Investigators combed through handwritten records and other documents to identify people who may have undergone the microneedling procedure.

“Incomplete spa client records posed a substantial challenge during this investigation, necessitating a large-scale outreach approach to identify potential cases, as opposed to direct communication with all clients,” researchers said. “Requiring maintenance of sufficient client records to ensure adequate traceback by regulated businesses that provide injection services could ensure adequate capability to conduct traceback.”

CRISPR could disable and cure HIV, suggests promising lab experiment

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The gene-editing technique CRISPR disabled HIV that lay dormant in immune cells in a lab experiment, raising hopes for an eventual cure

An electron micrograph of HIV, which currently requires lifelong medication

A new way to eradicate HIV from the body could one day be turned into a cure for infection by this virus, although it hasn’t yet been shown to work in people.

The strategy uses a relatively recent genetic technique called CRISPR, which can make cuts in DNA to introduce errors into viral genetic material within immune cells. “These findings represent a pivotal advancement towards designing a cure strategy,” researcher Elena Herrera Carrillo at the University of Amsterdam in the Netherlands said in a statement.

While infection with HIV was once nearly always fatal, those with the virus can now take drugs that stop it from reproducing. This gives them a nearly normal lifespan, as long as they diligently take their medicines every day.

But when people are first infected, some of the virus inserts its DNA into their immune cells, where it stays dormant. If they stop taking their HIV medicines, this DNA “reawakens” and the virus starts spreading through their immune systems again.

For a cure, we need some way of killing any dormant virus in the body. Several strategies have been tried, but none has so far been found to work.

The latest approach uses a gene-editing system called CRISPR. Originally discovered in bacteria, this homes in on a specific DNA sequence, making cuts in it. By changing the DNA sequence being targeted, the system can potentially be turned into a form of gene therapy for many conditions, with the first such treatment having been approved last year in the US and UK as a cure for sickle cell anaemia.

Several groups are investigating using CRISPR that targets a gene in HIV as a way of disabling dormant virus. Now, Carrillo and her team have shown that, when tested on immune cells in a dish, their CRISPR system could disable all virus, eliminating it from these cells. The work is due to be presented at the European Congress of Clinical Microbiology and Infectious Diseases in Barcelona, Spain, next month.

Jonathan Stoye at the Francis Crick Institute in London says that although the results are encouraging, the next step is trials in animals and eventually people to show the treatment can reach all the immune cells with dormant HIV. Some of these cells are thought to reside in bone marrow, but there may be other body sites involved too, he says. “There’s still a fair amount of uncertainty about whether there are other reservoirs in other parts of the body,” he says.

A Californian firm called Excision BioTherapeutics has previously shown that a CRISPR-based approach can reduce the amount of dormant virus in monkeys infected with a similar virus to HIV.

SCIENTISTS MANAGE TO CUT HIV OUT OF INDIVIDUAL CELLS

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“THESE FINDINGS REPRESENT A PIVOTAL ADVANCEMENT TOWARDS DESIGNING A CURE STRATEGY.”

Getty Images

Scientists say they’ve been able to literally cut out the “bad” bits of DNA from infected cells to eliminate HIV using CRISPR gene editing.

While it’s still far too early to conclude whether the technique could be used to cure HIV, as the BBC reports — let alone whether it’s safe and effective in the long run — scientists are hopeful that gene therapy could be part of a treatment.

HIV, or human immunodeficiency virus, attacks the body’s immune system and has raged around the world for decades, causing untold deaths.

Despite considerable progress in the development of highly effective treatments, there still isn’t a cure.

Now, scientists at the University of Amsterdam have presented early findings of a “proof of concept” gene editing process that eliminates any trace of “dormant” HIV in cell samples.

“We have developed an efficient combinatorial CRISPR-attack on the HIV virus in various cells and the locations where it can be hidden in reservoirs, and demonstrated that therapeutics can be specifically delivered to the cells of interest,” said project lead and University of Amsterdam researcher Elena Herrera Carrillo in a statement.

“These findings represent a pivotal advancement towards designing a cure strategy,” she added.

CRISPR is a group of DNA sequences that were derived from bacteriophages. By combining them with an enzyme called Cas9, scientists are able to edit — essentially cut and paste — genes with revolutionary results, from making the human liver produce less cholesterol to restoring color vision and treating sickle cell disease.

Carrillo and her colleagues tried to address the problem of dormant HIV DNA reawakening while hiding in the human body’s immune system. Using CRISPR, they managed to disable the dormant virus in immune cells arranged on a dish.

But many questions remain. For one, cells infected with dormant HIV could lurk in other areas of the body, as New Scientist reports.

Then there’s the question of whether such a procedure would be safe in animals or humans, instead of the cell samples Carrillo’s team was working on.

“Much more work will be needed to demonstrate results in these cell assays can happen in an entire body for a future therapy,” University of Nottingham gene-therapy technologies associate professor James Dixon told the BBC.

But the proof of concept is giving researchers hope. For instance, pharmaceutical company Excision BioTherapeutics announced a new approach to use CRISPR to treat HIV late last year, though whether it’s actually effective remains unclear.

At the end of the day, the possibility of these treatments having unintended consequences could eventually slow down progress significantly.

“Off-target effects of the treatment, with possible long-term side effects, remain a concern,” Francis Crick Institute, London virus expert Jonathan Stoye told the BBC.

“It therefore seems likely that many years will elapse before any such CRISPR-based therapy becomes routine,” he added, “even assuming that it can be shown to be effective.”

Invasive meningococcal disease risk sixfold higher for people with HIV

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Key takeaways:

  • Between 2009 and 2019, people with HIV had a sixfold higher risk of invasive meningococcal disease.
  • Many people with HIV (50%) had not received the recommended MenACWY vaccine.

People with HIV continue to have a higher risk for invasive meningococcal disease compared with people without HIV regardless of the 2016 recommendation that they be vaccinated against it.

“This analysis was a follow-up to a previous evaluation of invasive meningococcal disease (IMD) risk in persons with HIV to better understand how the declining incidence of IMD in the U.S., along with the 2016 Advisory Committee on Immunization Practices MenACWY recommendation for people with HIV, has affected IMD risk in people with HIV,” Gabrielle Cooper, DrPH, MPH, epidemiologist at the CDC’s National Center for Immunization and Respiratory Diseases, told Healio.

IDN0224Rudmann_Graphic_01_WEB
Data derived from Rudmann KC, et al. Open Forum Infect Dis. 2024;doi:10.1093/ofid/ofad696.

To better understand the incidence of IMD and how the 2016 routine quadrivalent meningococcal conjugate vaccine recommended for people with HIV has affected IMD risk, Cooper and colleagues evaluated cases of IMD reported between 2009 and 2019 within the Active Bacterial Core surveillance area among patients aged 13 and older. In total, 636 cases were reported — 16 of which were among people with HIV.

After comparing the incidence of IMD in people with HIV and people without HIV between 2009 and 2019, data showed a sixfold higher IMD risk among people with HIV vs. those without (0.96 vs. 0.16 cases per 100,000).

According to the study, most people with HIV had not received the MenACWY vaccine (50%) or had an unknown vaccination history (43.8%), with only one patient (6.3%) reporting previous MenACWY vaccination.

Additionally, five (31.3%) of the cases occurred after the 2016 ACIP recommendation for routine MenACWY vaccination in people with HIV. Of those five, four (80%) were unvaccinated and one (20%) had an unknown vaccination history.

“As persons with HIV continue to experience increased IMD risk, there is a growing importance of improving implementation of the ACIP MenACWY vaccine recommendation for people with HIV,” Cooper said. “There is also need for continued monitoring of IMD in people with HIV.”

Perspective

Susan Kline, MD, MPH

This article reports the analysis of the CDC’s Active Bacterial Core surveillance data regarding invasive meningococcal disease from 2009-2019. Of note the authors found a sixfold increase in the risk for invasive meningococcal disease in persons living with HIV compared with those without HIV infection.

Despite the relatively new availability of a quadrivalent meningococcal vaccine, and the 2016 US ACIP recommendation for routine quadrivalent meningococcal conjugate vaccination among persons with HIV infection, ages 2 months and up, there remain many unvaccinated persons living with HIV. The mortality rate of invasive meningococcal disease in this study was 18.8% in persons living with HIV, and a majority were still unvaccinated.

There remains a large opportunity to immunize many more persons living with HIV with the new quadrivalent meningococcal vaccine. Doctors providing medical care to persons living with HIV should focus efforts on encouraging their patients to take the available quadrivalent MenACWY meningococcal vaccine because these patients have a sixfold higher risk for invasive meningococcal disease than those not infected with HIV and because mortality from invasive meningococcal disease is still high (approximately 20%).

Susan Kline, MD, MPH

Professor of medicine, Infectious Disease Division

University of Minnesota Medical School

Cannabis use may limit HIV tissue reservoirs in ART-treated men

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Key takeaways:

  • The odds of tissues harboring HIV DNA and viral DNA copies in those tissues were significantly lower in people who used cannabis.
  • Levels of proinflammatory cytokines were also significantly lower.

A postmortem study of men with HIV who were being treated with ART revealed that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs.

“[This study was prompted] due to an urgent need to eliminate potential HIV tissue reservoirs in infected and ART-treated individuals to prevent a rebound of HIV when people are off ART, to achieve true HIV cure,” Charles Wood, PhD, cancer crusader professor in the department of Interdisciplinary Oncology and associate director of basic science at the Stanley S. Scott Cancer Center, told Healio.

IDN0224Liu_Graphic_01
A recent study in The Journal of Infectious Diseases showed that cannabis use was associated with reduced sizes and reduced inflammatory cytokine expression of subtype C HIV reservoirs in men with suppressed viral load.Image: Adobe Stock.

“Numerous prior attempts [at eliminating latent HIV reservoirs], such as using HDAC inhibitors, have mostly been unsuccessful. Novel approaches need to be developed,” Wood said.

He added that although it is controversial, cannabis has been shown to reduce simian immunodeficiency viral load in infected macaques because of its potential anti-inflammatory effects.

“We have decided that in order to test this directly on humans, we conducted the study through studying autopsy tissues of HIV-infected individuals, either on cannabis users or nonusers,” Wood said.

The researchers systematically collected postmortem brain tissues — including tissue from the frontal lobe, parietal lobe, temporal lobe, occipital lobe, hippocampus, cerebellum, basal ganglia and choroid plexus — as well as peripheral tissues and plasma samples from 20 men with subtype C HIV and with suppressed viral load in Zambia. Ten of these men tested positive for cannabis use.

The researchers then compared viral burden and inflammatory cytokine in tissues among people with HIV and suppressed viral load who used cannabis and those who did not.

Overall, the study demonstrated that the odds of tissues harboring HIV DNA and the viral DNA copies in those tissues were significantly lower in people who used cannabis. Specifically, the data showed that tissues of people using cannabis showed 0.16 times, or sixfold lower odds, of harboring HIV long terminal repeats (LTR)DNA (95% CI, 0.08-0.32) and 0.07 times, or 14-fold lower odds, of harboring all 3 LTR/gag proteins/envproteins DNAs (95% CI, 0.03-0.17).

The researchers also found that the transcription levels of proinflammatory cytokines IL-1 beta and IL-6 in lymphoid and appendix tissues of people using cannabis were also significantly lower, as were messenger RNA levels of IL-1 beta and IL-6 in appendix tissues. The team also analyzed cytokine mRNA levels in tissues and found very low levels of viral DNA and RNA.

Taken together, the researchers wrote that these results indicate that cannabis use is associated with “reduced proinflammatory cytokine expression but did not alter anti-inflammatory cytokine expression in subtype C HIV lymphoid tissue reservoirs that harbored most of proviruses.”

“Cannabis use may have potential positive effects in limiting HIV tissue reservoirs and reduced the number of copies of residual HIV in antiviral treated aviremic individuals,” Wood said. “However, the circulating HIV subtype in Zambia and in sub-Saharan Africa are subtype C HIV, which is different from the most common strains in the West. Thus, further studies need to determine whether this holds true for other HIV subtypes.”

Advanced HIV as a Neglected Disease

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In the early decades of the global response to HIV/AIDS, the focus was on saving lives. And rightly so: without antiretroviral treatment (ART), people lived less than a year, on average, from the time they developed AIDS. But over the past 15 years, the focus has shifted to virologic control. Since modeling and trials have shown that treating HIV could not only benefit the infected person but also eliminate transmission, viral suppression has become the main measure of success for HIV programs. Global targets have focused attention on the numbers of people who are tested, who begin receiving treatment, and in whom viral suppression is achieved. Reducing mortality is no longer a central metric.

For many years, HIV treatment was given only to people with a low CD4 count, who were at the highest risk for severe illness and death. In 2015, two large randomized trials showed that treatment should be started as soon as possible after infection. These results led to a rapid global shift in policy and funding, with the goal of getting as many people on treatment as early as possible. This change led to the perception that CD4 testing was no longer essential. To help pay for increased treatment coverage and assessment of its impact on virologic outcomes, donors and countries reduced their support for CD4 testing, and testing rates within ART programs declined rapidly. This shift occurred despite consistent inclusion of CD4 testing in clinical guidelines from the World Health Organization (WHO) and other leading authorities, who deemed it essential at baseline and when a patient returned to care.

Although treatment coverage has increased substantially in recent years, any associated reductions in AIDS-related deaths have been smaller and slower than expected. The proportion of people with advanced HIV disease (defined by a CD4 count of less than 200 cells per cubic millimeter) remains high: it is estimated that more than 4 million people have advanced HIV disease, and each year more than 600,000 of them are expected to die.1 Many of these deaths can be prevented — if the global HIV/AIDS community reconsiders who is at risk for the worst outcomes; determines what infections lead to the greatest morbidity and mortality; invests in new tools for diagnosing, preventing, and treating these conditions; and supports the systems required for delivering those tools effectively.

Until recently, advanced HIV was viewed as a problem of late presentation, so the solution was thought to be testing more people and diagnosing the disease earlier. Although late presentation remains problematic, however, advanced HIV is now predominantly seen among people who started care but were not effectively engaged or have disengaged, returning only when they’re ill. Loss to care has long been recognized as a challenge, but we’ve only recently begun to recognize the extent to which cycling in and out of care increases the burden of advanced HIV disease.2 The health risk posed by interrupting treatment is established: trial data show a precipitous drop in CD4 cell count within the first 2 months after treatment is stopped.3

The leading causes of HIV-related deaths appear to have changed little over time: they include tuberculosis, cryptococcal meningitis, and pneumocystis pneumonia, among others. But there have been few recent attempts to confirm empirically whether these infections are still the major killers of people with HIV in the highest-burden countries. Hospitalized HIV patients continue to routinely test positive for tuberculosis and cryptococcal meningitis, but these findings partly reflect availability bias: the diagnostics for these diseases are the ones most frequently available to clinicians. To address this gap, Emory University plans to launch a study in 2024 combining minimally invasive tissue sampling with rigorous cause-of-death analysis. The study will take place at hospitals in four African countries with varying geography, resources, and progress in epidemic response.

Meanwhile, all opportunistic infections remain challenging to manage with existing tools, and there are few new developments on the horizon. Recently, the WHO surveyed the research pipeline for advanced HIV and found very little research and development.4 Overall, HIV is not a neglected disease — tens of billions of dollars have been invested in scaling up access to prevention and treatment. In the past decade, however, advanced HIV has become neglected, with limited attention paid to either consistently using existing tools or finding new tools for preventing AIDS-related deaths. As defined by the WHO, the “neglected tropical diseases” comprise 20 diseases and disease groups that cause devastating health, social, and economic consequences among the world’s poorest people; they are defined by a lack of sufficient resources for and inadequate research attention to prevention, screening, diagnosis, and treatment. The same shortcomings now apply to advanced HIV disease.

Driving the neglect of advanced HIV is a shrinking ability to diagnose the problem. Key manufacturers of CD4 cell count tests are withdrawing from the market in low- and middle-income countries, judging that decreased demand means these tests are no longer needed. Conventional laboratory-based CD4 testing capacity is being defunded and dismantled, leaving treatment programs reliant on a very small number of rapid CD4 testing devices of variable performance, with no guarantees of sustainable access.

Once HIV disease becomes advanced, there are few tools for preventing and treating the resulting opportunistic infections. A survey conducted in 48 African countries up to the end of 2022 found limited capacity for diagnosing common opportunistic infections — in particular, pneumocystic pneumonia, cryptococcal diseases, and histoplasmosis.5 There has been recent progress in some areas, including simpler, safer treatment for cryptococcal meningitis and promising new diagnostic tools for histoplasmosis and talaromycosis. The Drugs for Neglected Diseases Initiative is investing in new tools for managing cryptococcal meningitis; this investment is very welcome but also underscores the point that advanced HIV is being neglected by the pharmaceutical industry.

Meanwhile, for other opportunistic infections, progress remains minimal. These opportunistic infections include severe bacterial infections, pneumocystis pneumonia, and toxoplasmosis — all among the leading causes of deaths since the HIV pandemic began, but all difficult to diagnose and treat in resource-limited settings where the burden is greatest. In November 2023, the Bill and Melinda Gates Foundation granted the University of Cape Town funding to conduct a large trial to assess whether providing azithromycin to all people with severe immunosuppression can reduce mortality from severe bacterial infections. This research is necessary but insufficient: results are not expected for 4 to 5 years, and with current funding the trial can include only adults. A key priority remains development and deployment of tools for preventing, diagnosing, and treating severe bacterial infections as part of a public health response attentive to risks of antibiotic resistance. Many other causes of AIDS-related death, including cytomegalovirus infection and cancers such as Kaposi’s sarcoma, are extremely challenging to manage, and little research into new diagnostics and treatments is under way.

Measurement drives and directs action. As global targets have focused attention on viral suppression, attention to mortality has diminished. National programs generally do not collate or report data on causes of HIV-related deaths; we therefore lack reliable estimates of mortality and the true scale of deaths related to advanced HIV disease. Although these data are complex to capture, reliable measurement of AIDS-related deaths, disaggregated by major causes, needs to be at the heart of surveillance at the national, regional, and international levels. A better understanding of the primary causes of death may motivate funders and policymakers to strengthen systems for delivering the services required for preventing deaths associated with advanced HIV disease.

Neglect of advanced HIV disease is an unintended consequence of the global shift in objectives from treating the sickest people to treating all who are infected. Improved access to antiretroviral therapy is necessary for reducing deaths, but it is not sufficient. We believe donors should continue supporting CD4 testing for diagnosing advanced HIV and guiding diagnosis and treatment of opportunistic infections. For patients with advanced HIV, medicine urgently needs better tools focused on the diseases that are confirmed to be the most prevalent in the relevant setting, so that we can respond effectively to the main causes of illness and death.

Controversial gene-editing procedure to fight AIDS is again being considered by scientists, despite disastrous results a decade ago

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When the Centers for Disease Control and Prevention announced last year that people who take HIV medication religiously for six months can theoretically get to point where they can’t transmit the virus, it was considered a huge advancement. There remains no cure for HIV and AIDS, although it is not the death sentence that it used to be. There have been triumphs and setbacks in the quest to find a cure, and now scientists are considering revisiting a past disaster in hopes of emerging victorious this time around.

A controversial gene editing procedure is at the heart of the new approach. Gene editing recently gained FDA approval for treating cancer and one type of blindness, and some researchers are hoping that HIV/AIDS can soon be added to the list.

Gene therapy has already helped some patients make their cells more resistant to HIV. In 2014, scientists removed some of Matt Chappell’s blood cells, disabled a gene in order to help the cells resist the HIV virus, and then returned the edited cells to his body. It has been the closest thing to a cure for Chappell, who has gone from taking the strongest AIDS drugs available for more than a decade to not needing the medications at all for more than three years. His body even managed to keep the virus in check in the midst of cancer treatments that wreaked havoc on his immune system last year.

Chappell’s story is far from ordinary. Of the 100 people who took part in those experiments, just a few of them were able to give up their HIV drugs in the long run. The rest of them still have to take medication to suppress their HIV.

Despite these discouraging numbers, the researchers want to give it another try. They believe that they can improve this treatment and are now testing some tweaked approaches in which they’ve doctored DNA in a different way.

Temple University researchers have developed a method of gene editing that can detect HIV DNA in a person’s T-cell genome, which is a set of DNA pertaining to a certain kind of white blood cells. When this DNA has been edited out, the loose genome ends that were previously attached to the HIV will be rejoined by the DNA repair system within the cell. This leaves the cell free from HIV and protected from new infections.

An Incarcerated Individual With Weight Loss and Interstitial Pulmonary Infiltrates

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Case

A 60-year-old man incarcerated in Ohio presented to the emergency department after a syncopal episode. He reported recent exposure to COVID-19 but had no fevers, chest pain, cough, dyspnea, or diarrhea. He had unintentionally lost 13.6 kg over 2 years. His temperature was 37 °C (98.5 °F); blood pressure, 124/75 mm Hg; pulse, 123/min; respiratory rate, 22/min; and oxygen saturation, 96% on room air. Findings on physical examination were unremarkable. His white blood cell count was 3300/μL (reference, 4500-11 000/μL) with an absolute lymphocyte count of 200/μL (reference, 1000-4800/μL). Chest radiograph showed bilateral reticulonodular opacities. He was hospitalized and treated with azithromycin, remdesivir, and dexamethasone despite 3 negative SARS-CoV-2 polymerase chain reaction (PCR) test results. Two days after hospital discharge, he presented to the emergency department with recurrent syncope. His temperature was 38.1 °C (100.6 °F); blood pressure, 122/82 mm Hg; pulse, 135/min; and oxygen saturation, 86% on room air. A computed tomography scan revealed diffuse bilateral pulmonary micronodular opacities, a 2.2-cm nodule in the lingula, and mediastinal and hilar lymphadenopathy (Figure 1). Results of HIV testing were positive for HIV-1 antibodies.

Patient’s computed tomography pulmonary angiogram.

Patient’s computed tomography pulmonary angiogram.

What Would You Do Next?

  1. Check urine and serum Histoplasma antigen test results
  2. Order a positron emission tomography scan
  3. Perform bronchoscopy with transbronchial biopsy
  4. Treat with 7 days of intravenous cefepime and vancomycin

Discussion

Diagnosis

Disseminated histoplasmosis

What to Do Next

A. Check urine and serum Histoplasma antigen test results

Discussion

The key to the correct diagnosis is recognizing that hypoxemia and diffuse micronodular pulmonary opacities in a patient with HIV is characteristic of disseminated histoplasmosis. A positron emission tomography scan (choice B) is not recommended because it will not provide a definitive diagnosis. Less invasive testing should be pursued prior to bronchoscopy and transbronchial biopsy (choice C). The imaging findings were inconsistent with bacterial pneumonia, so intravenous antibiotics (choice D) are not indicated.

Histoplasma capsulatum is a soil-based fungus associated with bird and bat droppings.1 Exposure occurs via inhalation of fungal spores.1 While endemic in the Ohio and Mississippi River valleys, all US continental states have documented cases of histoplasmosis.2 H capsulatum is endemic in Central and South America, sub-Saharan Africa, and South/Southeast Asia.3 Most patients with acute pulmonary histoplasmosis are asymptomatic or have mild, self-limited cough and remain undiagnosed.4 However, severe pneumonia can occur, especially in patients with immunosuppression or who inhale a large quantity of spores.4 Infants and adults older than 55 years are at higher risk of severe histoplasmosis. Risk factors for dissemination include HIV with CD4 cell count less than 150/mm3, immunosuppressive medications (eg, corticosteroids, tumor necrosis factor inhibitors), hematologic malignancies, and solid organ transplantation.4 Patients with disseminated histoplasmosis typically have fever, fatigue, weight loss, and shortness of breath, and may also have diarrhea, headaches, altered mental status, and rash.5,6 Common laboratory findings include anemia, thrombocytopenia, leukopenia, and elevated liver enzyme and lactodehydrogenase levels.5 The differential diagnosis of disseminated histoplasmosis includes tuberculosis, cryptococcus, coccidioidomycosis, blastomycosis, malignancy, and sarcoidosis.5,6

To diagnose disseminated histoplasmosis, serum and urine tests for Histoplasma antigen are the tests of choice and have sensitivities of 95% and specificities of 97%.7 Disseminated histoplasmosis is fatal if untreated.5 Mild to moderate disseminated histoplasmosis is treated with 200 mg of oral itraconazole 3 times daily, followed by twice-daily dosing for 12 months.7,8 For severe disseminated histoplasmosis (eg, respiratory, circulatory, or kidney failure; neurologic signs; coagulation abnormalities; or symptoms that limit self-care), induction therapy consists of intravenous liposomal amphotericin B for 2 weeks, or for 4 to 6 weeks if there is central nervous system (CNS) involvement.7,8 Recommended maintenance therapy is oral itraconazole for 12 months to lifelong, depending on risk of reinfection or relapse, which occurs most commonly in patients with CNS disease.7,8 Mortality rates in patients with HIV and disseminated histoplasmosis range from 10% to 60%, depending on access to care.9

Patient Outcome

The patient’s urine Histoplasma antigen level was greater than 25 ng/mL and serum Histoplasma antigen level was greater than 20.0 ng/mL (reference positive, >0.20 ng/mL for both). Serum testing revealed negative T-spot, negative Cryptococcus antigen, and negative Coccidioides antibody findings. Results of Mycobacterium tuberculosis PCR and Pneumocystis jirovecii pneumonia PCR of bronchoalveolar lavage (BAL) fluid were negative. Results of brain magnetic resonance imaging were normal. Cerebrospinal fluid cell count, differential, total protein level, and glucose level were normal. HIV viral load was 3.9 million copies/mL, and CD4 cell count was 15/mm3. The patient was treated with 3 days of oral itraconazole (200 mg 3 times daily), followed by twice-daily dosing. Antiretroviral treatment (ART) with bictegravir-emtricitabine-tenofovir alafenamide was started on hospital day 10. On discharge, results of fungal, blood, BAL, and acid-fast bacillus cultures and cerebrospinal fluid Histoplasma antigen testing were pending. He was to continue ART, itraconazole (200 mg twice daily), and trimethoprim-sulfamethoxazole (160-800 mg 3 times per week) for P jirovecii pneumonia prophylaxis.

Twenty days later, the patient was readmitted to the hospital with headaches. Results of prior fungal blood and BAL cultures and CNS Histoplasma antigen testing were positive but had not been reported. He received treatment for CNS histoplasmosis with intravenous liposomal amphotericin B (3 mg/kg/d) for 6 weeks. Bronchoscopy with transbronchial biopsy, performed to evaluate the pulmonary nodule, showed necrotizing granulomas with yeast (Figure 2). After a 44-day hospitalization, the patient was discharged taking ART, itraconazole (200 mg 3 times daily), and trimethoprim-sulfamethoxazole. In clinic 18 months later, he was asymptomatic, with a CD4 count of 182/mm3 and HIV viral load of 100 copies/mL. All of his prior medications were continued, including itraconazole (200 mg twice daily) due to the high risk of reinfection or relapse associated with disseminated histoplasmosis involving the CNS, especially with CD4 cell count less than 200 cells/mm3.

Transbronchial biopsy pathology (Gomori methenamine silver stain, original magnification x40).

Transbronchial biopsy pathology

Early Tecovirimat Treatment for Mpox Disease Among People With HIV

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Key Points

Question  Is use of tecovirimat within 7 days of mpox symptom onset associated with lower rates of mpox disease progression among people with HIV (PWH)?

Findings  In this cohort study including 112 PWH after propensity matching, those treated with tecovirimat within 7 days of mpox symptom onset compared with those who were treated after 7 days or who did not receive tecovirimat were 13 times less likely to progress to severe mpox disease.

Meaning  The findings of this study support the use of tecovirimat in all PWH as soon as mpox is suspected.

Abstract

Importance  Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations.

Objective  To evaluate if PWH with mpox who were treated with tecovirimat within 7 days of symptom onset were less likely to have mpox disease progression.

Design, Setting, and Participants  This cohort study included PWH diagnosed with mpox at 4 hospitals in Atlanta, Georgia, between June 1 and October 7, 2022. Patients were grouped according to whether they were treated with tecovirimat within 7 days of mpox symptom onset (early tecovirimat cohort) or they did not receive tecovirimat or received the drug 7 or more days after symptom onset (late or no tecovirimat cohort). Multivariable logistic regression models were used to identify factors associated with progression of mpox disease. The 2 cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared.

Exposures  Treatment with tecovirimat within 7 days of mpox symptom onset.

Main Outcome and Measures  Progression of mpox disease, defined as the development of at least 1 severe mpox criterion established by the US Centers for Disease Control and Prevention, after symptom day 7.

Results  After propensity score matching, a total of 112 PWH were included in the analysis; 56 received tecovirimat within 7 days of mpox symptom onset (early tecovirimat group) and 56 were either treated later or did not receive tecovirimat (late or no tecovirimat group). In the early tecovirimat group, the median (IQR) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black individuals, and 10 (17.9%) were individuals of other races (American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or White) or unknown race. In the late or no tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black individuals, and 7 (12.5%) were individuals of other races or unknown race. Mpox disease progression occurred in 3 PWH (5.4%) in the early tecovirimat group and in 15 PWH (26.8%) in the late or no tecovirimat group (paired odds ratio, 13.00 [95% CI, 1.71-99.40]; P = .002).

Conclusion and Relevance  Results of this cohort study support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is warranted to confirm these findings.

Introduction

The 2022 global mpox outbreak disproportionately affected people with HIV (PWH).1,2 This population may develop more severe mpox disease manifestations and worse clinical outcomes,3,4 especially individuals with lower CD4+ T-cell counts5 and nonsuppressed HIV viremia,6 highlighting the urgent need for effective therapeutic agents for this population.

Tecovirimat (ST-246), an antiviral agent developed to treat smallpox, has antiviral activity against other orthopoxviruses, including mpox virus. In animal models, tecovirimat was shown to prevent morbidity and mortality associated with mpox, especially when started within 5 days of mpox inoculation.7–9

Based on these data, the US Food and Drug Administration approved tecovirimat for mpox treatment using expanded access for an investigational new drug. Data showing the effectiveness of tecovirimat for treating mpox disease in humans are lacking.10,11 Meeting enrollment goals for a randomized controlled trial assessing the efficacy of tecovirimat for mpox infection (the STOMP [Study of Tecovirimat for Human Monkeypox Virus] trial12) has been challenging due to declining number of mpox cases. We aimed to perform a matched cohort analysis to examine the association between early tecovirimat treatment (started within 7 days of mpox symptom onset) and progression of mpox disease among PWH.

Discussion

In this prospective matched cohort analysis, PWH with mpox disease who were prescribed tecovirimat within 7 days of symptom onset were significantly less likely to have progression of mpox disease compared with PWH who were not prescribed tecovirimat within 7 days of symptom onset. Results of the present study suggest that tecovirimat treatment should be started early at the time of suspected mpox diagnosis in all PWH, especially in those with nonsuppressed HIV viremia or mucosal site involvement.

Limitations

This study has limitations. First, it is possible that unmatched confounding variables could have contributed to fewer cases of severe mpox disease being observed in the early tecovirimat cohort. Second, this study has a small sample size and is inadequately powered to examine specific mpox complications or mortality. Third, most of our population (84.8%) were Black individuals, which reflected the population affected by the 2022 mpox outbreak in Atlanta but may limit generalizability to populations with different races and ethnicities. Fourth, the timing of tecovirimat initiation was determined based only on the time that the tecovirimat prescription was written, and we could not confirm if individuals took the medication or for how long. Fifth, we did not evaluate adverse events associated with tecovirimat. A large cohort study previously reported that tecovirimat is well tolerated.11

Conclusions

To our knowledge, this cohort study represents the first controlled analysis of tecovirimat for the treatment of mpox disease in PWH. The findings support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is needed to confirm these findings.

Mono: A Hidden Culprit in Chronic Illness

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Epstein Barr disease stretches further than the infectious mononucleosis—with frequently overlooked influence on chronic diseases such as multiple sclerosis.

Tanya Francis, 45, couldn’t have predicted that a virus she encountered at 14 would drastically affect her health years later. Diagnosed with mononucleosis, a common adolescent ailment caused by the Epstein-Barr virus (EBV), Ms. Francis’s experience deviated from the norm. Rather than being a fleeting teenage illness, EBV marked the beginning of a long-term battle.

Ms. Francis’ ensuing struggle with fatigue, joint pain, vertigo, and a 2018 multiple sclerosis diagnosis reflects a wider narrative. Her experience sheds light on EBV’s complex and frequently overlooked influence on chronic diseases.

​​Unveiling the Epstein-Barr Virus

The Epstein-Barr virus, less familiar to many than the common cold but arguably as widespread, is stepping into the spotlight of medical research, revealing its complex role in numerous health issues.

While best known for causing infectious mononucleosis, often called the “kissing disease,” the influence of EBV stretches much further. “EBV is one of the most common human viruses,” explains Dr. Jeffrey Dunn, a neurologist at Stanford Medicine focusing on immune-mediated neurological diseases. “If you checked everybody for whether they’ve been exposed to Epstein Barr virus, 95 percent plus will have it.”

As a member of the herpesvirus family, EBV is a double-stranded DNA virus capable of remaining latent in the body. “Much like herpes simplex virus, once you’re infected with EBV, you can never eradicate it,” Paul Gisbert Auwaerter, M.D. and professor at Johns Hopkins University School of Medicine, told The Epoch Times. He emphasizes that this ability to lie dormant is central to the virus’s nature, allowing it to stay hidden for prolonged periods.

EBV is commonly passed through oral secretions, often in simple acts like sharing drinks or kissing. However, its transmission extends to blood transfusions, organ transplants, and breast milk. The presence of EBV in genital secretions further underscores its capacity to spread via multiple bodily fluids.

EBV infection typically occurs in childhood or adolescence, frequently producing mild or unnoticeable symptoms. In teens or young adults, it often manifests as infectious mononucleosis, marked by fever, sore throat, and swollen glands. But the true concern lies in what unfolds long after these initial symptoms subside.

A Spectrum of Linked Diseases

Beyond its role in causing mononucleosis, the Epstein-Barr virus is now recognized as a key player in various autoimmune and inflammatory diseases. What was once speculative is now backed by growing scientific evidence.

A pivotal study tracking over 10 million U.S. military recruits for two decades revealed a startling connection between EBV and multiple sclerosis (MS). The research found a 32-fold increase in MS risk post-EBV infection, shedding light on the virus’s possible role in autoimmune diseases.

Alberto Ascherio, M.D., Harvard epidemiologist and senior author, reflected on the study in a press release. “This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.”

While the exact mechanisms by which EBV may lead to MS are still under investigation, a 2022 Stanford study may offer a clue. The research highlighted a unique aspect of EBV’s interaction with MS. The virus contains elements mimicking brain and spinal cord proteins, leading the immune system to mistakenly attack the body’s nerve cells, a phenomenon termed “molecular mimicry.”

Beyond MS, EBV is linked to other autoimmune diseases such as lupus, Type 1 diabetes, and rheumatoid arthritis. These findings suggest that EBV’s role extends beyond dormancy, potentially triggering various autoimmune responses.

Research is also probing potential connections between EBV and gastrointestinal disorders, including irritable bowel syndrome and celiac disease.

In cancer research, EBV’s influence is notably significant. It contributes to cancers like Burkitt’s lymphoma, Hodgkin’s lymphoma, gastric cancer, and nasopharyngeal carcinoma. Dr. Dunn highlights, “It’s been estimated that there may be 200,000 cancer cases per year associated with EBV,” a number that becomes meaningful when considering public health and potential treatments, he explains.

“We’re dealing with a virus that has the capability to affect the body in multiple ways,” explains Dr. Auwaerter. He emphasizes, however, that while there’s a noticeable link between EBV and certain autoimmune diseases, the exact ways EBV influences these conditions remain to be fully understood by researchers.

The Immune System’s Role in EBV Activation

The Epstein-Barr virus is not just widespread—its true danger lies in its ability to manipulate the human immune system. Its threat often becomes pronounced when our natural defenses are weakened.

“It’s a delicate balance,“ Dr. Michael Bauerschmidt, chief medical officer at Deeper Healing Wellness Center, told The Epoch Times. ”The virus itself can remain harmless for years, but under certain conditions, it can become a formidable adversary.”

A key element is the immune response to EBV. Usually, a robust immune system keeps the virus in check. However, if the immune system is compromised due to stress, illness, or other factors, EBV may reactivate.

“The diagnosis is not the disease,” states Dr. Bauerschmidt. “Yes, EBV causes problems, but only because the individual immune system is unable to keep it contained.”

Factors weakening the immune system and possibly reactivating EBV are numerous. “It’s about everything,” Dr. Bauerschmidt explains, emphasizing lifestyle influences, particularly nutrition. A nutrient-deficient diet can weaken immune defenses, allowing EBV reactivation. Conversely, a nutrient-rich diet might strengthen the immune response against EBV.

Environmental elements also play a role. Dr. Bauerschmidt points to exposure to mold, heavy metals, pesticides, and electric and magnetic fields as factors that can weaken the immune system. “These environmental factors can create a perfect storm for EBV reactivation,” says Dr. Bauerschmidt.

Dr. Bauerschmidt asserts that the approach to understanding and managing EBV must be holistic. “Focusing solely on the virus is insufficient. We must consider the body’s entire ecosystem.” He advocates for a strong, balanced immune system as the primary defense.

Ben Galyardt, chiropractor and founder and CEO of F8 Well Centers, aligns with this view, particularly considering recent findings on Long COVID and EBV reactivation. A 2023 study showed higher EBV reactivation rates in COVID-19 patients. “A range of physical stressors can provoke EBV reactivation, initiating an inflammatory response within the body,” he notes.

Dr. Auwaerter, however, questions the effectiveness of merely boosting the immune system against EBV-linked conditions. Acknowledging the benefits of a healthy lifestyle, he cautions, “There’s no definitive proof that less immune activation or reactivation leads to less disease.”

He points out the complexity, especially with autoimmune conditions, where stimulating the immune system might be counterproductive. “The critical question is whether the issues stem directly from the virus or from the immune response,” he adds, underlining the intricacies of EBV-related health challenges.

Navigating the Challenges of Diagnosis

Diagnosing conditions associated with EBV is a complex task in medicine, largely due to the virus’s prevalence and dormant nature. A significant issue is that standard EBV tests often fail to provide clear insights into the virus’s active role in current health issues.

EBV testing typically involves checking for antibodies against specific EBV antigens to assess recent or past infections. According to the Centers for Disease Control (CDC), anti-VCA IgM appears early in an EBV infection and usually vanishes within four to six weeks, signifying a recent infection. On the other hand, anti-VCA IgG emerges in the acute phase, peaks at two to four weeks post-onset, and then remains for life, indicating past exposure. The simultaneous presence of VCA and EBNA antibodies generally suggests past infection, a common finding in adults.

However, Mr. Galyardt points out the limitations of these tests. “Since most adults have encountered EBV, standard tests like anti-VCA IgG, IgM, or EBNA offer limited information about ongoing health issues.” Although these tests can identify past exposure or acute infections, they don’t conclusively show whether EBV is currently affecting a patient’s health.

Mr. Galyardt suggests a more comprehensive diagnostic method, focusing on white blood cell counts. “A low white blood cell count coupled with a high lymphocyte percentage often indicates chronic viral infection, irrespective of EBV test results.” This approach considers the body’s overall state, not just specific EBV markers.

Interpreting EBV antibody tests requires considering the patient’s symptoms and medical history. The connection between EBV and various chronic conditions, like autoimmune diseases or cancers, isn’t widely acknowledged in general practice, potentially leading to diagnostic and treatment oversights.

While EBV testing can be instrumental in diagnosing conditions like infectious mononucleosis or chronic active Epstein-Barr Virus (CAEBV), Dr. Auwaerter recommends a cautious approach when it comes to testing for other issues, such as chronic fatigue, Long COVID, MS, lupus, or lymphoma. “In my opinion, there’s no benefit,” he remarks, highlighting that the scientific community is still working to fully understand how EBV is connected to various health conditions.

EBV Treatment: Searching for Effective Strategies

Current medical understanding acknowledges the absence of a specific treatment or cure for EBV, as per the CDC. Although no vaccine is yet available, the National Institutes of Health began a clinical trial for an EBV vaccine in 2022.

This lack of a targeted cure has led to diverse treatment approaches. Health care providers often use antiviral treatments like acyclovir, but these have shown limited effectiveness against EBV’s latent presence in cells.

Catherine Bollard, M.D., and Jeffrey Cohen, M.D., note in a paper, “Once EBV infection is established, acyclovir has no effect on virus-infected T cells in T-cell CAEBV.” Echoing this, Mr. Galyardt adds, “There’s no great antiviral. COVID proved that,” highlighting the limitations of current treatments.

Other treatments like interferons and immunoglobulin therapy have shown inconsistent results, and while immune cell therapy is promising in post-transplant EBV cases, stem cell transplants have had varied success. This underlines the ongoing challenge of finding effective EBV treatments.

Mr. Galyardt advocates a proactive health approach, emphasizing the importance of strengthening the body’s defenses against viruses like EBV. “The vast majority of people carry some form of chronic viral load, but it’s not inevitable for it to become problematic,” he says. His recommendations for keeping EBV inactive include adequate sleep, adrenal function maintenance, and blood sugar level stabilization.

“Chronic viral infections like EBV significantly impact the body,” Mr. Galyardt notes, stressing the importance of overall health. “Keeping our body systems in optimal condition will help prevent and treat chronic viral loads better than any medication out there.”

Dr. Bauerschmidt takes a similar approach, focusing on the roots of immune dysfunction. He promotes oxygen therapy: “Oxygen is essential to eliminate the body’s toxin burden.” He compares traditional treatments like antibiotics and antivirals to using premium fuel without improving the engine—more expensive but not more effective.

At Deeper Healing, Dr. Bauerschmidt uses altitude contrast oxygen therapy, hyperbaric methods, and nighttime oxygen concentrators. He finds a combination of ozone therapy and ultraviolet blood radiation especially effective. For active viral infections, he has found nebulizing with high-quality colloidal silver or 0.3 percent hydrogen peroxide beneficial for some patients.

As research into EBV and the immune system progresses, it holds the promise of new management and treatment strategies for the virus’s associated conditions.

For individuals like Ms. Francis, this research offers hope and the promise of a more proactive approach to managing their health. As the medical community gains a deeper understanding of EBV’s interactions with the immune system, the potential for more targeted and effective treatments grows, bringing hope to millions affected by this pervasive virus.