Infectious disease prevention and management is constantly changing, leading to challenges for the interprofessional healthcare team to stay updated on recent advancements in the field. This article covers key developments in management of 2 important public health topics, HIV and long COVID, that may have important implications for clinical practice.

LOW HIV LEVELS LINKED TO 'ALMOST ZERO' RISK FOR SEXUAL TRANSMISSION

One primary mode of HIV transmission is through anal or vaginal sex.^[1] Moreover, within 28 days of initial infection, antibody levels can remain below detection limits, leading to false negative results if HIV tests are administered within this time frame.^[2] Rapid and simple detection of viral load is important for both patients and the healthcare team to monitor HIV progression and antiretroviral treatment efficiency.^[3]

According to new guidelines from the World Health Organization, people with undetectable or very low HIV levels have zero or "almost zero" risk of transmitting the virus sexually if they are taking suppression medication.

The announcement was made concurrently with the publication over the weekend of definitive new research in The Lancet.^[4] The findings were presented virtually at the 12th International AIDS Society Conference on HIV Science taking place in Brisbane, Australia.

The WHO estimates that 76% of the 39 million people worldwide living with HIV take antiretroviral therapy (ART).

"Antiretroviral therapy continues to transform the lives of people living with HIV," a WHO news release stated.^[5] "People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.”

The Lancet study showed that people who have a viral load of less than 1000 copies per milliliter of blood have a tiny chance of transmitting the virus to sexual partners. Of 320 cases of transmission reviewed during the study, only 2 transmissions involved a partner with a load below that threshold. Those cases may have been impacted by viral loads rising between the time of testing and transmission. The previous guideline for zero risk of transmission was 200 copies per milliliter.

People living with HIV who do not take ART can have viral loads ranging from 30,000 to more than 500,000 copies per milliliter, according to a summary of the study distributed by The Lancet to the media.^[6]

The new findings do not apply to the transmission of HIV from mother to child, including during pregnancy, childbirth, and breastfeeding.

"The ultimate goal of antiretroviral therapy for people living with HIV is to maintain undetectable viral loads, which will improve their own health and prevent transmission to their sexual partners and children," said researcher Lara Vojnov, PhD, diagnostics advisor to the WHO Department of Global HIV, Hepatitis and STI Programmes, in a statement. "But these new findings are also significant as they indicate that the risk of sexual transmission of HIV at low viral loads is almost zero. This provides a powerful opportunity to help de-stigmatize HIV, promote the benefits of adhering to antiretroviral therapy, and support people living with HIV."

MULTIPLE TRIALS OF LONG COVID TREATMENTS ADVANCING, MORE ON THE WAY

Coronavirus disease 2019 (COVID-19 or COVID) has caused significant morbidity and mortality worldwide. Similar to the previous endemics of SARS-CoV and MERS-CoV, individuals who recover from COVID are often left with persistent symptoms of severe fatigue, decreased quality of life, persistent shortness of breath, and behavioral health problems. Persistent post-COVID syndrome (PPCS) is also known as long COVID, and the multiorgan mechanism behind the persistence of symptoms is still unclear, making effective treatment difficult.^[7]

Last month, the National Institutes of Health (NIH) announced at a media briefing that enrollment is opening for four clinical trials to evaluate new treatments for long COVID.^[8] Additional clinical trials to test at least seven more treatments are expected to launch in the coming months, officials said.

The trials are part of the NIH's research effort known as the Researching COVID to Enhance Recovery (RECOVER) Initiative. In December 2020, Congress approved $1.15 billion for the NIH to research and test treatments for long COVID. The new clinical trials are phase 2, meant to test safety and effectiveness.

However, some advocates are concerned the process is still moving too slowly. The Long COVID Alliance "is both encouraged and concerned by the announcement today from NIH," the group said in a statement. "We welcome the NIH's efforts to finally fund much needed and long overdue trials on long COVID.... Today's announcement unfortunately leaves many important questions unanswered and seems fraught with the same lack of transparency that has become all-to-familiar with RECOVER and its $1.15 billion budget."

Long COVID patients have grown increasingly frustrated at the lack of effective treatments. Some clinicians have turned to off-label use of some drugs to treat them. Walter J. Koroshetz, MD, director of the NIH National Institute of Neurological Disorders and Stroke and co-lead of the RECOVER Initiative, said the agency is not sure exactly how many people have long COVID. "The answer kind of depends on how you define the problem and also what variant caused it. The incidence was higher in Delta," he said during today's briefing. Some estimates suggest 5% to 10% of those infected develop long COVID. "I don't think we have solid numbers as it's a moving target," Koroshetz said.

The four trials include the following:

• RECOVER-VITAL will focus on a treatment for viral persistence, which can occur if the virus lingers and causes the immune system to not work properly.^[9] One treatment will test a longer dose regimen of the antiviral combination of nirmatrelvir and ritonavir, which is currently used to treat mild to moderate COVID to halt progression to severe COVID
• RECOVER-NEURO will target treatments for symptoms such as brain fog, memory problems, and attention challenges.^[10] Among the potential treatments are a program called BrainHQ, which provides web-based training, and PASC-Cognitive Recovery (post-acute sequelae of COVID), a web-based program developed by Mount Sinaia Health System in New York. Also being tested is a direct current stimulation program to improve brain activity
• RECOVER-SLEEP will evaluate treatments for sleep problems, which can include daytime sleepiness and other problems. According to Koroshetz, melatonin, light therapy, and an educational coaching system are among the treatments that will be studied
• RECOVER-AUTONOMIC will evaluate treatments to address symptoms linked with problems of the autonomic nervous system. The first trial will target postural orthostatic tachycardia syndrome (POTS), which can include irregular heartbeat, fatigue, and dizziness. A treatment for immune disease and a drug currently used to treat chronic heart failure will be tested

Timelines

The first trial, on viral persistence, has launched, said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute, the clinical trials data coordinating center for the trials. "We are actively working to launch the second on cognitive dysfunction." The sleep and autonomic trials will launch in the coming months, she said. Also planned is a trial to study exercise intolerance, which is reported by many with long COVID.

But the Long COVID Alliance said, again, that NIH's plan is lacking in details. "The NIH has not presented a timeline for results: They have highlighted that enrollment will begin over the next several months, likely meaning that results to benefit many millions with long COVID are still at least a year away," the group said. By then, long COVID will have been around for more than 4 years, "an unacceptable wait for patients to see meaningful results from this billion dollar investment."

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