This Week in Infectious Disease — May 21, 2026

Welcome to This Week in Infectious Disease. This week we're covering 8 notable papers spanning advances in HIV prevention and management, antimicrobial stewardship in common outpatient infections, and the global landscape of surveillance, new drugs, and prevention. Let's dive in.

Our first theme is advances in HIV prevention and management, with three papers from Clinical Infectious Diseases that highlight the drug pipeline and real-world challenges in HIV care.

First, a phase 1 study introduces a novel oral nucleoside reverse transcriptase translocation inhibitor, or NRTTI, called MK-8527 [8]. This agent is being developed for HIV prevention. In this study of 37 treatment-naive adults with HIV, a single oral dose of MK-8527, as low as 0.5 milligrams, led to a mean viral load reduction of at least 1.0 log10 copies per milliliter by day seven. The drug was well tolerated, with only mild or moderate adverse events deemed unrelated to treatment. The potent and durable antiretroviral activity from a single low dose suggests promise for this new class of agent, particularly for long-acting prevention strategies.

Moving from a new agent in development to one in early implementation, another paper reports on the real-world rollout of lenacapavir for PrEP [3]. This study looked at 501 individuals across 17 United States sites. Unlike in clinical trials, the key finding was that delays in initiating therapy were common, primarily driven by payer processes and insurance hurdles. While early discontinuation of therapy was uncommon at just under 4 percent, it was higher than seen in trials. This non-persistence was strongly associated with two modifiable factors: abdominal injections and injection-site reactions that required clinical contact. For clinicians, this highlights critical structural and clinical barriers to address for successful lenacapavir PrEP implementation.

Rounding out our HIV section, we turn to a common comorbidity: excess visceral abdominal fat, or EVAF. A case report [4] highlights the different ways this can present in people living with HIV and why a one-size-fits-all approach to treatment may fail. The authors describe two patients with well-controlled HIV and central adiposity. The first patient had a normal-range BMI of 27 but significant visceral fat. He was treated with tesamorelin, a growth hormone-releasing hormone analog that selectively reduces visceral fat, and saw marked improvements in waist circumference and lipid levels. The second patient had a higher BMI consistent with obesity. She was started on a GLP-1 receptor agonist, which causes generalized weight loss, but had intermittent access to the medication, leading to fluctuating weight. Adding tesamorelin provided a more targeted approach to her persistent abdominal fat. The clinical takeaway is that EVAF can exist independent of a patient's BMI category. Management should be individualized based on fat distribution rather than weight alone, with tesamorelin being a targeted option for the visceral adiposity phenotype.

Next, two major studies reinforce key principles of antimicrobial stewardship, one in adults and one in children.

First, a study in JAMA addresses a perennial question in outpatient medicine: for uncomplicated acute sinusitis in adults, should we use amoxicillin or amoxicillin-clavulanate? [7].

The Study

Investigators conducted a large retrospective cohort study using a nationwide database, comparing outcomes for adults aged 18 to 64 treated for acute sinusitis.

Population

After propensity score matching, the study included over 234,000 patients, with half receiving standard-dose amoxicillin-clavulanate and half receiving standard-dose amoxicillin.

Results

Overall, treatment failure was rare, occurring in about 3 percent of patients. The key finding was no difference in the risk of treatment failure between the two groups. However, amoxicillin-clavulanate was associated with a higher risk of adverse events. The risk of yeast infections was increased by 40 percent, and the risk of Clostridioides difficile infection, while rare, was roughly doubled.

Conclusions

The clinical implication is clear: for uncomplicated acute sinusitis in adults, standard-dose amoxicillin should be the preferred first-line treatment. It offers equivalent efficacy with a better safety profile.

In a similar vein, a trial in The New England Journal of Medicine examined the use of azithromycin for preschoolers with acute wheezing [2]. Wheezing is a top reason for hospitalization in this age group, and antibiotics are often prescribed despite unclear benefit.

The Study

This was a multicenter, randomized, placebo-controlled trial. Children aged 18 to 59 months presenting to an emergency department with moderate-to-severe wheezing were assigned to receive a 5-day course of azithromycin or placebo. The rationale was based on observational studies showing pathogenic bacteria in the nasopharynx of children with recurrent wheezing.

Results

The trial was stopped for futility. There was no significant difference in symptom scores over five days between the azithromycin and placebo groups. This held true even when the analysis was restricted to the cohort of children who tested positive for pathogenic bacteria. While azithromycin was effective at clearing the bacteria—with a 59 percent clearance rate compared to 11 percent with placebo—this microbiological success did not translate into any clinical improvement. Secondary outcomes like length of stay were also similar.

Conclusions

This trial provides a definitive answer: azithromycin does not reduce the severity of wheezing-related symptoms in preschoolers and should not be used for this indication.

Finally, we'll take a broader view with three papers from The Lancet and The Lancet Infectious Diseases, covering global surveillance, a new weapon against resistant bacteria, and the impact of vaccination programs.

First, a massive systematic review in The Lancet Infectious Diseases provides an updated look at the global molecular epidemiology of HIV-1 [1]. Analyzing over 1.3 million samples from 154 countries collected between 1990 and 2024, the study maps the complex genetic diversity of the virus.

Key Findings

In the most recent period, 2020 to 2024, subtype C remains dominant, accounting for nearly half of all global infections, and is concentrated in southern Africa and south Asia. Subtype A is prevalent in east Africa and eastern Europe, while subtype B dominates in North America and western Europe. The greatest genetic diversity is found in Central Africa. While the overall global distribution has been broadly stable for two decades, the study notes a concerning increase in recombinant forms in Europe.

Implications

This evolving genetic diversity has major implications for the efficacy of diagnostic assays, the emergence of drug resistance, and the development of an effective vaccine. The authors stress that continued surveillance is essential.

Addressing the threat of antimicrobial resistance, a phase 3 trial in The Lancet evaluates two new beta-lactam/beta-lactamase inhibitor combinations for complicated urinary tract infections [6]. The Integral-1 study compared intravenous cefepime-nacubactam and aztreonam-nacubactam against the carbapenem imipenem-cilastatin.

The Study

This was a double-blind, randomized trial in adults with complicated UTI or acute pyelonephritis. The primary endpoint was a composite of clinical and microbiological success.

Results

Cefepime-nacubactam was not only non-inferior but also superior to imipenem-cilastatin, with a success rate of 82 percent versus 61 percent. Aztreonam-nacubactam was non-inferior, with a success rate of 72 percent. Both new agents were well-tolerated, with fewer adverse events reported than in the imipenem-cilastatin group.

Implications

Cefepime-nacubactam and aztreonam-nacubactam are powerful potential new treatment options for Gram-negative UTIs, including those caused by antimicrobial-resistant strains.

Finally, a modeling study in The Lancet quantifies the health impact of vaccines supported by Gavi, the Vaccine Alliance, across 117 low- and middle-income countries [5]. The study calculated vaccine impact ratios, defined as the number of deaths or disability-adjusted life-years averted per 1000 vaccinations.

Key Findings

Overall, the HPV and measles vaccines were found to avert the highest number of deaths per 1000 vaccinations. For other vaccines in the portfolio, the impact ratios varied significantly across different geographical subregions. The authors note that because of uncertainty in the models, the ranges for these ratios often overlap.

Implications

As global health resources become more constrained, robust metrics like these are essential to help national immunization programs plan and prioritize which vaccines will have the greatest impact in their specific context.

If you only have time for one paper this week, make it the study in JAMA comparing amoxicillin with amoxicillin-clavulanate for acute sinusitis [7]. This large, real-world study provides strong evidence to support using narrower-spectrum amoxicillin as first-line therapy, a simple change that can reduce side effects and promote stewardship in one of the most common outpatient scenarios.

Here are the key takeaways from this week in Infectious Disease:

First: For uncomplicated acute sinusitis in adults, choose standard-dose amoxicillin over amoxicillin-clavulanate. There is no difference in efficacy, but amoxicillin has a better safety profile with a lower risk of yeast infections and C. difficile [7].

Second: Do not treat acute wheezing in preschoolers with azithromycin. A large, high-quality RCT in The New England Journal of Medicine showed no clinical benefit, even in children with documented bacterial colonization [2].

Third: In HIV management, be aware of two distinct presentations of excess abdominal fat. A non-obese phenotype with visceral adiposity may benefit from targeted therapy with tesamorelin, while generalized obesity may call for GLP-1 agonists, underscoring the need for individualized assessment beyond BMI [4].

Fourth: For complicated UTIs, cefepime-nacubactam has demonstrated superiority to imipenem-cilastatin in a phase 3 trial and represents a significant new tool against resistant Gram-negative infections [6].

And finally: New long-acting HIV prevention agents like lenacapavir face real-world hurdles. A study in Clinical Infectious Diseases shows that payer delays are a major barrier to initiation, and injection site reactions can drive early discontinuation, highlighting areas for clinical and structural intervention [3].

That's your roundup for This Week in Infectious Disease. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.