Jared Kaltwasser


A new cross-sectional analysis of sex workers in South Africa suggests that they have an “extraordinarily high” HIV incidence rate, and thus require significantly more outreach and intervention in order to curb HIV transmission within the population as a whole.

, showed an HIV incidence rate of 5 cases per 100 person-years. The authors said the data show that viral 

 among HIV-positive sex workers will be a key facet of achieving the United Nations’ “95-95-95” goals, which 

 95% of people who are HIV positive to be aware of their status, 95% of people who know they are HIV positive to be on treatment, and 95% of people on treatment to achieve viral suppression by 2030.

Corresponding author Reshma Kassanjee, PhD, of the University of Cape Town, and colleagues, said an estimated 7.3 million adults in South Africa are HIV-positive, but women make up nearly two-thirds of those cases. In fact, one-quarter of women between the ages of 15 and 49 are believed to be infected with the virus, they said. Still, rates are much higher among sex workers, who face challenges such as economic insecurity, violence, and the burden of engaging in a criminalized profession.

South Africa has responded to the problem by creating a number of programs designed to help lower rates of infection and transmission amongst sex workers, in part by leveraging workers themselves as peer educators. Still, the investigators said analyzing the success of such programs is difficult without clear data on HIV incidence within this population.

Kassanjee and colleagues decided to analyze a 2019 national survey of sex workers that included data on self-reported HIV status, demographic characteristics, and exposure to violence. They enrolled 3,005 people, of whom 2999 had HIV test results available. Among those respondents, HIV-positivity and the experience of sexual violence were common. More than half (1714 people; 57.2%) said they tested positive for HIV, and 48.3% said they had experienced violence from a client within the past year. Overall, the measured HIV prevalence was 62.1% (95% confidence interval, 60.3-65.7), the investigators said.

A subsequent analysis of recency-of-infection biomarkers suggested an incidence of around 5 cases per 100 person-years, though the authors said varying sensitivity analyses produced a range of incidence rates, including one that suggested the rate could be as high as 11 cases per 100 person-years.

Though very high, Kassanjee and colleagues said the estimates in their study were not out of line with other studies showing that HIV is a significant health burden among sex workers. Yet, they added that there is evidence that some of the public health outreach programs are producing results.

“The extraordinarily high risk of HIV acquisition is only partly offset, in terms of net harm, by high treatment coverage with moderate viral suppression rates,” they wrote.

The investigators added, however, that economic and healthcare burdens caused by the COVID-19 pandemic could potentially reverse some of the positive trends.

“We are concerned that the broadly positive cascade of care indicators that are observed among populations of female sex workers who are linked to sex worker programs are under threat and will need to be reviewed,” they said.

Kassanjee and colleagues said the role of sex work in spreading HIV demands that programs for sex workers remain a key part of HIV prevention. They said these new data should help provide guidance with which to assess the success of such programs.

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There are a number of programs designed to help lower rates of infection and transmission amongst this industry's workforce in South Africa.

HIV Prevalence High Among Female Sex Workers But Interventions Have Positive Effect


A tool that helps predict the likelihood that a particular case of diarrhea has a viral cause could help reduce the rate of inappropriate antibiotics prescriptions, according to a new study.

World Health Organization (WHO) recommendations indicate that children should only be prescribed antibiotics for diarrhea if they have bloody diarrhea or are suspected of having cholera. Yet, previous research has shown that many healthcare providers do not follow those guidelines, a problem that contributes to early 

 among children in low- and middle-income countries.

, corresponding author Eric J. Nelson, MD, PhD, of the University of Florida, and colleagues, described the impact of a diarrheal etiology prediction (DEP) algorithm that can help providers better understand the likely cause of particular cases of diarrhea. The DEP tool uses a variety of data, including patient-specific factors like medical history and symptoms, as well as 

, such as the clinical presentation of previous patients and local weather patterns, to predict the probability that a particular case is viral in nature. Nelson and colleagues hoped that such a tool might help curb the overuse of antibiotics by highlighting cases for which an antibiotics prescription would probably be ineffective.

The investigators took their tool to 7 clinics in Mali and Bangladesh. There, they provided training to physicians on WHO treatment guidelines and introduced them to a clinical decision support tool. Next, physicians were randomly assigned to use the tool without the DEP algorithm (control arm) or with the DEP algorithm. The study was conducted with a crossover design; after 4 weeks and a one-week washout period, clinicians switched tools for the remaining 4 weeks of the study.

Altogether, 30 physicians and 941 patients with diarrhea (with a median age of 12 months) were enrolled in the study. The investigators found that 69.8% of children whose physicians had the DEP tool were given antibiotics, while 76.5% of children whose physicians did not have the DEP tool were prescribed antibiotics. Though the rate of antibiotic prescriptions was lower in the DEP group, the difference did not reach statistical significance.

However, when the investigators conducted a post-hoc analysis to account for the predicted probability of a viral-only etiology, they found that a 10% increase in the predicted probability of viral-only diarrhea resulted in a 14% drop in the likelihood that a patient received antibiotics.

The investigators noted that both groups had lower-than-expected rates of diarrhea prescription. Based on previous literature, Nelson and colleagues said they expected that around 90% of patients would be given an antibiotics prescription.

“This lower rate may be due to inclusion criteria that did not discriminate based on dehydration levels and/or a Hawthorne effect on physicians in the context of research cognizant that indications for antibiotic use are few for diarrheal illnesses,” Nelson and colleagues wrote.

On a physician level, the data showed that some providers did not change their behavior at all when they had access to the DEP prediction tool, and those physicians had the highest rates of antibiotic use during their time in the control arm. This suggests some physicians are less receptive to clinical decision tools, they said.

“This finding reveals a need to delineate these physician types, and to identify other modifiable factors that influence antibiotic prescribing,” Nelson and colleagues wrote.

The investigators concluded that the study served as a meaningful proof of concept for probability-based decision-support tools, and offered evidence that such tools can reduce unnecessary antibiotics use, particularly in under-resourced countries.

“If replicated, the use of etiological prediction in decision support tools represents an important advancement to improve antibiotic stewardship in a clinical context prone to high rates of inappropriate antibiotic use,” they wrote.

When physicians were told that a case was likely viral they were less likely to prescribe antibiotics, a new study shows.

Causation Prediction Tool May Lower Rates of Pediatric Antibiotic Prescriptions for Diarrhea


Direct-acting antivirals (DAA) cure around 95% of cases of 

 virus (HCV) infection, and yet a new report from the Centers for Disease Control and Prevention (CDC) shows uptake of the therapy remains low.

, found only about 3 in 10 people who tested positive for HCV infection initiated DAA therapy within 360 days. The 

 was true regardless of insurance type, though people on Medicare and Medicaid were less likely than those on private insurance to start DAA treatment.

“Hepatitis C treatment saves lives, prevents transmission, and is cost saving,” noted Carolyn Wester, MD, MPH, of the CDC’s National Center for HIV, Viral Hepatitis, Sexually Transmitted Disease, and Tuberculosis Prevention. “...However, only an estimated 1.2 million persons initiated hepatitis C treatment with DAA agents in the United States during 2014–2020, far below the number needed to achieve national hepatitis C elimination goals.”

Wester and colleagues wanted to get a better sense of the current utilization and trends regarding DAAs, as well as disparities in usage between different ages, sexes, racial/ethnic groups, and insurance types. The investigators used administrative claims and encounters data from HealthVerity to identify nearly 47,000 people between the ages of 18 and 69 years who were diagnosed with HCV infection between January 30, 2019, and October 31, 2020, and who had insurance continuously for at least 60 days before diagnosis and 360 days following diagnosis.

Among the cohort, the investigators found that just 23% of Medicaid patients, 28% of Medicare patients, and 35% of privately insured patients who were diagnosed with HCV infection initiated DAA therapy within 360 days of their diagnosis.

After adjusting for insurance type, the authors found younger patients (those 18-29 and those 30-39) were less likely than older patients (those 50-59) to start therapy with DAAs. Among people on Medicaid, the authors found living in a state that imposed restrictions on medication access made a person less likely to start therapy compared to people in states without restrictions (adjusted odds ratio [aOR] = 0.77; 95% confidence interval [CI] = 0.74–0.81). Restrictions included requiring the presence of liver fibrosis meeting fibrosis stage criteria, mandating that patients be sober or abstain from alcohol or drugs for a month before treatment, or requiring a prescription by or in consultation with a specialist before the drug would be provided. Also among the Medicaid cohort, the authors found people who were Black or African American (aOR = 0.93; 95% CI = 0.88–0.99), or another racial minority (aOR = 0.73; 95% CI = 0.62–0.88) were less likely to start DAA therapy, compared to White patients.

Wester and colleagues noted that while the first DAAs initially cost more than $90,000 for a full course of treatment, the cost of therapy has dropped significantly. Still, they said, that has not translated into wider uptake

“Treating all eligible patients without restriction would result in substantially reducing downstream negative clinical outcomes, decreasing the proportion of total costs attributable to future care, and producing considerable cost savings,” they said.

In cases where patients were treated with DAAs, the authors found most patients began therapy within 180 days (75-84%, depending on insurance type). Those who did not begin therapy within 6 months likely faced difficulty accessing providers or may have had to push back after an initial insurance denial, the authors said.

The investigators said removing restrictions on DAA prescriptions is necessary, but they said it is not sufficient to solve the problem.

“Addressing other barriers, including burdensome preauthorization requirements as well as integrating 

 and treatment into primary care and other settings where persons with hepatitis C receive services, could also increase treatment coverage,” they said.

A new report underscores a persistent problem of patients not receiving antivirals despite their high curative rate.

Most People with HCV Infection Are Not Treated with Direct-Acting Antivirals

Booster shots of coronavirus disease 2019 (

) vaccines lead to an increase in neutralizing antibodies against the 

 variant of the SARS-CoV-2 virus, according to a new study, but a stronger response is generated when patients who initially received mRNA vaccines are boosted with an adenovirus-based vaccine, the report said.

, corresponding author Dan H. Barouch, MD, PhD, of Beth Israel Deaconess Medical Center, and colleagues, explained that both the Pfizer/BioNTech vaccine (a two-dose mRNA vaccine called BNT162b2) and the Janssen adenovirus serotype 26 vector-based vaccine (called Ad26.COV2.S) prompt neutralizing antibody responses (NAb). However, both also have drawbacks. While the mRNA vaccine induces higher initial NAb titers, the response tends to be less durable than that of the Janssen vaccine.

The investigators wanted to know whether the

 to a patient might impact the level and duration of their protection against COVID-19 and against the Omicron variant, in particular. To find out, they recruited 68 people who had received the initial 2-dose Pfizer/BioNTech mRNA vaccination at least 6 months prior. Forty-one patients were boosted with the Janssen vaccine, and the remaining 27 were boosted with an additional dose of the Pfizer BioNTech vaccine. Enrollment took place between August and October 2021, and immune responses were tracked for 14 weeks following the booster dose.

The participants in the study ranged in age from 23-84 years, though most were female (82%) and White (78%).

Both booster shots helped protect patients against SARS-CoV-2 

. The Pfizer/BioNTech shot led to a peak median titer of 1,018 Omicron neutralizing antibodies at week 2, but that level fell to a median titer of 148 by week 16. The Janssen booster took longer to achieve a peak response but also led to a more durable response. In patients boosted with that vaccine, the median titer level peaked at 859 antibodies at week 4, but the median number was 403 by week 16.

Barouch and colleagues said these data appear to support the “mix-and-match” approach to booster doses.

“We speculate that the differences in the kinetics of the immune responses may be related to differences in the kinetics of immunogen expression in vivo,” they wrote.

The Janssen booster also led to superior increases in CD8+ T cells, which some evidence suggests can also be protective against SARS-CoV-2, especially when NAb responses are insufficient.

The authors said their study has significant limitations. Among them, it was done in a small study population, at a single site, and with just 4 months of follow-up. They said larger studies with longer follow-up times would be required to find out whether the results were generalizable and durable.

Still, they said the data highlight the benefits of having different types of vaccines, and of using those different types strategically.

“These data suggest potential immunologic benefits of mix-and-match heterologous COVID-19 vaccine regimens and emphasizes the importance of durability for COVID-19 vaccine boosting strategies,” they concluded. “Future studies could explore reduced booster doses as well as Omicron-containing boosters.”

People who initially received an mRNA vaccine but were boosted with the Janssen vaccine had superior immune responses, the study found.

Report Finds "Mix-and-Match" COVID-19 Booster Approach More Effective

A new first-of-its-kind study shows that people who are infected with HIV experience significant epigenetic aging right away from the time of infection.

The finding adds new context to the question of how HIV affects the body over the long term. The study was 

Beth D. Jamieson, PhD, of the University of California Los Angeles, and colleagues, explained that evidence suggests people with HIV experience an 

heart disease, kidney disease and frailty

 than their non-HIV peers, even if their HIV is well-controlled with antiretroviral medications.

“It has been suggested that this represents premature or accelerated aging, but consensus on this point has been hampered by a lack of agreement on, or methods by which to define, what constitutes normal aging,” Jamieson and colleagues wrote.

One increasingly prominent method of tracking aging is so-called “epigenetic aging.” The authors said this process entails “assessing the process of human aging at a subcellular level by examining patterns of DNA methylation (DNAm) in various cell types and tissues.”

There have already been studies that attempted to gauge HIV’s impact on epigenetic age by comparing people with HIV to people without HIV. However, Jamieson and colleagues said those studies have largely been cross-sectional, point-in-time comparisons between people with infections and uninfected people of the same age.

In the new study, Jamieson and colleagues took a longitudinal approach, seeing how epigenetic age changed over time in people who were infected with HIV compared to matched controls. The investigators recruited 102 subjects into the study, taking epigenetic measures prior to HIV infection and approximately 3 years after infection. All of the subjects in the study were participants in the Multicenter AIDS Cohort Study (MACS). The subjects were all considered at-risk for HIV infection, and due to their participation in the cohort study, the investigators had access to data regarding other factors that might also lead to epigenetic aging, such as smoking status and body mass index (BMI).

From the time of their pre-infection until up to 3 years after infection, the investigators found that people who were infected with HIV had a median estimated epigenetic age acceleration of 1.9-4.8 years. Those with HIV also experienced significant shortening of the telomeres at the ends of their chromosomes, a phenomenon that occurs with repeated cell division and age.

In the healthy controls who did not become infected, no such acceleration was seen. Moreover, the investigators said their analysis suggested that potentially confounding factors like smoking, BMI, and hepatitis B infection status, did not account for the changes.

“These longitudinal observations clearly demonstrate an early and substantial impact of HIV infection on the epigenetic aging process, and suggest a role for HIV itself in the earlier onset of clinical aging,” Jamieson and colleagues wrote.

The investigators noted that their study was made up entirely of men who have sex with men, and so the results may not be generalizable to other groups of people, such as women. They added that their sample size was limited by the need to have viably preserved pre-infection blood samples from all subjects. They also noted that other factors, aside from HIV infection, can affect epigenetic age.

Still, they said their study is the first to show that, among people with similar demographic and lifestyle characteristics, HIV infection is associated with a significant and rapid uptick in epigenetic age.

“Although it is likely that at least some of the epigenetic changes observed over the course of HIV infection may not be unique among viral infections, the current longitudinal study design offers a rare insight before and after initial infection with a virus that directly infects and impacts immune cells circulating in the blood,” they said.

The study was longitudinal in nature, comparing at-risk people who became infected with HIV to at-risk people who did not.

HIV Associated with Rapid Age Acceleration, New Study Finds

) pandemic prompted schools worldwide to cancel in-person learning for weeks and months, but a new study argues schools can—and should—safely operate with a mix of vaccination and regular testing of unvaccinated students.

, is based on a model of school transmission developed based on contact data and pilot screenings from 683 French schools.

Corresponding author Vittoria Colizza, PhD, of Sorbonne University, said the experience of the pandemic has made 2 things clear: having schools open leads to an increase in community transmission and yet keeping schools open should be a “primary objective” to safeguard the educational, emotional, and social needs of children.

 in schools is therefore key to maintaining schools open in light of a continuously evolving pandemic,” Colizza and colleagues said.

Using data from 2 periods in 2021, the authors created a model that could be used to see how various interventions might affect transmission and risk in a school setting. The authors calculated school-specific reproductive numbers for COVID-19 for both the Alpha and Delta variants.

For the Alpha variant, the reproductive number was 1.40 (95% confidence interval [CI] 1.35-1.45) in the primary school and 1.46 (95% CI 1.41-1.51) in secondary schools. They noted that that rate was higher than the rate estimated via community surveillance.

For the Delta variant, they found something of a divergence, with a significantly higher reproductive number in primary schools, 1.66 (95% CI 1.60-1.71), and a lower reproductive number in secondary schools, 1.10 (95% CI 1.06-1.14).

Using those rates, the investigators calculated that if the schools tested 75% of unvaccinated students on a weekly basis and tested any 

, they could reduce cases by 34% in primary schools and 36% in secondary schools.

Moreover, such a regime would translate into fewer lost days of instruction. In fact, the authors said such a strategy could reduce lost days by 80% compared to simply testing symptomatic children and then closing their classes.

“Our analysis indicates that regularly screening the school population is efficient in preventing infections while reducing absence from school, especially in settings where the school population is not yet vaccinated, coverage is low to moderate, or vaccine protection has largely waned,” Colizza and colleagues wrote.

The investigators said even with masks and other precautions, transmission is likely at schools. They said their model affirms that a regular testing protocol is a critical component of viral mitigation at school.

“It also provides a cost-benefit analysis considering successive variants, comparing multiple protocols, and evaluating the key role of adherence in the context of partly vaccinated school populations,” they wrote.

Notably, while the authors said their goal was to limit both community spread and missed days of school, they said it is not clear that reactive classroom closures are even particularly effective, given that the virus can spread silently, and some people do not have obvious symptoms. They said proactive screening allows school officials to detect more cases, enabling them to take a more targeted approach when deciding which students need to isolate.

Colizza and colleagues emphasized that vaccinating students is essential. While vaccination of teachers is beneficial, the authors said it does not significantly limit spread, even if a school’s entire teaching staff is vaccinated.

“This results from the small number of teachers and the observed lower rate of interaction they have with students, and it is confirmed even when community incidence in adults is much higher than in the student-age classes,” they wrote.

The authors concluded that COVID-19 is likely to continue to be a factor affecting public health and education for the foreseeable future.

“​​Regular testing remains a key strategy to epidemic control in school settings with moderate vaccination coverage or following waned vaccine protection, all the while minimizing days lost,” they concluded.

The model suggests screening unvaccinated students could reduce absences by 80% compared to reactively closing classes with infected students.

Jared Kaltwasser

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