IDWeek 2020

Infectious Disease Week 2020 (IDWeek 2020) is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medical Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP). A diverse array of health professionals addressed important topics in infectious disease including a few highlights featured here.

Switch to injectable regimen maintains virologic suppression in HIV, is preferred over daily oral regimen

Presenter: Anthony Mills, MD

The combination of cabotegravir and rilpivirine long-acting (LA), administered every 2 months, maintained high levels of virologic suppression in HIV-positive antitretroviral therapy (ART)-experienced patients, with a favorable safety profile, according to data from the POLAR study. (1)

In addition, patients in POLAR preferred the injectable regimen as maintenance therapy over a daily oral fixed-dose combination of dolutegravir plus rilpivirine.

“Taken together, these results indicate that cabotegravir and rilpivirine LA given every 2 months is an efficacious and well-tolerated maintenance therapy for HIV-1 infection that may be preferable to daily oral therapy,” said Anthony Mills, MD, from the Men’s Health Foundation in Los Angeles, who presented the results.

POLAR is a phase IIb open-label study that included 97 patients who were rolled over from the phase IIb LATTE study. Eligible patients completed a minimum of 312 weeks of a two-drug regimen consisting of once-daily oral cabotegravir 30 mg plus rilpivirine 25 mg, and had demonstrated HIV-1 RNA suppression < 50 copies/mL on this oral regimen as part of LATTE.

Patients enrolled in POLAR were offered the option to switch to long-acting intramuscular injections of cabotegravir and rilpivirine LA every 2 months or the oral fixed-dose combination of dolutegravir plus rilpivirine for the continued maintenance of HIV-1 RNA suppression; 90 patients chose the injectable regimen, and 7 chose the daily oral regimen.

Baseline characteristics were similar between the treatment groups. The median age of the overall cohort was 4, with 21% age 50 and older; 69% were White, 25% were Black or African American; median body mass index was 27 kg/m2; and the median CD4+ cell count was 842 cells/mm3.

“What is worth noting is that greater than 90% of the individuals in the trial chose injectable therapy regardless of gender or race,” said Dr. Mills.

The primary end point was the proportion of patients with HIV-1 RNA ≥ 50 copies/mL at month 12 as per the FDA Snapshot algorithm.

Overall, 98% of participants in the cabotegravir-rilpivirine LA arm and 100% of participants in the dolutegravir-rilpivirine oral arm maintained virologic suppression at month 12. At month 12, no participant had HIV-1 RNA ≥ 50 copies/mL per the FDA Snapshot algorithm in either treatment arm, and no participant in either arm met the confirmed virologic failure criterion.

Through month 12, 96% of participants in the cabotegravir-rilpivirine LA arm and 43% of those in the dolutegravir-rilpivarine arm reported adverse events. “This difference was primarily due to the occurrence of injection site reactions in the cabotegravir plus rilpivirine LA arm,” said Dr. Mills.

Cumulatively, 78% of participants in the cabotegravir-rilpivirine LA arm reported injection site reactions (total of 463 events); reaction events were mild in 84% of cases and moderate in 16%. The majority of reactions resolved within 7 days (median 3). No participant withdrew because of injection site reactions.

Adverse events excluding injection site reactions in the cabotegravir-rilpivirine LA arm were nasopharyngitis (11%), upper respiratory tract infection (11%), diarrhea (10%), pyrexia (10%), headache (7%), fatigue (7%), syphilis (7%), cough (6%), hemorrhoids (6%), and nausea (6%).

Only one participant withdrew due to an adverse event (a case of drug-related depression in the cabotegravir-rilpivirine LA arm). There was one drug-related serious adverse event in the cabotegravir-rilpivirine LA arm (injection site extravasation). No clinically relevant patterns in clinical laboratory results over the 12-month period were observed.

At month 12, 88% of patients in the cabotegravir-rilpivirine LA arm who responded to a survey preferred cabotegravir-rilpivirine LA over the oral cabotegravir-rilpivirine regimen they had received in the LATTE study. The most commonly cited reasons for preference were superior convenience (69%) and less frequent administration (57%).

Dr. Mills has disclosed financial interests (grant, research support, advisor or review panel member) with Gilead, Janssen Pharmaceutica, Merck, Shionogi, and ViiV Healthcare.

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HIV testing falls during COVID-19 pandemic, but rate of acute HIV infection diagnoses increases

Presenter: David Pitrak, MD

HIV testing has declined by half at healthcare emergency departments (EDs) throughout Chicago, IL, during the COVID-19 pandemic. Despite this decline in testing, the rate of acute HIV infections diagnosed in patients presenting to EDs with influenza-like illness has increased since the first case of COVID-19 was diagnosed in Chicago.

The data also show that rapid linkage to care and initiation of antiretroviral therapy (ART) can still be achieved during the COVID pandemic.

These are among the findings of a review of HIV screening data from the Expanded HIV Testing and Linkage to Care (x-TLC) program, a consortium of 15 affiliated healthcare sites in the Chicago area that have implemented routine HIV screening.

Symptoms of COVID-19 infection and acute HIV infection overlap, so screening patients with an influenza-like illness for HIV is an opportunity to identify patients with acute HIV infection, said the presenter, David Pitrak, MD, from the University of Chicago Medicine (UCM).

“HIV screening programs, especially those in EDs, need to maintain HIV screening volumes during the COVID-19 pandemic,” he said.

Testing volumes were analyzed at UCM and affiliated sites in the x-TLC program during the COVID-19 pandemic. Acute HIV infection was defined as a positive fourth-generation HIV combination Ab/Ag assay, with a negative or indeterminate supplemental Ab test and a positive HIV quantitative polymerase chain reaction test.

The number of tests in the x-TLC program decreased from 22,502 in January-February 2020 to 11,766 in April-May 2020, a reduction of 48%. The median reduction in the number of HIV screens was 58%. At the end of June 2020, testing was still reduced by a median of 32%.

UCM performed 119,111 HIV screens, 11,133 of them in an ED setting, between January 1 and August 17, 2020. Nine patients (7 men, and 2 cisgender women) were diagnosed with acute HIV infection after the first case of COVID-19 in Chicago. All 9 were diagnosed in the ED, and 8 of the 9 presented with an illness indistinguishable from COVID-19. The rate of acute HIV diagnoses was more than twice that of the previous 4 years (14.4 vs 6.8/year; incidence ratio 1.24; 95% confidence interval 1.01–4.54).

“Acute HIV diagnoses comprised 25.7% of all new diagnoses; the highest proportion ever observed,” said Dr. Pitrak.

UCM’s model of care delivery assigns all responsibilities for test review, patient notification, linkage to care, initiation of ART, and partner services to the HIV Care Program.

All 9 patients were notified and had ART initiated. “We were able to link 100% of these patients to care and get them on ART within a few days,” said Dr. Pitrak. “Our findings show that blood-based screening programs for HIV should be incorporated into all COVID-19 testing programs, especially in EDs, and we think this can be replicated everywhere—urban, suburban, rural communities—as long as you have a partnership between the ED and the infectious diseases or HIV care program.”

Since the abstract was submitted to IDWeek 2020, the trend has continued, said Dr. Pitrak, with an additional 3 patients (2 heterosexual men and 1 heterosexual woman) with acute HIV infection being identified. All 3 were notified and had ART initiated at 2 days, 3 days, and 4 days, he said.

There are multiple possibilities for the increased incidence of acute HIV infections diagnosed in the ED. Patients with acute HIV infection may be more likely to seek medical care because of a concern for COVID-19 infection. The incidence of acute HIV infection diagnoses may also be due to an increase in new transmissions due to disruptions of the continuum of care for persons living with HIV. Behavioral changes may also have been precipitated by the pandemic.

Dr. Pitrak has disclosed financial interests (grant/research support) with Gilead Sciences.

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Persistent symptoms, especially cough and dyspnea, common in patients testing positive for COVID-19

Presenter: Aditi Ramakrishnan, MD

Symptom persistence—primarily cough, chest tightness, and dyspnea on exertion—is common in patients testing positive for COVID-19, even up to 96 days from symptom onset.

This finding, in addition to the emerging literature on the outpatient landscape of COVID-19, indicates the need for primary care clinicians to target primary care towards the need of these “long-haulers,” said Aditi Ramakrishnan, MD, from Emory University, Atlanta, who presented findings from a chart review of patients testing positive for COVID-19 at Emory.

Previous surveys indicate that 1 in 10 COVID-19 patients report symptoms 3 weeks after the acute illness. To get a better handle on COVID-19 symptomatology in outpatients, Dr. Ramakrishnan and colleagues conducted a retrospective chart review of 127 patients at Emory with a positive real-time polymerase chain reaction test for SARS- CoV-2 between April 3 and May 16, 2020. A total of 107 unique patients with 1 to 4 visits were included in the analysis.

About three-fourths (75.7%) were female, 48.6% were Black, and 21.2% were healthcare workers. The median age was 55 (range 24–89). The most common comorbid conditions were hypertension (39.3%), obesity (27.1%), asthma (21.5%), and diabetes (20.6%). Patients presented to the clinic 1 to 96 days from symptom onset (median 14 days); and 60.6% of patients reported persistent symptoms in the convalescent phase (> 28 days after onset).

Fever was present in 60.0% of patients during the acute phase (< 7 days), declining to 27.0% in the subacute phase (7–28 days) and 30.3% in the convalescent phase. “Cough was a persistent complaint throughout the stages, at around 75%,” said Dr. Ramakrishnan. In the convalescent phase, dyspnea was still present in 42.4%, dyspnea only on exertion in 66.7%, chest tightness in 60.6%, sinus congestion in 30.3%, body aches and headache in 24.2%, and altered taste or smell in 24.2%.

Lung auscultation was normal in most encounters overall. Abnormal findings included rales, rhonchi, and decreased air movement. Resting pulse oximetry was greater than 95% in 89% of encounters overall. Few patients experienced oxygen desaturation. Of 64 chest radiographs performed, 68.8% were normal, with abnormal being defined as chest infiltrates.

More than 80% of patients were discharged home, but 17.3% of encounters resulted in direct transfer to the emergency department, including patients too unstable for the floor or to the inpatient ward. Dyspnea, hypoxia, and chest pain were the primary reasons for transfer or hospitalization.

“Studies are now emerging describing long-term cardiopulmonary damage in young, otherwise healthy individuals, which has been concerning in the setting of reopening schools,” she said. “Reassuringly, only a minority of patients were found to have exam and imaging abnormalities. However, the rate of direct transfers to the ED and admissions from the clinic was notable.”

The findings indicate that “clinics must be aware of and prepared to manage prolonged symptoms, including providing attention and reassurance when appropriate, adequate pulmonary care, and the awareness and ability to direct patients to higher levels of care or appropriate subspecialists,” Dr. Ramakrishnan added.

One limitation of the chart review was a study sample that represented the early phase of the pandemic in metropolitan Atlanta. “But as we know, younger patients have been more affected in recent months and may present with different patterns,” said Dr. Ramakrishnan.

As the pandemic evolves, more research is needed regarding longitudinal symptoms of COVID-19 in different patient populations, she added.

Dr. Ramakrishnan has disclosed no relevant relationships.

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20-valent pneumococcal conjugate vaccine as immunogenic as 13-valent vaccine with coverage of 7 additional serotypes

Presenter: Brandon Essink, MD

A 20-valent pneumococcal conjugate vaccine (PCV20) proved as immunogenic as a 13-valent pneumococcal conjugate vaccine (PCV13) in adults in a phase III pivotal evaluation.

PCV20 met the noninferiority criterion for each of the 13 matching serotypes and for 6 of the 7 additional serotypes compared with PCV13 and PPSV23, respectively, in adults age 60 and older, said Brandon Essink, MD, Meridian Clinical Research, Omaha, Neb.

The immunogenicity of PCV in adults ages 18 to 59 was bridged to that in adults ages 60 to 64, supporting PCV20 use in adults age 18 and older, he said.

PCV20 is being developed to expand pneumococcal serotype coverage beyond PCV13. It was granted breakthrough therapy designation by the US Food and Drug Administration based on results in adults in a phase II study. It contains all the components of PCV13 along with conjugates for 7 additional serotypes responsible for a substantial amount of the residual disease burden. “The additional 7 serotypes [8, 10A, 11A, 12F, 15B, 22F, and 33F] in PCV20 were selected based on their relative prevalence for causing disease, generalized geographic distribution, and associations with antibiotic resistance, invasive potential, or more severe disease,” said Dr. Essink.

Eligible for inclusion into the double-blind study were people age 18 and older, who were stratified into 1 of 3 cohorts based on age at the time of enrollment. Cohort 1 comprised 3,009 adults age 60 and older randomized 1:1 to a single dose of either PCV20 or PCV13, followed at month 1 by saline in the PCV20 arm and by PPSV23 in the PCV13 arm.

PPSV23, another pneumococcal vaccine used in adults, contains unconjugated polysaccharides and additional serotypes. “There are known limitations of PPSV23, which elicits T cell-independent responses, which do not result in long-lasting protection against disease. PPSV23 also does not prevent mucosal transmission of disease, and several studies have failed to show effectiveness against nonbacteremic pneumonia in adults,” Dr. Essink said.

Cohort 2 consisted of 445 adults ages 50 to 59, and cohort 3 included 448 adults ages 40 to 49. In cohorts 2 and 3, participants were randomized 3:1 to a single dose of PCV20 or PCV13.

Demographics were similar between vaccine groups within each age cohort. The study was completed by 92.9% to 98.2% of participants in each group. The most common reason for study withdrawal in each arm was participants being lost to follow-up.

“PCV20 immunogenicity was noninferior to PCV13 or PPSV23 for 19 of 20 serotypes,” Dr. Essink said. All 13 matching serotypes and 6 of 7 additional serotypes met noninferiority criteria. Only serotype 8 narrowly missed the noninferiority comparison: the 2-sided 95% lower bound of geometric mean titer ratio (20vPnC/PPSV23) was 0.49, with a noninferiority criterion of greater than 0.5, which is unlikely to be clinically significant.

After PCV20 administration, there was a 22.1-fold rise in geometric mean titer ratio from baseline to serotype 8, 77.8% of participants had at least a 4-fold rise for serotype 8, and 92.8% achieved a serotype 8 titer at or above the lower limit of quantitation. “The totality of pivotal study immunogenicity data support PCV20 inducing protective responses for serotype 8,” he said. “There is no threshold of protection for pneumococcal disease, particularly in adults, and missing noninferiority of OPA [opsonophagocytic activity] geometric mean titers, particularly by a very narrow margin, does not equate with lower protection.”

PCV20 immune responses in adults ages 50 to 59 or ages 18 to 49 were noninferior to those in the oldest age group.

The frequency and severity of local reactions within 10 days after either vaccine was similar. Pain at the injection site was the most frequently reported local reaction; the vast majority were mild or moderate in severity. The frequency and severity of systemic events within 7 days of administration of PCV20 or PCV13 were also similar, and almost all were considered mild or moderate in severity. Muscle pain was the most common systemic event; fever was reported by 0.9% to 1.5% of PCV20 recipients and by 0.8% to 1.8% of PCV13 recipients.

The frequency of adverse events 1 month after administration was 8.1% to 15.2% in the vaccine groups, with higher percentages recorded in the youngest age group, and was similar between PCV20 and PCV13 arms in each-age specific cohort.

“These findings provide confidence that the adult indication of PCV20 will likely be successful and protect against invasive pneumococcal disease and pneumonia due to the 13 serotypes in PCV13, and also effective against disease due to the 7 additional pneumococcal serotypes in adults age 18 or older,” Dr. Essink said.

Dr. Essink has disclosed no relevant relationships.

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Seven days of antibiotics as effective as 14 in afebrile men with UTI

Presenter: Dimitri Drekonja, MD

Seven days of antimicrobial therapy is noninferior to 14 days on resolution of symptoms in afebrile men with urinary tract infection (UTI). In addition, no significant differences were observed in UTI recurrence and the rate of adverse events between men prescribed 7 vs 14 days of treatment, according to data presented by Dimitri Drekonja, MD, from the Minneapolis VA Health Care System.

“Based on these results, treatment beyond 7 days should not be prescribed to afebrile men with UTI,” he said.

Unlike in women, the optimal duration of treatment for UTI in men is poorly defined. To address the appropriate duration of antimicrobial treatment in afebrile men with UTI, a randomized controlled trial of 7 vs 14 days of antimicrobial therapy was performed using a pragmatic design that enrolled symptomatic patients taking trimethoprim-sulfamethoxazole (TMP-SMZ) or ciprofloxacin for UTI. After 7 days of initial (prescribed) therapy, patients were randomized to placebo (the 7-day group) or their original antimicrobial, but from a different manufacturer, so that all patients received a medication that appeared different from their initial medication (the 14-day group). All patients were followed by phone on days 0, 7, 14, and 28 after stopping the study drug. Patients were randomized in blocks of 4 and were stratified by catheter use and initial medication. 

The primary outcome, symptom resolution in the per-protocol analysis, was assessed on day 14 after stopping active antibiotic (7-day assessment for the placebo group; 14-day for active antimicrobial group).

Eligible patients were those who were treated in the outpatient setting (although 24 hours of observation in the hospital was allowed), were prescribed 7 to 14 days of TMP-SMZ or ciprofloxacin, and had new onset of at least 1 of the following symptoms: dysuria, frequency, urgency, hematuria, costovertebral angle tenderness, or perineal, flank, or suprapubic pain. 

A total of 273 patients (mean age 67.8) were enrolled and 272 were randomized. The study was a noninferiority design, and the prespecified minimally clinically significant difference for the primary 0utcome was set at 10%, with a P value of .05 considered as significant.

Race of the cohort was as follows: 77.9% were White, 18.4% were Black, 2.2% were Native American, and 1.8% declined to answer or indicated multiple races; 93.3% identified as non-Hispanic/Latino, 4.8% as Hispanic/Latino, and 2.2% as unknown.

All patients received 7 days of TMP-SMZ or ciprofloxacin before randomization. A total of 131 of 136 patients assigned to placebo for days 8 to 14 took as directed, defined as at least 26 of 28 doses and missing no more than 2 consecutive scheduled doses, as did 123 of the 136 assigned to antimicrobial therapy for days 8 to 14.

Indwelling catheter use (5.9% vs 5.8%) and intermittent catheter use (17.6% vs 16.9%) were not different between the 7-day and 14-day groups. At baseline, 33.8% of the 7-day group and 44.1% of the 14-day group had diabetes, and the presence of a cerebrovascular accident at baseline was 9.6% and 3.7% in the 2 groups, respectively, with neither difference being statistically significant.

In the 254 men in the per-protocol analysis, symptom resolution occurred in 93.1% who received 7 days of treatment and in 90.2% who received 14 days (difference 2.9%; 95% confidence interval -4.7% to 10.5%; P = .50), confirming noninferiority. On an intention-to-treat analysis, rates of symptom resolution were 91.9% and 90.4%, respectively (difference 1.5%; 95% confidence interval -6.0% to 8.9%; P = .80). 

In the per-protocol analysis, UTI recurrence rates were 9.9% in the 7-day group compared with 12.2% in the 14-day group (P = .69), and in the intention-to-treat analysis, UTI recurrence rates were 10.3% and 16.9%, respectively (P = .16). Rates of adverse events were similar between groups in both the per-protocol and intention-to-treat analyses.

Dr. Drekonja has disclosed no relevant relationships.

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Loss to follow-up after HIV pre-exposure prophylaxis is common

Presenter: Robert Williams Jr.

Patients receiving HIV pre-exposure prophylaxis (PrEP) are at highest risk of being lost to follow-up at the early stage of PrEP initiation, according to results from a longitudinal study of data from an academic PrEP program in Rhode Island. 

Only about one-fourth of patients who were lost to follow-up after PrEP initiation were later re-engaged in PrEP care, said lead investigator Robert Williams Jr., medical student at Brown University, Providence, RI.

Tenofovir disoproxil fumarate with emtricitabine was approved in the United States in 2012 as a once-daily agent for prevention of HIV infection; emtricitabine/tenofovir alafenamide was subsequently approved for this purpose in 2019 and was adopted given its more benign adverse-effect profile. PrEP has been demonstrated to be a safe and effective biomedical preventive approach against HIV infection in seronegative individuals.

“Given its nature as a once-daily pill to properly continuously confer protection, retention of PrEP is critical to achieving the optimal protective effect,” said Mr. Williams. “Few studies have focused on long-term retention of care—loss to follow-up—and re-engagement of PrEP care and its implications,” he added. “While many at-risk individuals enter into HIV PrEP consultations and receive 3 months of supplies, retaining these patients is paramount when looking at public health and reducing lifelong risk of HIV infection.”

The goal of the study was to evaluate the long-term loss to follow-up and re-engagement at various time intervals using patient data collected from the major academic PrEP program in Rhode Island and to observe trends in time and demographic correlates.

Medical record data from all cisgender patients presenting to a major Rhode Island PrEP clinic from 2013 to 2019 were included in the study. Loss to follow-up was defined as no PrEP follow-up appointment within 98 days of the first appointment. Re-engagement in care was defined as missing at least 2 consecutive follow-ups (196 days [6.54 months]) and later attending a follow-up appointment.

A total of 654 cisgender patients (median age 31) met the inclusion criteria, 380 of whom were lost to follow-up without further re-engagement of care. A total of 274 were retained in care by the end of the study despite any intermittent loss events. Of the entire cohort, 64% identified as White and 81% as non-Hispanic; 96% were men, 62% had a college education or above, and 97% had health insurance. Those who were lost to follow-up were younger (median age 30 vs 34; P < .001) and had a lower reported median income ($30,000 vs $50,000; P < .001) compared with those retained in care.

“We found that only 28% of participants were ever retained in care from their initial appointment until the end of the study, and 72% were instead lost to follow-up at least once,” he said. “Among those who were lost to follow-up, the median observation time that they were connected to care during their first engagement was 6.2 months, compared with 10.1 months for those retained without any gaps [P < .001]. Additionally, of the 469 patients who were lost to follow-up at least once, only 27% re-engaged in care at any point afterwards.”

A Cox hazard regression analysis adjusted for race and sex and race–ethnicity showed that achieving a college education or greater (hazard ratio 0.69; 95% confidence interval 0.57–0.82) and identifying as bisexual (hazard ratio 2.25; 95% confidence interval 1.70–2.99) or heterosexual (hazard ratio 2.35; 95% confidence interval 1.15–4.82) were significant predictors of persistence in PrEP care.

Of the 654 patients initially in care, only 67% were retained in care at 3 months (first follow-up visit), 52% at 6 months, 33% at 1 year, 20% at 2 years, 13% at 3 years, 7% at 4 years, 5% at 5 years, and 5% at 6 years.

“For patients during their second and third engagements, rate of loss to follow-up was markedly higher than the rates of those who had a single engagement, possibly indicating that it is easier for those who have been lost to follow-up once to do so again,” said Mr. Williams.

Mr. Williams has disclosed no relevant relationships.

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