Asymptomatic SARS-CoV-2 Infection Is Common Among ART-Treated People With HIV.

BACKGROUND: Limited data are available regarding asymptomatic COVID-19 among people with HIV (PWH). Data on a representative subset of PWH enrolled in Randomized Trial to Prevent Vascular Events in HIV, a global clinical trial, are presented here. METHODS: Randomized Trial to Prevent Vascular Events in HIV is an atherosclerotic cardiovascular disease prevention trial among 7770 PWH on antiretroviral therapy. Beginning April 2020, targeted data on coronavirus disease 2019 (COVID-19) diagnosis and symptoms were collected during routine trial visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was defined as either COVID-19 clinical diagnosis or presence of SARS-CoV-2 Immunoglobulin G (IgG) or Immunoglobulin A (IgA) receptor binding domain protein (antispike) antibodies in the absence of prior COVID-19 vaccine. RESULTS: The group (N = 2464) had a median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm 3 , and 97% with HIV VL <400 cp/m. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical diagnosis and 260 with detectable antibodies. Of these PWH, 304 completed symptom questionnaires: 121 (40%) reported symptoms, but 183 (60%) were asymptomatic. PWH with asymptomatic SARS-CoV-2 infection were more likely to be from low-income or middle-income regions, of Black or African American race, older in age, and with higher atherosclerotic cardiovascular disease risk score. Symptomatic COVID was more common with obesity, metabolic syndrome, and low HDL levels. CD4 counts and HIV viral suppression rates were similar among PWH with symptomatic vs. asymptomatic COVID. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common among antiretroviral therapy-treated PWH globally. We determined that 60% of infections in PWH were asymptomatic. HIV clinicians must remain vigilant about COVID-19 testing among PWH to identify asymptomatic cases.

Recurrent COVID-19 in Hemodialysis: A Case Report of 2 Possible Reinfections.

Patients receiving in-center hemodialysis are at high risk for infections due to relative immunosuppression, limited ability to physically distance, and frequent encounters with the health care setting. This has been particularly evident during the coronavirus disease 2019 (COVID-19) pandemic. We describe 2 patients with suspected recurrent COVID-19 infection, each with documented clearance of virus between episodes. The duration between a negative reverse-transcription polymerase chain reaction test result for severe acute respiratory syndrome coronavirus 2 and symptomatic reinfection was 31 and 55 days, respectively, in the 2 patients. A higher risk for infection with COVID-19 and poor outcomes if infected, including ≥20% short-term mortality risk, is worrisome in this patient population. Continued measures such as infection prevention, community outreach, and early testing may play a role in establishing protocols to protect the vulnerable dialysis population.

COVID-19 Vaccination Rates in a Global HIV Cohort.

Little is known regarding coronavirus disease 2019 (COVID-19) vaccination rates in people with HIV (PWH), a vulnerable population with significant morbidity from COVID-19. We assessed COVID-19 vaccination rates among 6952 PWH in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) compared to region- and country-specific vaccination data. The global probability of COVID-19 vaccination through end of July 2021 was 55% among REPRIEVE participants with rates varying substantially by Global Burden of Disease (GBD) superregion. Among PWH, factors associated with COVID-19 vaccination included residence in high-income regions, age, white race, male sex, body mass index, and higher cardiovascular risk. Clinical Trials Registration. NCT02344290.

Alternative strategies of posttransplant influenza vaccination in adult solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at increased risk of influenza disease and associated complications. The mainstay of prevention is the annual standard-dose influenza vaccine, as studies showed decreased influenza-related morbidity and mortality in vaccinated SOT recipients compared to those unvaccinated. Nonetheless, the immune response in this high-risk population is suboptimal compared to healthy individuals. Over the past two decades, several vaccination strategies have been investigated to overcome this inadequate immune response in SOT recipients. Howbeit, the best vaccination strategy and optimal timing of influenza vaccination remain unclear. This review will provide a detailed summary of studies of various influenza vaccination strategies in adult SOT recipients, discussing immunogenicity results, and addressing their limitations and knowledge gaps.

Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPARE

BACKGROUND: People with human immunodeficiency virus (PWH) are at risk for accelerated development of physical function impairment and frailty;both associated with increased risk of falls, hospitalizations, and death. Identifying factors associated with physical function impairment and frailty can help target interventions. METHODS: The REPRIEVE trial enrolled participants 40-75 years of age, receiving stable antiretroviral therapy with CD4+ T-cell count >100 cells/mm3, and with low to moderate cardiovascular disease risk. We conducted a cross-sectional analysis of those concurrently enrolled in the ancillary study PREPARE at enrollment. RESULTS: Among the 266 participants, the median age was 51 years;81% were male, and 45% were black, and 28% had hypertension. Body mass index (BMI;calculated as weight in kilograms divided by height in meters squared) was 25 to <30 in 38% and ≥30 in 30%, 33% had a high waist circumference, 89% were physically inactive, 37% (95% confidence interval, 31%, 43%) had physical function impairment (Short Physical Performance Battery score ≤10), and 6% (4%, 9%) were frail and 42% prefrail. In the adjusted analyses, older age, black race, greater BMI, and physical inactivity were associated with physical function impairment;depression and hypertension were associated with frailty or prefrailty. CONCLUSIONS: Physical function impairment was common among middle-aged PWH;greater BMI and physical inactivity are important modifiable factors that may prevent further decline in physical function with aging. CLINICAL TRIALS REGISTRATION: NCT02344290.

An Evaluation of Baseline Kidney Function in the REPRIEVE Trial of Pitavastatin in Human Immunodeficiency Virus

BACKGROUND: Chronic kidney disease is a common comorbid condition among persons living with human immunodeficiency virus (PWH). We characterized baseline kidney function in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial cohort. METHODS: REPRIEVE enrolled PWH with low to moderate cardiovascular risk based on traditional risk factors to evaluate the effect of statin therapy on cardiovascular events. We determined baseline estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease, and Cockcroft-Gault equations, and we evaluated baseline factors associated with eGFR <90 mL/min/1.73 m2 by logistic regression. We performed Bland-Altman plots and scatterplots to assess agreement between equations. RESULTS: Among 7770 participants enrolled, the median age was 50 years, 31% were female (natal sex), 43% black or African American and 15% Asian, the median body mass index (calculated as calculated as weight in kilograms divided by height in meters squared) was 25.8, and the median CD4 cell count 620/µL. The median CKD-EPI eGFR was 97 mL/min/1.73 m2, and 38% had an eGFR <90 mL/min/1.73 m2. In the adjusted model, factors associated with eGFR <90 mL/min/1.73 m2 included white race, older age, higher body mass index, high-income region of enrollment, hypertension, and tenofovir disoproxil fumarate. The CKD-EPI and Modification of Diet in Renal Disease equations demonstrated strong agreement, particularly at lower eGFR values. Overall, there was 56% concordance between the 3 equations (categories <60, 60 to <90, ≥90 mL/min), improving to 73% after accounting for individual body surface area. CONCLUSIONS: REPRIEVE enrolled a diverse cohort including a substantial number of PWH with reduced kidney function. Factors associated with reduced eGFR included traditional risk factors and tenofovir disoproxil fumarate exposure. Three commonly used equations have only fair agreement, with potential implications for both clinical care and epidemiologic studies. CLINICAL TRIALS REGISTRATION: NCT02344290.

Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial

BACKGROUND: Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described. METHODS: The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics. RESULTS: A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years);31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count;CD4 and CD8 cell counts were also associated with body mass index and smoking status. CONCLUSIONS: There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV. CLINICAL TRIALS REGISTRATION: NCT02344290.