Analysis of the effect of HDAC inhibitors on the formation of the HIV reservoir.

The HIV reservoir is more dynamic than previously thought with around 70% of the latent reservoir originating from viruses circulating within 1 year of the initiation of antiretroviral therapy (ART). In an ex vivo model system of HIV latency, it was reported that early exposure to class I histone deacetylase (HDAC) inhibitors might prevent these more recently infected cells from entering a state of stable viral latency. This finding raises the possibility that co-administration of HDAC inhibitors at the time of ART initiation may prevent the establishment of much of the HIV reservoir. Here, we tested the effects of the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and panobinostat co-administered at the time of ART initiation on the formation of the viral reservoir in HIV-infected humanized mice. As previously shown, SAHA and panobinostat were well tolerated in humanized mice. Unexpectedly, co-administration of SAHA resulted in an increase in the frequency of CD4+ cells carrying HIV DNA but did not alter the frequency of cell-associated HIV RNA in HIV-infected, ART-treated humanized mice. Co-administration of panobinostat did not alter levels of cell-associated HIV DNA or RNA. Our in vivo findings indicate that co-administration of HDAC inhibitors initiated at the same time of ART treatment does not prevent recently infected cells from entering latency.IMPORTANCECurrent antiretroviral therapy (ART) does not eradicate cells harboring replication-competent HIV reservoir. Withdrawal of ART inevitably results in a rapid viremia rebound. The HIV reservoir is more dynamic than previously thought. Early exposure to class I histone deacetylase (HDAC) inhibitors inhibit these more recently infected cells from entering a state of stable viral latency in an ex vivo model of latency, raising the possibility that co-administration of HDAC inhibitors at the time of ART initiation may reduce much of the HIV reservoir. Here, we tested the effects of the HDAC inhibitors suberoylanilide hydroxamic acid or panobinostat during ART initiation on the formation of the viral reservoir in HIV-infected humanized mice. Our in vivo study indicates that in contrast to in vitro observations, the co-administration of HDAC inhibitors at the same time of ART initiation does not prevent recently infected cells from entering latency.

Associations Between Social Networks and COVID-19 Vaccine Uptake in 4 Rural Alabama Counties: Survey Findings.

OBJECTIVES: The COVID-19 pandemic demonstrated how vaccination decisions are influenced by misinformation, disinformation, and social pressures, leading to varied and inequitable uptake rates. In this study, we examined how COVID-19 vaccine messages received via social networks were associated with vaccine uptake in rural Alabama. METHODS: From November 2021 through March 2022, we collected 700 responses to a telephone survey administered in 4 rural Alabama counties. We asked respondents to indicate whether certain social relationships (eg, family, businesses) tried to influence them to (1) obtain or (2) avoid a COVID-19 vaccine. We used χ2 tests, Kruskal-Wallis tests, Mantel-Haenszel χ2 tests, and Fisher exact tests to examine the associations between vaccination status and survey responses. RESULTS: Respondents in majority-African American counties were significantly more likely than those in majority-White counties to have received ≥1 dose of COVID-19 vaccine (89.8% vs 72.3%; P < .001). Respondents who received ≥1 dose had a significantly higher mean age than those who had not (58.0 vs 39.0 years; P < .001). Respondents who were encouraged to get vaccinated by religious leaders were more likely to have received ≥1 dose (P = .001), and those who were encouraged to avoid vaccination by family (P = .007), friends (P = .02), coworkers (P = .003), and health care providers (P < .001) were less likely to have received ≥1 dose. Respondents with more interpersonal relationships that encouraged them to avoid vaccination were more likely to be unvaccinated (P < .001). CONCLUSIONS: Interpersonal relationships and demographic characteristics appeared to be important in COVID-19 vaccine decision-making in rural Alabama. Further research needs to identify how to facilitate vaccine-positive interpersonal relationships, such as peer mentoring and trusted messenger interventions.

Physical activity is associated with adiposity in older adults with HIV in the modern HIV era.

OBJECTIVES: People with HIV (PWH) are aging and are experiencing higher rates of abdominal adiposity. Physical activity is an effective nonpharmacological strategy to reduce adiposity in the general aging population. Yet, the relationship between physical activity and adiposity in people with well controlled HIV is unclear. Our objective was to describe the association between objectively-measured physical activity and abdominal adiposity in PWH. METHODS: As part of the multisite, observational PROSPER-HIV study, virologically suppressed, adult PWH wore an Actigraph accelerometer for 7-10 days and completed duplicate waist and hip circumference measures. Demographic and medical characteristics were abstracted from the CFAR Network of Integrated Clinical Systems dataset. Descriptive statistics and multiple linear regressions were used to analyze the data. RESULTS: On average, our 419 PWH were 58 years of age [interquartile range (IQR): 50, 64], male (77%), Black (54%), and currently taking an integrase inhibitor (78%). PWH completed a mean of 7.06 (±2.74) days of total actigraphy wear time. They took an average of 4905 (3233, 7140) steps per day and engaged in 5.4 h of sedentary time per day. Controlling for age, sex, employment and integrase inhibitor use, the number of steps taken per day was associated with reduced abdominal adiposity ( F  = 3.27; P  < 0.001) and the hours of daily sedentary time was associated with increased abdominal adiposity ( F  = 3.24; P  < 0.001). CONCLUSIONS: Greater physical activity is associated with reduced abdominal adiposity in aging PWH. Future work should investigate how to tailor the amount, type and intensity of physical activity needed to reduce adiposity in PWH taking contemporary HIV medication. REGISTRATION NUMBER: NCT03790501.

Quality of prereferral care in patients with chronic renal insufficiency.

BACKGROUND: Appropriate care in chronic renal insufficiency (CRI) includes blood pressure and diabetes control, as well as the investigation and management of anemia, acidosis, and bone disease. There is a lack of data on the control of these parameters at the time of referral to a nephrologist. Similarly, early referral has been emphasized in the literature, yet very little published has examined current referral patterns. METHODS: A single-center retrospective/prospective review of all new outpatient referrals to nephrologists in Halifax, Canada, in 1998 and 1999 was conducted to identify patients with CRI (serum creatinine > 1.6 mg/dL [141 micromol/L] for men or >1.2 mg/dL [106 micromol/L] for women). Quality of prereferral care was based on data from the initial clinic visit. RESULTS: Of 1,050 charts reviewed, 411 patients met the study criteria. Twenty-six percent of patients had diabetes mellitus, 18% were referred with a calculated glomerular filtration rate less than 15 mL/min, and blood pressure was optimally controlled (<130 mm Hg systolic and <80 mm Hg diastolic) in only 24%. Only 44% of patients were administered an angiotensin-converting enzyme inhibitor. Patients were administered an average of 1.9 antihypertensive agents. Significant anemia (hemoglobin < 10 g/dL) was present in 21%, and appropriate investigations were performed in only 35% of these patients. Calcium levels less than 8.6 mg/dL (2.15 mmol/L) were found in 19% of patients, and only 14% of these patients were started on calcium supplement therapy. Phosphate levels greater than 5.0 mg/dL (1.6 mmol/L) were seen in 20% of patients, and 14% of these patients were on phosphate-binder therapy. Parathyroid hormone levels were more than five times normal values in 18% of patients, and 25% of patients had bicarbonate levels less than 23 mmol/L. CONCLUSIONS: A significant proportion of patients referred with CRI receive inadequate prereferral care. Continuing education programs and referral guidelines must not only emphasize the importance of early referral, but also address the related consequences of CRI to delay the progression of renal disease and avoid complications.