HIV-1-infected T cell clones are shared across cerebrospinal fluid and blood during ART.

The central nervous system HIV reservoir is incompletely understood and is a major barrier to HIV cure. We profiled people with HIV (PWH) and uninfected controls through single-cell transcriptomic and T cell receptor (TCR) sequencing to understand the dynamics of HIV persistence in the CNS. In PWH on ART, we found that most participants had single cells containing HIV-1 RNA, which was found predominantly in CD4 central memory T cells, in both cerebrospinal fluid (CSF) and blood. HIV-1 RNA-containing cells were found more frequently in CSF than blood, indicating a higher burden of reservoir cells in the CNS than blood for some PWH. Most CD4 T cell clones containing infected cells were compartment specific, while some (22%) - including rare clones with members of the clone containing detectable HIV RNA in both blood and CSF - were found in both CSF and blood. These results suggest that infected T cells trafficked between tissue compartments and that maintenance and expansion of infected T cell clones contributed to the CNS reservoir in PWH on ART.

Willingness to Be Vaccinated Against COVID-19 Among People With HIV in the United States: Results From a National Survey.

Background: Approximately 215 million Americans have been fully vaccinated for COVID-19, representing over 65% of the total population. People with HIV (PWH) may be more susceptible to COVID-19 infection or severe disease, elevating the importance of COVID-19 vaccination uptake in the population. We report results from a national survey of PWH to evaluate the likelihood of receiving a COVID-19 vaccine. Methods: We conducted an online survey of 1,030 PWH living in the United States between December 6, 2020 and January 8, 2021 to evaluate likelihood of receiving a COVID-19 vaccine. Results: Overall, participants were highly willing to be vaccinated, with 83.8% stating they "strongly agree" (65.7%) or "somewhat agree" (18.1%). Participants' top vaccine-related concerns were side-effects (39.3%), safety (14.7%), and fair/equitable distribution of the vaccine to affected communities (13.6%). Participants were more willing to be vaccinated if they reported receiving an annual influenza vaccination (p < 0.001), had previously tested positive for (p = 0.043) COVID-19, had been hospitalized for (p = 0.027) COVID-19 infection, or had an undetectable HIV viral load (p = 0.002). Black (p < 0.001), politically conservative (p < 0.001), and participants with an annual income of ≤ $19,999 (p = 0.005) were significantly less willing to be vaccinated for COVID-19. Conclusions: The vast majority of PWH were willing to be vaccinated, though predominantly those who were already engaged in HIV care or directly affected by COVID-19. Findings from this large survey of PWH suggest intensive outreach efforts are needed to support engagement in vaccination programs, particularly among Black and politically conservative PWH.

High HIV Detection in a Tertiary Facility in Liberia: Implications and Opportunities.

Background: HIV/AIDS remains one of the world's most significant public health challenges; sub-Saharan Africa accounts for 71% of the global burden of HIV. Testing for HIV is pivotal to achieving UNAIDS 95-95-95 target towards bringing an end to the epidemic. Objective: The study assessed five-year HIV testing data from the largest tertiary hospital in Monrovia, Liberia and highlights risk groups that would benefit from targeted testing and prevention interventions. Methods: This was a single-center academic hospital-based retrospective analysis of HIV testing data from January 2014 to December 2018 obtained from all testing sites at John F. Kennedy Medical Center in Monrovia, Liberia. Pooled HIV testing data during the study period were analyzed using descriptive statistics and stratified by age, gender and pregnancy status. Annual diagnoses rates were reported as proportion of individuals tested within a specified category (age [<15 years, age 15-24 years and >=25 years], gender, and pregnancy status) that had a positive HIV test. Five-year trends were analyzed. Results: Over the study period, 41,343 non-pregnant individuals were screened for HIV. In addition, the antenatal clinic performed 24,913 tests. Of non-pregnant individuals tested, 4,066 (10%) were diagnosed with HIV ranging from 7% (909/12821) in 2018 to 13% (678/5079) in 2014. Case detection rates for individuals aged 15-24 were 7%, 5%, 4%, 6% and 3% for years 2014, 2015, 2016, 2017 and 2018 respectively. Annually, 2-3% of all pregnant women tested were diagnosed with HIV. While HIV detection rates decreased over time overall, children less than 15 years of age showed an annual increase from 6.7% in 2014 to 12.3% in 2018. Conclusion: A large five-year dataset from the largest tertiary facility in Liberia shows broad HIV detection rates that are much higher than national prevalence estimates. Ramping up HIV testing and prevention interventions including pre-exposure prophylaxis are sorely needed.

Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19.

BACKGROUND: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients. CASE PRESENTATION: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion. CONCLUSION: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

Development of a Novel Competency-Based Evaluation System for HIV Primary Care Training: the HIV Entrustable Professional Activities.

BACKGROUND: There is an anticipated shortage of primary care providers trained to care for patients with HIV. The Yale School of Medicine developed and implemented a novel HIV training track within our Primary Care Internal Medicine Residency Program. A set of 12 Entrustable Professional Activities (EPAs) were developed to guide curriculum development and resident assessment. AIM: To describe the process of implementing a novel EPA-based curriculum for the HIV Primary Care Training Track including EPA-based trainee evaluation tools. PARTICIPANTS/SETTINGS: Two to three residents were enrolled annually from 2012 to 2017 (total n = 11). Training sites included the outpatient academic center HIV clinic and inpatient HIV ward. PROGRAM DESCRIPTION: An expert panel developed 12 HIV-specific EPAs. These were mapped to curricular and reporting internal medicine milestones. Curricular activities and evaluation tools were developed to guide EPA progress. PROGRAM EVALUATION: Graduating residents were ready for unsupervised practice in 91% of EPAs at the end of the 3-year program. DISCUSSION: Development of HIV-specific training EPAs was effective for driving curricular development and resident evaluation, and served as an effective method to communicate expectations to resident participants. These HIV-specific EPAs could serve as a useful template to enhance HIV education in academic settings.

Training the next generation of HIV providers: impact of trainees on patient satisfaction in an urban HIV clinic.

For persons living with HIV and AIDS (PLWHA), care by an HIV-specialist improves outcomes and satisfaction with one's HIV primary care provider (PCP) promotes engagement with care. In the United States, we are facing a workforce shortage of HIV providers. As we aim to train a new generation of HIV providers, it is unclear how PLWHA perceive their experience when cared for by trainees compared to experienced providers. Therefore we assessed patient satisfaction with HIV providers, both trainees in an HIV Primary Care residency program and HIV-specialists. A secondary objective was to evaluate providers' performance in adhering to standard management guidelines for HIV-associated and non-HIV-associated conditions. We surveyed 75 PLWHA, including 51 (68%) assigned to an HIV-specialist PCP and 24 (32%) to a trainee PCP. Overall patient satisfaction on a 10-point scale was similar (mean 9.6 HIV-specialist vs 9.7 trainee, p = 0.71) and remained similar in multivariate logistic regression analysis when controlling for patient age, gender, race, and recently establishing care (Odds Ratio 1.1, 95% Confidence Interval 0.3-5.0). Participants in the trainee group were more likely to feel their provider "always" spent enough time with them (100% vs 81%, p = 0.03). Adherence to HIV guidelines was similar, though trainees were more likely to document counseling on risk reduction (83% vs 47%, p = 0.005) and adherence to antiretroviral therapy (100% vs 66%, p = 0.001). In conclusion, in a structured HIV-training program, residents can provide subspecialty level care in an HIV continuity clinic with levels of performance and patient satisfaction equivalent to those of experienced specialists.

Dolutegravir/rilpivirine for the treatment of HIV-1 infection.

Much progress has been made in the development of antiretroviral therapies (ARTs) for HIV-1 infection. Beginning a little over a decade ago, single tablet combination regimens (STRs) became available, and subsequently, newer STR formulations with improved safety profiles have emerged. Recently, there is a growing interest in regimen simplification with the primary goal of further reducing long-term toxicities of ART and improving medication adherence. Dolutegravir/rilpivirine (DTG/RPV) was approved by the US Food and Drug Administration (FDA) as the first dual antiretroviral STR for the maintenance therapy of HIV-1 infection. Following an extensive review of all published papers on RPV and DTG, administered alone and in combination, extracted from databases including PubMed, Google scholar, and EMBASE, as well as drug package inserts and conference abstracts and proceedings, this review discusses the chemical properties and composition, pharmacodynamics and pharmacokinetic properties, clinical trial efficacy and safety data, as well as important drug-drug interactions associated with DTG/RPV. An expert opinion section discusses ideal candidates for DTG/RPV in the context of available but limited data and in comparison to currently available and emerging ART alternatives.

The Changing Face of HIV Care: Expanding HIV Training in an Internal Medicine Residency Program.

PROBLEM: People with HIV/AIDS are living longer and are at an increased risk of comorbidities. A qualified physician workforce is needed to care for this growing population. APPROACH: In 2012, a novel three-year HIV training track (HIV TT) was implemented as part of the Yale Primary Care Residency Program. To prepare for the implementation of this program, a needs assessment was performed, a web-based curriculum and 12 HIV-specific entrustable professional activities (EPAs) were created, and adequate clinical training opportunities in HIV and primary care were established. Program evaluation included process, learner, and outcome evaluations from 2012 to 2017. OUTCOMES: Since its inception, the HIV TT has enrolled a total of 11 residents (6-7 at a time), with 5 graduating to date. Residents delivered high-quality HIV and primary care for a diverse panel of patients; improved their knowledge and performance in HIV care, including according to the HIV-specific EPAs; and were highly satisfied with the program. All faculty remained with the program, and patients indicated satisfaction. NEXT STEPS: Next steps include enhanced coordination of residents' schedules, improved EPA documentation, evaluation of residents' HIV and non-HIV competence beyond residency, and monitoring graduates' career trajectories. Expanding HIV training within internal medicine residency programs is feasible and effective and has the potential to alleviate the shortage of physicians trained to provide HIV care and primary care in a single setting.

Characterizing Patients with Very-Low-Level HIV Viremia: A Community-Based Study.

OBJECTIVE: Very-low-level viremia (VLLV) is a relatively new concept in the realm of human immunodeficiency virus (HIV) care. Newer generation assays are now able to detect plasma HIV RNA Viral Load (VL) levels as low as 20 copies/mL. The authors characterized patients with VLLV (VL between 20 and 50 copies/mL) in order to identify possible risk factors associated with virologic failure and poor clinical outcomes. METHODS: The authors reviewed 119 consecutive charts of patients with VLLV. Sociodemographic data were extracted and viral load and CD4 counts were trended over a 12 month period (February 2013-February 2014). Regression analysis was used to assess the role of different factors on virologic failure at 1 year. RESULTS: Of the study participants with evaluable data (n = 100), the median age was 53 years (interquartile range: 43-57.5), 67% were nonwhite, 34% were women, 58% were smokers, 47% were alcoholics, 58% had a history of intravenous drug use, and 40% were coinfected with hepatitis C virus. More than half of the participants had 3 or more comorbidities and their HIV pill burden was high (more than 2 pills daily). After 12 months, 65 participants achieved undetectable viral load levels, whereas 15 experienced virologic failure (2 consecutive viral loads > 50 copies/mL) and the remaining 20 had persistent VLLV. In the virologic failure group, there was a predominance of white males (66%) with a significant number of comorbidities and pill burden. Univariate logistic regression suggested that there was a difference between the failure versus nonfailure groups in terms of race, ethnicity, and alcohol use. Multivariate regression with virological failure as the outcome suggested a trend only in terms of participant's alcohol use. CONCLUSION: Most patients with initial VLLV (70%) achieved virologic suppression at 1 year with no antiretroviral therapy changes. Thus, VLLV does not necessarily predict virologic failure and should not prompt more frequent clinic visits or antiretroviral regimen changes. Further research is needed in order to determine the predictors of virologic failure in this subset of patients and the clinicians' attitude toward VLLV.

Trends in hospital deaths among human immunodeficiency virus-infected patients during the antiretroviral therapy era, 1995 to 2011.

OBJECTIVE: Mortality in hospitalized human immunodeficiency virus (HIV)-infected patients is not well described. We sought to characterize in-hospital deaths among HIV-infected patients in the antiretroviral (ART) era and identify factors associated with mortality. METHODS: We reviewed the medical records of hospitalized HIV-infected patients who died from January 1, 1995 to December 31, 2011 at an urban teaching hospital. We evaluated trends in early and late ART use and deaths due to acquired immunodeficiency syndrome (AIDS) and non-AIDS, and identified clinical and demographic correlates of non-AIDS deaths. RESULTS: In-hospital deaths declined significantly from 1995 to 2011 (P < 0.0001); those attributable to non-AIDS increased (43% to 70.5%, P < 0.0001). Non-AIDS deaths were most commonly caused by non-AIDS infection (20.3%), cardiovascular (11.3%) and liver disease (8.5%), and non-AIDS malignancy (7.8%). Patients with non-AIDS compared to AIDS-related deaths were older (median age 48 vs 40 years, P < 0.0001), more likely to be on ART (74.1% vs 55.8%, P = 0.0001), less likely to have a CD4 count of <200 cells/mm(3) (47.2% vs 97.1%, P < 0.0001), and more likely to have an HIV viral load of ≤400 copies/mL (38.1% vs 4.1%, P < 0.0001). Non-AIDS deaths were associated with 4.5 and 4.2 times greater likelihood of comorbid underlying liver and cardiovascular disease, respectively. CONCLUSIONS: Non-AIDS deaths increased significantly during the ART era and are now the most common cause of in-hospital deaths; non-AIDS infection, cardiovascular and liver disease, and malignancies were major contributors to mortality. Higher CD4 cell count, liver, and cardiovascular comorbidities were most strongly associated with non-AIDS deaths. Interventions targeting non-AIDS-associated conditions are needed to reduce inpatient mortality among HIV-infected patients.