SARS-CoV-2 infection does not induce HIV viral escape in the central nervous system: A case series.

We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS.

HIV MDR is still a relevant issue despite its dramatic drop over the years.

OBJECTIVES: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. METHODS: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). RESULTS: Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010-18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. CONCLUSIONS: A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

Training Child Care Inspectors to Deliver Health Messaging: A Quality Improvement Pilot Project.

Early childhood obesity is at epidemic proportions. Early child care providers have a unique opportunity to instill healthy eating and active living behaviors in children that can foster lifelong health. Academic-community partnerships that involve collaborations between child care centers, local public health departments, and universities provide one avenue to strengthening healthy eating and active living-related knowledge and skills among early child care providers. This quality improvement pilot intervention, titled Healthy Child Care Makes a Healthy Start, is one example of this type of collaboration. This quality improvement pilot project consisted of two complementary intervention components. Inspectors were trained to cofacilitate a strategic planning process with university researchers to help providers implement healthy eating and active living-related policy, system, and environment changes in their child care homes and centers. An average of five changes were implemented in participating child care locations. Inspectors also received training on health-related best practices and delivered 1-minute health messages to child care providers during routine inspection visits. This type of innovative partnership has the potential to leverage a currently existing relationship between child care providers and licensing and regulation inspectors and shift the relationship to include dissemination and implementation of health messaging in child care center and home settings.

Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14.

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047]. Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.

Reduced risk of Efavirenz Discontinuation in Naïve Patients Starting First-Line Antiretroviral Therapy with Single Tablet versus dual Tablet Regimen.

OBJECTIVES: Despite not being approved in Europe as first-line therapy, the efavirenz (EFV)-containing single tablet regimen (STR) is frequently used in clinical practice in naïve patients but few data are available on this strategy. In our study, we aimed to assess the risk of EFV discontinuation in patients starting antiretroviral therapy with STR vs. nonSTR. METHODS: This was a multicentre study retrospectively enrolling naïve patients starting EFV+TDF+FTC. Patients were followed from the time of treatment initiation to the discontinuation of the EFV-containing regimen, comparing STR vs. nonSTR. Two different analyses were performed: (A) nonSTR patients censored at the last observation (switch to STR not considered as the end of observation); (B) nonSTR patients censored at the time of switch to STR. RESULTS: The study included 235 patients, of whom 74 (31.5%) directly started STR. Among patients starting nonSTR, 108 (67.1%) switched to STR after a median period of 6 months. Forty-four EFV discontinuations were observed (13 among STR vs. 31 among nonSTR patients). The overall estimated probability of discontinuation was 30% at 5 years, about half (14.8%) of these occurring during the first year. Analysis A did not show significant differences between STR and nonSTR regarding the probability of efavirenz discontinuation (19.9% vs. 24.7% at 5 years, P = 0.630). In contrast, Analysis B showed that the probability of EFV discontinuation was similar (8.3%) between STR and nonSTR patients up to 8 months. Thereafter, a significantly higher rate of discontinuation was observed in nonSTR patients (47.5% vs. 19.9% at 5 years, P = 0.034). CONCLUSIONS: Our data suggest that an early switch to STR during the first months of treatment could reduce the risk of EFV discontinuation.

Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study.

OBJECTIVES: AtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir + lamivudine in virologically suppressed HIV-positive patients. Here, we report data from the 144 week follow-up. METHODS: At baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA >50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL). RESULTS: After 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm(3); P = 0.002) and Week 144 (+94 cells/mm(3); P = 0.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P = 0.001), HDL cholesterol (+6 mg/dL; P = 0.024) and LDL cholesterol (+12 mg/dL; P = 0.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m(2); P < 0.001) and lumbar spine T-score and Z-score (+0.2, P = 0.011; and +0.35, P = 0.001, respectively) and a decrease in trunk fat (-1.898 g; P = 0.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients. CONCLUSIONS: Data from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial.

Effect of local and remote ischemic preconditioning on endothelial function in young people and healthy or hypertensive elderly people.

To verify whether age affects remote preconditioning, we compared healthy young people (mean age = 28.0 years, SD: 7.2), healthy elderly people (age = 69.2 years, SD: 5.0), and hypertensive elderly people (group 3, age = 72.8 years, SD: 3.9). Each group included 10 participants. The flow-mediated-dilation (FMD) was measured after local (same arm) and remote (leg) ischemic preconditioning. Healthy elderly people had the greatest increase of FMD after ischemic preconditioning compared to baseline (173% after local and 181% after remote preconditioning) and young participants the smallest increase (77% after local and 69% after remote preconditioning) while hypertensive elderly had an intermediate increase (P for comparison across groups: 0.347 for local and 0.064 for remote preconditioning). However, absolute values of FMD after preconditioning were much lower in elderly hypertensive than in healthy young adults. Remote preconditioning increases endothelial reactivity in healthy and hypertensive elderly. The potential clinical relevance of this finding deserves consideration.

Eliminating inequities in health care: understanding perceptions and participation in an antiracism initiative.

Antiracism training for staff of health care institutions is a promising intervention strategy to address racial and ethnic disparities in health care. In 2001, Southern County Public Health Department (SCPHD) staff completed a mandatory Dismantling Racism (DR) training, and some continued with an optional DR process to challenge institutional racism within their agency. To explore factors influencing participation in optional DR activities (i.e., caucuses and Change Team), a process evaluation was conducted involving in-depth interviews with 28 SCPHD administrators and staff members, whose participation in the DR process varied. Findings demonstrate that familiarity with and receptiveness to the relationship between racism and health care inequities influenced participation in DR activities. Perceived relevance and impact of the DR process on the organization and staff were also major factors affecting participation. Improvements for implementing such efforts including the consideration of institutional power and other implications for addressing racial health care inequities through antiracism initiatives are discussed.

A structural approach to examining prostate cancer risk for rural southern African American men.

Physical, cultural, and social factors influence health risk and behavior, but few have explored how the environmental context affects African American men's prostate cancer screening and treatment. This paper describes a structural analysis of data from eight focus groups of rural, southern African American men (n=66). A structural approach highlights the interrelationships between individuals, the health service system, and community factors that directly and indirectly affect screening and treatment for prostate cancer. The availability of accurate and timely health information and health services, social norms regarding health and professional help-seeking, and the sociopolitical context shaped men's screening and treatment behaviors. These proximal and distal health factors affected men's prostate cancer knowledge, perceived risk, willingness to seek care and trust in the health service system. The findings suggest that prostate cancer screening and treatment occurs in a larger structural context that has important implications for help-seeking and health promotion.