The role of HIV as a risk modifier for coronary endothelial function in young adults.

BACKGROUND: People living with HIV have an increased risk of cardiovascular disease (CVD). Although coronary endothelial function (CEF) is an early direct indicator of CVD, only a few studies have been able to interrogate CEF directly. Most studies have examined vascular endothelial function through indirect assessment of brachial flow-mediated dilatation (FMD). However, peripheral arteries are significantly larger and manifest atherogenesis differently from the coronary arteries, and so produce conflicting results. Additionally, none of these studies focused on young adults who acquired HIV perinatally or in early childhood. OBJECTIVE: The present study investigates CEF in a unique population of young adults with lifelong HIV using direct magnetic resonance imaging (MRI) of coronary FMD (corFMD) with an in-house developed MRI-integrated isometric handgrip exercise system with continuous feedback and monitoring mechanisms (fmIHE). METHODS: Young adults who acquired HIV perinatally or in early childhood (n = 23) and group-matched healthy participants (n = 12) completed corFMD-MRI with fmIHE. CorFMD was measured as the coronary cross-sectional area response to the fmIHE. RESULTS: In univariable and multivariable regression analysis, HIV status was a significant risk modifier. CD8+ T-cell count and smoking pack-years and their interaction with HIV status were independently associated with impaired coronary artery response to fmIHE. In people living with HIV, corFMD was significantly inversely correlated with CD8+ T-cells and smoking pack-years. In a multivariable regression analysis adjusted for age and body mass index, CD8+ T-cells and smoking and their interaction with HIV status remained significant independent predictors of coronary endothelial dysfunction. DISCUSSION: In this unique population of young adults, HIV status was a significant risk modifier, and immune activation and smoking were associated with decreased CEF, directly measured from the coronary vascular response to fmIHE. CONCLUSIONS: Management of CVD risk factors such as smoking and developing strategies that target immune activation in people living with HIV are warranted.

High-level dolutegravir resistance can emerge rapidly from few variants and spread by recombination: implications for integrase strand transfer inhibitor salvage therapy.

The integrase strand transfer inhibitor (INSTI) dolutegravir is commonly used in combination antiretroviral therapy regimens and retains strong potency even with primary resistance mutations to some other INSTIs. Acquisition of accessory mutations to primary mutations results in significant increases in dolutegravir resistance. Previously, we reported that addition of the secondary mutation T97A can result in rapid treatment failure in individuals with INSTI mutations at positions 140 and 148. Here, we conducted a detailed case study of one of these individuals and find that T97A-containing HIV emerged from a large replicating population from only a few (≤4) viral lineages. When combined with primary INSTI resistance mutations, T97A provides a strong selective advantage; the finding that T97A-containing variants spread by replication and recombination, and persisted for months after discontinuing dolutegravir, has important implications as dolutegravir is rolled out worldwide.

Eight-day Inpatient Directly Observed Therapy for Antiretroviral Therapy (ART) Failure: A Tool For Preventing Unnecessary ART Changes and Optimizing Adherence Support.

Eight-day inpatient directly observed therapy confirmed nonadherence as the major cause of virologic failure for 9 (45%) of 20 highly treatment-experienced persons with human immunodeficiency virus, extensive antiretroviral drug resistance, and high self-reported adherence rates, preventing unnecessary regimen changes.

Reproductive and sexual health knowledge, experiences, and milestones in young adults with life-long HIV.

Reproductive and sexual health outcomes of adults with perinatal human immunodeficiency virus (PHIV) have not been well-characterized. This prospective cross-sectional study of 35 adult persons living with HIV (PLWH) from early life and 20 matched HIV-negative controls assessed quality of life, depressive symptoms, HIV transmission knowledge, and sexual/reproductive behaviors through self-report questionnaires. PLWH scored significantly worse than controls on depressive symptoms (p = 0.04) and two of six quality of life domains (p = 0.03, p = 0.0002). In contrast, PLWH scored significantly higher on transmission knowledge in the context of family planning (p = 0.002). PLWH were more likely to learn about sex from healthcare providers (p = 0.002) and were more confident in their sexual/reproductive health knowledge (p < 0.05). Both groups reported inconsistent condom use, but PLWH were more likely to have planned pregnancies (p = 0.005) and to share pregnancy planning with their partners (p < 0.05). Despite the challenges of living with a chronic stigmatized condition, adults with PHIV were knowledgeable about HIV transmission and family planning and demonstrated sexual practices and reproductive outcomes similar to age-matched controls. However, sub-optimal rates of viral suppression, inconsistent condom use, and the psychosocial impact of living with HIV continue to require the attention of healthcare provides for young adults with PHIV.

Increased Prevalence of Hepatic Steatosis in Young Adults With Lifelong HIV.

Little is known about the effects of lifelong human immunodeficiency virus (HIV) or antiretroviral therapy on hepatic steatosis and fibrosis. Using transient elastography, we evaluated 46 young adults with lifelong HIV and 20 matched HIV-negative controls. Steatosis was present in 33% of persons with HIV and only 10% of controls (P = .04). Hepatic fibrosis scores were not elevated and did not differ between groups. Metabolic parameters, particularly increased waist circumference, and not HIV-specific factors, were significantly associated with steatosis. While this finding should be examined in larger cohorts, modifiable metabolic disturbances may be important targets to optimize liver health in this population.

Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.

HIV integrase mutation T97A emerges after suboptimal therapy with integrase strand transfer inhibitors (INSTIs), but the contribution of T97A to dolutegravir resistance remains uncertain. Here we report >10-fold increase in dolutegravir resistance after the single addition of T97A in 2 individuals with prior INSTI resistance receiving dolutegravir salvage therapy.