Addressing coloniality of power to improve HIV care in South Africa and other LMIC

We describe the appropriateness and potential for effectiveness of three strategic approaches for improving HIV care in South Africa: community-based primary healthcare, local/community-based stakeholder engagement, and community-engaged research. At their core, these approaches are related to overcoming health inequity and inequality resulting from coloniality of power's heterogenous structural processes impacting health care in many low- and middle-income countries (LMIC). We turn to South Africa, a middle-income country, as an example. There the HIV epidemic began in the 1980s and its ending is as elusive as achieving universal healthcare. Despite impressive achievements such as the antiretroviral treatment program (the largest in the world) and the country's outstanding cadre of HIV experts, healthcare workers and leaders, disadvantaged South Africans continue to experience disproportionate rates of HIV transmission. Innovation in global public health must prioritize overcoming the coloniality of power in LMIC, effected through the imposition of development and healthcare models conceived in high-income countries (HIC) and insufficient investment to address social determinants of health. We advocate for a paradigm shift in global health structures and financing to effectively respond to the HIV pandemic in LMIC. We propose ethically responsive, local/community-based stakeholder engagement as a key conceptual approach and strategy to improve HIV care in South Africa and elsewhere. We join in solidarity with local/community-based stakeholders' longstanding efforts and call upon others to change the current status quo characterized by global public health power concentrated in HIC

Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa

In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine--in routine practice--the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment

Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members.

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable

Spontaneous virologic suppression in HIV controllers is independent of delayed-type hypersensitivity test responsiveness

<p>Abstract</p> <p>Background</p> <p>Delayed-type hypersensitivity (DTH) testing, an in vivo assessment of cell-mediated immunity, is a predictor of HIV disease progression beyond CD4 cell count. We investigated whether preserved DTH responsiveness was characteristic of HIV controllers compared to non-controllers and individuals on suppressive HAART.</p> <p>Findings</p> <p>DTH testing consisted of ≥ 3 recall antigens applied approximately every 6 months. DTH responses were classified by the number of positive skin tests: anergic (0), partial anergic (1), or non-anergic (≥ 2). HIV controllers were compared to treatment naïve non-controllers (n = 3822) and a subgroup of non-controllers with VL < 400 copies/mL on their initial HAART regimen (n = 491). The proportion of non-anergic results at first DTH testing was similar for HIV controllers compared to non-controllers (81.9% vs. 77.6%; P = 0.22), but tended to be greater in HIV controllers compared to the HAART subgroup (81.9% vs. 74.5%; P = 0.07). Complete anergy was observed in 14 (10.1%) HIV controllers with CD4 counts ≥ 400 cells/uL. For longitudinal testing, the average percentage of non-anergic DTH determinations per participant was higher in HIV controllers compared to non-controllers (81.2 ± 31.9% vs. 70.7 ± 36.8%; P = 0.0002), however this difference was eliminated with stratification by CD4 count: 200-399 (83.4 ± 35.6% vs. 71.9 ± 40.9%; P = 0.15) and > 400 cells/uL (81.2 ± 31.5% vs. 80.4 ± 32.7%; P = 0.76).</p> <p>Conclusions</p> <p>Spontaneous virologic control was not associated with DTH responsiveness, and several HIV controllers were anergic despite having elevated CD4 counts. These findings suggest that cellular immunity assessed by DTH is not a principal factor contributing to spontaneous virologic suppression in HIV controllers.</p

A cluster randomized controlled trial of a modified vaccination clinical reminder for primary care providers

Objective: Adult vaccination rates in the United States fall short of national goals, and rates are particularly low for Black Americans. We tested a provider-focused vaccination uptake intervention: a modified electronic health record clinical reminder that bundled together three adult vaccination reminders, presented patient vaccination history, and included talking points for providers to address vaccine hesitancy. Method: Primary care teams at the Atlanta Veterans Affairs Medical Center, who saw 28,941 patients during this period, were randomly assigned to receive either the modified clinical reminder (N = 44 teams) or the status quo (N = 40 teams). Results: Uptake of influenza and other adult vaccinations was 1.6 percentage points higher in the intervention group, which was not statistically significant (CI = [-1.3, 4.4], p = 0.28). The intervention had similar effects on Black and White patients and did not reduce the disparity in vaccination rates between these groups. Conclusion: Provider-focused interventions are a promising way to address vaccine hesitancy, but they may need to be more intensive than a modified clinical reminder to have appreciable effects on vaccination uptake

Increasing Rates of Obesity among HIV-Infected Persons during the HIV Epidemic

The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown.We evaluated prospective data from a U.S. Military HIV Natural History Study (1985-2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models.Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era.HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care

Insomnia as an Independent Predictor of Incident Cardiovascular Disease in HIV: Data from the Veterans Aging Cohort Study

Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. Methods: Using the Veterans Aging Cohort Study-Survey Cohort, insomnia symptoms were measured and dummy coded with the item, “Difficulty falling or staying asleep?” (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with VA and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. Results: HIV-infected (N=3,108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics (HR=1.64, 95%CI=1.16-2.31, p=.005), CVD risk factors (HR=1.62, 95%CI=1.14-2.30, p=.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, cocaine use; HR=1.70, 95%CI=1.19-2.43, p=.003), and HIV-specific factors (HIV-1 RNA, CD4+ T-cell count, ART; HR=1.66, 95%CI=1.16-2.37, p=.005). Additional adjustment for non-benzodiazepine sleep medication (HR=1.62, 95%CI=1.13-2.32, p=.009) did not attenuate the association; however, it fell short of significance at p < .01 after adjustment for depressive symptoms (HR=1.51, 95%CI=0.98-2.32, p=.060) or antidepressant medication (HR=1.51, 95%CI=1.04-2.19, p=.031). Conclusion: Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV

Laws of crack motion and phase-field models of fracture

Recently proposed phase-field models offer self-consistent descriptions of brittle fracture. Here, we analyze these theories in the quasistatic regime of crack propagation. We show how to derive the laws of crack motion either by using solvability conditions in a perturbative treatment for slight departure from the Griffith threshold, or by generalizing the Eshelby tensor to phase-field models. The analysis provides a simple physical interpretation of the second component of the classic Eshelby integral in the limit of vanishing crack propagation velocity: it gives the elastic torque on the crack tip that is needed to balance the Herring torque arising from the anisotropic interface energy. This force balance condition reduces in this limit to the principle of local symmetry in isotropic media and to the principle of maximum energy release rate for smooth curvilinear cracks in anisotropic media. It can also be interpreted physically in this limit based on energetic considerations in the traditional framework of continuum fracture mechanics, in support of its general validity for real systems beyond the scope of phase-field models. Analytical predictions of crack paths in anisotropic media are validated by numerical simulations. Simulations also show that these predictions hold even if the phase-field dynamics is modified to make the failure process irreversible. In addition, the role of dissipative forces on the process zone scale as well as the extension of the results to motion of planar cracks under pure antiplane shear are discussed

Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility

Duffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs) influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with DARC -46C/C genotype, which confers a DARC negative phenotype, are resistant to vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting trans-infection of target cells. In African Americans, DARC -46C/C is associated with 40% increase in the odds of acquiring HIV-1. If extrapolated to Africans, ~11% of the HIV-1 burden in Africa may be linked to this genotype. After infection occurs, however, DARC-negative RBC status is associated with slower disease progression. Furthermore, the disease-accelerating effect of a previously described CCL5 polymorphism is evident only in DARC-expressing and not in DARC-negative HIV-infected individuals. Thus, DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation