Activated monocytes/macrophages play a role in severe forms of HIV-associated neurocognitive disorders (HAND), but little is known about the mechanisms driving milder forms that are prevalent despite ...combination antiretroviral therapy (cART). To examine relationships of monocyte activation markers to HAND of varying severity, we compared plasma and cerebrospinal fluid (CSF) biomarker levels with neurocognitive test scores in HIV+ subjects.
Plasma and CSF soluble CD14 (sCD14), CCL2, and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay in 67 HIV+ subjects with nadir CD4 <300, and CSF inflammatory biomarkers were measured by multiplex assay in 14 subjects on suppressive cART.
Eighty-two percent were on cART, with 31% having undetectable plasma viral load (VL). CSF sCD14 was increased in subjects with impaired neurocognitive testing (P = 0.02), correlated inversely with global T scores in subjects with detectable but not undetectable plasma VL (P = 0.02), and yielded higher area under the receiver operating characteristic curve values for predicting impaired T scores (0.659) than plasma or CSF VL and current or nadir CD4 counts in single-marker and multivariate models. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and interferon (IFN) gamma were increased in subjects on suppressive cART regardless of cognitive status and predicted patient class in unsupervised analyses, with IL-8, CCL2, and IFNγ explaining most of the variance.
CSF sCD14 is associated with impaired neurocognitive testing in patients with HIV on nonsuppressive cART, suggesting potential utility as a biomarker to monitor HAND progression. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and IFNγ remain elevated in patients on suppressive cART regardless of cognitive status, implying ongoing intrathecal inflammation even in the absence of clinical manifestations.
Since the 1980s HIV/AIDS has occupied a singular position because of the rapidly emergent threat and devastation the disease has caused, particularly in sub-Saharan Africa. New infections continue to ...create a formidable challenge to households, communities, and health systems: last year alone, 2.7 million new infections occurred globally. Sub-Saharan Africa remains the epicenter of the suffering, with around two-thirds of infected individuals worldwide found there, and a disproportionate number of deaths and new infections.
For years there have been widespread and concerted efforts to prevent the spread of HIV/AIDS, identify a cure, and understand and mitigate the deleterious social and economic ramifications of the disease. Despite these efforts, and some apparent successes, there is still a long way to go in terms of altering behaviors in order to realize the objective of dramatic reductions in the spread of HIV/AIDS in Africa. The authors in this volume examine the HIV/AIDS crisis in Africa, which persists despite major strides in averting deaths due to antiretroviral therapy. They tell an important story of the distinct nature of the disease and its socioeconomic implications.
Viral Frictions takes the reader along a trail of
intersecting narratives to uncover how and why it is that
HIV-related stigma persists in the age of treatment. Pfeiffer
convincingly argues that ...stigma is a socially constructed process
co-produced at the nexus of local, national, and global
relationships and storytelling about and practices associated with
HIV. Based on a decade of fieldwork in one highway trading center
in Kenya, Viral Frictions offers compelling stories of
stigma and discrimination as a lens for understanding broader
social processes, the complexities of globalization and health, and
their profound impact on the everyday social lives and
relationships of people living through the ongoing HIV epidemic in
sub-Saharan Africa. This highly engaging book is ideal reading for
those interested in teaching and learning about intersectionality,
as Pfeiffer meticulously demonstrates how HIV stigma interacts with
issues of treatment, race, ethnicity, class, gender, sexuality,
social change, and international aid systems.
To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of HAART.
This study is an observational cohort study.
...MRS was performed in 268 patients: HIV-negative controls (N = 28), HIV-positive neuroasymptomatic individuals (N = 124), and individuals with AIDS dementia complex (ADC; N = 50) on stable antiretroviral therapy (ART) with a mean duration of infection of 12 years and CD4 cell count of 309 cells/μl. Four metabolites were measured over creatine: N-acetyl aspartate (NAA), marker of neuronal integrity; choline (Cho), myoinositol, markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia, frontal white matter (FWM), and mid-frontal cortex. Analyses included analysis of variance, analysis of covariance, linear, and nonparametric regression models.
Cognitive impairment was found in 48% of HIV-infected individuals. Both HIV-positive groups showed significant increases in myoinositol/creatine or Cho/creatine in all brain regions when compared to controls; a significant decrease in Glx/creatine in the FWM was observed in the neuroasymptomatic group; and only individuals with ADC showed a significant reduction in NAA/creatine, although a significant trend for decreasing NAA/creatine in the basal ganglia was found across the groups. Effects related to aging and duration of infection, but not central nervous system penetration effectiveness were observed.
Brain inflammatory changes remain ubiquitous among HIV-infected individuals, whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.
Over the past ten years, standard diagnostics for cryptococcal meningitis in HIV-infected persons have evolved from culture to India ink to detection of cryptococcal antigen (CrAg), with the recent ...development and distribution of a point-of-care lateral flow assay. This assay is highly sensitive and specific in cerebrospinal fluid (CSF), but is also sensitive in the blood to detect CrAg prior to meningitis symptoms. CrAg screening of HIV-infected persons in the blood prior to development of fulminant meningitis and preemptive treatment for CrAg-positive persons are recommended by the World Health Organization and many national HIV guidelines. Thus, CrAg testing is occurring more widely, especially in resource-limited laboratory settings. CrAg titer predicts meningitis and death and could be used in the future to customize therapy according to burden of infection.
The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered ...trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.
"I am an AIDS doctor. When I began that work in 1992, we knew what caused AIDS, how it spread, and how to avoid getting it, but we didn't know how to treat it or how to prevent our patients' ...seemingly inevitable progression toward death. The stigma that surrounded AIDS patients from the very beginning of the epidemic in the early 1980s continued to be harsh and isolating. People looked askance at me: What was it like to work in that kind of environment with those kinds of people? My patients are 'those kinds of people.' They are an array and a combination of brave, depraved, strong, entitled, admirable, self-centered, amazing, strange, funny, daring, gifted, exasperating, wonderful, and sad. And more. At my clinic most of the patients are indigent and few have had an education beyond high school, if that. Many are gay men and many of the patients use or have used drugs. They all have HIV, and in the early days far too many of them died. Every day they brought us the stories of their lives. We listened to them and we took care of them as best we could."—from the IntroductionIn 1992, Dr. Susan C. Ball began her medical career taking care of patients with HIV in the Center for Special Studies, a designated AIDS care center at a large academic medical center in New York City. Her unsentimental but moving memoir of her experiences bridges two distinct periods in the history of the epidemic: the terrifying early years in which a diagnosis was a death sentence and ignorance too often eclipsed compassion, and the introduction of antiviral therapies that transformed AIDS into a chronic, though potentially manageable, disease. Voices in the Band also provides a new perspective on how we understand disease and its treatment within the context of teamwork among medical personnel, government agencies and other sources of support, and patients. Deftly bringing back both the fear and confusion that surrounded the disease in the early 1990s and the guarded hope that emerged at the end of the decade, Dr. Ball effectively portrays the grief and isolation felt by both the patients and those who cared for them using a sharp eye for detail and sensitivity to each patient's story. She also recounts the friendships, humor, and camaraderie that she and her colleagues shared working together to provide the best care possible, despite repeated frustrations and setbacks. As Dr. Ball and the team at CSS struggled to care for an underserved population even after game-changing medication was available, it became clear to them that medicine alone could not ensure a transition from illness to health when patients were suffering from terrible circumstances as well as a terrible disease.
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