In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 ...years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.
Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases ...Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003–2008 has been incorporated into this document.
To measure the incidence and risk factors of AIDS-defining opportunistic illnesses (AOIs) in the pre-highly active antiretroviral therapy (HAART) (1993-1995), early-HAART (1996-2000), and late-HAART ...(2001-2008) periods.
Prospective cohort analysis of AIDS surveillance data.
Individuals living with, or diagnosed with AIDS from 1993 through 2008 were included. Poisson regression models were used to estimate annual incidence rates of the eight most frequently occurring AOIs, and to compare these rates in the pre-HAART (1993-1995), early-HAART (1996-2000), and late-HAART (2001-2008) periods.
There were 18 733 individuals with AIDS included; 5788 were diagnosed prior to 1993 and 12 945 were diagnosed between 1 January 1993 and 31 December 2008. The incidence rates of Pneumocystis jiroveci pneumonia, wasting syndrome, Kaposi's sarcoma, HIV encephalopathy, cytomegalovirus retinitis, cytomegalovirus, and esophageal candidiasis decreased during the study period, with the largest declines observed between the pre-HAART and early-HAART periods. Incidence rates also decreased between the early-HAART and late-HAART periods, though not as sharply. Incidence rate reductions between the earliest and latest period ranged from 84 to 99%.
Steep declines in incidence of AOIs were found following the introduction of HAART and continued into the late-HAART era. These declines reflect the impact of HIV diagnosis and treatment on a population level.
Despite immune recovery in individuals on combination antiretroviral therapy (CART), the frequency of HIV-associated neurocognitive disorders (HANDs) remains high. Immune recovery is typically ...achieved after initiation of ART from the nadir, or the lowest historical CD4. The present study evaluated the probability of neuropsychological impairment (NPI) and HAND as a function of CD4 nadir in an HIV-positive cohort.
One thousand five hundred and twenty-five HIV-positive participants enrolled in CNS HIV Antiretroviral Therapy Effects Research, a multisite, observational study that completed comprehensive neurobehavioral and neuromedical evaluations, including a neurocognitive test battery covering seven cognitive domains. Among impaired individuals, HAND was diagnosed if NPI could not be attributed to comorbidities. CD4 nadir was obtained by self-report or observation. Potential modifiers of the relationship between CD4 nadir and HAND, including demographic and HIV disease characteristics, were assessed in univariate and multivariate analyses.
The median CD4 nadir (cells/μl) was 172, and 52% had NPI. Among impaired participants, 603 (75%) had HAND. Higher CD4 nadirs were associated with lower odds of NPI such that for every 5-unit increase in square-root CD4 nadir, the odds of NPI were reduced by 10%. In 589 virally suppressed participants on ART, higher CD4 nadir was associated with lower odds of NPI after adjusting for demographic and clinical factors.
As the risk of NPI was lowest in patients whose CD4 cell count was never allowed to fall to low levels before CART initiation, our findings suggest that initiation of CART as early as possible might reduce the risk of developing HAND, the most common source of NPI among HIV-infected individuals.
Mild forms of HIV-associated neurocognitive disorders (HAND) remain prevalent in the era of combination antiretroviral therapy (cART). Although elevated lipopolysaccharide (LPS) and immune activation ...are implicated in HAND pathogenesis, relationships of LPS and inflammatory markers to mild forms of HAND or impairment in specific cognitive domains are unknown. To examine these relationships, we compared plasma soluble CD14 (sCD14), CCL2, and LPS levels with neurocognitive test scores in a cART era cohort.
We analyzed plasma from HIV+ subjects (n = 97) with nadir CD4 counts <300 and high frequency of hepatitis C virus coinfection and illicit drug use for relationships between sCD14, CCL2, and LPS levels and neurocognitive test scores.
Plasma sCD14 levels were higher in subjects with test scores indicating global impairment (P = 0.007), particularly in attention and learning domains (P = 0.015 and P = 0.03, respectively), regardless of HAND diagnosis. Plasma sCD14 levels correlated inversely with global, attention, and learning T scores (P = 0.036, 0.047, and 0.007, respectively) and yielded higher area under receiver operating characteristic values for predicting impaired scores than single-marker models based on plasma or cerebrospinal fluid viral load or CD4 count (area under receiver operating characteristic values = 0.71, 0.81, and 0.71, respectively) and in 4-marker models based on plasma sCD14 and 3 conventional markers compared with the 3-marker models.
Plasma sCD14 is a biomarker associated with impaired neurocognitive testing in attention and learning domains in HIV-infected individuals with advanced disease, suggesting involvement of cortical and limbic pathways by inflammatory processes in the cART era. Plasma sCD14 is a potential biomarker to monitor HAND progression and therapeutic responses.
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.
We undertook a longitudinal study in rural Uganda to understand the association of food insecurity with morbidity and patterns of healthcare utilization among HIV-infected individuals enrolled in an ...antiretroviral therapy program.
Longitudinal cohort study.
Participants were enrolled from the Uganda AIDS Rural Treatment Outcomes cohort, and underwent quarterly structured interviews and blood draws. The primary predictor was food insecurity measured by the validated Household Food Insecurity Access Scale. Primary outcomes included health-related quality of life measured by the validated Medical Outcomes Study-HIV Physical Health Summary (PHS), incident self-reported opportunistic infections, number of hospitalizations, and missed clinic visits. To estimate model parameters, we used the method of generalized estimating equations, adjusting for sociodemographic and clinical variables. Explanatory variables were lagged by 3 months to strengthen causal interpretations.
Beginning in May 2007, 458 persons were followed for a median of 2.07 years, and 40% were severely food insecure at baseline. Severe food insecurity was associated with worse PHS, opportunistic infections, and increased hospitalizations (results were similar in concurrent and lagged models). Mild/moderate food insecurity was associated with missed clinic visits in concurrent models, whereas in lagged models, severe food insecurity was associated with reduced odds of missed clinic visits.
Based on the negative impact of food insecurity on morbidity and patterns of healthcare utilization among HIV-infected individuals, policies and programs that address food insecurity should be a critical component of HIV treatment programs worldwide.
Why have governments responded to the HIV/AIDS pandemic in such different ways? During the past quarter century, international agencies and donors have disseminated vast resources and a set of best ...practice recommendations to policymakers around the globe. Yet the governments of developing countries in sub-Saharan Africa, Asia, Latin America, and the Caribbean continue to implement widely varying policies.Boundaries of Contagionis the first systematic, comparative analysis of the politics of HIV/AIDS. The book explores the political challenges of responding to a stigmatized condition, and identifies ethnic boundaries--the formal and informal institutions that divide societies--as a central influence on politics and policymaking.
Evan Lieberman examines the ways in which risk and social competition get mapped onto well-institutionalized patterns of ethnic politics. Where strong ethnic boundaries fragment societies into groups, the politics of AIDS are more likely to involve blame and shame-avoidance tactics against segments of the population. In turn, government leaders of such countries respond far less aggressively to the epidemic. Lieberman's case studies of Brazil, South Africa, and India--three developing countries that face significant AIDS epidemics--are complemented by statistical analyses of the policy responses of Indian states and over seventy developing countries. The studies conclude that varied patterns of ethnic competition shape how governments respond to this devastating problem. The author considers the implications for governments and donors, and the increasing tendency to identify social problems in ethnic terms.
HIV is a highly adaptive, rapidly evolving virus, which is associated with renal diseases including collapsing glomerulopathy-the classic histomorphological form of HIV-associated nephropathy. Other ...nephropathies related to viral factors include HIV-immune-complex kidney disease and thrombotic microangiopathy. The distribution of HIV-associated kidney diseases has changed over time and continues to vary across geographic regions worldwide. The reasons for this diversity are complex and include a critical role of APOL1 variants and possibly other genetic factors, disparities in access to effective antiviral therapies, and likely other factors that we do not yet fully understand. The mechanisms responsible for HIVAN, including HIV infection of podocytes and tubular epithelial cells, the molecules responsible for HIV entry, and diverse mechanisms of cell injury, have been the focus of much study. Although combined antiretroviral therapy is effective at preventing and reversing HIVAN, focal segmental glomerulosclerosis, arterionephrosclerosis and diabetic nephropathy are increasingly common in individuals who have received such therapy for many years. These diseases are associated with metabolic syndrome, obesity and premature ageing. Future directions for HIV-related kidney disease will involve regular screening for drug nephrotoxicity and incipient renal disease, as well as further research into the mechanisms by which chronic inflammation can lead to glomerular disease.
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