Function In HIV-infected Individuals Research Articles

Evaluation of Testicular Function and Structural Changes of Wistar Rats Following Antiretroviral Exposure: Protective Role of Cyperus Esculentus.

Long-term antiretroviral drug toxicity may exacerbate the impact of HAART-Cyperus esculentus (C. esculentus) interactions on testicular function in HIV-infected individuals. This study examined the ability of C. esculentus plants to treat testicular dysfunction, which is thought to be a probable side effect of antiretroviral toxicity. Adult Wistar male rats weighing 90-110 g were divided into six groups and administered the prescribed treatments. In addition to testicular histology and stereological parameters, testosterone levels, follicle-stimulating hormone levels, antioxidant markers, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione levels were also evaluated. The adverse consequences of highly active antiretroviral therapy (HAART) include considerable loss of germ cells, enlargement of the tubular lumen, widening of interstitial gaps, and severe hypocellularity. Compared to the other treatment groups, MDA levels dramatically increased, whereas GSH and antioxidant enzyme (SOD) levels significantly decreased. Testicular architecture was largely conserved after treatment with C. esculentus, with a notable increase in the cellular densities of germinal and interstitial cells and a notable decrease in the tubular lumen. Vacuolation, architectural malformations, and hypoplastic changes were reduced. Significant improvements were also observed in C. esculentus in terms of elevated antioxidant SOD and GSH levels and decreased MDA levels. C. esculentus reduced architectural distortions and testicular dysfunction caused by HAART, and improved testicular morphology. Further exploration of these pathways is required.

Predictors of Daily Life Functioning in HIV-Infected Individuals

Background: Daily life functioning refers to the skills needed to independently perform day to day routines and deficits of daily life functioning common among people living with HIV. This study aimed to investigate the role of immunologic, virologic, cognitive functioning, and demographic variables to predict daily life function in HIV-infected individuals.
 Methods: We recruited 67 HIV-positive individuals who were under the treatment of Anti-Retroviral Therapy (ART) in Imam Khomeini hospital, Tehran, Iran, in 2016. Prospective-retrospective memory questionnaire (PRMQ), Instrumental Activities of Daily Living interview (IADLs), and flow cytometry test to assess CD4 count were used. The data were analyzed with stepwise regression analysis using SPSS-22 software.
 Results: The results of stepwise regression analysis showed that the prospective/retrospective memory complaints are predictive of daily functioning in people living with HIV (p<0.001, F (1,42) =26.86, R2 adj=0.381). Our results also indicated that CD4 cell count, viral load, age, gender, and education do not predict instrumental activities of daily living scores among HIV-infected individuals (p>0.05).
 Conclusion: Future studies should focus on the effects of prospective/retrospective memory rehabilitation to improve the daily function of HIV-infected individuals. Future studies should also focus on the mediating role of muscle mass decreases between the association of daily life functioning with CD4 and viral load.

Impact of acute, oral ingestion of hypoxoside from African potato on hepatic and renal function tests in HIV infected patients on combination antiretroviral therapy

ObjectivesAfrican potato (hypoxis hemerocallidea) is used against HIV to enhance immune-function, although no studies have evaluated its use in HIV infected individuals on combination antiretroviral therapy. The study aimed to evaluate the acute effects of orally administered hypoxoside, a constituent of African potato, on the hepatic and renal function in HIV infected individuals on tenofovir disoproxil fumarate/ lamivudine/ efavirenz regimen. MethodsThis was an open-label, two-period, fixed-sequence, pre-post test study, pilot design. Ethical approval was obtained from Medical Research Council of Zimbabwe (MRCZ A/2045) and Medicines Control Authority of Zimbabwe (MCAZ CT134/2016). Blood samples were collected before and after administration of African potato tablets. Tablets were administered orally once daily at 15 mg/ kg hypoxoside for 10 days. Hepatic function tests (ALT, AST, ALP, GGT, albumin, total/ direct bilirubin); renal function tests (eGFR, blood urea nitrogen, creatinine), serum electrolytes (sodium, potassium, chloride) were assayed. STATA was used for statistical analysis. ResultsTwenty-six participants were enrolled (85 % female). Median age (range) was 43 (28–52) years. Most had overweight Body Mass Index (46 %) and were married (54 %). No statistical difference was noted during hypoxoside for AST/ ALT/ ALP/ GGT/ albumin/ bilirubin. There were no changes in creatinine/ eGFR/ electrolytes. A mean significant increase in total protein (p = 0.04) and decrease in blood urea nitrogen (p = 0.04) were noted. ConclusionShort-term exposure to hypoxoside from African potato appeared safe and was not associated with clinically significant changes in hepatic, renal function tests/ electrolytes. There is further need to evaluate extent of systemic exposure during long-term use in a larger population. Clinical trial registration numberPACTR201909691101062

Combination of resistance and aerobic exercise for six months improves bone mass and physical function in HIV infected individuals: A randomized controlled trial.

To evaluate the effect of combined resistance and aerobic training (RT+AT) on regional bone mineral density (BMD) and physical performance in people living with HIV (PLWH). Forty PLWH (20 men and 20 women) were randomized into RT+AT group (n=20; age = 38.3 ± 4.9) or non-exercise control group (n=20; age = 37.9 ± 5.1). The RT+AT group was required to perform a nonlinear periodized resistance training program targeting large muscle groups followed by 20 min aerobic exercise at 65-80% of maximal heart rate. Participants in RT+AT performed three supervised sessions per week for 6-months, whereas participants in the control group were instructed to continue with their current lifestyle habits. The primary outcome was bone mineral density (lumbar spine (L2-L4), femoral neck, and distal 1/3 radius). Secondary outcomes included physical function, anthropometry, inflammatory markers, and growth factors. The RT+AT group demonstrated a significant increase in BMD at follow-up for the Lumbar spine (L2-L4), femoral neck, and 1/3 radius (all, P <.05), and There were no gender differences in the training response between men and women for any of the BMD regions. Similar findings were also observed for lean body mass, IGF1and Adiponectin (P<.001). We observed a decrease in percent body fat, fat mass, IL-6, TNF-α, and myostatin in the RT+AT group (P<.001). Finally, there was a significant increase in handgrip strength and gait speed for both women and men in the RT+AT group (P <.001). A combination of resistance and aerobic training appears to be a feasible and effective means for counteracting bone loss and improving various inflammatory markers, physical function, and growth hormones in PLWH.

Acute supplementation with beetroot juice improves endothelial function in HIV-infected individuals.

Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. Nitrate-rich beetroot juice (BJ) has been shown to acutely increase NO availability and vascular function in healthy and individuals at high risk for cardiovascular disease. Thus, we tested the effects of BJ ingestion on flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in healthy and HIV-infected patients. Thirteen HIV-infected individuals (age, 36 ± 10 years) and 18 healthy (age, 27 ± 8 years) participated in the study. Individuals were submitted to vascular tests such as FMD and pulse PWV at pre (T0) and at 120 min (T120) after BJ and placebo (PLA) ingestion. The %FMD at T0 of the control group was significantly higher than the %FMD at T0 of the HIV individuals in both interventions. BJ improved the %FMD at T120 when compared with T0 in the HIV and control groups. There was no change in %FMD after PLA ingestion in the control and HIV groups. There were no differences between groups (control vs HIV), time points (T0 vs T120), and interventions (BJ vs PLA) for PWV. Our findings showed that nitrate-rich BJ ingestion acutely improved vascular function in healthy and HIV-infected patients. Clinical Trials Registry no. NCT03485248. Novelty: HIV is associated with lower NO bioavailability and vascular dysfunction. Acute supplementation with nitrate-rich BJ has been shown to acutely increases NO bioavailability. We showed for the first time that BJ acutely improves endothelial function in HIV-infected patients.

Elevated CD54 Expression Renders CD4+ T Cells Susceptible to Natural Killer Cell-Mediated Killing

Natural killer (NK) cells are an important type of effector cell in the innate immune response, and also have a role in regulation of the adaptive immune response. Several studies have indicated that NK cells may influence CD4+ T cells during HIV infection. In total, 51 HIV-infected individuals and 15 healthy controls participated in this study. We performed the flow cytometry assays and real-time PCR for the phenotypic analysis and the functional assays of NK cell-mediated deletion of CD4+ T cells, phosphorylation of nuclear factor-κB (NF-κB/p65) and the intervention of metformin. Here we detected high CD54 expression on CD4+ T cells in HIV-infected individuals, and demonstrate that upregulated CD54 is associated with disease progression in individuals infected with HIV. We also show that CD54 expression leads to the deletion of CD4+ T cells by NK cells in vitro, and that this is modulated by NF-κB/p65 signaling. Further, we demonstrate that metformin can suppress CD54 expression on CD4+ T cells by inhibiting NF-κB/p65 phosphorylation. Our data suggest that further studies to evaluate the potential role of metformin as adjunctive therapy to reconstitute immune function in HIV-infected individuals are warranted.

Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients

This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIV-infected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load −10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin –IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals.

Osteopontin counters human immunodeficiency virus type 1\u2013induced impairment of neurite growth through mammalian target of rapamycin and beta-integrin signaling pathways

Despite the fact that human immunodeficiency virus type 1 (HIV-1) does not enter or replicate in neurons, its infection of a subset of resident brain glia cells (microglia and astrocytes) induces via disparate mechanisms, dysregulation of glutamate metabolism, neurotoxicity, and inflammation. Antiretroviral therapies suppress viral load, but cellular activation and release of proinflammatory factors, some of which is likely related to viral reservoirs, continue to promote a microenvironment that is injurious to neurons. However, the molecular mechanisms remain to be identified. Osteopontin (OPN) is a proinflammatory cytokine-like, extracellular matrix protein that is elevated within the brain and CSF in several neurodegenerative disorders, including HIV-associated cognitive disorder. However, the impact of elevated OPN on neuronal integrity and function in HIV-infected individuals who exhibit cognitive dysfunction remains unknown. In this study, using a neuronal cell line and primary cultures of cortical rat neurons, we identify the mammalian target of rapamycin pathway involvement in a signaling interaction between OPN-β1-integrins and the HIV-1 envelope glycoprotein, which stimulates neurite growth. These findings link for the first time HIV X4-envelope receptor engagement and osteopontin-mediated signaling through β1-integrin receptors to the mTOR pathway and alterations in the cytoskeleton of cortical neurons.

HIV-1 intron-containing RNA expression induces innate immune activation and T cell dysfunction

Low levels of type I interferon (IFN-I) are thought to be a driving force for immune activation and T-cell exhaustion in HIV-1 infected individuals on combination antiretroviral therapy (cART), though the causative mechanisms for persistent IFN-I signaling have remained unclear. Here, we show Rev–CRM1-dependent nuclear export and peripheral membrane association of intron-containing HIV-1 RNA, independent of primary viral sequence or viral protein expression, is subject to sensing and signaling via MAVS, resulting in IFN-I-dependent pro-inflammatory responses in macrophages. Additionally, HIV-1 intron-containing-RNA-induced innate immune activation of macrophages leads to upregulation of inhibitory receptor expression and functional immune exhaustion of co-cultured T cells. Our findings suggest that persistent expression of HIV-1 intron-containing RNA in macrophages contributes to chronic immune activation and T-cell dysfunction and that use of HIV RNA expression inhibitors as adjunct therapy might abrogate aberrant inflammation and restore immune function in HIV-infected individuals on cART.

Chronic kidney disease in Australian Human Immunodeficiency Virus-infected patients: Analysis of the Australian HIV Observational Database.

The aim of the present study was to examine data from the Australian HIV Observational Database (AHOD), and firstly, to describe the incidence of chronic kidney disease (CKD) and the rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population. AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 March 2016 and an initial estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m3 . Cox proportional hazards models were used to assess risk factors for CKD, which included key patient demographic data and antiretroviral therapy (ART) exposure. Of 1924 patients included in the analysis between April 2008 and March 2016, 81 (4.2%) developed CKD (confirmed eGFR of less than 60 mL/min per 1.73 m3 through two consecutive eGFR measurements at least 3 months apart). Of the examined risk factors, baseline age, baseline eGFR, and the route of HIV acquisition were statistically significant predictors of development of CKD. ART exposure, viral hepatitis co-infection, high viral load and low CD4 lymphocyte count were not found to be significant risk factors for CKD. This is the first study to investigate the risk factors for development of CKD among Australian HIV-infected patients using cohort data. It highlights the need for awareness of renal risk factors, particularly among older patients or in those with pre-existing renal dysfunction. Further research is required to explore the discrepancy between patients who have acquired HIV through different means of exposure.

The investigation of CD4+T-cell functions in primary HIV infection with antiretroviral therapy.

Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function.

Immune activation is associated with decreased thymic function in asymptomatic, untreated HIV-infected individuals.

BackgroundReduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIV-positive treatment-naive individuals has thus far not been investigated.Aims and objectivesTo optimise a five-colour flow cytometric assay for measurement of thymic function by measuring recent thymic emigrants (RTEs) in treatment-naive HIV-infected patients and healthy controls and correlate results with levels of immune activation, CD4 counts and viral load.MethodsBlood obtained from 53 consenting HIV-positive individuals and 32 controls recruited from HIV prevention and testing clinic in Cape Town, South Africa. RTEs were measured (CD3+/CD4+/CD45RA+/CD31+/CD62L+) and levels were correlated with CD4 counts of HIV-infected individuals, log viral load and levels of immune activation (CD8+/CD38+ T-cells).ResultsHIV-infected individuals had reduced frequencies of RTEs when compared to controls (p = 0.0035). Levels of immune activation were inversely correlated with thymic function (p = 0.0403), and the thymic function in HIV-infected individuals showed no significant correlation with CD4 counts (p = 0.31559) and viral load (p = 0.20628).ConclusionsThere was impaired thymic function in HIV-infected individuals, which was associated with increased levels of immune activation. The thymic dysfunction was not associated with CD4 counts and viral load. Immune activation may result in inflammatory damage to the thymus and subsequent thymic dysfunction, and CD4 counts and viral load may not necessarily reflect thymic dysfunction in HIV.

Immune activation is associated with decreased thymic function in asymptomatic, untreated HIV-infected individuals

Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART).The association between immune activation and thymic function in asymptomatic HIV positive treatment-naive individuals has thus far not been investigated. Aims and objectives: To optimise a five-colour flow cytometric assay for measurement of thymic function by measuring recent thymic emigrants (RTEs) in treatment-naive HIV-infected patients and healthy controls and correlate results with levels of immune activation, CD4 counts and viral load. Methods: Blood obtained from 53 consenting HIV-positive individuals and 32 controls recruited from HIV prevention and testing clinic in Cape Town, South Africa. RTEs were measured (CD3 + /CD4 + /CD45RA + /CD31 + /CD62L + ) and levels were correlated with CD4 counts of HIV-infected individuals, log viral load and levels of immune activation (CD8 + /CD38 + T-cells). Results: HIV-infected individuals had reduced frequencies of RTEs when compared to controls ( p = 0.0035). Levels of immune activation were inversely correlated with thymic function( p = 0.0403), and the thymic function in HIV-infected individuals showed no significant correlation with CD4 counts ( p = 0.31559) and viral load ( p = 0.20628). Conclusions: There was impaired thymic function in HIV-infected individuals, which was associated with increased levels of immune activation. The thymic dysfunction was not associated with CD4 counts and viral load. Immune activation may result in inflammatory damage to the thymus and subsequent thymic dysfunction, and CD4 counts and viral load may not necessarily reflect thymic dysfunction in HIV.

Characterization of lipid composition and high-density lipoprotein function in HIV-infected individuals on stable antiretroviral regimens.

There is an increase in the cardiovascular disease (CVD) morbidity in individuals infected with HIV that may be due to inflammatory lipid modulation not captured by traditional lipid measures. The objective of this study was to perform advanced lipoprotein phenotyping inclusive of the high-density lipoprotein (HDL) cholesterol efflux capacity and lipoprotein particle concentration and size in a well-phenotyped group of 118 patients infected with HIV. We used simple and multivariable analyses to determine the associations between advanced lipoprotein parameters and known cardiometabolic risk factors. Participants were on stable antiretroviral therapy (ART) and had benign traditional lipid panels [median total cholesterol, low-density lipoprotein (LDL)-C, HDL-C, and triglycerides of 178 mg/dl, 108 mg/dl, 44 mg/dl, and 122.5 mg/dl, respectively]. However, advanced lipoprotein phenotyping demonstrated an elevation of LDL particle number (median of 1,233 nmol/liter) and a decrease in LDL size (median of 20.4 nm), along with a decrease in protective, large HDL particles (median of 3.15 μmol/liter) and reduced HDL cholesterol efflux capacity in comparison to controls of other studies. HDL cholesterol efflux capacity was associated with HDL levels (β=0.395, p<0.001), small LDL particle concentration (β=-0.198, p=0.031), insulin sensitivity by the Matsuda index (β=0.218, p=0.029), and the Framingham Risk Score (β=-0.184, p=0.046). We demonstrate an atherogenic lipoprotein profile by NMR spectroscopy and HDL efflux measurement in a group of HIV-infected patients on stable ART with normal lipid panels.

Genetic predictor of working memory and prefrontal function in women with HIV.

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

The role of extended-release niacin on immune activation and neurocognition in HIV-infected patients treated with antiretroviral therapy - CTN PT006: study protocol for a randomized controlled trial.

BackgroundApproximately 30% of HIV-1-infected patients receiving antiretroviral therapy who achieve virologic control have unsatisfactory immune reconstitution, with CD4+ T-cell counts persistently below 350 cells/μL. These patients are at elevated risk for clinical progression to AIDS and non-AIDS events. CD4+ T-cell depletion following infection and persistent immune activation can partially explain this low CD4+ T-cell recovery. Recent data suggest a link between the tryptophan oxidation pathway, immune activation and HIV disease progression based on overstimulation of the tryptophan oxidation pathway by HIV antigens and by interferon-gamma. This overstimulation reduces levels of circulating tryptophan, resulting in inflammation which has been implicated in the development of neurocognitive dysfunction. Niacin (vitamin B3) is able to control the excess tryptophan oxidation, correcting tryptophan depletion, and therefore represents an interesting strategy to improve CD4 recovery.We aim to design a crossover proof-of-concept study to assess supplementation with an extended-release form of niacin (Niaspan FCT™) in combination with antiretroviral therapy, compared to antiretroviral therapy alone, on T-cell immune activation as defined by changes in the percentage of CD8+ CD38+ HLA-DR+ T-cells.Methods/DesignThis randomized, open-label, interventional crossover study with an immediate versus deferred use of Niaspan FCT for 24 weeks will assess its ability to reduce immune activation and thus increase CD4 recovery in 20 HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression. A substudy evaluating neurocognitive function will also be conducted.DiscussionThis randomized trial will provide an opportunity to evaluate the potential benefit of oral extended-release niacin, a drug that can indirectly increase tryptophan, to reduce immune activation and in turn increase CD4+ T-cell recovery. The study will also allow for the evaluation of the impact of Niaspan FCT on neurocognitive function in HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression.Trial registrationThis study was registered with ClinicalTrials.gov on 17 December 2013 (registration number: NCT02018965).Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-15-390) contains supplementary material, which is available to authorized users.

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals.

To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV. This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally. Cross-sectional analysis revealed significant inverse associations between IL-6, hsCRP and d-dimer with SDNN and rMSSD (p < 0.01 for all comparisons). However, longitudinal analysis failed to show a significant association between baseline IL-6, hsCRP and d-dimer with change in CAF over time. Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were associated with lower levels of CAF in the Strategies for Management of Antiretroviral Therapy trial. Although deterioration in CAF was observed during followup, baseline levels of inflammatory and coagulation markers were not predictive of the decline in CAF over time.

Brain abnormalities in HIV and stimulant users: Interventions and prevention

The session, “HIV and other Infectious Diseases,” was chaired by Dr. Jacques Normand, Director of the AIDS Research Program of the US National Institute on Drug Abuse. The two presenters (and their presentation topics) were: Dr. Linda Chang (“Neural Correlates of Cognitive Deficits and Training Effects on Brain Function in HIV-infected Individuals”) and Dr. Steven Shoptaw (“HIV Prevention in Substance Users”).

Antiretroviral Monocyte Efficacy Score Linked to Cognitive Impairment in Hiv

Monocytes transmigrating to the brain play a central role in HIV neuropathology. We hypothesized that the continued existence of neurocognitive impairment (NCI) despite potent antiretroviral (ARV) therapy is mediated by the inability of such therapy to control this monocyte/macrophage reservoir. Cross-sectional and longitudinal analyses were conducted within a prospectively enrolled cohort. We devised a monocyte efficacy (ME) score based on the anticipated effectiveness of ARV medications against monocytes/macrophages using published macrophage in vitro drug efficacy data. We examined, within an HIV neurocognitive database, its association with composite neuropsychological test scores (NPZ8) and clinical cognitive diagnoses among subjects on stable ARV medications unchanged for >6 months prior to assessment. Among 139 subjects on ARV therapy, higher ME score correlated with better NPZ8 performance (r=0.23, P<0.01), whereas a score devised to quantify expected penetration effectiveness of ARVs into the brain (CPE score) did not (r=0.12, P=0.15). In an adjusted model (adjusted r(2)=0.12), ME score (β=0.003, P=0.02), CD4(+) T-cell nadir (β=0.001, P<0.01) and gender (β=-0.456, P=0.02) were associated with NPZ8, whereas CPE score was not (β=0.003, P=0.94). A higher ME score was associated with better clinical cognitive status (P<0.01). With a range of 12.5-433.0 units, a 100-unit increase in ME score resulted in a 10.6-fold decrease in the odds of a dementia diagnosis compared with normal cognition (P=0.01). ARV efficacy against monocytes/macrophages correlates with cognitive function in HIV-infected individuals on ARV therapy within this cohort. If validated, efficacy against monocytes/macrophages may provide a new target to improve HIV NCI.

Tipranavir in the Protease Inhibitors Arena

Tipranavir in the Protease Inhibitors Arena