Antiretroviral medications have been shown to benefit neurocognition in HIV/AIDS, and neurocognitive deficits are a risk factor for poor adherence to these medications. However, little is known about the predictive pathways linking medication adherence with cognitive ability.
In the current 6-month cohort study, antiretroviral medication adherence was tracked prospectively among 91 HIV-positive adults using electronic monitoring. Comprehensive neuropsychological evaluations were performed at baseline and 6 months.
Multivariate path analyses provided evidence that antiretroviral adherence and cognitive ability are reciprocally related, although the neurocognitive pathways of this relationship appear to vary by predictive direction. Executive function and learning/memory were most strongly predictive of levels of medication adherence achieved, whereas higher levels of adherence were predictive of relative improvements in a wide range of frontostriatal brain functions including processing speed, attention, executive functions, and motor functioning.
These data provide evidence that cognition and adherence are reciprocally related in HIV/AIDS. In particular, executive dysfunction may play a key role in this relationship. Interventions aimed at improving or preserving executive functions could hold promise for interrupting progressive declines in adherence and neurocognitive ability in HIV/AIDS.
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= highly active antiretroviral therapy;
= Medication Event Monitoring System;
= protease inhibitor.
The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance.
Antiretroviral therapy; Contingent negative variation; Event-related potential; HIV; MRI
Sexual dysfunctions in HIV-positive men are associated with an increase in risky sexual behavior and decreased adherence to antiretroviral drug regimens. Because of these important public health issues, we reviewed the literature on the pathophysiology, associated factors and clinical management of sexual dysfunction in HIV-positive men. The goal was to investigate the current research on these issues. Literature searches were performed in June 2011 on PubMed, Web of Science, and PsycInfo databases with the keywords “AIDS” and “sexual dysfunction” and “HIV” and “sexual dysfunction”, resulting in 54 papers. Several researchers have investigated the factors associated with sexual dysfunction in HIV-positive men. The association between sexual dysfunction and antiretroviral drugs, particularly protease inhibitors, has been reported in many studies. The lack of standardized measures in many studies and the varying study designs are the main reasons that explain the controversial results. Despite some important findings, the pathophysiology of sexual dysfunction in the HAART era still not completely understood. Clinical trials of testosterone replacement therapy have shown the treatment to be beneficial to the improvement of sexual dysfunctions related to hypogonadism. However, there are not enough psychological intervention studies to make conclusions regarding the therapeutic effects of psychotherapy.
Human immunodeficiency virus (HIV)-infected adults frequently evidence both neurocognitive and psychiatric dysfunction. It was hypothesized that apathy and irritability, but not anxiety and depression, are related to HIV effects on frontal–subcortical systems. This hypothesis was evaluated by determining the degree to which these psychiatric features are associated with neurocognitive functioning that is dependent upon frontal–subcortical circuitry and, therefore, thought to be sensitive to the central nervous system effects of HIV. Rating scales assessing irritability, apathy, depression, and anxiety and a dual-task paradigm were administered to 189 HIV-seropositive (HIV+) and 53 HIV-seronegative participants. Deficits in dual-task performance and greater anxiety, depression, apathy, and irritability were observed in HIV+ participants. Simultaneous multivariate regression and communality analyses revealed that only apathy and irritability were associated with dual-task performance in HIV+ participants. Thus, these findings suggest that apathy and irritability, but not depression and anxiety, are likely associated with the effects of HIV on frontal–subcortical circuitry.
Human immunodeficiency virus; Apathy; Irritability; Depression; Anxiety; Cognition
To determine factors associated with baseline neurocognitive performance in HIV-infected participants enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) neurology substudy.
Participants from Australia, North America, Brazil, and Thailand were administered a 5-test neurocognitive battery. Z scores and the neurocognitive performance outcome measure, the quantitative neurocognitive performance z score (QNPZ-5), were calculated using US norms. Neurocognitive impairment was defined as z scores <−2 in two or more cognitive domains. Associations of test scores, the QNPZ-5, and impairment with baseline factors including demographics and risk factors for HIV-associated dementia (HAD) and cardiovascular disease (CVD) were determined in multiple regression.
The 292 participants had a median CD4 cell count of 536 cells/mm3, 88% had an HIV viral load ≤400 copies/mL, and 92% were taking antiretrovirals. Demographics, HIV, and clinical factors differed between locations. The mean QNPZ-5 score was −0.72; 14% of participants had neurocognitive impairment. For most tests, scores and z scores differed significantly between locations, with and without adjustment for age, sex, education, and race. Prior CVD was associated with neurocognitive impairment. Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance but conventional HAD risk factors and the CNS penetration effectiveness rank of antiretroviral regimens were not.
In this HIV-positive population with high CD4 cell counts, neurocognitive impairment was associated with prior CVD. Lower neurocognitive performance was associated with prior CVD, hypertension, and hypercholesterolemia, but not conventional HAD risk factors. The contribution of CVD and cardiovascular risk factors to the neurocognition of HIV-positive populations warrants further investigation.
= Alzheimer disease;
= antiretroviral therapy;
= blood pressure;
= Center for Epidemiologic Studies-Depression scale;
= Color Trails;
= cardiovascular disease;
= Finger Tapping Test;
= Grooved Pegboard;
= HIV-associated dementia;
= neurocognitive impairment;
= quantitative neurocognitive performance z score;
= Strategies for Management of Antiretroviral Therapy;
= Timed Gait.
Prior studies have shown improved neurocognition with initiation of antiretroviral treatment (ART) in HIV. We hypothesized that stopping ART would be associated with poorer neurocognitive function.
Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count >350 cells/mm3, had HIV RNA viral load <55,000 cp/mL, and were on ART (≥2 drugs) for ≥6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination.
A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm3 and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p < 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed.
Subjects with preserved immune function found that neurocognition improved significantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration.
Classification of evidence:
This study provides Class III evidence that discontinuing ART is associated with an improvement in 2 neuropsychological tests (Trail-Making Test A & B and the Wechsler Adult Intelligence Scale–Revised Digit Symbol subtest) for up to 96 weeks. Resuming ART was not associated with a decline in these scores for up to 45 weeks.
= AIDS Clinical Trials Group;
= antiretroviral treatment;
= highly active antiretroviral therapy;
= HIV-associated dementia;
= neuropsychological summary score;
= treatment interruption;
= viral load.
Cocaine abuse among HIV patients is associated with faster disease progression and mortality. This study examined the relationship between neurocognitive functioning and medication adherence in HIV patients with (n= 25) and without (n= 39) current cocaine dependence. Active users had greater neurocognitive impairment (mean T-score= 35.16 vs. 40.97, p < .05) and worse medication adherence (mean z-score= −0.44 vs. 0.27, p < .001). In a multiple regression model, neurocognitive functioning (β= .33, p < .01) and cocaine dependence (β= −.36, p < .01) were predictive of poorer adherence. There was a significant indirect effect of cocaine dependence on medication adherence through neurocognitive impairment (estimate= −0.15, p < .05), suggesting that neurocognitive impairment partially mediated the relationship between cocaine dependence and poorer adherence. These results confirm that cocaine users are at high risk for poor HIV outcomes and underscore the importance of treating both neurocognitive impairment and cocaine dependence among HIV patients.
HIV/AIDS; cocaine dependence; antiretroviral therapy; medication adherence; neurocognitive functioning
In view of the rising prevalence of an overweight body mass among patients living with HIV/AIDS, clinicians must now be mindful of possible adverse outcomes resulting from the co-occurrence. The present study was designed to examine the additive and interactive effects of HIV/AIDS and an excess body mass, as well as the additional contributions of substance abuse or dependence. The dependent variable was brain function estimated by the measurement of P300 electroencephalographic potentials. P300 potentials were recorded during a task designed to elicit subcomponents with frontal (P300a) and both frontal and nonfrontal (P300b) generators. Analyses revealed greater frontal P300a latencies among the 102 HIV-1 seropositive versus the 68 seronegative participants. In addition, frontal P300a latency was further increased by a synergistic interaction of HIV-1 serostatus with a body mass index (BMI) ≥ 25 kg/m2. A history of substance abuse/dependence did not alter these changes. However, it did combine with HIV/AIDS to produce a smaller P300a amplitude than was seen in participants with neither disorder. The findings suggest that white matter changes accompanying an excess BMI may exacerbate those that attend HIV/AIDS and thereby slow frontal brain function. Substance abuse likewise interacts with HIV/AIDS but may impair frontal brain function via a different mechanism.
HIV-1; Obesity; BMI; Evoked Potentials; EEG; White Matter; Substance Dependence
To assess the P300 latency and amplitude in recently diagnosed human immunodeficiency virus (HIV)-positive patients and compare the same with a healthy control group. Further an attempt was made to study the correlation between P300 amplitude and latency (in milliseconds) with neurocognitive functions.
Materials and Methods:
Thirty newly diagnosed HIV-positive patients who on self report did not have any cognitive dysfunction were recruited. The patients were evaluated for P300 evoked response using the odd-ball paradigm, MMSE and a comprehensive neuropsychological battery. The P300 latencies were compared with 30 normal control subjects.
The mean P300 latency (in milliseconds) of the HIV-positive subjects was significantly more than the healthy control group. The mean amplitude of HIV group was significantly less than the normal control group. On MMSE, 7 HIV-positive subjects had mild cognitive impairment (MMSE total score 20-23), six patients had minimal cognitive impairment (MMSE total score 24-27) and 17 patients had no cognitive impairment (MMSE total score >27). On neuropsychological test battery only three (10%) of HIV-positive subjects had cognitive dysfunction. There was negative correlation between P300 latency (in milliseconds) and MMSE total score and performance on Koh's Block subtest.
P300 may be a reliable indicator of cognitive impairments in HIV patients.
Cognitive functions; evoked potential; human immunodeficiency virus
To determine whether subjects with HIV-associated neurocognitive disorder (HAND) show altered concentrations of brain glutamate (GLU), and whether lower GLU levels correlate with cognitive deficits.
Materials and Methods
GLU concentrations were measured in the basal ganglia, frontal gray and white matter, and parietal gray matter of 45 HIV-positive and 46 age-and-education-matched HIV-negative subjects, using echo-time averaged proton magnetic resonance spectroscopy (1H MRS).
Compared to controls, HIV subjects with cognitive deficits had lower GLU in the parietal gray matter, while those without cognitive deficits tended to show higher basal ganglia GLU. Lower parietal and frontal gray matter GLU were associated with a greater number of nucleoside reverse transcriptase inhibitors, and were predictive of poorer cognitive performance. Correlations between GLU and cognitive performance, but not the other findings, remained significant after correction for multiple comparisons.
Parietal gray matter GLU is lower in HIV subjects with cognitive deficits. This reduction might result from reduced astrocytic reuptake of GLU, secondary excitotoxicity, and mitochondrial toxicity from antiretroviral treatments. The glutamatergic system may play an important role in the pathophysiology of HAND, and brain GLU on 1H MRS may provide an early surrogate marker for monitoring disease severity and treatment effects.
Glutamate; brain; magnetic resonance spectroscopy (MRS); HIV; cognition
The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency of HIV brain pathology was lower than previous pre-antiretroviral reports, and was predicted by lower nadir CD4 and higher plasma viral load. Noninfectious pathologies and minimal changes correlated with HIV-associated neurocognitive disorder, suggesting a shift in pathogenesis from florid HIV replication to other, diverse mechanisms.
all infections; HIV dementia; risk factors in epidemiology
The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity.
To evaluate whether autonomic dysfunction is present in an ART treated HIV population and if so to identify factors of importance.
HIV patients receiving ART for at least 12 months (n = 97) and an age-matched control group of healthy volunteers (n = 52) were included. All were non-diabetic and had never received medication for hypertension. Following a 10 min resting period a 15 min ECG recording was performed. Heart-rate variability (HRV) analysis was performed in accordance with current guidelines and data reported as mean [interquartile range].
Mean normal-to-normal (NN) and total HRV measured as standard deviation of normal-to-normal (SDNN) was lower in HIV patients compared to controls (905 vs. 982 ms; p<0.001 and 48 vs. 54 ms; p = 0.028, respectively). No differences were found between the groups in parasympathetic activity measured as square root of the mean squared difference of successive NN-intervals (RMSSD) or the percent of differences between adjacent NN intervals greater than 50 ms (pNN50). In the HIV positives, haemoglobin A1c correlated inversely with SDNN, RMSSD and pNN50 (p<0.05). Total cholesterol and LDL-C correlated inversely with RMSSD and pNN50 (p<0.05). Neither HIV duration, HIV-RNA, CD4 cell count nor CD4 nadir correlated with time or phase domain HRV variables.
Moderate autonomic dysfunction is present in HIV positives patients even with suppressed viral load due to ART. The dysfunction is correlated with HbA1c and hypercholesterolemia but not to duration of HIV or whether the patients were receiving protease inhibitors as part of the ART regime.
This review focuses on the “real world” implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.
HIV/AIDS; Neuropsychology; Medication adherence; Employment; Driving
The aim of this study was to examine the complex relationships among neurocognition, insight and nonadherence in patients with schizophrenia.
Design: Cross-sectional study. Inclusion criteria: Diagnosis of schizophrenia according to the DSM-IV-TR criteria. Data collection: Neurocognition was assessed using a global approach that addressed memory, attention, and executive functions; insight was analyzed using the multidimensional ‘Scale to assess Unawareness of Mental Disorder;’ and nonadherence was measured using the multidimensional ‘Medication Adherence Rating Scale.’ Analysis: Structural equation modeling (SEM) was applied to examine the non-straightforward relationships among the following latent variables: neurocognition, ‘awareness of positive symptoms’ and ‘negative symptoms’, ‘awareness of mental disorder’ and nonadherence.
One hundred and sixty-nine patients were enrolled. The final testing model showed good fit, with normed χ2 = 1.67, RMSEA = 0.063, CFI = 0.94, and SRMR = 0.092. The SEM revealed significant associations between (1) neurocognition and ‘awareness of symptoms,’ (2) ‘awareness of symptoms’ and ‘awareness of mental disorder’ and (3) ‘awareness of mental disorder’ and nonadherence, mainly in the ‘attitude toward taking medication’ dimension. In contrast, there were no significant links between neurocognition and nonadherence, neurocognition and ‘awareness of mental disorder,’ and ‘awareness of symptoms’ and nonadherence.
Our findings support the hypothesis that neurocognition influences ‘awareness of symptoms,’ which must be integrated into a higher level of insight (i.e., the ‘awareness of mental disorder’) to have an impact on nonadherence. These findings have important implications for the development of effective strategies to enhance medication adherence.
Successful medication management is an essential ingredient for effective treatment for HIV. Risk factors for poor medication adherence, including neurocognitive impairment and low health literacy, are common in HIV patients. To better understand the most salient risks for poor management of HIV medications, we tested the interrelation of neurocognitive functioning, reading literacy for health related information, and numeracy and their effect on self-management of a simulated HIV medication regimen. Cross-sectional data on 191 HIV-positive men and women recruited from HIV outpatient clinics in South Florida were collected. Exploratory factor analysis was conducted with literacy, numeracy, and neurocognitive scores and suggested that four factors were present representing executive skill, verbal memory, planning, and motor speed. Both the literacy and numeracy scores loaded on the executive factor. Adjusted analyses showed that executive and planning skills were significantly related to medication management. Findings suggest that patients must rely on higher order cognitive skills to successfully navigate medication self-management, and that efforts to simplify health information that merely lowers readability are likely to meet with limited success.
Infection with hepatitis C virus (HCV) is commonly seen in persons with human immunodeficiency virus (HIV) infection, because the viruses share risk factors for transmission; coinfection is a leading cause of morbidity and mortality among HIV-infected persons. Neuropsychological consequences of HIV infection are well established, and studies of HCV-infected persons have revealed neuropsychiatric dysfunction in this population as well. Investigators now are focusing on neuropsychological sequelae of coinfection with HIV and HCV, and preliminary results suggest that coinfection has a possible deleterious effect on global cognitive functioning consistent with frontal-subcortical dysfunction. Data on neuropsychiatric symptoms in coinfected persons are inconclusive at this time and are complicated by important differences in study populations (e.g., injection drug use and disease severity). This review summarizes what is known about neuropsychological aspects of monoinfection with HIV and HCV, as well as coinfection, discusses implications of these findings, and suggests future directions for this research area.
The extent to which highly active antiretroviral therapy (HAART) era cognitive disorders are due to active processes, incomplete clearance of reservoirs, or comorbidities is controversial. This study aimed to determine if immunologic and virologic factors influence cognition after first-time HAART in Thai individuals with HIV-associated dementia (HAD) and Thai individuals without HAD (non-HAD).
Variables were captured longitudinally to determine factors predictive of degree of cognitive recovery after first-time HAART. Neuropsychological data were compared to those of 230 HIV-negative Thai controls.
HIV RNA and CD4 lymphocyte counts were not predictive of HAD cross-sectionally or degree of cognitive improvement longitudinally. In contrast, baseline and longitudinal HIV DNA isolated from monocytes correlated to cognitive performance irrespective of plasma HIV RNA and CD4 lymphocyte counts pre-HAART (p < 0.001) and at 48 weeks post HAART (p < 0.001). Levels exceeding 3.5 log10 copies HIV DNA/106 monocyte at baseline distinguished all HAD and non-HAD cases (p < 0.001). At 48 weeks, monocyte HIV DNA was below the level of detection of our assay (10 copies/106 cells) in 15/15 non-HAD compared to only 4/12 HAD cases, despite undetectable plasma HIV RNA in 26/27 cases. Baseline monocyte HIV DNA predicted 48-week cognitive performance on a composite score, independently of concurrent monocyte HIV DNA and CD4 count (p < 0.001).
Monocyte HIV DNA level correlates to cognitive performance before highly active antiretroviral therapy (HAART) and 48 weeks after HAART in this cohort and baseline monocyte HIV DNA may predict 48-week cognitive performance. These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir.
= confidence interval;
= circulating recombinant form;
= global deficit score;
= highly active antiretroviral therapy;
= HIV-associated dementia;
= International HIV Dementia Scale;
= interquartile range;
= neurocognitive impairment;
= peripheral blood mononuclear cell;
= Thai Depression Inventory score.
To assess the association of HIV infection, HIV disease parameters (including CD4+ T-cell counts, HIV viral load, and AIDS) and antiretroviral medication use with subclinical carotid artery atherosclerosis.
Cross-sectional study nested within a prospective cohort study
Among participants in the Women's Interagency HIV Study (1,331 HIV-infected women, 534 HIV-uninfected women) and Multicenter AIDS Cohort Study (600 HIV-infected men, 325 HIV-uninfected men), we measured subclinical carotid artery lesions and common carotid artery intima-media thickness (CIMT) using B-mode ultrasound. We estimated adjusted mean CIMT differences and prevalence ratios (PRs) for carotid lesions associated with HIV-related disease and treatments, with multivariate adjustment to control for possible confounding variables.
Among HIV-infected individuals, a low CD4+ T cell count was independently associated with an increased prevalence of carotid lesions. Compared to the reference group of HIV-uninfected individuals, the adjusted PR for lesions among HIV-infected individuals with CD4+ T-cell count <200 cells/mm3 was 2.00 (95% confidence interval 1.22, 3.28) in women and 1.74 (95% confidence interval 1.04, 2.93) in men. No consistent association of antiretroviral medications with carotid atherosclerosis was observed, except for a borderline significant association between protease inhibitor use and carotid lesions in men (with no association among women). History of clinical AIDS and HIV viral load were not significantly associated with carotid atherosclerosis.
Beyond traditional cardiovascular disease risk factors, low CD4+ T-cell count is the most robust risk factor for increased subclinical carotid atherosclerosis in HIV-infected women and men.
Objective—To investigate the prevalence of left ventricular dysfunction in African patients infected with the human immunodeficiency virus (HIV). The hypothesis was that HIV infected patients with left ventricular dysfunction are asymptomatic.
Methods—M mode, cross sectional, and Doppler echocardiography were performed in 49 consecutive patients (30 HIV positive (HIV+) carriers and 19 AIDS patients). None of the patients or 58 controls had a medical history of cardiovascular abnormalities.
Results—Cardiac abnormalities were not suspected on physical, electrocardiographic, and radiological examination. Forty two of the HIV infected patients had left ventricular diastolic dysfunction; this was more pronounced in AIDS patients than in HIV+ carriers. Systolic function was normal in both stages of HIV infection. Left ventricular isovolumic relaxation time (mean (SD)) increased from 87.2 (12.4) ms in the carrier state to 103.9 (19.3) ms in AIDS (p < 0.05, Bonferoni correction), peak early filling velocity declined from 0.54 (0.1) to 0.44 (0.1) m/s (p < 0.05), and late velocity increased from 0.64 (0.1) to 0.69 (0.2) m/s. A restrictive filling pattern was explained by concentric hypertrophy in 23 HIV infected patients, and by systemic amyloidosis with left ventricular dilatation in 12 of 49 HIV infected patients.
Conclusions—Echocardiography is a useful technique for detecting left ventricular diastolic dysfunction in HIV infected patients with clinically unsuspected cardiac lesions. Systolic function was normal despite the presence of such cardiac abnormalities.
Keywords: HIV infection; AIDS; diastolic dysfunction; black Africans; echocardiography
Clinical, immunologic and virologic outcomes at large HIV/AIDS care clinics in resource poor settings are poorly described beyond the first year of highly active antiretroviral treatment (HAART). We aimed to prospectively evaluate long-term treatment outcomes at a large scale HIV/AIDS care clinic in South Africa.
Cohort study of patients initiating HAART between April 1, 2004 and March 13, 2007, and followed up until April 1, 2008 at a public HIV/AIDS care clinic in Johannesburg, South Africa. We performed time to event analysis on key treatment outcomes and program impact parameters including mortality, retention in care, CD4 count gain, virologic success and first line regimen durability.
7583 HIV-infected patients initiated care and contributed to 161,000 person months follow up. Overall mortality rate was low (2.9 deaths per 100 person years, 95% CI 2.6-3.2), but high in the first three months of HAART (8.4 per 100 person years, 95% CI 7.2-9.9). Long-term on-site retention in care was relatively high (74.4% at 4 years, 95%CI 73.2-75.6). CD4 count was above 200 cells/mm3 after 6 months of treatment in almost all patients. By the fourth year of HAART, the majority (59.6%, 95%CI 57.8-61.4) of patients had at least one first line drug (mainly stavudine) substituted. Women were twice as likely to experience drug substitution (OR 1.97, 95% CI 1.80-2.16). By 6 months of HAART, 90.8% suppressed virus below 400 copies. Among those with initial viral suppression, 9.4% (95% CI 8.5-10.3%) had viral rebound within one year of viral suppression, 16.8% (95% CI 15.5-18.1) within 2 years, and 20.6% (95% CI 18.9-22.4) within 3 years of initial suppression. Only 10% of women and 13% of men initiated second line HAART.
Despite advanced disease presentation and a very large-scale program, high quality care was achieved as indicated by good long-term clinical, immunologic and virologic outcomes and a low rate of second line HAART initiation. High rates of single drug substitution suggest that the public health approach to HAART could be further improved by the use of a more durable first line regimen.
Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIV+ men, though HIV+ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women.
Participants included 54 HIV+ and 12 HIV− women (mean age = 43 years; 86% African American) recruited from the Chicago site of the Women's Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task.
HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIV+ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory.
Verbal episodic memory deficits are evident in HIV+ women and may be associated with hippocampal dysfunction at both encoding and retrieval.
= antiretroviral therapy;
= Center for Epidemiologic Studies–Depression Scale;
= functional MRI;
= highly active antiretroviral therapy;
= hepatitis C virus antibody;
= Hopkins Verbal Learning Task;
= region of interest;
= echo time;
= repetition time;
= Women's Interagency HIV Study;
= Wide Range Achievement Test–Revised.
Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals.
HIV; Stress; Amygdala; Neuroimaging; Cognition
Introduction. HIV-associated neurocognitive disorder (HAND) remains common despite the availability of antiretroviral therapy. Routine screening will improve early detections. Objective. To compare the performance of the minimental state examination (MMSE) and international HIV dementia scale (IHDS) in assessing neurocognitive function in HIV/AIDS patients on antiretroviral therapy. Methods. A case-control study of 208 HIV-positive and 121 HIV-negative individuals. Baseline demographic data were documented and cognitive function assessed using the two instruments. CD4 cell counts were recorded. Results. Cases comprised 137 females and 71 males. Controls were 86 females and 35 males. Mean MMSE score of cases was 27.7 ± 1.8 compared to 27.8 ± 1.3 in controls (P = 0.54). Mean IHDS score in cases was 8.36 ± 3.1 compared to 10.7 ± 0.9 in controls (P < 0.001). Using the MMSE scale, 6 cases but no controls had HAND (P = 0.09). Using the IHDS, 113 (54.3%) had HAND compared with 10 (8.3%) controls (P < 0.0001). Using IHDS, 56.5% cases with CD4 count > 200 had HAND compared with 92.5% with CD4 count < 200 (P < 0.001). Conclusion. These findings indicate that the IHDS detects higher rates of HAND and may identify HIV/AIDS patients who require further cognitive assessment using more robust assessment batteries.
Alcohol use is a barrier to medication adherence. Beyond the cognitive effects of intoxication, people living with HIV/AIDS who believe that alcohol should not be mixed with their medications may temporarily stop taking medications when drinking. To examine the effects of alcohol-treatment beliefs on HIV treatment adherence. People living with HIV/AIDS who were receiving treatment (n = 145) were recruited from community and clinical services during the period between January 2006 and May 2008 to complete measures of substance use and alcohol-antiretroviral (ARV) interactive toxicity beliefs (e.g., alcohol breaks down HIV medications so they will not work). Medication adherence was monitored using unannounced telephone-based pill counts. Forty percent of participants were currently using alcohol and nearly one in four drinkers reported stopping their medications when drinking. Beliefs that mixing alcohol and medications is toxic were common among drinkers and nondrinkers, with most beliefs endorsed more frequently by non-drinkers. Hierarchical regression analysis showed that stopping ARVs when drinking was associated with treatment nonadherence over and above quantity/frequency of alcohol use and problem drinking. Beliefs that alcohol and ARVs should not be mixed and that treatments should be interrupted when drinking are common among people living with HIV/AIDS. Clinicians should educate patients about the necessity of continuing to take ARV medications without interruption even if they are drinking alcohol.
Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/AIDS disease progression and mortality. In a sample of 181 African American (n=144) and Caucasian (n=37) HIV-positive drug-using individuals [age (M=42.31; SD=6.6) education (M=13.41; SD=2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002–2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use).