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1.
AIDS ; 33(12): 1871-1880, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259766

RESUMO

AIMS: To assess associations of comorbidity patterns observed in people living with HIV (PLWH) with risk factors and health outcomes. METHODS: Common patters of comorbidities in PLWH participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study were determined using principal component analysis and a severity score for each pattern was derived. Associations between each pattern's severity score and risk factors were assessed using median regression. The independent associations of patterns' severity scores with self-reported physical and mental health (SF-36 summary scores) were assessed using linear regression, with functional impairment (Lawton IADL < 8) and hospitalization in last year using logistic regression and with number of general practitioner visits using Poisson regression. RESULTS: A total of 1073 PLWH were analysed: 85.2% male, median (interquartile range) age 52 (47-59) years, 98% on therapy. Duration of HIV was associated with higher severity in 4/6 of patterns: cardiovascular diseases, mental health problems, metabolic disorders and chest/other infections (all P ≤ 0.001). Prior AIDS was associated with higher severity scores for the same patterns and for the pattern of cancers (P < 0.001). The pattern of cardiovascular diseases was associated with poorer physical health (P = 0.02), higher risk of functional impairment (P = 0.02) and hospitalization (P < 0.001) and with higher number of general practitioner visits (P < 0.001). Severity of mental health (all P < 0.001) and of chest/other infections patterns negatively affected all the five health outcomes. CONCLUSION: Common patterns of comorbidities seen in PLWH appear to have different risk factors and to differently affect health outcomes. These findings may assist the development of targeted intervention to prevent, treat and manage the increasingly prevalent multimorbidity in PLWH.

2.
Sex Transm Infect ; 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101723

RESUMO

OBJECTIVE: Technology-based approaches to distribute HIV self-tests (HIVST) have the potential to increase access to HIV testing in key populations. We evaluate the acceptability and feasibility of using vending machines (VMs) in a community setting to distribute HIVST to men who have sex with men at high-risk of HIV. METHODS: First, a predevelopment survey of targeted potential users explored attitudes towards HIVST and the use of a VM to deliver HIVST. Second, participatory design workshops between designers and community volunteers informed the production of a bespoke VMs dispensing free BioSureHIVST. Uptake of HIVST and user experiences were evaluated using information supplied directly from the machines interface (number of tests dispensed, user demographics), an online questionnaire and semistructured interviews. RESULTS: The predevelopment survey found that 32% of 232 sauna users had never tested for HIV, despite high-risk behaviours. A total of 265 testing kits were dispensed: mean age 31 range (18-70); 4%(n = 7) had never tested for HIV before and 11% (n = 22) had tested within the last 1-5 years. Uptake of tests was significantly higher via the VMs compared with outreach testing by community workers in the same venue during a comparable period (34 vs 6 tests per month). Qualitative interviews and online questionnaires demonstrated high acceptability for this intervention, which was considered accessible and appropriately targeted. CONCLUSIONS: VMs to distribute HIVST was feasible and acceptable. This intervention could be used in different settings to improve access to HIV testing for key populations.

3.
PLoS One ; 14(5): e0216787, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31083692

RESUMO

BACKGROUND: Musculoskeletal symptoms in people living with HIV (PLWH) such as pain, joint stiffness, and fatigue are commonly reported. Prevalence rates of up to 45%, 79% and 88% respectively have been reported. However, very little is known about differences in prevalence and impact of musculoskeletal symptoms on physical functioning and quality of life of PLWH on effective combined antiretroviral treatment (cART) in high and low-resource settings. METHODS: A cross-sectional study of PLWH on effective cART enrolled from two large urban clinics in the UK and Zambia was conducted in 2016. Eligible participants had no history of trauma to the joints within 4 weeks of recruitment, or documented evidence of previous rheumatic disease. Current musculoskeletal symptoms, functional ability, and health-related quality of life were evaluated using the health assessment (HAQ) and quality-of-life short form (SF-36) self-reported questionnaires. RESULTS: 214 patients were enrolled (108:UK and 106:Zambia). Participants from Zambia were younger (47 vs 44 years) and had significantly lower CD4 counts (640 vs 439 cells/mL p = 0.018) compared to those from the UK, while the UK group had lived with HIV longer (11 vs 6 years; p<0.001) and reported more comorbidities than the Zambian group (66% vs 26%; p<0.001). Musculoskeletal pain was common in both groups (UK:69% vs Zambia:61% p = 0.263) but no significant differences in physical functional capacity between the groups were observed. However, the UK group had significantly worse quality of life measurements (general health, vitality, mental health, emotional, and social functioning) associated with musculoskeletal symptoms compared to the Zambian group (p<0.001). CONCLUSIONS: Musculoskeletal symptoms in PLWH from both the UK and Zambia were common. PLWH in the UK reported worse quality of life measures associated with musculoskeletal symptoms compared to those in Zambia, suggesting that factors such as mental health, patient expectations and multimorbidity might play a role in determining well-being and quality of life of PLWH with musculoskeletal symptoms.

4.
Int J STD AIDS ; 30(5): 440-446, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999830

RESUMO

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53-63) and 58 (53-63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders.


Assuntos
Cognição/fisiologia , Depressão/diagnóstico , Infecções por HIV/epidemiologia , Sífilis/diagnóstico , Estudos de Casos e Controles , Depressão/epidemiologia , Depressão/psicologia , Feminino , Infecções por HIV/psicologia , Soronegatividade para HIV , Humanos , Masculino , Pessoa de Meia-Idade , Neurossífilis/diagnóstico , Neurossífilis/epidemiologia , Prevalência , Sífilis/epidemiologia , Sorodiagnóstico da Sífilis
5.
AIDS Care ; 31(5): 589-598, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30712360

RESUMO

As life expectancy in people living with HIV (PWH) has increased, the focus of management has shifted to preventing and treating chronic illnesses. Regular physical activity (PA) has been shown to reduce the impact of HIV on both physical and mental health. Our objectives were to assess the PA levels of PWH compared to HIV negative controls; investigate factors associated with PA; and determine the effect of PA levels on quality of life and mental well-being. We recruited 110 PWH and 110 HIV negative controls in this cross-sectional, single-centre study. Physical activity, quality of life and mental well-being were assessed using the rapid assessment of physical activity tool, EQ-5D-5L Questionnaire, and the Warwick-Edinburgh Mental Well-being Score. Binary logistic regression and multiple linear regression were used to identify factors associated with PA levels and mental well-being scores respectively. PWH were less likely to meet the WHO-recommended PA requirements compared to controls (50.0% vs. 64.5%; p = 0.041) and had significantly lower mental wellbeing and quality of life scores. Additionally, in PWH higher PA levels were associated with improved self-rated quality of life scores (p = 0.027). Our results suggest that targeted exercise programmes could have a beneficial effect on health status in PWH.

6.
J Neurol ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30446965

RESUMO

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive fatal neurodegenerative disorder. We report an unusual case of pathologically confirmed sporadic CJD developing in a HIV-positive patient but presenting with clinical and radiological features suggestive of variant CJD. CASE PRESENTATION: A 63-year-old man with chronic stable HIV developed progressive difficulties with decision-making, obsessive compulsive disorder and visual hallucinations over 3 months. CSF examination detected a weakly positive 14-3-3 protein, elevated S-100 protein, and siginificantly elevated total-Tau protein. Brain MRI revealed bilateral abnormal signal within the posterolateral thalami compatible with pulvinar sign. Further investigations revealed a negative tonsillar biospy and positive blood test consistent with variant CJD. However, prion protein genotyping detected MV heterozygosity at codon 129 and post-mortem histopathological examination was consistent with sporadic CJD. CONCLUSION: Although MRI findings were suggestive of variant CJD, the short residence in the UK and MV heterozygosity are aytpical, and the histopathological examination was consistent with sporadic CJD. With only two cases of HIV and sporadic CJD reported so far, the association of CJD with HIV remains unclear.

7.
AIDS ; 32(18): 2697-2706, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30289809

RESUMO

OBJECTIVE: We describe the prevalence of pain and its associations with healthcare resource utilization and quality-of-life. DESIGN: The POPPY Study recruited three cohorts: older people living with HIV (PLWH; ≥50 years, n = 699), younger demographically/lifestyle similar PLWH (less than 50 years, n = 374) and older demographically/lifestyle similar HIV-negative (≥50 years, n = 304) people from April 2013 to February 2016. METHODS: Current pain and pain-related healthcare use was collected via a self-reported questionnaire. Logistic regression assessed between-group differences in the prevalence of pain in the past month and current pain after controlling for potential confounders. Associations between current pain and healthcare resource use, reported joint problems, depressive symptoms, quality-of-life and functional status were assessed in PLWH using Mann-Whitney U and chi-squared tests. RESULTS: Pain in the past month was reported by 473 out of 676 (70.0%) older PLWH, 224 out of 357 (62.7%) younger PLWH and 188 out of 295 (63.7%) older HIV-negative controls (P = 0.03), with current pain reported in 330 (48.8%), 134 (37.5%) and 116 (39.3%), respectively (P = 0.0007). Older PLWH were more likely to experience current pain, even after adjustment for confounders. Of those with pain in the past month, 56 out of 412 (13.6%) had missed days of work or study due to pain, and 520 (59%) had seen a doctor about their pain. PLWH experiencing current pain had more depressive symptoms, poorer quality-of-life on all domains and greater functional impairment, regardless of age group. CONCLUSION: Even in the effective antiretroviral therapy era, pain remains common in PLWH and has a major impact on quality-of-life and associated healthcare and societal costs. Interventions are required to assist clinicians and PLWH to proactively manage pain.

8.
Clin Infect Dis ; 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29912307

RESUMO

Background: Both immediate or deferred switching from a PI/r to DTG may improve lipid profile. Methods: NEAT022 is a European, open label, randomized, trial. HIV-infected adults ≥ 50 years or with a Framingham score ≥10% were eligible if HIV RNA < 50 copies/mL. Patients were randomized to switch the PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D) . Week 96 end-points were: proportion of patients with HIV RNA < 50 copies/ml, percentage change of lipid fractions and adverse events. Results: 415 patients were randomized: 205 to DTG-I and 210 to continue PI/r plus a deferred switch (DTG-D) at week 48 . The primary objective of non-inferiority at week 48 was met. At week 96, treatment success rate was 92.2 % in DTG-I arm and 87% in DTG-D arm (difference 5.2%, 95% CI -0.6 to 11). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AE´s or treatment modifying AE´s. Total cholesterol and other lipid fractions (except HDL) significantly (p<0.001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions: Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV patients ≥ 50 years old or with a Framingham score ≥10% was highly efficacious, well tolerated and improved lipid profile.

9.
Clin Infect Dis ; 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29771285

RESUMO

Background: Demographic data show an increasingly aging HIV population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older HIV patients. We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50mg once daily in people living with HIV (PLWH) aged 60 and older. Additionally, to address the call for prospective neuropsychiatric toxicodynamic data, we evaluate changes in sleep quality and cognitive function after switching to abacavir (ABC)/lamivudine (3TC)/DTG, over 6 months in this population. Methods: PLWH aged≥60years with HIV-RNA<50copies/mL on any non-DTG based antiretroviral combination were switched to ABC/3TC/DTG. On day 28, 24-hour PK sampling was undertaken. Steady-state PK parameters were compared to a published historical control population aged≤50years. Six validated sleep questionnaires and neurocognitive (Cogstate®) testing were administered pre-switch and over 180 days (NCT02509195). Results: Forty-three participants were enrolled; 40 completed the PK phase. Overall, five discontinued (two due adverse events, both sleep related, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients≥60 versus controls (GM 4246ng/mL versus 3402ng/mL, p=0.005). In those who completed day 180 (n=38), sleep impairment was higher at day 28 (PSQI median global score 5.0 versus 6.0 p=0.02) but not at day 90 or 180. Insomnia, daytime function, fatigue test scores did not change statistically over time. Conclusion: DTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH.

11.
Pract Neurol ; 18(3): 211-218, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29478035

RESUMO

Syphilis is a resurgent sexually transmitted infection in the UK that is disproportionately diagnosed in patients living with HIV, particularly in men who have sex with men. Syphilis appears to present differently in patients with HIV, particularly in those with severe immunosuppression. Progression to neurosyphilis is more common in HIV coinfection and can be asymptomatic, often for several years. The presentations of neurosyphilis vary but can include meningitis, meningovascular disease, general paresis and tabes dorsalis. There is debate about the circumstances in which to perform a lumbar puncture, and the current gold standard diagnostics have inadequate sensitivity. We recommend a pragmatic approach to lumbar punctures, interpreting investigations and deciding when to consider treatment with a neuropenetrative antibiotic regimen.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Neurossífilis/complicações , Adulto , Diagnóstico Diferencial , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Neurossífilis/diagnóstico , Neurossífilis/terapia
13.
J Acquir Immune Defic Syndr ; 77(2): 199-205, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040166

RESUMO

BACKGROUND: To compare retinal vascular measurements, biomarkers of cerebral small vessel disease, in HIV-positive men aged 50 years and older with similarly aged HIV-negative men and younger HIV-positive men. METHODS: We recruited white, nondiabetic men into a cross-sectional substudy of a larger cohort including 3 demographically matched groups. Optic disc-centered 45-degree color fundus photographs were used to calculate central retinal arterial and venous caliber and the arterial-venous ratio (AVR). We used univariate and multivariable linear regression to compare retinal vessel measurements in the 3 groups and to identify factors associated with AVR. RESULTS: All HIV-positive men were virologically suppressed. In a multivariable model, study group was not associated with AVR [adjusted ß 0.010 for HIV-positive men <50 (n = 39) compared with HIV-positive men aged ≥50 years (n = 120), 95% confidence interval [CI] -0.018 to 0.038, P = 0.47; adjusted ß 0.00002 for HIV-negative men ≥50 years (n = 52), 95% CI -0.022 to 0.022, P = 0.99]. Factors associated with lower AVR were systolic blood pressure (adjusted ß -0.009 per +10 mm Hg, 95% CI -0.015 to -0.003, P = 0.002), history of stroke or transient ischemic attack (adjusted ß -0.070, 95% CI -0.12 to -0.015, P = 0.01), and recent recreational drug use (adjusted ß -0.037, 95% CI -0.057 to -0.018, P = 0.0002). CONCLUSIONS: There were no differences in retinal vascular indices between HIV-positive men aged ≥50 years and HIV-negative men aged ≥50 years or HIV-positive men aged <50 years, suggesting that HIV is not associated with an increased burden of cerebral small vessel disease.

14.
Eur J Nucl Med Mol Imaging ; 44(5): 895-902, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28058461

RESUMO

Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV.


Assuntos
Complexo AIDS Demência/diagnóstico por imagem , Complexo AIDS Demência/tratamento farmacológico , Antirretrovirais/uso terapêutico , Encéfalo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Complexo AIDS Demência/metabolismo , Antirretrovirais/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Combinação de Medicamentos , Humanos , Neurotransmissores/metabolismo
15.
J Acquir Immune Defic Syndr ; 74(2): e45-e53, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27552076

RESUMO

BACKGROUND: The use of combination antiretroviral therapy (cART) has substantially improved the outlook for patients with HIV infection. However, lifelong exposure to cART is also associated with adverse metabolic changes and an enhanced risk of renal, hepatic, and cardiovascular dysfunction. This study investigated disruptions of the urinary metabolome of cART-exposed patients, thereby furthering our understanding of some of the side effects of pharmaceutical intervention. METHODS: HIV-positive patients were recruited from an HIV clinic and divided into cART-naive and cART-exposed groups. HIV-negative patients were recruited from a sexual health clinic. All 89 subjects were white males. Targeted biochemistry analyses were performed on plasma samples. Urine samples were collected after an overnight fast and analyzed with a highly sensitive untargeted metabolomic method using nanoflow/nanospray liquid chromatography-time-of-flight mass spectrometry. Data sets were analyzed using projection modeling to detect metabolite markers of cART exposure. RESULTS: Metabolites or parent compounds of all cART drugs were detected in urine extracts of all but one of the cART-exposed patients confirming adherence to the pharmaceutical regimen. Analysis of urine samples from patients on cART revealed significant reductions in selected bile acids, lipid, nucleoside, and androgen metabolites. However, plasma concentrations of free or conjugated testosterone remained unchanged indicating possible disruption of androgen transport or excretion in urine of patients on cART. CONCLUSIONS: Discovery-based metabolomics reveals the potential to identify novel markers of cART intervention and metabolite disruption in HIV-positive patients, which may enable investigation of the efficacy, compliance, and side effects of these pharmaceutical mixtures to be investigated.


Assuntos
Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Espectrometria de Massas , Metabolômica , Urinálise , Urina/química , Adulto , Idoso , Grupo com Ancestrais do Continente Europeu , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Plasma/química , Adulto Jovem
16.
BMC Infect Dis ; 16(1): 617, 2016 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-27793128

RESUMO

BACKGROUND: The reported prevalence of cognitive impairment (CI) varies widely in cohorts of people living with HIV (PLWH); this may partly be due to the use of different diagnostic criteria. Agreement between diagnostic criteria of CI, the optimal definition to use, and associations with patient-reported cognitive symptoms have not been fully investigated. METHODS: Two hundred ninety PLWH aged >50 years and 97 matched negative controls completed a detailed assessment of cognitive function and three questions regarding cognitive symptoms. Age- and education-adjusted test scores (T-scores) determined if subjects met the following definitions of CI: Frascati, global deficit score (GDS) and the multivariate normative comparison (MNC) method. RESULTS: PLWH were more likely than controls to meet each definition of CI (ORs were 2.17, 3.12 and 3.64 for Frascati, GDS and MNC, respectively). Agreement of MNC with Frascati and GDS was moderate (Cohen's k = 0.42 and 0.48, respectively), whereas that between Frascati and GDS was good (k = 0.74). A significant association was found between all the three criteria and reporting of memory loss but not with attention and reasoning problems. The 41 (14 %) PLWH meeting all the three criteria had the lowest median global T-score (36.9) and highest rate of symptom reporting (42 %). CONCLUSIONS: Different CI criteria show fair diagnostic agreement, likely reflecting their ability to exclude CI in the same group of individuals. Given the lower overall cognitive performance and higher rates of symptom reporting in those meeting all three criteria of CI, further work assessing this as a definition of CI in PLWH is justified.


Assuntos
Disfunção Cognitiva/etiologia , Infecções por HIV/complicações , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Feminino , Infecções por HIV/psicologia , Soropositividade para HIV , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Papaver , Autorrelato
18.
Neurology ; 86(15): 1425-1432, 2016 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-26911637

RESUMO

OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.


Assuntos
Antirretrovirais/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/imunologia , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/imunologia , Receptores de GABA/metabolismo , Acetamidas , Adulto , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Relação CD4-CD8 , Radioisótopos de Carbono , Quimiocinas/líquido cefalorraquidiano , DNA Bacteriano/sangue , DNA Ribossômico/sangue , Imagem de Tensor de Difusão , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos , Masculino , Testes Neuropsicológicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Piridinas , RNA Viral/líquido cefalorraquidiano , Compostos Radiofarmacêuticos , Receptores de GABA/genética , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos dos fármacos , Substância Branca/imunologia
19.
J Acquir Immune Defic Syndr ; 71(5): 514-21, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26579986

RESUMO

OBJECTIVE: Premature atherosclerosis has been observed among HIV-infected individuals with high cardiovascular risk using one-dimensional ultrasound carotid intima-media thickness. We evaluated the assessment of HIV-infected individuals with low traditional cardiovascular disease risk using cardiovascular magnetic resonance, which allows three-dimensional assessment of the carotid artery wall. METHODS: Carotid cardiovascular magnetic resonance was performed in 33 HIV-infected individuals (cases) (19 male, 14 female), and 35 HIV-negative controls (20 male, 15 female). Exclusion criteria included smoking, hypertension, hyperlipidemia (total cholesterol/HDL ratio > 5) or family history of premature atherosclerosis. Cases were stable on combination antiretroviral therapy with plasma HIV-1 RNA <50 copies per milliliter. Using computer modeling, the arterial wall, lumen, and total vessel volumes were calculated for a 4-cm length of each carotid artery centered on the bifurcation. The wall/outer-wall ratio (W/OW), an index of vascular thickening, was compared between the groups. RESULTS: Cases had a median CD4 cell count of 690 cells per microliter. Mean (±SD) age and 10-year Framingham coronary risk scores were similar for cases and controls (45.2 ± 9.7 years versus 46.9 ± 11.6 years and 3.97% ± 3.9% versus 3.72% ± 3.5%, respectively). W/OW was significantly increased in cases compared with controls (36.7% versus 32.5%, P < 0.0001); this was more marked in HIV-infected females. HIV status was significantly associated with increased W/OW after adjusting for age (P < 0.0001). No significant association between antiretroviral type and W/OW was found-W/OW lowered comparing abacavir to zidovudine (P = 0.038), but statistical model fits poorly. CONCLUSIONS: In a cohort of treated HIV-infected individuals with low measurable cardiovascular risk, we have observed evidence of premature subclinical atherosclerosis.


Assuntos
Aterosclerose/diagnóstico , Artérias Carótidas/patologia , Infecções por HIV/complicações , Imagem por Ressonância Magnética , Adulto , Idoso , Antirretrovirais/uso terapêutico , Aterosclerose/etiologia , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
20.
HIV Clin Trials ; 16(1): 39-42, 2015 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25777188

RESUMO

BACKGROUND: Antiretroviral safety and efficacy and may differ in older versus younger HIV-infected patients. The objective of this study was to assess the pharmacokinetic (PK) profile in older HIV-infected subjects (>60 years) switching combination antiretroviral therapy (cART) to a raltegravir (RAL) containing regimen. METHODS: Nineteen HIV-infected patients over 60 years of age on effective cART (HIV-RNA < 50 copies/ml) were enrolled in this prospective 24-week study. On day 1, patients switched to tenofovir/emtricitabine (245/200 mg once daily) and RAL (400 mg twice daily). On day 28, intensive PK sampling was undertaken in a fasted state and RAL plasma concentrations determined. Neurocognitive function was assessed at baseline and week 24 using a neuropsychological battery. RAL PK parameters were compared to those of two younger historical HIV-infected control groups that received twice-daily RAL co-administered with darunavir/ritonavir (DRV/r) 800/100 once daily by nonlinear mixed effects modelling. RESULTS: In HIV-infected subjects over the age of 60 (mean ± SD age: 66 ± 3.4 years, n = 19) switching to a RAL containing regimen, we observed no safety concerns, no plasma virological rebounds, and no differences in RAL apparent oral clearance when compared to younger HIV-infected populations (mean ± SD age: 41 ± 9.2 years, n = 38) based on population pharmacokinetic analysis. After 24 weeks of study therapy a decline in cognitive function was observed [change in (SD) global score of (0.91 (1.3), P = 0.018]. CONCLUSIONS: No significant changes in RAL exposure associated with age were observed.


Assuntos
Fármacos Anti-HIV/farmacocinética , Emtricitabina/farmacocinética , Infecções por HIV/tratamento farmacológico , Raltegravir Potássico/farmacocinética , Tenofovir/farmacocinética , Adulto , Fármacos Anti-HIV/farmacologia , Área Sob a Curva , Contagem de Linfócito CD4 , Quimioterapia Combinada , Emtricitabina/farmacologia , Feminino , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estudos Prospectivos , Raltegravir Potássico/farmacologia , Tenofovir/farmacologia , Reino Unido , Carga Viral/efeitos dos fármacos
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