RESUMO
BACKGROUND: Older people with human immunodeficiency virus (HIV, PWH) are prone to using multiple medications due to higher rates of medical comorbidities and the use of antiretroviral therapy (ART). We assessed the prevalence and clinical impact of polypharmacy among PWH. METHODS: We leveraged clinical data from the AIDS Clinical Trials Group A5322 study "Long-Term Follow-up of Older HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation" (HAILO). We included PWH aged ≥40 years with plasma HIV RNA levels <200 copies/µL. We assessed the relationship between polypharmacy (defined as the use of 5 or more prescription medications, excluding ART) and hyperpolypharmacy (defined as the use of 10 or more prescription medications, excluding ART) with slow gait speed (less than 1 meter/second) and falls, including recurrent falls. RESULTS: Excluding ART, 24% of study participants had polypharmacy and 4% had hyperpolypharmacy. Polypharmacy was more common in women (30%) than men (23%). Participants with polypharmacy had a higher risk of slow gait speed (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.27-2.50) and increased risk of recurrent falls (OR = 2.12; 95% CI = 1.06-4.23). The risk for recurrent falls was further increased in those with hyperpolypharmacy compared with those without polypharmacy (OR = 3.46; 95% CI = 1.32-9.12). CONCLUSIONS: In this large, mixed-sex cohort of PWH aged ≥40 years, polypharmacy was associated with slow gait speed and recurrent falls, even after accounting for medical comorbidities, alcohol use, substance use, and other factors. These results highlight the need for increased focus on identifying and managing polypharmacy and hyperpolypharmacy in PWH.
Assuntos
Acidentes por Quedas , Infecções por HIV , Polimedicação , Humanos , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Acidentes por Quedas/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Velocidade de Caminhada , Adulto , Comorbidade , Fatores de RiscoRESUMO
BACKGROUND: Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants. METHODS: Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change. RESULTS: A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNAâ <â 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNAâ <â 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P â <â 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain. CONCLUSION: CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Humanos , Masculino , Feminino , Citocromo P-450 CYP2B6/genética , Farmacogenética , Inibidores de Integrase de HIV/uso terapêutico , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Aumento de Peso/genética , RNA/uso terapêutico , Fármacos Anti-HIV/efeitos adversosRESUMO
BACKGROUND: We sought to characterize in people with human immunodeficiency virus (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained. METHODS: Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection nor reported heavy alcohol use were included. Clinical and demographic characteristics, including medication use, the hepatic steatosis index (HSI), and metabolic syndrome (MetS) were compared between participants with and without ALT elevation. RESULTS: Six hundred sixty-two participants were included; 444 (67%) had ≥1 and 229 (35%) ≥2 consecutive ALT elevations during a median of 4.0 years of follow-up. HSI and Hispanic or other (non-White or Black) race/ethnicity were consistently associated with higher odds of abnormal ALT (odds ratio [OR] 1.1 for HSI as a continuous variable, OR 1.9-2.8 for Hispanic/other race/ethnicity for ≥1 or ≥2 ALT elevations); older age and current smoking were associated with lower odds of abnormal ALT. Associations with metabolic disease, as well as with incident HBV and HCV infection, were strengthened by restricting outcomes to persistent and higher degrees of ALT elevation. CONCLUSIONS: ALT elevation was common in this cohort of PWH and associated with metabolic disease and hepatic steatosis markers. Nonalcoholic fatty liver disease is likely a common cause of liver inflammation in PWH receiving suppressive antiretrovirals, deserving targeted diagnosis and intervention.
Assuntos
Infecções por HIV , Hepatite B , Hepatite C , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , HIV , Alanina Transaminase , Hepatite B/complicações , Hepatite C/complicações , Vírus da Hepatite B , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Inflamação/complicaçõesRESUMO
BACKGROUND: Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established. METHODS: AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI. RESULTS: In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46-56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR]â =â 2.06; 95% confidence interval [CI]â =â .94, 4.48; Pâ =â .07). Further adjustment for confounding strengthened this association (ORâ =â 2.79; 95% CIâ =â 1.21, 6.43; Pâ =â .02). Baseline frailty however was not associated with NCI development. CONCLUSIONS: NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population.
Assuntos
Fragilidade , Infecções por HIV , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Fragilidade/epidemiologia , HIV , Infecções por HIV/complicações , Humanos , Pessoa de Meia-Idade , Razão de ChancesRESUMO
BACKGROUND: Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation-this metabolic shift may contribute to NCI and slowed gait speed in PWH. METHODS: Plasma citrate and succinate were assayed by liquid chromatography-mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. RESULTS: Median age was 51 (range 40-78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P = .03), 0.07 SD lower time-updated NPZ-4 score (P = .01), and 0.02 m/s slower time-updated gait speed (P < .0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤ .01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. CONCLUSIONS: Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH.
Assuntos
Infecções por HIV , Ácido Succínico , Adulto , Idoso , Ácido Cítrico , Estudos Transversais , Infecções por HIV/complicações , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Cardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH. METHODS: We constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit. RESULTS: Among 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P = .003; lower by 2.17 [SD, 0.67] in women, P = .001; lower by 0.78 [SD, 0.32] in men, P = .016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women. CONCLUSIONS: Baseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time.
Assuntos
Doenças Cardiovasculares , Infecções por HIV , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Cognição , Feminino , Infecções por HIV/complicações , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Treatment initiation with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain. Whether similar gains are seen after switch to INSTIs among virologically suppressed persons is less clear. We assessed pre/post-INSTI weight changes from AIDS Clinical Trials Group participants (A5001 and A5322). METHODS: Participants who were in follow-up from 1997-2017 and switched to INSTI-based antiretroviral regimens were included. Piecewise linear mixed-effects models adjusting for age, sex, race/ethnicity, baseline BMI, nadir and current CD4+ T-cell count, smoking, diabetes and follow-up time with suppressed HIV-1 RNA examined weight and waist circumference change before and after first switch to INSTIs. Linear spline models with a single knot at time of switch accounted for nonlinear trends. RESULTS: The 972 participants who switched to INSTIs were 81% male and 50% nonwhite with a median age at switch of 50 years, CD4+ T-cell count 512 cells/µL, and BMI 26.4 kg/m2. Restricting to persons with suppressed HIV-1 RNA at switch (nâ =â 691), women, blacks, and persons ≥60 years experienced greater weight gain in the 2 years after versus before switch. In adjusted models, white or black race, ageâ ≥60, and BMIâ ≥30 kg/m2 at switch were associated with greater weight gain following switch among women; ageâ ≥60 was the greatest risk factor among men. Trends for waist circumference were similar. CONCLUSIONS: Yearly weight gain increased following switch to INSTIs, particularly for women, blacks, and persons agedâ ≥60. Concomitant increases in waist circumference suggest that this weight gain is associated with an increase in fat mass.
Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Idoso , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Masculino , Fatores de Risco , Aumento de PesoRESUMO
INTRODUCTION: Taiwan's national health insurance currently only covers the use of osteoporosis drugs for the secondary prevention of fractures and does not provide coverage for primary prevention. The purpose of this study is to develop a model for analyzing the budgetary impact of the use of osteoporosis medications of primary prevention. METHODS: The budget impact model in this study is the "actual medication cost" minus the "medical expenses for all types of fractures that can be avoided by taking osteoporosis medications." We developed six possible insurance payment plans for primary prevention based on the age of the patients and T-scores and performed eleven steps to estimate the budget impact of each payment plan. RESULTS: The results of this study indicated that there may be 71,220 (T-score ≤ - 3.0, 75 + y/o) to 157,515 (T-score ≤ - 2.5, 65 + y/o) people using the drugs, and the budget impact may be US$26.28-58.98 million in 2019. However, the payment plans may avoid 492-766 fracture events and save medical expenditures for fracture treatment by US$1.30-2.02 million. The average costs for primary prevention within a year will be US$53,386-77,006. CONCLUSION: The budget impact of using osteoporosis medications to primary prevention of fractures is significant, but it can be compensated due to savings in fracture treatment costs.
Assuntos
Orçamentos , Fraturas Ósseas/complicações , Fraturas Ósseas/prevenção & controle , Osteoporose/tratamento farmacológico , Osteoporose/economia , Prevenção Primária , Idoso , Feminino , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , TaiwanRESUMO
Background: Cardiovascular comorbidities are risk factors for human immunodeficiency virus (HIV)-associated cognitive impairment. Given differences in cardiometabolic risk profiles between women and men with HIV, we investigated whether associations between cardiometabolic risk factors and prevalent cognitive impairment differ by sex. Methods: Separate logistic regression models were constructed for women and men at entry into a prospective study of older persons with HIV (PWH) to assess the association of cardiometabolic and other risk factors with cognitive impairment. Results: Of 988 participants, 20% were women. Women had higher total cholesterol (194 vs 186 mg/dL; P = .027), hemoglobin A1c (5.9% vs 5.7%; P = .003), and body mass index (30.8 vs 27.4 kg/m2; P < .001) compared with men, and were less physically active (43% vs 55%; P = .005). In a multivariable model, physical activity was associated with lower odds of cognitive impairment in women (odds ratio, 0.35 [95% confidence interval, .15-.80]; P = .013) but not men. Conclusions: Physical activity may have a greater positive impact on cognitive health in women than in men with HIV. This finding should be confirmed in studies examining the longitudinal association between physical activity and incident cognitive impairment in PWH and the effect of interventions that increase physical activity on cognitive impairment in women with HIV.
Assuntos
Disfunção Cognitiva/epidemiologia , Exercício Físico , Infecções por HIV/complicações , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , Comorbidade , Estudos Transversais , Feminino , Hemoglobinas Glicadas , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Estudos Prospectivos , Fatores de Risco , Caracteres Sexuais , Fatores SexuaisRESUMO
BACKGROUND: We characterized associations between frailty and incident cardiovascular disease (CVD), diabetes mellitus (DM), bone disease, and mortality within a cohort of aging persons with human immunodeficiency virus (PWH). METHODS: Participants underwent frailty evaluations using the Fried frailty assessment (baseline and annually). Frailty was defined as having ≥3 frailty criteria. Clinical outcomes of mortality, CVD events, DM, and bone disease events were recorded throughout the study period (baseline to most recent study or clinic visit, or date of clinical outcome, whichever came first). Poisson regression models were used to evaluate associations between baseline frailty, change in frailty score over 48 weeks, and each clinical outcome. RESULTS: Among 821 men and 195 women (median age 51 years), 62 (6%) were frail at baseline. Frailty scores increased by ≥1 component among 194 participants (19%) from baseline to 48 weeks. Baseline frailty was associated with an increased risk of incident CVD and DM, with a trend toward a significant association with bone events. Among frailty components, slow gait speed was associated with incident DM and borderline associated with incident CVD. An increase in frailty from baseline to week 48 was associated with mortality but not with the other clinical outcomes. CONCLUSIONS: Baseline frailty was associated with multiple adverse health outcomes (incident CVD, DM, and bone disease), while increase in frailty score was associated with mortality among PWH engaged in care. Incorporation of frailty assessments into the care of PWH may assist in improvement of functional status and risk stratification for age-related chronic diseases.
Assuntos
Doenças Ósseas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Fragilidade , Infecções por HIV/complicações , Adulto , Fatores Etários , Envelhecimento , Doenças Ósseas/complicações , Doenças Cardiovasculares/complicações , Doença Crônica , Estudos de Coortes , Demografia , Complicações do Diabetes/epidemiologia , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Medição de Risco , Fatores de RiscoRESUMO
The impact of antiretroviral therapy (ART) on frailty among human immunodeficiency virus (HIV)-infected adults has not been well described. HIV-infected participants aged ≥40 years with initial ART receipt through a randomized, controlled AIDS Clinical Trials Group trial completed a frailty assessment. Ordinal logistic regression models examined factors associated with frailty. Of 1016 participants, 6% were frail, and 38% were prefrail. Frailty was associated with lower education, older age, Medicare/Medicaid, initial efavirenz, smoking, obesity, and neurocognitive impairment; physical activity and alcohol use were protective. The associations with ART require further investigation, and associations between frailty and modifiable factors provide targets for future interventions.
Assuntos
Terapia Antirretroviral de Alta Atividade , Idoso Fragilizado/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Estados Unidos , Velocidade de Caminhada , Redução de PesoRESUMO
BACKGROUND: Older human immunodeficiency virus (HIV)-infected adults may experience higher rates of frailty and disability than the general population. Improved understanding of the prevalence, risk factors, and types of impairment can better inform providers and the healthcare system. METHODS: HIV-infected participants within the AIDS Clinical Trials Group A5322 HAILO study self-reported disability by the Lawton-Brody Instrumental Activities of Daily Living (IADL) Questionnaire. Frailty was measured by 4-m walk time, grip strength, self-reported weight loss, exhaustion, and low activity. Logistic regression models identified characteristics associated with any IADL impairment. Agreement between IADL impairment and frailty was assessed using the weighted kappa statistic. RESULTS: Of 1015 participants, the median age was 51 years, 15% were aged ≥60 years, 19% were female, 29% black, and 20% Hispanic. At least 1 IADL impairment was reported in 18% of participants, most commonly with housekeeping (48%) and transportation (36%) and least commonly with medication management (5%). In multivariable models, greater disability was significantly associated with neurocognitive impairment, lower education, Medicare/Medicaid insurance (vs private/other coverage), smoking, and low physical activity. Although a greater proportion of frail participants had IADL impairment (52%) compared to non-frail (11%) persons, agreement was poor (weighted kappa <0.18, 95% confidence interval, 0.13, 0.23). CONCLUSION: IADL disability occurs frequently among middle-aged and older HIV-infected adults on effective antiretroviral therapy. Potentially modifiable risk factors (smoking, physical activity) provide targets for interventions to maintain independent living. Systematic recognition of persons at greater risk for disability can facilitate connection to resources that may help preserve independence.
Assuntos
Infecções por HIV/epidemiologia , Atividades Cotidianas , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Fragilidade , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The purpose of this study was to evaluate associations of pre-ART CD4 with peripheral neuropathy (PN) and estimate the prevalence of PN in HIV-positive patients starting modern combination antiretroviral therapy (cART) regimens. ART-naïve subjects initiating cART were followed longitudinally and screened for signs/symptoms of PN. Lower pre-ART CD4 count was associated with post-ART PN. After 7 years (n = 117), the prevalence (95% CI) of PN and SPN were 31% (23, 40%) and 5% (2, 11%) with pre-ART CD4 count >250 copies/µL. PN continues to be identified in HIV-infected individuals on modern cART by targeted assessment but is generally without symptoms.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/imunologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/imunologia , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m(2) (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.
Assuntos
Nefropatia Associada a AIDS/sangue , Apolipoproteínas/sangue , Lipoproteínas HDL/sangue , Insuficiência Renal Crônica/sangue , Nefropatia Associada a AIDS/genética , Adulto , Negro ou Afro-Americano/genética , Apolipoproteína L1 , Apolipoproteínas/genética , Estudos de Casos e Controles , Citocinas/sangue , Progressão da Doença , Dislipidemias/sangue , Feminino , Genótipo , Taxa de Filtração Glomerular , Humanos , Lipoproteínas HDL/genética , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/genéticaRESUMO
OBJECTIVE: Risk factors for progression from prediabetes (pre-DM) to diabetes (DM) among people with HIV (PWH) receiving modern antiretroviral therapy (ART) require better characterization. DESIGN: AIDS Clinical Trials Group (ACTG) A5322 (HAILO) was an observational cohort study of PWH ≥40âyears old. Participants initiated ART through ACTG randomized clinical trials. METHODS: We used Cox proportional hazards regression models to identify risk factors for development of DM among HAILO participants with pre-DM. RESULTS: Among 1035 HAILO participants, 74 (7%) had pre-DM at entry and another 679 (66%) developed pre-DM during follow-up. Of 753 PWH with pre-DM, 167 (22%) developed DM. In multivariable models, the risk of developing DM was greater with higher BMI, lower CD4 count (≤200âcells/âmm3), hypertriglyceridemia, or higher waist circumference at pre-DM diagnosis (pâ<â0.01). CONCLUSION: Rates of pre-DM and progression to DM remain high among virally suppressed PWH receiving modern ART regimens. Traditional risks for DM, such as higher BMI or waist circumference, are associated with increased risk of incident DM among PWH with pre-DM. The association between lower CD4 and progression to DM suggests a role for advanced immunodeficiency and inflammation. Further investigation of interventions aimed at preventing DM among PWH with pre-DM is needed. Optimizing prevention and treatment for DM may be an intervenable opportunity to improve long-term outcomes for PWH.
RESUMO
Peripheral neuropathy (PN) is a common neurological complication of HIV infection that has debilitating effects on quality of life. While there has been a comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART-naïve patients, similar evaluation in ART-experienced patients is limited. This study investigated the prevalence and RFs for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy studies. Between February 2000 and June 2007, 522 ART-experienced participants who experienced virologic failure with a prior regimen and started new regimens were followed longitudinally and annually screened for signs and symptoms of PN. Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %, respectively. Aging, taller height, protease inhibitor use, and female sex were significant RFs for PN/SPN. The use of statin drugs was significantly associated with lower odds of SPN, and it may prevent progression from no SPN to SPN.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/fisiopatologia , HIV-1 , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Contagem de Linfócito CD4 , Progressão da Doença , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/virologia , Prevalência , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Integrase inhibitors (INSTIs) have been associated with poorer cognition in people with HIV (PWH). We examined the impact of switching to INSTIs on neuropsychological (NP) outcomes in PWH 40 years of age and older. METHODS: From the AIDS Clinical Trials Group observational cohort study, HAILO, we identified PWH who switched to INSTIs, had ≥2 NP assessments before and at least 1 after switch, and maintained viral suppression while on INSTIs. NP performance was assessed with a composite score (NPZ4) including Hopkins Verbal Learning Test (HVLT-R), Digit Symbol test (DSY), Trail Making A, and Trail Making B, while adjusting for covariates and learning effects. Outcomes changes from preswitch and postswitch periods were estimated using piecewise linear mixed models. RESULTS: Among 395 PWH (mean age 54 years, 81% male, 20% Hispanic, and 29% Black) NPZ4 increased preswitch and postswitch. There was no difference in slopes between periods for NPZ4 [preswitch 0.036/year (95% CI: 0.03 to 0.043); postswitch 0.022/year (95% CI: 0.006 to 0.005); P = 0.147]. All tests scores improved preswitch (P < 0.01). Postswitch, Trail Making A and DSY increased (all P < 0.01) without differences in rate of change (all P > 0.05). HVLT-R had a nonsignificant decrease postswitch (P = 0.22), resulting in a significant preswitch vs postswitch difference in slopes (P = 0.03). CONCLUSIONS: NP performance improved regardless of INSTI use. There was an attenuation of improvement in verbal memory in the postswitch vs preswitch period. The clinical significance of these changes is unclear but, overall, INSTIs did not have a consistent detrimental effect on NP outcomes.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Inibidores de Integrase de HIV/farmacologia , Cognição , Fármacos Anti-HIV/uso terapêutico , IntegrasesRESUMO
The purpose of this study is to evaluate risk factors for progression from asymptomatic peripheral neuropathy (APN) to symptomatic peripheral neuropathy (SPN). Antiretroviral therapy (ART)-naïve patients initiating combination ART were followed longitudinally and screened for signs/symptoms of PN. Having APN was associated with higher odds of future SPN (odds ratio (OR) = 1.58, 95 % confidence interval (CI) = (1.08, 2.29), p = 0.027). Neurotoxic ART use was associated with increased odds of progression to SPN (OR = 2.16, 95 % CI = (1.21, 3.85), p = 0.009) while use of glucose-lowering drugs (non-insulin) was protective (OR = 0.12, 95 % CI = (0.02, 0.83), p = 0.031). Use of glucose-lowering drugs (non-insulin) may prevent progression from APN to SPN.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-1 , Hipoglicemiantes/uso terapêutico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Adolescente , Adulto , Doenças Assintomáticas , Glicemia/metabolismo , Criança , Progressão da Doença , Quimioterapia Combinada , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/etiologia , Fatores de RiscoRESUMO
BACKGROUND: While increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial. METHODS: We selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, and A5257 who had achieved viral suppression at year 2. We examined the effect of CD8+ T cell counts and CD4/CD8 at year 2 on the probability of AIDS and serious non-AIDS events in years 3-7. We used inverse probability weighting methods to address informative censoring, combined with multivariable logistic regression models. FINDINGS: We analyzed 5133 participants with a median age of 38 years; 959 (19%) were female, pre-ART median CD4 counts were 249 (Q1-Q3 91-372) cell/µL. Compared to participants with CD8 counts between 500/µL and 1499/µL, those with >1500/µL had a higher risk of clinical events during years 3-7 (aOR 1.75; 95%CI 1.33-2.32). CD4/CD8 ratio was not predictive of greater risk of events through year 7. Additional analyses revealed consistent CD8 count effect sizes for the risk of AIDS events and noninfectious non-AIDS events, but opposite effects for the risk of severe infections, which were more frequent among individuals with CD8 counts <500/µL (aOR 1.70; 95%CI 1.09-2.65). INTERPRETATION: The results of this analysis with pooled data from clinical trials support the value of the CD8 count as a predictor of clinical progression. People with very high CD8 counts during suppressive ART might benefit from closer monitoring and may be a target population for novel interventions. FUNDING: This research was supported by NIH/NIAID awards UM1 AI068634, UM1 AI068636, and UM1 AI106701 and Carlos III Health Institute and FEDER funds (BA21/00017 and BA21/00022).
Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD8-Positivos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Carga ViralRESUMO
Hematopoietic stem cells (HSCs) with age-associated somatic mutations that disproportionally contribute to hematopoiesis generate the condition known as clonal hematopoiesis (CH). While CH conveys increased risk of hematologic cancer, there is also strong association between CH and cardiovascular disease (CVD). Accumulating evidence suggests that inflammation mechanistically links CH to CVD, and we hypothesized that CH may be a predictive biomarker of CVD in conditions of chronic inflammation. One such patient population comprises people living with HIV (PLWH) who also have substantially increased incidences of CVD and CH . We studied the association between CH and CVD in PLWH using samples from ACTG Study A5001 (or ALLRT), a prospective clinical trial of HIV-infected persons with long-term follow-up. We observed a positive association between CH and CVD in PLWH independent of traditional CVD risk factors. Moreover, in CVD cases, the CH clone was identifiable in the blood years before CVD diagnosis, unlike in PLWH with CH who did not have CVD. With the life span of PLWH increasing because of advances in treatment, our results indicate that the presence of CH and its clonal dynamics could be used as a prognostic biomarker of the risk for CVD in PLWH.