Effect of Immediate Initiation of Antiretroviral Treatment in HIV-Positive Individuals Aged 50 Years or Older.
Ontology highlight
ABSTRACT: Background
Clinical guidelines recommend immediate initiation of combined antiretroviral therapy for all HIV-positive individuals. However, those guidelines are based on trials of relatively young participants.Methods
We included HIV-positive antiretroviral therapy-naive, AIDS-free individuals aged 50-70 years after 2004 in the HIV-CAUSAL Collaboration. We used the parametric g-formula to estimate the 5-year risk of all-cause and non-AIDS mortality under (1) immediate initiation at baseline and initiation at CD4 count, (2) <500 cells/mm, and (3) <350 cells/mm. Results were presented separately for the general HIV population and for a US Veterans cohort with high mortality.Results
The study included 9596 individuals (28% US Veterans) with median (interquantile range) age of 55 (52-60) years and CD4 count of 336 (182-513) at baseline. The 5-year risk of all-cause mortality was 0.40% (95% confidence interval (CI): 0.10 to 0.71) lower for the general HIV population and 1.61% (95% CI: 0.79 to 2.67) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm. The 5-year risk of non-AIDS mortality was 0.17% (95% CI: -0.07 to 0.43) lower for the general HIV population and 1% (95% CI: 0.31 to 2.00) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm.Conclusions
Immediate initiation seems to reduce all-cause and non-AIDS mortality in patients aged 50-70 years.
SUBMITTER: Lodi S
PROVIDER: S-EPMC5704899 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundRecommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL.MethodsWe used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.FindingsMedian CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).InterpretationThe benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.FundingNational Institutes of Health.
| S-EPMC4643831 | biostudies-literature
Project description:This study aims to characterize associations between depression symptom severity and HIV infection, both prior to and in years after ART initiation, among older adults. The Ugandan Non-Communicable Diseases & Aging Cohort Study (UGANDAC) is a study of 154 PLWH on ART and 142 community-based, HIV-negative controls. The Hopkins Checklist (HSCL), a 15-item depression scale, was used to screen for depression. We estimate differences in depressive symptoms by HIV and ART status and use multivariable log binomial regression to quantify differences in probable depression between PLWH on ART. HIV-infected and HIV-uninfected participants had a similar age (mean 52.0 vs. 51.9, p?=?0.854) and sex distribution (47.4 vs. 47.9% female, p?=?0.934). PLWH on ART had lower depression symptom severity than HIV-uninfected controls (mean score: 1.50 vs. 1.60, p?=?0.006) and a lower prevalence of probable depression (21.4 vs. 33.8%, p?=?0.017). Among 102 PLWH with pre-ART depression screening scores available, their mean depression symptom severity was similar to HIV-uninfected participants (mean 1.56 vs. 1.60, p?=?0.512). In adjusted models, PLWH on ART had a lower prevalence of probable depression than HIV-negative controls [adjusted prevalence ratio: 0.68 (95% CI 0.47-0.99)]. In an observational cohort of PLWH over 40 on long-term ART and matched, community-based HIV-uninfected controls in rural Uganda, we found a lower prevalence of self-reported depression among aging PLWH on ART.
| S-EPMC6719297 | biostudies-literature
Project description:BackgroundFor people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated.MethodsWe included individuals from the HIV-CAUSAL Collaboration who enrolled <6 months of HIV diagnosis between 2006 and 2015, were ART-naive, and had measured CD4 count and HIV-RNA. Follow-up started at the date when all inclusion criteria were first met (baseline). We compared 2 strategies: (1) TDR testing within 3 months of baseline versus (2) no TDR testing. We used inverse probability weighting to estimate the 5-year proportion and hazard ratios (HRs) of virological suppression (confirmed HIV-RNA <50 copies/mL), and of AIDS or death under both strategies.ResultsOf 25,672 eligible individuals (82% males, 52% diagnosed in 2010 or later), 17,189 (67%) were tested for TDR within 3 months of baseline. Of these, 6% had intermediate- or high-level TDR to any antiretroviral drug. The estimated 5-year proportion virologically suppressed was 77% under TDR testing and 74% under no TDR testing; HR 1.06 (95% confidence interval: 1.03 to 1.19). The estimated 5-year risk of AIDS or death was 6% under both strategies; HR 1.03 (95% confidence interval: 0.95 to 1.12).ConclusionsTDR prevalence was low. Although TDR testing improved virological response, we found no evidence that it reduced the incidence of AIDS or death in first 5 years after diagnosis.
| S-EPMC7830777 | biostudies-literature
Project description:BackgroundThe incidence of testicular cancer in the United States (US) has substantially increased in recent decades. The majority of testicular cancers are germ cell tumors (TGCT), which are the most commonly occurring malignancies among men aged 15-44 years in the US. To date, few studies have focused on testicular cancer among men aged ≥ 50 years. Thus, we sought to examine detailed descriptive features, including incidence rates and age patterns, of tumors that arise in the testes among men aged ≥ 50 years.MethodsData from forty-one US cancer registries were included for the years 1999-2014. Incidence rates per 100,000 person-years and their 95% confidence intervals (CI) were calculated by race/ethnicity, histology, and age at diagnosis. Estimates of annual percent change (APC) were also calculated.ResultsAge-specific incidence rates of spermatocytic tumors, sex cord stromal tumors and lymphomas rose with age, while age-specific incidence rates of seminomas and nonseminomas declined. Between 1999 and 2014, the incidence of nonseminoma (APC = 3.26, 95% CI: 2.27-4.25) increased more than any other tumor type. The incidence of seminoma (APC: 1.15, 95% CI: 0.59-1.71) also increased, while rates of testicular lymphoma (APC: -0.66, 95% CI: -1.16 to -0.16), spermatocytic tumors (APC: 0.42, 95% CI: -1.42 to 2.29), and sex cord stromal tumors (APC: 0.60, 95% CI: -3.21 to 4.55) remained relatively unchanged.ConclusionGiven the distinct time-trends and age-specific patterns of testicular cancer in men aged ≥50 years, additional investigation of risk factors for these tumors is warranted.
| S-EPMC6668029 | biostudies-literature
Project description:BACKGROUND:Little is known about the clinical presentation and outcomes amongst older HIV infected populations accessing ART in sub-Saharan Africa. We compared mortality amongst HIV infected patients accessing ART that were?<? 50 years to those ?50 years in Kwa-Zulu Natal, South Africa. METHODS:We undertook a retrospective review of medical records of patients that accessed HIV services at the CAPRISA AIDS Treatment program (CAT) between June 2004 to December 2012 (N?=?4003). HIV infected patients, 14 years or older were enrolled. All-cause mortality and treatment response to ART in those <?50 years to those ?50 years were compared. A Kaplan-Meier curve and log-rank test were used to compare the cumulative probability of death between the two age groups with the primary endpoint being mortality. Statistical analysis was done using SAS (version 9.4.; SAS Institute Inc., Cary, NC, USA). RESULTS:Of 4003 individuals, 262 (6.5%) were???50 years (older group). The median age in those ?50 years and?<? 50 year was 54.5 and 32.0 years, respectively. The younger group was mainly female (64.7%). There was no difference in mortality rate, between the older (6.9/100 person-years (py), 95% confidence interval (CI): 4.7-9.6) and younger group (5.3/100 py, 95% CI: 4.7-5.8) at 60 months (p?=?0.137). In the multivariable model older patients had a significantly higher risk of death compared to younger patients. (hazard ratio (HR) 1.60, 95% CI: 1.08-2.39, p?=?0.019).The rate of CD4+ cell count increase was higher in those <?50 years (??=?0.34, 95% CI: 0.19-0.50, p?<?0.001) with no difference in viral suppression. The older group showed significantly higher prevalence of diabetes (6.3%) and hypertension (21.5%), p?<?0.001. CONCLUSION:ART initiation in older HIV infected patients was associated with a higher mortality compared to those younger than 50 years. ART immunological response was less robust in older individuals. The increase in hypertension and diabetes among older patients suggests the need to restructure and integrate primary and specialized health care services into ART services.
| S-EPMC5894176 | biostudies-literature
Project description:BackgroundPeople with HIV (PWH) are aging. Frailty is an age-related condition predictive of hospitalization and mortality. Here, we assessed the frequency and factors associated with frailty transitions at 1-year follow-up in elderly PWH.MethodsFive hundred eight PWH aged 70 years or older who were on antiretroviral treatment were included in the French multicenter SEPTAVIH study in 2019-2020. Participants were classified as robust, prefrail, or frail according to Fried frailty phenotype at baseline and at 1 year. Logistic regression models were used to evaluate socioeconomic and medical factors associated with transition between frailty states. Models were adjusted for gender, age at baseline, education, and period of HIV diagnosis (before vs after 1996).ResultsSeventeen PWH died during the 1-year follow-up. Of the remaining 491 PWH (median age, 73 years), frailty status worsened for 18% of participants and improved for 14% at 1 year. Advanced age, baseline CD4+ T-cell count <350 cells/mm3, and type 2 diabetes were associated with transition from prefrailty to frailty (adjusted odds ratio [aOR], 1.10 per 1-year positive difference; 95% CI, 1.01-1.20; aOR, 3.05; 95% CI, 1.14-8.18; and aOR, 2.63; 95% CI, 1.05-6.57; respectively). Being female was associated with more frequent improvement from prefrailty to robustness (aOR, 2.50; 95% CI, 1.09-5.55).ConclusionsPreventing frailty in elderly PWH is a long-term problem, beginning with the early diagnosis of HIV infection and the management of comorbidities.
| S-EPMC11222971 | biostudies-literature
Project description:ObjectiveTo present the most recent 2013 UNAIDS estimates of HIV prevalence among people aged 50 years and older, and to validate these estimates using data from national household surveys.DesignModelled estimates of HIV prevalence were validated against nationally representative household survey measures of HIV prevalence.MethodsThe UNAIDS 2013 HIV estimates were used to compute HIV prevalence and number of people living with HIV aged 50 years and older. Sex-specific HIV-prevalence rates by the 5-year age group were calculated from nationally representative household surveys conducted between 2003 and 2013, and were compared to prevalence rates from the modelled estimates. The ratios (Spectrum/Survey) of the prevalence rates from the two sources were analysed.ResultsIn 2013, an estimated 4.2 million (4.0-4.5 million) people aged 50 years and older were living with HIV. The global HIV prevalence among older individuals more than doubled in almost all the 5-year age groups since 1995. There was a relatively good agreement between the modelled HIV-prevalence rates and the survey-based rates among men and women aged 50-54 years (0.90 and 1.00 median ratio, respectively), whereas for 55-59 year-olds, the differences were more notable (ratios of 0.63 for men and 0.90 for women).ConclusionBoth data sources suggest HIV-prevalence rates among people aged over 50 have increased steadily in the recent years. Care and treatment services need to address the specific needs of older people living with HIV. Action is needed to incorporate older age groups into HIV surveillance systems.
| S-EPMC4247270 | biostudies-literature
Project description:HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048.
| S-EPMC5524070 | biostudies-literature
Project description:BackgroundNumerous population-based studies have suggested that socio-economic status (SES) is associated with cognitive performance, but few nationally representative epidemiological studies on cognitive performance with a large sample of older adults are available in China. And many studies explore the factors associated with cognitive performance, mainly focusing on individual level and more rarely on multiple levels that include the individual and community.MethodsThis study uses SAGE-China Wave 1 data which consisted of 13,157 adults aged 50 years and older to explore socioeconomic inequalities in the cognitive performance from a multilevel perspective (individual and community levels). The overall cognition score was based on the seven separate components of the cognition tests, including the four verbal recall trials, the verbal fluency test, the forward digit span test and the backward digit span test. Factor analysis was applied to evaluate and generate a single overall score. A two-level hierarchical linear model was used to evaluate the association between SES at these two levels and the overall cognition score adjusted for age, sex and marital status.ResultsAt individual level, years of education was significantly associated with overall cognition score for both urban and rural dwellers. At the community level, a positive association was obtained between median household income and median years of education and overall cognition score among urban participants.ConclusionA significant association between SES at both individual-level and community-level (only for urban area) and cognitive performance were found in this study of a national sample of 13,157 Chinese aged 50 years and older, even after adjusting for demographic characteristics. Identifying community-based SES variables that are associated with cognitive performance in the older population provides further evidence for the need to address community characteristics associated with deprivation.
| S-EPMC5115845 | biostudies-literature
Project description:BackgroundAge is a major risk factor for herpes zoster (HZ) and its potential long-term complication post-herpetic neuralgia (PHN). Due to the significant burden of HZ and PHN on patients' quality of life, it is vital that effective and well-tolerated vaccines are available to prevent HZ in older adults. ZOSTAVAX(®) vaccine was developed to prevent HZ and PHN in individuals ≥50 years (y) of age, and its clinical efficacy and safety have been demonstrated.Aims and methodsThis phase 4, open-label, multicenter study was undertaken to assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator-stable formulation) given within 6 mo of its expiry date in individuals ≥50 y of age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post-vaccination in varicella zoster virus (VZV) antibody titers was calculated. An acceptable antibody response was defined as a lower 95% confidence interval (CI) of GMFR > 1.4. Solicited and unsolicited injection-site reactions and systemic adverse events were recorded.ResultsThe GMFR in VZV antibody titers was 3.1 (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV antibody titers was observed in individuals of 50-59 y of age (GMFR 3.9; 95% CI: 2.9, 5.1) and in those ≥60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was well tolerated; no serious adverse events were reported.ConclusionZOSTAVAX elicits an acceptable immune response in immunocompetent individuals ≥50 y of age when stored as directed and administered during the 6 mo prior to expiration.
| S-EPMC3256327 | biostudies-literature