Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not ...been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.
Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.
The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 standard error (SE) 0.5 to 51.4 SE 0.5 years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm(3).
A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation.
DESIGN:A prospective cohort study.
...METHODS:Biomarkers were measured with multiplex assays in centralized laboratories using stored serum samples contributed by 1697 men during 8903 person-visits in the Multicenter AIDS Cohort Study (MACS) from 1984 to 2009. Using generalized gamma models, we compared biomarker values across three groups, adjusting for possible confoundersHIV-uninfected (NEG); HIV-positive, HAART-naive (NAI); and HAART-exposed with HIV RNA suppressed to less than 50 copies/ml plasma (SUP). We also estimated changes in biomarker levels associated with duration of HIV suppression, using splined generalized gamma regression with a knot at 1 year.
RESULTS:Most biomarkers were relatively normalized in the SUP group relative to the NAI group; however, 12 biomarkers in the SUP group were distinct (P < 0.002) from NEG valuesCXCL10, C-reactive protein (CRP), sCD14, sTNFR2, tumour necrosis factor-alpha (TNF-α), sCD27, sGP130, interleukin (IL)-8, CCL13, BAFF, GM-CSF and IL-12p70. Thirteen biomarkers exhibited significant changes in the first year after viral suppression, but none changed significantly after that time.
CONCLUSION:Biomarkers of inflammation and immune activation moved towards HIV-negative levels within the first year after HAART-induced HIV suppression. Although several markers of T-cell activation returned to levels present in HIV-negative men, residual immune activation, particularly monocyte/macrophage activation, was present. This residual immune activation may represent a therapeutic target to improve the prognosis of HIV-infected individuals receiving HAART.
To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to ...detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parametric and semiparametric competing risks methods were used to estimate proportions, timing, and predictors of acquired immune deficiency syndrome (AIDS)-related and non-AIDS-related mortality ...among individuals both positive and negative for the human immunodeficiency syndrome (HIV) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) from 1984 to 2008 and 1996 to 2008, respectively. Among HIV-positive MACS participants, the proportion of deaths unrelated to AIDS increased from 6% before the introduction of highly active antiretroviral therapy (HAART) (before 1996) to 53% in the HAART era (P < 0.01); the median age of persons who died from non-AIDS-related causes after age 35 years increased from 49.0 to 66.0 years (P < 0.01). In both cohorts during the HAART era, median ages at time of non-AIDS-related death were younger for HIV-positive individuals than for comparable HIV-negative individuals (8.7 years younger in MACS (P < 0.01) and 7.6 years younger in WIHS (P < 0.01)). In a multivariate proportional cause-specific hazards model, unemployment (for non-AIDS death, hazard ratio (HR) = 1.8; for AIDS death, HR = 2.3), depression (for non-AIDS death, HR = 1.4; for AIDS death, HR = 1.4), and hepatitis B or C infection (for non-AIDS death, HR = 1.8, for AIDS death; HR = 1.4) were significantly (P < 0.05) associated with higher hazards of both non-AIDS and AIDS mortality among HIV-positive individuals in the HAART era, independent of study cohort. The results illuminate the changing face of mortality among the growing population infected with HIV.
The COVID-19 pandemic-and its associated restrictions-have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those ...resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes. Within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether there were pandemic-related changes in behavior that may be associated with environmental exposures. A total of 1535 participants from nine cohorts completed a survey via RedCap from December 2020 through May 2021. The questionnaire identified behavioral changes associated with the COVID-19 pandemic in expected directions, providing evidence of construct validity. Behavior changes reported by at least a quarter of the respondents include eating less fast food and using fewer ultra-processed foods, hair products, and cosmetics. At least a quarter of respondents reported eating more home cooked meals and using more antibacterial soaps, liquid soaps, hand sanitizers, antibacterial and bleach cleaners. Most frequent predictors of behavior change included Hispanic ethnicity and older age (35 years and older). Respondents experiencing greater COVID-related stress altered their behaviors more than those not reporting stress. These findings highlight that behavior change associated with the pandemic, and pandemic-related psychological stress often co-occur. Thus, prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic. Analyzing biomarker data in these participants will be helpful to determine if behavior changes reported associate with measured changes in exposure.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Human immunodeficiency virus (HIV)–induced inflammation and immune activation persist after initiation of combination antiretroviral therapy (cART) and HIV suppression and may contribute ...to mortality risks that exceed those in HIV-uninfected populations, though associations are unclear. Methods. In the prospective Multicenter AIDS Cohort Study, comprising men who have sex with men from Baltimore, Chicago, Los Angeles, and Pittsburgh, concentrations of 24 biomarkers of inflammation and immune activation were measured in stored serum from HIV-positive men obtained after cART-induced HIV suppression between 1996 and 2009. The outcome was nonaccidental death, with follow-up until 2014. We used Cox proportional hazards models to test whether biomarker concentrations predict time from HIV suppression to death and adjusted for multiple tests. Exploratory factor analysis (EFA) was employed to identify groupings of biomarkers that predict mortality risk. Results. Of 670 men followed up from HIV suppression, 54 died by the end of 2013. After adjustment for age, CD4+ cell count, hepatitis B or C virus infection, and smoking, concentrations in the highest quartile of 4 biomarkers were significantly associated with mortality risk after controlling the false discovery rate at 5%: interleukin (IL) 6 (hazard ratio, 3.54; 95% confidence interval, 2.06–6.10), soluble IL 2Rα (3.29, 1.85–5.85), soluble CD14 (2.67, 1.55–4.61), and chemokine (CXC motif) ligand 13 (CXCL13; 2.26; 1.29–3.95). EFA yielded 2 biomarker groupings that were independent predictors of mortality risk. Conclusions. Despite having undetectable HIV RNA levels during cART, men with higher concentrations of several biomarkers (particularly IL 6, soluble IL 2Rα, soluble CD14, and CXCL13) had higher hazards of long-term mortality. Correlations observed among biomarker concentrations may represent underlying inflammatory processes that contribute to mortality risk.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Adults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty ...phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men.
A prospective, observational cohort study was nested in the Multicenter AIDS Cohort Study from October 2007-September 2011. FP conversion was defined as the onset of FP over two consecutive study visits. Adjusted odds ratios and 95% confidence intervals (,) for FP conversion were estimated using logistic regression models with generalized estimating equations.
Of 10,571 completed study visits from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV- men, respectively (p = .002). The proportion of FP+ visits increased with age regardless of HIV status, but was significantly greater in HIV+ compared to HIV- men aged 50-64 years. Of the 10,276 consecutive visit pairs contributed by participants, 5% (537) were classified as FP conversion, and 45% of the men with FP conversion had only one FP+ study visit. FP conversion was significantly associated with a history of AIDS (adjusted odds ratios = 2.26 1.50, 3.39, but not with HIV+ alone (adjusted odds ratios = 1.26 0.98, 1.64). Among men who had one or more FP+ visits, 34% of HIV+ and 38% of HIV- men had less than two comorbidities.
These findings suggest that expression of the FP can be measured in men who have sex with men with and without HIV infection and reflects multisystem dysfunction in this population; further investigations are needed to better understand clinical utility.
The timing of the initiation of antiretroviral therapy in asymptomatic patients with HIV infection is unclear. In this retrospective study involving patients in North America from 1996 through 2005, ...the deferral of therapy until the patient's CD4+ count had fallen below one of the two thresholds of interest (a range of 351 to 500 cells or >500 cells per cubic millimeter) was associated with a relative hazard of death of 1.69 and 1.94, respectively.
In this retrospective study involving patients in North America, deferral of therapy until the patient's CD4+ count had fallen below one of the two thresholds of interest (a range of 351 to 500 cells or >500 cells per cubic millimeter) was associated with an increase in the risk of death of 69% and 94%, respectively.
The use of antiretroviral therapy has dramatically reduced disease progression and death among patients with human immunodeficiency virus (HIV) infection,
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but the optimal time to begin therapy is uncertain.
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Current guidelines recommend treatment for asymptomatic patients who have a CD4+ count of less than 350 cells per cubic millimeter on the basis of accumulating observational data.
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However, these guidelines note the lack of data from randomized clinical trials regarding the timing of the initiation of antiretroviral therapy.
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Data from randomized trials are limited to an analysis of a subgroup of 477 patients
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from the Strategies for . . .
OBJECTIVE:To examine the incidence and risk factors for anal cancer in a multicenter cohort of human immunodeficiency virus (HIV) positive and HIV-negative men who have sex with men followed between ...1984 and 2006 (Multicenter AIDS Cohort Study).
METHODS:Prospective analysis using Poisson regression and Cox proportional hazard models and a nested case-control study using conditional logistic regression.
RESULTS:There were 28 cases of anal cancer among the 6972 men who were evaluated. The incidence rate was significantly higher in HIV-positive men than in HIV-negative men (incidence rate = 69 vs 14 per 100,000 person-years). Among HIV-positive men, anal cancer incidence was higher in the highly active antiretroviral therapy (HAART) era than the pre-HAART era (incidence rate = 137 vs 30 per 100,000 person-years). In multivariate analysis restricted to the HAART era, anal cancer risk increased significantly with HIV infection (relative hazard = 4.7, 95% confidence interval = 1.3 to 17) and increasing number of unprotected receptive anal sex partners at the first 3 study visits (P trend = 0.03). Among HIV-positive men, current HAART use did not decrease anal cancer risk.
CONCLUSIONS:HIV-positive men had increased risk of anal cancer. Improved survival of HIV-positive individuals after HAART initiation may allow for sufficient time for human papillomavirus-associated anal dysplasias to develop into malignancies, thus explaining the increased incidence of anal cancer in the HAART era.
Coronary artery disease (CAD) has been associated with HIV infection, but data are not consistent.
To determine whether HIV-infected men have more coronary atherosclerosis than uninfected men.
...Cross-sectional study.
Multicenter AIDS Cohort Study.
HIV-infected (n = 618) and uninfected (n = 383) men who have sex with men who were aged 40 to 70 years, weighed less than 136 kg (200 lb), and had no history of coronary revascularization.
Presence and extent of coronary artery calcium (CAC) on noncontrast cardiac computed tomography (CT) and of any plaque; noncalcified, mixed, or calcified plaque; or stenosis on coronary CT angiography.
1001 men had noncontrast CT, of whom 759 had coronary CT angiography. After adjustment for age, race, CT scanning center, and cohort, HIV-infected men had a greater prevalence of CAC (prevalence ratio PR, 1.21 95% CI, 1.08 to 1.35; P = 0.001) and any plaque (PR, 1.14 CI, 1.05 to 1.24; P = 0.001), including noncalcified (PR, 1.28 CI, 1.13 to 1.45; P < 0.001) and mixed (PR, 1.35 CI, 1.10 to 1.65; P = 0.004) plaque, than uninfected men. Associations between HIV infection and any plaque or noncalcified plaque remained significant (P < 0.005) after CAD risk factor adjustment. HIV-infected men had a greater extent of noncalcified plaque after CAD risk factor adjustment (P = 0.026). They also had a greater prevalence of coronary artery stenosis greater than 50% (PR, 1.48 CI, 1.06 to 2.07; P = 0.020), but not after CAD risk factor adjustment. Longer duration of highly active antiretroviral therapy (PR, 1.09 CI, 1.02 to 1.17; P = 0.007) and lower nadir CD4+ T-cell count (PR, 0.80 CI, 0.69 to 0.94; P = 0.005) were associated with coronary stenosis greater than 50%.
Cross-sectional observational study design and inclusion of only men.
Coronary artery plaque, especially noncalcified plaque, is more prevalent and extensive in HIV-infected men, independent of CAD risk factors.
National Heart, Lung, and Blood Institute and National Institute of Allergy and Infectious Diseases.
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