The need to achieve ≥95 % adherence to HAART for treatment effectiveness may be a barrier for universal initiation at early stages of HIV. Using longitudinal data collected from 2006 to 2011 from ...cohort studies of MSM (MACS) and IDUs (ALIVE study), we estimated the minimum adherence needed to achieve HIV RNA suppression (<50 copies/mL), defined as the level at which at least 80 % were virally suppressed, and the odds of suppression was not significantly different than that observed with ≥95 % adherence. In the MACS, ≥80 % suppression was observed with 80–84 % adherence and the odds ratio for suppression (vs. ≥95 % adherence) was 1.43 (0.61, 3.33). In the ALIVE study where <35 % were on newer drugs, only 71.4 % were suppressed among those who reported ≥95 % adherence. Although IDUs on older HAART regimens may need to be ≥95 % adherent, concerns related to non-adherence may be less of a barrier to initiation of modern HAART regimens.
BACKGROUND:Previous studies of cardiovascular disease (CVD) among HIV-infected individuals have been limited by the inability to validate and differentiate atherosclerotic type 1 myocardial ...infarctions (T1MIs) from other events. We sought to define the incidence of T1MIs and risk attributable to traditional and HIV-specific factors among participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC) cohort.
METHODS:We ascertained and adjudicated incident MIs among individuals enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs, adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA-ACCORD with those from ARIC.
RESULTS:Among 29,169 HIV-infected individuals, the IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was significantly higher compared with participants in ARIC 1.30 (1.09 to 1.56). In multivariable analysis restricted to HIV-infected individuals and including traditional CVD risk factors, the rate of T1MI increased with decreasing CD4 count ≥500 cells/μLref; 350–499 cells/μLaIRR = 1.32 (0.98 to 1.77); 200–349 cells/μLaIRR = 1.37 (1.01 to 1.86); 100–199 cells/μLaIRR = 1.60 (1.09 to 2.34); <100 cells/μLaIRR = 2.19 (1.44 to 3.33). Risk associated with detectable HIV RNA <400 copies/mLref; ≥400 copies/mLaIRR = 1.36 (1.06 to 1.75) was significantly increased only when CD4 was excluded.
CONCLUSIONS:The higher incidence of T1MI in HIV-infected individuals and increased risk associated with lower CD4 count and detectable HIV RNA suggest that early suppressive antiretroviral treatment and aggressive management of traditional CVD risk factors are necessary to maximally reduce MI risk.
BACKGROUND:Falls and fall risk factors are common among people living with HIV (PLWH). We sought to identify fall risk factors among men with and without HIV.
METHODS:Men aged 50–75 years with (n = ...279) and without HIV (n = 379) from the Bone Strength Substudy of the Multicenter AIDS Cohort Study were included. Multinomial logistic regression models identified risk factors associated with falling.
RESULTS:One hundred fourteen (41%) PLWH and 149 (39%) of uninfected men had ≥1 fall; 54 (20%) PLWH and 66 (17%) of uninfected men experienced ≥2 falls over 2 years. Five and 3% of PLWH and uninfected men, respectively, had a fall-related fracture (P = 0.34). In multivariate models, the odds of ≥2 falls were greater among men reporting illicit drug use, taking diabetes or depression medications, and with peripheral neuropathy; obesity was associated with a lower risk (all P < 0.05). In models restricted to PLWH, detectable plasma HIV-1 RNA, current use of efavirenz or diabetes medications, illicit drug use, and peripheral neuropathy were associated with greater odds of having ≥2 falls (P < 0.05). Current efavirenz use was associated with increased odds of an injurious fall; longer duration of antiretroviral therapy was protective (both P < 0.05). Greater physical activity was associated with lower risk of falls with fracture (P < 0.05).
CONCLUSIONS:Identified risk factors for recurrent falls or fall with fracture included low physical activity, detectable HIV-1 RNA, use of efavirenz, or use of medications to treat diabetes and depression. Fall risk reduction should prioritize interventions targeting modifiable risk factors including increased physical activity, antiretroviral therapy adherence, and transition off efavirenz.
IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, ...cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.
We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies.
We found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 95% confidence interval, .76-1.11), cytomegalovirus infection (0.94 .71-1.24), herpes simplex virus infection (1.37 .68-2.93), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count.
The absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.
OBJECTIVEObesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We ...examined body mass index (BMI) and central obesity (waist circumference WC) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV−) men.
METHODSA total of 316 MWH and 656 HIV− Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV− men and 41% of MWH and 56% of HIV− men were ≥60 years, respectively.
RESULTSCross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV− men, and attention/working memory in HIV− men. WC was inversely associated with motor function in MWH and HIV− men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV− men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations.
CONCLUSIONHigher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV− men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.
Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due
to consumption of aflatoxin-contaminated foods, and are exposed to high ...levels of phenanthrene, a sentinel of hydrocarbon
air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens. Glucoraphanin, the principal glucosinolate
in broccoli sprouts, can be hydrolyzed by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication enzymes.
In a randomized, placebo-controlled chemoprevention trial, we tested whether drinking hot water infusions of 3-day-old broccoli
sprouts, containing defined concentrations of glucosinolates, could alter the disposition of aflatoxin and phenanthrene. Two
hundred healthy adults drank infusions containing either 400 or <3 μmol glucoraphanin nightly for 2 weeks. Adherence to the
study protocol was outstanding; no problems with safety or tolerance were noted. Urinary levels of aflatoxin- N 7 -guanine were not different between the two intervention arms ( P = 0.68). However, measurement of urinary levels of dithiocarbamates (sulforaphane metabolites) indicated striking interindividual
differences in bioavailability. An inverse association was observed for excretion of dithiocarbamates and aflatoxin-DNA adducts
( P = 0.002; R = 0.31) in individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti -phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was detected in urine of all participants and
showed a robust inverse association with dithiocarbamate levels ( P = 0.0001; R = 0.39), although again no overall difference between intervention arms was observed ( P = 0.29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use
of broccoli sprouts in human interventions.
Immune activation and inflammation are hallmarks of chronic HIV infection and are etiologically linked to major causes of morbidity and mortality among HIV-infected persons, including coronary artery ...disease and cancer. Systemic immune activation is dampened, but not resolved, with use of combination antiretroviral therapy (cART). Statins are cardioprotective drugs that also appear to have immunomodulatory and anti-inflammatory properties. We sought to understand the association between statin use, cART, and levels of circulating immune markers in a longitudinal cohort study. From 2004 to 2009, statin use was ascertained in male participants of the Multicenter AIDS Cohort Study (MACS) using interviewer-administered questionnaires. Twenty-four circulating markers of immune activation and inflammation were measured in archived serial samples from a subset of cohort members using multiplex assays. Propensity-adjusted generalized gamma models were used to compare biomarkers' distributions by statin use, and multivariable linear regression models were used to assess the effect of initiating statin on these biomarkers. Overall, 1,031 cART-exposed individuals with HIV infection were included in this study. Statin use was reported by 31.5% of cART-exposed participants. Compared to nonstatin users on cART, statin users on cART had lower levels of IP-10, IL-10, and IL-12p70, and the effect of statin use was decreased in participants using lipophilic statins (atorvastatin, simvastatin, fluvastatin, or lovastatin); these results were statistically significant (
< .05). Among cART users not on aspirin, starting statins decreased levels of high sensitivity c-reactive protein (hsCRP), IL-12p70, and IL-6. Statin therapy is associated with reduced levels of certain biomarkers of immune activation and inflammation in cART users, which may contribute to a lower burden of disease.
To assess the association of HIV infection, HIV disease parameters (including CD4+ T-cell counts, HIV viral load, and AIDS) and antiretroviral medication use with subclinical carotid artery ...atherosclerosis.
Cross-sectional study nested within a prospective cohort study.
Among participants in the Women's Interagency HIV Study (1331 HIV-infected women, 534 HIV-uninfected women) and Multicenter AIDS Cohort Study (600 HIV-infected men, 325 HIV-uninfected men), we measured subclinical carotid artery lesions and common carotid artery intima-media thickness using B-mode ultrasound. We estimated adjusted mean carotid artery intima-media thickness differences and prevalence ratios for carotid lesions associated with HIV-related disease and treatments, with multivariate adjustment to control for possible confounding variables.
Among HIV-infected individuals, a low CD4+ T-cell count was independently associated with an increased prevalence of carotid lesions. Compared with the reference group of HIV-uninfected individuals, the adjusted prevalence ratio for lesions among HIV-infected individuals with CD4+ T-cell count less than 200 cells/mul was 2.00 (95% confidence interval, 1.22-3.28) in women and 1.74 (95% confidence interval, 1.04-2.93) in men. No consistent association of antiretroviral medications with carotid atherosclerosis was observed, except for a borderline significant association between protease inhibitor use and carotid lesions in men (with no association among women). History of clinical AIDS and HIV viral load were not significantly associated with carotid atherosclerosis.
Beyond traditional cardiovascular disease risk factors, low CD4+ T-cell count is the most robust risk factor for increased subclinical carotid atherosclerosis in HIV-infected women and men.
Background. Accurate testing algorithms are needed for estimating human immunodeficiency virus (HIV) incidence from cross-sectional surveys. Methods. We developed a multiassay algorithm (MAA) for HIV ...incidence that includes the BED capture enzyme immunoassay (BED-CEIA), an antibody avidity assay, HIV load, and CD4⁺ T-cell count. We analyzed 1782 samples from 709 individuals in the United States who had a known duration of HIV infection (range, 0 to >8 years). Logistic regression with cubic splines was used to compare the performance of the MAA to the BEDCEIA and to determine the window period of the MAA. We compared the annual incidence estimated with the MAA to the annual incidence based on HIV seroconversion in a longitudinal cohort. Results. The MAA had a window period of 141 days (95% confidence interval CI, 94-150) and a very low false-recent misclassification rate (only 0.4% of 1474 samples from subjects infected for >1 year were misclassified as indicative of recent infection). In a cohort study, annual incidence based on HIV seroconversion was 1.04% (95% CI, .70%-1.55%). The incidence estimate obtained using the MAA was essentially identical: 0.97% (95% CI, .5196-1.71%). Conclusions. The MAA is as sensitive for detecting recent HIV infection as the BED-CEIA and has a very low rate of false-recent misclassification. It provides a powerful tool for cross-sectional HIV incidence determination.
Chronic inflammation and B-cell hyperactivation are seen in HIV infection, contributing to an increased risk for the accrual of genetic errors that may result in B-cell lymphoma. The primary ...objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) on serum levels of molecules that are associated with immune activation and/or inflammation, including several that are associated with B-cell activation, specifically IL-6, sCD30, sCD27, IgG, IgA, CXCL13 (B lymphocyte chemoattractant, BLC), a B-lymphocyte chemokine involved in B-cell trafficking, as well as C-reactive protein, an acute-phase protein.
We used a retrospective cohort study design, measuring serum levels of these markers at each of four 1-year intervals, 2 years before and 2 years after HAART initiation, in a subgroup of 290 HIV-infected men enrolled in the Multicenter AIDS Cohort Study (MACS).
Serum levels of immune activation-associated molecules were measured by ELISA and multiplexed immunometric assays. Reference values were determined by the 5th to 95th percentiles from a sample of 109 HIV-uninfected MACS men.
HAART use was associated with a reduction, but not normalization, of most biomarkers tested. Serum levels of IL-6 and C-reactive protein appeared to be unaffected by HAART.
These results suggest a partial normalization of serum cytokine levels post HAART. However, a chronic state of B-cell hyperactivation continues 2-3 years after HAART initiation. These findings may explain, in part, the excess incidence of lymphoma still occurring in HIV-infected persons in the post-HAART era.
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