To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up.
The Multicenter AIDS ...Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification.
The frequency of HAND for the 364 HIV+ individuals seen in 2007-2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007-2008, 2009-2010, and 2011-2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009-2010 to 2011-2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition.
HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period.
HIV-infected (HIV+) women seem to be more vulnerable to neurocognitive impairment (NCI) than HIV+ men, perhaps in part due to mental health factors. We assessed the association between elevated ...depressive symptoms and NCI among HIV+ and HIV-uninfected (HIV-) women and men.
Women's Interagency HIV Study and Multicenter AIDS Cohort Study.
Eight hundred fifty-eight HIV+ (429 women; 429 men) and 562 HIV- (281 women; 281 men) completed the Center for Epidemiologic Studies Depression (16 cutoff) Scale and measures of psychomotor speed/attention, executive, and motor function over multiple visits (or time points). Women's Interagency HIV Study and Multicenter AIDS Cohort Study participants were matched according to HIV status, age, race/ethnicity, and education. Generalized linear mixed models were used to examine interactions between biological sex, HIV serostatus, and depression on impairment (T-scores <40) after covariate adjustment.
Despite a higher frequency of depression among men, the association between depression and executive function differed by sex and HIV serostatus. HIV+ women with depression had 5 times the odds of impairment on a measure of executive control and inhibition versus HIV- depressed women and 3 times the odds of impairment on that measure versus HIV+ depressed men. Regardless of group status, depression was associated with greater impairment on processing speed, executive (mental flexibility), and motor function (P's < 0.05).
Depression contributes to NCI across a broad range of cognitive domains in HIV+ and HIV- individuals, but HIV+ depressed women show greater vulnerabilities in executive function. Treating depression may help to improve cognition in patients with HIV infection.
Women may be more vulnerable to HIV-related cognitive dysfunction compared with men because of sociodemographic, lifestyle, mental health, and biological factors. However, studies to date have ...yielded inconsistent findings on the existence, magnitude, and pattern of sex differences. We examined these issues using longitudinal data from 2 large, prospective, multisite, observational studies of US women and men with and without HIV.
The Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS).
HIV-infected (HIV+) and uninfected (HIV-) participants in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study completed tests of psychomotor speed, executive function, and fine motor skills. Groups were matched on HIV status, sex, age, education, and black race. Generalized linear mixed models were used to examine group differences on continuous and categorical demographically corrected T-scores. Results were adjusted for other confounding factors.
The sample (n = 1420) included 710 women (429 HIV+) and 710 men (429 HIV+) (67% non-Hispanic black; 53% high school or less). For continuous T-scores, sex by HIV serostatus interactions were observed on the Trail Making Test parts A & B, Grooved Pegboard, and Symbol Digit Modalities Test. For these tests, HIV+ women scored lower than HIV+ men, with no sex differences in HIV- individuals. In analyses of categorical scores, particularly the Trail Making Test part A and Grooved Pegboard nondominant, HIV+ women also had a higher odds of impairment compared with HIV+ men. Sex differences were constant over time.
Although sex differences are generally understudied, HIV+ women vs men show cognitive disadvantages. Elucidating the mechanisms underlying these differences is critical for tailoring cognitive interventions.
The multivariate normative comparison (MNC) method has been used for identifying cognitive impairment. When participants' cognitive brain domains are evaluated regularly, the longitudinal MNC (LMNC) ...has been introduced to correct for the intercorrelation among repeated assessments of multiple cognitive domains in the same participant. However, it may not be practical to wait until the end of study for diagnosis. For example, in participants of the Multicenter AIDS Cohort Study (MACS), cognitive functioning has been evaluated repeatedly for more than 35 years. Therefore, it is optimal to identify cognitive impairment at each assessment, while the family‐wise error rate (FWER) is controlled with unknown number of assessments in future. In this work, we propose to use the difference of consecutive LMNC test statistics to construct independent tests. Frequency modeling can help predict how many assessments each participant will have, so Bonferroni‐type correction can be easily adapted. A chi‐squared test is used under the assumption of multivariate normality, and permutation test is proposed where this assumption is violated. We showed through simulation and the MACS data that our method controlled FWER below a predetermined level.
Background. Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)—infected and —uninfected men who have sex with men (MSM) over the entire ...HIV epidemic has not been comprehensively conducted. Methods. To determine the trends in and risk factors associated with incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)—negative MSM in the Multicenter AIDS Cohort Study were prospectively followed during 1984–2011 for anti-HCV seroconversion. Results. During 55 343 person-years (PYs) of follow-up, there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered throughout the study period. In a multivariable analysis with time-varying covariates, older age (incidence rate ratio IRR, 1.40/10 years, P < .001), enrollment in the later (2001–2003) recruitment period (IRR, 3.80, P = .001), HIV infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR, 1.68, (P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001), syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with >1 male partner (IRR, 3.37, P < .001) were independently associated with incident HCV. Among HIV-infected subjects, every 100 cell/mm 3 increase in CD4 count was associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4 count of 500 cells/mm 3 , whereas there was no association with highly active antiretroviral therapy. Conclusions. The spread of HCV among both HIV-infected and -uninfected MSM in the United States has been ongoing since the beginning of the HIV epidemic. In HIV-infected men with <500 CD4 + T cells, the HCV incidence rate was inversely proportional to CD4 T-cell count.
Although coinfection with HIV-1 and hepatitis B virus (HBV) is common, few long-term studies on liver-disease mortality in coinfected people have been undertaken. Our aim was to examine liver-related ...mortality among people at risk for HIV-1 and HBV infections.
We used data from a multicentre, prospective cohort study to classify 5293 men who had sex with men, according to their HIV-1 antibody status, ascertained semiannually, and their hepatitis-B surface antigen status (HBsAg), which we ascertained at baseline. Mortality rates were estimated in terms of person-years and Poisson regression methods were used to test for signifiance of relative risks.
326 (6%) men were HBsAg positive, of whom 213 (65%) were HIV-1 positive. Of the 4967 HBsAg negative men, 2346 (47%) were infected with HIV-1. The liver-related mortality rate was 1·1/1000 person years, and was higher in men with HIV-1 and HBsAg (14·2/1000) than in those with only HIV-1 infection (1·7/1000, p<0·001) or only HBsAg (0·8/1000, p<0·001). In coinfected individuals, the liver-related mortality rate was highest with lower nadir CD4+ cell counts and was twice as high after 1996, when highly active antiretroviral therapy (HAART) was introduced.
Individuals coinfected with HIV-1 and HBV, especially those with low CD4+ nadir counts, are at increased risk for liver-related mortality, underscoring the importance of prevention, identification, and comprehensive management of hepatitis B in people infected with HIV-1.
In the United States, hepatitis D is not a reportable condition, leading to gaps in epidemiological and clinical knowledge. We aim to estimate the incidence of hepatitis D‐associated hospitalizations ...in the United States and describe the clinical, demographic and geographic characteristics of those hospitalizations. We utilized hospitalization data from the 2010–2018 National Inpatient Sample from the Healthcare Cost and Utilization Project. Hepatitis D and hepatitis B only (HBV only) hospitalizations were identified by International Classification of Diseases, Ninth Revision (ICD‐9) and International Classification of Diseases, Tenth Revision (ICD‐10) codes. We identified 3825 hepatitis D‐associated hospitalizations. The hospitalization rate of hepatitis D was between 6.9 and 20.7 per 10,000,000 but did not change significantly over time. Compared to HBV only, the hepatitis D cohort had a greater proportion of males, Hispanics, hospitalizations in the Northeast region. The hepatitis D‐associated hospitalizations also had significantly greater frequencies of liver failure, non‐alcoholic cirrhosis, portal hypertension, ascites and thrombocytopenia. While mortality in hepatitis D was similar to that of HBV only, age >65 years (odds ratio OR = 3.79; p = .020) and having a diagnosis of alcoholic cirrhosis (OR = 3.37; p = .044) increased the odds of mortality within the hepatitis D cohort. Although the hepatitis D‐associated hospitalizations were relatively uncommon, they were associated with severe complications.
Significance Statement
Hepatitis D‐associated hospitalizations were relatively uncommon in the United States, but they were associated with severe complication and affect certain groups and regions disproportionally.
Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase the risk of fatty liver disease. We determined the prevalence of and risk factors for fatty liver by ...comparing HIV-infected men with HIV-uninfected men who have sex with men in the Multicenter AIDS Cohort Study (MACS).
In 719 MACS participants who consumed less than three alcoholic drinks daily, fatty liver was defined as a liver-to-spleen attenuation ratio <1 on noncontrast computed tomography (CT). We genotyped single nucleotide polymorphisms in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene and in other genes previously associated with nonalcoholic fatty liver disease. Risk factors for fatty liver were determined using multivariable logistic regression.
Among 254 HIV-uninfected men and 465 HIV-infected men, 56% were White with median age 53 years and median body mass index 25.8 kg/m(2). The vast majority of HIV-infected men (92%) were on ART, and 87% of the HIV-infected men were treated with a nucleoside reverse transcriptase inhibitor for a median duration of 8.5 years. Overall, 15% of the cohort had fatty liver, which was more common in the HIV-uninfected compared with the HIV-infected men (19 vs. 13%, P=0.02). In multivariable analysis, HIV infection was associated with a lower prevalence of fatty liver (odds ratio (OR)=0.44, P=0.002), whereas a higher prevalence of fatty liver was seen in participants with PNPLA3 (rs738409) non-CC genotype (OR=2.06, P=0.005), more abdominal visceral adipose tissue (OR=1.08 per 10 cm(2), P<0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) ≥4.9 (OR=2.50, P=0.001). Among HIV-infected men, PNPLA3 (rs738409) non-CC genotype was associated with a higher prevalence of fatty liver (OR=3.30, P=0.001) and cumulative dideoxynucleoside exposure (OR=1.44 per 5 years, P=0.02).
CT-defined fatty liver is common among men at risk for HIV infection and is associated with greater visceral adiposity, HOMA-IR, and PNPLA3 (rs738409). Although treated HIV infection was associated with a lower prevalence of fatty liver, prolonged exposure to dideoxynucleoside analogs is associated with higher prevalence.
A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been ...few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.
We determined steatotic liver disease (SLD) incidence in a prospective cohort of men with HIV (MWH) and men without HIV (MWOH).
Incident SLD was defined using paired noncontrast computed tomography ...scans performed during 2010-2013 and repeated during 2015-2017.
Of 268 men, 173 MWH and 95 MWOH, 33 had incident SLD (11.1%, incidence rate 2.4 and 2.7/100 person-years for MWH and MWOH, respectively). Overall, higher abdominal visceral adipose tissue was independently associated with increased SLD risk. In MWH, increased visceral adipose tissue, insulin resistance, chronic hepatitis B, and cumulative etravirine use were associated with SLD.
Metabolic factors, but not HIV, were associated with incident SLD. The high incidence rate suggests that SLD will continue to increase in PWH.
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