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Aging & HIV Highlights at CROI 2021
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Here are some selected highlights by me reflecting key reporting & studies on aging & comorbidities & related published papers: cognitive impairment appears worse in HIV+ and does appear to get worse with aging in older PLWH, and both HIV and comorbidities contribute to cognitive impairment; women suffer worse from aging with HIV with worse inflammation markers, worse risk for comorbidities; prescription opioid use in WIHS; a look at Medicare Optum database shows higher rates for PLWH having 4-4 comorbidities vs HIV- & doubles the rates of 5 comorbidities or more and have higher rates of poly pharmacy. Jules Levin, NATAP
Aging "Silver Tsunami" Predicted - CROI: Multimorbidity in people with HIV using ART in the US: Projections to 2030 - (03/08/21)
The largest increase in number of cases of mutimorbidty will be in MSM, the highest increase in prevalence will be in heterosexual women [24%] & men who inject drugs [17%]. See graph below. Women have highest prevalence. This is an UNDERESTIMATE because only PLWH in care were included & the CDC reports 40% of HIV+ in USA have detectable viral load; and this study does not include ART-naive PLWH; data does not include nor trans/bisexual subpopulations. This is an underestimate because the CDC estimated 40% of HIV+ in the USA have detectable viral load and they are NOT included in this dataset. Also detectable viral load is associated with higher risk for comorbidties & mortality.
Burden of Hypertension, Diabetes, Cardiovascular Disease, and Lung Disease Among Women Living With Human Immunodeficiency Virus (HIV) in the United States - (03/18/21)
CROI: BEYOND PAIN: PRESCRIPTION OPIOID USE IN THE WOMEN'S INTERAGENCY HIV STUDY - (03/12/21)
CROI: HIGHER COMORBIDITY BURDEN PREDICTS WORSENING NEUROCOGNITION IN PEOPLE WITH HIV - (03/11/21)
CROI: 12-Year Cognitive Decline is Associated with Lung Disease, Diabetes, and Depression - (03/08/21)
Cognitive ageing is premature among a community sample of optimally treated people living with HIV - (02/26/21)
The main study finding was evidence of premature cognitive ageing. The current study identified premature cognitive ageing in a community sample of well‐educated and well‐treated HIV‐positive gay and bisexual men with low AIDS rate, compared with demographically comparable HIV‐negative counterparts.
Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable - (02/26/21)
We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease.
CROI: COMORBIDITY BURDEN IN PEOPLE LIVING WITH HIV IN THE UNITED STATES - (03/06/21)
Retrospective analyses of administrative claims data for commercial and Medicare Advantage enrollees from the Optum Research Database was conducted. Presence of ≥3 comorbidities (Figure 1), and mean CCI were higher in PLWH than PLWoH (0.93 vs 0.61, p<0.001). Conclusion: Multimorbidity and polypharmacy were more prevalent in PLWH compared to matched PLWoH. The study findings suggest the need for clinicians to consider comorbidities and comedications when selecting ARV regimens to minimize drug interactions and adverse events and thereby improve patient outcomes.
CROI: SEX DIFFERENCES IN DIABETES PREVELANCE AMONG PERSONS WITH HIV IN THE UNITED STATES...40% of HIV+ Women >65 have diabetes. - (03/19/21)
CROI: SEX MODIFIES THE ASSOCIATION BETWEEN INFLAMMATION AND VASCULAR EVENTS IN TREATED HIV - (03/08/21) "Clear interaction between age & inflammation for women". HIV+ women have 2-4 fold higher levels of inflammation, and they have these higher levels at older ages. THIS appears to drive greater numbers & risk\ks for CVD events.
CROI: HIV DIFFERENTIALLY IMPACTS AGE-RELATED COMORBIDITY BURDEN AMONG US WOMEN AND MEN - (03/06/21) PWH and HIV- participants followed in the MACS/WIHS Combined Cohort Study (MWCCS) since 2008/2009 (when >80% of male/female participants used antiretroviral therapy) were included with outcomes measured up to 03/2019. Conclusion: The prevalence and burden of NACM was high in the MWCCS among men and women with or at-risk for HIV, particularly for hypertension, psychiatric illness, dyslipidemia, liver, and bone disease. NACM burden was higher in women vs men, particularly among PWH, and the distribution of specific NACM prevalence differed by sex. Given HIV is associated with differential effects on age-related comorbidities by sex, HIV serostatus- and sex-specific strategies for NACM screening and prevention are needed. When HIV+ men & women reach 70 years old the rates of having 5 or more comorbidities jump a lot higher. For HIV+ women these rates jump a lot higher after 60 years of age. These big jumps occur for HIV+ men too after 60 but the jumps are bigger for HIV+ women.
CROI: IMPACT OF REPRODUCTIVE AGING ON IMMUNE FUNCTION IN CISGENDER MEN AND WOMEN WITH HIV - (03/07/21)
Longitudinal samples (N=415) from virally suppressed cis-gendered women (N=61) and men (N=31) were retrospectively identified from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) population.. The most dynamic T cell cluster was a phenotypic mixture of naïve and central memory with high PD-1 expression (cluster 9), suggesting associated inflammatory responses and functional exhaustion with a possible link to HIV reservoir expansion. This cell subset was increased significantly over time in women, but not in men (Fig.1A) Conclusion: Women have increasing exhausted T cells as they age, whereas men have an increasing population of regulatory type T cells. These changes in immune cell phenotype may be linked to comorbidities associated with sex- specific patterns of inflammaging and HIV persistence.
CROI: NEUROCOGNITIVE DYSFUNCTION, INFLAMMATION, AND ADIPOSITY IN TREATED HIV PATIENTS - (03/24/21)
Compared to controls, HIV+ participants had a lower overall cognitive score (76% vs 83%, p=0.01), and performed poorer across different cognitive domains [visuospatial, memory, executive function, naming/language, delayed recall, and abstraction, (all p<0.05)]. In the HIV+ group, lower cognitive testing domain scores were associated with higher inflammatory markers(IL6, TNFR-I, TNFR-II, hsCRP), and with higher body fat compositions (total percent fat and visceral adipose tissue). Overall, 53% were male, 47% were African American, with a mean age of 43 years. Among HIV + individuals, all were on ART by design and 80% had an undetectable HIV-1 RNA level (≤20 copies/ml).
CROI: NEURON DAMAGE AND RESERVOIR ARE SECONDARY TO HIV TRANSCRIPTS DESPITE SUPPRESSIVE ART - (03/17/21)
CROI: EPIGENETIC AGING ASSOCIATED WITH COGNITIVE IMPAIRMENT IN OLDER BLACK ADULTS WITH HIV - (03/24/21)
Conclusion: Epigenetic age acceleration in blood was observed in African-American older PWH using two measures, including EEAA which reflects immunosenescence. There was no evidence of age acceleration independent of cell type composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function in the HIV group.
CROI: PWH AND ALZHEIMER'S DISEASE RISK: CLARIFYING THE HAND PHENOTYPE OVER TIME - (03/24/21)
CROI: URINE MITOCHONDRIAL DNA, WEIGHT LOSS, AND BODY COMPOSITION IN OLDER ADULTS WITH HIV - (03/14/21)
This is a cross sectional analysis of OAH (age 55 and over) who had frailty testing (Fried Frailty phenotype), bioelectric impedance analysis (BIA), and measurement of urine cfmtDNA by quantitative PCR. Skeletal muscle and fat mass indices were calculated using BIA results.
Two thirds (67%) met criteria for a pre-frail or frail state. Mean urine cfmtDNA level was higher in participants who met frailty criteria for unintentional weight loss (p=0.01) by t-test [Figure 1].
CROI: BIOLOGICAL PROFILES PREDICT CORONARY ARTERY DISEASE IN PWH AND RISK-MATCHED CONTROLS - (03/08/21)
CROI: IDENTIFICATION OF UNIQUE PROTEINS PREDICTIVE OF MORTALITY AND MECHANISMS IN HIV - (03/08/21)
CROI: PREVENTION OF CARDIOVASCULAR DISEASE IN PERSONS WITH AND WITHOUT HIV - (03/08/21) High risk profile in PLWH
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