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Poor adherence to antiretroviral therapy (ART) contributes to disease progression and emergence of drug-resistant HIV in youth with perinatally acquired HIV infection (PHIV +), necessitating reliable measures of adherence. Although electronic monitoring devices have often been considered the gold-standard assessment in HIV research, they are costly, can overestimate nonadherence and are not practical for routine care. Thus, the development of valid, easily administered self-report adherence measures is crucial for adherence monitoring. PHIV+youth aged 7–16 (n= 289) and their caregivers, enrolled in a multisite cohort study, were interviewed to assess several reported indicators of adherence. HIV-1 RNA viral load (VL) was dichotomized into >/≤400 copies/mL. Lower adherence was significantly associated with VL >400 copies/mL across most indicators, including ≥1 missed dose in past seven days [youth report: OR = 2.78 (95% CI, 1.46–5.27)]. Caregiver and combined youth/caregiver reports yielded similar results. Within-rater agreement between various adherence indicators was high for both youth and caregivers. Inter-rater agreement on adherence was moderate across most indicators. Age ≥13 years and living with biological mother or relative were associated with VL >400 copies/mL. Findings support the validity of caregiver and youth adherence reports and identify youth at risk of poor adherence. [ABSTRACT FROM AUTHOR]

Among 330 perinatally infected youths (mean age, 13.5 years), 28% reported sexual intercourse. Most reported unprotected sex and human immunodeficiency virus nondisclosure to first partners. Viral resistance to ≥1 antiretroviral medication was detected in 81% of sexually active youths with viral load ≥5000 copies/mL.Background. Factors associated with initiation of sexual activity among perinatally human immunodeficiency virus (HIV)–infected (PHIV+) youth, and the attendant potential for sexual transmission of antiretroviral (ARV) drug-resistant HIV, remain poorly understood.Methods. We conducted cross-sectional and longitudinal analyses of PHIV+ youth aged 10–18 years (mean, 13.5 years) enrolled in the US-based Pediatric HIV/AIDS Cohort Study between 2007 and 2009. Audio computer-assisted self-interviews (ACASI) were used to collect sexual behavior information.Results. Twenty-eight percent (95% confidence interval [CI], 23%–33%) (92/330) of PHIV+ youth reported sexual intercourse (SI) (median initiation age, 14 years). Sixty-two percent (57/92) of sexually active youth reported unprotected SI. Among youth who did not report history of SI at baseline, ARV nonadherence was associated with sexual initiation during follow-up (adjusted hazard ratio, 2.87; 95% CI, 1.32–6.25). Youth living with a relative other than their biological mother had higher odds of engaging in unprotected SI than those living with a nonrelative. Thirty-three percent of youth disclosed their HIV status to their first sexual partner. Thirty-nine of 92 (42%) sexually active youth had HIV RNA ≥5000 copies/mL after sexual initiation. Viral drug resistance testing, available for 37 of these 39 youth, identified resistance to nucleoside reverse transcriptase inhibitors in 62%, nonnucleoside reverse transcriptase inhibitors in 57%, protease inhibitors in 38%, and all 3 ARV classes in 22%.Conclusions. As PHIV+ youth become sexually active, many engage in behaviors that place their partners at risk for HIV infection, including infection with drug-resistant virus. Effective interventions to facilitate youth adherence, safe sex practices, and disclosure are urgently needed. [ABSTRACT FROM PUBLISHER]

Mental health problems (MHPs) among children with perinatal HIV infection have been described prior to and during the highly active antiretroviral therapy (HAART) era. Yet child, caregiver and socio-demographic factors associated with MHPs are not fully understood. We examined the prevalence of MHPs among older children and adolescents with perinatal HIV exposure, including both perinatally HIV-infected (PHIV + ) and perinatally HIV-exposed but uninfected (PHEU) youth. Our aims were to identify the impact of HIV infection by comparing PHIV+ and PHEU youth and to delineate risk factors associated with MHPs, in order to inform development of appropriate prevention and intervention strategies. Youth and their caregivers were interviewed with the Behavior Assessment System for Children, 2nd edition (BASC-2) to estimate rates of at-risk and clinically significant MHPs, including caregiver-reported behavioral problems and youth-reported emotional problems. The prevalence of MHPs at the time of study entry was calculated for the group overall, as well as by HIV status and by demographic, child health, and caregiver characteristics. Logistic regression models were used to identify factors associated with youth MHPs. Among 416 youth enrolled between March 2007 and July 2009 (295 PHIV+, 121 PHEU), the overall prevalence of MHPs at entry was 29% and greater than expected based on recent national surveys of the general population. MHPs were more likely among PHEU than among PHIV+ children (38% versus 25%, p<0.01). Factors associated with higher odds of MHPs at p<0.10 included caregiver characteristics (psychiatric disorder, limit-setting problems, health-related functional limitations) and child characteristics (younger age and lower IQ). These findings suggest that PHEU children are at high risk for MHPs, yet current models of care for these youth may not support early diagnosis and treatment. Family-based prevention and intervention programs for HIV affected youth and their caregivers may minimize long-term consequences of MHPs. [ABSTRACT FROM PUBLISHER]

Knowledge about the meanings and consequences of behaviors associated with drug use among diverse populations is essential for developing effective public health and clinical strategies. In this study we identify racial/ethnic variations in patterns of drug use, Addiction Severity Index (ASI) scores, response to intervention, concordance between self-report of drug use and biochemical confirmation, and treatment system contacts in a sample of 175 out-of-treatment cocaine and heroin users drawn from a trial of brief motivation in the outpatient clinics of an inner-city academic hospital. Key differences were identified in drug of choice, in all of the ASI domains except medical, in validity of self-report of use, and in rate of treatment contact. Differences related to race and ethnicity should be evaluated to determine needs for a variety of substance abuse treatment modalities, assure timely access to culturally competent care, and develop policies that are tailored to real conditions. [ABSTRACT FROM AUTHOR]

Background Conflicting evidence exists on the impact of cannabis use on antiretroviral therapy (ART) adherence among people with human immunodeficiency virus (PWH). We leveraged data collected among older PWH to characterize longitudinal associations between cannabis use and ART adherence. Methods AIDS Clinical Trials Group (ACTG) A5322 study participants were categorized as <100% (≥1 missed dose in past 7 days) or 100% (no missed doses) ART adherent. Participants self-reported current (past month), intermittent (past year but not past month), and no cannabis (in past year) use at each study visit. Generalized linear models using generalized estimating equations were fit and inverse probability weighting was used to adjust for time-varying confounders and loss to follow-up. Results Among 1011 participants (median age, 51 years), 18% reported current, 6% intermittent, and 76% no cannabis use at baseline; 88% reported 100% ART adherence. Current cannabis users were more likely to be <100% adherent than nonusers (adjusted risk ratio [aRR], 1.53 [95% CI, 1.11–2.10]). There was no association between ART adherence and current versus intermittent (aRR, 1.39 [95% CI,.85–2.28]) or intermittent versus no cannabis use (aRR, 1.04 [95% CI,.62–1.73]). Conclusions Among a cohort of older PWH, current cannabis users had a higher risk of <100% ART adherence compared to nonusers. These findings have important clinical implications as suboptimal ART adherence is associated with ART drug resistance, virologic failure, and elevated risk for mortality. Further research is needed to elucidate the mechanisms by which cannabis use decreases ART adherence in older PWH and to advance the development of more efficacious methods to mitigate nonadherence in this vulnerable population. [ABSTRACT FROM AUTHOR]

The article focuses on according to a study antiretroviral therapy (ART) with increased fractures in HIV infected are not associated with activation of CD8+ T Cell. It states that Activated CD8+ T cells were measured on peripheral blood mononuclear cell (PBMC) samples and activated CD8 was associated with increased hazard of fracture but continuous activated CD8 was not associated with fracture. It mentions that there is no role of chronic immune activation with HIV infection in bone loss.

Background Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established. Methods AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI. Results In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46–56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR] = 2.06; 95% confidence interval [CI] = .94, 4.48; P  = .07). Further adjustment for confounding strengthened this association (OR = 2.79; 95% CI = 1.21, 6.43; P  = .02). Baseline frailty however was not associated with NCI development. Conclusions NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population. [ABSTRACT FROM AUTHOR]

Background Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation—this metabolic shift may contribute to NCI and slowed gait speed in PWH. Methods Plasma citrate and succinate were assayed by liquid chromatography–mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. Results Median age was 51 (range 40–78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P =.03), 0.07 SD lower time-updated NPZ-4 score (P =.01), and 0.02 m/s slower time-updated gait speed (P <.0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤.01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. Conclusions Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH. Methods We constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit. Results Among 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P =.003; lower by 2.17 [SD, 0.67] in women, P =.001; lower by 0.78 [SD, 0.32] in men, P =.016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women. Conclusions Baseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time. [ABSTRACT FROM AUTHOR]

Ferroptosis is implicated in viral neuropathogenesis and may underlie HIV-associated neurocognitive impairment (NCI). Emerging data also suggest differences in brain iron transport by sex. We hypothesized that circulating ferritins that inhibit ferroptosis associate with neurocognitive function and NCI in people with HIV (PWH) in a sex-biased manner. Serum ferritin heavy-chain-1 (FTH1), ferritin light-chain (FTL), and urinary F 2 -isoprostanes (uF 2 -isoPs, specific lipid peroxidation marker) were quantified in 324 PWH (including 61 women) with serial global (NPZ-4) and domain-specific neurocognitive testing. Biomarker associations with neurocognitive test scores and NCIs were evaluated by multivariable regression; correlations with uF 2 -isoPs were also assessed. Higher FTL and FTH1 levels were associated with less NCI in all PWH (adjusted odds ratios 0.53, 95% confidence interval (95% CI) 0.36-0.79 and 0.66, 95% CI 0.45-0.97, respectively). In women, higher FTL and FTH1 were also associated with better NPZ-4 (FTL adjusted beta (β) = 0.15, 95% CI 0.02-0.29; FTL-by-sex β interaction = 0.32, p = 0.047) and domain-specific neurocognitive test scores. Effects on neurocognitive performance persisted for up to 5 years. Levels of both ferritins correlated inversely with uF 2 -isoPs in women (FTL: rho = -0.47, p < 0.001). Circulating FTL and FTH1 exert sustained, sex-biased neuroprotective effects in PWH, possibly by protecting against iron-mediated lipid peroxidation (ferroptosis). Larger studies are needed to confirm the observed sex differences and further delineate the underlying mechanisms.

Background: Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants., Methods: Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change., Results: A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P  < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain., Conclusion: CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Older persons with HIV (PWH) experience high rates of cognitive impairment and frailty, and accelerated decline in physical function compared with the general population. Metformin use has been associated with beneficial effects on cognitive and physical function among older adults without HIV. The relationship between metformin use on these outcomes in PWH has not been evaluated. AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH with annual assessments for cognition and frailty, including measures of physical function (e.g., gait speed and grip strength). Participants with diabetes who were prescribed antihyperglycemic medications were included in this analysis to evaluate the association between metformin and functional outcomes. Cross-sectional, longitudinal, and time-to-event models were used to evaluate the relationship between metformin exposure with cognitive, physical function, and frailty outcomes. Ninety-eight PWH met inclusion criteria and were included in at least one model. No significant associations between metformin use, frailty, physical, or cognitive function were noted in unadjusted or adjusted cross-sectional, longitudinal, or time-to-event models ( p  > .1 for all models). This study is the first to examine the association between metformin use on functional outcomes among older PWH. Although it did not ascertain significant associations between metformin use and functional outcomes, our small sample size, restriction to persons with diabetes, and lack of randomization to metformin therapy were limitations. Larger randomized studies are needed to determine whether metformin use has beneficial effects on cognitive or physical function in PWH. Clinical Trial Registration numbers: 02570672, 04221750, 00620191, and 03733132.

Background: Hypercholesterolemia is common in perinatally HIV-infected (HIV+) children, but little is known about the clinical course and management in this population., Methods: We studied HIV+ children in a multisite prospective cohort study (Pediatric AIDS Clinical Trials Group 219C) and considered follow-up for 2 years after development of hypercholesterolemia. We estimated the time and factors associated with resolution of hypercholesterolemia and described changes in antiretroviral regimen and use of lipid-lowering medications. We defined incident hypercholesterolemia as entry total cholesterol (cholesterol) <220 mg/dL and 2 subsequent consecutive cholesterol ≥ 220 mg/dL and defined resolution of hypercholesterolemia as 2 consecutive cholesterol <200 mg/dL after incident hypercholesterolemia., Results: Among 240 incident hypercholesterolemia cases, 81 (34%) had resolution to normal cholesterol within 2 years of follow-up (median follow-up = 1.9 years). The median age of cases was 10.3 years with 54% non-Hispanic black and 53% male. Resolution to normal cholesterol was more likely in children who changed antiretroviral regimen (adjusted hazard ratio = 2.37, 95% confidence interval: 1.45 to 3.88) and who were 13 years and older (aHR = 2.39, 95% confidence interval: 1.33 to 4.27). Types of regimen changes varied greatly, and 15 children began statins., Conclusion: The majority of children who develop hypercholesterolemia maintain elevated levels over time, potentially placing them at risk for premature cardiovascular morbidity.