Human Immunodeficiency Virus Disease Severity Research Articles

Evaluation of Urinary Free Light Chains as a Marker of Severity of HIV Disease and Its Correlation with CD4 Count: A Pilot Study.

Human immunodeficiency virus (HIV) infection weakens immunity. Monitoring the immune status of the patient has become an important aspect of evaluating the progression of the disease and informing follow-up after treatment. Estimation of CD4 counts is quite costly and requires expertise in flow cytometry. In certain pathologies, free light chains (FLCs) are secreted in serum and urine and the magnitude can be used to monitor the severity, progression, and therapeutic monitoring of the disease. Urine as a specimen proves cost-effective and presents reduced risks during sample collection. The stability of light chains in urine at room temperature over extended periods simplifies the management of sample transportation as well. Hence, a pilot cross-sectional study was planned to evaluate the levels of urinary immunoglobulins in patients with HIV. The study was conducted at PGIMER, Dr. Ram Manohar Lohia Hospital (presently ABVIMS), New Delhi. Sixty-nine consecutive ART-naive HIV patients aged between 18 and 40 years and 69 age- and sex-matched healthy controls were included in the study. Urinary FLC kappa (κ) and lambda (λ) were measured using an immunoglobulin ELISA kit. Baseline urinary κ light chain levels were significantly higher in cases when compared with controls (p < .001) and were found to be increased with increasing WHO immunological classes (p < .001) and inversely related to CD4 cell count. However, no significant difference in mean urinary λ immunoglobulin light chain between cases and controls was found and no correlation with CD4 cell count or with stages of WHO immunological classification of HIV disease was observed. It is suggested that urinary free κ chain measurements combined with serum light chain measurements may be a useful marker in the follow-up and monitoring of response to therapies in patients with HIV where testing by flow cytometry is not available.

Anemia and Iron Supplementation in Relation to Viral Load and Mortality among 70,442 People Living with Human Immunodeficiency Virus in Tanzania

BackgroundAnemia may be associated with poor clinical outcomes among people living with human immunodeficiency virus (HIV) (PLHIV) despite highly active antiretroviral therapy (HAART). There are concerns that iron supplementation may be unsafe to prevent and treat anemia among PLHIV. ObjectiveThe objective of the study was to evaluate the associations of anemia and iron supplementation with mortality and viral load among PLHIV in Tanzania. MethodsWe analyzed data from a cohort of 70,442 nonpregnant adult PLHIV in Tanzania conducted between 2015 and 2019. Regression models evaluated the relationships between anemia severity and iron supplement use with mortality and unsuppressed HIV-1 viral load among all participants and stratified by whether participants were initiating or continuing HAART. ResultsAnemia was associated with an increased risk of mortality and unsuppressed viral load for participants who initiated or continued HAART. Iron supplement use was associated with reduced mortality risk but also had a greater risk of an unsuppressed viral load among participants continuing HAART. There was no association of iron supplement use with mortality, and unsuppressed viral load among PLHIV that were initiating HAART. There was a stronger negative association between iron supplement use and the risk of having an unsuppressed viral load among participants with stage III/IV disease compared with stage I/II disease. ConclusionsAnemia is associated with increased risk of mortality and unsuppressed viral load, but the benefits and safety of iron supplements appear to differ for those initiating compared with continuing ART as well as by HIV disease severity.

Symptomatic human immunodeficiency virus infection is associated with advanced presentation and perioperative mortality in patients undergoing surgery for peripheral arterial disease

ObjectivePrior studies have demonstrated an increased risk of developing cardiovascular and peripheral arterial disease (PAD) in patients with human immunodeficiency virus (HIV). However, the effect of chronic HIV infection in patients with preexisting PAD and requiring vascular intervention is unclear. In the present study, we assessed the differences in clinical presentation and perioperative outcomes for patients with PAD who had undergone revascularization or amputation with and without HIV infection. MethodsInternational Classification of Diseases, 9th and 10th Revisions, Clinical Modification, codes were used to identify patients with a prior diagnosis of PAD who had undergone lower extremity revascularization or amputation in the National Inpatient Sample (2003-2017). From this group, the patients were divided for analysis into those with and without HIV infection. Of the patients with HIV infection (PWHs), we identified additional subsets of patients: those with any prior or current diagnosis of an HIV-related illness, including acquired immunodeficiency syndrome, designated as symptomatic HIV, and those without such a diagnosis, designated as asymptomatic HIV infection. Propensity score matching was performed to create matched cohorts. Population-based comparative analyses were performed of the clinical characteristics of the HIV-infected and HIV-uninfected groups. Univariate and multivariate logistic regression analyses of the perioperative in-hospital outcomes were performed on the matched cohorts. ResultsA total of 224,912 patients aged 18 to 85 years were identified who had been admitted with an established diagnosis of PAD and had undergone a lower extremity procedure. Of these patients, 1264 (0.56%) also had a diagnosis of HIV infection. Symptomatic PWHs were more likely to present with critical limb ischemia than were the HIV-uninfected patients or asymptomatic PWHs (66.2% vs 46.3% and 43.6%; P < .01). However, both asymptomatic and symptomatic PWHs were more likely to have required minor (7.5% and 6.7% vs 2.6%; P < .01) and major (12.9% and 27.4% vs 7.0%; P < .01) amputations than were matched HIV-uninfected controls. Although adjusted multivariate logistic regression analysis demonstrated symptomatic HIV infection to be a significant, independent predictor of in-hospital mortality (odds ratio, 2.46; 95% confidence interval, 1.37-4.40; P = .003), the perioperative mortality for the asymptomatic PWH was comparable to that of matched HIV-uninfected controls. ConclusionsSymptomatic PWHs, including patients living with acquired immunodeficiency syndrome, who had required a PAD-related procedure had presented with more advanced vascular disease and were most at risk of early perioperative mortality. However, the presentation and mortality between asymptomatic PWHs with well-controlled disease and HIV-uninfected patients were comparable. All PWHs with PAD were more likely to undergo lower extremity amputations than were HIV-uninfected matched controls. Asymptomatic, well-controlled HIV infection should not be a contraindication to elective PAD-related procedures because the mortality was similar to that of HIV-uninfected controls. However, the limb salvage rates might be lower for all PWHs with PAD, regardless of HIV disease severity. Taken together, these findings can improve perioperative risk stratification and surgical management of PAD in this high-risk population.

Trends in Bacterial Vaginosis Prevalence in a Cohort of U.S. Women with and at Risk for HIV.

Background: Women with human immunodeficiency virus (HIV) often have bacterial vaginosis (BV). The goal of this analysis was to assess how BV prevalence changed over time and across U.S. regions in enrollment cohorts of the Women's Interagency HIV Study. Methods: In a multisite study, BV was diagnosed retrospectively when pH and two of three other Amsel criteria were met. Prevalence was determined across four recruitment waves: 1994-5, 2001-2, 2011-2, and 2013-5. Generalized estimating equation multivariable logistic regression models assessed changes in visit prevalence across waves after controlling for HIV disease severity and other risks. Results: Among 4,790 women (3,539 with HIV and 1,251 without HIV), BV was diagnosed at 7,870 (12%) of 64,444 visits. Baseline prevalence across enrollment waves was 15.0%-19.2%, but declined in all cohorts, with prevalence in the initial cohort falling to 3.9% in the 1994-5 cohort after up to 21 years of continuous observation. Prevalence varied within U.S. regions. HIV status was not associated with BV. Conclusion: BV prevalence decreased with time in study. Prevalence varied across sites, but was not uniformly increased or decreased in any U.S. region. Clinical Trials.gov identifier: NCT00000797.

The associations of population mobility in HIV disease severity and mortality rate in China.

BackgroundHuman immunodeficiency virus (HIV) infection has become a chronic disease and attracted public attention globally. Population migration was considered hindering the control and management of HIV infection, but limited studies have explored how population mobility could influence the development of HIV-related complications and overall prognosis.MethodsWe enrolled hospitalized HIV patients in this cross-sectional study between January 1, 2006, and December 31, 2016. We extracted demographic, hospitalization, and patient diagnosis data. Patients were divided into three groups according to the population type: (I) resident of Guangzhou City (local resident); (II) migrant outside of Guangzhou City but within Guangdong Province (migrant within the province); and (III) migrant outside of Guangdong Province (migrant outside the province). To represent the prognosis of HIV, in-hospital death was defined as the worst outcome, whereas vision-related events were considered moderate-to-severe complications. Logistic regression models were used to analyze factors influencing the prognosis of HIV.ResultsEight thousand and six hundred thirty-one inpatients (14,954 cases) were enrolled. The overall mortality was 7.9%, decreasing from 21.5% in 2006 to 3.8% in 2016. The prevalence of vision-related events was 14.4% between 2015 and 2016. Compared to local patients, migrant patients (within and outside the province) were younger, had significantly less access to health insurance, fewer hospitalization admissions, longer hospital stays, and a higher proportion of physical work (P<0.01). Furthermore, they had a higher prevalence of vision-related events (16.2% and 17.4% in migrant patients within the province and outside the province, respectively vs. 9.5%) and infectious diseases, but lower in-hospital mortality (5.9% and 7.0% vs. 12.3%) than local patients. Migrants correlated negatively with in-hospital death [odds ratio (OR) 95% CI, 0.37 (0.29–0.48) and 0.52 (0.40–0.68)] but correlated positively with vision-related events [OR (95% CI), 2.08 (1.54–2.80) and 2.03 (1.47–2.80)].ConclusionsMigrant patients have significantly poorer access to health insurance, with an increased risk of developing moderate-to-severe HIV infection but a decreased risk of in-hospital death, indicating a trend toward withdrawing treatment in migrant patients when they have advanced diseases. Managements such as optimizing access to health insurance and improving follow-up visits for HIV infection should be considered in the context of the population mobility of HIV patients.

Prevalence of Vitamin B12deficiency in antiretroviral therapy naïve adults with human immunodeficiency virus infection in a human immunodeficiency virus treatment center in Lagos, Nigeria

Background: Vitamin B12 deficiency is reportedly higher in human immunodeficiency virus (HIV) infection, according to reports from developed countries and is associated with worsening anemia, progressing immunodeficiency (reduced CD4 count), and reduced survival rates. The status in Nigerians with HIV has not been extensively studied. The objective of the study was to determine the frequency and correlates of Vitamin B12 deficiency in HIV-positive antiretroviral therapy (ART) naive patients attending an outpatient HIV clinic in Lagos, Nigeria. Specifically, the study compared HIV-positive ART-naïve patients to age- and gender-matched HIV-negative controls and determined the relationship between B12 status and HIV disease severity (CD4 count) and hemoglobin (Hb). Methodology: The study was a descriptive study of the prevalence of Vitamin B12 deficiency and its correlation with disease severity in HAART-naïve newly diagnosed HIV infection. Seventy-five ART naïve, HIV-positive patients and 75 controls fulfilling the study criteria were included. Baseline hematologic (Hb, white blood cell, platelets, and CD4 count) and Vitamin B12 levels were measured. Vitamin B12 levels were measured using urine methylmalonic acid (MMA) on spot urine normalized for urine creatinine. B12 deficiency was defined as urine MMA >3.6 mmol/mol urinary creatinine. CD4 count (cells/μL) was categorized as <200, 200–499, and >500. Results: The frequency of B12 deficiency was 29.3% (22/75) in HIV-positive cases and 0% (0/75) in controls (P < 0.001). There was no difference in the frequency of anemia in HIV cases with or without B12 deficiency (54.5% vs. 58.5%; P = 0.75). There was no significant difference in the proportions of HIV cases with or without B12 deficiency in the CD4 categories 1 (>500), 2 (200-499) and 3 (<200), (1: 31.8% vs. 24.5%; 2: 40.9% vs. 50.9%; 3: 27.5% vs. 24.5%, respectively; P = 0.71). Neither severity of HIV infection nor Hb levels was found to be associated with B12 status (P > 0.05). Conclusion: Vitamin B12 deficiency was more prevalent in HIV-positive ART naïve cases compared to age- and gender-matched HIV-negative controls. However, the presence of B12 deficiency was not associated with anemia or the severity of HIV infection in this study.

SAT-050 Low Serum Testosterone (T) Is Associated with Poor Health Status in Young to Middle-Aged Human Immunodeficiency Virus (HIV)-Infected Men

BACKGROUND: The relationship between health status, defined by frailty and comorbidities, and serum T levels has been widely demonstrated in general population, while only one previous retrospective study has explored it in HIV-infected men1. AIM: To investigate the association between frailty and gonadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS: Prospective, cross-sectional, observational study on HIV-infected men (age <50 years) with ongoing Highly Active Antiretroviral Therapy. Serum TT was assessed by the gold standard ID-LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent immunoassay. Calculated free T (cFT) was obtained by Vermeulen equation. Multimorbidity was defined as at least 3 comorbid conditions, including: hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, osteoporosis, chronic viral hepatitis and cancers. Frailty was calculated through the validated 37-item frailty index (FI)2. Patients with FI>0.21 were considered frail. Statistical analysis: Mann-Whitney U test was used to compare continuous variables. Correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.3±5.3 years; average duration of HIV-infection 16.3±8.8 years). 128 patients (40.5%) were comorbid and 207 (64.9%) were frail. Either cFT (p=0.001) or TT (p<0.001) were lower in comorbid patients than others. FT was inversely related to the number of comorbidities (p<0.001, R2=0.045). Accordingly, cFT (p=0.003) and TT (p<0.001) were significantly lower in frail patients. Frailty score was inversely correlated with cFT (p<0.001, R2=0.058), TT (p=0.041, R2=0.014) and SHBG (p=0.003, R2=0.029). However, after adjustment for age and duration of HIV-infection, cFT, TT and SHBG were excluded from the regression model. CONCLUSIONS: Low cFT and TT levels are associated with multimorbidity and poor health status in HIV infected men. The bidirectional nature of this relationship leads to the figuration of an intriguing vicious circle where T deficiency triggers the onset of comorbidities or, vice versa, poor health status induces hypogonadism. At the same time, notwithstanding the inverse relation between FT and frailty, it seems that other stronger predictive factors, and in particular the duration of infection, are involved in determining the health outcome in this clinical setting.REFERENCES 1Rochira V et al. Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology. 2015 Mar;3(2):298-308. 2Guaraldi et al. A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity. AIDS. 2015 Aug 24;29(13):1633-41.

PB2039 PLATELET INDICES, COAGULATION BIOMARKERS AND CARDIOVASCULAR RISK FACTORS IN TREATMENT‐NAÏVE HIV‐INFECTED ADULTS IN LAGOS UNIVERSITY TEACHING HOSPITAL

Background:With the use of antiretroviral therapy, the incidence of AIDS‐defining illnesses and opportunistic infections has reduced significantly, leading to increased life span of human immunodeficiency virus (HIV)‐infected individuals. Non‐infectious causes of morbidity and mortality, including cardiovascular diseases, have since emerged. Platelet indices and coagulation biomarkers are surrogate markers of cardiovascular risk in several disease conditions but their relevance in HIV infection is uncertain.Aims:The aim of this study was to evaluate platelet indices and coagulation biomarkers in untreated HIV infection and to determine their relationship with HIV disease severity and cardiovascular risk factors.Methods:A cross‐sectional study of 115 treatment‐naïve HIV‐infected adult patients attending the HIV clinic of the Lagos University Teaching Hospital and 115 age‐ and gender‐matched non‐infected adults was carried out. Socio‐demographic characteristics and history of cardiovascular risk factors were obtained from all participants, followed by body mass index (BMI) and blood pressure measurements and World Health Organization (WHO) clinical staging of the HIV‐infected subjects.Laboratory evaluation of full blood count, including platelet indices; platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT), CD4+ T lymphocyte count, fasting lipid profile, fasting plasma glucose, fibrinogen and D‐dimer levels were done for all participants.Results:The HIV‐infected group had significantly higher MPV (9.2 ± 1.0fL vs.8.5 ± 0.8 fL, P &lt; 0.01), PDW (15.7 ± 0.4% vs.15.6 ± 0.4%, P = 0.01), PCT (0.236 ± 0.095% vs. 0.201 ± 0.051%, P &lt; 0.01) and fibrinogen levels (250.2 ± 93.4 mg/dL vs. 193.6 ± 46.8 mg/dL, P &lt; 0.01) than the non‐infected group. There was no significant difference in the platelet count [244 (187‐305) vs. 241 (192‐271) x109/L, P = 0.31] and D‐dimer levels [395.08 (303.23‐519.45) vs. 399.42 (316.35‐483.58) ng/mL, P = 0.96) between the HIV‐infected subjects and the non‐infected controls.The CD4+ T lymphocyte count inversely correlated with PDW (r = ‐0.248, P &lt; 0.01) and fibrinogen levels (r = ‐0.229, P = 0.01) while the WHO clinical stage directly correlated with fibrinogen levels (r = 0.193, P = 0.04) in the HIV‐infected subjects. Lower BMI was associated with higher PLT (β = ‐0.258, P &lt; 0.01) and PCT (β = ‐0.278, P &lt; 0.01) while higher triglyceride (β = 0.292, P &lt; 0.01) and HDL‐cholesterol levels (β = 0.213, P = 0.04) were associated with higher PDW in the HIV‐infected subjects. Diabetes was associated with higher fibrinogen levels in the HIV‐infected subjects (β = 0.276, P &lt; 0.01).Summary/Conclusion:Platelet indices and fibrinogen levels are increased in HIV infection. Platelet distribution width and fibrinogen levels increase with HIV disease severity. Cardiovascular risk factors including diabetes mellitus and dyslipidaemia are associated with increase in platelet indices and fibrinogen levels in HIV infection.image

Understanding the association between chromosomally integrated human herpesvirus 6 and HIV disease: a cross-sectional study.

We conducted a cross-sectional investigation to identify evidence of a potential modifying effect of chromosomally integrated human herpes virus 6 (ciHHV-6) on human immunodeficiency virus (HIV) disease progression and/or severity. ciHHV-6 was identified by detecting HHV-6 DNA in hair follicle specimens of 439 subjects. There was no statistically significant relationship between the presence of ciHHV-6 and HIV disease progression to acquired immunodeficiency syndrome. However, after adjusting for use of antiretroviral therapy, all subjects with ciHHV-6 had low severity HIV disease; these findings were not statistically significant. A multi-center study with a larger sample size will be needed to more precisely determine if there is an association between ciHHV-6 and low HIV disease severity.

Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease.

Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

The ABCs of Trait Anger, Psychological Distress, and Disease Severity in HIV.

Trait anger consists of affective, behavioral, and cognitive (ABC) dimensions and may increase vulnerability for interpersonal conflict, diminished social support, and greater psychological distress. The concurrent influence of anger and psychosocial dysfunction on Human Immunodeficiency Virus (HIV) disease severity is unknown. The purpose of this study was to examine plausible psychosocial avenues (e.g., coping, social support, psychological distress), whereby trait anger may indirectly influence HIV disease status. Three hundred seventy-seven HIV seropositive adults, aged 18-55 years (58% AIDS-defined), completed a battery of psychosocial surveys and provided a fasting blood sample for HIV-1 viral load and T lymphocyte count assay. A second-order factor model confirmed higher levels of the multidimensional anger trait, which was directly associated with elevated psychological distress and avoidant coping (p<.001) and indirectly associated with greater HIV disease severity (p<.01) (comparative fit index (CFI)=0.90, root-mean-square error of approximation (RMSEA)=0.06, standardized root-mean-square residual (SRMR)=0.06). The model supports a role for the ABC components of anger, which may negatively influence immune function through various psychosocial mechanisms; however, longitudinal study is needed to elucidate these effects.

Understanding the association between chromosomally integrated human herpesvirus 6 and HIV disease: a cross-sectional study

We conducted a cross-sectional investigation to identify evidence of a potential modifying effect of chromosomally integrated human herpes virus 6 (ciHHV-6) on human immunodeficiency virus (HIV) disease progression and/or severity. ciHHV-6 was identified by detecting HHV-6 DNA in hair follicle specimens of 439 subjects. There was no statistically significant relationship between the presence of ciHHV-6 and HIV disease progression to acquired immunodeficiency syndrome. However, after adjusting for use of antiretroviral therapy, all subjects with ciHHV-6 had low severity HIV disease; these findings were not statistically significant. A multi-center study with a larger sample size will be needed to more precisely determine if there is an association between ciHHV-6 and low HIV disease severity.

Understanding the association between chromosomally integrated human herpesvirus 6 and HIV disease: a cross-sectional study

We conducted a cross-sectional investigation to identify evidence of a potential modifying effect of chromosomally integrated human herpes virus 6 (ciHHV-6) on human immunodeficiency virus (HIV) disease progression and/or severity. ciHHV-6 was identified by detecting HHV-6 DNA in hair follicle specimens of 439 subjects. There was no statistically significant relationship between the presence of ciHHV-6 and HIV disease progression to acquired immunodeficiency syndrome. However, after adjusting for use of antiretroviral therapy, all subjects with ciHHV-6 had low severity HIV disease; these findings were not statistically significant. A multi-center study with a larger sample size will be needed to more precisely determine if there is an association between ciHHV-6 and low HIV disease severity.

Apolipoprotein-E genotype and human immunodeficiency virus-associated neurocognitive disorder: the modulating effects of older age and disease severity.

The apolipoprotein-E (APOE) ε4 allele is a risk factor for vascular dementia and Alzheimer's disease. Recent studies are equivocal with regards to whether or not the ε4 allele confers increased risk for the development of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), but suggest that age and/or disease severity may be modulating factors. The aim of this study was to assess the interactions and contributions of APOE genotype, age, and HIV disease severity as risk factors for HAND in HIV-infected adults. Participants were 259 HIV-positive individuals who underwent APOE genotyping, a standardized neurological evaluation, a comprehensive neuropsychological evaluation, and laboratory testing. Older ε4 carriers showed a higher frequency of HAND compared with age-matched non-ε4 carriers. Analysis by discrete neurocognitive domain revealed that advanced age modulated the effect of the ε4 allele, such that older ε4 allele carriers showed reduced executive functioning and information processing speed. Exploratory analyses assessing the relationship between ε4 and disease severity in the overall sample revealed that disease severity modulated the effect of the ε4 allele on cognition. Lower absolute CD4+ cell count among ε4 allele carriers was associated with poorer working memory ability. Advancing age and degree of immunosuppression may influence the association between APOE ε4 allele status and HAND. These two factors need to be taken into account in future research.

A Case-Controlled Study of Successful Aging in Older HIV-Infected Adults

There is a growing public health interest in the aging human immunodeficiency virus (HIV)-infected (HIV+) population, although there is a dearth of research on successful aging with HIV. This study aimed to understand the risk and protective factors associated with self-rated successful aging (SRSA) with HIV. Cross-sectional, case-controlled. HIV Neurobehavioral Research Program and the Stein Institute for Research on Aging at University of California, San Diego. Eighty-three community-dwelling HIV+ and 83 demographically matched HIV-uninfected (HIV-) individuals, enrolled between December 1, 2011, and May 10, 2012, mean age of 59 years, primarily white men, 69% with acquired immune deficiency syndrome (AIDS), who had been living with an HIV diagnosis for 16 years. Diagnostic criteria for HIV/AIDS were obtained through a blood analysis. Participants provided ratings of SRSA, the primary outcome measure, as part of a comprehensive survey that included measures of physical and emotional functioning and positive psychological traits. Relationships between how the different variables related to SRSA were explored. While SRSA was lower in the HIV+ individuals than their HIV- counterparts, 66% of adults with HIV reported scores of 5 or higher on a 10-point scale of SRSA. Despite worse physical and mental functioning and greater psychosocial stress among the HIV+ participants, the 2 groups had comparable levels of optimism, personal mastery, and social support. Higher SRSA in HIV+ individuals was associated with better physical and emotional functioning and positive psychological factors, but not HIV disease status or negative life events. Successful psychosocial aging is possible in older HIV+ individuals. Positive psychological traits such as resilience, optimism, and sense of personal mastery have stronger relationship with SRSA than duration or severity of HIV disease. Research on interventions to enhance these positive traits in HIV+ adults is warranted.

Atrial Fibrillation and Atrial Flutter in Human Immunodeficiency Virus-Infected Persons: Incidence, Risk Factors, and Association With Markers of HIV Disease Severity

The purpose of this study was to investigate the associations of traditional risk factors and longitudinal measures of human immunodeficiency virus (HIV) disease severity with risk of incident atrial fibrillation (AF) in a contemporary cohort of HIV-infected individuals. Cardiovascular disease is common in HIV-infected persons; however, the most common cardiac arrhythmia, AF, has not been adequately studied in this population. We studied a national sample of 30,533 HIV-infected veterans followed in the Veterans Affairs HIV Clinical Case Registry from 1996 to 2011. We examined the independent associations of demographic characteristics, time-updated comorbidities, and time-updated clinical measurements including CD4(+) cell count and viral load with the outcome of incident AF using proportional hazards regression for multivariable analysis. Over a median follow-up of 6.8 years, 780 (2.6%) patients developed AF. After multivariable adjustment for traditional risk factors, a lower CD4(+) cell count (<200 compared with >350 cells/mm(3); hazard ratio [HR]: 1.4; 95% confidence interval [CI]: 1.1 to 1.8; p= 0.018) and higher viral load (>100,000 compared with<500 copies/ml; HR: 1.7; 95% CI: 1.2 to 2.4; p= 0.002) were independently associated with increased risk of incident AF. Additional risk factors independently associated with risk of AF included older age, White race, coronary artery disease, congestive heart failure, alcoholism, proteinuria, reduced kidney function, and hypothyroidism. In a large HIV-infected cohort, markers of HIV disease severity represented by low CD4(+) cell count and high viral load, assessed by multiple time-updated measures, were independently associated with development of AF.

Human Immunodeficiency Virus Disease Severity, Psychiatric Symptoms, and Functional Outcomes in Perinatally Infected Youth

To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. Cross-sectional analysis of entry data from an observational,prospective 2-year study.Logistic and linear regression models adjusted for potential confounders were used. Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. Youth aged 6 to 17 years who had HIV infection (N=319). Antiretroviral treatment and perinatal HIV infection. Youth and primary caregivers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social,and academic functioning; and quality of life. Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms,older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms,higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage atstudy entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms.A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic,and social functioning, all of which warrant additional study.

Immunogenicity and Safety of 1 vs 2 Doses of Quadrivalent Meningococcal Conjugate Vaccine in Youth Infected with Human Immunodeficiency Virus

To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥ 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥ 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥ 15. Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. In youth infected with HIV with a CD4% ≥ 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.

Risk Factors for the Development of Atrial Fibrillation in HIV Infected Patients.

Background: Patients with Human Immunodeficiency Virus (HIV) have an array of multi-organ involvement, including cardiovascular disease. CD4 count is one of the best parameters to monitor the severity of HIV disease. The arrythmogenic potential of HIV disease has not been well defined. The aim of the study is to establish whether an association between the severity of HIV and atrial fibrillation (AF) exists. Methods: Out of a retrospective cohort of 780 HIV patients from January 2006 to December 2008, 40 patients were selected that developed AF during this period .The age and sex matched controls (n=40) were selected for comparison. The comparison between both groups was done using Fischer Exact Test. Bivariate and multivariate analysis was also performed to analyze the results. Results: The data shows that 47%(19/40) of the patients with HIV who developed AF had CD4 count lower than 250 as compared to 20%(8/40) in the control group (P value = 0.017) Conclusion: The data supports the presence of a relationship between HIV and AF. Patients with lower CD4 counts are more susceptible to develop AF.