Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

Identifying cardiovascular disease risk and outcome: use of the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio versus metabolic syndrome criteria.

BACKGROUND: Metabolic syndrome (MetS) has been shown to predict both risk and CVD events. We have identified sex-specific values for the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio associated with an unfavourable cardio-metabolic risk profile, but it is not known whether it also predicts CVD outcome. METHODS: To quantify risk for CVD outcomes associated with a high TG/HDL-C ratio and to compare this risk with that predicted using MetS, a population longitudinal prospective observational study was performed in Rauch City, Buenos Aires, Argentina. In 2003 surveys were performed on a population random sample of 926 inhabitants. In 2012, 527 women and 269 men were surveyed again in search of new CVD events. The first CVD event was the primary endpoint. Relative risks for CVD events between individuals above and below the TG/HDL-C cut-points, and with or without MetS, were estimated using Cox proportional hazard. MAIN OUTCOME: The first CVD event was the primary endpoint. Relative risks for CVD events between individuals above and below the TG/HDL-C cut-points, and with or without MetS, were estimated using Cox proportional hazard. RESULTS: The number of subjects deemed at 'high' CVD risk on the basis of an elevated TG/HDL-C ratio (30%) or having the MetS (35%) was relatively comparable. The unadjusted hazard risk was significantly increased when comparing 'high' versus 'low' risk groups no matter which criteria was used, although it was somewhat higher in those with the MetS (HR = 3.17, 95% CI:1.79-5.60 vs. 2.16, 95% CI:1.24-3.75). However, this difference essentially disappeared when adjusted for sex and age (HR = 2.09, 95% CI:1.18-3.72 vs. 2.01, 95% CI:1.14-3.50 for MetS and TG/HDL-C respectively). CONCLUSIONS: An elevated TG/HDL-C ratio appears to be just as effective as the MetS diagnosis in predicting the development of CVD.

Should the first blood pressure reading be discarded?

We evaluated the consequences of excluding the first of three blood pressure (BP) readings in different settings: a random population sample (POS, n=1525), a general practice office (GPO, n=942) and a specialized hypertension center (SHC, n=462). Differences between systolic and diastolic BP (SBP and DBP) estimates obtained including and excluding the first reading were compared and their correlation with ambulatory BP monitoring (ABPM) was estimated. The samples were divided into quartiles according to the difference between the third and the first SBP (3-1ΔSBP). SBP decreased through sequential readings, 3-1ΔSBP was -5.5 ± 9.7 mm Hg (P<0.001), -5.1 ± 10.4 mm Hg (P<0.001) and -6.1 ± 9.3 mm Hg (P<0.001) for POS, GPO and SHC, respectively. However, individuals included in the top quartile of 3-1ΔSBP showed their highest values on the third reading. The mean SBP estimate was significantly higher excluding the first reading (P<0.001), but the differences among both approaches were small (1.5-1.6 mm g). Moreover, the correlation between SBP values including and excluding the first reading and daytime ABPM were comparable (r = 0.69 and 0.68, respectively). Similar results were observed for DBP. In conclusion, our study does not support the notion of discarding the first BP measurement and suggests that it should be measured repeatedly, regardless the first value.

Relative preservation of natural killer cell cytotoxicity and number in healthy AIDS patients with low CD4 cell counts.

OBJECTIVE: This study examines whether there may be an immune component that protects a relatively rare group of HIV-infected people with very low CD4 cell counts (< or = 50 x 10(6)/l) who have prolonged asymptomatic periods. DESIGN/METHODS: Three groups were recruited in Miami: (i) healthy low CD4 cell count patients (HLC; n = 30) who, for 9 months had < 50 x 10(6) CD4 cells/l, were asymptomatic and were not on protease inhibitors during that time; (ii) HIV comparison group (Comp; n = 60) who had CD4 cell counts predominantly 150 x 10(6) to 400 x 10(6)/l and never had AIDS Category C symptoms; this group was also followed for CD4 cell count and viral load change over 6 months; and (iii) healthy community controls (n = 33). The study was replicated at the University of California at Los Angeles (UCLA) with HLC (n = 31) versus HIV-negative laboratory controls (n = 28). RESULTS: The HLC patients were significantly higher than the Comp group on natural killer cell cytotoxicity (NKCC) and natural killer cell number (NK#) despite their lower CD4 cell numbers and higher viral loads. In fact, there was no difference between the HLC group and the healthy community control group in NK# or NKCC. The NK findings were replicated at UCLA. A retrospective analysis showing that higher NKCC was related to fewer prior symptoms in the HLC group, and prospective analysis in the Comp group showing that NK# predicted a lower increase in viral load over 6 months further supported the importance of NK# and NKCC. CONCLUSIONS: Non-specific cellular immunity may be a factor protecting the health of HIV sero-positive individuals with very low CD4 cell counts.

Stress and coping: the psychoneuroimmunology of HIV/AIDS.

A considerable body of evidence, reviewed in this chapter, suggests that psychosocial factors play an important role in progression of HIV infection, its morbidity and mortality. Psychosocial influences relating to faster disease progression include life-event stress, sustained depression, denial/avoidance coping, concealment of gay identity (unless one is rejection-sensitive), and negative expectancies. Conversely, protective psychosocial factors include active coping, finding new meaning, and stress management. In studying long survivors of HIV/AIDS, our group has found protective effects on health of life involvement, collaborative relationship with doctor, emotional expression, depression (conversely), and perceived stress (conversely). Reviewed and discussed are psychoneuroimmunological pathways by which immune and neuroendocrine mechanisms might link psychosocial factors with health and long survival. Finally, biological factors are also a major determinant of disease progression and include genetics and age of the host, viral strain and virulence, medication and several immune response factors on which psychosocial influences could impact.