Skip to main content

The relationship of hair glucocorticoid levels to immunological and virological outcomes in a large cohort of combination antiretroviral therapy treated people living with HIV

Abstract

Background

Existing literature mostly investigated the relationship of acute or short-term glucocorticoid exposure to HIV disease progression using cortisol levels in serum, saliva, or urine. Data are limited on the relationship of long-term glucocorticoid exposure to HIV disease progression. This study examined whether hair glucocorticoid levels, novel retrospective indicators of long-term glucocorticoid exposure, are associated with two common indicators of HIV disease progression (CD4 count and HIV viral load) among a large cohort of combination antiretroviral therapy treated Chinese people living with HIV (PLHIV).

Methods

A total of 1198 treated PLHIV provided hair samples for glucocorticoid (cortisol and cortisone) assay and completed a survey assessing sociodemographic, lifestyle, and HIV-related characteristics. Meanwhile, CD4 count and HIV viral load were retrieved from their medical records. Spearman correlation was used to examine the associations of hair cortisol and cortisone levels to continuous CD4 count and HIV viral load. Multivariate logistic regression was used to predict CD4 count < 500 cells/mm3.

Results

Both hair cortisol and cortisone levels were negatively associated with CD4 count but not with HIV viral load. The odds ratio for CD4 count < 500 cells/mm3 was 1.41 [95% CI 0.99–2.00] and 2.15 [95% CI 1.51–3.05] for those with hair cortisol and cortisone levels in the highest quartile compared to the lowest when controlling for sociodemographic, lifestyle, HIV-related covariates, and HIV viral load.

Conclusion

Hair glucocorticoid levels were associated with CD4 count but not viral load in treated Chinese PLHIV. Our data furtherly supported the hypothesis that elevated glucocorticoid levels are associated with the lower CD4 count.

Peer Review reports

Background

With the help of combination antiretroviral therapy (cART), HIV has shifted from a terminal illness with high mortality to chronic disease [1], and people living with HIV (PLHIV) have a nearly normal life expectancy when given access to adequate cART [2]. However, HIV disease progression on an individual basis varies widely. While the HIV disease progression is influenced by various factors, activation of the hypothalamic–pituitary–adrenal (HPA) axis, resulting in elevated glucocorticoid levels, has been proposed as one of the critical pathways to hasten HIV disease progression. Theoretically, high glucocorticoid levels could induce T-lymphocyte production of cytokines, trigger the destruction of CD4 T cell (CD4) through programmed cell death and bolster HIV viral replication [3, 4].

Several studies have examined whether cortisol (active glucocorticoid) levels are associated with indicators of HIV disease progression among PLHIV. However, the findings are inconsistent, with some studies found that elevated cortisol levels were associated with indicators of HIV disease progression [5,6,7,8,9,10,11], whereas other studies suggested no such association [12,13,14,15,16,17,18,19,20]. Previous studies used acute or short-term cortisol levels in liquid biological samples (e.g., serum, saliva, or urine). These measurements reflect cortisol levels of that specific time window varying from a few minutes (single-point blood and saliva sample) up to a maximum of 24 h (multi-point saliva and urine sample), which may not well-match the etiology of chronic disease progression. In addition, cortisol levels in these liquid biological samples showed significant circadian rhythm and were easily affected by state reactivity. Recently, several studies used cortisol levels in hair among PLHIV [21,22,23,24]. In comparison with cortisol levels in liquid biological samples, cortisol levels in hair can better estimate long-term cortisol exposure (weeks to months) [25]. To the best of our knowledge, only two published studies reported additional data about the relationship between hair cortisol levels and two common indicators of HIV disease progression (CD4 count and HIV viral load), and a nonsignificant association was found [21, 23]. The two previous studies are limited in enrolling small sample size participants and not considering some potential factors related to hair cortisol levels (e.g., hair washing). Thus, a study of hair cortisol levels and HIV disease progression in a large cohort of PLHIV is warranted, further considering potential confounders.

Recently, hair cortisone levels have been served as a useful additional biomarker for assessing long-term glucocorticoid exposure. As well known, circulating cortisol levels are dynamically regulated partially through the activity of the 11β hydroxysteroid dehydrogenase (11β-HSD) enzyme, where cortisol is converted to cortisone by the activity of 11β-HSD type 2 enzyme, and cortisone can be regenerated from cortisol by the activity of 11β-HSD type1 enzyme [26]. Therefore, cortisol and cortisone could regulate physiological and psychological responses together [27, 28]. However, it is unknown about hair cortisone levels in PLHIV and their relationship with indicators of HIV disease progression.

Accordingly, to extend knowledge on the associations of long-term glucocorticoid levels with HIV disease progression, we assessed hair cortisol and cortisone levels and two common indicators of HIV disease progression (CD4 count and HIV viral load) in a large cohort of cART treated Chinese PLHIV in Guangxi, China. We aimed to examine whether hair cortisol and cortisone levels were associated with those indicators of HIV disease progression when controlling for potential confounders, including sociodemographic, lifestyle, and HIV-related characteristics.

Methods

Participants

Participants were recruited from November 2017 to February 2018 as part of a longitudinal HIV stigma project, which aimed to investigate the effect of HIV-related stigma on clinical outcomes in Guangxi, China [29, 30]. In collaboration with the Guangxi center for disease control and prevention (CDC), PLHIV, who aged 18 years, willing to provide hair samples and retrieve virologic and immunological outcomes from their medical record, were eligible for participation. PLHIV with any of the following characteristics were excluded: (1) linguistic, mental or physical inability to respond to assessment questions; (2) opportunistic infections or endocrine diseases (e.g., Cushing’s syndrome); (3) currently taking hormonal medications (e.g., oral contraceptive) or known history of illegal drug use; (4) chemical hair treated (e.g., dyed, permed, or bleached) or scalp hair in the posterior vertex was less than 1 cm.

Medical staff or HIV case managers at the study sites referred potential participants to the research team members. PLHIV were checked for eligibility, informed of the study's benefits and risks, and invited to the study when they finished their routine visit. Research team members were local CDC staff or health care workers in the HIV clinics who had received intensive training on research ethics and interview skills with PLHIV before the field data and hair specimen collection. Finally, a total of 1198 PLHIV participated in this study.

Hair and data collection

Hair samples were cut from the posterior vertex region as close as possible to the scalp following a standard protocol [31, 32] in private rooms of local CDC or HIV clinics. The hair thatch then was completely enclosed by a piece of foil, and a small label indicating the study ID number was placed over the distal end of the hair thatch. Then, the interviewer-administered questionnaire was used for the collection of sociodemographic and lifestyle information. Each participant received compensation for their time spent to respond to the questionnaire and to provide hair samples with a value equal to $5.00 (≈ 35 Chinese Yuan) after finishing the survey.

Hair cortisol and cortisone

The proximal 1 cm of hair segments (approximately reflecting the last month of accumulative cortisol and cortisone levels) was cut finely with scissors, and 20 mg processed and analyzed using liquid chromatography-tandem mass spectrometry (LC/MS/MS) followed the protocol described by Gao and colleagues [33]. The method showed excellent linearity (R2 > 0.99) in the range of 0.5–1250 pg/mg for both cortisol and cortisone, the limits of detection and quantitation at 0.2 pg/mg and at 0.5 pg/mg for both cortisol and cortisone, respectively. Intra-day and inter-day percentage coefficients of variation were less than 5% at standard concentrations of 1.25, 25, and 250 pg/mg, and recovery ranged between 95 and 107% for both cortisol and cortisone.

CD4 count and HIV viral load

CD4 count and HIV viral load data were extracted from their clinical records after their routine visit. Given that CD4 count and HIV viral load data are generally skewed, CD4 count was dichotomized as ≥ 500 cells/mm3 vs. < 500 cells/mm3 because the low limit of CD4 count is 500 cells/mm3 in healthy adults. HIV viral load was dichotomized as ≥ 200 copies/ml vs. < 200 copies/ml because the “Undetectable = Untransmittable” initiative defined undetectable viral load as viral load less than 200 copies/ml that cannot sexually transmit HIV to others [34].

Sociodemographic, lifestyle, and other HIV-related characteristics

Participants provided information on their sociodemographic and lifestyle characteristics that might have a potential influence on hair cortisol and cortisone levels [35,36,37], including age, gender, ethnicity, marital status, education level, employment status, monthly household income level, height, weight, smoking status, drinking status and frequency of hair washing. Body Mass Index (BMI) was calculated using an established formula BMI = weight (kg)/ [height (m)]2 based on weight and height for each participant.

Years of HIV diagnosis, current cART status (first-line vs. second-line), and years of current cART were also extracted from their clinical records. cART adherence (≥ 95% vs. < 95%) was measured using the single-item question: “In last month, how many days were you able to take your medications exactly as prescribed?” Adherence was calculated by dividing the reported number of days by 30 days [38].

Statistical analyses

Of the 1198 PLHIV, one participant was excluded due to insufficient weight of hair samples (less than 20 mg) for cortisol assaying, and six participants were excluded because of unavailable hair cortisol levels due to the analysis mistake, leaving an effective sample of 1191 participants for analysis.

As indicated by the Kolmogorov–Smirnov test, continuous hair cortisol, hair cortisone, CD4 count, or HIV viral load was not the normal distribution, then Spearman’s correlation was used to examine the associations of continuous hair cortisol and hair cortisone levels with continuous CD4 count and HIV viral load. Logistic regression models were used to estimate the association of hair cortisol and cortisone levels with CD4 count < 500 cells/mm3 but not HIV viral load ≥ 200 copies/ml because the number of viremic participants is very low (n = 35, 2.9%). Hair cortisol and cortisone levels quartiles were calculated, and the second, third, and fourth quartiles were contrasted with the first quartile as the reference category. Crude odds ratios (cOR) and their 95% confidence interval (95%CI) were reported for univariate analysis. Adjusted odds ratios (aOR) and their 95% CI were derived from multivariate analyses after controlling for sociodemographic, lifestyle, and HIV-related characteristics, including HIV viral load. All analyses were performed using SPSS for Windows, version 26 (IBM, Chicago, Illinois).

Results

Of the 1191 participants with a median age of 38 years (Table 1), 64.3% were male, 65.1% were Han ethnicity, 56.6% were married, 81.6% were employed, 67% were never smoking, 50.3% were never drinking, 88.2% were washing their hair less than four times per week, 79.7% were receiving the first-line cART, and 92.8% reported optimal cART adherence (≥ 95%), 2.9% had HIV viral load ≥ 200 copies/ml. Most of the participants had low income and education levels, with 60.3% reporting a monthly household income of less than 3000 Chinese Yuan (or approximately $460 during the survey) and 60.2% reporting not finishing junior high school. The median BMI was 21.29 kg/m2. The median years of HIV diagnosis and years of cART were 5.33 and 4.42 years, respectively.

Table 1 Distribution of variables in the participants (n = 1191)

The median hair cortisol levels were 28.17 pg/mg and hair cortisone levels were 27.45 pg/mg. As presented in Table 2, spearman’s correlation revealed that hair cortisol levels and hair cortisone levels were positively correlated (r = 0.226, p < 0.001); hair cortisol and cortisone levels were negatively correlated with CD4 count (r = − 0.129, p < 0.001 for hair cortisol levels; r = − 0.148, p < 0.001 for hair cortisone levels); neither hair cortisol nor cortisone levels were correlated with HIV viral load (r = 0.025, p = 0.395 for hair cortisol levels; r = − 0.025, p = 0.396 for hair cortisone levels).

Table 2 Correlation between hair cortisol, hair cortisone, CD4 count, and HIV viral load

Of 1191 PLHIV, 55.0% had CD4 count < 500 cells/mm3 (see Table1). The results of logistic regression models of CD4 count < 500 cells/mm3 are presented in Table 3. The cORs were 1.77 [95% CI 1.28–2.45] and 2.39 [95% CI 1.72–3.33] for those with hair cortisol and cortisone levels in the highest quartile compared to the lowest quartile in univariate analysis. The aORs were 1.41 [95% CI 0.99–2.00] and 2.15 [95% CI 1.51–3.05] for those with hair cortisol and cortisone levels in the highest quartile compared to the lowest quartile when controlling for sociodemographic, lifestyle, and HIV-related characteristics.

Table 3 Logistic regression models of CD4 count < 500 cells/mm3

Discussion

The central question investigated in this study was whether hair cortisol and cortisone levels, novel retrospective indicators of long-term glucocorticoid exposure, were associated with two common indicators of HIV disease progression (CD4 count and HIV viral load) among a large cohort of Chinese PLHIV. We found that hair glucocorticoid levels were negatively associated with CD4 count but not HIV viral load.

Notably, we found that hair glucocorticoid levels were negatively associated with CD4 count and the aORs for CD4 count < 500 cells/mm3 were 1.41 times and 2.15 times for those with hair cortisol and cortisone levels in the highest quartile compared to the lowest quartile. The result regarding the significant association between hair cortisol levels and CD4 count was in line with part of previous studies that also reported a negative association between CD4 count and cortisol levels in plasma and saliva [5,6,7,8,9] but differed from the results from some published studies in which a nonsignificant association was reported by using serum cortisol levels [15, 18,19,20], urinary cortisol levels [12, 13, 16, 17], or hair cortisol levels [21]. Interestingly, we found stronger associations between hair cortisone levels and CD4 count than hair cortisol levels did, which was in line with some previous studies that also reported stronger associations between hair cortisone levels and variables studied than hair cortisol levels did, including Parkinson’s disease [39], Cushing’s syndrome [40], cardiometabolic variables [41, 42], and stress-related variables [39, 43]. In addition, we found hair cortisone levels and hair cortisol levels were positively correlated, which is similar to the findings in previous studies [39, 41, 42, 44,45,46]. Previous studies indicated that salivary cortisone levels were more closely associated with unbound, biologically active cortisol levels than total cortisol levels [26], and hair cortisone levels were significantly associated with salivary cortisone levels [45, 47]. Therefore, hair cortisone levels may provide a valuable surrogate for assessing long-term free cortisol levels. Our findings with large sample size and better controlling potential confounders could further support the hypothesis that elevated glucocorticoid levels are associated with CD4 declining and provide implications for future research to consider both hair cortisol and cortisone levels to reflect the long-term glucocorticoid exposure. Furthermore, previous studies indicated linkages among gut dysbiosis, leaky gut, CD4 count, and cortisone in the HIV-related research field [48,49,50,51]. Future research could explore those linkages using hair levels of cortisol and cortisone.

We found that neither hair cortisol levels nor hair cortisone levels were associated with HIV viral load. Our results regarding the nonsignificant association between hair glucocorticoid levels and HIV viral load were generally in line with previous cross-sectional studies by employing hair cortisol levels [21, 23], serum cortisol levels [14, 52], and urinary cortisol levels [16]. However, one longitudinal study reported that urinary cortisol levels could predict a faster increase in HIV viral load over 4 years [12]. Thus, further research is needed to explore this association with a longitudinal design.

While our study does hold some strengths, including enrolling a large cohort of PLHIV as participants, controlling various confounders, and using 1-cm hair to measure the past month's glucocorticoid exposure, several limitations need to be acknowledged. First, the current study was based on cross-sectional data. Our findings cannot draw causal inferences. Future research should examine the predictive value of hair glucocorticoid levels for incident HIV disease progression using longitudinal designs. Second, several other glucocorticoid measurements (e.g., cortisol awakening response and diurnal slope) in blood or saliva [8, 53], cortisol regulations (e.g., the sensitivity of the glucocorticoid receptor) [54,55,56], and other indicators of HIV disease progression (e.g., HIV DNA levels, CD8 and CD16) should be considered in future research in that they may yield robust conclusions. Third, because all participants are from Guangxi, China, these findings may not be generalizable to other PLHIV settings. Fourth, while data were not available in the current study on some other potential factors (e.g., physical exercise, depression, and some other medications) that might influence hair cortisol levels, CD4 count, and HIV viral load [35, 57], those factors should be considered in future research.

Conclusion

In summary, this study found that hair cortisol and cortisone levels were negatively associated with CD4 count, but not HIV viral load, in a large cohort of Chinese PLHIV. Our data furtherly supported the hypothesis that elevated cortisol levels are associated with lower CD4 counts. Future work will focus on the longitudinal relationship of cortisol and cortisone levels in various biological samples to indicators of HIV disease progression.

Availability of data and materials

The datasets generated and/or analyzed in the current study are available from the corresponding author on reasonable request.

Abbreviations

11β-HSD:

11β Hydroxysteroid dehydrogenase

BMI:

Body mass index

cART:

Combination antiretroviral therapy

CD4:

CD4 + T-lymphocytes

CDC:

Center for disease control and prevention

CI:

Confidence interval

HIV:

Human immunodeficiency virus

HPA:

Hypothalamic–pituitary–adrenal

LC/MS/MS:

Liquid chromatography-tandem mass spectrometry

OR:

Odds ratio

aOR:

Adjusted odds ratio

cOR:

Crude odds ratio

PLHIV:

People living with HIV

SPSS:

Statistical product and service solutions

References

  1. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. The Lancet. 2013;382(9903):1525–33.

    Google Scholar 

  2. Saag MS, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the international antiviral society-USA panel. JAMA. 2018;320(4):379–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Clerici M, et al. Immunoendocrinologic abnormalities in human immunodeficiency virus infection. Ann N Y Acad Sci. 2000;917:956–61.

    CAS  PubMed  Google Scholar 

  4. Cole SW. Psychosocial influences on HIV-1 disease progression: neural, endocrine, and virologic mechanisms. Psychosom Med. 2008;70(5):562–8.

    PubMed  Google Scholar 

  5. Christeff N, et al. Serum cortisol and DHEA concentrations during HIV infection. Psychoneuroendocrinology. 1997;22(Suppl 1):S11–8.

    CAS  PubMed  Google Scholar 

  6. Christeff N, Nunez EA, Gougeon ML. Changes in cortisol/DHEA ratio in HIV-infected men are related to immunological and metabolic perturbations leading to malnutrition and lipodystrophy. Ann N Y Acad Sci. 2000;917:962–70.

    CAS  PubMed  Google Scholar 

  7. Lortholary O, et al. Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men. J Clin Endocrinol Metab. 1996;81(2):791–6.

    CAS  PubMed  Google Scholar 

  8. Patterson S, et al. Cortisol patterns are associated with T cell activation in HIV. PLoS ONE. 2013;8(7):e63429.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Chittiprol S, et al. HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: a two-year follow-up study. Clin Chim Acta. 2009;409(1–2):4–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Leserman J, et al. Impact of stressful life events, depression, social support, coping, and cortisol on progression to AIDS. Am J Psychiatry. 2000;157(8):1221–8.

    CAS  PubMed  Google Scholar 

  11. Leserman J, et al. Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and physiological predictors. Psychol Med. 2002;32(6):1059–73.

    CAS  PubMed  Google Scholar 

  12. Ironson G, et al. Psychosocial and neurohormonal predictors of HIV disease progression (CD4 cells and viral load): a 4 year prospective study. AIDS Behav. 2015;19(8):1388–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kertzner RM, et al. Cortisol levels, immune status, and mood in homosexual men with and without HIV infection. Am J Psychiatry. 1993;150(11):1674–8.

    CAS  PubMed  Google Scholar 

  14. Collazos J, et al. Serum cortisol in HIV-infected patients with and without highly active antiretroviral therapy. AIDS. 2003;17(1):123–6.

    PubMed  Google Scholar 

  15. de la Torre B, et al. Blood cortisol and dehydroepiandrosterone sulphate (DHEAS) levels and CD4 T cell counts in HIV infection. Clin Exp Rheumatol. 1997;15(1):87–90.

    PubMed  Google Scholar 

  16. Fekete EM, et al. Stress buffering effects of oxytocin on HIV status in low-income ethnic minority women. Psychoneuroendocrinology. 2011;36(6):881–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Gorman JM, et al. Glucocorticoid level and neuropsychiatric symptoms in homosexual men with HIV infection. Am J Psychiatry. 1991;148(1):41–5.

    CAS  PubMed  Google Scholar 

  18. Tripathy SK, Agrawala RK, Baliarsinha AK. Endocrine alterations in HIV-infected patients. Indian J Endocrinol Metab. 2015;19(1):143–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Wen Y, et al. Correlation of baseline hormonal disorders with immunological failure and mortality in male HIV patients during follow-up. Medicine (Baltimore). 2016;95(52):e5732.

    Google Scholar 

  20. Wisniewski TL, et al. The relationship of serum DHEA-S and cortisol levels to measures of immune function in human immunodeficiency virus-related illness. Am J Med Sci. 1993;305(2):79–83.

    CAS  PubMed  Google Scholar 

  21. Langerak T, et al. The relation between long-term cortisol levels and the metabolic syndrome in HIV-infected patients. Clin Endocrinol (Oxf). 2015;83(2):167–72.

    CAS  Google Scholar 

  22. Qiao S, et al. Hair Measurements of cortisol, DHEA, and DHEA to cortisol ratio as biomarkers of chronic stress among people living with hiv in China: known-group validation. PLoS ONE. 2017;12(1):e0169827.

    PubMed  PubMed Central  Google Scholar 

  23. Cooper RL, et al. The effects of perceived stress and cortisol concentration on antiretroviral adherence when mediated by psychological flexibility among southern black men living with HIV. AIDS Behav. 2021;25(2):645–52.

    PubMed  Google Scholar 

  24. Murnane PM, et al. Perinatal food insecurity and postpartum psychosocial stress are positively associated among kenyan women of mixed HIV status. AIDS Behav. 2020;24(6):1632–42.

    PubMed  PubMed Central  Google Scholar 

  25. Stalder T, Kirschbaum C. Analysis of cortisol in hair–state of the art and future directions. Brain Behav Immun. 2012;26(7):1019–29.

    CAS  PubMed  Google Scholar 

  26. Perogamvros I, et al. Salivary cortisone is a potential biomarker for serum free cortisol. J Clin Endocrinol Metab. 2010;95(11):4951–8.

    CAS  PubMed  Google Scholar 

  27. Vanaelst B, et al. Cortisone in hair of elementary school girls and its relationship with childhood stress. Eur J Pediatr. 2013;172(6):843–6.

    CAS  PubMed  Google Scholar 

  28. Wang W, et al. Hair cortisone level is associated with PTSDs dysphoric arousal symptoms in highly traumatized Chinese females. J Affect Disord. 2015;182:18–22.

    CAS  PubMed  Google Scholar 

  29. Yang X, et al. Socioeconomic disparity of immunologic outcome among people living with HIV in Guangxi. China AIDS Care. 2020;33:1–5.

    CAS  Google Scholar 

  30. Zeng C, et al. Anticipated stigma and medication adherence among people living with HIV: the mechanistic roles of medication support and ART self-efficacy. AIDS Care. 2020;8:1–9.

    Google Scholar 

  31. Cooper GA, et al. Society of hair testing guidelines for drug testing in hair. Forensic Sci Int. 2012;218(1–3):20–4.

    CAS  PubMed  Google Scholar 

  32. Sachs H. Quality control by the society of hair testing. Forensic Sci Int. 1997;84(1–3):145–50.

    CAS  PubMed  Google Scholar 

  33. Gao W, et al. Quantitative analysis of steroid hormones in human hair using a column-switching LC-APCI-MS/MS assay. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;928:1–8.

    CAS  PubMed  Google Scholar 

  34. Eisinger RW, Dieffenbach CW, Fauci AS. HIV viral load and transmissibility of HIV infection: undetectable equals untransmittable. JAMA. 2019;321(5):451–2.

    PubMed  Google Scholar 

  35. Wosu AC, et al. Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress. Ann Epidemiol. 2013;23(12):797–811.

    PubMed  PubMed Central  Google Scholar 

  36. Rippe RC, et al. Splitting hair for cortisol? Associations of socio-economic status, ethnicity, hair color, gender and other child characteristics with hair cortisol and cortisone. Psychoneuroendocrinology. 2016;66:56–64.

    CAS  PubMed  Google Scholar 

  37. Staufenbiel SM, et al. Determinants of hair cortisol and hair cortisone concentrations in adults. Psychoneuroendocrinology. 2015;60:182–94.

    CAS  PubMed  Google Scholar 

  38. Zhang Q, et al. Comparing self-reported medication adherence measures with hair antiretroviral concentration among people living with HIV in Guangxi, China. AIDS Res Ther. 2020;17(1):8.

    PubMed  PubMed Central  Google Scholar 

  39. van den Heuvel LL, et al. Hair glucocorticoid levels in Parkinson’s disease. Psychoneuroendocrinology. 2020;117:104704.

    PubMed  Google Scholar 

  40. Savas M, et al. Hair glucocorticoids as a biomarker for endogenous cushing’s syndrome: validation in two independent cohorts. Neuroendocrinology. 2019;109(2):171–8.

    CAS  PubMed  Google Scholar 

  41. Stalder T, et al. Cortisol in hair and the metabolic syndrome. J Clin Endocrinol Metab. 2013;98(6):2573–80.

    CAS  PubMed  Google Scholar 

  42. Feeney JC, O’Halloran AM, Kenny RA. The association between hair cortisol, hair cortisone, and cognitive function in a population-based cohort of older adults: results from the irish longitudinal study on ageing. J Gerontol Ser A. 2018.

  43. Davison B, Singh GR, McFarlane J. Hair cortisol and cortisone as markers of stress in Indigenous and non-Indigenous young adults. Stress. 2019;22:1–11.

    Google Scholar 

  44. Kuehl LK, et al. Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions. Psychoneuroendocrinology. 2015;51:365–70.

    CAS  PubMed  Google Scholar 

  45. Zhang Q, et al. Correlations of hair level with salivary level in cortisol and cortisone. Life Sci. 2018;193:57–63.

    CAS  PubMed  Google Scholar 

  46. Zhang Q, et al. Intraindividual stability of cortisol and cortisone and the ratio of cortisol to cortisone in saliva, urine and hair. Steroids. 2017;118:61–7.

    CAS  PubMed  Google Scholar 

  47. Chen Z, et al. Determination, intercorrelation and intraindividual stability of five steroids in hair, saliva and urine among chinese college students. Steroids. 2019;149:108418.

    CAS  PubMed  Google Scholar 

  48. Zheng G, et al. Corticosterone mediates stress-related increased intestinal permeability in a region-specific manner. Neurogastroenterol Motil. 2013;25(2):e127–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Ellis RJ, et al. Markers of gut barrier function and microbial translocation associate with lower gut microbial diversity in people with HIV. Viruses. 2021;13(10):1891.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Lu W, et al. Association between gut microbiota and CD4 recovery in HIV-1 infected patients. Front Microbiol. 2018;9:1451.

    PubMed  PubMed Central  Google Scholar 

  51. Ramendra R, et al. Circulating LPS and (1–>3)-beta-D-glucan: a folie a deux contributing to HIV-associated immune activation. Front Immunol. 2019;10:465.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Collazos J, Ibarra S, Loureiro M. Cortisol serum levels and their relationship to certain antiretroviral drugs. Scand J Infect Dis. 2004;36(6–7):480–2.

    CAS  PubMed  Google Scholar 

  53. Hantsoo L, et al. Glucocorticoid-immune response to acute stress in women and men living with HIV. J Behav Med. 2019;42:1153.

    PubMed  PubMed Central  Google Scholar 

  54. Koutkia P, et al. Increased adrenal androgen secretion with inhibition of 11beta-hydroxylase in HIV-infected women. Am J Physiol Endocrinol Metab. 2006;290(5):E808–13.

    CAS  PubMed  Google Scholar 

  55. Norbiato G. Endocrine, metabolic, and immunologic components of HIV infection. Ann N Y Acad Sci. 2012;1262:51–5.

    CAS  PubMed  Google Scholar 

  56. Chrousos GP, Zapanti ED. Hypothalamic-pituitary-adrenal axis in HIV infection and disease. Endocrinol Metab Clin North Am. 2014;43(3):791–806.

    PubMed  Google Scholar 

  57. Garcia A, et al. Effects of combined exercise training on immunological, physical and biochemical parameters in individuals with HIV/AIDS. J Sports Sci. 2014;32(8):785–92.

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank all participants who gave their time for the current study and HIV care providers for their collaboration during the data collection.

Funding

This study was supported by the National Institutes of Health (Grant number R01MH0112376) and the National Nature Science Foundation of China (Grant number 81761128004). The funding body had no role in the data collection, analysis, interpretation of the data, and writing of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

XML, ZYS, and SQ designed the study. ZYS, YJZ, and SFL were important collaborators and helped with participant recruitment. QZ and SFL analyzed the data, interpreted the results, and wrote the initial manuscript. XML and SQ revised the manuscript critically for important intellectual content and overviewed the whole process. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Quan Zhang or Zhiyong Shen.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Institutional Review Boards at both University of South Carolina (Columbia, USA) and the Guangxi CDC (Nanning, China). All methods in this study were carried out in accordance with relevant guidelines and regulations. All participants provided written informed consent to participate in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Li, X., Qiao, S. et al. The relationship of hair glucocorticoid levels to immunological and virological outcomes in a large cohort of combination antiretroviral therapy treated people living with HIV. BMC Infect Dis 22, 268 (2022). https://doi.org/10.1186/s12879-022-07257-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-022-07257-x

Keywords

  • Hair cortisol
  • Hair cortisone
  • CD4 count
  • HIV viral load
  • People living with HIV