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Abstract

Background:

We aimed to study the effect of reflexology on the immunological parameters of people living with HIV (PLWH).

Methods:

We performed a retrospective cohort study evaluating the effect of reflexology treatment on the immunological parameters of PLWH. All patients who received at least one treatment were included and compared with the group of PLWH who were not treated with reflexology. Measured parameters included CD4 count, CD4%, CD8 count, CD8%, CD4/CD8 ratio, and HIV viral load (VL). Changes in these parameters before and after the treatment were compared with changes in two consecutive measurements in the control group.

Results:

In total, 74 patients who received reflexology treatment were matched to 144 controls. There was a male predominance of 86% in both groups. Patients in the control group were slightly older, with a median age of 45 versus 43 in the treatment group (p = 0.022). The median baseline CD4 count (730 vs. 795, p = 0.187) and CD8 count (890 vs. 832, p = 0.32) did not differ between the groups. Baseline CD4% tended to be lower in the treatment group (34% vs. 36%, p = 0.058), CD8% was higher in the treatment group (40% vs. 38%, p = 0.03), and the CD4/CD8 ratio was lower in the treatment group (0.8 vs. 1, p = 0.002). After therapy, there was a significantly higher increase in CD4, CD4%, and CD4/CD8 in the treatment group (p = 0.006, 0.0004, <0.001, respectively), whereas CD8% decreased significantly and CD8 tended to decrease in the treatment group (p < 0.001, 0.054, respectively).

Conclusions:

Reflexology showed a positive impact on the immunological parameters of PLWH.

Introduction

Reflexology is a well-known holistic theory and is an important part of integrative medicine as one of the therapies of complementary medicine, touch therapy.

Classical reflexology, as an ancient therapy, is based on the claim of reflection of physical, mental, and spiritual body on feet. Reflexology claims that different types of touch or pressing on reflex points on the feet stimulate systems and organs to balance their various functions. Pressure applied on specific zones of feet is referred to organs by stimulating specific nerve receptors, and the body is able to interpret the signals and change the function. Modern classical reflexology is associated with the names of American physician William Fitzgerald and physiotherapist Eunice Igham from the first half of the 20th century.^1–2

The majority of studies published in the field of reflexology focused on improving quality of life, pain relief, and effectiveness in sleep disturbances, especially in patients with cancer. For example, the study by Alexandra Mantoudi showed reflexology to be effective in decreasing anxiety and depression in patients with cancer. It was shown to have a significant impact on the physical aspects of quality of life and pain management in this group of patients.³

People living with HIV (PLWH) are a diverse group of patients who, along with chronic physical illness affecting the immune system, suffer from the negative impact of stigma. PLWH face situations that have a negative impact on mental health. Those include fear of being denied because of the diagnosis and fear of disclosing the status not only to the sexual partners but also to family and medical services. They often suffer from anxiety and depressive disorders.⁴ The rates of smoking, alcohol, and substance abuse are higher in PLWH than in the general population.^5–6 Patients are being refused to receive conventional and complementary medical services because of stigma.

No studies were performed previously to evaluate the effect of reflexology on the physiological parameters of PLWH. Our study aimed to evaluate the impact of reflexology treatment on the immunological parameters of PLWH followed in the HIV clinic, Tel-Aviv Sourasky Medical Center.

Materials and Methods

Study population and study design

We performed a retrospective single center cohort study, evaluating the effect of reflexology therapy on immunological laboratory parameters of PLWH.

Tel-Aviv Sourasky Medical Center is a tertiary hospital situated in central Israel that provides medical services to patients of Tel-Aviv and surrounding cities in the Gush Dan area. The Crusaid Kobbler AIDS Center is a large HIV clinic with more than 2000 PLWH on active medical follow-up. It includes medical doctors, medical nurses, HIV laboratories, and social services.

The majority of patients on active follow-up receive antiretroviral therapy (ART) and are stable with undetectable HIV viral load (VL). Routine follow-up testing is performed every 4–6 months and includes CD4 count, CD4%, CD8 count and CD8%, CD4/CD8 ratio, HIV VL, as well as complete blood count and blood chemistry.

During 2015–2017 and 2022–2023, reflexology therapy was implemented in our center. Treatment was performed by a single advanced reflexologist with over 10 years of experience in field. Patients could be self-referred or advised by HIV physicians. Patients could be referred if they were stable on antiretroviral medications with no contraindication to reflexology treatment (acute medical condition [active coronary artery disease, stroke, and sepsis], advanced thrombocytopenia, and active rash, involving feet). The main reasons for referral included weakness, sleep disturbances, mental illnesses, psychosomatic and mental pain, rehabilitation after myocardial infarction, withdrawal from recreational drugs, rehabilitation after opportunistic infections or cancer, etc.

The first reflexology session lasted 90 min and included patient interview to understand the symptoms and complaints and to provide individualized symptom-derived treatment. Treatment was based on the nature of the disease, both physical and mental, and patient specificity. The further sessions lasted 60 min. Before and after each session, blood pressure was measured. Classical foot reflexology was an applied reflexology method. No other complementary therapies were concurrently used. All the patients who had received at least one reflexology treatment were included into the treatment group.

For control group selection, we used a clinical database and first patients in the alphabetical order who met the inclusion criteria and were included into the control group. Group matching by age and sex was performed. Patients were included if they were stable on ART and were on active follow-up with available consequent laboratory analyses.

The analyzed laboratory parameters included absolute CD4 count (cells/mm³), CD4%, absolute CD8 count (cells/mm³), CD8%, CD4/CD8 ratio, and HIV VL, copies/mL. All laboratory tests were performed in a single HIV laboratory. We collected the laboratory data of patients before and after reflexology treatment and compared them to two consequent tests of patients in the control group.

Laboratory methods

HIV VL was determined with a Cepheid Xpert HIV-1 VL, and a result of less than 40 copies/mL was considered undetectable. CD4⁺ and CD8⁺ T-cell counts were determined by flow cytometry analysis of freshly collected peripheral blood (within 4–6 h after blood sampling).

Statistical analyses

Categorical variables were summarized as frequencies and percentages. Continuous variable distribution was evaluated using histograms and the Shapiro–Wilk test. Continuous variables are reported as medians and interquartile ranges. The chi-square test and Mann–Whitney test were applied to compare categorical and continuous variables between the groups. Spearman correlation was used to study the association between continuous variables. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. NCSS software was used for statistical analyses (NCSS 2020 Statistical Software. Ver.22.0.5, NCSS, LLC. Kaysville, UT, USA 2022).

Ethical approval

The study was approved by the Institutional Ethical Committee (0079-20 TLV). Owing to the retrospective study design, the requirement for informed consent was waived.

Results

During the study period, 74 PLWH received reflexology treatment, 45 patients were treated in 2015–2017 and 29 in 2022–2023. They were matched to 144 control patients.

Baseline characteristics

The majority of patients were male in both groups. Patients in the control group were slightly older, with a median age of 45 versus 43 in the treatment group (p = 0.022) (see Table 1). The baseline absolute CD4 count did not differ significantly between the groups, with a median of 730 cells/mm³ (549–949) in the treatment group versus 795 cells/mm³ (602–1026) in the control group (p = 0.18), while CD4% tended to be higher at baseline in the control group (36% vs. 34%, p = 0.058). There were no significant differences in the absolute CD8 count at baseline, while the CD8% was lower in the control group, with a median of 38% (32%−43%) versus 40% (35%−46%) (p = 0.03). The CD4/CD8 ratio was higher in controls, with a median of 1 (0.7–1.3) versus 0.83 (0.6–1), p = 0.002. The patients in both groups were on effective ART with an undetectable HIV VL (<40 copies/mL). Blood pressure decreases were observed at the end of each therapy session in all patients.

Table 1.

Baseline Characteristics of Treatment and Control Groups

Parameter	Treatment group	Control group	p-value
Number of patients	74	144
Age, median (IQR)	43 (26–67)	45 (29–71)	0.022
Sex, n (%) male female	64 (86) 10 (14)	125 (87) 19 (13)	0.94
Number of treatment sessions, median (IQR)	5 (3–7)
Absolute CD4, cells/mm³, baseline, median (IQR)	730 (549–949)	795 (602–1026)	0.18
CD4%, baseline median (IQR)	34 (26–39)	36 (30–41)	0.058
Absolute CD8, cells/mm³, baseline, median (IQR)	890 (664–1123)	832 (641–1126)	0.3
CD8%, baseline, median (IQR)	40 (35–46)	38 (32–43)	0.03
CD4/CD8 ratio, baseline, median (IQR)	0.83 (0.6–1)	1 (0.7–1.3)	0.002
HIV viral load, copies/mL baseline, median (IQR)	0 (0–20)	0 (0–25)	0.61
Absolute CD4, cells/mm³, after treatment, median (IQR)	807 (585–1020)	776 (570–960)	0.6
CD4%, after treatment, median (IQR)	35 (30–40)	34 (29–40)	0.79
Absolute CD8, cells/mm³, after treatment, median (IQR)	850 (642–1115)	852 (627–1169)	0.62
CD8%, after treatment, median (IQR)	38 (33–44)	40 (33–46)	0.43
CD4/CD8 ratio, after treatment, median (IQR)	1 (0.7–1.2)	0.9 (0.6–1.2)	0.5
HIV viral load, copies/mL, after treatment, median (IQR)	0 (0–21)	0 (0–39)	0.49

IQR, interquartile range, bold indicates significant.

The effect of treatment

The median number of reflexology sessions was 5 (3–7) per patient in the treatment group. After the treatment, the absolute CD4 count did not differ between the groups, nor did the CD4%, absolute CD8, CD8%, or CD4/CD8 ratio (see Table 1).

To analyze the changes between the baseline parameters and after reflexology treatment, the delta (parameter level after the treatment minus level at baseline) was calculated. In the treatment group, we observed CD4 elevation with a median of 43 (−77to 160) cells/mm³, while in the control group, the absolute CD4 count decreased with a median of — 15 (−131 to 91), p = 0.006. CD4% delta increased in the treatment group with a median of 2% (−1% to 4%) versus −0.5% (−3% to 2%) in the control group, p = 0.004. The changes in absolute CD8 T cells tended to be better in the treatment group, with a median of −14 (−174 to 114) versus 26 (−100 to 190), p = 0.054. CD8% and CD4/CD8 ratio also improved in the treatment group versus controls (−3% [−6% to 1%] versus 1% [−1% to 5%], p < 0.001, 0.1 [0–0.2] versus −0.1 [−0.2 to 0], p < 0.001, respectively). HIV VL remained undetectable after the treatment (Table 2).

Table 2.

Changes in Laboratory Parameters (Delta) Before and After Treatment

Parameter	Treatment group	Control group	p-value
CD4 delta, cells/mm³, median (IQR)	43 (−77 to 160)	−15 (−131 to 91)	0.006
CD4% delta, median (IQR)	2 (−1to 4)	−0.5 (−3 to 2)	0.004
CD8 delta, cells/mm³, median (IQR)	−14 (−174 to 114)	26 (−100 to 190)	0.054
CD8% delta, median (IQR)	−3 (−6 to 1)	1 (−1 to 5)	<0.001
CD4/CD8 ratio delta, median (IQR)	0.1 (0–0.2)	−0.1 (−0.2 to 0)	<0.001

Bold values are statistically significant.

Delta, parameter after—parameter before.

IQR, interquartile range.

Discussion

This is the first study evaluating the effect of reflexology on the immunological parameters of PLWH. Previous studies have focused on the types and reasons for the usage of complementary medicine among PLWH, with the main reasons being nausea, depression, insomnia, and weakness.^7–10 It has been shown that patients with more advanced and symptomatic disease tend to refer more often to complementary medicine services.¹¹ Other studies investigated the role of complementary therapy in approving adherence to ART.^12–13

Our study focused on the effect on physiological parameters and showed a statistically significant improvement in absolute CD4 and CD4 percentages as well as the CD4/CD8 ratio in patients who received reflexology therapy.

HIV infection leads to severe depletion of CD4 T cells in the gut-associated lymphoid tissue with subsequent reduced levels of circulating CD4 lymphocytes in the peripheral blood. CD4 cells are reduced in acute HIV infection but usually rebound in the blood over several weeks as HIV-specific CD8 T cells help to lower plasma viremia.¹⁴ In the untreated patient, CD4 T cells subsequently decline over several years. CD4/CD8 ratio is calculated by dividing the number of CD4⁺ T-cells by the number of CD8+ T-cells. This ratio is usually greater than 1 in immunocompetent individuals. However, in HIV-infected patients, the CD4/CD8 ratio is usually less than 1.¹⁵ This reflects increasing numbers of CD8+ T cells and depletion of CD4⁺ T cells in chronic infection. This ratio usually increases with the initiation of ART although the CD4:CD8 ratio normalizes in only a minority of patients.¹⁶ Apart from the association between low CD4 count and higher risk of infections and malignancy in PLWH, studies have shown an association between low CD4/CD8 ratio and increased cardiovascular morbidity.^17–18

Our study showed an elevation of CD4 cells with a median of 43 cells/mm³ and an elevation of CD4/CD8 ratio by a median of 0.1 after the treatment, which was statistically significant. While we cannot establish an immediate clinical significance of these findings in preventing infections or long-term cardiovascular morbidity, this effect can be considered plausible. Interestingly, the effect was achieved after the first sessions (median 5) and was not influenced by the number of treatments, probably reflecting the prolonged effect of reflexology. The prolonged effect was shown in previous studies evaluating the influence of this technique in patients with cancer. However, our study checked the difference between the two consequent tests, performed 4–6 months apart, thus it was not able to confirm the durability of the effect for more than 6 months.

A probable explanation of the study findings is the modulation of the sympathetic nervous system during reflexology therapy. Physical changes, emotional arousal, and changes in the environment can evoke stress, requiring the altered activity of visceral organs and glands with the rise of circulating epinephrine and norepinephrine.¹⁹ Sympathetic innervation in secondary lymphoid organs plays a major role in immune regulation. Catecholamines released from nerve terminals serve as major mediators when bound to the adrenergic receptor of immunocompetent cells. Sympathetic nerve activity is generally suppressive for immune cells with a more profound effect on Th-1 responses,^20–22 thus reducing cellular immunity.

A study by Wan-An Lu²³ showed decreased sympathetic modulation and increased vagal stimulation with the use of foot reflexology in patients with coronary artery disease. The systolic, diastolic, and mean blood pressure was decreased in patients treated with foot reflexology in this study—a finding that was similar to our observation. Another study by CM Hughes showed a decrease in systolic and diastolic blood pressure following reflexology therapy in patients experiencing mental stress,²⁴ with a probable explanation for the effect on the autonomic nervous system.

Our study has limitations that should be mentioned. First, we could not assess the durability of the effect on immunological parameters as only two consequent measurements before and after the treatment were checked. Second, we performed group matching rather than individual matching. Third, only laboratory parameters were used without evaluation of parameters of life quality. Further studies are needed with a combination of evaluating physiological parameters and questionnaires and for evaluating the durability of the effect.

To conclude, this is the first study investigating the effect of reflexology therapy on immune system parameters in PLWH, showing a statistically significant positive impact. Further studies are needed to address the impact on life quality parameters and the durability of the effect.

Footnotes

Acknowledgments

The article was published in a pre-print server. The Effect of Reflexology on Immunological Parameters of People Living with HIV (PLWH)

Authors’ Contributions

E.N.: conceptualization, methodology, and investigation; D.T.: data curation and article review and editing; T.Z.-B.: data curation and formal analysis, L.T.: methodology, original draft writing, and data curation

Disclaimer

Gilead Sciences was not involved in the study design or article writing.

Availability of Data and Materials

The dataset used and analyzed during the current study is available from the corresponding author on reasonable request.

Author Disclosure Statement

Elena Nison and Luba Tau had received a grant for reflexology therapy in HIV clinic from Gilead Sciences.

Funding Information

Reflexology therapy was supported via a grant from Gilead Sciences. Grant number 13038.

Abbreviations Used

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